Alper Demirbas

Calcineurin Inhibitor Minimization in the Symphony Study: Observational Results 3 Years after Transplantation

The Symphony study showed that at 1 year posttransplant, a regimen based on daclizumab induction, 2 g mycophenolate mofetil (MMF), low‐dose tacrolimus and steroids resulted in better renal function and lower acute rejection and graft loss rates compared with three other regimens: two with low‐doses of cyclosporine or sirolimus instead of tacrolimus and one with no induction and standard cyclosporine dosage. This is an observational follow‐up for 2 additional years with the same endpoints as the core study. Overall, 958 patients participated in the follow‐up. During the study, many patients changed their immunosuppressive regimen (e.g. switched from sirolimus to tacrolimus), but the vast majority (95%) remained on MMF. During the follow‐up, renal function remained stable (mean change: −0.6 ml/min), and rates of death, graft loss and acute rejection were low (all about 1% per year). The MMF and low‐dose tacrolimus arm continued to have the highest GFR (68.6 ± 23.8 ml/min vs. 65.9 ± 26.2 ml/min in the standard‐dose cyclosporine, 64.0 ± 23.1 ml/min in the low‐dose cyclosporine and 65.3 ± 26.2 ml/min in the low‐dose sirolimus arm), but the difference with the other arms was not significant (p = 0.17 in an overall test and 0.077, 0.039 and 0.11, respectively, in pair‐wise tests). The MMF and low‐dose tacrolimus arm also had the highest graft survival rate, but with reduced differences between groups over time, and the least acute rejection rate. In the Symphony study, the largest ever prospective study in de novo kidney transplantation, over 3 years, daclizumab induction, MMF, steroids and low‐dose tacrolimus proved highly efficacious, without the negative effects on renal function commonly reported for standard CNI regimens.

Early and late urological complications corrected surgically following renal transplantation

The purpose of this study was to assess outcomes of urological complications after kidney transplantation operation. Nine‐hundred and sixty‐five patients received a kidney transplant between 2000 and 2006. In total, 58 (6.01%) developed urological complications, including urinary leakage (n = 15, 1.55%), stenosis (n = 29, 3%), vesicoureteral reflux (VUR) (n = 12, 1.2%), calculi (n = 1, 0.1%) and parenchymal fistulae (n = 1, 0.1%). Urinary leakage cases were treated by ureteroneocystostomy (UNS) via a double‐J stent and stenosis cases by UNS. Fenestration was performed in patients developing lymphoceles and unresponsive to percutaneous drainage. VUR treatment was performed by ureteroneocystostomy revision or UNS. Stent usage during ureteric reimplantation was observed to reduce urinary leakage. Surgical complication rates in renal transplantation recipients according to donor type (living versus cadaveric) and the status of stent use (with stent versus without stent) were 5.53% vs. 7.27% (P = 0.064) and 5.24% vs. 20% (P < 0.01) respectively. No recurrence, graft loss or death was seen after these interventions. Comparison of recipients with and without urological complication showed that there was no difference between groups (P > 0.05) with respect to last creatinine level. No graft or patient loss was associated with urological complications. Urological complications that can be surgically corrected should be aggressively treated by experienced surgeons and graft loss avoided.

Comparing two ureter reimplantation techniques in kidney transplant recipients

We compared the incidence of urological and anastomotic complications for the ureteroureterostomy and Lich–Gregoir techniques in kidney transplant recipients. Between May 2003 and February 2004, 75 kidney transplant recipients from living donors were divided into two similar groups to receive ureteroureterostomy (n = 41, 28 male, 13 female) and Lich–Gregoir techniques (n = 34, 24 male, 10 female) for ureteral reimplantation. Patients with vesicoureteral reflux (VUR) to the native kidneys were excluded from the study. The urological complications included complicated hematuria, ureteral stenosis, symptomatic VUR, recurrent urinary tract infection (UTI). There was no statistical significance between two groups in terms of gender, age, end‐stage renal disease etiology, human leucocyte antigen (HLA) mismatch numbers, type and duration of dialysis, and cold ischemia time. The incidence of urologic and anastomotic complications was 12%. Complications in the Lich–Gregoir group included symptomatic VUR in 8.8% and stent migration in 2.9% of cases. Complications observed in the ureteroureterostomy group were ureteral stricture 7.3% and complicated hematuria in 4.9% of cases. However, symptomatic reflux was not observed in the ureteroureterostomy group. UTI frequency was similar in both groups. Ureteroureterostomy can be safely performed as a primary choice in kidney transplant recipients.

Hemophagocytic Syndrome in Kidney Transplant Recipients: Report of Four Cases from a Single Center

Background: The prognosis of hemophagocytic syndrome (HPS) in kidney transplant recipients is reported to be poor, however the optimal therapeutic approach is still unclear. Patients and Methods: The clinical and follow-up data of the 4 patients with HPS (3 male, 1 female; age 39.7 ± 11.3 years) among 368 kidney transplant recipients during a 5-year period were retrospectively analyzed. Results: HPS developed 35–61 days in the post-transplant period. All 4 patients presented with fever. Hepatosplenomegaly and lymphadenopathy were observed only in the first patient. Laboratory tests revealed pancytopenia and hyperferritinemia in all patients, but elevated liver enzymes were observed in 3. Two patients had cytomegalovirus infection, and 1 had Epstein-Barr virus infection. Three patients died despite aggressive supportive therapy, however the fourth case survived after graft nephrectomy. Conclusion: HPS pathogenesis in kidney transplants appears to be related with the graft itself. Graft nephrectomy may be the preferable therapeutic approach for kidney transplant recipients with HPS resistant to standard supportive therapy.

Low toxicity regimens in renal transplantation: a country subset analysis of the Symphony study

Regional transplant practices may affect clinical outcomes within multinational studies. This study evaluated whether the overall results from the Symphony study can be generalized to the participating countries. De novo adult renal transplant recipients (n = 1645) were randomized to receive standard‐dose cyclosporine, or daclizumab induction plus low‐dose cyclosporine, low‐dose tacrolimus, or low‐dose sirolimus, all in addition to mycophenolate mofetil and steroids. Data for the highest patient‐recruiting countries, Spain (n = 275), Germany (n = 316) and Turkey (n = 258), were compared. Patient transplant characteristics were different among the country subsets; only deceased donors in Spain, more expanded criteria donors in Germany, and mainly living donors in Turkey. Efficacy results for the three countries were consistent with that of the overall study – renal function and biopsy‐proven acute rejection (BPAR) rates were superior with low‐dose tacrolimus. Turkey had higher mean calculated glomerular filtration rate across all treatment groups (60.6–72.2 ml/min) compared with that of Spain (51.1–57.5 ml/min) and Germany (51.3–62.9 ml/min). Spain and Turkey had lower BPAR rates across the four treatment groups compared with the overall study; Germany had much higher rates (21.0–54.2%). These findings confirm the general applicability of the Symphony study results and highlight the importance of inclusion of patients from different geographic origins in randomized clinical trials.

Choice of immunosuppressants and the risk of warts in renal transplant recipients.

Sir, Graft-preserving immunosuppressive therapy is associated with many dermatological complications, as shown in renal transplant recipients (RTR) (1–7). Human papillomavirus (HPV) infection is one of the most frequently occurring infections (1–4, 6–8). The presence of HPV may augment the risk of skin cancer. A wide diversity of HPV types can be detected in biopsies from premalignant lesions and skin cancer of transplant recipients (9–10). It is well known that therapy with cyclosporine and azathioprine leads to an increased risk of developing viral warts (3, 11, 12). However, the risk with the new immunosuppressive agents, such as mycophenolate mofetil, which are designed to provide immunosuppression with fewer side-effects, is unknown.

Endovascular Treatment of a Recipient Celiac Trunk Stenosis after Orthotopic Liver Transplantation

Purpose: To present the successful endovascular treatment of a severe recipient celiac trunk stenosis that led to allograft ischemia following liver transplantation. Case Report: A 56-year-old woman underwent orthotopic liver transplantation because of hepatitis C—induced cirrhosis. After the operation, routine hepatic Doppler ultrasonography showed a tardus parvus flow pattern in the hepatic artery, suggesting an impending hepatic artery thrombosis. Digital subtraction angiography (DSA), however, showed severe stenosis of the recipient celiac trunk and moderate splenic artery steal. The stenosis was dilated and stented in the same session. The postprocedural DSA showed good dilation of the lesion with immediate improvement of hepatic opacification. Follow-up Doppler ultrasound scans showed normal flow patterns in the hepatic artery at 3 and 6 months. Conclusions: In the presence of a tardus parvus flow pattern on Doppler ultrasound after liver transplantation, the possibility of an undetected recipient celiac stenosis should be considered in the differential diagnosis. Such lesions can successfully be treated with angioplasty and stenting.

Outcomes of combined cardiac surgery and kidney transplant compared with kidney transplant after cardiac surgery.

Context Patients with chronic renal failure have a high prevalence of coronary artery disease and cardiovascular death. The mortality and the morbidity rates of cardiac surgery are particularly high in these patients with end-stage renal disease. Performing cardiac surgery and kidney transplant in the same session can reduce these complications in the early postoperative period by normalizing renal function. Objective To compare the mortality and morbidity rates between patients who had undergone cardiac surgery and kidney transplant separately and patients who had combined surgeries. Methods This retrospective study consisted of 75 patients. One group of 60 patients underwent cardiac surgery and kidney transplant in separate sessions, and the other group of 15 patients had combined surgeries in the same session, between March 2008 and September 2012. Results Patients who had combined surgeries achieved fluid electrolytic balance more easily, had shorter extubation times, used less blood and blood products, and had fewer major complications. The patients recovered faster and thus had shorter stays in the intensive care unit and hospital. This combined surgical approach allows normalized kidney function in patients with end-stage renal disease, so mortality and morbidity in the early postoperative period could be significantly reduced.