Nada Dimkovic

Vascular access calcification predicts mortality in hemodialysis patients

Vascular calcification is a recognized risk factor for cardiovascular mortality in patients with end-stage renal disease. The aim of this study was to identify risk factors for vascular access calcification and to determine if patients with this disorder are at increased risk of death. Vascular access calcification was found in 49 of 212 hemodialysis patients as measured by plain X-ray (arteriovenous fistula or synthetic graft) in two dimensions. Male gender, diabetes mellitus, and length of time on dialysis were independent predictors for access calcification determined by logistic regression multivariate analysis. Serum parameters were not independently related to access calcification. Kaplan-Meier analysis showed an increased mortality risk, and Cox regression analysis confirmed that vascular access calcification was an independent mortality predictor. Our study suggests that detection of vascular access calcification is a cost-effective method to identify patients at increased mortality risk.

Geriatric Nephrology is Coming of Age

Contrary to predictions in the Gottschalk report to the US Congress in 1960 that the projected incidence of new end-stage renal disease patients will be on the order of 20 new patients per year, this number has been exceeded tenfold, mainly because no one anticipated the increase of elderly patients

Assisted peritoneal dialysis as a method of choice for elderly with end-stage renal disease

In the last two decades, most developed countries have seen a continuous growth in the number of elderly patients with end-stage renal disease commencing renal replacement therapy. Despite the many advantages that peritoneal dialysis (PD) offers to elderly patients with ESRD, it is still underutilized in older patients. Older patients are much more vulnerable to the problems associated with aging, which may affect their level of independence and their long-term prognosis. Those patients have physiological changes related to aging and common health problems such as anxiety, depression, dementia, visual impairment, and cognitive impairment, all of which interfere with self-performing PD. Assistance with home-care nurses and assistance by a family member may overcome this problem. Some old but also more recent literature data justifies the idea that assisted PD may significantly contribute to increase the overall number of elderly patients who can be treated with PD at home. With assisted PD, free choice can be offered to patients with high comorbidity index who cannot perform their peritoneal exchanges by themselves. Automated peritoneal dialysis is the ideal treatment modality for elderly patients with end-stage renal disease who require assistance since this limits home-care nurse visits to only two a day. As expected, the elderly have a higher mortality rate than younger patients treated by assisted PD, but technique failure rate, overall peritonitis rate, and most quality-of-life (QoL) measures are comparable with those of younger patients. Peritoneal dialysis in nursing homes offers treatment for elderly patients without family support. In this regard, automated PD or nightly PD keeps the patient’s daytime free for nursing home activities, increases socialization, and enables better rehabilitation that improves their QoL. Although withdrawal from dialysis is more frequent among nursing-home dialysis patients, this high discontinuation rate is not due to dialysis per se but rather to associated social and medical circumstances. Better communication between nursing staff and renal team is crucial for improving staff confidence and will contribute to higher utilization of PD in nursing homes.

Glutathione S-transferase A1, M1, P1 and T1 null or low-activity genotypes are associated with enhanced oxidative damage among haemodialysis patients

BACKGROUNDnIncreased oxidative stress is a hallmark of end-stage renal disease (ESRD). Glutathione S-transferases (GST) are involved in the detoxification of xenobiotics and protection of oxidative damage. We hypothesized that genetic polymorphism in antioxidant enzymes GSTA1, GSTM1, GSTP1 and GSTT1 is more frequent in ESRD and modulates the degree of oxidative stress in these patients.nnnMETHODSnGSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 199 ESRD patients and 199 age- and gender-matched controls. Markers of protein and lipid oxidative damage [thiol groups, carbonyl groups, advanced oxidative protein products, nitrotyrosine, malondialdehyde (MDA) and MDA adducts], together with total oxidant status and pro-oxidant-antioxidant balance were determined.nnnRESULTSnIndividual GST polymorphisms influence vulnerability to both protein and lipid oxidation, with GSTM1-null gene variant having the most pronounced effect. Furthermore, a strong combined effect of null/low-activity GSTM1, GSTT1, GSTA1 and GSTP1 genotypes in terms of susceptibility towards oxidative and carbonyl stress was found in ESRD patients. When patients were stratified according to GSTM1 and GSTT1, the highest oxidant damage was noted in those with the GSTM1-null/GSTT1-null genotype. The observed effect was even stronger in patients with the third low-activity GSTP1 or GSTA1 genotype. Finally, the level of oxidative and carbonyl stress was most pronounced in the subgroup of patients with all four null or low-activity GSTM1, GSTT1, GSTP1 and GSTA1 genotypes.nnnCONCLUSIONSnAccording to the GST genotype, ESRD patients may be stratified in terms of the level of oxidative and carbonyl stress that might influence cardiovascular prognosis, but could also improve efforts towards individualization of antioxidant treatment.

Evaluation of Oxidative Stress after Repeated Intravenous Iron Supplementation

Parenteral iron has been recommended for the treatment of iron deficiency in the majority of maintenance hemodialyzed (HD) patients. However, iron supplementation and consequent over saturation of transferrin and high iron levels, may aggravate oxidative stress already present in these patients. This study aimed to further clarify the role of repeated intravenous iron therapy as a supplementary cause of oxidative stress in HD patients. Markers of free radical activities (carbonyl reactive derivatives, CRD, thiol groups, SH, malondialdehyde, MDA) and antioxidant enzyme activities (superoxide dismutase, SOD and glutathione peroxidase, GPX) were determined in plasma and red blood cells (RBC) of 19 hemodialysis patients given a total iron dose of 625 mg (ferrogluconat, Ferrlecit, 62.5 mg). Blood samples were taken before the first and after the last dose of iron. Twenty apparently normal subjects served as healthy controls. Before iron treatment, HD patients exhibited increased concentrations of MDA and CRD in plasma and red blood cells, accompanied with impaired antioxidant capacity. All patients responded to iron therapy with a significant increase in their serum ferritin, serum iron, hemoglobin, and red blood cells levels. However, iron treatment resulted in enhanced oxidative stress in plasma of HD patients, since significant increase in plasma MDA and CRD concentrations, together with a decrease in nonprotein SH groups levels were detected. Supplementation with iron did not significantly influence plasma SOD and GPX activities, nor did any of the red blood cell parameters tested. Our data show that, despite improvement in hematological parameters, an increase in iron stores due to supplementation could also contribute to increased free radical production in HD patients.

The effects of colestilan versus placebo and sevelamer in patients with CKD 5D and hyperphosphataemia: a 1-year prospective randomized study

Background This study compared the effects of short-term titrated colestilan (a novel non-absorbable, non-calcium, phosphate binder) with placebo, and evaluated the safety and efficacy of colestilan over 1 year compared with sevelamer, in patients with chronic kidney disease (CKD) 5D. Methods This prospective multicentre study comprised a 4-week phosphate binder washout period, a 16-week short-term, flexible-dose, treatment period (including a 4-week placebo-controlled withdrawal period) and a 40-week extension treatment phase. Results At Week 16 (the end of the 4-week placebo-controlled withdrawal period), serum phosphorus level was 0.43 mmol/L (1.32 mg/dL) lower with colestilan than placebo (P < 0.001; primary end point). Serum LDL-C level was also lower with colestilan than with placebo (P < 0.001). Both colestilan and sevelamer produced significant reductions from baseline in serum phosphorus levels (P < 0.001), maintained for 1 year, and the proportion of patients achieving target levels of ≤1.78 mmol/L (5.5 mg/dL) or ≤1.95 mmol/L (6.0 mg/dL) at study end were similar (65.3 and 73.3%, respectively, for colestilan, and 66.9 and 77.4%, respectively, for sevelamer). Serum calcium level remained stable in the colestilan group but tended to increase slightly in the sevelamer group (end-of-study increase of 0.035 mmol/L over baseline). Both binders produced similar reductions from baseline in LDL-C level (P < 0.001), and responder rates after 1 year, using a target of <1.83 mmol/L (70 mg/dL) or <2.59 mmol/L (100 mg/dL) were similar in both groups (50.7 and 85.3% for colestilan and 54.0 and 80.6% for sevelamer). Colestilan was generally well tolerated. Conclusions Colestilan is effective and safe for the treatment of hyperphosphataemia in patients with CKD 5D, and affords similar long-term phosphorus and cholesterol reductions/responder rates to sevelamer.

Evaluation of colestilan in chronic kidney disease dialysis patients with hyperphosphataemia and dyslipidaemia: a randomized, placebo-controlled, multiple fixed-dose trial

BACKGROUNDnColestilan is a non-absorbed, non-calcium-based, phosphate binder. It also binds bile acids and reduces serum levels of low-density lipoprotein cholesterol (LDL-C). This study evaluated the efficacy of a range of fixed doses of colestilan compared with placebo for the control of serum phosphorus and LDL-C levels in patients with CKD stage 5 on dialysis.nnnMETHODSnThis was a multicentre, randomized, double-blind, placebo-controlled, multiple fixed-dose trial in which 642 patients with CKD stage 5 on dialysis who had both hyperphosphataemia and dyslipidaemia, were randomized to treatment with colestilan 3, 6, 9, 12 or 15 g/day or placebo for 12 weeks. The co-primary endpoints were the mean changes in serum phosphorus and the mean per cent change in LDL-C from baseline to Week 12.nnnRESULTSnA significantly greater mean reduction in serum phosphorus level from baseline to Week 12 than seen with placebo was seen with 9 g (-0.28 mmol/L) and pooled colestilan 12/15 g (-0.34 mmol/L). The per cent reduction in LDL-C level was significantly greater with colestilan 3, 6 and 9 g and pooled colestilan 12/15 g than with placebo (reduction ranged from 15.9 to 27.6% dependent on dose). Colestilan also reduced total cholesterol, oxidized LDL-C, HbA1c and uric acid levels, and did not increase serum calcium levels. Colestilan was generally well tolerated; the most common adverse events affected the gastrointestinal system.nnnCONCLUSIONSnColestilan is an effective treatment for hyperphosphataemia, and provides beneficial effects on other metabolic parameters associated with cardiovascular risk, notably LDL-C.

Management of Elderly Patients With End-Stage Kidney Disease

The number of elderly patients requiring renal replacement therapy will continue to increase in the future. Previously, these patients were believed to have a poor prognosis on renal replacement therapy and therefore they were treated with conservative measures. Although there are no controlled randomized studies, an increasing amount of literature indicates that elderly persons with end-stage kidney disease are a heterogeneous population and that, in many of them, dialysis provides a good quality of life and survival. Both hemodialysis and peritoneal dialysis have their own advantages and disadvantages and therefore it is important to individualize treatment to achieve the best result for each patient, taking into account the patients wishes, local circumstances, availability of dialysis centers, and proper social support. Home treatments are the most suitable for frail elderly patients. In the latter population, peritoneal dialysis may be the method of choice because it can be performed by visiting nurses, thus allowing the patient to receive treatment at home without increasing the overall cost.

Chronic Peritoneal Dialysis in the Elderly: CHRONIC PERITONEAL DIALYSIS IN THE ELDERLY

Available data indicate that peritoneal dialysis (PD) offers some advantages for the increasing number of elderly patients with ESRD, such as hemodynamic stability, steady‐state metabolic control, good control of hypertension, independence from hospital visits, and avoidance of repeated vascular access. Early referral promotes the establishment of peritoneal access and minimizes the consequences of uremia and subsequent morbidity and frequent hospitalization. Elderly patients have similar modality‐related complications such as peritonitis, catheter‐related complications, exit‐site and tunnel infection, and hernias as younger patients. Comorbid conditions, malnutrition, and psychosocial status influence the survival of elderly patients on PD. Elderly patients are compliant and highly motivated to cooperate in treatment. They are more tolerant of changes and losses and have a greater sense of well‐being, less illness and modality‐related stress, and fewer mood disturbances. Despite comorbid conditions, that significantly impair self‐performance of dialysis, PD can be performed successfully if they have family support or access to a network of medical and social support, that is, home nurses, rehabilitation services, and chronic care dialysis units, or nursing homes.

GLP-1 Levels Predict Mortality in Patients with Critical Illness as Well as End-Stage Renal Disease

BACKGROUNDnGlucagon-like peptide 1 (GLP-1) is an incretin hormone, which stimulates glucose-dependent insulin secretion from the pancreas and holds immune-regulatory properties. A marked increase of GLP-1 has been found in critically ill patients. This study was performed to elucidate the underlying mechanism and evaluate its prognostic value.nnnMETHODSnGLP-1 plasma levels were determined in 3 different patient cohorts: 1) critically ill patients admitted to our intensive care unit (nxa0= 215); 2) patients with chronic kidney disease on hemodialysis (nxa0=xa0173); and 3) a control group (no kidney disease, no acute inflammation, nxa0= 105). Inxa0vitro experiments were performed to evaluate GLP-1 secretion in response to human serum samples from the above-described cohorts.nnnRESULTSnCritically ill patients presented with 6.35-fold higher GLP-1 plasma level in comparison with the control group. There was a significant correlation of GLP-1 levels with markers for the severity of inflammation, but also kidney function. Patients with end-stage renal disease displayed 4.46-fold higher GLP-1 concentrations in comparison with the control group. Inxa0vitro experiments revealed a strong GLP-1-inducing potential of serum from critically ill patients, while serum from hemodialysis patients only modestly increased GLP-1 secretion. GLP-1 levels independently predicted mortality in critically ill patients and patients with end-stage renal disease.nnnCONCLUSIONSnChronic and acute inflammatory processes like sepsis or chronic kidney disease increase circulating GLP-1 levels. This most likely reflects a sum effect of increased GLP-1 secretion and decreased GLP-1 clearance. GLP-1 plasma levels independently predict the outcome of critically ill and end-stage renal disease patients.