Survival In Chronic Kidney Disease Research Articles

#840 Kidney cancer, treatment with nephrectomy and survival in chronic kidney disease (CKD)

Abstract Background and Aims People with chronic kidney disease (CKD) have increased incidence of kidney cancer and poorer survival post-diagnosis compared to people without CKD. Nephrectomy, either partial or radical is the primary treatment for many kidney cancers and can be curative even in cases with locally advanced disease or single metastasis. We hypothesised that nephrectomy may be less frequently undertaken in people with kidney cancer and pre-existing CKD and that this might contribute to poorer survival in this group. Method Using data from the prospective research cohort UK Biobank (n = 502,536) linked to cancer registry, participants with available biochemistry and a new diagnosis of kidney cancer during follow-up were identified. Occurrence of nephrectomy was extracted from linked hospital data and all-cause mortality data from death certification records. Estimated glomerular filtration rate (eGFRCr) was calculated by CKD-EPI 2009 formula with race coefficient, as this was the formula recommended for use in the UK at the time of recruitment to UK Biobank. Cox proportional hazards models tested associations between eGFRCr and i) undergoing nephrectomy and ii) all-cause mortality by 10 ml/min/1.73 m2 decline from a reference value of 90 ml/min/1.73 m2. We additionally conducted subgroup analyses for nephrectomy and all-cause mortality within eGFRCr categories >105, 90-105, 75-90 (reference), 60-75, 45-60, 30-45 and <30 ml/min/1.73 m2. Both models were adjusted for age, sex, diabetes mellitus, hypertension, stroke, ischaemic heart disease, body mass index and socioeconomic deprivation. The all-cause mortality model was additionally adjusted for undergoing nephrectomy. Results There were 2053 participants with a new diagnosis of kidney cancer and sufficient biochemical data for inclusion. Of these, 935 (46%) had eGFRCr 60-90 ml/min/1.73 m2 and 139 (7%) had eGFRCr <60 ml/min/1.73 m2. Median time from baseline to kidney cancer diagnosis was 5.8 (IQR 0.9, 8.8) years. Median follow-up time after a diagnosis of kidney cancer was 3.4 (IQR 0.9, 6.6) years. For each 10 ml/min/1.73 m2 decline in eGFRCr below 90 ml/min/1.73 m2, there was no significant difference in likelihood of receiving nephrectomy (HR 1.05, p = 0.08) and no significant difference in likelihood of all-cause mortality (HR 1.03, p = 0.23). People with moderate-advanced CKD had increased hazards of all-cause mortality compared to the reference group (eGFRCr 75-90 ml/min/1.73 m2) when models were run by eGFRCr category (eGFRCr 30-45—HR 1.9 95% CI 1.3-3.0; eGFRCr <30—HR 2.0 95% CI 1.0-4.0). Conclusion In UK Biobank participants with kidney cancer and mild CKD, there was no significant difference in likelihood of nephrectomy or in hazards of all-cause mortality associated with declining eGFRCr as a continuous variable. Moderate to advanced CKD (eGFR <45) was associated with increased all-cause mortality despite adjustment for nephrectomy, suggesting that this finding is not explained by reduced access to surgical treatment.

The role of exercise training on cardiovascular risk factors and heart disease in patients with chronic kidney disease G3-G5 and G5D: A Clinical Consensus Statement of the European Association of Preventive Cardiology (EAPC) of the ESC and the European Association of Rehabilitation in Chronic Kidney Disease (EURORECKD).

Cardiovascular (CV) morbidity and mortality is high in patients with chronic kidney disease (CKD). Most patients reveal a high prevalence of CV risk factors such as diabetes or arterial hypertension and many have manifest cardiovascular disease (CVD), such as coronary artery disease and chronic heart failure with an increased risk of clinical events including sudden cardiac death. Diabetes mellitus and hypertension contribute to the development of CKD and the prevalence of CKD is in the range of 20%-65% in diabetic and 30%-50% in hypertensive patients. Therefore, prevention and optimal treatment of CV risk factors and comorbidities are key strategies to reduce CV risk and improve survival in CKD. Beyond common CV risk factors, patients with CKD are often physically inactive and have low physical function leading to subsequent frailty with muscle fatigue and weakness, sarcopenia and increased risk of falling. Consequently, the economic health burden of CKD is high, requiring feasible strategies to counteract this vicious cycle. Regular physical activity and exercise training have been shown to be effective in improving risk factors, reducing CVD and reducing frailty and falls. Nonetheless, combining exercise training and a healthy lifestyle with pharmacological treatment is not frequently applied in clinical practice. For that reason, this Clinical Consensus Statement reviews the current literature and provides evidence-based data regarding the role of exercise training in reducing CV and overall burden in patients with CKD. The aim is to increase awareness among cardiologists, nephrologists, and health care professionals of the potential of exercise therapy in order to encourage implementation of exercise training in clinical practice, eventually reducing CV risk and disease, as well as reducing frailty in patients with CKD G3 to G5D.

Gut-immune axis and cardiovascular risk in chronic kidney disease.

Patients with chronic kidney disease (CKD) suffer from marked cardiovascular morbidity and mortality, so lowering the cardiovascular risk is paramount to improve quality of life and survival in CKD. Manifold mechanisms are hold accountable for the development of cardiovascular disease (CVD), and recently inflammation arose as novel risk factor significantly contributing to progression of CVD. While the gut microbiome was identified as key regulator of immunity and inflammation in several disease, CKD-related microbiome-immune interaction gains increasing importance. Here, we summarize the latest knowledge on microbiome dysbiosis in CKD, subsequent changes in bacterial and host metabolism and how this drives inflammation and CVD in CKD. Moreover, we outline potential therapeutic targets along the gut-immune-cardiovascular axis that could aid the combat of CVD development and high mortality in CKD.

Free triiodothyronine predicts the risk of developing diabetic kidney disease

BackgroundLow levels of Free Triiodothyronine (FT3) are associated with poor survival in chronic kidney disease, and the aim of this study was to further assess the relationship between changes in FT3 levels and renal damage in patients with type 2 diabetes based on glomerular and tubular markers.MethodsWe retrospectively studied 452 type 2 diabetic patients, measured glomerular damage markers (UACR, eGFR) and tubular damage markers (NAG/Cr,β2-MG), analyzed the relationship between FT3 and renal damage by logistic regression models, and plotted restrictive cubic splines.Results41.6% of subjects had diabetic kidney disease (DKD), and the prevalence of DKD decreased progressively with increasing FT3 levels in the third quartile. Spearman correlation analysis showed that FT3 was negatively associated with UACR, NAG/Cr and β2-MG, while eGFR was positively associated with FT3. Multifactorial analysis, after adjusting for relevant confounders, revealed that compared with the lowest quartile of FT3, the highest quartile reduced the risk of developing urinary albumin (OR = 0.499,95% CI:0.289–0.856), moderate to severe impairment of glomerular filtration rate (OR = 0.106,95% CI:0.032–0.354), renal tubular marker β2 -MG positive (OR = 0.516,95% CI:0.299 to 0.883) and the risk of DKD occurrence (OR = 0.450,95% CI:0.260 to 0.774). In the sample model, FT3 levels below 4.39 pmol/L were associated with an increased risk of glomerular tubule injury and DKD occurrence.ConclusionsFT3 is closely associated with glomerular tubular injury and is a protective factor. As FT3 levels (< 4.39 pmol/L) decrease, the risk of developing DKD becomes higher, and FT3 can be used as an independent predictor of developing DKD.

The Novel Bone Alkaline Phosphatase Isoform B1x Is Associated with Improved 5-Year Survival in Chronic Kidney Disease.

Circulating alkaline phosphatase (ALP) is an independent cardiovascular risk marker. Serum bone ALP (BALP) isoforms indicate bone turnover and comprise approximately 50% of total circulating ALP. In chronic kidney disease (CKD), mortality is highest in patients with increased ALP and BALP and low bone turnover. However, not all low bone turnover states are associated with increased mortality. Chronic inflammation and oxidative stress, features of protein energy wasting syndrome, induce cardiovascular BALP activity and fibro-calcification, while bone turnover is suppressed. Circulating BALP isoform B1x is associated with low ALP and low bone turnover and has been exclusively detected in CKD. We investigated the association of serum B1x with survival, abdominal aortic calcification (AAC) score, and aortic pulse wave velocity (PWV) in CKD. Serum ALP, BALP isoforms, parathyroid hormone (PTH), PWV, and AAC were measured repeatedly over 2 years in 68 prevalent dialysis patients. Mortality was assessed after 5 years. B1x was detected in 53 patients. A competing risk analysis revealed an association of B1x with improved 5-year survival; whereas, baseline PWV, but not AAC score, predicted mortality. However, PWV improved in 26 patients (53%), and B1x was associated with variation of PWV over time (p = 0.03). Patients with B1x had lower PTH and total ALP, suggesting an association with lower bone turnover. In conclusion, B1x is associated with time-varying PWV, lower circulating ALP, and improved survival in CKD, and thus may be an indicator of a reduced cardiovascular risk profile among patients with low bone turnover.

Rescuing kidney patients from early demise: role of anti-cytokine therapies

Biomarkers of the inflammatory state are elevated in individuals with chronic kidney disease (CKD) and are also robust predictors of cardiovascular disease (CVD) and mortality in this population. In addition to its predictive ability, inflammation has been implicated in the pathogenesis of atherosclerotic CVD, primarily through NLRP3 inflammasome and interleukin-1 (IL-1) and interleukin-6 (IL-6) signaling pathways.1 On the basis of these data, it has been suggested that ameliorating the inflammatory response through anti-cytokine therapies could improve CVD risk factors and potentially survival in CKD.

Obesity Paradox in Kidney Diseases

Obesity is one of the most important health problem in the world. Elevated mortality risk can be seen with obesity, diabetes, hypertension, glomerular hyperfiltration, chronic kidney disease, and cardiovascular diseases. However, it has been observed that obesity positively affects survival especially in people with chronic kidney disease, elderly people, chronic heart failure, chronic obstructive pulmonary disease, cancer, acquired immune deficiency syndrome and rheumatoid arthritis. This situation has been called the obesity paradox. Studies are showing that the obesity paradox is valid in dialysis patients. Examinations have shown that the obesity paradox is affected by many factors such as ethnic origin, fat-muscle mass, and body mass index (BMI). The hypothetical pathophysiology of the obesity paradox reveals how obesity improves survival in chronic kidney disease.

Muscle Mass Assessed by Computed Tomography at the Third Lumbar Vertebra Predicts Patient Survival in Chronic Kidney Disease

Muscle mass is a key element for the evaluation of nutritional disturbances in patients with chronic kidney disease (CKD). Low muscle mass is associated with increased morbidity and mortality. The assessment of muscle mass by computed tomography at the third lumbar vertebra region (CTMM-L3) is an accurate method not subject to errors from fluctuation in the hydration status. Therefore, we aimed at investigating whether CTMM-L3 was able to predict mortality in nondialyzed CKD 3-5 patients. This is a prospective observational cohort study. We evaluated 223 nondialyzed CKD patients (60.3±10.6years; 64% men; 50% diabetics; glomerular filtration rate 20.7±9.6mLmin1.73m2). Muscle mass was measured by CTMM-L3 using the Slice-O-Matic software and analyzed according to percentile adjusted by gender. Nutritional parameters, laboratory data, and comorbidities were evaluated, and mortality was followed up for 4years. During the study period, 63 patients died, and the main cause of death was cardiovascular disease. Patients who died were older, had lower hemoglobin and albumin, as well as lower muscle markers. CTMM-L3 below the 25th percentile was associated with higher mortality according to the Kaplan-Meier curve (P=.017) and in Cox regression analysis (crude hazard ratio, 1.87 [95% confidence interval, 1.11-3.16]), also when adjusting for potential confounders (hazard ratio 1.83 [95% confidence interval 1.02-3.30]). Low muscle mass measured by computed tomography at the third lumbar vertebra region is an independent predictor of increased mortality in nondialyzed CKD patients.

Gut microbiota and chronic kidney disease: evidences and mechanisms that mediate a new communication in the gastrointestinal-renal axis.

Chronic kidney disease (CKD) represents a growing public health problem associated with loss of kidney function and cardiovascular disease (CVD), the main leading cause of morbidity and mortality in CKD. It is well established that CKD is associated with gut dysbiosis. Over the past few years, there has been a growing interest in studying the composition of the gut microbiota in patients with CKD as well as the mechanisms by which gut dysbiosis contributes to CKD progression, in order to identify possible therapeutic targets to improve the morbidity and survival in CKD. The purpose of this review is to explore the clinical evidence and the mechanisms involved in the gut-kidney crosstalk as well as the possible interventions to restore a normal balance of the gut microbiota in CKD. It is well known that the influence of the gut microbiota on the gut-kidney axis acts in a reciprocal way: on the one hand, CKD significantly modifies the composition and functions of the gut microbiota. On the other hand, gut microbiota is able to manipulate the processes leading to CKD onset and progression through inflammatory, endocrine, and neurologic pathways. Understanding the complex interaction between these two organs (gut microbiota and kidney) may provide novel nephroprotective interventions to prevent the progression of CKD by targeting the gut microbiota. The review is divided into three main sections: evidences from clinical studies about the existence of a gut microbiota dysbiosis in CKD; the complex mechanisms that explain the bidirectional relationship between CKD and gut dysbiosis; and reports regarding the effects of prebiotic, probiotic, and synbiotic supplementation to restore gut microbiota balance in CKD.

Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: the UBI Study

BackgroundMetabolic acidosis is associated with accelerated progression of chronic kidney disease (CKD). Whether treatment of metabolic acidosis with sodium bicarbonate improves kidney and patient survival in CKD is unclear.MethodsWe conducted a randomized (ratio 1:1). open-label, controlled trial (NCT number: NCT01640119. www.clinicaltrials.gov) to determine the effect in patients with CKD stage 3–5 of treatment of metabolic acidosis with sodium bicarbonate (SB) on creatinine doubling (primary endpoint), all-cause mortality and time to renal replacement therapy compared to standard care (SC) over 36-months. Parametric, non-parametric tests and survival analyses were used to assess the effect of SB on these outcomes.ResultsA total of 376 and 364 individuals with mean (SD) age 67.8 (14.9) years, creatinine clearance 30 (12) ml/min, and serum bicarbonate 21.5 (2.4) mmol/l were enrolled in SB and SC, respectively. Mean (SD) follow-up was 29.6 (9.8) vs 30.3 (10.7) months in SC and SB. respectively. The mean (SD) daily doses of SB was 1.13 (0.10). 1.12 (0.11). and 1.09 (0.12) mmol/kg*bw/day in the first, second and third year of follow-up, respectively. A total of 87 participants reached the primary endpoint [62 (17.0%) in SC vs 25 (6.6%) in SB, p < 0.001). Similarly, 71 participants [45 (12.3%) in SC and 26 (6.9%) in SB, p = 0.016] started dialysis while 37 participants [25 (6.8%) in SC and 12 (3.1%) in SB, p = 0.004] died. There were no significant effect of SB on blood pressure, total body weight or hospitalizations.ConclusionIn persons with CKD 3–5 without advanced stages of chronic heart failure, treatment of metabolic acidosis with sodium bicarbonate is safe and improves kidney and patient survival.

Association of self-reported physical function with survival in patients with chronic kidney disease.

BackgroundReduced physical function is associated with an increased risk of mortality among patients with chronic kidney disease (CKD) not requiring renal replacement therapy (RRT). Assessments of physical performance can help to identify those at risk for adverse events. However, objective measures are not always feasible and self-reported measures may provide a suitable surrogate.MethodsWe performed a cohort study examining associations between self-reported physical function and walking behaviour with survival in patients with CKD not requiring RRT. Data were analysed from the QCKD study (Physical activity opinions in kidney disease) (ISRCTN 87066351), a prospective observational mixed methods study of physical activity in patients with CKD. A total of 450 patients with CKD not requiring RRT, ages 17–93 years, were followed up for a median of 43 months. Upon enrolment, participants completed two questionnaires: Duke Activity Status Index (DASI) (physical function) and General Practice Physical Activity Questionnaire (GPPAQ) (habitual activity). Mortality data were collected from electronic records in September 2016; RRT was considered a competing event.ResultsA total of 74 deaths occurred during follow-up and 101 participants were started on RRT. The adjusted subdistribution hazard ratio (SHR) of mortality in participants scoring >19.2 on the DASI was 0.51 [95% confidence interval (CI) 0.30–0.88] while a one-unit increase in the DASI was associated with an SHR of 0.97 (95% CI 0.95–0.99). The adjusted SHRs of mortality were 0.48 (95% CI 0.26–0.90), 0.25 (0.11–0.57) and 0.48 (0.23–0.80) for participants walking <1, 1–3 and ≥3 h/week, respectively, compared with no walking. A walking pace >3 mph was associated with a reduced risk of mortality [SHR 0.37 (95% CI 0.20–0.71)] compared with a walking pace <3 mph.ConclusionsPhysical function and walking behaviours were independently associated with survival in CKD and may help to identify patients at risk for adverse events.

The Role of Gut Microbiota and Diet on Uremic Retention Solutes Production in the Context of Chronic Kidney Disease.

Uremic retention solutes (URS) are associated with cardiovascular complications and poor survival in chronic kidney disease. The better understanding of the origin of a certain number of these toxins enabled the development of new strategies to reduce their production. URS can be classified according to their origins (i.e., host, microbial, or exogenous). The discovery of the fundamental role that the intestinal microbiota plays in the production of many URS has reinstated nutrition at the heart of therapeutics to prevent the accumulation of URS and their deleterious effects. The intestinal microbiota is personalized and is strongly influenced by dietary habits, such as the quantity and the quality of dietary protein and fibers. Herein, this review out lines the role of intestinal microbiota on URS production and the recent discoveries on the effect of diet composition on the microbial balance in the host with a focus on the effect on URS production.

The association of profilin-1 levels with survival in chronic kidney disease.

Profilin-1 is a ubiquitous, actin-binding protein that plays an important role in the regulation of actin polymerization and cytoskeleton remodelling and contributes to vascular dysfunction. We conducted this study to investigate the association of serum profilin-1 levels with fatal and nonfatal CVE in a cohort of patients with stage 1-5 CKD. Serum concentrations of profilin-1 levels were determined by enzyme-linked immunosorbent assay. Endothelium-dependent vasodilatation (flow-mediated dilatation [FMD]) and endothelium-independent vasodilatation (nitroglycerine-mediated dilatation [NMD]) of the brachial artery were assessed noninvasively, using high-resolution ultrasound. Both fatal and nonfatal CVE were significantly higher in patients with high profilin-1 levels. Kaplan-Meier survival curves showed that patients with profilin-1 below the median value (114pg/mL) had higher cumulative survival compared with patients who had profilin-1 levels above the median value (log-rank test, P<.001). This is the first study that demonstrates the serum profilin-1 is independently associated with endothelial dysfunction, cardiovascular events and survival in patients with CKD.

Communicating projected survival with treatments for chronic kidney disease: patient comprehension and perspectives on visual aids

BackgroundMortality in end stage renal disease (ESRD) is higher than many malignancies. There is no data about the optimal way to present information about projected survival to patients with ESRD. In other areas, graphs have been shown to be more easily understood than narrative. We examined patient comprehension and perspectives on graphs in communicating projected survival in chronic kidney disease (CKD).MethodsOne hundred seventy-seven patients with CKD were shown 4 different graphs presenting post transplantation survival data. Patients were asked to interpret a Kaplan Meier curve, pie chart, histogram and pictograph and answer a multi-choice question to determine understanding.ResultsWe measured interpretation, usefulness and preference for the graphs. Most patients correctly interpreted the graphs. There was asignificant difference in the percentage of correct answers when comparing different graph types (p = 0.0439). The pictograph was correctly interpreted by 81% of participants, the histogram by 79%, pie chart by 77% and Kaplan Meier by 69%. Correct interpretation of the histogram was associated with educational level (p = 0.008) and inversely associated with age > 65 (p = 0.008). Of those who interpreted all four graphs correctly, there was an association with employment (p = 0.001) and New Zealand European ethnicity (p = 0.002).87% of patients found the graphs useful. The pie chart was the most preferred graph (p 0.002).The readability of the graphs may have been improved with an alternative colour choice, especially in the setting of visual impairment.ConclusionVisual aids, can be beneficial adjuncts to discussing survival in CKD.

APOL1 genotype, blood pressure, and survival in African Americans with nondiabetic nephropathy

Several landmark trials have assessed the effects of aggressive hypertension control on the progression of nondiabetic chronic kidney disease. Results generally have been disappointing. With the realization that lowering blood pressure, including with renin-angiotensin system blockade, failed to reliably prevent end-stage kidney disease, studies now are analyzing longer-term effects of hypertension control on survival in chronic kidney disease. This commentary reviews the current findings and extends the discussion to apolipoprotein L1 gene by blood pressure (or gene by environment) interactions.

MP41-01 COMPARISON OF OVERALL SURVIVAL RATE BETWEEN PARTIAL AND RADICAL NEPHRECTOMY FOR RENAL CELL CARCINOMA IN PATIENTS WITH PRE-EXISTING CHRONIC KIDNEY DISEASE: A MULTICENTER STUDY

You have accessJournal of UrologyKidney Cancer: Localized: Surgical Therapy I1 Apr 2016MP41-01 COMPARISON OF OVERALL SURVIVAL RATE BETWEEN PARTIAL AND RADICAL NEPHRECTOMY FOR RENAL CELL CARCINOMA IN PATIENTS WITH PRE-EXISTING CHRONIC KIDNEY DISEASE: A MULTICENTER STUDY Jae Seung Chung, Seok-Soo Byun, Sang Eun Lee, Sung Kyu Hong, Sang Chul Lee, Cheol Kwak, Sung Hoo Hong, Yong June Kim, and Seok Ho Kang Jae Seung ChungJae Seung Chung More articles by this author , Seok-Soo ByunSeok-Soo Byun More articles by this author , Sang Eun LeeSang Eun Lee More articles by this author , Sung Kyu HongSung Kyu Hong More articles by this author , Sang Chul LeeSang Chul Lee More articles by this author , Cheol KwakCheol Kwak More articles by this author , Sung Hoo HongSung Hoo Hong More articles by this author , Yong June KimYong June Kim More articles by this author , and Seok Ho KangSeok Ho Kang More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.168AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We examine the impact of PN relative to RN on overall survival and renal function in patients with chronic kidney disease (CKD) stage III. METHODS We studied 4178 patients who underwent PN or RN for pathological T1a-T2NOMO RCC from 1988 to 2014. To investigate the relative effectiveness of PN in terms of OS according to CKD stage, we divided the RCC patients into two subgroups: CKD I-II (eGFR≥60 ml/min/1.73m2) and CKD III (30≤eGFR<60 ml/min/1.73m2). To achieve equal distributions of patients between PN and RN, we pair-matched the patients using propensity scores in terms of age, gender, diabetes, hypertension, charlson index, BMI, tumor size, preoperative kidney function. Overall survival, cancer specific survival (CSS) were estimated using the Kaplan-Meier and Cox hazard method. Renal function was evaluated by using the estimated glomerular filtration rate (eGFR). RESULTS Of 3534 patients with CKD I-II groups, 878 RN patients were matched with 878 PN patients. In CKD III group, which was comprised of 628 patients, 138 RN patients were matched with 138 PN patients. The median follow-up durations in the RN and PN arms were 52.3 and 43.2 months in CKD I-II group, 56.2 and 50.3 months in CKD III group, respectively. The 5-year OS rates after PN and RN differed in CKD I-II groups (99.4% for PN and 96.5% for RN, p=0.001). 5-year CSS rate were 99.7% for PN and 99.5% for RN (p=0.551). However, the 5-year OS rate after surgery were not different between RN and PN in CKD III-IV groups ( 97.8% vs 93.5%, p=0.069). The difference in kidney cancer specific survival (PN vs RN) was not statistically significant (p=0.524). The Cox hazard analysis showed that the operative method was a significant factor for overall survival in CKD I-II (HR 0.275, CI 0.121-0.623, p=0.002). However, PN was not beneficial in terms of OS in CKD III (HR 0.317, CI 0.086-1.172, p=0.085). PN had better postoperative renal function preservation compared to RN regardless of CKD stages. CONCLUSIONS Our study showed that PN is associated with a higher overall survival rate for patients with preoperative CKD I and II. However, benefits for PN were not observed in CKD III patients. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e559-e560 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Jae Seung Chung More articles by this author Seok-Soo Byun More articles by this author Sang Eun Lee More articles by this author Sung Kyu Hong More articles by this author Sang Chul Lee More articles by this author Cheol Kwak More articles by this author Sung Hoo Hong More articles by this author Yong June Kim More articles by this author Seok Ho Kang More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Body mass index, mortality, and gender difference in advanced chronic kidney disease.

Background and AimA higher body mass index (BMI) appears to be reversely associated with mortality in dialysis patients. Moreover, although women have better survival in chronic kidney disease (CKD), this survival advantage is cancelled in dialysis. The association between BMI and mortality and the gender difference remain controversial in advanced CKD.MethodsThis study enrolled 3,320 patients (1,938 men and 1,382 women) from southern Taiwan who had CKD stages 3–5 with a BMI of 15.0–35.0 kg/m2.ResultsDuring a median 2.9-year follow-up, there were 328 (16.9%) all-cause mortality and 319 (16.5%) cardiovascular (CV) events and death in male patients, 213 (15.4%) all-cause mortality and 224 (16.2%) CV events and death in female patients. Compared with the reference BMI of 27.6–30.0 kg/m2 in an adjusted Cox model, lower-BMI groups in men, BMI 15.0–20.0 kg/m2 and 20.1–22.5 kg/m2, were associated with higher risks of all-cause mortality: hazard ratios (HRs) 3.19 (95% confidence interval [CI], 1.97–5.18) and 2.01 (95% CI, 1.29–3.14), respectively. Higher-BMI group in men, BMI 30.1–35.0 kg/m2, was associated with a higher risk of all-cause mortality: HR 1.72 (95% CI, 1.02–2.96). Likewise, lower- and higher-BMI groups in men were associated with a higher risk of CV events and death. In women, these associations between BMI and poor outcomes were not observed.ConclusionsIn advanced CKD, there was a reverse J-shaped association between BMI and all-cause mortality, and a U-shaped association between BMI and CV outcomes in men. Neutral associations between BMI and poor outcomes were detected in women. Gender could modify the effect of BMI on mortality in patients with CKD.

Ankle-brachial blood pressure index predicts cardiovascular events and mortality in Japanese patients with chronic kidney disease not on dialysis.

The ankle-brachial blood pressure index (ABPI) has been recognized to have a predictive value for cardiovascular (CV) events and mortality in general or dialysis populations. However, the associations between ABPI and those outcomes have not been fully investigated in predialysis patients. The present study aimed to clarify the relationships between ABPI and both CV events and mortality in Japanese chronic kidney disease (CKD) patients not on dialysis. In this prospective observational study, we enrolled 320 patients with CKD stages 3-5 who were not on dialysis. At baseline, ABPI was examined and a low ABPI was defined as <0.9. CV events and all-cause deaths were examined in each patient. A Cox proportional hazards model was applied to determine the risk factors for CV events, as well as for mortality from CV and all causes. The median follow-up period was 30 months. CV events occurred in 56 patients and all-cause deaths occurred in 48, including 20 CV deaths. Multivariate analysis showed that age and low ABPI were risk factors for CV events. It was demonstrated that age, a history of cerebrovascular disease and low ABPI were determined as independent risk factors for CV mortality. In addition, age, body mass index and low ABPI were independently associated with all-cause mortality. In patients with CKD, low ABPI during the predialysis period is independently associated with poor survival and CV events, suggesting the usefulness of measuring ABPI for predicting CV events and patient survival in CKD.

Plasma endocan levels associate with inflammation, vascular abnormalities, cardiovascular events, and survival in chronic kidney disease.

Plasma endocan levels are elevated in a large number of diseases, and may reflect endothelial cell dysfunction. There are currently no data on endocan in patients with chronic kidney disease (CKD). Therefore, we measured plasma endocan in 251 patients with CKD (stage 1-5) and 60 control individuals. Plasma endocan concentrations correlated with estimated glomerular filtration rate (eGFR), different markers of inflammation (pentraxin 3 and high-sensitivity C-reactive protein), and vascular abnormalities (flow-mediated vasodilation (FMV) and carotid intima media thickness (CIMT)). All-cause mortality and cardiovascular events (CVE) were also analyzed with respect to plasma endocan. Patients with CKD showed significantly increased plasma endocan (4.7 [IQR 1.9-9.4] compared with controls [IQR 1.1-1.5] ng/ml), with values progressively higher across stages of CKD. On univariate analysis, plasma endocan concentrations correlated negatively with eGFR and FMV, but positively with both markers of inflammation and CIMT. However, on multivariate analysis only high-sensitivity C-reactive protein, FMV, and CIMT remained significantly associated with plasma endocan. On Cox survival analysis, endocan levels were associated with all-cause mortality and CVE in these patients. Thus, plasma endocan increases in the presence of decreasing eGFR and influences all-cause mortality and CVE in patients with CKD independent of traditional and nontraditional risk factors.

Effect of paricalcitol on renin and albuminuria in non-diabetic stage III-IV chronic kidney disease: a randomized placebo-controlled trial

BackgroundVitamin D receptor activators reduce albuminuria, and may improve survival in chronic kidney disease (CKD). Animal studies suggest that these pleiotropic effects of vitamin D may be mediated by suppression of renin. However, randomized trials in humans have yet to establish this relationship.MethodsIn a randomized, placebo-controlled, double-blinded crossover study, the effect of oral paricalcitol (2 μg/day) was investigated in 26 patients with non-diabetic, albuminuric stage III-IV CKD. After treatment, plasma concentrations of renin (PRC), angiotensin II (AngII) and aldosterone (Aldo) were measured. GFR was determined by 51Cr-EDTA clearance. Assessment of renal NO dependency was performed by infusion of NG-monomethyl-L-arginine (L-NMMA). Albumin excretion rate (AER) was analyzed in 24-h urine and during 51Cr-EDTA clearance.ResultsParicalcitol did not alter plasma levels of renin, AngII, Aldo, or urinary excretion of sodium and potassium. A modest reduction of borderline significance was observed in AER, and paricalcitol abrogated the albuminuric response to L-NMMA.ConclusionsIn this randomized, placebo-controlled trial paricalcitol only marginally decreased AER and did not alter circulating levels of renin, AngII or Aldo. The abrogation of the rise in albumin excretion by paricalcitol during NOS blockade may indicate that favourable modulation of renal NO dependency could be involved in mediating reno-protection and survival benefits in CKD.Trial registrationClinicalTrials.gov identifier: NCT01136564