steven james kellner

Methamphetamine is a highly addictive drug that acts as a stimulant for the central nervous system. It increases alertness and physical activity but can cause cardiac dysrhythmias, hypertension, hallucinations and violent behavior. The excretion rate of methamphetamine by the kidney can be seriously altered by urinary pH. Methamphetamine is a weak base, consequently, the proportion of the excreted amount of unchanged drug can vary from as little as 2% in alkaline (pH ≥8.0) to 76% in acidic urine (pH ≤5.0). Methamphetamine is metabolized by hepatic metabolism and renal excretion via cytochrome P450 2D6 (CYP2D6). The effects of methamphetamine on the kidneys can be divided into the following sub-groups: vascular effects, non-traumatic rhabdomyolysis and direct nephrotoxicity. Additionally, methamphetamine directly stimulates the release of ET-1, a potent vasoconstrictor. ET-1 stimulates vasoconstriction, inflammation and fibrosis in kidney, thus promoting hypertension, atherosclerosis and chronic kidney disease.

There are few publications reporting adverse effects of metformin for patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Although some of these reports have made big claims about the adverse effects of metformin in patients with renal failure, the majority of studies showed a superior safety profile for metformin compared with other antidiabetic medications in these patients. Further, metformin use is not contributing to an increased incidence of acute kidney injury (AKI). In conclusion, we suggest that a low dose of metformin is safe to use in patients with or without CKD. Multicenter randomized trials are required to further discover the benefits of the risk of metformin therapy in different stages of CKD and its effect on progression of CKD.

Chemotherapy has been accepted as the most common choice for cancer treatment. However, chemotherapy-induced toxicity and chemotherapy resistance are the two challenging barriers to the treatment. Metformin is a safe, inexpensive, and the first line drug to treat type II diabetes. It has also a significant anti-tumor effect with a selective cytotoxic efficacy on cancer stem cells. It also has renoprotective efficacy. The current study contributes to incorporating metformin to chemotherapeutic agents to develop treatment efficiency and reduce the chemotherapy-induced side-effects (such as toxicity and resistance) and also to benefit the nephroprotective impact of this drug.