Wen-Yu Zhao

Mitochondria-targeted antioxidant peptide SS31 prevents hypoxia/reoxygenation-induced apoptosis by down-regulating p66Shc in renal tubular epithelial cells.

Background/Aims: Ischemia/reperfusion injury plays a crucial role in renal transplantation and represents a significant risk factor for acute kidney injury and delayed graft function. Mitochondria-targeted antioxidant peptide SS31 has been shown to attenuate ischemia/reperfusion injury by inhibiting oxidative stress. The present study was carried out to investigate whether the pretreatment of SS31 could reduce hypoxia/reoxygenation (H/R)-induced injury by inhibiting p66Shc. Methods: The cultured rat renal proximal tubular cell line NRK52E cells were exposed to 24 h hypoxia (5% CO2, 1% O2, 94% N2) followed by 6 h reoxygenation (5% CO2, 21% O2, 74% N2). SS31 was added to the culture medium 4 h prior to the treatment. Then the cell viability, apoptosis, and oxidative stress levels were determined. In addition, western blot analysis was performed to determine the expression of p66Shc, p-p66Shc, cytochrome c, and caspase-3. Results: H/R induced apoptotic cell death, accompanied with activation of total and p-p66Shc in NRK52E cells. Pretreatment with SS31 or overexpression of a dominantnegative Ser36 mutant p66Shc (p66Shc S36A) or p66Shc siRNA prevented cell death, whereas the protection effect of SS31 was completely blocked by overexpression of wild-type p66Shc. Furthermore, SS31 pretreatment reduced H/R-induced intracellular oxidative stress, cytochrome c translocation to the cytoplasm, and caspase-3 activation through inhibiting p66Shc. Conclusion: This study revealed that SS31 pretreatment serves a protective role against H/R-induced apoptosis of human renal tubular epithelial cells, and the mechanism is related to suppression of p66Shc.

En bloc kidneys transplanted from infant donors less than 5 kg into pediatric recipients.

Background Given the shortage of donor kidneys, the use of grafts from deceased infant donors is a potential approach to expand the donor pool. Four infant en bloc kidney transplants in pediatric recipients were reported, performed between 2012 and 2013 in the center. Methods The en bloc graft was implanted extraperitoneally in the right iliac fossa. The distal end of the donor aorta was anastomosed end-to-end to the internal iliac artery, while the donor vena cava was anastomosed (end-to-side) to the external iliac vein. Both ureters were anastomosed individually to the bladder, with the exception of one case in which a donor bladder patch was anastomosed to the bladder. After the operation, the recipients received basiliximab as induction therapy followed by tacrolimus and mycophenolic acid for immunosuppression. Prophylactic anticoagulation was used postoperatively. Results Recipients included two girls and two boys with age ranging from 4.6 to 11.6 years. Donor age ranged from 33 to 56 days with weight ranging from 2.5 to 5.0 kg. After a follow-up of 2 to 14 months, patient and graft survivals were 100% and 75%, respectively. Complications included delayed graft function in one patient, urine leak in one, and anticoagulation-related hemorrhage in one. One graft was lost early from vascular thrombosis. The remaining three recipients had excellent graft function with median serum creatinine of 1.1 mg/dL (range, 0.8–1.3 mg/dL) at last follow-up. Conclusions Promising outcomes can be obtained from en bloc transplantation from infant donors. The use of this donor population for pediatric recipients should be encouraged.

A comparison of prediction equations for estimating glomerular filtration rate in Chinese potential living kidney donors

Abstract:  Background:  Accurate measurement of donor renal function has important long‐term implications for both donors and recipients. In clinical practice, renal function may be estimated by using 24‐h urinary creatinine clearance (urine‐CrCl) and various specifically derived prediction equations. We assessed the suitability of urine‐CrCl and prediction equations for evaluating Chinese kidney donors.

Protective effects of sirtuin 3 in a murine model of sepsis-induced acute kidney injury

Acute kidney injury (AKI) is a rapid loss of kidney function characterized by damage to renal tubular cells driven by mitochondrial dysregulation and oxidative stress. Here, we used a murine caecal ligation and puncture (CLP) model of sepsis-induced AKI to study the role of sirtuin 3 (SIRT3), a NAD+ dependent deacetylase critical for the maintenance of mitochondrial viability, in AKI-related renal tubular cell damage and explored the underlying mechanisms. CLP induced alterations in kidney function and morphology were associated with SIRT3 downregulation, and SIRT3 deletion exacerbated CLP-induced kidney dysfunction, renal tubular cell injury and apoptosis, mitochondrial alterations, and ROS production in a knockout mouse model. SIRT3 deletion increased the CLP-induced upregulation of the NLRP3 inflammasome and apoptosis-associated speck-like protein, resulting in the activation of oxidative stress, increased production of the proinflammatory cytokines interleukin (IL)-1β and IL-18, and the enhancement of apoptosis, and these effects were reversed by antioxidant NAC. Our results suggest that SIRT3 plays a protective role against mitochondrial damage in the kidney by attenuating ROS production, inhibiting the NRLP3 inflammasome, attenuating oxidative stress, and downregulating IL-1β and IL-18.

In vitro effects of polyethylene glycol in University of Wisconsin preservation solution on human red blood cell aggregation and hemorheology.

Addition of hydroxyethyl starch (HES) to UW (University of Wisconsin) solution increases viscosity of the solution and red blood cell (RBC) aggregation. Recently, it was suggested that HES could be replaced by a new colloid, polyethylene glycol (PEG), in UW solution. The aim of this study was to see whether and how PEG affected RBC aggregation, and whether RBC aggregation parameters had any correlation with the molecular weight and concentration of PEG. After giving informed consent and signing consent documents, 12 healthy volunteers were enrolled in the study. Blood samples obtained from these volunteers were mixed with the test solutions with blood/solutions ratios of 5:1 and 1:1. Human RBC aggregation was investigated with an automatic hemorheological analyzer. Blood viscosity was measured with a cone-plate viscometer. Morphological characters of RBC aggregates were evaluated by light microscopy. It was found that viscosity was not affected by the Colloid-free UW solution. PEG20kDa (1 and 10 g/L) and PEG35kDa (1 g/L) had little effect on RBC aggregation, while PEG20kDa (30 g/L) and PEG35kDa (10 and 30 g/L) had a significant hyperaggregating effect on RBC. In conclusion, PEGs had a potential hyperaggregating effect on human RBC. This effect is correlated with PEG molecular weight and concentration. The use of large molecular weight and high concentration PEG in UW solution accounts for extended and accelerated aggregation of erythrocytes. The use of low concentration PEG35kDa (1 g/L) would be the optimal choice.

Evaluation of living related kidney donors in China: policies and practices in a transplant center

Zhao W‐Y, Zhang L, Han S, Zhu Y‐H, Wang L‐M, Zhou M‐S, Zeng L. Evaluation of living related kidney donors in China: policies and practices in a transplant center.
Clin Transplant 2010 DOI: 10.1111/j.1399‐0012.2010.01229.x.
© 2010 John Wiley & Sons A/S.

Psychosocial evaluation of Chinese living related kidney donors

Zhao W‐Y, Zeng L, Zhu Y‐H, Wang L‐M, Zhou M‐S, Han S, Zhang L. Psychosocial evaluation of Chinese living related kidney donors. 
Clin Transplant 2010: 24: 766–771.

Optimizing the utilization of kidneys from small pediatric deceased donors under 15 kg by choosing pediatric recipients

Currently, most kidneys from small pediatric deceased donors are transplanted into adult recipients (i.e., PTA). However, due to the weight mismatch, there is a high discard rate and a high ratio of EBKTs if adopting PTA. Here, we sought both to optimize utilization of these challenging but scarce donor grafts by selecting pediatric recipients and to characterize the feasibility and efficacy of this PTP allocation strategy. From February 2012 to October 2014, kidneys from 27 infant donors ≤15 kg were procured and distributed to 38 pediatric candidates in our center. The grafts were utilized for EBKT if the donor weighed 2.5–5 kg and for SKT if the donor weighed 5–15 kg, leading to 10 EBKTs and 28 SKTs. The overall utilization rate from small pediatric deceased donors was 94.12%. After a follow‐up of 3–26 months, the graft survival rate was 89.47%, with four graft losses due to vascular thrombosis. Kidneys from low‐body‐weight donors should be applied to pediatric recipients, and the kidneys from infant donors ≥5 kg can be used in single‐kidney‐transplant procedures at experienced centers to optimize utilization.

Cost analysis of living donor kidney transplantation in China: A single-center experience

BACKGROUND Kidney transplantation is the most cost-effective option for the treatment of end-stage renal disease, but the financial aspects of kidney transplantation have not yet been fully investigated. The purpose of this study was to determine the hospital cost of living donor kidney transplantation in China and to identify factors associated with the high cost. MATERIAL/METHODS Demographic and clinical data of 103 consecutive patients who underwent living donor kidney transplantation from January 2007 to January 2011 at our center were reviewed, and detailed hospital cost of initial admission for kidney transplantation was analyzed. A stepwise multiple regression analysis was computed to determine predictors affecting the total hospital cost. RESULTS The median total hospital cost was US

Single kidneys transplanted from small pediatric donors less than 15 kilograms into pediatric recipients.

10,531, of which 69.2% was for medications, 13.2% for surgical procedures, 11.4% for para clinics, 3.7% for accommodations, 0.5% for nursing care, and 2.0% for other miscellaneous medical services. A multivariate stepwise logistic regression model for overall cost of transplantation revealed that the length of hospital stay, induction therapy, steroid-resistant rejection, maintenance therapy, infection status and body weight were independent predictors affecting the total hospitalization cost. CONCLUSIONS Although the cost of living donor kidney transplantation in China is much lower than that in developed countries, it is a heavy burden for both the government and the patients. As medications formed the greater proportion of the total hospitalization cost, efforts to reduce the cost of drugs should be addressed.