Renal sarcoidosis with superimposed postinfectious glomerulonephritis presenting as acute renal failure.

We describe two patients with sarcoidosis with lesions of granulomatous interstitial nephritis (GIN) and postinfectious glomerulonephritis (GN). Both patients presented with heavy proteinuria, hematuria, and renal failure. Renal histology in both showed GIN and glomerular changes of proliferative GN with hump-like subepithelial deposits by electron microscopy of postinfectious GN. Antecedent history of pneumonia was present in one, and ASO titer was elevated in the other. The proteinuria and azotemia improved in both with steroid therapy. Reports of "postinfectious" or diffuse proliferative GN in patients with sarcoidosis are rare. The authors are unaware of reports of concomitant sarcoid GIN and postinfectious GN. Although acute renal insufficiency or failure can occur with GIN or other more common renal lesions primary glomerular disease should be considered in patients with sarcoidosis who present with renal dysfunction. This is a US government work. There are no restrictions on its use.

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.

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.

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.

Acute renal allograft rejection following pegylated IFN-alpha treatment for chronic HCV in a repeat allograft recipient on hemodialysis: a case report.

Interferon alpha (IFN-alpha) can be effective therapy for patients with chronic kidney disease who have chronic hepatitis C (HCV). However, acute allograft rejection has been reported in association with IFN-alpha following kidney transplantation, and therefore IFN therapy is recommended prior to, rather than after, kidney transplantation whenever feasible. The special case of repeat allograft recipients who contract HCV after the first transplantation presents special difficulties. This report features the case of a repeat allograft recipient who presented with neutropenic fevers after 5 months of pegylated IFN-alpha therapy, initiated 6 months following the functional loss of his third graft and the reinitiation of hemodialysis (HD). Physical exam, radiographic and laboratory findings led to allograft nephrectomy. The pathologic findings supported a diagnosis of acute-on-chronic rejection. This represents a rare case of IFN-alpha induced rejection following allograft failure and return to HD in a repeat allograft recipient. It also calls attention to the need for a high index of suspicion for the development of allograft rejection, which may require allograft nephrectomy even after allograft 'failure'.

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.

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.

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.

Renal tubular hyperplasia, polycystic disease, and glomerulosclerosis in transgenic mice overexpressing hepatocyte growth factor/scatter factor.

Hepatocyte growth factor/scatter factor (HGF/SF) has been implicated as a renotrophic agent, capable of stimulating renal regeneration after unilateral nephrectomy or acute kidney failure. However, evaluation of the therapeutic utility of HGF/SF requires thorough analysis of its effects in an appropriate in vivo model system. To this end, the renal structure and function in HGF/SF transgenic mice were examined. Mice overexpressing HGF/SF in the kidney and serum demonstrated prominent tubular cystic disease and progressive glomerulosclerosis, and were susceptible to premature death from renal failure. The tubular phenotype appeared to result from HGF/SF-Met autocrine stimulation of the tubular epithelium and consequent hyperplasia. Electron microscopic examination of glomeruli, which also showed enhanced cellular proliferation, revealed ultrastructural features consistent with focal segmental glomerulosclerosis: an increase in mesangial matrix, effacement of foot processes, and thickening of basement membrane. These changes were not present at birth but developed progressively with age, which is consistent with the notion that HGF/SF may not be essential for the early stages of nephrogenesis, but may play an important role in renal epithelial renewal and regeneration. Thus, HGF/SF transgenic mice could be a useful model for dissecting the molecular mechanisms leading to polycystic disease and focal segmental glomerulosclerosis. Moreover, our results suggest that caution should be used when considering HGF/SF as a future therapeutic agent.

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)

A syndrome of immune complex glomerulonephritis and ophthalmic abnormalities.

Two sibs (one male and one female) suffering from a combination of immune complex glomerulonephritis and various ophthalmologic disorders are presented. The two cases belong to a family in which the parents are not related and seven sibs are affected, three females and a male with the combination, and three males with severe ophthalmological changes and proteinuria. Clinically, case 2 had only ophthalmological manifestations but renal biopsy findings were similar to those of case 1, which could mean that all the others with eye abnormalities also had renal disease. Although there are several reports of combinations of eye and renal disorders, the sibs reported here do not fit into any of the known syndromes.

Morphologic differences between polyarteritis and Wegener's granulomatosis using light, electron and immunohistochemical techniques.

The differential diagnosis of renal biopsies of patients with polyarteritis nodosa (PAN) versus those with Wegener's granulomatosis (WG) is difficult because in both the morphologic expression is a focal proliferating and necrotizing glomerulonephritis (GN) with crescents. Twenty-nine biopsies of PAN and 29 of WG were studied by light, electron microscopy and immunohistochemistry. Whereas in PAN the dominent feature is severe focal fibrinoid necrosis of glomerular tufts, WG is characterized by destructive extracapillary GN with capsular breaks and periglomerulitis leading to complete glomerular destruction and replacement by a localized inflammatory exudate in the form of a granuloma. In PAN necrotizing arteritis is common (19 of 29), whereas only 1 of 29 cases of WG showed arteritis. Depending on the stage of the disease, various types of hematogenous cells can be seen in both. In general, the dominent cell type in PAN is polymorphonuclear cells (PMNs) with or without eosinophils, whereas in WG mononuclear cells dominate the picture. Monocytes and macrophages, including giant cells in the crescents, periglomerular infiltrates, and in the granulomas are seen, whereas in the interstitium, plasma cells predominate. The histologic ultrastructural and immunohistochemical findings in both groups will be discussed.

Nephrotic syndrome associated with chronic persistent hepatitis B in an HIV antibody positive patient.

Several renal diseases have been reported to complicate both hepatitis B and human immunodeficiency virus infection. Establishing the exact renal diagnosis in patients with multiple viral infections requires renal biopsy. Exposure to human immunodeficiency virus may not determine renal histopathology. Although exact prognosis depends on a definitive diagnosis, treatment options may be limited in the face of several viral infections and concurrent exposure to human immunodeficiency virus.

Evolution of ciclosporin nephrotoxicity in patients treated for autoimmune uveitis.

Among 73 patients treated with ciclosporin (CS) for autoimmune uveitis, a 50% elevation of serum creatinine was observed in 37% within 3 months of starting CS and in 25% after more than 6 months of relatively uncomplicated therapy. Sequential renal function and histologic evaluations were performed in 17 patients to further characterize the nephrotoxic effects of long-term CS therapy. Inulin clearance remained essentially unchanged in 12 patients despite CS dosage reductions in the majority. In 2 such patients, repeat renal biopsy specimens revealed evidence of progressive irreversible kidney injury even though renal function was stable. Inulin clearance decreased substantially in 3 patients; in 1 case a follow-up renal biopsy showed increased severity of chronic histologic change. For 2 patients, the inulin clearance more than doubled after CS dosage reduction; and in 1 of those cases, repeat renal biopsy showed no evidence of progressive renal scarring. Overall, the morphologic attributes of irreversible kidney injury (designated by a chronicity index including glomerular sclerosis, tubular atrophy and interstitial fibrosis) were increased in 3 of 6 follow-up renal biopsy specimens. Histologic alterations of renal arterioles, including hyaline change, were observed in all CS-treated patients. The hyaline change of arterioles was either extensive in the first renal biopsy specimen or became extensive in the second biopsy in the 3 cases manifesting an increased chronicity index on the follow-up renal biopsy. Thus, parenchymal injury can progress in some cases despite CS dosage reduction and stable renal function; renal arteriolar histologic change is a prominent finding in these patients. Patients that exhibit a substantial improvement in renal function after dosage reduction may experience a more favorable course.

Chronic dialysis in a patient with cystic fibrosis.

To our knowledge this is the first case reported in the literature of a patient with cystic fibrosis and end-stage renal disease, who was on dialysis for 2 years. We discuss here the possible mechanisms responsible for what has been called 'the cystic fibrosis nephropathy' and its consequences.