The association of kidney function with repetitive breath-hold diving activities of female divers from Korea, Haenyeo.

BACKGROUND: Voluntary apnea during breath-hold diving (BHD) induces cardiovascular changes including bradycardia, reduced cardiac output, and arterial hypertension. Although the impacts of repetitive BHD on cardiovascular health have been studied previously, the long-term risk for kidney dysfunction has never been investigated. METHODS: A cross-sectional propensity score-matched study was performed to evaluate the influence of repetitive long-lasting BHD on kidney function. Using matching propensity scores (PS), 715 breath-hold female divers (Haenyeo) and non-divers were selected for analysis from 1,938 female divers and 3,415 non-divers, respectively. The prevalence of chronic kidney disease (CKD) defined as an estimated glomerular filtration rate (eGFR) calculated to be less than 60 ml/min/1.73 m2 was investigated in both diver and non-diver groups. RESULTS: The prevalence of CKD was significantly higher in breath-hold divers compared with non-divers after PS matching (12.6% vs. 8.0%, P = 0.004). In multivariate analysis, BHD activity was significantly associated with the risk of CKD in an unmatched cohort (OR, 1.976; 95% CI, 1.465-2.664). In the PS-matched cohort, BHD remained the independent risk factor for CKD even after adjusting for multiple covariates (OR 1.967; 95% CI, 1.341-2.886). CONCLUSION: Shallow but repetitive intermittent apnea by BHD, sustained for a long period of time, may potentially cause a deterioration in kidney function, as a long-term consequence.

The Impact of Renin-Angiotensin System Blockade on Renal Outcomes and Mortality in Pre-Dialysis Patients with Advanced Chronic Kidney Disease.

Renin-angiotensin-system (RAS) blockade is thought to slow renal progression in patients with chronic kidney disease (CKD). However, it remains uncertain if the habitual use of RAS inhibitors affects renal progression and outcomes in pre-dialysis patients with advanced CKD. In this multicenter retrospective cohort study, we identified 2,076 pre-dialysis patients with advanced CKD (stage 4 or 5) from a total of 33,722 CKD patients. RAS blockade users were paired with non-users for analyses using inverse probability of treatment-weighted (IPTW) and propensity score (PS) matching. The outcomes were renal death, all-cause mortality, hospitalization for hyperkalemia, and interactive factors as composite outcomes. RAS blockade users showed an increased risk of renal death in PS-matched analysis (hazard ratio [HR], 1.381; 95% CI, 1.071-1.781; P = 0.013), which was in agreement with the results of IPTW analysis (HR, 1.298; 95% CI, 1.123-1.500; P < 0.001). The risk of composite outcomes was higher in RAS blockade users in IPTW (HR, 1.154; 95% CI, 1.016-1.310; P = 0.027), but was marginal significance in PS matched analysis (HR, 1.243; 95% CI, 0.996-1.550; P = 0.054). The habitual use of RAS blockades in pre-dialysis patients with advanced CKD may have a detrimental effect on renal outcome without improving all-cause mortality. Further studies are warranted to determine whether withholding RAS blockade may lead to better outcomes in these patients.

Fragile maintenance of allograft tolerance induced by lymphocyte sequestration and co-stimulation blockade.

The induction of long-term graft survival has been a goal for the last decade. Nevertheless, the issues of stable maintenance of allograft have not yet been evaluated thoroughly. Here, we studied new approaches for induction of tolerance by lymphocyte sequestration (FTY720) and co-stimulatory blockade (MR1) in skin graft model (DBA/2 to BALB/c), thus evaluating the mechanisms incorporated into the maintenance of allograft in proper function. FTY720+MR1 treatment significantly prolonged graft survival than single agent treatment did, and induced long-term graft survival in 60% of recipients expressing the up-regulation of IL-4 and FoxP3. To assess the stability of graft maintenance, we performed the second transplantation on recipients that had shown long-term graft survival. While recipients accepted the second graft from the same strain of first donor, the recipients not only rejected the third-party skin (C57BL/6) promptly but also rejected the first graft soon after the third-party skin was transplanted. The expression patterns of IL-4 and FoxP3 were changed according to the strains of second graft in lymph nodes and in the first graft. T(reg) cells from tolerant recipients effectively suppressed allo-antigen driven T cell proliferation, but T(reg) cells from recipients primed with third-party antigen had significantly hampered suppressive capacity against previously tolerant antigens. Our data indicate that the combination treatment provides effective tool for the induction of long-term graft survival, and the maintenance of allograft in proper function is an actively regulated process.

Kidney transplantation in sensitized recipients; a single center experience.

A successful transplantation, across a positive crossmatch barrier, is one of the most persistent long-standing problems in the field of kidney transplant medicine. The aim of this study was to describe seven consecutive living renal transplantations in recipients with positive crossmatch for donors or positive for donor specific antibodies (DSAs). A preconditioning regimen including plasmapheresis and intravenous immunoglobulin was delivered three times a week until the crossmatch and/or DSAs became negative. Mycophenolate mofetil and tacrolimus were started two days before the plasmapheresis. The protocol was modified to include administration of anti-CD 20 antibody (rituximab, 375 mg/m(2)) from the patient number 3 through the patient number 7. All seven patients achieved negative conversion of the crossmatch or DSAs, and the kidney transplantations were successfully performed in all cases. Acute cellular rejection occurred in two patients, which were subclinical and controlled with high dose steroid treatment. Antibody-mediated rejection occurred in one patient, which was easily reversed with plasmapheresis. All recipients attained normal graft function during the 7-24 months of follow up. Our study suggests that sensitized patients can be transplanted successfully with desensitization pretreatment.