Biopsy-proven CKD etiology and outcomes: the Chronic Kidney Disease Japan Cohort (CKD-JAC) study

Abstract

Background: The Kidney Disease: Improving Global Outcomes guidelines advocate the cause-glomerular filtration rate (GFR)-albuminuria (CGA) classification for predicting outcomes. However, there is a dearth of data supporting the use of the cause of chronic kidney disease. This study aimed to address how to incorporate a prior biopsy-proven diagnosis in outcome prediction.

Methods: We examined the association of biopsy-proven kidney disease diagnoses with kidney failure with replacement therapy (KFRT) and all-cause death before KFRT in patients with various biopsy-proven diagnoses (n = 778, analysis A) and patients with diabetes mellitus labeled with biopsy-proven diabetic nephropathy (DN), other biopsy-proven diseases and no biopsy (n = 1117, analysis B).

Results: In analysis A, adding biopsy-proven diagnoses to the GFR-albuminuria (GA) classification improved the prediction of 8-year incidence of KFRT and all-cause death significantly regarding integrated discrimination improvement and net reclassification index. Fine-Gray (FG) models with KFRT as a competing event showed significantly higher subdistribution hazard ratios (SHRs) for all-cause death in nephrosclerosis {4.12 [95% confidence interval (CI) 1.11-15.2)], focal segmental glomerulosclerosis [3.77 (95% CI 1.09-13.1)]} and membranous nephropathy (MN) [2.91 (95% CI 1.02-8.30)] than in immunoglobulin A nephropathy (IgAN), while the Cox model failed to show significant associations. Crescentic glomerulonephritis had the highest risk of all-cause death [SHR 5.90 (95% CI 2.05-17.0)]. MN had a significantly lower risk of KFRT than IgAN [SHR 0.45 (95% CI 0.24-0.84)]. In analysis B, other biopsy-proven diseases had a lower risk of KFRT than biopsy-proven DN in the FG model, with death as a competing event [SHR 0.62 (95% CI 0.39-0.97)].

Conclusions: The CGA classification is of greater value in predicting outcomes than the GA classification.

Keywords: CKD; diabetic kidney disease; epidemiology; kidney biopsy; prognosis.

Graphical Abstract

Figure 1:

Study population. Of 2966 participants, 988 had documented biopsy results and 133 had undergone kidney biopsy before baseline but did not have documented results. Of the 988 participants, after excluding 210 participants with other kidney diseases or no diagnosis, analysis A had 778 participants. Analysis B had 1117 participants who had a medical history of DM. Analysis A was composed of six disease categories: IgAN, MN, focal segmental glomerulosclerosis FSGS, crescentic GN, classic DN and nephrosclerosis. Analysis B was composed of three groups: biopsy results not available (n = 880), DN (n = 46) and other pathological diagnoses (n = 191)

Figure 2:

Kidney disease diagnoses based on past kidney biopsy results in (A) analysis A and (B) analysis B.

Figure 3:

Cumulative incidence of CVD, all-cause death and KFRT. (A) The incidence rates of CVD, all-cause death and KFRT for each cause of kidney disease. (B) The cumulative incidence functions of CVD, all-cause death other than fatal CVD and KFRT in analysis A.

Figure 4:

Incidence of CVD, all-cause death and KFRT. (A) The incidence rates of CVD, all-cause death and KFRT in each group. Cumulative incidence of (B) all-cause death before KFRT, (C) KFRT and (D) CVD event before KFRT.