Paricalcitol versus placebo for reduction of proteinuria in kidney transplant recipients: a double-blind, randomized controlled trial.

Proteinuria after kidney transplantation is accompanied by an increased risk of graft failure. In this single-center, placebo-controlled, double-blind trial we studied whether vitamin D receptor activator paricalcitol might reduce proteinuria. Patients with urinary protein-to-creatinine ratio (UPCR) ≥20 mg/mmol despite optimization of the renin angiotensin aldosterone system (RAAS) blockade were randomly assigned to receive 24 weeks' treatment with 2 µg/day paricalcitol or placebo. Primary endpoint was change in UPCR, and main secondary endpoints were change in urinary albumin-to-creatinine ratio (UACR) and 24-h proteinuria. Analysis was by intention to treat. One hundred and sixty-eight patients undergo randomization, and 83 were allocated to paricalcitol, and 85 to placebo. Compared with baseline, UPCR declined in the paricalcitol group (-39%, 95% CI -45 to -31) but not in the placebo group (21%, 95% CI 9 to 35), with a between group difference of -49% (95% CI -57 to -41; P < 0.001). UACR and 24-h proteinuria decreased only on paricalcitol therapy and significantly differed between groups at end-of-treatment (P < 0.001). Paricalcitol was well tolerated but incidence of mild hypercalcemia was higher than in placebo. In conclusion, addition of 2 µg/day paricalcitol lowers residual proteinuria in kidney transplant recipients. Long-term studies are needed to determine if the reduction in proteinuria improves transplant outcomes (ClinicalTrials.gov, number NCT01436747).

Effects of paricalcitol on biomarkers of inflammation and fibrosis in kidney transplant recipients: results of a randomized controlled trial.

AIMS: Paricalcitol, a selective vitamin D activator, decreases proteinuria and may reduce graft failure risk in kidney transplant recipients. In this study, we evaluated the effect of paricalcitol on renin-angiotensin system (RAS) activity as well as interleukin (IL)-6 and transforming growth factor (TGF)-ß plasma concentrations as biomarkers of inflammation and fibrosis. METHODS: This placebo-controlled, double-blind trial enrolled a national cohort of kidney transplant recipients with urinary protein-to-creatinine ratio (UPCR) ≥ 20 mg/mmol despite optimization of the RAS blockade. Patients were randomly assigned to receive 24 weeks of treatment with 2 µg/day paricalcitol or placebo. The primary endpoint was the percent change in geometric mean UPCR. In this secondary analysis, we examined the effect of paricalcitol on plasma renin activity (PRA) and aldosterone levels as well as IL-6 and TGF-ß plasma concentrations from baseline to last measurement during treatment. RESULTS: Of the 168 patients with UPCR ≥ 20 mg/mmol who consented to undergoing randomization, 83 were allocated to paricalcitol and 85 to placebo. Baseline patient demographics, clinical characteristics, PRA, and aldosterone levels were similar between groups. Mean change in IL-6 was -29% (from 2.53 to 2.02 pg/mL) in the paricalcitol group and 23% (from 2.07 to 2.54 pg/mL) in the placebo group (p < 0.001). Mean change in TGF-ß was -12% (from 8,011 to 6,935 pg/mL) in the paricalcitol group and 21% (from 7,418 to 8,992 pg/mL) in the placebo group (p < 0.001). CONCLUSION: In kidney transplant recipients, the addition of 2 µg/day paricalcitol to RAS inhibition lowers IL-6 and TGF-ß concentrations, which may be beneficial for reducing graft inflammation and fibrosis.
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Role of dry lean body mass for estimation of glomerular filtration rate in kidney transplant recipients.

BACKGROUND: The use of equations that predict glomerular filtration rate (GFR) in patients with a kidney graft is still a matter of debate. The purpose of this study was to determine the level of accuracy of GFR equations and the relevance of dry lean body mass in the assessment of GFR. METHODS: In a prospective clinical study, 100 patients with a kidney graft were included. Estimated GFR with Modification of Diet in Renal Disease equation (MDRD), Chronic Kidney Disease Epidemiology Collaboration equation (CKD EPI) with serum creatinine concentration (CKD EPI Cr), serum cystatin C concentration (CKD EPI CysC) or both (CKD EPI Cr-CysC), and creatinine clearance calculated with Cockcroft-Gault equation (CG) was compared with GFR measured by 51Cr-EDTA clearance (mGFR 51Cr-EDTA). Dry lean body mass (body mass without fat mass and body water) was measured with bioimpedance analysis. RESULTS: All of the estimating equations overestimated mGFR 51Cr-EDTA by a significant degree (bias ± SD in mL/min/1.73m2, 30% accuracy in brackets): CG 16.8 ± 14.1 (44%), MDRD 12.5 ± 15.3 (54%), CKD EPI Cr 15.1 ± 15.3 (50%), CKD EPI CysC 8.0 ± 16.6 (56%), CKD EPI Cr-CysC 10.3 ± 13.4 (55%). Dry lean body mass significantly correlated with mGFR 51Cr-EDTA, but not with estimated GFRs. CONCLUSION: The estimating GFR equations are neither accurate nor precise in renal transplant recipients. Dry lean body mass is an important parameter that could potentially improve the GFR estimation in this population.
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Increase in spot urine protein excretion is associated with late kidney graft rejection and predicts rejection phenotype.

AIMS: A noninvasive test that foretells kidney graft rejection before loss of kidney function would be desirable. We hypothesized that an increase in estimated protein excretion rate (ePER) from spot urine samples is associated with graft rejection and predicts rejection phenotype. METHODS: 151 patients who had undergone first-indication kidney biopsy due to graft dysfunction beyond 3 months after transplant were identified from a national cohort of 616 transplant recipients between 2000 and 2012 (25%). ePER were calculated from spot urine protein-to-creatinine ratios at baseline, 3 months before biopsy (ePER-3m), and at the time of biopsy (ePERbiopsy) and were correlated with histologic biopsy findings. RESULTS: Levels of ePER 3 months before biopsy and at the time of biopsy were greater in 32 patients with antibody-mediated rejection (ABMR) than in 77 patients with T-cell-mediated rejection (TCMR) and 42 patients with other findings (median ePER-3m 912 vs. 320 vs. 232 mg/day/1.73m2; and median ePERbiopsy 1,672 vs. 356 vs. 268 mg/day/1.73m2; p < 0.001). Receiver operator characteristics (ROC) analyses demonstrated that ePER-3m and ePERbiopsy had good diagnostic accuracy to discriminate between biopsy specimens showing ABMR vs. those showing TCMR or other histologic findings (area under the ROC curve 0.84, 95% CI 0.75 - 0.93 and 0.89, 95% CI 0.82 - 0.97, respectively; p < 0.001). CONCLUSIONS: An increase in ePER before kidney graft dysfunction appears to be associated with graft rejection and predicts ABMR phenotype.
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The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients.

BACKGROUND: Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. METHODS: Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many 'operationally tolerant' patients (TOL; defined as having a serum creatinine <1.7 mg/dL and proteinuria <1 g/day or g/g creatinine despite at least 1 year without any immunosuppressive drug) and 'almost tolerant' patients (minimally immunosuppressed patients (MIS) receiving low-dose steroids) as possible. We reported their number and the total number of kidney transplants performed at each centre to calculate their frequency. RESULTS: One hundred and forty-seven questionnaires were returned and we identified 66 TOL (61 with complete data) and 34 MIS patients. Of the 61 TOL patients, 26 were previously described by the Nantes group and 35 new patients are presented here. Most of them were noncompliant patients. At data collection, 31/35 patients were alive and 22/31 still operationally tolerant. For the remaining 9/31, 2 were restarted on immunosuppressive drugs and 7 had rising creatinine of whom 3 resumed dialysis. Considering all patients, 10-year death-censored graft survival post-immunosuppression weaning reached 85% in TOL patients and 100% in MIS patients. With 218 913 kidney recipients surveyed, cumulative incidences of operational tolerance and almost tolerance were estimated at 3 and 1.5 per 10 000 kidney recipients, respectively. CONCLUSIONS: In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival.

Transmission of pancreatic adenocarcinoma by a single multiorgan donor to two kidney transplant recipients: A case report.

We present two cases of transmission of a pancreatic adenocarcinoma from a single donor to two kidney transplant recipients. Autopsy of the donor revealed a pancreatic adenocarcinoma that had already spread locally to the regional lymph nodes and had not been detected at the time of organ procurement. Both recipients were carefully monitored, as neither consented to graft nephrectomy. In one patient, the tumor was discovered on surveillance biopsy of the graft approximately 14 months after transplantation, and in the second patient, ultrasound-guided aspiration needle biopsy of a growing formation in the lower pole of the graft revealed poorly differentiated metastatic adenocarcinoma. Both patients were successfully treated with graft nephrectomy and complete discontinuation of immunosuppression. None of the follow-up imaging showed persistent or recurrent malignancy, and both patients were candidates for re-transplantation. These exceptional cases of donor-derived pancreatic adenocarcinoma suggest that removal of the donor organ and restoration of immunity may lead to complete recovery.

Decrease in 1-year Kidney Graft Size Predicts Inferior Outcomes After Deceased Donor Kidney Transplantation.

BACKGROUND: Longest bipolar length of the kidney graft is routinely measured for ultrasonographic assessment of graft size (GS), although the value of the graft length remains unclear. METHODS: In a single-center, observational study involving 319 deceased-donor kidney transplant recipients, we assessed variations in absolute and adjusted GS (corrected for body surface area) between 1 and 12 months after transplantation ([INCREMENT]GS1m→12m). We tested whether variations in GS during the first year were predictive of the composite outcome of a reduction of 50% or more in the estimated glomerular filtration rate or end-stage graft failure. RESULTS: At 1 year after transplantation, 121 patients (38%) had a decrease in GS ([INCREMENT]GS1m→12m <0), and 198 patients (62%) had an increase in GS ([INCREMENT]GS1m→12m ≥0). After a median follow-up of 53 months, 41 patients with a decrease in GS reached the composite outcome as compared with 12 patients with an increase in GS (34% and 6%, respectively; P < 0.001). Areas under the receiver operating characteristics curves of absolute and adjusted [INCREMENT]GS1m→12m for composite outcome were 0.81 (95% confidence interval [95% CI], 0.74-0.88) and 0.78 (95% CI, 0.70-0.86), respectively. In multivariate analysis, the risk of the composite outcome was significantly higher among patients with a decrease in GS during the first year after transplantation (hazard ratio, 4.55; 95% CI, 2.35-8.81; P < 0.001). CONCLUSIONS: A decrease in kidney GS during the first year after transplantation, as compared with an increase in GS, is a powerful predictor of subsequent graft dysfunction or end-stage graft failure.

Kidney Transplantation in Slovenia From 1970 to 2015.

This report gives an overview of kidney transplantation in Slovenia, a country with a population of 2.1 million and one transplant center. The establishment of a national transplant organization resulted in the acceptance of Slovenia into Eurotransplant (ET) in 2000. Between 1970 and 2015, 1158 kidney transplantations were performed. From 1970 to 2009, 126 patients were transplanted from living related donors, only two in the ET period. From 1986 to 1999, 239 patients received kidney grafts from deceased donors, while 793 patients were transplanted from deceased donors after joining ET. In ET period, 1- and 5-year patient survival rates were 98.1% and 93.8%, and the concomitant graft survival rates were 94.3% and 87.5%, respectively. During the ET period, the number of deceased donor kidney transplants per year was three times higher than in the 14 years before. Patient and graft survival rates have been very good and entirely comparable to those in large reports.

Post-Transplant Recurrence of Focal Segmental Glomerulosclerosis in a Child With Heterozygous Mutations in NPHS1 and NPHS2.

Renal transplantation is the optimal renal replacement therapy (RRT) in children, but some primary diseases can recur after transplantation, and recurrence accounts for a significant proportion of graft losses, being second only to acute rejection. The risk of disease recurrence is highest among patients with idiopathic focal segmental glomerulosclerosis (FSGS), presumably due to a circulating permeability factor. Less is clear about the genetic forms of FSGS, where the data regarding the frequency of recurrence are rather conflicting. We present a 12-year-old girl with rapidly progressive FSGS and end-stage renal disease in her native kidneys associated with heterozygous mutations in NPHS1 and in NPHS2, suffering from early post-transplant recurrence. On the basis of reviewed literature, and until further and more conclusive evidence considering pathogenicity is provided, we propose that FSGS patients with heterozygous mutations in NPHS1 or NPHS2 should be considered as having idiopathic FSGS, and post-transplant recurrence should be anticipated.

Treatment of Antibody-Mediated Rejection After Kidney Transplantation - 10 Years' Experience With Apheresis at a Single Center.

Antibody-mediated rejection (AMR) is a major cause of kidney graft failure. We aimed to analyze treatment and outcome of AMR in a national cohort of 75 biopsy-proven acute (43 patients, 57%) or chronic active (32 patients, 43%) AMR episodes between 2000 and 2015. The mean patients' age was 46 ± 16 years, the majority was treated with plasma exchange, 4% received immunoadsorption and 7% received both. The majority received pulse methylprednisolone and low-dose CMV hyperimmune globulin, 20% received bortezomib and 13% rituximab. Concomitant infection was treated in 40% of patients. The immediate treatment outcome was successful in 91%, the 1- and 3-year graft survival rates were 71% and 57%, while 3-year patient survival was 97%. Chronic active AMR was associated with worse graft survival than acute AMR (log rank P = 0.06). To conclude, intensive treatment with apheresis and additional immunosuppression was effective in reversing AMR, but long-term graft survival remains markedly decreased, especially in chronic active AMR.

Renal Replacement Therapy in Slovenia: Excerpts From 2013 Data.

This report provides a summary of the 2013 Slovenian renal replacement therapy (RRT) data, obtained from 24 renal centers: 23 dialysis and one transplant center, referring from 31 December 2013, with 100% response rate to individual patient questionnaires. Slovenia had a population of 2 061 085 on 1 January 2014. The total number of patients treated by RRT was 2077, i.e. 1008.3 per million of population (pmp); 1349 (65%) were treated by hemodialysis, 52 (2.5%) by peritoneal dialysis, and 676 (32.5%) had a functioning kidney graft. A total of 260 incident patients, 126.2 pmp (at day one), started RRT, their median age was 69 years, 59.8% were men,. 58.5% of hemodialysis patients were treated with on-line hemodiafiltration. Vascular access was arteriovenous fistula in 79%, polytetrafluoroethylene graft in 8%, and catheter in 13% of patients, mean blood flow 276 ± 41 mL/min, 5.5% dialyzed in a single-needle mode. The crude death rate was 11.4% in all RRT patients (incident patients day 1 included, 15.9% in hemodialysis, 12.3% in peritoneal dialysis, 2.1% in transplant recipients). 60 kidney transplantations were performed in 2013, from deceased donors.

Our experience with epoetins in treating renal anemia.

Epoetin treatment of renal anemia has been practiced in Slovenia since 1988. More than 90% of hemodialysis patients and 83% of peritoneal dialysis patients have been treated with epoetin. Epoetin has also been available for patients with renal anemia in the pre-dialysis period and for those with a failing kidney allograft. Although epoetin treatment did not accelerate the worsening of native kidney function or allograft function, intensified antihypertensive treatment was required in kidney graft recipients. In patients on peritoneal dialysis, hypervolemia had a greater effect on hypertension than did epoetin treatment. Epoetin resistance was connected with C-reactive peptide cryptorchidism, intact parathyroid hormone, and treatment with angiotensin-converting enzyme inhibitors. In hemodialysis patients, lower doses of epoetin were required for patients receiving low molecular heparin and those with lower iPTH. Epoetin alpha, epoetin beta and epoetin omega seemed to be effective and safe in the treatment of renal anemia. In the past 2 years, epoetins were administered to hemodialysis patients only intravenously.

Prevention of early acute rejection with daclizumab and triple immunosuppression in cadaveric renal allograft recipients.

We carried out a prospective study of the safety and efficacy of daclizumab combined with triple immunosuppression in adult recipients of at least one HLA-mismatched cadaveric renal allograft. All studied patients received the same immunosuppression: a daclizumab infusion of 1 mg/kg immediately before transplantation, and at 2, 4, 6, and 8 weeks following the transplantation. Infusion of cyclosporine (CsA) (0.08 mg/kg/h) was started at the time of the operation and continued by CsA microemulsion (CsA-Neoral), 3 mg/kg twice daily on day 2, methylprednisolone, 0.4 mg/kg intravenously at operation, and mycophenolate mofetil started on day 1. The dose of CsA-Neoral was adjusted to maintain target blood trough levels. Oral methylprednisolone was tapered by 4 mg per week to achieve a maintenance dose of 0.08 mg/kg/day. Fifty-five patients, with a mean age of 48 +/- 11 years, were studied. Six of them received a second renal allograft. The mean donor age was 38 +/- 14 years. Mean cold ischemia time was 19.5 +/- 6.5 h, mean value of HLA-antigen mismatches was 2.7 +/- 0.9, mean latest PRA value was 3 +/- 7%. Fifteen patients experienced delayed graft function. During a follow-up period of 3 months three acute rejection episodes occurred. One patient died because of systemic aspergillosis. After 3 months mean serum creatinine was 104 +/- 38 micromol/L. Five renal allografts failed, one of them due to rejection. Patient and graft survival was 98.2% and 90.9%, respectively. Daclizumab with this triple therapy represents safe and efficient immunosuppression strategy, demonstrated with low incidence of early acute rejection episodes and an acceptable adverse event profile in cadaveric renal allograft recipients.

Epoetin responsiveness in peritoneal dialysis patients: a multi-center Slovenian study.

The objective of our study was to assess the influence of residual renal function and other factors on epoetin requirements in chronic peritoneal dialysis patients. Fifty-one stable patients (mean age +/- SD: 52 +/- 13 years; 20 women) without recent bleeding, bone marrow disease or malignancy were recruited in four Slovenian centers. The target hemoglobin was above 110 g/L. The peritoneal equilibration test results and relevant clinical and laboratory parameters were recorded. The epoetin resistance index was expressed as a weekly epoetin dose/body weight/hemoglobin concentration. Twenty-four percent of the patients did not need epoetin treatment, the rest were treated with epoetin-beta in a dose of 70 +/- 56 U/kg per week s.c.; the hemoglobin concentration was 124 +/- 15 g/L. Ferritin >100 microg/L and transferrin saturation >20% fulfilled 63% of patients whose epoetin resistance index was not significantly lower (0.43 +/- 0.5 U/kg per week per g/L vs 0.6 +/- 0.72 U/kg per week per g/L, P = 0.502). No difference was found between diabetic and non-diabetic patients. Treatment with angiotensin system antagonists, but not with aluminum phosphate binders, was associated with increased epoetin resistance index (0.56 +/- 0.59 vs 0.3 +/- 0.4 U/kg per week per g/L, P = 0.038). No correlation between epoetin resistance index and residual glomerular filtration rate was found (r = -0.2, P = 0.173). A multiple linear regression analysis showed C-reactive protein, intact parathormone level, female sex and treatment with angiotensin system antagonists to be the independent predictors influencing epoetin resistance index. Our results show that systemic inflammation, secondary hyperparathyroidism and angiotensin system antagonist treatment are the most important modifiable parameters affecting epoetin requirements in stable peritoneal dialysis patients.

Hemodialysis arteriovenous fistula-related complications and surgery in kidney graft recipients.

Arteriovenous fistula (AVF) remains functional after kidney transplantation in many patients. The aim of this historical cohort study was to evaluate the data on AVF-related complications and surgery performed after kidney transplantation in our patients. The study cohort included the recipients of a kidney transplant with AVF complications between January 2006 and April 2012. 74 renal transplant recipients (47% male, mean age 51 ± 10, range 14 to 73 years) with complications related to AVF were analyzed. Among all AVFs, 51 (72%) were located in the forearm, nine (13%) in the upper arm, and 14 (15%) in the elbow. Complications occurred in 12.5% (74/592) of kidney graft recipients who were treated at our Outpatient Transplant Unit during the study period. The most common complication was painful thrombosis with or without thrombophlebitis, which occurred in 32 patients (43.2%). Other complications included growing aneurysms (27%, 20/74), venous hypertension with arm edema (8.1%, 6/74), distal hypoperfusion (8.1%, 6/74), high flow AVF with cardiac failure (8.1%, 6/74), trauma (1.3%, 1/74), and cosmetic appearance (4%, 3/74). Fifty-one surgical interventions were performed in 49 patients (mean age 52 ± 12, range 28 to 73 years). AVF closure was performed in 29/51 (56%) patients. Furthermore, an extirpation of aneurysm was performed in 12/51 (23%) and an extirpation of thrombosed AVF was performed in 1/51 (2%) patients, simple trombectomies were performed in 5/51 (10%) and a thrombectomy with reanastomosis was performed in 4/51 (8%) patients. One patient underwent percutaneous transluminal angioplasty for underlying stenosis after surgery. The most common AVF-related complications in kidney graft recipients are painful thrombosis (often accompanied with thrombophlebitis) and growing aneurysms. Surgical intervention is performed in a significant proportion of patients, mainly AVF closure, aneurysm extirpation, and thrombectomy.

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.

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.

Association of pretransplant renal replacement therapy duration with outcome in kidney transplant recipients: a prevalent cohort study in Slovenia.

The effect of renal replacement therapy (RRT) duration on kidney transplant outcome is controversial. The aim of this study was to analyze the association between pretransplant RRT duration versus patient and graft survival. The study cohort included 445 recipients of a deceased-donor kidney transplant between January 2000 and December 2009. Pretransplant RRT duration as a continuous variable and divided into time categories was the risk factor of interest. Patient and death-censored graft survival were the outcomes. Survival since the onset of RRT was calculated to avoid lead-time bias. Median pretransplant RRT duration was 4.7 years. The duration of RRT was longer in 33 patients who died (median 6.8 vs. 4.6 years; P = 0.022) and 56 patients who lost their graft (5.7 vs. 4.6 years; P = 0.035). Pretransplant RRT duration, as a continuous variable, was associated with a non-significant increase in the risk of recipient death (hazard ratio [HR] 1.01 per year of RRT; P = 0.09) and death-censored graft loss (HR 1.02; P = 0.12). When RRT was studied as a categorical variable, the mortality risk reached statistical significance when the patient had been on RRT for more than 4.7 years (HR 2.12; P = 0.042). Pretransplant RRT duration was not associated with an increased risk for recipient death if patient survival was calculated since the onset of RRT (HR 0.98 per year; P = 0.21). This study suggests that a longer RRT duration negatively impacts on post-transplant patient and graft survival; however, when pretransplant patient survival is accounted for, RRT duration has no significant effect on patient outcome.

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.

Dialysis patients after kidney graft failure: Slovenian experience.

Increased mortality has been reported in patients starting dialysis after kidney graft failure. In this study we analyzed this subgroup of dialysis patients based on the data from the Slovenian Renal Replacement Therapy Registry. Patients starting dialysis after graft failure in the period between 2004 and 2008 were identified from the registry. Demographic, clinical and treatment data, as well as survival were compared to incident dialysis patients, who were on the waiting list or preparing for enrollment. There were 49 patients starting dialysis after 7.9 ± 6.4 years spent with a functioning graft and a total of 13.7 ± 7.4 years on renal replacement therapy. Their mean age was 48.3 ± 11.0 years (vs. 48.2 ± 13.9 years in incident patients, P = 0.96), 53% were male, and all were on hemodialysis. By the end of 2008, 8 (16%) patients had been re-transplanted (after a median of 27.5 months) and 11 (23%) had died (after a median of 1.4 months of dialysis). The cause of death was infection in five patients, a cardiovascular event in three, malignancy in two, and a cerebrovascular event in one patient. Deceased patients were significantly older, but similar to survivors in other parameters. Unadjusted one- and three-year survival rates after graft failure were both 77%, which was significantly worse than in incident patients (P < 0.001). To conclude, patients after graft failure have increased mortality in the first year after starting dialysis, but patients surviving the first year have good survival thereafter. Studies focusing on the early period after graft failure are necessary to improve outcomes.