Early Switch to Mammalian Target of Rapamycin Inhibitors Is a Sustainable Treatment Approach in Renal Transplant Recipients: 7-Year Results.

OBJECTIVE: The aim of this study was to investigate the safety and sustainability of mammalian target of rapamycin inhibitor (m-TORi)-based treatment protocols in renal transplant patients. METHODS: We retrospectively evaluated a total of 206 patients who were switched to low-dose calcineurin inhibitors (CNI) + m-TORi or mycophenolate mofetil (MMF) + m-TORi treatment protocols in the first 3 months of renal transplantation between January 2010 and August 2011 in our center. Demographic and laboratory features of the patients were recorded. RESULTS: Of the patients included in the study, 89 (43.2%) were female and 117 (56.8%) were male. The mean age was 41.9 ± 13.8 years. Panel reactive antibody was negative in 95% of the recipients. One hundred thirty-four (65%) patients received anti-thymocyte globulin induction therapy. Initially, 108 patients were treated with cyclosporine and 98 (47.6%) were treated with tacrolimus-based regimens. One hundred thirty-five patients (65.5%) were switched to low-dose CNI + m-TORi and 71 patients (34.5%) were switched to MMF + m-TORi. The mean switching time was 3 months. At the end of the study, 161 patients (78.2%) were still continuing the m-TORi treatment protocol and 45 patients (21.8%) could not continue for various reasons (11.4% proteinuria, 5.5% edema, 2.9% acute rejection, 1% acne + oral aphthae, 1% neuropathy). The biopsy-proven acute rejection rate was 4.5% (n = 9). The mean duration of sustainability of m-TORi treatment protocol was 84.15 ± 6.79 months. Mean serum creatinine of patients who were still continuing m-TORi was 1.42 ± 1.09 mg/dL. CONCLUSION: Switching to m-TORi in the early posttransplant period is a safe and sustainable treatment approach.

Oxidative DNA Damage Is Increased in Living Kidney Donors.

BACKGROUND: Long-term consequences of donor nephrectomy might be reduced kidney function, increased risk for cardiovascular disease, and impaired quality of life. The purpose of the current cross-sectional study was to evaluate the relationship between clinical, laboratory, and donation-specific outcomes of living kidney donors and systemic oxidative DNA damage. METHODS: We conducted a cross-sectional study and assessed retrospectively pre- and postdonation data from 60 donors who donated between 2010 and 2015. Plasma malondialdehyde levels and 8-hydroxy-2'-deoxyguanosine/deoxyguanosine ratio (8-OHdG/dG ratio) were determined as oxidative stress markers. Catalase, carbonic anhydrase, and paraoxonase (PON) activities were measured as antioxidants. RESULTS: Approximately 3 years after donation, the hypertensive donor ratio was 12%, and 11% of the donors had glomerular filtration rate <60 mL/min/1.73 m2. Mean serum urea (P = .001) and serum creatinine levels (P = .001) were increased; creatinine clearance level (126.2 ± 35.5 vs 94.6 ± 26.8, P = .001) was decreased in the postdonation period. There was a significant positive correlation between predonation serum urea and 8-0HdG/dG ratio (r = 0.338, P = .016) and predonation serum creatinine and 8-0HdG/dG ratio (r = 0.442, P = .001), while there was a significant negative correlation between serum creatinine and PON activity (r = -0.545, P < .001). CONCLUSION: Our data have demonstrated that kidney donors exhibit increased oxidative DNA damage and decreased antioxidant activity. We propose that predonation serum creatinine is positively correlated with 8-0HdG/dG ratio and negatively correlated with antioxidant PON activity. This is the first study to demonstrate that plasma oxidative DNA damage increases in healthy kidney donors.

End-To-Side Versus End-to-End Uretero-Ureteral Anastomosis in Kidney Transplant Recipients With Disused Atrophic Bladder.

BACKGROUND: Extravesical Lich-Gregoir ureteroneocystostomy (UC) is the most widely used method for urinary reconstruction during kidney transplantation. Sometimes it is difficult to perform UC in cases with disused atrophic bladder. Pyelo-ureteral anastomosis (PUA) and uretero-ureteral anastomosis (UUA) may be preferred to UC for these patients. METHODS: We retrospectively reviewed the charts of 833 kidney transplant recipients operated on by our transplantation team between July 2010 and November 2014. The patients were divided into two groups: Group I consisted of 16 patients who underwent end-to-side UUA and Group II consisted of 20 patients who underwent end-to-end UUA. The two groups were compared in terms of efficacy, safety, and graft function. RESULTS: As we performed end-to-side UUA as a relatively new technique compared with end-to-end UUA, the post-transplantation follow-up period of Group II was significantly longer than Group I (P = .000), but all the patients in both groups had at least 1 year of follow-up. Because the first two patients in Group II, who underwent native ureteral ligation without nephrectomy, developed hydronephrosis in their native kidneys, requiring nephrectomy in the post-transplantation period, we performed native nephrectomy in all of the remaining patients in this group. That is why the mean operative time was significantly longer in Group II compared with Group I (P = .000). There was no significant difference between the two groups in terms of postoperative surgical complications, post-transplantation urinary infections, and graft function. CONCLUSION: End-to-side UUA without native ureteral ligation is a safe surgical technique for urinary tract reconstruction during kidney transplantation in patients with disused atrophic bladder.

Comparison of Surgical Correction Techniques for Post-Renal Transplantation Vesicoureteral Reflux.

BACKGROUND: Symptomatic urinary tract infection (UTI) after renal transplantation (RT) is an important morbidity in transplant recipients and may cause pyelonephritis and sepsis. Surgical correction of high-grade vesicoureteral reflux (VUR) after RT is suggested, performing ureteral reimplantation or pyelo-ureteral/uretero-ureteral anastomosis. Recently, extravesical seromuscular tunnel lengthening techniques have been reported with favorable results and low complication rates. METHODS: We retrospectively reviewed the charts of 38 patients with post-transplantation VUR who underwent reflux correction surgery. Patient characteristics were analyzed to compare our extravesical seromuscular tunnel lengthening technique with uretero-ureteral and pyelo-ureteral anastomosis techniques. RESULTS: Twenty patients were treated with the extravesical approach (group I) and 18 patients by pyelo-ureteral or uretero-ureteral anastomosis with the use of native ureter (group II). Mean operative time was significantly shorter in group I than in group II (64.8 vs 110.1 min; P < .05), and mean duration of hospital stay after the operation also was shorter in group I (1.5 vs 5.1 d; P < .05). We determined persistent VUR in postoperative voiding cystouretrography in 2 patients (10%) in group I, but there was regression in VUR grades of all of the patients. There was no significant difference in postoperative number of UTI episodes and serum creatinine levels between the 2 groups. CONCLUSIONS: Extravesical seromuscular tunnel lengthening is an effective and safe technique for post-transplantation VUR management.

Femoro-femoral Bypass for Graft Salvage in a Renal Transplant Patient With Aorto-iliac Occlusion: A Case Report.

As vascular diseases are becoming more prevalent among renal transplant recipients, complications related to renal artery anastomosis are likely to occur more often. Here we report a renal transplant patient treated with femoro-femoral bypass who had renal allograft dysfunction due to aorto-iliac occlusive disease (AIOD) proximal to renal artery anastomosis. We performed living donor renal transplantation in the left iliac fossa of a 41-year-old male. At post-transplant 30 months, he was admitted with hypertension, increase in serum creatinine, and claudication of his left leg. Doppler ultrasonography showed poor flow characteristics of the renal allograft. Total occlusion of the left common iliac artery was diagnosed on angiography. Since endovascular approach was unsuccessful, we performed right-to-left femoro-femoral bypass to provide retrograde blood flow to the renal allograft. The patient was discharged at postoperative day 3 with decreased serum creatinine, normal blood pressure, no claudication, and normal flow characteristics in Doppler ultrasonography. AIOD should be suspected in renal transplant patients in case of hypertension, allograft dysfunction, and ipsilateral leg ischemia. Femoro-femoral bypass is a safe surgical procedure that may be performed in patients who cannot be treated using an endovascular approach.

Escherichia Coli-Related Necrotizing Fasciitis After Renal Transplantation: A Case Report.

A 39-year-old man who had received cadaveric renal transplantation (RT) 1 month previously presented with rash and pain on his left lower extremity. Initially, bacterial cellulitis was suspected, and ampicillin/sulbactam was initiated; however, 3 days later, skin necrosis occurred and pain increased. Ampicillin/sulbactam was replaced with imipenem+ciprofloxacin, and surgical debridement was performed. Escherichia coli was identified in the wound culture, urine culture, and blood culture. After repeated debridement, wound care, and appropriate antimicrobial treatment, wounds began to heal and skin grafting was planned at the 4th month of therapy. However, the patient died of viral pneumonia. To date, 20 cases of necrotizing fasciitis (NF) after RT have been reported (including our case), and, as far as we know, this is the second E coli-related NF case. An analysis of all 20 cases showed that the most common infection site was the extremities (90%) and that 45% of pathogens were fungus. The mortality rate was 30%. NF is a rare but rapidly developing and life-threatening soft-tissue infection in RT patients. To reduce mortality rates, early diagnosis, recurrent surgical debridement, and aggressive therapy are mandatory.

Renal Transplantation After Thoracic Endovascular Repair of Type B Aortic Dissection--A Case Report.

Because of the strong association between uremia and atherosclerosis, incidence of aortic aneurysms is increasing among renal failure patients awaiting renal transplantation (RT). Successful RTs have been performed in these patients after surgical repair of the aneurysms. Since Parodi et al introduced endovascular aortic aneurysm repair (EVAR) in patients with high risk for conventional surgery, a new era has begun. The 1st successful RT after EVAR was published in 2001. Herein we report the 1st successful RT after thoracic EVAR (TEVAR) reported to date. We performed RT in a 54-year-old man with end-stage renal failure due to diabetic nephropathy, who had undergone TEVAR for type B aortic dissection (TBAD) 6 months earlier. The postoperative period was uneventful and the patient was discharged from the hospital at postoperative day 6 with a serum creatinine of 0.9 mg/dL. At follow-up examination at postoperative 6 months, graft function was stable. Because of its advantages over open surgery, including low mortality and morbidity, TEVAR is becoming more common among renal failure patients with thoracic aortic aneurysms and TBAD. Our case shows that successful RT can be performed in renal failure patients who have undergone TEVAR.

Absence of Inferior Vena Cava in a Renal Transplant Recipient: A Case Report.

A 27-year-old woman was admitted to our department with end-stage renal failure due to reflux nephropathy. She had no history of deep venous thrombosis. After pretransplantation evaluation, her father was accepted for kidney donation. We observed intraoperatively that the patient's iliac veins and inferior vena cava (IVC) were absent. There were many venous collaterals, but none of them was dilated enough for renal vein anastomosis. Since we could not find a suitable vein for venous drainage of the allograft, we decided to stop donor surgery and postpone renal transplantation (RT) for detailed radiologic examination. Contrast-enhanced computed tomography revealed the absence of an infrahepatic segment of IVC. Superior mesenteric vein was thin. Portal and splenic veins were normal, but we decided not to use them for venous drainage because of increased risk of torsion. We informed the patient and her family about the situation and cancelled RT. Iliac vein and IVC anomalies are not absolute contraindications for RT, but when a dilated collateral vein is not present or when there is no option for safe renal vein anastomosis as in our case, RT may not be possible.

Exchange donor transplantation: ethical option for living renal transplantation.

PURPOSE: Taking in consideration the opinion of our team, which necessitates obligation of a relative relation between donors and recipients (genetic or matrimonial), we performed donor exchanges as an ethical alternative in living donor transplantations. We reviewed the outcomes of our exchange series. METHODS: Between July 2003 and August 2010 we performed 110 exchange donor transplantations in four hospitals: one four-way, two three-way, and 100 two-way cases. Donors were mostly spouses (n = 71) or mothers (n = 15). The mean age of the donors was 48.8 (range = 23-69) and the recipients 41.4 years (range = 5-66). Two were transplanted preemptively and the others had a mean dialysis duration of 43 months (range = 1-120). RESULTS: Among 110 patients, three compatible pairs joined the group voluntarily; 71, due to ABO incompatibility and 36, due to crossmatch positivity. Induction therapy was used in 92 patients. HLA mismatches (MM) were: one MM in three; two MM in three; three MM in 18, four MM in 36; five MM in 34; and six MM in 18. Among 90 patients tested for panel-reactive antibodies PRA, five showed class I and 10, class II positivity. In 11 patients, B-cell positivity was detected by flow cytometry. Delayed graft function (n = 2), acute rejection (n = 11), BK virus infection (n = 1), and cytomegalovirus infection (n = 3) were seen postoperatively. Three (2.7%) patients died due to sepsis. Five patients returned to dialysis program due to interstitial fibrosis tubular atrophy (IFTA) (n = 2), renal vein thrombosis (n = 1), de novo glomerulopathy (n = 1), or primary nonfunction (n = 1). The 1- and 5-year patient and graft survival rates were 96% and 96%, 95% and 89%, respectively. CONCLUSION: We believe that exchange donor transplantation is as successful as direct transplants; it is a good, ethical alternative to unrelated living transplantations.

Anastomosis of accessory arteries via microsurgical technique in renal transplantation.

PURPOSE: For many years there has been reluctance to use kidneys having multiple arteries of <2 mm diameter, especially where they supply the lower pole. The usage of these kidneys has increased using microsurgical anastomosis techniques. We reviewed the anastomotic techniques among renal transplantations with multiple arteries. MATERIALS AND METHODS: Between January 2008 and August 2010, we examined the perfusion of 605 live donor kidneys bearing multiple arteries at 1 week and after 3 months using Doppler ultrasonography and magnetic resonance imaging (MRI) angiography. In addition, we reviewed vascular and urinary complications. The diameters of the arteries were measured using multi-slice computerized tomographic (CT) angiography. RESULTS: Multiple arteries were detected in 49 (8.1%) kidneys, including 14 from the right and 35 left: namely, 45 with double and 4 with 3 arteries. In 26 patients an end-to-side microsurgical anastomosis was performed using the accessory artery; 23 organs underwent other techniques. The average diameter of all arteries was 3.89 ± 1.38 mm (thinnest, 1.2; widest, 8 mm). The average diameter of the main arteries was 5.12 ± 1.16 mm (thinnest, 3; widest, 8 mm) and the accessory arteries 2.81 ± 0.69 mm (thinnest, 1.2; widest, 3.8 mm). In patients with microsurgical techniques the average diameters of all arteries and accessory arteries were 3.7 ± 1.6 mm and 2.6 ± 0.69 mm, respectively. In those undergoing techniques other than microsurgery, the average diameters of all arteries and accessory arteries were 4.11 ± 1.34 mm and 3.1 ± 0.43 mm, respectively. The average diameters of the arteries in both groups were significantly different (P < .001). Kidney perfusion was intact upon ultrasonographic and MRI angiography of all patients. In 1 subject with a microsurgical technique used, anastomostic dehiscence with bleeding was observed after removal of the arterial clamps. Also in this group, 1 patient experienced a ureteral stricture beyond postoperative month one. CONCLUSION: Microsurgery is a reliable technique for kidneys with thin accessory renal arteries.

Conversion to proliferation signal inhibitors-based immunosuppressive regimen in kidney transplantation: to whom and when?

BACKGROUND: Despite significant advances in kidney transplantation, long-term graft survival has not dramatically improved leading to strategies to change immunosuppression during the posttransplantation period. Proliferation signal inhibitors (PSI) sirolimus or everolimus possess immunosuppressive and antiproliferative properties. METHODS: We evaluated 62 kidney transplant recipients who underwent conversion from a calcineurin inhibitors (CNI)- to a PSI-based regimen for various reasons. The statistical analysis used SPSS v.15.0 software. We compared calculated glomerular filtration rates (GFRs) before initiation of PSI (baseline) and at 6 months after conversion. RESULTS: We converted to a PSI-based triple regimen at 172.0 ± 116.5 days after transplantation. The mean serum creatinine at the time of conversion was 2.0 ± 1.1 mg/dL, and it was 1.5 ± 0.7 mg/dL at 6 months after conversion. The rate of change in serum creatinine was -17.1 ± 23.5%. The mean calculated GFR at the time of conversion was 53.6 ± 25.5 mL/min and at 6 months after conversion was 65.8 ± 23.7 mL/min. The rate of change in calculated GFR was 37.9 ± 71.7% (16.4/59.4) at 6 months. Thus we observed significant improvements in creatinine and GFR (P values <.001) after conversion. The Improved GFR significantly correlated with prior dialysis duration and time to conversion (P = .025; P = .012). Patients who had a shorter duration on dialysis and shorter time to conversion experienced more benefit from conversion. Four of the 62 patients reported gastrointestinal toxicity, which resolved with dose reduction in 3 patients: 15 patients experienced acne; 16 reported oral ulcers. None of these toxicities resulted in discontinuation of PSI therapy. Serum cholesterol and tryglyceride levels tended to increase among the conversion group, but they did not show statistical significance. CONCLUSION: We observed that minimization or withdrawal of CNI with addition of a PSI was a good treatment for deterioration of renal allograft function.

Intensive polyoma virus nephropathy treatment as a preferable approach for graft surveillance.

BACKGROUND: Polyoma BK virus nephropathy (BKVN) is one of the important causes of graft failure and loss among renal transplant patients. Reduction of immunosuppression is the most important preferred treatment approach; however, there is no agreed protocol for additional treatments. OBJECTIVE: Our aim was to investigate the effects on graft survival of intensive treatment protocols for BKVN among renal transplant patients. METHODS: 214 patients were included in the study. All patients underwent investigation for the presence of BKV in plasma samples every 3 months starting from the third month after transplantation. Biopsies were obtained upon detection of graft dysfunction or viremia. If BKVN was positive, viremia was investigated monthly. RESULTS: Plasma plus biopsy-proven BKVN were detected in 19 patients (8.9%), whose mean age was 45.8 ± 12.0 years; 68.4% (n = 13) were male and 94.7% (n = 18) were recipients of a living-donor kidney. There were 5.2% (n = 1) diabetic subjects, and the mean time prior to dialysis was 39.6 ± 44.8 (3-125) months. BKVN was observed at a mean of 6.8 ± 2.9 (4-14) months after the transplantation. It positively correlated with the baseline serum creatinine level (r = 0.159; P = .02), application and cumulative dose of antithymocyte globulin (r = 0.177; r = 0.165; respectively; P = .01), mean tacrolimus dose (r = 0.303; P < .001), and hepatitis B virus positivity (r = 0.169; P = .01). Immunosuppression was decreased in all patients who developed BKVN. In addition, leflunomide was applied in 68%, intravenous immunoglobulin in 74%, and cidofovir in 32% of patients. Acute rejection rates did not increase significantly after lowering immunosuppression (P > .05). CONCLUSION: BKVN is one of the important problems in renal transplant patients. Intensive treatment of BKVN with heterogeneous regimens, including combined treatment with leflunamide + IVIG together with immunosuppressive dose reduction, was an effective approach to prolong graft survival.