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 excretion mostly of less than 500 mg. We describe eight patients (four men and four women between 32 and 66 years of age) with TBMD who presented with heavy
proteinuria or
nephrotic syndrome. Among the seven cases with family history,
hematuria was noted in five. All patients had a long history of microscopic
hematuria, with episodic gross
hematuria in two. Renal biopsies showed diffuse thinning of the GBM 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). Three cases showed thinning of GBM only (group I); the remaining five cases showed thinning of GBM associated with
focal segmental glomerulosclerosis. All 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 patient. Among the five patients in group II,
nephrotic syndrome and normal renal 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 mildly decreased renal function (serum
creatinine 1.8, 1.3, and 1.5 mg/dL, respectively). At last follow-up, although the renal function was stable in all five, only the three who received
steroid treatment had remission or marked improvement of
proteinuria.
Hematuria, however, persisted in all eight patients of both groups. Whether specific gene mutations are translated into structural changes responsible for both excessive GBM thinning and increased transcapillary permeability remains to be elucidated. Alternatively, the heavy
proteinuria/
nephrotic syndrome may not be related to TBMD, but rather is the manifestation of associated glomerular diseases. Follow-up, including a response to
steroids, supports the latter hypothesis.