Zhongli Huang

Calcineurin Inhibitors Associated Posterior Reversible Encephalopathy Syndrome in Solid Organ Transplantation: Report of 2 Cases and Literature Review.

AbstractPosterior reversible encephalopathy syndrome (PRES) is a rare neurologic side effect of calcineurin inhibitors (CNIs) with poorly understood clinical features.We report cases of 2 patients with PRES developing after kidney transplantation and summarize PRES clinical features through a literature review.The 1st case was a 28-year-old man who received a kidney transplant from a deceased donor. Initial immunosuppressive therapy consisted of tacrolimus/mycophenolate mofetil/prednisolone. He developed headache and blurred vision with visual field loss15 days after transplantation and generalized seizures 4 days later. The 2nd case was a 34-year-old man who received a living kidney transplant. His initial immunosuppressive therapy comprised tacrolimus/mycophenolate mofetil/prednisolone. Two months after transplantation, he developed seizures. Both patients were diagnosed with PRES based on neurological symptoms and magnetic resonance imaging (MRI) findings; they recovered after switching from tacrolimus to either a cyclosporine or a lower tacrolimus dose. CNI-associated PRES is an acute neurological syndrome with seizures, encephalopathy, visual abnormalities, headache, focal neurological deficits, and nausea/vomiting. It is always accompanied by hypertension. A fluid-attenuated inversion recovery signal MRI scan typically shows reversible subcortical white matter changes in the posterior cerebral hemisphere that usually occur within the 1st month after transplantation. CNI-associated PRES has a generally favorable prognosis with early diagnosis and prompt treatment including alternating or discontinuing CNIs and blood pressure control.CNI-associated PRES should be considered in patients exhibiting acute neurological symptoms after transplantation. Early diagnosis and immediate treatment are critical for a favorable prognosis.

Controlled-dose versus fixed-dose mycophenolate mofetil for kidney transplant recipients: a systematic review and meta-analysis of randomized controlled trials.

Background Although mycophenolate mofetil (MMF) is recommended at a fixed dose, there is increasing interest in controlled-dose (CD) MMF based on therapeutic drug monitoring. We systematically evaluated published randomized controlled trials (RCTs) on the efficacy and safety of CD versus fixed-dose MMF for kidney transplant recipients. Methods The electronic databases Medline, Embase, and Cochrane Library (up to June 2012) were searched to identify relevant RCTs. Two reviewers independently applied the study selection criteria, examined the study quality, and extracted the data. Dichotomous measures were expressed as relative risk (RR) and continuous outcomes were expressed as weighted mean difference, both with 95% confidence intervals (CIs). All statistical analyses were performed using Review Manager 5.1.6. Results Four RCTs met our selection criteria and included 1755 de novo recipients. The differences between CD and fixed-dose MMF in treatment failure (RR, 0.95; 95% CI, 0.82–1.10; P=0.52), serum creatinine clearance (weighted mean difference, 2.46; 95% CI, −1.15 to 6.07; P=0.18), total gastrointestinal adverse events (RR, 1.23; 95% CI, 0.65–2.35; P=0.53), diarrhea (RR, 1.08; 95% CI, 0.92–1.25; P=0.35), anemia (RR, 1.24; 95% CI, 0.95–1.64; P=0.12), leukopenia (RR, 1.12; 95% CI, 0.93–1.35; P=0.25), thrombocytopenia (RR, 0.80; 95% CI, 0.47–1.36; P=0.41), and malignancy (RR, 0.61; 95% CI, 0.27–1.38; P=0.23) were not statistically significant. Furthermore, total infections were more frequent in the CD group (36.0% vs. 30.9%; RR, 1.16; 95% CI, 1.03–1.30; P=0.01). Conclusions Based on current evidence, CD MMF administration cannot be recommended as routine practice for kidney transplant recipients. Therapeutic drug monitoring for MMF may be targeted toward high-risk recipients, who should be identified in future studies.

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.

Kidneys from Older Living Donors Provide Excellent Short and Intermediate Outcomes--A Single China Center's Experience.

Background Transplantation with kidneys from older living donors is on the rise, yet controversy still exists over whether the outcomes are as satisfactory as with kidneys from younger donors. Methods We retrospectively analyzed 1009 living donor kidney transplants performed at our center between 2006 and 2013. Graft and patient outcomes were compared between transplants with kidneys from old living donors (OLD, 55-65 years) (n = 264) and from young living donors (YLD, <55 years) (n = 745). Results The age was 32.80 ± 9.71 years and 33.91 ± 5.98 years for recipient in YLD and OLD group, respectively. Death-censored graft survival at 1, 3, and 5 years was 98.8%, 97.1%, and 95.8% in patients receiving YLD kidneys, similar to the corresponding values of 97.6%, 95.5% and 95.5% in patients receiving OLD kidneys (P = 0.356). Patient survival at 1, 3, and 5 years after transplantation was also similar for patients receiving YLD kidneys (98.5%, 97.1%, and 96.7%) and for patients receiving OLD kidneys (99.6%, 99.6%, and 96.8%; P = 0.110). The OLD kidneys were not associated with increased risk of death-censored graft failure (hazard ratio, 2.5; 95% confidence interval, 0.57 to 11.11) and patient death (hazard ratio, 1.67; 95% confidence interval, 0.75 to 3.73). In addition, there is no increased graft loss or patient death for each 10-year increase in donor age. Transplantation with OLD kidneys was not associated with reduced patient or graft outcomes in the short term (⩽12 months) or medium term (>1 year). Conclusions Graft and patient outcomes after living-donor kidney transplantation are similar in the short-term and medium-term for donors aged 55 to 65 years and for younger donors. Therefore, the use of OLD kidneys should be encouraged in China.

Short-term therapeutic drug monitoring of mycophenolic acid reduces infection: a prospective, single-center cohort study in Chinese living-related kidney transplantation.

The role of therapeutic drug monitoring (TDM) of mycophenolic acid (MPA) in kidney transplant recipients (KTRs) is not clear. We performed a prospective cohort study to evaluate the efficiency of MPA TDM in the Chinese population.

Factors affecting willingness to receive a kidney transplant among hemodialysis patients in West China: A cross-sectional survey

Abstract Many factors are associated with the willingness of ESRD patients to receive a kidney transplant. No data are available for patients in China. The study aim was to describe the attitudes toward transplantation in a cohort of patients at a single dialysis center in China. A study questionnaire derived from previously published literature was completed by 239 hemodialysis outpatients. Factors associated with willingness to receive a transplant were identified by univariate and multivariate logistic regression analyses. The respondents were primarily men 50.7 ± 15.1 years of age; 46.4% were willing to receive a transplant. Younger age (OR = 0.928, 95% CI: 0.898–0.959), good self-reported health (OR = 0.203, 95% CI: 0.081–0.51), and awareness of the benefits of transplantation (OR = 0.195, 95% CI: 0.083–0.456) were less likely to deny the transplant. Patients ⩽60 years of age were about 13 times more likely to favor transplantation than those >60 years of age (OR = 12.99, 95% CI: 3.75–45.45). For every 10 years under 60, participants were 2.16 times more willing to receive a kidney transplant (OR = 2.16, 95% CI: 1.53–3.02). Older patients were also less likely to be referred for evaluation (OR = 0.955, 95% CI: 0.923–0.989, P = .009). The percentage of ESRD patients in China, particularly older patients, who are willing to accept a transplant, is relatively low. A better understanding of the benefits of transplantation is needed to increase their acceptance.

The pre-transplant anemic condition is independent of long-term outcome in living-related kidney transplantation.

Abstract The relationship between pre-transplant Hemoglobin (Hb) concentration and long-term outcome of living-related kidney transplantation is far from well addressed. A retrospective cohort study was conducted by reviewing the medical profile of the patients who received living-related kidney transplantations at our center from January 2006 to January 2013. Patients were divided into two groups: high Hb group (≥10 g/dL) and low Hb group (<10 g/dL). Cox regression model was utilized to analyze the effect of pre-transplant hemoglobin concentration on the patient and graft survival. About 422 patients were of Hb level <10 g/dL (78.30 ± 14.18 g/dL), 280 were >10 g/dL (116.2 ± 14.43 g/dL) (p < 0.001). In a follow-up of 35.34 ± 18.12 months, we did not find any difference in serum creatinine between the two groups. Low Hb concentration is not associated with increased risk of developing DGF (HR = 1.186, 95% CI: 0.53–2.654), acute rejection (HR = 1.338, 95% CI: 0.919–1.947), overall infection (HR = 1.263, 95% CI: 0.847–1.885) nor perioperational infection (HR = 1.019, 95% CI: 0.513–2.026). Though we detected a trend that low Hb level group were of higher incidence of patient death and graft failure, the two groups did not differ significantly (2.38% vs. 0.71%, p = 0.096; and 4.04% vs. 2.14%, p = 0.165, respectively). Cox regression model revealed that pre-transplant Hb level <10 g/dL was independent of increased overall mortality (HR = 3.379; 95% CI: 0.706–17.172) and increased death censored allograft failure risk (HR = 1.556; 95% CI: 0.595–4.069). Pre-transplant Hb concentration <10 g/dL is independent of poor long-term outcome of living-related kidney transplantation.

Outcomes of single kidney transplantation from pediatric donors: A single-center experience

Kidneys from pDDs are increasingly used to narrow the huge gap between incremental demand and static supply. However, there is still controversy on the clinical outcome of SKT from pDDs. We conducted a retrospective cohort study of 452 adult recipients in our center between March 2012 and February 2017. Outcomes of 3 groups, transplants with organs from pDDs (n=50), aDDs (n=207), and LDs (n=195), were compared. The mean age and weight of pDDs were 8.98 years (range 8 months‐17 years) and 30.05 kg (range 8.2‐55 kg), respectively. There was no difference in 1‐year (96.0%, 98.1%, and 99.0%, respectively, P=.277) and 3‐year patient survival (96.0%, 98.1%, and 99.0%, respectively, P=.277) or in 1‐year (96.0%, 96.6%, and 98.5%, P=.307) and 3‐year (96.0%, 96.6% and 97.9%, P=.437) graft survival. SCr, eGFR, and allograft size were similar among the 3 groups at 6th month post‐transplant and thereafter. Incidence of DGF was higher in patients of the aDD group than those in the pDD group (22.7% vs 10.0%, P<.001), but there was no difference in AR and infection. SKT from pDDs to adult recipients is effective and safe with acceptable outcomes, and it will be a promising expansion to the donor pool.

miR-17-92 ameliorates renal ischemia reperfusion injury

There is limited information on the role of miR‐17‐92 in renal tubular pathophysiology. Therefore, the present study was performed to determine whether miR‐17‐92 plays a role in ischemia‐reperfusion injury (IRI)‐induced acute kidney injury. We originally demonstrated that miR‐17‐92 is up‐regulated following IRI in vivo. To explore the roles of miR‐17‐92 in the IRI process, we first generated a renal proximal tubule‐specific miR‐17‐92 deletion (PT‐miR‐17‐92−/−) knockout mouse model with Cre driven by the Kap promoter. We found that PT‐deficient miR‐17‐92 mice had more severe renal dysfunction and renal structures than their littermates. Compared with sham‐operated mice, both wide‐type (WT) mice and PT‐miR‐17‐92−/− mice showed increased serum levels of creatinine and urea. However, the levels of serum urea and creatinine in PT‐miR‐17‐92−/− mice after the IRI operation were significantly higher than the levels in WT mice. In addition, PT‐miR‐17‐92−/− mice showed higher levels of serum potassium and phosphonium after the IRI operation. Histological analysis revealed that PT‐miR‐17‐92−/− mice had substantial histopathologic changes, such as tubular dilation and tubular necrosis. Overexpression of miR‐17‐92 could partially reverse the side‐effects of IRI on the proximal tubules in vivo. Furthermore, we employed a quantitative proteomic strategy and identified 16 proteins as potential targets of miR‐17‐92. Taken together, our findings suggested that miR‐17‐92 may ameliorates IRI‐induced acute kidney injury. Our results indicate that pharmacologic modulation of these miRNAs may have therapeutic potential for acute kidney injury.

Impact of remaining kidney volume to body weight ratio on renal function in living kidney donors

To investigate whether the ratio of remnant kidney volume to body weight (V/W ratio) can impact renal function in donors, 45 living kidney donors were enrolled. Kidney volume was analyzed by magnetic resonance imaging. Renal function was compared between donors with a V/W ratio of < 2.0 mL/kg (n = 23) or ≥ 2.0 mL/kg (n = 22). Donors in both V/W groups showed similar serum creatinine levels and estimated glomerular filtration rates (eGFRs) at 7 days and 1 year, whereas donors with a V/W ratio of < 2.0 mL/kg had significantly higher 24‐hour urine protein levels at 1 year (0.54 ± 0.23 g/d vs. 0.33 ± 0.19 g/d, p = 0.028). Multivariate analysis revealed no correlation between the V/W ratio and eGFR at 7 days or 1 year, and a V/W ratio of < 2 mL/kg was not associated with an increased incidence of eGFR < 60 mL/min/1.73 m2 at 1 year (risk ratio 1.73, 95% confidence interval 0.10–29.47). The V/W ratio correlated inversely with 24‐hour urine protein (r = −0.377, p = 0.021) at 1 year, and donors with a V/W ratio of < 2.0 mL/kg were more likely to show 24‐hour urine protein >300 mg (risk ratio 1.70, 95% confidence interval 1.08–2.67) at 1 year. Donors with lower V/W ratios have higher 24‐hour urinary protein levels at 1 year after transplantation. These findings suggest that the V/W ratio may be useful for kidney selection.