Understanding Chronic Kidney Disease of Unknown Origin in Chhattisgarh: Hospital and Community level Detection, Epidemiology, Risk Factors and Prevention Strategies.

· Background:  In recent years several geographical hotspots of Chronic Kidney Disease have been identified where CKD is not due to known traditional causes like diabetes and hypertension and has been aptly called CKD of Unknown Origin (CKDu). Recent reports from AIIMS Raipur have identified such hotspots in the Gariyaband and Mahasamund districts of Chhattisgarh. However, the identification and etiology and thereby the preventive strategies for CKDu are hampered by the lack of both hospital-based and community-based well-designed cohort and longitudinal studies.

 **Purpose:**The purpose of this study is to

·         Determine the clinical profile of CKDu by forming a Hospital and Community based Cohort of CKDu patients

·          To determine the prevalence and incidence of CKDu.

·          To determine the outcomes and natural history of progression of CKDu

·         To determine the risk factors and underlying causes of CKDu.

Rationale:  In recent years several geographical hotspots of Chronic Kidney Disease have been identified where CKD is not due to known traditional causes like diabetes and hypertension and has been aptly called CKD of Unknown Origin (CKDu). Recent reports from AIIMS Raipur have identified such hotspots in the Gariyaband and Mahasamund districts of Chhattisgarh. However, the identification and etiology and thereby the preventive strategies for CKDu are hampered by the lack of both hospital-based and community-based well-designed cohort and longitudinal studies.

·         Novelty: To our knowledge, there is no community-based or cohort study in CKDu from central India. The study will also look into various risk factors including host-related, environmental, and genetic risk factors associated with CKDu.

·         Objectives:  The primary aim of the study will be to determine the community-level prevalence and risk factors (epidemiological, behavioral, environmental, and genetic risk factors) of CKDu in the endemic village of Chhattisgarh and the secondary objective will be to develop a cohort of CKDu patients for prospective follow-up to determine the rate of GFR decline thereby developing a strategy for the prevention and treatment of CKDu.

·         Methods:

·         The study proposes cross section screening for CKD using serum creatinine and Urine Protein Creatinine ratio of identified village reporting the highest number of CKDu at AIIMS Raipur for using a randomsampling technique to determine the prevalence of CKD and CKDu.

·         The study also proposes to form a Hospital-based Case-Cohort of CKDu patients fulfilling the case definition of CKDu visiting AIIMS Raipur and a comparative cohort of CKD patients with a known traditional cause of CKD like diabetes and hypertension.

·         Socio-demographic, environmental history, medical, family, treatment history, and physical examination including anthropometric parameters and blood pressure will be collected. Biological Sample Collection including blood, urine, hair, and nail samples will be collected.

·         Laboratory studies will include random blood sugar, HbA1C, complete blood count, sickling test, urinary protein-creatinine ratio, urine routine microscopy, urine electrolytes, serum sodium, potassium, chloride, urea, creatinine, uric acid, fasting urine and serum osmolality, magnesium, and eGFR. and USG KUB will be done in all hospital-based cohorts. Additionally, random samples (10%) will be subjected to testing for heavy metal (Lead, Mercury, Lithium, Chloride, Arsenic, Chromium, Cadmium, Nickle), agrochemical (Fertilizer, Paraquat), and genetic analysis (Whole Exome Sequencing).

·         The cohort will be followed up at AIIMS Raipur to determine the trajectory of GFR.

·         Data will be compared with a comparative cohort of CKD of traditional causes to find out epidemiological, behavioral, and medical risk factors of CKD patients with those of the individuals with CKD due to known causes. The environmental (heavy metals, pesticides) and genetic factors (whole exome sequencing) will be compared to patients with those with CKD due to known causes.

·         Preventive and treatment strategies will be developed based on the outcomes of the above phase and will be shared with the community for implementation

·         Expected outcome: The study is expected to find out the prevalence of CKD and CKDu  anduncover the specific risk factors (host and, environmental specific) for CKDu which may differ from those in other hotspots. The Cohort study should find out the rate of decline of GFR in this cohort of patients