End-stage Renal Disease Controls Research Articles

#3459 GLUCOSE-LOWERING THERAPIES IN END STAGE RENAL DISEASE: HOW CAN WE PREDICT THE RISK OF HYPOGLYCAEMIA?

Abstract Background and Aims Diabetes is a common co-morbidity in patients with end stage renal disease (ESRD) receiving renal replacement therapy (RRT). Glucose-lowering therapies (GLT) such as sulphonylureas and insulin are commonly used treatments in diabetes but increase the risk of hypoglycaemia. Dialysis is also a risk factor for hypoglycaemia due to reduced drug clearance, decreased gluconeogenesis and glucose loss into the dialysate. Guidelines suggest an HbA1c target of 58 mmol/mol for patients with ESRD receiving glucose lowering therapies, given that tight HbA1c control has not been shown to improve cardiovascular risk, and HbA1c under 58mmol/mol will incur risk of hypoglycaemia in a potentially vulnerable population. We evaluated the clinical and demographic features associated with HbA1c <58 mmol/mol in an ESRD cohort aiming to define characteristics that predict the need for closer glycaemic monitoring. Method We performed a retrospective observational study of patients receiving RRT and treated with GLT attending a single centre nephrology unit using data collected from a clinically used electronic database. Patients with HbA1c <58 mmol/mol in the last 12 months were identified. Clinical, biochemical and demographic factors were compared between groups. Deprivation was measured using the Scottish Index of Multiple Deprivation (SIMD), whereby 1 represented the most deprived areas within Glasgow, while 5 represented the most affluent. Between group characteristics were analysed using Pearson's Chi-squared test or Wilcoxon test, and logistic regression was used to evaluate factors contributing to hypoglycaemia. Results We identified 607 patients, 51.6% of whom had an HbA1c below 58 mmol/mol. 298 patients were on haemodialysis, 14 on peritoneal dialysis and 291 had a kidney transplant. Patients with HbA1c<58 mmol/mol were older, (58±16.8 vs 60±15 years, p = 0.004) but there was no difference in duration of diabetes (9.1±10.2 vs 8.3±12.3 years, p = 0.42) or ESRD vintage (4.6±6.9 vs 4.1±7.5 years, p = 0.44). There was a higher proportion of type 2 diabetes in the group with HbA1c <58 mmol/mol(26 vs 36%, p = 0.04). There was no association between HbA1c and SIMD (p = 0.46) nor gender (p = 0.55). In logistic regression, increasing age (OR 1.19, 95% CI 1.03, 1.38) and ESRD vintage (OR 1.03, 95% CI 1.01, 1.06) increase the likelihood of tight glycaemic control. Transplantation reduced the risk (OR 0.64, 95% CI 0.44, 0.93). There was no association between type of GLT and risk of tight glycaemic control. Subgroup analyses of the haemodialysis and transplant populations was also performed with broadly similar findings. In patients on haemodialysis, increasing age and ESRD increased the risk of HbA1c <58 mmol/mol. In patients with a kidney transplant, there was no association between current estimated glomerular filtration rate and HbA1c <58 mmol/mol. Conclusion Tight glycaemic control is very common in patients with ESRD on GLT. We found signals that patients with type 2 diabetes, receiving haemodialysis, increasing age, and ESRD vintage, increased risk of tight glycaemic control and hypoglycaemia. Transplantation was a substantial protective factor. In patients with a kidney transplant, no trend was found in eGFR and HbA1c. This is a huge concern and suggests HbA1c checks need to be included as part of regular renal profile monitoring every 3 months. More regular follow-up with the Diabetes team may also be useful in this patient group. Continuous glucose monitoring (CGM) devices have revolutionised diabetes care by allowing easy access to data such as time in range and trends in blood sugar throughout the day, thus making it easier to optimise treatment. These devices also provide the patient with a warning when they are approaching hypoglycaemia. This study provides an argument that existing indications for CGM do not match risk factors for tight glycaemic control in ESRD. Hypoglycaemia is difficult to predict in ESRD patients and access to CGM should be widened.

CARDIOVASCULAR DISEASE AFTER KIDNEY TRANSPLANTATION: A NATIONWIDE STUDY IN SOUTH KOREA

Background: Cardiovascular disease (CVD) is the most common cause of death in end-stage renal disease (ESRD). Kidney transplantation (KT) is an effective treatment for ESRD, and is known as lowering risk for CVD compared to the ESRD patients on the transplantation waiting list. However, there is a lack of large-population studies especially for Asians. Method: We analyzed the nationwide health insurance database of South Korea and identified patients who received kidney transplantation from the year of 2007 to 2015. Patients who were under 20 years of age, had previous CVD identified, or had multiorgan transplantation were excluded from the study. As controls, ESRD and GP groups were extracted after same exclusion and matching with KT recipients by age, sex, and inclusion year. CVD was defined as major cardiovascular events (MACEs) consisted of myocardial infarction, ischemic stroke, and all-cause mortality. Result: During the study period, a total of 13,179 patients received KT. After exclusion, 4,156 KT recipients were selected. The same number of ESRD and GP control were extracted after matching. Mean age was 41.3 ± 10.2 years and 55.2% were men in all 3 groups. KT recipients had similar proportions of diabetes and hypertension and a lower proportion of dyslipidemia compared with ESRD controls, although significantly higher co-morbidities than GP controls. The total number of MACEs was 76 (3.7 per 1000 person-year) in KT recipients, 377 (21.7 per 1000 person-year) in ESRD, 51 (2.5 per 1000 person-year) in GP, respectively. KT recipients showed a significantly lower MACE risk (adjusted HR 0.16, 95% CI 0.12-0.20, p <0.001) than ESRD controls. And the MACE risks were not significantly different between KT recipients and matched GP controls (adjusted HR 0.81, 95% CI 0.52-1.27, p=0.365). When subgroup analysis of age, sex, diabetes and hypertension was performed, similar trends were observed regardless of subgroups. Meanwhile, KT recipients who occurred MACE showed significant elevated risk of all-cause mortality and graft failure (HR 7.45, 95% CI 4.21-13.21, p<0.001 and HR 2.49, 95% CI 1.52-4.09, p<0.001, respectively). Conclusion: In this study, we found that the KT recipients had a lower risk of newly onset MACE after transplantation compared to patients maintaining dialysis in Korea, and showed a similar MACE risk compared to the general population.

The Relationship Between Volume Overload in End-Stage Renal Disease and Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is common, underdiagnosed, and undertreated among patients with end-stage renal disease (ESRD). As in all cases, pathogenesis of OSA is related to repeated upper airway (UA) occlusion or narrowing, but in ESRD, additional contributory factors likely include uremic destabilization of central respiratory control and anatomic changes in the UA related to fluid status. Pulmonary congestion is common in acute and chronic kidney failure and is a consequence of cardiomyopathy and fluid overload, two potentially reversible risk factors. Emerging evidence suggests that volume overload also reduces the UA caliber. The diminution in UA area as well as destabilization of ventilatory control in ESRD have been postulated as causes of increased OSA prevalence and severity in these patients, and creates a vicious cycle wherein OSA exacerbates fluid overload disorders such as in congestive heart failure (CHF) and ESRD, which then further worsen OSA. Dialysis modalities may differ in their effects on volume status, the accumulation of uremic toxins, and acid-base status, and as a consequence, on the emergence and severity of OSA. Given the contribution of excess fluid to both the severity of nocturnal hypoxia and UA narrowing, establishing and maintaining dry weight is of particular importance when managing OSA in ESRD. Clinical trials to determine the extent to which more aggressive fluid removal in ESRD patients may alleviate OSA are needed.

Activation of the alternative pathway of complement during the acute phase of typical haemolytic uraemic syndrome.

Haemolytic uraemic syndrome (HUS) is characterized by haemolytic anaemia, thrombocytopenia and acute renal failure. We studied the activation state of classical and alternative pathways of complement during the acute phase of Shiga toxin-associated HUS by performing a prospective study of 18 patients and 17 age-matched healthy controls to evaluate C3, C3c, C4, C4d, Bb and SC5b-9 levels. SC5b-9 levels were increased significantly in all patients at admission compared to healthy and end-stage renal disease controls, but were significantly higher in patients presenting with oliguria compared to those with preserved diuresis. C3 and C4 levels were elevated significantly at admission in the non-oliguric group when compared to controls. No significant differences were found for C4d values, whereas factor Bb was elevated in all patients and significantly higher in oliguric patients when compared to both controls and non-oliguric individuals. A positive and significant association was detected when Bb formation was plotted as a function of plasma SC5b-9 at admission. Bb levels declined rapidly during the first week, with values not significantly different from controls by days 3 and 5 for non-oligurics and oligurics, respectively. Our data demonstrate the activation of the alternative pathway of complement during the acute phase of Stx-associated HUS. This finding suggests that complement activation may represent an important trigger for the cell damage that occurs during the syndrome.

Self-Motivation Is Associated With Phosphorus Control in End-Stage Renal Disease

Hyperphosphatemia is common in end-stage renal disease and associates with mortality. Phosphate binders reduce serum phosphorus levels; however, adherence is often poor. This pilot study aims to assess patients' self-motivation to adhere to phosphate binders, its association with phosphorus control, and potential differences by race. Cross sectional design. Subjects were enrolled from one academic medical center dialysis practice from July to November 2012. Self-motivation to adhere to phosphate binders was assessed with the autonomous regulation (AR) scale (range: 1-7) and self-reported medication adherence with the Morisky Medication Adherence Scale. Linear regression models adjusting for age, sex, health literacy, and medication adherence were applied to determine associations with serum phosphorus level, including any evidence of interaction by race. Among 100 participants, mean age was 51 years (±15 years), 53% were male, 72% were non-white, 89% received hemodialysis, and mean serum phosphorus level was 5.7 ± 1.6 mg/dL. More than half (57%) reported the maximum AR score (7). Higher AR scores were noted in those reporting better health overall (P = .001) and those with higher health literacy (P = .01). AR score correlated with better medication adherence (r = 0.22; P = .02), and medication adherence was negatively associated with serum phosphorus (r = -0.40; P < .001). In subgroup analysis among non-whites, higher AR scores correlated with lower serum phosphorus (high vs lower AR score: 5.55 [1.5] vs 6.96 [2.2]; P = .01). Associations between AR score (β 95% confidence interval: -0.37 [-0.73 to -0.01]; P = .04), medication adherence (β 95% confidence interval: -0.25 [-0.42 to -0.07]; P = .01), and serum phosphorus persisted in adjusted analyses. Self-motivation was associated with phosphate binder adherence and phosphorus control, and this differed by race. Additional research is needed to determine if personalized, culturally sensitive strategies to understand and overcome motivational barriers may optimize mineral bone health in end-stage renal disease.

Variation in infection prevention practices in dialysis facilities: results from the national opportunity to improve infection control in ESRD (End-Stage Renal Disease) project.

OBJECTIVE To observe patient care across hemodialysis facilities enrolled in the National Opportunity to Improve Infection Control in ESRD (end-stage renal disease) (NOTICE) project in order to evaluate adherence to evidence-based practices aimed at prevention of infection. SETTING AND PARTICIPANTS Thirty-four hemodialysis facilities were randomly selected from among 772 facilities in 4 end-stage renal disease participating networks. Facility selection was stratified on dialysis organization affiliation, size, socioeconomic status, and urban/rural status. MEASUREMENTS Trained infection control evaluators used an infection control worksheet to observe 73 distinct infection control practices at the hemodialysis facilities, from October 1, 2011, through January 31, 2012. RESULTS There was considerable variation in infection control practices across enrolled facilities. Overall adherence to recommended practices was 68% (range, 45%-92%) across all facilities. Overall adherence to expected hand hygiene practice was 72% (range, 10%-100%). Compliance to hand hygiene before and after procedures was high; however, during procedures hand hygiene compliance averaged 58%. Use of chlorhexidine as the specific agent for exit site care was 19% overall but varied from 0% to 35% by facility type. The 8 checklists varied in the frequency of perfect performance from 0% for meeting every item on the checklist for disinfection practices to 22% on the arteriovenous access practices at initiation. CONCLUSIONS Our findings suggest that there are many areas for improvement in hand hygiene and other infection prevention practices in end-stage renal disease. These NOTICE project findings will help inform the development of a larger quality improvement initiative at dialysis facilities.

Phosphate control in end-stage renal disease: barriers and opportunities

Hyperphosphatemia is a nearly universal complication of end-stage renal disease that is widely recognized as one of the most important and most challenging clinical targets to meet in the care of dialysis patients. Left untreated, it can lead to bone pain, pruritus and worsening secondary hyperparathyroidism. Data from observational studies demonstrate that an elevated serum phosphorus level is an independent risk factor for mortality, and that treatment with phosphate binders is independently associated with improved survival. Experimental studies provide support for the epidemiologic findings: phosphate excess promotes vascular calcification, induces endothelial dysfunction and may contribute to other emerging chronic kidney disease-specific mechanisms of cardiovascular toxicity. On the basis of this evidence, clinical practice guidelines recommend specific targets for serum phosphorus levels in the dialysis population. The purpose of this review is to summarize common challenges in meeting these targets and to identify potential opportunities for improvement.

Blood pressure control in end-stage renal disease

Blood pressure control in end-stage renal disease

Prevalence of cardiovascular disease in uraemia and relevance of cardiovascular risk factors

To evaluate the prevalence of cardiovascular disease (CVD) and its association with cardiovascular risk factors, as well as their control in end-stage renal disease (ESRD) patients under maintenance hemodialysis (HD). A total of 265 patients with ESRD on maintenance HD from a University Hospital and 4 dialysis units were included in this multicenter and cross-sectional study that analyzed the prevalence of CVD and the possible association with classic and new cardiovascular risk factors. Usual biochemical and haemathological parameters were analyzed, as well as plasma levels of homocysteine, troponin-I, BNP, lipoprotein(a), C reactive protein, IL-6, fibrinogen, asymmetrical dimethylarginine (ADMA), advanced oxidation protein products (AOPP), malondialdehyde, adiponectin, osteoprotegerin, and fetuin. In a subset of patients an echocardiography and carotid artery Doppler echography were also performed. The prevalence of CVD was 52.8%. Factors positively associated with prevalent CVD were age, BMI, left ventricular hypertrophy, hypertension, dyslipidemia and diabetes mellitus, dialysis vintage, Charlson s comorbility index, levels of fibrinogen, osteoprotegerin, BNP and CRP, as well as carotid intima-media thickness, left ventricular mass and pulse pressure. Factors negatively associated with prevalent CVD were: previous renal transplant, ejection fraction or levels of LDL-c and phosphorous. In the multivariate analysis dyslipidemia, left ventricular hypertrophy, age and LDL-c (negatively) were associated with CVD. In HD patients the prevalence of CVD is high and is associated with the presence of cardiovascular risk factors and subclinical CVD.

The impact of glycaemic control on outcomes in patients with end‐stage renal disease and type 2 diabetes (Review Article)

In Australia and New Zealand the prevalence and incidence of end-stage renal disease (ESRD) has increased. In Australia alone the financial burden is estimated to reach $500 million by 2007 (data from the National Chronic Kidney Disease Strategy Workshop Report 2005). The leading cause of ESRD in Australia and New Zealand, and throughout the developed world, is type 2 diabetes, having overtaken glomerulonephritis in 2004.(1) To date, management of patients with diabetes and ESRD has been, according to guidelines, given for patients without ESRD. This commentary raises three important emerging concerns in the clinical care of these patients: (i) the lack of reliable tools to measure glycaemic control; (ii) limitations of the current data set supporting a relationship between outcome and glycaemic control in ESRD; and (iii) lack of studies examining the effect of intensive diabetes care and glucose control in patients with ESRD.