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1.
Kidney Int ; 105(2): 364-375, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37914088

ABSTRACT

Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplant. This is partly because doctors give very large volumes of artificial fluids to keep the new kidney working. When severe, fluid imbalance can lead to seizures, cerebral edema and death. In this pragmatic, open-label, randomized controlled trial, we randomly assigned (1:1) pediatric kidney transplant recipients to Plasma-Lyte-148 or standard of care perioperative intravenous fluids (predominantly 0.45% sodium chloride and 0.9% sodium chloride solutions). We then compared clinically significant electrolyte and acid-base abnormalities in the first 72 hours post-transplant. The primary outcome, acute hyponatremia, was experienced by 53% of 68 participants in the Plasma-Lyte-148 group and 58% of 69 participants in the standard fluids group (odds ratio 0·77 (0·34 - 1·75)). Five of 16 secondary outcomes differed with Plasma-Lyte-148: hypernatremia was significantly more frequent (odds ratio 3·5 (1·1 - 10·8)), significantly fewer changes to fluid prescriptions were made (rate ratio 0·52 (0·40-0·67)), and significantly fewer participants experienced hyperchloremia (odds ratio 0·17 (0·07 - 0·40)), acidosis (odds ratio 0·09 (0·04 - 0·22)) and hypomagnesemia (odds ratio 0·21 (0·08 - 0·50)). No other secondary outcomes differed between groups. Serious adverse events were reported in 9% of participants randomized to Plasma-Lyte-148 and 7% of participants randomized to standard fluids. Thus, perioperative Plasma-Lyte-148 did not change the proportion of children who experienced acute hyponatremia compared to standard fluids. However fewer fluid prescription changes were made with Plasma-Lyte-148, while hyperchloremia and acidosis were less common.


Subject(s)
Acidosis , Hyponatremia , Kidney Transplantation , Water-Electrolyte Imbalance , Humans , Child , Sodium Chloride/adverse effects , Hyponatremia/epidemiology , Hyponatremia/etiology , Electrolytes/adverse effects , Acidosis/etiology , Acidosis/chemically induced , Water-Electrolyte Imbalance/etiology , Water-Electrolyte Imbalance/chemically induced , Fluid Therapy/adverse effects , Isotonic Solutions/adverse effects , Gluconates , Potassium Chloride , Magnesium Chloride , Sodium Acetate
2.
Pediatr Nephrol ; 39(2): 521-530, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37658875

ABSTRACT

BACKGROUND: Renovascular hypertension (RenoVH) is a cause of hypertension in children. A common cause of RenoVH is renal artery stenosis which acts by reducing blood supply to renal parenchyma and activating the renin-angiotensin-aldosterone axis, often leading to cardiac remodelling. This longitudinal observational study aims to describe occurrence of cardiovascular changes secondary to RenoVH and also any improvement in cardiac remodelling after successful endovascular and/or surgical intervention. METHODS: All patients with RenoVH referred to our centre, who received ≥ 1 endovascular intervention (some had also undergone surgical interventions) were included. Data were collected by retrospective database review over a 22-year period. We assessed oscillometric blood pressure and eight echocardiographic parameters pre- and post-intervention. RESULTS: One hundred fifty-two patients met inclusion criteria and had on average two endovascular interventions; of these children, six presented in heart failure. Blood pressure (BP) control was achieved by 54.4% of patients post-intervention. Average z-scores improved in interventricular septal thickness in diastole (IVSD), posterior Wall thickness in diastole (PWD) and fractional shortening (FS); left ventricular mass index (LVMI) and relative wall thickness (RWT) also improved. PWD saw the greatest reduction in mean difference in children with abnormal (z-score reduction 0.25, p < 0.001) and severely abnormal (z-score reduction 0.23, p < 0.001) z-scores between pre- and post-intervention echocardiograms. Almost half (45.9%) had reduction in prescribed antihypertensive medications, and 21.3% could discontinue all antihypertensive therapy. CONCLUSIONS: Our study reports improvement in cardiac outcomes after endovascular + / - surgical interventions. This is evidenced by BP control, and echocardiogram changes in which almost half achieved normalisation in systolic BP readings and reduction in the number of children with abnormal echocardiographic parameters. A higher resolution version of the Graphical abstract is available as Supplementary information.


Subject(s)
Hypertension, Renovascular , Hypertension , Child , Humans , Hypertension, Renovascular/etiology , Hypertension, Renovascular/surgery , Antihypertensive Agents , Retrospective Studies , Ventricular Remodeling , Blood Pressure/physiology
3.
Transpl Int ; 36: 11374, 2023.
Article in English | MEDLINE | ID: mdl-37547751

ABSTRACT

The advent of Machine Perfusion (MP) as a superior form of preservation and assessment for cold storage of both high-risk kidney's and the liver presents opportunities in the field of beta-cell replacement. It is yet unknown whether such techniques, when applied to the pancreas, can increase the pool of suitable donor organs as well as ameliorating the effects of ischemia incurred during the retrieval process. Recent experimental models of pancreatic MP appear promising. Applications of MP to the pancreas, needs refinement regarding perfusion protocols and organ viability assessment criteria. To address the "Role of pancreas machine perfusion to increase the donor pool for beta cell replacement," the European Society for Organ Transplantation (ESOT) assembled a dedicated working group comprising of experts to review literature pertaining to the role of MP as a method of improving donor pancreas quality as well as quantity available for transplant, and to develop guidelines founded on evidence-based reviews in experimental and clinical settings. These were subsequently refined during the Consensus Conference when this took place in Prague.


Subject(s)
Organ Preservation , Organ Transplantation , Humans , Organ Preservation/methods , Pancreas , Perfusion/methods , Tissue Donors
4.
Pediatr Transplant ; 27(3): e14470, 2023 05.
Article in English | MEDLINE | ID: mdl-36651195

ABSTRACT

BACKGROUND: We used the BSAi (Donor BSA/Recipient BSA) to assess whether transplanting a small or large kidney into a pediatric recipient relative to his/her size influences renal transplant outcomes. METHODS: We included 14 322 single-kidney transplants in pediatric recipients (0-17 years old) (01/2000-02/2020) from the United Network for Organ Sharing database. We divided cases into four BSAi groups (BSAi ≤ 1, 1 < BSAi ≤ 2, 2 < BSAi ≤ 3, BSAi > 3). RESULTS: There were no differences concerning delayed graft function (DGF) or primary non-function (PNF) rates, whether the grafts were from living or brain-dead donors. In both transplants coming from living donors and brain-dead donors, cases with BSAi > 3 and cases with 2 < BSAi ≤ 3 had similar graft survival (p = .13 for transplants from living donors, p = .413 for transplants from brain-dead donors), and both groups had longer graft survival than cases with 1 < BSAi ≤ 2 and cases with BSAi ≤ 1 (p < .001). The difference in 10-year graft survival rates between cases with BSAi > 3 and cases with BSAi ≤ 1 reached around 25% in both donor types. The better graft survival in transplants with BSAi > 2 was confirmed in multivariable analysis. CONCLUSIONS: There is no significant impact of donor-recipient size mismatch on DGF and PNF rates in pediatric renal transplants. However, graft survival is significantly improved when the donor's size is more than twice the pediatric recipient's size.


Subject(s)
Kidney Diseases , Kidney Transplantation , Humans , Child , Male , Female , Infant, Newborn , Infant , Child, Preschool , Adolescent , Tissue Donors , Living Donors , Graft Survival , Survival Rate , Brain Death , Registries
5.
Pediatr Nephrol ; 38(11): 3803-3810, 2023 11.
Article in English | MEDLINE | ID: mdl-37209174

ABSTRACT

BACKGROUND: Kidney transplantation is the treatment of choice in chronic kidney disease (CKD) stage 5. It is often delayed in younger children until a target weight is achieved due to technical feasibility and historic concerns about poorer outcomes. METHODS: Data on all first paediatric (aged < 18 years) kidney only transplants performed in the United Kingdom between 1 January 2006 and 31 December 2016 were extracted from the UK Transplant Registry (n = 1,340). Children were categorised by weight at the time of transplant into those < 15 kg and those ≥ 15 kg. Donor, recipient and transplant characteristics were compared between groups using chi-squared or Fisher's exact test for categorical variables and Kruskal-Wallis test for continuous variables. Thirty day, one-year, five-year and ten-year patient and kidney allograft survival were compared using the Kaplan-Meier method. RESULTS: There was no difference in patient survival following kidney transplantation when comparing children < 15 kg with those ≥ 15 kg. Ten-year kidney allograft survival was significantly better for children < 15 kg than children ≥ 15 kg (85.4% vs. 73.5% respectively, p = 0.002). For children < 15 kg, a greater proportion of kidney transplants were from living donors compared with children ≥ 15 kg (68.3% vs. 49.6% respectively, p < 0.001). There was no difference in immediate graft function between the groups (p = 0.54) and delayed graft function was seen in 4.8% and 6.8% of children < 15 kg and ≥ 15 kg respectively. CONCLUSIONS: Our study reports significantly better ten-year kidney allograft survival in children < 15 kg and supports consideration of earlier transplantation for children with CKD stage 5. A higher resolution version of the Graphical abstract is available as Supplementary information.


Subject(s)
Kidney Failure, Chronic , Kidney Transplantation , Humans , Child , Kidney Transplantation/adverse effects , Graft Survival , Living Donors , United Kingdom/epidemiology , Registries , Retrospective Studies , Treatment Outcome
6.
Pediatr Nephrol ; 38(8): 2887-2896, 2023 08.
Article in English | MEDLINE | ID: mdl-36840752

ABSTRACT

BACKGROUND: As modern medicine is advancing, younger, small, and more complex children are becoming multi-organ transplant candidates. This brings up new challenges in all aspects of their care. METHODS: We describe the first report of a small child receiving a simultaneous liver and kidney transplant and abdominal rectus sheath fascia transplant on the background of Williams syndrome and methylmalonic acidaemia. At the time of transplantation, the child was 3 years old, weighed 14.0 kg, had chronic kidney disease stage V, and had not yet started any other form of kidney replacement therapy. RESULTS: There were many anaesthetic, medical, metabolic, and surgical challenges to consider in this case. A long general anaesthetic time increased the risk of cardiac complications and metabolic decompensation. Additionally, the small size of the patient and the organ size mis-match meant that primary abdominal closure was not possible. The patient's recovery was further complicated by sepsis, transient CNI toxicity, and de novo DSAs. CONCLUSIONS: Through a multidisciplinary approach between 9 specialties in 4 hospitals across England and Wales, and detailed pre-operative planning, a good outcome was achieved for this child. An hour by hour management protocol was drafted to facilitate transplant and included five domains: 1. management at the time of organ offer; 2. before the admission; 3. at admission and before theatre time; 4. intra-operative management; and 5. post-operative management in the first 24 h. Importantly, gaining a clear and in depth understanding of the metabolic state of the patient pre- and peri-operatively was crucial in avoiding metabolic decompensation. Furthermore, an abdominal rectus sheath fascia transplant was required to achieve abdominal closure, which to our knowledge, had never been done before for this indication. Using our experience of this complex case, as well as our experience in transplanting other children with MMA, and through a literature review, we propose a new perioperative management pathway for this complex cohort of transplant recipients.


Subject(s)
Amino Acid Metabolism, Inborn Errors , Kidney Failure, Chronic , Kidney Transplantation , Liver Transplantation , Child , Humans , Child, Preschool , Liver Transplantation/adverse effects , Liver Transplantation/methods , Amino Acid Metabolism, Inborn Errors/complications , Kidney Failure, Chronic/complications , Liver , Kidney Transplantation/adverse effects , Kidney Transplantation/methods
7.
Pediatr Nephrol ; 38(2): 529-535, 2023 02.
Article in English | MEDLINE | ID: mdl-35695967

ABSTRACT

BACKGROUND: There is increasing evidence of good short-term and medium-term outcomes of ABO incompatible (ABOi) and HLA incompatible (HLAi) kidney transplantation with pre-transplant positive crossmatches in paediatric practice. However, there remain concerns regarding the higher risks of infective complications and antibody-mediated rejections. The aim of our study is to show longer-term follow-up on all ABOi and HLAi paediatric kidney transplant recipients (pKTR) in the UK. METHODS: Questionnaires specifying kidney transplant type, desensitisation requirement and kidney allograft function were sent to 13 paediatric nephrology centres that performed kidney transplantation in children and young people under 18 years of age who received an ABOi and/or HLAi transplant between 1 January 2006 and 31 December 2016. Patient and kidney allograft survival were compared between ABOi, HLAi and ABO/HLA compatible (ABOc/HLAc) groups. RESULTS: Among 711 living donor kidney transplants performed in the UK, 23 were ABOi and 6 were HLAi. Patient survival was 87%, 100% and 96% in ABOi, HLAi and ABOc/HLAc groups, respectively, at median follow-up of 6.8 (3.6-14.0) years post-transplant. Death-censored kidney allograft survival was 100% in all 3 groups at last follow-up. There were no cases of primary non-function in ABOi or HLAi groups, but 2% in the ABOc/HLAc group. There was one reported case of Epstein-Barr viral-induced post-transplant lymphoproliferative disorder. CONCLUSION: Longer term follow-up has shown that ABOi and HLAi kidney transplantation are feasible for pKTR where no compatible donors are available, and that minimising desensitisation should be achieved where possible. A higher resolution version of the Graphical abstract is available as Supplementary information.


Subject(s)
Kidney Transplantation , Humans , Child , Adolescent , Graft Rejection , Retrospective Studies , Living Donors , Blood Group Incompatibility , United Kingdom , ABO Blood-Group System , Graft Survival
8.
Eur J Pediatr ; 181(9): 3367-3375, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35792951

ABSTRACT

Renovascular hypertension in most cases requires endovascular treatment and/or surgery. This is technically much more difficult in small children and there is very limited published knowledge in this age group. We here present treatment and outcome of young children with renovascular hypertension at our institution. Children below 2 years of age, with renovascular hypertension between January 1998 and March 2020 were retrospectively reviewed. Demographics and treatment modalities were noted. Primary outcome was blood pressure within a week after the procedures and at last available visit. Sixty-six angiographies were performed in 34 patients. Median age at time of first angiography was 1.03 (interquartile range (IQR) 0.4-1.4) years and systolic blood pressure at presentation 130 (IQR 130-150) mm Hg. Thirty-eight percent (13/34) of children were incidentally diagnosed and 18% (6/34) presented with heart failure. Twenty-six (76%) children had main renal artery stenosis and 17 (50%) mid-aortic syndrome. Seventeen (50%) children showed intrarenal, six (18%) mesenteric, and three (9%) cerebrovascular involvement. Twenty patients underwent 45 percutaneous transluminal angioplasty procedures and seven children surgeries. In 44% of the 16 patients who underwent only percutaneous transluminal angioplasty blood pressure was normalized, 38% had improvement on same or decreased treatment and 19% showed no improvement. Complications were seen in 7.5% (5/66) of angiographies. In four of the seven (57%) children who underwent surgery blood pressure was normalized, two had improved (29%) and one unchanged (14%) blood pressure. CONCLUSION: In small children with renovascular hypertension below the age of 2 years, percutaneous transluminal angioplasty caused significant improvement in blood pressure with low complication profile. Surgery can be recommended where percutaneous transluminal angioplasty and medical treatments failed. WHAT IS KNOWN: • Renovascular hypertension is diagnosed in all age groups from a few weeks of life until adulthood. • Both angioplasty and surgery are significantly more difficult to perform in small children and the published information on short and long-term outcome in these children is very scarce. WHAT IS NEW: • Children below the age of two years can safely and successfully undergo selective renal angiography and also safely be treated with angioplasty. • We here present a large group of babies and infants where angioplasty and in some cases surgery effectively and safely improved their blood pressure.


Subject(s)
Angioplasty, Balloon , Hypertension, Renovascular , Renal Artery Obstruction , Adult , Angioplasty, Balloon/adverse effects , Blood Pressure , Child , Child, Preschool , Humans , Hypertension, Renovascular/diagnosis , Hypertension, Renovascular/etiology , Hypertension, Renovascular/therapy , Infant , Renal Artery Obstruction/complications , Renal Artery Obstruction/diagnosis , Renal Artery Obstruction/therapy , Retrospective Studies , Treatment Outcome
9.
Nephrol Dial Transplant ; 36(9): 1742-1753, 2021 08 27.
Article in English | MEDLINE | ID: mdl-33585931

ABSTRACT

BACKGROUND: Publications from the last decade have increased knowledge regarding long-term risks after kidney donation. We wanted to perform a survey to assess how transplant professionals in Europe inform potential kidney donors regarding long-term risks. The objectives of the survey were to determine how they inform donors and to what extent, and to evaluate the degree of variation. METHODS: All transplant professionals involved in the evaluation process were considered eligible, regardless of the type of profession. The survey was dispatched as a link to a web-based survey. The subjects included questions on demographics, the information policy of the respondent and the use of risk calculators, including the difference of relative and absolute risks and how the respondents themselves understood these risks. RESULTS: The main finding was a large variation in how often different long-term risks were discussed with the potential donors, i.e. from always to never. Eighty percent of respondents stated that they always discuss the risk of end-stage renal disease, while 56% of respondents stated that they always discuss the risk of preeclampsia. Twenty percent of respondents answered correctly regarding the relationship between absolute and relative risks for rare outcomes. CONCLUSIONS: The use of written information and checklists should be encouraged. This may improve standardization regarding the information provided to potential living kidney donors in Europe. There is a need for information and education among European transplant professionals regarding long-term risks after kidney donation and how to interpret and present these risks.


Subject(s)
Kidney Transplantation , Humans , Kidney , Kidney Transplantation/adverse effects , Living Donors , Surveys and Questionnaires , Tissue and Organ Harvesting
10.
Clin Transplant ; 35(10): e14435, 2021 10.
Article in English | MEDLINE | ID: mdl-34292634

ABSTRACT

Simultaneous pancreas and kidney (SPK) transplantation, in uremic women with insulin-dependent diabetes, increases the chance of a successful pregnancy and minimizes the risk to infants. The aim of this study was to document pregnancy and explore the challenges in this cohort of women. Retrospective analysis of women who underwent pancreas transplantation between January 1, 1998 and 8 January, 2019 was conducted. Seventeen pregnancies were identified in 13 women. Mean transplant-to-pregnancy interval was 4.6 years (range, 1.1-10.2 years). Eleven pregnancies resulted in live birth (65%), and six (35%) ended in miscarriage/fetal loss at a median gestational age of 8.5 weeks. Mean gestational age at delivery was 34.9 weeks (SD ±3 weeks). Preeclampsia and C-section rates were 77% and 67%, respectively. Adverse fetal and graft outcomes were observed in 100% of unplanned pregnancies, compared to 10% of planned pregnancies (P < .001). One kidney allograft was lost during pregnancy; one pancreas and two kidney allografts were lost within 3 years of pregnancy. This is a high-risk group for grafts and offspring. Pre-pregnancy planning is vital. A multidisciplinary approach by obstetric and transplant teams is important pre-pregnancy, antenatally, and peripartum. This is the largest published series of pregnancies in SPK recipients from a single center.


Subject(s)
Diabetes Mellitus, Type 1 , Kidney Transplantation , Pancreas Transplantation , Diabetes Mellitus, Type 1/surgery , Female , Graft Survival , Humans , Infant , Pancreas , Pregnancy , Pregnancy Outcome , Retrospective Studies
11.
Transpl Int ; 34(6): 1005-1018, 2021 06.
Article in English | MEDLINE | ID: mdl-33786891

ABSTRACT

Detection of circulating antibodies directed against human leukocyte antigen (HLA) molecules, which corresponds to the current definition of 'sensitized patient', has been shown to have a severe impact on both access to transplantation and, if the anti-HLA antibodies are specific to the selected donor, survival of the graft. However, not all donor-specific antibodies (DSA) are equally harmful to the graft and progress in the understanding of humoral memory has led to the conclusion that absence of DSA at transplantation does not rule out the possibility that the patient has a preformed cellular humoral memory against the graft (thereby defining a category of DSA-negative sensitized recipients). Technological progress has led to the generation of new assays that offer unprecedented precision in exploring the different layers (serological and cellular) of alloimmune humoral memory. Based on this recent knowledge, the EuropeaN Guidelines for the mAnagement of Graft rEcipients (ENGAGE) working group to propose an updated definition of sensitization in candidates for solid organ transplantation - one that moves away from the current binary division towards a definition based on homogenous strata with similar humoral risk.


Subject(s)
Kidney Transplantation , Organ Transplantation , Graft Rejection , Graft Survival , HLA Antigens , Humans , Isoantibodies
12.
Pediatr Nephrol ; 36(10): 3271-3275, 2021 10.
Article in English | MEDLINE | ID: mdl-34272986

ABSTRACT

BACKGROUND: A 3-year-old girl with clinical features of atypical HUS (complement Factor I mutation inherited from an asymptomatic mother and Factor H autoantibodies) was treated with plasma exchange, progressed to kidney failure (KF) aged 4 years, and received an en bloc kidney DCD transplant aged 8 years with primary graft non-function necessitating transplant nephrectomy at the time of transplantation. She subsequently underwent re-transplantation from her father. This is a retrospective study of electronic patient records and medical notes. CASE-DIAGNOSIS/TREATMENT: A 9-year-old girl received an ABO-incompatible (ABOi) living-related kidney transplant from her father with recipient and donor blood groups of O and A, respectively, with baseline recipient anti-A titers 1:128 reducing to 1:4 at the time of transplant with B lymphocyte depletion with rituximab and four sessions of immunoadsorption. Six hours post-transplant, she had recurrence of aHUS and received the first dose of eculizumab. She continues on monthly home eculizumab infusions with stable kidney allograft function and negative anti-A titers 7 years post-kidney transplantation. CONCLUSIONS: This is the first report of a pediatric high-risk ABOi living-related kidney transplantation in whom early relapse of aHUS was successfully treated with eculizumab with good long-term patient and allograft outcome.


Subject(s)
Antibodies, Monoclonal, Humanized , Atypical Hemolytic Uremic Syndrome , Kidney Transplantation , Atypical Hemolytic Uremic Syndrome/drug therapy , Atypical Hemolytic Uremic Syndrome/etiology , Child , Child, Preschool , Chronic Disease , Female , Humans , Kidney , Kidney Transplantation/adverse effects , Recurrence , Retrospective Studies
13.
Pediatr Nephrol ; 36(8): 2575-2585, 2021 08.
Article in English | MEDLINE | ID: mdl-34143297

ABSTRACT

BACKGROUND: After the major changes with regard to acute and chronic ABMR in the Banff classification initiated in 2013, there has been an improvement in diagnosing antibody-mediated rejection (ABMR) in adult studies but no data have been published in the paediatric population. METHODS: We assessed 56 paediatric kidney transplant biopsies due to kidney dysfunction in patients with donor-specific antibodies (DSA) in a retrospective single-centre study between January 2006 and March 2012. The results were compared with 2003/2007 Banff classification noting the subsequent 2017 and 2019 modifications do not change the 2013 Banff classification with regard to acute antibody-mediated rejection (apart from the addition of gene transcripts/classifiers that do not affect our analysis). RESULTS: Following the 2013 Banff classification, there were seven cases (12.5%) diagnosed with ABMR that would have been misclassified when applying the 2003/2007 classification. Evaluating the histological features of all ABMR-related cases, we report the importance of v- (intimal arteritis) and t- (tubulitis) lesions: absence of v- and t- lesions in the biopsy is related to significantly higher kidney allograft survival (OR 7.3, 95%CI 1.1-48.8, p = 0.03 and OR 5.3, 95%CI 1.2-25.5, p = 0.04 respectively). Moreover, absence of t- lesions was associated with significantly fewer rejection episodes the year after the initial biopsy (OR 5.1, 95%CI 1.4-19.8, p = 0.01). CONCLUSIONS: Our study supports that the updated 2013 Banff classification shows superior clinicopathological correlation in identifying ABMR in paediatric kidney transplant recipients. Our results can be extrapolated to the recently updated 2019 Banff classification.


Subject(s)
Kidney Transplantation , Adult , Child , Graft Rejection/diagnosis , Humans , Isoantibodies , Kidney , Kidney Transplantation/adverse effects , Retrospective Studies
14.
Ann Surg ; 272(1): 65-71, 2020 07.
Article in English | MEDLINE | ID: mdl-31714309

ABSTRACT

BACKGROUND: Postoperative infection after hand-assisted laparoscopic donor nephrectomy (HALDN) confers significant morbidity to a healthy patient group. Current UK guidelines cite a lack of evidence for routine antibiotic prophylaxis. This trial assessed if a single preoperative antibiotic dose could reduce post HALDN infections. METHODS: Eligible donors were randomly and blindly allocated to preoperative single-dose intravenous co-amoxiclav or saline. The primary composite endpoint was clinical evidence of any postoperative infection at 30 days, including surgical site infection (SSI), urinary tract infection (UTI), and lower respiratory tract infection (LRTI). FINDINGS: In all, 293 participants underwent HALDN (148 antibiotic arm and 145 placebo arm). Among them, 99% (291/293) completed follow-up. The total infection rate was 40.7% (59/145) in the placebo group and 23% (34 of 148) in the antibiotic group (P = 0.001). Superficial SSIs were 20.7% (30/145 patients) in the placebo group versus 10.1% (15/148 patients) in the antibiotic group (P = 0.012). LRTIs were 9% (13/145) in the placebo group and 3.4% (5/148) in the antibiotic group (P = 0.046). UTIs were 4.1% (6/145) in the placebo group and 3.4% (5/148) in the antibiotic group (P = 0.72).Antibiotic prophylaxis conferred a 17.7% (95% confidence interval 7.2%-28.1%), absolute risk reduction in developing postoperative infection, with 6 donors requiring treatment to prevent 1 infection. INTERPRETATION: Single-dose preoperative antibiotic prophylaxis dramatically reduces post-HALDN infection rates, mainly impacting SSIs and LRTIs.


Subject(s)
Amoxicillin-Potassium Clavulanate Combination/administration & dosage , Antibiotic Prophylaxis , Living Donors , Nephrectomy , Surgical Wound Infection/prevention & control , Adult , Double-Blind Method , Female , Humans , Laparoscopy , Male , Middle Aged , Respiratory Tract Infections/prevention & control , United Kingdom , Urinary Tract Infections/prevention & control
15.
Nephrol Dial Transplant ; 35(9): 1628-1634, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32865209

ABSTRACT

BACKGROUND: The donor hypoperfusion phase before asystole in renal transplants from donors after circulatory death (DCD) has been considered responsible for worse outcomes than those from donors after brain death (DBD). METHODS: We included 10 309 adult renal transplants (7128 DBD and 3181 DCD; 1 January 2010-31 December 2016) from the UK Transplant Registry. We divided DCD renal transplants into groups according to hypoperfusion warm ischaemia time (HWIT). We compared delayed graft function (DGF) rates, primary non-function (PNF) rates and graft survival among them using DBD renal transplants as a reference. RESULTS: The DGF rate was 21.7% for DBD cases, but ∼40% for DCD cases with HWIT ≤30 min (0-10 min: 42.1%, 11-20 min: 43%, 21-30 min: 38.4%) and 60% for DCD cases with HWIT >30 min (P < 0.001). All DCD groups showed higher DGF risk than DBD renal transplants in multivariable analysis {0-10 min: odds ratio [OR] 2.686 [95% confidence interval (CI) 2.352-3.068]; 11-20 min: OR 2.531 [95% CI 2.003-3.198]; 21-30 min: OR 1.764 [95% CI 1.017-3.059]; >30 min: OR 5.814 [95% CI 2.798-12.081]}. The highest risk for DGF in DCD renal transplants with HWIT >30 min was confirmed by multivariable analysis [versus DBD: OR 5.814 (95% CI 2.798-12.081) versus DCD: 0-10 min: OR 2.165 (95% CI 1.038-4.505); 11-20 min: OR 2.299 (95% CI 1.075-4.902); 21-30 min: OR 3.3 (95% CI 1.33-8.197)]. No significant differences were detected regarding PNF rates (P = 0.713) or graft survival (P = 0.757), which was confirmed by multivariable analysis. CONCLUSIONS: HWIT >30 min increases the risk for DGF greatly, but without affecting PNF or graft survival.


Subject(s)
Brain Death , Graft Survival , Kidney Transplantation/mortality , Perfusion , Tissue Donors/supply & distribution , Warm Ischemia/methods , Adult , Female , Humans , Male , Middle Aged , Prognosis , Registries , Retrospective Studies , Survival Rate , Time Factors
16.
Ann Surg ; 269(2): e18-e23, 2019 02.
Article in English | MEDLINE | ID: mdl-30247323

ABSTRACT

OBJECTIVE: The authors investigated a novel application of patient-specific three-dimensional (3D) printing, to enhance preoperative, multidisciplinary planning in complex, living-donor pediatric renal transplantation. SUMMARY BACKGROUND DATA: For children with end-stage kidney disease, the transplantation of adult-sized, living-donor kidneys into small recipients (<20 kg) with increasingly complex structural anomalies can be difficult. Establishing the operative feasibility in such cases demands a surgical understanding of anatomy to be derived from medical imaging. However, this is hampered by the representation of complex structures in 2D, the inherent interpretive expertise this demands, and the challenge of conveying this appreciation to others. METHODS: We report the novel use of patient-specific 3D printed models to achieve personalized management for 3 children who underwent living-donor renal transplantation. Each presented a unique surgical challenge that would otherwise prevent preoperative determination of transplantation feasibility. Patient-specific geometries were segmented from imaging data and fabricated using polyjet, 3D printing technology. Models were verified by an expert radiologist and presented during multidisciplinary discussion and surgical simulation. RESULTS: 3D printed models enhanced preoperative deliberation and surgical simulation and allowed on-table exploration of a small child to be avoided. We have critically determined specific clinical indications, technical insights, limitations, and outcomes of this approach. At latest follow-up (>16 mo) all patients remain well with functioning renal allografts. CONCLUSIONS: We report the new and safe integration of patient-specific 3D printing into complex pediatric renal transplantation. This technique enhances surgical planning and can inform operative feasibility in those cases which would otherwise be uncertain.


Subject(s)
Kidney Transplantation/methods , Printing, Three-Dimensional , Adult , Age Factors , Child , Child, Preschool , Humans , Kidney/anatomy & histology , Kidney/surgery , Organ Size
17.
Transpl Int ; 32(6): 635-645, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30685880

ABSTRACT

The impact of the duration of delayed graft function (DGF) on graft survival is poorly characterized in controlled donation after circulatory death (DCD) donor kidney transplantation. A retrospective analysis was performed on 225 DCD donor kidney transplants between 2011 and 2016. When patients with primary nonfunction were excluded (n = 9), 141 recipients (65%) had DGF, with median (IQR) duration of dialysis dependency of 6 (2-11.75) days. Longer duration of dialysis dependency was associated with lower estimated glomerular filtration rate at 1 year, and a higher rate of acute rejection. On Kaplan-Meier analysis, the presence of DGF was associated with lower graft survival (log-rank test P = 0.034), though duration of DGF was not (P = 0.723). However, multivariable Cox regression analysis found that only acute rejection was independently associated with lower graft survival [HR (95% CI) 4.302 (1.617-11.450); P = 0.003], whereas the presence of DGF and DGF duration were not. In controlled DCD kidney transplantation, DGF duration itself may not be independently associated with graft survival; rather, it may be that acute rejection associated with prolonged DGF is the poor prognostic factor.


Subject(s)
Delayed Graft Function/physiopathology , Kidney Diseases/surgery , Kidney Transplantation/methods , Tissue Donors , Adult , Aged , Female , Glomerular Filtration Rate , Graft Rejection/mortality , Graft Survival , Humans , Kaplan-Meier Estimate , Kidney/physiopathology , Kidney Diseases/mortality , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Tissue and Organ Procurement , Treatment Outcome
18.
Transpl Int ; 32(5): 523-534, 2019 May.
Article in English | MEDLINE | ID: mdl-30636065

ABSTRACT

The use of preimplantation kidney biopsies (PIKBs) to aid deceased donor kidney utilization decisions is controversial. Outcomes of transplants that had been biopsied after the decision had been made to implant were analysed, in order to determine the association between chronic histological changes at implantation and graft outcomes. A retrospective analysis of transplants between the year range 2006-2015 was performed. Karpinski scores on biopsies were collected, and graft outcomes were analysed using univariate and multivariable techniques. Also, Karpinski scores from single and dual kidney transplants from older donors were examined to determine if knowledge of the score preoperatively would have altered utilization. Four hundred and eight single kidneys were transplanted. Although kidneys with scores >4 had lower 1- and 3-year median (IQR) estimated glomerular filtration rates (eGFRs) than those scoring 0-4 (51 (37-66) vs. 35 (26-52) ml/min/1.73 m2 , P < 0.001, and 52 (34-64) vs. 35 (24-52) ml/min/1.73 m2 , P < 0.001, respectively), there was no significant association between Karpinski score and death-censored graft survival on univariate or multivariable analyses. The utilization analysis (75 single and 25 dual kidney transplant recipients) suggested that systematic use of PIKBs would have resulted in 29% fewer patients being transplanted. This analysis does not support the systematic use of PIKBs to determine deceased donor kidney utilization.


Subject(s)
Kidney Failure, Chronic/surgery , Kidney Transplantation , Kidney/pathology , Adult , Algorithms , Biopsy , Female , Glomerular Filtration Rate , Graft Survival , Humans , Male , Middle Aged , Multivariate Analysis , Retrospective Studies , Time Factors , Tissue Donors , Tissue and Organ Procurement , Transplant Recipients , Treatment Outcome
19.
Transpl Int ; 32(4): 431-442, 2019 04.
Article in English | MEDLINE | ID: mdl-30549305

ABSTRACT

Blood group O or B recipients wait longer for a kidney transplant. We studied the distribution of anti-ABO blood group antibody titres in patients awaiting a kidney transplant, and modelled the effect of altering the UK National Kidney Allocation Scheme to allow for patients with 'LOW' titres (≤1:8, ≤3 dilutions) to receive a deceased donor ABOi (ddABOi) transplant. In a prospective study of 239 adult patients on the waiting list for a transplant in 2 UK centres, ABO-antibody titres (anti-A and anti-B) were measured. Based on the proportions of 'LOW' anti-A or anti-B antibodies, four simulations were performed to model the current allocation rules compared with variations allowing ddABOi allocation under various conditions of blood group, HLA matching, and waiting time. The simulations permitting ddABOi resulted in more blood group B recipients being transplanted, with median waiting time reduced for this group of recipients, and more equitable waiting times across blood groups. Additionally, permitting ddABOi resulted in greater numbers of 000MM allocations overall in compatible transplants under modelled conditions. Changing allocation in the UK to permit ddABOi in patients with 'LOW' titres would not change the total number of transplants, but redistributes allocation more equitably amongst blood groups, altering waiting times accordingly.


Subject(s)
ABO Blood-Group System , Kidney Transplantation , Tissue Donors , Waiting Lists , ABO Blood-Group System/immunology , Adult , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Tissue and Organ Procurement
20.
Pediatr Transplant ; 23(4): e13411, 2019 06.
Article in English | MEDLINE | ID: mdl-30973673

ABSTRACT

BACKGROUND: In current practice, pediatric kidney transplant recipients receive large volumes of intravenous fluid intraoperatively to establish allograft perfusion, and further fluid to replace urinary and insensible losses postoperatively. Acute electrolyte imbalance can result, with potential for neurological sequelae. We aimed to determine the incidence and severity of postoperative plasma electrolyte imbalance in pediatric kidney transplant recipients managed with the current standard intravenous crystalloid regimen. METHODS: A retrospective analysis of plasma electrolytes in the first 72 hours post-kidney transplant in 76 children transplanted between January 1, 2015, and January 31, 2018, managed with a standard intravenous fluid strategy used in most UK pediatric transplant centers. RESULTS: Of 76 pediatric transplant recipients of median age 9.9 (range 2.2-17.9) years predominantly managed with 0.45% sodium chloride 5% glucose, 45 (59%) developed acute hyponatremia, 23 (30%) hyperkalemia, and 43 (57%) non-anion-gap acidosis in the postoperative period. Hyperglycemia occurred in 74 (97%) patients. Hyperkalemia was more prevalent in deceased than live donor recipients (P = 0.003) and was significantly associated with non-anion-gap acidosis (P < 0.001). Recipient weight was not associated with overt electrolyte imbalance. CONCLUSION: Postoperative plasma electrolyte imbalance is common in pediatric kidney transplant recipients. Current clinical care strategies mitigate the associated risks of neurological sequelae to some degree. Further studies to optimize intravenous fluid therapy and minimize electrolyte disturbance in this group of patients are needed.


Subject(s)
Electrolytes/blood , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/surgery , Kidney Transplantation , Acid-Base Equilibrium , Adolescent , Allografts , Child , Child, Preschool , Glucose/administration & dosage , Humans , Incidence , Infusions, Intravenous , Perfusion , Postoperative Complications/therapy , Postoperative Period , Retrospective Studies , Sodium Chloride/administration & dosage
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