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Chronic kidney disease (CKD) is emerging as a significant cause of morbidity and mortality worldwide. While diabetes and hypertension are the top chief causes globally, CKD of unknown etiology (CKDu) is now a well recognized entity. Multiple potential risk factors like agrochemical, alternative medication, heavy metals, etc have been investigated with inconclusive findings. We aimed to study the heavy metal exposure in a cohort of Indian patients with CKDu .
We assessed out patient records of all patients with CKD attending our renal clinic from January 2015-June 2022. We identified a total of 370 patients who met the clinical criteria for CKDu as per our protocol.
Inclusion Criteria:
1. Patients with eGFR less than 60 ml/min/1.73 m2 by CKD-EPI formula and/or proteinuria <1 gm/day confirmed twice at-least 3 months apart with bland urinary sediment
2. No hypertension or if present controlled (<140/90mm of Hg) with single antihypertensive agent. The duration of hypertension should be less than 3 years without any evidence of target organ damage on fundus or electrocardiogram (ECG) evaluation.
Exclusion Criteria:
1. Absence of diabetes (defined as self-reported history of diabetes on treatment, fasting blood sugar more than 126mg/dl or HbA1C>6.5%).
2. Ultrasound showing structural abnormalities suggestive of other causes of CKD like obstruction, polycystic kidneys, congenital abnormalities of kidneys and urinary tract (CAKUT), nephrolithiasis etc
3. Hematuria>5 RBC/hpf
4. Hypertension present for more than 3 years and/or requiring ≥2 anti-hypertensive drugs and/or evidence of any target organ damage
5. Any other causes of CKD like probable or proven glomerular diseases, other tubulointerstitial diseases (eg granulomatous interstitial nephritis) etc. Presumed chronic glomerulonephritis (CGN)was defined in any patient with proteinuria ≥1 gm with or without edema who could not be biopsied due to clinical contraindication(s).
6. Alternate diagnosis on kidney biopsy done when feasible
7. Patients unwilling to give consent (for collection of bio-samples for heavy metals analysis).
For exploring the association between heavy metals and CKDu we aimed to recruit 200 patients (convenience sampling). We could collect bio-samples(urine and blood) of 81 patients for heavy metal analysis due to reduced patient footfall during the COVID-19 pandemic. Arsenic, Mercury, Lead, Chromium and Cadmium levels were measured.
28(34.5%) patients were detected to have any heavy metals and all 28 had levels above the normal range. The mean Blood Arsenic Levels was 11.30 ± 6.48 μg/L, mean Blood Pb Lead Levels was 11.7 ± 6.1 μg/L, mean Urine Pb Lead Levels was 5.00 ± 2.20 μg/L, mean Blood Mercury Levels was 22.00 ± 4.89 μg/L μg/L, mean Urine Mercury Levels was 22.50 ± 13.69 μg/L. We found a statistically significant association of heavy metal exposure with age(p=0.024), state of residence(p=0.002), income(p=0.022) and urine protein excretion(p=0.048). The mean age of the cohort in which heavy metal was detected was 36.1±10.9 years. Heavy metals were detected in 16 females and 12 males. 22 (78%) patients belonged to urban area and 6 (22%) belonged to rural area. Patients in whom heavy metal was detected had lower income levels. Patients in whom heavy metals were detected were more likely to have higher proteinuria(>0.5g-<1g/day) compared to those in whom heavy metals were not detected.
There was a significant burden of abnormal level of heavy metals in the studied subjects. However association between CKDu and heavy metal exposure could not be ascertained as the sample size was small and we did not have a control group of healthy individual without kidney disease. Large scale studies are needed to look for causality.