INTRODUCTION — Chronic lead exposure can affect a variety of organ systems, including the kidney, where it can produce lead nephropathy, a chronic interstitial nephritis. The high level of lead exposure required to cause lead nephropathy is now increasingly rare, particularly in developed countries, due to occupational controls and removal of lead from paint, gasoline, and other environmental sources (figure 1).

However, prolonged lead exposure at the lower levels encountered in developed countries may still contribute to kidney toxicity, an association that has been referred to as lead-related nephrotoxicity [1]. This is most likely to occur in patients who have chronic kidney disease (CKD) or are at risk because of diabetes mellitus or hypertension.

The impact of chronic lead exposure on the kidney will be reviewed here. Other clinical manifestations of lead poisoning, as well as the evaluation and management of lead poisoning in adults and children, are discussed separately. (See "Lead exposure and poisoning in adults" and "Childhood lead poisoning: Clinical manifestations and diagnosis" and "Childhood lead poisoning: Management".)

SOURCES OF LEAD EXPOSURE — There are a number of current sources of lead exposure, which are primarily related to occupational exposures in adults and to ingestion or inhalation of environmental lead in adults and children (table 1). In addition, since lead accumulates in bone, the body lead burden from past exposures also contributes to current exposure.

Exposure sources are discussed in detail elsewhere. (See "Lead exposure and poisoning in adults", section on 'Sources of exposure' and "Childhood lead poisoning: Exposure and prevention", section on 'Exposure'.)

MEASUREMENT OF LEAD DOSE — Blood lead is a short-term measurement with a half-life of approximately 30 days that reflects both exposure from current exogenous sources and the release of endogenous lead from bone and soft-tissue stores [2,3].

Blood lead data from the National Health and Nutrition Examination Survey (NHANES) II, obtained between 1976 and 1980 during the phase out of leaded gasoline in the United States, showed that lead exposure was significant and widespread [4]. The removal of lead from gasoline (figure 1) resulted in substantial reductions in lead exposure. Geometric mean blood lead levels in adults in the United States fell from 15.8 and 11 mcg/dL (0.76 and 0.53 micromol/L) in men and women, respectively, in NHANES II [4] to 0.92 and 0.74 mcg/dL (0.04 micromol/L) in NHANES data from 2015 and 2016 [5]. However, levels remain substantially higher than preindustrial levels [6,7] due in part to release from lead body stores and continued external exposure.

In comparison with blood lead, cortical bone lead reflects cumulative lead exposure and the potential for endogenous exposure since bone lead is mobilizable into the circulation [2,8]. Cortical bone lead is measured by x-ray fluorescence (XRF) in the mid-shaft of the tibia. The half-life is estimated to be 10 to 30 years [2]. Body burden from past environmental exposure can be substantial. For example, the average bone lead in chronically exposed lead workers [9] was only twice that found in a study of Baltimore residents between 50 and 70 years of age [10].

Lead in trabecular bone (measured in the patella or calcaneus) is more bioavailable than lead in cortical bone and has a shorter half-life. As a result, it may be the best measure of lead dose that is both cumulative and bioavailable, although measurement precision is lower than cortical bone lead, which has been a limiting factor in the use of this measure [2]. (See "Childhood lead poisoning: Management".)

LEAD NEPHROPATHY — Lead nephropathy, which is characterized histologically by chronic interstitial nephritis, is a potential complication of prolonged (5 to 30 years), high-level lead exposure (ie, blood lead levels persistently >60 mcg/dL [2.9 micromol/L]) [11-15]. At this level of exposure, lead is generally the primary cause of kidney pathology.

In addition to nephrotoxicity, lead exposure may be associated with hypertension, increased cardiovascular risk, and other adverse effects. These issues are discussed elsewhere. (See "Lead exposure and poisoning in adults", section on 'Clinical manifestations'.)

Lead nephropathy is increasingly rare, particularly in developed countries where lead exposure has been reduced through occupational and environmental controls.

Pathology — Acute, high-level lead poisoning (blood lead level >100 mcg/dL [4.8 micromol/L]) initially injures the proximal tubules in association with intranuclear inclusion bodies composed of a lead-protein complex [16]. With chronic lead exposure, at levels >60 mcg/dL, kidney biopsy reveals the typical changes of a chronic interstitial nephritis, including nonspecific tubular atrophy, interstitial fibrosis, a paucity of inflammatory cells, and hypertrophic arteriolar changes; glomerular scarring is a secondary event [11,17,18]. However, in this setting, proximal tubular intranuclear inclusion bodies are often absent [16,18].

Clinical manifestations — The clinical kidney manifestations of high-level lead exposure vary by time of the exposure. Signs of a Fanconi-type syndrome, such as glucosuria, aminoaciduria, and renal phosphate wasting, have been observed in patients (generally children) with acute, high-level lead poisoning [18]. These findings reflect diminished reabsorption due to proximal tubular injury and are associated with intranuclear inclusion bodies. The Fanconi syndrome generally resolves with treatment of lead poisoning, although glucosuria and aminoaciduria may persist for a prolonged period [19].

Patients with lead nephropathy due to more prolonged exposure usually present with an elevated serum creatinine, little or no proteinuria, a relatively normal urine sediment, and hyperuricemia; a history of gout is frequently obtained [13,15,18]. These manifestations are not specific, and lead nephropathy may be confused with hypertensive nephrosclerosis or chronic urate nephropathy, which, in the absence of tophaceous gout, is a relatively rare condition. (See "Uric acid kidney diseases".)

Careful evaluation of patients considered to have hypertensive nephrosclerosis or chronic urate nephropathy in selected studies performed in the 1980s revealed that many actually had lead nephropathy [20-22]. However, the applicability of these findings to current practice is uncertain since the high-level lead exposure required to cause lead nephropathy is increasingly rare, at least in developed countries.

The signs and symptoms of lead poisoning in other organ systems may increase suspicion for lead nephropathy; these manifestations are discussed separately. (See "Lead exposure and poisoning in adults" and "Childhood lead poisoning: Clinical manifestations and diagnosis".)

Diagnosis — Lead nephropathy should be considered in the differential diagnosis of patients who present with the triad of chronic kidney disease (CKD) of unknown etiology, hypertension, and gout.

The diagnosis of lead nephropathy requires the following:

●Identification of potential current or past sources of lead exposure (table 1). A patient-administered questionnaire is useful as a screening tool to identify the need to explore specific lead sources in greater detail (figure 2). (See "Lead exposure and poisoning in adults", section on 'Sources of exposure' and "Childhood lead poisoning: Exposure and prevention", section on 'Exposure'.)

●Assessment for the extrarenal signs and symptoms of lead poisoning.

●Lead-dose assessment by measuring lead in whole blood. However, blood lead may be less elevated if high-level lead exposure has declined or stopped. In the original studies describing lead nephropathy, diagnostic chelation was performed. Urinary lead excretion >600 mcg (2.9 micromol) in the 72 hours after administration of 1 gram of calcium ethylenediaminetetraacetic acid (EDTA) intravenously (IV) over one to two hours indicated a lead body burden capable of causing lead nephropathy. However, as discussed below, chelation has potential side effects and should only be performed if the results would change patient management. (See 'Treatment' below.)

The diagnosis of lead poisoning in both adults and children is discussed in detail elsewhere. (See "Childhood lead poisoning: Clinical manifestations and diagnosis", section on 'Evaluation'.)

Treatment — Minimizing further exogenous lead exposure is essential in the treatment of lead nephropathy. If exposure is occupational, referral to an occupational medicine clinician with expertise in lead exposure, workplace accommodations, and workers' compensation are important. Follow-up blood lead measurements, if elevated initially, are also recommended. (See "Lead exposure and poisoning in adults", section on 'Initial management' and "Childhood lead poisoning: Management" and "Lead exposure and poisoning in adults", section on 'Monitoring blood lead levels'.)

Chelation therapy, based on blood lead levels and symptoms, is clearly indicated for certain patients with lead poisoning. In the absence of such indications, the data are limited concerning the renal benefits of therapeutic chelation in patients with lead nephropathy [13,23,24]. One study described the results of chelation therapy in eight lead workers with excessive body lead burdens, defined as urinary lead excretion >1000 mcg (4.8 micromol) in the 24 hours after calcium EDTA chelation, and glomerular filtration rates (GFRs) <90 mL/min/1.73 m² [13]. Kidney biopsy confirmed the diagnosis of chronic interstitial nephritis, consistent with lead nephropathy, and excluded other causes. The patients were treated with calcium EDTA three times weekly for 6 to 50 months; four had an increase in GFR of ≥20 percent.

The mechanism of benefit from chelation therapy in patients with lead nephropathy is not well understood. Studies in rodent models of lead nephropathy found that the improvement in GFR was not associated with a similar degree of histologic improvement, particularly in regard to tubulointerstitial fibrosis [25,26].

A potential adverse effect of chelation therapy is redistribution of lead into the central nervous system [27-29]. Mobilization of lead from bone and subsequent excretion via the kidneys is also a potential concern; both are greater at the higher lead body burdens present in lead nephropathy than in the chelation studies discussed below. (See 'Lead-related nephrotoxicity' below.)

Acute kidney injury (AKI) was noted in reports from the early 1980s of calcium EDTA therapy given at high doses and, in children, when combined with another chelator [28,30]. Adverse renal effects were not observed in subsequent studies in adults using lower EDTA doses [28,31-35]. However, published chelation experience in patients with CKD, particularly those with high lead body burdens, is limited.

Thus, in the absence of elevated blood lead levels and symptoms, the decision to chelate must be made on a case-by-case basis. Referral to a clinician with experience in lead toxicity and chelation is recommended. If chelation is indicated, patients with underlying CKD should have the dose adjusted for kidney function. Careful follow-up is required. Calcium disodium EDTA, rather than disodium EDTA, should be used to avoid the potential for hypocalcemia from chelation.

LEAD-RELATED NEPHROTOXICITY — Prolonged lead exposure at the lower levels encountered in developed countries may contribute to renal toxicity, which we refer to as lead-related nephrotoxicity [1]. This is most likely to occur in patients at increased risk for kidney disease, including those with diabetes mellitus or hypertension, and in patients with underlying chronic kidney disease (CKD) from non-lead causes. These patients typically do not have extrarenal manifestations of lead poisoning.

Studies supporting the association of lead with nephrotoxicity — The risk of lead-related nephrotoxicity has been evaluated in studies in the general population and in specific susceptible patient populations.

Risk in general or occupational populations — The following prospective studies provide evidence generally supporting a link between chronic lead exposure and nephrotoxicity:

●A cohort study compared the incidence of end-stage kidney disease (ESKD) over a median follow-up of 12 years among 58,307 individuals with different blood lead levels identified from a blood lead surveillance program conducted by the National Institute for Occupational Safety and Health [36]. ESKD status was determined by matching the cohort against individuals with ESKD identified by the United States Renal Data Systems (USRDS). Among those followed for more than five years, compared with the United States population, individuals with blood lead concentrations >51 mcg/dL had a greater risk of ESKD (standardized incidence ratio 1.56, 95% CI 1.02-2.29). In contrast, a study of 10,303 Swedish lead workers followed for 20 years did not have an increased risk of ESKD, even in the highest blood lead concentration group (>41 mcg/dL) following the current occupational recommendations for Sweden [37].

●A population-based, nested, case-control study of 118 participants with ESKD and 378 controls, matched for sex, age, geographic area, and calendar time, modeled erythrocyte lead levels, obtained a mean of eight years before ESKD diagnosis [38]. Mean erythrocyte lead values were 66 and 55 mcg/L in cases and controls, respectively. Elevated blood lead levels were associated with an increased risk of incident ESKD (adjusted odds ratio 1.013 for each unit increase in erythrocyte lead, 95% CI 1.003-1.023).

●In an analysis of the Malmo Diet and Cancer Study-Cardiovascular Cohort, 2567 patients with a median baseline blood lead level of 2.5 mcg/dL were followed prospectively to evaluate the association of blood lead levels with incident CKD [39]. After a mean of 16 years, compared with patients with lower lead levels, patients in the highest quartile of blood lead levels (median 4.6 mcg/dL) had an increased risk of incident CKD (adjusted hazard ratio 1.49, 95% CI 1.1-2.1).

●In prospective analyses of the Normative Aging Study (NAS), a higher long-term lead burden, assessed by tibia lead levels, was associated with a significantly greater 10-year increase in serum creatinine in individuals with diabetes and/or hypertension (1.08 versus 0.06 mg/dL [99.5 versus 5.5 micromol/L], comparing the highest and lowest quartiles of tibia lead in diabetics) [40]. Blood lead was associated with change in serum creatinine in the 428 participants with blood lead ≤25 mcg/dL [41].

Risk in susceptible patient populations — Studies in selected patient populations have focused on CKD, gout, and/or hypertension since these diseases have been observed in high-level lead exposure. In earlier studies, body lead burden assessed by diagnostic chelation was high [22,31].

More recent studies included longitudinal assessment of patients at earlier stages of CKD and with much lower body lead burdens (72-hour post-calcium ethylenediaminetetraacetic acid [EDTA] lead excretion <600 mcg [2.9 micromol]) (table 2) [32-34,42].

The longest prospective study evaluated 121 patients with nondiabetic CKD in Taiwan who, at study entry, had a mean serum creatinine of 2.1 mg/dL (186 micromol/L) and a mean estimated glomerular filtration rate (eGFR) of 36 mL/min/1.73 m² [42]. The patients had no history of exposure to lead and had a normal body lead burden, defined as a 72-hour post-calcium EDTA lead excretion <600 mcg (2.9 micromol). The 72-hour post-calcium EDTA lead excretion was between 80 and 599 mcg (0.4 and 2.9 micromol) in 63 patients (high-normal body lead burden) and below 80 mcg (0.4 micromol) in 58 (low-normal body lead burden); mean blood lead levels were 4.9 and 3.4 mcg/dL (0.24 and 0.16 micromol/L), respectively. Kidney function was similar in the two groups at baseline.

The primary endpoint of doubling of the serum creatinine or the need for dialysis at four years occurred significantly more often in the patients with high-normal body lead burden (23.8 versus 3.4 percent). In addition, each 1 mcg/dL (0.05 micromol/L) higher blood lead level at baseline was associated with a 4 mL/min/1.73 m² reduction in eGFR over the four-year follow-up period.

Further evidence for the importance of low-level lead exposure in patients with nondiabetic and diabetic CKD comes from randomized trials, performed by the same group in Taiwan, showing that chelation therapy slows the rate of loss of GFR compared with controls not treated with chelation therapy. (See 'Chelation therapy and chronic kidney disease progression' below.)

However, two studies of CKD patients whose lead exposure was higher than in the above studies did not observe associations [43,44]. A study of 434 participants with ESKD compared survival across categories of highest measured blood lead level to the reference group of <5 mcg/dL; the median highest blood lead level was 25 mcg/dL. Predialysis blood lead level was not associated with survival from the time of ESKD diagnosis over a median follow-up of 2.7 years [43].

In a population-based case-control study of 926 patients with severe CKD (defined as creatinine >3.4 mg/dL for men and >2.8 mg/dL for women) and 998 controls, the adjusted OR was 0.97 for those with occupational lead exposure compared with those not exposed via their occupation [44]. Lead exposure was defined using an expert rating method based on job history rather than using blood lead levels. The patients with severe CKD from this study were then followed prospectively for a mean of 2.5 years. The rate of progression of CKD was similar in those exposed and not exposed to lead through their occupations [44]. The severity of CKD in the population (mean Modification of Diet in Renal Disease [MDRD] eGFR <20 mL/min/1.73 m²) and the small number of participants with a history of occupational lead exposure (n = 70) may have limited the ability of the study to detect a difference.

Risk in children — The general manifestations of lead poisoning in children are discussed elsewhere. The renal manifestations will be reviewed here. (See "Childhood lead poisoning: Clinical manifestations and diagnosis".)

The Queensland, Australia epidemic of ESKD in children who had chronic lead poisoning and were not treated with chelation demonstrated the nephrotoxicity of chronic, high-level lead exposure [11]. However, studies in children and adults who had less severe childhood lead poisoning and/or were treated with chelation have not observed this degree of clinical disease [19,45,46].

Three general population studies of low-level lead exposure that assessed clinical renal outcomes reported inconsistent findings. A positive association between blood lead and serum cystatin C was observed in 200 Belgian adolescents [47], while higher blood lead was associated with lower serum creatinine and cystatin C in 600 European children [48].

Among 769 adolescents aged 12 to 20 years who participated in National Health and Nutrition Examination Survey (NHANES) III (1988 to 1994), higher blood lead levels were associated with lower cystatin-C-based eGFRs; those with lead levels >3 mcg/dL had lower eGFRs compared with those whose levels were <1 mcg/dL [49]. In a model adjusted for age, sex, race/ethnicity, urban versus rural residence, tobacco smoke exposure, obesity, household income, and education, a twofold higher blood lead level was associated with a 2.9 mL/min/1.73 m² lower eGFR. Analyses using creatinine-based equations showed similar associations between blood lead and eGFR, although the associations were not significant. Notably, 99 percent of the study participants had blood lead levels <10 mcg/dL.

An analysis in 391 participants in the Chronic Kidney Disease in Children (CKiD) prospective cohort study, whose mean blood lead and measured GFR were 1.2 mcg/dL and 44.4 mL/min/1.73 m², respectively, observed an association that was significant only among the 73 children with CKD due to glomerular disease. In this group, each 1 mcg/dL increase in blood lead level was associated with a -12.1 (95% CI -22.2 to -1.9) percent decrease in GFR.

Childhood lead poisoning is a risk for hypertension in adulthood. In a 50-year follow-up study, 21 adults with documented lead poisoning between 1930 and 1942 were compared with 21 control subjects matched for age, sex, race, and neighborhood [45]. Although blood lead and serum creatinine levels were low in both groups, the individuals with prior lead poisoning had a marked sevenfold increase in the risk of hypertension compared with controls (relative risk [RR] 7.0, 95% CI 1.2-42.3).

The impact of prenatal lead exposure was assessed in Bangladeshi children at 4.5 years of age. Blood pressure and eGFR were not associated with maternal erythrocyte lead levels. However, an inverse association between maternal lead and kidney volume, measured by sonography, was observed [50].

Chelation studies — Further support for lead-induced nephrotoxicity as a risk factor for the progression of underlying CKD comes from trials of chelation therapy. (See 'Chelation therapy and chronic kidney disease progression' below.)

Lead-induced hyperfiltration — There appears to be an association between higher lead dose and an initial increase in GFR, as manifested by a lower serum creatinine concentration and/or a higher creatinine clearance. These findings have been reported in lead workers in Korea, Belgium, and Taiwan [9,51,52]; in European children [48]; and in adult survivors of childhood lead poisoning [45]. A study of 53 Polish male steel workers (exposed group) and 40 office workers (control group) reported a positive association between blood lead (geometric mean of 14.6 microg/dL) and glomerular function assessed by a renal scan [53].

In the Korean lead workers, the associations of higher lead dose with lower serum creatinine and higher creatinine clearance were noted in younger workers, while older workers had the expected association between higher lead dose and higher serum creatinine concentrations [9]. These findings are consistent with initial lead-induced hyperfiltration followed by later lead-induced decline in kidney function. Similar findings have been noted in a rat model of lead-related nephrotoxicity [14].

Evaluation and therapy — Given the observed association between low-level lead exposure and an increased rate of progression of CKD in selected patients, we suggest screening patients who have stage 3 or greater CKD (eGFR <60 mL/min/1.73 m²) for lead exposure using the provided questionnaire (figure 2).

If the screening questionnaire indicates current or substantial past (eg, occupational) exposure to lead, we recommend eliminating all sources of exposure (table 1) and obtaining a whole blood lead measurement. Although blood lead does not adequately assess lead body burden, other lead-dose assessment options (eg, bone lead by x-ray fluorescence [XRF]) are not readily available or commonly used in clinical practice.

Interpretation of the blood lead level requires an understanding of data from the general population. NHANES data from 2015 to 2016, well after the removal of lead from gasoline in the United States, revealed a geometric mean blood lead level of 0.92 mcg/dL (0.04 micromol/L) in adults aged ≥20 years [5]. (See 'Measurement of lead dose' above.)

In developed countries, blood lead levels >5 mcg/dL (0.24 micromol/L) should be rechecked approximately four weeks after the identified source of lead exposure is eliminated. In developed countries, such values are more likely to be due to exogenous exposure that can be identified and reduced.

Patients who have repeated blood lead levels >5 mcg/dL (0.24 micromol/L) should be referred to a clinician with expertise in occupational and environmental medicine. A higher blood lead referral level may be necessary in countries in which there is a greater degree of lead exposure (eg, leaded gasoline has not been banned) and occupational and environmental medicine specialists are rare.

Occupationally exposed patients with CKD should have their lead exposure minimized to levels far below those legally mandated. Referral to an occupational medicine clinician with expertise in lead exposure and workplace accommodation may minimize adverse effects on employment and earning capacity while preserving health.

Chelation therapy and chronic kidney disease progression — Chelation therapy in patients with lead nephropathy resulting from high-level lead exposure is discussed above. (See 'Treatment' above.)

A number of clinical trials, all from the same group in Taiwan, have demonstrated efficacy from chelation therapy in patients with nondiabetic and diabetic CKD who had no history of exposure to lead [32-35]. One of these trials included 64 patients with nondiabetic, progressive CKD who had baseline serum creatinine concentration between 1.5 and 3.9 mg/dL (133 and 345 micromol/L), had 72-hour post-calcium EDTA lead excretion of 80 to 599 mcg (0.4 to 2.9 micromol), and had been observed for 24 months [32].

The patients were randomly assigned to placebo infusions or weekly calcium EDTA chelation therapy (1 g) for three months, unless 72-hour post-calcium EDTA lead excretion fell below 60 mcg (0.29 micromol). Weekly chelation was repeated over the next two years if there were increases in serum creatinine in association with rebound increases in 72-hour post-calcium EDTA lead excretion. Baseline mean blood lead levels were approximately 6 mcg/dL (0.29 micromol/L) in the treated and control groups. At 27 months, chelation therapy was associated with a slowing or reversal of the progressive decline in GFR compared with placebo (mean change of +2.1 versus -6 mL/min/1.73 m²).

A later randomized trial by the same group demonstrated a similar magnitude of benefit from chelation therapy in CKD patients with the lowest body lead burden studied to date (defined as 72-hour post-calcium EDTA lead excretion between 20 and 79 mcg [0.1 and 0.38 micromol]) [34]. The baseline mean blood lead level in the treated group in this study was 2.6 mcg/dL (0.13 micromol/L).

In summary, the demonstration of benefit from chelation therapy in CKD patients with low-level lead exposure raises two mechanistic possibilities, both of which may be involved:

●Lead-related nephrotoxicity contributes to progression in CKD patients, a hypothesis supported by longitudinal observational data on lead as a risk factor for progression in CKD patients.

●The benefits of chelation therapy may be due to mechanisms other than removal of body lead stores. Consistent with this hypothesis is the observation that chelation therapy with dimercaptosuccinic acid (DMSA) had a beneficial effect on nephrosclerosis in a non-lead-exposed rat model [54].

However, important questions remain regarding the benefits of chelation in selected patients with CKD. As discussed above, there are potential concerns about the safety of chelation related to both redistribution of lead into the central nervous system and toxicity of the chelating agents (see 'Treatment' above). Of particular relevance for the low-lead setting, cognitive impairment has been reported in non-lead-exposed control rats following chelation with succimer [29]. In addition, all of the above studies were performed at one medical center in small groups of patients [32-35].

Confirmation of the efficacy and safety of chelation therapy in CKD patients with low-level lead exposure is required in larger, racially diverse populations at additional centers. Given the size of the potentially affected population, this approach could yield important public health benefits.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic kidney disease in adults" and "Society guideline links: Lead and other heavy metal poisoning".)

SUMMARY AND RECOMMENDATIONS

●High levels of chronic lead exposure can cause lead nephropathy. In addition, lower levels of chronic lead exposure may contribute to lead-related nephrotoxicity in patients who already have or are at increased risk for chronic kidney disease (CKD). (See 'Introduction' above and 'Lead-related nephrotoxicity' above.)

●Lead may be measured in whole blood, bone, and, following administration of a chelating agent, urine. Blood lead is used most commonly in the clinical setting, while bone lead is primarily a research tool. Diagnostic chelation is sometimes used to assess bioavailable lead body burden. (See 'Measurement of lead dose' above and "Childhood lead poisoning: Management".)

●Lead nephropathy is characterized by chronic interstitial nephritis. (See 'Pathology' above.)

●Clinical manifestations of acute lead poisoning include the Fanconi syndrome. After more prolonged high-level exposure, patients present with an elevated serum creatinine, little or no proteinuria, and a relatively normal urine sediment. Hyperuricemia, gout, and hypertension may also be present. (See 'Clinical manifestations' above.)

●Prolonged lead exposure at the lower levels encountered in developed countries may contribute to renal toxicity. This is referred to as lead-related nephrotoxicity. These patients typically do not have extrarenal manifestations of lead poisoning. (See 'Lead-related nephrotoxicity' above.)

●Given the possibility of lead-related nephrotoxicity in those with CKD, we suggest screening patients who have stage 3 or greater CKD (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m²) for lead exposure using a self-administered questionnaire (figure 2). (See 'Evaluation and therapy' above.)

●If the screening questionnaire indicates current exposure to lead, all sources of exposure should be eliminated (table 1) and a blood lead level measured. If the blood lead level is >5 mcg/dL (0.24 micromol/L), levels should be rechecked four weeks after the identified source of lead exposure is eliminated. We recommend referral to a clinician with expertise in occupational and environmental medicine if the blood lead is persistently >5 mcg/dL (0.24 micromol/L). (See 'Evaluation and therapy' above.)

●Minimizing further lead exposure is essential in the treatment of lead nephropathy. Chelation therapy is indicated for select patients with nephropathy in the setting of acute lead poisoning based on elevated blood lead levels and lead-related symptoms. In the absence of such indications, the decision to chelate must be made on an individualized basis, and referral to a clinician with experience in lead toxicity and chelation is recommended. (See 'Treatment' above and "Lead exposure and poisoning in adults", section on 'Initial management' and "Childhood lead poisoning: Management".)

●Confirmation of the efficacy and safety of chelation therapy in CKD patients with low-level lead exposure is required in larger, racially diverse populations in additional research centers before such therapy can be recommended. (See 'Chelation therapy and chronic kidney disease progression' above.)