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Kamel El-Reshaid et al Journal of Drug Delivery & Therapeutics. 2019; 9(6):126-129
ISSN: 2250-1177 [126] CODEN (USA): JDDTAO
Available online on 15.11.2019 at http://jddtonline.info
Journal of Drug Delivery and Therapeutics
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Open Access Research Article
Dietary Restriction: A Major Factor in Prophylaxis against Calcium Oxalate
Urolithiasis
Kamel El-Reshaid *, Shaikha Al-Bader **
*Department of Medicine, Faculty of Medicine, Kuwait University, P O Box 24923, 13110 Safat, Kuwait
** Department of Medicine, Nephrology Unit, Amiri Hospital, Ministry of Health, Kuwait
ABSTRACT
Urolithiasis (Ur) Is A Worldwide Problem That Affects All Groups Of Ages. Nearly 80% Of Renal Stones Are Calcium Oxalate (Cao) And 50% Of
The Affected Patients Have Recurrent Disease Within 10 Years. Our Prospective Study Was Conducted Over 4 And ½ Years And Eva luated The
Role Of Dietary Manipulation In Prophylaxis Against Cao Ur. A Total Of 212 Patients With Recurrent Cao Ur, Who Lacked Anatomical Or
Metabolic Derangement, Were Subjected To A Practical And Specific Diet. The Latter Had: (A) Low Salt, Red-Meat And Green Leafy Vegetable,
(B) Moderate Amounts Of Milk, Dairy Products, Poultry And Certain Fish-Items, And (C) High Water Intake (2 Liters/Day). A Total Of 66/70
(96%), 87/108(88%) And 146/167(87.4%) Patients Were Stone-Free By The End Of 1, 2 And 3 Years Of Follow Up. The Median Time For
Stone-Free Duration Was 33 (28.7-37.3) Months. Adding A Thiazide And Allopurinol To The 19 Patients Who Had Failed Dietary Prophylaxis
Prevented Stone Formation In 16 More Patients Leaving Only 3 True Failures. Four Patients Could Not Tolerate The Latter 2 Drugs For Allergy.
In Conclusion; Our Practical Dietary Modification Can Aid In Prophylaxis Against Cao Ur.
Keywords: Diet, Calcium Oxalate, Urolithiasis, Urinary Tract Stones, Prophylaxis
Article Info: Received 10 Sep 2019; Review Completed 23 Oct 2019; Accepted 28 Oct 2019; Available online 15 Nov 2019
Cite this article as:
El-Reshaid K, Al-Bader S, Dietary Restriction: A Major Factor in Prophylaxis against Calcium Oxalate Urolithiasis , Journal
of Drug Delivery and Therapeutics. 2019; 9(6):126-129 http://dx.doi.org/10.22270/jddt.v9i6.3716
*Address for Correspondence:
Dr. Kamel El-Reshaid, Professor, Dept. Of Medicine, Faculty of Medicine, Kuwait University, P O Box 24923, 13110 Safat,
Kuwait
INTRODUCTION
Urolithiasis (Ur) Is A Worldwide Problem Which Can Affect
All Groups Of Ages And Is A Major Source Of Morbidity
Around The World. The Incidence Of Ur Is About 0.5% Per
Year In North America And Europe [1]. Between 1-15% Of
People Globally Are Affected By Kidney Stones At Some Point
In Their Lives. In 2015, 22.1 Million Cases Occurred And Had
Resulted In 16,000 Deaths Despite All The New Innovations
In Its Urological Interventions [2, 3]. The Etiology Of Ur
Includes; Genetic/Familial Predisposition, Metabolic
Disorders And Anomalies In The Urinary Tract [4]. Nearly
80% Of Renal Stones Are Calcium Oxalate (Cao) And 50% Of
Patients Have Recurrent Disease Within 10 Years Despite
Lack Of Metabolic And Anatomical Diseases [5]. The Latter
Phenomenon Manifests As An Effect Of The Socioeconomic
Status And Geographic Residency (Stone Belts) [4].
Fortunately, A Wide-Range Of Surgical Options Are Currently
Available For Treatment Of Cao Ur Yet The Role Of Its
Prophylaxis Is Under-Estimated And Especially The Dietary
One [6]. In The Present Study We Evaluated The Role Of
Dietary Manipulation In Prevention Of New Stone-Formation
In Patients With Recurrent Cao Ur.
PATIENTS AND METHODS:
Study Design:
Patients With Uncomplicated Yet Recurrent Cao Ur Who
Attended Dr. El-Reshaid Kidney Clinic From 1st January 2014
To 31st June 2019 Were Analyzed Prospectively For Stone
Prophylaxis. The Clinic Was Established In 1997 In The
Center Of Kuwait City. It Is A Referral Center And With
Adequate Diagnostic As Well As Therapeutic Facilities To
Care For Both In- And Out-Patients With All Medical And
Renal Diseases.
Inclusion Criteria:
Patients Were Included, In The Study, If They Have Recurrent
Cao Stones. The Latter Was Defined As (A) Having > Than 2
Radio-Opaque Renal Stones < 6 Mm, (B) Has 1 Stone < 6 Mm
And Had Passed > 1 Before, And (C) Had Passed > 2 Stones
Before.
Exclusion Criteria:
1- Patients Older Than 60 Years At Start Of Symptoms Or
Less Than 14 Years.
Kamel El-Reshaid et al Journal of Drug Delivery & Therapeutics. 2019; 9(6):126-129
ISSN: 2250-1177 [127] CODEN (USA): JDDTAO
2- Those With Morbid Obesity, Hyperparathyroidism,
Nephrocalcinosis, Gastrointestinal Disorders (Short
Bowels, Inflammatory Bowel Disease And
Malabsorption), Chronic Inflammatory Conditions
Associated With Hypercalcemia Viz. Sarcoidosis Or
Malignancy, Cystinuria, Primary Hyperoxaluria, Distal
Renal Tubular Acidosis. Moreover, Patients With
Medullary Sponge Kidneys, Adult Polycystic Kidney
Disease, Urinary Tract Obstruction Or Anomalies Were
Also Excluded. The Exclusion Was Done With
Laboratory And Radiological Testing (Vida Infra).
3- Patients with Hypercalcemia (Corrected Serum Calcium
> 2.3 Mmol/L), Hyperuricemia (Serum Uric Acid > 450
Umol/L), Hypercalcuria (Urinary Calcium Excretion >
200 Mg/Day), Hyperuricosuria (Urinary Uric Acid >
800 Mg/Day), Hyperoxaluria (Urinary Oxalate > 50
Mg/Day), Hypocitraturia (Urinary Citrate < 320
Mg/Day) And Cystinuria (Urinary Cysteine > 350
Mg/Day) Or Positive Nitroprusside Cyanide Test.
4- Patients with Creatinine Clearance < 60 Ml/Minute.
5- Patients with Osteoporosis Requiring Maintenance
Calcium + Vitamin D Supplementation.
Initial Assessment:
Included; Laboratory And Radiological Testing. The
Laboratory Ones Were: (A) Serum Electrolytes Viz. Corrected
Calcium, Magnesium And Bicarbonate Content, Uric Acid (B)
Urine Routine And Microscopy (C) Urine Ph, Sodium,
Calcium, Uric Acid, Oxalate, Citrate And Nitroprusside
Cyanide Test. Radiological Tests Included; Ultrasound As
Well As CT Of The Abdomen And Pelvis When Indicated
Initially Or On Follow Up.
Follow Up Testing:
Included; Routine Clinical, Laboratory And Ultrasound
Assessment Every 2 Months. Twenty Four Hour Urine
Collections Were Done Every 6 Months To Ensure
Compliance. Adherence To Low-Salt Diet Was Confirmed By
Having Urinary Sodium < 225 Mmol/Day.
Stone Prophylaxis:
All Patients Had Instructions Regarding Dietary Measures
That Included Increasing Water Intake To 2 Liters/Day Via 5
Bottles-Regimens. A 250 Ml Of Water Upon Waking Up And
1 Hour Before Night Sleep As Well As 500 Ml ½ Hour Before
Respective Meals. In Addition; (A) Avoidance Of Calcium And
Vitamin D Supplementation Yet Permission Of Moderate
Low-Fat Milk And Dairy Products, (B) Avoidance Of Red Meat
And Their Internal Organs Yet Permission Of < 30 G Of Lean
Poultry Products As Well As Fish In Moderation Except For
Sardines, Tuna And Shrimps, (C) Dark-Green Leafy
Vegetables And (D) Stored Or Frozen Food-Products. The
Latter Was Intended To Limit Salt Intake Which Was
Complemented With Normal Intake Of Home Food Except
For Extra Salt Addition After Cooking And Salty Appetizers
Such As Pickles, Mustard, Salad Dressings, Yogurt And
Frozen Foods. Patients Who Did Not Improve (Recurrent
Renal Colics Or Had Increase Stone Load) Were Further
Retested After Addition Of A Combination Of Thiazide (250
Mg Daily And Allopurinol 100 Mg Daily).
Statistical Analysis:
Since The Age, Duration Of Stone Formation Prior To
Treatment And Duration Of Follow Up Were Not Normally
Distributed; The Median And (Interquartile Range) Were
Used To Express The Groups. Moreover, For Estimation Of
Efficacy Of Prophylaxis/Treatment Years; The Kaplan-Meier
Method Was Used To Calculate The Median Survival Time
And Its 95% Confidence Interval.
RESULTS
Over The Past 4 And 1/2 Years, A Total Of 258 Patients With
Ur Were Screened. Sixteen Patients Were Excluded For The
Following Reasons; (A) 5 With Isolated Hyperuricosuria (B)
2 With Isolated Hypercalcemia (C) 2 Patients With
Hyperuricemia (D) 2 Patients With Cysteine Stones (E) 2
With Distal Renal Tubular Acidosis (F) 2 With Primary
Hyperoxaluria (G) 1 With Hyperparathyroidism. Moreover,
14 Had Congenital Or Acquired Urinary Tract Disease, 11
Had Creatinine Clearance < 60 Ml/Minute And 5 Patients
Lost To Follow Up. Demographical Data And Results Of Their
Treatment Is Summarized In Table 1.
Table 1. The Demographical Data on 212 Patients with Recurrent Idiopathic Cao Urolithiasis and Results of Their
Treatment
Kamel El-Reshaid et al Journal of Drug Delivery & Therapeutics. 2019; 9(6):126-129
ISSN: 2250-1177 [128] CODEN (USA): JDDTAO
Demographical Data:
A Total Of 212 Patients Were Included In The Study. All
Patients Were Adults With A Median Age Of 32(11) And
Youngest Was 21 And Eldest Was 56 Years. The Median Of
Duration Of Follow Up Was 30(21) Months And Shortest Was
3 And Longest Was 54 Months.
Efficacy of Prophylaxis:
During The Study, Only 23 (11%) Patients Had Failed Dietary
Prophylaxis And Formed New Stones. Using Survival Time
Analysis; A Total of 66/70 (96%), 87/108(88%) And
146/167(87.4%) Patients Were Stone-Free By The End Of 1,
2 And 3 Years Of Follow Up. The Median Time for Stone-Free
Duration Was 33 (28.7-37.3) Months.
Management of the Initial Non-Responders:
Adding A Thiazide And Allopurinol To Those Who Failed
Dietary Prophylaxis Prevented New Stone Formation In 13
Of 19 Patients Who Could Tolerate The Drugs.
Tolerance to Prophylaxis:
In General There Was No Major Complaint With Our Dietary
Management. However, 2 Patients Could Not Tolerate
Thiazide For Pruritus. Two Patients Had Mild Hypokalemia
That Was Corrected By Increase In Intake Of Lemon Juice.
Two More Patients Could Not Tolerate Allopurinol For
Urticaria Which Persisted Despite Shifting To Febuxostat.
DISCUSSION
Treatment of Patients with Recurrent Ur Is Cost Effective
Even It Involves Drug Prophylaxis [7]. In The Latter Study,
The Savings Achieved By Reducing Hospitalization And
Urological Procedures In 1,092 Patients With Ur Prophylaxis
By Using Diagnostic Testing, Metabolic Evaluation And Use
Of Inexpensive Drugs Viz. Thiazides, Potassium Citrate And
Allopurinol Was $2,158 Per Patient Per Year. Given The
Proven Benefit Of Prophylaxis, Medicare And Most Managed-
Care Organizations Typically Cover The Costs Of Diagnosis
And These Particular Medical Treatments. In Our
Prospective Study; Few Patients with Recurrent Cao Ur Had
Metabolic Disorders (Hypocitremia, Hyperoxaluria and
Hyperuricemia) And Secondary (Anatomical, Infection And
Metabolic) Causes. The Latter Indicates That The Most Cao
Renal Stones Are Of Benign Nature And Amenable To Dietary
Manipulations Aimed At Calcium And Urate Absorptive
Mechanisms [8, 9]. Moreover, The Success Of Our Additional
Drug-Therapy In Those Who Failed The Dietary
Manipulation Confirms Our Findings. Thiazides Decrease
Urinary Calcium Excretion and Zyloric Decrease Synthesis of
Uric Acid and Hence It’s Excretion Leading To Further
Prevention Of Paroxysms Of Hypercalcuria And
Hyperuricosuria In Partially Compliant Patients [10, 11].
Our Study Further Emphasizes The Role Of Metabolic
Screening In Patients With Cao Ur To Decrease The Cost Of
Their Management. Patients With Recurrent Stone-
Formation And Normal Metabolic Screen; Can Benefit From
Our Practical Dietary Manipulations And The Use Of
Inexpensive Drugs Viz. Thiazides And Allopurinol If
Compliance Is An Issue. In Our Study; And To Improve Our
Patient’s-Compliance, We Limited The Water Intake To 2
Liters Divided At Regular Intervals. The Timing Is Essential
To Improve Patient’s Compliance And The Night Dose Was 1
Hour Before Sleep With Instruction To Have A Minimum Of 2
Urinary Voids Prior To Sleep To Avoid Nocturia That May
Decrease Compliance With The Last Dose. The Restriction
Of Dietary Calcium, Sodium, Animal Proteins, And Leafy
Vegetables Was Calculated To Improve Patient’s-Compliance
[12]. Dietary Calcium Was Moderate To Assist In Providing
Adequate Supply To The Growing Teeth And Bones As Well
As To Bind With Meal-Oxalate And Prevent Their Absorption
[13]. High Salt Intake Leads To Hypercalcuria Due To
Inhibition Of Re-Absorbency Of Calcium In The Proximal
Tubule [14]. Our Limitation Of Sodium-Intake Was Practical
And Acceptable By Our Patients. It Kept The Members Of
The Family Together By Just Limiting External Food Intake
And In-House High Salt-Content Items. The Restrictions Of
Animal Proteins Were Limited To Red Meat And Internal
Organs Which Are Purine-Rich Items And Result In High Uric
Acid Levels. Moderate Poultry Products and Most Fish-Items
Were Acceptable Alternatives And Did Not Significantly
Increase Uric Acid Excretion Or Result In Hyperuricosuria.
The Latter May Have Been Due To Their Higher Content Of
Guanine And Xanthine Compared To Adenine And Xanthine
In Meat As Well As Their Alkalization Effect (Similar To The
Milk And Dairy Products) Which Facilitates Uric Acid
Elimination In Urine [15]. Lastly, Leafy Vegetables Are A
Major Source Of Oxalates. The Latter Is A Major Risk Factor
For Cao Ur [16]. They Were Neglected By Most Of Our
Patients And Even Large-Percentage Of Our Population Still
Believes That The Drinks Containing “Bagdonis” Aids In
Stone Expulsion. This Believe Stemmed From Misconception
Of Higher Frequency Of Stone Passage Masquerading A
Rather More New Ur. In Conclusion; Our Dietary
Manipulations Offers Patients With Recurrent Idiopathic Cao
Ur A Simple And Palatable Diet With Adequate Essential
Elements To Improve Their Compliance And Prevent Disease
Progression.
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