Influence of Peritoneal Transport Characteristics on Nutritional Status and Clinical Outcome in Chinese Diabetic Nephropathy Patients on Peritoneal Dialysis

Background： High peritoneal transport status was previously thought to be a poor prognostic factor in peritoneal dialysis （PD） patients. However, its effect on diabetic nephropathy PD patients is unclear in consideration of the adverse impact of diabetes itself. The purpose of this study was to investigate the influence of peritoneal transport characteristics on nutritional status and clinical outcome in diabetic nephropathy patients on PD. Methods： One hundred and two diabetic nephropathy patients on PD were enrolled in this observational cohort study. According to the initial peritoneal equilibration test result, patients were divided into two groups： Higher transport group （HT, including high and high average transport） and lower transport group （LT, including low and low-average transport）. Demographic characteristics, biochemical data, dialysis adequacy, and nutritional status were evaluated. Clinical outcomes were compared. Risk factors for death-censored technique failure and mortality were analyzed. Results： Compared with LT group （n = 37）, serum albumin was significantly lower and the incidence of malnutrition by subjective global assessment was significantly higher in HT group （n = 65） （P 〈 0.05）. Kaplan-Meier analyses showed that death-censored technique failure and mortality were significantly increased in HT group compared with that in LT group. On multivariate Cox analyses, higher peritoneal transport status and lower residual renal function （RRF） were independent predictors of death-censored technique failure when adjusted for serum albumin and total weekly urea clearance （Kt/V）. Independent predictors of mortality were advanced age, anemia, hypoalbuminemia, and lower RRF, but not higher peritoneal transport status. Conclusions： Higher peritoneal transport status has an adverse influence on nutrition for diabetic nephropathy patients on PD. Higher peritoneal transport status is a significant independent risk factor for death-censored technique failure, but not for mortality in diabetic nephropathy patients on PD.

PI-3 kinase pathway can mediate the effect of TGF-β1 in inducing the expression of SHARP-2 in LLC-PK1 cells

We aim to investigate the effect of transforming growth factor （TGF）-β1 on the expression of enhancer of split- and hairy-related protein-2 （SHARP-2） messenger RNA （mRNA） and its signaling pathway. In this study, several cell lines including LLC-PK1 （a porcine kidney tubular epithelial cell line）, MDCK （Madin-Darby canine kidney） and CTLL-2 （cytotoxic T-lymphocyte line） were treated with recombinant human TGF-131, and a series of experiments were carried out, involving Northern blot analysis of total RNA from these cells. Further, several specific chemical inhibitors were applied before TGF-β1 treatment to probe the signaling pathway. The results showed that TGF-β1 can significadtly up-regulate SHARP-2 mRNA expression in the LLC-PK1 cell line. The peak level of induction was found 2 h after TGF-β1 stimulation. While one phospho- inositide 3-kinases （PI-3） kinase inhibitor, LY294002, completely blocked the effect of TGF-131 on SHARP-2 mRNA expression in LLC-PK1 cells at a low concentration, other inhibitors, including PD98059, staurosporine, AG490, wortmannin, okadaic acid and rapamycin, had no effect. The effect of LY294002 was dose-dependent. We conclude that, in LLC-PK1 cells at least, TGF-β1 can effectively induce the SHARP-2 mRNA expression and that the PI-3 kinase pathway can mediate this effect.

Peritoneal dialysis for autosomal dominant polycystic kidney disease: a retrospective study

To describe the long-term clinical outcomes of patients with autosomal dominant polycystic kidney disease （ADPKD） who are on peritoneal dialysis （PD） therapy. We performed a retrospective matched-cohort analysis com- paring the clinical outcomes of 30 ADPKD patients with those of 30 non-diabetic patients who had bilateral small kidneys between July 1 2007 and July 31 2014. The patient groups were matched by age, gender, and time of PD initiation. There were no significant differences in the demographic or biochemical parameters, comorbid conditions, residual glomerular filtration rate, or Charison comorbidity score at the beginning of PD. The median renal volume was 1315 ml for the ADPKD group and 213 ml for the control group. Patients with ADPKD had similar 3-year patient survival （90.6% versus 86.3%, ,~=-0.807） and technique survival （89.2% versus 74.3%, P=0.506） compared with non-ADPKD patients. Also, there was no significant difference in the peritonitis-free survival between the ADPKD and control groups （P=0.22）, and rates of peritonitis were similar （0.19 versus 0.21 episodes per patient-year, P=-0.26）. No differences were observed in the incidence of PD-related complications, such as hernia and dialysate leak. ADPKD is not a con- traindication for PD, and a subgroup of ADPKD patients with relatively small kidney volume can be treated using PD.

Proteins induced by telomere dysfunction are associated with human IgA nephropathy

Aging is one of the contributing risk factors for kidney diseases. Accumulating evidence prompts the view that telomere length in kidney tissue cells is an indicator for organismal aging. Previously identified aging markers （cathelin-related antimicrobial peptide （CRAMP）, stathmin, elongation factor-1α （EF-1α）, and chitinase） were associated not only with telomere driven aging in mice but also with human aging and chronic diseases. This study focuses on the relationship between these biomarkers and IgA nephropathy （IgAN） progression in the Chinese population. For 260 individuals, the four markers are determined in blind datasets using direct enzyme-linked immunosorbent assay （ELISA） and immunofluorescence staining. The expression levels of CRAMP and chitinase increased in blood plasma, urine, and kidney tissues during human IgAN progression. And for the other nephropathy, such as systemic lupus erythematosus （SLE）, diabetic nephropathy （DN）, and focal segmental glomerulosclerosis （FSGS）, there is no protein upregulaUon with telomere shortening. Moreover, a combination of CRAMP and chitinase can distinguish patients with IgAN from healthy individuals with 88.2%/92.5% （plasma） and 74.3%/84.2% （urine） sensitivity/specificity. These data provide the experimental evidence that telomere shortening and related inflammatory proteins are associated with human IgAN, and it could be a new direction for the disease progression study.