Urinary TGF-β1 reduction related to a decrease of systolic blood pressure in patients with type 2 diabetes and clinical diabetic nephropathy

Bertoluci, Marcello Casaccia; Uebel, Deise; Schmidt, Alexandre; Thomazelli, Fulvio Clemo Santos; Oliveira, Fernanda Ramos de; Schmid, Helena

doi:10.1016/j.diabres.2005.10.027

Cited by 16 publications

(11 citation statements)

References 21 publications

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“…Because all groups underwent 6 months of aggressive BP reduction before entering the protocol, 25 sustained effects of this BP reduction might have reduced UTGF similarly in all three CKD 1 groups. 26 Similar to UNAG, UTGF increased in CKD 2 without intervention but UTGF decreased significantly in CKD 2 patients given NaHCO 3 and F þ V, and the net UTGF decrease between the two interventions to reduce dietary acid was not different. These latter data support the fact that reduced dietary acid decreased UTGF and, similar to the data described for UNAG, the lower Sys BP in CKD 2 given F þ V compared with NaHCO 3 appears not to have been additive after 30 days.…”

Section: Discussionmentioning

confidence: 65%

Dietary acid reduction with fruits and vegetables or bicarbonate attenuates kidney injury in patients with a moderately reduced glomerular filtration rate due to hypertensive nephropathy

Goraya

Simoni

et al. 2012

Kidney International

280

210

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The neutralization of dietary acid with sodium bicarbonate decreases kidney injury and slows the decline of the glomerular filtration rate (GFR) in animals and patients with chronic kidney disease. The sodium intake, however, could be problematic in patients with reduced GFR. As alkali-induced dietary protein decreased kidney injury in animals, we compared the efficacy of alkali-inducing fruits and vegetables with oral sodium bicarbonate to diminish kidney injury in patients with hypertensive nephropathy at stage 1 or 2 estimated GFR. All patients were evaluated 30 days after no intervention; daily oral sodium bicarbonate; or fruits and vegetables in amounts calculated to reduce dietary acid by half. All patients had 6 months of antihypertensive control by angiotensin-converting enzyme inhibition before and during these studies, and otherwise ate ad lib. Indices of kidney injury were not changed in the stage 1 group. By contrast, each treatment of stage 2 patients decreased urinary albumin, N-acetyl β-D-glucosaminidase, and transforming growth factor β from the controls to a similar extent. Thus, a reduction in dietary acid decreased kidney injury in patients with moderately reduced eGFR due to hypertensive nephropathy and that with fruits and vegetables was comparable to sodium bicarbonate. Fruits and vegetables appear to be an effective kidney protective adjunct to blood pressure reduction and angiotensin-converting enzyme inhibition in hypertensive and possibly other nephropathies.

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Section: Discussionmentioning

confidence: 65%

Dietary acid reduction with fruits and vegetables or bicarbonate attenuates kidney injury in patients with a moderately reduced glomerular filtration rate due to hypertensive nephropathy

Goraya

Simoni

et al. 2012

Kidney International

280

210

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“…Individuals with higher levels of either biomarker were also more likely to have prevalent diabetes. 25–27 NT-proBNP levels were higher among individuals with higher PIIINP, but not among individuals with higher TGF-β. TGF-β levels were weakly positively correlated with PIIINP levels (Spearman r = 0.08, P = 0.001).…”

Section: Resultsmentioning

confidence: 82%

Fibrosis-Related Biomarkers and Incident Cardiovascular Disease in Older Adults

Agarwal

Glazer

Barasch

et al. 2014

Circ: Arrhythmia and Electrophysiology

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Background Fibrotic changes in the heart and arteries have been implicated in a diverse range of cardiovascular diseases (CVD), but whether circulating biomarkers that reflect fibrosis are associated with CVD is unknown. Methods and Results We determined the associations of two biomarkers of fibrosis, transforming growth factor- β (TGF-β) and procollagen type III N-terminal propeptide (PIIINP), with incident heart failure, myocardial infarction (MI), and stroke among community-living older adults in the Cardiovascular Health Study. We measured circulating TGF-β (n=1,371) and PIIINP (n=2,568) from plasma samples collected in 1996 and ascertained events through 2010. Given TGF-β’s pleiotropic effects on inflammation and fibrogenesis, we investigated potential effect modification by C-reactive protein (CRP) in secondary analyses. After adjustment for sociodemographic, clinical, and biochemical risk factors, PIIINP was associated with total CVD (hazard ratio [HR] per standard deviation [SD]=1.07, 95% confidence interval [CI]: 1.01-1.14) and heart failure (HR per SD=1.08, CI: 1.01-1.16), but not MI or stroke. TGF-β was not associated with any CVD outcomes in the full cohort, but was associated with total CVD (HR per SD=1.16, CI: 1.02-1.31), heart failure (HR per SD=1.16, CI: 1.01-1.34), and stroke (HR per SD=1.20, CI: 1.01-1.42) among individuals with CRP above the median, 2.3 mg/L (P-interaction < 0.05). Conclusions Our findings provide large-scale, prospective evidence that circulating biomarkers of fibrosis, measured in community-living individuals late in life, are associated with CVD. Further research on whether TGF-β has a stronger fibrogenic effect in the setting of inflammation is warranted.

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“…The latter was upregulated in urine of patients with diabetic nephropathy (DN) (Wada et al, 2000) and was decreased by spironolactone treatment (Takebayashi et al, 2006) suggesting regulation by the MR. TGF-β 1 has been demonstrated to reduce collagenase production thereby leading to accumulation of extracellular matrix components (Wolf, 2006). Importantly, Tgf-β 1 is increased in plasma of type 2 diabetics (Pfeiffer et al, 1996) and urine of type 2 diabetics with clinical diabetic nephropathy (Bertoluci et al, 2006) further supporting its role in the pathogenesis of this disease. In accordance with our findings, aldosterone infusion has been shown to increase TGF-β 1 protein expression in rat kidney (Juknevicius et al, 2004) and both TGF-β 1 and aldosterone independently stimulated connective tissue growth factor (CTGF), an inducer of renal fibroblast growth and synthesis of extracellular matrix proteins (Yokoi et al, 2001).…”

Section: Discussionmentioning

confidence: 96%

PF-03882845, a non-steroidal mineralocorticoid receptor antagonist, prevents renal injury with reduced risk of hyperkalemia in an animal model of nephropathy

et al. 2013

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The mineralocorticoid receptor (MR) antagonists PF-03882845 and eplerenone were evaluated for renal protection against aldosterone-mediated renal disease in uninephrectomized Sprague-Dawley (SD) rats maintained on a high salt diet and receiving aldosterone by osmotic mini-pump for 27 days. Serum K+ and the urinary albumin to creatinine ratio (UACR) were assessed following 14 and 27 days of treatment. Aldosterone induced renal fibrosis as evidenced by increases in UACR, collagen IV staining in kidney cortex, and expression of pro-fibrotic genes relative to sham-operated controls not receiving aldosterone. While both PF-03882845 and eplerenone elevated serum K+ levels with similar potencies, PF-03882845 was more potent than eplerenone in suppressing the rise in UACR. PF-03882845 prevented the increase in collagen IV staining at 5, 15 and 50 mg/kg BID while eplerenone was effective only at the highest dose tested (450 mg/kg BID). All doses of PF-03882845 suppressed aldosterone-induced increases in collagen IV, transforming growth factor-β 1 (Tgf-β 1), interleukin-6 (Il-6), intermolecular adhesion molecule-1 (Icam-1) and osteopontin gene expression in kidney while eplerenone was only effective at the highest dose. The therapeutic index (TI), calculated as the ratio of the EC50 for increasing serum K+ to the EC50 for UACR lowering, was 83.8 for PF-03882845 and 1.47 for eplerenone. Thus, the TI of PF-03882845 against hyperkalemia was 57-fold superior to that of eplerenone indicating that PF-03882845 may present significantly less risk for hyperkalemia compared to eplerenone.

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Urinary TGF-β1 reduction related to a decrease of systolic blood pressure in patients with type 2 diabetes and clinical diabetic nephropathy

Cited by 16 publications

References 21 publications

Dietary acid reduction with fruits and vegetables or bicarbonate attenuates kidney injury in patients with a moderately reduced glomerular filtration rate due to hypertensive nephropathy

Dietary acid reduction with fruits and vegetables or bicarbonate attenuates kidney injury in patients with a moderately reduced glomerular filtration rate due to hypertensive nephropathy

Fibrosis-Related Biomarkers and Incident Cardiovascular Disease in Older Adults

PF-03882845, a non-steroidal mineralocorticoid receptor antagonist, prevents renal injury with reduced risk of hyperkalemia in an animal model of nephropathy

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