Heart Failure in a Cohort of Patients with Chronic Kidney Disease: The GCKD Study

Background and Aims Chronic kidney disease (CKD) is a risk factor for development and progression of heart failure (HF). CKD and HF share common risk factors, but few data exist on the prevalence, signs and symptoms as well as correlates of HF in populations with CKD of moderate severity. We therefore aimed to examine the prevalence and correlates of HF in the German Chronic Kidney Disease (GCKD) study, a large observational prospective study. Methods and Results We analyzed data from 5,015 GCKD patients aged 18–74 years with an estimated glomerular filtration rate (eGFR) of 500 mg/d). We evaluated a definition of HF based on the Gothenburg score, a clinical HF score used in epidemiological studies (Gothenburg HF), and self-reported HF. Factors associated with HF were identified using multivariable adjusted logistic regression. The prevalence of Gothenburg HF was 43% (ranging from 24% in those with eGFR >90 to 59% in those with eGFR<30 ml/min/1.73m2). The corresponding estimate for self-reported HF was 18% (range 5%-24%). Lower eGFR was significantly and independently associated with the Gothenburg definition of HF (p-trend <0.001). Additional significantly associated correlates included older age, female gender, higher BMI, hypertension, diabetes mellitus, valvular heart disease, anemia, sleep apnea, and lower educational status. Conclusions The burden of self-reported and Gothenburg HF among patients with CKD is high. The proportion of patients who meet the criteria for Gothenburg HF in a European cohort of patients with moderate CKD is more than twice as high as the prevalence of self-reported HF. However, because of the shared signs, symptoms and medications of HF and CKD, the Gothenburg score cannot be used to reliably define HF in CKD patients. Our results emphasize the need for early screening for HF in patients with CKD

Prevalence and correlates of gout in a large cohort of patients with chronic kidney disease: the German Chronic Kidney Disease (GCKD) study

Background: Reduced kidney function is a risk factor for hyperuricaemia and gout, but limited information on the burden of gout is available from studies of patients with chronic kidney disease (CKD). We therefore examined the prevalence and correlates of gout in the large prospective observational German Chronic Kidney Disease (GCKD) study. Methods: Data from 5085 CKD patients aged 18–74 years with an estimated glomerular filtration rate (eGFR) of 30–<60 mL/min/1.73 m2 or eGFR ≥60 and overt proteinuria at recruitment and non-missing values for self-reported gout, medications and urate measurements from a central laboratory were evaluated. Results: The overall prevalence of gout was 24.3%, and increased from 16.0% in those with eGFR ≥60 mL/min/1.73 m2 to 35.6% in those with eGFR <30. Of those with self-reported gout, 30.7% of individuals were not currently taking any gout medication and among gout patients on urate lowering therapy, 47.2% still showed hyperuricaemia. Factors associated with gout were serum urate, lower eGFR, advanced age, male sex, higher body mass index and waist-to-hip ratio, higher triglyceride and C-reactive protein (CRP) concentrations, alcohol intake and diuretics use. While lower eGFR categories showed significant associations with gout in multivariable-adjusted models (prevalence ratio 1.46 for eGFR <30 compared with eGFR ≥60, 95% confidence interval 1.21–1.77), associations between gout and higher urinary albumin-to-creatinine ratio in this CKD population were not significant. Conclusions: Self-reported gout is common among patients with CKD and lower GFR is strongly associated with gout. Pharmacological management of gout in patients with CKD is suboptimal. Prospective follow-up will show whether gout and hyperuricaemia increase the risk of CKD progression and cardiovascular events in the GCKD study

Heart failure in a cohort of patients with chronic kidney disease: the GCKD study.

BACKGROUND AND AIMS:Chronic kidney disease (CKD) is a risk factor for development and progression of heart failure (HF). CKD and HF share common risk factors, but few data exist on the prevalence, signs and symptoms as well as correlates of HF in populations with CKD of moderate severity. We therefore aimed to examine the prevalence and correlates of HF in the German Chronic Kidney Disease (GCKD) study, a large observational prospective study. METHODS AND RESULTS:We analyzed data from 5,015 GCKD patients aged 18-74 years with an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73m² or with an eGFR ≥60 and overt proteinuria (>500 mg/d). We evaluated a definition of HF based on the Gothenburg score, a clinical HF score used in epidemiological studies (Gothenburg HF), and self-reported HF. Factors associated with HF were identified using multivariable adjusted logistic regression. The prevalence of Gothenburg HF was 43% (ranging from 24% in those with eGFR >90 to 59% in those with eGFR<30 ml/min/1.73m2). The corresponding estimate for self-reported HF was 18% (range 5%-24%). Lower eGFR was significantly and independently associated with the Gothenburg definition of HF (p-trend <0.001). Additional significantly associated correlates included older age, female gender, higher BMI, hypertension, diabetes mellitus, valvular heart disease, anemia, sleep apnea, and lower educational status. CONCLUSIONS:The burden of self-reported and Gothenburg HF among patients with CKD is high. The proportion of patients who meet the criteria for Gothenburg HF in a European cohort of patients with moderate CKD is more than twice as high as the prevalence of self-reported HF. However, because of the shared signs, symptoms and medications of HF and CKD, the Gothenburg score cannot be used to reliably define HF in CKD patients. Our results emphasize the need for early screening for HF in patients with CKD

Heart Failure in a Cohort of Patients with Chronic Kidney Disease: The GCKD Study

Background and Aims Chronic kidney disease (CKD) is a risk factor for development and progression of heart failure (HF). CKD and HF share common risk factors, but few data exist on the prevalence, signs and symptoms as well as correlates of HF in populations with CKD of moderate severity. We therefore aimed to examine the prevalence and correlates of HF in the German Chronic Kidney Disease (GCKD) study, a large observational prospective study. Methods and Results We analyzed data from 5,015 GCKD patients aged 18-74 years with an estimated glomerular filtration rate (eGFR) of = 60 and overt proteinuria (>500 mg/d). We evaluated a definition of HF based on the Gothenburg score, a clinical HF score used in epidemiological studies (Gothenburg HF), and self-reported HF. Factors associated with HF were identified using multivariable adjusted logistic regression. The prevalence of Gothenburg HF was 43% (ranging from 24% in those with eGFR >90 to 59% in those with eGFR<30 ml/min/1.73m2). The corresponding estimate for self-reported HF was 18% (range 5%-24%). Lower eGFR was significantly and independently associated with the Gothenburg definition of HF (p-trend <0.001). Additional significantly associated correlates included older age, female gender, higher BMI, hypertension, diabetes mellitus, valvular heart disease, anemia, sleep apnea, and lower educational status. Conclusions The burden of self-reported and Gothenburg HF among patients with CKD is high. The proportion of patients who meet the criteria for Gothenburg HF in a European cohort of patients with moderate CKD is more than twice as high as the prevalence of self-reported HF. However, because of the shared signs, symptoms and medications of HF and CKD, the Gothenburg score cannot be used to reliably define HF in CKD patients. Our results emphasize the need for early screening for HF in patients with CKD

Drugs linked to plasma homoarginine in chronic kidney disease patients—a cross-sectional analysis of the German Chronic Kidney Disease cohort

Background Elevated plasma concentrations of symmetric and asymmetric dimethylarginine (SDMA and ADMA, respectively) and a lower plasma concentration of the structurally related homoarginine are commonly observed in patients with chronic kidney disease (CKD) and independently predict total mortality as well as progression of renal disease. We aimed to identify drugs that may alter this adverse metabolite pattern in a favourable fashion. Methods Plasma ADMA, SDMA, homoarginine and l-arginine were determined by liquid chromatography–tandem mass spectrometry in 4756 CKD patients ages 18–74 years with an estimated glomerular filtration rate (eGFR) of 30–60 mL/min/1.73 m2 or an eGFR >60 mL/min/1.73 m2 and overt proteinuria who were enrolled in the German Chronic Kidney Disease (GCKD) study. Associations between laboratory, clinical and medication data were assessed. Results Intake of several commonly used drugs was independently associated with plasma concentrations of homoarginine and/or related metabolites. Among these, the peroxisome proliferator-activated receptor alpha (PPAR-α) agonist fenofibrate was associated with the most profound differences in ADMA, SDMA and homoarginine plasma concentrations: 66 patients taking fenofibrate had a multivariable adjusted odds ratio (OR) of 5.83 [95% confidence interval (CI) 2.82–12.03, P < 0.001] to have a plasma homoarginine concentration above the median. The median homoarginine plasma concentration in patients taking fenofibrate was 2.30 µmol/L versus 1.55 in patients not taking the drug (P < 0.001). In addition, fibrates were significantly associated with lower plasma SDMA and higher l-arginine concentrations. In contrast, glucocorticoids were associated with lower plasma homoarginine, with adjusted ORs of 0.52 (95% CI 0.40–0.67, P < 0.001) and 0.53 (95% CI 0.31–0.90, P = 0.018) for prednisolone and methylprednisolone, respectively. Conclusions In a large cohort of CKD patients, intake of fenofibrate and glucocorticoids were independently associated with higher and lower plasma homoarginine concentrations, respectively. Effects on plasma homoarginine and methylarginines warrant further investigation as potential mechanisms mediating beneficial or adverse drug effects

Characteristics of 5015 GCKD study participants by eGFR categories.

<p>Data are mean (SD) for continuous variables and percentages (count) for categorical variables. Missing values in following variables (number of missings): BMI (57), atrial fibrillation (12), valvular heart disease (42), anemia & hemoglobin (145), serum albumin (1), heart rate (49), current smoker (12), alcohol intake (28), education (101).</p><p>Valvular heart disease: aortic stenosis (n = 73), aortic insufficiency (n = 142), mitral stenosis (n = 15), mitral insufficiency (n = 251), other (n = 169). Some individuals had more than one type of valvular heart disease.</p><p>Characteristics of 5015 GCKD study participants by eGFR categories.</p

Validation analyses within a subsample of the regional center Freiburg (n = 118).

<p>Data are percentages.</p><p>Reference is heart failure diagnosis based on abstraction of medical records of the treating nephrologists or former hospitalizations. Sensitivity is the proportion of patients with heart failure according to the respective evaluated definition out of the patients with heart failure according to the reference definition. Specificity is the proportion of patients without heart failure according to the respective definition out of the patients without heart failure according to the reference definition. Positive predictive value (PPV) is the proportion of patients with heart failure according to the reference definition out of the patients with heart failure according to the evaluated definition. Negative predictive value (NPV) is the proportion of patients without heart failure according to the reference definition out of the patients without heart failure according to the evaluated definition.</p><p>Validation analyses within a subsample of the regional center Freiburg (n = 118).</p

Multivariable adjusted analyses of factors associated with Gothenburg HF and self-reported HF (n = 4,604).

<p>Of 5,015 observations, values were missing values in BMI (57), valvular heart disease (42), anemia (145), serum albumin (1), education (101), heart rate (49), current smoker (12), alcohol intake (28).</p><p>Multivariable adjusted analyses of factors associated with Gothenburg HF and self-reported HF (n = 4,604).</p