Hyperuricemia And Diabetes Mellitus When Occurred Together Have Higher Risks Than Alone On All-cause Mortality And End-stage Renal Disease in Patients With Chronic Kidney Disease Ⅲ

Abstract

ORGANIC TRADITIONAL HERB FOR KIDNEY HEALTH

Introduction

Chronic kidney disease (CKD) is a public health burden worldwide due to its rapidly expanding patient populations, high risk of progression into end-stage kidney disease (ESKD), and poor prognosis of morbidity and mortality [1, 2]. The leading mortality of these patients is cardiovascular (CV) related deaths. With CKD progression, the CV outcomes become worse, including CV death, re-infarction, congestive heart failure, stroke, and resuscitation [3]. The most common cause of CKD is diabetes mellitus (DM) [4]. The 2002 National Cholesterol Education Program report designated DM a coronary heart disease risk equivalent, and DM is placed in the highest risk category [5]. Furthermore, DM and CKD are both potent independent risk factors for CV events and progression to ESKD [6, 7]. DM has a huge burden of atherosclerosis-related intimal thickeninging and CKD also causes medial calcification [8]. Therefore, patients with both conditions at the same time are therefore at exceedingly high risk of adverse events and would end with poor patient outcomes.

The serum level of uric acid (UA) is also a risk factor for kidney disease [9], cardiovascular disease (CVD) [10–12], and atherosclerosis [13]. Serum UA is an independent risk factor for CKD, even in those without diabetes [14, 15]. Two large epidemiologic studies showed that UA is a major predictor of the incidence of renal disease [15, 16]. Moreover, hyperuricemia is often prevalent in CKD patients and is associated with a higher incidence of ESKD [16]. Several studies showed that UA independently predicts the development of type 2 DM [17–19] and the progression of CKD [20]. For about 20 years, UA has been known to be a potential risk factor for CKD and CVD with pathological implications [21, 22, 23]. Given the complex interplay among hyperuricemia, DM, and the progression of CKD, we are interested in exploring the complicated interactions regarding renal and patient outcomes. Here, we aimed to investigate the effects of DM and hyperuricemia on patient mortality and the development of ESKD in a large cohort of CKD patients.

Methods 

Study cohort and definition

In this retrospective cohort study, we enrolled 4380 patients with CKD from the outpatient clinic of the nephrology department, Taichung Veterans General Hospital (TVGH), Taiwan. Our hospital, a medical center with 1500 beds, is the referral hospital for the critically ill and difficult cases in central Taiwan. During the past 30 years, the CKD care program treated >10,000 outpatients with CKD. CKD was defined as an estimated Glomacular filtration rate (eGFR) <60ml/min/1.73m2 for > 3 months irrespective of the cause. The eGFR equaltion was from Modification of Diet in Renal Disease (ml/min/1.732m2 ) [24]. DM was confrmed according to the diagnosis of medical records. Hyperuricemia was defined as UA levels >7.0mg/dl for men, or>6.0mg/dl for women [21, 25]. These laboratory data were measured in our institute (TVGH).

Data collections

We enrolled patients (> 20 years old) with CKD 3–5 from 2007 to 2013 in this study. After follow-up (2.5 years of mean duration) (end data of this study: 31-December-2015), the outcomes were analyzed by mortality and participants received regular dialysis for at least 3 months or renal transplantation (ESKD). Their baseline variables were collected from medical records, including age, gender, stages of CKD, systolic blood pressure (SBP) (baseline and 1 year mean value), and diastolic blood pressure (DBP) (baseline and 1 year mean value), history of coronary artery disease, history of ever smoker, UA (baseline and 1 year mean value), baseline total cholesterol, usage of statin and usage of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB). The stage of CKD was based on the baseline renal function (the frst laboratory data during the recruitment period). We chose the Modification of Diet in Renal Disease (MDRD) formula, instead of the Cockcroft and Gault formula, due to its superior accuracy in diabetic patients with impaired renal functions [26]. Although CKD-EPI (Epidemiology Collaboration) is more accurate than the MDRD equation for subjects with eGFR >60ml/min/1.73 m2, the MDRD formula is the one applied in the Taiwan National Database to evaluate dialysis initiation and CKD prevalence [27–29].

Ethical approval and consent to participate

Statistical analysis

Data were presented as the mean standard deviation for continuous variables and proportions for category cal variables. An independent two-tailed t-test was used

hazards model, adjusted for important covariates known to be associated with the predictors and outcomes of interests (adjusted for age, sex, ever smoke, CKD stage, 1year mean SBP, use of statin, hyperuricemia drug usage, and ACEi/ARB usage.). In addition, since mortality was a competing event with dialysis, an extended Cox proportional hazards model was used to calculate the sub-distribution hazard ratio (SHR) of dialysis as a sensitivity test [30]. We also analyzed the effect of DM and hyperuricemia on all-cause mortality and ESKD according to different stages of CKD. Statistical significance was set at p< 0.05. Statistical analyses were all carried out by using SPSS 22.0 (SPCC, Chicago, Illinois). The extended Cox proportional hazards model was analyzed by SAS software (version 9.4; SAS Institute, Inc., Cary, NC, USA).