Glomerulonephritis for the generalist.

Glomerulonephritis is a common renal disorder, and a leading cause of end-stage renal disease. Glomerulonephritis can present in protean ways, with general features including proteinuria, hematuria, renal failure, and hypertension. Recent advances in our knowledge of glomerulonephritis have indicated that in many cases early therapeutic intervention can lead to improvement in renal function, long-term preservation of renal function, or slowing of the progression to end-stage renal failure. The goal of this review is to describe the method of evaluation of glomerulonephritis, stress the importance of general measures to preserve renal function or slow the rate of progression of disease, and finally to familiarize the reader with distinct categories of disease and their treatment.

Interferon-alpha-associated focal segmental glomerulosclerosis with massive proteinuria in patients with chronic myeloid leukemia following high dose chemotherapy.

BACKGROUND: Acute renal failure, with or without massive proteinuria, is a rare idiosyncratic toxicity of interferon (IFN)-alpha therapy. The authors sought to review their experience with this toxicity as well as the world literature on the subject. METHODS: The authors describe two patients with chronic myeloid leukemia treated with IFN-alpha following high dose chemotherapy who developed renal failure and proteinuria after 3 and 4 weeks of IFN-alpha therapy, respectively. Fifteen previously reported cases of renal failure and proteinuria associated with IFN-alpha therapy are also reviewed. RESULTS: Renal biopsies performed on the authors' two patients revealed focal segmental glomerulosclerosis. However, the other reported patients with IFN-alpha-associated renal failure and massive proteinuria had an assortment of pathologic findings. CONCLUSIONS: The specific renal pathology associated with proteinuria may be a consequence of the condition and not its cause; differences in renal pathology may be caused by other predisposing factors. Patients treated with IFN-alpha following high dose chemotherapy, with or without autologous transplantation, should be followed for the development of proteinuria and renal failure.

Periodic disklike structures of the adult human loop of Henle. Light and electron microscopic studies.

A total of 51 adult human kidneys was examined for the presence of the periodic disklike thickenings recently described by Belliveau in the basement membrane of the loop of Henle. These "Belliveau bodies" formed a PAS-positive rectangular lattice within the basement membrane and appeared limited to the loop of Henle. The bodies were seen in the medulla of every kidney examined but varied considerably in the frequency of their appearance from case to case. This variability did not correlate with predominant illness, organ weight, or time interval between death and autopsy. They averaged 9 to 14 micron in diameter with a horizontal and vertical periodicity of 12 and 16 micron, respectively. Although the bodies were PAS positive and diastase resistant, they did not stain with Congo red, mucicarmine, reticulin, or elastin staining techniques. Ultrastructurally, they consisted of multilaminated areas of basement membrane material. The constancy of their appearance in the material examined suggests that they are a normal anatomic feature or possibly an age-related change of the basement membrane of Henle's loop in the human kidney.

Gold-associated nephropathy.

Renal biopsy specimens from 11 cases of gold-associated nephropathy were studied by light, immunofluorescence, and electron microscopy. Seven biopsy specimens disclosed the typical glomerular lesions of membranous nephropathy. Four cases disclosed other patterns of glomerular injury, including minimal-change nephrotic syndrome. Although a membranous pattern of immune complex deposition is the most frequent type seen in gold nephropathy, our data indicate that other patterns of immune complex deposition may occur in renal biopsy specimens of patients receiving gold therapy.

Test for C3 nephritic factor activity by immunofixation electrophoresis.

This report describes a relatively simple test for C3 nephritic factor (C3NeF) activity utilizing immunofixation electrophoresis to quantitate the production of the breakdown product C3c. Tests performed on plasmas from 22 control patients and 93 renal patients have biopsy diagnoses other than basement membrane dense deposit disease (BMDDD) yielded negative results for C3NeF activity. Tests performed on plasmas from three patients with BMDDD were positive for C3NeF activity, yielding values significantly higher than those for the control group and the patients with other renal diseases. The test can be performed on specimens collected in EDTA to prevent in vitro C3 degradation during storage or transport at ambient temperature.

Variability of anti-GBM binding in hereditary nephritis.

Anti-GBM staining by indirect immunofluorescence microscopy was performed on renal biopsies from 64 patients with a variety of diseases in which no in vivo bound immunoglobulin or complement components were identified by direct immunofluorescence microscopy. The glomeruli of all of the entities examined bound anti-GBM antibodies except for four of nine cases of hereditary nephritis of the Alport-type. The absence of anti-GBM staining was found to correlate with the severity of GBM splitting identified by electron microscopy.

Skeletal muscle in polymyositis. Immunohistochemical study.

Thirty-two patients with adult-onset polymyositis uncomplicated by cancer or systemic connective tissue disease were studied. Muscle biopsy specimens were examined with direct immunofluorescence microscopy and results were compared with those in 94 control subjects. Sarcolemmal and sarcoplasmic staining were observed in both groups and considered to be nonspecific. Immune deposits in the muscle microvasculature were present in some cases of systemic lupus erythematosus and dermatomyositis but were not present in polymyositis. Our data suggest that the finding of vascular immunofluorescence excludes the diagnosis of adult polymyositis and implies that the pathogenesis of this disease and other idiopathic inflammatory myopathies may differ.

Alternative C3 pathway activiation in pneumococcal glomerulonephritis.

Glomerulonephritis following pneumococcal infection has been observed, but possible immunopathologic mechanisms have not been adequately explored. Multiple serologic studies as well as light, immunofluorescence and electron microscopic evaluation of kidney biopsy tissue from a 4 year old girl with pneumococcal glomerulonephritis were performed. Clinical studies at the onset of the disease showed normal serum C3 and C4 levels (third and fourth components of complement) with progression to selective C3 hypocomplementemia from days 2 to 58. A serum factor capable of breaking down C3 in normal human serum was present during the period of maximum C3 hypocomplementemia. Renal glomerular histology revealed a mesangial proliferative glomerulonephritis. Glomerular bound C3 and type 14 pneumococcal antigen were associated with similar, but less extensive, deposits of properdin. Minimal immunoglobulin M (IgM) and C4 were seen, but immunoglobulin G (IgG) and fibrinogen were absent. Ultrastructurally, subepithelial "humps" and intramembranous electron dense deposits were noted. It is hypothesized that the pneumococcal polysaccharide can activate the alternate complement pathway and may be responsible for a limited course of glomerulonephritis.