Viera Spustová

Renal replacement therapy in Europe: a summary of the 2012 ERA-EDTA Registry Annual Report

Background This article summarizes the 2012 European Renal Association—European Dialysis and Transplant Association Registry Annual Report (available at www.era-edta-reg.org) with a specific focus on older patients (defined as ≥65 years). Methods Data provided by 45 national or regional renal registries in 30 countries in Europe and bordering the Mediterranean Sea were used. Individual patient level data were received from 31 renal registries, whereas 14 renal registries contributed data in an aggregated form. The incidence, prevalence and survival probabilities of patients with end-stage renal disease (ESRD) receiving renal replacement therapy (RRT) and renal transplantation rates for 2012 are presented. Results In 2012, the overall unadjusted incidence rate of patients with ESRD receiving RRT was 109.6 per million population (pmp) (n = 69 035), ranging from 219.9 pmp in Portugal to 24.2 pmp in Montenegro. The proportion of incident patients ≥75 years varied from 15 to 44% between countries. The overall unadjusted prevalence on 31 December 2012 was 716.7 pmp (n = 451 270), ranging from 1670.2 pmp in Portugal to 146.7 pmp in the Ukraine. The proportion of prevalent patients ≥75 years varied from 11 to 32% between countries. The overall renal transplantation rate in 2012 was 28.3 pmp (n = 15 673), with the highest rate seen in the Spanish region of Catalonia. The proportion of patients ≥65 years receiving a transplant ranged from 0 to 35%. Five-year adjusted survival for all RRT patients was 59.7% (95% confidence interval, CI: 59.3–60.0) which fell to 39.3% (95% CI: 38.7–39.9) in patients 65–74 years and 21.3% (95% CI: 20.8–21.9) in patients ≥75 years.

Effects of Long-Term Cholecalciferol Supplementation on Mineral Metabolism and Calciotropic Hormones in Chronic Kidney Disease

Background: Data on the efficacy and safety of long-term vitamin D supplementation in chronic kidney disease (CKD) are scarce. We assessed the effects of the 12-month vitamin D3 treatment on mineral metabolism and calciotropic hormones in patients with CKD stages 2–4. Methods: Eighty-seven patients (mean age 66 years, men/women 33/54) were randomized to cholecalciferol treatment with either 5,000 or 20,000 IU/week. Serum calcium, phosphate, 25(OH)D3, 1,25(OH)2D3, PTH and urinary mineral concentrations were obtained at baseline and after 4, 8 and 12 months. Results: The median serum mineral concentrations were normal and not changed throughout the study. The number of hypercalciuric patients slightly increased with higher dose, but no sustained rise in calciuria was present. Vitamin D insufficiency/deficiency was revealed in 72 (83%) patients at baseline and 37 (43%) at month 12. The 25(OH)D3 levels increased more with higher dose; a rise in 1,25(OH)2D3 was less impressive. The parathyroid hormone (PTH) concentrations were reduced, but the number of subjects with PTH below the lower limit for CKD stage 3 increased equally with both doses. Conclusions: Vitamin D insufficiency/deficiency in CKD significantly improved after the 12-month cholecalciferol treatment, with higher dose being more effective and equally safe. Further studies of vitamin D3 effects on bone metabolism are warranted.

Renal replacement therapy in Europe: a summary of the 2013 ERA-EDTA Registry Annual Report with a focus on diabetes mellitus

Background This article provides a summary of the 2013 European Renal Association–European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report (available at http://www.era-edta-reg.org), with a focus on patients with diabetes mellitus (DM) as the cause of end-stage renal disease (ESRD). Methods In 2015, the ERA-EDTA Registry received data on renal replacement therapy (RRT) for ESRD from 49 national or regional renal registries in 34 countries in Europe and bordering the Mediterranean Sea. Individual patient data were provided by 31 registries, while 18 registries provided aggregated data. The total population covered by the participating registries comprised 650 million people. Results In total, 72 933 patients started RRT for ESRD within the countries and regions reporting to the ERA-EDTA Registry, resulting in an overall incidence of 112 per million population (pmp). The overall prevalence on 31 December 2013 was 738 pmp (n = 478 990). Patients with DM as the cause of ESRD comprised 24% of the incident RRT patients (26 pmp) and 17% of the prevalent RRT patients (122 pmp). When compared with the USA, the incidence of patients starting RRT pmp secondary to DM in Europe was five times lower and the incidence of RRT due to other causes of ESRD was two times lower. Overall, 19 426 kidney transplants were performed (30 pmp). The 5-year adjusted survival for all RRT patients was 60.9% [95% confidence interval (CI) 60.5–61.3] and 50.6% (95% CI 49.9–51.2) for patients with DM as the cause of ESRD.

Inhibition of Glucose Utilization in Isolated Rat Soleus Muscle by Pseudouridine: Implications for Renal Failure

Pseudouridine (psi) is an outstanding nucleoside which is not rebuilt into the tRNA once the parent tRNA is broken down. psi inhibits basal glucose utilization in isolated rat soleus muscle with intact membrane with AD(50)42 mumol/l and Cmax 66%. Psi at concentrations found in renal failure patients inhibits both the insulin- and tolbutamide-stimulated glucose utilization. Its inhibitory activity is partially additive with diltiazem inhibition and nonadditive in the case of magnesium depletion. It is concluded that psi inhibits glucose utilization at the level of Ca modulation in the insulin regulatory cascade.

Effects of angiotensin-converting enzyme inhibitors on glucose and lipid metabolism in essential hypertension.

Summary Data of 52 patients, 29 women and 23 men aged 32–68 years (mean age 47 years) with essential hypertension, participating in three open therapeutic trials with either enalapril, lisinopril, or perindopril were evaluated to assess the effects of angiotensin-converting enzyme (ACE) inhibition on glucose and lipid metabolism. The 75-g oral glucose tolerance test (oGTT) was performed, and plasma glucose and insulin levels, as well as total cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides levels were determined before and after the 8− to 12-week treatment. Minor differences in the blood pressure (BP)-lowering effect and metabolic response were obtained with the ACE inhibitors studied; only lisinopril improved glucose tolerance significantly; blood lipids were not changed by any drug. The entire patient population showed only a slight reduction in 1-h postload glucose after treatment. More obvious improvement in glucose tolerance was evident in hypertensive patients who were glucose intolerant and/or insulin resistant (GI/IR, 53.8% of all), however. This subgroup also showed a slight but not significant increase in HDL-cholesterol and a decrease in triglycerides levels. Only a slight change or no change in plasma glucose, insulin, and lipid values was noted in hypertensive patients with normal glucose tolerance (NGT) and insulin sensitivity. These favorable effects were expressed only after ACE inhibitor monotherapy, but not when hydrochlorothiazide was added. The results indicate that a lack of stratification of hypertensive patients with regard to glucose tolerance or insulin sensitivity could be a confounding factor in evaluation of metabolic effects of ACE inhibitors.

Intracellular calcium homeostasis in patients with early stagesof chronic kidney disease: effects of vitamin D3 supplementation

BACKGROUND Chronic renal failure has been referred to as a state of cellular calcium toxicity. The aim of this study was to investigate the status of free cytosolic calcium ([Ca(2+)](i)), intracellular calcium reserves and the capacitative calcium entry in peripheral blood mononuclear cells (PBMCs) of early-stage chronic kidney disease (CKD) patients, and to determine the effect of vitamin D(3) supplementation on these parameters. METHODS The study involved 44 patients with CKD stages 2-3; 27 of them were treated with cholecalciferol (5000 IU/week) for 12 months. [Ca(2+)](i) was measured using Fluo-3 AM fluorimetry. Intracellular calcium reserves were emptied by the application of thapsigargin (Tg), a specific inhibitor of endoplasmic reticulum Ca(2+)-ATPase. 2-Aminoethyl-diphenyl borate (2APB) was used to examine the capacitative calcium entry. RESULTS [Ca(2+)](i) of CKD patients was substantially higher in comparison with healthy subjects: 123 (115-127) versus 102 (98-103) nmol/l, P < 0.001. The calcium concentration of Tg-sensitive stores and the capacitative calcium entry were also significantly increased in CKD patients. After the 12-month vitamin D(3) supplementation, there was a marked decrease in [Ca(2+)](i) [105 (103-112) nmol/l, P < 0.001 versus baseline], independently of the increase in 25(OH)D(3) or the decrease in PTH levels. No significant changes in intracellular calcium reserves and the capacitative calcium entry were found. CONCLUSIONS Our results demonstrate that (1) [Ca(2+)](i), intracellular calcium stores and the capacitative calcium entry were significantly increased already in early stages of CKD; (2) long-term vitamin D(3) supplementation normalized [Ca(2+)](i) without any effect on intracellular calcium reserves or the capacitative calcium entry.

The European Renal Association - European Dialysis and Transplant Association Registry Annual Report 2014: a summary.

Abstract Background This article summarizes the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) Registry’s 2015 Annual Report. It describes the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2015 within 36 countries. Methods In 2016 and 2017, the ERA-EDTA Registry received data on patients who were undergoing RRT for ESRD in 2015, from 52 national or regional renal registries. Thirty-two registries provided individual patient-level data and 20 provided aggregated-level data. The incidence, prevalence and survival probabilities of these patients were determined. Results In 2015, 81 373 individuals commenced RRT for ESRD, equating to an overall unadjusted incidence rate of 119 per million population (pmp). The incidence ranged by 10-fold, from 24 pmp in Ukraine to 232 pmp in the Czech Republic. Of the patients commencing RRT, almost two-thirds were men, over half were aged ≥65 years and a quarter had diabetes mellitus as their primary renal diagnosis. Treatment modality at the start of RRT was haemodialysis for 85% of the patients, peritoneal dialysis for 11% and a kidney transplant for 4%. By Day 91 of commencing RRT, 82% of patients were receiving haemodialysis, 13% peritoneal dialysis and 5% had a kidney transplant. On 31 December 2015, 546 783 individuals were receiving RRT for ESRD, corresponding to an unadjusted prevalence of 801 pmp. This ranged throughout Europe by more than 10-fold, from 178 pmp in Ukraine to 1824 pmp in Portugal. In 2015, 21 056 kidney transplantations were performed, equating to an overall unadjusted transplant rate of 31 pmp. This varied from 2 pmp in Ukraine to 94 pmp in the Spanish region of Cantabria. For patients commencing RRT during 2006–10, the 5-year unadjusted patient survival probabilities on all RRT modalities combined was 50.0% (95% confidence interval 49.9–50.1).

Pseudouridine excretion in healthy subjects and its accumulation in renal failure.

Pseudouridine (psi) is a unique nucleoside accumulated in the sera of renal failure (RF) patients. Surprisingly data on its excretion are lacking. To get an overview, the psi serum level and urinary excretion were investigated in 73 healthy subjects (C), 16 patients not on dialysis (ND) and 12 hemodialysis patients (D). It was found: (a) psi accumulates in the sera of both ND and D patients. An inverse power correlation fits best with the relationship between serum psi and the clearance of endogenous creatinine (CCr). The amount of psi filtered in glomeruli of ND patients increases while it remains practically unchanged in D patients. However, the psi filtration load of residual nephrons increases with the decreasing CCr as a consequence of its increased serum concentration. (b) Both psi net resorption and secretion have been found in C subjects. The increased psi resorption diminishes the necessary increase of psi urinary excretion both in ND and D patients. The increase of psi resorption is marked if calculated on residual nephrons. (c) The slightly decreased psi excretion excludes the participation of its increased synthesis in its accumulation in RF. It is concluded that psi accumulation in RF is caused by the impairment of its kidney excretion and the increased psi resorption participates markedly in its retention.

Pathogenesis and Consequences of the Alteration of Glucose Metabolism in Renal Insufficiency

The decreased hyperglycemic response of patients in renal insufficiency (RI) to the applied glucagon or epinephrine and abnormal galactose tolerance test pointed to the abnormal liver glycogen metabolism and its decreased liver concentration (Cohen, 1962; Westervelt and Schreiner, 1962). However, later on the glucagon and epinephrine studies have not been confirmed and normal liver glycogen concentration was found in a group of patients with normal caloric intakte in our laboratory (Dzurik and Brixova, 1968). The liver glycogen concentration was normal even in patients with abnormal glucose tolerance test. Similar findings were published on muscle glycogen by Bergstrom (Bergstrom and Hultman, 1969). It appears now that the glycogen concentration and metabolism depend primarily on nutritional state and not on renal insufficiency. Consequently, adequate caloric intake is the best prevention of this abnormality.

Effect of Hippurate on Glucose Utilization in Rat Kidney Cortex Slices

Hippurate action on glucose utilization was evaluated in rat kidney cortex slices. Studies have shown the following. (1) Hippurate inhibits markedly basal as well as insulin-stimulated glucose utilization and basal gluconeogenesis. (2) Ca deficiency and specific Ca channel blockers diltiazem and isradipine abolish the hippurate inhibition of glucose utilization. (3) K+ channel blockers, i.e. the increased K+ concentration in incubation medium, procaine and sulfonylurea drugs also abolish the hippurate inhibition of glucose utilization. It is concluded that hippurate and benzoate operate through the ATP-dependent K+ channel.