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Biomedical subjects

T T Antonovych

Publications and source records attributed to T T Antonovych.

At least 19 recordsLinked to original sources
PubMed1994

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)

Animals↗
PubMed1992

NIH conference. Membranous nephropathy.

Membranous nephropathy is a worldwide problem that accounts for about 20% of the cases of the adult-onset nephrotic syndrome. This disease places many patients at risk for both end-stage renal failure and the complications of hyperlipidemia. Immune-mediated injury to the glomerular capillary wall in patients with membranous nephropathy is characterized by subepithelial immune complex formation and generation of the membrane attack complex of complement. Glomerular capillary hypertension, hyperlipidemia, and possibly cytokines could contribute to the glomerular sclerosis seen in the advanced stages of the disorder. In some cases, production of pathogenic antibody can be suppressed by treating the underlying condition. The mechanisms of action of immunosuppressive agents are being investigated and treatments are being tested in clinical trials to optimize the balance of efficacy and toxicity. Alternate-day treatment with corticosteroids is often recommended for nephrotic patients with idiopathic membranous nephropathy, but this approach has not been proved beneficial. Ongoing studies are evaluating whether cytotoxic drugs or cyclosporin A combined with prednisone is more effective than treatment with corticosteroids alone. Lipid-lowering drug therapy is warranted in cases of the persistent nephrotic syndrome to avert the cardiovascular sequelae of hyperlipidemia.

Animals↗
PubMed1992

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)

Administration, Oral↗
PubMed1991

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.

Actin Cytoskeleton↗
PubMed1989

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.

Autoimmune Diseases↗
PubMed1989

Renal medullary amyloidosis in Dorcas gazelles.

Between January 1976 and September 1987 renal medullary amyloidosis (RMA) was diagnosed in 17 Dorcas gazelles; the necropsy prevalence rate was 17/32 (53%). The most severe amyloid deposits were in the renal medulla; glomeruli were spared. Renal cortical lesions of interstitial fibrosis and tubular atrophy and dilatation significantly correlated with RMA (P less than 0.01) and were considered to be secondary changes. There were varying degrees of lymphoplasmacytic inflammation and tubular cast formation which did not significantly correlate with RMA. Amyloid was confirmed histochemically and by electron microscopy and was identified as AA type by the permanganate method. Progressive renal failure was the cause of death or necessitated euthanasia in 7/17 (41%) gazelles. RMA in Dorcas gazelles does not appear to be familial. A high prevalence of chronic or recurring Actinomyces (Corynebacterium) pyogenes infections may be an important factor.

Actinomyces↗
PubMed1989

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.

Adolescent↗
PubMed1989

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.

Animals↗
PubMed1987

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.

Acquired Immunodeficiency Syndrome↗
PubMed1987

NIH conference. Lupus nephritis.

Nephritis has long been considered one of the most ominous components of systemic lupus erythematosus. Accumulations of immune complexes and lymphoid cells in several locations within the kidney are the best-described elements of lupus nephritis. The extreme diversity of the renal changes indicates that many variables are likely to be involved. Inbred strains of lupus-prone mice have provided homogeneous subjects for study of pathogenesis and response to treatment. Comparable grouping of lupus nephritis in humans according to unique or dominant pathogenetic mechanisms is imprecise and limited by insufficient knowledge of the primary stimulus for the disease. Treatment is also imperfect and, at times, hazardous. Certain regimens incorporating cytotoxic drugs provide a significant therapeutic advantage over corticosteroids alone in the management of this disease.

Adult↗
PubMed1986

Renal histopathologic alterations in patients treated with cyclosporine for uveitis.

To evaluate abnormalities of renal morphology associated with long-term cyclosporine therapy, we obtained percutaneous renal biopsy specimens from 17 patients who had been treated for autoimmune uveitis with cyclosporine for an average of two years. For comparison, we also analyzed renal biopsy specimens from patients with idiopathic hematuria who had not received cyclosporine. The atrophic and sclerosing glomerular and tubulointerstitial lesions in the specimens were assessed to derive a chronicity index. The specimens from the patients treated with cyclosporine showed a significantly higher chronicity index than those from the controls (P less than 0.00005). All patients who had received cyclosporine had interstitial fibrosis, tubular atrophy, or both. A good functional predictor of the abnormalities in renal morphology was the length of time that a patient's serum creatinine had exceeded the base-line value by more than 50 percent. Chronic pathologic alterations were seen even in patients who had normal renal function at the time of the biopsy. In conjunction with sequential measurements of renal function, renal biopsy may have an important role in defining the type and degree of nephrotoxicity that can develop in patients receiving long-term cyclosporine therapy for autoimmune disease.

Adolescent↗
PubMed1985

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.

Adolescent↗
PubMed1984

Effect of treatment on the evolution of renal abnormalities in lupus nephritis.

We retrospectively studied the evolution of histopathologic features in successive renal biopsies in patients with lupus nephritis, to evaluate the effects of various treatment regimens. Repeat renal biopsies had been performed in 62 patients after more than 18 months of observation (median interval, 44 months) in randomized therapeutic trials comparing prednisone with cytotoxic drugs. Renal histopathologic features were graded individually, and a composite score reflecting the number and severity of irreversible lesions was defined as a chronicity index. The chronicity index for patients treated with conventional high-dose prednisone increased linearly with the interval between biopsies, whereas the index in the group receiving cytotoxic-drug treatments did not increase over time. After statistical adjustment for important prognostic factors (age and initial chronicity index) identified by multiple linear regression, the difference in the slopes between the group receiving prednisone and the group receiving cytotoxic drugs was significant (P less than 0.0001). We conclude that cytotoxic-drug treatment reduces the likelihood of progressive renal scarring in lupus nephritis.

Adult↗
PubMed1984

Diffuse proliferative lupus nephritis: identification of specific pathologic features affecting renal outcome.

Prerandomization renal biopsy specimens were examined in 102 patients upon entry into prospective therapeutic trials of lupus nephritis in an attempt to identify early predictors of renal failure outcome. All 11 renal failures occurred among the 72 individuals with diffuse proliferative or membranoproliferative glomerulonephritis (DPGN/MPGN); thus, these patients were at modestly, but significantly, increased risk of endstage renal disease compared to those with focal proliferative, membranous, or mesangial glomerulonephritis. Considering the low incidence of endstage renal disease among patients with DPGN/MPGN, we sought to refine the prognostic information obtained from renal morphology by semiquantitative scoring of individual histologic features and by derivation of composite histologic scores specified by Activity (AI) and Chronicity (CI) Indices. Among the 72 patients with DPGN/MPGN, the composite AI was more strongly predictive of renal failure than were the individual active histologic features; cellular crescents and extensive fibrinoid necrosis yielded positive associations, while endocapillary proliferation, leucocytic exudation, and hyaline thrombi in glomeruli and interstitial inflammation by themselves did not emerge as useful prognostic indicators. However, chronicity items (glomerular sclerosis, fibrous crescents, tubular atrophy, and interstitial fibrosis) considered individually, as well as in the composite CI, were highly predictive of renal failure outcome. Particularly striking was the prognostic value of tubular atrophy; all 11 renal failures were among the 43 patients with tubular atrophy on prerandomization renal biopsy. While no single pathologic variable improved outcome predictions among those with tubular atrophy, examination for interactions among variables revealed that glomerular sclerosis and cellular crescents had a synergistic effect which augmented the prognostic information derived from analysis of tubular atrophy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

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.

Animals↗