Thin basement membrane disease with heavy proteinuria or nephrotic syndrome at presentation

Thin basement membrane disease (TBMD) is a condition originally defined as diffuse thinning of the glomerular basement membrane (GBM) associated with hematuria in all patients. Although proteinuria has been described in up to 60% of patients with TBMD, it is almost always mild, with a 24-hour excret ion mostly of less than 500 mg. We describe eight patients (four men and fo ur women between 32 and 66 years of age) with TBMD who presented with heavy proteinuria or nephrotic syndrome. Among the seven cases with family histo ry, hematuria was noted in five. All patients had a long history of miscros copic hematuria, with episodic gross hematuria in two. Renal biopsies showe d diffuse thinning of the GEM in each patient (mean between 185.3 x 29.8 nm and 232.6 x 34.5 nm versus control between 325 x 35 nm and 350 x 15 nm). T hree cases showed thinning of GEM only (group I); the remaining five cases showed thinning of GEM associated with focal segmental glomerulosclerosis. Atl three patients of group I presented with nephrotic syndrome and normal renal function. Treatment with steroids resulted in remission of nephrotic syndrome in two, whereas nephrotic syndrome persisted in the untreated pati ent. Among the five patients in group It, nephrotic syndrome and normal ren al function at presentation were noted in two, whereas the other three had heavy proteinuria (2.2, 2.5, and 2.6 g/d, respectively) associated with mil dly decreased renal function (serum creatinine 1.8, 1.3, and 1.5 mg/dL, res pectively). At last follow-up, although the renal function was stable in al l five, only the three who received steroid treatment had remission or mark ed improvement of proteinuria. Hematuria, however, persisted in all eight p atients of both groups. Whether specific gene mutations are translated Into structural changes responsible for both excessive GEM thinning and increas ed transcapillary permeability remains to be elucidated. Alternatively, the heavy proteinuria/nephrotic syndrome may not be related to TBMD, but rathe r is the manifestation of associated glomerular diseases. Follow-up, includ ing a response to steroids, supports the latter hypothesis. (C) 2000 by the National Kidney Foundation, Inc.