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Biomedical subjects

H A Austin

Publications and source records attributed to H A Austin.

68 records · Page 4Linked to original sources
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↗
PubMed1983

Prognostic factors in lupus nephritis. Contribution of renal histologic data.

The predictive value of laboratory results and renal histologic data was examined in 102 patients upon entry into prospective, randomized, therapeutic trials of lupus nephritis. Three clinical features at the time of entry into the study were individually associated with increased rates of renal failure: age less than 24 years, male gender, and an elevated serum creatinine level. Subjects with diffuse proliferative or membranoproliferative glomerulonephritis were at a modest but significantly increased risk for the development of end-stage renal disease compared with patients with other classes of lupus nephritis. Semiquantitative scores of histologic features (specified by activity and chronicity indexes) identified subgroups of patients with comparatively high renal failure rates. To address the controversial issue of whether renal histologic data significantly improve the outcome predictions in patients with lupus nephritis, multivariate survival models were generated, permitting simultaneous consideration of multiple prognostic factors. Outcome predictions based on the strongest clinical predictors (age, sex, and serum creatinine level) were significantly enhanced by the addition of activity and chronicity indexes. Only age and chronicity index contributed significantly to the five-variable model and together constituted a two-variable model, the predictions of which were similar to observed outcomes. In the context of the highly significant prognostic indicators (age and chronicity index), immunosuppressive agents appeared to provide a slight therapeutic advantage over oral corticosteroids alone.

Adolescent↗
PubMed1983

Henoch-Schönlein nephritis: prognostic features and the challenge of therapy.

Henoch-Schönlein purpura is an intriguing entity of uncertain etiology associated with circulating IaA immune complexes, enhanced spontaneous immunoglobulin production, and an apparent imbalance in T cell regulatory functions. The associated glomerulonephritis is highly variable in nature and may profoundly influence clinical outcome. Prognostic features are reviewed in an effort to identify high-risk patients. Age, non-renal manifestations, non-selectivity of proteinuria, and evidence of preceding streptococcal infection are relatively weak predictors of end-stage renal disease. The presenting clinical and histologic expressions of nephritis are more useful prognosticators, but neither are completely reliable. Patients with greater than 50% crescents, and those with nephrotic syndrome complicated by various combinations of hypertension, azotemia, oliguria, and/or hypoproteinemia, are at increased risk of renal failure and might benefit from therapeutic interventions. Experience with various modalities is reviewed. Faced with uncontrolled clinical data, it is unclear whether immunosuppressive agents or plasmapheresis offer a therapeutic advantage over oral corticosteroids alone.

Adolescent↗
PubMed1983

Polyamine metabolism in compensatory renal growth.

The aliphatic polyamines, putrescine, spermidine, and spermine, appear to play an important role in many forms of rapid growth including embryonic, regenerative, hormone-induced, and neoplastic. While the exact biochemical function of polyamines is unclear, current evidence suggests they are probably involved in the biosynthesis and accumulation of nucleic acids and proteins. Increased levels of polyamines and their biosynthetic enzymes are associated with augmented kidney growth stimulated by renal mass extirpation, as well as by various hormones, toxins, and carcinogens. These observations are reviewed and additional data is provided pertaining to alterations in polyamine metabolism during compensatory renal growth following unilateral nephrectomy (uni). To further explore the effect of growth stimuli on renal polyamine synthesis, an in vitro system was employed which previously provided evidence for a circulating renal growth factor after unilateral nephrectomy. These in vitro observations underscore the rapid inducibility of ornithine decarboxylase, the rate limiting enzyme for polyamine biosynthesis; illustrate the association of polyamine and nucleic acid synthesis during enhanced kidney growth; and support the existence of a circulating renal growth regulator which apparently contributes to compensatory responses following loss of functional renal parenchyma.

Animals↗
PubMed1983

Controlled studies of oral immunosuppressive drugs in lupus nephritis. A long-term follow-up.

From 1969 to 1975, 53 patients with lupus nephritis took part in randomized trials comparing prednisone, oral azathioprine plus low-dose prednisone, and oral cyclophosphamide plus low-dose prednisone. After a mean follow-up of 85 months, cyclophosphamide appears marginally superior to prednisone for maintaining renal function (p = 0.03) and preventing end-stage renal failure (p = 0.07). Chronic change shown by renal biopsy assessed by a chronicity index was found useful in predicting renal function outcomes and response to immunosuppressive therapy. Three of 21 patients with a low chronicity index and 9 of 10 patients with a high chronicity index doubled their serum creatinine (p less than 0.00003). The probability of renal functional deterioration was not different among the treatments studied. However, in 14 patients with an intermediate chronicity index, 1 of 11 patients treated with azathioprine or cyclophosphamide doubled the serum creatinine level whereas all 3 patients treated with prednisone have progressed to end-stage renal failure (p = 0.005). The study suggests that single-drug oral immunosuppressive treatment combined with prednisone is most beneficial in lupus patients with intermediate chronic change shown by renal biopsy.

Administration, Oral↗
PubMedDate not supplied

Clearance of gadolinium chelates by hemodialysis: an in vitro study.

Although the gadolinium (Gd)-chelates currently approved for clinical use in the United States are considered "readily dialyzable," the actual clearance rates have not been published. The purpose of this study was to establish in vitro dialysis clearance rates of Gd-chelates to develop rational strategies for removing the agents with dialysis. Three agents, Gd-diethylenetriaminopentaacetic acid (Gd-DTPA), Gd-HP-DO3A and Gd-DTPA-BMA were diluted separately in plasma and saline and were dialyzed by using a clinical dialyzer unit with a commercially available capillary filter at rates of 0-300 cc/min. Predialyzer and postdialyzer concentrations were determined by inductively coupled atomic emission photometry. Urea and creatinine clearance rates also were determined. The clearance rate for Gd-chelates were considerably lower than that of urea and creatinine, which are generally considered benchmarks of dialysis efficiency. At 300 cc/min flow rates, the clearances were (clearance in cubic centimeters per minute with 95% confidence interval): Gd-DTPA-74 cc/min (68-80 cc/min) delta-HP-DO3A 67 cc/min (63-71cc/min); and Gd-DTPA-BMA 67 cc/min (63-71cc/min). In comparison, urea and creatinine were 180 cc/min (178-181 cc/min) and 142 cc/min (124-131 cc/min), respectively. There was no difference between clearance rates of Gd-chelates in saline and plasma, implying there was no protein binding. By using a first order kinetic model of dialysis time, more than 12.2 to 14.7 hours of dialysis would be necessary to remove 97% of the injected dose of Gd-chelate.(ABSTRACT TRUNCATED AT 250 WORDS)

Contrast Media↗
PubMedDate not supplied

Gadolinium-DTPA enhanced dynamic MR imaging in the evaluation of cisplatinum nephrotoxicity.

Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) enhanced dynamic magnetic resonance (MR) imaging was used to monitor the nephrotoxic effects of cis-platinum (cis-diamminedichloroplatinum; CDDP), a chemotherapeutic agent that produces damage in the proximal convoluted tubule. Ten New Zealand white rabbits (NZWs) were divided into two groups and were evaluated at two clinically relevant doses of CDDP. Group 1 (four NZWs) received CDDP intravenously at 125 mg/m2 over 1 h. Rabbits in Group 2 (six NZWs) were infused with CDDP at 40 mg/m2 each day for 5 consecutive days. Dynamic MR images were performed in the axial plane at 1.5 T using a gradient recalled acquisition in the steady state sequence with an echo time of 11 ms, a repetition time of 20 ms, and a flip angle of 10 degrees after a bolus injection of Gd-DTPA 0.1 mmol/kg. Thirty-two sequential post Gd-DTPA images (5.12 s/image) were obtained over 2 min 45 s at a single location. All rabbits underwent baseline normal and serial post CDDP Gd-DTPA enhanced dynamic MR scans. Analysis of the alterations in the normal pattern of renal enhancement caused by CDDP was facilitated by using a stacked profile image and quantitative region of interest measurements of signal intensity. Normally, after the injection of Gd-DTPA, a dark band promptly appears in the outer cortex of the kidneys and migrates centripetally toward the papilla, reflecting the tubular concentration of Gd-DTPA. In Group 1 rabbits, nephrotoxicity due to CDDP was observed as early as 9 h after administration of the drug, with a complete disappearance of the dark band by 7 days. In Group 2 rabbits, the band disappeared gradually and reappeared 2-10 days after the completion of CDDP treatment, indicative of tubular damage and recovery with return of the concentrating ability of the kidney. These results illustrate the feasibility of using Gd-DTPA dynamic MR as a sensitive monitor of drug induced alterations of renal function.

Acute Kidney Injury↗