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

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

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

Composition of the Gothenburg score and proportions of GCKD participants within the cardiac score components.

<p>Composition of the Gothenburg score and proportions of GCKD participants within the cardiac score components.</p

Prevalence of heart failure across eGFR categories.

<p>The prevalence of both self-reported and Gothenburg score heart failure is higher with lower eGFR category, with Gothenburg heart failure observed at least twice as much in each category compared to self-report. P-trend was determined from logistic regressions of each heart failure definition on categorized eGFR.</p

Prevalence of heart failure in UACR categories, by gender, presence of diabetes mellitus and CHD.

<p>Data are percentages (count). P-values are provided for a comparison of characteristics within a given definition of HF, e.g. proportion of men and women with self-reported HF.</p><p>Prevalence of heart failure in UACR categories, by gender, presence of diabetes mellitus and CHD.</p

Additional file 5: Table S3. of Glycaemic control and antidiabetic therapy in patients with diabetes mellitus and chronic kidney disease – cross-sectional data from the German Chronic Kidney Disease (GCKD) cohort

Correlates of median HbA1C levels >7.0 % (53 mmol/mol) including the most frequently used antidiabetic therapies according to logistic regression analysis (entire model). (DOCX 24 kb

Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial

Background Sparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis. Methods PROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850. Findings Between Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals. Interpretation Over 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function.</p