Table 1 Comparisons of Key Characteristics Among Areas with Reported CKDu

Reported Areas

North Central Province [3]

Most reports from El Salvador and Nicaragua but appears to extend across Pacific coast areas of Central America [37]

In state of Andhra Pradesh: coastal in Uddanam area and 30–40 km inland in Chimakurthy mandal [52]

Reported in El-Minia Governorate [53]

Present, although to a lesser extent, in Uva and North Western Provinces [36]

In India overall, highest in south which included Andhra Pradesh [44]

Age

Wide age range; increased prevalence of eGFR ≤ 60 ml/min per 1.73 m² in fourth and fifth decades [12]

Third to fifth decade [37]

In India overall, younger than patients with diabetic nephropathy [44]

Mean age of 46 (n = 800 patients on renal replacement therapy) [53]

Sex

Female > male overall but male > female for CKD stage III –IV [3]

Male > female [37]

Male > female in Uddanam area, [6] and in India overall [44]

Male > female [53]

Geographical Characteristics

Rural [12]

Rural, especially the lowlands along the Pacific coast [37]

Rural - coastal and inland [52]

Rural [53]

Dry weather except for two monsoon periods [36]

Coastal communities at lower elevations (<500 m) [45]

Occupations

Chena (vegetable and other crops) farmers; rice farming had a lower risk compared to chena farming [3]

Risk in coastal agricultural workers but not in agricultural workers employed at elevations > 500 m; sugarcane workers studied in both locations [45]

In Uddanam area, agricultural cultivation of coconuts, rice, jackfruit and cashews [6]

Farming [54]

Compared to coastal agricultural workers, risk lower in service sector and agricultural workers at higher elevations [55]

Intense heat noted in working conditions in Central America [49]

Socio-economic Status

Low

Low

In India overall, lower than those with diabetic nephropathy [44]

Not reported

Pathology

In biopsies from 211 CKDu patients, the main pathological features were interstitial fibrosis, interstitial inflammation and tubular atrophy of varying degrees [10]. Authors concluded that interstitial fibrosis was the earliest detectable pathological change.

A study of 57 CKDu patients observed chronic tubulointerstitial nephropathy [56]. The authors considered the glomerular and vascular damage also observed to be secondary to the tubulointerstitial damage.

Chronic tubulointerstitial nephritis (no details as reported in abstract from conference proceedings) [6]

Not reported, biopsies rarely performed [53]

Interstitial fibrosis and tubular atrophy, sometimes with nonspecific interstitial mononuclear cell infiltration, predominated; glomerular sclerosis, glomerular collapse, and features of vascular pathology such as fibrous intimal thickening and arteriolar hyalinosis also common (n = 57) [11]

A study of 8 CKDu patients reported extensive glomerulosclerosis (29 %-78 %) and signs of chronic glomerular ischemia in combination with tubular atrophy and interstitial fibrosis but only mild vascular lesions [9]. The authors concluded that both glomerular and tubulointerstitial compartments were damaged by CKDu.

Biopsies in 26 patients (19 in CKD stages 1–3) reported as consistent with tubulointerstitial disease; immunofluorescence tests for immune-mediated kidney injury were negative [12]

Presentation

Slow progression; minimal proteinuria (mean 24 h urine protein = 612.8 mg in 109 participants) without active sediment; bilateral small echogenic kidneys [12]

Minor or no proteinuria or albuminuria [6, 55]

In India overall, advanced CKD, few initial symptoms, absent or mild hypertension and little or no proteinuria [44]

Not reported

Urinary excretion of alpha-1-microglobulin elevated in CKDu patients, even in the earliest CKD stage, compared with first-generation related controls residing in the same community and Japanese controls, suggesting early renal tubular damage in CKDu [57]

Small echogenic kidneys on ultrasound [37]

In Uddanam area, proteinuria prevalence of 20 % in males and 12 % in females [6]

Urinary symptoms, when present, are positive for pyuria and leukocyte esterase but urine culture negative [37]

Magnitude

Age-standardized prevalence (95 % CI) of albumin–creatinine ratio ≥30 mg/g on two separate tests [3]:

Mortality from chronic renal failure (2007) [58]

CKDu is second most common cause of CKD in India (16.0 %) after diabetic nephropathy (31.3 %) [44]

Unknown etiology, at 27 %, was leading cause of end-stage renal disease (ESRD) followed by hypertension at 20 % and glomerulonephritis at 11 % [53]

El Salvador

15.1 % in Anuradhapura

Men: 85.5/100,000

20.6 % in Polonnaruwa

Women: 34.1/100,000

Nicaragua

22.9 % in Badulla

Men: 66.2/100,000

16.9 % (15.5 %–18.3 %) in women

Women: 22.3/100,000

USA

12.9 % (11.5 %–14.4 %) in men

Men: 9.5/100,000

Stage 3 and 4, respectively:

Women: 7.0/100/000

Cuba

23.2 % and 22 % in men

Men: 3.0/100,000

7.4 % and 7.3 % in women

Women: 2.5/100,000