Effect of nephrotic syndrome on homocysteine metabolism.
Summary of "Effect of nephrotic syndrome on homocysteine metabolism."
BACKGROUND:
Proteinuria and hyperhomocysteinaemia are independently associated with increased risk of atherosclerosis and cardiovascular disease. The available data on plasma homocysteine (Hcy) level in patients with nephrotic syndrome (NS) are contradictory with increased, decreased and unchanged values reported by different investigators. The majority of Hcy in the plasma is bound to albumin whose urinary losses and diminished plasma concentration are the defining features of NS. The present study was designed to explore the effect of NS on plasma concentration and urinary excretion of Hcy and hepatic expression of methylenetetrahydrofolate reductase (MTHFR) and cystathionine-β-synthase (CBS), the key enzymes in re-methylation and trans-sulphuration of Hcy, respectively.
METHODS:
Sprague-Dawley rats were rendered nephrotic by IP injection of puromycin aminonucleoside. Urine and plasma were used for measurement of Hcy, and the liver was processed for assessment of MTHFR and CBS protein expression.
RESULTS:
Compared with the controls, nephrotic rats showed heavy proteinuria, hypoalbuminaemia, hypercholesterolaemia, normal plasma creatinine and creatinine clearance, reduced plasma Hcy, increased urinary Hcy, and downregulation of CBS but not MTHFR expression. Plasma Hcy correlated directly with plasma albumin and inversely with urinary protein excretion. The urinary Hcy excretion correlated directly with urine protein excretion.
CONCLUSIONS:
NS results in significant reduction in plasma total Hcy concentration which is due to the reduction in albumin-bound Hcy as opposed to the free Hcy fraction. This is coupled with increased urinary excretion of albumin-bound Hcy. In addition, NS results in down-regulation of CBS which can curtail conversion of Hcy to cysteine and reduce production of H(2)S which is an important endogenous signalling molecule.
Affiliation
Division of Nephrology and Hypertension, University of California, Irvine, CA, USA.
Journal Details
This article was published in the following journal.
Name: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Rena
ISSN: 1460-2385
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20826746
- DOI: http://dx.doi.org/10.1093/ndt/gfq551
Medical and Biotech [MESH] Definitions
Nephrotic Syndrome
A condition characterized by severe PROTEINURIA, greater than 3.5 g/day in an average adult. The substantial loss of protein in the urine results in complications such as HYPOPROTEINEMIA; generalized EDEMA; HYPERTENSION; and HYPERLIPIDEMIAS. Diseases associated with nephrotic syndrome generally cause chronic kidney dysfunction.
Homocysteine S-methyltransferase
An enzyme that catalyzes the demethylation of L-homocysteine to L-METHIONINE.
Aids-associated Nephropathy
Renal syndrome in human immunodeficiency virus-infected patients characterized by nephrotic syndrome, severe proteinuria, focal and segmental glomerulosclerosis with distinctive tubular and interstitial changes, enlarged kidneys, and peculiar tubuloreticular structures. The syndrome is distinct from heroin-associated nephropathy as well as other forms of kidney disease seen in HIV-infected patients.
5-methyltetrahydrofolate-homocysteine S-methyltransferase
An enzyme that catalyzes the formation of methionine by transfer of a methyl group from 5-methyltetrahydrofolate to homocysteine. It requires a cobamide coenzyme. The enzyme can act on mono- or triglutamate derivatives. EC 2.1.1.13.
Nephrosis
Pathological processes of the KIDNEY without inflammatory or neoplastic components. Nephrosis may be a primary disorder or secondary complication of other diseases. It is characterized by the NEPHROTIC SYNDROME indicating the presence of PROTEINURIA and HYPOALBUMINEMIA with accompanying EDEMA.
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