Aeddula, Narothama Reddy

Background: C3 glomerulopathy (C3G), a rare glomerular disease mediated by alternative complement pathway dysregulation, is associated with a high rate of recurrence and graft loss after kidney transplantation (KTx). We aimed to assess the efficacy of different treatments for C3G recurrence after KTx. Methods: Databases (MEDLINE, EMBASE, and Cochrane Database) were searched from inception through 3 May, 2019. Studies were included that reported outcomes of adult KTx recipients with C3G. Effect estimates from individual studies were combined using the random-effects, generic inverse variance method of DerSimonian and Laird., The protocol for this meta-analysis is registered with PROSPERO (no. CRD42019125718). Results: Twelve studies (7 cohort studies and 5 case series) consisting of 122 KTx patients with C3G (73 C3 glomerulonephritis (C3GN) and 49 dense deposit disease (DDD)) were included. The pooled estimated rates of allograft loss among KTx patients with C3G were 33% (95% CI: 12–57%) after eculizumab, 42% (95% CI: 2–89%) after therapeutic plasma exchange (TPE), and 81% (95% CI: 50–100%) after rituximab. Subgroup analysis based on type of C3G was performed. Pooled estimated rates of allograft loss in C3GN KTx patients were 22% (95% CI: 5–46%) after eculizumab, 56% (95% CI: 6–100%) after TPE, and 70% (95% CI: 24–100%) after rituximab. Pooled estimated rates of allograft loss in DDD KTx patients were 53% (95% CI: 0–100%) after eculizumab. Data on allograft loss in DDD after TPE (1 case series, 0/2 (0%) allograft loss at 6 months) and rituximab (1 cohort, 3/3 (100%) allograft loss) were limited. Among 66 patients (38 C3GN, 28 DDD) who received no treatment (due to stable allograft function at presentation and/or clinical judgment of physicians), pooled estimated rates of allograft loss were 32% (95% CI: 7–64%) and 53% (95% CI: 28–77%) for C3GN and DDD, respectively. Among treated C3G patients, data on soluble membrane attack complex of complement (sMAC) were limited to patients treated with eculizumab (N = 7). 80% of patients with elevated sMAC before eculizumab responded to treatment. In addition, all patients who responded to eculizumab had normal sMAC levels after post-eculizumab. Conclusions: Our study suggests that the lowest incidence of allograft loss (33%) among KTX patients with C3G are those treated with eculizumab. Among those who received no treatment for C3G due to stable allograft function, there is a high incidence of allograft loss of 32% in C3GN and 53% in DDD. sMAC level may help to select good responders to eculizumab.

AbstractObjectiveCannabis is the most commonly used recreational drug in the United States, and transplant acceptability for cannabis using candidates varies among transplant centers. However, the prevalence and impact of cannabis use on outcomes of kidney transplant recipients remain unclear. This study aimed to summarize the prevalence and impact of cannabis use on outcomes after kidney transplantation.MethodsA literature search was performed using Ovid MEDLINE, EMBASE, and The Cochrane Library Databases from inception until September 2019 to identify studies assessing the prevalence of cannabis use among kidney transplant recipients, and reported adverse outcomes after kidney transplantation. Effect estimates from the individual studies were obtained and combined utilizing random‐effects, generic inverse variance method of DerSimonian‐Laird.ResultsA total of four cohort studies with a total of 55 897 kidney transplant recipients were enrolled. Overall, the pooled estimated prevalence of cannabis use was 3.2% (95% CI 0.4%‐20.5%). While the use of cannabis was not significantly associated with all‐cause allograft failure (OR = 1.31, 95% CI 0.70‐2.46) or mortality (OR = 1.52, 95% CI 0.59‐3.92), the use of cannabis among kidney transplant recipients was significantly associated with increased death‐censored graft failure with pooled OR of 1.72 (95% CI 1.13‐2.60).ConclusionsThe overall estimated prevalence of cannabis use among kidney transplant recipients is 3.2%. The use of cannabis is associated with increased death‐censored graft failure, but not mortality after kidney transplantation.

α-Klotho is a known anti-aging protein that exerts diverse physiological effects, including phosphate homeostasis. Klotho expression occurs predominantly in the kidney and is significantly decreased in patients with chronic kidney disease. However, changes in serum klotho levels and impacts of klotho on outcomes among kidney transplant (KTx) recipients and kidney donors remain unclear. A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through October 2019 to identify studies evaluating serum klotho levels and impacts of klotho on outcomes among KTx recipients and kidney donors. Study results were pooled and analyzed utilizing a random-effects model. Ten cohort studies with a total of 431 KTx recipients and 5 cohort studies with a total of 108 living kidney donors and were identified. After KTx, recipients had a significant increase in serum klotho levels (at 4 to 13 months post-KTx) with a mean difference (MD) of 243.11 pg/mL (three studies; 95% CI 67.41 to 418.81 pg/mL). Although KTx recipients had a lower serum klotho level with a MD of = −234.50 pg/mL (five studies; 95% CI −444.84 to −24.16 pg/mL) compared to healthy unmatched volunteers, one study demonstrated comparable klotho levels between KTx recipients and eGFR-matched controls. Among kidney donors, there was a significant decrease in serum klotho levels post-nephrectomy (day 3 to day 5) with a mean difference (MD) of −232.24 pg/mL (three studies; 95% CI –299.41 to −165.07 pg/mL). At one year following kidney donation, serum klotho levels remained lower than baseline before nephrectomy with a MD of = −110.80 pg/mL (two studies; 95% CI 166.35 to 55.24 pg/mL). Compared to healthy volunteers, living kidney donors had lower serum klotho levels with a MD of = −92.41 pg/mL (two studies; 95% CI −180.53 to −4.29 pg/mL). There is a significant reduction in serum klotho levels after living kidney donation and an increase in serum klotho levels after KTx. Future prospective studies are needed to assess the impact of changes in klotho on clinical outcomes in KTx recipients and living kidney donors.

AbstractBackgroundIn the United States, increasing ethnic diversity has been apparent. However, the epidemiology and trends of BKV genotypes remain unclear. This meta‐analysis was conducted with the aim to assess the prevalence of BKV genotypes among kidney transplant (KTx) recipients in the United States.MethodsA comprehensive literature review was conducted through October 2018 utilizing MEDLINE, Embase, and Cochrane Database to identify studies that reported the prevalence of BKV subtypes and/or subgroups in KTx recipients in the United States. Pooled prevalence rates were combined using random effects, generic inverse variance method. The protocol for this study is registered with PROSPERO (no. CRD42019134582).ResultsA total of eight observational studies with a total of 193 samples (urine, blood, and kidney tissues) from 188 BKV‐infected KTX recipients were enrolled. Overall, the pooled estimated prevalence rates of BKV subtypes were 72.2% (95% confidence of interval [CI]: 62.7‐80.0%) for subtype I, 6.8% (95% CI: 2.5‐16.9%) for subtype II, 8.3% (95% CI: 4.4‐15.1%) for subtype III, and 16.1% (95% CI: 10.4‐24.2%) for subtype IV, respectively. While metaregression analysis demonstrated a significant positive correlation between year of study and the prevalence of BKV subtype I (slopes = +0.1023, P = .01), there were no significant correlations between year of study and percentages of BKV subtype II‐IV (P > .05). Among KTx recipients with BKV subtype I, the pooled estimated percentages of BKV subgroups were 22.4% (95% CI: 13.7‐34.5%) for subgroup Ia, 30.6% (95% CI: 17.7‐47.5%) for subgroup Ib1, 47.7% (95% CI: 35.8‐59.9%) for subgroup Ib2, and 4.1% (95% CI:1.2‐13.3%) for subgroup Ic, respectively.ConclusionBKV subtype I is the most prevalent subtype among KTx recipients in the United States and its prevalence seems to increasing overtime. Subgroup Ib2 is the most common subgroup among BKV subtype I.

Background This study aimed to evaluate the hospitalization rate for Hepatitis A virus (HAV) among kidney transplant (KTx) recipients and its outcomes as well as resource utilization. Methods The 2005–2014 National Inpatient Sample database was used to identify all hospitalized KTx recipients with an associated diagnosis of HAV. The hospital mortality, resource utilization, and associated liver conditions were compared between patients with and without HAV, adjusting for potential confounders. Results Of 871 024 KTx recipients identified, 204 had HAV. The overall inpatient prevalence of HAV in KTx recipients over 10 years in the United States was 23.42 cases per 100 000 admissions. There were no statistically significant changes in the inpatient prevalence of HAV in KTx recipients during the study period (P = 0.77), ranging from 9.2 to 34.3 per 100 000 admissions. Among hospitalized KTx recipients with HAV, 27.9% were from Northeast, 29.2% were from Midwest, 23.8% were from South, and 19.1% were from West. HAV was not significantly associated with increased hospital mortality, multiorgan failure, need for abdominal ultrasound, hospital length of stay, and total hospitalization costs and charges when compared with those without HAV. However, it is significantly associated with increased ICU stay, coexisting hepatitis B and C infection, and liver failure. Conclusion Overall, inpatient prevalence of HAV in KTx recipients in the United States (years 2005–2014) was 23.42 cases per 100 000 admissions. Hospitalization for HAV after KTx is associated with increased ICU stay, coexisting hepatitis B and C infection, and liver failure.

Background: Acute kidney injury (AKI) is a well-established complication of extra-corporal membrane oxygenation (ECMO) in the adult population. The data in the pediatric and neonatal population is still limited. Moreover, the mortality risk of AKI among pediatric patients requiring ECMO remains unclear. Thus, this meta-analysis aims to assess the incidence of AKI, AKI requiring renal replacement therapy and AKI associated mortality in pediatric/neonatal patients requiring ECMO. Methods: A literature search was performed utilizing MEDLINE, EMBASE, and the Cochrane Database from inception through June 2019. We included studies that evaluated the incidence of AKI, severe AKI requiring renal replacement therapy (RRT) and the risk of mortality among pediatric patients on ECMO with AKI. Random-effects meta-analysis was used to calculate the pooled incidence of AKI and the odds ratios (OR) for mortality. Results: 13 studies with 3523 pediatric patients on ECMO were identified. Pooled incidence of AKI and AKI requiring RRT were 61.9% (95% confidence interval (CI): 39.0–80.4%) and 40.9% (95%CI: 31.2–51.4%), respectively. A meta-analysis limited to studies with standard AKI definitions showed a pooled estimated AKI incidence of 69.2% (95%CI: 59.7–77.3%). Compared with patients without AKI, those with AKI and AKI requiring RRT while on ECMO were associated with increased hospital mortality ORs of 1.70 (95% CI, 1.38–2.10) and 3.64 (95% CI: 2.02–6.55), respectively. Conclusions: The estimated incidence of AKI and severe AKI requiring RRT in pediatric patients receiving ECMO are high at 61.9% and 40.9%, respectively. AKI among pediatric patients on ECMO is significantly associated with reduced patient survival.

Background: Acute kidney injury (AKI) is a common complication following solid-organ transplantation. However, the epidemiology of AKI and mortality risk of AKI among patients undergoing cardiac transplantation is not uniformly described. We conducted this study to assess the incidence of AKI and mortality risk of AKI in adult patients after cardiac transplantation. Methods: A systematic review of EMBASE, MEDLINE, and Cochrane Databases was performed until June 2019 to identify studies evaluating the incidence of AKI (by standard AKI definitions), AKI requiring renal replacement therapy (RRT), and mortality risk of AKI in patients undergoing cardiac transplantation. Pooled AKI incidence and mortality risk from the included studies were consolidated by random-effects model. The protocol for this study is registered with PROSPERO (no. CRD42019134577). Results: 27 cohort studies with 137,201 patients undergoing cardiac transplantation were identified. Pooled estimated incidence of AKI and AKI requiring RRT was 47.1% (95% CI: 37.6–56.7%) and 11.8% (95% CI: 7.2–18.8%), respectively. The pooled ORs of hospital mortality and/or 90-day mortality among patients undergoing cardiac transplantation with AKI and AKI requiring RRT were 3.46 (95% CI, 2.40–4.97) and 13.05 (95% CI, 6.89–24.70), respectively. The pooled ORs of 1-year mortality among patients with AKI and AKI requiring RRT were 2.26 (95% CI, 1.56–3.26) and 3.89 (95% CI, 2.49–6.08), respectively. Conclusion: Among patients undergoing cardiac transplantation, the incidence of AKI and severe AKI requiring RRT are 47.1% and 11.8%, respectively. AKI post cardiac transplantation is associated with reduced short term and 1-year patient survival.

Background: Lung transplantation has been increasingly performed worldwide and is considered an effective therapy for patients with various causes of end-stage lung diseases. We performed a systematic review to assess the incidence and impact of acute kidney injury (AKI) and severe AKI requiring renal replacement therapy (RRT) in patients after lung transplantation. Methods: A literature search was conducted utilizing Ovid MEDLINE, EMBASE, and Cochrane Database from inception through June 2019. We included studies that evaluated the incidence of AKI, severe AKI requiring RRT, and mortality risk of AKI among patients after lung transplantation. Pooled incidence and odds ratios (ORs) with 95% confidence interval (CI) were obtained using random-effects meta-analysis. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42019134095). Results: A total of 26 cohort studies with a total of 40,592 patients after lung transplantation were enrolled. Overall, the pooled estimated incidence rates of AKI (by standard AKI definitions) and severe AKI requiring RRT following lung transplantation were 52.5% (95% CI: 45.8–59.1%) and 9.3% (95% CI: 7.6–11.4%). Meta-regression analysis demonstrated that the year of study did not significantly affect the incidence of AKI (p = 0.22) and severe AKI requiring RRT (p = 0.68). The pooled ORs of in-hospital mortality in patients after lung transplantation with AKI and severe AKI requiring RRT were 2.75 (95% CI, 1.18–6.41) and 10.89 (95% CI, 5.03–23.58). At five years, the pooled ORs of mortality among patients after lung transplantation with AKI and severe AKI requiring RRT were 1.47 (95% CI, 1.11–1.94) and 4.79 (95% CI, 3.58–6.40), respectively. Conclusion: The overall estimated incidence rates of AKI and severe AKI requiring RRT in patients after lung transplantation are 52.5% and 9.3%, respectively. Despite advances in therapy, the incidence of AKI in patients after lung transplantation does not seem to have decreased. In addition, AKI after lung transplantation is significantly associated with reduced short-term and long-term survival.

Background: Although acute kidney injury (AKI) is a frequent complication in patients receiving extracorporeal membrane oxygenation (ECMO), the incidence and impact of AKI on mortality among patients on ECMO remain unclear. We conducted this systematic review to summarize the incidence and impact of AKI on mortality risk among adult patients on ECMO. Methods: A literature search was performed using EMBASE, Ovid MEDLINE, and Cochrane Databases from inception until March 2019 to identify studies assessing the incidence of AKI (using a standard AKI definition), severe AKI requiring renal replacement therapy (RRT), and the impact of AKI among adult patients on ECMO. Effect estimates from the individual studies were obtained and combined utilizing random-effects, generic inverse variance method of DerSimonian-Laird. The protocol for this systematic review is registered with PROSPERO (no. CRD42018103527). Results: 41 cohort studies with a total of 10,282 adult patients receiving ECMO were enrolled. Overall, the pooled estimated incidence of AKI and severe AKI requiring RRT were 62.8% (95%CI: 52.1%–72.4%) and 44.9% (95%CI: 40.8%–49.0%), respectively. Meta-regression showed that the year of study did not significantly affect the incidence of AKI (p = 0.67) or AKI requiring RRT (p = 0.83). The pooled odds ratio (OR) of hospital mortality among patients receiving ECMO with AKI on RRT was 3.73 (95% CI, 2.87–4.85). When the analysis was limited to studies with confounder-adjusted analysis, increased hospital mortality remained significant among patients receiving ECMO with AKI requiring RRT with pooled OR of 3.32 (95% CI, 2.21–4.99). There was no publication bias as evaluated by the funnel plot and Egger’s regression asymmetry test with p = 0.62 and p = 0.17 for the incidence of AKI and severe AKI requiring RRT, respectively. Conclusion: Among patients receiving ECMO, the incidence rates of AKI and severe AKI requiring RRT are high, which has not changed over time. Patients who develop AKI requiring RRT while on ECMO carry 3.7-fold higher hospital mortality.

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.