PMID- 11918749
OWN - NLM
STAT- MEDLINE
DCOM- 20020624
LR  - 20131121
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 61
IP  - 4
DP  - 2002 Apr
TI  - L-arginine deficiency and supplementation in experimental acute renal failure and 
      in human kidney transplantation.
PG  - 1423-32
AB  - BACKGROUND: The "L-arginine paradox" refers to situations where L-arginine 
      (L-Arg) supplementation stimulates nitric oxide (NO) synthesis, despite 
      saturating intracellular concentrations. This paradox is frequently observed in 
      acute renal failure (ARF). First, the effects of L-Arg on renal function of rats 
      with ARF were studied. Based on the promising results from these initial studies, 
      the second part of our study searched for a form of ARF in humans that could be 
      studied easily under conditions with little variance and yet was linked with 
      endothelial dysfunction. Thus, we investigated the effects of L-Arg 
      supplementation immediately after kidney transplantation in 54 patients. METHODS: 
      In uranyl nitrate-induced ARF in rats the effects of L-Arg and L-NNA (inhibitor 
      of nitric oxide synthase; NOS) on glomerular filtration rate (GFR), renal plasma 
      flow (RPF), blood pressure (BP) and NOx (NO2- +NO3-) excretion were examined. 
      Tissue L-Arg levels, NOS activities, immunodetection of NOS and superoxide 
      dismutase (SOD), activities of nicotinamide adenine dinucleotide phosphate 
      (NADPH) oxidase and xanthine oxidase, and nitrotyrosine immunoreactive protein 
      (NT-IR) were determined and compared to sham operated animals. Secondly, in a 
      randomized, double-blind study, the effects of L-Arg on GFR and RPF were 
      investigated in 54 kidney transplant recipients, receiving IV L-Arg for three 
      days. GFR and RPF were measured on days 1, 3, 5 and 10 by scintigraphy. RESULTS: 
      In experimental ARF, decreased RPF and GFR were associated with reduced tissue 
      L-Arg levels, endothelial NOS-III expression, NO formation and NOx excretion. 
      Reduction in GFR, RPF and NOx excretion were reversed upon administration of 
      exogenous L-Arg. There also was a loss of Cu,Zn-SOD, a key enzyme against 
      oxidative stress, and an elevation of NT-IR, an indicator of nitrosative stress 
      and suggested marker for pathological actions of NO. However, NT-IR was not 
      dependent on de novo NO synthesis and not related to the functional effects of 
      l-Arg administration. In kidney transplant recipients receiving organs with a 
      short cold ischemia time (CIT) and from young donors, that is, those with a 
      higher likelihood of a functional endothelium, early administration of L-Arg 
      improved renal function. CONCLUSION: Both experimental and clinical data show 
      that \L-Arg deficiency and endothelial dysfunction are pathomechanistically 
      relevant in ARF. The data suggest a therapeutic potential for the administration 
      of L-Arg in ARF and kidney transplantation, at least in patients receiving 
      kidneys with shorter CIT and from younger donors.
FAU - Schramm, Lothar
AU  - Schramm L
AD  - Department of Medicine, Division of Nephrology, Julius-Maximilians-University, 
      Wurzburg, Germany. L.schramm@dialyse-wuerzburg.de
FAU - La, Mylinh
AU  - La M
FAU - Heidbreder, Ekkehart
AU  - Heidbreder E
FAU - Hecker, Markus
AU  - Hecker M
FAU - Beckman, Joe S
AU  - Beckman JS
FAU - Lopau, Kai
AU  - Lopau K
FAU - Zimmermann, Josef
AU  - Zimmermann J
FAU - Rendl, Johann
AU  - Rendl J
FAU - Reiners, Christoph
AU  - Reiners C
FAU - Winderl, Sabine
AU  - Winderl S
FAU - Wanner, Christoph
AU  - Wanner C
FAU - Schmidt, Harald H H W
AU  - Schmidt HH
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 14691-52-2 (Peroxynitrous Acid)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Acute Kidney Injury/*drug therapy/physiopathology
MH  - Animals
MH  - Arginine/*deficiency/metabolism/*therapeutic use
MH  - Double-Blind Method
MH  - Female
MH  - Glomerular Filtration Rate
MH  - Humans
MH  - Kidney/drug effects/physiopathology
MH  - *Kidney Transplantation
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase/metabolism
MH  - Oxygen/metabolism
MH  - Peroxynitrous Acid/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Renal Circulation
EDAT- 2002/03/29 10:00
MHDA- 2002/06/25 10:01
CRDT- 2002/03/29 10:00
PHST- 2002/03/29 10:00 [pubmed]
PHST- 2002/06/25 10:01 [medline]
PHST- 2002/03/29 10:00 [entrez]
AID - S0085-2538(15)48364-4 [pii]
AID - 10.1046/j.1523-1755.2002.00268.x [doi]
PST - ppublish
SO  - Kidney Int. 2002 Apr;61(4):1423-32. doi: 10.1046/j.1523-1755.2002.00268.x.