IgAN, FSGS Linked to Greater Kidney Replacement Therapy Risk Than Common CKD Etiologies

Patients with IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) are at an increased risk of disease progression requiring kidney replacement therapy (KRT) than patients with other common chronic kidney disease (CKD) etiologies, according to findings from a recent study.1

Leveraging data from the Swedish Renal Registry, the study found patients with IgAN and FSGS had a reduced risk of hospitalization, cardiovascular events, and death, but had a faster eGFR decline and were more likely to require KRT than patients with membranous nephropathy (MN), minimal change disease (MCD), and CKD due to the most common non-communicable diseases.1

“Existing evidence, as well as clinical guidelines, stress that the underlying cause of CKD differentially impacts the patient's risk of adverse health outcomes. However, the specific health trajectories of patients with glomerular diseases have not been well described,” Anne-Laure Faucon, MD, PhD, a post-doctoral researcher in the department of medical epidemiology and biostatistics at Karolinska Institutet in Sweden, and colleagues wrote.1 “Characterizing the long-term health trajectories of primary glomerular diseases is important for risk stratification, tailoring monitoring strategies, and optimizing control for risk factors.”

Among the leading causes of kidney failure, primary glomerular diseases are characterized by histologically and clinically distinct entities/subtypes, with IgAN and FSGS being some of the most common.2 Despite frequently being grouped together, etiologies of primary glomerular disease are distinct from each other and can lead to different health outcomes, although these differences are not currently well understood.

To compare the rate of adverse health events between patients with primary glomerular diseases and patients with CKD from the most common etiologies, investigators examined data from the Swedish Renal Registry of CKD patients with an incident estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 attending nephrology specialist care in Sweden. The present analysis included non-transplanted adults ≥18 years of age with a primary glomerular disease or with CKD attributed to a noninflammatory etiology who were registered between January 1, 2005, and December 31, 2021.1

The primary study outcomes were KRT initiation, major cardiovascular events (MACE), death, and healthcare resource utilization. Secondary outcomes included each component of MACE, hospitalization for heart failure, acute kidney injury (AKI), and venous thromboembolic events. Patients were followed until the occurrence of an event, death, or the end of follow-up on December 31, 2021.1

In total, investigators identified 2396 patients with glomerular disease and 37,697 controls with common CKD etiologies. Among those with glomerular disease, the mean age was 57 years, 69% were male, 1524 had IgAN, 398 had FSGS, 94 had MCD, and 380 had MN. Among the controls, the mean age was 74 years, 64% were male, and most patients had diabetic nephropathy and nephroangiosclerosis.1

During a median follow-up of 6.3 (3.3 to 9.9) years, there were a median 3.0 (1.0 to 7.0) hospitalizations per patient. Compared with controls, investigators noted patients with primary glomerular disease, regardless of etiology, had a lower rate of all-cause and cardiovascular-related hospitalizations.1

In total, 9216 KRT events, 11,242 MACE, and 20,292 deaths occurred. Compared with controls, the adjusted 5-year absolute risks of death and MACE were lower in patients with primary glomerular diseases, but the adjusted relative rate of KRT differed between etiologies: relative risks were lower in patients with MCD (Hazard ratio [HR], 0.06; 95% CI, 0.01 to 0.42) and MN (HR, 0.65; 95% CI, 0.51 to 0.82), but they were 26% higher in patients with IgAN (HR, 1.26; 95% CI, 1.15 to 1.37) and 34% higher in patients with FSGS (HR, 1.34; 95% CI, 1.15 to 1.57) relative to controls.1

Investigators pointed out the relative risks of cardiovascular death and heart failure hospitalization were lower in glomerular disease etiologies than in controls. While the adjusted risk for myocardial infarction and stroke was lower for IgAN and MN, patients with FSGS had a similar risk as controls.1

Among the entire study population, the overall crude eGFR slope was −1.79 (95% CI, −1.84 to −1.74) mL/min/1.73 m2/year. Compared with controls (−1.74; 95% CI, −1.78 to −1.69), the rate of eGFR decline was faster in patients with IgAN (−2.71; 95% CI, −2.91 to −2.51) and FSGS (−3.55; 95% CI, −3.96 to −3.15), slower in patients with MN (−1.18; 95% CI, −1.58 to −0.77) and stable in patients with MCD (0.61; 95% CI, −0.36 to 1.57).1

In multivariable analyses and compared with controls, investigators noted patients with IgAN had a faster eGFR decline (mean difference, −0.57; 95% CI, −0.80 to −0.33), but the difference was abrogated after adjustment for albuminuria. However, patients with FSGS also had a faster eGFR decline than control patients (mean difference, −1.69; 95% CI, −2.13 to −1.24) which was not abrogated with adjustment for albuminuria.1

Investigators outlined multiple limitations to these findings, including potential misclassification of primary glomerular disease; the lack of information on IV immunosuppressive therapy and histological features affecting kidney outcomes; the inclusion of patients at the time of their first registration in the registry rather than initial referral or diagnosis; and the potential lack of generalizability to other populations.1

“This study identifies patients with IgAN and FSGS as a population that, despite a lower relative risk of cardiovascular events and death, needs improved pharmacological management and risk factor control to reduce their heightened risk of KRT,” investigators concluded.1

References

1. Faucon AL, Lando S, Chrysostomou C, et al. Primary glomerular diseases and long-term adverse health outcomes: A nationwide cohort study. Journal of Internal Medicine. https://doi.org/10.1111/joim.20024
2. Kramer A, Boenink R, Stel VS, et al. The ERA-EDTA registry annual report 2018: a summary. Clin Kidney J. doi:10.1093/ckj/sfaa271