J Korean Med Sci.  2014 Dec;29(12):1658-1664. 10.3346/jkms.2014.29.12.1658.

Effects of Sodium Citrate on Salt Sensitivity and Kidney Injury in Chronic Renal Failure

• Kim S
• Yang JY
• Jung ES
• Lee J
• Heo NJ
• Lee JW
• Na KY
• Han JS

• KMID: 2069955
• DOI: http://doi.org/10.3346/jkms.2014.29.12.1658

Abstract

Metabolic acidosis, which is observed in salt-sensitive hypertension, is also associated with kidney injury. Alkali therapy in chronic renal failure (CRF) may ameliorate the progression of kidney disease; however, few studies have examined the effects of alkali therapy on salt sensitivity and kidney injury in CRF. We randomly administered standard diet (SD), sodium chloride with 20% casein diet (NACL), or sodium citrate with 20% casein diet (NACT) to Sprague-Dawley rats after a CRF or a sham operation. Four weeks after 5/6 nephrectomy, serum bicarbonate levels were higher in the NACT-treated group. On the pressure-natriuresis curve, NACT-treated CRF rats were more salt-resistant than NACL-treated CRF rats. Additionally, the NACT-treated CRF group showed less tubulointerstitial damage than the NACL-treated CRF group. The expression and immunoreactivity of NHE3 in the kidney in the NACT-treated CRF group were lower than those in the NACL-treated CRF group. We observed that dietary NACT as alkali therapy in CRF might improve the altered salt-sensitivity and ameliorate the progression of kidney injury compared to the NACL diet, which may be related to reduced renal NHE3 expression.

Keyword

Kidney Failure, Chronic; Citrates; Acidosis; Natriuresis

MeSH Terms

Acute Kidney Injury/diagnosis/*drug therapy/*physiopathology
Administration, Oral
Animals
Citrates/*administration & dosage
*Dietary Supplements
Kidney Failure, Chronic/*diet therapy/*physiopathology
Male
Rats
Rats, Sprague-Dawley
Salt-Tolerance/*drug effects
Treatment Outcome
Citrates

Figure

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  Fig. 1 Pressure-natriuresis curves by group. Data are presented as the means ± SEM. SD, standard diet; Nx, nephrectomy; NACL, sodium chloride with 20% casein diet; NACT, sodium citrate (NACT) with 20% casein diet.

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  Fig. 2 Histological analysis of kidney tissue. Histological sections include glomerular lesions (A) on periodic-acid Schiff-stained sections at a magnification of ×400 and cortical (B) and medullary (C) tubulointerstitial lesions on Masson's trichrome stained sections at a magnification of ×100. Data are presented as the means ± SEM. P values are presented between the groups. SD, standard diet; Nx, nephrectomy; NACL, sodium chloride with 20% casein diet; NACT, sodium citrate with 20% casein diet.

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  Fig. 3 Immunoblots (A) of NHE3 and NaDC1, and immunohistochemistry of NHE3 (B). Immunoblot analysis shows band density values that were standardized by dividing them by the average value of the control group, and the mean for the control group was defined as 100%. Data are presented as the means±SEM. P values are presented between the groups. SD, standard diet; Nx, nephrectomy; NACL, sodium chloride with 20% casein diet; NACT, sodium citrate (NACT) with 20% casein diet.

• 

  Fig. 4 Immunoblots of NBC and Na-K-ATPase. In immunoblot analysis, the band density values were standardized by dividing them by the average value of the control group, and the mean for the control group was defined as 100%. Data are presented as the means ± SEM. P values are presented between the groups. SD, standard diet; Nx, nephrectomy; NACL, sodium chloride with 20% casein diet; NACT, sodium citrate (NACT) with 20% casein diet.

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  Fig. 5 Kidney tissue endothelin-1 levels in the animals treated with the standard diet (SD), sodium chloride (NACL) with 20% casein diet, and sodium citrate (NACT) with 20% casein diet after nephrectomy (Nx) or sham operation. Data are presented as the means±SEM. P values are presented between the groups.

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