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

Conall M. O'Seaghdha, Shih Jen Hwang, Nrupen A. Bhavsar, Anna Kttgen, Josef Coresh, Brad C. Astor, Caroline S. Fox

Research output: Contribution to journalArticlepeer-review


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 m2 (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 m2 at follow-up in both studies. Predictors: Urinary CTGF concentrations. Outcomes: Incident CKD stage 3, defined as eGFR <60 mL/min/1.73 m2. 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.

Original languageEnglish (US)
Pages (from-to)841-849
Number of pages9
JournalAmerican Journal of Kidney Diseases
Issue number6
StatePublished - Jun 2011


  • Chronic kidney disease
  • connective tissue growth factor
  • epidemiology

ASJC Scopus subject areas

  • Nephrology


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