Metabolism of 25-OH-vitamin D3 by peritoneal macrophages from CAPD patients

The active metabolite of vitamin D, 1,25-dihydroxycholecalciferol (1,25(OH)2D3), is produced mainly by the kidney, but there is evidence for extrarenal production in certain circumstances. We studied whether peritoneal macrophages (PM) from CAPD patients were capable of metabolizing 25-OH-D3 to 1,25(OH)2D3. We found that PM were able to metabolize 25-OH-D3 in vitro; the main product following 16 hours of incubation was 19-nor, 10-oxo, 25-OH-D3 with smaller amounts of 1,25(OH)2D3. However, after shorter incubations of three and five hours a larger portion of 1,25(OH)2D3 was produced. The metabolism of 25-OH-D3 was greatly enhanced in PM harvested during episodes of peritonitis. This property was specific for PM of CAPD patients, and was not found in PM from normal subjects. However, incubation of control PM with peritoneal effluent from CAPD patients resulted in induction of the ability of these cells to metabolize 25-OH-D3. This induction was enhanced by preincubation with peritoneal effluent from CAPD patients suffering from peritonitis. Prostaglandin E2 was found to be involved in this synthesis: addition of PGE2 to normal PM induced metabolism of 25-OH-D3, and incubation of PM from CAPD patients with indomethacin decreased the metabolism of 25-OH-D3. The vitamin D metabolites produced by PM from CAPD patients could have a role in immunological resistance to peritoneal infections.     

Enhancement of ionized calcium and 1,25-dihydroxycholecalciferol loss from peritoneal fluid during peritonitis in patients treated with continuous ambulatory peritoneal dialysis

This study was to evaluate whether peritoneal loss of vitamin D metabolites during peritonitis leads to more depletion of 1,25-hydroxycholecalciferol [1,25(OH)2D3] and 25-hydroxycholecalciferol [25(OH)D] in continuous ambulatory peritoneal dialysis (CAPD) patients, especially in the high peritonitis occurrence group (HPOG). A series of ionized calcium, pH values, 1,25(OH)2D3 and 25(OH)D levels in dialysate during peritonitis were studied in 30 CAPD patients. In addition, bone mineral content (BMC) was determined during peritonitis. On the basis of peritonitis occurrence, 14 patients were in the low peritonitis occurrence group (LPOG) and 6 patients in the HPOG. Increase in peritoneal loss of ionized calcium, 1,25(OH)2D3, 25(OH)D and a decrease of pH value in dialysate may appear in the early period of peritonitis in both groups. When peritonitis occurs too frequently in a short period, the peritoneal membrane function cannot recover completely. Frequent peritonitis may impair peritoneal function and cause persistent loss of calcium. 1,25(OH)2D3 amd 25(OH)D loss is also higher in the HPOG than in the LPOG. The persistent loss of calcium, low plasma vitamin D levels and increased parathyroid hormone level with hyperparathyroidism in the HPOG are the important factors contributing to renal osteodystrophy. The lower BMC in the bone study confirmed this. Therefore, adequate calcium and vitamin D supplementation is necessary in the HPOG.     

Interferon-gamma (IFN-gamma) as in vitro enhancing factor of peritoneal macrophage defective bactericidal activity during continuous ambulatory peritoneal dialysis (CAPD)

Interferon-gamma (IFN-gamma) can be considered a primary factor required in vitro and in vivo for inducing endocellular lysis of microorganisms by peritoneal macrophages (PM luminal diameter), an essential activity in continuous ambulatory peritoneal dialysis (CAPD) patients that prevents bacterial peritonitis. In 22 uremic patients treated with CAPD we analyzed: (1) the amount of IFN-gamma released by elicited peritoneal lymphocytes (PL); (2) oxidative metabolism and microbicidal activity by elicited PM luminal diameter; (3) immunoglobulin G (IgG) Fc-receptor expression on PM luminal diameter membrane; (4) the effect on PM luminal diameter hydrogen peroxide (H2O2) generation, bactericidal activity, and IgG Fc-receptor expression exerted in vitro by human recombinant IFN-gamma (rIFN-gamma). Results demonstrate that IFN-gamma release by elicited PL is lower in some CAPD patients with high peritonitis incidence (HPI) than in healthy donors or in CAPD patients with low peritonitis incidence (LPI). Simultaneously, PM luminal diameter from CAPD patients with HPI are characterized by a decreased ability to generate oxygen metabolites, to kill bacteria, and by a lack in IgG Fc-receptor expression; these defects were completely cured after being treated with rIFN-gamma. These results show that the IFN-gamma treatment in vitro could strengthen PM luminal diameter phagocytosis, oxygen metabolite generation, and bacterial killing in CAPD patients with HPI, and suggest that IFN-gamma may be considered a possible therapy in vivo for these patients.     

Suppressor resident peritoneal macrophages and peritonitis incidence in continuous ambulatory peritoneal dialysis

Our study was designed to see if peritoneal macrophages (PM) of continuous ambulatory peritoneal dialysis (CAPD) uremic patients, by weakening local defense, could contribute to an increase of peritonitis incidence. Coincubation of nonadherent control responding cells (NACRC) and PM from normal subjects or CAPD patients with low peritonitis incidence (LPI) did not modify blastogenic response of cells to PHA. Coincubation of NACRC and PM from CAPD patients with high peritonitis incidence (HPI) produced noticeable decrease in blastogenic response; these PM, unable to produce normal amounts of Interleukin-1 (IL-1), released large amounts of prostaglandin E2 (PGE2). CAPD patients with LPI and normal subjects produced both substances in similar amounts. PM of CAPD patients with HPI were less able to kill bacteria than those from normal subjects and CAPD patients with LPI, showing a stronger suppressor effect on local defense. This suppressor activity correlated directly to PGE2 release and inversely to IL-1 production. We can hypothesize that in some uremic patients, subpopulations of macrophages growing in response to local stimuli produce humoral substances, negatively affecting cellular-mediated defense and favoring elevated bacterial expansion in peritoneum.     

Losses of 1,25- and 24,25-dihydroxycholecalciferol in the peritoneal fluid of patients treated with continuous ambulatory peritoneal dialysis

We measured peritoneal losses of the active vitamin D metabolites 1,25(OH)2D3 and 24,25(OH)2D3 in patients receiving continuous ambulatory peritoneal dialysis (CAPD). The serum concentration of 24,25(OH)2D3 was considerably lower than in hemodialysis patients. The serum concentration of 1,25(OH)2D3 was undetectable and rose to levels similar to those in hemodialysis patients only after loading with much higher oral doses of 1-alpha-vitamin D3 than those received by hemodialysis patients. Losses of both metabolites in peritoneal fluid were considerable, averaging approximately 6-8% of the plasma pool per day. These losses lead to low serum levels of these active vitamin D metabolites in CAPD patients, which may be an important factor in exacerbating renal osteodystrophy. Our results indicate the need for increased replacement doses of vitamin D metabolites in CAPD patients.     

Platelet activating factor is produced during infectious peritonitis in CAPD patients

Peritonitis, a frequent complication of continuous ambulatory peritoneal dialysis (CAPD), is a model of inflammation which provides the opportunity to recover the exudate fluid. To date, various endogenous mediators (histamine, bradykinin, activated complement factors, prostanoids) have been implicated in the mediation of peritoneal inflammation and increased peritoneal permeability. In the present study, a lipid compound with physicochemical and biological characteristics similar to platelet activating factor (PAF) (1-0-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) was extracted in significant amounts from the dialysate of eight out of nine peritonitis episodes in seven CAPD patients (Group A; 6771.4 +/- 3025.9 pM, mean +/- SEM at the first exchange during peritonitis). The amounts of PAF recovered in the first exchange dialysate from patients of Group A were linearly correlated with the loss of albumin (y = -3157.64 + 91.4x; r = 0.7394; N = 9; P less than 0.03) and number of leukocytes (y = 902.45 + 1.52x; r = 0.7576 N = 9; P less than 0.02). PAF was not detectable in the dialysate fluid from patients of Group A after recovery. Twelve patients on CAPD who had no past or present history of peritonitis (Group B) were used as controls; no PAF (9 patients) or only minimal amounts (3 patients: 7.0 pM; 23.0 pM; 70.0 pM) of this mediator were detected. This is the first direct demonstration of the local generation of PAF in a septic inflammatory reaction involving the peritoneal serosa in man. PAF produced by various cell types (neutrophils, peritoneal macrophages, endothelial cells) during peritoneal inflammation may contribute to the increased permeability of the peritoneal vascular bed.     

The effects of intraperitoneal calcitriol on calcium and parathyroid hormone

Parathyroid suppression by intraperitoneal calcitriol (1,25(OH)2D3) during peritoneal dialysis. The purpose of this study was to determine if parathyroid hormone (PTH) suppression could be achieved by increasing calcium mass transfer (Ca MT) with high dialysate Ca (4 mEq/liter) or via intraperitoneal (i.p.) 1,25(OH)2D3 in patients undergoing continuous ambulatory peritoneal dialysis. Eleven patients were dialyzed for two months with standard Ca dialysate (3.5 mEq/liter) followed by two months with 4.0 mEq/liter Ca, then by three months of i.p. 1,25(OH)2D3. During the latter period, patients were randomized to groups whose dialysate contained either 3.5 mEq/liter or 4.0 mEq/liter Ca. We found that 4.0 mEq/liter Ca dialysate more than doubled Ca MT (37 +/- 17 mg/day to 84 +/- 6 mg/day) leading to a modest fall (P less than 0.05) in PTH levels (84 +/- 5.5% of controls). Ionized calcium levels did not change. With i.p. 1,25(OH)2D3, however, ionized calcium rose significantly (P less than 0.001) leading to a decline in PTH levels to 53.9 +/- 7.9% of control values. Serum 1,25(OH)2D3 levels rose from undetectable to 47.7 +/- 7.2 pg/dl (normal range 20 to 35). These studies indicate that increasing Ca MT using a 4.0 mEq/liter Ca dialysate leads to a small reduction in PTH concentrations. On the other hand, i.p. 1,25(OH)2D3 is well absorbed into the systemic circulation, raises ionized calcium levels, and leads to a marked suppression of PTH. Thus, i.p. 1,25(OH)2D3 may be a simple and effective means to suppress secondary hyperparathyroidism in patients undergoing CAPD.     

Comparison of blood and peritoneal lymphocytes from continuous ambulatory peritoneal dialysis patients, asymptomatic and with peritonitis

OBJECTIVE: The purpose of this study was to compare the characteristics of the blood immunophenotype of CAPD patients with and without peritonitis and to compare the phenotypes of peripheral blood lymphocytes (PBL) and peritoneal lymphocytes (PL) in CAPD patients with peritonitis. METHODS: Fifty-seven CAPD patients (20 with peritonitis and 37 without peritonitis) were recruited in the study (mean age 66,88 +/- 13,48, male/ female 16/21). Lymphocyte subsets (CD2+, CD3+, CD3+/4+, CD3+/8+, CD3-/16 + 56+, CD4/CD8 ratio) were quantitated by using monoclonal antibodies and dual-color flow cytometric analysis. With the above method we measured PBL in patients with and without peritonitis. In patients with peritonitis we also measured PL. RESULTS: CD2 were slightly decreased in patients with peritonitis. Those patients also had more intense CD3 + / CD4+ lymphopenia (p < 0.05) and larger expansion of NK cells (p < 0.05). Patients with peritonitis appeared to have a lower ratio of CD4/CD8 (p < 0.05). All the above results are shown to Table 2. Following the onset of peritonitis, a consistent finding in all patients was a significant increase in CD2 population of PL compared with PBL (85.71 +/- 9.20 versus 82.60 +/- 7.34, p < 0.05) as well as in CD3 population (77.01 +/- 13.09 versus 68.74 +/- 13.43, p < 0.05). An increased number of CD3/8 in PL compared with PBL (33.70 +/- 9.34 versus 27.98 +/- 10.77, p < 0.05) was also noted. CONCLUSIONS: In the present study, we found important immune activation in asymptomatic CAPD patients. The activation increases during peritonitis. The causes and the clinical consequences of chronic activation remain unknown.     

Free and total 1,25-dihydroxyvitamin D levels in subjects with renal disease.

Patients with nephrotic syndrome and varying degrees of renal failure, including those on chronic hemo- and peritoneal dialysis, may have low serum concentrations of total 1,25-dihydroxyvitamin D [1,25(OH)2D]. However, it is unknown whether the true activity of 1,25(OH)2D is better reflected by the free 1,25(OH)2D fraction. We measured total 1,25(OH)2D, free 1,25(OH)2D, and vitamin-D-binding protein (DBP) in normal subjects (group A), subjects with moderate renal failure (group B), subjects on hemodialysis (group C), subjects on peritoneal dialysis (group D), and subjects with nephrotic syndrome (group E). The serum concentrations of total and free 1,25(OH)2D decreased with worsening renal function in groups A through C, with a high degree of correlation (r = 0.974, P less than 0.0001). Levels of DBP and the percent free 1,25(OH)2D remained constant in these groups. Patients on peritoneal dialysis and nephrotic patients had lower levels of DBP (203 +/- 14 micrograms/ml and 371 +/- 46 micrograms/ml, respectively) than normal subjects (436 +/- 33 micrograms/ml) and had significantly higher percent free 1,25(OH)2D (0.98 +/- 0.13% and 1.27 +/- 0.14%, respectively) compared to 0.63 +/- 0.03% (P less than 0.05). Thus, the loss of DBP in these patients correlated with a rise in the percent free 1,25(OH)2D. We conclude that levels of total 1,25(OH)2D are an accurate representation of 1,25(OH)2D status in normal subjects, subjects with renal insufficiency without nephrotic syndrome, and hemodialysis patients. In peritoneal dialysis and nephrotic patients, who lose DBP, measurements of free 1,25(OH)2D may be necessary in order to accurately assess 1,25(OH)2D status.     

Serial peritoneal macrophage function studies in new and established continuous ambulatory peritoneal dialysis patients

Peritoneal macrophages (PM) perform first-line defense activity against peritonitis, the most important complication in continuous ambulatory peritoneal dialysis (CAPD) therapy. Our longitudinal study has compared the PM function in 20 uremic patients during periods free of peritonitis since they started CAPD therapy in January 1987. The results showed that at the initiation of CAPD, there was a higher bactericidal activity, phagocytosis index, H2O2 production and interleukin-1 (IL-1), gamma-interferon (IFN-gamma) and tumor necrosis factor (TNF) production ability and MHC expression. As time went on, these progressively decreased, and by 9 months after CAPD therapy had started they were significantly lower than at the beginning. During the 1.5-year follow-up period, there was a significantly increased peritonitis rate in the period 6 months after the beginning of CAPD than in the period before the 6th month (88.3 vs. 11.7% respectively; p less than 0.001). These results indicate that PM of new CAPD patients have a more active function than those of established patients. The established patients had a greater risk of peritonitis. A comparison of the immunological profiles of PM from patients who had a peritonitis history shows that phagocytosis index, bactericidal activity and IL-1 and TNF production of PM were significantly decreased during the period free of peritonitis. This result suggests that these parameters may serve as an indicator in developing peritonitis.     

In vivo effect of 1,25-dihydroxyvitamin D3 on phagocyte function in hemodialysis patients.

1,25-dihydroxyvitamin D3 [1,25(OH)2D3] has been shown to modulate the immune function of monocytes and macrophages. Patients with end-stage renal disease (ESRD) on chronic hemodialysis treatment usually present a deficiency of this active form of vitamin D3. The aim of this study was to investigate the effect of 1,25(OH)2D3 replacement therapy on phagocytosis, bactericidal capacity, and oxidative metabolism of peripheral blood polymorphonuclear leukocytes (PMNL) and monocytes (MN) in chronic hemodialysis patients. Phagocyte function tests were performed before and after four weeks of an oral replacement therapy with 0.5 micrograms/day of 1,25(OH)2D3 (Rocaltrol). The superoxide (O2-) generation of monocytes, measured by cytochrome c reduction and lucigenin-enhanced chemiluminescence (CL) from patients receiving hemodialysis treatment was significantly diminished compared to healthy controls. After the replacement therapy with 1,25(OH)2D3 the O2- production showed a significant improvement, resulting in an increased cytochrome c reduction and lucigenin-CL response. The bactericidal capacity of MN was also impaired and exhibited a significant enhancement of their killing activity after the administration of 1,25(OH)2D3. On the other hand, the luminol-enhanced CL, which reflects the myeloperoxidase-dependent oxidative metabolism, and the phagocytic ability of MN was not affected by the hormone. The function of polymorphonuclear leukocytes (PMNL) from hemodialysis patients showed no impairment in the state of 1,25(OH)2D3 deficiency and the replacement of the hormone did not enhance their function. These results suggest that the deficiency of 1,25(OH)2D3 in patients with ESRD on chronic hemodialysis treatment may be responsible for an impaired monocyte function, which could be improved by an in vivo replacement of the hormone.     

Cultured osteoblasts from normal and hypophosphatemic mice: calcitriol receptors and biological response to the hormone

The content and affinity of calcitriol receptors were analyzed in cultured osteoblasts from normal and hypophosphatemic mice. Hypertonic cell extracts were prepared by sonication followed by centrifugation at 200,000 g x 30 min. Analysis, at saturating levels of labeled 1,25(OH)2D3, revealed that binding of the hormone was dependent on the density of the cells plated and on the length of time in culture. It reached a maximum at 5 days of culture when 1.0 x 10(6) cells were plated. Under those conditions the binding capacity of Hyp osteoblasts was 6306 +/- 1267 sites/ng protein (mean +/- SEM) not different from N cells (7594 +/- 1713). The dissociation constant (Kd) was 18.3 +/- 5.4 and 20.0 +/- 5.7 pM for mutant and normal mouse osteoblasts respectively (NS). In both genotypes, a single peak for specific binding, migrating at approximately 3.0-3.5 S was observed by sucrose gradient centrifugation. 25-hydroxycholecalciferol-24-hydroxylase (24-OHase) was induced at 1 and 10 nM 1,25(OH)2D3 in a dose-dependent fashion. However, the induction was higher in mutant than in normal cells when the medium contained 1 mM and 2 mM phosphate salts. The difference vanished when cells were incubated in the presence of 3 and 4 mM phosphate salts. The effect of calcitriol on cultured osteoblasts was also analyzed in terms of collagen synthesis and alkaline phosphatase activity. In the range of 10(-10) M to 10(-7) M, 1,25(OH)2D3 was found to inhibit collagen synthesis in a dose-dependent fashion. At physiological levels, 1,25(OH)2D3 (10(-11)M-10(-10)M), stimulated alkaline phosphatase activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

1,25-Dihydroxycholecalciferol and peritoneal macrophage chemotaxis in patients on continuous ambulatory peritoneal dialysis.

Single graded doses of 1,25-dihydroxycholecalciferol of 2 and 4 micrograms were added intraperitoneally into the overnight 1.5% glucose dialysate of 6 patients on continuous ambulatory peritoneal dialysis. The effect on peritoneal macrophage chemotaxis and random migration was studied and compared with the baseline when no 1,25-(OH)2D3 was added. No consistent effect on peritoneal macrophage chemotaxis was observed. Random migration was significantly depressed at 4 micrograms when compared with baseline (5.4 +/- 1.9 vs. 12.2 +/- 3.7 cells/high-power field, p less than 0.05). The potential clinical role of 1,25-(OH)2D3 as an immune modulator requires further study.     

Evidence that stimulation of 1,25(OH)2D3 production in primary cultures of mouse kidney cells by cyclic AMP requires new protein synthesis

When primary culture of C75BL6 mouse cortical kidney cells in serum-free medium were incubated with unlabeled 25(OH)D3, they produced a metabolite which co-migrated with authentic 1,25(OH)2D3 and which could be measured by competitive receptor assay. A metabolite co-migrating with authentic 10-oxo-19-nor-25-OH-D3 was also produced. However, when cultures were incubated with 25(OH)D3 for 1 hour or longer, 10-oxo-19-nor-25-OH-D accounted for less than 15% of the total 3H-1,25(OH)2D3 displacement activity. Production of 1,25(OH)2D3 increased with increasing content of the culture, with time of incubation, and with substrate concentration. The apparent Km was 1.4 +/- 0.6 microM and Vmax 2.6 +/- 0.4 pM/mg protein/hr. These cultures possessed a very high level of phosphodiesterase activity, as indicated by their high cyclic AMP (cAMP) response to IBMX. This high phosphodiesterase activity may have been responsible for the lack of stimulation of 1,25(OH)2D3 production by physiologic or near physiologic concentrations of parathyroid hormone (PTH) in the absence of IBMX. However, when IBMX 10(-6) M was present, bPTH 10(-9) M significantly increased production of both cAMP and 1,25(OH)2D3. There was a close correlation between 1,25(OH)2D3 production and cAMP content of the cultures (basal or stimulated). An incubation time of at least 4 hours was required for cAMP to increase 1,25(OH)2D3 production and was inhibited in the presence of cycloheximide and actinomycin D. This study further documents the regulation of renal 1,25(OH)2D3 synthesis by PTH in mammalian kidney and provides evidence for cAMP as a possibly important second messenger in this effect.(ABSTRACT TRUNCATED AT 250 WORDS)     

Leukotriene release from peripheral and peritoneal leukocytes following exposure to peritoneal dialysis solutions

During continuous ambulatory peritoneal dialysis (CAPD), peritoneal host defence mechanisms are repeatedly exposed to dialysis solutions (with unphysiological composition) which may compromise peritoneal immune cell functions. In this context, the current study focused on the capacity of peripheral and peritoneal PMN to release leukotrienes following exposure to conventional CAPD dialysates. PMN were obtained from peripheral blood of healthy volunteers and from the peritoneal effluent of CAPD patients with acute peritonitis. Following isolation, cells were incubated in fresh CAPD dialysates or control buffer, and calcium ionophore A23187-stimulated leukotriene synthesis was measured. Additional experiments included RP-HPLC analysis and radioactivity monitoring of lipoxygenase products in PMN labelled with 14C-arachidonic acid. Leukotriene B4 and leukotrienes C4/D4/E4 were determined by radioimmunoassay. Ionophore-triggered leukotriene release from cells exposed to control buffer was pronounced in inflammatory peritoneal PMN (70.4 +/- 31.3 ng/5 x 10(6) cells LTB4 and 13.4 +/- 19.8 ng/5 x 10(6) cells LTC4/D4/E4, mean +/- SD, n = 14) when compared to healthy peripheral PMN (26.6 +/- 16.9 ng/ml LTB4 and 6.3 +/- 6.6 ng/ml LTC4/D4/E4, n = 12). Incubation in fresh solutions for peritoneal dialysis severely depressed leukotriene release from both cell populations. These results indicate a severe inhibition of cellular responsiveness as a consequence of dialysate exposure which could contribute to the impairment of host defence early in the CAPD cycle.     

Down-regulation of osteoclast differentiation by daidzein via caspase 3.

Phytoestrogens are plant-derived compounds with estrogen-like activity. Phytoestrogen-rich diets may prevent postmenopausal osteoporosis and these molecules maintain bone mass in ovariectomized animals. We compared the effects of the isoflavone daidzein, which has no action on tyrosine kinases, and 17beta-estradiol on the development and activity of osteoclasts in vitro. Nonadherent porcine bone marrow cells were cultured on dentine slices or on culture slides in the presence of 10-8 M of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], with or without 10(-8) M of daidzein, 10(-8) M of 17beta-estradiol for 9-11 days. Multinucleated tartrate-resistant acid phosphatase-positive (TRAP+) cells that resorbed bone (osteoclasts) developed in the presence of 1,25(OH)2D3. The number of osteoclasts formed in response to 1,25(OH)2D3 was reduced by 58 +/- 8% by daidzein and 52 +/- 5% by estrogen (p < 0.01); these effects were reversed by 10-6 M of ICI 182,780. The area resorbed by mature osteoclasts was reduced by 39 +/- 5% by daidzein and 42 +/- 6% by estradiol (p < 0.01). Both compounds also inhibited the 1,25(OH)2D3-induced differentiation of osteoclast progenitors (mononucleated TRAP+ cells), 53 +/- 8% by daidzein and 50 +/- 7% by estradiol (p < 0.05). Moreover, daidzein and estradiol promoted caspase-8 and caspase-3 cleavage and DNA fragmentation of monocytic bone marrow cells. Caspase-3 cleavage was reversed by 10-8 M of ICI 182,780. Both compounds up-regulated the expression of nuclear estrogen receptors ER-alpha and ER-beta. Thus, daidzein, at the same concentration as 17beta-estradiol, inhibits osteoclast differentiation and activity. This may be caused by, at least in part, greater apoptosis of osteoclast progenitors mediated by ERs.     

Relationship between serum 25-hydroxycholecalciferol deficiency and the risk of peritoneal dialysis associated peritonitis

Objective To investigate the relationship between serum 25-hydroxycholecalciferol[25(OH)D3] deficiency and the risk of peritoneal dialysis associated peritonitis. Methods Baseline clinical data (before the peritoneal dialysis catheter insertion) of peritoneal dialysis patients treated with CAPD in the First Affiliated Hospital of Guangxi Medical University from May 1, 2013 to February 1, 2016 were retrospective analyzed. All the patients were followed-up until July 31, 2016. According to the baseline serum 25(OH)D3 levels, patients were divided into deficiency group (25(OH)D3＜15 ng/ml) and non deficiency group (25(OH)D3 ≥15 ng/ml), the baseline clinical data of the two groups were also analyzed. Kaplan-Meier method was used to compare the time-to-peritonitis of two groups. Cox proportional hazard model was used to analyze the relationship between the 25(OH)D3 deficiency and the risk of peritonitis. ROC curve was used to analyze the predictive value of the baseline serum 25(OH)D3 for the risk of PDAP in peritoneal dialysis patients. Results Compared with the 25(OH)D3 non deficiency group, 25(OH)D3 deficiency group had a significant increase incidence of peritonitis, high diastolic blood pressure and mean arterial pressure, but serum albumin, total serum protein decreased significantly (P＜0.05). Kaplan-Meier survival analysis showed that, compared with 25(OH)D3 non deficiency group, the time-to-peritonitis episode of patients with 25(OH)D3 deficiency were shorter (P＜0.05). Cox proportional hazard model showed that after adjusting for age, sex, hemoglobin, serum albumin, C-reactive protein, total Kt/V, eGFR, diabetes or not, 25(OH)D3 deficiency is the independent risk factor of peritoneal dialysis associated peritonitis (HR 5.247, 95%CI 1.180-23.340, P＜0.05). ROC curve showed the area under the curve that baseline serum 25(OH)D3 deficiency predict the occurrence of PDAP was 0.714, and the best cut-off point of baseline serum 25(OH)D3 was 11.35 ng/ml (sensitivity 75%, specificity 63%). Conclusions Peritoneal dialysis associated peritonitis occurred earlier in peritoneal dialysis patients whose baseline serum 25(OH)D3 deficiency. Baseline serum 25(OH)D3 deficiency is the independent risk factor of peritoneal dialysis associated peritonitis, which may predict the incidence of peritoneal dialysis associated peritonitis.     

Specific characteristics of peritoneal leucocyte populations during sterile peritonitis associated with icodextrin CAPD fluids.

BACKGROUND: Icodextrin dialysate used for peritoneal dialysis contains an iso-molar glucose polymer solution, which provides sustained ultrafiltration over long dwell times and is considered a valuable approach to reduce intraperitoneal glucose exposure. However, several side effects have been described, including abdominal pain and allergic and hypersensitivity reactions. Also, reactions compatible with chemical peritonitis have been reported. Over the period of a few months (January 2002-May 2002), a remarkable increase in the number of continuous ambulatory peritoneal dialysis (CAPD) patients using icodextrin dialysate diagnosed with sterile peritonitis was observed in our unit. METHODS: Five of the CAPD patients using icodextrin dialysate in our unit and diagnosed with sterile peritonitis were screened for leucocyte count and leucocyte differentiation during a follow-up period of 77 +/- 23 days. In addition, expression of CD14, a receptor for lipopolysaccharide (LPS), on the peripheral and peritoneal monocyte population was analysed. These results were compared to CAPD patients suffering from bacterial peritonitis. RESULTS: The peritoneal leucocyte count of CAPD patients using icodextrin dialysate and diagnosed with sterile peritonitis did not decrease significantly before treatment with icodextrin dialysate was interrupted, whereas it currently disappeared within 2-4 days in proven bacterial peritonitis. The sterile, cloudy icodextrin effluent contained an excess of macrophages on the day of diagnosis, whereas in bacterial peritonitis essentially an increase in the granulocyte population was observed. No elevation in the eosinophil population was observed. In contrast to bacterial peritonitis, we observed no increase in CD14 expression on the peripheral and peritoneal macrophages on the day of presentation and during the follow-up period. CONCLUSIONS: Specific batches of the icodextrin CAPD fluids contain a macrophage chemotactic agent, which causes a sustained inflammatory state in the peritoneal cavity. Because no increase in the expression of the LPS receptor CD14 could be observed, the increased peritoneal leucocyte count is probably not caused by LPS or LPS-like (possibly peptidoglycan-like) contamination.     

Peritoneal fluid and solute transport: influence of treatment time, peritoneal dialysis modality, and peritonitis incidence

The integrity of the peritoneal membrane in peritoneal dialysis (PD) is of major importance for adequate dialysis and fluid balance. However, alterations in peritoneal fluid transport, such as ultrafiltration failure, often develop during long-term PD. To investigate peritoneal solute and fluid transport and to analyze the influence of treatment time, peritonitis incidence, and PD modality (continuous ambulatory PD [CAPD] or automated PD [APD]), a cross-sectional study with an extended peritoneal transport test that used dextran 70 in 2 L of glucose was performed in 23 nonselected chronic PD patients. Compared were long-term (>40 mo) with short-term PD patients (<40 mo), CAPD with APD patients, and those with a peritonitis incidence of >0.25/yr to those with an incidence of <0.25/yr. Dialysate/plasma (D/P) ratio and mass transfer area coefficient of creatinine, lymphatic absorption rate (LAR), transcapillary ultrafiltration, and effective ultrafiltration were measured. Long-term PD patients had higher D/P ratio of creatinine (73.5 +/- 2.3% versus 65.9 +/- 2.2%; P < 0.01) and higher LAR (243 +/- 69 ml/4 h versus 96 +/- 31 ml/4 h; P < 0.03), both resulting in lower effective ultrafiltration (242 +/- 35 ml/4 h versus 324 +/- 30 ml/4 h; P < 0.05). D/P ratio (r = 0.66) and LAR (r = 0.67) were positively correlated to PD duration. Patients on APD compared with those on CAPD and patients with a history of peritonitis compared with those without did not differ in terms of D/P ratio, mass transfer area coefficient, LAR, transcapillary ultrafiltration, and effective ultrafiltration. Lower ultrafiltration after long-term PD is both the result of increased small solute transport and increased lymphatic absorption. APD or CAPD modality and peritonitis incidence do not have a significant influence on small solute transport or fluid kinetics.