sitagliptin-phosphate and Acute-Kidney-Injury

We report a case of an 86-year-old woman admitted to the hospital with rhabdomyolysis and acute kidney injury 3 weeks after starting sitagliptin while on long-term atorvastatin therapy. She also had low levels of 25-hydroxyvitamin D and mild chronic kidney disease, which may have contributed to the development of rhabdomyolysis. A review of the literature reveals four previous reports of this drug interaction in elderly patients, some with underlying kidney disease.

Topics: Acute Kidney Injury; Aged, 80 and over; Atorvastatin; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rhabdomyolysis; Sitagliptin Phosphate; Vitamin D

A 56-year-old man with a history of diabetes mellitus type-2 and stage-2 chronic kidney disease secondary to diabetic nephropathy presented with an acute deterioration of kidney function. Non-invasive work-up failed to reveal the underlying aetiology for the acute kidney failure. Kidney biopsy revealed acute tubulointerstitial nephritis (ATIN) which was attributed to sitagliptin use. Only few case reports have shown this correlation. Our aim is to alert physicians and other providers of the potential effect of sitagliptin to cause ATIN with this biopsy-proven case.

Topics: Acute Kidney Injury; Biopsy; Diabetes Mellitus, Type 2; Drug Hypersensitivity; Humans; Hypoglycemic Agents; Kidney; Male; Middle Aged; Nephritis, Interstitial; Sitagliptin Phosphate

The goal of this study was to investigate the possible protective effects of sitagliptin against dyslipidemia-related kidney injury in apolipoprotein E knockout (apoE-/-) mice. Eight-week-old male apoE-/- mice were randomized to receive either a high fat diet (HFD, apoE-/- group) or HFD mixed with sitagliptin (sita + apoE-/- group) for 16 weeks. A control group of age- and gender-matched C57BL/6J mice were fed a HFD. The apoE-/- group exhibited increases in body weight and serum lipid levels in addition to high-density lipoprotein, and increases in 24-h urinary 8-hydroxy-2-deoxyguanosine and albuminuria excretion. Decreased insulin sensitivity was also observed in the apoE-/- group. These mice additionally contained enlargements of the glomerular mesangial matrix area, lipid deposition area, and renal interstitium collagen area. The apoE-/- group also demonstrated down-regulation of phosphorylated AMP-activated protein kinase (AMPK), increases in renal mRNA expression of transforming growth factor-beta 1 (TGF-β1) and fibronectin (FN), and increased protein expression of Akt, TGF-β1, FN and p38/ERK mitogen-activated protein kinase (MAPK). Sitagliptin treatment successfully ameliorated all the deleterious effects of dyslipidemia tested. To our knowledge, this is the first time that sitagliptin has been shown to reverse the renal dysfunction and structural damage induced by dyslipidemia in apoE-/- mice. Our results suggest that the renoprotective mechanism of sitagliptin may be due to a reduction in Akt levels, a restoration of AMPK activity, and inhibition of TGF-β1, FN, and p38/ERK MAPK signaling pathways.

Topics: Acute Kidney Injury; AMP-Activated Protein Kinases; Animals; Apolipoproteins E; Dipeptidyl-Peptidase IV Inhibitors; Dyslipidemias; Fibronectins; Kidney; Male; Mice; Mice, Inbred C57BL; p38 Mitogen-Activated Protein Kinases; Proto-Oncogene Proteins c-akt; Pyrazines; Sitagliptin Phosphate; Transforming Growth Factor beta1; Triazoles

The inhibition of dipeptidyl peptidase (DPP) IV shows protective effects on tissue injury of the heart, lung, and kidney. Forkhead box O (FoxO) transcriptional factors regulate cellular differentiation, growth, survival, the cell cycle, metabolism, and oxidative stress. The aims of this study were to investigate whether the DPP IV inhibitor sitagliptin could attenuate kidney injury and to evaluate the status of FoxO3a signaling in the rat remnant kidney model.. Rats were received two-step surgery of 5/6 renal mass reduction and fed on an oral dose of 200 mg/kg/day sitagliptin for 8 weeks. Before and after the administration of sitagliptin, physiologic parameters were measured. After 8 weeks of treatment, the kidneys were harvested.. The sitagliptin treatment attenuated renal dysfunction. A histological evaluation revealed that glomerulosclerosis and tubulointerstitial injury were significantly decreased by sitagliptin. Sitagliptin decreased DPP IV activity and increased the renal expression of glucagon-like peptide-1 receptor (GLP-1R). The subtotal nephrectomy led to the activation of phosphatidylinositol 3-kinase (PI3K)-Akt and FoxO3a phosphorylation, whereas sitagliptin treatment reversed these changes, resulting in PI3K-Akt pathway inactivation and FoxO3a dephosphorylation. The renal expression of catalase was increased and the phosphorylation of c-Jun N-terminal kinase (JNK) was decreased by sitagliptin. Sitagliptin treatment reduced apoptosis by decreasing cleaved caspase-3 and -9 and Bax levels and decreased macrophage infiltration.. In rat remnant kidneys, DPP IV inhibitor attenuated renal dysfunction and structural damage. A reduction of apoptosis, inflammation and an increase of antioxidant could be suggested as a renoprotective mechanism together with the activation of FoxO3a signaling. Therefore, DPP IV inhibitors might provide a promising approach for treating CKD, but their application in clinical practice remains to be investigated.

Topics: Acute Kidney Injury; Animals; Dipeptidyl-Peptidase IV Inhibitors; Forkhead Box Protein O3; Forkhead Transcription Factors; Kidney; Male; Pyrazines; Rats; Rats, Sprague-Dawley; Sitagliptin Phosphate; Triazoles

This study evaluated whether the risk of acute renal failure (ARF) increases with exenatide and sitagliptin use.. A retrospective cohort study of a large medical and pharmacy claims database was performed. Data for 4 91 539 patients were analysed. Cox proportional hazard models were used to compare the risk of ARF between diabetic and non-diabetic subjects and between diabetic patients treated with exenatide, sitagliptin and control medications.. Adjusted Cox analyses showed diabetic subjects had a higher risk of ARF [HR 1.51, confidence interval (CI) 1.26-1.81, p < 0.001] than non-diabetic controls. Compared with diabetic controls, neither exenatide (HR 0.77, CI 0.42-1.41, p = 0.40) nor sitagliptin (HR 1.17, CI 0.82-1.65, p = 0.39) increased the risk of ARF.. Our study revealed an increased incidence of ARF in diabetic versus non-diabetic patients but no association between use of exenatide or sitagliptin and ARF. Because of the limitations of this observational analysis, we cannot exclude the possibility of a very small increased risk.

Topics: Acute Kidney Injury; Adolescent; Adult; Cohort Studies; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Labeling; Exenatide; Female; Humans; Incidence; Male; Middle Aged; Peptides; Proportional Hazards Models; Pyrazines; Retrospective Studies; Risk Assessment; Sitagliptin Phosphate; Triazoles; Venoms; Young Adult

Sitagliptin is a recent oral antidiabetic drug for type 2 diabetes patients. This report is the first case of a severe drug reaction with eosinophilia and systemic symptoms (DRESS), which resolved with systemic corticosteroids. However, vigilance is necessary during the prescription of these compounds.

Topics: Acute Kidney Injury; Aged; Back; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Ear; Edema; Eosinophilia; Exanthema; Female; Glucocorticoids; Humans; Prednisone; Pyrazines; Sitagliptin Phosphate; Triazoles

Sitagliptin is a new oral glucose-lowering medication that acts via the incretin hormone system. The most common side-effects are headache and pharyngitis, and few serious adverse events were observed during clinical trials. Dose adjustment is recommended in renal insufficiency, but long-term safety experience is limited.. We present a patient with chronic renal insufficiency who developed leg pain, weakness and tenderness after starting treatment with high-dose sitagliptin while on simvastatin. The patient had acute renal failure and rhabdomyolysis that resolved with cessation of sitagliptin, simvastatin, ezetimibe, diuretics and olmesartan. All drugs except sitagliptin, ezetimibe and simvastatin were resumed, and the patient was subsequently started on lovastatin without recurrence of rhabdomyolysis.. High doses of sitagliptin may have worsened this patient's renal failure and precipitated rhabdomyolysis by increasing circulating levels of simvastatin. Given the high likelihood that sitagliptin will be co-administered with statins and renally active medications, further study of long-term safety of sitagliptin in renal sufficiency may be warranted.

Topics: Acute Kidney Injury; Aged; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Pyrazines; Rhabdomyolysis; Simvastatin; Sitagliptin Phosphate; Triazoles