ARS | Publication request: CERAMIDE PATHWAY CONSTITUENTS IN HUMAN POLYCYSTIC KIDNEY DISEASE (PKD)

Submitted to: Annual Conference on Peritoneal Dialysis Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: February 23, 1996
Publication Date: N/A

Technical Abstract: To examine the potential for ceramide pathway anomalies in kidney disease, we assess sphingoid base levels in human kidney tissues obtained from PKD patients at nephrectomy and in non-transplantable (normal) kidneys. Free sphinganine (SA), sphingosine (SO), and ceramide are potent intracellular messengers of likely importance during peritoneal dialysis. Free SA and SO were found in 3 normal kidneys in an SA:SO ratio that ranged from 0.27 to 0.38; free SA was not found in cyst walls and tissue devoid of cyst fluid; free SO levels were lower in PKD than normal kidney (18.5 +/- 8.2 vs. 26.4 +/- 8.1 pmol free SO/mg protein; N=3). Acid hydrolysis of complex sphingolipids removes the headgroup and N-acyl chain to give SA and SO, an index of total sphingoid base levels. Total SA and SO levels were slightly lower in PKD than normal tissue (3.8 +/- 2.1 [N=3] versus 5.1 and 8.8 nmol Total SO/mg protein). Acid hydrolysis of cyst fluid showed increasing SO content (83, 127, and 272 nmol Total SO/ml) and SA:SO ratio (0.1, 0.12, and 0.17) for yellow, turbid yellow, and chocolate cyst fluids, respectively. Autosomal recessive PKD renal epithelial cells grown in culture showed lower sphingoid base content (2.7 vs. 11.9 nmol Total SO/mg cell protein) than normal rabbit mesothelial cells, despite a 10-fold higher serum requirement for growth of the PKD cells. Taken together, the possibility of derangement of sphingoid base and ceramide metabolism in PKD is revealed.