Effects of antiproteinuric intervention on elevated connective tissue growth factor (CTGF/CCN-2) plasma and urine levels in nondiabetic nephropathy.

Abstract

BACKGROUND AND OBJECTIVES:

Connective tissue growth factor (CTGF/CCN-2) is a key player in fibrosis. Plasma CTGF levels predict end-stage renal disease and mortality in diabetic chronic kidney disease (CKD), supporting roles in intra- and extrarenal fibrosis. Few data are available on CTGF in nondiabetic CKD. We investigated CTGF levels and effects of antiproteinuric interventions in nondiabetic proteinuric CKD.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:

In a crossover randomized controlled trial, 33 nondiabetic CKD patients (3.2 [2.5 to 4.0] g/24 h proteinuria) were treated during 6-week periods with placebo, ARB (100 mg/d losartan), and ARB plus diuretics (100 mg/d losartan plus 25 mg/d hydrochlorothiazide) combined with consecutively regular and low sodium diets (193 ± 62 versus 93 ± 52 mmol Na(+)/d).

RESULTS:

CTGF was elevated in plasma (464 [387 to 556] pmol/L) and urine (205 [135 to 311] pmol/24 h) of patients compared with healthy controls (n = 21; 96 [86 to 108] pmol/L and 73 [55 to 98] pmol/24 h). Urinary CTGF was lowered by antiproteinuric intervention, in proportion to the reduction of proteinuria, with normalization during triple therapy (CTGF 99 [67 to 146] in CKD versus 73 [55 to 98] pmol/24 h in controls). In contrast, plasma CTGF was not affected.

CONCLUSIONS:

Urinary and plasma CTGF are elevated in nondiabetic CKD. Only urinary CTGF is normalized by antiproteinuric intervention, consistent with amelioration of tubular dysfunction. The lack of effect on plasma CTGF suggests that its driving force might be independent of proteinuria and that short-term antiproteinuric interventions are not sufficient to correct the systemic profibrotic state in CKD.

• Authors: Maartje C J Slagman, Tri Q Nguyen, Femke Waanders, Liffert Vogt, Marc H Hemmelder, Gozewijn D Laverman, Roel Goldschmeding, Gerjan Navis
• Journal: Clinical journal of the American Society of Nephrology : CJASN (Clin J Am Soc Nephrol) Vol. 6 Issue 8 Pg. 1845-50 (Aug 2011) ISSN: 1555-905X [Electronic] United States
• PMID: 21784839 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Biomarkers
• CCN2 protein, human
• Diuretics
• Hydrochlorothiazide
• Connective Tissue Growth Factor
• Losartan

Topics

• Angiotensin II Type 1 Receptor Blockers (therapeutic use)
• Biomarkers (blood, urine)
• Chronic Disease
• Combined Modality Therapy
• Connective Tissue Growth Factor (blood, urine)
• Cross-Over Studies
• Diet, Sodium-Restricted
• Diuretics (therapeutic use)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Humans
• Hydrochlorothiazide (therapeutic use)
• Kidney Diseases (blood, therapy, urine)
• Losartan (therapeutic use)
• Male
• Middle Aged
• Netherlands
• Proteinuria (blood, therapy, urine)
• Time Factors
• Treatment Outcome
• Up-Regulation