To the Editor: Obesity-related glomerulopathy (ORG) is a condition that is partially reversible by weight loss.

A 48-year-old morbidly obese man presented with massive proteinuria (8.4 g/day; reference range[RR], < 0.03 g/day). His medical history included hypertension of 4 years, morbid obesity, gout and impaired fasting glycaemia. His hypertension had been relatively well controlled, with no known end-organ complication until the current review. His urinary protein excretion rate measured 6 months earlier had been 0.13 g/day. Longstanding medications included aspirin, lisinopril and allopurinol.

The patient weighed 125 kg and was 1.77 m in height (body mass index, 40 kg/m2 [class III obesity]). His blood pressure was 130/70 mmHg, with no postural hypotension. The fundi were normal, with no evidence of hypertensive retinopathy. There was no peripheral pitting oedema and there were no tendon xanthomata.

A repeat urinary protein measurement showed an excretion rate of 7.9 g/day, confirming the earlier result. Renal and liver function tests were normal. Other laboratory tests produced the following results: fasting cholesterol, 5.5 mmol/L (RR, < 4.0 mmol/L); triglycerides, 2.4 mmol/L (RR, < 1.8 mmol/L); serum creatinine, 92 μmol/L (RR, 60–110 μmol/L); albumin, 38 g/L (RR, 35–45 g/L); fasting glucose, 6.8 mmol/L (RR, < 5.5 mmol/L); serum insulin, 66 mU/L (RR, 5–25 mU/L); and C-peptide, 6.8 nmol/L (RR, 0.2–0.6 nmol/L). All relevant tests for glomerulonephritis, including serum antinuclear antibodies, antinuclear cytoplasmic antibodies, C3 and C4 levels, protein electrophoretic studies, and hepatitis B and C serology were negative, making a diagnosis of glomerulonephritis unlikely.

While awaiting the renal biopsy, the patient decided to attempt rapid weight loss. He began consuming mostly one meal a day of about 5000 kJ (which included about 2000 kJ of protein). Six weeks later, his weight had fallen to 118 kg and his blood pressure was 130/80, with no oedema. His urinary protein excretion rate was 7.6 g/day.

After 18 weeks, the patient weighed 110 kg and his urinary protein excretion rate had fallen to 2.1 g/day. At 6 months, his weight loss had plateaued at 102 kg and urinary protein excretion was 0.85 g/day.

The renal biopsy showed features consistent with ORG1 (Box). No other abnormality was detected. A concomitant minimal change lesion with spontaneous remission would be a possible explanation, but such a lesion is exceedingly rare and difficult to exclude in the absence of electron microscopy. It is also unlikely given the patient’s age and abnormal light microscopy finding.

It is apparent that class III obesity, through unknown mechanisms,2 is a major contributing factor in causing ORG and massive proteinuria — conditions that can be readily improved by weight loss. It remains to be seen in this case whether further weight reduction will further reduce the proteinuria, which, on the other hand, may also be confounded by the hypertension. Impaired fasting glycaemia is not a cause of proteinuria.3

This clinical vignette reinforces the need to check vigilantly for proteinuria and rigorously advise obese patients to attempt weight reduction, especially now that obesity has been confirmed to be an independent risk factor for end-stage renal disease.4