Lower urinary connective tissue growth factor levels and incident CKD stage 3 in the general population.

Abstract

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.

• Authors: Conall M O'Seaghdha, Shih-Jen Hwang, Nrupen A Bhavsar, Anna Köttgen, Josef Coresh, Brad C Astor, Caroline S Fox
• Journal: American journal of kidney diseases : the official journal of the National Kidney Foundation (Am J Kidney Dis) Vol. 57 Issue 6 Pg. 841-9 (Jun 2011) ISSN: 1523-6838 [Electronic] United States
• PMID: 21292366 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)
• Copyright: Published by Elsevier Inc.

Chemical References

• Biomarkers
• CCN2 protein, human
• Connective Tissue Growth Factor

Topics

• Biomarkers (urine)
• Connective Tissue Growth Factor (urine)
• Disease Progression
• Female
• Follow-Up Studies
• Glomerular Filtration Rate
• Humans
• Incidence
• Kidney Failure, Chronic (epidemiology, urine)
• Male
• Middle Aged
• Nephelometry and Turbidimetry
• Population Surveillance
• Prognosis
• Prospective Studies
• Severity of Illness Index
• United States (epidemiology)