Upper white bar depicts the positions of identified SNPs (Table 2) relative to the location of gene ATG (A denoted as 1)

Singleton polymorphisms were excluded from calculations.<p><b>Copyright information:</b></p><p>Taken from ", a positional candidate for blood pressure and renal regulation: resequencing, association and study"</p><p>http://www.biomedcentral.com/1471-2350/9/25</p><p>BMC Medical Genetics 2008;9():25-25.</p><p>Published online 10 Apr 2008</p><p>PMCID:PMC2330028.</p><p></p

Arrows pointing at polymorphic amino acid positions (14 Arg-His, 73 Ala-Val, 121 Met-Thr, 130 Pro-Pro, 143 Phe-Ser)

<p><b>Copyright information:</b></p><p>Taken from ", a positional candidate for blood pressure and renal regulation: resequencing, association and study"</p><p>http://www.biomedcentral.com/1471-2350/9/25</p><p>BMC Medical Genetics 2008;9():25-25.</p><p>Published online 10 Apr 2008</p><p>PMCID:PMC2330028.</p><p></p

Correlations to renal diagnosis, patient sex and patient age.

<p>No. patients (%).</p

Primary reasons for chronic dialysis initiation (DI) in 446 patients with CKD5.

<p>Clinical reasons accounted for 63% and biochemical reasons for 37% of all DI. The 12 most common motivations accounted for 91% of all DI prescriptions, “fatigue” being most common (22%) among clinical motivations, and “low GFR” (13%) most common among DI based on biochemical grounds.</p

Uremic symptoms at dialysis initiation (DI) in 446 patients with CKD5 in percent.

<p>Symptoms were present in 83% of patients, the most common being fatigue (44%), nausea (24%) and anorexia (22%). Black bars: primary symptoms; hatched bars: secondary or other symptoms.</p

Proportion of clinical causes as reason for dialysis initiation and selected measurements in relation to number of comorbidities.

<p>Proportion of clinical causes as reason for dialysis initiation and selected measurements in relation to number of comorbidities.</p

Primary, secondary and additional other reasons, clinical and biochemical, for prescribing chronic dialysis initiation in 446 patients.

<p>Primary, secondary and additional other reasons, clinical and biochemical, for prescribing chronic dialysis initiation in 446 patients.</p

The stated primary reason for dialysis initiation in 446 patients and characteristics of prescribing physicians (n = 52) who agreed to provide their details.

<p>Number and percent (in brackets).</p

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