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Chronic kidney disease of uncertain etiology in Sri Lanka is a possible sequel of interstitial nephritis!:

July 2016
Clinical Nephrology 86 (2016)(13)

DOI:10.5414/CNP86S115

Authors:

Zeid Badurdeen

University of Peradeniya

Nishantha Nanayakkara

Teaching Hospital, Kandy

Neelakanthi Ratnatunga

faculty of Medicine university of Peradeniya sri lanka

Show all 11 authorsHide

Introduction: The majority of published data on chronic kidney disease of uncertain etiology (CKDu) is on asymptomatic patients who were detected in screening programs. The clinicopathological profile of a group of patients presenting with acute symptoms and renal dysfunction from CKDu endemic regions in Sri Lanka was studied. Methods: 59 patients > 10 years of age with backache, feverish fatigue feeling, dysuria, joint pain, or dyspepsia, singly or in combination with elevated serum creatinine (> 116 and > 98 µmol/L for male and females, respectively) were included in the study. Those patients who had normal-sized kidneys were biopsied after excluding clinically detectable causes for renal dysfunction. Histology was scored with activity and chronicity indices. These patients' urinary sediment and inflammatory markers were checked. Patients were stratified into three groups based on duration of symptom onset to the time of biopsy. The natural course of the disease was described using serial mean serum creatinine and histological activity as well as chronicity indices in these 3 groups. Results: These patients' mean age, occupation, and sex ratio were 44 (9) years, 57 farmers, and male : female 55 : 4, respectively. Mean serum creatinine at biopsy was 143.8 (47.9) µmol/L. Elevated inflammatory markers and active urine sediment were reported. Histology was compatible with an interstitial nephritis with a mixture of acute and chronic tubulointerstitial lesions and glomerular scarring. In the natural course of an acute episode of CKDu, serum creatinine and histological activity were reduced while histological chronicity increased. Conclusion: CKDu may be preceded by an acute episode of tubulointerstitial nephritis (TIN).

. The clinical and demographic characteristics of 59 symptomatic CKDu patients.

…

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Original

ISSN 0301-0430

DOI 10.5414/CNP86S115

e-pub: July 29, 2016

Correspondence to

Dr. Zeid Badurdeen

Centre for Education

Research and Training

on Kidney Diseases

(CERTKiD), Faculty of

Medicine, University of

Peradeniya, Sri Lanka

zeid1964@gmail.com

Key words

symptomatic CKDu –

clinicopathological

– tubulointerstitial

nephritis – natural

course

Chronic kidney disease of uncertain etiology in

Sri Lanka is a possible sequel of interstitial

nephritis!

Clinicopathological prole of symptomatic, newly-diagnosed CKDu

patients

Zeid Badurdeen1, Nishantha Nanayakkara1,4, Neelakanthi V.I. Ratnatunga1,2,

Abdul W.M. Wazil4, Tilak D.J. Abeysekera1, Premil N. Rajakrishna4,

Jalitha P. Thinnarachchi4, Ranjith Kumarasiri3, Dulani D. Welagedera4,

Needika Rajapaksha4, and Adambarage P.D. Alwis4

1Centre for Education Research and Training on Kidney Diseases (CERTKiD),

2Department of Pathology, 3Department of Community Medicine, Faculty of

Medicine, University of Peradeniya, Peradenya, and 4Renal Transplant and

DialysisUnit, Teaching Hospital, Kandy, Sri Lanka

Abstract. Introduction: The majority of

published data on chronic kidney disease of

uncertain etiology (CKDu) is on asymptom-

atic patients who were detected in screening

programs. The clinicopathological prole

of a group of patients presenting with acute

symptoms and renal dysfunction from CKDu

endemic regions in Sri Lanka was studied.

Methods: 59 patients > 10 years of age with

backache, feverish fatigue feeling, dysuria,

joint pain, or dyspepsia, singly or in combi-

nation with elevated serum creatinine (> 116

and > 98 µmol/L for male and females, re-

spectively) were included in the study. Those

patients who had normal-sized kidneys were

biopsied after excluding clinically detectable

causes for renal dysfunction. Histology was

scored with activity and chronicity indices.

These patients’ urinary sediment and inam-

matory markers were checked. Patients were

stratied into three groups based on duration

of symptom onset to the time of biopsy. The

natural course of the disease was described

using serial mean serum creatinine and his-

tological activity as well as chronicity in-

dices in these 3 groups. Results: These pa-

tients’ mean age, occupation, and sex ratio

were 44 (9) years, 57 farmers, and male :

female 55 : 4, respectively. Mean serum cre-

atinine at biopsy was 143.8 (47.9) µmol/L.

Elevated inammatory markers and active

urine sediment were reported. Histology was

compatible with an interstitial nephritis with

a mixture of acute and chronic tubulointer-

stitial lesions and glomerular scarring. In the

natural course of an acute episode of CKDu,

serum creatinine and histological activity

were reduced while histological chronicity

increased. Conclusion: CKDu may be pre-

ceded by an acute episode of tubulointersti-

tial nephritis (TIN).

Introduction

Chronic kidney disease of uncertain eti-

ology (CKDu) is an alarming environmental

nephropathy among agricultural communi-

ties in the tropical climates of the world [1].

CKDu is prevalent among the paddy cultivat-

ing farmers in the North Central region of Sri

Lanka [2]. CKDu in Sri Lanka is described as

an asymptomatic, insidious, and slowly pro-

gressive nephropathy, predominately affect-

ing young males [3]. The changes in hydro-

geochemical environment, agrochemicals,

aristolochic acid, and ochratoxins have been

the most studied causative agents in CKDu

Sri Lanka [4]. Previous studies have reported

interstitial brosis and tubular atrophy with-

out signicant interstitial inammation and

glomerular sclerosis as signicant histologi-

cal features in asymptomatic CKDu patients

of Sri Lanka [5, 6].

The clinical presentation of CKDu was

either asymptomatic subnephrotic range pro-

teinuria detected on population screening or

presenting with symptoms of end-stage renal

failure (ESRF). The physicians in CKDu en-

demic regions had observed in the recent past

that apparently healthy individuals presented

with acute symptoms associated with renal

dysfunction. This research was designed to

Clinical Nephrology, DOI 10.5414/CNP86S115

Badurdeen, Nanayakkara, Ratnatunga, et al. S2

study the clinicopathological prole of those

acutely ill, symptomatic patients with renal

dysfunction in CKDu endemic regions.

Methods

This prospective study was conducted in

the Nephrology and Transplant Unit at the

Teaching Hospital Kandy and Department of

Pathology, Faculty of Medicine, University

of Peradeniya. Informed written consent was

obtained from each patient. Ethical approval

for this study was taken from the Ethical Re-

view Committee of the Faculty of Medicine,

University of Peradeniya (2012/EC/54 dated

15/11/2012).

Previously healthy males and females

from the CKDu endemic North Central re-

gion in Sri Lanka, aged > 10 years present-

ing to a renal clinic with recent onset of

backache, feverish fatigue feeling, dysuria,

joint pain, and dyspepsia, either singly or in

combination, were tested for serum creati-

nine levels. Those patients who had persis-

tently elevated serum creatinine (> 116 and

> 98 µmol/L for male and females) for up to

2 weeks were recruited for the study. Those

with clinically identiable causes for the

renal dysfunction and small-sized kidneys

were excluded. Serial serum creatinine was

measured from symptom onset to the time

of biopsy. Renal biopsy was done after ob-

taining informed consent within 90 days of

symptom onset. Serum calcium, phosphate,

uric acid, white blood cell count (WBC),

erythrocyte sedimentation rate (ESR), C-re-

active protein (CRP), urine for bacterial cul-

ture, urine deposit for microscopy, and sulfo-

salicylic acid test for proteins were done at

the time of biopsy.

Parafn sections of the biopsies were ex-

amined with routine and special stains. Di-

rect immunouorescence staining was done

to detect immune complexes of IgG, A, and

M, and complement. Those with no evidence

of immune complex mediated glomerular

disease and no other identiable primary or

secondary renal pathology were followed up.

The renal lesions were scored 0, 1, 2, 3; if

there was no lesion up to 30%, 30 – 60%, and

> 60% area affected, respectively. The dis-

ease activity index (AI) was scored as a sum

of interstitial lymphocyte inltration and tu-

bulitis (0 – 6) and chronicity index (CI) as a

sum of glomerular sclerosis, tubular atrophy,

interstitial brosis, and periglomerular bro-

sis (0 – 12). Patients were placed into one of

3 groups based on duration of symptom on-

set to the time of biopsy. 28 patients between

1 and 30 days, 10 patients between 31 and 60

days, and 8 patients between 61 and 90 days

after onset of symptoms were biopsied and

assigned to groups 1, 2, and 3, respectively.

The clinicopathological data were ex-

pressed with mean, standard deviation (SD),

and percentages. In the dened 3 groups, the

serial changes of serum creatinine on a linear

graph and activity and chronicity scores to-

gether on a separate bar chart were plotted.

All statistical procedures were performed

using SPSS version 20 (IBM, Armonk, NY,

USA).

Results

The demographic and clinical character-

istics of 59 symptomatic CKDu patients are

shown in Table 1. The salient pathological

lesions as a percentage of total number of

biopsies observed were interstitial lympho-

cyte inltration (ILI) 96.7%, tubulitis (TU)

81.4%, glomerular sclerosis (GS) 81.4%,

interstitial brosis (IF) 88.1%, tubular atro-

phy (TA) 93.2%, and periglomerular brosis

(PGF) 42.4%. The semiquantitative scores

Table 1. The clinical and demographic characteristics of 59 symptomatic

CKDu patients.

Parameters Description

Mean age, SD 44(9) years

Male : female 55 : 4

Farmer : other jobs 57 : 2

Mean systolic blood pressure, SD 122 (15) mmHg

Mean diastolic blood pressure, SD 79 (10) mmHg

Mean serum creatinine, SD 143.8 (47.9) ref: 53 – 116 µmol/L

Mean serum calcium, SD 2.3(0.2) ref: 2.2 – 2.7 mmol/L

Mean serum phosphate, SD 1.3(0.5) ref: 0.81 – 1.45 mmol/L

Mean uric acid, SD 6.4(1.9) ref: 3.5 to 7.2 mg/dL

Urine protein (sulfosalicylic acid test) 80% cases trace or Nil

20% cases 1+ and 2+

Microscopic hematuria 20.7% cases RBC > 3/HPF (positive)

Pyuria 48.6% cases WBC > 5/HPF (positive)

Erythrocyte sedimentation rate (ESR) 65.6% cases > 20 mm/hour

C-reactive protein (CRP) 48.5% cases > 10 mg/L

SD = standard deviation; RBC = red blood cells; WBC = white blood cells;

HPF = high power eld.

Acute episode of CKDu in Sri Lanka S3

of salient histological lesions of symptom-

atic CKDu as a percentage of total number

of patients is shown in Table 2.

The mean serum creatinine decline was

observed serially from 189 to 153 µmol/L

in group 1, from 179 to130 µmol/L and 130

to 129 µmol/L in group 2, and from 171 to

123 µmol/L and 123 to 158 µmol/L and 158

to 148 µmol/L in group 3 (Figure 1a). The

mean histological activity scores of groups 1,

2, and 3 were 3.4, 2.7, and 2.75, respectively

(Figure 1b). The mean histological chronic-

ity scores of groups 1, 2, and 3 were 4.17,

4.50, and 5.75, respectively (Figure 1b).

Discussion

In our study, > 90% symptomatic patients

were male farmers with a mean age of 44

years. A CKDu epidemiological study in the

North Central region of Sri Lanka has report-

ed that the majority of the diagnosed CKDu

cases were asymptomatic, > 90% farmers

with a mean age 54 years, detected in screen-

ing programs [7]. Conversely, acute symp-

tomatic CKDu is presenting at a younger age

than asymptomatic CKDu.

Michael et al. [8] have reported arthralgia

45%, rash 21%, fever 30%, loin pain 21%,

and dysuria 15% as presenting symptoms

of patients with acute tubulointerstitial ne-

phritis (TIN). However, none of the acute

symptomatic CKDu patients presented with

typical clinical features of TIN like fever and

rash or oligo anuria [9]. Subnephrotic range

proteinuria, hematuria, sterile pyuria, and

elevated inammatory markers observed in

these patients were compatible with the clin-

ical prole of TIN [10].

The dominant histological features in

asymptomatic CKDu patients in Sri Lanka

were interstitial brosis and tubular atrophy

without signicant interstitial inamma-

tion and glomerular sclerosis. Wijetunga et

al. [6] has reported tubulitis as a feature in

just 1% of asymptomatic CKDu cases. The

salient histological lesions observed in acute

symptomatic CKDu were signicant inter-

stitial inammation and wide-spread tubuli-

tis in the background of brosis and tubular

atrophy.

We described the natural course of an

acute episode of interstitial nephritis in Fig-

ure 1. We propose that this acute episode of

interstitial nephritis is followed by residual

scarring as the possible pathological process

Table 2. The semiquantitative scores of salient histological lesions of symptomatic CKDu as a percent-

age of total number of patients.

Histological lesions Percentages of scores

“0” scores “1” score “2” score “3” score

Interstitial lymphocyte inltration (ILI) 3.3% 43.5% 35.5% 17.7%

Tubulitis (TU) 19.4% 33.9% 24.2% 22.6%

Glomerular sclerosis (GS) 22.6% 50.0% 16.1% 11.3%

Interstitial brosis (IF) 12.9% 35.5% 46.8% 4.8%

Tubular atrophy (TA) 8.1% 35.5% 51.6% 4.8%

Peri-glomerular brosis (PGF) 58.1% 35.5% 4.8% 1.6%

Figure 1. The change of mean serum creatinine, mean histological activity, and chronicity scores of 3

groups of patients in relation to duration of symptom onset to point of biopsy. a: the serial mean serum

creatinine; b: the mean histological activity and chronicity scores.

Badurdeen, Nanayakkara, Ratnatunga, et al. S4

that leads to CKDu. This acute episode could

be either the rst episode or one of multiple

episodes.

Conclusion

We described for the rst time the clini-

copathological prole of a group of patients,

the majority being young healthy male farm-

ers presenting with acute symptoms and re-

nal dysfunction from CKDu endemic North

Central region of Sri Lanka. Their biomarker

prole was compatible with an early CKD

with evidence of systemic inammation.

Histology is compatible with a signicant

interstitial inltrate, tubulitis, and brosis in

the absence of primary glomerular disease.

We described an acute episode of TIN in

these symptomatic CKDu patients. We rec-

ommend keeping these symptomatic patients

in endemic regions under surveillance for

early detection of CKDu. Further studies are

recommended targeting this specic group to

identify the etiology and possible interven-

tions.

Acknowledgement

We acknowledge the staff of the Nephrol-

ogy and Renal Transplant Unit, Teaching

hospital, Kandy and staff of renal sentinel

clinics in the North Central region of Sri

Lanka. We thank H.M.N.D. Herath, Depart-

ment of Pathology, Faculty of Medicine, Per-

adeniya for the preparation of histological

slides. Finally, we thank Rusiru Hemage and

Yashoda Somarathne of CERTKiD, Faculty

of Medicine, Peradeniya for their technical

support in manuscript preparation.

Conict of interest

All the authors declared no competing

interests.

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Jul 2022

© 2022 Environmental Disease | Published by Wolters Kluwer - Medknow 47Comparison of biochemical characteristics between anendemic and a nonendemic area for CKDu Sri LankaA. Medagedara1,2, Pasan Hewavitharane1, Rohana Chandrajith3, Hemalika T. K. Abeysundara4,R. O. Thatil5, S. Thennakoon6, Buddhisha Mahanama1, N. Weerasuriya7, A. Thilakarathne7,Nishantha Nanayakkara11Center for Research, National Hospital, Kandy, Sri Lanka, 2Department of Fundamentals of Nursing, Faculty of Nursing,University of Colombo, 3Department of Geology, Faculty of Science, University of Peradeniya, 4Department of Statistics and ComputerSciences, Faculty of Science, University of Peradeniya, 5Department of Crop Sciences, Faculty of Agriculture,University of Peradeniya, 6Department of Community Medicine, Faculty of Medicine, University of Peradeniya,7Provincial Director of Health Services, Central Province, Sri LankaIntroduction: Chronic kidney disease with uncertain etiology (CKDu) was first recognized in the 1990s inSri Lanka. Considering the distribution of CKDu in the country, clusters of endemic and nonendemic areascan be identified. This study was carried out to compare the biochemical characteristics between CKDuendemic and nonendemic areas in Sri Lanka.Materials and Methods:A cross‑sectional study was carried out among randomly selected males between theage category of 30 and 60 years in selected villages of Wilgamuwa (endemic) and Hanguranketha (nonendemic),located in the dry and wet zone, respectively.Results: The total participation percentage from the endemic area was 74.7% (224 out of 300 invitees). Outof 150 participants invited from the nonendemic area, only 100 participated in the study cohort. There wasa striking difference between the two areas in serum creatinine levels (P = 0.001). When considering thebehavioral patterns of the two study areas, the main occupation was farming and there was no significantdifference between the behaviors of the people in the selected areas. A significant number of participants(n = 31, 13.8%) from the endemic area had high serum creatinine levels with a mean of 109 μmol/L(standard deviation [SD] = 66.41) (normal: 90–116 μmol/L). Whereas, in the nonendemic area, only 3 (3%)participants had elevated creatinine levels with a mean value of 85.41 μmol/L (SD = 18.78). A significantdifference was observed in the two groups in the mean values of serum creatinine levels (P = 0.001). Themean value of random blood sugar (RBS) was 113.56 mg/dL (SD = 44.38) and 119.10 mg/dL (SD = 50.48)in endemic and nonendemic areas, respectively. There was no significant difference between the meanvalues of RBS (P = 0.2). The mean serum cholesterol was slightly higher in Wilgamuwa (119.26 mg/dl,SD = 45.31) compared to Hanguranketha (189.02 mg/dl, SD = 45.09). However, that was not statisticallysignificant (P = 0.6) (7) (PDF) Comparison of biochemical characteristics between an endemic and a nonendemic area for CKDu Sri Lanka. Available from: https://www.researchgate.net/publication/361684614_Comparison_of_biochemical_characteristics_between_an_endemic_and_a_nonendemic_area_for_CKDu_Sri_Lanka [accessed Aug 08 2022].

Renal dysfunction in general overheating (literature review)

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Sep 2023

Over the past 30 years, climate change has taken one of the leading places among the ten main causes of death due to natural disasters. Rising temperatures have been shown to increase emergency department admissions for a wide range of kidney diseases, including acute kidney injury (AKI), chronic kidney disease, kidney stones, and urinary tract infections. The occupational effect of heat stress is also associated with AKI, which can quickly progress to acute kidney failure with high mortality. The basis of the pathogenetic mechanisms of heat-induced AKI is a decrease in the circulating blood volume and electrolyte disturbances due to increased perspiration. Water evaporation from the surface of the skin contributes to dehydration with an increase in serum osmolarity. In response to this, vasopressin is activated, the specific gravity of urine increases, and the amount of urine decreases. The glomerular filtration rate progressively decreases. Hypokalemia develops, which changes to hyperkalemia within 12 hours. Tubular endothelium is damaged, which leads to microthrombosis of afferent and efferent renal arteries, the development of an inflammatory response, and exhaustion of the renal interstitium. Possible rhabdomyolysis and myoglobinemia with subsequent tubular obstruction worsen existing kidney damage. According to the leading mechanism of damage, there are two types of acute heat damage to the kidneys: classical rhabdomyolysis and acute interstitial nephritis. Although modern medical advances have contributed to the development of effective treatment and management strategies (rapid cooling, extracorporeal detoxification methods, etc.), mortality in kidney damage due to general overheating has decreased slightly over the past decades. For health care and industry researchers, it is necessary to identify the harmful occupational conditions that lead to heat stress nephropathy and to develop certain occupational safety strategies.

Chronic Kidney Disease of Unknown Etiology

Chapter

Mar 2022

A kidney disease of unknown cause is affecting up to 20% of men living in agricultural communities recognized to be hotspots, among them Nicaragua, El Salvador, Guatemala, and Sri Lanka. The disease often manifests in the third or fourth decade of life. Kidney biopsy indicates that the major finding is chronic tubulointerstitial nephritis in a majority of patients, although a subset may also present with symptoms of dysuria or fever and have acute interstitial nephritis on histology. In this chapter we review the epidemiology, pathology, and prominent hypotheses regarding potential causes of this mysterious kidney disease. We also provide a brief overview of ongoing population and occupational cohorts conducting promising investigations and/or interventions to prevent the disease.

Epidemiology of Chronic Kidney Disease, With Special Emphasis on Chronic Kidney Disease of Uncertain Etiology, in the North Central Region of Sri Lanka

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Mar 2015
J EPIDEMIOL

The aim of the study was to identify the epidemiology of chronic kidney disease of uncertain etiology in Sri Lanka. A cross-sectional study was carried out by analyzing health statistics, and three cohort studies were conducted (n = 15 630, 3996, and 2809) to analyze the demographic information, age-specific prevalence, etiology, and stage of presentation. We screened 7604 individuals for chronic kidney disease of uncertain etiology. The results showed that the male:female ratio was 2.4:1, the mean age of patients was 54.7 ± 8 years, 92% of the patients were farmers, and 93% consumed water from shallow dug wells. Familial occurrence was common (36%). The prevalence of chronic kidney disease in different age groups was 3% in those aged 30-40 years; 7% in those aged 41-50 years, 20% in those aged 51-60 years, and 29% in those older than 60 years. Chronic kidney disease of uncertain etiology was diagnosed in 70.2% of patients, while 15.7% and 9.6% were due to hypertension and diabetic mellitus, respectively. The majority of patients were stage 4 (40%) at first presentation, while 31.8% were stage 3 and 24.5% were stage 5. Stage 1 and 2 presentation accounted for only 3.4%. Low prevalence of CKDU was noticed (1.5%) among those who consumed water from natural springs. Prevalence was highest among males, rice farming communities, and those presenting at later disease stages.

Chronic Kidney Disease of Unknown Etiology in Agricultural Communities

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Apr 2014
MEICC REV

ABSTRACT In recent years, Central America, Egypt, India and Sri Lanka have reported a high prevalence of chronic kidney disease of unknown etiology in agricultural communities, predominantly among male farmworkers. This essay examines the disease’s case definitions, epidemiology (disease burden, demographics, associated risk factors) and causal hypotheses, by reviewing published findings from El Salvador, Nicaragua, Costa Rica, Sri Lanka, Egypt and India. The range of confirmed chronic kidney disease prevalence was 17.9%–21.1%. Prevalence of reduced glomerular filtration (<60 mL/min/1.73 m2 body surface area) based on a single serum creatinine measurement was 0%–67% men and 0%–57% women. Prevalence was generally higher in male farmworkers aged 20–50 years, and varied by community economic activity and altitude. Cause was unknown in 57.4%–66.7% of patients. The dominant histopathological diagnosis was chronic tubulointerstitial nephritis. Associations were reported with agricultural work, agrochemical exposure, dehydration, hypertension, homemade alcohol use and family history of chronic kidney disease. There is no strong evidence for a single cause, and multiple environmental, occupational and social factors are probably involved. Further etiological research is needed, plus interventions to reduce preventable risk factors.

Retrospective analysis of renal histology in asymptomatic patients with probable chronic kidney disease of unknown aetiology in Sri Lanka

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Dec 2013

To study the early pathological changes in renal lesions of asymptomatic patients with kidney diseases, with no definite aetiology living in regions endemic for chronic kidney disease of unknown etiology (CKDUe). Design Retrospective study. Regions endemic for CKDUe in and around the North Central Province of Sri Lanka. Two hundred and eleven asymptomatic patients living in endemic regions detected with renal disease by screening for proteinuria using the dipstick method. Those with long standing hypertension, diabetes mellitus, histological diagnosis of primary glomerular diseases, immunocomplex mediated diseases or renal lesions secondary to systemic diseases were excluded. Renal lesions were divided into seven histological categories depending on the pathological changes: Category 0: no detectable changes. Category 1: Interstitial fibrosis ± mild interstitial inflammation ± tubular atrophy; no glomerulosclerosis. Category 2: Interstitial fibrosis ± mild interstitial inflammation ± tubular atrophy; glomerulosclerosis. Category 3: Moderate or severe interstitial fibrosis, interstitial inflammation and tubular atrophy ± glomerulosclerosis; Category 4: Interstitial inflammation ± tubular atrophy ± glomerulosclerosis; no interstitial fibrosis. Category 5: The prominent change is interstitial inflammation with tubulitis. Category 6: Severely scarred kidney. Histological categories were compared with calculated glomerular filtration rates and age of the patients. Number of cases in histological categories 0 to 6 were: 7 (3.3%), 71 (33.6%), 53 (25.1%), 63 (29.9%), 0, 2 (0.9%) and 15 (7.1%) respectively. The mean glomerular filtration rate was >90 ml/min in patients in category 0 and 1 and declined progressively in categories 2 and 3. Apart from category 0, all had interstitial fibrosis and in category 1, 62 (87.3%) had interstitial fibrosis without inflammation. Severity of interstitial inflammation increased from category 1 to 3. The early disease among asymptomatic patients is characterized by interstitial fibrosis without significant interstitial inflammation and glomerular sclerosis with preserved glomerular function. Although the role of interstitial inflammation in the initiation of the disease is not clear, it appears to have a role in the progression of the disease.

Increased prevalence of acute tubulointerstitial nephritis

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Jul 2012
NEPHROL DIAL TRANSPL

Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury (AKI) for which early treatment improves prognosis. The recent increase in prevalence has not been reflected in the literature. The aim of our study was to analyse all native kidney biopsies performed from 1994 to 2009 and included in the Spanish Registry of Glomerulonephritis with a histological diagnosis of ATIN. We assessed the prevalence of ATIN, associated clinical syndromes and urinary sediment abnormalities. We divided the population into two groups according to age: adults (15-65 years) and elderly patients (>65 years). We collected a total of 17 680 native kidney biopsies from 120 hospitals in Spain. The overall prevalence of ATIN was 2.7%. When the analysis was restricted to patients with AKI, the prevalence increased to 12.9%. During the 16 years of follow-up, there was a significant increase in prevalence (from 3.6% in the first 4 years to 10.5% in the last 4 years), which was more marked among elderly patients (from 1.6 to 12.3%). The most common clinical manifestations were AKI, microscopic haematuria, non-nephrotic proteinuria, leucocyturia and arterial hypertension, which were more frequent in the elderly. The prevalence of ATIN has increased in recent years, especially in patients aged >65 years. This could be due to an increase in drug-associated ATIN, which would justify early renal biopsy to identify ATIN and reduce the probability of progression to chronic kidney disease. Although, our data are not able to corroborate this fact.

Tubulointerstitial damage as the major pathological lesion in endemic chronic kidney disease among farmers in North Central Province of Sri Lanka

Article

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Oct 2011
Environ Health Prev Med

Chronic kidney disease of uncertain etiology (CKDu) in North Central Province of Sri Lanka has become a key public health concern in the agricultural sector due to the dramatic rise in its prevalence and mortality among young farmers. Although cadmium has been suspected as a causative pathogen, there have been controversies. To date, the pathological characteristics of the disease have not been reported. Histopathological observations of 64 renal biopsies obtained at Anuradhapura General Hospital from October 2008 to July 2009 were scored according to Banff 97 Working Classification of Renal Allograft pathology. The correlations between the histological observations and clinical parameters were statistically analyzed. Interstitial fibrosis and tubular atrophy with or without nonspecific interstitial mononuclear cell infiltration was the dominant histopathological observation. Glomerular sclerosis, glomerular collapse, and features of vascular pathology such as fibrous intimal thickening and arteriolar hyalinosis were also common. Although hypertension was identified as one of the common clinical features among the cases, it did not influence the histopathological lesions in all the cases. This study concludes that tubulointerstitial damage is the major pathological lesion in CKDu. Exposure(s) to an environmental pathogen(s) should be systematically investigated to elucidate such tubulointerstitial damage in CKDu.

The clinical spectrum of tubulointerstitial nephritis

Article

Full-text available

Sep 1998

end-stage renal disease, analgesic-induced tubulointerstitial nephritis, urinary tract obstruction, hyperuricemia, nephrocalcinosis, lead nephropathy, sarcoid nephropathy, acute drug-induced tubulointerstitial nephritis

Acute Interstitial Nephritis: Etiology, Pathogenesis, Diagnosis, Treatment and Prognosis

Article

Mar 2013

Acute interstitial nephritis (AIN) is an important and common cause of acute kidney injury, particularly in hospitalized patients. The classic presentation of AIN includes fever, rash, arthralgias, eosinophilia, and acute kidney injury. While renal biopsy is considered the gold standard for diagnosis, the clinical presentation of fever and rash along with laboratory evidence of peripheral blood eosinophilia, eosinophiluria, and low-grade proteinuria strongly suggest the diagnosis. Histologically, interstitial inflammation with interstitial edema and tubulitis is the hallmark of interstitial nephritis. The most common causative factors are drugs, infections, and certain immune-mediated disorders. Discontinuation of the offending agent is considered the mainstay of therapy while the use of corticosteroids to hasten renal recovery may be beneficial. The role of interstitial nephritis in the pathogenesis of chronic kidney disease and end-stage renal disease is increasingly recognized, further emphasizing the importance of its early diagnosis and timely treatment.

Chronic Kidney Disease of Unknown Etiology Should Be Renamed Chronic Agrochemical Nephropathy

Article

Apr 2014
MEICC REV

Saroj Jayasinghe

Epidemics of chronic kidney disease not attributable to common causes have recently been observed in Central America and Asia. Since the etiology is unclear, the disease is often known by terms such as chronic kidney disease of unknown etiology. There is growing evidence that risk factors include rural agricultural work and agrochemical exposure. The disease should be renamed chronic agrochemical nephropathy to highlight the most likely etiology and draw attention to the condition. KEYWORDS Chronic kidney diseases/etiology; renal insufficiency, chronic/etiology; kidney failure, chronic/etiology; agrochemicals/adverse effects; pesticides/adverse effects; nephropathy; occupational exposure; environmental exposure; environmental health.

On uncertain etiologies of proteinuric-chronic kidney disease in rural Sri Lanka Reply

Article

Aug 2011
KIDNEY INT

The global prevalence of chronic kidney disease (CKD) of uncertain etiology may be underreported. Community-level epidemiological studies are few due to the lack of national registries and poor focus on the reporting of non-communicable diseases. Here we describe the prevalence of proteinuric-CKD and disease characteristics of three rural populations in the North Central, Central, and Southern Provinces of Sri Lanka. Patients were selected using the random cluster sampling method and those older than 19 years of age were screened for persistent dipstick proteinuria. The prevalence of proteinuric-CKD in the Medawachchiya region (North Central) was 130 of 2600 patients, 68 of 709 patients in the Yatinuwara region (Central), and 66 of 2844 patients in the Hambantota region (Southern). The mean ages of these patients with CKD ranged from 44 to 52 years. Diabetes and long-standing hypertension were the main risk factors of CKD in the Yatinuwara and Hambantota regions. Age, exceeding 60 years, and farming were strongly associated with proteinuric-CKD in the Medawachchiya region; however, major risk factors were uncertain in 87% of these patients. Of these patients, 26 underwent renal biopsy; histology indicated tubulointerstitial disease. Thus, proteinuric-CKD of uncertain etiology is prevalent in the North Central Province of Sri Lanka. In contrast, known risk factors were associated with CKD in the Central and Southern Provinces.

Dose-dependent Na and Ca in fluoride-rich drinking water -Another major cause of chronic renal failure in tropical arid regions

Article

Jan 2011

Endemic occurrence of chronic kidney disease with unknown etiology is reported in certain parts of the north central dry zone of Sri Lanka and has become a new and emerging health issue. The disease exclusively occurs in settlements where groundwater is the main source of drinking water and is more common among low socio-economic groups, particularly among the farming community. Due to its remarkable geographic distribution and histopathological evidence, the disease is believed to be an environmentally induced problem. This paper describes a detailed hydrogeochemical study that has been carried out covering endemic and non-endemic regions. Higher fluoride levels are common in drinking water from both affected and non-affected regions, whereas Ca-bicarbonate type water is more common in the affected regions. In terms of the geochemical composition of drinking water, affected households were rather similar to control regions, but there is a large variation in the Na/Ca ratio within each of the two groups. Fluoride as shown in this study causes renal tubular damage. However it does not act alone and in certain instances it is even cytoprotective. The fine dividing line between cytotoxicity and cytoprotectivity of fluoride appears to be the effect of Ca(2+) and Na(+) of the ingested water on the F(-) metabolism. This study illustrates a third major cause (the other two being hypertension and diabetes) of chronic kidney diseases notably in tropical arid regions such as the dry zone of Sri Lanka.

Chronic kidney disease of uncertain etiology in Sri Lanka is a possible sequel of interstitial nephritis!:

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