Therapy of anti-glomerular basement membrane antibody disease: analysis of prognostic significance of clinical, pathologic and treatment factors.

We have compared the effect of therapy with immunosuppression alone to immunosuppression plus plasma exchange on the clinical course and rate of disappearance of antibody in 17 patients with anti-glomerular basement membrane (anti-GBM) antibody-induced renal disease. Patients receiving immunosuppression (n = 9) and those receiving plasma exchange (n = 8) were similar in terms of entry clinical characteristics, pulmonary manifestations and complications associated with therapy. Rate of disappearance of anti-GBM antibody as estimated from serial estimates of antibody binding was significantly more rapid in patients receiving plasma exchange, and mean serum creatinine in these patients at end of therapy was half that of the patients receiving immunosuppression alone. Analysis of clinical and pathologic values at study entry, however, indicated that the percent of crescents on initial renal biopsy and entry serum creatinine correlated better with outcome than did therapeutic modality. Thus, though plasma exchange may offer some advantage over immunosuppression alone in the treatment of this disease, degree of pathologic involvement appears to be the major factor affecting outcome. Patients with low cresents (less than 30%) and well preserved function did well with either treatment, while patients with severe crescentic involvement and impaired glomerular filtration rate did poorly.

Immune complex glomerulonephritis in sicca syndrome.

In three patients with the sicca syndrome (Sjögren's syndrome), who were followed for one to seven years, glomerulonephritis developed. None of these patients fulfilled the diagnostic criteria for systemic lupus erythematosus. All of these patients had circulating immune complexes as detected by the Clq binding assay. Glomerular histology by light and electron microscopy revealed changes compatible with membranoproliferative glomerulonephritis in two of the patients and membranous glomerulonephritis in the third. All patients showed rapid improvement in renal function following moderate doses of corticosteroids. In addition, the treatment decreased the level of circulating immune complexes in two patients who were followed for a sufficient period of time.

Renal proliferative arteriopathies and associated glomerular changes: a light and electron microscopic study.

This presentation reports the light and electron microscopic findings relating to the vascular and glomerular changes in the kidney in a series of 25 patients having malignant hypertension, the hemolytic-uremic syndrome, scleroderma, or toxemia of pregnancy. The pathologic changes were generally similar in each of the diseases studied, the changes being related more to the severity and duration of injury than to the specific disease. Vascular narrowing was due mainly to intimal thickening, and by light microscopy the lesions were categorized as onionskin, mucinous, or fibrous with or without associated elastosis. Intimal erythrocyte extravasation, fibrinoid necrosis, and luminal thrombosis were also seen. Electron microscopy provided additional morphologic information: Myointimal cells were found to be the cellular component in each type of intimal thickening; it was possible to distinguish collagen from large intimal accumulations of basement membrane material; mucinous intimal material was characterized ultrastructurally; and fibrinoid necrosis was identified as a lesion inconstantly associated with cellular necrosis and consisting mainly of fibrinoid material and small deposits of fibrin. It seems likely that there is a common pathogenesis for intimal thickening in a variety of diseases and that this involves endothelial cell damage and increased permeability, leakage of serum and erythrocytes into the intima, and a healing reaction of the vessel wall was developing from migration of smooth muscle cells into the intima with subsequent myointimal cell proliferation and fibrogenesis. A common glomerular change in all diseases studied was a striking accumulation of electron lucent material between the endothelium and the lamina densa of the basement membrane. This lesion was interpreted as a manifestation of acute ischemia.

High sucrose diets increase blood pressure of both salt-sensitive and salt-resistant rats.

We examined the effects of a diet relatively high in sugar and low in protein content on systolic blood pressure (SBP) in rats with known pressure responses to salt (NaCl) in order to compare "sugar/protein sensitivity" to "salt sensitivity." Dahl salt-sensitive (DSS) and salt-resistant (DSR) rats were fed one of two low salt diets containing either high sugar (sucrose 51.5% w/w)/low protein (14.6% w/w) or low sugar (sucrose 12.5% w/w)/high protein (52.2% w/w) content. After 3 weeks, the DSS ingesting the high sugar diet/low protein diet developed significantly elevated SBP relative to DSR eating the same high sugar/low protein diet and the DSS and DSR consuming the low sugar/high protein diet. After 2 to 3 months, the SBP of DSR eating the high sugar diet began to rise markedly and eventually both DSS and DSR ingesting the high sugar/low protein diet maintained similarly elevated SBP, significantly higher than DSS and DSR ingesting the low sugar/high protein diet. When Fischer 344 rats, a normotensive, salt-resistant rat strain, were fed the high sucrose/low protein diet, SBP also rose significantly into hypertensive ranges over 2 to 3 months. Since the SBP of DSR and Fischer 344 rats are not influenced to any great extent by high salt intake, even after prolonged exposure, the SBP rise associated with the high sugar/low protein diet may be via a mechanism different from salt-induced hypertension. However, it is also possible that the high sugar/low protein diet creates in DSS and DSR the situation responsible for salt induction in DSS.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal function of baboons (Papio hamadryas) with a remnant kidney, and impact of different protein diets.

To assess progression of renal disease and the effects of protein intake in a species phylogenically close to man, 10 young adult baboons (Papio hamadryas) were subjected to 20 to 30% infarction of the left kidney and, two months later, to right nephrectomy. They were then randomized to a synthetic diet containing either 8% or 25% protein. Hemodynamic and metabolic measurements were obtained in awake animals every four months. Baseline mean blood pressure, inulin clearance, protein and urea nitrogen excretion in intact animals on 15% protein averaged 75.5 +/- 3.5 (SE) mm Hg, 42.9 +/- 2.7 ml/min, 52 +/- 4.3 mg/24 hr, and 3.8 +/- 0.4 g/24 hr, respectively. At 12 months, values in the same baboons with a remnant kidney on 8% versus 25% protein averaged 100.6 versus 96.7 mm Hg, 29.2 versus 54.9 ml/min (P less than 0.01), 111 versus 108 mg/24 hr, and 3.4 versus 11.0 g/24 hr (P less than 0.001), respectively. Electron microscopic examination of renal biopsies obtained eight months after nephrectomy was normal but for slightly increased mesangial matrix in three animals. Thus, blood pressure increased (P less than 0.01), proteinuria doubled (P less than 0.01) and adaptations in GFR developed within four months of renal mass reduction, without significant changes occurring between four and 12 months. The adaptations in GFR were markedly attenuated by low protein intake. Further follow-up is necessary to assess progression of renal disease and the impact of different protein diets.

Goodpasture's syndrome--local and diffuse deposition of antibody in glomerular basement membrane. Case report.

An unusual case of Goodpasture's syndrome in a 22 year old white female is presented. The diagnosis of antiglomerular basement membrane disease was made on the basis of circulating anti-GBM antibodies in the presence of linear IgG deposits along the glomerular basement membrane by immunofluorescent microscopy. An additional finding was the presence of discrete granular subepithelial deposits on electron microscopy. Possible pathogenetic mechanisms are discussed.

Nail-patella syndrome.

Three cases with collagenation of glomerular basement membrane are presented. The ages of the patients are 8, 13, and 27 years. An 8-year-old boy presented with nephrotic syndrome; a 13-year-old girl presented with recurrent urinary tract infections, proteinuria, and edema; and a 27-year-old woman was noted during the evaluation of a cardiac murmur to have proteinuria and renal insufficiency. The changes on electron microscopy were identical to those observed in nail-patella syndrome, a rare hereditary disease with ectodermal and mesodermal involvement, manifested as bony and nail abnormalities. Nephropathy is now a well established part of this syndrome. Our cases did not have the typical bony and nail changes. We feel these three cases represent a partial gene penetrance or manifestation of only a portion of gene complex involved in this syndrome.

Gold nephropathy.

The early use of gold in medicine and dentistry dates back to the ancient Chinese and Egyptians. The discovery in 1890 that gold salts were toxic in vitro to tubercle bacilli led to the extensive treatment of tuberculosis with gold salts in the first three decades of this century. Eventually, gold therapy was extended to arthritis and lupus erythematosus, because of the belief that these diseases were forms of tuberculosis. Because of its beneficial effect particularly on active rheumatoid arthritis, chrysotherapy has remained one of the most widely used treatments of rheumatoid arthritis for the past half century. Toxicity of gold salts includes hypersensitivity reaction of skin and mucous membranes, bone marrow depression, and nephrotoxicity. The nephrotoxic clinical manifestations are renal insufficiency, proteinuria and hematuria, and the nephrotic syndrome. The pathologic changes are tubular degeneration, acute tubular necrosis or immune complex glomerulonephritis. The justification that any of these possible changes are the result of gold therapy rests clinically upon the time relationship of gold therapy and the renal symptoms, and pathologically upon the presence of gold inclusions (aurosomes) in proximal tubular epithelial cells. Aurosomes can at times be visualized by light microscopy, are usually seen by electron microscopy, and can be identified by microprobe analysis. Their pathology will be illustrated and pathogenic mechanisms discussed.

Effect of chronic growth hormone administration on diabetic nephropathy in the rat.

Indirect data exist which implicate elevated growth hormone (GH) as a factor in the development of diabetic nephropathy. The administration of somatostatin (SRIH) has been shown to reverse many of the changes found in early diabetic nephropathy; however, it is unknown whether SRIH causes these effects by the suppression of GH or by other unspecified factors. To study directly the possible effect of excess GH in the development of diabetic nephropathy, either ovine growth hormone (0.2 mg oGH) or diluent buffer was administered IM daily for 19 weeks to diabetic rats and to controls. Severity of nephropathy was assessed by 24 hour urine albumin excretion (UAE), relative kidney weight, and kidney histology. Results showed that diabetic rats overall had elevated UAE and kidney weight vs non-diabetic rats (46.2 +/- 8.6 vs 5.4 +/- 1.3 mg per day and 5.7 +/- 0.2 vs 2.7 +/- 0.1 mg per g of body weight, respectively, p < 0.001). However, no differences were detected between diabetic rats treated with GH compared to control diabetic rats. Additionally, diabetic rats had histopathologic changes consistent with early diabetic nephropathy, but no difference in severity scores was found between diabetic groups. These data provide evidence against GH as an etiologic factor in the development of diabetic nephropathy and it is speculated by the authors that SRIH exerts its protective renal effects in diabetes by mechanisms other than GH suppression.

A study of membranoproliferative glomerulonephritis in Iran.

BACKGROUND: The aim of this study was to review the morphologic patterns of membranoproliferative glomerulonephritis (MPGN) in 100 Iranian patients using light microscopy (LM) and electron microscopy (EM), and to compare the treatment and outcome in 13 patients with two biopsies. PATIENTS AND METHODS: A retrospective study of 713 kidney biopsies of Iranian patients received between 1981 to 1994 was carried out. Of the 713 kidney biopsies, MPGN (n=106) and membranous glomerulopathy (n=112) made up the highest numbers of cases. RESULTS: Among 100 MPGN patients, 55 (55%) were MPGN type I, 10 were type II (10%), and 35 type III (35%). Eighty-three (83%) had nephrotic proteinuria, 39 (39%) had hematuria, and 52 (52%) were hypertensive. Complement levels were estimated in 58, with low C3 in 10. The glomerular involvement was irregular, with focal hypercellularity in 47 patients (47%), widely patent capillaries in 50 (50%), arteriosclerosis in 48 (48%), and with hyaline change in 25 (25%). Follow-up data (22-130 months) was available in 61 (61%) patients: 6 (10%) died after 14-56 months, 27 (44%) were on maintenance hemodialysis for 15-110 months, and three received transplants. Thirteen patients had detailed follow-up and a second biopsy after 24-120 months. All 13 presented with edema and nephrotic range proteinuria, with hematuria and hypertension in five and azotemia in four. Seven of the 13 patients received initial steroids, followed by antiplatelet or antihypertensive drugs. Four (type III) patients received antiplatelet and antihypertension drugs, and two (type III) received only antihypertensive drugs. In the first biopsy, glomerular changes by light microscopy were non-uniform in 7 of 10 (70%) type III MPGN cases. Vascular changes were absent or mild in 11, and moderate in two. In the second biopsies, 10 showed decrease in cellularity, with many open capillaries, persistence of deposits by EM in all, and progression of vascular sclerosis in eight, and tubulointerstitial changes in 10. Among the 13, six were clinically stable, another six received dialysis followed by transplant in three, and one had relapses with episodes of cryoglobulinemia. Three patients died. CONCLUSION: There is a high incidence of MPGN in Iranian patients, with a substantial number of type III MPGN cases. Second biopsies showed decreased cellularity, but increase in chronic tubulointerstitial and vascular cases. Steroids did not appear to benefit the outcome in types I and III MPGN patients compared to patients who received antihypertensive and antiplatelet treatment without steroids.

Diabetic nephropathy with superimposed immune complex glomerulonephritis.

We describe six diabetic patients with superimposed immune complex glomerulonephritis. Renal manifestations included sudden change in renal function with hematuria in three patients and massive proteinuria in the other three. Renal histology showed the characteristic changes of diabetic nephropathy along with those of immune complex glomerulonephritis. Biopsy revealed the explanation for the sudden renal changes, thus emphasizing its importance in management of these patients.

Nonamyloidotic fibrillary glomerulopathy, immunotactoid glomerulopathy, and the differential diagnosis of filamentous glomerulopathies.

Kidney biopsies from 12 patients between the ages of 10 and 63 yr were diagnosed as nonamyloidotic fibrillary glomerulopathy (NAFG) or immunotactoid glomerulopathy (IG) on the basis of the electron microscopic finding of filamentous or tubular material within the glomerular capillaries and mesangium. Six patients were male and six were female. Eleven presented with nephrotic syndrome and one with acute renal failure. Eight were hypertensive, and four of these patients had gross or microscopic hematuria as well. Biopsies from 11 patients were Congo red negative; one was weakly positive. By light microscopy, the predominant glomerular change was thickening of the capillary basement membrane with or without widening of the mesangium; these changes were suggestive of membranous glomerulonephritis. Immunofluorescent studies performed in four of the cases were positive for immunoglobulin G (IgG). Immunoperoxidase staining for beta 2-microglobulin was negative in four patients. Ultrastructurally, filaments or tubules were identified in the glomerular capillary basement membrane and/or mesangium in each patient. The filaments in NAFG, IG, amyloidosis, and other paraprotein deposits can be differentiated by size, arrangement, and location of filamentous material.

Some unusual features of mesangioproliferative glomerulonephritis in horses.

Seven horses ranging from three to 15 years of age had nephrotic syndrome; at necropsy, renal tissue of all seven horses had the morphologic lesions of mesangioproliferative glomerulonephritis (membranoproliferative glomerulonephritis). Homogeneous eosinophilic material which filled the glomerular capillary lumina was found in five horses. Ultrastructurally, this material primarily consisted of electron-dense deposits with a fibrillar pattern in five horses and in one horse, rhomboid crystalline deposits which resembled deposits seen in human cryoglobulinemia. The association of mesangioproliferative glomerulonephritis with cryoglobulinemia is well documented in man. The presence of intracapillary deposits, with the histologic and ultrastructural lesion of mesangioproliferative glomerulonephritis, suggests a similar association in these horses.

Focal glomerulosclerosis in children: correlation of histology with prognosis.

The clinical and pathologic data of 32 nephrotic children diagnosed as having focal glomerulosclerosis were retrospectively analyzed to determine what factors were responsible for progression to renal failure in 12 of these children. The patients were classified into three groups based on the histologic findings in their initial renal biopsies: Group I (n = 19) had a combination of global and segmental lesions; Group II (n = 8) had only globally sclerotic or obsolescent glomeruli; and Group III (n = 5) had only segmentally sclerosed glomeruli. Ten of the 12 patients with end-stage renal failure came from Group I and two from Group II. The median period from recognition of symptoms to renal failure was four years. Clinical features were of little prognostic value. However, comparison of the histopathologic data of the ten patients in Group I with renal failure (Group Ia) and Groups Ib, II, and III revealed that the risk of progressing to renal failure was significantly higher in patients having greater than 20% of their glomeruli involved by both global and segmental lesions (P = 0.005). Furthermore, patients in Group I and III had a lower probability of responding to treatment as compared to patients in Group II (P less than 0.025).

Effect of protein diets on the renal function of baboons (Papio hamadryas) with remnant kidneys: a 5-year follow-up.

To assess the progression of renal disease and the effects of protein intake in a species phylogenically close to humans, 14 adolescent baboons (Papio hamadryas) were subjected to infarction of one third of the left kidney and, 2 months later, to right nephrectomy. They were then randomized to a synthetic protein diet containing either 8% or 25% casein. Hemodynamic and metabolic measurements were obtained in awake animals every 4 months. Modest proteinuria developed immediately after left kidney infarction, and hypertension after right nephrectomy. Proteinuria and hypertension, however, were similar in both groups and did not progress for the next 60 months. Inulin clearance markedly increased with implementation of the synthetic diet in baboons given 25% protein, in contrast to animals given 8% protein, averaging 46.6 +/- 4.7 mL/min versus 28.2 +/- 2.6 mL/min, respectively, after 4 months. The glomerular filtration rate (GFR) changed little immediately thereafter and, at 1 year, averaged 43.0 +/- 1.4 mL/min and 28.0 +/- 4.3 mL/min, respectively. During the next 4 years, however, inulin clearance steadily decreased in baboons fed 25% protein. The inverse correlation between inulin clearance and time of follow-up was y = 48.5 - 0.36x (r = -0.879, P < 0.001) in baboons fed 25% protein and y = 29.0 - 0.11x (r = -0.625, P < 0.02) in baboons fed 8% protein. Nevertheless, after 5 years, the mean GFR was still significantly greater in animals given the 25% protein diet than in baboons fed 8% protein, averaging 29.1 +/- 0.6 mL/min and 24.1 +/- 1.0 mL/min, respectively (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)