[Renal transplantations in the Centre for Nephrology in Szombathely, 1976-2016]. / Veseátültetések a szombathelyi nefrológiai centrumban, 1976­2016.

INTRODUCTION: The organized nephrological care in Szombathely commenced its activities in 1976. AIM: Follow-up of our patients who has undergone a kidney transplantation. METHOD: We used the local and national databases. RESULTS: 213 patients (7 preemptive, 206 dialyzed) had 240 renal transplantations. Only 11 of them were living organ donation. Between 69 transplantations (Tx) were carried out between 1976-1995, and 163 Tx were done in the second 20 years. 122 patients (57%) are still alive (the average survival of these patients in renal replacement therapy - RRT - are 11.4 years), and 7 of them had transplantation between 1976-1995. The longest survival time was 35.1 years. Prevalence of patients on RRT at the end of 2016 was 1367 pmp in our county (32.5% living with functioning graft). CONCLUSIONS: Number of transplanted patients has grown in the last decade. Proportion of living organ donation was minimal. Orv Hetil. 2017; 158(25): 984-991.

Effect of angiotensin-converting enzyme gene insertion/deletion polymorphism and angiotensin-converting enzyme inhibition on erythropoiesis in patients on haemodialysis.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEis) improve survival; however, their effect on erythropoiesis remains a matter of debate in this population. Since insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene largely influences serum ACE activity, its effect on erythropoiesis is also anticipated. METHOD: In this multicentre, cross-sectional study of 660 patients on maintenance haemodialysis, we analysed the effect of ACEi use and ACE gene I/D polymorphism on haemoglobin levels and erythropoietin resistance. Patients were allocated in groups based on genotype and ACEi therapy. We identified 128 matched pairs with I/I and D/D genotypes. RESULT: There was no difference in haemoglobin levels between genotype groups. Haemoglobin levels were lower in patients on ACEi therapy in the entire cohort (95.5±12.1 g/l vs 97.4±13.4 g/l, p=0.02) and patients with I/D (95.2±11 g/l vs 98.2±11.9 g/l, p=0.04) and D/D (93.3±13.2 g/l vs 97.4±14.2 g/l, p=0.02) genotypes. In patient pairs treated with ACEi therapy, subjects with D/D genotype had lower Haemoglobin level (93.0±12.8 g/l vs 98.2±11.9 g/l, p=0.006) and higher erythropoietin resistance index (ERI) (199.1 vs 175.0, p=0.046) than individuals with I/I genotype. CONCLUSION: These results indicate that ACEi therapy may increase erythropoietin resistance and worsen erythropoiesis in haemodialysis patients with the D allele.

Interaction between angiotensin-converting enzyme gene insertion/deletion polymorphism and angiotensin-converting enzyme inhibition on survival in hemodialyzed patients.

The association between ACE (angiotensin-converting enzyme) gene insertion/deletion (I/D) polymorphism and mortality has been inconsistently observed in earlier studies in patients on maintenance hemodialysis. We hypothesized that the effect of ACE gene I/D polymorphism on mortality may be influenced by concurrent ACE inhibitor therapy in this population. In this prospective, multicenter cohort, observational study, data was collected from 716 prevalent chronic hemodialysis patients, blood samples were genotyped for I/D single nucleotide polymorphism. Patient mortality was assessed in tree genotype groups insertion/insertion, insertion/deletion and deletion/deletion (I/I, I/D, and D/D) using multivariate Cox proportional hazard models. The most frequent genotype was I/D (42.6%), followed by D/D (37.7%) and I/I (19.7%) genotypes. The mean age was 54.9±15.5 years, 53.2% of all patients were male and in the total group the prevalence of diabetes was 19.3%. ACE inhibitor therapy was prescribed for 47.9% of all patients. The median duration of dialysis before blood sampling was 23.8 months (IQR 11.2-47.1). Patients were followed for 10 years, the median follow-up time was 29.8 months (IQR 12.6-63.4). Patient characteristics were well balanced among the genotype groups. D/D genotype, was associated with inferior survival (I/I vs D/D: log-rank test: P=0.04) in patients not receiving ACE inhibitor therapy, and the presence of this therapy diminished this difference. There was no difference in survival among unselected patients with different genotypes. In multivariate Cox regression models, D/D genotype (compared to I/I) was a significant predictor of mortality only in patients without ACE inhibitor therapy (HR 0.67, 95% CI 0.46-0.97, P=0.03). Our data suggests that hemodialyzed patients with the deletion/deletion (D/D) genotype might have inferior outcome, and ACE inhibitor therapy may be associated with improved survival in this subgroup.

Age-dependent parathormone levels and different CKD-MBD treatment practices of dialysis patients in Hungary--results from a nationwide clinical audit.

BACKGROUND: Achieving target levels of laboratory parameters of bone and mineral metabolism in chronic kidney disease (CKD) patients is important but also difficult in those living with end-stage kidney disease. This study aimed to determine if there are age-related differences in chronic kidney disease-mineral and bone disorder (CKD-MBD) characteristics, including treatment practice in Hungarian dialysis patients. METHODS: Data were collected retrospectively from a large cohort of dialysis patients in Hungary. Patients on hemodialysis and peritoneal dialysis were also included. The enrolled patients were allocated into two groups based on their age (<65 years and ≥65 years). Characteristics of the age groups and differences in disease-related (epidemiology, laboratory, and treatment practice) parameters between the groups were analyzed. RESULTS: A total of 5008 patients were included in the analysis and the mean age was 63.4±14.2 years. A total of 47.2% of patients were women, 32.8% had diabetes, and 11.4% were on peritoneal dialysis. Diabetes (37.9% vs 27.3%), bone disease (42.9% vs 34.1%), and soft tissue calcification (56.3% vs 44.7%) were more prevalent in the older group than the younger group (p<0.001 for all). We found an inverse relationship between age and parathyroid hormone (PTH) levels (p<0.001). Serum PTH levels were lower in patients with diabetes compared with those without diabetes below 80 years (p<0.001). Diabetes and age were independently associated with serum PTH levels (interaction: diabetes × age groups, p=0.138). Older patients were more likely than younger patients to achieve laboratory target ranges for each parameter (Ca: 66.9% vs 62.1%, p<0.001; PO4: 52.6% vs 49.2%, p<0.05; and PTH: 50.6% vs 46.6%, p<0.01), and for combined parameters (19.8% vs 15.8%, p<0.001). Older patients were less likely to receive related medication than younger patients (66.9% vs 79.7%, p<0.001). CONCLUSIONS: The achievement of laboratory target ranges for bone and mineral metabolism and clinical practice in CKD depends on the age of the patients. A greater proportion of older patients met target criteria and received less medication compared with younger patients.

Rapid, enhanced, and persistent protection of patients with renal insufficiency by AS02(V)-adjuvanted hepatitis B vaccine.

The adjuvanted hepatitis B vaccine, HB-AS04, elicits more rapid and persistent protective antibody concentrations than double doses of conventional recombinant vaccines in patients with renal insufficiency. We compared the immunogenicity, reactogenicity, and safety of the AS02(V)-adjuvanted hepatitis B vaccine HB-AS02 with that of HB-AS04. In this phase III, open, randomized study, 151 hepatitis B vaccine-naïve pre-dialysis, peritoneal dialysis, and hemodialysis patients aged 15 years and older received three doses of HB-AS02 at 0, 1, and 6 months. Another 149 similar patients received four doses of HB-AS04 at 0, 1, 2, and 6 months, and all were followed up for 12 months. HB-AS02 elicited more rapid and persistent seroprotection than HB-AS04, with rates of 77 and 39%, respectively, 1 month after the second vaccine dose, and 94 and 79%, respectively, at 12 months. Superiority of HB-AS02 over HB-AS04 in anti-hepatitis B geometric mean concentrations was found at all time points. HB-AS02 was more reactogenic than HB-AS04, but adverse events were mainly transient, of mild to moderate intensity with no reportable vaccine-related serious events. We conclude that a three-dose primary course of HB-AS02 induced more rapid, enhanced, and persistent protection in patients with renal insufficiency than the licensed four-dose primary schedule of HB-AS04. This adjuvanted vaccine affords greater protection with reduced need for booster doses in patients at high risk of hepatitis B infection.

[Hemoglobin variability in chronic renal failure patients]. / Hemoglobinvariabilitás krónikus veseelégtelenségben szenvedo betegekben.

In recent years, the question of hemoglobin (Hb) stability in patients with chronic renal failure has attracted the interest of medical experts. One of the most important reasons behind this interest is that maintaining the hemoglobin level within the new narrower target range is highly challenging in clinical practice. According to the results available from observational trials, instability of inter-patient hemoglobin levels may be associated with increased morbidity and mortality. To clarify the questions and answers related to this topic and to prepare an updated summary, we reviewed the scientific literature. With the help of the PubMed portal, the incidence, clinical importance, and reasons of Hb variability were summarized according to the available scientific literature. Hb variability is affected by multiple factors which are connected to the general condition of the patient as well as medical interventions and treatments. Also the fluctuation of serum Hb level is a physiological process and is a healthy sign of the capability of the normal human body to adapt. The characteristics and extent of Hb variability vary in patients with chronic renal failure and this topic requires further clinical research. More precise studies are needed in order to explore the differences in possible Hb variability as well as the change in variability caused by particular treatment methods. Finally, based on the available data, the results of future research, and on board scientific consensus, in a strategy for treatment of renal anemia, we should take into account the questions related to Hb stability and variability.

The effect of frequent or occasional dialysis-associated hypotension on survival of patients on maintenance haemodialysis.

BACKGROUND: While frequent or occasional symptomatic intradialytic hypotension (IDH) may influence patient well-being, its effects on survival-independent of comorbidities-has not previously been investigated. In this study, therefore, our objective was to assess the effect of frequent IDH (f-IDH) or occasional IDH (o-IDH) on survival. METHODS: During a 10 month run-in period in 1998, 77 patients with f-IDH (> or =10 hypotensive events/10 months, responding only to medical intervention) and 101 patients with o-IDH (1 or 2 events/10 months) were identified among all 958 patients of a dialysis network. Eighty-five patients who had no hypotensive episodes (no-IDH) during this run-in phase served as controls. Patients were followed for a median of 27 months (range: 0.3-37) and survival of patients in the three groups was compared by log-rank test. Independent association of f-IDH and o-IDH with survival, compared with no-IDH, was assessed by a proportional hazards model that included patient demographics, laboratory data and antihypertensive medication as well as comorbidity. RESULTS: Forty-five patients (58%) with f-IDH, 47 (47%) with o-IDH and 33 (39%) with no-IDH died during the follow-up. Mortality rates (deaths/100 patient years) were 37 (log-rank P = 0.013 vs no-IDH), 26 (log-rank P = 0.375 vs no-IDH) and 21 in the three groups, respectively. This indicates significantly decreased survival in patients with f-IDH as compared to those with no-IDH. In multivariate proportional hazards regression, however, where age, sex, time spent on dialysis, presence of coronary heart disease, diabetes, Kt/V, albumin level and use of beta-blockers, calcium-channel blockers and long-acting nitrates has been adjusted for, neither f-IDH nor o-IDH was associated with survival. CONCLUSIONS: Mortality in patients with f-IDH is significantly higher than in those without such events. After adjustments for covariates, however, there is no independent effect of frequent or occasional episodes of IDH on mortality.

Comparison of dialysis and clinical characteristics of patients with frequent and occasional hemodialysis-associated hypotension.

BACKGROUND: Symptomatic dialysis hypotension (DH) continues to be a common problem. By comparing patients prone and resistant to DH, several dialysis session and patient related characteristics have been identified that confer susceptibility to DH. Less is known, however, about the comparison of patients with frequent and only occasional DH. The aim of the study was to compare clinical and dialysis-session- (complicated by hypotension) related data between those with frequent (fDH) and those with occasional dialysis hypotension (oDH). METHODS: Nine hundred and fifty-eight patients at 11 dialysis units were followed for 10 months and characteristics of patients with fDH (> or = 10 hypotensive events necessitating medical intervention) (n = 96) were compared to that of patients with oDH (1 or 2 events/10 months) (n = 130). Significant and independent predictors of fDH were obtained by multivariate logistic regression. RESULTS: Significant differences between fDH vs. oDH patients were older age (64.4 vs. 56.9 years, p < 0.001), more females (66 vs. 46%, p < 0.005) in fDH. More fDH patients had diabetes (27 vs. 15%, p < 0.05) and less had glomerulonephritis (15 vs. 35%, p < 0.001) as the cause for ESRD. Coronary artery disease (68 vs. 50%, p < 0.01) and long-acting nitrate treatment (51 vs. 30%, p < 0.001) was more frequent while treatment with ACEI (33 vs. 48%, p < 0.05) or Ca-channel blockers (40 vs. 53%, p < 0.05) were less frequent in patients with fDH. Patients with fDH had higher serum phosphorus levels (1.99 vs. 1.79 mmol, p < 0.005). Dialysis session related data were similar but the hypotensive episode occurred earlier during dialysis in fDH (136 vs. 156 min, p < 0.01). In multivariate analysis, significant independent predictors of fDH were older age (OR = 1.04 [1.02-1.07]), lack of glomerulonephritis as renal diagnosis (2.63 [1.18-5.87]), high phosphorus levels (5.0 [2.45-10.0]), lack of use of Ca-channel blockers (2.09 [1.12-3.91]), and the use of nitrates (2.38 [1.24-4.55]). CONCLUSION: Features of the dialysis sessions complicated by DH seem to be similar between patients with fDH and oDH, while patient characteristics such as older age, renal diagnosis other than glomerulonephritis, higher serum phosphorus levels, use of nitrates, and lack of use of calcium channel blockers are significantly and independently associated with fDH.