Albuminuria predicts kidney events in IgA nephropathy

Abstract

Background and hypothesis: KDIGO recommends proteinuria <1 g/d as a treatment target in patients with immunoglobulin A nephropathy (IgAN) because of high risk of progression to kidney failure. However, long-term kidney outcomes in patients with low-grade proteinuria remain insufficiently studied.

Methods: We enrolled patients with biopsy-proven primary IgAN from the Swedish Renal Registry and analyzed associations between urine albumin-to-creatinine ratio (uACR, in categories <0.3, 0.3-0.5, 0.5-1.0, 1.0-1.5, 1.5-2.0, and ≥2.0 g/g) and the occurrence of major adverse kidney events [MAKE, a composite of kidney replacement therapy (KRT) and >30% decline in estimated glomerular filtration rate (eGFR)]. We also explored the risk of kidney events associated with change in uACR within a year.

Results: We included 1269 IgAN patients (74% men, median 53 years, mean eGFR 33 ml/min/1.73 m², median uACR 0.7 g/g). Over a median follow-up of 5.5 [2.8; 9.2] years, 667 MAKE and 517 KRT events occurred, and 528 patients experienced >30% eGFR decline. Compared with uACR < 0.3 g/g, any higher uACR category was strongly and incrementally associated with the risk of MAKE [adjusted hazard ratios (HR) ranging from 1.56 (95%CI 1.14-2.14) if uACR 0.3-0.5 g/g to 4.53 (3.36-6.11) if uACR ≥ 2.0 g/g], KRT (HR ranging from 1.39 to 4.65), and eGFR decline >30% (HR ranging from 1.76 to 3.47). In 785 patients who had repeated uACR measurements within a year, and compared with stable uACR, the risk of kidney events was lower if uACR decreased by 2-fold (HR ranging from 0.47 to 0.49), and higher if uACR increased by 2-fold (HR from 1.18 to 2.56), irrespective of baseline uACR.

Conclusions: There is substantial risk of adverse kidney outcomes among patients with IgAN and uACR between 0.3 and 1.0 g/g, a population currently considered at low risk of CKD progression. Reduction in uACR is associated with better kidney outcomes, irrespective of baseline uACR.

Keywords: IgA nephropathy; albuminuria; chronic kidney disease; kidney replacement therapy.

Graphical Abstract

Figure 1:

Distribution of baseline uACR (A) and percentage of patients by category of uACR (B).

Figure 2:

Evolution of eGFR and uACR in patients with IgA nephropathy (N = 1269), according to baseline categories of uACR. The evolution eGFR and uACR was estimated using linear mixed models with random intercept and slope, accounting for all eGFR and uACR measurements, respectively, over the study period.

Figure 3:

Adjusted cumulative incidence curves for MAKE and its individual components, according to categories of baseline uACR (N = 1269). The cumulative incidence curves were estimated using the Aalen–Johansen estimator considering the competing risk of death and were adjusted for age, sex, hypertension, diabetes, history of myocardial infarction, cerebrovascular disease, peripheral artery disease, heart failure, arrhythmia, acute kidney injury, systolic and diastolic blood pressure, eGFR, hemoglobin, CRP, serum albumin, phosphate, RASi, mineralocorticoid receptor antagonists, statins, antiplatelet therapy, corticosteroids, immunosuppressive therapy, all-cause hospitalizations, and number of out-patient visits in the year prior.