This study aimed to evaluate how 5 preservation solutions for static cold storage affected kidney transplant outcomes. It included all first single kidney transplants during 2010‐2014 from donations ...after brain death in the French national transplant registry, excluding preemptive transplants and transplants of kidneys preserved with a hypothermic perfusion machine. The effects of each preservation solution on delayed graft function (DGF) and 1‐year transplant failure were evaluated with hierarchical multivariable logistic regression models. The study finally included 7640 transplanted kidneys: 3473 (45.5%) preserved with Institut Georges Lopez‐1 solution (IGL‐1), 773 (10.1%) with University of Wisconsin solution, 731 (9.6%) with Solution de Conservation des Organes et Tissus (SCOT, organ and tissue preservation solution), 2215 (29.0%) with Celsior, and 448 (5.9%) with histidine–tryptophan–ketoglutarate. Primary nonfunction rates did not differ by solution. After adjustment for donor, recipient, and transplant characteristics, the DGF risk was significantly lower with IGL‐1 than with all other solutions (odds ratio OR 0.55, 95% confidence interval CI 0.48‐0.64). Conversely, SCOT was associated with a DGF risk significantly higher than the other solutions (OR 2.69, 95% CI 2.21‐3.27) and triple that of IGL‐1 (OR 3.37, 95% CI 2.72‐4.16). One year after transplantation, the transplant failure rate did not differ significantly by preservation solution. The difference between the groups for 1‐year mean creatinine clearance was not clinically relevant.
This study compares outcomes in a French multicenter cohort of donation after brain death kidney transplants according to the 5 preservation solutions used for static cold storage, showing that preservation solution type was associated with differential risk of delayed graft function but not 1‐year graft survival.
In recent decades, the allocation policies of many countries have moved from center‐based to patient‐based approaches. The new French kidney allocation system (KAS) of donations after brain death for ...adult recipients, implemented in 2015, was principally designed to introduce a unified allocation score (UAS) to be applied locally for one kidney and nationally for the other and to replace regional borders by a new geographical model. The new KAS balances dialysis duration and waiting time to compensate for listing delays and provides more effective longevity matching between donors and recipients with better HLA and age matching. We report these changes, with their rationale and main results. Results show improved HLA matching for young recipients and more rapid access to transplant for older recipients. Young recipients also had better access to transplantation. Transplant access decreased for recipients aged 60–69 and required tuning of KAS parameters. In conclusion, our results strongly indicate that national or adequately broad geographic allocation areas, combined with multiplicative interactions between allocation criteria, permit multivariate optimization of organ allocation and thus improve national kidney sharing and balance HLA matching and age matching, at the price of longer cold ischemic times and more logistical constraints than with local allocation.
This study of the French Kidney Allocation Scheme strongly advocates for allocation areas of sufficient size, combined with multiplicative interactions among allocation criteria, to optimally balance competing considerations.
Our objectives were to evaluate kidney transplantation survival benefit in people aged ≥70 who were receiving renal replacement therapy (RRT) and to identify their risk factors for posttransplant ...mortality. This study included all patients in the national French Renal Epidemiology and Information Network registry who started RRT between 2002 and 2013 at age ≥70. Mortality risk was compared between patients with transplants; on the waiting list; and on dialysis matched for age, gender, comorbidities, and time on dialysis. Of the 41 716 elderly patients starting RRT, 1219 (2.9%) were on the waiting list and 877 (2.1%) underwent transplantation during the follow‐up. Until month 3, transplant patients had a risk of death triple that of the wait‐listed group. Although the risk was halved at month 9, the perioperative risk was still not offset by month 36. Compared with matched dialysis patients (n = 2183), transplant patients were not at significantly increased perioperative risk and had a lower mortality risk starting at month 3. Risk factors for posttransplant mortality were diabetes, cardiovascular comorbidities, and dialysis duration >2 years. Among older dialysis patients, 20% had neither cardiovascular comorbidity nor diabetes. Systematic early assessment of the eligibility of elderly patients for kidney transplantation is recommended to expand registration to patients with poor survival on dialysis and no cardiovascular comorbidity.
This European study assessing the survival benefit of kidney transplantation for a national cohort of patients beginning renal replacement therapy at the age of 70 years or older shows that elderly patients currently on the waiting list obtain lower survival benefits after kidney transplantation compared to potential benefits to a significant proportion of dialysis patients who are not currently on this list.
Alport syndrome is an inherited nephropathy associated with mutations in genes encoding type IV collagen chains present in the glomerular basement membrane. COL4A5 mutations are associated with the ...major X-linked form of the disease, and COL4A3 and COL4A4 mutations are associated with autosomal recessive and dominant forms (thought to be involved in 15% and 1%-5% of the families, respectively) and benign familial hematuria. Mutation screening of these three large genes is time-consuming and expensive. Here, we carried out a combination of multiplex PCR, amplicon quantification, and next generation sequencing (NGS) analysis of three genes in 101 unrelated patients. We identified 88 mutations and 6 variations of unknown significance on 116 alleles in 83 patients. Two additional indel mutations were found only by secondary Sanger sequencing, but they were easily identified retrospectively with the web-based sequence visualization tool Integrative Genomics Viewer. Altogether, 75 mutations were novel. Sequencing the three genes simultaneously was particularly advantageous as the mode of inheritance could not be determined with certainty in many instances. The proportion of mutations in COL4A3 and COL4A4 was notably high, and the autosomal dominant forms of Alport syndrome appear more frequently than reported previously. Finally, this approach allowed the identification of large COL4A3 and COL4A4 rearrangements not described previously. We conclude that NGS is efficient, reduces screening time and cost, and facilitates the provision of appropriate genetic counseling in Alport syndrome.
Background
Several studies have demonstrated that rituximab (RTX) improves relapse-free survival in patients with steroid-dependent nephrotic syndrome (SDNS). However, these studies used various RTX ...regimens and there are few data comparing these regimens in children with SDNS. In this retrospective study, we assessed the effect of three different initial RTX regimens on both time to B cell reconstitution and to first relapse.
Methods
Sixty-one SDNS patients receiving a first course of RTX were included. Group 1 received one injection of 100 mg/m
2
, group 2 received one injection of 375 mg/m
2
, and group 3 received two injections of 375 mg/m
2
at day 0 and day 7. Time to B cell reconstitution and time to first relapse and respective risk factors were studied.
Results
Median time to B cell reconstitution was 2.5 1.8–3.5, 5.0 3.9–6.0, and 6.6 4.6–7.8 months in groups 1, 2, and 3, respectively. RTX regimen was associated with time to B cell reconstitution (HRs group 2 vs. 3, 4.07 1.96–8.48; group 1 vs. 3, 11.13 4.04–30.67). One-year relapse-free survival was 50% 58–77, 59% 42–76, and 72% 46–87 in groups 1, 2, and 3, respectively. RTX regimen was associated with risk of relapse (HRs group 2 vs. 3, 1.55 0.51–4.65; group 1 vs. 3, 4.98 1.15–21.60).
Conclusions
The initial dose of rituximab impacts time to B cell reconstitution and the probability of relapse. Risk of relapse is also associated with patient characteristics, suggesting that RTX regimen could be modified for each patient to balance efficacy, cost, and side effects.
Dense deposit disease and glomerulonephritis with isolated C3 deposits are glomerulopathies characterized by deposits of C3 within or along the glomerular basement membrane. Previous studies found a ...link between dysregulation of the complement alternative pathway and the pathogenesis of these diseases. We analyzed the role of acquired and genetic complement abnormalities in a cohort of 134 patients, of whom 29 have dense deposit disease, 56 have glomerulonephritis with isolated C3 deposits, and 49 have primary membranoproliferative glomerulonephritis type I, with adult and pediatric onset. A total of 53 patients presented with a low C3 level, and 65 were positive for C3 nephritic factor that was significantly more frequently detected in patients with dense deposit disease than in other histological types. Mutations in CFH and CFI genes were identified in 24 patients associated with a C3 nephritic factor in half the cases. We found evidence for complement alternative pathway dysregulation in 26 patients with membranoproliferative glomerulonephritis type I. The complement factor H Y402H variant was significantly increased in dense deposit disease. We identified one at-risk membrane cofactor protein (MCP) haplotype for glomerulonephritis with isolated C3 deposits and membranoproliferative glomerulonephritis type I. Thus, our results suggest a critical role of fluid-phase alternative pathway dysregulation in the pathogenesis of C3 glomerulopathies as well as in immune complex–mediated glomerular diseases. The localization of the C3 deposits may be under the influence of MCP expression.
Mutations in factor H (CFH), factor I (IF), and membrane cofactor protein (MCP) genes have been described as risk factors for atypical hemolytic uremic syndrome (aHUS). This study analyzed the impact ...of complement mutations on the outcome of 46 children with aHUS. A total of 52% of patients had mutations in one or two of known susceptibility factors (22, 13, and 15% of patients with CFH, IF, or MCP mutations, respectively; 2% with CFH+IF mutations). Age <3 mo at onset seems to be characteristic of CFH and IF mutation-associated aHUS. The most severe prognosis was in the CFH mutation group, 60% of whom reached ESRD or died within <1 yr. Only 30% of CFH mutations were localized in SCR20. MCP mutation-associated HUS has a relapsing course, but none of the children reached ESRD at 1 yr. Half of patients with IF mutation had a rapid evolution to ESRD, and half recovered. Plasmatherapy seemed to have a beneficial effect in one third of patients from all groups except for the MCP mutation group. Only eight (33%) of 24 kidney transplantations that were performed in 15 patients were successful. Graft failures were due to early graft thrombosis (50%) or HUS recurrence. In conclusion, outcome of HUS in patients with CFH mutation is catastrophic, and posttransplantation outcome is poor in all groups except for the MCP mutation group. New therapies are urgently needed, and further research should elucidate the unexplained HUS group.
Background
This study is aimed at comparing ultrasound dilution (UD) and thermodilution (TD) with color Doppler ultrasound (CDU) for arteriovenous fistula (AVF) assessment in children on hemodialysis ...(HD).
Material and methods
All patients were dialysed with the Fresenius 5008 HD machine. UD was performed using the Transonic device. The two methods were compared with CDU performed on a non-HD day. AVF flow rate was expressed as ml/min/1.73 m
2
.
Results
Sixteen measurements of AVF flow rate and recirculation with UD and TD were compared with CDU in 16 patients with a median weight of 39 kg. Both UD and TD overestimated AVF flow rate when compared with CDU (+437 (95% CI + 200, + 674) and + 476 (95% CI + 80, + 871) ml/min/1.73 m
2
for UD and TD, respectively). CDU flow rate was significantly correlated to UD flow rate (
r
2
= 0.761,
p
< 0.001), but not to TD flow rate (
r
2
= 0.164,
p
= 0.120). Although recirculation in all AVF was estimated to be 0% and < 15% with UD and TD, respectively, 7 significant stenoses were diagnosed by CDU. AVF with stenosis had lower flow rates when measured by CDU, UD or TD, but only CDU measurements reached statistical significance (
p
= 0.008,
p
= 0.142 and
p
= 0.174, respectively).
Conclusion
UD and TD overestimate AVF flow rate when compared with CDU, which is the most reliable non-invasive method for screening vascular access for stenosis. UD seems more accurate than TD for AVF flow rate assessment. Recirculation via UD or TD should not be used for early screening of AVF stenosis in children on HD.
Background
This study aimed to describe the efficiency and longevity of arteriovenous fistula (AVF) for hemodialysis (HD) in children weighing ≤20 kg.
Methods
We collected data of all AVFs created ...using microsurgery techniques between 1988 and 2015. Success was considered as the ability to use the AVF for HD. Primary and secondary patency rates were measured.
Results
Forty-eight AVFs (35 forearm, 13 upper arm) were created in 41 children with a median weight of 13.5 kg (range 5.5–20). The need for a second AVF was significantly higher in younger and thinner children at the time of AVF creation (
p
= 0.046 and
p
= 0.019, respectively). Successful use for HD occurred in 42 AVFs (87.5%), while six (12.5%) resulted in failure for early thrombosis or nonmaturation. Median time to first cannulation was 18.8 weeks (range 2–166.3). Primary and secondary patency rates at 1, 5, and 10-year follow-ups were 54.2%, 29.2%, and 13.7%; and 85.4%, 57.7%, and 33%, respectively. Almost one third of thromboses after first AVF cannulation were observed at kidney transplantation (KT) perioperatively. At the end of the follow-up (median duration 5.07 years, range 0–17.95), one patient was still on HD via AVF, two died of unrelated reason, and 38 were transplanted—one of whom returned to HD with a new AVF.
Conclusions
AVF using microsurgery techniques is feasible in young children, showing an early failure rate of 12.5%. Time to first cannulation may be rather long, but secondary patency is excellent. Thrombosis rate is high during KT.
BACKGROUND.Considerable differences exist among the living donor Kidney Exchange Programmes (KEPs) that are in use and being built in Europe, contributing to a variation in the number of living donor ...transplants (Newsletter Transplant; International figures on donation and transplantation 2016). Efforts of European KEPs to exchange (best) practices and share approaches to address challenges have, however, been limited.
METHODS.Experts from 23 European countries, collaborating on the European Network for Collaboration on Kidney Exchange Programmes Cooperation on Science and Technology Action, developed a questionnaire to collect detailed information on the functioning of all existing KEPs in Europe, as well as their opportunities and challenges. Following a comparative analysis, results were synthesized and interpreted by the same experts.
RESULTS.The practices, opportunities and challenges reported by 17 European countries reveal that some of the 10 operating programs are mature, whereas others are in earlier stages of development. Over 1300 transplants were performed through existing KEPs up to the end of 2016, providing approximately 8% of their countries’ living kidney donations in 2015. All countries report challenges to either initiating KEPs or increasing volumes. Some challenges are shared, whereas others differ because of differences in context (eg, country size, effectiveness of deceased donor program) and ethical and legal considerations (eg, regarding living donation as such, nonrelated donors, and altruistic donation). Transnational initiatives have started in Central Europe, Scandinavia, and Southern Europe.
CONCLUSIONS.Exchange of best practices and shared advancement of national programs to address existing challenges, aided by transnational exchanges, may substantially improve access to the most (cost) effective treatment for the increasing number of patients suffering from kidney disease.
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