hydroxocobalamin and Kidney-Failure--Chronic

End-stage renal disease (ESRD) is associated with marked hyperhomocysteinemia which is only partially corrected by folic acid and pyridoxine supplementation. We and others have reported that various forms of parenteral cobalamin reduce plasma total homocysteine (tHcy) concentrations of patients with ESRD substantially below the lowest levels attainable with folic acid. We here report a 16-week randomized controlled crossover trial which directly compared the Hcy-lowering effect of intravenous hydroxocobalamin (HC) with that of cyanocobalamin (CC). Folic acid- and vitamin B12-replete maintenance hemodialysis patients were randomly assigned to receive either 1 mg intravenous HC weekly for 8 weeks followed by CC for a further 8 weeks, or CC for 8 weeks followed by HC for 8 weeks. Hydroxocobalamin increased serum cobalamin concentrations 40-fold, whereas CC increased them only 10-fold, but both treatments reduced plasma tHcy concentrations similarly by 33% (P < .001). Crossover to the alternate form of the vitamin greatly affected the serum cobalamin concentration but was without further effect on the plasma tHcy concentration. These results confirm that weekly cobalamin injections lower plasma tHcy concentrations of hemodialysis patients well below the level attainable with folic acid. Hydroxocobalamin and CC are equipotent despite producing very different serum cobalamin concentrations.

Topics: Cross-Over Studies; Female; Homocysteine; Humans; Hydroxocobalamin; Kidney Failure, Chronic; Male; Vitamin B 12

Renal failure causes hyperhomocysteinemia, an important risk factor for cardiovascular disease and venous access thrombosis in end-stage renal disease (ESRD). Folic acid is necessary for homocysteine (Hcy) metabolism, and therapy with 1 mg/d or more of folic acid reduces plasma total Hcy (tHcy) concentrations in ESRD, although seldom to normal. In contrast to folic acid, the Hcy-lowering effect of vitamin B(12) has not been well studied in ESRD. We performed a prospective randomized controlled clinical trial involving 24 maintenance hemodialysis patients with normal or supranormal serum folate and vitamin B(12) concentrations who received either standard therapy, which included 5 to 6 mg folic acid, 5 to 10 mg pyridoxine, and 6 to 10 microg oral vitamin B(12) per day, or standard therapy plus 1 mg hydroxocobalamin administered subcutaneously once per week after dialysis. Plasma tHcy and serum methylmalonic acid (MMA) concentrations were measured before and after 8 and 16 weeks of continuous treatment. Hydroxocobalamin reduced plasma tHcy by an average of 32% (P <.005) and serum MMA by an average of 19% (P <.001). The Hcy-lowering effect of hydroxocobalamin was independent of baseline serum vitamin B(12), folic acid, and MMA concentrations. Patients with higher baseline plasma tHcy concentrations had the greatest response (r = 0.80; P <.002). These results show that parenteral hydroxocobalamin reduces plasma tHcy dramatically in vitamin B(12)-replete hemodialysis patients. Persons with considerable persisting hyperhomocysteinemia despite high-dose folic acid therapy are likely to respond to the addition of hydroxocobalamin, irrespective of their serum vitamin B(12) concentrations.

Topics: Aged; Female; Folic Acid; Homocysteine; Humans; Hydroxocobalamin; Hyperhomocysteinemia; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Methylmalonic Acid; Middle Aged; Prospective Studies; Renal Dialysis; Treatment Outcome; Vitamin B 12

A 40-year-old male with alcoholic cirrhosis and end-stage renal disease presented for simultaneous liver and kidney transplantation. Hemodialysis was utilized intraoperatively during liver transplantation. During the procedure, the patient developed refractory hypotension and ultimately received hydroxocobalamin for vasoplegia. Shortly after administration, the hemodialysis machine ceased working after a "blood leak" alarm developed. Without the ability to continue intraoperative dialysis, the kidney transplantation portion of his surgery was postponed. The patient was transferred to the intensive care unit, where he underwent continuous renal replacement therapy overnight, and his kidney transplant proceeded the following morning.

Topics: Adult; Humans; Hydroxocobalamin; Kidney Failure, Chronic; Kidney Transplantation; Liver Cirrhosis, Alcoholic; Liver Transplantation; Male; Renal Dialysis; Vasoplegia

Hydroxocobalamin is a treatment for cyanide toxicity with few side effects. We report a case of a hemodialysis patient whose treatment was compromised by hydroxocobalamin interference with the blood leak detector.

Topics: Antidotes; Clinical Alarms; Color; Equipment Design; Equipment Failure; Humans; Hydroxocobalamin; Kidney Failure, Chronic; Kidneys, Artificial; Male; Middle Aged; Nitroprusside; Poisoning; Renal Dialysis; Vasodilator Agents

Chronic renal failure is a well-known long-term complication of methylmalonic aciduria (MMA-uria), occurring even under apparently optimal metabolic management. The onset of renal dysfunction seems to be dependent on the type of defect and vitamin B12-responsiveness. We report on a patient with a vitamin B12-responsive cobalamin A type (cblA) MMA-uria caused by a homozygous stop mutation (p.R145X) in the cobalamin A gene (MMAA). She was diagnosed with chronic kidney disease (CKD) stage III at the age of 12 years. Following re-evaluation, the patient received vitamin B12 (hydroxocobalamin) treatment, resulting in a significant decrease in the concentration of methylmalonic acid (MMA) in urine and plasma. Until age 29 years glomerular filtration rate remained stable probably due to hydroxocobalamin treatment slowing down progression to end-stage renal failure. Kidney biopsies showed non-specific manifestations of chronic interstitial inflammation. The patient received a renal transplant at age 35 years. Under continuous treatment with hydroxocobalamin there is no evidence of kidney damage due to MMA-uria until the last follow-up 6 years after transplantation. This case report illustrates (i) a long-term follow-up of a patient with MMA-uria due to cblA deficiency, (ii) the involvement of the kidney as a target organ and (iii) the importance of early and adequate vitamin B12 substitution in responsive patients. Further investigation will be necessary to prove the protective effect of hydroxocobalamin in the kidney in vitamin B12-responsive patients.

Topics: Amino Acid Metabolism, Inborn Errors; Child; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hydroxocobalamin; Kidney Failure, Chronic; Kidney Transplantation; Mitochondrial Membrane Transport Proteins; Mutation; Vitamin B 12