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Urinary complement factor D is increased in primary malignant hypertension: a single-center, cross-sectional study
Yaqi Cheng1, Weiwei Qin2,3, Liling Lin4
1Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China.
Insights
Researchers identified urinary complement factor D (CFD) as a potential non-invasive biomarker for kidney damage in primary malignant hypertension (pMHTN). Elevated CFD levels may indicate alternative complement pathway activation in pMHTN patients.
Area of Science:
- Nephrology
- Biochemistry
- Proteomics
Background:
- Kidney injury is a serious complication of primary malignant hypertension (pMHTN).
- Non-invasive biomarkers are needed for diagnosing pMHTN-related renal damage and understanding its mechanisms.
- Urine protein analysis offers a promising avenue for biomarker discovery.
Purpose of the Study:
- To identify and validate urinary protein biomarkers for renal damage associated with pMHTN.
- To explore the diagnostic potential of these biomarkers in differentiating pMHTN from other conditions.
Main Methods:
- Discovery phase: In-gel digestion coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) on urine samples from pMHTN patients, disease controls (DCs), and healthy controls (HCs).
- Validation phase: Enzyme-linked immunosorbent assay (ELISA) to quantify differentially expressed proteins in a larger cohort.
- Receiver operating characteristic (ROC) curve analysis to assess diagnostic performance.
Main Results:
- LC-MS/MS identified 5 differentially expressed proteins in pMHTN patients.
- Urinary complement factor D (CFD) was significantly upregulated in pMHTN patients compared to DCs and HCs.
- Urinary CFD/Creatinine ratio demonstrated moderate potential in discriminating pMHTN from DCs (AUC = 0.822).
Conclusions:
- Urinary CFD is a potential non-invasive biomarker for renal damage in pMHTN.
- Elevated urinary CFD suggests activation of the alternative complement pathway in pMHTN.
- Further research is warranted to confirm CFD's clinical utility in pMHTN management.
Abstract:
Kidney injury is one of the detrimental consequences of primary malignant hypertension (pMHTN). There is a paucity of non-invasive biomarkers to enhance diagnosis and elucidate the underlying mechanisms. This study aims to explore urine protein biomarkers for pMHTN associated renal damage. In the discovery phase, urine samples were collected from 8 pMHTN, 19 disease controls (DCs), and 5 healthy controls (HCs). In-gel digestion combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach was used for identification of proteins associated with pMHTN. In the validation phase, the differentially expressed proteins were validated by ELISA assay in cohort with 10 pMHTN patients, 37 DCs, and 30 HCs. Compared to DCs and HCs, a specific band between 15 and 25 kDa was found in 7 out of 8 patients with pMHTN. Further LC-MS/MS analysis revealed 5 differentially expressed proteins. ELISA validation demonstrated that urinary complement factor D (CFD) was significantly up regulated in pMHTN. By receiver operating characteristic curve analysis, urinary CFD/Cr showed moderate potential in discriminating pMHTN from DCs (the area under curve: 0.822, 95% CI 0.618-0.962). Urinary CFD may be a potential biomarker for pMHTN with its elevation indicative of the activation of the alternative complement pathway in pMHTN.
