Andrej Bren

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.

Short-term effects of bicarbonate/lactate-buffered and conventional lactate-buffered dialysis solutions on peritoneal ultrafiltration: a comparative crossover study

BACKGROUND This study was designed to compare the effects of a conventional lactate-based peritoneal dialysis (PD) solution (D) and a new biocompatible bicarbonate/lactate-based solution with a low concentration of glucose degradation products (P) on peritoneal ultrafiltration (UF) and other peritoneal membrane indices. METHODS Twenty-six stable, prevalent PD patients were enrolled in this prospective study. They sequentially underwent 3 months of therapy with the D solution and 3 months with the P solution in a randomized order. Daily, overnight and 4-h UF on PET were measured and other peritoneal membrane indices were also assessed using PET with 2.27% glucose solution. RESULTS Twenty-one patients successfully completed the study. The mean daily peritoneal UF with D was 1324 +/- 602 ml and 881 +/- 633 ml with P (P < 0.001) and this lower daily UF of 443 ml (95% CI 275-610 ml) with P was associated with a similarly lower daily total fluid removal of 394 ml (95% CI 210-577 ml), as urine volume did not differ between D and P. The decrement in UF with the P solution was reversible. There were no significant differences in other peritoneal membrane indices (D/P creatinine, D/D0 glucose, 4-h UF at PET, weekly creatinine clearance, weekly urea Kt/V) or blood pressure and body weight between the solutions whereas calculated peritoneal fluid absorption rate was significantly higher with the P than with the D solution. CONCLUSION This study shows that the daily UF with the P solution may be lower than with the D solution. The mechanism for this short-term and reversible effect that conceivably reflects differences in biocompatibility is not clear although our results implicate that the peritoneal fluid absorption rate may differ between the two solutions.

Regular Exercise as a Part of Treatment for Patients With End‐stage Renal Disease

Abstract:  Physical inactivity and its negative influence on health and the quality of life is a common problem generally, especially in patients with chronic illness and also in patients with end‐stage renal disease. Motivation for regular physical exercise could be a problem. A supervised outpatient program in a rehabilitation center, a home exercise rehabilitation program and an exercise rehabilitation program during the first hours of the hemodialysis treatment with a bed bicycle ergometer in the renal unit could be carried out. Low intensity aerobic activity has a favorable effect on cardiovascular risk factor, and gymnastics to increase strength, flexibility and coordination, as well as relaxation techniques are very effective exercises in a rehabilitation program. The positive influence of individual regular exercise on health, quality of life, physical exercise capacity, endurance, muscle strength, social, professional and emotional status is also very high in patients. Side effects of exercise are very rare.

Cell-free DNA in the peritoneal effluent of peritoneal dialysis solutions.

The beneficial effects of novel peritoneal dialysis solutions low in glucose degradation products regarding peritoneal cell apoptosis and necrosis are well established in vitro, however in vivo data is lacking. Cell‐free DNA quantification is a possible method to determine cell damage through apoptosis and necrosis in vivo. We performed a prospective, cross‐over study on 26 stable continuous ambulatory peritoneal dialysis (CAPD) patients, treating each patient for 3 months in a randomized order with a conventional, lactate‐buffered, acidic solution (solution D) and a novel, bicarbonate/lactate‐buffered neutral solution (solution P). The timed overnight peritoneal effluent was sampled for cell‐free DNA quantification using a fluorometric assay. The effluent samples of eighteen patients were finally available for DNA quantification. The concentration range of cell‐free DNA in the peritoneal effluents was 1.8–9.5 µg/L. The coefficient of intrapatient variation in overnight effluent cell‐free DNA appearance was 15.6 ± 12.4%. Cell‐free DNA peritoneal appearance using solutions D and P was 14.9 ± 6.8 µg and 11.8 ± 3.4 µg, respectively (P = 0.02), with the average difference of 3.1 µg (95% CI, 0.7–5.6 µg). Our results show that cell‐free DNA is present in the overnight peritoneal effluent of stable CAPD patients. A significant decrease in the cell‐free DNA appearance with solution P was found; however, before accepting this as an indicator of a more biocompatible profile causing less peritoneal membrane cell necrosis and apoptosis, confirmatory data on larger patient samples are needed. Our results indicate the potential future role of cell‐free DNA in the diagnosis and prognosis of therapy‐related peritoneal membrane degeneration.

Acute Renal Failure Due to Hemorrhagic Fever with Renal Syndrome

The aim of our study was to analyze the clinical course and outcome of acute renal failure (ARF) in patients with hemorrhagic fever with renal syndrome (HFRS). From 1983 to 1995, we treated 33 patients (27 males, 6 females) aged from 16 to 71 years. Half of patients were connected with work at a farm or in a forest. The disease was confirmed serologically with indirect immunofluorescence test (IFT) and enzyme-linked immunosorbent assay (ELISA). In 18 patients percutaneous kidney needle biopsies were analyzed. In 85% of the cases, the disease broke out from June to October. The most frequently expressed clinical signs and symptoms were fever, nausea/vomiting, headache, backache, abdominal pain, myalgia, diarrhea, conjunctival injection, and hemorrhages. Four patients had concomitant pancreatitis. In 25 patients, oliguria was present, and transient hemodialysis treatment was needed in 19 patients. Infection with Hantaan virus was established in 20 patients and with Puumala virus in 13 patients. At renal biopsy, acute interstitial nephritis accompanied with hemorrhages and necrosis was found, and at a later biopsy there were also signs of interstitial fibrosis. All patients were cured, but renal function was not completely recovered in some. We conclude that ARF is a serious complication in patients with HFRS. Although not lethal in our group of patients, many of them showed severe signs and symptoms of illness. Transient hemodialysis was necessary in two-thirds of the patients. Some degree of functional defects and morphological changes might persist.

Fibroblast Growth Factor 23 and Left Ventricular Mass Index in Maintenance Hemodialysis Patients: Standard Versus Long Nocturnal Hemodialysis

Elevated levels of fibroblast growth factor 23 (FGF23) and phosphorus (P) have been linked to greater risks of left ventricular hypertrophy (LVH) in patients with end stage renal disease (ESRD). The aim of this study was to test if differences exist in a long nocturnal HD group in comparison with a group treated with standard daily thrice weekly dialysis. The attempt was to evaluate if elevated FGF‐23 levels, intact parathyroid hormone and P might be associated with left ventricular mass index (LVMI). Quantitative echocardiographic analyses were performed at baseline in 50 maintenance HD patients (17 women and 33 men, mean age: 56.4 ± 15.35 years, mean HD vintage: 9.06 ± 8.86 years, all patients are on HD thrice a week‐median duration 15 h/week, 10 of them on long nocturnal HD, median duration 24 h/week). LVMIs were calculated. FGF23 was measured in duplicate using a second generation C‐terminal enzyme‐linked immunosorbent assay and log of FGF‐23 values were computed. Mean LVMI was 136.44 ± 44.44 g/m2. Serum FGF‐23 levels were elevated when compared to population data with preserved kidney function (median 1388.5 RU/mL, range 252 to 24 336 RU/mL). There were no correlations recorded between log FGF‐23 levels and LVMI (r = 0.2, P = 0.66). LVMI was significantly lower in HD patients on long nocturnal dialysis procedure (r = −0.31, P = 0.05). Patients treated with long nocturnal HD showed lower LV mass, lower P‐values and higher 25‐OH‐D3 supply. Plasma FGF‐23 concentration was comparable between the groups and was not associated with LVMI in our maintenance HD patients.

Antioxidant Enzymes Show Adaptation to Oxidative Stress in Athletes and Increased Stress in Hemodialysis Patients

The aim of the study is to compare oxidative stress in hemodialysis patients in controls and in rowers. The patients are a model of decreased antioxidant capacity, and the athletes (rowers) are a model of the highest antioxidant capacity due to their chronic adaptation to demanding training. Thirty‐five subjects participated in the study, 9 patients with end‐stage renal disease treated by hemodialysis, 12 healthy young subjects from the normal population, and 14 rowers. The antioxidant enzymes catalase, superoxide dismutase, and glutathione peroxidase, as well as non‐transferrin‐bound iron as a promoter of free radical damage, were determined. Blood analysis was taken in dialysis patients in the morning, before the dialysis procedure. There was significantly higher activity of catalase in dialysis patients (catalase 4.26 ± 0.35 mkat/g Hb) compared to the controls (catalase 2.73 ± 0.38 mkat/g Hb) and rowers (catalase 1.71 ± 0.30 mkat/g Hb). Superoxide dismutase activity was significantly lower (10.42 ± 1.46 µkat/g Hb) than in the controls (11.94 ± 1.18 µkat/g Hb) and rowers (14.09 ± 0.92 µkat/g Hb). There was no significant differences between glutathione peroxidase activities in the three groups. Superoxide dismutase and Se were higher in rowers than in dialysis patients (P < 0.05). The concentrations of both non‐transferrin‐bound iron and ferritin were significantly higher in dialysis patients. Hemodialysis patients might have increased oxidative stress, which is characterized by significantly higher erythrocyte enzyme activity of catalase and lower activity of superoxide dismutase. Top rowers had increased superoxide dismutase and glutathione peroxidase, perhaps because of adaptation during training, which was not the case in dialysis patients and controls.

Influence of Renin‐Angiotensin‐Aldosterone System‐Blocking Drugs on Peritoneal Membrane in Peritoneal Dialysis Patients

Therapy with renin‐angiotensin‐aldosterone system (RAAS)‐blocking drugs prevents the development of fibrosis and angiogenesis in animal models and humans. In our study we have evaluated the systemic effect of RAAS blockade and the effect on peritoneal growth factors, cytokine production and membrane transport characteristics in patients on peritoneal dialysis. Thirty‐seven peritoneal dialysis (PD) patients were enrolled in our cross‐sectional study. Aldosterone and angiotensin II concentrations were measured in serum to determine the RAAS activity. The inflammatory and profibrotic activity was evaluated by measuring the concentration of C‐reactive protein (CRP), serum albumin, and peritoneal concentration of interleukin‐6 (IL‐6), vascular endothelial growth factor (VEGF), plasminogen activator inhibitor‐1 (PAI‐1), transforming growth factor‐β (TGF‐β) and cancer antigen‐125 (CA‐125). The transport characteristics of the peritoneal membrane were analyzed with a peritoneal equilibration test (PET). Results were compared between the group with RAAS‐blocking drugs (RAAS group) and the group without them (non‐RAAS group). Mean serum aldosterone concentration was significantly lower in patients treated with ARB‐blocking drugs (P = 0.001) and serum angiotensin II concentration was lower in patients treated with ACE inhibitors (P = 0.009). RAAS blockade resulted in lower peritoneal PAI‐1 levels (748.1 to 1222.7 ng/L; P = 0.07) without any influence on CRP, peritoneal concentrations of IL‐6, VEGF, TGF‐β and CA‐125, or alteration in peritoneal membrane characteristics tested by PET. RAAS‐blocking drugs could be effective in preventing peritoneal fibrosis due to possible reduction of peritoneal PAI‐1 concentrations that have already been etiologically linked with fibrin deposition in the pathogenesis of encapsulating peritoneal sclerosis.

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.