Miha Arnol

Basiliximab versus daclizumab combined with triple immunosuppression in deceased donor renal transplantation: a prospective, randomized study.

Background. In this prospective, randomized, open-label, single-center study, we compared the efficacy and safety of two anti-interleukin-2 receptor monoclonal antibodies combined with triple immunosuppression. Methods. The adult recipients of at least one human leukocyte antigen-mismatched deceased donor renal graft on cyclosporine microemulsion, mycophenolate mofetil, and methylprednisolone were randomized to induction with basiliximab or daclizumab, given in standard doses. An intent-to-treat analysis of 1-year data assessed the incidence of acute rejections, graft function, patient and graft survival, and safety of this therapy. Results. Two hundred twelve patients were studied. At 12 months, 11 (10.3%) and 10 (9.5%) patients experienced biopsy-confirmed first acute rejection in basiliximab and daclizumab groups, respectively. Estimated glomerular filtration rate was 69±19 mL/min/1.73 m2 in the basiliximab and 66±21 mL/min/1.73 m2 in the daclizumab group. Patient survival was 97.2% with basiliximab and 97.1% with daclizumab, and graft survival was 94.4% vs. 90.5%, respectively. Hospital treatment was required for 50 and 59 infections in basiliximab and daclizumab groups, respectively. One renal cell carcinoma of native kidney and one basal cell carcinoma were detected in the basiliximab group, and one melanoma of skin in the daclizumab group. One hypersensitivity reaction was observed with daclizumab. No significant differences were found between the groups. Conclusion. Basiliximab or daclizumab combined with triple therapy was an efficient and a safe immunosuppression strategy, demonstrated with low incidence of acute rejections, excellent graft function, high survival rates, and acceptable adverse event profile in adult recipients within the 1st year after deceased donor renal transplantation.

Late Steroid Withdrawal and Cardiovascular Events in Kidney Transplant Recipients

Introduction. Cardiovascular events (CVE) are the leading cause of mortality in kidney transplant recipients. The adverse effects of long-term therapy with steroids on cardiovascular risk have motivated increasing interest in steroid withdrawal (SW). The objective of this study was to compare the incidences of CVE and all-cause mortality between patients who had undergone SW at 1 year posttransplant and control patients who continued on steroids. Methods. A cohort of 400 consecutive adult recipients of a kidney transplant between 1993 and 1998 who qualified for late SW was studied. At 1 year posttransplant 188 patients underwent SW, whereas 212 patients continued on steroids. Cox proportional-hazards analysis was used to estimate CVE (cardiac and cerebrovascular events) and all-cause mortality hazard ratios (HR) for patients who had undergone SW versus controls who continued on steroids beyond 1 year. Results. The average follow-up was 61 months. There were 44 (11%) cardiac events, 18 (4.5%) cerebrovascular events, and 41 deaths (10.3%). The composite outcome of CVE and all-cause mortality was reached in 26 (13.8%) subjects who had undergone SW and 50 (23.6%) controls (P=0.013). In adjusted analyses, SW was associated with decreased risk for the composite outcome (HR 0.46, 95% confidence interval [CI] 0.28–0.76), cardiac events (HR 0.48, 95% CI 0.28–0.84), and all-cause mortality (HR 0.27, 95% CI 0.12–0.59). There was no association of SW with the risk for cerebrovascular events (HR 1.76, 95% CI 0.45–7.01). Conclusion. In this retrospective analysis, SW at 1 year posttransplant was associated with decreased risk for future CVE and all-cause mortality.

Long-Term Kidney Regraft Survival From Deceased Donors : Risk Factors and Outcomes in a Single Center

Background. Although survival of kidney regrafts is similar to that of primary grafts, risk factors associated with regraft survival have not been defined clearly. The aim of this study was to investigate risk factors for regraft outcome, including characteristics of the previous and current transplant, and time to retransplant. Methods. In a historical cohort study, 966 primary and 176 repeat deceased donor kidney graft recipients transplanted between January 1, 1990 and December 31, 2004 were studied. Cox regression analysis was used to estimate graft loss hazard ratios (HR) for regrafts versus primary grafts. Adjustments were made for recipient and donor demographics, transplant-related factors (transplant era, panel reactive antibodies, human leukocyte antigens mismatches, immunosuppression, delayed graft function, acute rejection [AR]), previous transplant characteristics (graft survival, graft loss because of AR), and time to retransplant. Results. A total of 508 kidney grafts were lost in the period between January 1990 and May 2007: 427 primary grafts and 81 regrafts. Regraft recipients had a covariate-adjusted 6% increase in graft loss (HR=1.06; P=0.69). Regraft loss was significantly associated with previous graft survival less than or equal to 1 year (HR=2.01; P=0.004), previous graft loss because of AR (HR=2.26; P=0.017) and time to retransplant more than 1 year (HR=2.42; P=0.002). Other significant predictors of regraft loss were diabetes (HR=1.81), donor age more than 50 years (HR=1.86) and delayed graft function after retransplant (HR=1.95). Conclusions. Kidney regrafts seem to have similar long-term outcome as primary grafts. However, additional risk factors significantly associated with regraft survival are previous graft survival, graft loss because of rejection, and time to retransplant.

Survey of Renal Transplantation in Slovenia

This brief survey presents data on renal transplantation in Slovenia, a country with a population of 2 million, which has one renal transplant center. The establishment of an appropriate national transplantation organization resulted in an increase in transplantations and the acceptance of Slovenia into Eurotransplant (ET) at the beginning of 2000. Current immunosuppression is composed of cyclosporine microemulsion (Neoral), mycophenolate mofetil, methylprednisolone, and anti‐interleukin‐2 receptor monoclonal antibodies. By the end of 2008, 766 renal transplantations had been performed, and from 1970 to 2007, 125 patients had been transplanted from living related donors. From 1986 to 1999, 239 patients received renal grafts from deceased donors. From 2000 to 2008, 402 patients were transplanted from deceased donors. In 2004, 55 renal transplantations were done. Two hundred and twenty‐eight (56.7%) renal grafts were shipped from other ET countries. The HLA‐antigen mismatch of 2.7 ± 1.1 was not significantly different to that before 2000. From 2000 to 2008, the one‐ and five‐year patient survival rates were 98.2% and 95.2%, respectively. The concomitant graft survival rates were 94.4% and 90.9%, respectively. In the ET era, the number of deceased donor renal transplants per year was 2.6 times higher than in the 14 years before. In 2004 we reached the average number of deceased donor renal transplants per million population of ET. Short‐ and medium‐term results of the last nine‐year period have been very good and entirely comparable to those in large reports.

Plasmapheresis and immunoadsorption for treatment and prophylaxis of recurrent focal segmental glomerulosclerosis in adult recipients of deceased donor renal grafts.

Recurrent focal segmental glomerulosclerosis has a great impact on kidney graft survival. This retrospective study presents immunoadsorption‐plasmapheresis treatment and outcome in our renal graft recipients with significant post‐transplant proteinuria (>1 g/day) and focal segmental glomerulosclerosis in native kidneys. Recurrence was defined as occurrence of nephrotic range proteinuria or biopsy‐confirmed diagnosis. Successful treatment was defined as sustained reduction of proteinuria to <1 g/day. From 2000 through 2011, 548 adult patients received kidney grafts from deceased donors. In 20 of these patients (3.6%) end‐stage renal disease was a consequence of focal segmental glomerulosclerosis. Recurrence was confirmed in five of seven treated patients. Immunoadsorption‐plasmapheresis treatment was successful in five patients (70%). Their age at disease diagnosis in native kidneys was 12 to 44 years. Time to end‐stage renal disease was 3 to 14 years. Recipient age at transplantation was 21 to 61 years. Onset of significant proteinuria was 2 to 87 days after transplantation. Immunoadsorption or plasmapheresis started 1 to 7 days after recurrence of significant proteinuria. Treatment period was 1 to 103 months and 12 to 206 procedures were performed per patient. Follow‐up period after cessation of plasmapheresis was 11 to 58 months. Final urine protein/creatinine ratio was 8.8 to 98.0 mg/mmol and final serum creatinine was 63 to 148 μmol/L. Follow‐up after transplantation was 18 to 135 months. One patient was still on treatment. One graft was lost to recurrence. No serious adverse effects occurred during immunoadsorption and plasmapheresis. Immunoadsorption and plasmapheresis appears to be successful in the majority of patients, probably due to their early start.

Intermittent high-volume predilution on-line haemofiltration versus standard intermittent haemodialysis in critically ill patients with acute kidney injury: a prospective randomized study

Recent experiences in other fields of medicine show that more intensive treatment does not lead to better outcomes […] We may need to re-consider the value of careful monitoring and conservative treatment as a valid and independent option in the treatment of AKI.

Dialysis Patients Refusing Kidney Transplantation: Data From the Slovenian Renal Replacement Therapy Registry

Kidney transplantation is considered the best renal replacement therapy (RRT) for patients with end‐stage renal disease; nevertheless, some dialysis patients refuse to be transplanted. The aim of our registry‐based, cross‐sectional study was to compare kidney transplant candidates to dialysis patients refusing transplantation. Data were collected from the Slovenian Renal Replacement Therapy Registry database, as of 31 December 2008. Demographic and some RRT data were compared between the groups. There were 1448 dialysis patients, of whom 1343 were treated by hemodialysis and 105 by peritoneal dialysis (PD); 132 (9%) were on the waiting list for transplantation, 208 (14%) were preparing for enrollment (altogether 340 [23%] dialysis patients were kidney transplant candidates); 200 (13.7%) patients were reported to refuse transplantation, all ≤65 years of age; 345 (24%) were not enrolled due to medical contraindications, 482 (33%) due to age, and 82 (6%) due to other or unknown reasons. No significant difference was found in age, gender, or presence of diabetes between kidney transplant candidates vs. patients refusing transplantation (mean age 50.5 ± 13.9 vs. 51.3 ± 9.6 years, males 61% vs. 63%, diabetics 18% vs. 17%). The proportion of patients ≤ 65 years old who were refusing transplantation was 28% (187/661) for hemodialysis and 17% (13/79) for PD patients (P = 0.03). There is a considerable group of dialysis patients in Slovenia refusing kidney transplantation. Compared to the kidney transplant candidates, they are similar in age, gender and prevalence of diabetes. Patients treated by peritoneal dialysis refuse kidney transplantation less often than hemodialysis patients.

Slovenian Renal Replacement Therapy Registry: Excerpts From the 2006 Annual Report

The total number of end‐stage renal disease patients treated by renal replacement therapy (RRT) in Slovenia on 31 December 2006 was 1835, that is, 913 per million population (pmp). Of these patients, 1271 (69%) were treated by hemodialysis, 102 (6%) by peritoneal dialysis, and 461 (25%) had a functioning kidney graft. Two hundred and forty‐nine incident patients, 124 pmp (at day one), started RRT: median age 66 years, 60% men, 30.5% diabetics. Of the hemodialysis patients, 77% were dialyzed in hospital and 23% in private dialysis centers. Hemodiafiltration was used in 38% of the hemodialysis patients. The vascular accesses were native arteriovenous fistulas in 84%, polytetrafluoroethylene grafts in 5%, and hemodialysis catheters in 11% of patients. The crude death rate of dialysis patients was 14.7%, of transplant recipients 1.35%, of both dialysis and transplant patients 11.4%. The number of patients positive for hepatitis B or C viruses is stable and low at 2.3% of the dialysis patients.

Renal Replacement Therapy in Slovenia: Excerpts From 2011 Data

This report provides a summary of the 2011 Slovenian renal replacement therapy (RRT) data. Data were obtained from 24 renal centers: 23 dialysis and one transplant center, referred as of 31 December 2011, with 100% response rate to individual patient questionnaires. Slovenia has a population of approximately 2 million (2 052 496 in 2011). The total number of patients treated by RRT was 2011,that is, 980 per million of population (pmp); 0.4% decrease compared to 2010. 1347 (67.0%) were treated by hemodialysis, 60 (3.0%) by peritoneal dialysis, and 604 (30.0%) had a functioning kidney graft. A total of 236 incident patients, 115 pmp (at day one), started RRT, their median age was 68 years, 64.8% were men, 36.4% were diabetics. Regarding hemodialysis patients, 59.3% were treated with on‐line hemodiafiltration, 86% with ultrapure dialysis fluid. Median weekly duration of hemodialysis was 12.5 h, median dry body weight 70 kg, mean blood flow 275 ± 46 mL/min, 7.1% were dialyzed in a single‐needle mode. Vascular accesses were native arteriovenous fistula in 79%, polytetrafluoroethylene graft in 6%, and catheter in 15%. The crude death rate was 15.9% in dialysis patients, 1.9% in transplant recipients, and 12.0% in all RRT patients (both dialysis and transplant, incident patients at day 1 included). Slovenia has been a member of Eurotransplant since 2000. Forty‐six kidney transplantations were performed in 2011, all from deceased donors. A slight decrease in prevalent number of RRT patients was observed in 2011, for the first time in 40 years. The number and proportion of patients with functioning kidney grafts is increasing, reaching 30% in 2011.

Slovenian Renal Replacement Therapy Registry: Excerpts from the 2008 Annual Report: Renal Replacement Therapy in Slovenia

This report provides a summary of the 2008 Slovenian Renal Replacement Therapy Registry Annual Report. Data on renal replacement therapy (RRT) were obtained from 20 dialysis centers and one transplant center, referring 31 December 2008, with 100% response rate to individual patient questionnaires. Slovenia has a population of approximately two million. The total number of patients treated by RRT was 1967, i.e. 968 per million of population (pmp), a 3.7% increase compared to 2007. In total, 1343 (68.3%) were treated by hemodialysis, 105 (5.3%) by peritoneal dialysis, and 519 (26.4%) had a functioning kidney graft. A total of 235 incident patients, 116 pmp (at day one), started RRT: their median age was 67 years, 61.8% were men, and 28% were diabetics. Regarding hemodialysis patients, 77% were dialyzed in hospital and 23% in private centers, 48% were treated with on‐line hemodiafiltration and 74% with ultrapure dialysis fluid. The median weekly duration of hemodialysis was 13.5 hours, median dry body weight 68 kg, mean blood flow 283 ± 51 mL/min, and 9.2% were dialyzed using a single‐needle mode. Vascular access was provided by a native arteriovenous fistula in 82%, a polytetrafluoroethylene graft in 6%, and a catheter in 12%. The crude death rate was 12.4% in dialysis patients, 1.4% in transplant recipients, and 9.4% in all RRT patients (both dialysis and transplant, incident patients at day 1 included). The longest survival on RRT is 38 years (with hemodialysis only). Slovenia has been a member of Eurotransplant since 2000; 52 kidney transplantations were performed in 2008, all from deceased donors.