Deceased donor vein extension grafts for right living donor kidney transplantation.

INTRODUCTION: In an effort to maximize living donor kidney utilization, we describe the use of deceased donor vein extension grafts for right-sided living donor kidneys and report our single-center experience using this technique. METHODS: A retrospective review of kidney transplant recipients (KTR) who received a right living donor kidney with deceased donor vein extension graft. Recipient demographics, postoperative graft function, and surgical complications were reviewed. Living donor nephrectomies were performed laparoscopically. Vein grafts were obtained from recent deceased donor procurements. End-to-end anastomosis of the graft to the renal vein was performed prior to implantation. RESULTS: Thirty-eight KTR received a right kidney transplant with deceased donor extension grafts. The median recipient age and BMI were 53.0 years and 29.3 kg/m2 . Total 71% were male. Ninety-five percent of grafts displayed immediate graft function, with two recipients requiring temporary dialysis due to anaphylaxis from induction therapy. Median serum creatinine at two weeks was 1.6 mg/dL and at three months was 1.5 mg/dL. There were no graft thromboses. CONCLUSION: Utilization of deceased donor extension grafts for short right renal veins is a simple technique that expands the donor pool for living donor renal transplantation. Our experience resulted in no technical complications and excellent early graft function.

Risk Factors Associated With an Impaired Antibody Response in Kidney Transplant Recipients Following 2 Doses of the SARS-CoV-2 mRNA Vaccine.

BACKGROUND: Data about vaccine efficacy in solid organ transplant patients are limited. We previously reported our initial observation of a 6.2% immunogenicity rate in kidney transplant recipients (KTRs) after administration of 1 dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine. We sought to report our observations of anti-SARS-CoV-2 antibody in KTRs after 2 doses of the SARS-CoV-2 mRNA vaccine. METHODS: We identified 105 KTRs who received 2 doses of the Pfizer-BioNTech or Moderna mRNA-1273 vaccine per availability and had anti-SARS-CoV-2 labs obtained at least 2 wk following administration of the second dose. Antibody testing was performed using 3 clinically validated qualitative and semiquantitative assays. RESULTS: KTRs had a 36.2% antibody response rate, whereas an age ≥68 years and a longer time from transplant were factors associated with antibody response. CONCLUSIONS: The low antibody response in KTRs may be associated with the immunosuppressive state. More data are needed to evaluate if KTRs may require higher vaccine doses or an additional booster dose to increase their ability to mount an immune response to the SARS-CoV-2 vaccine.

Neurogenic Orthostatic Hypotension: a Common Complication of Successful Pancreas Transplantation.

BACKGROUND: Orthostatic hypotension (OH) is a poorly understood complication of simultaneous pancreas-kidney (SPK) transplantation. We sought to determine the incidence, timing, and relationship of OH to rapid glycemic control in the early posttransplant period. METHODS: This was a nonrandomized retrospective single-center review of 75 SPK and 19 kidney-alone (KA) recipients with type 1 diabetes (DM). RESULTS: OH occurred in 57 (76%) SPK versus 2 (10%) KA recipients (odds ratio [OR] 61.72, 95% confidence interval [CI], 9.69-393.01; P < 0.001). The median onset of OH was 12 (interquartile range [IQR] 9-18) days posttransplant and resolved in 85% of SPK recipients after a median of 2.5 (IQR 1.2-6.3) months. Among SPK recipients, independent risk factors for OH were a shorter duration of DM (OR 0.85, 95% CI, 0.73-0.98; P = 0.03) and rapid glycemic control in the early posttransplant period (OR 1.13, 95% CI, 1.01-1.27; P = 0.04), as evidenced by a larger percent change in hemoglobin A1c (HbA1c) from transplant to month 3. OH patients had a higher median baseline HbA1c [8.3% (IQR 7.2-10.0) versus 7.1% (IQR 6.8-8.3); P = 0.07], lower median 3-month HbA1c [4.8% (IQR 4.6-5.2) versus 5.2% (IQR 5.0-5.4); P = 0.02], and a larger reduction in HbA1c over time as compared to recipients without OH (P < 0.01). CONCLUSIONS: Our results show that OH is more likely to occur following SPK versus KA transplantation and is strongly associated with rapid glucose normalization within the early posttransplant period.

Donation after circulatory death liver transplantation: An in-depth analysis and propensity score-matched comparison.

BACKGROUND: Careful donor-recipient matching and reduced ischemia times have improved outcomes following donation after circulatory death (DCD) liver transplantation (LT). This study examines a single-center experience with DCD LT including high-acuity and hospitalized recipients. METHODS: DCD LT outcomes were compared to a propensity score-matched (PSM) donation after brain death (DBD) LT cohort (1:4); 32 DCD LT patients and 128 PSM DBD LT patients transplanted from 2008 to 2018 were included. Analyses included Kaplan-Meier estimates and Cox proportional hazards models examining patient and graft survival. RESULTS: Median MELD score in the DCD LT cohort was 22, with median MELD of 27 for DCD LT recipients with decompensated cirrhosis. No difference in mortality or graft loss was found (p < .05) between DCD LT and PSM DBD LT at 3 years post-transplant, nor was DCD an independent risk factor for patient or graft survival. Post-LT severe acute kidney injury was similar in both groups. Ischemic-type biliary lesions (ITBL) occurred in 6.3% (n = 2) of DCD LT recipients, resulting in 1 graft loss and 1 death. CONCLUSION: This study supports that DCD LT outcomes can be similar to DBD LT, with a low rate of ITBL, in a cohort including high-acuity recipients. Strict donor selection criteria, ischemia time minimization, and avoiding futile donor/recipient combinations are essential considerations.

Delayed Implantation of Pumped Kidneys Decreases Renal Allograft Futility in Combined Liver-Kidney Transplantation.

BACKGROUND: Combined liver-kidney transplantation (CLKT) improves survival for liver transplant recipients with renal dysfunction; however, the tenuous perioperative hemodynamic and metabolic milieu in high-acuity CLKT recipients increases delayed graft function and kidney allograft failure. We sought to analyze whether delayed KT through pumping would improve kidney outcomes following CLKT. METHODS: A retrospective analysis (University of California Los Angeles [n = 145], Houston Methodist Hospital [n = 79]) was performed in all adults receiving CLKT at 2 high-volume transplant centers from February 2004 to January 2017, and recipients were analyzed for patient and allograft survival as well as renal outcomes following CLKT. RESULTS: A total of 63 patients (28.1%) underwent delayed implantation of pumped kidneys during CLKT (dCLKT) and 161 patients (71.9%) received early implantation of nonpumped kidneys during CLKT (eCLKT). Most recipients were high-acuity with median biologic model of end-stage liver disease (MELD) score of, 35 for dCLKT and 34 for eCLKT (P = ns). Pretransplant, dCLKT had longer intensive care unit stay, were more often intubated, and had greater vasopressor use. Despite this, dCLKT exhibited improved 1-, 3-, and 5-year patient and kidney survival (P = 0.02) and decreased length of stay (P = 0.001), kidney allograft failure (P = 0.012), and dialysis duration (P = 0.031). This reduced kidney allograft futility (death or continued need for hemodialysis within 3 mo posttransplant) for dCLKT (6.3%) compared with eCLKT (19.9%) (P = 0.013). CONCLUSIONS: Delayed implantation of pumped kidneys is associated with improved patient and renal allograft survival and decreased hospital length of stay despite longer kidney cold ischemia. These data should inform the ethical debate as to the futility of performing CLKT in high-acuity recipients.

Weight Gain After Simultaneous Kidney and Pancreas Transplantation.

BACKGROUND: Excessive weight (EW) gain is common after solid organ transplantation, but there is little information concerning obesity after pancreas transplantation. The study goal was to characterize EW gain after kidney-pancreas (KP) transplantation. METHODS: This was a retrospective single-center review of 100 KP recipients transplanted between September 2007 and June 2015. RESULTS: The median percent weight gain for all recipients at 1 year posttransplant was 10% (interquartile range, 2.7%-19.3%) of baseline weight. EW gain, defined as greater than or equal to a 19% 1-year increase in weight, included all recipients (n = 26) above the upper limit of interquartile range for weight gain at 1 year. In multivariate analysis, recipient age <40 years, the use of tacrolimus/mammalian target of rapamycin immunosuppression, and an acute rejection event were independent risk factors for EW gain. At a mean follow-up of 43±23 months, there was no difference in patient or graft survival between the EW and non-EW cohorts. Although mean hemoglobin A1c levels between groups were equivalent, the EW versus non-EW cohort displayed a significant increase in mean insulin levels and a trend towards higher C-peptide levels. Criteria for posttransplant metabolic syndrome was met in 34.6% of EW versus 17.6% of non-EW cohorts (P = 0.07). CONCLUSIONS: At intermediate-term follow-up, EW gain after KP transplantation was not associated with an increased risk of death or graft loss, although there was a trend toward a greater risk of posttransplant metabolic syndrome. There may be a metabolic consequence of successful pancreas transplantation that results in EW gain in a proportion of recipients, leading to an increased risk of long-term cardiovascular complications.

Unexplained fever after pancreas transplantation.

BACKGROUND: Fever occurs frequently early after pancreas transplant, however, the exact cause is often undetermined. Limited data are available on pancreas recipients experiencing unexplained, noninfectious fever. This study aims to characterize unexplained fever (UF) in pancreas recipients and its effect on patient and graft outcomes. METHODS: We performed a retrospective cohort study of UF among consecutive pancreas or simultaneous pancreas-kidney transplant recipients from 1 January 2011 to 31 August 2015. Classification of UF was based on the absence of positive cultures, radiologic findings, and other diagnostic features of infection or rejection. RESULTS: Twenty-three of 92 (25%) patients experienced UF. The UF episode first occurred at a mean of 31 ± 17 days post-transplant and accounted for 34 admissions with an average length of stay of 5.1 ± 3.4 days. Intravenous corticosteroid was administered following confirmation of negative diagnostic tests in 77% of patients, with fever resolution occurring in all. No differences were seen in rates of biopsy-proven rejection, graft loss, death, or documented infections compared to UF-free patients during the first-year post-transplant. CONCLUSION: UF is a common cause for readmission following pancreas transplantation. While the etiology of UF remains difficult to identify, UF occurrence was not associated with adverse outcomes during the first-year post-transplant.

Intermediate-Term Outcomes of Dual Adult versus Single-Kidney Transplantation: Evolution of a Surgical Technique.

Background. Acceptance of dual kidney transplantation (DKT) has proven difficult, due to surgical complexity and concerns regarding long-term outcomes. We herein present a standard technique for ipsilateral DKT and compare outcomes to single-kidney transplant (SKT) recipients. Methods. A retrospective single-center comparison of DKT and SKT performed between February 2007 and July 2013. Results. Of 516 deceased donor kidney transplants, 29 were DKT and 487 were SKT. Mean follow-up was 43 ± 67 months. DKT recipients were older and more likely than SKT recipients to receive an extended criteria graft (p < 0.001). For DKT versus SKT, the rates of delayed graft function (10.3 versus 9.2%) and acute rejection (20.7 versus 22.4%) were equivalent (p = ns). A higher than expected urologic complication rate in the DKT cohort (14 versus 2%, p < 0.01) was reduced through modification of the ureteral anastomosis. Graft survival was equivalent between DKT and SKT groups (p = ns) with actuarial 3-year DKT patient and graft survivals of 100% and 93%. At 3 years, the groups had similar renal function (p = ns). Conclusions. By utilizing extended criteria donor organs as DKT, the donor pool was enlarged while providing excellent patient and graft survival. The DKT urologic complication rate was reduced by modification of the ureteral anastomosis.

Combined lung and liver transplantation: analysis of a single-center experience.

Patients with end-stage lung disease complicated by cirrhosis are not expected to survive lung transplantation alone. Such patients are potential candidates for combined lung-liver transplantation (CLLT), however few reports document the indications and outcomes after CLLT. This is a review of a large single-center CLLT series. Eight consecutive CLLT performed during 2009-2012 were retrospectively reviewed. One patient received a third simultaneous heart transplant. Mean age was 42.5 ± 11.5 years. Pulmonary indications included cystic fibrosis (CF) (n = 3), idiopathic pulmonary fibrosis (n = 2), α1-antitrypsin deficiency (AATD) (n = 1) and pulmonary hypertension (n = 2). Liver indications were CF (n = 3), hepatitis C (n = 2), AATD (n = 1), cryptogenic (n = 1), and cardiac/congestive (n = 1). Urgency was reflected by median lung allocation score (LAS) of 41 (36.0-89.0) and median predicted FEV1 of 25.7%. Median donor age was 25 (20-58) years with median cold ischemia times of 147 minutes and 6.1 hours for lung and liver, respectively. Overall patient survival at 30 days, 90 days and 1 year was 87.5%, 75.0% and 71.4% respectively. One patient had evidence of acute lung rejection, and no patients had liver allograft rejection. Early postoperative mortalities (90 days) were caused by sepsis in 2 recipients who exhibited the highest LAS of 69.9 and 89.0. The remaining recipients had a median LAS of 39.5 and 100% survival at 1-year. Median length of stay was 25 days (7-181). Complications requiring operative intervention included bile duct ischemia (n = 1) and bile leak (n = 1), ischemia of the bronchial anastomosis (n = 1), and necrotizing pancreatitis with duodenal perforation (n = 1). This series reflects a large single-center CLLT experience. Sepsis is the most common cause of death. The procedure should be considered for candidates with LAS < 50.

Comparing an early corticosteroid/late calcineurin-free immunosuppression protocol to a sirolimus-, cyclosporine A-, and prednisone-based regimen for pancreas-kidney transplantation.

AIM: A prednisone and calcineurin inhibitor (CNI)-free protocol was compared with a sirolimus, cyclosporine A (CsA), and prednisone-based immunosuppressive regimen for simultaneous pancreas-kidney transplantation (SPK). METHODS: A nonrandomized, single-center, sequential study enrolled low-immune responder SPK transplant recipients. The prednisone/CNI-free (minimization) group of 22 patients received thymoglobulin followed by sirolimus and reduced-dose CsA. Prednisone was withdrawn on day 5, and recipients were converted from CsA to mycophenolic acid at 6 months posttransplantation. The sirolimus/CsA group of 20 consecutive recipients transplanted immediately before this series received thymoglobulin followed by sirolimus, reduced-dose CsA, and prednisone. RESULTS: Donor and recipient demographic variables were equivalent between groups. The 24-month actual patient, kidney, and pancreas survivals for the minimization group were 100%, 100%, and 91% vs. 100%, 95%, and 95% for the sirolimus/CsA group (P=not significant [NS] for patient, kidney, and pancreas survivals). One acute rejection occurred in the minimization group and none in the sirolimus/CsA group. After withdrawal of CsA at 6 months, the minimization group showed an increase in mean estimated glomerular filtration rate, resulting in a significant improvement in renal function compared with the sirolimus/CsA group. At 24 months, the mean glomerular filtration rate of the minimization and sirolimus/CsA groups was 71.6+/-11.2 mL/min/1.73 m and 60.1+/-13.4 mL/min/1.73 m, respectively (P<0.05). Mean fasting blood glucose levels were equivalent between groups at all time points studied. CONCLUSION: Low-immune responder SPK recipients receiving a prednisone/CNI-free protocol achieved similar 2-year graft survivals and improved renal function compared with those treated with a sirolimus, CsA, and prednisone regimen.

BK virus-associated nephropathy in sirolimus-treated renal transplant patients: incidence, course, and clinical outcomes.

BACKGROUND: Because the course of polyoma virus-associated nephropathy (PVAN) has not been evaluated in a large cohort of patients receiving sirolimus (SRL)-based regimens, we have herein presented the incidence, clinical characteristics, and outcomes of 378 renal transplant recipients treated with SRL-based immunosuppression. METHODS: This retrospective single center study evaluated 344 kidney alone (KTX) and 34 simultaneous pancreas-kidney (SPK) transplantations performed between June 2000 and December 2004. RESULTS: At a mean follow-up of 43.3 months, six kidney (1.7%) and three kidney-pancreas (9.0%) transplanted patients displayed biopsy-proven PVAN. The mean time to diagnosis after transplantation was 18.2 months (range: 3.5-31.1 months), with a higher incidence among patients exposed (4.23%) versus not exposed to rabbit antithymocyte globulin (rATG; 0.53%; P=0.019) or SPK (9.0%) versus KTX (1.7%) recipients (odds ratio: 5.43; confidence interval: 1.29-22.8; P=0.038). Despite treatment with cidofovir, reduced immunosuppression and maintenance therapy with no agents other than SRL (C0=10.2+/-2.7 ng/dL) plus modest doses of prednisone (< or =5 mg), five patients (55.5%) experienced renal allograft failure. No rejection episodes were documented during the PVAN treatment and pancreatic function continued to be excellent among the SPK patients. CONCLUSIONS: Patients treated with SRL-based immunosuppression showed an incidence at the lower end of the range described with various other contemporaneous immunosuppressive regimens and with other cohorts not undergoing BK virus polymerase chain reaction surveillance. Exposure to rATG and SPK transplantation represented risk factors for the occurrence of PVAN, which showed a pernicious course despite withdrawal of calcineurin antagonists and/or mycophenolate mofetil.

[Double kidney transplantation--a method to increase the donor pool]. / Kettos vese átiltetés--egy lehetoség a transzplantációk számának növelésére.

The patients number on the transplant waiting lists are continuously increasing. The number of donors and transplantations can not reach this acceleration. To increase the number of organs we can use living donor organs or carefully selected extended criteria organs. To achieve appropriate function with marginal donor kidneys we need to transplant both kidneys into the same recipient. At the Transplant Division of University of Texas during a two years period we performed 5 double kidney transplantations with organs refused by the local transplant services. We placed both kidneys to the same side, retroperitoneally. The recipients mean age was 44.4 years and two of them belonged to the immunological risk ethnic group. After the transplantation all kidneys showed immediate function. During the patients mean hospital stay (6.25 days) the serum creatinine level decreased from 1000 micromol/l to 350 micromol/l. The Glomerular Filtration Rate (GFR) increased from 7 ml/min to 41 ml/min. Two patients suffered acute rejection which influenced their kidney function. During our two year follow up all patients avoided haemodyalsis. Double kidney transplantation is an acceptable solution for expanding the donor pool. After consistent and cautious selection previously rejected kidneys can be used.

Risk factors for impaired wound healing in sirolimus-treated renal transplant recipients.

AIM: As sirolimus has been implicated in impaired wound healing, the aim of this study was to evaluate risk factors for wound complications after renal transplantation in patients treated with this drug de novo. METHODS: This single center retrospective review of wound complications included 194 renal transplant recipients, all of whom received sirolimus immunosuppression in combination with reduced doses of cyclosporine (CsA) and corticosteroids de novo. A wound complication was defined as an infection, incisional hernia, or lymphocele. RESULTS: The overall incidence of wound complications within the first year post-transplantation was 36% (n = 70) including infection in 12% (n = 23), lymphocele formation in 18% (n = 34), and incisional hernia in 18% (n = 34) of patients. Seventeen patients suffered more than one wound complication. A multivariate analysis showed that independent risk factors for the development of wound complications were recipients over the age of 40 yr (odds ratio 2.536, p = 0.011), subjects with body mass index (BMI) >26 (odds ratio 2.498, p = 0.027) and especially BMI >30 (odds ratio 3.738, p = 0.007), the use of thymoglobulin for induction immunosuppression (odds ratio 3.627, p = 0.002), and a cumulative dose of sirolimus of at least 35 mg by post-transplant day 4 (odds ratio 2.694, p = 0.023). African-American (odds ratio 0.139, p < 0.001) or Hispanic recipients (odds ratio 0.337, p = 0.014) were less likely to experience a wound problem than Caucasian recipients. CONCLUSION: A number of potentially modifiable risk factors independently increase the incidence of wound complications among renal transplant recipients receiving sirolimus-based immunosuppression de novo.

Long-term outcomes of single paediatric vs. ideal adult renal allograft transplants in adult recipients.

AIM: To compare the outcomes of single paediatric vs. adult kidneys transplanted into adult recipients. METHODS: A retrospective single-centre review of 38 single cadaver kidney transplants from donors less than five yr of age to wait-listed patients of low body mass index (BMI). Survival of grafts and quality of renal function were compared with 121 similarly low BMI recipients of grafts from donors 18-45 yr of age that were transplanted during the same period. Immunosuppression consisted of sirolimus, minimal-dose cyclosporine and prednisone. The mean age of the paediatric vs. adult donors was 2.8+/-1.0 and 31.1+/-9.2 yr, respectively (p<0.01) and of the recipients, 42.0+/-12.4 and 45.7+/-14.8 yr, respectively (p=NS). The mean BMI of paediatric vs. adult donor kidney recipients was 21.8+/-2.9 and 22.4+/-2.0 kg/m2 (p=NS). Sixty-six per cent of paediatric donor recipients were women compared with 44% of adult donor recipients (p=0.03). RESULTS: Death censored actuarial graft survivals at one and five yr for recipients of paediatric vs. adult donor grafts were 93 and 84% compared with 93 and 85% (p=NS). There were no graft losses because of technical complications in the paediatric kidney donor group. At one and five yr post-transplantation, the mean estimated creatinine clearances of the paediatric donor graft recipients were 52.9+/-19.6 and 54.0+/-17.8 mL/min, respectively, compared with 56.4+/-19.8 and 49.1+/-21.7 mL/min for recipients of adult donor grafts at the same times (p=NS). CONCLUSION: Transplantation of single paediatric donor kidneys into low BMI adult recipients provided equivalent outcomes to those of grafts from adult donors between the ages of 18 and 45 yr.

Pancreas transplantation utilizing thymoglobulin, sirolimus, and cyclosporine.

BACKGROUND: This study aims to determine the impact of thymoglobulin-sirolimus-cyclosporine immunosuppression on the alloimune response of pancreas-kidney transplant recipients. METHODS: Thirty-six pancreas transplant recipients received an induction protocol of thymoglobulin, sirolimus, reduced-dose cyclosporine, and corticosteroids. Ten recipients were also enrolled in a study to measure immune responsiveness. Flow PRA determined HLA antibody, donor-specific flow cytometry crossmatching (FCXM), T-cell subset, and suppressor cell assays were performed during the first posttransplant year. RESULTS: One-year patient, kidney, and pancreas graft survivals were 97%, 94%, and 92%, respectively. There was one death and three graft losses. There were no acute rejection episodes. Recipients in the immune-monitoring study (n=10) displayed>80% depression of CD3, CD4, and CD8 (+) cell counts up to 3 months posttransplant. At transplantation 9/10 patients displayed<10% class I and no class II HLA antibody. By 3 months, 7/10 monitored recipients showed a transient elevation in class I HLA antibodies, including 2 patients who expressed>80% Flow PRA. One patient was pretransplant FCXM positive, whereas by 3 months posttransplant 2/10 patients demonstrated a positive FCXM. There were no clinical consequences of the presence of HLA antibody or the positive FCXMs. By 6 months, 7/9 patients demonstrated immunoregulatory suppressor cells. CONCLUSIONS: The absence of acute rejection events was likely due to inhibition of donor-specific immunity by the immunosuppressive regimen. Seventy percent of patients demonstrated an early, non-donor-directed HLA antibody response that had no adverse effect on graft function and 78% of the monitored patients displayed immunoregulatory cells probably contributing to the successful outcomes.

The Mannich base NC1153 promotes long-term allograft survival and spares the recipient from multiple toxicities.

JAK3 is a cytoplasmic tyrosine kinase with limited tissue expression but is readily found in activated T cells. Patients lacking JAK3 are immune compromised, suggesting that JAK3 represents a therapeutic target for immunosuppression. Herein, we show that a Mannich base, NC1153, blocked IL-2-induced activation of JAK3 and its downstream substrates STAT5a/b more effectively than activation of the closely related prolactin-induced JAK2 or TNF-alpha-driven NF-kappaB. In addition, NC1153 failed to inhibit several other enzymes, including growth factor receptor tyrosine kinases, Src family members, and serine/threonine protein kinases. Although NC1153 inhibited proliferation of normal human T cells challenged with IL-2, IL-4, or IL-7, it did not block T cells void of JAK3. In vivo, a 14-day oral therapy with NC1153 significantly extended survival of MHC/non-MHC mismatched rat kidney allografts, whereas a 90-day therapy induced transplantation tolerance (>200 days). Although NC1153 acted synergistically with cyclosporin A (CsA) to prolong allograft survival, it was not nephrotoxic, myelotoxic, or lipotoxic and did not increase CsA-induced nephrotoxicity. In contrast to CsA, NC1153 was not metabolized by cytochrome P450 3A4. Thus, NC1153 prolongs allograft survival without several toxic effects associated with current immunosuppressive drugs.

[Improved outcome with sirolimus-cyclosporine regimen in high-risk renal transplant recipients]. / Sirolimus-ciclosporin alapú immunszuppresszív kezelés sikeres alkalmazása vesetranszplantáción atesett, rejectio szempontjábó1 magas kockázatú betegekben.

AIM: The immunosuppressive agents have a broad spectrum of adverse effects. In the absence of selective and specific drugs the decrease incidence and severity of side effects can be achieved by the combination of synergistic drugs only. Without wise selection and use of the combination of the potent immunosuppressive agents for the immunosuppressive maintenance therapy better results cannot be achieved without or fewer toxicities particularly in high-risk patients who lose their grafts prematurely. Therefore, a good combination will allow not only to reduce individual immunosuppressive drug induced toxicities but will also allow to achieve better graft and patient survival. MATERIAL AND METHODS: To assess the 6-year impact of a sirolimus-based regimen with, modest exposures to cyclosporine among three ethnic groups with different rejection risk, the authors performed a retrospective analysis of 470 renal transplant recipients who were treated contemporaneously: Group 1, high risk African Americans (n = 122); Group 2, moderate risk Hispanics (n = 132); Group 3, mild risk Caucasians (n = 216). Multivariate models were used to compare the outcomes in Group 1 with those of the other two groups. RESULTS: The cumulative incidence of acute rejection episodes over the entire follow-up period was similar among the groups: Group 1, 22.0%, Group 2, 24.2% and Group 3, 23.0%. Although there were no significant differences in overall or individual infection rates, Group 1 and 2 recipients displayed a significantly lower incidence of diarrhea at all times during follow-up compared with Group 3. All recipients showed similar rates of lymphocele formation. However, Group 1 displayed a reduced incidence and decreased severity of hypertriglyceridemia than Group 2 or Group 3 (89.3% vs. 97.2% vs. 93.2%), a similar incidence of hypercholesteremia (94.3% vs. 97.2% vs. 98.5%) was observed. The occurrence of post-transplant diabetes mellitus was greater in Group 1. than Group 3. but similar to Group 2. CONCLUSIONS: A concentration-controlled sirolimus-cyclosporine-prednisone regimen (with steroid withdrawal by 3 months) reduced the incidence of acute rejection episodes and increased 6-year graft survivals among high-risk African Americans to rates similar to other ethnic groups without an augmented toxicity profile.