Association between urinary C4d levels and disease progression in IgA nephropathy

Yaping Dong; Zi Wang; Weiyi Guo; Li Zhu; Xujie Zhou; Sufang Shi; Lijun Liu; Jicheng Lv; Hong Zhang

doi:10.1093/ndt/gfae001

Association between urinary C4d levels and disease progression in IgA nephropathy

Nephrol Dial Transplant. 2024 Jan 4:gfae001. doi: 10.1093/ndt/gfae001. Online ahead of print.

Authors

Yaping Dong^{1

2

3}, Zi Wang^{1

2

3}, Weiyi Guo^{1

2

3

4}, Li Zhu^{1

2

3}, Xujie Zhou^{1

2

3}, Sufang Shi^{1

2

3}, Lijun Liu^{1

2

3}, Jicheng Lv^{1

2

3}, Hong Zhang^{1

2

3}

Affiliations

¹ Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China.
² Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China.
³ Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China.
⁴ Renal Division, Beijing Anzhen Hospital Capital Medical University.

PMID: 38178632
DOI: 10.1093/ndt/gfae001

Abstract

Background: C4d mesangial deposition, a hallmark of lectin pathway activation in IgA nephropathy (IgAN), has been shown to be associated with risk of kidney failure. To date, the relationship between urinary C4d and renal outcome remain unelucidated.

Methods: A total of 508 patients with biopsy-proven IgAN were enrolled in this study, whose baseline urine samples at the time of biopsy were collected and the levels of urinary C4d were quantified by enzyme-linked immunosorbent assay. The time-averaged C4d (TA-C4d) and the change in proteinuria were measured in sequential urine samples obtained from IgAN patients. The kidney progression event was defined as a 50% estimated glomerular filtration rate (eGFR) decline or end-stage kidney disease (ESKD) or death.

Results: After a median follow-up of 36 months, 70 (13.8%) of the participants reached the kidney progression event. Higher levels of urinary C4d/creatinine were found to be associated with decreased eGFR, massive proteinuria, lower serum albumin levels, hypertension, and severe Oxford E and T scores. Upon adjusting for traditional risk factors (including demographics, eGFR, proteinuria, hypertension, Oxford pathologic score, and immunosuppressive therapy), elevated levels of urinary C4d/creatinine were independently associated with an increased risk of CKD progression (adjusted HR per standard deviation increment of log-transformed C4d/creatinine: 1.46; 95% CI: 1.04 to 2.06; P=0.030). In reference to the low C4d group, the risk of poor renal outcome increased for the high C4d group (adjusted HR: 1.93; 95% CI: 1.05 to 3.54; P=0.033). Additionally, a low baseline C4d level was independently assosicated with a favorable proteinuria response to immunosuppressive therapy at three months (adjusted relative risk: 2.20; 95% CI: 1.04-4.63, P=0.038).

Conclusion: The urinary C4d, serving as a non-invasive biomarker, is associated with the progression of IgAN and holds the potential to predict proteinuria response in this disease.

Keywords: IgA nephropathy; biomarker; lectin pathway; renal progression; urinary C4d.