Automated and continuous ambulatory peritoneal dialysis have similar outcomes.

We compared survival and death-censored technique survival in patients on automated peritoneal dialysis (automated dialysis) or on continuous ambulatory peritoneal dialysis. All 4128 patients from the Australia and New Zealand Dialysis and Transplant Registry who started peritoneal dialysis over a 5-year period through March 2004 were included. Times to death and death-censored technique failure were analyzed by Cox proportional hazards models while a conditional risk set model computed technique failure. Compared to patients treated entirely with continuous ambulatory peritoneal dialysis, automated peritoneal dialysis patients were more likely to be young, Caucasian, have marginally lower body mass index, and were less likely to have baseline cardiovascular disease or diabetes. Using univariate and multivariate analysis, our study showed there were no significant differences in patient survival and death-censored technique failure between the two types of peritoneal dialysis modalities.

Urine macrophage migration inhibitory factor concentrations as a diagnostic tool in human renal allograft rejection.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that is a potent activator of macrophages and T cells. Previous studies have shown that local MIF production is increased in acute renal allograft rejection, suggesting that it may play an important role in the rejection process. AIMS: To determine if urine and serum MIF concentrations: (1) are increased in acute rejection, and (2) can be used as noninvasive tools to discriminate between acute rejection (AR) and cyclosporine nephrotoxicity (CyA toxicity). METHODS: In a prospective study of nine renal allograft patients (five acute rejection and four stable), serial urine MIF concentrations were measured by ELISA in the first 14 days after transplantation. In a retrospective study, MIF concentrations in urine and serum were measured in 24 patients who were biopsied for acute renal transplant dysfunction (11 AR, 13 CyA toxicity). Urine and serum MIF were also measured in 23 stable renal transplant patients and 10 normals. RESULTS: MIF was readily detected in the urine of normal healthy controls (106+/-61 pg/micromol creatinine). In the prospective study, the urinary MIF concentration was increased substantially on day 1 posttransplantation and subsequently fell in parallel with the serum creatinine. However, urine MIF increased before episodes of biopsy proven acute rejection. The retrospective study showed that urine MIF concentrations in patients with AR were increased 5-fold compared to normal controls (439+/-313 pg/micromol Cr; P<0.01). In contrast, urine MIF concentrations in CyA toxicity were not significantly different to normal controls (145+/-119 pg/micromol Cr; P=NS). A marked increase in MIF immunostaining was seen in biopsies of AR, but not in CyA toxicity. No significant differences were evident in serum MIF levels between normals and any transplant patient group. CONCLUSIONS: These results suggest that measurement of urine MIF concentration may be useful in monitoring renal transplant patients for acute rejection and as a discriminator from cyclosporine nephrotoxicity.

Up-regulation of macrophage migration inhibitory factor in acute renal allograft rejection in the rat.

Recent studies have identified a key role for macrophage migration inhibitory factor (MIF) in a number of immune cell-mediated diseases. The current study investigated the potential role of MIF in acute allograft rejection. Lewis rats underwent bilateral nephrectomy and then received an orthotopic DA renal allograft or an orthotopic Lewis renal isograft. Groups of six animals were killed at day 1 or 5 after transplantation. No immunosuppression was used. Animals receiving a renal allograft exhibited severe rejection on day 5, as shown by high levels of serum creatinine, very low rates of creatinine clearance, and severe tubulitis with a dense macrophage and T cell infiltrate. In contrast, isografts had normal renal function on day 5 with no histological evidence of rejection. Northern blotting showed that renal MIF mRNA expression was unchanged at day 1, but was increased 3.5-fold on day 5. In situ hybridization showed a marked increase in MIF mRNA expression by tubular cells and MIF mRNA expression by many infiltrating mononuclear cells in day 5 allografts. Immunostaining confirmed an increase in tubular MIF protein expression, particularly in areas of severe tubular damage with prominent leucocytic infiltration. Double staining showed that many infiltrating macrophages and T cells expressed the MIF protein in day 5 allografts. There was only a minor increase in MIF expression in day 5 isografts, demonstrating that neither surgical injury nor stress cause significant up-regulation of MIF expression in allograft rejection. In conclusion, this study has demonstrated that local MIF production is specifically increased in acute renal allograft rejection. These results suggest that MIF may play an important role in the cellular immune response mediating acute allograft rejection.

Macrophage migration inhibitory factor expression in human renal allograft rejection.

BACKGROUND: Macrophage migration inhibitory factor (MIF) plays a pivotal role in immune-mediated diseases. Despite the long-standing association of MIF with the delayed-type hypersensitivity response, the potential role of MIF in allograft rejection is unknown. METHODS: MIF expression was assessed by in situ hybridization and immunohistochemistry staining in 62 biopsies of human renal allograft rejection and in normal human kidney. RESULTS: MIF mRNA and protein is constitutively expressed in normal kidney, being largely restricted to tubular epithelial cells, some glomerular epithelial cells, and vascular smooth muscle cells. In both acute and chronic renal allograft rejection, there was marked up-regulation of MIF mRNA and protein expression by intrinsic kidney cells such as tubular epithelial cells and vascular endothelial and smooth muscle cells. There was also MIF expression by infiltrating macrophages and T cells. Of note, macrophage and T cell infiltrates were largely restricted to areas with marked up-regulation of MIF expression, potentially contributing to the development of severe tubulitis and intimal or transmural arteritis. Quantitative analysis found that increased MIF expression in allograft rejection gave a highly significant correlation with macrophage and T cell accumulation in both the glomerulus and interstitium (P<0.001). In addition, the number of MIF+ tubules and interstitial MIF+ cells correlated significantly with the severity of allograft rejection (P<0.01), and the loss of renal function (P<0.01). In contrast, no up-regulation of renal MIF expression and no leukocyte accumulation was seen in allograft biopsies without evidence of rejection. CONCLUSIONS: This is the first study to demonstrate that local MIF expression is up-regulated during allograft rejection. The association between up-regulation of MIF expression, macrophage and T cell infiltration and the severity of renal allograft rejection suggests that MIF may be an important mediator in the process of allograft rejection.