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Biomedical subjects

Rino Munda

Publications and source records attributed to Rino Munda.

12 recordsLinked to original sources

Simultaneous corticosteroid avoidance and calcineurin inhibitor minimization in renal transplantation.

Steroids and calcineurin inhibitors (CNI) have been mainstays of immunosuppression but both have numerous side effects that are associated with substantial morbidity and mortality. This study was carried out to determine if steroids can be eliminated with early discontinuation of cyclosporine A (CsA) and later discontinuation of mycophenolate mofetil (MMF). Ninety-six patients with kidney transplants were entered into four subgroups of two pilot studies. All patients received Thymoglobulin induction, rapamycin (RAPA), and the immunonutrients arginine and an oil containing omega-3 fatty acids. Mycophenolate mofetil was started in standard doses and discontinued by 2 years. CsA was given in reduced doses for either 4, 6, or 12 months. Follow-up was 12-36 months. Thirteen first rejection episodes occurred during the first year (14%). Combining all patients, 86% were rejection-free at 1 year, 80% at 2 years and 79% at 3 years. No kidney has been lost to acute rejection. Ninety percent of the 84 patients at risk at the end of the study were steroid-free and 87% were off CNI. Fifty-seven percent of 54 patients with a functioning kidney at 3 years were receiving monotherapy with RAPA. We conclude that this therapeutic strategy is worthy of a prospective multi-center clinical trial.

Adrenal Cortex Hormones↗

Body weight alterations under early corticosteroid withdrawal and chronic corticosteroid therapy with modern immunosuppression.

BACKGROUND: Weight gain is a known complication of corticosteroid maintenance therapy. The purpose of the present study was to compare patterns of weight gain under chronic corticosteroid therapy (CCST) with that observed under early (i.e., within 7 days posttransplant) corticosteroid withdrawal (CSWD) in renal-transplant recipients. METHODS: Renal-transplant recipients who underwent early CSWD under four prospective, institutional review board-approved clinical trials were compared with a historic control group of patients receiving maintenance CCST. RESULTS: One hundred sixty-nine patients with early CSWD were compared with 132 patients who received CCST. Mean population weight gain was significantly higher in CCST patients at 3, 6, and 12 months posttransplant. Race influenced weight gain because white CSWD patients demonstrated greater reductions in weight gain compared with African-American patients. Sex also influenced weight gain: women demonstrated a greater benefit from CSWD than did men. Corticosteroid rejection therapy in CSWD patients completely restored weight gain because these patients showed weight gains similar to the CCST group. Finally, pretransplant body mass index (BMI) also influenced weight gain because patients who were overweight (BMI 25-30) or obese (BMI>30) demonstrated a greater reduction in weight gain with CSWD than did patients of normal weight (BMI<25). CONCLUSIONS: Early CSWD minimizes weight gain in renal-transplant recipients. Women, whites, and patients with high pretransplant BMI had greater reductions in weight gain with early CSWD.

Adrenal Cortex Hormones↗

The influence of immunomodulatory diets on transplant success and complications.

BACKGROUND: Animal studies have shown that dietary supplementation with arginine and lipids containing the omega-3 and omega-9 fatty acids prolong allograft survival in animals receiving a short course of low-dose cyclosporine. They also reduce cardiovascular complications and infections in humans. METHODS: Adult renal transplant patients receiving standard immunosuppression were stratified according to gender, diabetic state, donor source (LD or CD), and first versus repeat transplant, and randomized to receive or not receive supplemental arginine and canola oil (containing both omega-3 and omega-9 fatty acids) twice daily. Patients were followed for a minimum of 3 years. RESULTS: Seventy-six patients were randomized to the supplement group (S) and 71 patients to the control group (C). Intent-to-treat analysis revealed that S patients had fewer post-30 day first rejection episodes (5.4%) when compared with the C group (23.7%) (P=0.01) and fewer post-30 day episodes of calcineurin inhibitor (CNI) drug toxicity (9.2% vs. 35.3%, P=0.003). S patients developed new onset diabetes mellitus (NODM) less frequently by 3 years (2.3% vs. 14.5%, P=0.04), had fewer cardiac events (5.0% vs. 17.1%, P=0.05), and fewer episodes of sepsis (6.5% vs. 18.7%, P=0.05). CONCLUSIONS: Dietary supplementation with L-arginine and canola oil is a safe, inexpensive, and unique treatment, which is associated with decreased rejection rates and CNI toxicity after the first month in renal transplant patients. Due to reductions in NODM and cardiac events, long-term benefits for patient survival may be particularly important.

Body Weight↗

Vascular access in hemodialysis: issues, management, and emerging concepts.

This article (1) identifies the types of hemodialysis access, (2) summarizes the clinical standard of care for dialysis access grafts and fistulae, (3) describes the pathology and pathogenesis of venous stenosis in dialysis access grafts and fistulae, (4) tabulates avail-able therapies for hemodialysis vascular access dysfunction and speculates on the rea-sons for the lack of effective therapies, and (5) discusses the development and application of novel therapeutic interventions for this difficult clinical problem. The possibility that dialysis access grafts and fistulae could be the ideal clinical model for testing novel local therapies to block neointimal hyperplasia is discussed.

Arteriovenous Anastomosis↗

Laparoscopic donor nephrectomy vs. open live donor nephrectomy: a quality of life and functional study.

BACKGROUND: Few studies have compared the quality of life (QoL) and functional recuperation of laproscopic donor nephrectomy (LDN) vs. open donor nephrectomy (ODN) donors. This study utilized the SF-36 health survey, single-item health-related quality of life (HRQOL) score, and a functional assessment questionnaire ('Donor Survey'). METHODS: Questionnaires were sent to 100 LDN and 50 ODN donors. These donors were patients whose procedures were performed at The University Hospital and The Christ Hospital in Cincinnati, Ohio. RESULTS: A total of 46 (46%) LDN and 21 (42%) ODN donors returned the completed surveys. The demographics of the two groups were similar. LDN patients reported a more rapid return to 100% normal health (69 vs. 116 d; p = 0.24), part-time work (21.9 vs. 23.2 d; p = 0.09), and necessitated fewer physician office visits post-operative (2.8 vs. 4.4; p = 0.01). ODN patients reported shorter duration of oral pain medication use (13.4 vs. 7.2 d; p = 0.02). However, a greater number of ODN patients reported post-surgical chronic pain (3 vs. 6; p < 0.05) and hernia (0 vs. 2; p = 0.19). The overall QoL for both groups was comparable with the general USA population. CONCLUSIONS: The results of this study support the decisions of many kidney transplant centers to adopt LDN programs as standard of care.

Adult↗

African-American renal transplant recipients benefit from early corticosteroid withdrawal under modern immunosuppression.

African-Americans (AAs) have historically been considered high-risk renal transplant recipients due to increased rejection rates and reduced long-term graft survival. As a result, AAs are often excluded from corticosteroid withdrawal (CSWD) protocols. Modern immunosuppression has reduced rejections and improved graft survival in AAs and may allow successful CSWD. Outcomes in 56 AAs were compared to 56 non-AAs. All patients were enrolled in one of four early CSWD protocols. Results are reported as AA versus non-AA. Acute rejection at 1-year was 23% and 18%; (p = NS); creatinine clearance at 1-year was 75 versus 80 mL/min (p = NS); patient and graft survival was 96% versus 98% and 91% versus 91%; (p = NS). AAs benefit from early CSWD with significantly improved blood pressure, LDL < 130 mg/dL and HDL > 45 mg/dL at 1-year, post-transplant diabetes of 8.7%, and mean weight change at 1-year of 4.8 +/- 7.2 kg. In conclusion, early CSWD in AAs is associated with acceptable rejection rates, excellent patient and graft survival, and improved cardiovascular risk, indicating that the risks and benefits of early CSWD are similar between AAs and non-AAs. Additional follow-up is needed to determine long-term renal function, graft survival, and cardiovascular risk in AAs with early CSWD.

Adrenal Cortex Hormones↗

Multivariate analysis of risk factors for acute rejection in early corticosteroid cessation regimens under modern immunosuppression.

The purpose of this study was to define risk factors for acute rejection with early corticosteroid withdrawal (CSWD; within 7 days posttransplant) in renal transplantation. Data from prospective, IRB-approved early CSWD trials were analyzed. Overall acute rejection rate in 308 patients was 17.1%. Acute rejection rates and observed risks (OR) in patients with individual risk factors were: repeat transplants 38.6%; current PRA >25%; 29.4%; African Americans 23.5%; delayed graft function (DGF) 26.1%; HLA DR mismatches >0 17.9%; female gender 19.7%; Thymoglobulin induction 15.3%; type 1 diabetes 30.8%; type 2 diabetes 11.1%; deceased donor recipients 21%; and living donor recipients 14%. Logistic regression analysis provided the following risks (OR) for acute rejection: repeat transplant 2.51; current PRA > 25% 1.53; African Americans 1.47; DGF 1.58; HLA DR mismatches > 0 1.61; female gender 1.43; Thymoglobulin induction 0.61; type 1 diabetes 2.23, type 2 diabetes 0.5, deceased donor recipients 1.11, and living donor recipients 0.9. Risk factors for acute rejection under early corticosteroid withdrawal are similar to those previously defined under chronic corticosteroid therapy. These observations provide implications for future CSWD trials including: use of T cell depleting antibody induction therapy (thymoglobulin) to reduce acute rejection risk, 2) enrollment stratification for high risk groups, and 3) modified immunosuppression for high risk groups.

Acute Disease↗

Novel therapies for hemodialysis vascular access dysfunction: fact or fiction!

Hemodialysis vascular access dysfunction is a major cause of morbidity in the hemodialysis population and contributes significantly to the overall cost of end-stage renal disease programs. At a histological level, most hemodialysis vascular access dysfunction (in both native arteriovenous fistulae and PTFE dialysis access grafts) is due to venous stenosis and thrombosis, secondary to venous neointimal hyperplasia. However, despite a wealth of experimental and clinical data on the use of novel therapeutic interventions that target neointimal hyperplasia in the setting of coronary artery disease, there are unfortunately no effective therapeutic interventions for hemodialysis vascular access dysfunction at the present time. This is particularly unfortunate, since neointimal hyperplasia in the setting of hemodialysis vascular access fistulae and grafts could be the ideal clinical model to test novel therapeutic interventions for neointimal hyperplasia.

Arteriovenous Shunt, Surgical↗

Hand-assisted laparoscopic living-donor nephrectomy as an alternative to traditional laparoscopic living-donor nephrectomy.

The benefits of laparoscopic living-donor nephrectomy (LDN) are well described, while similar data on hand-assisted laparoscopic living-donor nephrectomy (HALDN) are lacking. We compare hand-assisted laparoscopic living-donor nephrectomy with open donor nephrectomy. One hundred consecutive hand-assisted laparoscopic living-donor nephrectomy (10/98-8/01) donor/recipient pairs were compared to 50 open donor nephrectomy pairs (8/97-1/00). Mean donor weights were similar (179.6 +/- 40.8 vs. 167.4 +/- 30.3 lb; p = NS), while donor age was greater among hand-assisted laparoscopic living-donor nephrectomy (38.2 +/- 9.5 vs. 31.2 +/- 7.8 year; p < 0.01). Right nephrectomies was fewer in hand-assisted laparoscopic living-donor nephrectomy [17/100 (17%) vs. 22/50 (44%); p < 0.05]. Operative time for hand-assisted laparoscopic living-donor nephrectomy (3.9 +/- 0.7 vs. 2.9 +/- 0.5 h; p < 0.01) was longer; however, return to diet (6.9 +/- 2.8 vs. 25.6 +/- 6.1 h; p < 0.01), narcotics requirement (17.9 +/- 6.3 vs. 56.3 +/- 6.4h; p < 0.01) and length of stay (51.7 +/- 22.2 vs. 129.6 +/- 65.7 h; p < 0.01) were less than open donor nephrectomy. Costs were similar ($11072 vs. 10840). Graft function and 1-week Cr of 1.4 +/- 0.9 vs. 1.6 +/- 1.1 g/dL (p = NS) were similar. With the introduction of HALDN, our laparoscopic living-donor nephrectomy program has increased by 20%. Thus, similar to traditional laparoscopic donor nephrectomy, hand-assisted laparoscopic living-donor nephrectomy provides advantages over open donor nephrectomy without increasing costs.

Activities of Daily Living↗

Hemodialysis vascular access dysfunction from basic biology to clinical intervention.

Hemodialysis vascular access dysfunction is a major cause of morbidity and hospitalization in the hemodialysis population at a cost of over 1 billion dollars per annum. Venous stenosis and thrombosis as a result of venous neointimal hyperplasia are the major causes of hemodialysis vascular access dysfunction. Despite the magnitude of the clinical problem, there are currently no effective therapies for this condition. We believe that this could be because of an inadequate understanding of the pathogenesis of this condition. At a histological level, venous neointimal hyperplasia (both in human specimens and in a pig model) is characterized by the presence of smooth muscle cells/myofibroblasts, microvessel formation (angiogenesis), and the accumulation of extracellular matrix components, all of which could be potential targets for therapeutic intervention. In particular, polytetrafluoroethylene dialysis access grafts could be the ideal clinical model for testing out novel local therapies to block neointimal hyperplasia. The current review describes the lesion of venous neointimal hyperplasia in human samples and in a pig model and suggests possible future directions for the development of effective local therapies for this condition.

Arteriovenous Shunt, Surgical↗