Metabolic Syndrome Linked to Renal, Cardiovascular Outcomes in IgA Nephropathy

Tibor József Kovács, MD, PhD

Credit: ResearchGate

Findings from a recent study are calling attention to the prognostic role of the metabolic profile for predicting renal and cardiovascular endpoints in patients with IgA nephropathy (IgAN).¹

Specifically, results point to the predictive value of body mass index (BMI), hyperuricemia, hypertension, and diabetes for determining the prognosis of IgAN, suggesting the importance of early risk stratification based on patients’ metabolic profiles.¹

“There are limited data about the prevalence of metabolic syndrome and the metabolic profile association between metabolic syndrome and renal and cardiovascular outcomes in IgAN patients,” Tibor József Kovács, MD, PhD, a professor in the 2nd department of internal medicine and nephrology at the University of Pécs in Hungary, and colleagues wrote.¹ “More focus is being placed on identifying and treating the modifiable risk factors that can stop or slow down the deterioration of renal function.”

According to the American Kidney Fund, a bidirectional relationship between chronic kidney disease (CKD) and heart disease exists, with heart disease recognized as the most common cause of death among people on dialysis. Metabolic health is also an important consideration in both renal and cardiovascular health, with the American Heart Association formally defining the overlap between cardiovascular disease, kidney disease, type 2 diabetes, and obesity as cardiovascular-kidney-metabolic (CKM) syndrome. However, the specific impact of metabolic factors on renal and cardiovascular outcomes in patients with IgAN is not well understood.^2,3

To investigate the effects of metabolic syndrome and metabolic profiles on the renal and cardiovascular outcomes of IgAN, investigators prospectively assessed patients ≥ 18 years of age with confirmed IgAN who were not currently or previously on immunosuppressive treatment or had severe comorbidities. Metabolic syndrome was defined based on the National Cholesterol Education Program Adult Treatment Panel III criterion, which necessitates any 3 of the following 5 factors: waist circumference (>102 cm in males, >90 cm in females) or BMI > 27 kg/m2, fasting glucose ≥ 5.6 mmol/L, triglyceride ≥ 1.7 mmol/L, HDL cholesterol <1.0 mmol/L in males and <1.3 in females, and systolic/diastolic blood pressure >130/85 mmHg.¹

In total, 145 patients with chronic kidney disease (CKD) stages 1–4 diagnosed with IgA nephropathy were examined, although 20 patients were eventually excluded due to immunosuppressive therapy (n = 10), loss to follow-up (n =9), and withdrawn informed consent (n = 1), Thus, the remaining 125 patients’ data were investigated.¹

The primary composite endpoints were all-cause mortality and any cardiovascular event. Secondary cardiovascular endpoints were any cardiovascular event, such as stroke, myocardial infarction, or any revascularization. Secondary renal endpoints were reaching end-stage renal disease and starting renal replacement therapy. Investigators collected these data prospectively.¹

Among the study cohort, the average age was 53.0 ± 12.7 years, 74% of patients were male, and 52% had metabolic syndrome. The median follow-up time was 190 ± 170 months.¹

Investigators called attention to significant differences between the groups with and without metabolic syndrome, specifically in systolic blood pressure, pulse pressure, systolic diurnal rhythm, diastolic dysfunction, BMI, pre-diabetes, estimated glomerular filtration rate (eGFR), pulse wave velocity, high-density lipoprotein cholesterol, triglyceride, and uric acid, but not in age or gender.¹

Upon analysis of metabolic syndrome components, Kaplan–Meier curves showed significantly worse survival in cases of hypertension (primary endpoint: P = .004, secondary renal endpoint: P = .020; secondary CV endpoint: P = .0038), diabetes mellitus (P = .002, P = .008, P = .007), and a higher BMI (cut-off 25 kg/m2) (P = .028, P = .015, P = NS) in both primary and secondary endpoints. Of note, there was a non-significant difference in the primary and secondary outcomes in the case of dyslipidemia, but investigators found significant differences in the case of hyperuricemia (cut-off 360 µmol/L) (P <.001, P <.001, P = .029).¹

When comparing patients with IgAN with and without metabolic syndrome, investigators observed significant differences in survival on the Kaplan–Meier curves in the case of the primary combined endpoint (P <.001) and the secondary renal (P = .001) and cardiovascular endpoints (P = .001). Further analysis revealed the primary endpoint independent predictors of survival were dyslipidemia, eGFR, hemoglobin, urine albuminuria, and diabetes mellitus, as determined using Cox regression analysis. The secondary renal endpoint independent predictors were dyslipidemia, hemoglobin, urine albuminuria, and eGFR, while the secondary cardiovascular endpoint predictors were gender, BMI, and diabetes.¹

Cox regression analysis adjusted for metabolic syndrome components showed the primary endpoint and the secondary renal endpoint independent predictors were uric acid and diabetes. Of note, with more metabolic syndrome components, the primary endpoint rate increased significantly (MetS comp. 0 vs MetS comp. 2+, primary endpoints, P = .012).¹

Investigators outlined several potential limitations to these findings, including the small sample size and endpoint event rate, residual confounding, and the notably larger proportion of male participants versus female participants.¹

“Our study proved that despite the lower number of cases, but longer prospective follow-up, the importance of metabolic changes at the start of IgAN have an important impact on the outcome,” investigators concluded.¹ “Therefore, risk stratification of IgAN patients is very helpful in identifying high-risk individuals, especially when the metabolic profile is combined with an increased arterial stiffness evaluation for additional risk.”

References

1. ^{Sági B, Vas T, Csiky B, et al. Does Metabolic Syndrome and Its Components Have Prognostic Significance for Renal and Cardiovascular Outcomes in IgA Nephropathy? Biomedicines. 2024; 12(6):1250. https://doi.org/10.3390/biomedicines12061250}
2. ^{American Kidney Fund. Heart disease and chronic kidney disease (CKD). Accessed July 2, 2024. https://www.kidneyfund.org/all-about-kidneys/risk-factors/heart-disease-and-chronic-kidney-disease-ckd}
3. ^{Campbell, P. Kidney Week 2023: Evolving Recognition of Cardiovascular, Kidney, and Metabolic Disease. HCPLive. November 7, 2023. Accessed July 2, 2024. https://www.hcplive.com/view/kidney-week-2023-evolving-recognition-of-cardiovascular-kidney-metabolic-disease}