Peritoneal Mononuclear Cell Differentiation and Cytokine Production in Intermittent and Continuous Automated Peritoneal Dialysis Eike Wrenger, MD, Carsten Baumann, MD, Matthias Behrend, MD, Enrico Zamore, RN, Ralf Schindler, MD, and Reinhard Brunkhorst, MD ● The long period without dialysate exchanges in nightly intermittent peritoneal dialysis (NIPD; no peritoneal filling during the day) and continuous cyclic peritoneal dialysis (CCPD; peritoneal filling during the day) might lead to an improved repopulation and functional regeneration of peritoneal macrophages (PMOs). We investigated this issue in seven stable, noninfected CCPD patients and seven stable, noninfected NIPD patients. PMO differentiation and cytokine production were measured after automated peritoneal dialysis and after a 12- to 14-hour period without dialysate exchanges. PMO maturation was evaluated by antibody staining. The proportion of ‘‘young’’ monocytes (positive for 27E10 and RM3/1) was decreased, whereas the proportion of mature macrophages (positive for 25F9) was significantly increased after the exchange-free interval. No differences between NIPD and CCPD were observed. The cytokine response to lipopolysaccharide was significantly increased after the exchange-free interval in both NIPD and CCPD. The interleukin-1 receptor antagonist (IL-1Ra) content of PMO lysates significantly increased after the exchange-free interval in both groups, but no changes were found in dialysate and serum IL-1Ra. We conclude that the long daytime interval without dialysate exchanges allows for additional PMO differentiation. Furthermore, the potential for cytokine release, which is inhibited (possibly by dialysate effects) after automated peritoneal dialysis, is restored after a 12- to 14-hour interval without peritoneal dialysis exchanges. The ‘‘dry’’ day in NIPD seems to have no important additional positive effect compared with CCPD.  1998 by the National Kidney Foundation, Inc. INDEX WORDS: Continuous cyclic peritoneal dialysis; nightly intermittent peritoneal dialysis; cell differentiation; cytokines. P ERITONEAL INFECTION remains the most serious complication in peritoneal dialysis patients. 1 The integrity of local peritoneal de- fense mechanisms plays a key role in the preven- tion and recovery of bacterial peritonitis. The peritoneal cavity of uninfected peritoneal dialy- sis patients contains variable numbers of perito- neal macrophages (PMOs), both within the cav- ity and resident in the peritoneal membrane. 2-6 PMOs are important in the first-line host defense and have the capability of phagocytosis and digestion of microorganisms. 7-9 A further important function of these cells is to provide the initial signals for subsequent recruitment of neutrophils via secretion of chemotactic mol- ecules such as leukotrienes and cytokines. 10,11 Various studies also have shown a contribution by peritoneal membrane mesothelial cells to first-line host defense mechanisms. 12 Several investigators have reported that PMOs from continuous ambulatory peritoneal dialysis (CAPD) patients appear to be in a state of chronic activation. 13,14 Others have described an increased expression of transferrin receptors on peripheral monocytes and on PMOs from perito- neal dialysis patients. 15,16 It was stated that due to the repeated removal of peritoneal cells during dialysis, relatively immature monocytes are con- stantly invading from the blood into the perito- neal cavity. The phagocytic capacity seems to be decreased following exposure to the currently available peritoneal dialysate at least after short dwell times. 17,18 This was attributed to the high osmolality and low pH of the peritoneal dialysis dialysate 19,20 and to the lactate buffer of the dialysate. 21 Furthermore, it was shown that the PMO capacity to release cytokines was de- creased as a result of the dialysate exposure. 22-24 These host defense mechanisms recover with longer dialysate dwell times, 17 and may possibly further benefit from an intermittent technique of peritoneal dialysis (intervals without rapid ex- changes of dialysate). 25 From the Division of Nephrology, Otto von Guericke University, Magdeburg, Germany; Divisions of Nephrology and Transplantation Surgery, Medizinische Hochschule Han- nover, Hannover, Germany; and the Division of Nephrology, Virchow Klinikum, Humboldt University, Berlin, Germany. Received February 19, 1997; accepted in revised form August 1, 1997. Address reprint requests to Eike Wrenger, MD, Division of Nephrology, Department of Internal Medicine, Otto von Guericke University, Leipziger Str, 44 D-39120 Magdeburg, Germany. E-mail: Eike.Wrenger@medizin.uni-magdeburg.de  1998 by the National Kidney Foundation, Inc. 0272-6386/98/3102-0007$3.00/0 234 American Journal of Kidney Diseases, Vol 31, No 2 (February), 1998: pp 234-241