Benefits of Preserving Residual Urine Output in Patients Undergoing Maintenance Haemodialysis.

Introduction: Chronic kidney disease is a widespread medical problem that leads to higher morbidity, mortality, and a decrease in the overall well-being of the general population. This is especially expressed in patients with end-stage renal disease (ESRD) undergoing maintenance haemodialysis. Several variables could be used to evaluate those patients' well-being and mortality risk. One of them is the presence of residual urine output. Materials and Methods: The study was conducted on 485 patients treated with maintenance haemodialysis. After enrollment in the study, which consisted of medical history, physical examination, hydration assessment, and blood sampling, each patient was followed up for 24 months. We used residual urine output (RUO) as a measure of residual renal function (RRF). The entire cohort was divided into 4 subgroups based on the daily urinary output (<=100mL per day, >100mL to <=500mL, >500mL to <=1000mL and >1000mL). Results: The data show that the mortality rate was significantly higher in groups with lower RUO, which was caused mainly by cardiovascular events. Also, patients with higher RUO achieved better sodium, potassium, calcium, and phosphate balance. They were also less prone to overhydration and had a better nutritional status. Preserved RRF also had a positive impact on markers of cardiovascular damage, such as NT-proBNP as well as TnT. Conclusion: In conclusion, preserving residual urine output in ESRD patients undergoing maintenance haemodialysis is invaluable in reducing their morbidity and mortality rates and enhancing other favourable parameters of those patients.

Can Overnutrition Lead to Wasting?-The Paradox of Diabetes Mellitus in End-Stage Renal Disease Treated with Maintenance Hemodialysis.

BACKGROUND: The population of end-stage renal disease (ESRD) patients with diabetes mellitus (DM) may be at increased risk of protein energy wasting (PEW). The aim of the study was to investigate the impact of DM on selected indicators of PEW in the ESRD population that was undergoing maintenance hemodialysis (MHD). METHODS: A total of 515 MHD patients were divided into two subgroups with and without DM. The evaluation of diet composition, Charlson Comorbidity Index (CCI), SGA, and laboratory and BIS analyses were performed. All-cause and cardiovascular mortality was recorded. RESULTS: DM patients had lower albumin (3.93 (3.61-4.20) vs. 4.10 (3.80-4.30) g/dL, p < 0.01), total cholesterol (158 (133-196) vs. 180 (148-206) mg/dL, p < 0.01), and creatinine (6.34 (5.08-7.33) vs. 7.12 (5.70-8.51) mg/dL, p < 0.05). SGA score (12.0 (10.0-15.0) vs. 11.0 (9.0-13.0) points, p < 0.001), BMI (27.9 (24.4-31.8) vs. 25.6 (22.9-28.8) kg/m2, p < 0.001), fat tissue index (15.0 (11.4-19.6) vs. 12.8 (9.6-16.0) %, p < 0.001), and overhydration (2.1 (1.2-4.1) vs. 1.8 (0.7, 2.7) L, p < 0.001) were higher in the DM group. Increased morbidity, reflected in the CCI and mortality-both all-cause and cardiovascular-were observed in DM patients. CONCLUSIONS: Hemodialysis recipients with DM experience overnutrition with a paradoxically higher predisposition to PEW, expressed by a higher SGA score and lower serum markers of nutrition. This population is also more comorbid and is at higher risk of death, including from cardiovascular causes.

Overhydration as a modifiable cardiovascular risk factor in patients undergoing hemodialysis.

Introduction: Cardiovascular mortality in patients with end-stage renal disease (ESRD) remains high despite advances in dialysis techniques. This can be attributed to several traditional and nontraditional risk factors. Overhydration seems to be one of the promising cardiovascular risk factors that could be targeted to improve survival. Objectives: We aimed to assess the effect of chronic overhydration as well as changes in the degree of overhydration over time on cardiovascular and all-cause morbidity and mortality in patients undergoing hemodialysis. Patients and methods: We enrolled 511 patients with ESRD undergoing hemodialysis. The hydration status was assessed with whole-body bioimpedance spectroscopy. Patients were divided into 4 subgroups according to baseline hydration status. Additionally, patients with at least 2 follow-up visits (n = 277) were classified into 4 subgroups according to changes in the hydration status over time. Results: Statistical analysis showed that male sex (P <⁠0.001), diabetes (P <⁠0.001), cardiac insufficiency (P <⁠0.001), smoking (P = 0.049), and cerebrovascular events (P = 0.007) were significant risk factors for overhydration. Cardiovascular toxicity of overhydration was reflected by elevated levels of N-terminal pro-B-type natriuretic peptide (P <⁠0.001) and cardiac troponin T (P <⁠0.001). Albumin and total cholesterol levels were the lowest in patients with severe overhydration (P <⁠0.001). Mortality was lower in patients with normal hydration status and mild overhydration (P <⁠0.001) as well as in those with stable low or descending overhydration pattern (P = 0.002). Conclusions: We showed that the degree of overhydration is significantly associated with the incidence of cardiovascular complications and prognosis in patients with ESRD undergoing hemodialysis.

Is Preptin a New Bone Metabolism Parameter in Hemodialysis Patients?

BACKGROUND: Preptin is a bone-anabolic pancreatic peptide hormone. Its role in bone metabolism has been studied in rats and in patients with diabetes, but its levels and significance in bone metabolism in hemodialyzed (HD) patients is unknown. METHODS: The relationships between preptin and anthropometric and biochemical parameters related to bone metabolism were studied in 73 patients on chronic hemodialysis (48 males, 25 females; mean age of 57 years; HD vintage of 69.7 months). Of these subjects, 36 patients had diabetes or impaired glucose tolerance (DM/IGT), and 37 patients had normal glucose tolerance (NGT). Dual-energy X-ray absorptiometry of the femoral neck and lumbar spine were also performed. RESULTS: No differences were observed in preptin levels between DM/IGT and NGT HD patients. Preptin was positively correlated with HD vintage (r = 0.312, p = 0.007). Negative correlations between preptin and bone mineral density (BMD), T-score, and Z-score in the lumbar spine (L2-L4) were observed (r = -0.319, p = 0.009; r = -0.341, p = 0.005; r = -0.375, p = 0.002). Preptin was positively correlated with parathormone (PTH) levels (r = 0.379, p < 0.001) and osteocalcin levels (r = 0.262, p = 0.027). CONCLUSIONS: The results indicate that preptin may reflect on bone and mineral metabolism disturbances seen in HD patients. The significant correlation of preptin with PTH and osteocalcin suggests that preptin may be important in indirect measurement of bone turnover in HD patients.

Adropin and irisin: New biomarkers of cardiac status in patients with end-stage renal disease? A preliminary study.

BACKGROUND: The new polypeptide hormones adropin and irisin have a broad impact on human metabolism and energy homeostasis. They could be potential biomarkers of cardiac injury. In end-stage renal disease (ESRD), the clinical importance of adropin and irisin is yet to be investigated. OBJECTIVES: The aim of this study was to determine the relationship between these peptides and cardiac status in ESRD patients. MATERIAL AND METHODS: Seventy-nine ESRD patients on hemodialysis (HD), peritoneal dialysis (PD) or after renal transplantation (Tx), and 40 healthy, ageand sex-matched controls (CON) were included in this study. Serum concentrations of adropin and irisin were measured with enzyme-linked immunosorbent assay (ELISA). Cardiac status was estimated by transthoracic echocardiography and the plasma concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT). RESULTS: The levels of irisin were significantly lower in HD patients as compared to CON. During HD sessions, the concentrations of adropin did not change significantly, whereas the concentrations of irisin increased with borderline significance. Positive correlations were evident between adropin concentration and cTnT as well as NT-proBNP. Adropin was also correlated with left ventricular systolic internal diameter (LVIDs) (r = 0.375, p = 0.045) and relative wall thickness (RWT) (r = -0.382, p = 0.034). Irisin was correlated with right ventricular diameter (RVd) (r = -0.363, p = 0.045). No correlations were found between irisin and adropin, and blood pressure (BP) measurements. CONCLUSIONS: Adropin could be a new candidate marker of cardiac dysfunction in HD patients. The cause of low levels of irisin found in HD patients is still unclear. These 2 myokines should be further investigated as potential prognostic markers of cardiac status in HD patients.

Dialysis vintage stratified comparison of body composition, hydration and nutritional state in peritoneal dialysis and hemodialysis patients.

INTRODUCTION: Body mass decomposition and hydration state imbalances affect patients on maintenance dialysis. We compared body composition, hydration and nutritional state of patients on peritoneal dialysis (PD) and hemodialysis (HD) based on dialysis vintage (DV). MATERIAL AND METHODS: Three hundred and fifty-nine prevalent patients on HD (n = 301) and PD (n = 58) were divided into 3 subgroups depending on DV: < 2 years HD (n = 41) and PD (n = 28), 2-4 years HD (n = 111) and PD (n = 17), > 4 years HD (n = 149) and PD (n = 13). Bioimpedance analysis delivered data including overhydration (OH), Lean (LTM) and adipose lipids mass (FAT). Other measurements included daily diuresis (DD), subjective global assessment (SGA) and serum albumin (alb), C-reactive protein (CRP) and total cholesterol (TChol), and hemoglobin (Hb). RESULTS: Dialysis vintage < 2 years. Hemodialysis patients were older (65.5 ±18.5 vs. 50.9 ±17.1; p < 0.01) with a higher mortality (28 vs. 1; p < 0.01) and OH (8.0 ±4.3 vs. 1.6 ±3.1; p < 0.001). Hemoglobin (10.6 ±1.5 vs. 11.8 ±1.7; p < 0.05), TChol (180.2 ±47.0 vs. 211.7 ±46.3; p < 0.05), DD (871 ±729 vs. 1695 ±960; p < 0.001) and LTM (46.5 ±12.9 vs. 53.8 ±14.4; p < 0.05) were lower on HD. Dialysis vintage 2-4 years: when compared to PD, HD patients had higher OH (11.7 ±5.9 vs. 2.1 ±3.2; p < 0.001) and lower Hb (10.8 ±1.5 vs. 11.9 ±1.4; p < 0.01). Dialysis vintage > 4 years: compared to PD, HD patients had higher LTM (44.3 ±11.7 vs. 38.6 ±7.9; p < 0.05) and lower FAT (34.4 ±11.1 vs. 42.8 ±6.4; p < 0.01). CONCLUSIONS: Dialysis patients' body composition depends on dialysis modality and DV. Dialysis vintage < 2 years is associated with better hydration, nutritional state, and survival in PD patients, but longer DV reduces these benefits. Dialysis vintage > 4 years associated with similar hydration and mortality in both PD and HD while body composition was better on HD.

Dialysis vintage and cardiovascular injury as factors influencing long-term survival in peritoneal dialysis and hemodialysis.

BACKGROUND: Cardiovascular (CV) incidents are the major cause of mortality in maintenance dialysis (MD) patients undergoing peritoneal dialysis (PD) or hemodialysis (HD). CV injury indicators may be useful to investigate the dialysis modality influence on survival. OBJECTIVES: The aim of this study was to compare selected laboratory and echocardiographic (ECHO) markers of CV injury in terms of dialysis vintage (DV), CV-related mortality and all-cause mortality. MATERIAL AND METHODS: The study involved 301 patients on HD (n = 301) and PD (n = 58), who were divided into subgroups according to DV. The subjects' medical histories included diabetes mellitus (DM), myocardial infarction (MI), stroke, CV deaths and deaths from non-CV causes. Their CV parameters were measured with ECHO for the left ventricle ejection fraction (EF), posterior wall (LVW) and interventricular septum (IVS). Serum analyses of cardiac troponin T (TnT) and N-terminal pro-brain natriuretic peptide (BNP) were also carried out. RESULTS: In the subgroup with a DV of 4 years, the PD and HD patients were of a similar age, and had similar mortality and morbidity rates and CV markers, except for thicker IVS in the HD patients. CONCLUSIONS: Focusing on the data analysis based on mortality, and both laboratory and echocardiographic markers of cardiovascular injury, PD seems to be a more favorable method of dialysis. The advantage of PD was noted in subjects with a DV < 2 years. HD showed no outcome benefit over PD in longer DV.

Adropin and irisin levels in relation to nutrition, body composition, and insulin resistance in patients with end-stage renal disease on chronic hemodialysis and peritoneal dialysis.

INTRODUCTION    Newly discovered myokines, adropin, and irisin, are regulators of energy homeostasis and metabolism in humans. In end-stage renal disease (ESRD), the significance and role of irisin and adropin as metabolism regulators are still unclear. OBJECTIVES    The aim of this study was to evaluate serum adropin and irisin levels and establish their relation to insulin resistance, nutritional status, and hydration status in patients on chronic hemodialysis (HD) and on peritoneal dialysis (PD). PATIENTS AND METHODS    The study consisted of 71 subjects, including 48 patients (18 women, 30 men; median age, 56.5 years; range, 26-84 years) either on HD (n = 41) or PD (n = 7) and 36 healthy controls matched for age and sex. We measured the serum levels of adropin, irisin, creatinine, albumin, glucose, and insulin, as well as the plasma levels of lipids. The bioimpedance method was used to evaluate the body composition and overhydration in patients with ESRD. RESULTS    Irisin levels were significantly lower in patients with ESRD compared with controls, but there were no differences in adropin levels between both study groups. Adropin levels were inversely correlated with body mass, lean tissue mass, total, intracellular, and extracellular water, and albumin concentrations in patients with ESRD. Irisin levels were positively correlated with glucose levels and homeostasis model assessment of insulin resistance. No significant correlations were observed between adropin and irisin concentrations and overhydration. CONCLUSIONS    Adropin may be considered as a new marker of nutritional status in patients with ESRD. The significance and cause of low irisin levels characteristic for these patients are still unclear. Adropin and irisin should be further investigated as possible markers of cachexia and insulin resistance in patients with ESRD.

Animal Models of Peritoneal Dialysis: Thirty Years of Our Own Experience.

Experimental animal models improve our understanding of technical problems in peritoneal dialysis PD, and such studies contribute to solving crucial clinical problems. We established an acute and chronic PD model in nonuremic and uremic rats. We observed that kinetics of PD in rats change as the animals are aging, and this effect is due not only to an increasing peritoneal surface area, but also to changes in the permeability of the peritoneum. Changes of the peritoneal permeability seen during chronic PD in rats are comparable to results obtained in humans treated with PD. Effluent dialysate can be drained repeatedly to measure concentration of various bioactive molecules and to correlate the results with the peritoneal permeability. Additionally we can study in in vitro conditions properties of the effluent dialysate on cultured peritoneal mesothelial cells or fibroblasts. We can evaluate acute and chronic effect of various additives to the dialysis fluid on function and permeability of the peritoneum. Results from such study are even more relevant to the clinical scenario when experiments are performed in uremic rats. Our experimental animal PD model not only helps to understand the pathophysiology of PD but also can be used for testing biocompatibility of new PD fluids.

N­terminal pro­B-type natriuretic peptide as a marker of hypervolemia and predictor of increased mortality in patients on hemodialysis.

INTRODUCTION: N­terminal pro­B­type natriuretic peptide (NT­proBNP) is an established biomarker of heart failure in the general population. However, its diagnostic value is unclear in hemodialysis (HD) patients owing to renal insufficiency. OBJECTIVES: The aim of the study was to establish the usefulness of NT­proBNP for hydration assessment and the relation of NT­proBNP to the nutritional state and prognosis of survival. PATIENTS AND METHODS: In 321 HD patients (206 men; mean age, 65.1 ±21.4 years), we assessed NT­proBNP levels, overhydration (OHBIA), and the indices of the nutritional state (using a bioimpedance analysis [BIA]) in relation to cardiac troponin T (cTnT), hemoglobin, albumin, total cholesterol (TC), and C­reactive protein (CRP) levels. The efficacy of HD was assessed using Kt/V, weekly HD dose, and HD session ultrafiltration. The cohort was divided into NT­proBNP quartiles. Patients with 2 NT­proBNP measurements were categorized also into change­over­time subgroups. A follow­up lasted for a median period of 23.8 ±26.3 months. RESULTS: Relative OHBIA increased across the NT­proBNP quartiles (Q1/Q2/Q3/Q4, 1.31% ±2.56%/2.06% ±2.35%/2.92% ±2.97%/4.62% ±4.22%; P <0.0001). NT­proBNP was also closely associated with other OH parameters. In addition, there was a significant correlation between NT­proBNP and cTnT (r = 0.55; P <0.0001). Body mass index (BMI) and fat tissue index (FTI) decreased across the quartiles (BMI, 28.5 ±7.7/26.0 ±6.6/25.8 ±5.4/23.7 ±5.5 kg/m2; FTI, 14.4 ±9.0/14.1 ±7.3/12.3 ±6.8/11.6 ±6.1; P <0.001). The highest albumin level was present in Q1 (4.10 ±0.63/3.99 ±0.51/3.90 ±0.62/3.97 ±0.78 g/dl; P = 0.006). The TC level was the lowest in Q4 (190 ±60/169 ±56/173 ±51/153 ±56 mg/dl; P = 0.002). The hemoglobin level decreased across the quartiles (11.44 ±1.25/11.15 ±2.50/10.79 ±1.51/10.45 ±1.67 g/dl; P = 0.0006). The differences in CRP levels and HD­related parameters were nonsignificant. During the follow­up, 97 deaths were recorded (11/26/21/39, P <0.0001). CONCLUSIONS: NT­proBNP seems to be a useful biomarker of hypervolemia in HD patients. Nevertheless, it has to be interpreted with regard to the patient's individual residual renal function and cardiovascular status.

Cardiac Troponin T and Hydration Status as Prognostic Markers in Hemodialysis Patients.

This study aimed to assess cardiac troponin T (cTnT) and hydration state as cardiovascular (CV) risk markers in hemodialysis (HD) patients. Two hundred and forty one patients were divided according to HD vintage into two groups: SV (HD ≤24 months) and LV. Water balance was assessed with overhydration (OH%; bioimpedance analysis) and daily diuresis (DD); CV dysfunction with cTnT and heart ultrasound; nutrition with subjective global assessment (SGA), cholesterol (TC) and albumin. SV had lower OH% (2.8 vs. 3.5, p < 0.05) and higher DD (1,161 vs. 637 ml, p < 0.001), while LV had higher cTnT (0.1 ± 0.04 vs. 0.1 ± 0.07 ng/ml, p < 0.05) and lower interventricular septum thickness (IVS; 13.4 vs. 14.5 mm, p < 0.05). Nutritional state as reflected by lower TC was worse in LV (184.7 vs. 169.5 mg/dl, p < 0.05). Mortality was higher in patients in the LV group (15 vs. 27 deaths, p < 0.05). OH% correlated inversely with albumin (r = -0.36, p < 0.001), TC (r = -0.31, p < 0.001) and cTnT (r = -0.4, p < 0.001). cTnT correlated positively with IVS (r = 0.39, p < 0.001), SGA (r = 0.23, p = 0.001) and mortality rate (r = 0.21, p < 0.01), and negatively with DD (r = -0.34, p < 0.001) and albumin (r = -0.25, p < 0.001). Longer dialysis vintage associates with CV dysfunction, overhydration and increased mortality, which may be predicted with OH% and cTnT. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=376603.

The polymorphism of the ACE gene affects left ventricular hypertrophy and causes disturbances in left ventricular systolic/diastolic function in patients with autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most frequently occurring autosomal diseases inherited in the dominant manner. Due to this, lesions in the cardiovascular system of ADPKD patients have caught the attention of clinical investigators worldwide. The aim of the study was to analyse cardiovascular complications in ADPKD patients with a focus on left ventricular hypertrophy (LVH) and selected components of its systolic/diastolic function based on echocardiography. The study was conducted on 55 patients with ADPKD (24 males, 31 females), subdivided into three groups according to the stage of chronic kidney disease (CKD). The patient group with ADPKD and ESRD (group C) manifested an increased incidence of the D allele as compared to group A and group B (χ(2) = 4.217, P = 0.04). In all ADPKD patients with the DD genotype, left ventricular mass (LVM), posterior wall thickness (PWT), and interventricular septal thickness (IVS) were significantly higher compared to patients possessing the II and ID genotypes (P < 0.02, P < 0.003, and P < 0.009, resp.). The DD genotype exists more frequently in ADPKD patients with ESRD and is associated with a higher occurrence of LVH and disturbances in systolic-diastolic function when compared to ADPKD ESRD patients with the II and ID genotypes.

Acute Progression of Adult-Onset Atypical Hemolytic-Uremic Syndrome due to CFH Mutation: A Case Report.

Atypical hemolytic-uremic syndrome (aHUS), unlike typical HUS, is not due to bacteria but rather to an idiopathic or genetic cause that promotes dysregulation of the alternative complement pathway. It leads to hemolytic anemia, thrombocytopenia, and renal impairment. Although aHUS secondary to a genetic mutation is relatively rare, when occurring due to a mutation in Factor H (CFH), it usually presents with younger onset and has a more severe course, which in the majority ends with end-stage renal failure. Paradoxically to most available data, our case features acute aHUS due to a CFH mutation with late onset (38-year-old) and rapid progression to end-stage renal disease. Due to current data indicating a high risk of graft failure in such patients, the diagnosis of aHUS secondary to a genetic cause has disqualified our patient from a living (family) donor renal transplantation and left her with no other option but to begin permanent renal replacement therapy.