1. What data in particular will be shared?
   Response - Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).
   


2. What additional supporting information will be shared?
   Response - None of the above
   
   
3. Who will be able to view these files?
   Response - Researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose.
   


4. For what types of analyses will this data be available?
   Response - For individual participant data meta-analysis.
   


5. By what mechanism will data be made available?
   Response - Proposals should be directed to [snamratarao@yahoo.co.in].
   


6. For how long will this data be available start date provided 02-11-2027 and end date provided 02-11-2032?
   Response - Beginning 3 months and ending 5 years following article publication.
   


7. Any URL or additional information regarding plan/policy for sharing IPD? 
   Additional Information - NIL

CKDu has been described in endemic hotspots globally for the last few decades, appearing as chronic interstitial nephritis in predominantly agricultural communities in tropical climates such as India, Sri Lanka, and many South and Central American countries.The majority of reports of CKDu in India come from southern India, where the climate remains hot and humid through the year; however, CKDu hotspots have been described in Kanpur from Uttar Pradesh, and in Chattisgarh and Punjab too, where temperature and relative humidity dip significantly in the winter months. Whether these northern Indian hotspots correspond to CKDu or not, is presently unclear. 

The histopathologic characteristics in CKDu are predominantly those of chronic tubulointerstitial nephritis, albeit with a host of other biopsy findings (glomerulosclerosis, interstitial fibrosis, microvascular changes) described in biopsies done from identified hotspots of CKDu. These histologic features may vary between various agricultural communities from different parts of the world. Characterizing these histopathologic features, correlating the same with the history of exposure to agrochemicals, heat stress and other putative CKDu causative factors, and also measuring blood and urine levels of these heavy metals and agrochemicals, will prove to be an essential step in further research work into CKDu in this region. In the last two decades, various epidemiologic and environmental studies have elucidated on the role of exposure to pesticides in the development of CKD. These studies have been performed, both in patients affected by CKD as well as in population-based studies in farming communities. Pesticides such as organophosphate and glyphosate have been linked to the development of CKDu in Sri Lanka, to a certain extent. However, the lack of uniformity of findings across studies in the MesoAmerican region, and the lack of similar studies in India, make it difficult to attribute the disease to these causes alone.

Assessment

On the day of the biopsy, 5 ml of blood and be drawn from patients of “unexplained renal failure” undergoing biopsy with informed consent.

Pathological Assessments:

 Renal biopsy sample would be analysed under light microscopy and Immunofluoroscence (IF) study and reported by Nephropathologist at Dr. RMLIMS, Lucknow

Findings on the biopsy are noted – including percentage of sclerosed glomeruli, percentage of tubular atrophy, percentage of interstitial fibrosis, percentage of TI inflammation, whether glomerular immune deposits are seen or not on IF (+/- endocapillary/mesangial hypercellularity). They will be divided into following groups

1.CTIN- Purely chronic tubulointerstitial inflammation/ fibrosis OR Chronic tubulointerstitial inflammation more intense than glomerulosclerosis (viable glomeruli unremarkable) and negative IF

2. DGGS + CTIN (negative IF)- Equal intensity of chronic tubulointerstitial inflammation/ fibrosis and glomeruloslerosis (viable glomeruli unremarkable) and negative IF

3. CGN: More intense glomerulosclerosis (viable glomeruli showing abnormalities other than periglomerular fibrosis) than chronic tubulointerstitial inflammation/ fibrosis. Negative/ positive IF

Biochemical Assessments: Estimation of heavy metals in serum (Cadmium, Lead, Aluminum, Copper, Mercury, Calcium, Iron, Sodium, and Zinc)

The clinical and biochemical details will be noted from the file and hospital information system, after taking informed consent from the patients

Statistical analysis (relevant to thesis)

Data analysis will be done by using SPSS version 16 (IBM Inc., WA, USA). A p-value of < 0.05 will be considered statistically significant

Comparisons between CTIN, DGGS + CTIN (Negative IF) and CGN groups in terms of clinical, biochemical characteristics and parameters as per questionnaire  would be done.

Continuous variables would be assessed using unpaired t-test, while categorical variables would be assessed using Pearson chi-square test.

Logistic regression will be performed to look for risk factors for CTIN on renal biopsies.