Gordon N. Gephardt

Long-Term Follow-up after Partial Removal of a Solitary Kidney

BACKGROUND The removal of more than one kidney in animals leads to proteinuria and progressive renal failure due to focal segmental glomerulosclerosis. This injury may be the result of chronic glomerular hyperfiltration. The purpose of this study was to determine the effect of a reduction in renal mass of more than 50 percent on residual renal function and morphology in humans. METHODS We evaluated long-term renal function in 14 patients with a solitary kidney who had undergone partial nephrectomy for renal-cell or transitional-cell carcinoma. In 12, the first kidney had been removed 2 months to 21 years previously for the same type of cancer; in 2, the other kidney was congenitally atrophic. Before surgery, no patient had clinical or histopathological evidence of primary renal disease. All 14 patients underwent partial nephrectomy to remove a localized tumor, with 25 to 75 percent of the solitary kidney being excised. They were evaluated 5 to 17 years after surgery (mean, 7.7). RESULTS Twelve patients had stable postoperative renal function, and end-stage renal failure developed in two. There were no changes in blood pressure in any patient during follow-up. Nine patients had proteinuria, which was mild (0.15 to 0.8 g of urinary protein per day) in five. The extent of proteinuria was inversely correlated with the amount of remaining renal tissue (P = 0.0065) and directly correlated with the duration of follow-up (P = 0.0005). Four patients with moderate-to-severe proteinuria had renal biopsies, which revealed focal segmental glomerulosclerosis in three patients and global glomerulosclerosis in one. CONCLUSIONS Long-term renal function remains stable in most patients with a reduction in renal mass of more than 50 percent. These patients are, however, at increased risk for proteinuria, glomerulopathy, and progressive renal failure.

Light chain nephropathy

In 13 specimens of renal tissue from 11 patients, deposits of monoclonal immunoglobulin light chains and continuous granular electron-dense material within tubular basement membranes and in association with the glomerular basement membrane were identified. All but one patient were men n the fifth to seventh decades of life, and each presented with azotemia and features of glomerular rather than tubulointerstitial disease. Osteolytic bone lesions occurred in only three patients, and a bone marrow plasmacytosis greater than 30 percent consistent with plasma cell myeloma was identified in only four patients. Light chain distribution in the nephron was confirmed with immunoelectron microscopy and was not associated with deposition of other serum proteins such as immunoglobulin heavy chains, complement, transferrin, alpha 2 macroglobulin and albumin. The electron dense deposits differed in distribution and character from those associated with membranoproliferative glomerulonephritis type II (dense deposit disease), amyloidosis, cryoglobulinemia, macroglobulinemia and benign monoclonal gammopathy. Serum from six of these patients did not bind to normal human or rat renal parenchyma in vitro. Kappa light chain nephropathy was characterized by predominant linear tubular basement membrane kappa deposits, and nodular mesangial and linear glomerular basement membrane kappa immunostaining. Lambda light chain nephropathy was characterized by linear lambda glomerular basement membrane and tubular basement membrane immunostaining. Manifestations of glomerular dysfunction dominated the clinical presentation of light chain nephropathy, and most patients did not have typical features of multiple myeloma. The diagnosis was predicated upon thorough immmunohistologic assessment of renal biopsy material.

Pulmonary vasculitis (Wegener's granulomatosis): Immunohistochemical study of T and B cell markers

A case of pulmonary vasculitis (Wegeners granulomatosis) is reported in which immunoperoxidase studies demonstrated that the vascular lymphoid infiltrates were composed predominantly of T cells and monocytes. Occasional T cells, B cells and monocytes were identified in the alveolar septa. IgG, IgA, IgM, and C3 were not identified in pulmonary vessels, septa, or alveoli. These findings suggest that cellular rather than humoral-immune mechanisms predominate in pulmonary vasculitis.

Clinical outcome of three discrete histologic patterns of injury in severe lupus glomerulonephritis.

There is a spectrum of glomerular pathology in patients with severe lupus glomerulonephritis (GN) that includes (1) severe segmental GN (SEG) with greater than or equal to 50% of glomeruli involved by active segmental inflammation, (2) diffuse GN, and (3) membranous GN with associated severe SEG or diffuse GN (MGN + PGN). The clinical and laboratory characteristics at entry and at follow-up of 85 patients in a prospective therapeutic trial of plasmapheresis were examined to determine if these morphologic variants had prognostic implications. Addition of plasmapheresis to the therapeutic regimen did not affect outcome, and the two treatment groups were analyzed together. Patients with the three patterns of lupus GN were similar demographically and clinically, and they had similar serum creatinines at entry (SEG, 1.87 +/- 0.28 mg/dL [mean +/- SE], v diffuse GN, 2.11 +/- 0.21, v MGN + PGN, 2.12 +/- 0.26; P = 0.75). Although significant differences were found in the initial serum C3 (SEG, 46 +/- 5 mg/dL, v diffuse GN, 34 +/- 3, v MGN + PGN, 45 +/- 3; P = 0.02) and urinary protein excretion (SEG, 3.6 +/- 0.6 g/24 h, v diffuse GN, 6.0 +/- 0.7, v MGN + PGN, 6.7 +/- 0.9; p = 0.03), none of the clinical or laboratory data predicted the morphologic pattern of the glomerular lesion. Adverse outcomes included defined clinical stop points, nonfatal renal failure, and death. One half of the patients with MGN + PGN (13/26) had an adverse outcome, compared with 5/24 patients with SEG and 11/35 patients with diffuse GN. This trend was supported by actuarial analysis of outcomes showing that patients with MGN + PGN had the lowest cumulative proportion without adverse outcome after 175 weeks of follow-up (MGN + PGN, 0.40, v SEG, 0.77, v diffuse GN, 0.64; P = 0.04). We concluded that (1) at presentation, the specific glomerular lesion in severe lupus GN cannot be predicted on clinical or serological criteria alone; (2) on the basis of morbidity and mortality, cases with all three morphologic variants should be classified as severe lupus GN; and (3) patients with MGN + PGN appear to experience more adverse outcomes than patients with SEG or diffuse GN.

Amyloidosis and Pleural Disease

Pleural involvement with systemic amyloidosis has been reported rarely in the literature. Diagnosis of this entity by percutaneous needle biopsy of the pleura has been described only in two prior case reports. We describe five patients in whom the diagnosis of pleural amyloidosis was established by Cope needle biopsy during evaluation of pleural effusions of indeterminate cause. Three patients presented with a history suggestive of multiorgan disease and a pleural biopsy performed despite a transudative effusion demonstrated amyloid infiltration of the pleura, obviating the need for other organ biopsies. We conclude that in patients with pleural effusions, if history suggests multiorgan involvement and there is suspicion for amyloidosis, then a closed pleural biopsy with special stains for amyloid should be performed even if the effusions are transudative. This may be the diagnostic procedure of choice in such patients.

Membranous glomerulopathy associated with captopril therapy

Two cases of nephrotic syndrome and biopsy-proved membranous glomerulopathy (membranous glomerulonephritis) were encountered during captopril treatment of 53 hypertensive subjects in our institution. Both patients had impaired renal function before treatment and were treated with 600 mg per day. Discontinuation of captopril led to transient partial remission of proteinuria but was followed by a recurrent, fluctuating course over one year later. Repeat biopsies, eight and 12 months after discontinuation of the drug, demonstrated persistent subepithelial deposits in the glomerular basement membrane. There has been a decline in glomerular filtration rate since discontinuation of the drug, apparently due to arterionephrosclerosis. These studies suggest that glomerular basement membrane deposits in captopril-associated membranous glomerulonephritis are not readily reversible and may be associated with persistent proteinuria, contrary to some previous reports.

Peripheral small cell undifferentiated carcinoma of the lung. Clinicopathologic features of 17 cases.

Seventeen cases of resectable peripheral small cell undifferentiated carcinoma of the lung were studied (average size, 2.1 cm; range, 0.9–3.5 cm). The carcinomas exhibited predominantly mixed intermediate and fusiform/spindle subtypes; in seven carcinomas there were at least some foci of oat cell subtype. There was no histologic evidence of typical carcinoid tumor. Seven cases were fixed in solutions appropriate for immunohistologic study; these exhibited prominent neuron‐specific enolase activity but less prominent and more variable staining for the carcinoembryonic antigen and cytokeratins. All 17 cases were deemed resectable and had no clinical or radiologic evidence of metastasis. Seven (41%) patients died with recurrent and/or metastatic carcinoma (average survival, 1.7 years); five of these patients had carcinomas with at least some foci of oat cell foci subtype.

Malignant melanoma of the bronchus.

A case of malignant melanoma of the bronchus is presented. The tumor obstructed the left main stem bronchus. Secondary pneumonia was probably caused by Hemophilus influenzae.

Comparison of alternative chromogens for renal immunohistochemistry

Renal immunomicroscopy using enzyme labeled reagents has been shown to be a reliable method for the identification of immunoglobulins and complement in the routine evaluation of glomerular disease. However, the potential carcinogenicity of benzidine derivatives used in the procedure represents a major disadvantage of the technique. With a series of 55 renal biopsy specimens evaluated by light microscopy, immunofluorescence, and electron microscopy from patients with a variety of renal diseases, a study was done comparing aminoethylcarbazole and the Hanker-Yates reagent (p-phenylenediamine and pyrocatechol), chromogens chemically unrelated to benzidine. Aminoethylcarbazole was not suitable for renal immunomicroscopy, since in cases of antiglomerular basement membrane disease the color reaction product was finely granular at high magnification. Specimens immunostained with the Hanker-Yates reagent yielded permanent water insoluble reaction products and immunomicroscopic patterns identical to the results observed with immunofluorescence in all cases. To our knowledge, no carcinogenic properties have been identified for p-phenylenediamine or pyrocatechol. The Hanker-Yates reagent may be used routinely for renal enzyme immunomicroscopic studies with no currently identified carcinogenic hazard to laboratory personnel.

Renal pathology in patients with primary hyperaldosteronism secondary to an adrenal cortical adenoma.

OBJECTIVES The cause of persistent hypertension following the removal of an aldosterone-producing adrenal adenoma is unknown. The purpose of this study was to determine whether this occurrence is due to existing renal histopathologic damage. METHODS Thirty-two patients with primary hyperaldosteronism due to an aldosterone-secreting adrenal cortical adenoma underwent open renal biopsy at the time of unilateral adrenalectomy. Biopsy results were correlated with the duration and severity of hypertension before and after surgery. RESULTS Nineteen patients were cured of their hypertension postoperatively, whereas 13 patients had persistent diastolic hypertension. Statistical analysis of these two groups revealed no difference when renal histopathologic variables, preoperative severity of hypertension, or preoperative duration of hypertension were compared. CONCLUSIONS Persistent hypertension in these patients does not appear to be due to renal histopathologic changes; coexisting essential hypertension is a more likely cause.