Different effects of amino acid-based and glucose-based dialysate from peritoneal dialysis patients on mesothelial cell ultrastructure and function.
BACKGROUND
Peritoneal dialysis fluid (PDF) containing amino acids has been introduced recently aiming to improve the nutritional status of PD patients. Dextrose-based PDFs have been implicated in progressive functional and structural deterioration of the peritoneal membrane. Limited data are currently available regarding the effect of amino acid-based PDF on the function and ultrastructure of human peritoneal mesothelial cells (HPMCs), which play a critical role in peritoneal membrane pathophysiology.


METHODS
We investigated the effects of two commercially available PDFs, which utilized dextrose (1.5% Dianeal) or amino acids (1.1% Nutrineal) as the osmotic agent, obtained from patients after a 4 h dwell, on HPMC proliferation (MTT assay and cell counting) and viability [lactate dehydrogenase (LDH)release], interleukin-6 (IL-6) secretion (commercial enzyme-linked immunosorbent assay) and ultrastructure (scanning and transmission electron microscopy).


RESULTS
Exposure of HPMCs to 1.5% Dianeal reduced cell proliferation, total cellular protein synthesis, IL-6 secretion and cell attachment, but prolonged the cell doubling time on recovery, and increased LDH release (P<0.001, P<0.001, P<0.0001, P<0.0001, P<0.001 and P<0.001, respectively). The 1.1% Nutrineal reduced HPMC proliferation (P<0.001) and increased IL-6 secretion (P<0.0001), but did not affect cell attachment, LDH release, protein synthesis or cell doubling time. Ultrastructural studies of HPMCs exposed to Dianeal showed cell flattening, increased cell surface area, reduced microvilli, and intracellular organelles compatible with dysfunctional mitochondria. In contrast, the ultrastructural morphology of HPMCs was relatively preserved after incubation with Nutrineal.


CONCLUSIONS
Our results showed that HPMC ultrastructure, viability and protein synthesis were better preserved with amino acid-based PDF, compared with conventional dextrose-based PDF. The significance of IL-6 induction by Nutrineal remains to be elucidated.
Division of Nephrology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China. dtmchan@hkucc.hku.hk
Tak-Mao
TM
Chan
Jack Kok-Hung
JK
Leung
Yuling
Y
Sun
Kar-Neng
KN
Lai
Ryan Chi-Wai
RC
Tsang
Susan
S
Yung
D000328:Adult; D000596:Amino Acids / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D015314:Dialysis Solutions / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000166:cytology / Q000187:drug effects*
D000596:Amino Acids; D015314:Dialysis Solutions; D015850:Interleukin-6; D005947:Glucose