Urinary and renal interstitial concentrations of TNF-α increase prior to the rise in albuminuria in diabetic rats

Kalantarinia, Kambiz; Awad, Alaa S.; Siragy, Helmy M.

doi:10.1046/j.1523-1755.2003.00237.x

Cited by 156 publications

(137 citation statements)

References 26 publications

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“…Additionally, many studies have shown that changes in hormone levels, vasoactive peptides, cytokine, and growth factors are associated with diabetic nephropathy development and progression. Specifically, rat studies have suggested a functional role for the proinflammatory cytokine tumor necrosis factor (TNF)-␣ in the pathogenesis of diabetic nephropathy (19,20). Supporting this finding are intervention studies in patients with either diabetic or membranous nephropathy that found that the nonspecific TNF-␣ inhibitor pentoxifylline reduced both TNF-␣ and urinary proteinura (21,22).…”

Section: Drb1*04 and Reduced Diabetic Nephropathysupporting

confidence: 53%

Nephropathy in Type 1 Diabetes Is Diminished in Carriers of HLA-DRB1*04

et al. 2008

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OBJECTIVE—The purpose of this study was to examine whether known genetic risk factors for type 1 diabetes (HLA-DRB1, -DQA1, and -DQB1 and insulin locus) play a role in the etiology of diabetic nephropathy. RESEARCH DESIGN AND METHODS—Genetic analysis of HLA-DRB1, -DQA1, -DQB1 and the insulin gene (INS) was performed in the Genetics of Kidneys in Diabetes (GoKinD) collection of DNA (European ancestry subset), which includes case patients with type 1 diabetes and nephropathy (n = 829) and control patients with type 1 diabetes but not nephropathy (n = 904). The availability of phenotypic and genotypic data on GoKinD participants allowed a detailed analysis of the association of these genes with diabetic nephropathy. RESULTS—Diabetic probands who were homozygous for HLA-DRB1*04 were 50% less likely to have nephropathy than probands without any DRB1*04 alleles. In heterozygous carriers, a protective effect of this allele was not as clearly evident; the mode of inheritance therefore remains unclear. This association was seen in probands with both short (<28 years, P = 0.02) and long (≥28 years, P = 0.0001) duration of diabetes. A1C, a marker of sustained hyperglycemia, was increased in control probands with normoalbuminuira, despite long-duration diabetes, from 7.2 to 7.3 to 7.7% with 0, 1, and 2 copies of the DRB1*04 allele, respectively. This result is consistent with a protective effect of DRB1*04 that may allow individuals to tolerate higher levels of hyperglycemia, as measured by A1C, without developing nephropathy. CONCLUSIONS—These data suggest that carriers of DRB1*04 are protected from some of the injurious hyperglycemic effects related to nephropathy. Interestingly, DRB1*04 appears to be both a risk allele for type 1 diabetes and a protective allele for nephropathy.

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Section: Drb1*04 and Reduced Diabetic Nephropathysupporting

confidence: 53%

Nephropathy in Type 1 Diabetes Is Diminished in Carriers of HLA-DRB1*04

et al. 2008

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“…We also found that serum and urinary TNF-α levels were significantly higher in macroalbuminuric and microalbuminuric group compared to normoalbuminuric patients, similar results detected by Kalantarinia et al, (2003) they showed higher serum TNF-α levels both in macroalbuminuric and in microalbuminuric compared with normoalbuminuric patients [27]. In agreement with our results also, Wong et al, (2007) reported that the serum and urinary concentrations of TNF-α were elevated in DN as compared with non-diabetic individuals or with diabetic subjects without kidney disease and that these concentrations increase concomitantly with the progression of DN.…”

Section: Similar To Our Results Molitch Et Al (2004)supporting

confidence: 78%

Association of serum and urinary tumor necrosis factor-alpha (TNF-α) with albuminuria in diabetic nephropathy.

Rashad¹,

Al-Barshomy²,

Wadea³

et al. 2016

IJAR

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“…However, TNFa levels showed a close relationship with Hcy levels. In a study, urinary and interstitial TNFa concentrations were shown to be elevated in diabetic rats before the commencement of microalbuminuria (31). This finding suggests that TNFa may have a role in the complex pathogenesis of diabetic nephropathy.…”

Section: Discussionmentioning

confidence: 79%

Relation of plasma homocysteine levels to atherosclerotic vascular disease and inflammation markers in type 2 diabetic patients

Akalın¹,

Alataş²,

Çolak³

2008

European Journal of Endocrinology

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Objective: Both hyperhomocysteinemia and increased inflammatory activity are shown to be associated with atherosclerosis. The relation of inflammatory activity to homocysteine (Hcy) levels is not well established. In the present study, we aimed to evaluate the relation of plasma Hcy levels to atherosclerotic vascular disease and inflammatory activity in type 2 diabetic patients. Design and methods: In total 90 type 2 diabetic patients were included in the study. Of these patients, 41 had established atherosclerotic vascular disease and 49 had no evidence of atherosclerotic vascular disease. Hcy levels and markers of inflammation, namely C-reactive protein, fibrinogen, erythrocyte sedimentation rate, interleukin-6, and tumor necrosis factor a (TNFa), were measured. Glucose regulation, C-peptide, lipid parameters, and renal functions were also studied. Results: Both Hcy levels and inflammation markers were all significantly elevated in patients with atherosclerotic vascular disease when compared with patients without vascular disease. Reduced renal functions were responsible for the majority of Hcy elevation in patients with vascular disease. Also, renal functions were significantly associated with both Hcy levels and inflammatory markers. There was no correlation between Hcy levels and inflammation markers except for TNFa. Conclusions: Inflammatory activity and Hcy levels are increased in type 2 diabetic patients with atherosclerotic vascular disease. Impairment of renal functions is the key factor that affects both Hcy levels and inflammation markers. Inflammation is not involved in the process by which Hcy leads atherosclerosis in type 2 diabetes.European Journal of Endocrinology 158 47-52

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Urinary and renal interstitial concentrations of TNF-α increase prior to the rise in albuminuria in diabetic rats

Abstract: We found an early rise in renal TNF-alpha levels after induction of diabetes with STZ, which precedes the rise in UAE by about 2 weeks. These findings suggest a possible contribution of TNF-alpha in the complicated pathogenic process resulting in microalbuminuria in diabetes.

Cited by 156 publications

References 26 publications

Nephropathy in Type 1 Diabetes Is Diminished in Carriers of HLA-DRB1*04

Nephropathy in Type 1 Diabetes Is Diminished in Carriers of HLA-DRB1*04

Association of serum and urinary tumor necrosis factor-alpha (TNF-α) with albuminuria in diabetic nephropathy.

Relation of plasma homocysteine levels to atherosclerotic vascular disease and inflammation markers in type 2 diabetic patients

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