ArticlePDF Available

Pears and renal stones: possible weapon for prevention? A comprehensive narrative review

Authors:

Abstract and Figures

Urinary stones have been recognized as a human disease since dawn of history and treatment of this condition is reported by Egyptian medical writings. Also, pears have a very long history, being one of the earliest cultivated fruit trees and also known for medicinal use. Urinary tract stone formation represents a common condition and also a significant burden for health care service, due also to possible frequent relapses. Furthermore, urinary stones have been reported to have relationship with different metabolic derangements, and appropriate diet could contribute to avoid or reduce urinary stone formation. Citrate is an inhibitor of crystal growth in the urinary system, and hypocitraturia represents a main therapeutical target in stone formers. Pears contain a significant amount of malic acid, a precursor of citrate, and have antioxidant activity as well. A diet supplemented with pears, and associated with low consumption of meat and salt could impact positively cardiometabolic risk and urinary tract stone formation. However, very few studies evaluated the impact of pears utilization on health, and none on urinary tract stone formation in particular. High content in malate could warrant protection against stone formation, avoiding patients at high risk to be compelled to assume a considerable and expensive amount of pills.
Content may be subject to copyright.
414
Abstract. – Urinary stones have been recog-
nized as a human disease since dawn of history
and treatment of this condition is reported by
Egyptian medical writings. Also, pears have a
very long history, being one of the earliest culti-
vated fruit trees and also known for medicinal
use. Urinary tract stone formation represents a
common condition and also a significant burden
for health care service, due also to possible fre-
quent relapses. Furthermore, urinary stones
have been reported to have relationship with dif-
ferent metabolic derangements, and appropriate
diet could contribute to avoid or reduce urinary
stone formation. Citrate is an inhibitor of crystal
growth in the urinary system, and hypocitraturia
represents a main therapeutical target in stone
formers. Pears contain a significant amount of
malic acid, a precursor of citrate, and have an-
tioxidant activity as well. A diet supplemented
with pears, and associated with low consump-
tion of meat and salt could impact positively car-
diometabolic risk and urinary tract stone forma-
tion. However, very few studies evaluated the im-
pact of pears utilization on health, and none on
urinary tract stone formation in particular. High
co nt en t in m al at e could warrant pr ot ec ti on
against stone formation, avoiding patients at
high risk to be compelled to assume a consider-
able and expensive amount of pills.
Key words:
Renal stones, Urolithiasis, Prevention, Pears, Organ-
ic acids, Fruit, Diet.
Renal stones and pears:
a brief of a long history
Urinary stones have afflicted humans since the
dawn of history, and gone parallel with the histo-
ry of civilization, as reported in a recent review1.
The first known stones were discovered in Egypt-
ian mummies, and the English archeologist E.
Smith1found a bladder stone from a 4500-5000
Corresponding Author: Roberto Manfredini, MD; e-mail: roberto.manfredini@unife.it
year old mummy in El Amrah, Egypt, in 1901.
Some relevant paleopathology findings are re-
ported in Table I. Treatments for stones were
mentioned in ancient Egyptian medical writings
from 1500 b.C., and surgery to treat stones was
first described by Sushruta, an Indian surgeon liv-
ing around 600 b.C., who provided detailed infor-
mation on urinary stones, urinary anatomy, and
surgery for stones in his writings, compiled as the
Sushruta Samhita1. Medical texts from ancient
Mesopotamia, India, China, Persia, Greece, all
mentioned such disease. Part of the Hippocratic
Oath suggests there were practicing surgeons in
ancient Greece to whom physicians were to defer
for lithotomies. The Roman medical treatise De
Medicina by Aulus Cornelius Celsus contained a
description of lithotomy2, and this work served as
the basis for this procedure until the 18th century.
Also as an anedoctal report, we here report only a
short list of a series of historical or distinguished
in any field figures documented to be kidney
stone formers (Table II).
Pear has a very long history behind as well. In
fact, it is one of the earliest cultivated of fruit
trees. In 5,000 b.C., Feng Li, a Chinese diplomat,
abandoned his responsibilities when he became
consumed by grafting peaches, almonds, persim-
mons, pears and apples as a commercial venture.
There are records in China and Europe of pears
more than 4,000 years ago reporting that dried
pears were used medicinally in those days. Greek
mythology refers to the pear as a wholesome,
tasty fruit, favourite of gods and heroes, and
Homer himself (9th century b.C.) in The Odyssey
gave confirmation that the pear was cultivated in
Greece as early as three thousand years ago.
Homer included the pear as one of the ‘gifts of
the gods’3. More than 350 years b.C. the cultiva-
tion and the production of the pear was quite
widespread in the Magna Graecia, and the ancient
greek author Theophrastus mentioned both the
European Review for Medical and Pharmacological Sciences
Pears and renal stones: possible weapon for
prevention? A comprehensive narrative review
R. MANFREDINI1, A. DE GIORGI1, A. STORARI2, F. FABBIAN1
1Department of Medical Sciences, University of Ferrara, School of Medicine; Clinica Medica Unit, Azienda
Ospedaliero-Universitaria, Ferrara, Italy.
2Department of Specialistic Medicine, Nephrology Unit, Azienda Ospedaliero-Universitaria, Ferrara, Italy.
2016; 20: 414-425
415
Pears and renal stones
wild varieties of pears and the varieties cultivated
by men. From Greece the pear spread to Rome,
where it was highly regarded. Marcus Procius
Cato (234-149 b.C.), known as Cato the Censor,
in his famous agricultural manual De Agri Cul-
tura (De Re Rustica), wrote extensively on pomo-
logical subjects and described six types of pear3.
In the Roman Empire, the varieties of pears
Geographic area Date Finding
Europe Italy, Sicily 6.500 b.C. Bladder stone
Southern France 2.100 b.C. Bladder stone
United Kingdom, Yorkshire 2.000-700 b.C. Bladder stone
Hungary Bronze age Bladder stone
Germany 500-250 b.C. Bladder stones (probably)
United Kingdom, Somerset 450-1.000 a.D. Bladder stones
Hungary VI-VII century a.D. Bladder stone
Denmark 1.300-1.500 a.D. Renal stone
Italy Early XIX century Bladder stone
Africa Predynastic skeleton 3.900-3.100 b.C. 3 bladder stones
Abido, Egypt 3.500 b.C. Bladder stone
Helouan, Egypt 3.100 b.C. Renal stones (several individuals)
Naga-el-Deir, Egypt 2.800 b.C. 4 renal stones
Mummy, Old Kingdom, Egypt 2.650-2.150 b.C. Renal stone
Mummy, XXI dynasty, Egypt 1.069-945 b.C. Triangular stone located into the naris
Jebel Moya, Sudan 1.000-100 b.C. Bladder stones (several individuals)
America Kentucky 3.500-3.000 b.C. Renal and bladder stones (3 individuals)
Illinois 1.500 b.C. Renal stone
Arizona 100 b.C.-500 a.D. Bladder stone (mummy)
Utah 950-1.100 a.D. Bladder stone
Chile 1.000 a.D. Urethra stone (mummy)
Arizona 1.100-1.250 a.D. Bladder stone
Indiana 1.500 a.D. Bilateral renal stones
West Virginia 1.600-1.700 a.D. Renal stone
Table I. Renal stones and some relevant paleopathology findings.
Emperors, kings, Politicians, religious Artists, philosophers, Performers
popes, presidents persons, statesmen physicians, scientists, (music, cinema)
writers
Caesar Augustus Martin Luther Epicurus Cole Porter
(63 b.C.-14 a.D.) (1483-1546) (341-270 b.C.) (1891-1964)
James I Stuart John Calvin Michelangelo Buonarroti Alfred Hitchcock
(1566-1625) (1509-1564) (1475-1564) (1899-1980)
Innocent XI Oliver Cromwell Michele de Montaigne Bing Crosby
(1611-1689) (1599-1658) (1533-1592) (1903-1977)
Luois XIV Cardinal Jules Mazarin Francis Bacon Ava Gardner
(1638-1715) (1602-1661) (1561-1626) (1922-1990)
Peter the Great Samuel Pepys William Harvey Roger Moore
(1672-1725) (1633-1703) (1578-1657) (1927- )
Anna of Russia Benjamin Franklin Thomas Sydenham Burt Reynolds
(1693-1740) (1706-1790) (1624-1689) (1936- )
George IV Mother Teresa Robert Boyle Billy Joel
(1762-1830) (1910-1997) (1627-1691) (1949-)
Napoleon I Indira Ghandi Isaac Newton Tim Burton
(1769-1821) (1917-1984) (1642-1727) (1958-)
Leopold I of Belgium Gottfried von Leibnitz
(1790-1865) (1646-1716)
Napoleon III Antonio Scarpa
(1808-1873) (1752-1832)
Lyndon B. Johnson Jack London
(1908-1973) (1876-1916)
Table II. Some historical persons or distinguished in any field figures documented to be kidney stone formers.
416
known were about fourty. After the Middle Ages,
pears were carried by Spanish missionaries to the
New World. Pear strains with fruit of really good
eating qualities were not developed until the 18th
and 19th centuries in Europe and today more than
5000 varieties are known worldwide. From a geo-
graphical point of view, the major areas for the
production of pears are three: (a) East, with China
being the first world producer; (b) Europe and the
Mediterranean basin, with Italy ranking second
among the world countries that produce pears; (c)
the American continent, with the USA third in the
international ranking for the production of pears.
Renal stones:
clinical and economic burden
Urinary tract stones formation represents
common condition occurring in the great majori-
ty of cases in adults, and stone formers are also
notorious recidivists so that economic impact of
this disease is impressive4. In Western countries,
calculated yearly incidence was 0.5% and preva-
lence in the mid-1990 was 5.2%5. Scales et al6
analyzed the prevalence of stone disease in the
United States, and identified factors associated
with history of kidney stones. They reported a
prevalence of 8.8% (10.6% in men, 7.1% in
women), with obesity and diabetes strongly asso-
ciated with history of kidney stones. In order to
estimate the economic impact of the disease in
the United States, Pearle et al7estimated the bur-
den of urolithiasis evaluating the use of health
care resources. Almost 2 million outpatient visits
for a primary diagnosis of urolithiasis were
recorded in the year 2000. Hospital outpatient
visits for urinary tract stones increased by 40%
between 1994 and 2000, and in the same period
physician office visits increased by more than
40% as well. Regarding treatment, shock wave
lithotripsy was the most commonly performed
procedure, followed by ureteroscopy, and such
treatments impact on economic burden. Totally,
in 2000 the estimated annual expenditure for in-
dividuals with claims for a diagnosis of urolithia-
sis was almost $2.1 billion. Moreover, since the
prevalence of nephrolithiasis was higher among
working age adults, the average work loss for
treated subjects had been estimated to be 19
hours per person, with additional costs of 3,494
US dollars per person8. Data from the United
States Nationwide Emergency Department (ED)
Sample of patients evaluated between 2006 and
R. Manfredini, A. De Giorgi, A. Storari, F. Fabbian
2009, showed that, out of 120 million visits to
the ED annually, an average of 1.2 million pa-
tients per year were diagnosed with urolithiasis9.
Overall average rate of admission was higher
than 19%. Nonmetropolitan hospitals had the
lowest costs, but a consistent number of patients
were tran sf er red to other hospitals. In Italy
prevalence of male stone formers increased from
6.8% in 1986 to 10.1% in 1998, and in female
patients from 4.9% to 5.8%. Incidence was cal-
culated to be 0.4% yearly (0.6% in men and
0.18% in women)10.
Furthermore, urolithiasis it is very likely to re-
cur. Italian data reported that 27% of stone formers
experienced symptomatic stone recurrence after a
mean period of 7.5 years, and 28% had recurrent
stones at ultrasound examination being patients
symptom-free. Recurrence was not influenced by
sex, family history of stones and urinary risk fac-
tors11. More recent data from United States12 indi-
cate that up to 50% of patients develop recurrence
after their initial event. Recently, it has been devel-
oped a nomogram in order to predict stone recur-
rence13. Younger age, male sex, white race, family
history of stones, prior asymptomatic stone on
imaging, prior suspected stone episode, gross
hematuria, non-obstructing (asymptomatic) stone
on imaging, symptomatic renal pelvic or lower-
pole stone on imaging, no ureterovesicular junction
stone on imaging, and uric acid stone composition
were the risk factors entered in their model. The
authors calculated that 10-year recurrence rates
varied from 12% to 56% between the first and
fifth quintiles of nomogram score.
Urinary tract stones are made of organic and
inorganic crystals mixed with proteins, and
urolithiasis is not a real diagnosis, but stone for-
mation could be a complication of different un-
derlying diseases. Incidence and prevalence of
stones are increasing globally, across sex, race,
and age, and it is likely that changes in dietary
habits could be a key driving force14. In order to
determine if kidney stone composition could pre-
dict the underlying medical diagnosis, Pak et al15
studied a large cohort of subjects who underwent a
complete ambulatory evaluation and who submit-
ted one or more stones for analysis. The most
common kidney stones were composed of calcium
oxalate (74.8%), followed by mixed calcium ox-
alate-calcium apatite (34.8%), and calcium apatite
alone (10.5%). The most common medical diag-
noses were hypocitraturia (44.3%), absorptive hy-
pe rcalc iuria (36.7%), and hy perur icosu ria
(28.4%). Calcium apatite and mixed calcium ox-
alate-calcium apatite stones were associated with
the diagnoses of renal tubular acidosis and prima-
ry hyperparathyroidism. Calcium oxalate stones
were associated with chronic diarrheal syndromes,
but not with renal tubular acidosis. Pure and
mixed uric acid stones were strongly associated
with a gouty diathesis, and vice versa. Moreover,
there was a very strong association between infec-
tion stones and infection, and between cystine
stones and cystinuria. Urinary tract lithiasis is
rarely the results of hereditary disease such as
cystinuria, primary hyperoxaluria, medullary
sponge kidney, primary hyperparathyroidism or
secondary to well defined disorders such as infec-
tions, anatomical defects of urinary tract. In the
great majority of cases lithiasis could be classified
as idiopathic and in this case dietary habits plays a
major role16. Nowadays lithiasis of urinary tract is
not considered a disease per se, but as a risk factor
and a consequence of metabolic syndrome and
cardiovascular disease17. New approaches to treat-
ment and prevention depend on the identification
of frequent modifiable risk factors for kidney
stones. Obesity appears to be a major determinant
of urinary oxalate excretion18, and body size was
independently associated with the development of
incident kidney stones. Aiming to determine if
weight, weight gain, BMI, and waist circumfer-
ence were associated with lithiasis of urinary tract,
Taylor et al19 conducted a prospective study of 3
large cohorts: the Health Professionals Follow-up
Study, the Nurses' Health Study I, and the Nurses’
Health Study II. They found that obesity and
weight gain increased the risk of kidney stone for-
mation. Besides, also diabetes mellitus is a risk
factors for development of kidney stones in both
sexes20. Rule and coworkers evaluated 4,564 stone
formers and 10,860 control subjects among resi-
dents in Olmsted County, MN, USA21. During a
mean of 9 years of follow-up, stone formers had a
38% increased risk for myocardial infarction, and
this risk remained high (31%) after adjustment for
mellitus, chronic kidney disease, hypertension, di-
abetes, obesity, dyslipidemia, gout, alcohol depen-
dence, and tobacco use and other comorbidities.
Renal stones formation
The milestone in the urinary stone formation
is the precipitation of crystal occurring when the
concentration of salts exceeds the solubility lim-
it, a phenomenon called ‘supersaturation’. In ad-
dition, it is also possible that a deficit of protec-
417
Pears and renal stones
tive substances, defined as crystallization in-
hibitors, may play a role. As always in medicine,
equilibrium represents crucial node (Figure 1).
Pathophysiologic pathways described for kid-
ney stone formation are the following: 1) stones
attached to the surface of a renal papilla where
interstitial apatite plaques develop (defined as
Randall’s plaque); 2) stones protruding from the
openings of ducts of Bellini; 3) stones forming in
free solution in the renal collection system22. The
main lithogenic risk factors are widely recog-
nized, and include low volume of urinary output,
high calcium high oxalate, high uric acid, high
phosphate, low citrate, low magnesium and uri-
nary pH alteration. It is known that conditions
causing chronic dehydration, such as living in ar-
eas with high ambient temperatures, high degree
of physical activity and insufficient replacement
of water losses, may increase the risk of urolithi-
asis23. Urine dilution is the most important pre-
ventive measure for stone recurrence. On the oth-
er hand, high fluid intake not only lowers urinary
concentration of substances inducing stone for-
mation, but dilutes urinary concentration of in-
hibitors as well. However an increase in fluid to
at least 2500 ml daily is the first step strategy in
order to prevent stone24. In order to maintain cal-
cium in solution, urine contains inhibitors of
crystallization. Inhibitors could be classified in
macromolecules and smaller molecules. Osteo-
pontin, prothrombin F1 fragments, inter-α-trypsin
inhibitor molecule calgranulin, Tamm-Horsfall
glycoprotein, albuminRNA and DNA fragments,
and glycosaminoglycans are classified as macro-
molecular species, while citrate, pyrophosphate,
magnesium, and zinc are small molecules16. Stone
forming inhibitors act on kinetics by interfering
with nucleation, growth and aggregation of crys-
tals. Urinary stone formation inhibitors could be
also defined as multivalent metallic cations such
as magnesium, and small organic and inorganic
anions such as citrate and pyrophosphate. How-
ever, in clinical practice the effect of inhibitors is
evaluated by citrate dosage5. At this moment, cit-
Figure I. Lithogenenesis as a syndrome.
418
rate is the only natural inhibitor which could be
measured in urine, and used in medical treat-
ment. It exhibits a double action, opposing urine
crystal formation by both thermodynamic and ki-
netic mechanisms25. Therefore, correction of
hypocitraturia represents a main therapeutical
target, since citrate binds calcium ions increasing
their solubility, and furthermore it binds the crys-
tal surface and inhibits crystal growth and aggre-
gation.
Citrate is an inhibitor of calcium oxalate crystal
growth, and a reduction in its urinary excretion is
considered a risk factor for urinary tract stone for-
mation. Hypocitraturia has been reported to be the
most common urine abnormality with a prevalence
of about 60%26,27. Potassium citrate has been recog-
nized for long time as a mainstay of medical thera-
py for nephrolithiasis28, and in a couple of decades
ago its ingestion was suggested as an useful adjunc-
tive treatment for patients with hypocitraturic calci-
um nephrolithiasis29. Urinary excretion of citrate is
linked to its plasma levels and renal tubular reab-
sorption, and citrate salt ingestion determines sys-
temic alkalinization, decreasing renal reabsorption
and increasing urinary excretion. On one hand, cit-
rate is absorbed in the gastrointestinal tract and is
transformed in the liver forming bicarbonate, on the
other ingestion of citrate as citric acid cause con-
sumption of bicarbonate due to the accompanying
protons. Only if ingested in the form of a potassium
or sodium salt, citrate is converted to alkali without
bicarbonate titration, obtaining a systemic alkalin-
ization. This difference is important in stone form-
ing patients, in fact renal citrate excretion is regulat-
ed by proximal sodium-dicarboxylase cotrans-
porter. The latter mechanism is activated in case of
systemic acidosis. In acidosis states, in fact, citrate
is reabsorbed by the cotransporter and incorporated
into the Krebs cycle, so that citraturia decreases. On
the contrary, alkalosis decreases citrate reabsorption
increasing citraturia30. Increased excretion sec-
ondary to increased synthesis of citrate occurs when
citric acid cycle precursors, i.e., malate or succinate,
(Figure 2) are infused31.
Renal stones and metabolism
alterations
Alteration of metabolism is frequently associ-
ated with renal stones. Obesity and type II dia-
betes mellitus appear to be risk factors for stone
fo rmati on3 2, and in th e case of u ric aci d
nephrolithiasis being diagnosed in overweight pa-
R. Manfredini, A. De Giorgi, A. Storari, F. Fabbian
tients, diabetes mellitus type 2 (type 2DM) should
always be suspected and investigated33. Patients
with type 2DM defined as stone-forming had a
high prevalence of uric acid stones, and shared a
key feature of those with gouty diathesis probably
due to the passage of unusually acid urine34. Uri-
nary pH, in fact, is inversely related to body
weight among patients with stones35. In subjects
with metabolic syndrome, prevalence of uric acid
nephrolithiasis is higher as well. Low urinary pH
is the major determinant in the development of id-
iopathic uric acid stones and the two major abnor-
malities implicated in the development of overly
acidic urine are: (i) increased net acid excretion,
and (ii) impaired buffering caused by defective
urinary ammonium excretion36. Patients with re-
current uric acid nephrolithiasis have been shown
to have insulin resistance (IR)37, and in subjects
with IR also low urinary citrate excretion could
be an increased risk mechanism responsible for
calcium stone formation38. It has been suggested
that patients with normouricosuric uric acid
nephrolithiasis had altered renal acidification39.
Thus, ammonium excretion was altered by in-
sulin-resistant state, and alteration in acid urine
pH and hyp ocitraturia res ult in uric ac id
nephrolithiasis.
Furthermore, Stoller et al40 found that stones
contain free and esterified cholesterol. Esterified
cholesterol accounted for 14% to 16% of total
cholesterol related to stone composition.
Renal stones and diet
Dietary and lifestyle habits can predispose to
urinary tract stone formation, and diet may play
an important role in the pathogenesis of kidney
stones. In fact, the trends in the American diet
modifications and stone prevalence between
Figure 2. Lithogenesis: promoters (left) and inhibitors (right).
1974 to 2010 showed that an increase of total
calories, fat, protein, fruit and vegetables in-
creased stone prevalence; only citrus fruits were
negatively related to kidney stone disease41.
Animal proteins
Dietary excesses in animal protein and salt
are risk factors in calcium oxalate urolithiasis.
High protein intake (2 g/kg daily) significantly
changes urinary calcium, uric acid, and citrate
excretion rates, and similar changes in calcium
and citrate are induced by a high sodium intake
(310 mmol/day). Moreover, the changes are more
pronounced when a high protein is combined
with a high sodium diet. These dietary regimens
induce a significant decrease in the ability of
urines to inhibit calcium oxalate monohydrate
crystal agglomeration, which is most marked if
diet is combined. The ability of urines to inhibit
crystal agglomeration is related to their citrate
content. High animal protein and sodium diet in-
take decreases the ability of urines to inhibit the
agglomeration of calcium oxalate crystals pro-
viding a physicochemical explanation for the ad-
verse effects of dietary aberrations on renal stone
formation42. Animal protein-rich diet has been re-
ported to be associated with the highest excretion
of undissociated uric acid, reduction in urinary
pH and citrate excretion because of the acid load
due to high sulfur contents, whereas oxalate ex-
cretion was lower than during vegetarian diet.
Noori et al43 performed a randomized controlled
trial in recurrent stone formers with hyperox-
aluria (urine oxalate > 40 mg/d). A group of pa-
tients underwent 8 weeks diet following a calo-
rie-controlled Dietary Approaches to Stop Hyper-
tension (DASH) d iet whereas in the second
group a 8 weeks low-oxalate diet was prescribed.
Authors evaluated change in urinary calcium ox-
alate supersaturation and changes in 24-hour uri-
nary composition. Urinary oxalate excretion in-
creased in the DASH versus the low-oxalate
group, but there was a trend for calcium oxalate
supersaturation to decrease in the DASH versus
the low-oxalate group in association with an in-
crease in magnesium, citrate excretion and urine
pH in the DASH versus low-oxalate group.
Fruit and vegetables
The concept that a vegetarian diet reduces the
risk of forming urinary stone has been known for
long time, and it is known that vegetable proteins
have been shown to have a lower lithogenic po-
tential than animal proteins44. As far as in the ear-
419
Pears and renal stones
ly 80’s, a UK study45 reported that prevalence of
urinary tract lithiasis was 40-60% of that predict-
ed for a group of individuals taken from the gen-
eral population and matched for age, sex and so-
cial class with the vegetarians. Taylor et al46 eval-
uated the impact of diet on kidney stone forma-
tion examining prospectively patients enrolled in
three studies i) Health Professional Follow-up
Study (n=45,821 men; 18 years of follow-up), ii)
Nurses’ Health Study I (n=94,108 older women;
18 years of follow-up), and iii) Nurses’ Health
Study II (n=101,837 younger women; 14 years of
follow-up). Authors focused on eight compo-
nents: high intake of fruits, vegetables, nuts and
legumes, low-fat dairy pr oducts, and whole
grains and low intake of sodium, sweetened bev-
erages, and red and processed meats, calculating
a DASH score. Participants with higher DASH
score had higher intakes of calcium, potassium,
magnesium, oxalate, and vitamin C, and lower
intakes of sodium. A diet with high consumption
in fruit and vegetables, moderate consumption in
low-fat dairy products, and low in animal protein
was associated with a marked decrease in the risk
of incident kidney stone. Data from the Women's
Health Initiative observational study47 on about
84,000 postmenopausal women showed that
those with no history of kidney stones had higher
total dietary fiber, greater fruit intake and greater
vegetable intake. In particular, even only a mod-
erate use of fruits (2-3 portions/days) had higher
impact on kidney stone preventions (HR=0.75
for intake of 2-3 portions/days respect to 0-1 por-
tion/day). However, in women with history of
stones there were no significant protective effects
of fiber, fruit or vegetable intake on the risk of
kidney stone recurrence. Again, also European
data48 gave further confirmation on the relation-
ship between high intakes of fresh fruit, fiber ce-
reals and magnesium and lower risk of kidney
stone compared to patients with high intake of
meat. Therefore, the fear of doctors in prescrib-
ing a diet rich in fruits and vegetables in stone
formers, due to the fact that they are an important
source of oxalate, is not understandable. An Ital-
ian group49 studied the effect of diet on urinary
stone risk profile in normal adults, and in idio-
pathic calcium stone formers characterized by
hypocitraturia. In normal subjects, the elimina-
tion of fruits and vegetables from the diet de-
creased the urinary excretion of potassium, mag-
nesium, citrate and oxalate, and increased calci-
um and ammonium. On the contrary, the relative
saturation for calcium oxalate and calcium phos-
420
phate increased. In the hypocitraturic stone form-
ers, the introduction of these foods in the diet in-
creased urinary volume, pH, excretion of potassi-
um, magnesium, and citrate, while it decreased
the excretion of ammonium. The relative satura-
tion for calcium oxalate and uric acid decreased.
Organic anions are mainly contained in plant
foods, in the form of potassium citrate, potassi-
um malate while animal foods supply potassium
anions as phosphate or lactate. Organic anions fi-
nally yield KHCO3 which is used by the kidneys
to neutralize fixed acidity related to the dietary
protein level. Failure to neutralize acidity leads to
low-grade metabolic acidosis. Therefore, provid-
ing a sufficient supply of potassium organic an-
ions through fruit and vegetable intake should be
recommended50. Moreover dietary calcium influ-
ences the bioavailability of ingested oxalate51 .
Compared with diets consumed in the past, actual
human diet contains large amount of salt and it is
deficient in fruit and vegetables, being the latter
rich in potassium and organic anions. This kind
of diet could be defined as net-acid-producing
one, causing a low-grade systemic metabolic aci-
dosis52. Foods’ acidity is related to the presence
of organic anions such as malate, citrate or lac-
tate. Their metabolism, after absorption in the di-
gestive tract, produces CO2and energy50.
Coffee, and alcoholic,
and non-alcoholic beverages
Coffee, both caffeinated and decaffeinated,
tea, beer and wine are reported to reduce risk of
stone formation, whereas soft drink acidified
with phosphoric acid are associated with recur-
rence of urinary stone formation23.
Prevention against
renal stones: why pears?
A systematic review of PubMed database lit-
erature up to July 2014 has been recently pub-
lished by an Italian group53, aimed to collect evi-
dence from studies on dietary treatment of uri-
nary stone formation. The main key-point was
the mainstay concept of a forced increase in fluid
intake. As for hypercalciuria: (i) non recommen-
dation of dietary calcium restriction, (ii) moder-
ate dietary salt restriction, (iii) low-normal pro-
tein intake; hyperoxaluria: (i) a diet low in ox-
alate and/or a calcium intake normal to high
(800-1200 mg/day for adults) reduces the urinary
excretion of oxalate, whereas a diet rich in ox-
R. Manfredini, A. De Giorgi, A. Storari, F. Fabbian
alates and/or low calcium increase urinary ox-
alate, (ii) the addition of supplements of fruit and
vegetables to a mixed diet does not involve an
increased excretion of oxalate in the urine; hype-
ruricosuria: (i) restriction of dietary protein and
purine is suggested although not clearly demon-
strated; hypocitraturia: the administration of al-
kaline-citrates salts is recommended, although
compliance to this treatment is limited by gas-
trointestinal side effects and costs, (ii) high in-
take of fruit and vegetables increases citrate ex-
cretion and involves a significant protection
against the risk of stone formation. Again, it has
been suggested that a diet rich in vegetables and
fruit with high organic anion content, such as cit-
rate and malate, is associated with higher urine
pH and prevent formation of stones54.
We made a search on PubMed library, both us-
ing the specific Medical Sub Headings (MeSH)
terms and a free term search (Table III). Only 542
hits when using the MeSH term ‘pyrus’ (but dras-
tically reduced to 42 when adding the term ‘hu-
mans’), and 931 for ‘pear + fruit’, reduced to 143
when adding humans’. Very few articles were
found dealing with ‘diseases’, whereas the topic of
renal stone has not been investigated yet. Thus, we
reviewed the available evidence.
Pears and organic acids
Pears are characterized by several advanta-
geous features in their nutritional composition.
Fructose is the major sugar, followed by glucose
and sucrose55-56, and potassium is the most abun-
dant mineral, followed by magnesium and calci-
um55. Linoleic acid, palmatic acid, oleic acid, and
α-linoleic acid (C18:3) were found to be the most
abundant fatty acids, and among essential amino
acids leucine, lysine and isoleucine were most
prominent while among non-essential amino
acids aspartic acid and glutamine were abun-
dant56.
Even if various amounts of citric, tartaric, and
oxalic acids may also be found, the major organ-
ic acid in pears is malic acid. Table pears contain
more of malic acid, while in some juicy pears,
citric acid account for up to 45% of total acids57.
The acidity level of pears varies from pH 2.6 to
5.458. It has been recently shown that concentra-
tion of malic acid was greater than 1,000 mg/kg
of fresh pear556, and European pears have been
shown to contain more malic acid than Asian
ones (2.5 g/kg vs. 0.68 g/kg) and a similar con-
tents of citric acid (0.71 g/kg vs. 0.75 g/kg). The
malic/citric acid ratio in the Asian pear was on
421
Pears and renal stones
average lower than in European ones59. Malic
acid is transformed in citrate and its supplemen-
tations induce systemic alkalinization and reduce
renal tubular reabsorption of citrate and represent
a conservative treatment of calcium renal stone
disease60.
Studies61 on pears cultivars varieties present
in Korea, Japan, and East of Russia showed high
concentration of total organic acids, such as mal-
ic and citric acid, and the Italian Pyrus communis
had less total organic acid, but a satisfactory mal-
ic and citric acid concentrations.
Pears and antioxidant activity
Chronic metabolic acidosis is often associated
with common clinical conditions such as aging
and excessive meat ingestion. Body’s homeostat-
ic response to these pathologic processes is very
A, Medical Sub Headings (MeSH) terms search.
MesH Results + add ‘humans’
Pyrus 574 42
Pyrus + chemistry 13 0
Pyrus + biochemistry 10 0
Pyrus + nutritional sciences 0
Pyrus + nutrition policy 0
Pyrus + nutrition processes 43
Pyrus + disease 0
Pyrus + cardiovascular diseases 33
Pyrus + kidney 0
Pyrus + kidney calculi 0
Pyrus + urolithiasis 0
Pyrus + kidney diseases 0
Pyrus + citrates 20
Pyrus + citric acid 0
Pyrus + malic acid 10
Pyrus + urinary bladder calculi 0
Pyrus + urinary calculi 0
Pyrus + urinary bladder calculi 0
Pyrus + urolithiasis 0
B, Free search.
Free terms Results + add ‘humans’
Pear + fruit 931 143
Pear + fruit + chemistry 370 60
Pear + fruit + biochemistry 19 2
Pear + fruit + nutrition 50 19
Pear + fruit + nutritional sciences 63
Pear + fruit + nutritional processes 14 11
Pear + fruit + disease 90 20
Pear + fruit + cardiovascular disease 98
Pear + fruit + kidney 0
Pear + fruit + kidney calculi 0
Pear + fruit + urolithiasis 0
Pear + fruit + kidney disease 0
Pear + fruit + citrates 72
Pear + fruit + citric acid 11 3
Pear + fruit + malic acid 81
Pear + fruit + urinary bladder calculi 0
Pear + fruit + urinary calculi 0
Pear + fruit + urolithiasis 0
Pear + fruit + lithiasis 0
Pear + fruit + renal stone 0
Pear + fruit + kidney stone 0
Table III. PubMed search (update July 31, 2015).
422
efficient, the serum HCO3- and blood pH are fre-
quently maintained within the “normal” range,
on the other hand it causes hypercalciuria and
hypocitraturia leading to nephrolithiasis62. High
intake of fruits and vegetables is beneficial for
chronic diseases such as cancer, diabetes, cardio-
vascular, and neurodegenerative impairments,
and this effect is mainly due to the antioxidant
capacity derived from the phenolic compounds
present in edible plants63. Pears have been report-
ed to have a good phenolic profile and antioxi-
dant activity64, contain high total phenolics and
total flavonoids, and have also high anti-inflam-
matory activity65. It is important remember that
high concentrations of these elements were pre-
sent in the pear peel approximately 6-20 times
higher than those in the flesh of pear66. Experi-
mental animal studies67 have documented that di-
ets supplemented with fruit peels (pears and ap-
ples) exercised a significantly higher positive in-
fluence on plasma lipid levels and on plasma an-
tioxidant capacity of rats fed cholesterol-content
than diets with fruit pulps. Fruits should be con-
sumed rapidly after purchase and with their peel.
In fact, after one week of domestic storage, the
ascorbic acid content was found to decrease by
75%, and peeling decreased total phenolics and
ascorbic acid of more than 25%68. Finally, in ani-
mals, pears also exhibit moderate anti-microbial
activities against bacteria strains, and anti-in-
flammatory action69.
Conclusions
Low consumption of meat and meat products,
moderate consumption of ethanol, mostly from
wine, and high consumption of legumes, olive oil
vegetables and fruits, are the components of the
Mediterranean diet and the latter impacts posi-
tively cardiometabolic risk, and urinary tract
stone formation. Consumption of such a diet fa-
vorably affects numerous cardiovascular disor-
ders including dyslipidemia, hypertension, meta-
bolic syndrome, and diabetes, and formation and
recurrence of stone in the urinary tract. Although
pears could be crucial in such a diet, due to their
peculiarities, a very few studies are available in
literature. To the best of our knowledge, this is
the first comprehensive review on a possible re-
lationship between renal stone disease and poten-
tial benefits not only by fruit in general, but
specifically by pears. In fact, high content in
malic (and also citric acid) warrant effective pro-
R. Manfredini, A. De Giorgi, A. Storari, F. Fabbian
tection against stone formation at a low coast,
and without exposing patients to the potential
gastrointestinal side effects of alkaline-citrates
salts, and significantly higher costs. It is known
that renal colics, both in subjects with or without
stones, show a highest risk period during early
morning hours70. This is possibly due to different
factors, such as a morning peak of glomerular fil-
tration rate, urine supersaturation during night
time, highest lithogenic risk for calcium oxalate
du ring lat e ni ght or ear ly m ornin g, altered
rhythm of the inhibitory activity of calcium ox-
alate crystallization in stone formers, and so on70.
Thus, on one hand, abundant fluid intake could
be suggested in people free of congestive heart
failure or risk of nocturnal falls during late
evening and before retiring to bed. On the other
hand, every time could be the right time for con-
suming a pear. Surely, more than one peer a day
is needed to take the renal stone away. However,
in association with appropriate diet and hydra-
tion, daily consume of pears could be considered
a sort of really healthy and inexpensive diet ther-
apy, avoiding patients to be compelled to in-
crease their amount of pills.
—————————–
Acknowledgements
The Authors thank Luciano Ricci, MD, for precious sugges-
tions and friendly continuous support.
—————————–
Conflict of Interests
The Authors declare that they have no conflict of interests.
———————––
Funding support
This work has been supported, in part, by a scientific grant
from the University of Ferrara (Fondo Ateneo Ricerca
FAR).
References
1. TEFEKLI A, CEZAYRLI F. The history of urinary stone:
in parallel with civilization. ScientificWorldJournal
2013; 2013: 423964.
2. AULUS CORNELIUS CELSUS. Book VII, Chapter XXVI:
Of the operation necessary in a suppression of
urine, and lithotomy”. In Collier GF: A translation
of the eight books of Aul. Corn. Celsus on medi-
cine, 2nd ed., London: Simpkin and Marshall,
1831; pp. 306-314.
3. JANICK J. The pear in history, literature, popular
culture, and art. ISHS Acta Horticulturae 596: VIII
Internation al Symposium on Pear. In Corelli-
Grappadelli L, Janick J, Sansavini S, Tagliavini M,
Sugar D, Webster AD (Eds), 2002; pp.1-14.
423
Pears and renal stones
4. HYAMS ES, MATLAGA BR. Economic impact of uri-
nary stones. Transl Androl Urol 2014; 3: 278-283.
5. Moe OW. Kidney stones: pathophysiology and
medical management. Lancet 2006; 367: 333-
344.
6. SCAL ES CD JR, SMITH AC, HANLEY JM, SAIGAL CS.
Prevalence of kidney stones in the United States.
Eur Urol 2012; 62: 160-165.
7. PEARLE MS, CALHOUN EA, CURHAN GC. Urologic dis-
eases in America pro ject: uro lithiasi s. J Urol
2005; 173: 848-857.
8.SAIGAL CS, JOYCE G, TIMILSINA AR. Direct and indirect
costs of nephrolithiasis in an employed popula-
tion: opportunity for disease management? Kid-
ney Int 2005; 68: 1808-1814.
9. EATON SH, CASHY J, PEARL JA, STEIN DM, PERRY K,
NADLER RB. Admission rates and costs associated
with emergency presentation of urolithiasis: analysis
of the Nationwide Emergency Department Sample
2006-2009. J Endourol 2013; 27: 1535-1538.
10. TRINCHIERI A, COPPI F, MONTANARI E, DEL NERO A,
ZANETTI G, PISANI E. Increase in the prevalence of
symptomatic upper urinary tract stones during the
last ten years. Eur Urol 2000; 37: 23-25.
11. TINCHIERI A, OSTINI F, NESPOLI R, ROVERA F, MONTA-
NARI E, ZANETTI G. A prospective study of recur-
rence rate and risk factors for recurrence after a
first renal stone. J Urol 1999; 162: 27-30.
12. GRASES F, COSTA-BAUZA A, RAMIS M, MONTESINOS V,
CONTE A. Recurrence of renal lithiasis. Scand J
Urol Nephrol 2003; 37: 482-486.
13. RULS AD, LIESKE JC, LIX, MELTON LJ 3RD, KRAMBECK
AE, BERGSTRAHL EJ. The ROKS nomogram for pre-
dicting a second symptomatic stone episode. J
Am Soc Nephrol 2014; 25: 2878-2886.
14. ROMERO V, AKPINAR H, ASSIMOS DG. Kidney stones:
a global picture of prevalence incidence, and as-
sociated risk factors. Rev Urol 2010; 12: e86-96.
15. PAK CY, POINDEXTER JR, ADAMS-HUET B, PEARLE MS.
Predictive value of kidney stone composition in
the detection of metabolic abnormalities. Am J
Med 2003;115:26-32.
16. BORGHI L, MESCHI T, MAGGIORE U, PRATI B. Dietary
therapy in idiopathic nephrolithiasis. Nutr Rev
2006; 64: 301-312.
17. SHOAG J, TASIAN GE, GOLDFARB DS, EISNER BH. The
new epidemiology of nephrolithiasis. Adv Chronic
Kidney Dis 2015; 22: 273-278.
18. LEMANN J JR, PLEUSS JA, WORCESTER EM, HORNICK L,
SCHRAB D, HOFFMANN RG. Urinary oxalate excretion
increases with body size and decreases with in-
creasing dietary calcium intake among healthy
adults. Kidney Int 1996; 49: 200-208.
19. TAYLOR EN, STAMPFER MJ, CURHAN GC. Obesity,
weight gain, and the risk of kidney stones. JAMA
2005; 293: 455-462.
20. TAYLOR EN, STAMPFER MJ, CURHAN GC. Diabetes
mellitus and the risk of nephrolithiasis. Kidney Int
2005; 68: 1230-1235.
21. RULE AD, ROGER VL, MELTON LJ 3RD, BERGSTRAHL EJ,
LI X, PEYSER PA, KRAMBECK AE, LIESKE JC. Kidney
stones associate with increased risk for myocar-
dial infarction. J Am Soc Nephrol 2010; 21: 1641-
1644.
22. EVAN AP. Physiopathology and etiology of stone
formation in the kidney and the urinary tract. Pe-
diatr Nephrol 2010; 25: 831-841.
23. SIENER R, HESSE A. Fluid intake and epidemiology of
urolithiasis. Eur J Clin Nutr 2003; 57 Suppl 2:
S47-51.
24. PEARL MS, GOLDFARB DS, ASSIMOSS DG, CURHAM G,
DENU-CIOCCA CJ, MATLAGA BR, MONGA M, PENNISTON
KL, PREMINGER GM, TURK TMT, WHITE JR. Medical
management of kidney stones: American urologi-
cal association guidelines 2014; Available from:
https://www.auanet.org/common/pdf/education/cli
nical-guidance/Medical-Management-of-Kidney-
Stones.pdf.
25. MARANGELLA M, BAGNIS C, BRUNO M, VITALE C, PE-
TRARULO M, RAMELLO A.Crystallization inhibitors in
the pathophysiology and treatment of nephrolithi-
asis. Urol Int 2004; 72 Suppl 1: 6-10.
26. BEK-JENSEN H, FOMANDER AM, NILLSSON MA, TISELIUS
HG. Is citrate an inhibitor of calcium oxalate crys-
tal growth in high concentrations of urine? Urol
Res 1996; 24: 67-71.
27. TRACY CR, PEARLE MS. Update on the medical man-
agement of stone disease. Curr Opin Urol 2009;
19: 200-204.
28. PAK CY, FULLER C, SAKHAEE K, PREMINGER GM, BRITTON
F. Long-term treatment of calcium nephrolithiasis
with potassium citrate. J Urol 1985; 134: 11-19.
29. SELTZER MA, LOW RK, MCDONALD M, SHAMI GS,
STOLLER ML. Dietary manipulation with lemonade
to treat hypocitraturic calcium nephrolithiasis. J
Urol 1996; 156: 907-909.
30. EISNER BH, ASPLIN JR, GOLDFARB DS, AHM AD A,
STOLLER ML. Citrate, malate and alkali content in
commonly consumed diet sodas: implications for
nephrolithiasis treatment. J Urol 2010; 183: 2419-
2423.
31. SIMPSON DP. Citrate excretion: a window on renal
metabolism. Am J Physiol 1983; 244: F223-234.
32. EKERUO WO, TAN YH, YOUNG MD, DAHM P, MAL-
ONEY ME, MATHIAS BJ, ALBALA DM, PREMINGER GM.
Metabolic risk factors and the impact of med-
ical therapy on the management of nephrolithi-
asis in obese patients. J Urol 2004; 172: 159-
163.
33. DAUDON M, LACOUR B, JUNGERS P. High prevalence
of uric acid calculi in diabetic st one formers.
Nephrol Dial Transplant 2005; 20: 468-469.
34. PAK CY, SAKHAEE K, MOE O, PREMINGER GM, POINT-
DEXTER JR, PETERSON RD, PIETROW P, EKERUO W. Bio-
chemical profile of stone-forming patients with di-
abetes mellitus. Urology 2003; 61: 523-527.
35. MAALOUF NM, SAKHAEE K, PARKS JH, COE FL, ADAMS-
HUET B, PAK CY. Association of urinary pH with
body weight in nephrolithiasis. Kidney Int 2004;
65: 1422-1425.
36. SAKHAEE K, MAALOUF NM. Metabolic syndrome and
uric acid nephrolithiasis. Semin Nephrol 2008; 28:
174-180.
37. ABATE N, CHANDALIA M, CABO-CHAN AV JR, MOE OW,
SAKHAEE K. The metabolic syndrome and uric acid
nephrolithiasis: novel features of renal manifesta-
tion of insulin resistance. Kidney Int 2004; 65:
386-392.
424
R. Manfredini, A. De Giorgi, A. Storari, F. Fabbian
38. CUPISTI A, MEOLA M, D'ALESSANDRO C, BERNABINI G,
PASQUALI E, CARPI A, BARSOTTI G. Insulin resistance
and low urinary citrate excretion in calcium stone
formers. Biomed Pharmacother 2007; 61: 86-90.
39. SAKAHEE K, ADAMS-HUET B, MOE OW, PAK CY. Patho-
physiologic basis for normouricosuric uric acid
nephrolithiasis. Kidney Int 2002; 62: 971-979.
40. STOLLER ML, MENG MV, ABRAHAMS HM, KANE JP. The
primary stone event: a new hypothesis involving
a vascular etiology. J Urol 2004; 171: 1920-1924.
41. DESK, LIUX, MONGA M. Changing trends in the
American diet and the rising prevalence of kidney
stones. Urology 2014; 84: 1030-1033.
42. KOK DJ, IESTRA JA, DOORENBOS CJ, PAPAPOULOS SE.
The effects of dietary excesses in animal protein
and in sodium on the composition and the crystal-
lization kinetics of calcium oxalate monohydrate
in urines of healthy men. J Clin Endocrinol Metab
1990; 71: 861-867.
43. NOOR I N, HONARKAR E, GOLDFARB DS, KALANTAR-
ZADEH K, TAHERI M, SHAKHSSALIM N, PARVIN M, BASIRI
A. Urinary lithogenic risk profile in recurrent stone
formers with hyperoxaluria: a randomized con-
trolled trial comparing DASH (Dietary Approaches
to Stop Hypertension)-style and low-oxalate diets.
Am J Kidney Dis 2014; 63: 456-463.
44. BRESLAU NA, BRINKLEY L, HILL KD, PAK CY. Relation-
ship of animal protein-rich diet to kidney stone
formation and calcium metabolism. J Clin En-
docrinol Metab 1988; 66: 140-146.
45. ROBERTSON WG, PEACOCK M, MARSHALL DH. Preva-
lence of urinary stone disease in vegetarians. Eur
Urol 1982; 8: 334-339.
46. TAYLOR EN, FUNG TT, CURHAN GC. DASH-style diet
associates with reduced risk for kidney stones. J
Am Soc Nephrol 2009; 20: 2253-2259.
47. SORENSEN MD, HIS RS, CHI T, SHARA N, WACTAWSKI-
WENDE J, KAHN AJ, WANG H, HOU L, STOLLER ML. Di-
etary intake of fiber, fruit and vegetables decreas-
es the risk of incident kidney stones in women: a
Women’s Health Initiative report. J Urol 2014;
192: 1694-1699.
48. TURNEY BW, APPLEBY PN, REYNARD JM, NOBLE JG, KEY
TJ, ALLEN NE. Diet and risk of kidney stones in the
Oxford cohort of the European Prospective Inves-
tigation into Cancer and Nutrition (EPIC). Eur J
Epidemiol 2014; 29: 363-369.
49. MESCHI T, MAGGIORE U, FIACCADORI E, SCIANCHI T,
BOSI S, ADORNI G, RIDOLO E, GUERRA A, ALLEGRA F,
NOVARINI A, BORGHI L. The effect of fruits and veg-
etables on urinary stone risk factors. Kidney Int
2004; 66: 2402-2410.
50. DEMIGNE C, SABBOH H, PUEL C, REMESY C, COXAM V.
Organic anions and potassium salts in nutrition
and metabolism. Nutr Res Rev 2004; 17: 249-258.
51. HOLMES RP, GOODMAN HO, ASSIMOS DG. Contribu-
tion of dietary oxalate to urinary oxalate excre-
tion. Kidney Int 2001; 59: 270-276.
52. FRASSETTO L, MORRIS RC JR, SELLMEYER DE, TODD K,
SEBASTIAN A. Diet, evolution and aging--the patho-
physiologic effects of the post-agricultural inver-
sion of the potassium-to-sodium and base-to-
chloride ratios in the human diet. Eur J Nutr 2001;
40: 200-213.
53. PREZIOSO D, STRAZZULLO P, LOTTI T, BIANCHI G, BORGHI
L, CAIONE P, CARINI M, CAUDARELLA R, GAMBARO G,
GELOSA M, GUTTILLA A, ILLIANO E, MARTINO M, MESCHI
T, MESSA P, MIANO R, NAPODANO G, NOUVENNE A,
RENDINA D, ROCCO F, ROSA M, SANSEVERINO R, SALER-
NOA, SPATAFORA S, TASCA A, TICINESI A, TRAVAGLINI F,
TRINCHIERI A, VESPASIANI G, ZATTONI F. Dietary treat-
ment of urinary risk factors for renal stone forma-
tion. A review of CLU Working Group. Arch Ital
Urol Androl 2015; 87: 105-120.
54. HEILBERG IP, GOLDFARB DS. Optimum nutrition for
kidney stone disease. Adv Chronic Kidney Dis
2013; 20: 165-174.
55. CHEN J, WANG Z, WUJ, WANG Q, HUX. Chemical
compositional characterization of eight pear culti-
vars grown in China. Food Chem 2007; 104: 268-
275.
56. SHEZAD H, TARIQ M, RAHAT B, HONGBIN W, SARTAI A,
AMJAD A. Comparative study of two pear (Pyrus
communis L.) cultivars in terms of nutritional com-
position. Food Sci Qual Manag 2015; 36: 48-54.
57. KADAM, DHUMAL SA, SHINDE NN. PEAR.In: Salunke
DK, Kadam SS (eds) Handbook of fruit science
and technology: production, composition, stor-
age, and processing. CRC Press, 1995; pp. 183-
202.
58. VISSER T, SHARP AA, DEVRIES DP. Acidity and sweet-
ness in apple and pear. Euphytica 1968: 17: 153.
59. HUDINA M, STAMPAR F. Sugars and organic acids
contents of European (Pyrus communis L.) and
Asian (Pyrus serotina Rehd.) pear cultivars. Acta
Aliment 2000; 29: 217-230.
60. RODGERS AL, WEBBER D, DECHARMOY R, JACKSON GE,
RAVENSCROFT N. Malic acid supplementation increas-
es urinary citrate excretion and urinary pH: implica-
tions for the potential treatment of calcium oxalate
stone disease. J Endourol 2014; 28: 229-236.
61. SHA S, LIJ, WUJ, ZHANG S. Characteristics of or-
ganic acids in the fruit of different pear species.
Afr J Agric Res 2011; 6: 2403-2410.
62. ALPERN RJ, SAKHAEE K. The clinical spectrum of
chronic metabolic acidosis: homeostatic mecha-
nisms produce significant morbidity. Am J Kidney
Dis 1997; 29: 291-302.
63. GALVIS SANCHEZ AC, GIL-IZQUIERDO A, GIL MI. Com-
parative study of six pear cultivars in terms of
their phenolic and vitamin C contents and antioxi-
dant capacity. J Sci Food Agric 2003; 83: 995-
1003.
64. SALTA J, MARTINS A, SANTOS RG, NENG NR, NOGUEIRA
JMF, JUSTINO J, RAUTER AP. Phenolic composition
and antioxidant activity of Rocha pear and other
pear cultivars--A compa rative stud y. J Funct
Foods 2010; 2: 153-157.
65. LIX, ZHANG JY, GAO WY, WANG Y, WANG HY, CAO
JG, HUANG LQ. Chemical composition and anti-in-
flammatory and antioxidant activities of eight pear
cultivars. J Agric Food Chem 2012; 60: 8738-
8744.
66. LIX, WANG T, ZHOU B, GAO W, CAO J, HUANG L.
Chemical composition and antioxidant and anti-
inflammatory potential of peels and flesh from 10
different pear varieties (Pyrus spp.). Food Chem
2014; 152: 531-538.
425
Pears and renal stones
67. LEO N TO WIC Z M, GORINSTEIN S, LEO N TO WIC Z H,
KRZEMINSKI R, LOJEK A, KATRICH E, CIZ M, MARTIN-BEL-
LOSO O, SOLIVA-FORTUNY R, HARUENKIT R, TRAKHTEN-
BERG S. Apple and pear peel and pulp and their in-
fluence on plasma lipids and antioxidant poten-
tials in rats fed cholesterol-containing diets. J
Agric Food Chem 2003; 51: 5780-5785.
68. KEVERS C, PINCEMAI L J, TABART J, DE FRA IGNE JO,
DOMMES J. Influence of cultivar, harvest time, stor-
age conditions, and peeling on the antioxidant ca-
pacity and phenolic and ascorbic acid contents of
apples and pears. J Agric Food Chem 2011; 59:
6165-6171.
69. LIX, ZHANG J, GAO W, WANG H. Study on chemical
composition, anti-inflammatory and anti-microbial
activ ities of extracts fr om Chi nese pear fr uit
(Pyrus bretschneideri Rehd.). Food Chem Toxicol
2012; 50: 3673-3679.
70. MANFREDINI R, GALLERANI M, LACECILIA O, BOARI B,
FERSINI C, PORTALUPPI F.Circadian pattern in occur-
rence of renal colic in an emergency department:
analysis of patients’ notes. Br Med J 2002; 324:
767.
... sativa) provided 70% protection and flaxseed extracts 50% protection against the nephrotoxic effects of cisplatin. In veterinary and human medicine, a diet high in fruits and vegetables has been shown to be protective against kidney disease (Hall et al. 2016;Manfredini et al. 2016). ...
... A diet high in fruits and vegetables has been shown in veterinary and human medicine to be protective against kidney disease (Hall et al. 2016;Manfredini et al. 2016). ...
... The concentrations of proanthocyanidin phytochemicals (polyphenol flavonoids) in the cranberry extract were not reported. Pears are being recommended in human medicine as a prophylactic for uroliths (Manfredini et al. 2016). The organic acids in pears are likely important in the prevention of uroliths. ...
Chapter
Nutraceuticals are used as prophylactics and remedies for genitourinary maladies in domestic animals and have been used throughout recorded history. They are also used to control and improve reproductive performance, improve the storability of semen and enhance ovum maturation, and improve in vitro fertilization. In the last decade, the effects and mechanisms of oxidative stress on reproductive performance and immune dysfunction have been elucidated. The antioxidative effects of certain nutraceuticals during periods of the reproductive cycle with high oxidative stress improve reproductive performance and reduce infections and other gentiourinary diseases. This chapter also reviews the current use of nutraceuticals to prevent and treat genitourinary diseases.
... For other medicinal functions of pears, excretion of urinary stones [114] and wound healing for poor wound healing patients, such as diabetes [115], have been carefully described in some reports as new applications of pears. In addition, a wide plethora of traditional, integrative, complementary and alternative medicines have been touted as the solution for COVID-19, despite the paucity of evidence surrounding the safety and effectiveness of such therapies [116]. ...
Article
Full-text available
Background Pears have been world-widely used as a sweet and nutritious food and a folk medicine for more than two millennia. Methods We conducted a review from ancient literatures to current reports to extract evidence-based functions of pears. Results We found that pears have many active compounds, e.g., flavonoids, triterpenoids, and phenolic acids including arbutin, chlorogenic acid, malaxinic acid, etc. Most of researchers agree that the beneficial compounds are concentrated in the peels. From various in vitro , in vivo , and human studies, the medicinal functions of pears can be summarized as anti-diabetic,-obese, −hyperlipidemic, −inflammatory, −mutagenic, and -carcinogenic effects, detoxification of xenobiotics, respiratory and cardio-protective effects, and skin whitening effects. Therefore, pears seem to be even effective for prevention from Covid-19 or PM 2.5 among high susceptible people with multiple underlying diseases. Conclusion For the current or post Covid-19 era, pears have potential for functional food or medicine for both of communicable and non-communicable disease.
... Hence, calculi are not formed easily. However, when the concentration or activity of calculus inhibitors is decreased or changed due to various reasons, the inhibition of calculi formation can be reduced, causing urolithiasis to form easily (16)(17)(18). The investigators in this study believe that the mechanism of HJFD for urolithiasis formation prevention may be correlated with the regulation of the content and active expression of urinary calculus inhibitors. ...
Article
Full-text available
Background: This study aims to explore the mechanism of the Huayu Jianpi Fangshi decoction in urolithiasis prevention. Methods: The present study was designed as a randomized, double-blinded, placebo-controlled clinical trial. Sixty patients with the qi stagnation and blood stasis, spleen deficiency, and dampness obstruction types of urolithiasis were randomly divided into two groups: the treatment group and the control group (n=30 in both groups). Patients in the treatment group were treated with the Huayu Jianpi Fangshi decoction, while patients in the control group were treated with the Huayu Fangshi placebo decoction. Both treatments were taken orally two times per day. All patients received treatment over the course of four weeks. The main outcome indicators included the Tamm-Horsfall protein (THP) expression levels, osteopontin, and inter-αtrypsin inhibitor heavy chain 3 (ITIH3) in the patients' urine as well as changes in 24-h urinary citric acid, urinary magnesium levels, and Traditional Chinese Medicine (TCM) syndrome scores. Results: The results of the present study revealed a significant increase in the total citric acid excretion level (244.75±59.62 vs. 297.48±57.91 mmol/L, P<0.01), significant decrease in the total urinary THP level (10.83±7.73 vs. 6.37±6.10 mg/L, P<0.05), significant decrease in the total ITIH3 level (9.51±6.32 vs. 6.14±4.46 mg/L, P<0.05) in the patients' 24-h urine, and a significant elevation of the total TCM syndrome score (5% vs. 23%, P<0.01) in the treatment group when compared with the control group. Conclusions:
... Recent studies have shown that keratin-malate supplementation can be used as a performance-enhancing agent and increases the physical performance of athletes [12]. It has been investigated that a diet high in malic acid, which is the precursor of citrate, increases kidney stone formation [13]. The malic acid spray has been used orally to treat mouth dryness. ...
Article
Full-text available
This study aimed to investigate the anticarcinogenic and genotoxic damage potentials of malic acid on human fibroblast cells (HDFa) and glioblastoma (U87-MG) cell lines. MTT cell viability and LDH release assays were performed to understand cytotoxic features of malic acid on different cell lines. Also, Hoechst 33258 fluorescent staining was used to monitor nuclear abnormalities including micronucleus, lobbed, and notched structures. Furthermore, cellular death mechanisms behind the malic acid application were investigated via the use of flow cytometry analysis. According to cell viability analysis, malic acid showed a greater effect on U87-MG compared to HDFa cell line in terms of cytotoxicity. Similarly, chromosomal integrity assay put forth a higher number of nuclear abnormalities in U87-MG cells when compared to HDFa cell lines, and aberrations were analyzed to amplify when malic acid concentration increased. Finally, flow cytometry analysis demonstrated higher necrotic cell death in U87-MG cells than HDFa cell line. On the other hand, apoptotic cell death was the main cytotoxic mechanism against malic acid exposure in the HDFa cell line. In light of these results, it can be concluded that in higher concentrations, malic acid has an anticarcinogenic effect on glioblastoma cells via the necrotic pathway, and it also shows apoptotic properties on the fibroblast cell line. When mutagenic properties are compared, it could be understood that malic acid had a greater impact on glioblastoma cells.
... Los citratos son compuestos formados a partir del ácido cítrico con funciones de inhibición de la cristalización de oxalato y fosfato cálcico. 46 Normalmente se utilizan suplementos de citrato de potasio para aumentar las concentraciones de éstos en la orina; sin embargo, este tratamiento suele causar molestias gastrointestinales que pueden hacer que el paciente suspenda el tratamiento, 14 por lo que el citrato dietético puede ser una alternativa a estos suplementos. Las frutas y jugos cítricos representan una fuente natural de citratos y pueden proveer cargas de citrato equivalentes a los suplementos. ...
Article
Full-text available
Resumen Múltiples factores influyen en la aparición de litiasis renal, siendo la dieta uno de los más importantes. Se ha asociado el consumo en exceso de proteínas, sodio, oxalatos e hidratos de carbono refinados, así como un índice de masa corporal (IMC) elevado con un incremento en la incidencia de cálculos renales. Así mismo, un menor consumo de calcio, líquidos y citratos, favorece la formación de estos. Simples modificaciones dietéticas pueden alterar las características de la orina, confiriéndole rasgos litogénicos o haciéndola resistente a la formación de cristales. La dieta debe enfocarse tanto en cambios generales que prevengan la formación de cálculos, como en modificaciones específicas, dependiendo de la composición de los mismos y del perfil urinario de cada paciente. Es de especial importancia no restringir el calcio en la dieta, favorecer el consumo de líquidos, frutas y verduras, así como mantener un peso corporal saludable, moderar la ingestión de proteínas, sodio y oxalatos. Abstract Multiple factors influence the occurrence of nephrolithiasis, being the diet one of the most important. There is an association between overconsumption of protein, sodium, oxalates and refined carbohydrates, as well as a high body mass index (BMI) with an increased incidence of kidney stones. Also a lower consumption of calcium, citrates and liquids favors the formation of these. Simple dietary modifications can alter the characteristics of urine, giving lithogenic features or making it resistant to the formation of crystals. The diet should focus both on general changes to prevent stone formation, such as specific modifications depending on the composition of the calculi and the urinary profile of each patient. It is especially important not to restrict dietary calcium, encourage fluid intake, fruits and vegetables and also maintain a healthy body weight, moderate protein, sodium and oxalates intake.
... In detail, compared to healthy controls, creatinine, citrate, creatine and guanidoacetate were obviously decreased whereas lactate was significantly increased in urine samples from kidney stone patients. As a famous inhibitory factor of calcium oxalate (CaOx) stone formation, citrate also is a key energy metabolite in the TCA cycle [35,36]. Meanwhile, lactate is the end product of the anaerobic glycolysis and the Creatine-phosphocreatine system, including creatine, creatinine and guanidoacetate (a precursor of creatine), is crucial for the transportation of mitochondria-produced energy [37][38][39][40]. ...
Article
Full-text available
Kidney stone is a chronic metabolic disease that caused by many factors, especially by the metabolic disturbances of urine compositions, but the metabolic profiling of the urine from kidney stone patients remains poorly explored. In the present study, ¹H NMR spectroscopy and multivariate pattern recognition analytical techniques were combined to explore the metabolic profiling of the urine from kidney stone patients. A total of 216 urine samples obtained from kidney stone patients (n = 110) and healthy controls (n = 106) were investigated. The results indicated that principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) models were capable of distinguishing kidney stone patients from healthy controls. In addition, a total of 15 metabolites was obviously different in concentration between the two groups. Furthermore, four metabolic pathways, including glyoxylate and dicarboxylate metabolism, glycine, serine and threonine metabolism, phenylalanine metabolism and citrate cycle (TCA cycle), were closely associated with kidney stone. Together, our results established a preliminary metabolic profiling of the urine from kidney stone patients via using ¹H NMR-based analytical techniques for the first time and provided a novel method for recognizing and observing the kidney stone disease.
... While fruit juices offer a more palatable and less costly therapy than potassium citrate medication, fruit juices can be high in calories and oxalate content and this may temper their use [59,73]. Fruits with a high malic acid (precursor to citrate) content, such as pears, may theoretically increase urinary citrate but few studies have examined this [74]. Unfortunately, no citrus fruits or juices have been tested in a randomized trial to assess their benefit in reducing stone recurrence rates. ...
Article
Full-text available
The prevalence of nephrolithiasis is increasing worldwide. Understanding and implementing medical therapies for kidney stone prevention are critical to prevent recurrences and decrease the economic burden of this condition. Dietary and pharmacologic therapies require understanding on the part of the patient and the prescribing practitioner in order to promote compliance. Insights into occupational exposures and antibiotic use may help uncover individual risk factors. Follow-up is essential to assess response to treatment and to modify treatment plans to maximize therapeutic benefit.
Article
Full-text available
Nutraceuticals are the pharmaceutically blended products that possess both nutritional as well as the medicinal value. Such a product is designed to improve the physical health, fight against day-to-day challenges such as stress, increase longevity, etc. Nowadays, emphasis is given to those herbs which are used as food and medicine due to its greater acceptance. Due to dynamic action, the popularity of nutraceuticals among people as well as healthcare providers has been increased over medicines and health supplements. This review documents herbs with a wide variety of therapeutic values such as immunity booster, antidiabetic, anticancer, antimicrobial, and gastroprotective. These herbs could be better options to formulate as nutraceuticals. Several nutraceuticals are described based on their availability as food, chemical nature, and mechanism of action.
Chapter
Urolithiasis has been described in all civilizations in the antiquity, including India, China, Egypt, Persia, Greece, and Rome. This disease along with the herbal treatment attempting to prevent or to cure it are as old as the mankind itself. Perineal lithotomy was reported in the ancient India, the Greco-Roman period, throughout the islamic medieval period, and in the european renaissance. Nonetheless this procedure was associated with a very high mortality rate. Lithotripsy and litholapaxy were developed in the 19th century resulting in a dramatic decrease of the related mortality. Further important surgical advances have been achieved throughout the 20th and the beginning 21th centuries.
Chapter
This section will be approached systematically starting with the management of incidentally discovered urinary stones, then the treatment of a painful episode of urinary stones presenting in the emergency department as well as the management of obstructed kidneys with sepsis. Thereafter we will discuss the various active modalities performed when symptoms persist, or when at first glance the stone appears not to be prone for spontaneous passage. Active stone removal is also recommended when there is stone growth, de novo obstruction, or associated infection [1]. We will also develop the topic of dietary and medical preventive measures and will give a brief account on phytotherapy.
Article
Full-text available
Objective: Diet interventions may reduce the risk of urinary stone formation and its recurrence, but there is no conclusive consensus in the literature regarding the effectiveness of dietary interventions and recommendations about specific diets for patients with urinary calculi. The aim of this study was to review the studies reporting the effects of different dietary interventions for the modification of urinary risk factors in patients with urinary stone disease. Materials and Methods: A systematic search of the Pubmed database literature up to July 1, 2014 for studies on dietary treatment of urinary risk factors for urinary stone formation was conducted according to a methodology developed a priori. Studies were screened by titles and abstracts for eligibility. Data were extracted using a standardized form and the quality of evidence was assessed. Results: Evidence from the selected studies were used to form evidencebased guideline statements. In the absence of sufficient evidence, additional statements were developed as expert opinions. Conclusions: General measures: Each patient with nephrolithiasis should undertake appropriate evaluation according to the knowledge of the calculus composition. Regardless of the underlying cause of the stone disease, a mainstay of conservative management is the forced increase in fluid intake to achieve a daily urine output of 2 liters. Hypercalciuria: Dietary calcium restriction is not recommended for stone formers with nephrolithiasis. Diets with a calcium content ≥ 1 g/day (and low protein-low sodium) could be protective against the risk of stone formation in hypercalciuric stone forming adults. Moderate dietary salt restriction is useful in limiting urinary calcium excretion and thus may be helpful for primary and secondary prevention of nephrolithiasis. A low-normal protein intake decrease calciuria and could be useful in stone prevention and preservation of bone mass. Omega-3 fatty acids and bran of different origin decreases calciuria, but their impact on the urinary stone risk profile is uncertain. Sports beverage do not affect the urinary stone risk profile. Hyperoxaluria: A diet low in oxalate and/or a calcium intake normal to high (800-1200 mg/day for adults) reduce the urinary excretion of oxalate, conversely a diet rich in oxalates and/or a diet low in calcium increase urinary oxalate. A restriction in protein intake may reduce the urinary excretion of oxalate although a vegetarian diet may lead to an increase in urinary oxalate. Adding bran to a diet low in oxalate cancels its effect of reducing urinary oxalate. Conversely, the addition of supplements of fruit and vegetables to a mixed diet does not involve an increased excretion of oxalate in the urine. The intake of pyridoxine reduces the excretion of oxalate. Hyperuricosuria: In patients with renal calcium stones the decrease of the urinary excretion of uric acid after restriction of dietary protein and purine is suggested although not clearly demonstrated. Hypocitraturia: The administration of alkaline-citrates salts is recommended for the medical treatment of renal stone-formers with hypocitraturia, although compliance to this treatment is limited by gastrointestinal side effects and costs. Increased intake of fruit and vegetables (excluding those with high oxalate content) increases citrate excretion and involves a significant protection against the risk of stone formation. Citrus (lemons, oranges, grapefruit, and lime) and non citrus fruits (melon) are natural sources of dietary citrate, and several studies have shown the potential of these fruits and/or their juices in raising urine citrate levels. Children: There are enought basis to advice an adequate fluid intake also in children. Moderate dietary salt restriction and implementation of potassium intake are useful in limiting urinary calcium excretion whereas dietary calcium restriction is not recommended for children with nephrolithiasis. It seems reasonable to advice a balanced consumption of fruit and vegetables and a low consumption of chocolate and cola according to general nutritional guidelines, although no studies have assessed in pediatric stone formers the effect of fruit and vegetables supplementation on urinary citrate and the effects of chocolate and cola restriction on urinary oxalate in pediatric stone formers. Despite the low level of scientific evidence, a low-protein (< 20 g/day) low-salt (< 2 g/day) diet with high hydration (> 3 liters/day) is strongly advised in children with cystinuria. Elderly: In older patients dietary counseling for renal stone prevention has to consider some particular aspects of aging. A restriction of sodium intake in association with a higher intake of potassium, magnesium and citrate is advisable in order to reduce urinary risk factors for stone formation but also to prevent the loss of bone mass and the incidence of hypertension, although more hemodynamic sensitivity to sodium intake and decreased renal function of the elderly have to be considered. A diet rich in calcium (1200 mg/day) is useful to maintain skeletal wellness and to prevent kidney stones although an higher supplementation could involve an increase of risk for both the formation of kidney stones and cardiovascular diseases. A lower content of animal protein in association to an higher intake of plant products decrease the acid load and the excretion of uric acid has no particular contraindications in the elderly patients, although overall nutritional status has to be preserved.
Article
Full-text available
Nutritional composition of two pear cultivars (Pyrus communis) was analyzed for sugar composition, amino acid and fatty acid profile by using high-performance liquid chromatography (HPLC) equipped with RI and ultra violet detectors and GC equipped with FID detector. Proximate composition was determined by using the standard methods of AOAC (2000). The results revealed that the Shughri contain 83.1% moisture content, 13.58% TSS, 3.94% ash content, 11.72% crude protein, 9.47% crude fiber, 3.39% lipids and 96.46% carbohydrates, while Physhu contains less amounts of moisture, TSS, ash, protein, fiber, lipids and carbohydrates (54.51, 13.71, 1.86, 8.81, 7.83, 2.14 and 87.67% respectively). The results further revealed that the fructose was the major sugar in both pear cultivars, followed by glucose and sucrose. Linoleic acid (C18:2), palmatic acid (C16:0) oleic acid (C18:1) and α-linoleic acid (C18:3) were most abundant fatty acids found in both cultivars. Among essential amino acids leucine, lysine and isoleucine are most prominent in both cultivars while among non-essential amino acids aspartic acid and glutamine are abundant. Anti-nutritional content analysis revealed that hydrocyanic, nitrate, oxalate and phytate were in lower amounts than the reference toxic standards. Thus, both pear cultivars have potential nutraceutical uses. The findings of this investigation provide important information on how to make the best use of pear cultivars studied for different uses, which is meaningful for both processing practices and technological research.
Article
Full-text available
The contents of organic acids in the fruit of 40 cultivars of four major pear species, Pyrus ussuriensis, Pyrus bretschneideri, Pyrus pyrifolia, and Pyrus communis, were examined using high performance liquid chromatography (HPLC). The results showed that the major components of organic acids present in the pear fruit were malic and citric acids. The total organic acid content and the individual contents of malic, citric, and quinic acids were significantly higher in the fruit of P. ussuriensis than in the other three species. Among the ten organic acids examined, both malic and citric acids exhibited highly significant positive correlation with quinic acid, whereas extremely significant negative correlation was observed between acetic and lactic acids, and between succinic and fumaric acids. Furthermore, significant positive correlation was observed between malic and citric acids, and between quinic acid and shikimic acids, whereas significant negative correlation was found between quinic and tartaric acids. The differences in the contents of the 10 individual organic acids and the total organic acid content in the fruit of the 40 pear cultivars reached a significant and strong level.
Article
Full-text available
Purpose: We evaluated the relationship between dietary fiber, fruit and vegetable intake, and the risk of kidney stone formation. Materials and methods: Overall 83,922 postmenopausal women from the Women's Health Initiative observational study were included in the analysis and followed prospectively. Cox proportional hazards regression analyses were used to evaluate the associations between total dietary fiber, fruit and vegetable intake, and the risk of incident kidney stone formation, adjusting for nephrolithiasis risk factors (age, race/ethnicity, geographic region, diabetes mellitus, calcium supplementation, hormone therapy use, body mass index and calibrated caloric intake; and dietary water, sodium, animal protein and calcium intake). Women with a history of kidney stones (3,471) were analyzed separately. Results: Mean age of the women was 64±7 years, 85% were white and 2,937 (3.5%) experienced a kidney stone in a median followup of 8 years. In women with no history of kidney stones higher total dietary fiber (6% to 26% decreased risk, p <0.001), greater fruit intake (12% to 25% decreased risk, p <0.001) and greater vegetable intake (9% to 22% decreased risk, p=0.002) were associated with a decreased risk of incident kidney stone formation in separate adjusted models. In women with a history of stones there were no significant protective effects of fiber, fruit or vegetable intake on the risk of kidney stone recurrence. Conclusions: Greater dietary intake of fiber, fruits and vegetables was associated with a reduced risk of incident kidney stones in postmenopausal women. The protective effects were independent of other known risk factors for kidney stones. In contrast, there was no reduction in risk in women with a history of stones.
Article
Full-text available
The lifetime prevalence of kidney stones is around 10 % and incidence rates are increasing. Diet may be an important determinant of kidney stone development. Our objective was to investigate the association between diet and kidney stone risk in a population with a wide range of diets. This association was examined among 51,336 participants in the Oxford arm of the European Prospective Investigation into Cancer and Nutrition using data from Hospital Episode Statistics in England and Scottish Morbidity Records. In the cohort, 303 participants attended hospital with a new kidney stone episode. Cox proportional hazards regression was performed to calculate hazard ratios (HR) and their 95 % confidence intervals (95 % CI). Compared to those with high intake of meat (>100 g/day), the HR estimates for moderate meat-eaters (50-99 g/day), low meat-eaters (<50 g/day), fish-eaters and vegetarians were 0.80 (95 % CI 0.57-1.11), 0.52 (95 % CI 0.35-0.8), 0.73 (95 % CI 0.48-1.11) and 0.69 (95 % CI 0.48-0.98), respectively. High intakes of fresh fruit, fibre from wholegrain cereals and magnesium were also associated with a lower risk of kidney stone formation. A high intake of zinc was associated with a higher risk. In conclusion, vegetarians have a lower risk of developing kidney stones compared with those who eat a high meat diet. This information may be important to advise the public about prevention of kidney stone formation.
Article
Full-text available
Background Patients with nephrolithiasis and hyperoxaluria generally are advised to follow a low-oxalate diet. However, most people do not eat isolated nutrients, but meals consisting of a variety of foods with complex combinations of nutrients. A more rational approach to nephrolithiasis prevention would be to base dietary advice on the cumulative effects of foods and different dietary patterns rather than single nutrients. Study Design Randomized controlled trial. Setting & Participants Recurrent stone formers with hyperoxaluria (urine oxalate > 40 mg/d). Intervention The intervention group was asked to follow a calorie-controlled Dietary Approaches to Stop Hypertension (DASH)-style diet (a diet high in fruit, vegetables, whole grains, and low-fat dairy products and low in saturated fat, total fat, cholesterol, refined grains, sweets, and meat), whereas the control group was prescribed a low-oxalate diet. Study length was 8 weeks. Outcomes Primary: change in urinary calcium oxalate supersaturation. Secondary Changes in 24-hour urinary composition. Results 57 participants were randomly assigned (DASH group, 29; low-oxalate group, 28). 41 participants completed the trial (DASH group, 21; low-oxalate group, 20). As-treated analysis showed a trend for urinary oxalate excretion to increase in the DASH versus the low-oxalate group (point estimate of difference, 9.0 mg/d; 95% CI, −1.1 to 19.1 mg/d; P = 0.08). However, there was a trend for calcium oxalate supersaturation to decrease in the DASH versus the low-oxalate group (point estimate of difference, −1.24; 95% CI, −2.80 to 0.32; P = 0.08) in association with an increase in magnesium and citrate excretion and urine pH in the DASH versus low-oxalate group. Limitations Limited sample size, as-treated analysis, nonsignificant results. Conclusions The DASH diet might be an effective alternative to the low-oxalate diet in reducing calcium oxalate supersaturation and should be studied more.
Article
Kidney stones have been rising in prevalence in the United States and worldwide, and represent a significant cost burden. Cost effectiveness research in this area may enable improvements in treatment efficiency that can benefit patients, providers and the healthcare system. There has been limited research in the cost effectiveness of surgical interventions for stone disease, despite the diverse treatment approaches that are available. Medical expulsive therapy (MET) has been shown to improve rates of stone passage for ureteral stones, and there is evidence that this practice should be liberalized from the standpoint of both clinical and cost effectiveness. While conservative treatment following a primary stone event appears to be cost effective, the economic impact of medical therapy for recurrent stone formers requires clarification despite its clinical efficacy. Future study regarding the cost effectiveness of prevention and interventions for stone disease are likely to improve both the quality and efficiency of care.
Article
Historically nephrolithiasis was considered a disease of dehydration and abnormal urine composition. However, over the past several decades, much has been learned about the epidemiology of this disease and its relation to patient demographic characteristics and common systemic diseases. Here we review the latest epidemiologic studies in the field. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Article
Objective To evaluate the trends in the American diet over the last 40 years (1974-2010), during which time the National Health and Nutrition Examination Survey data set has documented an increase in stone prevalence from 3.8% to 8.8%. Materials and Methods We used the National Health and Nutrition Examination Survey reported rates for stone disease (1974-2010) to compare the United States Department of Agriculture's food distribution data during the same period. Three data points for prevalence were used from the literature. We correlated these to changing lithogenic food distributions using linear models to interpolate annual changes in prevalence. Spearman correlations were performed (P ≤.05) using SAS 9.2 (SAS Institute, Cary, NC). Results Increased total daily calories (rho, 0.96; P <.001), fat (rho, 0.79; P <.001), protein (rho, 0.85; P <.001), fruit (rho, 0.6; P = .01), and vegetables (rho, 0.73; P <.001) correlated strongly with increasing stone prevalence. Dark green vegetables, flour or cereal products, fish or shellfish, corn products (including high fructose corn syrup), and added sugars also showed strong correlations with stone prevalence. Citrus fruits were negatively correlated to stone disease (rho, −0.18; P = .31). Protein, fruits and vegetables, and added sugars actually decreased in proportion to daily caloric per capita increases. Conclusion Increases in caloric intake and several lithogenic foods correlate temporally with increasing stone prevalence. The nature of this relationship is difficult to determine from this data; although, clearly, American diets have changed over the last 4 decades.