Mao, Michael A.

Background: Kidney transplantation in patients with atypical hemolytic uremic syndrome (aHUS) is frequently complicated by recurrence, resulting in thrombotic microangiopathy in the renal allograft and graft loss. We aimed to assess the use of eculizumab in the prevention and treatment of aHUS recurrence after kidney transplantation. Methods: Databases (MEDLINE, EMBASE and Cochrane Database) were searched through February 2019. Studies that reported outcomes of adult kidney transplant recipients with aHUS treated with eculizumab were included. Estimated incidence rates from the individual studies were extracted and combined using random-effects, generic inverse variance method of DerSimonian and Laird. Protocol for this systematic review has been registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018089438). Results: Eighteen studies (13 cohort studies and five case series) consisting of 380 adult kidney transplant patients with aHUS who received eculizumab for prevention and treatment of post-transplant aHUS recurrence were included in the analysis. Among patients who received prophylactic eculizumab, the pooled estimated incidence rates of recurrent thrombotic microangiopathy (TMA) after transplantation and allograft loss due to TMA were 6.3% (95%CI: 2.8–13.4%, I2 = 0%) and 5.5% (95%CI: 2.9–10.0%, I2 = 0%), respectively. Among those who received eculizumab for treatment of post-transplant aHUS recurrence, the pooled estimated rates of allograft loss due to TMA was 22.5% (95%CI: 13.6–34.8%, I2 = 6%). When the meta-analysis was restricted to only cohort studies with data on genetic mutations associated with aHUS, the pooled estimated incidence of allograft loss due to TMA was 22.6% (95%CI: 13.2–36.0%, I2 = 10%). We found no significant publication bias assessed by the funnel plots and Egger’s regression asymmetry test (p > 0.05 for all analyses). Conclusions: This study summarizes the outcomes observed with use of eculizumab for prevention and treatment of aHUS recurrence in kidney transplantation. Our results suggest a possible role for anti-C5 antibody therapy in the prevention and management of recurrent aHUS.

ABSTRACTAimThis study aimed to assess the relationship between admission Calcium‐phosphate (CaP) and in‐hospital mortality in hospitalized patients.MethodsAll adult hospitalized patients who had both admission serum calcium and phosphate levels available between years 2009 and 2013 were enrolled. Admission CaP was categorized based on its distribution into six groups (<21, 21–<27, 27–<33, 33 39, 39–<45 and ≥45 mg2/dL2). Multivariate logistic regression was used to assess the association between admission CaP and in‐hospital mortality, using the CaP of 27–<33 mg2/dL2 as the reference group.ResultsAbut 14 772 patients were included in the analysis. The association between CaP and in‐hospital mortality was U‐shaped with the lowest in‐hospital mortality in CaP of 27–<33 mg2/dL2. After adjusting for potential confounders, both CaP <21 and ≥39 mg2/dL2 were associated with higher in‐hospital mortality. Subgroup analysis demonstrated that the highest in‐hospital mortality risk in both chronic kidney disease (CKD) and non‐CKD patients occurred when CaP ≥ 45 mg2/dL2.ConclusionCaP levels on admission were associated with in‐hospital mortality. Highest mortality risk was observed in hospitalized patients with admission CaP of ≥45 mg2/dL2 in both CKD and non‐CKD patients.

Introduction Significant tricuspid regurgitation is a well recognized indicator of right ventricular dysfunction. Recent studies have shown that significant tricuspid regurgitation is potentially associated with increased mortality in patients with severe aortic stenosis who underwent transcatheter aortic valve replacement (TAVR). However, data remained sparse and inconclusive. Thus, we performed a systematic review and meta-analysis of the literature to assess the association between significant tricuspid regurgitation and mortality in post TAVR patients. Hypothesis Significant tricuspid regurgitation is predictive for higher mortality in patients undergoing TAVR. Methods We comprehensively searched the databases of MEDLINE and EMBASE from inception to October 2018. Included studies were published observational studies that reported multivariate analysis of the effects of significant tricuspid regurgitation on all-cause mortality among patients undergoing TAVR. Data from each study were combined utilizing the random-effects, generic inverse variance method of DerSimonian and Laird to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results Nine cohort studies from August 2011 to May 2018 consisting of 27 614 patients with severe aortic stenosis undergoing TAVR (6255 with and 21 359 without significant tricuspid regurgitation) were included in this meta-analysis. The presence of significant tricuspid regurgitation was associated with higher all-cause mortality (pooled OR = 2.26, 95% CI: 1.45–3.52, P < 0.001). We found that all-cause mortality remained statistically substantial in all subgroups (30-day all-cause mortality: OR = 2.05, 95% CI: 1.20–3.49, P = 0.009; midterm all-cause mortality: OR = 9.67, 95% CI: 2.44–38.31, P = 0.001; and long-term all-cause mortality: OR = 1.48, 95% CI: 1.19–1.85, P < 0.001). Funnel plots and Egger's regression asymmetry test were performed and showed no publication bias. Conclusion Significant tricuspid regurgitation increased risk of mortality by up to two-fold among patients with severe aortic stenosis undergoing TAVR. Our study suggests that significant tricuspid regurgitation should be considered a component of risk stratification tools.

Background: The incidence and mortality of renal cell carcinoma (RCC) after kidney transplantation (KTx) remain unclear. This study’s aims were (1) to investigate the pooled incidence/incidence trends, and (2) to assess the mortality/mortality trends in KTx patients with RCC. Methods: A literature search was conducted using the MEDLINE, EMBASE and Cochrane databases from inception through October 2018. Studies that reported the incidence or mortality of RCC among kidney transplant recipients were included. The pooled incidence and 95% CI were calculated using a random-effect model. The protocol for this meta-analysis is registered with PROSPERO; no. CRD42018108994. Results: A total of 22 observational studies with a total of 320,190 KTx patients were enrolled. Overall, the pooled estimated incidence of RCC after KTx was 0.7% (95% CI: 0.5–0.8%, I2 = 93%). While the pooled estimated incidence of de novo RCC in the native kidney was 0.7% (95% CI: 0.6–0.9%, I2 = 88%), the pooled estimated incidence of RCC in the allograft kidney was 0.2% (95% CI: 0.1–0.4%, I2 = 64%). The pooled estimated mortality rate in KTx recipients with RCC was 15.0% (95% CI: 7.4–28.1%, I2 = 80%) at a mean follow-up time of 42 months after RCC diagnosis. While meta-regression analysis showed a significant negative correlation between year of study and incidence of de novo RCC post-KTx (slopes = −0.05, p = 0.01), there were no significant correlations between the year of study and mortality of patients with RCC (p = 0.50). Egger’s regression asymmetry test was performed and showed no publication bias in all analyses. Conclusions: The overall estimated incidence of RCC after KTX was 0.7%. Although there has been a potential decrease in the incidence of RCC post-KTx, mortality in KTx patients with RCC has not decreased over time.

Background: The study’s aim was to summarize the incidence and impacts of post-liver transplant (LTx) acute kidney injury (AKI) on outcomes after LTx. Methods: A literature search was performed using the MEDLINE, EMBASE and Cochrane Databases from inception until December 2018 to identify studies assessing the incidence of AKI (using a standard AKI definition) in adult patients undergoing LTx. Effect estimates from the individual studies were derived and consolidated utilizing random-effect, the generic inverse variance approach of DerSimonian and Laird. The protocol for this systematic review is registered with PROSPERO (no. CRD42018100664). Results: Thirty-eight cohort studies, with a total of 13,422 LTx patients, were enrolled. Overall, the pooled estimated incidence rates of post-LTx AKI and severe AKI requiring renal replacement therapy (RRT) were 40.7% (95% CI: 35.4%–46.2%) and 7.7% (95% CI: 5.1%–11.4%), respectively. Meta-regression showed that the year of study did not significantly affect the incidence of post-LTx AKI (p = 0.81). The pooled estimated in-hospital or 30-day mortality, and 1-year mortality rates of patients with post-LTx AKI were 16.5% (95% CI: 10.8%–24.3%) and 31.1% (95% CI: 22.4%–41.5%), respectively. Post-LTx AKI and severe AKI requiring RRT were associated with significantly higher mortality with pooled ORs of 2.96 (95% CI: 2.32–3.77) and 8.15 (95%CI: 4.52–14.69), respectively. Compared to those without post-LTx AKI, recipients with post-LTx AKI had significantly increased risk of liver graft failure and chronic kidney disease with pooled ORs of 3.76 (95% CI: 1.56–9.03) and 2.35 (95% CI: 1.53–3.61), respectively. Conclusion: The overall estimated incidence rates of post-LTx AKI and severe AKI requiring RRT are 40.8% and 7.0%, respectively. There are significant associations of post-LTx AKI with increased mortality and graft failure after transplantation. Furthermore, the incidence of post-LTx AKI has remained stable over the ten years of the study.

Background and objectives: Fluid overload and central sleep apnea are highly prevalent in patients with heart failure (HF). We performed this meta-analysis to assess the effects of acetazolamide therapy on acid/base balance and apnea indexes. Methods: A literature search was conducted using EMBASE, MEDLINE, and Cochrane Database from inception through 18 November 2017 to identify studies evaluating the use of acetazolamide in HF. Study results were analyzed using a random effects model. The protocol for this systematic review is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017065401). Results: Nine studies (three randomized controlled trials and six cohort studies) with a total of 229 HF patients were enrolled. After acetazolamide treatment, there were significant decreases in serum pH (mean difference (MD) of −0.04 (95% CI, −0.06 to −0.02)), pCO2 (MD of −2.06 mmHg (95% CI, −3.60 to −0.53 mmHg)), and serum bicarbonate levels (MD of −6.42 mmol/L (95% CI, −10.05 to −2.79 mmol/L)). When compared to a placebo, acetazolamide significantly increased natriuresis (standardized mean difference (SMD) of 0.67 (95% CI, 0.08 to 1.27)), and decreased the apnea-hypopnea index (AHI) (SMD of −1.06 (95% CI, −1.75 to −0.36)) and central apnea index (CAI) (SMD of −1.10 (95% CI, −1.80 to −0.40)). Egger’s regression asymmetry tests revealed no publication bias with p = 0.20, 0.75 and 0.59 for analysis of the changes in pH, pCO2, and serum bicarbonate levels with use of acetazolamide in HF patients. Conclusion: Our study demonstrates significant reduction in serum pH, increase in natriuresis, and improvements in apnea indexes with use of acetazolamide among HF patients.

AbstractBackgroundBone and mineral metabolism disorders are common among end‐stage renal disease (ESRD) patients, which could lead to hip fracture. It is unclear whether the hip fracture risk is different among patients on hemodialysis (HD) versus peritoneal dialysis (PD). This meta‐analysis was conducted to evaluate the hip fracture risk in ESRD patients on HD, when compared to PD.MethodsA literature review was conducted in EMBASE, MEDLINE, and Cochrane databases through January 31, 2018 to identify studies that appraised the rate or risk of hip fracture among patients on HD, when compared to PD. Effect estimates from the individual studies were derived and consolidated utilizing random‐effect, generic inverse variance approach of DerSimonian and Laird.ResultsFive cohort studies with 1 276 677 ESRD patients were enrolled. HD status was associated with a significantly higher risk of hip fracture with the pooled odds ratio (OR) of 1.61 (95% confidence interval [CI] 1.50‐1.73, I2 = 10.0%), compared with PD. When the analysis was limited to studies with confounder‐adjusted analysis, the pooled OR of hip fracture among HD patients was 1.57 (95% CI 1.43‐1.72, I2 = 13.6%). Funnel plots and Egger's regression test demonstrated no significant publication bias in our meta‐analysis.ConclusionsAmong ESRD patients, HD status is associated with a 61% higher risk of hip fracture compared to PD.