When to Suspect Non-diabetic Kidney Disease in a Diabetic Patient?

The diagnosis of non-diabetic kidney disease (NDKD) in a diabetic patient has significant therapeutic and prognostic implications. There are certain proven clinical predictors of NDKD, which, when present in an appropriate clinical setting, would warrant a kidney biopsy. Herein, we describe four cases of NDKD diagnosed in rather unusual clinical settings, which add to the list of clinical predictors of NDKD. The first case was a "parainfectious glomerulonephritis" diagnosed in a 50-year-old diabetic woman who presented with persistent renal dysfunction despite successful treatment of urinary tract infection. The second case was "membranous nephropathy" diagnosed in a 43-year-old man with long-standing type 1 diabetes, which was associated with other microvascular complications. In this case, the only predictor was disproportionately low serum albumin. The third case was "amyloid light chain (AL) amyloidosis" diagnosed in an elderly diabetic who presented with progressive anasarca over six months. In this case, the only clinical predictor was a disassociation observed between urine dipstick and 24-hour protein estimation. In the fourth case, an elderly diabetic woman without underlying diabetic retinopathy presented with sudden onset nephrotic syndrome. A kidney biopsy was suggestive of diffuse nodular glomerulosclerosis. Immunofluorescence and electron microscopic evaluation were diagnostic of "gamma heavy chain deposition disease." In all four cases, diagnosis of NDKD led to major therapeutic changes and attainment of renal remission. We have extensively reviewed all major biopsy cohorts of NDKD and have formulated an approach to the diagnosis of NDKD.