Three-year safety observation of subcutaneous administration of epoetin-zeta in patients with chronic renal anemia: Results from PASCO II study.

Epoetin has been used to treat patients with renal anemia since 1988. -Anti-erythropoietin antibody-mediated pure red cell aplasia (PRCA) has been associated with epoetin usage, and a PRCA incidence of 4.5 per 10,000 patient-years was observed for epoetin-α (Eprex) in 2002. The PASCO II study (post-authorization safety cohort observation of Retacrit and Silapo (epoetin-ζ) administered subcutaneously for the treatment of renal anemia) followed 6,346 patients (4,501 Retacrit (group R); 1,845 Silapo (group S)) for up to 3 years of subcutaneous treatment with the biosimilar epoetin-ζ. One PRCA in 1 (0.02%) patient in group R who tested positive for neutralizing antibodies was reported. Overall, 527 adverse events of special interest (AESI) including PRCA occurred in 418 (6.60%) patients, lack of efficacy occurred in 34 (0.54%), and thromboembolic events in 389 (6.14%) patients. 41 adverse drug reactions other than AESIs were reported in 28 (0.44%) patients. The exposure-adjusted incident rate of PRCA was 0.84 per 10,000 patient-years. This real-world study showed that among patients with renal anemia receiving subcutaneous administration of the biosimilar product epoetin-ζ, the incidence rate of PRCA was substantially below the risk observed in 2002 for Eprex and that there was no immunogenicity concern or other new safety concern.

ACE2 polymorphism and susceptibility for SARS-CoV-2 infection and severity of COVID-19.

OBJECTIVES: The RNA virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19). Cell entry is mediated by the human angiotensin-converting enzyme II (ACE2). ACE2 and its close homolog angiotensin-converting enzyme I (ACE) are currently discussed candidate genes, in which single-nucleotide polymorphisms (SNPs) could alter binding or entry of SARS-CoV-2 and enhance tissue damage in the lung or other organs. This could increase the susceptibility for SARS-CoV-2 infection and the severity of COVID-19. PATIENTS AND METHODS: We performed genotyping of SNPs in the genes ACE2 and ACE in 297 SARS-CoV-2-positive and 253 SARS-CoV-2-negative tested patients. We analyzed the association of the SNPs with susceptibility for SARS-CoV-2 infection and the severity of COVID-19. RESULTS: SARS-CoV-2-positive and SARS-CoV-2-negative patients did not differ regarding demographics and clinical characteristics. For ACE2 rs2285666, the GG genotype or G-allele was significantly associated with an almost two-fold increased SARS-CoV-2 infection risk and a three-fold increased risk to develop serious disease or COVID-19 fatality. In contrast, the ACE polymorphism was not related to infection risk or severity of disease. In a multivariable analysis, the ACE2 rs2285666 G-allele remained as an independent risk factor for serious disease besides the known risk factors male gender and cardiovascular disease. CONCLUSIONS: In summary, our report appears to be the first showing that a common ACE2 polymorphism impacts the risk for SARS-CoV-2 infection and the course of COVID-19 independently from previously described risk factors.

Comparable outcome of acute unplanned peritoneal dialysis and haemodialysis.

BACKGROUND: The impact of dialysis modality on outcome, especially on infection early in the course of dialysis, in unplanned acute dialysis initiation has not been well evaluated. The aim of the study was to compare the rates and causes of mortality and morbidity in incident dialysis patients started unplanned acute peritoneal dialysis (PD) or haemodialysis (HD). PATIENTS AND METHODS: In this observational cohort study, incident dialysis patients with initiation of unplanned and acute PD (n = 66) or HD (n = 57) at a single centre from March 2005 to June 2010 were included and followed up for 6 months (0-183 days, mean follow-up time 4.72 months). For PD, surgically placed Tenckhoff catheters were used. All HD patients were dialysed with a central venous catheter (non-tunnelled or tunnelled). There were no significant differences in terms of gender, age and prevalence of diabetes mellitus in either group. The prevalence of heart failure [New York Heart Association (NYHA) Stage III-IV] was significantly higher in the PD group (73 versus 46% in HD group, P < 0.01). The population was stratified to PD and HD comparing mortality, infection, bacteraemia and hospitalization. RESULTS: Of the 123 patients who commenced acute and unplanned dialysis, n = 44 (35.8%) died during the follow-up period of 0-183 days. There were no significant difference in half-year mortality in n = 20 PD patients (30.3%) versus n = 24 HD patients (42.1%) (P = 0.19). The cardiovascular mortality in PD and HD patients were 9.1 and 10.5%, respectively (P = 1.00). Overall mortality due to infection was higher in the HD (17.5%) versus in the PD group (9.1%), however, not significant (P = 0.19). HD patients had significantly higher probability of bacteraemia in the first 183 days compared to PD patients (21.1 versus 3.0%, P < 0.01). Group comparison by Poisson regression analyses showed that the relative risk of bacteraemia in the PD group versus HD group was 0.16 (95% confidence interval, 0.05-0.57, P = 0.005). The significant difference was not affected by the confounder's patient age at time of dialysis, male sex, heart failure (NYHA III-IV), diabetes, malignancy and peripheral arterial occlusive disease Stage IV. There were high proportions of hospitalization after the initiation of dialysis in both groups (PD 75.0% and HD 67.3%, P = 0.40). Univariate and multiple regression analyses revealed only age at initiation of dialysis to be significantly associated with overall mortality (P < 0.05). CONCLUSIONS: Dialysis modality (PD versus HD) in an acute unplanned dialysis setting showed, in our population, no significant influence on survival. HD patients had a significantly higher risk of bacteraemia, perhaps due to central venous dialysis catheter. PD seems to be a safe and efficient, at least comparable, alternative to HD in acute unplanned dialysis settings.

Peritoneal dialysis relieves clinical symptoms and is well tolerated in patients with refractory heart failure and chronic kidney disease.

AIMS: The aim of the study was to evaluate the efficacy and clinical outcome of peritoneal dialysis (PD) treatment in patients with severe refractory heart failure (HF) and chronic kidney disease (CKD). METHODS AND RESULTS: The PD treatment was performed in 118 patients [49.2% New York Heart Association (NYHA) III and 50.8% NYHA IV] with a mean age of 73.2 ± 11.4 years as an in-centre-based and intermittent automated PD at least three times per week for 12 h per session and followed up for 1.11 ± 1.17 years. The functional status of those surviving for 6 months improved (P < 0.0001): 18 (32.1%) of all 60 patients with NYHA IV at baseline died within 6 months, 3 (5.4%) converted to NYHA III, 33 (58.9%) to NYHA II, and 2 (3.6%) to NYHA I. In all 58 patients with NYHA III at baseline, 14 (25.0%) died within 6 months, 27 (48.2%) converted to NYHA II, 12 (21.4%) to NYHA I, and 3 (5.4%) showed no improvement. In those surviving for 6 months, fluid overload was significantly reduced as body weight decreased, from 78.7 [95% confidence interval (CI) 75.8-81.7] to 74.7 (71.5-77.9) after 6 months after multiple imputation (P < 0.001). The overall survival rates after 3, 6, and 12 months were 77% (95% CI 70-85), 71% (95% CI 62-79), and 55% (95% CI 45-64). In the multivariate analyses, age, diabetes mellitus, serum urea, and brain natriuretic peptide were significantly associated with mortality. The incidence of peritonitis and catheter dysfunction was 0.053 (95% CI 0.014-0.093) and 0.084 (95% CI 0.034-0.133), respectively. CONCLUSION: The data suggest that PD is a safe, efficient, and well tolerated therapeutic tool for patients with refractory chronic HF and CKD.

A case report of successful long-term relapse control by protein-a immunoadsorption in an immunosuppressive-treated patient with end-stage renal disease due to Wegener's granulomatosis.

A long-term female hemodialysis patient with end-stage renal disease due to Wegener's granulomatosis (WG) experienced a severe relapse when immunosuppressive therapy was switched from prednisone and cyclophosphamide to azathioprine maintenance therapy. Ten courses of protein A immunoadsorption therapy and switching immunosuppressive therapy to mycophenolate mofetil have proved to be very successful and free of side effects. The patient has fully recovered from all clinical WG symptoms and is still in remission ten months after the treatment.

Ezetimibe treatment in hypercholesterolemic kidney transplant patients is safe and effective and reduces the decline of renal allograft function: a pilot study.

BACKGROUND: Ezetimibe has shown efficacy in the therapy of hypercholesterolemia in renal transplant patients. This is the first study investigating the effect of ezetimibe on renal function in kidney transplant recipients. METHODS: Fifty-six patients with statin-resistant hypercholesterolemia (total cholesterol >200 mg/dl) after renal transplantation received additional ezetimibe therapy (10 mg/day) for 12 months. A group receiving statin therapy (n=28) served as controls in this prospective study. RESULTS: Total cholesterol and LDL cholesterol concentrations decreased significantly in the ezetimibe-treated patients but remained stable in the control group (delta total cholesterol: -24+/-49 mg/dl vs 19+/-49 mg/dl, P<0.01; delta LDL: -30+/-39 mg/dl vs -3+/-31 mg/dl, P<0.01). Mean creatinine clearance remained stable in ezetimibe-treated patients but decreased significantly in control group (delta Cockcroft-Gault: 0.9+/-7.3 ml/min vs - 4.8+/-12.8 ml/min, P=0.025; delta Modification of Diet in Renal Disease: -0.4+/-6.2 ml/min/1.73 m(2) vs 4.7+/-8.8 ml/min/1.73 m(2), P=0.033). CONCLUSIONS: The data of our prospective case-control study suggest that ezetimibe appears to ameliorate the decline of renal function after renal transplantation.

[Quality of life in patients before and after kidney transplantation]. / Die Lebensqualität von Patienten vor und nach Nierentransplantation.

The presented study was carried out to differentially assess the quality of life (QOL) of two patient groups with end-stage renal disease (ESRD) with regard to the replacement therapy (dialysis vs. transplantation) and healthy controls. Successfully transplanted patients (n = 149) and patients treated by dialysis (n = 149) on the waiting list for transplantation at the Transplant Center Essen, Germany were enrolled. Additionally, 149 healthy controls were enrolled by an accumulative process starting from employees of the University Hospital Essen. Members of these three groups were strictly matched by age and gender. Medical data were gained from the patient record, QOL was measured by a global inventory, the Munich Quality of Life Dimension List (MLDL), and two specific inventories, the Brief Symptom Inventory (BSI) and the Questionnaire for Social Support - Short Form (K-22). Transplanted patients and healthy controls reported similar QOL, which was significantly higher than in dialysis patients (p < 0.0001). This was particularly true for the physical and the psychological status, but not for the social situation. Both patient groups reported similar social support, which was significantly lower than in controls (p < 0.006). Both ESRD groups described higher satisfaction with social support than the healthy controls (p < 0.0001). Successful kidney transplantation not only improved distinct aspects of QOL, but even put the patients on par with healthy controls regarding physical, psychological and functional QOL. Lower social support and higher satisfaction with social support in both patient groups should be evaluated further. From a clinical viewpoint, the improvement of QOL due to transplantation is impressive, but more attention should be paid to the interpersonal relations of ESRD patients. International multicenter longitudinal studies to investigate QOL in ESRD patients under different treatment modalities are emphasized.