Abstract
CKDu needs to be characterized in fundamental areas to improve etiological understanding and disease management. In a cross-sectional study, blood cell profile and plasma inflammatory cytokines were followed by automated analysis and sandwich ELISA, respectively. Disease development stages and proteinuria were ascertained by eGFR and UACR. Comparison among control and stages (ANOVA/Dunnett’s MRT) revealed time-specific changes (p < 0.05), including decreased erythrocytes (G5) and hematocrit (G5), and increased MCHC (G3b, G4), MCV (G5), and MCH (G5). CKDu decreased (p < 0.05) lymphocytes (G3b, G4, G5), monocytes (G3b), MPV (G3b, G4, G5), and plateletcrit (G3b, G4), and increased basophils (G3a, G3b, G4), N/L (G4) and PLR (G4–G5). MCHC and aforesaid leukocyte variables were in correlation (rho > ±0.03, p < 0.05, Pearson’s test) with disease development. MCP-1 and IL-6 spiked (p > 0.05) at G3b. Multivariate analyses confirmed that MCP-1, lymphocytes, and BMI were related to renal dysfunction, pointing to inflammation, compromised immunity, and muscle wasting as CKDu effects. Nonproteinuric CKDu was prevalent (23.2–35.6% of total CKDu) with (p < 0.05) elevated basophils (G3a), N/L (G4), and depleted lymphocytes (G4). In both forms, G1–G2 were unaffected, and the earliest change was G3a basophils. Results suggest that MCP-1, lymphocyte count, N/L, and PLR may verify the stage and predict impending ESRD in advance proteinuric CKDu.
Highlights
Chronic kidney disease of unknown etiology (CKDu) in Sri Lanka is endemic nephropathy in the country’s North Central and Uva provinces [1]
CKDu is marked by inflammatory infiltration into tubulointerstitium, tubulitis, fibrosis and glomerular scarring [4] that progresses to end-stage renal disease (ESRD) possibly via chronic ischemia attributed to interstitial damage [5]
Results of the present study showed albuminuria amongst the majority of CKDu cases (64–76%), which spanned from G1 to G5 (ESRD) in both endemic areas studied
Summary
Chronic kidney disease of unknown etiology (CKDu) in Sri Lanka is endemic nephropathy in the country’s North Central and Uva provinces [1]. CKDu is distinct as it lacks etiologic association with CKD initiation risk factors such as diabetes mellitus and hypertension [2]. It obeys diagnostic criteria based on poor renal outcomes in terms of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR) [3]. CKDu is marked by inflammatory infiltration into tubulointerstitium, tubulitis, fibrosis and glomerular scarring [4] that progresses to end-stage renal disease (ESRD) possibly via chronic ischemia attributed to interstitial damage [5]. Histopathology and tissue damage points to an inflammatory component in disease progression. CKD effects such as anemia [6], compromised immunity [7] and inflammation [8] manifest in blood
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