Abstract:
The global burden of kidney diseases has dis proportionally increased over the last 2 decades.1
Although diabetes and hypertension are leading cau ses of chronic kidney disease (CKD), environmental risk
factors contribute to a significant disease burden in hot
spots of Mesoamerican countries, such as India, and Sri
Lanka.2,3 CKD associated with environmental risk fac tors, CKD of uncertain or unknown etiology (CKDu), is
prevalent among farming communities living in these
at-risk areas. Recently, a subcategory of patients has
been reported from these at-risk areas for CKDu in
Nicaragua and Sri Lanka.4,5 There was tubulitis and
significant interstitial cell infiltrate in the background
of glomerular sclerosis, tubulointerstitial fibrosis and
tubular atrophy in their biopsies, compatible to acute
interstitial nephritis. CKDu patients with acute lesions
(CKDu-A) subsequently transform into commonly
encountered CKDu patients with chronic features
(CKDu-NA),6 or to a distinct subclinical phenotype
(CKDu-S) with normal renal functions, besides irre versible histologic changes.7
Transforming growth factor-beta 1 (TGF-b1) activated
in acute kidney injury, while positively or negatively
regulating the process that is associated with cellular
responses to the nature of toxin. Any persistent kidney
injury causes a rise in TGF-b1, which promote kidney
fibrosis and suppress the ongoing inflammation.8 There fore, TGF-b1 is an antiinflammatory as well as profibrotic
biomarker that positively regulates the glomerular and
tubulointerstitial fibrosis in CKD/CKDu.9
In this milieu, current study sought to evaluate the
performance of serum TGF-b1 and serum creatinine
(SCr) as potential candidate biomarkers to predict
subphenotypes of CKDu. This is a cross-sectional case control study where one-time serum TGF-b1 and cor responding SCr measurements were used. We recruited
38 CKDu-A cases (acute interstitial nephritis) and
45 CKDu-NA cases (chronic interstitial nephritis).
Among the total cases (N ¼ 83), there were 23 sub clinical cases (CKDu-S). Cases were further divided into
high-activity (18 cases with activity index $ 3/6) and
low-activity (65 cases with activity index < 3) groups
based on activity index grades of histologic classifica tion. Healthy individuals from a CKDu nonendemic
region were recruited as controls (N ¼ 85). The case control study design is depicted in Figure 1a. The
predictive value of TGF-b1 and TGF-b1/SCr index
(adjusted) for the differentiation of CKDu phenotypes
were explored. More details about the “methods” are
given in the Supplementary Methods.
