Cholecalciferol supplementation effectively improved tertiary hyperparathyroidism, FGF23 resistance and lowered coronary calcification score: a prospective study.

Introduction: Tertiary hyperparathyroidism (THPT) and vitamin D deficiency are commonly seen in kidney transplant recipients, which may result in persistently elevated fibroblast growth factor 23 (FGF23) level after transplantation and decreased graft survival. The aim of this study is to evaluate the effect of vitamin D supplementation on THPT, FGF23-alpha Klotho (KLA) axis and cardiovascular complications after transplantation. Materials and methods: Two hundred nine kidney transplant recipients were included and further divided into treated and untreated groups depending on whether they received vitamin D supplementation. We tracked the state of THPT, bone metabolism and FGF23-KLA axis within 12 months posttransplant and explored the predictors and risk factors for intact FGF23 levels, KLA levels, THPT and cardiovascular complications in recipients. Results: Vitamin D supplementation significantly improved FGF23 resistance, THPT and high bone turnover status, preserved better graft function and prevented coronary calcification in the treated group compared to the untreated group at month 12. The absence of vitamin D supplementation was an independent risk factor for THPT and a predictor for intact FGF23 and KLA levels at month 12. Age and vitamin D deficiency were independent risk factors for coronary calcification in recipients at month 12. Conclusion: Vitamin D supplementation effectively improved THPT, FGF23 resistance and bone metabolism, preserved graft function and prevented coronary calcification after transplantation.

Soluble Tim-3/Gal-9 as predictors of adverse outcomes after kidney transplantation: A cohort study.

BACKGROUND: In our previous study, serum soluble T-cell immunoglobulin and mucin structure-3 (sTim-3) and galactosin-9 (sGal-9) were found to be associated with renal function after kidney transplantation. However, it is unclear whether these two indicators can predict adverse outcomes after transplantation. METHODS: Ninety-one recipients of kidney transplantation were enrolled and divided into a stable group and an adverse outcome group (consisting of biopsy-proven rejection, graft loss, death and clinically diagnosed rejection). The expression levels of sTim-3 and sGal-9 before (pre-Tim-3 and pre-Gal-9) and one month after transplantation (post-Tim-3 and post-Gal-9) were measured by ELISA. RESULTS: The level of pre-Tim-3 was significantly higher in the stable group than in the adverse outcome group [median (range), 2275 (840-4236) pg/mL vs. 1589 (353-3094) pg/mL, P = 0.002]. The level of post-Gal-9 was significantly lower in the stable group than in the adverse outcome group [median (range), 4869 (1418-13080) pg/mL vs. 6852: (4128-10760) pg/mL, P = 0.003]. The areas under the curve (AUCs) for pre-Tim-3 and post-Gal-9 were 0.737 (P = 0.002) and 0.751 (P = 0.003), respectively, better than AUC of post-eGFR (0.633) (P = 0.071), according to the receiver operating characteristic (ROC) curve. Through Cox regression analysis, including pre-Tim-3, post-Gal-9, post-eGFR, sex, age, BMI of recipients and donors, pre-Tim-3 and post-Gal-9 were independent risk factors for adverse outcomes after kidney transplantation (P = 0.016, P = 0.033, respectively). CONCLUSION: Serum sTim-3 and sGal-9 can predict adverse outcomes within two years after kidney transplantation.

Pre-transplant donor HBV DNA+ and male recipient are independent risk factors for treatment failure in HBsAg+ donors to HBsAg- kidney transplant recipients.

BACKGROUND: In order to reduce the burden on organ shortage around the world, using potential infectious donor might be an option. However, scarce evidences have been published on kidney transplantation (KTx) from hepatitis B surface antigen (HBsAg) + donors to HBsAg- recipients [D (HBsAg+)/R(HBsAg-)] without hepatitis B virus (HBV) immunity. Here, we reported the results of D(HBsAg+/HBV DNA- or +)/R(HBsAg-) living KTx recipients with or without HBV immunity. METHODS: We retrospectively identified 83 D(HBsAg+)/R(HBsAg-) living KTx recipients, and 83 hepatitis B core antibody (HBcAb) + living donors to HBcAb- recipients [D(HBcAb+)/R(HBcAb-)] were used as control group by reviewing medical archives and propensity score matching. Treatment failure (defined as any HBV serology conversion, liver injury, graft loss, or recipient death) is the primary endpoint. RESULTS: Twenty-four donors (28.9%) were HBV DNA+, and 20 recipients had no HBV immunity in the D(HBsAg+)/R(HBsAg-) group pre-transplantation. HBV prophylaxis was applied in all D(HBsAg+)/R(HBsAg-) recipients, while none was applied in the D(HBcAb+)/R(HBcAb-) group. We observed a significant higher treatment failure in D(HBsAg+)/R(HBsAg-) than D(HBcAb+)/R(HBcAb-) group (21.7% vs. 10.8%, P < 0.001). Interestingly, no significant difference was found between groups on HBV seroconversion, liver and graft function, rejection, infection, graft loss, or death. However, 2/20 recipients without HBV immunity in the D(HBsAg+)/R(HBsAg-) group developed HBV DNA+ or HBsAg+, while none observed in the D(HBcAb+)/R(HBcAb-) group. HBV DNA+ donor and male recipient were significant risk factors for treatment failure. CONCLUSION: D(HBsAg+)/R(HBsAg-) should be considered for living kidney transplantation, but with extra caution on donors with HBV DNA+ and male candidates.

Kidney Transplantation From Hepatitis B Surface Antigen (HBsAg)-Positive Living Donors to HBsAg-Negative Recipients: Clinical Outcomes at a High-Volume Center in China.

BACKGROUND: Data on kidney transplantation (KTx) from hepatitis B surface antigen (HBsAg)-positive (HBsAg+) donors to HBsAg-negative (HBsAg-) recipients [D(HBsAg+)/R(HBsAg-)] are limited. We aimed to report the outcomes of D(HBsAg+)/R(HBsAg-) KTx in recipients with or without hepatitis B surface antibody (HBsAb). METHODS: Eighty-three D(HBsAg+)/R(HBsAg-) living KTx cases were retrospectively identified. The 384 cases of KTx from hepatitis B core antibody-positive (HBcAb+) living donors to HBcAb-negative (HBcAb-) recipients [D(HBcAb+)/R(HBcAb-)] were used as the control group. The primary endpoint was posttransplant HBsAg status change from negative to postive (-- →+). RESULTS: Before KTx, 24 donors (28.9%) in the D(HBsAg+)/R(HBsAg-) group were hepatitis B virus (HBV) DNA positive, and 20 recipients were HBsAb-. All 83 D(HBsAg+)/R(HBsAg-) recipients received HBV prophylaxis, while no D(HBcAb+)/R(HBcAb-) recipients received prophylaxis. After a median follow-up of 36 months (range, 6-106) and 36 months (range, 4-107) for the D(HBsAg+)/R(HBsAg-) and D(HBcAb+)/R(HBcAb-) groups, respectively, 2 of 83 (2.41%) D(HBsAg+)/R(HBsAg-) recipients and 1 of 384 (0.26%) D(HBcAb+)/R(HBcAb-) became HBsAg+, accompanied by HBV DNA-positive (P = .083). The 3 recipients with HBsAg-→+ were exclusively HBsAb-/HBcAb- before KTx. Recipient deaths were more frequent in the D(HBsAg+)/R(HBsAg-) group (6.02% vs 1.04%, P = .011), while liver and graft function, rejection, infection, and graft loss were not significantly different. In univariate analyses, pretransplant HBsAb-/HBcAb- combination in the D(HBsAg+)/R(HBsAg-) recipients carried a significantly higher risk of HBsAg-→+, HBV DNA-→+, and death. CONCLUSIONS: Living D(HBsAg+)/R(HBsAg-) KTx in HBsAb+ recipients provides excellent graft and patient survivals without HBV transmission. HBV transmission risks should be more balanced with respect to benefits of D(HBsAg+)/R(HBsAg-) KTx in HBsAb-/HBcAb- candidates.

Modulatory effect of aquaporin 5 on estrogen-induced epithelial-mesenchymal transition in prostate epithelial cells.

BACKGROUND: Estrogen is involved in the pathophysiological process of benign prostatic hyperplasia (BPH), in which epithelial-mesenchymal transition (EMT) plays an important role. Upregulation of aquaporin (AQP) 5, which is directly activated by estrogen, has been reported to promote EMT in multiple cells. This study aimed to examine the effects of AQP5 on estrogen-induced EMT in the prostate. METHODS: Normal prostate (NP) tissue samples without any histopathological changes and BPH tissue samples with pathologically confirmed hyperplasia were obtained. An EMT cell model was subsequently established by adding estradiol (E2) to RWPE-1 cells, after which AQP5 knockdown was performed. Tissue morphological and immunohistochemical features were examined using hematoxylin-eosin and immunohistochemical staining. Western blot analysis was performed to determine the expression of AQPs, estrogen receptors, and EMT-related proteins. Cell proliferation was assessed and supernatants were collected for enzyme-linked immunosorbent assay to determine transforming growth factor-ß1 (TGF-ß1) concentrations. Immunofluorescence staining was performed to assess protein expressions in RWPE-1 cells. RESULTS: BPH tissues exhibited greater EMT (TGF-ß1: 1.362 ±â€Š0.196 vs. 0.107 ±â€Š0.067, P = 0.003; vimentin: 1.581 ±â€Š0.508 vs. 0.221 ±â€Š0.047, P < 0.001; E-cadherin: 0.197 ±â€Š0.188 vs. 1.344 ±â€Š0.088, P < 0.001), higher AQP5 (1.268 ±â€Š0.136 vs. 0.227 ±â€Š0.055, P < 0.001) and estrogen receptor (ER) α (1.250 ±â€Š0.117 vs. 0.329 ±â€Š0.134, P < 0.001) expression but lower ERß (0.271 ±â€Š0.184 vs. 1.564 ±â€Š0.130, P < 0.001) expression than NP tissues. E2-stimulated cells had higher AQP5 expression (1.298 ±â€Š0.058 vs. 1.085 ±â€Š0.104, P = 0.049), increased cell proliferation (1.510 ±â€Š0.089 vs.1.000 ±â€Š0.038, P < 0.001), and EMT (TGF-ß1 concentration: 0.352 ±â€Š0.021 ng/mL vs. 0.125 ±â€Š0.014 ng/mL, P < 0.001; vimentin: 1.641 ±â€Š0.120 vs. 0.188 ±â€Š0.020, P = 0.002; E-cadherin: 0.075 ±â€Š0.030 vs. 0.843 ±â€Š0.046, P < 0.001) than controls. E2-stimulated cells with AQP5 knockdown exhibited decreased EMT (TGF-ß1 concentration: 0.223 ±â€Š0.041 ng/mL vs. 0.352 ±â€Š0.021 ng/mL, P = 0.016; vimentin: 0.675 ±â€Š0.056 vs. 1.641 ±â€Š0.120, P = 0.001; E-cadherin: 0.159 ±â€Š0.037 vs. 0.075 ±â€Š0.030, P = 0.040) than E2-stimulated cells with non-related small interfering RNA (siRNA). CONCLUSION: Our findings suggest that estrogen induces BPH possibly by promoting AQP5 expression. Hence, AQP5 might be a novel target for modulating EMT in prostate epithelial cells.

Development of nanotechnology in andrology.

Since first introduced in 1980s, nanotechnology has always been the eye-catching point as its providing us with new approaches to explore the microscopic world. Many nanotechnology-associated novel technologies have been brought into clinical use in the past decades and uncountable patients benefited from them, which convinces us of a bright prospect of nanotechnology in the field of medicine. In this review, literatures concerning nanotechnology applications in andrology were retrieved and we made a comprehensive discussion on drug delivery, gene therapy and stem cell therapy use in andrology, which calls for the engagement of nanotechnology.

Individualized Preconditioning for ABO-Incompatible Living-Donor Kidney Transplantation: An Initial Report of 48 Cases from China.

BACKGROUND ABO-incompatible (ABOi) living-donor kidney transplantation (KTx) is well established in developed countries, but not yet in China. MATERIAL AND METHODS We developed individualized preconditioning protocols for ABOi KTx based on initial ABO antibody titers. After propensity score matching of ABOi with ABO-compatible (ABOc) KTx, post-transplant outcomes were compared. RESULTS Between September 2014 and June 2018, 48 ABOi living-donor KTx candidates received individualized preconditioning, and all underwent subsequent KTx (median initial ABO titers: 16 for IgM and 16 for IgG). Thirty-one recipients (64.6%) were preconditioned with rituximab (median dose: 200 mg, range: 100-500 mg). Among 37 patients (77.1%) who received pre-transplant antibody removal, the median number of sessions of antibody removal required to achieve ABOi KTx was 2 (range: 1-5), which was conducted between days -10 and -1. Eleven ABOi recipients (22.9%) were preconditioned with oral immunosuppressants alone. Hyperacute rejection led to the loss of 2 grafts in the ABOi group. After a median follow-up of 27.6 months (ABOi group) and 29.8 months (ABOc group), there were no significant differences in graft/recipient survival, rejection, and infection. There were marginally higher rates of severe thrombocytopenia (<50×109/L) (P=0.073) and delayed wound healing (P=0.096) in ABOi recipients. CONCLUSIONS Our individualized preconditioning protocol evolved as our experience grew, and the short-term clinical outcomes of ABOi KTx did not differ from those of matched ABOc patients. ABOi KTx may be a major step forward in expanding the kidney living-donor pool in China.

Protective effect of bone marrow mesenchymal stem cells modified with klotho on renal ischemia-reperfusion injury.

OBJECTIVE: To detect the combination protective effect of bone marrow mesenchymal stem cells (BMSCs) and Klotho gene on the renal ischemia-reperfusion injury (RIRI). METHODS: BMSCs isolated from rats were transfected with Klotho gene to form BMSCKl. We injected BMSCKl to allogenic rat RIRI model. After 24 h and 72 h, we detected the serum creatinine (SCr), malondialdehyde (MDA), and superoxide dismutase (SOD) in renal tissue, Hematoxylin-eosin (HE) staining, and TUNEL of renal pathology. The expression of FoxO1 and p-FoxO1 in post-hypoxia tubular epithelial cells of normal rat kidney (NRK-52E) were detected by Western blot after cocultured with BMSCKl. RESULTS: Comparing with BMSCCon group, Rats in BMSCKl group had lower SCr and MDA but higher SOD. Both HE and TUNEL score of renal tissue in BMSCKl group were lower than that of BMSCCon group. Western blot indicated that FoxO1 was upregulated, while p-FoxO1 was downregulated in post-hypoxia NRK-52E cells. CONCLUSIONS: BMSCs transfected with Klotho gene can further ameliorate RIRI. The possible mechanism may be attributed to the upregulation of SOD in NRK-52E caused by Klotho-FoxO1 axis.

Steroid withdrawal or avoidance is safe in high-risk kidney transplants: A systematic review and meta-analysis.

The present study is aimed to assess the safety and efficacy of steroid withdrawal or avoidance (SWA) in high-risk kidney transplant (HRKT). We performed a systematic review of the literature and pooled analysis of the available data concerning SWA following HRKT. HRKT is associated with patients undergoing repeat kidney transplantation, in African American recipients, or in patients with panel-reactive antibody levels >20%. Seven cohort studies and one randomized controlled trial, involving a total of 22 075 patients, were included. Pooled analysis to estimate the risk ratio (RR) and 95% confidence interval (CI) demonstrated comparable graft loss (RR = 0.91, 95% CI 0.76-1.09) between the SWA and corticosteroid maintenance groups, but with reduced mortality in the SWA group (RR = 0.90, 95% CI 0.84-0.98). A subanalysis suggested that SWA was not associated with increased graft loss in patients undergoing steroid withdrawal within 1 week of transplantation, in African American recipients, or in patients with follow-up >5 years. Additionally, SWA was associated with reduced death in those undergoing withdrawal within 1 week (RR = 0.90, 95% CI 0.84-0.98), in African Americans (RR = 0.90, 95% CI 0.83-0.98), and in those with follow-up extended to >5 years (RR = 0.91, 95% CI 0.84-0.98). SWA was not associated with an increased risk of acute rejection (RR = 0.95, 95% CI 0.75-1.21) or cytomegalovirus infection (RR = 1.86, 95% CI 1-3.47); however, it was associated with a reduced risk of posttransplant diabetes mellitus (RR = 0.60, 95% CI 0.37-0.97). SWA following HRKT is safe in terms of graft survival and rejection, and patients undergoing an SWA regimen had a lower risk of death and posttransplant diabetes mellitus. Future prospective studies are required to confirm these findings.

Effect of renin-angiotensin system inhibitors on survival in kidney transplant recipients: A systematic review and meta-analysis.

Renin-angiotensin system inhibitors, specifically angiotensin II converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), have confirmed renoprotective benefits in patients with proteinuria and hypertension. However, it remains controversial whether these agents are beneficial to kidney recipients. We conducted this meta-analysis to evaluate the effects of ACEI/ARB treatment on patient and allograft survival after kidney transplant. The PubMed, Embase and Cochrane Library databases were searched for eligible articles from before May 2016, and we included 24 articles (9 randomised controlled trials [RCTs] and 15 cohort studies with 54,096 patients), in which patient or graft survival was compared between an ACEI/ARB treatment arm and a control arm. Pooled results showed that ACEI/ARB was associated with decreased risks of patient death (relative risk [RR] = 0.64; 95% confidence interval [CI]:0.49-0.84) and graft loss (RR = 0.59; 95%CI:0.47-0.74). Subgroup analysis of the cohorts revealed significantly reduced patient death (RR = 0.61; 95%CI:0.50-0.74) and graft loss (RR = 0.58; 95%CI:0.46-0.73), but this was not seen in RCTs (patient survival: RR = 0.84, 95%CI:0.39-1.81; graft survival: RR = 0.70, 95%CI:0.17-2.79). Significantly less graft loss was noted among patients with biopsy-proved chronic allograft nephropathy (CAN) (RR = 0.26, 95%CI:0.16-0.44). Furthermore, the benefit of ACEI/ARB on patient survival (RR = 0.62; 95%CI:0.47-0.83) and graft survival (RR = 0.58, 95%CI:0.47-0.71) was limited to those with ≥3years' follow-up. ACEI/ARB decreased proteinuria (P < 0.001) and lowered haemoglobin (P = 0.002), but the haemoglobin change requires no additional treatment (from 119-131 g/L to 107-123 g/L). We therefore concluded that ACEI/ARB treatment may reduce patient death and graft loss, but additional well-designed prospective studies are needed to validate these findings.

Fluoroquinolone prophylaxis in preventing BK polyomavirus infection after renal transplant: A systematic review and meta-analysis.

Previous studies regarding the prevention of BK viremia following renal transplantation with fluoroquinolone have yielded conflicting results. The purpose of this systematic review was to examine the evidence regarding the efficacy of fluoroquinolone in preventing BK polyomavirus infection following renal transplantation. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for research articles published prior to January 2015 using keywords such as "fluoroquinolone," "BK viremia," and "renal transplantation." We extracted all types of study published in English. The primary outcome was BK viremia and viruria at 1 year post-transplantation. Secondary outcomes were BK virus-associated nephropathy (BKVN), graft failure, and fluoroquinolone-resistant infection. We identified eight trials, including a total of 1477 participants with a mean duration of fluoroquinolone prophylaxis of >1 month. At 1 year, fluoroquinolone prophylaxis was not associated with a decreased incidence of BK viremia [risk ratio (RR), 0.84; 95% confidence interval (95% CI), 0.58-1.20). No significant differences in BKVN (RR, 0.88; 95% CI, 0.37-2.11), risk of graft failure due to BKVN (RR, 0.68; 95% CI, 0.29-1.59), or fluoroquinolone-resistant infection (RR, 1.08; 95% CI, 0.64-1.83) were observed between the fluoroquinolone prophylaxis and control groups. The results of this study suggest that fluoroquinolone is ineffective in preventing BK polyomavirus infection following renal transplantation.

[Learning Curve of Retroperitoneal Laparoscopic Donor Nephrectomy and Risk Analysis of Intraoperative Complications].

OBJECTIVES: To investigate the learning curve of retroperitoneal laparoscopic donor nephrectomy (LDN) and evaluate the risk factors of intraoperative complications with data from a single center. METHODS: We evaluated perioperative data of 527 consecutive kidney donors who received retroperitoneal LDN between April 2009 and April 2014. The patients were divided into two groups according to the learning curve which was determined by the operation time:group 1 (on the learning curve) and group 2 (learning curve completed). RESULTS: The mean operation time was (88.4±38.07) min. The asymptote of the surgeon's learning curve for retroperitoneal LDN was achieved at the 100th case. The operation time and the incidence of intraoperative complications in group 1 were significantly higher than those of group 2. When cases completed, body mass index (BMI) and intraoperative complications were correlated to operative time. The incidence of intraoperative complications was 1.90% and BMI was correlated to the incidence of intraoperative complications. When the learning curve was completed, renal artery numbers and right kidney were found being correlated to operative time. CONCLUSIONS: Retroperitoneal LDN is a safe and effective operation method with a low incidence of complications. Technical proficiency in retroperitoneal LDN could be achieved after 100 surgeries.

[Efficacy and safety of selective serotonin re-uptake inhibitors in the treatment of premature ejaculation: a systematic evaluation].

OBJECTIVE: To evaluate the efficacy and safety of selective serotonin re-uptake inhibitors (SSRIs) in the treatment of premature ejaculation (PE). METHODS: From MEDLINE (Jan, 1950-Mar, 2008), EMBASE (Jan, 1980-Mar, 2008), The Cochrane Library (Issue 1, 2008) and CNKI (Jan, 1979-Mar, 2008), we retrieved and screened the randomized controlled trials (RCT) and randomized crossover trials (RT) as well as various related data, published and unpublished, on the treatment of PE with SSRIs. The methodological quality of the included trials was evaluated by 2 reviewers. Meta-analyses were conducted with RevMan 5.0 on the homogeneous studies. RESULTS: Totally 22 studies on 4 291 patients were included. Meta-analyses showed that after treated with sertraline, fluoxetine, paroxetine, citalopram, dapoxetine and fluvoxamine, the WMD (95% CI) values of the changes in intravaginal ejaculatory latency time (IELT) were 2.63 (1.80, 3.46), 2.21 (1.50, 2.92), 4.31 (2.71, 5.91), 3.82 (3.39, 4.25), 1.57 (1.31, 1.84) and 0.01 (0.71, 0.73) respectively; the RR (95% CI) values of the sexual satisfaction rate of the patients were 1.65 (1.12, 2.43), 2.93 (0.50, 17.31), 3.08 (2.27, 4.17), 2.48 (1.99, 3.09) and 2.93 (2.36, 3.65), and those of their partners were 1.47 (0.98, 2.21), 2.88 (0.38, 21.77), 4.81 (3.15, 7.36), 5.38 (3.75, 7.72) and 2.91 (1.09, 7.78) respectively for sertraline, fluoxetine, paroxetine, citalopram and dapoxetine. CONCLUSION: All the known SSRIs but fluvoxamine could prolong IELT, and some could improve the sexual satisfaction of both the patients and their partners, but their adverse effects should be noted. The moderate possibility of selection bias and publication bias in the included studies might have a negative impact on the evidence intensity of our results. We expect more reliable evidence from more randomized controlled trials.