Patient Characteristics and Outcomes by GN Subtype in ESRD

Abstract

Background and objectives Outcomes-based research rarely focuses on patients with ESRD caused by GN. The hypotheses were that the GN subtype would clinically discriminate patient groups and independently associate with survival after ESRD therapy initiation.Design, setting, participants, & measurements Data were extracted from the US Renal Data System for adult patients with incident (1996-2011) ESRD attributed to six GN subtypes: FSGS, IgA nephropathy (IgAN), membranous nephropathy, membranoproliferative glomeruonephritis, lupus nephritis (LN), and vasculitis. ESRD attributed to diabetes and autosomal dominant polycystic kidney disease served as non-GN comparators. Unadjusted and adjusted mortality hazard ratios (aHRs) with 95% confidence intervals (95% CIs) were estimated using Cox regression (reference, IgAN). Models sequentially adjusted for sociodemographic (model 2), comorbidity/laboratory (model 3), and ESRD treatment modality (model 4) variables.Results Among 84,301 patients with ESRD attributed to GN, the median age ranged from 39 (LN) to 66 (vasculitis) years, male sex ranged from 18% (LN) to 68% (IgAN), and black race ranged from 7% (IgAN) to 49% (LN). Patients with IgAN had the fewest comorbidities and lowest use of hemodialysis (70.1%). After a median followup of 2.5 (interquartile range, 1.0-4.9) years, crude mortality was lowest in IgAN (3.7 deaths/100 person years). Compared to IgAN, adjusted mortality was highest in LN (model 4 aHR=1.75; 95% CI, 1.68 to 1.83) and in diabetes (aHR=1.73; 95% CI, 1.67 to 1.79), and was also higher in all other GN subtypes (membranous nephropathy: aHR=1.23; 95% CI, 1.17 to 1.29; FSGS: aHR=1.37; 95% CI, 1.32 to 1.42; membranoproliferative GN: aHR=1.38; 95% CI, 1.31 to 1.45; vasculitis: aHR=1.51; 95% CI, 1.45 to 1.58) and in autosomal dominant polycystic kidney disease (aHR=1.22; 95% CI, 1.18 to 1.27).Conclusions This study exposes substantial heterogeneity across GN subtypes at ESRD therapy initiation and identifies independent associations between GN subtype and post-ESRD mortality. These survival discrepancies warrant further study, and the utility of current research practice to group GN subtypes together when evaluating ESRD outcomes should be questioned.

ESRD Outcomes and GN Subtypes

“…Unfortunately, the most commonly attributed causes of kidney disease leading to end stage are based on descriptive phenotypes rather than defined etiologies. The study by O'Shaughnessy et al (2) illustrates the special case of this observation applied to GN. Of course, the current classification system for GN itself is far more descriptive than etiologic.…”

“…Patients with LN had the highest mortality, comparable to patients with ESRD attributed to diabetes (generally thought to be among the causes of ESRD with the highest mortality). The study by O'Shaughnessy et al (2) clearly shows large differences in patient characteristics and mortality risk by GN subtype. The findings warrant a reconsideration of the traditional categories used to classify the cause of ESRD in population registries.…”

“…In addition to classification convenience, this acceptance partly reflects the tendency for GN to become inactive and undifferentiated as kidney failure progresses to end stage. However, the article in this issue of CJASN by O'Shaughnessy et al (2) reminds us that GN remains heterogeneous, even when survival start time is shifted forward many years to the onset of ESRD. Using Medicare administrative claims data from the USRDS, O'Shaughnessy et al (2) were able to classify patients with ESRD and GN into six subtypes: FSGS, IgA nephropathy (IgAN), membranous nephropathy, membranoproliferative GN, lupus nephritis (LN), and vasculitis.…”

“…The diagnostic coding system provides a very limited description of pathology and clinical syndrome. However, O'Shaughnessy et al (2) made full use of the rich USRDS data sources to adjust for demographic and comorbid factors. Adjustment was applied in stages to clearly show the contribution of patient attributes to survival.…”

“…The study by O'Shaughnessy et al (2) was not designed to explain the differences in outcome by GN type. The differences could be attributable to differences in the underlying biology of these inflammatory conditions.…”