Association between chronic lead exposure and markers of kidney injury: A systematic review and meta-analysis

Abstract

In view of inconsistent reports on the association between chronic lead (Pb) exposure and renal injury markers (potential site of injury), the present systematic review explored their association by reviewing studies that investigated chronic Pb-exposed and those without obvious Pb exposure. Studies reporting blood Pb levels(BLL) and biomarkers of kidney injury [i.e. N-acetyl-β-D-glucosaminidase (NAG), Micro-Globulin(μG) and others] among chronic Pb-exposed and unexposed individuals were systematically searched from digital databases available until February 26, 2024. Preferred Reporting Items of Systematic Reviews and Meta-Analysis Guidelines were adhered to during the execution. Pooled effect size and heterogeneity were estimated using the random effect model and I2Studies reporting blood Pb levels(BLL) and biomarkers of kidney injury [i.e. N-acetyl-β-D-glucosaminidase (NAG), Micro-Globulin(μG) and others] among chronic Pb-exposed and unexposed individuals were systematically searched from digital databases available until February 26, 2024. Preferred Reporting Items of Systematic Reviews and Meta-Analysis Guidelines were adhered to during the execution. Pooled effect size and heterogeneity were estimated using the random effect model and I2. Pooled quantitative analysis revealed elevated BLL [25.64 (21.59-29.70) µg/dL] Pb-exposed group. The pooled analysis confirmed significantly higher urinary NAG [0.68(0.26-1.10) units], α1μG [3.82(0.96-6.68) mg/g creatinine] β₂μG [1.5(0.86-2.14) units and serum creatinine [0.03(0.00-0.05) mg/dL] levels in Pb-exposed group, with high heterogeneity. Current observations indicate the proximal tubular injury as the early and potential site of Pb-induced renal injury. Pb-exposed individuals experience proximal tubular injury (KIM-1, NAG) and dysfunction (β2μG, α1μG, Cystatin-C) prior to obvious clinical renal failure. Present observations should caution the policymakers towards drafting regulations for periodic screening with markers of renal injury and / or dysfunction among those chronically exposed to lead despite the certainty of evidence is very low.

Keywords: Kidney Injury Molecule-1; Kidney injury markers; Lead exposure; N-acetyl-β-D-glucosaminidase; Systematic review; β-2-microglobuline.

Graphical abstract

Fig. 1

PRISMA 2020 flow chart. Flow chart illustrating the number of citations / articles included and excluded at various stages.

Fig. 2

Forest plot for blood lead levels. Group differences in blood lead levels (BLL) between Pb-exposed and unexposed group. Forest plot demonstrates significantly higher BLL (25.64 µg/Dl with 95 % CI, 21.54–29.74 among Pb-exposed individuals, However the heterogeneity among the studies were unacceptably high (I² = 99.53 %).

Fig. 3

Forest plot for serum creatinine. Group differences in serum creatinine between Pb-exposed and unexposed group. Forest plot demonstrates trend of higher creatinine (0.03 mg/dL with 95 % CI 0.00–0.05) among Pb-exposed group, However the heterogeneity among the studies were unacceptably highly (I² = 79.37 %).

Fig. 4

Forest plot for NAG & β-2-Microglobulin reported as standardized mean differences. Group differences in NAG (Fig. 4a) and β-2-Microglobulin (Fig. 4b) between Pb-exposed and unexposed group. Forest plot demonstrates significantly higher urinary NAG (0.68 with 95 % CI 0.26–1.10) and β-2-microglobulin (1.5 with 95 % CI 0.86–2.14) levels among Pb-exposed group, However the heterogeneity among the studies were unacceptably highly (I² > 95 %).

Fig. 5

Forest plot for α-1-Microglobulin, effective glomerular filtration rate and Kidney Injury Molecule (KIM) – 1. Group differences in α-1-Microglobulin (5 A), effective glomerular filtration rate (5B) & Kidney Injury Marker - 1 (5 C) between Pb-exposed and unexposed group. Forest plot demonstrates significantly higher α-1-Microglobulin (3.82 mg/g creatinine with 95 % CI 0.96–6.68), KIM – 1 (0.88 SMD with 95 % CI 0.44 – 1.32) and significantly poor effective glomerular filtration rate (– 4.66 mL/min/1.73 m² with 95 % CI −8.64–0.69) among Pb-exposed individuals, However the heterogeneity among the studies were unacceptably highly (I² = 95.08 %, 72.98 % & 60.43 % respectively).