Increased dietary salt accelerates chronic allograft nephropathy in rats.
BACKGROUND
Chronic allograft nephropathy (CAN), a major problem in renal transplantation, is related to both alloantigen-dependent and -independent processes. Because dietary salt intake modulated glomerular production of transforming growth factor-beta, which has been shown to play an important role in CAN, we hypothesized that dietary salt would directly enhance renal injury in a rodent model of CAN.


METHODS
Dietary NaCl was increased from 1.0% (normal) to 8.0% in a group of Fisher/Lewis rats 25 days following orthotopic renal transplantation and was continued until 16 weeks after transplantation.


RESULTS
Blood pressure, which was recorded using radiotelemetry in the first eight-weeks post-transplantation, did not differ between the groups, but allograft recipients on the 8.0% NaCl diet rapidly demonstrated increased urinary albumin excretion. Renal function determined by dynamic functional imaging was worse in allograft recipients on the 8.0% NaCl diet by six weeks following transplantation. Histologic examination at 16 weeks confirmed a significant increase in allograft damage in the 8.0% NaCl group compared with allografts from rats on 1.0% NaCl diet. These findings included glomerulosclerosis and tubulointerstitial injury that consisted of fibrosis, tubular atrophy and dilation, intratubular casts, and tubular epithelial cell damage. Small arteries and arterioles did not show evidence of damage from hypertension or other abnormality.


CONCLUSIONS
In this model of CAN, renal allograft dysfunction preceded hypertension and was accelerated significantly by an increase in dietary salt.
Department of Medicine, University of Alabama, Birmingham, Alabama 35294-00007, USA. psanders@uab.edu
P W
PW
Sanders
C L
CL
Gibbs
K M
KM
Akhi
L A
LA
MacMillan-Crow
K R
KR
Zinn
Y F
YF
Chen
C J
CJ
Young
J A
JA
Thompson
D000419:Albuminuria; D000818:Animals; D002908:Chronic Disease; D004032:Diet; D007668:Kidney / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000209:etiology*; D016030:Kidney Transplantation; D008297:Male; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D012965:Sodium Chloride / Q000008:administration & dosage*; D017263:Technetium Tc 99m Mertiatide / Q000493:pharmacokinetics; D013997:Time Factors
D019275:Radiopharmaceuticals; D017263:Technetium Tc 99m Mertiatide; D012965:Sodium Chloride