Table 2.

Biomarker values and estimated glomerular filtration rate (eGFR) in studies that included both CKDu cases and controls

Study	CKDu definition	Control group definition	Biomarker(s) studied	Biomarker concentration		eGFR (ml/min per 1.73 m2)
				CKDu	Control	CKDu	Control
De Silva. PLOS Negl Trop Dis, 201629	Two values of UACR ≥30 mg/g in the absence of prior glomerular disease, pyelonephritis, nephrolithiasis, snake bite, diabetes, HbA1c >6.5%, or HTN (N = 14)a	Residence in a nonendemic area (N = 54)a	KIM-1 (μg/g)	64 ± 11	1.3 ± 0.2	96.5 ± 4.5	110.0 ± 2.6
			NGAL (ug/g)	2 ± 0.6	0.3 ± 0.03
Ekanayake. Int J Environ Res Publ Health, 202232	Clinically diagnosed with CKDu (N = 40)	Factory workers from CKDu-endemic regions (N = 33)b	KIM-1 (ng/mg)	5 [4–9]	2 [0.5–2]	20.0 [9.9–34.8]	115.1 [108.4–131.3]
			NGAL (ng/mg)	22 [4–154]	2 [0.7-5]
Fernando. KIR, 201930	Biopsy features consistent with CKDu from individuals living in a CKDu-endemic area for ≥ 5 years. Other causes of CKD were excluded by clinical judgment (N = 75)	Age- and sex-matched residents of nonendemic regions with no evidence of kidney disease (N = 85)	A1M (ng/g)	870 [6473]	54 [58.4]	Not reported	Not reported
			B2M (ng/g)	383 [1519]	48 [70]	42.7% with eGFR > 60	98.8% with eGFR > 60
			Cystatin c (ng/g)	4 [17]	1 [1]
			NGAL (ng/g)	20 [35]	3 [6]
			OPN (ng/g)	68 [99]	50 [40]
			RBP4 (ng/g)	478 [551]	188 [200]
			KIM-1 (ng/g)	0.05 [0.08]	0.05 [0.06]
			TIMP-1 (ng/g)	0.6 [1]	0.4 [0.8]
Nanayakkara. Environ Health Prev Med, 201263	CKDu previously diagnosed through a screening program (N = 106)	Apparently healthy adults from the general population of Kyoto, Japan (N = 50)c	A1M (mg/g)	Overall sample mean not reportedd	GM 0.6 ± 6	Not reported	Not reported
			NAG (U/g)	Overall sample mean not reported	GM 0.9 ± 4	28% with eGFR >60
Wanigasuriya. Ceylon Med J, 201748	Fulfilled the diagnostic criteria for suspected CKDu and had a SCr ≥2 mg/dl (N = 37)	Nonfarmer residents of a nonendemic area (N = 40)e	Fibrinogen (ng/mg)	20 [9–134]	6 [4–8]	23.5 ± 1.2	76.1 ± 8.3
			B2M (ng/mg)	4643 [249–15375]	118 [44–181]
			Clusterin (ng/mg)	372 [222–1587]	836 [366–1525]
			KIM-1 (pg/mg)	505 [346–1008]	403 [311–672]
			Cystatin c (ng/mg)	681 [43–3650]	243 [96–362]
Siriwardhana. BMC Nephrol, 201460	Diagnosed as having CKDu by a nephrologist. Known causes of CKD (e.g., glomerular disease, diabetes, longstanding HTN, snake bite, leptospirosis, congenital kidney disease, nephrolithiasis) were excluded by clinical judgment. (N = 30)	Age-matched and sex-matched residents of the same area; SCr <1.0 mg/dl, random glucose <140 mg/dl, blood pressure <120/80, and negative proteinuria (N = 30)	B2M (μg/ml)	1.24 ± 0.71	0.16 ± 0.05	Not reported	Not reported

A1M, alpha-1-microglobulin; B2M, beta-2-microglobulin; CKDu, chronic kidney disease of uncertain etiology; eGFR, estimated glomerular filtration rate; GM, geometric mean; HbA1c, hemoglobin A1c; HTN, hypertension; KIM-1, kidney injury molecule 1; NAG, N-acetyl-beta-D-glucosaminidase; NGAL, neutrophil gelatinase-associated lipocalin; RBP-4, retinol binding protein 4; SCr, serum creatinine; TIMP1, tissue inhibitor matrix metalloproteinase 1; UACR, urinary albumin-to-creatinine ratio.

Not all studies in the table employed a traditional case-control design. In some instances, case-control status was determined after receiving the test results of population-wide screening programs.

Values are reported as mean ± SD or median [interquartile range].

^aThis study evaluated participants from 2 endemic and 2 nonendemic regions separately. Data are presented for 1 of the 2 groups for simplicity.

^bThis study included multiple occupational groups. Factory workers were selected as the representative control as they were the only nonagricultural occupation.

^cThis study also included healthy, nonaffected relatives as a control group, which is not presented in the table for simplicity.

^dThis study provided mean biomarker concentration stratified by eGFR category only for those participants identified as having CKDu.

^eThis study also included a sample of farmer controls, which are not presented in the table for simplicity.