RASi Use Linked to Improved Survival, Lower Risk of ESKD in Patients with IgA Nephropathy

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Findings from a recent study are providing a novel overview of the long-term survival and risk factors associated with immunoglobulin A nephropathy (IgAN) in an Eastern European cohort, addressing the limited availability of data regarding patient survival for the rare autoimmune disease.¹

The retrospective analysis found a 20% mortality rate, attributed primarily to cardiovascular diseases and linked to older age, greater comorbidity burden, decreased renal function at disease diagnosis, and the absence of renin-angiotensin-system inhibitor (RASi) use. Along with improved survival, the use of RASis was also associated with a decreased risk of end-stage kidney disease (ESKD).¹

A disease that causes inflammation and eventual damage to the kidneys, IgAN can lead to chronic kidney disease, kidney failure, and even death. Kidney damage from IgAN can take years to develop, although some patients have a more aggressive form of the disease that progresses more quickly. Given its unpredictable prognosis, understanding the factors impacting patient outcomes and overall survival is important but currently underresearched.²

“Geographical disparities in IgAN incidence and prevalence are evident, with notably higher values reported in Asia,” wrote lead investigator Gabriel Stefan, of the department of nephrology at the Carol Davila University of Medicine and Pharmacy in Romania, and colleagues.¹ “As a result, mortality rates, causes, and risk factors are also expected to vary across different geographical regions.”

To investigate the long-term survival rate and predictive factors of survival in patients with IgAN in Eastern Europe, investigators conducted a retrospective, observational study of patients with biopsy-proven primary IgAN from 2010 - 2017 at a tertiary department of nephrology in Romania. Clinical variables were obtained from patients’ electronic medical records, and the diagnosis of IgAN was based on light microscopy, immunofluorescence, and electron microscopy.¹

The study’s primary endpoint was all-cause mortality, while the secondary endpoint was the onset of ESKD, defined as the initiation of kidney replacement therapy or undergoing renal transplantation. Investigators followed patients until they reached one of these endpoints or until the end of the study period on January 1, 2022, whichever occurred first.¹

Over a median 7.3-year follow-up, 20% of patients in the study cohort died. The main causes of death were cardiovascular diseases (60%) followed by infectious (19%), gastroenterological (12%), and neoplastic (9%) diseases.¹

When compared to the survivors, investigators noted deceased patients were significantly older and had an increased prevalence of diabetes mellitus and a higher Charlson comorbidity index. Deceased patients also had significantly higher serum creatinine levels, lower eGFR, and more hematuria.¹

RASi use was more common among patients who survived (68%) compared to those who died (37%; P <.001). Additionally, investigators pointed out the initiation of kidney replacement therapy was more frequent in the deceased patient group (47% vs 30%; P = .04).¹

Multivariate analysis revealed increased Charlson comorbidity index (Hazard ratio [HR], 1.31 95% CI, 1.09-1.57; P <.01), lower eGFR (HR, 0.98; 95% CI, 0.96-1.00; P = .04), and the absence of RASi use (HR, 2.21; 95% CI, 1.15-4.28; P = .01) were statistically significantly associated with all-cause mortality. Further analysis revealed the following factors were significantly predictive of ESKD:

• Male sex (HR, 2.36; 95% CI, 1.24-4.49 P <.01)
• Diabetes mellitus (HR, 2.28; 95% CI, 1.04-4.97; P = .03)
• Lower eGFR (HR, 0.93; 95% CI, 0.92–0.95; P <.001)
• Increased proteinuria (HR, 1.17; 95% CI, 1.07-1.27; P <.001),
• Absence of RASI use (HR, 0.63; 95% CI, 0.37–1.06; P = .08)

Investigators were careful to note these findings were based on a patient population from a single center, thus restricting the generalizability of the results to broader or more diverse populations.¹

“In conclusion, our study, the first of its kind from Eastern Europe, reports a 20% mortality rate in IgAN patients, chiefly attributed to cardiovascular disease. Risk factors include age, high comorbidity burden, and reduced eGFR at diagnosis, while the use of renin-angiotensin-system inhibitors potentially improves survival,” investigators concluded.¹

References:

1. ^{Ștefan G, Zugravu A, Stancu S. Mortality in IgA Nephropathy: A Long-Term Follow-Up of an Eastern European Cohort. Medicina (Kaunas). 2024;60(2):247. doi:10.3390/medicina60020247}
2. ^{American Kidney Fund. IgA nephropathy. January 29, 2024. Accessed March 8, 2024. https://www.kidneyfund.org/all-about-kidneys/other-kidney-diseases/iga-nephropathy}