A 41-year-old woman presented with progressive generalized edema and nephrotic-range proteinuria with preserved renal function. Evaluation revealed hypoalbuminaemia, dyslipidaemia, and elevated inflammatory markers. Renal biopsy showed membranous nephropathy. Detailed history revealed prolonged intake of an Ayurvedic medication for psoriasis. Heavy metal analysis showed elevated blood lead levels. After exclusion of autoimmune, infectious, and other secondary causes, a diagnosis of lead-induced secondary membranous nephropathy was made. The patient was managed with withdrawal of exposure and supportive therapy, with emphasis on RAAS blockade and edema control. This case highlights chronic lead toxicity as an uncommon but important cause of secondary membranous nephropathy.
Membranous nephropathy is one of the leading causes of nephrotic syndrome in adults. While primary membranous nephropathy accounts for the majority of cases, up to one-third are secondary to systemic diseases, infections, malignancies, drugs, or toxins. Identification of secondary causes is crucial, as treatment differs significantly from that of primary disease.
Lead toxicity is a well-recognised cause of chronic kidney disease, classically presenting as tubulointerstitial nephritis. However, immune-mediated glomerular involvement, including membranous nephropathy, has been rarely described. Traditional and alternative medicines, including Ayurvedic preparations, are increasingly implicated as sources of chronic heavy metal exposure. This case underscores the importance of considering heavy metal toxicity in unexplained nephrotic syndrome.
A 41-year-old woman presented with a two-month history of progressive bilateral lower limb swelling and generalised body swelling, accompanied by anorexia, weight gain, and constipation. There was no history of fever, rash, joint pain, photosensitivity, oral ulcers, haematuria, oliguria, or recurrent infections. She was a known case of systemic hypertension on treatment.
Clinical examination revealed generalised edema without features of heart failure or chronic liver disease. Blood pressure was controlled, and systemic examination was otherwise unremarkable.
Initial laboratory investigations showed haemoglobin 13.3 g/dL, total leukocyte count 5,000/µL, platelet count 3.23 × 10⁵/µL, and erythrocyte sedimentation rate of 97 mm/hr. Glycaemic parameters were normal (HbA1c 5.7%).
Biochemical evaluation revealed nephrotic syndrome with total protein 4.19 g/dL, albumin 2.06 g/dL, and nephrotic-range proteinuria (urinary microalbumin >2,000 mg). Lipid profile showed hypercholesterolaemia (total cholesterol 419 mg/dL, LDL 374 mg/dL). Liver enzymes were within normal limits. Renal function was preserved with serum creatinine 0.66 mg/dL and urea 27.9 mg/dL. Electrolytes were within normal limits. Thyroid function tests showed borderline elevated TSH with normal T3 and T4 levels. Vitamin D level was markedly deficient. Autoimmune screening including ANA profile was negative. Viral serology was non-reactive. Coagulation parameters were normal.
Given a history of prolonged intake of an Ayurvedic preparation for psoriasis, a heavy metal panel was performed, which revealed elevated blood lead levels (28.4 µg/dL) with mildly elevated zinc levels. Renal biopsy demonstrated features consistent with membranous nephropathy.
The Ayurvedic medication was discontinued immediately. The patient was managed conservatively with supportive therapy, including diuretics for oedema control, RAAS blockade therapy for proteinuria reduction, and statins for dyslipidaemia. Dietary salt restriction and vitamin D supplementation were advised. Chelation therapy was not initiated, as blood lead levels were moderately elevated and the patient was clinically stable. Close clinical and biochemical monitoring was planned.
The patient showed symptomatic improvement in edema following supportive therapy. She was advised regular follow-up for monitoring of proteinuria, serum albumin levels, renal function, and blood lead levels. Long-term prognosis was expected to depend on sustained avoidance of lead exposure and response of proteinuria to supportive management.
Nephrotic syndrome in adults represents a heterogeneous group of glomerular diseases, with incidence peaking in the fourth to sixth decades of life. Membranous nephropathy is one of the most common causes of nephrotic syndrome in this age group, accounting for a substantial proportion of adult-onset cases. While primary membranous nephropathy predominates, secondary forms must be carefully evaluated, particularly in patients with atypical features, relevant exposure history, or absence of autoimmune markers.
Nephrotic syndrome is characterised by heavy proteinuria, hypoalbuminaemia, edema, and hyperlipidaemia, all of which were evident in this patient. The preservation of renal function at presentation is typical of membranous nephropathy and helps differentiate it from rapidly progressive or inflammatory glomerulonephritides. The markedly elevated lipid levels and severe hypoalbuminaemia further supported a chronic nephrotic state rather than an acute inflammatory process.
Membranous nephropathy is pathologically defined by immune complex deposition along the subepithelial aspect of the glomerular basement membrane, leading to complement activation and podocyte injury. The disease is broadly classified into primary and secondary forms. Primary membranous nephropathy is most often associated with autoantibodies against podocyte antigens such as the phospholipase A2 receptor (PLA2R). Secondary membranous nephropathy is associated with systemic autoimmune diseases (notably systemic lupus erythematosus), chronic infections, malignancies, and exposure to certain drugs and toxins.
The diagnostic approach to membranous nephropathy requires exclusion of secondary causes through detailed clinical history, serological testing, and malignancy screening where appropriate. In this patient, autoimmune evaluation including ANA was negative, viral serologies were non-reactive, and there were no clinical features suggestive of malignancy or systemic inflammatory disease. The absence of lupus-specific clinical or serological features, combined with preserved renal function and isolated nephrotic syndrome, made lupus nephritis unlikely. These findings prompted further evaluation for toxin exposure.
Lead is a well-established nephrotoxin, traditionally associated with chronic tubulointerstitial nephropathy, hypertension, and progressive chronic kidney disease. However, experimental and clinical evidence indicates that lead can also induce immune-mediated glomerular injury. Proposed mechanisms include dysregulation of T-cell–mediated immunity, enhanced autoantibody production, oxidative stress–induced podocyte injury, and immune complex deposition along the glomerular basement membrane. These processes can culminate in a membranous pattern of glomerular injury.
Chronic lead exposure remains a significant public health issue, particularly in developing countries. Common sources include contaminated water, occupational exposure, lead-based paints, batteries, and traditional or alternative medicines. Ayurvedic preparations, in particular, have been increasingly implicated due to contamination or intentional inclusion of heavy metals as part of traditional formulations. Several studies have demonstrated elevated blood lead levels in users of such preparations, often without overt symptoms, leading to delayed diagnosis.
In this patient, prolonged intake of an Ayurvedic medication of unknown composition for psoriasis represented a critical diagnostic clue. The elevated blood lead level, in conjunction with renal biopsy-proven membranous nephropathy and exclusion of other secondary causes, strongly supports lead-induced secondary membranous nephropathy. Although the measured lead level was moderately elevated, chronic exposure even at lower levels can result in cumulative renal toxicity and immune-mediated injury.
Management of secondary membranous nephropathy focuses primarily on identification and elimination of the underlying cause. In contrast to primary membranous nephropathy, immunosuppressive therapy is generally not first-line and may be unnecessary if the inciting factor is removed. Supportive management remains the cornerstone of treatment and includes renin–angiotensin system blockade to reduce proteinuria, diuretics for edema control, statins for dyslipidaemia, and dietary sodium restriction.
Treatment guidelines for lead toxicity suggest immediate cessation of exposure (most critical intervention), Chelation therapy indicated when Blood lead levels >45 µg/dL in adults with symptoms, Levels >70 µg/dL irrespective of symptoms. Common chelating agents used are Dimercaptosuccinic acid (DMSA), EDTA in severe cases. In patients with lower levels and stable clinical status, conservative management with monitoring is recommended. In this case, withdrawal of the offending agent and supportive nephrotic syndrome management were considered sufficient, with plans for follow-up.
This case highlights the importance of maintaining a high index of suspicion for heavy metal toxicity in patients presenting with unexplained nephrotic syndrome. Detailed history-taking, including alternative and traditional medicine use, is essential. Early recognition of secondary causes can prevent unnecessary immunosuppression and may lead to reversal or stabilisation of renal disease with appropriate intervention.
Dr Vignesh A.S DNB General Medicine 3rd Year Resident, Kauvery Hospital, Chennai.
Dr Balaji Kirushnan MD, DNB Nephrology Senior consultant Nephrologist, Kauvery Hospital, Chennai.
Dr Ashwin Subramaniam DNB, MRCP(UK) Senior consultant Internal Medicine, Kauvery Hospital, Chennai.
