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Acute kidney injury (AKI) is common in lupus nephritis (LN) and a risk factor for development of chronic kidney disease. In adults with LN, AKI severity correlates with the incidence of kidney failure and patient survival. Data on AKI outcomes in children with LN, particularly those requiring kidney replacement therapy (KRT), are limited.A multicenter, retrospective cohort study was performed in children diagnosed between 2010 and 2019 with LN and AKI stage 3 treated with dialysis (AKI stage 3D). Descriptive statistics were used to characterize demographics, clinical data, and kidney biopsy findings; treatment data for LN were not included. Logistic regression was used to examine the association of these variables with kidney failure.Fifty-nine patients (mean age 14.3 years, 84.7% female) were identified. The most common KRT indications were fluid overload (86.4%) and elevated blood urea nitrogen/creatinine (74.6%). Mean follow-up duration was 3.9 ± 2.9 years. AKI recovery without progression to kidney failure occurred in 37.3% of patients. AKI recovery with later progression to kidney failure occurred in 25.4% of patients, and there was no kidney recovery from AKI in 35.6% of patients. Older age, severe ( 50%) tubular atrophy and interstitial fibrosis, and National Institutes of Health (NIH) chronicity index score 4 on kidney biopsy were associated with kidney failure.Children with LN and AKI stage 3D have a high long-term risk of kidney failure. Severe tubular atrophy and interstitial fibrosis at the time of AKI, but not AKI duration, are predictive of kidney disease progression. A higher resolution version of the Graphical abstract is available as Supplementary information. more...

INTRODUCTION There are no guidelines regarding management of failed pediatric renal transplants. MATERIALS & METHODS We performed a first of its kind multicenter study assessing prevalence of transplant nephrectomy, patient characteristics, and outcomes in pediatric renal transplant recipients with graft failure from January 1, 2006, to December 31, 2016. RESULTS Fourteen centers contributed data on 186 pediatric recipients with failed transplants. The 76 recipients that underwent transplant nephrectomy were not significantly different from the 110 without nephrectomy in donor or recipient demographics. Fifty-three percent of graft nephrectomies were within a year of transplant. Graft tenderness prompted transplant nephrectomy in 91% (P more...

Renal disease often crosses the boundaries of traditional medical specialties, and reduced renal function is a common consequence of diseases of the heart, liver, and gastrointestinal tract. Multiorgan transplant is a lifesaving procedure for children with multiorgan failure, yet in practice it can be challenging due to lack of clarity about the most appropriate timing and perioperative management strategies. The role of simultaneous versus sequential heart-kidney or liver-kidney transplant remains hotly debated, and governing organizations continue to work to create allocation policies that appropriately balance the needs of all stakeholders. Additionally, a child’s small size may complicate the placement of multiple allografts at one time, and the allografts often have competing needs for hydration and immunosuppression. In this chapter, we have collected and summarized the published literature on the allocation, incidence, indications, perioperative management, and outcomes of pediatric multiorgan transplants. more...

Dapsone has been utilized for the prevention of Pneumocystis jirovecii pneumonia in immunosuppressed patients including pediatric kidney transplant recipients, in whom trimethoprim-sulfamethoxazole (TMP-SMX) is contraindicated. Dapsone adverse effects include methemoglobinemia, but there are no reports of the burden and impact of methemoglobinemia in pediatric kidney recipients that are taking dapsone for PJP prophylaxis. We conducted a retrospective chart review of all pediatric kidney recipients who had received dapsone at any time posttransplant. The indication, duration, and adverse effects of dapsone therapy were assessed. In addition, methemoglobin levels were assessed, and summary statistics performed. Data demonstrated that more than half of the patients on dapsone were not screened for methemoglobinemia. Of those screened, there was a significantly higher acquired-methemoglobinemia (77%) than previously reported in the literature. We also demonstrate significantly more anemia in patients on dapsone. Methemoglobinemia did not affect patient or graft survival and resolved with cessation of dapsone. We conclude that pediatric kidney recipients often develop methemoglobinemia and / or anemia on dapsone. We recommend if pediatric transplant recipients are prescribed dapsone, routine testing for methemoglobinemia and anemia should be done. more...

Background No consensus exists on the optimal timing for native nephrectomy in pediatric kidney transplant recipients. Data comparing outcomes between recipients undergoing pretransplant nephrectomy (staged nephrectomy with subsequent transplant) and those undergoing nephrectomy simultaneously with the transplant are lacking. Method We studied 32 pediatric kidney transplant recipients who underwent native nephrectomy at a single center from 01/01/2011 to 12/31/2016. We divided recipients into two groups based on the nephrectomy timing (simultaneous nephrectomy/transplant and staged nephrectomy). We used Wilcoxon rank-sum test, Fisher's exact test, and Kaplan-Meier methods to compare outcomes. Results Of 32 recipients, 20 underwent simultaneous and 12 underwent staged nephrectomy. Simultaneous recipients were younger (median (years): 2.0 vs 7.0; P = .049). Staged recipients were more likely to have proteinuria/hypoalbuminemia, whereas simultaneous recipients were more likely to have hydronephrosis/vesicoureteral reflux/urinary infections as nephrectomy indications (P = .06). Median prenephrectomy albumin for patients with nephrotic syndrome was significantly lower in staged recipients (median g/dL: 1.9 vs 3.8; P = .02). Total number of hospital days (including both procedures) was higher for staged recipients compared with simultaneous (one procedure) recipients (median (days): 17.0 vs 11.5; P = .05). We observed no difference in 5-year graft survival between the groups (95.0% vs 91.7%, P = .73). Patient survival was 100% in both groups over a median follow-up of 44.2 months. Surgical complications were similar between the groups. Conclusion Staged and simultaneous native nephrectomy in pediatric kidney transplant recipients are associated with comparable outcomes. more...

Objective We examined the association between induction type and outcomes of live-donor pediatric kidney recipients on tacrolimus and mycophenolate maintenance. Material and methods We analyzed the SRTR standard analysis file to evaluate primary live-donor pediatric kidney recipients between 2000 and 2018. Recipients were grouped by induction type into three groups: alemtuzumab n = 289, anti-thymocyte n = 1197, and IL-2RA n = 1625. Kaplan-Meier curves were generated for recipient and death-censored graft survival. Predictors of recipient and allograft survival were examined using Cox proportional hazards models. Models were adjusted for age, sex, ethnicity, renal failure etiology, HLA-mismatches, transplant year, steroid maintenance, preemptive transplantation, payor type, and donor factors such as age, sex, and donor-recipient relationship. The transplant center was included as a random effect to account for inter-center variability. Results Rejection rates at 6 months (Alemtuzumab 9.5% vs. r-ATG 5.7% vs. IL2-RA 5.3%; P: .023) and 12 months (Alemtuzumab 14.5% vs. r-ATG 10.8% vs. IL2-RA 9%; P: .028) were significantly higher in the alemtuzumab group. PTLD rate (Alemtuzumab 0.8% vs. r-ATG 2.2% vs. IL2-RA 1%; P: .028) was significantly higher in the anti-thymocyte group. In the multivariable models, induction type did not influence patient or death-censored graft survival within ten years post-transplant. Conclusion In this large cohort of standard immunological risk primary pediatric live-donor kidney recipients, as compared to IL-2RA, neither alemtuzumab nor anti-thymocyte globulin was associated with improved long-term graft or recipient survival. In the first year post-transplant, recipients of alemtuzumab induction had a higher rejection rate, while PTLD was more frequently observed in the anti-thymocyte recipients. more...

ObjectiveTo evaluate the feasibility of a multicentre randomised controlled trial (RCT) comparing oestrogen treatment with no oestrogen supplementation in women undergoing pelvic organ prolapse (POP) surgery.Design and settingA randomised, parallel, open, external pilot trial involving six UK urogynaecology centres (July 2015–August 2016).ParticipantsPostmenopausal women with POP opting for surgery, unless involving mesh or for recurrent POP in same compartment.InterventionWomen were randomised (1:1) to preoperative and postoperative oestrogen or no treatment. Oestrogen treatment (oestradiol hemihydrate 10 μg vaginal pessaries) commenced 6 weeks prior to surgery (once daily for 2 weeks, twice weekly for 4 weeks) and twice weekly for 26 weeks from 6 weeks postsurgery.Outcome measuresThe main outcomes were assessment of eligibility and recruitment rates along with compliance and data completion. To obtain estimates for important aspects of the protocol to allow development of a definitive trial.Results325 women seeking POP surgery were screened over 13 months and 157 (48%) were eligible. Of these, 100 (64%) were randomised, 50 to oestrogen and 50 to no oestrogen treatment, with 89 (44/45 respectively) ultimately having surgery. Of these, 89% (79/89) returned complete questionnaires at 6 months and 78% (32/41) reported good compliance with oestrogen. No serious adverse events were attributable to oestrogen use.ConclusionsA large multicentre RCT of oestrogen versus no treatment is feasible, as it is possible to randomise and follow up participants with high fidelity. Four predefined feasibility criteria were met. Compliance with treatment regimens is not a barrier. A larger trial is required to definitively address the role of perioperative oestrogen supplementation.Trial registration numberISRCTN46661996. more...

BACKGROUND AND OBJECTIVES: Hypertension is highly prevalent in pediatric kidney transplant recipients and contributes to cardiovascular death and graft loss. Improper blood pressure (BP) measurement limits the ability to control hypertension in this population. Here, we report multicenter efforts from the Improving Renal Outcomes Collaborative (IROC) to standardize and improve appropriate BP measurement in transplant patients. METHODS: Seventeen centers participated in structured quality improvement activities facilitated by IROC, including formal training in quality improvement methods. The primary outcome measure was the proportion of transplant clinic visits with appropriate BP measurement according to published guidelines. Prospective data were analyzed over a 12-week pre-intervention period and a 20-week active intervention period for each center and then aggregated as of the program-specific start date. We used control charts to quantify improvements across IROC centers. We applied thematic analysis to identify patterns and common themes of successful interventions. RESULTS: We analyzed data from 5392 clinic visits. At baseline, BP was measured and documented appropriately at 11% of visits. Center-specific interventions for improving BP measurement included educating clinic staff, assigning specific team member roles, and creating BP tracking tools and alerts. Appropriate BP measurement improved throughout the 20-week active intervention period to 78% of visits. CONCLUSIONS: We standardized appropriate BP measurement across 17 pediatric transplant centers using the infrastructure of the IROC learning health system and substantially improved the rate of appropriate measurement over 20 weeks. Accurate BP assessment will allow further interventions to reduce complications of hypertension in pediatric kidney transplant recipients. more...

Clinicians in the United States today regularly face dilemmas about health disparities. Many patients and families cannot afford the medical care that doctors recommend. These problems are most stark when the medical care that is needed is lifesaving and expensive and involves scarce resources. Transplants are the best example of this. The most ethically disturbing situations occur when an undocumented immigrant child needs a transplant. We present such a case and analyze the ethical, legal, and policy issues that arise. more...

Pediatric kidney transplants have been performed for more than five decades. To achieve excellent patient outcomes, collaboration of multiple subspecialties is required. This manuscript will review recent advancements in different fields that relate to pediatric kidney transplantation. With improvements in patient selection, drugs, perioperative care, surgical technique and postoperative monitoring, outcomes including graft survival, patient survival, and delayed graft function/primary non-function have improved. Immunosuppressive regimens that minimize corticosteroids are increasingly implemented and long-term side effects of antirejection drugs such as infections and metabolic/endocrine dysregulation are better understood. The anesthetic management of pediatric kidney recipients has remained largely the same over the years, but newer technologies and drugs are beginning to be implemented. The field of pediatric kidney transplantation has seen significant improvements in outcomes but still suffers from a discrepancy between graft demand and supply. The future will likely see efforts directed towards improved graft allocation policies, attempts to increase living donations, and new approaches such as alternative graft sources from tissue engineering and recovery of kidney function using regenerative medicine. more...

In small children with end-stage renal disease, an adult-sized kidney transplant is the best option. However, in the face of a completely thrombosed inferior vena cava (IVC), such transplants can be challenging, given the difficulty of achieving adequate renal venous outflow and the risk of graft thrombosis. Using a new technique to anastomose the renal vein to the right hepatic vein/IVC junction, we successfully implanted an adult-sized graft in two small children (9.8 and 14 kg) who had end-stage renal disease and a completely thrombosed IVC. After mobilizing the right lobe of the liver and obtaining total vascular occlusion of the liver, we used a Fogarty catheter to dilate the retrohepatic IVC. In the right hepatic vein, we made a venotomy and extended it inferiorly onto the retrohepatic IVC. To that venotomy, we anastomosed the donor left renal vein, using continuous 7-0 Prolene sutures. Both patients attained excellent renal allograft function: One had a serum creatinine level of 0.30 mg/dL at 6 mo after transplant, and the other had a level of 0.29 mg/dL at 1 year. In these two small children with completely thrombosed IVC, our technique for transplanting an adult-sized kidney provided adequate venous outflow. more...

Background: Kidney transplant (KT) recipients have higher incidence of malignancies, including Human Papillomavirus (HPV)-associated cancers. Thus, HPV vaccines may have an important role in preventing HPV-related disease in this population; however, immunogenicity and safety data are lacking. Objective: To examine the immunological response and tolerability to HPV vaccination in pediatric KT recipients compared to future KT candidates. Methods: The quadrivalent HPV vaccine was administered to girls and boys age 9-18 recruited from seven centers part of the Pediatric Nephrology Research Consortium. Subjects were recruited for three groups: (1) CKD: chronic kidney disease stages 3, 4, and 5 not on dialysis; (2) Dialysis; (3) KT recipients. The outcome consisted of antibody concentrations against HPV 6, 11, 16, and 18. Geometric mean titers (GMTs) and seroconversion rates were compared. Vaccine tolerability was assessed. Results: Sixty-five participants were recruited: 18 in the CKD, 18 in the dialysis, and 29 into the KT groups. KT patients had significantly lower GMTs after vaccination for all serotypes. The percentages of subjects who reached seroconversion were overall lower for the KT group, reaching statistical significance for HPV 6, 11, and 18. Comparing immunosuppressed subjects (anyone taking immunosuppression medications, whether KT recipient or not) with the non-immunosuppressed participants, the former had significantly lower GMTs for all the HPV serotypes and lower seroconversion rates for HPV 6, 11, and 18. KT females had higher GMTs and seroconversion rates for certain serotypes. There were no adverse events in either group. Conclusions: HPV vaccine was well-tolerated in this population. Pediatric KT recipients had in general lower GMTs and seroconversion rates compared to their peers with CKD or on dialysis. Immunosuppression played a role in the lack of seroconversion. Our results emphasize the importance of advocating for HPV vaccination prior to KT and acknowledge its safety post transplantation. Future studies are needed to investigate the effect of a supplemental dose of HPV vaccine in KT recipients who do not seroconvert and to evaluate the long-term persistence of antibodies post-KT. more...

Contrast-induced nephropathy (CIN) remains a common and potentially serious complication in at risk patients after exposure to contrast agents. Risk factors for CIN include chronic kidney disease, hypotension, diabetes mellitus, recent previous exposure to contrast and all of these are potentially additive. Therefore, careful pre-procedural risk stratification is important. In high-risk patients, contrast should be avoided if possible. If avoidance is not possible, the volume of contrast should be minimized and the type of contrast used should if possible be non-ionic iso-osmolar contrast. In view of the clinical importance of CIN, numerous potential risk-reduction strategies have been evaluated. Adequate intravenous volume expansion with isotonic crystalloid (1.0-1.5 mL/kg per hr) for 3-12 hr before the procedure and continued for 6-24 hr afterward can lessen the probability of CIN in patients at risk. But there are insufficient data on oral fluids as a preventive strategy. Nephrotoxic drugs should be withdrawn before contrast administration in patients at risk for CIN. No adjunctive medical or mechanical treatment has been proved to be efficacious in reducing risk for CIN including prophylactic hemodialysis and hemofiltration, N-acetylcysteine, fenoldopam, dopamine, calcium channel blockers, atrial natriuretic peptide, and L-arginine. The CIN Consensus Working Panel considered that, of the pharmacologic agents that have been evaluated, theophylline, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), ascorbic acid, and prostaglandin E deserve further evaluation. more...

Effective treatment modalities for diarrhea in solid organ transplant recipients are lacking. We evaluated the effect of oral IgG on clinical course of diarrhea in pediatric kidney transplant recipients. We retrospectively studied all pediatric kidney transplant recipients who required hospitalization for diarrhea between January 1, 2015, and December 31, 2017. We divided the recipients into two groups based on whether they had received oral IgG to treat diarrhea. Sixteen pediatric kidney transplant recipients required hospitalization for diarrhea over 3 years. Median age at admission was 9.25 years (IQR:12.54). Fifty-six percent of recipients were male, and 81% were white. Four patients received oral IgG for prolonged diarrhea. Oral IgG recipients had longer diarrheal duration before admission (median (days) 14.5 vs1; P .02), a trend for greater weight loss at admission (median (kilogram) 1.4 vs 0.2; P .3), and a trend for higher acute kidney injury (>75% reduction in glomerular filtration rate: 100% vs 42%; P .36). Diarrhea resolved completely in 3 (75%) oral IgG recipients and 7 (58%) non-oral IgG patients by discharge (P .99). One oral IgG recipient showed partial improvement but also had biopsy evidence of mycophenolate-induced colitis. All patients tolerated oral IgG well. No patients required re-hospitalization within 30 days of discharge. Oral IgG may be used safely and effectively to treat prolonged diarrhea in pediatric kidney transplant recipients. A larger, randomized, prospective study is needed to further assess the efficacy of oral IgG in the treatment of diarrhea. more...

The etiology and treatment of transplant glomerulopathy (TG) is not clear. TG is associated with donor-specific antibodies but the lack of C4d deposition in the peritubular capillaries (ptc-C4d) in some cases has caused the role of complement in the pathogenesis of TG to be debated. There is however, little information on C4d deposition in the glomerulus itself. We retrieved random frozen sections from 25 cases with well-established TG by light microscopy (LM) and 25 cases without TG as controls and reviewed the LM and immunofluorescence (nine biopsies were excluded due to inadequate samples). Glomerular complement deposition was assessed in all included biopsies. Glomerular C3d and C4d deposition occurred in a distinct pattern in all TG biopsies: segmental or global double linear staining of the glomerular capillary wall in 23 (100%). This pattern was not present in any NON-TG biopsies. The distinct glomerular complement deposition patterns in all TG cases are suggestive that TG is a proximal complement-mediated process and therapies should focus on proximal complement inhibition. more...

Successful renal transplantation is the optimal treatment for chronic kidney failure, but this was not always so for children. Beginning with the first kidney transplants in the 1950s, children experienced poorer patient and graft survival rates than adult patients. But over the last 6 decades, an improved understanding of the immune system which has steered pediatric multi-center clinical/pharmacokinetic and mechanistic studies that have sculpted our immunosuppression with markedly better patient and graft survivals. In addition, uniquely pediatric issues related to growth, development, neurocognitive maturation, increased complications from primary viral infections, and comorbid congenital/inherited disorders, are now diagnosed and effectively managed in these children. Refined pretransplant preparation (vaccinations for preventable diseases, attention to cognitive delays, effective dialysis and nutrition) improved donor selection, and more potent immunosuppression have all contributed to enhanced outcomes. Similarly, improvements in pediatric surgical techniques, postoperative care and better antiviral prophylaxis have all shortened hospitalizations and reduced morbidity. Today pediatric kidney transplant outcomes are markedly improved and younger children today experience better long-term graft survival than adults! While difficult problems remain, we have made tremendous progress and anticipate even more advances in the future of pediatric kidney transplantation. more...

The association of blood transfusions with graft survival after pediatric kidney transplant (KTx) is unclear. We retrospectively analyzed blood transfusions post-KTx and subsequent outcomes. Between 1984 and 2013, 482 children ( 12 months. Transfused and non-transfused recipients were not significantly different. In univariate and multivariate analyses, there was no difference between transfused and non-transfused recipient patient survival; antibody-mediated and acute cellular rejection, and donor-specific antibody (DSA) free survival. Transfusions 12 months post-KTx had significantly lower 12 month estimated glomerular filtration rate (eGFR) (compared to non-transfused) and worse subsequent DCGS. Post-KTx blood transfusions have increased in pediatric KTx over time but have no negative association with rejection or DSA production. DCGS is unaffected by transfusion within first month. Transfusions after the first year occur in patients with more advanced chronic kidney disease and are associated with significantly worse DCGS. more...

Background and Objectives Platelet transfusions are common in clinical practice especially in the intensive care unit settings without acceptable clinical evidence. A retrospective audit was undertaken to evaluate the prevalence of thrombocytopenia, transfusion triggers and indications of transfusion and to assess the appropriateness of platelet transfusions based on current guidelines in patients admitted to a tertiary care intensive care unit (ICU) in South Australia. Methods Platelet counts on ICU admission, during ICU stay, use of platelet transfusion and clinical outcomes including bleeding for each consecutive admission to ICU over a 12-month period was collected. Results The prevalence of thrombocytopenia (platelet counts more...

The influenza vaccine is critical for preventing influenza-related complications in transplant patients. Previous studies demonstrated de novo donor-specific antibody formation and rejection following the influenza vaccination. This risk has not been adequately assessed in the pediatric population. We performed a single-center retrospective analysis of 187 unique pediatric kidney transplant recipients, transplanted from January 1, 2006, to December 31, 2015, assessing for an association of the influenza vaccination with various transplant outcomes. The influenza vaccine was received by 125 of 187 patients within the first year post-transplant. Using log-rank tests and Kaplan-Meier curves, vaccinated patients had a significantly lower risk of mortality (P = 0.048). There were no differences in death-censored graft survival (P = 0.253), graft survival (P = 0.098), or rejection (P = 0.195) between vaccinated and unvaccinated groups. To address the problem of multiple exposures for a yearly vaccine, Cox proportional hazards regression was utilized with post-transplant vaccination status considered as a time-dependent covariate; analyses were performed using both a 360- and 180-day vaccination period following any post-transplant influenza vaccination. In this model, being vaccinated did not result in a significant difference in mortality (HR 0.90 [0.16, 5.15], P = 0.91), death-censored graft survival (HR 0.70 [0.31, 1.58], P = 0.39), graft survival (HR 0.69 [0.32, 1.49], P = 0.34), or rejection (HR 0.67 [0.37, 1.19], P = 0.17). Eight patients developed de novo donor-specific antibodies following the first post-transplant influenza vaccination; three then developed biopsy-proven rejection. These results suggest influenza vaccination is safe in pediatric kidney transplant recipients, and larger prospective studies are required to conclusively confirm our findings. more...

In this single-center retrospective study, we analyzed kidney transplant outcomes in nine pediatric patients with VACTERL [vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, limb abnormalities] association-making this the largest study of its kind. Of 743 pediatric kidney transplant recipients at our center (1980-2017), nine had documented diagnoses of VACTERL association. All nine had congenital anorectal malformations and renal anomalies, five had vertebral defects, and one had a bifid thumb and tracheoesophageal fistula. Renal anomalies included dysplasia (n = 6), aplasia (n = 3), and horseshoe kidney (n = 2). Congenital lower urinary tract anomalies included neurogenic bladder (n = 6), obstructive uropathy (n = 4), anovesicular fistula (n = 1), rectourethral fistula (n = 1), and posterior urethral valves (n = 1). Age at transplant ranged from 1.2 to 15 years (mean, 7.3; standard deviation [SD], 5.5); 6 (67%) were male, and 3 (33%) were female; 6 (67%) had a living related donor, and 3 (33%) had a deceased donor. The overall graft survival rate was 78% (range, 1.5 to 25.2 years; mean, 10.5; SD, 8.9). One month post-transplant, one recipient died with a functioning graft. At 3.7 years post-transplant, one graft failed because of recurrent pyelonephritis. Post-transplant urologic complications included pyelonephritis (n = 6), vesicoureteral reflux (n = 5), and graft hydronephrosis (n = 4). We conclude that pediatric patients with VACTERL association can be safely transplanted-careful patient selection with vigilance and intervention for pre- and post-transplant urologic complications is essential. more...

Introduction There is conflicting evidence on whether mediolateral episiotomy (MLE) reduces the risk of obstetric anal sphincter injuries (OASI) in spontaneous vaginal deliveries (SVD). Objectives A systematic review was undertaken to compare rates of OASI amongst women who had undergone mediolateral episiotomy versus those who did not. Methods ᅟ Search strategy Electronic searches were performed in literature databases: CINAHL, Cochrane, EMBASE, Medline and MIDIRS from database inception to July 2015. Studies were eligible if MLE was compared to spontaneous tears and if OASI was the outcome of interest. Two reviewers independently selected and extracted data on study characteristics, quality and results. We computed events of OASI in those who did and did not have an episiotomy from individual studies and pooled these results in a meta-analysis where possible. Main results Of the 2090 citations, 16 were included in the review. All were non-randomised, population based or retrospective cohort studies. There was great variation in quality amongst these studies. Data from 7 studies was used for meta-analysis. On collating data from these studies where the majority of women (636755/651114) were nulliparous, MLE reduced the risk of OASI (RR 0.67 95 % CI 0.49-0.92) in vaginal delivery. Conclusion The pooled analysis of a large number of women undergoing vaginal birth, most of who were nulliparous, indicates that MLE has a beneficial effect in prevention of OASI. An accurately given MLE might have a role in reducing OASI and should not be withheld, especially in nulliparous women. Caution is advised as the data is from non-randomised studies. more...

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections are a significant cause of morbidity and mortality in transplant recipients and are often transmitted from the donor organ.In a pilot prospective, randomized, double-blinded, placebo-controlled trial, we studied whether 14 days of pretransplant donor treatment with valganciclovir (valG) versus placebo reduced donor-to-recipient transmission, making posttransplant recipient prophylaxis more effective in reducing EBV and CMV disease.Seventeen D+ R- donor-recipient pairs were enrolled: 7 and 10 donors were randomized to valG and placebo, respectively. At study initiation, no donor had detectable CMV replication, five had EBV replication (two in valG, three in placebo group): EBV replication was undetectable during valG treatment, but resumed on stopping valG. Valganciclovir was tolerated without side effects or leukopenia. All recipients received routine posttransplant viral prophylaxis with valG. For recipients, viremia-free survival time, incidence, range, peak, and duration of CMV and EBV viremia were not significantly different between groups. There was no disease in the valG group but two serious viral diseases occurred in the placebo group (one CMV; one EBV-related posttransplant lymphoproliferative disorder). In the case of posttransplant lymphoproliferative disorder, the EBV DNA from the donor's oral wash and the recipient's lymphoid tissue biopsy had identical latent membrane protein 1 (LMP-1) sequence variations from the reference EBV strain, making it highly probable that the recipient's virus was of donor origin.Based on this pilot trial, we recommend an adequately powered study to determine if pretransplant donor treatment with valG can reduce posttransplant CMV and EBV disease with merely routine posttransplant recipient viral prophylaxis. more...

Epstein-Barr virus (EBV) infects about 90% of adults worldwide. It is the main cause of infectious mononucleosis, which is observed most frequently in adolescents. The disease can last several weeks and is characterized by lymphocytosis, sore throat, lymphadenopathy, and fatigue. Exposure to oral secretions during deep kissing has been identified as the major source for primary EBV infection in adolescents. Oral secretions are also thought to be the source for younger children through intimate intact or sharing food and eating utensils, although this has not been confirmed. Unlike most acute viral illnesses such as influenza, the incubation period of symptomatic primary EBV infection is unusually long, lasting about six weeks. Diagnosis is typically made by heterophile antibody tests and/or EBV-specific antibody tests. Long-term consequences may result from acquisition of the virus, including nasopharyngeal carcinoma and lymphomas. Nevertheless, there remains a surprising dearth of knowledge regarding the establishment of an immune response to persistent EBV infection, especially during the incubation period. This lack of knowledge has impaired our ability to develop an effective prophylactic EBV vaccine, despite various attempts. Our greatest challenges in EBV research are to develop a prophylactic vaccine and devise treatment strategies for persons already infected with EBV. more...

Key content Constipation affects up to 38% of pregnancies. Rising progesterone levels in pregnancy contribute to slow gut motility. The standard clinical measures of chronic constipation are the Rome III criteria, which are based on frequency and difficulty in the passage of stool. Secondary constipation is due to primary disease of the colon (anal fissure, stricture and neoplasia), metabolic disturbances (hypothyroidism and hypercalcaemia) and neurological disorders. Severe constipation may result in faecal impaction, retention of urine, pain or abdominal discomfort, rectal bleeding and/or rectal prolapse. A treatment algorithm using laxatives that are effective, safe and non-teratogenic will be discussed. Learning objectives To understand the prevalence and pathophysiology of this condition in pregnancy. To understand the management of constipation in pregnancy. Ethical issues The studies on safety of laxatives in pregnancy have small sample sizes although they have not shown any effect on congenital malformations. When to involve a gastroenterologist or a colorectal surgeon in the care of a woman with constipation in pregnancy. more...

Many pediatric centers utilize a variety of protocols including preemptive plasmapheresis to prevent the recurrence of FSGS post-transplant. But the effectiveness of this expensive, time-consuming process of plasmapheresis in the prevention of FSGS recurrence is still unclear. We retrospectively reviewed all pediatric cases of FSGS in our center that received a kidney transplant and compared the transplant and patient outcomes of those transplanted after 2006 who received pretransplant plasmapheresis to those prior to 2006 who did not. Of the 57 children with FSGS, 31 and 26 were transplanted before and after 2006, respectively. The cohorts differed significantly in keeping with the center immunosuppression protocol changes, and prior to 2006, the recipients were significantly younger. All children with FSGS transplanted after 2006 underwent three and one sessions of 1.0 plasma volume/exchange plasmapheresis with fresh frozen plasma replacement prior to the transplant in living and deceased donors, respectively, in addition to five sessions of every other day post-transplant pheresis. The incidence (27% vs 26%, P = 1.0) and time to recurrence of FSGS in the kidney allograft (P = .22) were not significantly different in patients that did and did not undergo prophylactic plasmapheresis. We need to re-evaluate the role of preemptive plasmapheresis in the prevention of FSGS recurrence in a prospective multicenter study. more...

Epstein-Barr virus (EBV) poses a significant threat to patient and graft survival posttransplant. We hypothesized that recipients who shed EBV at transplant had less immunologic control of the virus and hence were more likely to have active EBV infection and disease posttransplant. To test this hypothesis, we conducted a 5-year prospective study in primary solid organ transplant recipients. We measured EBV DNA in oral washes and blood samples by quantitative PCR before transplant and periodically thereafter for up to 4 years. Pretransplant samples were available from 98 subjects. EBV DNA was detected pretransplant in 32/95 (34%) and 5/93 subjects (5%) in oral wash and blood respectively. Recipients with and without detectable pretransplant EBV DNA were not significantly different demographically; and had no significant difference in patient and graft survival (P=0.6 for both comparisons) or posttransplant EBV viremia free survival (P= 0.8). There were no cases of EBV-related disease or posttransplant lymphoproliferative disorder (PTLD) in any of the patients with detectable EBV DNA pretransplant. In conclusion, detectable EBV DNA pretransplant was not associated with differences in patient/graft survival, posttransplant EBV viremia, or EBV-related diseases including PTLD. This article is protected by copyright. All rights reserved. more...

MMF is commonly prescribed following kidney transplantation, yet its use is complicated by leukopenia. Understanding the genetics mediating this risk will help clinicians administer MMF safely. We evaluated 284 patients under 21 years of age for incidence and time course of MMF-related leukopenia and performed a candidate gene association study comparing the frequency of 26 SNPs between cases with MMF-related leukopenia and controls. We matched cases by induction, steroid duration, race, center, and age. We also evaluated the impact of induction and SNPs on time to leukopenia in all cases. Sixty-eight (24%) patients had MMF-related leukopenia, of which 59 consented for genotyping and 38 were matched with controls. Among matched pairs, no SNPs were associated with leukopenia. With non-depleting induction, UGT2B7-900A>G (rs7438135) was associated with increased risk of MMF-related leukopenia (P = .038). Time to leukopenia did not differ between patients by induction agent, but 2 SNPs (rs2228075, rs2278294) in IMPDH1 were associated with increased time to leukopenia. MMF-related leukopenia is common after transplantation. UGT2B7 may influence leukopenia risk especially in patients without lymphocyte-depleting induction. IMPDH1 may influence time course of leukopenia after transplant. more...

We previously demonstrated that detectable BK virus (BKV) replication in donor urine pre- transplant was significantly associated with post-transplant recipient BKV viremia. In this 4-year prospective study, we assessed whether recipient BKV replication pre-transplant was associated with post-transplant viremia/BKV nephropathy. We studied 220 primary adult and pediatric organ transplant recipients for 490 person-years and 2100 clinical visits. BKV viruria was detectable in 28 (16%), 26 adults and 2 children; and viremia in none pre- transplant. Post-transplant viruria occurred in all recipients with pre-transplant BKV viruria; significantly more than in recipients without pre-transplant viruria on univariate (p more...

Given the nephrotoxicity of calcineurin inhibitors (CNIs), we asked whether their addition improved living related donor (LRD) human leukocyte antigen (HLA) identical kidney transplant recipient outcomes.We performed a comprehensive literature review and a single-center study comparing patient survival (PS) and graft survival (GS) of LRD HLA-identical kidney transplants for three different immunosuppression eras: Era 1 (up to 1984): anti-lymphocyte globulin (ALG) induction and maintenance immunosuppression with prednisone and azathioprine (AZA) (n = 114); Era 2a (1984-99): CNI added; evolution from ALG to thymoglobulin; AZA to mycophenolate (n = 262). Era 2b (1999-2011): rapid discontinuation of prednisone (thymoglobulin induction, CNI and mycophenolate) in recipients having first or second transplant and not previously on prednisone (n = 77).Demographics differed by era: recipient (P0.0001) and donor age (P0.0001) increased and the proportion of Caucasian donors (P = 0.02) and recipients (P = 0.003) decreased with each advancing era. There was no significant difference in PS (P = 0.6); cause of death (P = 0.5); death-censored GS (P = 0.8) or graft loss from acute rejection by era. Graft loss from chronic allograft nephropathy (P = 0.02) and hypertension (P = 0.005) were greater in the CNI eras. There were no significant differences in the 1/creatinine slopes between eras for the first (P = 0.6), second (P = 0.9) or2 years post-transplant (P = 0.4). Literature review revealed no clear benefits for CNI in these human leukocyte antigen (HLA) identical LRD graft recipients.This study confirmed that there are no benefits of CNIs for HLA-identical LRD recipients. Moreover, we did find evidence of potential harm. Thus, monotherapy or early discontinuation of CNI should be given consideration in these patients. more...

The therapeutic options for management of stress urinary incontinence can be conservative, pharmacological or surgical. The treatment of patients with stress urinary incontinence should be tailored to the individual to optimize care. A multitude of surgical techniques have emerged to treat this condition in recent years. The objective of the present review was to present an overview of current practice in the management of stress urinary incontinence while considering the evidence supporting the clinical effectiveness of these procedures. more...

Pediatric patients requiring kidney transplant after hematopoietic cell transplant receive multiple courses of immunosuppression placing them at risk for infection. To elucidate potential risk factors for infection, we compared the immunosuppressive regimens and infectious complications of pediatric kidney transplant recipients at a single institution who had previously undergone hematopoietic cell transplant from different donors to similar patients reported in the literature. Among the initial four post-hematopoietic cell transplant kidney transplant patients reviewed, viremia episodes were universal, including BK virus, Epstein-Barr virus, and human herpesvirus-6, with one death from presumed BK virus encephalitis. No viremia was reported in five similar cases in the literature. Risk factors for increased infection include use of lymphodepleting serotherapy in HCT conditioning, multiple HCTs, limited immune reconstitution time between transplants, increased pre-KTx viral burden, and use of T-cell-depleting versus -suppressive induction immunosuppression for KTx. These findings suggest that pediatric post-HCT KTx recipients are at increased risk for viral infections, likely benefitting from thorough pre-KTx evaluation of immune reconstitution and preferential use of non-T-cell-depleting induction therapy for KTx. We applied these recommendations to one subsequent post-HCT patient requiring KTx at our institution with excellent outcomes one year post-KTx. more...

It is important to identify prognostically important morphologic criteria in post-transplant management to tailor therapy and improve outcomes. Therefore, using biopsies carried out for cause

Introduction and hypothesis The aim of this study was to establish if the management of women with overactive bladder (OAB) and patient-reported outcomes differed based on the findings of urodynamics (UDS). Methods A prospective, longitudinal observational study conducted in urogynaecology clinics in 22 UK hospitals participating in the Diagnostic Accuracy of Bladder Ultrasound Study (BUS). A total of 687 women with OAB symptoms or urgency-predominant mixed urinary incontinence were recruited into a diagnostic study that used UDS as the reference standard. Detailed clinical history and International Consultation on Incontinence OAB Short Form (ICIQ-OAB sf) questionnaire responses were obtained before the UDS test was carried out. These questionnaires were subsequently collected at a mean of 7 and 20 months, along with patient global impression of improvement and details on medical and surgical treatments. The relationship between UDS diagnosis and treatment was examined using a multinomial regression model; logistic and repeated measures regressions were used to examine other outcomes. Results We recruited 687 women and the response rate was 69% at 20 months. Treatment subsequent to UDS was highly associated with diagnosis (p more...

Background Advances in immunosuppression, surgical techniques, and management of infections in children receiving kidney transplants have affected outcomes. Study Design We analyzed a prospectively maintained database of pediatric kidney transplantations. Results From June 1963 through October 2016, we performed 1,056 pediatric kidney transplantations. Of these, 129 were in children less than 2 years old. The most common indications for transplant were congenital anomalies (dysplastic kidneys), obstructive uropathy, and congenital nephrotic syndrome. Living donors constituted 721 (68%) of all donors. The graft and patient survival rates remarkably improved for both deceased and living donor recipients (p = 0.001). Currently, graft survival rates for deceased donor recipients are 92% at 1 year, 76% at 5 years, and 57% at 10 years post-transplant; for living donor recipients, 96% at 1 year, 85% at 5 years, and 78% at 10 years. The graft half-life was 19 years in deceased donor recipients, compared with 25 years in living donor recipients (p ≤ 0.001). Acute rejection was the most common cause of graft loss in the first year post-transplant. The following risk factors were associated with an increased risk of graft loss: deceased donor grafts (p = 0.0001), retransplant (p = 0.02), ages 11 to 18 years (p = 0.001) and pre-transplant urologic issues (p = 0.04). Living donor grafts (p ≤ 0.0001) and pre-emptive transplants (p = 0.02) were associated with decreased risks of graft loss. Conclusions The success rates of pediatric kidney transplants have significantly improved. Pre-emptive kidney transplantation with a living donor graft continues to be superior and should be the choice in children with end-stage renal disease. more...

The etiology and treatment of transplant glomerulopathy (TG) is not clear. TG is associated with donor-specific antibodies but the lack of C4d deposition in the peritubular capillaries (ptc-C4d) in some cases has caused the role of complement in the pathogenesis of TG to be debated. There is however, little information on C4d deposition in the glomerulus itself. We retrieved random frozen sections from 25 cases with well-established TG by light microscopy (LM) and 25 cases without TG as controls and reviewed the LM and immunofluorescence (nine biopsies were excluded due to inadequate samples). Glomerular complement deposition was assessed in all included biopsies. Glomerular C3d and C4d deposition occurred in a distinct pattern in all TG biopsies: segmental or global double linear staining of the glomerular capillary wall in 23 (100%). This pattern was not present in any NON-TG biopsies. The distinct glomerular complement deposition patterns in all TG cases are suggestive that TG is a proximal complement-mediated process and therapies should focus on proximal complement inhibition. more...

BKV has emerged as a significant pathogen in the field of transplantation, predominantly causing BKV nephropathy in renal transplant recipients and hemorrhagic cystitis in HSCT recipients. However, case reports describe more diverse complications, and we too present three unusual cases of BKV infections in pediatric renal transplant recipients. First, we describe a case of biopsy-proven renal damage secondary to BKV prior to the onset of viremia, demonstrating that BKV nephropathy can occur without preceding viremia. We also present two renal transplant recipients with persistent BK viruria, one with BKV-associated hemorrhagic cystitis and the other with microscopic hematuria. Therefore, we conclude that BKV manifestations may be more diverse than previously thought and suggest clinical utility in urine BKV qPCR testing in specific transplant recipients. more...