Relaxin Is an Independent Risk Factor Predicting Death in Male Patients With End-Stage Kidney Disease

Abstract

Background-Patients with end-stage kidney disease (ESKD) have a reduced life expectancy mainly as the result of cardiovascular diseases. Relaxin has been implicated in the pathogenesis of cardiovascular diseases. We analyzed the impact of relaxin on death in patients with ESKD. Methods and Results-Patients (n ϭ245; 122 women, 123 men) on long-term hemodialysis were followed for 1140 days for death. Blood samples for analysis of relaxin, C-reactive protein, Troponin T, cholesterol, HDL, brain natriuretic peptide, and albumin were taken at study entry. Survival was compared by the Kaplan-Meier method and Cox regression analysis. One hundred seven patients died during the observation period; 66 died of cardiovascular diseases and 28 died of infectious diseases. Elevated serum relaxin concentrations (greater than median) predicted death in male but not in female patients with ESKD: All-cause death (men: relative risk, 2.63; 95% CI, njections of serum from pregnant rabbits induced relaxation of the interpubic ligament of guinea pigs. 1 The hormone responsible for this action was named relaxin. Corpus luteum, decidua, and placenta secrete this hormone during pregnancy. Relaxin has many important roles in pregnancy, including softening effects on connective tissue, reducing uterine contractility, and control of mammary gland growth and differentiation. 1 Recently, however, it was recognized that relaxin also plays a role in the cardiovascular system. Patients with chronic heart failure have increased myocardial relaxin gene expression and elevated plasma relaxin concentrations. 2 Relaxin stimulates cardiac ANP secretion 3 and increases coronary blood flow through a nitric oxide-mediated mechanism. 3 It was furthermore shown that relaxin is a vasodilator of small systemic resistance arteries. 4 Relaxin is also involved in the regulation of cardiac 5 and renal 6 collagen synthesis.We analyzed whether relaxin is a mortality risk factor in patients with end-stage kidney disease (ESKD). Patients with ESKD have a substantially reduced life expectancy. The mortality risk is about 50% higher in elderly patients with ESKD and even much more in younger patients with ESDK as compared with age-matched persons without renal disease. 7,8 MethodsThe 245 patients (122 women, 123 men) were recruited from two dialysis centers (KfH Dialysezentrum-Neukölln, Berlin, and KfH Dialysezentrum-Moabit, Berlin). The patients are dialyzed at least 3 times weekly in 4-to 6-hour sessions, sufficient to provide an urea kinetic on dialysis (KT/V) of at least 1.3. The included patients represent all patients being on stable hemodialysis in these centers without actual health problems. All patients were included in the study in March 2000 and followed for 1140 days. The following patients characteristics were documented: age, gender, body mass index, cause of ESKD, time on dialysis, diabetes, hypertension, and coronary heart disease (patients with a history of myocardial infarction, coronary heart disease confirmed by heart catheterization, or typical ...

Gender-Dependent Impact of Risk Factors for Cardiovascular and Non-Cardiovascular Mortality in End-Stage Renal Disease Patients on Haemodialysis

“…From the initial cohort of 245 prevalent patients [28][29][30] , 230 plasma probes were available for the current study. These 230 patients on maintenance haemodialysis were followed prospectively for 52 months.…”

“…The cohort was recruited in March 2000 from 2 dialysis centres in Berlin, Germany, as previously described [28,29] . The facilities are non-proprietary units of the Kuratorium für Heimdialyse (KfH, Neu-Isenburg, Germany), a unique non-profit facility.…”

Soluble CD154 Is a Unique Predictor of Nonfatal and Fatal Atherothrombotic Events in Patients Who Have End-Stage Renal Disease and Are on Hemodialysis

“…From the initial cohort of 245 prevalent patients (16,17), 232 plasma probes were available for the current study. These 232 patients who were on maintenance hemodialysis were followed prospectively for 52 mo.…”

“…The initial documentation (and the work by Hocher et al [16,17]) included age, gender, underlying renal disease, residual renal function and urinary output, presence of diabetes, hypertension (diagnostic criteria: need for any antihypertensive drug and/or elevated baseline BP), smoking, and presence of coronary heart disease (patients with a history of myocardial infarction, coronary heart disease confirmed by coronary angiograms, or typical stable angina confirmed by stress echocardiography or radionuclide studies). Blood samples were taken from all studied patients during March 2000, immediately before dialysis.…”

Current treatments for acute heart failure: focus on serelaxin

“…83 Interestingly, it has been reported that relaxin is released from the failing heart, producing circulating levels that can approach those reached during pregnancy, although the role played by cardiac-produced relaxin is unclear. [84][85][86][87][88][89][90] However, there are concerns about the lack of validation of the assay used for these studies, and therefore further study is needed to prove that relaxin is produced by the heart. 72 In addition to the heart, relaxin protects against ischemia-reperfusion injury in other organs including kidney, lung, liver, brain, and intestine.…”