tacrolimus and Acidosis

Hyperkalaemia with metabolic acidosis is common but under-reported following kidney transplantation. Calcineurin inhibitors, such as tacrolimus, are widely used in the management of transplant patients and are associated with the development of hyperkalaemia. We report on 10 renal transplant patients, treated with fludrocortisone, following identification of hyperkalaemic metabolic acidosis.. All 10 patients were male aged (mean ± SD) 53.0 ± 13.2 years; 7 were Caucasian and 3 South Asian. Before and after fludrocortisone administration, respective (mean ± SD) serum potassium was 6.1 ± 0.4 mmol/L and 5.3 ± 0.3 mmol/L (p = 0.0002); serum bicarbonate 18.5 ± 1.6 mmol/L and 20.5 ± 2.3 mmol/L (p = 0.002); serum sodium 135 ± 4.6 mmol/L and 137 ± 2.2 mmol/L (p = 0.0728); serum creatinine 181 ± 61 μmol/L and 168 ± 64 μmol/L (p = 0.1318); eGFR 42 ± 18 mL/min and 46 ± 18 mL/min (p = 0.0303); blood tacrolimus 10.1 ± 2.9 ng/mL and 10.4 ± 1.4 ng/mL (p = 0.7975); and blood pressure 129 ± 15/79 ± 25 mm Hg and 126 ± 24/75 ± 7 mm Hg. Pre-fludrocortisone, there were 7 episodes of serum potassium ≥6.5 mEq/L, with 4 patients requiring admission for the treatment of hyperkalaemia. Following fludrocortisone, no patients had hyperkalaemia requiring inpatient management.. Treatment of hyperkalaemic metabolic acidosis in transplant patients on tacrolimus with low-dose fludrocortisone resulted in rapid correction of hyperkalaemia and acidosis without significant effects on blood pressure or serum sodium. Fludrocortisone can be an effective short-term option for the treatment of hyperkalaemic metabolic acidosis in kidney transplant recipients on tacrolimus; however, patient selection remains important in order to reduce to risk of potential adverse effects.

Topics: Acidosis; Adult; Aged; Fludrocortisone; Humans; Hyperkalemia; Kidney Transplantation; Male; Middle Aged; Tacrolimus

Topics: Acidosis; Adult; Fludrocortisone; Humans; Hyperkalemia; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Tacrolimus; Treatment Outcome

Tacrolimus is an immunosuppressant widely used in recipients of solid organ transplants to prevent rejection. Toxicity is usually reported in transplant patients. We report the first case of tacrolimus toxicity in a non-transplant patient.. A 42 year-old, 48 kg woman complained of neck pain following a motor vehicle collision and was admitted for observation. On examination, her pulse was 112 beats/minute and her blood pressure 188/134 mmHg. Because the hypertension and tachycardia might be ethanol withdrawal, she was admitted and treated with multivitamins, folate, and thiamine in her maintenance fluids. She was discharged after 4 days in hospital. The day after her discharge, she was asked to return after it was discovered that she had inadvertently received tacrolimus (total of 400 mg) instead of thiamine. She was admitted with non-oliguric renal failure and metabolic acidosis. A tacrolimus concentration 27 hours after her last exposure was 96.8 ng/mL (therapeutic 5 to 20 ng/mL). Treatment was supportive and she was discharged after 4 days without sequellae.. Our patient's tacrolimus dose was 2.1 mg/kg/day for 4 days (therapeutic 0.03 to 0.05 mg/kg/day). Her tacrolimus elimination half-life was 16.5 hours, compared to a mean half-life in healthy volunteers of 34.2 +/- 7.7 hours.. Clinical toxicity, similar to that seen in transplant patients, can develop in non-transplant patients following intravenous administration of supra-therapeutic doses of tacrolimus.

Topics: Acidosis; Acute Kidney Injury; Adult; Female; Half-Life; Humans; Immunosuppressive Agents; Medication Errors; Pharmacy Service, Hospital; Tacrolimus; Thiamine

ortho-Substituted PCBs mobilize Ca2+ from isolated brain microsomes by interaction with FKBP12/RyR complexes. Investigation into the cellular importance of this mechanism was undertaken using PC12 cells by fluoroimaging the actions of specific PCB congeners on [Ca2+]i and pH. RyR and IP3R share a common intracellular Ca2+ store in PC12 cells. Perfusion of nM to low microM PCB95 caused a transient rise of [Ca2+]i that was not completely dependent on extracellular Ca2+. Pre-incubation of the cells with ryanodine or FK506 completely eliminated PCB95 responses, suggesting a primary action on the FKPP12/RyR-sensitive store. PCB95, but not PCB126, induced a gradual decrease in cytosolic pH that could be completely eliminated by FK506 pre-incubation of the cells. Direct respiration measurement using isolated brain mitochondria demonstrated that neither of the PCBs directly altered any stage of mitochondrial respiration. These results revealed that PCB95 disrupts intracellular Ca2+ signaling in PC12 cells by interaction with the FKBP12/RyR complex that in turn accelerated cellular metabolism, possibly affecting signaling between ER and mitochondria. Since ortho-substituted PCBs have been shown to be neurotoxic and may affect neurodevelopment, studies on the molecular mechanism by which they alter cellular signaling may provide valuable information on the physiological roles of FKPB12 and RyR on neuronal functions.

Topics: Acidosis; Animals; Bradykinin; Brain Chemistry; Calcium; Calcium Signaling; Cell Respiration; Enzyme Inhibitors; Estrogen Antagonists; Hydrogen-Ion Concentration; Immunophilins; Inositol Phosphates; Intracellular Fluid; Male; Mitochondria; PC12 Cells; Pheochromocytoma; Polychlorinated Biphenyls; Rats; Rats, Sprague-Dawley; Ryanodine; Structure-Activity Relationship; Tacrolimus