PubMed Health⌕ Search

Biomedical subjects

R W Steiner

Publications and source records attributed to R W Steiner.

At least 19 recordsLinked to original sources

A technique for presenting risk and outcome data to potential living renal transplant donors.

BACKGROUND: Transplant centers have become increasingly interested in living donor kidney transplantation and have always had the obligation to counsel these donors fairly. Counseling techniques vary markedly among centers and can include overly qualitative or unintentional but covertly prescriptive presentation of risk and benefit. METHODS: We describe a simple technique using preprinted fields of stick figures for presenting important risk and benefit data to potential renal donors. We also suggest an approach to formulating basic statistics for donor counseling. RESULTS: Risk and benefit statistics can be presented visually and quantitatively in a way that minimizes the need for donor sophistication and also displays the "all or nothing" nature of adverse events in donor and recipient populations, as opposed to using of percentages or prescriptive phrases by the donor counselor. CONCLUSION: Such stick figure field counseling for living renal transplant donors accurately provides information to both donor and center, appropriately facilitates center impartiality, and may increase the center's and the donor's confidence in the counseling process.

Counseling↗

Ethical selection of living kidney donors.

Renal transplant centers vary markedly in their rates of living donor kidney transplantation. Recent surveys also document marked differences among centers in both appreciation of medical risk for donation and what constitutes ethical donor selection. Because of this marked variability, some donors likely are being inappropriately denied or others are being inappropriately accepted. In addition to defensible donor education about risk and benefit, three fundamental obligations of the center are identified: (1) to recognize that it is often ethical to participate in acts of individual risk and sacrifice that are performed to benefit others; (2) to not deny transplantation without good reason to donors and recipients who apply to the center; and (3) to neutralize, but not overreact to, center self-interest, which stems from the professional benefits of transplantation and the center's desire to help potential transplant recipients. The basic medical facts surrounding donation must be understood by all parties as part of ethical decision making. Donor risk can be presented quantitatively using US Renal Data System data as a baseline. Confirmation of accurate donor understanding of risks, benefits, and alternatives is always a fundamental center obligation. Donors should not be rejected except for the general reasons we identify, and when these reasons do not seem to apply, the decision to deny transplantation should be reconsidered.

Academic Medical Centers↗

Posttransplant therapy using high-dose human immunoglobulin (intravenous gammaglobulin) to control acute humoral rejection in renal and cardiac allograft recipients and potential mechanism of action.

BACKGROUND: Intravenous gammaglobulin (i.v.IG) contains anti-idiotypic antibodies that are potent inhibitors of HLA-specific alloantibodies in vitro and in vivo. In addition, highly HLA-allosensitized patients awaiting transplantation can have HLA alloantibody levels reduced dramatically by i.v.IG infusions, and subsequent transplantation can be accomplished successfully with a crossmatch-negative, histoincompatible organ. METHODS: In this study, we investigated the possible use of i.v.IG to reduce donor-specific anti-HLA alloantibodies arising after transplantation and its efficacy in treating antibody-mediated allograft rejection (AR) episodes. We present data on 10 patients with severe allograft rejection, four of whom developed AR episodes associated with high levels of donor-specific anti-HLA alloantibodies. RESULTS: Most patients showed rapid improvements in AR episodes, with resolution noted within 2-5 days after i.v.IG infusions in all patients. i.v.IG treatment also rapidly reduced donor-specific anti-HLA alloantibody levels after i.v.IG infusion. All AR episodes were reversed. Freedom from recurrent rejection episodes was seen in 9 of 10 patients, some with up to 5 years of follow-up. Results of protein G column fractionation studies from two patients suggest that the potential mechanism by which i.v.IG induces in vivo suppression is a sequence of events leading from initial inhibition due to passive transfer of IgG to eventual active induction of an IgM or IgG blocking antibody in the recipient. CONCLUSION: I.v.IG appears to be an effective therapy to control posttransplant AR episodes in heart and kidney transplant recipients, including patients who have had no success with conventional therapies. Vascular rejection episodes associated with development of donor-specific cytotoxic antibodies appears to be particularly responsive to i.v.IG therapy.

Adult↗

Results of the double-blind, randomized, multicenter, phase III clinical trial of Thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation.

BACKGROUND: Thymoglobulin, a rabbit anti-human thymocyte globulin, was compared with Atgam, a horse anti-human thymocyte globulin for the treatment of acute rejection after renal transplantation. METHODS: A multicenter, double-blind, randomized trial with enrollment stratification based on standardized histology (Banff grading) was conducted. Subjects received 7-14 days of Thymoglobulin (1.5 mg/kg/ day) or Atgam (15 mg/kg/day). The primary end point was rejection reversal (return of serum creatinine level to or below the day 0 baseline value). RESULTS: A total of 163 patients were enrolled at 25 transplant centers in the United States. No differences in demographics or transplant characteristics were noted. Intent-to-treat analysis demonstrated that Thymoglobulin had a higher rejection reversal rate than Atgam (88% versus 76%, P=0.027, primary end point). Day 30 graft survival rates (Thymoglobulin 94% and Atgam 90%, P=0.17), day 30 serum creatinine levels as a percentage of baseline (Thymoglobulin 72% and Atgam 80%; P=0.43), and improvement in posttreatment biopsy results (Thymoglobulin 65% and Atgam 50%; P=0.15) were not statistically different. T-cell depletion was maintained more effectively with Thymoglobulin than Atgam both at the end of therapy (P=0.001) and at day 30 (P=0.016). Recurrent rejection, at 90 days after therapy, occurred less frequently with Thymoglobulin (17%) versus Atgam (36%) (P=0.011). A similar incidence of adverse events, post-therapy infections, and 1-year patient and graft survival rates were observed with both treatments. CONCLUSIONS: Thymoglobulin was found to be superior to Atgam in reversing acute rejection and preventing recurrent rejection after therapy in renal transplant recipients.

Acute Disease↗

Pentoxifylline does not prevent the cytokine-induced first dose reaction following OKT3--a randomized, double-blind placebo-controlled study.

The use of OKT3 as an immunosuppressive agent is accompanied by increased cytokine production and constellation of side effects collectively termed cytokine release syndrome (CRS). Pentoxifylline (PTF) inhibits synthesis of some cytokines, and has been shown to attenuate CRS when administered before OKT3. In this double-blinded, placebo-controlled study, 46 renal allograft recipients were randomized to receive either PTF (800 mg q 8 hr for at least 24 h) p.o. or placebo, along with methylprednisolone (7 mg/kg), diphenhydramine, and acetaminophen, prior to beginning OKT3 as therapy for acute rejection. Patients were observed, and symptoms scored semiquantitatively. Despite the presence of therapeutic PTF levels (721 +/- 726 ng/ml), the frequency and severity of side effects (fever, chills, headache, neurocortical symptoms, dyspnea, nausea, vomiting, diarrhea) did not differ between treatment groups. Likewise PTF did not affect renal function or immunologic response to OKT3, with similar graft and patient survival in both groups. Plasma levels of TNF alpha, IFN gamma, IL-6, and IL-8 increased as predicted following OKT3 administration, without significant differences between PTF and placebo groups. In this controlled, multicenter trial, pretreatment with oral PTF was ineffective in attenuating OKT3-related CRS in renal allograft recipients.

Adult↗

Effect of daily oral vitamin D and calcium therapy, hypophosphatemia, and endogenous 1-25 dihydroxycholecalciferol on parathyroid hormone and phosphate wasting in renal transplant recipients.

Ten stable, normocalcemic renal transplant patients with good allograft function, hyperparathyroidism, and variable hypophosphatemia were treated for 2 to 9 months with oral calcium carbonate and replacement doses of vitamin D analogues. Parathyroid hormone levels (PTH) and renal phosphate wasting were not autonomous or fixed but decreased with therapy. Although serum 1-25(OH)2D3 levels could be shown to rise appropriately during oral vitamin D therapy and fall afterwards, a separate study in a larger group of patients showed no effect of elevated parathyroid hormone or hypophosphatemia to increase endogenous 1-25(OH)2D3 levels. Some 42% of patients with elevated carboxy-terminal PTH, had elevated N-terminal PTH, which was closely associated with more severe phosphate wasting. Aggressive oral calcium and vitamin D supplementation in certain normocalcemic renal transplant patients may decrease endogenous PTH levels, improve hypophosphatemia, and provide a physiologic increase in levels of 1-25(OH)2D3.

Administration, Oral↗

Abdominal catastrophes and other unusual events in continuous ambulatory peritoneal dialysis patients.

Primary bacterial peritonitis and catheter-associated infections compose the large majority of abdominal events in continuous ambulatory peritoneal dialysis (CAPD) patients. Yet occasionally primary pathology involving the abdominal viscera develops, and surgery is frequently considered. The early manifestations of intraabdominal inflammation or bleeding in patients undergoing CAPD depend on the pathological process, its access to the peritoneal cavity, and whether generalized bacterial peritonitis supervenes to obscure helpful physical findings. Clear dialysate is not a reliable sign that major pathology is absent, nor does initial stabilization of the clinical course with antibiotic therapy uniformly indicate that surgery will not be necessary. Polymicrobial peritonitis may develop in cholecystitis, pancreatitis, or from a colonic source, the latter featuring more bacterial species and more gram-negative and anaerobic organisms. A history directed at progression of symptoms and sites of abdominal discomfort and an examination for deep local tenderness and bowel incarcerated in an abdominal wall hernia are essential. Measurement of dialysate amylase and Gram stain of dialysate for food fibers may be helpful. Imaging techniques such as abdominal radiographs for dilated bowel or free subdiaphragmatic air, ultrasonography of the gallbladder or pancreas, computed tomographic (CT) scanning of the lower abdomen, and water-soluble contrast colonic studies may help identify the pathologic process. Special studies such as these should be considered early in the course of suspected unusual abdominal events in patients on CAPD.

Digestive System Diseases↗

Kidney transplantation in the cyclosporine era.

Seventy-seven patients underwent transplantation, using a cyclosporine-prednisone immunosuppression protocol. No recipients died, and graft survival at one year was 100% for living related donor (LRD) recipients and 84% for cadaver donor (CD) recipients. Nineteen percent of locally harvested, flush-cooled kidney recipients required dialysis, whereas imported kidneys had a 66% dialysis rate. Infectious complications occurred in 17% of patients. Mean hospitalization was 12.8 days for LRD recipients and 13.6 days for CD recipients. Twenty-eight patients required 37 readmissions, mostly for treatment of rejection and infections. Total two-year cost for LRD transplants was +21,400; for CD transplants, +23,900.

Cyclosporins↗

A Bartter's-like syndrome from capreomycin, and a similar gentamicin tubulopathy.

Marked renal potassium and magnesium wasting, alkalosis, and a progressive increase in plasma renin and eventual hyperaldosteronemia developed during a 15-month course of in-hospital capreomycin therapy that was necessary for drug-resistant pulmonary tuberculosis. A prominent feature of the present case was renal chloride wasting, a feature of the capreomycin syndrome that has previously received little attention. Similar potentially life-threatening metabolic abnormalities, which resemble those found in Bartter's syndrome, can occur during prolonged therapy with the antibiotic gentamicin. In the present case, electrolyte abnormalities were unaffected by three days of indomethacin therapy but were partially corrected by large doses of spironolactone. Capreomycin, viomycin (an antibiotic closely related to capreomycin), and gentamicin are highly basic polypeptide antibiotics that may induce strikingly similar and potentially fatal syndromes of renal tubular dysfunction that can feature multiple electrolyte abnormalities.

Adult↗