Long-term outcomes of patients with IgA nephropathy in the German CKD cohort
Authors: Stamellou Eleni , Nadal Jennifer , Hendry Bruce , Mercer Alex , Seikrit Claudia , Bechtel-Walz Wibke , Schmid Matthias , Moeller Marcus J , Schiffer Mario , Eckardt Kai-Uwe , Kramann Rafael , Floege Jürgen ,   the GCKD study investigators, Eckardt Kai-Uwe , Meiselbach Heike , Schneider Markus P , Schiffer Mario , Prokosch Hans-Ulrich , Bärthlein Barbara , Beck Andreas , Reis André , Ekici Arif B , Becker Susanne , Alberth-Schmidt Ulrike , Marschall Sabine , Weigel Anke , Walz Gerd , Köttgen Anna , Schultheiß Ulla T , Kotsis Fruzsina , Meder Simone , Mitsch Erna , Reinhard Ursula , Floege Jürgen , Saritas Turgay , Schaeffner Elke , Baid-Agrawal Seema , Theisen Kerstin , Schmidt-Ott Kai , Zeier Martin , Sommerer Claudia , Aykac Mehtap , Wolf Gunter , Busch Martin , Steiner Andi , Sitter Thomas , Wanner Christoph , Krane Vera , Bauer Britta , Kronenberg Florian , Raschenberger Julia , Kollerits Barbara , Forer Lukas , Schönherr Sebastian , Weissensteiner Hansi , Oefner Peter , Gronwald Wolfram , Schmid Matthias , Nadal Jennifer 
Published: July 2024

ABSTRACT

Background
The importance of albuminuria as opposed to proteinuria in predicting kidney outcomes in primary immunoglobulin A nephropathy (IgAN) is not well established.

Methods
From 2010 to 2012, 421 patients with biopsy-proven IgAN have been enrolled into the German Chronic Kidney Disease (GCKD) cohort, a prospective observational cohort study (N = 5217). Adjudicated endpoints include a composite kidney endpoint (CKE) consisting of eGFR decline &gt;40%, eGFR &lt;15 ml/min/1.73 m2 and initiation of kidney replacement therapy; the individual components of the CKE; and combined major adverse cardiac events (MACE), including non-fatal myocardial infarction, non-fatal stroke and all-cause mortality. The associations between the incidence of CKE and baseline factors, including demographics, laboratory values and comorbidities were analysed using the Cox proportional hazards regression model.

Results
The mean age of IgAN patients at baseline was 51.6 years (± 13.6) and 67% were male. The patient-reported duration of disease at baseline was 5.9 ± 8.1 years. Baseline median urine albumin:creatinine ratio (UACR) was 0.4 g/g [interquartile range (IQR) 0.1–0.8] and mean eGFR was 52.5 ± 22.4 ml/min/1.73 m2. Over a follow-up of 6.5 years, 64 (15.2%) patients experienced a &gt;40% eGFR decline, 3 (0.7%) reached eGFR &lt;15 ml/min/1.73 m2, 53 (12.6%) initiated kidney replacement therapy and 28% of the patients experienced the CKE. Albuminuria, with reference to &lt;0.1 g/g, was most associated with CKE. Hazard ratios (HRs) at UACRs of 0.1–0.6 g/g, 0.6–1.4 g/g, 1.4–2.2 g/g and &gt;2.2 g/g were 2.03 [95% confidence interval (CI) 1.02–4.05], 3.8 (95% CI 1.92–7.5), 5.64 (95% CI 2.58–12.33) and 5.02 (95% CI 2.29–11-03), respectively. Regarding MACE, the presence of diabetes [HR 2.53 (95% CI 1.11–5.78)] was the most strongly associated factor, whereas UACR and eGFR did not show significant associations.

Conclusion
In the GCKD IgAN subcohort, more than every fourth patient experienced a CKE event within 6.5 years. Our findings support the use of albuminuria as a surrogate to assess the risk of poor kidney outcomes.