Przemyslaw Pisarski

Effects of Donor Pretreatment With Dopamine on Graft Function After Kidney Transplantation A Randomized Controlled Trial

CONTEXT Kidney graft function after transplantation can be improved through pharmacological donor pretreatment to limit organ injury from cold preservation. OBJECTIVE To determine whether pretreatment of brain-dead donors with low-dose dopamine improves early graft function in human renal transplant recipients. DESIGN, SETTING, AND PATIENTS Randomized, open-label, multicenter, parallel-group trial of 264 deceased heart-beating donors and 487 subsequent renal transplants performed at 60 European centers between March 2004 and August 2007 (final follow-up, December 31, 2008). Eligible donors were stable under low-dose norepinephrine with a normal serum creatinine concentration on admission. INTERVENTIONS Donors were randomized to receive low-dose dopamine (4 mug/kg/min). MAIN OUTCOME MEASURES Dialysis requirement during first week after transplantation. RESULTS Dopamine was infused for a median of 344 minutes (IQR, 215 minutes). Dialysis was significantly reduced in recipients of a dopamine-treated graft. Fewer recipients in the treatment group needed multiple dialyses (56/227; 24.7%; 95% CI, 19.0%-30.3%; vs 92/260; 35.4%; 95% CI, 29.5%-41.2%; P = .01). The need for multiple dialyses posttransplant was associated with allograft failure after 3 years (HR, 3.61; 95% CI, 2.39-5.45; P < .001), whereas a single dialysis was not (HR, 0.67; 95% CI, 0.21-2.18; P = .51). Besides donor dopamine (OR, 0.54; 95% CI, 0.35-0.83; P = .005), cold ischemic time (OR, 1.07; 95% CI, 1.02-1.11 per hour; P = .001), donor age (OR, 1.03; 95% CI, 1.01-1.05 per year; P < .001), and recipient body weight (OR, 1.02; 95% CI, 1.01-1.04 per kg; P = .009) were independent explanatory variables in a multiple logistic regression model. Dopamine resulted in significant but clinically meaningless increases in the donors systolic blood pressure (3.8 mm Hg; 95% CI, 0.7-6.9 mm Hg; P = .02) and urine production before surgical recovery of the kidneys (29 mL; 95% CI, 7-51 mL; P = .009) but had no influence on outcome. CONCLUSION Donor pretreatment with low-dose dopamine reduces the need for dialysis after kidney transplantation. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00115115.

Long-term outcome of ABO-incompatible living donor kidney transplantation based on antigen-specific desensitization. An observational comparative analysis

BACKGROUND ABO-incompatible living donor kidney transplantation based on specific conditioning has been successfully adopted by transplant centres worldwide. Excellent short-term results have been reported in small cohorts. However, long-term data and comparative analyses are still sparse. We report on the outcome of 40 consecutive ABO-incompatible living donor kidney transplant recipients and compare their clinical course to a control group of 43 ABO-compatible living donor transplant patients transplanted during the same time period. METHODS This is an observational single-centre analysis of 40 consecutive patients undergoing ABO-incompatible kidney grafting between April 2004 and April 2009, using a protocol of rituximab, antigen-specific immunoadsorption, intravenous immunoglobulin, basiliximab induction and oral triple immunosuppression with tacrolimus, mycophenolic acid and prednisone. Forty-three ABO-compatible kidney transplant recipients served as controls. The control group had also received basiliximab induction and an identical initial maintenance immunosuppression. The two groups were observed for an average of 39 and 19 months, respectively. RESULTS There was a significantly higher incidence of lymphoceles requiring surgical revisions in the ABO-incompatible group. However, this surgical complication did not affect patient or graft survival. Mean serum creatinine, estimated glomerular filtration rate and proteinuria did not differ between the two groups. Furthermore, ABO-incompatible and ABO-compatible patients had the same incidence of humoral and cellular rejections. Despite a more aggressive induction therapy, no differences in infectious or malignant complications were observed. CONCLUSIONS ABO-incompatible living donor kidney transplantation utilizing a combination of rituximab and antigen-specific immunoadsorption yielded results identical to ABO-compatible transplantation despite a significantly higher number of human leukocyte antigen mismatches.

ABO‐incompatible kidney transplantation using antigen‐specific immunoadsorption and rituximab: a single center experience

Abstract: Background: For years ABO‐incompatible kidney transplantations were preferentially performed in Japanese centers. In order to overcome the increased risk of humoral rejections, patients were treated with multiple sessions of plasmapheresis, intensified immunosuppressive therapy and splenectomy before transplantation. Despite good long‐term results regarding patient and organ survival rates, increased morbidity during the early post‐transplant period prevented a broad application of this method. Recently, a new protocol including the anti‐CD20‐antibody (Ab) rituximab and blood group‐specific immunoadsorption instead of splenectomy and plasmapheresis was published with excellent short‐term results.

Expression profiling on chronically rejected transplant kidneys.

Background. Chronic transplant nephropathy remains a poorly defined inflammatory process that limits the survival rate of most renal transplants. We analyzed the gene profile of chronically rejected kidney transplants to identify candidate genes that characterize chronic transplant nephropathy. Methods. To distinguish genes present in normal renal tissue or specific for end-stage renal failure, we compared the gene profiles of 13 chronically rejected kidney transplants with 16 normal kidneys and 12 end-stage polycystic kidneys using a 7K human cDNA microarray. After elimination of genes with signals close to background, 2,190 genes were available for statistical analysis. Results. More than 20% of the examined genes were significantly regulated when compared with the expression level of normal renal tissue (P <0.0003). Hierarchic clustering based on 571 genes differentiated normal and transplant tissue, and transplant and polycystic kidney tissue. Most of these genes encoded proteins involved in cellular metabolism, transport, signaling, transcriptional activation, adhesion, and the immune response. Notably, comprehensive gene profiling of chronically rejected kidneys revealed two distinct subsets of chronically rejected transplants. Neither clinical data nor histology could explain this genetic heterogeneity. Conclusions. Microarray analysis of rejected kidneys may help to define different entities of transplant nephropathy, reflecting the multifactorial cause of chronic rejection.

Liver transplantation for unresectable hepatocellular carcinoma in normal livers

BACKGROUND & AIMS The role of liver transplantation in the treatment of hepatocellular carcinoma in livers without fibrosis/cirrhosis (NC-HCC) is unclear. We aimed to determine selection criteria for liver transplantation in patients with NC-HCC. METHODS Using the European Liver Transplant Registry, we identified 105 patients who underwent liver transplantation for unresectable NC-HCC. Detailed information about patient, tumor characteristics, and survival was obtained from the transplant centers. Variables associated with survival were identified using univariate and multivariate statistical analyses. RESULTS Liver transplantation was primary treatment in 62 patients and rescue therapy for intrahepatic recurrences after liver resection in 43. Median number of tumors was 3 (range 1-7) and median tumor size 8 cm (range 0.5-30). One- and 5-year overall and tumor-free survival rates were 84% and 49% and 76% and 43%, respectively. Macrovascular invasion (HR 2.55, 95% CI 1.34 to 4.86), lymph node involvement (HR 2.60, 95% CI 1.28 to 5.28), and time interval between liver resection and transplantation < 12 months (HR 2.12, 95% CI 0.96 to 4.67) were independently associated with survival. Five-year survival in patients without macrovascular invasion or lymph node involvement was 59% (95% CI 47-70%). Tumor size was not associated with survival. CONCLUSIONS This is the largest reported series of patients transplanted for NC-HCC. Selection of patients without macrovascular invasion or lymph node involvement, or patients ≥ 12months after previous liver resection, can result in 5-year survival rates of 59%. In contrast to HCC in cirrhosis, tumor size is not a predictor of post-transplant survival in NC-HCC.

A randomized trial comparing renal function in older kidney transplant patients following delayed versus immediate tacrolimus administration

Background. This large, randomized, multicenter trial evaluated if basiliximab induction and delayed tacrolimus can preserve renal function in older kidney transplant patients. Methods. Patients aged 60 years and older received delayed tacrolimus with basiliximab and mycophenolate mofetil with early steroid discontinuation (Tac-d, n=132) or standard tacrolimus with mycophenolate mofetil and steroids until day 91 (Tac-s, n=122). Tacrolimus trough levels were 5 to 10 ng/mL after day 43 in both groups. Renal function at month 6 was measured by calculated creatinine clearance (Cockcroft-Gault formula). Results. In both groups, mean recipient age was 66 years, mean donor age was 63 years with 73% of donors aged 60 years and older. Steroid discontinuation was slower than protocol specified. In the Tac-d group, 56.1% were steroid free at day 14 and 81.8% at month 6. In the Tac-s group, 37.7% were steroid free at month 4 and 63.9% at month 6. Mean (±SD) calculated creatinine clearance was 45.7±16.1 mL/min (Tac-d) and 45.0±18.2 mL/min (Tac-s) (P=ns), mean glomerular filtration rate (modified diet in renal disease formula) was 44.9±16.2 mL/min and 41.6±16.8 mL/min, respectively. Incidences of biopsy-proven acute rejection were 18.9% (Tac-d) and 18.0% (Tac-s). Delayed graft function was 30.3% (Tac-d) and 23.8% (Tac-s). Estimated patient survival rates (Kaplan-Meier) in the Tac-d and Tac-s groups were 96.1% vs. 99.2% and estimated graft survival rates were 90% vs. 87.6%, respectively. Safety results were similar with both regimens. Conclusion. Delayed tacrolimus with basiliximab induction did not provide an advantage in preserving renal function or reducing delayed graft function in older kidney transplant patients.

Twenty-year graft survival and graft function analysis by a matched pair study between pediatric en bloc kidney and deceased adult donors grafts.

Background. Pediatric en bloc kidney grafts, especially those from donors aged younger than 12 months, are still regarded controversially with respect to long-term graft survival and function as well as the postoperative development of serious hypertension and proteinuria. Patients and Methods. This retrospective single-center study analyzed 78 pediatric en bloc kidney grafts transplanted between October 1989 and December 2008. Mean donor age was 15 months in the pediatric en bloc kidney donor group and 37.8 years in the matched pair group. The mean follow-up period was 9.3 years (range, 1-19 years). Statistical analysis was performed using the Kaplan-Meier test for patient and graft survival. Continuous variables were compared using independent sample t test. Results. Graft survival for the pediatric donors after 1, 5, and 10 years were 83.1%, 76.0%, 73.9% and for the matched pair control group 89.6%, 78.7%, and 57.8%, respectively. Serum creatinine levels after 1, 5, and 10 years were 1.0, 0.8, 1.1 mg/dL and for the matched pair control group 1.5, 1.7, and 1.6 mg/dL, respectively. No significant long-term differences were detected between the study cohort groups with respect to the postoperative development of hypertension and proteinuria. Conclusion. Overall, pediatric en bloc kidney grafts are well suited to extend the scarce kidney donor pool in experienced centers because of a superior long-term outcome for graft survival and function in comparison with deceased adult kidney grafts. Special attention has to be paid to the substantial higher initial graft loss rate during the first postoperative year.

Graft survival and graft function of pediatric en bloc kidneys in paraaortal position.

Background. En bloc kidneys from pediatric donors are regarded as questionable with respect to the safety and quality of the transplant outcome. Therefore, we retrospectively studied graft outcome and graft function of our 56 en bloc kidneys transplanted in paraaortal position between 1992 and 1999. Methods. Graft outcome of en bloc kidneys (group A) was compared with graft outcome of single cadaveric adult donor kidneys (group B). Matched pairs were generated regarding HLA-missmatch, cold ischemic time, recipient age, body mass index, and systolic arterial blood pressure. Results. Allograft survival rates of pediatric en bloc kidneys at 1, 3, and 5 years were significantly lower (group A: 78, 70, 70% vs. group B: 92, 92, 81%, P <0.05). Lower survival rate was caused by a higher number of graft losses in the early postoperative period (group A: 21% vs. group B: 4%, P <0.01) due to vascular complications. Main risk factor for graft loss was donor age of less than 12 months. Five years after transplantation serum creatinine of pediatric en bloc kidneys was significantly better than of adult kidneys (0.9±0.06 vs. 1.8±0.2 mg/dl, P <0.001). Conclusion. En bloc kidneys show a high percentage of graft survival with excellent long-term graft function. However, the early postoperative period carries a higher risk of graft loss in very young donors due to vascular complications. In the face of donor shortage en bloc kidneys from pediatric donors can successfully be transplanted in a paraaortal position.

Autosomal Dominant Polycystic Kidney Disease: Prevalence of Renal Neoplasias in Surgical Kidney Specimens

Background: The role of autosomal dominant polycystic kidney disease (ADPKD) as a risk factor for renal cell carcinoma (RCC) is still under discussion. Data on prevalence of RCC in ADPKD are limited, especially on a large population scale. The aim of this study was to analyze the prevalence of RCC in ADPKD kidneys and characterize the clinical features of this coincidence. Methods: Based on our histopathological registry for ADPKD and the Else Kröner-Fresenius Registry, we retrospectively reviewed malignant and benign renal lesions in patients with ADPKD who had undergone renal surgery from 1988 to 2011. Results: 240 ADPKD patients underwent 301 renal surgeries. Mean age at surgery was 54 years. Overall, 16 malignant and 11 benign lesions were analyzed in 301 kidneys (5.3%; 3.7%), meaning that 12/240 (5%; 1:20) patients presented with malignant renal lesions. 66.7% (8/12) of these patients had undergone dialysis prior to surgery. We found 10/16 (63%) papillary RCC, 5/16 (31%) clear cell RCC, and 1/16 (6%) papillary noninvasive urothelial cancer. Regarding all renal lesions, 6/17 (35.3%) patients had more than one histological finding in their kidneys. In 2 cases, metachronous metastases were removed. Mean follow-up was 66.7 months. Conclusion: Kidney-related prevalence of RCC in ADPKD kidneys was surprisingly high. Whether or not this is due to chronic dialysis or due to the underlying disease is still speculative. Like other cystic renal diseases with an increased risk for RCC, the attending physician should be aware of the malignant potential of ADPKD, especially with concomitant dialysis.

One hundred consecutive kidney transplantations with simultaneous ipsilateral nephrectomy in patients with autosomal dominant polycystic kidney disease

PURPOSE Surgical management of autosomal dominant polycystic kidney disease (ADPKD) in patients awaiting renal transplantation is a challenging task. METHODS From 1998 to 2009, a total of 100 consecutive renal transplantations with simultaneous unilateral nephrectomy were performed in 59 men and 41 women with ADPKD and end-stage renal failure. About 38% received kidney allografts from living donors. The ipsilateral polycystic kidney was removed at the time of renal transplantation. Immunosuppressive therapy was not modified. Cold ischaemia time was 155 (38-204 min) versus 910 min (95-2760 min) for living versus deceased donor transplantation. Mean weight of removed kidneys was 2002 g (414-8850 g). Mean follow-up was 3.0 years (0.8-10.0 years). RESULTS Overall patient and graft survival were 97 and 96% at 1 year and 93 and 80% at 5 years, respectively. Serum creatinine at current follow-up was 1.49 (0.8-2.8) mg/dL. Surgical complications, which might be associated with simultaneous nephrectomy requiring re-operation, occurred in 12% (lymphocele 4%, hernia 4%, post-operative haematoma or bleeding 4%). None of the patients died peri-operatively. CONCLUSION Renal transplantation with simultaneous unilateral nephrectomy in ADPKD is a reasonable procedure for patients suffering from massively enlarged native kidneys.