Causes of hyperhomocysteinemia in patients with chronic kidney diseases.
Plasma homocysteine (Hcy) levels are increased significantly in patients with moderate renal failure and increase markedly in patients with end-stage renal disease. An increase in plasma Hcy level theoretically could be caused by an increased production rate (ie, transmethylation), a decreased rate of removal by transsulfuration or remethylation, or a decrease in the excretion of Hcy. Current evidence indicates that the major mechanism for hyperhomocysteinemia in renal failure is a decrease in Hcy removal from the body. However, it is debated whether this effect is the result of a decrease in the renal metabolic clearance or a result of extrarenal metabolic changes. The human kidney plays a major role in the removal of several aminothiols or Hcy-related compounds from the circulation (eg, cysteine-glycine, glutathione, AdoMet, and AdoHcy). However, the glomerular filtration of Hcy seems to be restricted because of protein binding. Besides glomerular filtration, the normal kidney can remove Hcy by plasma flow and peritubular uptake. Although in the low normal range in absolute terms, the flow through the transsulfuration pathway is reduced if related to Hcy levels in uremia; in addition, the remethylation pathway also is impaired. Besides the potential effect of the reduced renal mass on Hcy removal, available evidence suggests the occurrence of a generalized down-regulation of the methionine cycle and catabolism in uremia. AdoHcy, sulfate, and dimethylglycine currently are being investigated as retained solutes that can inhibit 1 or more pathways of Hcy metabolism. In addition, the high Hcy levels decrease in malnourished end-stage renal disease patients and change according to nutrient intake and several other nutritional parameters, indicating that circulating Hcy levels become an expression of nutritional status.
Garibotto
Giacomo
G
Department of Internal Medicine, Nephrology Division, University of Genoa, Genoa, Italy. gari@unige.it
Sofia
Antonella
A
Valli
Alessandro
A
Tarroni
Alice
A
Di Martino
Massimiliano
M
Cappelli
Valeria
V
Aloisi
Francesca
F
Procopio
Vanessa
V
D002908:Chronic Disease; D006801:Humans; D020138:Hyperhomocysteinemia / Q000209:etiology*; D007674:Kidney Diseases / Q000150:complications*