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Lower urinary connective tissue growth factor levels and incident CKD stage 3 in the general population
Conall M O'Seaghdha1, Shih-Jen Hwang, Nrupen A Bhavsar
1Division of Intramural Research, National Heart, Lung and Blood Institute/NIH, Bethesda, MD 20892, USA.
Insights
Lower urinary connective tissue growth factor (CTGF) levels were associated with a reduced risk of developing chronic kidney disease (CKD) stage 3 in a general population study. These findings suggest CTGF may play a protective role in kidney health.
Area of Science:
- Nephrology
- Biomarkers
- Chronic Kidney Disease (CKD) Research
Background:
- Connective tissue growth factor (CTGF) is implicated in kidney disease progression and fibrosis.
- Its role in mesangial repair suggests potential protective functions.
- The association between urinary CTGF and the development of CKD stage 3 in the general population remains unclear.
Purpose of the Study:
- To investigate the relationship between baseline urinary CTGF levels and the incidence of CKD stage 3 in the general population.
- To determine if urinary CTGF can serve as a predictive biomarker for CKD development.
Main Methods:
- Nested case-control studies were conducted within the Framingham Heart Study and the Atherosclerosis Risk in Communities (ARIC) Study.
- Urinary CTGF concentrations were measured in participants who developed incident CKD stage 3 (eGFR <60 mL/min/1.73 m(2)) and matched controls with eGFR ≥60 mL/min/1.73 m(2).
- Multivariable regression analyses were performed, adjusting for known CKD risk factors.
Main Results:
- In the Framingham Heart Study, lower median baseline urinary CTGF concentrations were observed in cases compared to controls (P < 0.0001).
- A multivariable-adjusted odds ratio of 0.33 (P < 0.001) per 1-SD increase in log urinary CTGF was associated with a reduced risk of incident CKD stage 3.
- Similar inverse trends were observed in the ARIC study and in meta-analyses, particularly in participants without diabetes.
Conclusions:
- Lower urinary CTGF concentrations appear to precede the onset of CKD stage 3 in the general population.
- This suggests an inverse association between urinary CTGF and CKD development.
- Further research is needed to elucidate the precise mechanisms by which CTGF influences CKD risk.
Background:
Connective tissue growth factor (CTGF) is involved in the development and progression of kidney diseases, including diabetic nephropathy and kidney fibrosis, but also may have a role in mesangial repair after injury. It is unknown whether, in the general population, urinary CTGF levels are associated with a decrease in estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73 m(2) (ie, development of chronic kidney disease [CKD] stage 3).
Study Design:
Nested case-control.
Setting & Participants:
100 cases of incident CKD stage 3 and 100 age-and sex-matched controls in the Framingham Heart Study; 141 cases and 135 age-, sex-, and race-matched controls in the Atherosclerosis Risk in Communities (ARIC) Study. Controls had eGFR ≥60 mL/min/1.73 m(2) at follow-up in both studies.
Predictors:
Urinary CTGF concentrations.
Outcomes:
Incident CKD stage 3, defined as eGFR <60 mL/min/1.73 m(2).
Measurements:
Stored urine samples from Framingham Heart Study and ARIC were measured for CTGF. Covariates were obtained from Framingham Heart Study and ARIC participant examinations.
Results:
In the Framingham Heart Study, the median baseline urinary CTGF concentration was lower in cases (1.35 ng/mL) than controls (2.35 ng/mL; paired t test, P < 0.0001). The multivariable-adjusted OR for incident CKD stage 3 was 0.33 (95% CI, 0.17-0.64; P < 0.001) per 1-standard deviation in log urinary CTGF level after adjustment for CKD risk factors, baseline eGFR, and baseline log urinary albumin-creatinine ratio, with similar results in participants without diabetes (n = 184). Results were not materially different when urinary CTGF level was indexed to urinary creatinine level (multivariable-adjusted OR, 0.34; 95% CI, 0.21-0.56; P < 0.001). A similar, but nonsignificant, trend of risk of incident CKD stage 3 with lower baseline urinary CTGF concentration was observed in an independent case-control study conducted in the ARIC Study, with the strongest results observed in participants free of diabetes. This inverse relationship was robust in meta-analysis of both the overall and diabetes-free groups.
Limitations:
Observational study; causality cannot be inferred.
Conclusions:
Lower urinary CTGF concentrations precede the onset of CKD stage 3 in the general population. Further work is required to fully characterize how CTGF level influences risk of CKD.
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