Describing Natural History and Exploring Risk Factors for Kidney Function Decline in Persons With CKD of Uncertain Etiology in Sri Lanka

Abstract

Introduction: Chronic kidney disease of uncertain etiology (CKDu) is a leading cause of death of adults in Sri Lanka's dry region.

Methods: We initiated the Kidney Progression Project (KiPP) to prospectively follow 292 persons with Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (eGFR) 20 to 60 ml/min per 1.73 m² living in a CKDu endemic area. Using data from 3-year follow-up, we assessed kidney function decline (>30% from baseline eGFR), and the composite outcome of >30% eGFR decline, eGFR <15 ml/min or death, and explored the association of the 2 outcomes with baseline demographic, residential, and clinical parameters accounting for baseline eGFR.

Results: Median eGFR at enrollment was 28 ml/min among 71 women; 30 ml/min among 221 men; 91% to 99% had trace or no proteinuria during follow-up. At enrollment, median serum sodium, uric acid, and potassium were 143 mmol/l, 6.3 mg/dl, 4.5 meq/l, respectively among women; and 143 mmol/l, 6.9 mg/dl, 4.3 meq/l among men. Mean slope of eGFR decline was -0.5 (SD 4.9) ml/min/yr. In exploratory analyses, men with greater years of education and those living in northern region of the study area experienced lower likelihood of disease progression (hazard ratios [HR] 0.87 [0.77-0.98] per additional year and 0.33 [0.12-0.89] for northern versus other subregions, respectively). There was a suggestion that men drinking well water had higher likelihood and men living further away from reservoirs had lower likelihood of >30% decline in eGFR (HR 2.07 [0.95-4.49] for drinking well water versus not, and HR 0.58 [0.32-1.05] per kilometer distance, respectively).

Conclusions: The overall rate of kidney function decline was slow in this CKDu cohort, similar to other nonalbuminuric CKD, and event rates were similar among men and women. Further etiologic investigations could focus on specific residence locale and water use.

Keywords: agricultural work and kidney disease; chronic kidney disease of uncertain etiology; environmental epidemiology; epidemiology.

Graphical abstract

Figure 1

Study cohort. eGFR, estimated glomerular filtration rate.

Figure 2

Survival curves for kidney-related events among men and women. (a) Kaplan-Meier curve for the probability of the composite outcome of >30% sustained decline in eGFR, eGFR<15 ml/min, or death. (b) Kaplan-Meier curve for the probability of >30% sustained decline in eGFR. eGFR, estimated glomerular filtration rate.

Figure 3

Spatial distribution of wells according to participant’s CKDu progression as stratified by >30% sustained decline in eGFR. The plot of the participant well water is generated via ArcGIS. The base map is generated using USGS Earth Explorer and is available at https://earthexplorer.usgs.gov/. Also illustrated on maps are major reservoirs (R-1 to R-10) as well as topography.