Inflammatory parameters are independently associated with urinary albumin in type 2 diabetes mellitus

Navarro, Juan F.; Mora, Carmen; Macıéa, Manuel; Garcıéa, Javier

doi:10.1016/s0272-6386(03)00408-6

Cited by 216 publications

(185 citation statements)

References 29 publications

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“…TNF-α undoubtedly contributes to renal diabetic pathology- The presence (or absence) of DN was considered as the outcome. The following parameters were considered as predictor variables: age, sex, diabetes duration, systolic and diastolic BP, HbA 1c and the genotypes of 45 SNPs a This is a constant of the equation indicating the predicted log odds for the dependent variable (case/control) when all the coefficients for the different independent variables are set to zero TNF-α levels are correlated with urinary albumin excretion in patients with type 2 diabetes at an early stage of nephropathy [35,36], as well as in rodents with streptozotocin-induced diabetes [37], and TNF-α is a potent inducer of AGER expression in endothelial cells [38]. Taken together, although the telomeric part of the MHC III appears to be an interesting region in the context of DN, more detailed mapping and functional studies are warranted to clarify potential causality of the particular markers.…”

Section: Discussionmentioning

confidence: 99%

Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach

et al. 2007

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Aims/hypothesis In the present study we investigated potential associations of a set of 45 single nucleotide polymorphisms (SNP) in 20 candidate genes on eight chromosomes with diabetic nephropathy (DN) in type 2 diabetes mellitus. We aimed to compare two methodological approaches suitable for analysing susceptibility to complex traits: single-and multi-locus analyses. Materials and methods The study comprised a total of 647 subjects in one of three groups: diabetes with or without DN, or no diabetes. Genotypes were detected by PCRbased methodology (PCR only, PCR plus RFLP, or allelespecific PCR). Haplotypes were inferred in silico. Set association (tested using SUMSTAT software) was used for multilocus analysis.

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Section: Discussionmentioning

confidence: 99%

Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach

et al. 2007

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“…There has been increasing interest in the past few years in the relevance of inflammation in diabetes (2) and its role in the pathogenesis of diabetic complications, including nephropathy (7,8). Increased concentrations of inflammatory parameters (Creactive protein, sialic acid, fibrinogen, TNF-␣, IL-1, and IL-6) have been reported in patients with diabetes (3)(4)(5)(6)29).…”

Section: Discussionmentioning

confidence: 99%

“…This antiproteinuric effect has been related to an increase in erythrocyte deformability with reduction of blood viscosity and a subsequent decrease of glomerular hydraulic pressure (51), to a blockade of adenosine receptors (52), and based on its anti-TNF-␣ properties (53,54), the modulation of immune and inflammatory responses has also been suggested as a potential antiproteinuric mechanism of PTF (7,8,19). In our study, in addition to a decrease of UAE, a significant reduction of serum and urinary TNF-␣ levels was observed in patients who received PTF (14.9 and 13%, respectively).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, this inflammatory condition has been related to diabetic complications, including nephropathy. Several studies have reported that serum levels of inflammatory markers are higher in patients with diabetes and increased urinary albumin excretion (UAE) when compared with normoalbuminuric individuals (5)(6)(7). Furthermore, findings from the Insulin Resistance Atherosclerosis Study showed an association of C-reactive protein and fibrinogen with UAE in individuals with type 2 diabetes and microalbuminuria (6).…”

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confidence: 99%

“…Finally, in a previous study, we found that urinary TNF-␣ level was an independent predictor of UAE in individuals with type 2 diabetes (7). Therefore, inflammation emerges as a potential mechanism in the pathogenesis of renal injury in type 2 diabetes (7,8).…”

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Additive Antiproteinuric Effect of Pentoxifylline in Patients with Type 2 Diabetes under Angiotensin II Receptor Blockade

Navarro¹,

Mora²,

Muros³

et al. 2005

Journal of the American Society of Nephrology

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115

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Despite the beneficial effects of blockade of the renin-angiotensin system in diabetic nephropathy (DN), albuminuria and progression of renal disease are not completely halted by these agents. Therefore, it is necessary to explore potential antiproteinuric and renoprotective effects of innovative therapeutic approaches. This study tested the hypothesis that the combination of pentoxifylline (PTF) with angiotensin II receptor blockers in normotensive patients with type 2 diabetes produces an additive antiproteinuric effect. Sixty-one patients with DN and residual albuminuria despite treatment with the recommended doses of ARB for >1 yr were randomly assigned to receive the addition of 1200 mg of PTF daily (n ‫؍‬ 30) or to a control group (n ‫؍‬ 31). Baseline characteristics were similar between groups, and correlation analysis showed a significant association between urinary albumin excretion (UAE) and urinary TNF-␣ (R ‫؍‬ 0.53, P < 0.001). After 4 mo, albuminuria showed a significant decrease in patients who received PTF, from 900 mg/24 h (466 to 1542 mg/d) to 791 mg/24 h (309 to 1400 mg/d; P < 0.001), whereas no significant changes were observed in the control group: 920 mg/24 h (450 to 1489 mg/d) at baseline, and 900 mg/24 h (428 to 1800 mg/d) at the end of the study. The mean percentage variation of UAE in the treatment and control groups was ؊16.7 and 5.5%, respectively (between-group comparison, P < 0.001). This additive antiproteinuric effect was not dependent on changes in BP or metabolic control. However, both serum and urinary levels of TNF-␣ also decreased in patients who received PTF, from 6.4 pg/ml (2.1 to 9.7) and 16 pg/mg (8 to 29) at baseline to 4.6 pg/ml (0.4 to 9) and 14.2 pg/mg (3 to 26) at the end of the study, respectively (P < 0.01), without significant variations in control patients. Moreover, regression analysis at the end of the study showed a correlation between the change in UAE and the change in urinary TNF-␣ in patients who were treated with PTF (R ‫؍‬ 0.49, P < 0.001). In conclusion, administration of PTF to patients who have type 2 diabetes and are under long-term treatment with an ARB produces a significant additive antiproteinuric effect associated with a reduction of urinary TNF-␣ excretion.

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Pentoxifylline for diabetic kidney disease

Wu¹,

Yuan²,

Zhou³

et al. 2007

Cochrane Database of Systematic Reviews

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Inflammatory parameters are independently associated with urinary albumin in type 2 diabetes mellitus

Cited by 216 publications

References 29 publications

Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach

Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach

Additive Antiproteinuric Effect of Pentoxifylline in Patients with Type 2 Diabetes under Angiotensin II Receptor Blockade

Pentoxifylline for diabetic kidney disease

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