Soluble Tumor Necrosis Factor Receptor 1 and 2 Predict Outcomes in Advanced Chronic Kidney Disease: A Prospective Cohort Study

Background

Soluble tumor necrosis factor receptors 1 (sTNFR1) and 2 (sTNFR2) have been associated to progression of renal failure, end stage renal disease and mortality in early stages of chronic kidney disease (CKD), mostly in the context of diabetic nephropathy. The predictive value of these markers in advanced stages of CKD irrespective of the specific causes of kidney disease has not yet been defined. In this study, the relationship between sTNFR1 and sTNFR2 and the risk for adverse cardiovascular events (CVE) and all-cause mortality was investigated in a population with CKD stage 4-5, not yet on dialysis, to minimize the confounding by renal function.

Patients and methods

In 131 patients, CKD stage 4-5, sTNFR1, sTNFR2 were analysed for their association to a composite endpoint of all-cause mortality or first non-fatal CVE by univariate and multivariate Cox proportional hazards models. In the multivariate models, age, gender, CRP, eGFR and significant comorbidities were included as covariates.

Results

During a median follow-up of 33 months, 40 events (30.5%) occurred of which 29 deaths (22.1%) and 11 (8.4%) first non-fatal CVE. In univariate analysis, the hazard ratios (HR) of sTNFR1 and sTNFR2 for negative outcome were 1.49 (95% confidence interval (CI): 1.28-1.75) and 1.13 (95% CI: 1.06-1.20) respectively. After adjustment for clinical covariables (age, CRP, diabetes and a history of cardiovascular disease) both sTNFRs remained independently associated to outcomes (HR: sTNFR1: 1.51, 95% CI: 1.30-1.77; sTNFR2: 1.13, 95% CI: 1.06-1.20). A subanalysis of the non-diabetic patients in the study population confirmed these findings, especially for sTNFR1.

Conclusion

sTNFR1 and sTNFR2 are independently associated to all-cause mortality or an increased risk for cardiovascular events in advanced CKD irrespective of the cause of kidney disease.     

Association of Angiopoietin-2 with Renal Outcome in Chronic Kidney Disease

Background

The pathophysiological mechanisms of renal function progression in chronic kidney disease (CKD) have still not been completely explored. In addition to well-known traditional risk factors, non-traditional risk factors, such as endothelial dysfunction, have gradually attracted physicians'' attention. Angiopoietin-2 (Ang-2) impairs endothelial function through preventing angiopoietin-1 from binding to Tie2 receptor. Whether Ang-2 is associated with renal function progression in CKD is unknown.

Methods

This study enrolled 621 patients with stages 3–5 CKD to assess the association of circulating Ang-2 with commencing dialysis, doubling creatinine and rapid decline in renal function (the slope of estimated glomerular filtration rate (eGFR) greater than 5 ml/min per 1.73 m²/y) over follow-up of more than 3 years.

Results

Of all patients, 224 patients (36.1%) progressed to commencing dialysis and 165 (26.6%) reached doubling creatinine. 85 subjects (13.9%) had rapid decline in renal function. Ang-2 quartile was divided at 1494.1, 1948.8, and 2593.1 pg/ml. The adjusted HR of composite outcomes, either commencing dialysis or doubling creatinine was 1.53 (95% CI: 1.06–2.23) for subjects of quartile 4 compared with those of quartile 1. The adjusted OR for rapid decline in renal function was 2.96 (95% CI: 1.13–7.76) for subjects of quartile 4 compared with those of quartile 1. The linear mixed-effects model shows a more rapid decrease in eGFR over time in patients with quartile 3 or more of Ang-2 than those with the lowest quartile of Ang-2.

Conclusions

Ang-2 is an independent predictor of adverse renal outcome in CKD. Further study is needed to identify the pathogenic role of Ang-2 in CKD progression.     

Metformin increases cancer specific survival in colorectal cancer patients—National cohort study

PurposeWe aimed to assess oncological outcomes in colorectal cancer patients with type 2 diabetes mellitus (T2DM) using metformin.MethodsPatients with colorectal cancer and T2DM during 2000–2012 period were identified form Lithuanian Cancer Registry and the National Health Insurance Fund database. Colorectal cancer-specific survival (CS) was the primary outcome. It was measured from date of colorectal cancer diagnosis to date of death due to colorectal cancer, or last known date alive.Results15,052 people who met eligibility criteria for this analysis, including 1094 (7.27%) with pre-existing type 2 diabetes (271 metformin never users and 823 metformin users) and 13 958 people without diabetes assessed. During follow-up (mean follow-up time was 4.4 years, with range from 1 day to 17 years) there were 10,927 deaths including 8559 from colorectal cancer. Significantly lower risk in CS between diabetic and non-diabetic people with lower risk of cancer-specific mortality (HR 0.87, 95% CI 0.80–0.94) in diabetic patient population was seen. After adjustment for age, stage at diagnosis and metformin usage, significant difference in colorectal CS between metformin users in diabetic patient population compared to non-diabetics and metformin non-users in diabetic patient population was found (0.80 (0.72–0.89) vs 1.00 and vs 1.05 (0.91–1.23)). Overall survival (OS) was better for diabetic patients with significant difference in diabetic metformin users (HR 0.91, 95% CI 0.79–0.94).ConclusionsColorectal cancer patients with T2DM treated with metformin as part of their diabetic therapy appear to have a superior OS and CS. However, prospective controlled studies are still needed to evaluate the efficacy of metformin as an anti-tumor agent.     

Estimated Glomerular Filtration Rate Decline Is a Better Risk Factor for Outcomes of Systemic Disease-Related Nephropathy than for Outcomes of Primary Renal Diseases

Background

Currently, the contribution of kidney function decline in renal and patient outcomes is unclear. There are few data on the associations of different etiologies of estimated glomerular filtration rate (eGFR) decline with outcomes in multidisciplinary care. The purpose of this investigation was to establish whether eGFR decline in patients with disease is an important risk factor for developing end-stage renal disease (ESRD) and death.

Methods

From December 1, 2001 to December 31, 2011, 5097 adults with chronic kidney disease (CKD) received biochemical tests, physical examinations, a pathological examination, and a comprehensive questionnaire. We used linear regression models and multivariate Cox proportional hazards model to examine the outcome of eGFR decline in renal diseases with different etiologies.

Results

Mean age was 68.1±16.1 (standard deviation, SD) years, and 63.3% patients were male. In the studied cohort, 58.2% of the patients had systemic disease-related nephropathy (SDRN), 29.4% had primary renal diseases (PRDs), and 12.4% had other etiologies. The eGFR decline in SDRN had a significant association with dialysis in the Cox proportional hazards model [crude hazard ratio (HR) = 1.07, 95% confidence interval (CI), 1.04 to 1.10; adjusted HR 1.05, 95% CI, 1.02 to 1.08]. Diabetic nephropathy (DN) had the most severe eGFR decline in CKD stages 3, 4, and 5, and all contributed to the initiation of dialysis and death regardless of whether DN with or without eGFR decline was considered to be the cause. Although hypertensive nephropathy (HN) was related to significant acceleration of eGFR decline, it did not lead to poor outcome. There were still discrepancies between eGFR decline and outcomes in PRDs, hypertensive nephropathy, and lupus nephritis.

Conclusions

eGFR decline and CKD staging provide an informative guide for physicians to make proper clinical judgments in the treatment of CKD, especially SDRN. Poor control of the underlying systemic disease will thus lead to more rapid progression of SDRN.     

Association of Dyslipidemia with Renal Outcomes in Chronic Kidney Disease

Dyslipidemia is highly prevalent in patients with chronic kidney disease (CKD) and the relationship between dyslipidemia with renal outcomes in patients with moderate to advanced CKD remains controversial. Hence, our objective is to determine whether dyslipidemia is independently associated with rapid renal progression and progression to renal replacement therapy (RRT) in CKD patients. The study analyzed the association between lipid profile, RRT, and rapid renal progression (estimated glomerular filtration rate [eGFR] slope <−6 ml/min/1.73 m²/yr) in 3303 patients with stages 3 to 5 CKD. During a median 2.8-year follow-up, 1080 (32.3%) participants commenced RRT and 841 (25.5%) had rapid renal progression. In the adjusted models, the lowest quintile (hazard ratios [HR], 1.23; 95% confidence interval [CI], 1.01 to 1.49) and the highest two quintiles of total cholesterol (HR, 1.25; 95% CI, 1.02 to 1.52 and HR, 1.35; 95% CI, 1.11 to 1.65 respectively) increased risks for RRT (vs. quintile 2). Besides, the highest quintile of total cholesterol was independently associated with rapid renal progression (odds ratio, 1.36; 95% CI, 1.01 to 1.83). Our study demonstrated that certain levels of dyslipidemia were independently associated with RRT and rapid renal progression in CKD stage 3–5. Assessment of lipid profile may help identify high risk groups with adverse renal outcomes.     

Epidemiology of CKD Regression in Patients under Nephrology Care

Chronic Kidney Disease (CKD) regression is considered as an infrequent renal outcome, limited to early stages, and associated with higher mortality. However, prevalence, prognosis and the clinical correlates of CKD regression remain undefined in the setting of nephrology care. This is a multicenter prospective study in 1418 patients with established CKD (eGFR: 60–15 ml/min/1.73m²) under nephrology care in 47 outpatient clinics in Italy from a least one year. We defined CKD regressors as a ΔGFR ≥0 ml/min/1.73 m²/year. ΔGFR was estimated as the absolute difference between eGFR measured at baseline and at follow up visit after 18–24 months, respectively. Outcomes were End Stage Renal Disease (ESRD) and overall-causes Mortality.391 patients (27.6%) were identified as regressors as they showed an eGFR increase between the baseline visit in the renal clinic and the follow up visit. In multivariate regression analyses the regressor status was not associated with CKD stage. Low proteinuria was the main factor associated with CKD regression, accounting per se for 48% of the likelihood of this outcome. Lower systolic blood pressure, higher BMI and absence of autosomal polycystic disease (PKD) were additional predictors of CKD regression. In regressors, ESRD risk was 72% lower (HR: 0.28; 95% CI 0.14–0.57; p<0.0001) while mortality risk did not differ from that in non-regressors (HR: 1.16; 95% CI 0.73–1.83; p = 0.540). Spline models showed that the reduction of ESRD risk associated with positive ΔGFR was attenuated in advanced CKD stage. CKD regression occurs in about one-fourth patients receiving renal care in nephrology units and correlates with low proteinuria, BP and the absence of PKD. This condition portends better renal prognosis, mostly in earlier CKD stages, with no excess risk for mortality.     

P Wave Dispersion and Maximum P Wave Duration Are Associated with Renal Outcomes in Chronic Kidney Disease

P wave parameters measured by 12-lead electrocardiogram (ECG) are commonly used as a noninvasive tool to evaluate left atrial enlargement. This study was designed to assess whether P wave parameters were associated with renal outcomes in chronic kidney disease (CKD) patients. This longitudinal study enrolled 439 patients with CKD stages 3–5. Renal end points were defined as the commencement of dialysis or death. Change in renal function was measured using the estimated glomerular filtration rate (eGFR) slope. We measured two ECG P wave parameters corrected for heart rate, i.e., corrected P wave dispersion and corrected maximum P wave duration. The values of P wave dispersion and maximum P wave duration were 88.8±21.7 ms and 153.3±21.7 ms, respectively. During the follow-up period (mean, 25.2 months), 95 patients (21.6%) started hemodialysis and 30 deaths (6.8%) were recorded. Multivariate Cox regression analysis identified that increased P wave dispersion [hazard ratio (HR), 1.020; 95% confidence interval (CI), 1.009–1.032; P<0.001] and maximum P wave duration (HR, 1.013; 95% CI, 1.003–1.024; P = 0.012) were associated with progression to renal end points. Furthermore, increased P wave dispersion (unstandardized coefficient β = –0.016; P = 0.037) and maximum P wave duration (unstandardized coefficient β = –0.014; P = 0.040) were negatively associated with the eGFR slope. We demonstrated that increased P wave dispersion and maximum P wave duration were associated with progression to the renal end points of dialysis or death and faster renal function decline in CKD patients. Screening CKD patients on the basis of P wave dispersion and maximum P wave duration may help identify patients at high risk for worse renal outcomes.     

Is Fluid Overload More Important than Diabetes in Renal Progression in Late Chronic Kidney Disease?

Fluid overload is one of the major presentations in patients with late stage chronic kidney disease (CKD). Diabetes is the leading cause of renal failure, and progression of diabetic nephropathy has been associated with changes in extracellular fluid volume. The aim of the study was to assess the association of fluid overload and diabetes in commencing dialysis and rapid renal function decline (the slope of estimated glomerular filtration rate (eGFR) less than -3 ml/min per 1.73 m²/y) in 472 patients with stages 4-5 CKD. Fluid status was determined by bioimpedance spectroscopy method, Body Composition Monitor. The study population was further classified into four groups according to the median of relative hydration status (△HS =fluid overload/extracellular water) and the presence or absence of diabetes. The median level of relative hydration status was 7%. Among all patients, 207(43.9 %) were diabetic. 71 (15.0%) subjects had commencing dialysis, and 187 (39.6%) subjects presented rapid renal function decline during a median 17.3-month follow-up. Patients with fluid overload had a significantly increased risk for commencing dialysis and renal function decline independent of the presence or absence of diabetes. No significantly increased risk for renal progression was found between diabetes and non-diabetes in late CKD without fluid overload. In conclusion, fluid overload has a higher predictive value of an elevated risk for renal progression than diabetes in late CKD.     

Type 1 and Type 2 Diabetes and Cancer Mortality in the 2002-2009 Cohort of 39 811 French Dialyzed Patients

End-stage renal disease is a chronic and progressive pathology associated with several comorbidities, particularly diabetes. Indeed, diabetes is the first cause of end-stage renal disease and, in France, 42% of incident patients had diabetes in 2012. In the general population, diabetes is associated with increased cancer risk. The aim of this study was to examine the association between risk of cancer death and diabetes in a large French cohort of patients with end-stage renal disease. Data on all patients with end-stage renal disease who initiated dialysis in France between 2002 and 2009 were extracted from the Renal Epidemiology Information Network registry. The risk of dying by cancer was studied using the Fine and Gray model to take into account the competing risk of death by other causes. We analyzed 39 811 patients with end-stage renal disease. Their mean age was 67.7±15 years, 39.4% had diabetes and 55.3% at least one cardiovascular disease. Compared with the non-diabetic group, patients with diabetes were older and had more cardiovascular and respiratory comorbidities when they started dialysis. Conversely, fewer diabetic patients had also a tumor at the beginning of the renal replacement therapy. Cancer was indicated as the cause of death for 6.7% of diabetic and 13.4% of non-diabetic patients. The Fine and Gray multivariate analyses indicated that diabetes (HR=0.72 95% CI: [0.68-0.95], p<0.001) and also female gender, peritoneal dialysis, cardio-vascular disease and kidney transplantation were associated with decreased risk of death by cancer. In this French cohort of patients with end-stage renal disease, diabetes was not associated with a significant increased risk of dying from cancer. Studies on the incidence of cancer in patients with ESRD are now needed to evaluate the potential association between diabetes and specific malignancies in this population.     

Impact of Renal Dysfunction on Mid-Term Outcome after Transcatheter Aortic Valve Implantation: A Systematic Review and Meta-Analysis

Background

There is conflicting evidence regarding the impact of preexisting renal dysfunction (RD) on mid-term outcomes after transcatheter aortic valve implantation (TAVI) in patients with symptomatic aortic stenosis (AS).

Methods and results

Forty-seven articles representing 32,131 patients with AS undergoing a TAVI procedure were included in this systematic review and meta-analysis. Pooled analyses were performed with both univariate and multivariate models, using a fixed or random effects method when appropriate. Compared with patients with normal renal function, mid-term mortality was significantly higher in patients with preexisting RD, as defined by the author (univariate hazard ratio [HR]: 1.69; 95% confidence interval [CI]: 1.50–1.90; multivariate HR: 1.47; 95% CI: 1.17–1.84), baseline estimated glomerular filtration rate (eGFR) (univariate HR: 1.65; 95% CI: 1.47–1.86; multivariate HR: 1.46; 95% CI: 1.24–1.71), and serum creatinine (univariate HR: 1.69; 95% CI: 1.48–1.92; multivariate HR: 1.65; 95% CI: 1.36–1.99). Advanced stage of chronic kidney disease (CKD stage 3–5) was strongly related to bleeding (univariate HR in CKD stage 3: 1.30, 95% CI: 1.13–1.49; in CKD stage 4: 1.30, 95% CI: 1.04–1.62), acute kidney injure (AKI) (univariate HR in CKD stage 3: 1.28, 95% CI: 1.03–1.59; in CKD stage 4: 2.27, 95% CI: 1.74–2.96), stroke (univariate HR in CKD stage 4: 3.37, 95% CI: 1.52–7.46), and mid-term mortality (univariate HR in CKD stage 3: 1.57, 95% CI: 1.26–1.95; in CKD stage 4: 2.77, 95% CI: 2.06–3.72; in CKD stage 5: 2.64, 95% CI: 1.91–3.65) compared with CKD stage 1+2. Patients with CKD stage 4 had a higher incidence of AKI (univariate HR: 1.70, 95% CI: 1.34–2.16) and all-cause death (univariate HR: 1.60, 95% CI: 1.28–1.99) compared with those with CKD stage 3. A per unit decrease in serum creatinine was also associated with a higher mortality at mid-term follow-up (univariate HR: 1.24, 95% CI: 1.18–1.30; multivariate HR: 1.19, 95% CI: 1.08–1.30).

Conclusions

Preexisting RD was associated with increased mid-term mortality after TAVI. Patients with CKD stage 4 had significantly higher incidences of peri-procedural complications and a poorer prognosis, a finding that should be factored into the clinical decision-making process regarding these patients.     

PPARgamma activation by thiazolidinediones (TZDs) may modulate breast carcinoma outcome: the importance of interplay with TGFbeta signalling

The thiazolidinediones (TZDs) are a class of synthetic antidiabetic drugs exerting its action primarily upon activation of the peroxisome proliferator-activated receptor-gamma (PPARgamma). Given the widespread incidence of diabetes type II and lifelong exposure of these patients to TZDs, there is a possibility that chronic treatment with TZD modifies clinical phenotypes of other common human diseases, for example breast carcinoma. There is evidence that TZDs act as breast carcinoma suppression agents, at least in the in vitro and animal models. Stimulation of the PPARgamma by TZDs interferes with oestrogen receptor signalling, STAT5B and NF-kappaB signalling cascades. On the other hand, TZDs repress TGFbeta signalling, a well-known suppressor of the initial stages of breast carcinoma development. Another layer of complexity arises at the later stages of tumour development, when TGFbeta acts as a tumour promoter: its overexpression is associated with poor prognosis, higher degree of tumour vascularization and metastasis. Longitudinal studies of breast carcinoma development in chronic TZD users are needed. In this review, we dissect possible interplays between chronic exposure of breast tis-sue to TZDs and TGFbeta signalling and predict influence of TZD exposure on cancer-related clinical outcome.     

Body Mass Index,Mortality, and Gender Difference in Advanced Chronic Kidney Disease

Background and Aim

A 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.

Methods

This 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.

Results

During 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.

Conclusions

In 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.     

Factors Associated with Unplanned Dialysis Starts in Patients followed by Nephrologists: A Retropective Cohort Study

The number of patients starting dialysis is increasing world wide. Unplanned dialysis starts (patients urgently starting dialysis in hospital) is associated with increased costs and high morbidity and mortality. Risk factors for starting dialysis urgently in hospital have not been well studied. The primary objective of this study was to identify risk factors for unplanned dialysis starts in patients followed in a multidisciplinary chronic kidney disease (CKD) clinic. We performed a retrospective cohort study of 649 advanced CKD patients followed in a multidisciplinary CKD clinic at a tertiary care hospital from January 01, 2010 to April 30, 2013. Patients were classified as unplanned start (in hospital) or elective start. Multivariable logistic regression was used to identify variables associated with unplanned dialysis initiation. 184 patients (28.4%) initiated dialysis, of which 76 patients (41.3%) initiated dialysis in an unplanned fashion and 108 (58.7%) starting electively. Unplanned start patients were more likely to have diabetes (68.4% versus 51.9%; p = 0.04), CAD (42.1% versus 24.1%; p = 0.02), congestive heart failure (36.8% versus 17.6%; p = 0.01), and were less likely to receive modality education (64.5% vs 89.8%; p < 0.01) or be assessed by a surgeon for access creation (40.8% vesrus78.7% p < 0.01). On multivariable analysis, higher body mass index (OR 1.07, 95% CI 1.02, 1.13), and a history of congestive heart failure (OR 2.41, 95% CI 1.09, 5.41) were independently associated with an unplanned start. Unplanned dialysis initiation is common among advanced CKD patients, even if they are followed in a multidisciplinary chronic kidney disease clinic. Timely education and access creation in patients at risk may lead to lower costs and less morbidity and mortality.     

Association of Individual Non-Steroidal Anti-Inflammatory Drugs and Chronic Kidney Disease: A Population-Based Case Control Study

Background

Non-steroidal anti-inflammatory agents (NSAIDs) are known to be associated with renal damage. No clear evidence exists regarding differential risk of chronic kidney disease (CKD), specifically, across various NSAIDs.

Aim

The aim of this population-based case-control study was to evaluate the association between use of individual NSAIDs and risk of CKD in a general population of Southern Italy.

Methods

A nested case-control study was carried out using the general practice Arianna database, identifying incident CKD patients as cases and matched controls from 2006 to 2011. The date of first CKD diagnosis was defined as the index date (ID). Conditional logistic regressions were performed to estimate the risk of CKD associated with NSAIDs by class and individual drugs as compared to non-use during different time windows (within one year, six or three months prior to ID), with the latter being defined as current users. Among current users, the effect of cumulative exposure to these drugs was evaluated.

Results

Overall, 1,989 CKD cases and 7,906 matched controls were identified. A statistically significant increase in the risk of CKD was found for current users of oxicams (adjusted OR: 1.68; 95% CI: 1.15-2.44) and concerning individual compounds, for ketorolac (adj. OR: 2.54; 95% CI: 1.45-4.44), meloxicam (adj. OR: 1.98; 95% CI: 1.01-3.87) and piroxicam (adj. OR: 1.95; 95% CI: 1.19-3.21).

Conclusions

The risk of CKD varies across individual NSAIDs. Increased risk has been found for ketorolac, which may precipitate subclinical CKD through acute renal damage, and long-term exposure to oxicams, especially meloxicam and piroxicam.     

Effects of Clopidogrel on Mortality,Cardiovascular and Bleeding Outcomes in Patients with Chronic Kidney Disease - Data from Taiwan Acute Coronary Syndrome Full Spectrum Registry

Background

The efficacy of clopidogrel is inconclusive in the chronic kidney disease (CKD) population with acute coronary syndrome (ACS). Furthermore, CKD patients are prone to bleeding with antiplatelet therapy. We investigated the efficacy and safety of clopidogrel in patients with ACS and CKD.

Methods

In a Taiwan national-wide registry, 2819 ACS patients were enrolled. CKD is defined as an estimated glomerular filtration rate of less than 60 ml/min per 1.73 m². The primary endpoints are the combined outcomes of death, non-fatal myocardial infarction and stroke at 12 months.

Results

Overall 949 (33.7%) patients had CKD and 2660 (94.36%) patients received clopidogrel treatment. CKD is associated with increased risk of the primary endpoint at 12 months (HR 2.39, 95% CI 1.82 to 3.15, p<0.01). Clopidogrel use is associated with reduced risk of the primary endpoint at 12 months (HR 0.42, 95% CI: 0.29–0.60, p<0.01). Cox regression analysis showed that clopidogrel reduced death and primary endpoints for CKD population (HR 0.35, 95% CI: 0.21–0.61 and HR 0.48, 95% CI: 0.30–0.77, respectively, both p<0.01). Patients with clopidogrel(−)/CKD(−), clopidogrel(+)/CKD(+) and clopidogrel(−)/CKD(+) have 2.4, 3.0 and 10.4 fold risk to have primary endpoints compared with those receiving clopidogrel treatment without CKD (all p<0.01). Clopidogrel treatment was not associated with increased in-hospital Thrombolysis In Myocardial Infarction (TIMI) bleeding in CKD population.

Conclusion

Clopidogrel could decrease mortality and improve cardiovascular outcomes without increasing risk of bleeding in ACS patients with CKD.     

Drug-eluting stents in patients with chronic kidney disease: a prospective registry study

Background

Chronic kidney disease (CKD) is strongly associated with adverse outcomes after percutaneous coronary intervention (PCI). There are limited data on the effectiveness of drug-eluting stents (DES) in patients with CKD.

Methodology/Principal Findings

Of 3,752 consecutive patients enrolled in the Guthrie PCI Registry between 2001 and 2006, 436 patients with CKD - defined as a creatinine clearance <60 mL/min - were included in this study. Patients who received DES were compared to those who received bare metal stents (BMS). Patients were followed for a mean duration of 3 years after the index PCI to determine the prognostic impact of stent type. Study end-points were all-cause death, myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis (ST) and the composite of major adverse cardiovascular events (MACE), defined as death, MI or TVR. Patients receiving DES in our study, by virtue of physician selection, had more stable coronary artery disease and had lower baseline risk of thrombotic or restenotic events. Kaplan-Meier estimates of proportions of patients reaching the end-points were significantly lower for DES vs. BMS for all-cause death (p = 0.0008), TVR (p = 0.029) and MACE (p = 0.0015), but not MI (p = 0.945) or ST (p = 0.88). Multivariable analysis with propensity adjustment demonstrated that DES implantation was an independent predictor of lower rates of all-cause death (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.25–0.92), TVR (HR 0.50, 95% CI 0.27–0.94) and MACE (HR 0.62, 95% CI 0.41–0.94).

Conclusions

In a contemporary PCI registry, selective use of DES in patients with CKD was safe and effective in the long term, with lower risk of all-cause death, TVR and MACE and similar risk of MI and ST as compared with BMS. The mortality benefit may be a result of selection bias and residual confounding, or represent a true finding; a hypothesis that warrants clarification by randomized clinical trials.     

Adverse Outcomes of Anticoagulant Use among Hospitalized Patients with Chronic Kidney Disease: A Comparison of the Rates of Major Bleeding Events between Unfractionated Heparin and Enoxaparin

Background

Anticoagulation therapy is usually required in patients with chronic kidney disease (CKD) for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of bleeding.

Objectives

To determine the incidence of adverse outcomes of anticoagulants in hospitalized patients with CKD, and to compare the rates of major bleeding events between the unfractionated heparin (UFH) and enoxaparin users.

Methods

One year prospective observational study was conducted in patients with CKD stages 3 to 5 (estimated GFR, 10–59 ml/min/1.73 m²) who were admitted to the renal unit of Dubai Hospital. Propensity scores for the use of anticoagulants, estimated for each of the 488 patients, were used to identify a cohort of 117 pairs of patients. Cox regression method was used to estimate association between anticoagulant use and adverse outcomes.

Results

Major bleeding occurred in 1 in 3 patients who received anticoagulation during hospitalization (hazard ratio [HR], 4.61 [95% confidence interval [CI], 2.05–10.35]). Compared with enoxaparin users, patients who received anticoagulation with unfractionated heparin had a lower mean [SD] serum level of platelet counts (139.95 [113]×10³/µL vs 205.56 [123] ×10³/µL; P<0.001), and had a higher risk of major bleeding (HR, 4.79 [95% CI, 1.85–12.36]). Furthermore, compared with those who did not receive anticoagulants, patients who did had a higher in-hospital mortality (HR, 2.54 [95% CI, 1.03–6.25]); longer length of hospitalization (HR, 1.04 [95% CI, 1.01–1.06]); and higher hospital readmission at 30 days (HR, 1.79 [95% CI, 1.10–2.91]).

Conclusions

Anticoagulation among hospitalized patients with CKD was significantly associated with an increased risk of bleeding and in-hospital mortality. Hence, intensive monitoring and preventive measures such as laboratory monitoring and/or dose adjustment are warranted.