Document Detail

Pathophysiology of cyclosporine-induced nephrotoxicity in humans: a role for nitric oxide?
MedLine Citation:
PMID:  11435743     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The causes for the nephrotoxicity of cyclosporine A (CsA) have not been fully elucidated. Intrarenal vasoconstriction induced by several different mediators, both in humans and experimental animals, have been proposed. METHODS: We studied prostaglandin metabolites, endothelin and nitric oxide in kidney transplant patients receiving their first CsA dose. Prostaglandin metabolites in the urine and endothelin and nitric oxide (NO2/NO3 in urine and plasma were measured in 14 patients before and 3 and 6 h after oral ingestion of CsA (10 mg/kg b.w.). Clearances for inulin and p-aminohippuric acid (PAH) were measured before and in two separate 3-hour periods after CsA. Blood pressure, heart rate, and CsA blood levels were also determined. RESULTS: Clearances of inulin and PAH decreased progressively after CsA dosage while renal vascular resistance increased. Nitric oxide plasma levels decreased in nearly all patients from 21.0 +/- 2.8 to 19.1 +/- 2.6 (p = 0.003) and then rose slightly to 19.5 +/- 2.5 micromol/l (p = 0.1) 3 and 6 h after CsA ingestion, respectively. Urinary excretion of NO2/NO3 decreased nonsignificantly from 269 +/- 38.8 to 259 +/- 27.7 and 254 +/- 41.6 micromol/min (p = 0.5 and 0.5). At the same time, urinary prostaglandin E2 and 6-keto-prostaglandin F(1 alpha) excretion rate declined significantly [from 1,187 +/- 254 to 1,186 +/- 351 and 730 +/- 148 pg/min (p = 0.27 and 0.02) and from 697 +/- 115 to 645 +/- 134 and 508 +/- 58.2 pg/min (p = 0.34 and 0.05)]. Urinary thromboxane B2 and plasma and urinary endothelin first increased and then decreased nonsignificantly. Mean arterial pressure rose from 107 +/- 2.5 to 110 +/- 2.6 and 114 +/- 3.4 mm Hg (p = 0.1 and 0.05). CONCLUSION: The pathophysiology of CsA-induced acute renal vasoconstriction involves several different mechanisms including a decrease of the vasodilating prostaglandins E2 and 6-keto-prostaglandin F(1 alpha) and possibly nitric oxide.
J Gossmann; A Radounikli; A Bernemann; O Schellinski; H P Raab; R Bickeböller; E H Scheuermann
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Kidney & blood pressure research     Volume:  24     ISSN:  1420-4096     ISO Abbreviation:  Kidney Blood Press. Res.     Publication Date:  2001  
Date Detail:
Created Date:  2001-07-03     Completed Date:  2001-10-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9610505     Medline TA:  Kidney Blood Press Res     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  111-5     Citation Subset:  IM    
Funktionsbereich Nephrologie, Medizinische Klinik IV, Klinikum der J.W.-Goethe-Universität, Frankfurt am Main, Deutschland.
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MeSH Terms
6-Ketoprostaglandin F1 alpha / physiology,  urine
Administration, Oral
Blood Pressure / drug effects
Cyclosporine / adverse effects*,  pharmacology
Dinoprostone / physiology,  urine
Endothelins / metabolism
Heart Rate / drug effects
Immunosuppressive Agents / adverse effects*,  pharmacology
Inulin / metabolism
Kidney Diseases / chemically induced*,  metabolism
Kidney Transplantation
Metabolic Clearance Rate / drug effects
Nitrates / blood
Nitric Oxide / physiology*
Nitrites / blood
Prostaglandins / physiology*
Renal Artery / drug effects*
Renal Circulation / drug effects
Thromboxane B2 / urine
Vascular Resistance / drug effects
Vasoconstrictor Agents / adverse effects*,  pharmacology
p-Aminohippuric Acid / metabolism
Reg. No./Substance:
0/Endothelins; 0/Immunosuppressive Agents; 0/Nitrates; 0/Nitrites; 0/Prostaglandins; 0/Vasoconstrictor Agents; 10102-43-9/Nitric Oxide; 363-24-6/Dinoprostone; 54397-85-2/Thromboxane B2; 58962-34-8/6-Ketoprostaglandin F1 alpha; 59865-13-3/Cyclosporine; 61-78-9/p-Aminohippuric Acid; 9005-80-5/Inulin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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