Lead Nephropathy

Lead nephropathy is chronic tubulointerstitial kidney disease, with hypertension and gout, caused by long term exposure to lead. It is a recognised cause of kidney disease of uncertain cause in children and adults in low resource settings.

It is described as acute or chronic.

• Acute: proximal tubular dysfunction after high dose exposure in children, reversible.
• Chronic: progressive interstitial fibrosis and tubular atrophy after cumulative exposure.

Even low blood lead levels (above 5 microg/dL, or 0.24 micromol/L) are associated with faster decline in eGFR and hypertension.

Sources of exposure are:

• Occupational: battery manufacture and recycling, smelting, welding, soldering, paint removal, plumbing, ceramics, firearm ranges, construction, scrap metal.
• Environmental: lead paint in older housing, contaminated soil and dust, lead pipes, leaded fuel residues, mining areas, e-waste sites.
• Consumer: illicitly distilled whisky, lead glazed ceramics, traditional remedies (Ayurvedic and other herbal products), eye cosmetics such as kohl or surma, imported spices and toys, and contaminated cooking pots.

Pathophysiology. Lead is absorbed, stored in bone (half life of decades) and cleared through the kidney. In proximal tubular cells it produces intranuclear inclusion bodies, mitochondrial injury, oxidative stress, reduced uric acid secretion and later interstitial fibrosis. It also raises blood pressure through vascular effects.

• Chronic kidney disease with bland urine, little proteinuria (under 1 g daily), normal or small kidneys, and hypertension.
• Hyperuricaemia and gout (saturnine gout) out of proportion to the level of kidney function (reduced urate excretion).
• Acute high dose exposure: Fanconi syndrome (glycosuria, aminoaciduria, phosphaturia).
• Systemic: abdominal colic, constipation, anaemia (basophilic stippling), irritability, impaired concentration, peripheral neuropathy (wrist drop), lead line on gums, infertility, miscarriage.
• Children: developmental delay, behavioural problems, abdominal pain, pica.

Red flags

• Blood lead above 80 microg/dL (3.9 micromol/L) or any level with encephalopathy (headache, vomiting, seizures, coma).
• Chronic kidney disease with gout, hypertension and a history of exposure.
• Pregnancy with raised lead.
• Children with pica, anaemia or neurodevelopmental delay.
• Household members with similar exposure.

• Whole blood lead (venous, in a trace element tube): normal under 5 microg/dL (0.24 micromol/L).
• Above 10 microg/dL (0.48 micromol/L) in adults warrants exposure assessment. Above 40 microg/dL (1.9 micromol/L) removal from exposure is needed. Above 80 microg/dL treatment is usually required.
• Full blood count and film (microcytic hypochromic anaemia, basophilic stippling), erythrocyte protoporphyrin or zinc protoporphyrin, iron studies.
• Creatinine, eGFR, urate, urine protein:creatinine ratio, urine microscopy, urine beta-2 microglobulin; blood pressure.
• X-ray fluorescence of tibia (cumulative body burden) where available.
• 24-hour urine lead after a chelating challenge (calcium disodium edetate) is now reserved for research or specific centres and is not routinely used.
• Kidney biopsy rarely: interstitial fibrosis, tubular atrophy, arteriolar changes and intranuclear inclusion bodies in the acute phase.
• Check exposure sources (home, hobbies, workplace, remedies).

Differential diagnosis

• Hypertensive nephrosclerosis, diabetic kidney disease, other chronic tubulointerstitial diseases (cadmium, aristolochic acid, analgesic), gouty nephropathy, uric acid nephropathy, other causes of anaemia with basophilic stippling, chronic kidney disease of uncertain cause in agricultural communities, porphyria.

First line: stop exposure (essential)

• Identify and remove the source: workplace controls, removal from work (for example, once blood lead reaches 40 microg/dL, 1.9 micromol/L), covered or relocated housing, replacement of lead pipes, discontinuing remedies and ceramics, and screening of household members and workers.
• Wash hands and clothes after work; showering before leaving work; nutrition with adequate iron, calcium and vitamin C to reduce absorption.
• Public health notification and exposure investigation.

Chelation therapy (selected patients; with a toxicology unit)

• Adults: symptomatic patients with blood lead above 50 microg/dL, or any patient above 80 microg/dL. No routine chelation for asymptomatic patients with lower levels.
• Oral succimer 10 mg/kg (or 700 mg/m²) three times daily for 5 days, then twice daily for 14 days (total 19 days). Check liver tests and blood count. It can be repeated after 2 weeks if the level rebounds.
• Intravenous calcium disodium edetate 1 g (or 1000 mg/m² daily) diluted in 250 to 500 mL of 5% glucose over 4 to 6 hours daily for 5 days.
• Reduce the edetate dose or interval in kidney impairment: 500 mg every 24 to 48 hours when eGFR is 20 to 49. Avoid or use with dialysis support when eGFR is under 20.
• Never use disodium edetate. Give edetate only after adequate urine output is established. Check calcium, creatinine and urinalysis daily.
• Lead encephalopathy: dimercaprol 3 to 5 mg/kg intramuscularly every 4 hours for the first doses, with calcium disodium edetate 1500 mg/m² daily as a continuous infusion, in intensive care.
• In kidney failure on dialysis, chelation can be given with dialysis (calcium disodium edetate removed by haemodialysis).
• Check blood lead 7 to 14 days after chelation.
• Children: blood lead of at least 45 microg/dL treated with succimer 10 mg/kg three times daily for 5 days then twice daily for 14 days.
• Chelation does not clearly improve established kidney fibrosis, but may slow decline in patients with high body burden and eGFR 20 to 60.

Kidney and complication management

• Hypertension: blood pressure below 130/80 mmHg. Use ramipril 2.5 mg daily increased to 10 mg daily (creatinine and potassium at 1 to 2 weeks; accept a rise up to 30%; stop if potassium exceeds 6.0 mmol/L), or amlodipine 5 to 10 mg daily.
• Gout: allopurinol 100 mg daily increased by 100 mg every 2 to 4 weeks to urate under 360 micromol/L. Use lower doses when eGFR is under 30. Test for the HLA-B 5801 allele in high risk ancestry groups.
• Gout flare prophylaxis: colchicine 0.5 mg once or twice daily (0.5 mg every other day when eGFR is under 30). Avoid NSAIDs. Treat acute flares with prednisolone 30 mg daily for 5 days.
• Anaemia: iron if deficient (ferrous sulphate 200 mg daily); epoetin alfa 50 to 100 units/kg three times weekly if haemoglobin is under 100 g/L despite iron; target 100 to 120 g/L.
• Chronic kidney disease care: sodium under 2 g daily, dapagliflozin 10 mg daily (eGFR at least 25), avoid nephrotoxins, vaccination, bone and mineral monitoring.
• Kidney failure: dialysis at eGFR 5 to 10 with symptoms; transplantation after control of exposure.

Monitoring. Blood lead monthly until stable, then every 3 to 6 months while exposed. Creatinine, eGFR, urate and blood pressure every 3 months. Blood lead 1 to 2 weeks after chelation. Follow household members.

Referral and escalation. Nephrology when eGFR is under 60 or falling; toxicology and public health for high levels. Refer urgently for encephalopathy or abdominal colic with blood lead above 80 microg/dL.

Special groups

• Children: more severe neurotoxicity; screen siblings; correct iron and calcium deficiency; specialist chelation.
• Pregnancy: lead crosses the placenta and mobilises from bone. Chelation only for severe poisoning (blood lead above 80 microg/dL) with specialist care. Breastfeeding is generally continued when blood lead is below 40 microg/dL.
• Workers: occupational health surveillance with blood lead every 3 months while at risk.
• Sub-Saharan Africa and South Asia: ask about battery recycling, mining, traditional remedies and cosmetics.