To the Editor: The incidence of obesity is rising, and physicians are likely to face the problem of obesity-related glomerulopathy (ORG) recently illustrated by Tran.1 But how can the clinician distinguish ORG from primary (idiopathic) focal segmental glomerulosclerosis (FSGS)? Both may present with nephrotic-range proteinuria, but the prognosis and choice of treatment may differ.

To date, the largest published study comparing ORG with primary FSGS is one by Kambham et al.2 In an analysis of 6818 renal biopsies, 71 patients with ORG were identified and compared with a control group of 50 patients with classic FSGS. The study showed that ORG less frequently progressed to end-stage kidney failure, with a 5-year renal survival rate of almost 90% (compared with about 50% in primary FSGS).2 While weight loss can reduce hyperfiltration and albuminuria in ORG,3 spontaneous remission is uncommon in primary FSGS.4,5 Does every obese patient with nephrotic-range proteinuria have ORG and an “indolent” course?

The degree of weight loss reported in the case described by Tran may not be achievable or sustainable in most obese patients. Do we have the luxury of waiting to assess the impact of weight loss on proteinuria? In about 50% of patients with primary FSGS, the serum creatinine level doubles after an average of 39 months.2 Furthermore, patients with primary FSGS and nephrotic-range proteinuria who do not achieve remission have a 5-year renal survival of only 50%, compared with almost 100% for those who attain remission.4 In addition, patients treated with corticosteroids (with or without cyclosporin or cyclophosphamide) have higher remission rates (30%–63%) than untreated patients (11%–14%).4,5 Therefore, a delay in introduction of specific therapy is not ideal.

There are some clinicopathological differences between ORG and primary FSGS that may help distinguish the two entities (Box). However, Kambham et al found that only two parameters were independently significant: serum albumin level and age.2 Although their study was based on a US population, it serves to demonstrate the principle that the major distinguishing feature between ORG and primary FSGS is the presence of full-blown nephrotic syndrome in primary FSGS (as demonstrated by the severity of hypoalbuminaemia).

Obese patients have a similar risk of developing primary FSGS to people in the general population, and patients with nephrotic syndrome (particularly older adults) should not be presumed to have ORG and treated with weight loss alone. Certain pathological findings in a renal biopsy are helpful, but not definitive, in distinguishing ORG from primary FSGS. A biopsy would also exclude other treatable causes, such as minimal change disease. In addition to treatment with angiotensin-converting enzyme inhibitors, immunotherapy should be considered for obese, nephrotic patients, after discussing the potential risks and benefits with a nephrologist.