Clinical profile of chronic kidney disease of unknown origin in patients of Yavatmal district, Maharashtra, India

Introduction Chronic kidney disease of unknown origin (CKDu) has been reported from many hotspots across the globe from central America, Egypt, Srilanka, and coastal India (1). In the first report of Indian CKD Registry, CKDu is the cause of CKD in 18% of the population (2). The study of Global dimensions and perspectives of CKD by Jha et al have shown that the poorest populations are at the highest risk (3).


Implication for health policy/practice/research/ medical education
The study highlights the need for large epidemiological survey in Central India region to detect patients with CKDu and investigate the possible underlying etiologies. biopsy was negative for immunofluorescence deposits. Kidney biopsy could not be performed in majority of the patients as kidney size was already small, or there were logistic issues.

Discussion
The Yavatmal district lies in the southwestern part of the Wardha-Penganga-Wainganga plain. The District lies between 19o 26' and 20o 42' north latitudes and 77o 18' and 79o 9' east longitudes. The District has an area of 13,582 km 2 , and a population of 27,72,348 persons according to 2011 Census carried out by government of India. Most of the people of this district are engaged in agricultural activities. As per 2011 census, 24.59 % of the total workers are engaged as cultivators and 54.55% of the total workers are engaged as agricultural labourers in the district. Together it constitutes 79.14 % of the total workers of the district (6). They are exposed to various agrochemicals and extreme heat during their work. In this case series of a single specialty tertiary centre, there is a predominance of males amongst the affected (78.94%). This may be due to the fact that agricultural labourers and farmers are predominantly males. They are exposed to extreme heat while working due to which they have excessive sweating and continuous work without necessary water intake may lead to repeated dehydration. Such frequent dehydration episodes may cause subtle kidney injury which may go undetected. In a similar finding, young males were predominantly affected in the study on endemic nephropathy around the world (7). Author suggests that such hard working population must be made aware of importance of frequent hydration while working in such climatic conditions.
The age group in our study is nearly similar to the findings of Uddanam study where mean age of the subjects was 43.2 ± 14.2 years (range: 18-98). However, in their study 44.3% were men and 55.7% were women (8). Only five of the 19 patients had hypertension, and were on antihypertensive medications. All the patients had varying degrees of proteinuria, measured by the urine protein creatinine ratio but majority had proteinuria less than 1 gm per day. In a similar study in central America, there was little or no proteinuria (9). The lack of hypertension and proteinuria less than one gm per day in majority of our patients despite advanced CKD points possibly to tubulointerstitial pathology.
The article on global epidemic of CKDu (10) expresses concerns about the Tatapudi's study (8) which does not 7 patients (36.84%) with stage 5 CKD.
14 patients were normotensive while 5 patients were hypertensive. Mean systolic and diastolic blood pressure was 116.53 ± 18.67 and 77.27 ± 12.48 mm Hg respectively. Out of the 5 hypertensive patients, single drug therapy (80%) was sufficient to control blood pressure while one patient required two drugs. None of the patients included in study had hypertension for more than 5 years duration. Mean hemoglobin was 11.04 ± 1.75 g/dL. Mean serum sodium was 135 ± 3.33 meq/L and the mean serum potassium was 4.6 ± 0.7 meq/L ( Table 2).
Mean eGFR in first reading data set was 23.85 ± 14.24 (SD) mL/min/1.73 m 2 . Mean eGFR in second reading data set after a gap of three months was 21.62 ± 9.35 (SD) mL/min/1.73 m 2 . The 2003 Weissgerber Paired Data Scatterplot table shows difference in the two sets of readings, majority of which lie below the mean. Only four patients showed increase in eGFR but this was still below 60 mL/min/1.73 m 2 .

Histopathology
One patient underwent a kidney biopsy. Histopathological features showed 7 glomeruli of which 5 were globally sclerosed and the remaining two were normal by light microscopy. Foci of tubular atrophy and interstitial fibrosis (40%) were seen. Widespread flattening and loss of brush border of proximal tubules was noted. The interstitium showed diffuse mononuclear cell inflammatory infiltrate with few eosinophils. The blood vessels were normal. The have prevalence data as there are no repeat measurements of serum creatinine. Also, the Tatapudi's study does not address "long standing hypertension". Our study has taken only the patients with repeat serum creatinine measurements at 3 months. Hyponatremia was seen in six patients. Again euvolemic hyponatremia points towards the tubular pathology. Renal biopsy may help in arriving at anatomical etiology for which biopsy needs to be performed in earlier stages of CKDu. The kidney biopsy finding in our patient is consistent with CKDu biopsy findings compared in the study on global dimension of CKDu (11).
This case series although small in number and being a single centre experience, highlights the need for large epidemiological study in Yavatmal and adjoining districts. There is also need of CKDu registry in this area. This will help in identifying the geographic distribution of CKDu. Many suspected CKDu patients did not come for a follow up visit. Therefore many suspected CKDu patients could not be included as probable and CKDu patients in this study. This calls for better nephrology services in Yavatmal and adjoining areas.

Conclusion
Our limited sample study shows that CKDu affects mainly agricultural communities consuming well water. Although the total number of patients in this area must be many times more than the numbers reported here, only a registry and epidemiological study with protocol-based workup will help in bringing the true CKDu numbers to public notice.

Limitations of the study
Small sample size results could not be generalized.