Membranous glomerulonephropathy with tubular dysfunction and linear tubular basement membrane IgG deposition

Abstract

patient's condition progressed to end-stage renal disease. The decline in GFR was coincident with the development of poorly responsive and eventually severe and nonresponsive proteinuria. Glomerular damage and proteinuria may be causally related or independently related to another primary factor. We suggest that the proteinuric state might have been a causative factor in the progression of the mesangial sclerosis and glomerular capillary damage; there is experimental and clinical evidence to support such a causal relationship. Heavy proteinuria induced in rats by the injection of protein is associated with the development of focal glomerulosclerosis. 8' 9 These histologic changes are partially, and the functional changes completely, reversed when injections are discontinued? Fivesixths nephrectomy in the rat, with the accompanying increase in single nephron glomerular filtration and solute excretion, produces focal segmental glomerulosclerosis. 1~ The equivalent of these changes in the remnant kidney is seen in children with oligomeganephronia, a form of severe hypoplasia leading to renal insufficiency, and in children left with a marked decrease in GFR following relief of obstructive uropathy. All of these observations suggest that a large increase in the excretion of protein or other solute per nephron (functional overload) can lead to progressive glomerular sclerosis as was observed in our patient. If the degree of proteinuria is important in determining progressive glomerular damage, efforts to decrease the rate of protein excretion, including cytotoxic drugs, should be considered in patients with the most severe and persistent proteinuria. Unfortunately, no clear benefit has been shown for such therapy in patients with histologic patterns other than minimal lesion disease. Further, overly vigorous use of albumin infusions, together with diuretics, can produce increased protein excretion and lead potentially to epithelial Cell damage and mesangial sclerosis. The patient with the nephrotic syndrome described here developed end-stage renal disease after 18 years of steroidresponsive relapses, over which time there were 40 relapses, each responding to prednisone with disappearance of proteinuria. When resistance to steroid therapy developed, the renal histology was focal segmental glomerulosclerosis. We suggest that repeated episodes of heavy proteinuria were a factor in the development of the renal pathologic changes. REFERENCES