These data demonstrate that IL-17 activates RhoA/Rho-kinase leading to endothelial dysfunction and hypertension. Inhibitors of IL-17 or Rho-kinase may prove useful as anti-hypertensive drugs in IL-17-associated autoimmune diseases.
Metformin (MTF) is one of the most common oral agents used to treat diabetes mellitus. Intoxication is associated with lactic acidosis and has significant clinical consequences. We report 12 cases requiring dialytic intervention. Twelve patients were analyzed from 2005 to 2010; 10 of these patients were treated with dialysis. Conventional hemodialysis (HD) and continuous veno-venous hemodialysis treatments with bicarbonate dialysis were used, and the results were presented as mean and standard deviation. The results are as follows: 33% of the patients were male, hospital stay was 9.3 (± 12) days, average MTF dose 1.7 g/day, mortality was 25%. Baseline glomerular filtration rate for these patients was 51.5 mL/min, with an average age of 64 (± 11) years. On presentation, all had acute kidney injury with blood urea nitrogen/creatinine 75 (± 30)/8.1 (± 3.7) mg/dL, lactic acid 12.4 (± 8.1) mmol/L, pH 7.04 (± 0.19), bicarbonate 7.2 (± 4.5) mmol/L. Metformin level was 25 (± 17) µg/mL; anion gap was 28 (± 9), and serum potassium was 5.4 (± 1.3) mEq/L. Seventy percent of patients were treated with conventional HD. Patients required 4 (± 5) dialysis treatments at blood flow QB 330 (± 53), dialysis flow QD 571 (± 111) for 305 (± 122) minutes. Postdialysis, the acidosis parameters improved: bicarbonate 19.2 (± 4.1) mmol/L, lactic acid 6 (± 4) mmol/L and MTF levels decreased 8.9 (± 5.7) µg/mL. Metformin percentage removal was calculated to be 60% (± 24). No difference was found between HD and continous veno-venous hemodialysis. The only difference between survivors was the age 53 (± 7) vs. 78 (± 10) (P < 0.05). Metformin toxicity is a serious clinical condition and causes severe lactic acidosis and significant mortality. Hemodialysis is an efficient method to treat MTF intoxication and correct the metabolic abnormalities.
Severe cholestasis with anabolic androgenic steroids is well-known to cause acute liver injury. Treatment is usually supportive after withdrawal of the offending agent. Acute kidney injury (AKI) frequently occurs in acute liver injury and may complicate management and prognosis. We highlight the use of plasmapheresis resulting in rapid improvement in cholestatic jaundice with resolution of AKI. Plasmapheresis should be considered in special cases in which there is progressive clinical decline despite supportive care.
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