A pilot randomized controlled trial of renal protection with pioglitazone in diabetic nephropathy

Agarwal, Rajiv; Saha, Chandan; Battiwala, Meher; Vasavada, Nina; Curley, Timothy; Chase, Shawn D.; Sachs, Nadine G.; Semret, Merfake H.

doi:10.1111/j.1523-1755.2005.00416.x

Cited by 63 publications

(51 citation statements)

References 45 publications

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“…Glipizide produced a mean increase in proteinuria of 6.1%, whereas pioglitazone therapy was followed by a proteinuria reduction of 7.2%. This difference, however, was not statistically significant (78).…”

Section: Diabetic Nephropathymentioning

confidence: 54%

“…At 12 months, UAE was also significantly lower in pioglitazone-treated patients in comparison with those treated with glibenclamide and voglibose (77). More recently, Agarwal et al (78) reported the result of a randomised, open-label, study comparing glipizide with pioglitazone over 16 weeks in 44 type 2 diabetic patients with overt diabetic nephropathy. Glipizide produced a mean increase in proteinuria of 6.1%, whereas pioglitazone therapy was followed by a proteinuria reduction of 7.2%.…”

Section: Diabetic Nephropathymentioning

confidence: 94%

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Peroxisome proliferator-activated receptor gamma agonists in renal disease

Iglesias

Díez

2006

eur j endocrinol

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Type 2 diabetes is a well recognised cause of chronic renal failure (CRF). Only few oral antidiabetic drugs can be used for treating type 2 diabetes in patients with CRF. Among them are repaglinide, a rapid-acting prandial insulin releaser, and peroxisome proliferator-activated receptor gamma (PPARg) agonists, such as rosiglitazone and pioglitazone. These compounds are metabolised in the liver, therefore accumulation of the drug and the risk of severe and prolonged hypoglycaemia are minimised. PPARg receptors are expressed in many tissues including the kidney. Recently, numerous healthful effects of PPARg agonists on several aspects related to renal function have been increasingly reported. These drugs have shown to possess many advantageous anti-inflammatory, haemodynamic, vascular and metabolic effects. In the present paper we have reviewed the more recent experimental studies that evaluated these potential beneficial effects of PPARg agonists on renal function and revised the results of their utilisation in patients with different degrees of renal impairment, in dialysis patients, and in patients with diabetes mellitus after kidney transplantation. Finally, tolerability and safety profile of PPARg agonists in patients with reduced glomerular filtration rate are also analysed. European Journal of Endocrinology 154 613-621

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Section: Diabetic Nephropathymentioning

confidence: 54%

Section: Diabetic Nephropathymentioning

confidence: 94%

Peroxisome proliferator-activated receptor gamma agonists in renal disease

Iglesias

Díez

2006

eur j endocrinol

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“…146 Beyond their hypoglycemic actions, PPARЎ agonists exert a number of beneficial effects in diabetes including improvement in endothelial function, 147,148 reduction in pro-atherogenic inflammatory markers 149 and angiotensin-I and -II, 150 down regulation of AT 1 mRNA and protein in vascular smooth muscle cells, 151,152 decrease in urine endothelin-1 secretion, 153 attenuated lipid accumulation and its related injury in mesangial cells, 154,155 and inhibition of glomerular and tubular cell proliferation 156,157 . Several animal [158][159][160][161][162][163] and human studies 153,[164][165][166][167][168][169][170][171][172][173][174][175] using various TZDs have demonstrated a reduction in proteinuria and BP. Unfortunately; most of these studies were of short duration averaging 1-9 months in the animal studies 158-163 and 3-12 months in human studies.…”

Section: Emerging Therapeutic Agents For Diabetic Nephropathy Thiazolmentioning

confidence: 99%

“…Unfortunately; most of these studies were of short duration averaging 1-9 months in the animal studies 158-163 and 3-12 months in human studies. 153,[164][165][166][167][168][169][170][171][172][173][174][175] The use of TZDs has become less frequent due to higher rates of cardiovascular complications. A recent observational, retrospective, inception cohort of 227,571 Medicare patients who were treated with rosiglitazone or pioglitazone for a 12-month period and followed for up to 3 years after initiation of therapy showed rosiglitazone was associated with a higher risk of cardiovascular complications and all-cause mortality in patients 65 years or older compared with pioglitazone.…”

Section: Emerging Therapeutic Agents For Diabetic Nephropathy Thiazolmentioning

confidence: 99%

Therapeutic Modalities in Diabetic Nephropathy: Standard and Emerging Approaches

et al. 2011

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Diabetes mellitus is the leading cause of end stage renal disease and is responsible for more than 40% of all cases in the United States. Current therapy directed at delaying the progression of diabetic nephropathy includes intensive glycemic and optimal blood pressure control, proteinuria/albuminuria reduction, interruption of the renin-angiotensin-aldosterone system through the use of angiotensin converting enzyme inhibitors and angiotensin type-1 receptor blockers, along with dietary modification and cholesterol lowering agents. However, the renal protection provided by these therapeutic modalities is incomplete. More effective approaches are urgently needed. This review highlights the available standard therapeutic approaches to manage progressive diabetic nephropathy, including markers for early diagnosis of diabetic nephropathy. Furthermore, we will discuss emerging strategies such as PPAR-gamma agonists, Endothelin blockers, vitamin D activation and inflammation modulation. Finally, we will summarize the recommendations of these interventions for the primary care practitioner.

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“…Pioglitazone shows protective effect on obesity related diabetic nephropathy by reducing renal oxidative damage and advance glycation end-product deposition 9 . In patients with advanced diabetic nephropathy pioglitazone reduces proteinuria over 4 months 10 . Nateglinide is a short-acting pancreatic beta-cellselective K(ATP) potassium channel blocker that binds rapidly to the sulfonylurea SUR1 receptor with a relatively low affinity and dissociates extreme rapidly with a unique "fast on-fast off" effect.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Nateglinide and Pioglitazone Combination Therapy Compared With Monotherapy on Diabetic Nephropathy

Bigoniya¹,

Malvi²

2017

Int. J. Res. Ayurveda Pharm.

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The objective of present work is to explore combined effect of nateglinide and pioglitazone on diabetic nephropathy. Nateglinide and pioglitazone were administered to the diabetic nephropathic animals as monotherapy and in median and high dose combination for 28 days. Body weight, relative kidney weight, serum and urine biochemical parameters were analyzed along with kidney tissue antioxidant level and histology. Loss in body weight was efficiently controlled by pioglitazone monotherapy and, nateglinide and pioglitazone high dose combination. Nateglinide treatment significantly (P < 0.05-0.001) reduced serum glucose, blood urea nitrogen (BUN), creatinine and insulin along with decrease in urine albumin and increase in creatinine. Both nateglinide and pioglitazone has significantly (P < 0.05-0.01) reduced glomerular filtration rate (GFR). Nateglinide has nonsignificant effect on kidney antioxidant level but pioglitazone has increased (P < 0.05) superoxide dismutase (SOD) level. Both median and high dose combination significantly (P < 0.05-0.001) reduced the elevated level of serum glucose, cholesterol, triglyceride, low density lipoprotein, BUN, creatinine, insulin and glycated haemoglobin. Combination doses were equally effective in decreasing albumin and increasing creatinine urinary excretion with increase in GFR. High dose combination significantly increased catalase, SOD and glutathione level in the kidney tissue. Monotherapy with nateglinide and pioglitazone reduce hyperglycemia and improve kidney functional ability. Both high and median dose combination of nateglinide and pioglitazone was found effective against disturbed serum and urine biochemical parameters. High dose combination was more effective and beneficial in ameliorating kidney pathological damage and oxidative stress in the treatment of diabetic nephropathy.

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A pilot randomized controlled trial of renal protection with pioglitazone in diabetic nephropathy

Abstract: In patients with advanced diabetic nephropathy, we found no reduction in proteinuria over 4 months. These data are useful to design larger studies with longer duration of follow-up to demonstrate renal protection of PPAR-gamma agonists.

Cited by 63 publications

References 45 publications

Peroxisome proliferator-activated receptor gamma agonists in renal disease

Peroxisome proliferator-activated receptor gamma agonists in renal disease

Therapeutic Modalities in Diabetic Nephropathy: Standard and Emerging Approaches

Efficacy of Nateglinide and Pioglitazone Combination Therapy Compared With Monotherapy on Diabetic Nephropathy

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