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Causes of hyperhomocysteinemia in patients with chronic kidney diseases

Giacomo Garibotto1, Antonella Sofia, Alessandro Valli

  • 1Department of Internal Medicine, Nephrology Division, University of Genoa, Genoa, Italy. gari@unige.it

Seminars in Nephrology
|January 18, 2006
PubMed

Insights

Plasma homocysteine (Hcy) levels rise in kidney failure due to reduced removal. This impairment in Hcy clearance is linked to kidney dysfunction and nutritional status in patients with renal disease.

Area of Science:

  • Nephrology
  • Biochemistry
  • Metabolic Disorders

Background:

  • Plasma homocysteine (Hcy) levels are elevated in moderate renal failure and significantly higher in end-stage renal disease (ESRD).
  • Hyperhomocysteinemia in renal failure is primarily attributed to decreased Hcy removal, though the exact mechanisms (renal vs. extrarenal) are debated.

Purpose of the Study:

  • To investigate the mechanisms behind elevated plasma homocysteine levels in patients with renal failure.
  • To explore the role of the kidneys in Hcy metabolism and clearance.
  • To understand the impact of uremia on Hcy metabolic pathways.

Main Methods:

  • Review of current evidence on Hcy metabolism in renal failure.
  • Analysis of the kidney's role in removing Hcy and related compounds.
  • Examination of the transsulfuration and remethylation pathways in uremic conditions.

Main Results:

  • The human kidney is crucial for removing Hcy and related aminothiols.
  • Glomerular filtration of Hcy is limited by protein binding; renal clearance involves plasma flow and peritubular uptake.
  • Both transsulfuration and remethylation pathways for Hcy removal are impaired in uremia.
  • A generalized down-regulation of the methionine cycle and catabolism occurs in uremia.
  • Retained solutes like AdoHcy, sulfate, and dimethylglycine may inhibit Hcy metabolism.
  • Hcy levels in malnourished ESRD patients correlate with nutritional status.

Conclusions:

  • The primary cause of hyperhomocysteinemia in renal failure is reduced Hcy removal, involving both impaired renal and extrarenal metabolic changes.
  • Kidney function significantly impacts Hcy clearance, with reduced renal mass and generalized metabolic pathway down-regulation contributing to elevated levels.
  • Circulating Hcy levels in ESRD patients reflect their nutritional status and are influenced by nutrient intake.

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