Membranoproliferative glomerulonephritis with dense intramembranous alterations. A clinicopathologic study.

Two major categories of membranoproliferative glomerulonephritis (MPGN) designated type 1 and 2 MPGN are currently recognized, largely on the basis of characteristic morphologic and immunofluorescence features. In contrast to experience reported from outside the United States, type 2 MPGN has been observed rather infrequently in this country. In a retrospective clinicopathologic study, 24 kidney specimens obtained from 10 children and young adults including seven females and three males (mean age: 13 years) with type 2 MPGN were identified using light, immunofluorescence, and electron microscopy. The histopathologic findings were related to the clinical course of each patient. When initially seen all patients had hematuria and proteinuria, three were nephrotic, and five were mildly hypertensive. A single patient was mildly azotemic. Eight patients had experienced an upper respiratory ifnection preceding their illness, although only one patient had evidence of a streptococcal pharyngitis. During a period of follow-up averaging 10 years, eight patients were nephrotic at some time during their illness and seven were persistently so. Hypertension was a major problem in eight patients and renal function declined markedly within a year of its onset in five. Persistence of the nephrotic syndrome from early onset of the disease, especially when associated with hypertension, was an additional sign of poor prognosis. Four patients developed chronic renal failure and three received one or more renal allografts. Histologic evidence of recurrent disease was found in allografts from the three patients as early as 7 months after transplantation in the absence of clinical features indicative of recurrent glomerulonephritis. It is concluded that type 2 MPGN is a chronic progressive renal disease of unknown etiology and pathogenesis which chiefly afflicts children and young adults. Hypertension and the early and persistent presence of the nephrotic syndrome suggest a poor prognosis. The disease appears to be largely unresponsive to conventional forms of therapy. The disease recurs with great frequency in allografts, often in the absence of clinical evidence of recurrent glomerulonephritis.