Outcomes of Kidney Transplant Patients with Atypical Hemolytic Uremic Syndrome Treated with Eculizumab: A Systematic Review and Meta-Analysis

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.

Download Full-text

Thrombotic microangiopathy after kidney transplantation: Analysis of the Brazilian Atypical Hemolytic Uremic Syndrome cohort

PLoS ONE ◽

10.1371/journal.pone.0258319 ◽

2021 ◽

Vol 16 (11) ◽

pp. e0258319

Author(s):

Hong Si Nga ◽

Lilian Monteiro Pereira Palma ◽

Miguel Ernandes Neto ◽

Ida Maria Maximina Fernandes-Charpiot ◽

Valter Duro Garcia ◽

...

Keyword(s):

Kidney Transplantation ◽

Kidney Transplant ◽

Atypical Hemolytic Uremic Syndrome ◽

Graft Loss ◽

Complement Inhibitor ◽

Therapeutic Group ◽

Transplant Patients ◽

Uremic Syndrome ◽

Kidney Transplant Patients ◽

Brazilian Cohort

Background Atypical Hemolytic Uremic Syndrome (aHUS) is an ultra-rare disease that potentially leads to kidney graft failure due to ongoing Thrombotic Microangiopathy (TMA). The aim was evaluating the frequency of TMA after kidney transplantation in patients with aHUS in a Brazilian cohort stratified by the use of the specific complement-inhibitor eculizumab. Methods This was a multicenter retrospective cohort study including kidney transplant patients diagnosed with aHUS. We collected data from 118 transplant centers in Brazil concerning aHUS transplanted patients between 01/01/2007 and 12/31/2019. Patients were stratified into three groups: no use of eculizumab (No Eculizumab Group), use of eculizumab for treatment of after transplantation TMA (Therapeutic Group), and use of eculizumab for prophylaxis of aHUS recurrence (Prophylactic Group). Results Thirty-eight patients with aHUS who received kidney transplantation were enrolled in the study. Patients’ mean age was 30 years (24–40), and the majority of participants was women (63% of cases). In the No Eculizumab Group (n = 11), there was a 91% graft loss due to the TMA. The hazard ratio of TMA graft loss was 0.07 [0.01–0.55], p = 0.012 in the eculizumab Prophylactic Group and 0.04 [0.00–0.28], p = 0.002 in the eculizumab Therapeutic Group. Conclusion The TMA graft loss in the absence of a specific complement-inhibitor was higher among the Brazilian cohort of kidney transplant patients. This finding reinforces the need of eculizumab use for treatment of aHUS kidney transplant patients. Cost optimization analysis and the early access to C5 inhibitors are suggested, especially in low-medium income countries.

Download Full-text

Efficacy and Safety of Eculizumab in Kidney Transplant Patients With Primary Atypical Hemolytic-Uremic Syndrome

Transplantation Proceedings ◽

10.1016/j.transproceed.2021.09.063 ◽

2021 ◽

Author(s):

Cristina Casas González ◽

Verónica López-Jiménez ◽

Teresa Vázquez-Sánchez ◽

Elena Vázquez-Sánchez ◽

Mercedes Cabello ◽

...

Keyword(s):

Hemolytic Uremic Syndrome ◽

Kidney Transplant ◽

Atypical Hemolytic Uremic Syndrome ◽

Efficacy And Safety ◽

Transplant Patients ◽

Uremic Syndrome ◽

Kidney Transplant Patients

Download Full-text

Influence of polymorphisms in the vascular endothelial growth factor gene on allograft rejection after kidney transplantation: a meta-analysis

F1000Research ◽

10.12688/f1000research.27800.1 ◽

2021 ◽

Vol 10 ◽

pp. 90

Author(s):

Thanee Eiamsitrakoon ◽

Phuntila Tharabenjasin ◽

Noel Pabalan ◽

Hamdi Jarjanazi ◽

Adis Tasanarong

Keyword(s):

Kidney Transplantation ◽

Kidney Transplant ◽

Allograft Rejection ◽

Meta Analysis ◽

Clinical Genetics ◽

Nucleotide Polymorphisms ◽

Transplant Patients ◽

Increased Risk ◽

Kidney Transplant Patients ◽

Bonferroni Test

Background: Reported associations of allograft rejection in kidney transplant patients with VEGF single nucleotide polymorphisms (SNPs) have been inconsistent between studies, which prompted a meta-analysis to obtain more precise estimates. Methods: Using the PICO elements, kidney transplant patients (P) were compared by genotype data between rejectors (I) and non-rejectors (C) in order to determine the risk of allograft rejection (O) attributed to the VEGF SNPs. Literature search of four databases yielded seven articles. To calculate risks for allograft rejection, four SNPs were examined. Using the allele-genotype model we compared the variant (var) with the wild-type (wt) and heterozygous (var-wt) alleles. Meta-analysis treatments included outlier and subgroup analyses, the latter was based on ethnicity (Indians/Caucasians) and rejection type (acute/chronic). Multiple comparisons were corrected with the Bonferroni test. Results: Five highly significant outcomes (Pa < 0.01) survived Bonferroni correction, one of which showed reduced risk for the var allele (OR 0.61, 95% CI 0.45-0.82). The remaining four indicated increased risk for the wt allele where the chronic rejection (OR 2.10, 95% CI 1.36-3.24) and Indian (OR 1.44, 95% CI 1.13-1.84) subgroups were accorded susceptibility status. Conclusions: Risk associations for renal allograft rejection were increased and reduced on account of the wt and var alleles, respectively. These findings could render the VEGF polymorphisms useful in the clinical genetics of kidney transplantation.

Download Full-text

Epidemiology and Prognostic Importance of Atrial Fibrillation in Kidney Transplant Recipients: A Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm7100370 ◽

2018 ◽

Vol 7 (10) ◽

pp. 370 ◽

Cited By ~ 4

Author(s):

Charat Thongprayoon ◽

Ronpichai Chokesuwattanaskul ◽

Tarun Bathini ◽

Nadeen Khoury ◽

Konika Sharma ◽

...

Keyword(s):

Atrial Fibrillation ◽

Kidney Transplantation ◽

Kidney Transplant ◽

Meta Analysis ◽

Random Effect ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

The Individual ◽

Allograft Loss ◽

Over Time

This meta-analysis was conducted with the aims to summarize all available evidence on (1) prevalence of pre-existing atrial fibrillation (AF) and/or incidence of AF following kidney transplantation; (2) the outcomes of kidney transplant recipients with AF; and (3) the trends of estimated incidence of AF following kidney transplantation over time. A literature search was conducted utilizing MEDLINE, EMBASE, and the Cochrane Database from inception through March 2018. We included studies that reported (1) prevalence of pre-existing AF or incidence of AF following kidney transplantation or (2) outcomes of kidney transplant recipients with AF. Effect estimates from the individual study were extracted and combined utilizing random-effect, generic inverse variance method of DerSimonian and Laird. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018086192). Eight cohort studies with 137,709 kidney transplant recipients were enrolled. Overall, the pooled estimated prevalence of pre-existing AF in patients undergoing kidney transplantation was 7.0% (95% CI: 5.6–8.8%) and pooled estimated incidence of AF following kidney transplantation was 4.9% (95% CI: 1.7–13.0%). Meta-regression analyses were performed and showed no significant correlations between year of study and either prevalence of pre-existing AF (p = 0.93) or post-operative AF after kidney transplantation (p = 0.16). The pooled odds ratios (OR) of mortality among kidney transplant recipients with AF was 1.86 (3 studies; 95% CI: 1.03–3.35). In addition, AF is also associated with death-censored allograft loss (2 studies; OR: 1.55, 95% CI: 1.02–2.35) and stroke (3 studies; OR: 2.54, 95% CI: 1.11–5.78) among kidney transplant recipients. Despite advances in medicine, incidence of AF following kidney transplant does not seem to decrease over time. In addition, there is a significant association of AF with increased mortality, allograft loss, and stroke after kidney transplantation.

Download Full-text

HLA-G 14bp Ins/Del Polymorphism in the 3′UTR Region and Acute Rejection in Kidney Transplant Recipients: An Updated Meta-Analysis

Medicina ◽

10.3390/medicina57101007 ◽

2021 ◽

Vol 57 (10) ◽

pp. 1007

Author(s):

Sang Wook Kang ◽

Eunkyung Oh ◽

Wonwoo Cho ◽

Minseok Kim ◽

Eo Jin Park ◽

...

Keyword(s):

Kidney Transplantation ◽

Acute Rejection ◽

Kidney Transplant ◽

Meta Analysis ◽

Human Leukocyte ◽

Asian Population ◽

Kidney Transplant Recipients ◽

Deletion Polymorphism ◽

Transplant Patients ◽

G 14

Background and Objectives: Acute kidney injury (AKI) affects the survival rate of kidney transplant organs and patients. Acute rejection (AR) due to AKI may lead to kidney transplantation failure. It is known that there is a relationship between human leukocyte antigen-G (HLA-G), which is involved in immune regulation, and AR in transplant patients. Moreover, 14-bp insertion/deletion polymorphism in the 3′ untranslated region (UTR) region of the HLA-G gene is known to affect HLA-G expression. However, its relationship to AR is still controversial. The aim of this study was to investigate whether HLA-G 14-bp insertion/deletion polymorphism contributed to the development of AR in kidney transplant patients using a meta-analysis. Materials and Methods: To perform our meta-analysis, eligible studies about HLA-G 14-bp insertion/deletion polymorphism and AR were searched in electronic databases until 1 June 2021. Finally, a total of 336 patients with AR and 952 patients without AR in relation to kidney transplantation were analyzed from a total of nine studies. Results: In our results, the Del allele and Ins/Del+Del/Del and Del/Del genotypes significantly increased susceptibility of AR in Asian populations [odds ratio (OR) = 2.359, 95% confidence interval (CI) = 1.568–3.550, p = 3.8 × 10−5; OR = 3.357, 95% CI = 1.769–6.370, p = 0.002; OR = 2.750, 95% CI = 1.354–5.587, p = 0.0052 in each model, respectively]. Conclusions: Evidence of the present results indicate that HLA-G 14-bp insertion/deletion polymorphism is associated with susceptibility to AR in the Asian population.

Download Full-text