The natural history of iga nephropathy in the german chronic kidney disease (gckd) cohort

Abstract Background and Aims Primary IgA nephropathy (IgAN) is the most common form of glomerulonephritis and a major cause of kidney failure. Here we describe the natural history of individuals with IgAN in the German Chronic Kidney Disease (GCKD) cohort. Method From 2010 to 2012, 421 patients with biopsy-proven IgAN have been enrolled into the GCKD study, a prospective observational cohort study (N = 5217). Inclusion criteria were an estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73 m2 or overt proteinuria in the presence of an eGFR>60 mL/min/1.73 m2. The adjudicated composite renal endpoint (Major Adverse Kidney Events; MAKE) was defined as eGFR decline>40%, eGFR< 15 ml/min or initiation of kidney replacement therapy. The associations between the incidence of MAKE and baseline risk factors were analyzed using the Cox proportional hazards regression model. Data relating to baseline demographics, laboratory, comorbidity, and mortality were used. Results The mean age at baseline of IgAN patients was 51.6 years (±13.6) and 67% were male. Duration of disease at baseline was 5.9 ± 8.1 years. Baseline median UACR was 0.4 g/g (0.1-0.8) and mean eGFR was 52.5 ± 22.4 mL/min/1.73m2. Over a follow-up of 6.5 years, 53 (12.6%) initiated kidney replacement therapy, 64 (15.2%) experienced >40% eGFR decline and additional 3 (0.7%) reached eGFR< 15 ml/min, i.e. 28% of the patients experienced a MAKE. Albuminuria, with reference to < 0.1 g/g was most associated with MAKE. Hazard ratios at UACR 0.1-0.6 g/g, 0.6-1.4 g/g, 1.4-2.2 g/g and >2.2 g/g were 2.03 (1.02-4.05), 3.8 (1.92-7.5), 5.64 (2.58-12.33) and 5.02 (2.29-11-03), respectively. Relapse, defined as UACR >2.2g/g, after partial remission (defined as UACR ≥0.1 g/g to <0.6 g/g) or complete (defined as UACR < 0.1 g/g) remission developed in only 13 (3.1%) patients. Conclusion The GCKD study reflects a large cohort with long follow up allowing for a thorough analysis of the natural history of IgAN. More than every fourth patient experienced a MAKE event within 6.5 years. Our findings support the use of albuminuria as a surrogate for poor kidney outcomes.