Accumulation of indoxyl sulfate in OAT1/3-positive tubular cells in kidneys of patients with chronic renal failure.
Indoxyl sulfate shows nephrotoxicity and is a stimulating factor for progression of chronic renal failure (CRF). Indoxyl sulfate is taken up by renal proximal tubular cells through organic anion transporters 1 and 3 (OAT1/3), and is accumulated in the renal proximal tubular cells of uremic rats. To determine whether indoxyl sulfate is accumulated in human OAT1/3 (hOAT1/3)-positive renal proximal tubular cells, localization of indoxyl sulfate and hOAT1/3 in the kidneys of CRF patients was determined by immunohistochemistry. Kidney samples were obtained by autopsy from 9 CRF patients (mean serum creatinine 4.7 mg/dL, ranging from 2.0 to 14.5 mg/dL) and 9 patients with non-kidney disease (mean serum creatinine 0.6 mg/dL, ranging from 0.4 to 0.9 mg/dL). Immunohistochemistry was performed using antibodies against indoxyl sulfate, hOAT1, and hOAT3. Indoxyl sulfate was localized in the hOAT1- and hOAT3-positive renal tubular cells in the kidneys of CRF patients. The indoxyl sulfate-positive area in the kidneys was markedly increased in the kidneys of CRF patients compared with patients with non-kidney disease. The indoxyl sulfate-positive area was positively correlated with serum creatinine. In conclusion, in CRF patients, indoxyl sulfate is accumulated in the tubular cells with hOAT1 and/or hOAT3 localized at the basolateral membrane. The extent of indoxyl sulfate accumulation in the kidneys is more prominent in those patients with more severe CRF.
Taki
Kentaro
K
Department of Clinical Preventive Medicine, Nagoya University Hospital, Nagoya, Japan.
Nakamura
Sakurako
S
Miglinas
Marius
M
Enomoto
Atsushi
A
Niwa
Toshimitsu
T
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007200:Indican / Q000032:analysis / Q000378:metabolism*; D007668:Kidney / Q000737:chemistry; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D007684:Kidney Tubules / Q000737:chemistry / Q000378:metabolism*; D007686:Kidney Tubules, Distal / Q000737:chemistry; D007687:Kidney Tubules, Proximal / Q000737:chemistry; D008138:Loop of Henle / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D027362:Organic Anion Transport Protein 1 / Q000032:analysis*; D029362:Organic Anion Transporters, Sodium-Independent / Q000032:analysis*
D027362:Organic Anion Transport Protein 1; D029362:Organic Anion Transporters, Sodium-Independent; C114338:organic anion transport protein 3; D007200:Indican