Hemodialysis and biomarkers of myocardial infarction - a cohort study.

OBJECTIVES: End-stage renal disease is associated with a high risk of cardiovascular disease. We compared the concentration and prognostic ability of high sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) and cardiac myosin-binding protein C (cMyC) among stable hemodialysis patients. METHODS: Patients were sampled before and after hemodialysis. We measured hs-cTnI, hs-cTnT and cMyC and used Cox regressions to assess the association between quartiles of concentrations and all-cause mortality and a combination of cardiovascular events and all-cause mortality during follow-up. RESULTS: A total of 307 patients were included, 204 males, mean age 66 years (SD 14). Before dialysis, 299 (99 %) had a hs-cTnT concentration above the 99th percentile, compared to 188 (66 %) for cMyC and 35 (11 %) for hs-cTnI. Hs-cTnT (23 %, p<0.001) and hs-cTnI (15 %, p=0.049) but not cMyC (4 %, p=0.256) decreased during dialysis. Follow-up was a median of 924 days (492-957 days); patients in the 3rd and 4th quartiles of hs-cTnT (3rd:HR 3.0, 95 % CI 1.5-5.8, 4th:5.2, 2.7-9.8) and the 4th quartile of hs-cTnI (HR 3.8, 2.2-6.8) had an increased risk of mortality. Both were associated with an increased risk of the combined endpoint for patients in the 3rd and 4th quartiles. cMyC concentrations were not associated with risk of mortality or cardiovascular event. CONCLUSIONS: Hs-cTnT was above the 99th percentile in almost all patients. This was less frequent for hs-cTnI and cMyC. High cTn levels were associated with a 3-5-fold higher mortality. This association was not present for cMyC. These findings are important for management of hemodialysis patients.

Cardiac arrhythmia and hypoglycaemia in patients receiving haemodialysis with and without diabetes (the CADDY study): protocol for a Danish multicentre cohort study.

INTRODUCTION: Patients receiving haemodialysis are at increased risk of arrhythmias and sudden cardiac death, but data on arrhythmia burden and the pathophysiology remain limited. Among potential risk factors, hypoglycaemia is proposed as a possible trigger of lethal arrhythmias. The development of implantable loop recorders (ILR) and continuous glucose monitoring (CGM) enables long-term continuous ECG and glycaemic monitoring. The current article presents the protocol of a study aiming to increase the understanding of arrhythmias and risk factors in patients receiving haemodialysis. The findings will provide a detailed exploration of the burden and nature of arrhythmias in these patients including the potential association between hypoglycaemia and arrhythmias. METHODS AND ANALYSIS: The study is an investigator-initiated, prospective, multicentre cohort study recruiting 70 patients receiving haemodialysis: 35 with diabetes and 35 without diabetes. Participants are monitored with ILRs and CGM for 18 months follow-up. Data collection further includes a monthly collection of predialysis blood samples and dialysis parameters. The primary outcome is the presence of clinically significant arrhythmias defined as a composite of bradycardia, ventricular tachycardia, or ventricular fibrillation. Secondary outcomes include the characterisation of clinically significant arrhythmias and other arrhythmias, glycaemic characteristics, and mortality. The data analyses include an assessment of the association between arrhythmias and hypoglycaemia and hyperglycaemia, baseline clinical variables, and parameters related to kidney failure and the haemodialysis procedure. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee of the Capital Region of Denmark (H-20069767). The findings will be presented at national and international congresses as well as in international peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT04841304.

Mid-regional pro-atrial natriuretic peptide levels before and after hemodialysis predict long-term prognosis.

BACKGROUND: Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a strong prognostic biomarker in cardiovascular disease but there is limited data for its use among patients undergoing dialysis. METHODS: This was a cohort study of patients receiving maintenance hemodialysis from two Danish centers. Blood sampling and echocardiography were performed before and after a dialysis session. We calculated the area under the curve (AUC) for the receiver operating characteristics for diagnosing heart failure and Cox regressions for cardiovascular events and all-cause mortality. RESULTS: Of the 306 patients, 284 (93%) had MR-proANP measurements both before and after dialysis. Median concentration was 642 pmol/L (IQR 419-858) before and 351 pmol/L (IQR 197-537) after dialysis, a mean decrease of 330 pmol/L (43%, CI 296-364, P < 0.001). MR-proANP concentration both before and after dialysis was negatively correlated to left ventricular ejection fraction with no difference in predictive ability for heart failure, AUC before and after dialysis were 0.60 (CI 0.50-0.70) and 0.61 (CI 0.51-0.71) (P = 0.40). Median follow-up was 32 months (IQR 31-33), during which 99 patients (32%) had a cardiovascular event and 110 (36%) died. A doubling of MR-proANP concentration was associated with a hazard ratio (HR) of 1.6 (CI 1.3-1.9) before and 1.7 (CI 1.4-2.0) after dialysis for mortality and a HR of 1.5 (CI 1.2-1.9) before and 1.4 (CI 1.2-1.7) after dialysis for cardiovascular events (all P < 0.001). CONCLUSION: The MR-proANP concentration is elevated among patients undergoing hemodialysis and decreases during dialysis. MR-proANP concentration both before, after and intra-dialysis change strongly predicted cardiovascular events and all-cause mortality.

Left-sided heart disease and risk of death in patients with end-stage kidney disease receiving haemodialysis: an observational study.

BACKGROUND: Cardiovascular disease is the most common cause of death in patients with end-stage kidney disease on haemodialysis. The potential clinical consequence of systematic echocardiographic assessment is however not clear. In an unselected, contemporary population of patients on maintenance haemodialysis we aimed to assess: the prevalence of structural and functional heart disease, the potential therapeutic consequences of echocardiographic screening and whether left-sided heart disease is associated with prognosis. METHODS: Adult chronic haemodialysis patients in two large dialysis centres had transthoracic echocardiography performed prior to dialysis and were followed prospectively. Significant left-sided heart disease was defined as moderate or severe left-sided valve disease or left ventricular ejection fraction (LVEF) ≤40%. RESULTS: Among the 247 included patients (mean 66 years of age [95%CI 64-67], 68% male), 54 (22%) had significant left-sided heart disease. An LVEF ≤40% was observed in 31 patients (13%) and severe or moderate valve disease in 27 (11%) patients. The findings were not previously recognized in more than half of the patients (56%) prior to the study. Diagnosis had a potential impact on management in 31 (13%) patients including for 18 (7%) who would benefit from initiation of evidence-based heart failure therapy. After 2.8 years of follow-up, all-cause mortality among patients with and without left-sided heart disease was 52 and 32% respectively (hazard ratio [HR] 1.95 (95%CI 1.25-3.06). A multivariable adjusted Cox proportional hazard analysis showed that left-sided heart disease was an independent predictor of mortality with a HR of 1.60 (95%CI 1.01-2.55) along with age (HR per year 1.05 [95%CI 1.03-1.07]). CONCLUSION: Left ventricular systolic dysfunction and moderate to severe valve disease are common and often unrecognized in patients with end-stage kidney failure on haemodialysis and are associated with a higher risk of death. For more than 10% of the included patients, systematic echocardiographic assessment had a potential clinical consequence.

Effect of the Incretin Hormones on the Endocrine Pancreas in End-Stage Renal Disease.

CONTEXT: The insulin-stimulating and glucagon-regulating effects of the 2 incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), contribute to maintain normal glucose homeostasis. Impaired glucose tolerance occurs with high prevalence among patients with end-stage renal disease (ESRD). OBJECTIVE: To evaluate the effect of the incretin hormones on endocrine pancreatic function in patients with ESRD. DESIGN AND SETTING: Twelve ESRD patients on chronic hemodialysis and 12 matched healthy controls, all with normal oral glucose tolerance test, were included. On 3 separate days, a 2-hour euglycemic clamp followed by a 2-hour hyperglycemic clamp (3 mM above fasting level) was performed with concomitant infusion of GLP-1 (1 pmol/kg/min), GIP (2 pmol/kg/min), or saline administered in a randomized, double-blinded fashion. A 30% lower infusion rate was used in the ESRD group to obtain comparable incretin hormone plasma levels. RESULTS: During clamps, comparable plasma glucose and intact incretin hormone concentrations were achieved. The effect of GLP-1 to increase insulin concentrations relative to placebo levels tended to be lower during euglycemia in ESRD and was significantly reduced during hyperglycemia (50 [8-72]%, P = 0.03). Similarly, the effect of GIP relative to placebo levels tended to be lower during euglycemia in ESRD and was significantly reduced during hyperglycemia (34 [13-50]%, P = 0.005). Glucagon was suppressed in both groups, with controls reaching lower concentrations than ESRD patients. CONCLUSIONS: The effect of incretin hormones to increase insulin release is reduced in ESRD, which, together with elevated glucagon levels, could contribute to the high prevalence of impaired glucose tolerance among ESRD patients.

Changes in left ventricular filling parameters before and after dialysis in patients with end stage renal disease.

The aim of this study was to investigate the grading of diastolic dysfunction (DD) in relation to hemodialysis in patients with end stage renal disease (ESRD) on hemodialysis (HD) Cardiovascular disease is prevalent in patients with ESRD and accounts for significant morbidity and mortality. Left ventricular hypertrophy (LVH) is common in ESRD but little is known about the impact of HD on currently recommended grading schemes for DD. Comprehensive echocardiographic data was obtained in consecutive patients with ESRD before (n = 247) and immediately after (n = 239) standard HD regimen. Grading of DD was performed according to current recommendations both pre- and post HD. Prior to HD, DD was classified as present in 83 patients (34%), indeterminate in 51 patients (21%) and absent in 113 patients (45%). Patients with DD at baseline compared to those without were older [67.3 years (13.1) vs. 63.2 (14.3), p = 0.037], were more likely to have diabetic- or hypertensive ESRD (43.4% vs. 35.4%, p = ns) and LVMi was significantly higher [119 g/cm2 (27.5) vs. 103 g/cm2 (24.3), p < 0.001]. After HD [mean HD time = 221 min (27.6), mean ultrafiltration volume = 2 L (1.1)], 39 patients (16%) exhibited sustained DD. These patients were older [69.4 years (14.5) vs. 65.0 years (13.9), p = 0.071], were more likely to have diabetic- or hypertensive ESRD (59% vs. 36%, p = 0.010). Myocardial adverse remodeling was more advanced with higher LVMi [127.4 g/m2 (27.5) vs. 106.5 g/m2 (25.3), p < 0.001], lower LVEF [44.7% (11.0) vs. 54.5% (8.7), p < 0.001] and more impaired GLS [- 13.4% (4.3) vs. - 15.8% (4.0), p = 0.006]. Echocardiographic evaluation of diastolic function in patients with ESRD on HD is critically dependent on timing relative to dialysis. The presence of sustained DD after volume unloading by HD identifies a population of patients with an adverse phenotype of blunted vascular response and severe cardiac remodeling.

Gastrointestinal motility in patients with end-stage renal disease on chronic hemodialysis.

BACKGROUND: Previous studies indicated delayed gastric emptying in patients with end-stage renal disease (ESRD) using indirect methods. The objective of the current study was to examine gastrointestinal motility using a direct method as well as the role of the incretin hormones and glucagon. METHODS: Patients on chronic hemodialysis and with either normal glucose tolerance, impaired glucose tolerance or type 2 diabetes, and healthy control subjects (N = 8, respectively) were studied. Gastric emptying time was measured by repeated gamma camera imaging for 6 hours after intake of a radioactive labeled standardized mixed solid and liquid meal. Glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) levels were measured. KEY RESULTS: Patients were age, gender and BMI matched with controls. We found significantly higher gastric retention at 15 minutes, prolonged gastric mean emptying time, and gastric half-emptying time of the solid marker in all three groups of ESRD patients compared to controls. Significant differences in mean total area under the concentration curve (AUC) values across the four groups for GIP (P = 0.001), but not for GLP-1 and glucagon. The ESRD group had significant higher total AUC of GIP and glucagon compared to controls (P < 0.001 and P < 0.04) but not for GLP-1 (P = 0.4). No difference in incremental AUC was found. CONCLUSIONS AND INFERENCES: We found altered gastrointestinal motility in dialysis patients, with higher gastric retention and prolonged gastric emptying, and higher total AUC of GIP and glucagon independent of the presence of diabetes or prediabetes.

YKL-40 in patients with end-stage renal disease receiving haemodialysis.

PURPOSE: This study aimed to determine serum YKL-40 in patients with end-stage renal disease (ESRD) on haemodialysis (HD) and to evaluate the prognostic value of serum YKL-40. METHODS: Patients >18 years on maintenance HD were included. Serum YKL-40 was measured using ELISA before and after a single HD treatment. RESULTS: A total of 306 patients were included. Median serum YKL-40 concentration was 238 µgL-1 (IQR: 193-291 µgL-1) before HD treatment and 198 µgL-1 (IQR: 147-258 µgL-1) after HD treatment, which corresponded to age-corrected 93th percentile in healthy subjects. All-cause mortality after 2.8 years was 35.9%. Patients with serum YKL-40 in the highest quartile compared with the lowest quartile had a univariate HR of 4.0 (95% CI: 2.2-7.3, p < 0.001) for all-cause mortality which decreased to 2.4 (95% CI: 1.1-4.5, p = 0.01) in multivariate analysis. Time-dependent receiver operating characteristic curves showed that serum YKL-40 after HD treatment had significant higher area under the curves from 90 d (p = 0.004) and throughout the rest of the follow-up period when compared to serum YKL-40 before HD treatment. CONCLUSION: YKL-40 was highly elevated in patients with ESRD on HD, and dialysis reduced serum YKL-40 concentrations approximately one-sixth. YKL-40 measured after dialysis was independently associated with mortality in HD patients.

Chronic obstructive pulmonary disease in patients with end-stage kidney disease on hemodialysis.

The objectives of this study were to assess the prevalence of chronic obstructive pulmonary disease (COPD) in hemodialysis patients with spirometry and to examine the effects of fluid removal by hemodialysis on lung volumes. Patients ≥18 years at two Danish hemodialysis centers were included. Forced expiratory volume in one second (FEV1 ), forced vital capacity (FVC), and FEV1 /FVC ratio were measured with spirometry before and after hemodialysis. The diagnosis of COPD was based on both the GOLD criteria and the lower limit of normal criteria. There were 372 patients in treatment at the two centers, 255 patients (69%) completed spirometry before dialysis and 242 of these (65%) repeated the test after. In the initial test, 117 subjects (46%) had airflow limitation indicative of COPD with GOLD criteria and 103 subjects (40.4%) with lower limit of normal criteria; COPD was previously diagnosed in 24 patients (9%). Mean FVC and FEV1 decreased mildly after dialysis (FVC: 2.84 to 2.79 L, P < 0.01. FEV1 : 1.97 to 1.93 L, P < 0.01) Hemodialysis did not affect the FEV1 /FVC ratio or number of subjects with airflow limitation indicative of COPD (113 vs. 120, P = 0.324; n = 242). COPD is a frequent and underdiagnosed comorbidity in patients on chronic hemodialysis. Spirometry should be considered in all patients on dialysis in order to address dyspnea adequately. Hemodialysis induced a small fall in mean FEV1 and FVC, which was more pronounced in patients with little or no fluid removal, but the FEV1 /FVC ratio and the number of subjects with airflow limitation indicative of COPD were not affected by dialysis.

Anti-glomerular basement membrane glomerulonephritis and thrombotic microangiopathy in first degree relatives: a case report.

BACKGROUND: Anti-glomerular basement membrane glomerulonephritis and thrombotic microangiopathy are rare diseases with no known coherence. CASE PRESENTATION: A daughter and her biological mother were diagnosed with pregnancy-induced thrombotic microangiopathy and anti-glomerular basement membrane glomerulonephritis, respectively. Both developed end-stage renal disease. Exploration of a common aetiology included analyses of HLA genotypes, functional and genetic aspects of the complement system, ADAMTS13 activity and screening for autoantibodies.The daughter was heterozygous carrier of the complement factor I G261D mutation, previously described in patients with membranoproliferative glomerulonephritis and atypical haemolytic uremic syndrome. The mother was non-carrier of this mutation. They shared the disease associated complement factor H silent polymorphism Q672Q (79602A>G). CONCLUSION: An unequivocal functional or molecular association between these two family cases was not found suggesting that the patients probably share another, so far undiagnosed and unknown, predisposing factor. It seems highly unlikely that two infrequent immunologic diseases would occur by unrelated pathophysiological mechanisms within first degree relatives.

High prevalence of nephrogenic systemic fibrosis in chronic renal failure patients exposed to gadodiamide, a gadolinium-containing magnetic resonance contrast agent.

OBJECTIVE: Nephrogenic systemic fibrosis (NSF) is a serious disease affecting renal failure patients. It may be caused by some gadolinium (Gd)-containing contrast agents, including gadodiamide. The study aimed at estimating the prevalence of NSF after gadodiamide exposure for patients with chronic kidney disease (CKD). MATERIALS AND METHODS: Retrospective cohort study of 190 consecutive nephrological patients in different categories of kidney function referred for gadodiamide-enhanced magnetic resonance imaging in the period January 1, 2004 to March 21, 2006. RESULTS: Eighteen patients (18/190; 10%, 95% CI: 6%-15%) were diagnosed with NSF within a mean follow-up period of 29 months (range 16-43 months). All 18 cases had stage 5 CKD (ie, estimated glomerular filtration rate less than 15 mL/min/1.73 m2 or in dialysis therapy) at the time of their gadodiamide exposure. The prevalence of NSF among patients with stage 5 CKD at exposure (n = 102) was 18% (95% CI: 11%-27%). No cases were seen among 88 gadodiamide-exposed patients who had milder degrees of renal insufficiency (prevalence 0%, 95% CI: 0%-4%). CONCLUSIONS: The risk of NSF is unacceptably high among stage 5 CKD patients exposed to gadodiamide.