Metabolic Syndrome Components Influence IgA Nephropathy Prognosis, Study Finds

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New research is calling attention to a significant association between metabolic syndrome (MS) components and IgA nephropathy (IgAN) prognosis.¹

Study findings suggest that as the number of MS components increases, so does the risk of adverse outcomes. Of note, blood pressure was determined to be the most significant factor influencing IgAN outcomes.¹

According to the US Centers for Disease Control and Prevention, diabetes; high blood pressure; heart disease; and obesity are significant risk factors for chronic kidney disease. In recognition of the significant association between metabolic risk factors, chronic kidney disease, and the cardiovascular system, the American Heart Association released a Presidential Advisory on cardiovascular-kidney-metabolic syndrome.^2,3

“Patients with kidney disease often present with a complex interplay of metabolic abnormalities that reinforce each other,” Xiaoling Zhou, a professor at the General Hospital of Ningxia Medical University, and colleagues wrote.¹ “Nevertheless, most studies have concentrated on the function of distinct metabolic components in IgAN, frequently ignoring the combined effects of several metabolic elements.”

To address this gap in research, investigators conducted a retrospective cohort study of patients with primary IgAN seen at the General Hospital of Ningxia Medical University between August 2008 and December 2018. For inclusion, patients were required to have a primary IgAN diagnosis through renal biopsy with ≥ 8 glomeruli; be ≥ 18 years of age; and have ≥ 1 year of regular follow-up.¹

Study follow-up began on the date of the initial renal biopsy and continued until the occurrence of death; end-stage renal disease; a doubling of serum creatinine; acute cardiovascular or cerebrovascular events; or the study’s termination on June 30, 2020.¹

Of 1147 patients screened by investigators, 698 met the study’s inclusion criteria and were included in the final analysis. Among the cohort, the mean age was 35.83 ± 11.20 years and 51.86% of participants were male.¹

Investigators defined MS according to criteria from the Chinese Diabetes Society, which requires the presence of ≥ 3 of the following components:

• Overweight/obesity: a body mass index (BMI) ≥ 25 kg/m2
• Hyperglycemia: fasting plasma glucose ≥ 6.1 mmol/L, and/or 2-h postprandial blood glucose (2hPG) ≥ 7.8 mmol/L, and/or individuals diagnosed with glycosuria and under treatment
• Hypertension: blood pressure ≥ 140/90 mmHg, and/or individuals diagnosed and treated for hypertension
• Dyslipidemia: fasting triglycerides ≥ 1.7 mmol/L, and/or high-density lipoprotein cholesterol < 0.9 mmol/L in males, HDL-C < 1.0 mmol/L in females

Based on these criteria, 25.07% of the study cohort was classified as having MS. Investigators further categorized participants into groups according to the number of metabolic components they had: Group A (0 components), Group B (1 component), Group C (2 components), Group D (3 components), and Group E (≥ 4 components).¹

Upon analysis, 24-hour urinary protein quantification was positively correlated with BMI; systolic blood pressure; diastolic blood pressure; triglycerides; and the number of metabolic components. In contrast, eGFR was negatively correlated with BMI; systolic blood pressure; diastolic blood pressure; glucose; triglycerides; uric acid; and the number of metabolic components.¹

During a median follow-up of 115.25 (IQR, 12,136) months, 124 patients experienced endpoints, including 12 deaths, 93 combined renal endpoints (end-stage renal disease or creatinine doubling), and 19 cardiovascular events. Although significant differences were observed in the rates of composite renal endpoints and cardiovascular endpoints among the 5 groups of IgAN patients with varying numbers of metabolic components (P <.05), investigators did not find a significant difference in the rate of death among these groups (P >.05).¹

Kaplan-Meier survival analysis showed that renal survival decreased progressively with an increasing number of metabolic components. The worst prognosis was observed when ≥ 4 components were combined (Group E) (log-rank = 26.547; P <.001).¹

Investigators noted renal survival was significantly lower in Group E compared with Group A (log-rank = 25.816; P <.001); Group E compared with Group B (log-rank = 10.398; P <.001); and Group E compared with Group C (log-rank = 5.856; P = .016). However, no significant differences in renal survival were observed between Group E and Group D (log-rank = 2.789; P = .095).¹

Further analysis using the random forest method revealed blood pressure was the most critical factor influencing the occurrence of endpoint events, followed by uric acid, BMI, and low-density lipoprotein.¹

Investigators acknowledged multiple limitations to these findings, including the retrospective, single-center study; limited generalizability; the lack of data on medication management for individual metabolic components or the effects of lifestyle interventions; and the use of the Chinese Diabetes Society diagnostic criteria, using BMI as a surrogate for abdominal obesity.¹

“As the number of MS components increases, so does the risk of adverse outcomes in these patients. Blood pressure stands out as a critical factor, and elucidating its pathogenic mechanisms, particularly the role of MS and its components in the progression of IgA nephropathy, remains unclear and necessitates further research,” investigators concluded.¹

References

1. ^{Ma H, Lei C, Zhao B, et al. The impact of metabolic component count on IgA nephropathy prognosis. Sci Rep. https://doi.org/10.1038/s41598-024-81929-3}
2. ^{US Centers for Disease Control and Prevention. Risk Factors for Chronic Kidney Disease. May 15, 2024. Accessed January 9, 2025. https://www.cdc.gov/kidney-disease/risk-factors/index.html}
3. ^{Ndumele CE, Rangaswami J, Chow SL, et al. Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association. AHA Journals. https://doi.org/10.1161/CIR.0000000000001184}