Serious Treatment Related Adverse Drug Reactions amongst Anti-Retroviral Na?ve MDR-TB Patients

Background

Globally treatment outcomes for multidrug-resistant Mycobacterium tuberculosis (MDR-TB) remain poor and this is compounded by high drug toxicity. Little is known about the influence of adverse drug reactions (ADRs) on treatment outcomes in South Africa.

Methods

We evaluated the impact of severe ADRs among a prospective cohort of MDR-TB patients in South Africa (2000–2004). The HIV-infected study participants were anti-retroviral naïve.

Results

Of 2,079 patients enrolled, 1,390 (66.8%) were included in this analysis based on known HIV test results (39.1% HIV-infected). At least one severe ADR was reported in 83 (6.9%) patients with ototoxicity being the most frequent ADR experienced (38.9%).

Conclusions

We found that being HIV-infected but antiretroviral naïve did not increase occurrence of SADRs in patients on second-line anti-tuberculosis drugs. Early screening and proactive management of ADRs in this patient population is essential, especially given the rollout of decentralized care and the potential for overlapping toxicity of concomitant MDR-TB and HIV treatment.     

Relation between Mild to Moderate Chronic Kidney Disease and Coronary Artery Disease Determined with Coronary CT Angiography

Background

Both end-stage and milder stages of chronic kidney disease (CKD) are associated with an increased risk of adverse cardiovascular events. Several studies found an association between decreasing renal function and increasing coronary artery calcification, but it remains unclear if this association is independent from traditional cardiovascular risk factors. Therefore, the aim of this study was to investigate whether mild to moderate CKD is independently associated with coronary plaque burden beyond traditional cardiovascular risk factors.

Methods

A total of 2,038 patients with symptoms of chest discomfort suspected for coronary artery disease underwent coronary CT-angiography. We assessed traditional risk factors, coronary calcium score and coronary plaque characteristics (morphology and degree of luminal stenosis). Patients were subdivided in three groups, based on their estimated glomerular filtration rate (eGFR) Normal renal function (eGFR ≥90 mL/min/1.73 m²); mild CKD (eGFR 60–89 mL/min/1.73 m²); and moderate CKD (eGFR 30–59 mL/min/1.73 m²).

Results

Coronary calcium score increased significantly with decreasing renal function (P<0.001). Coronary plaque prevalence was higher in patients with mild CKD (OR 1.83, 95%CI 1.52–2.21) and moderate CKD (OR 2.46, 95%CI 1.69–3.59), compared to patients with normal renal function (both P<0.001). Coronary plaques with >70% luminal stenosis were found significantly more often in patients with mild CKD (OR 1.67 (95%CI 1.16–2.40) and moderate CKD (OR2.36, 95%CI 1.35–4.13), compared to patients with normal renal function (both P<0.01). After adjustment for traditional cardiovascular risk factors, the association between renal function and the presence of any coronary plaque as well as the association between renal function and the presence of coronary plaques with >70% luminal stenosis becomes weaker and were no longer statistically significant.

Conclusion

Although decreasing renal function is associated with increasing extent and severity of coronary artery disease, mild to moderately CKD is not independently associated with coronary plaque burden after adjustment for traditional cardiovascular risk factors.     

Respiratory paradoxical adverse drug reactions associated with acetylcysteine and carbocysteine systemic use in paediatric patients: a national survey

Objective

To report pediatric cases of paradoxical respiratory adverse drug reactions (ADRs) after exposure to oral mucolytic drugs (carbocysteine, acetylcysteine) that led to the withdrawal of licenses for these drugs for infants in France and then Italy.

Design

The study followed the recommendations of the European guidelines of pharmacovigilance for medicines used in the paediatric population.

Setting

Cases voluntarily reported by physicians from 1989 to 2008 were identified in the national French pharmacovigilance public database and in drug company databases.

Patients

The definition of paradoxical respiratory ADRs was based on the literature. Exposure to mucolytic drugs was arbitrarily defined as having received mucolytic drugs for at least 2 days (>200 mg) and at least until the day before the first signs of the suspected ADR.

Results

The non-exclusive paradoxical respiratory ADRs reported in 59 paediatric patients (median age 5 months, range 3 weeks to 34 months, 98% younger than 2 years old) were increased bronchorrhea or mucus vomiting (n = 27), worsening of respiratory distress during respiratory tract infection (n = 35), dyspnoea (n = 18), cough aggravation or prolongation (n = 11), and bronchospasm (n = 1). Fifty-one (86%) children required hospitalization or extended hospitalization because of the ADR; one patient died of pulmonary oedema after mucus vomiting.

Conclusion

Parents, physicians, pharmacists, and drug regulatory agencies should know that the benefit risk ratio of mucolytic drugs is at least null and most probably negative in infants according to available evidence.     

Adverse Reactions Due to Directly Observed Treatment Strategy Therapy in Chinese Tuberculosis Patients: A Prospective Study

Background

More than 1 million tuberculosis (TB) patients are receiving directly observed treatment strategy (DOTS) therapy in China every year. As to the profile of adverse drug reactions (ADRs) due to DOTS therapy, no consensus has been reached. There is no report regarding ADRs due to DOTS therapy with a large Chinese TB population. This study aimed to determine the incidence and prognosis of ADRs due to DOTS therapy, and to evaluate their impact on anti-TB treatment in China.

Methods

A prospective population-based cohort study was performed during 2007–2008. Sputum smear positive pulmonary TB patients who received DOTS therapy were included and followed up for six to nine months in 52 counties of four regions in China. The suspected ADRs were recorded and reviewed by Chinese State Food and Drug Administration.

Results

A total of 4304 TB patients were included in this study. 649 patients (15.08%) showed at least one ADR and 766 cases in total were detected. The incidence (count) of ADR based on affected organ was: liver dysfunction 6.34% (273), gastrointestinal disorders 3.74% (161), arthralgia 2.51% (108), allergic reactions 2.35% (101), neurological system disorders 2.04% (88), renal impairment 0.07% (3) and others 0.05% (2). Most cases of ADRs (95%) had a good clinical outcome, while two with hepatotoxicity and one with renal impairment died. Compared with patients without ADRs, patients with ADRs were more likely to have positive smear test results at the end of the intensive phase (adjusted OR, 2.00; 95%CI, 1.44–2.78) and unsuccessful anti-TB outcomes (adjusted OR, 2.58; 95%CI, 1.43–4.68).

Conclusions

The incidence of ADRs due to DOTS therapy was 15.08%. Those ADRs had a substantial impact on TB control in China. This highlighted the importance of developing strategies to ameliorate ADRs both to improve the quality of patient care and to control TB safely.     

Development and Validation of a Risk Model for Predicting Adverse Drug Reactions in Older People during Hospital Stay: Brighton Adverse Drug Reactions Risk (BADRI) Model

Background

Older patients are at an increased risk of developing adverse drug reactions (ADR). Of particular concern are the oldest old, which constitute an increasingly growing population. Having a validated clinical tool to identify those older patients at risk of developing an ADR during hospital stay would enable healthcare staff to put measures in place to reduce the risk of such an event developing. The current study aimed to (1) develop and (2) validate an ADR risk prediction model.

Methods

We used a combination of univariate analysis and multivariate binary logistic regression to identify clinical risk factors for developing an ADR in a population of older people from a UK teaching hospital. The final ADR risk model was then validated in a European population (European dataset).

Results

Six-hundred-ninety patients (median age 85 years) were enrolled in the development stage of the study. Ninety-five reports of ADR were confirmed by independent review in these patients. Five clinical variables were identified through multivariate analysis and included in our final model; each variable was attributed a score of 1. Internal validation produced an AUROC of 0.74, a sensitivity of 80%, and specificity of 55%. During the external validation stage the AUROC was 0.73, with sensitivity and specificity values of 84% and 43% respectively.

Conclusions

We have developed and successfully validated a simple model to use ADR risk score in a population of patients with a median age of 85, i.e. the oldest old. The model is based on 5 clinical variables (≥8 drugs, hyperlipidaemia, raised white cell count, use of anti-diabetic agents, length of stay ≥12 days), some of which have not been previously reported.     

Chronic kidney disease itself is a causal risk factor for stroke beyond traditional cardiovascular risk factors: a nationwide cohort study in Taiwan

Background

Cardiovascular disease (CVD) is a leading cause of mortality and morbidity in patients with chronic kidney disease (CKD). In Taiwan, CVD is dominated by strokes but there is no robust evidence for a causal relationship between CKD and stroke. This study aimed to explore such causal association.

Methods

We conducted a nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database from 2004 to 2007. Each patient identified was individually tracked for a full three years from the index admission to identify those in whom any type of stroke developed. The study cohort consisted of patients hospitalized with a principal diagnosis of CKD and no traditional cardiovascular risk factors at baseline (n = 1393) and an age-matched control cohort of patients hospitalized for appendectomies (n = 1393, a surrogate for the general population). Cox proportional hazard regression and propensity score model were used to compare the three-year stroke-free survival rate of the two cohorts after adjustment for possible confounding factors.

Results

There were 256 stroke patients, 156 (11.2%) in the study cohort and 100 (7.2%) in the control cohort. After adjusting for covariates, patients with primary CKD had a 1.94-fold greater risk for stroke (95% CI, 1.45–2.60; p<0.001) based on Cox regression and a 1.68-fold greater risk for stroke (95% CI, 1.25–2.25; p = 0.001) based on propensity score. This was still the case for two cohorts younger than 75 years old and without traditional cardiovascular risk factors.

Conclusions

This study of Taiwanese patients indicates that CKD itself is a causal risk factor for stroke beyond the traditional cardiovascular risk factors. Primary CKD patients have higher risk for stroke than the general population and all CKD patients, irrespective of the presence or severity of traditional cardiovascular risk factors, should be made aware of the stroke risk and monitored for stroke prevention.     

Consumption of diagnostic procedures and other cardiology care in chest pain patients after presentation at the emergency department

Objective

The HEART score serves risk stratification of chest pain patients at the emergency department (ED). Quicker and more solid decisions may be taken in these patients with application of this score. An analysis of medical consumption of 122 acute chest pain patients admitted before the introduction of this score may be indicative of possible savings.

Methods

Numbers of cardiology investigations and clinical admission days were counted. Charged cost of medicine was divided into three categories: ED, in-hospital, and outpatient clinic.

Results

The total cost of care was € 469,631, with an average of € 3849 per patient. Seventy-five percent of this cost was due to hospitalisation under the initial working diagnosis of acute coronary syndrome (ACS). This diagnosis was confirmed in only 29/122 (24 %) of the patients. The low-risk group (41 patients with HEART scores 0–3) included one patient with a previously scheduled CABG. In the remaining 40 patients, hospitalisation occurred in 12/40 (30 %) patients and 30/40 (75 %) patients visited the outpatient clinic. The total cost of medical care after presentation of these 40 patients was € 37,641; there were no cases where a new diagnosis of coronary artery disease was made. When medical care in this subgroup is declared redundant, major savings on national medical care budgets could be made.

Conclusion

If the HEART score were to be routinely applied, diagnostic pathways could be shortened and costs reduced, in particular in low-risk patients.     

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Contributes High Risk for Chronic Kidney Disease in Asian Male with Hypertension–A Meta-Regression Analysis of 98 Observational Studies

Background

Associations between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms and chronic kidney disease (CKD) have been extensively studied, with most studies reporting that individuals with the D allele have a higher risk. Although some factors, such as ethnicity, may moderate the association between ACE I/D polymorphisms and CKD risk, gender-dependent effects on the CKD risk remain controversial.

Objectives

This study investigated the gender-dependent effects of ACE I/D polymorphisms on CKD risk.

Data sources

PubMed, the Cochrane library, and EMBASE were searched for studies published before January 2013.

Study eligibility criteria, participants, and interventions

Cross-sectional surveys and case–control studies analyzing ACE I/D polymorphisms and CKD were included. They were required to match the following criteria: age >18 years, absence of rare diseases, and Asian or Caucasian ethnicity.

Study appraisal and synthesis methods

The effect of carrying the D allele on CKD risk was assessed by meta-analysis and meta-regression using random-effects models.

Results

Ethnicity [odds ratio (OR): 1.24; 95% confidence interval (CI): 1.08–1.42] and hypertension (OR: 1.55; 95% CI: 1.04–2.32) had significant moderate effects on the association between ACE I/D polymorphisms and CKD risk, but they were not significant in the diabetic nephropathy subgroup. Males had higher OR for the association between ACE I/D polymorphisms and CKD risk than females in Asians but not Caucasians, regardless of adjustment for hypertension (p<0.05). In subgroup analyses, this result was significant in the nondiabetic nephropathy group. Compared with the I allele, the D allele had the highest risk (OR: 3.75; 95% CI: 1.84–7.65) for CKD in hypertensive Asian males.

Conclusions and implications of key findings

The ACE I/D polymorphisms may incur the highest risk for increasing CKD in hypertensive Asian males.     

Low-Dose Aspirin for Prevention of Cardiovascular Disease in Patients with Chronic Kidney Disease

Background

Chronic kidney disease (CKD) is a major risk factor for the development of cardiovascular disease (CVD). Previous trials have investigated the effects of low-dose aspirin on CVD prevention in patients with diabetes; however, patients with CKD were not examined. The role of aspirin in diabetics is controversial, and the available literature is contradictory. Therefore, we studied whether low-dose aspirin would be beneficial for patients with CKD, a group that is at high risk for CVD.

Method

From a total of 25340 patients with CKD, 1884 recipients of low-dose aspirin (100 mg/day) were paired 1∶1 with non-recipients for analysis using propensity score matching. The primary endpoint was the development of atherosclerotic CVD, including coronary arterial disease, stroke, and peripheral arterial disease. Secondary endpoints included death from any cause, bleeding events, doubling of serum creatinine, and renal death.

Results

The incidence of a primary endpoint of any atherosclerotic CVD was significantly higher in the aspirin users than in the non-users (P<0.001). Secondary endpoints, including all-cause mortality and composite bleeding events, were not significantly different between the aspirin users and the non-users. However, the doubling of serum creatinine levels (P = 0.001) and renal death (P = 0.042) were significantly associated with the use of aspirin.

Conclusion

These results suggest that the use of low-dose aspirin in patients with CKD may have harmful consequences related to the development of CVD and renal progression.     

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.     

An Asian validation of the TIMI risk score for ST-segment elevation myocardial infarction

Background

Risk stratification in ST-elevation myocardial infarction (STEMI) is important, such that the most resource intensive strategy is used to achieve the greatest clinical benefit. This is essential in developing countries with wide variation in health care facilities, scarce resources and increasing burden of cardiovascular diseases. This study sought to validate the Thrombolysis In Myocardial Infarction (TIMI) risk score for STEMI in a multi-ethnic developing country.

Methods

Data from a national, prospective, observational registry of acute coronary syndromes was used. The TIMI risk score was evaluated in 4701 patients who presented with STEMI. Model discrimination and calibration was tested in the overall population and in subgroups of patients that were at higher risk of mortality; i.e., diabetics and those with renal impairment.

Results

Compared to the TIMI population, this study population was younger, had more chronic conditions, more severe index events and received treatment later. The TIMI risk score was strongly associated with 30-day mortality. Discrimination was good for the overall study population (c statistic 0.785) and in the high risk subgroups; diabetics (c statistic 0.764) and renal impairment (c statistic 0.761). Calibration was good for the overall study population and diabetics, with χ2 goodness of fit test p value of 0.936 and 0.983 respectively, but poor for those with renal impairment, χ2 goodness of fit test p value of 0.006.

Conclusions

The TIMI risk score is valid and can be used for risk stratification of STEMI patients for better targeted treatment.     

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.     

Anthropomorphic measurements that include central fat distribution are more closely related with key risk factors than BMI in CKD stage 3

Background

Body Mass Index (BMI) as a marker of obesity is an established risk factor for chronic kidney disease (CKD) and cardiovascular disease (CVD). However, BMI can overestimate obesity. Anthropomorphic measurements that include central fat deposition are emerging as a more important risk factor. We studied BMI, waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR) and conicity index (CI) in a cohort of patients with CKD stage 3 and compared the associations with other known risk factors for CKD progression and CVD.

Methods

1740 patients with CKD stage 3 were recruited from primary care for the Renal Risk in Derby study. Each participant underwent clinical assessment, including anthropomorphic measurements and pulse wave velocity (PWV), as well as urine and serum biochemistry tests.

Results

The mean age of the cohort was 72.9±9 years with 60% females. The mean eGFR was 52.5±10.4 ml/min/1.73 m² and 16.9% of the cohort had diabetes. With the cohort divided into normal and increased risk of morbidity and mortality using each anthropomorphic measurement, those measurements that included increased central fat distribution were significantly associated with more risk factors for CKD progression and CVD than increased BMI. Univariable analysis demonstrated central fat distribution was correlated with more risk factors than BMI. Subgroup analyses using recognised BMI cut-offs to define obesity and quartiles of WHR and CI demonstrated that increasing central fat distribution was significantly associated with more CKD and CVD risk factors than increasing BMI.

Conclusion

Anthropomorphic measurements that include a measure of central fat deposition are related to more key risk factors in CKD stage 3 patients than BMI. Central fat deposition may be of greater importance as a risk factor in CKD than BMI and reliance on BMI alone may therefore underestimate the associated risk.     

Understanding measurements of vitality in patients with chronic kidney disease: connecting a quality-of-life scale to daily activities

Background

Many patients with chronic kidney disease (CKD) suffer from fatigue caused by anemia, but that anemia can be reversed. Successful treatment can be measured as a decrease in fatigue and an increase in energy or vitality, particularly on the vitality (VT) subscale of the SF-36. Changes in VT scores are most commonly interpreted in terms of minimally important differences or standardized effect sizes, but neither a minimally important difference nor a standardized effect size provides information about how patients’ activities are affected. Therefore, we analyzed the association between differences in VT scores and a variable that is meaningful to patients and to society the frequency of going out.

Study Design

Questionnaire survey. Analyses of differences among participants at bseline, and analyses of differences within participants over time.

Setting and Participants

CKD patients who were not on dialysis and were involved in a study of anti-anemia therapy.

Predictor

VT scores.

Outcome

Frequency of going out.

Measurements

VT scores and the frequency of going out.

Results

At baseline, higher VT scores and younger age were associated with going out more often, while sex and the presence of diabetic nephropathy were not associated with the frequency of going out. Greater changes in VT scores over time were associated with greater changes in the frequency of going out, in univariate and multivariate analyses.

Conclusions

At baseline, VT was associated with the frequency of going out. Increases in VT were also associated with increases in the frequency of going out. These results show how VT scores can be linked to daily activities that are important to individual patients and to society.     

Low Ankle-Brachial Index Is Associated with Early-Stage Chronic Kidney Disease in Type 2 Diabetic Patients Independent of Albuminuria

Aims

The role of low ankle-brachial index (ABI) in early-stage chronic kidney disease (CKD) is not fully known. This study was designed to investigate the prevalence of low ABI in early-stage CKD defined as an estimated glomerular filtration rate (eGFR) between 60–89 ml/min/1.73 m² of type 2 diabetic patients without albuminuria and to determine the association between the low ABI and mildly decreased eGFR.

Methods

The cross-sectional study enrolled 448 type 2 diabetic patients with normoalbuminuria. The patients were stratified into two groups according to the CKD-EPI eGFR level: the normal group with eGFR level ≥90 mL/min/1.73 m² and the lower group with eGFR of 60–89. ABI was categorized as normal (1.0–1.39), low-normal (0.9–0.99), and low (<0.9). Both stepwise forward multiple linear regression and binary logistic regression analyses were performed to examine the association between ABI categories and eGFR levels and to assess the relation of low ABI and early-stage CKD.

Results

The prevalence of low ABI in early-stage CKD of type 2 diabetic patients without albuminuria was 39.5%. Low ABI was associated with an approximate 3-fold greater risk of early-stage CKD in bivariate logistic regression analysis, and remained significantly associated with a 2.2 fold risk (95% confidence interval: 1.188–4.077; P = 0.012) after adjusting traditional chronic kidney disease risk factors.

Conclusions

There was a high prevalence of low ABI in early-stage CKD patients of type 2 diabetes with normoalbuminuria and a close relation between low ABI and early-stage CKD, suggesting that we should pay much more attention to the patients who have only mildly decreased eGFR and normoalbuminuria but have already had a low ABI in clinic work and consider the preventive therapy in early stage.     

Circulating Adipocytokines and Chronic Kidney Disease

Background

Adipokines have been associated with atherosclerotic heart disease, which shares many common risk factors with chronic kidney disease (CKD), but their relationship with CKD has not been well characterized.

Methods

We investigated the association of plasma leptin, resistin and adiponectin with CKD in 201 patients with CKD and 201 controls without. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² or presence of albuminuria. Quantile regression and logistic regression models were used to examine the association between adipokines and CKD adjusting for multiple confounding factors.

Results

Compared to controls, adjusted median leptin (38.2 vs. 17.2 ng/mL, p<0.0001) and adjusted mean resistin (16.2 vs 9.0 ng/mL, p<0.0001) were significantly higher in CKD cases. The multiple-adjusted odds ratio (95% confidence interval) of CKD comparing the highest tertile to the lower two tertiles was 2.3 (1.1, 4.9) for leptin and 12.7 (6.5, 24.6) for resistin. Median adiponectin was not significantly different in cases and controls, but the odds ratio comparing the highest tertile to the lower two tertiles was significant (1.9; 95% CI, 1.1, 3.6). In addition, higher leptin, resistin, and adiponectin were independently associated with lower eGFR and higher urinary albumin levels.

Conclusions

These findings suggest that adipocytokines are independently and significantly associated with the risk and severity of CKD. Longitudinal studies are warranted to evaluate the prospective relationship of adipocytokines to the development and progression of CKD.     

Patient-reported health status prior to cardiac resynchronisation therapy identifies patients at risk for poor survival and prolonged hospital stays

Background

Patient-reported factors have largely been neglected in search of predictors of response to cardiac resynchronisation therapy (CRT). The current study aimed to examine the independent value of pre-implantation patient-reported health status in predicting four-year survival and cardiac-related hospitalisation of CRT patients.

Methods

Consecutive patients (N = 139) indicated to receive a first-time CRT-defibrillator at the University Medical Center Utrecht were asked to complete a set of questionnaires prior to implantation. The Kansas City Cardiomyopathy Questionnaire (KCCQ) was used to assess heart failure-specific health status. Data on patients’ demographic, clinical and psychological characteristics at baseline, and on cardiac-related hospitalisations and all-cause deaths during a median follow-up of 3.9 years were obtained from purpose-designed questionnaires and patients’ medical records.

Results

Results of multivariable Cox regression analyses showed that poor patient-reported health status (KCCQ score < 50) prior to implantation was associated with a 2.5-fold increased risk of cardiac hospitalisation or all-cause death, independent of sociodemographic, clinical and psychological risk factors (adjusted hazard ratio 2.46, 95 % confidence interval (CI) 1.30–4.65). Poor health status was not significantly associated with the absolute number of cardiac-related hospital admissions, but with the total number of days spent in hospital during follow-up (adjusted incidence rate ratio 3.20, 95 % CI 1.88–5.44).

Conclusions

Patient-reported health status assessed prior to CRT identifies patients at risk for poor survival and prolonged hospital stays, independent of traditional risk factors. These results emphasise the importance of incorporating health status measures in cardiovascular research and patient management. Heart failure patients reporting poor health status should be identified and offered appropriate additional treatment programs.     

Skin Autofluorescence Is Associated with the Progression of Chronic Kidney Disease: A Prospective Observational Study

Background

Advanced glycation end product (AGE) accumulation is thought to be a measure of cumulative metabolic stress that has been reported to independently predict cardiovascular disease in diabetes and renal failure. The aim of this study was to evaluate the association between AGE accumulation, measured as skin autofluorescence, and the progression of renal disease in pre-dialysis patients with chronic kidney disease (CKD).

Methods

Skin autofluorescence was measured noninvasively with an autofluorescence reader at baseline in 449 pre-dialysis patients with CKD. The primary end point was defined as a doubling of serum creatinine and/or need for dialysis.

Results

Thirty-three patients were lost to follow-up. Forty six patients reached the primary end point during the follow-up period (Median 39 months). Kaplan-Meier analysis showed a significantly higher risk of development of the primary end points in patients with skin autofluorescence levels above the optimal cut-off level of 2.31 arbitrary units, derived by receiver operator curve analysis. Cox regression analysis revealed that skin autofluorescence was an independent predictor of the primary end point, even after adjustment for age, gender, smoking history, diabetes, estimated glomerular filtration rate and proteinuria (adjusted hazard ratio 2.58, P = 0.004).

Conclusions

Tissue accumulation of AGEs, measured as skin autofluorescence, is a strong and independent predictor of progression of CKD. Skin autofluorescence may be useful for risk stratification in this group of patients; further studies should clarify whether AGE accumulation could be one of the therapeutic targets to improve the prognosis of CKD.