Evaluation of the implementation of a "Pediatric Feasibility Assessment for Transplantation" tool in children and adolescents at Red Cross War Memorial Children's Hospital, Cape Town, South Africa.

BACKGROUND: Kidney transplantation remains the treatment of choice for children with kidney failure (KF). In South Africa, kidney replacement therapy (KRT) is restricted to children eligible for transplantation. This study reports on the implementation of the Paediatric Feasibility Assessment for Transplantation (pFAT) tool, a psychosocial risk score developed in South Africa to support transparent transplant eligibility assessment in a low-resource setting. METHODS: Single-center retrospective descriptive analysis of children assessed for KRT using pFAT tool from 2015 to 2021. RESULTS: Using the pFAT form, 88 children (median [range] age 12.0 [1.1 to 19.0] years) were assessed for KRT. Thirty (34.1%) children were not listed for KRT, scoring poorly in all domains, and were referred for supportive palliative care. Fourteen of these 30 children (46.7%) died, with a median survival of 6 months without dialysis. Nine children were reassessed and two were subsequently listed. Residing >300 km from the hospital (p = .009) and having adherence concerns (p = .003) were independently associated with nonlisting. Of the 58 (65.9%) children listed for KRT, 40 (69.0%) were transplanted. One-year patient and graft survival were 97.2% and 88.6%, respectively. Only one of the four grafts lost at 1-year posttransplant was attributed to psychosocial issues. CONCLUSIONS: Short-term outcomes among children listed using the pFAT form are good. Among those nonlisted, the pFAT highlights specific psychosocial/socioeconomic barriers, over which most children themselves have no power to change, which should be systemically addressed to permit eligibility of more children and save lives.

A 6-year review of acute post-streptococcal glomerulonephritis at a public children's hospital in Cape Town, South Africa.

BACKGROUND: Acute post-streptococcal glomerulonephritis (APSGN) is the most common cause of acute nephritis in children globally and, in some cases, may be associated with progressive kidney injury and failure, cumulating in the need for long-term dialysis and/or kidney transplantation. METHODS: Our retrospective study describes the occurrence of APSGN among children (< 14 years) admitted to a tertiary children's hospital in Cape Town, South Africa, from January 2015 to December 2020. RESULTS: Of 161 children who presented with acute nephritis (haematuria, oedema, oliguria, and hypertension), 100 met the inclusion criteria. Demographic, clinical features, laboratory findings, management, and outcome data were collected. APSGN was defined by the clinical presentation of at least two clinical signs of acute nephritis, and low serum complement 3 (C3) level or evidence of a recent streptococcal infection. Most cases of APSGN were associated with streptococcal skin infections: 55/100 (55%); 10/100 (10%) children presented with hypertensive seizures; C3 levels were low in 86/92 (93.5%) children; 94/94 (100%) children had elevated anti-deoxyribonuclease-B (anti-DNase-B) levels; and 80/94 (85%) also had elevated anti-streptolysin O titre (ASOT) at presentation. Eleven (11%) children had a percutaneous kidney biopsy; 4/11 (36%) showed histological features of post-infectious nephritis, and 7/11(64%) also had crescentic glomerulonephritis with immune complex deposits. Sixty-two (62%) children confirmed recovered, and five (5%) progressed to kidney failure, but 29 presumed recovered as they did not return for follow-up to our institution. CONCLUSIONS: Childhood APSGN remains an important health problem in South Africa (SA) with favourable outcomes in most, apart from those with crescentic glomerulonephritis who progressed to kidney failure.

Effects of aminophylline therapy on urine output and kidney function in children with acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a frequent complication of children admitted to the paediatric intensive care unit. One key management modality of AKI is the use of diuretics to reduce fluid overload. Aminophylline, a drug that is well known for its use in the treatment of bronchial asthma, is also purported to have diuretic effects on the kidneys. This retrospective cohort study assesses the effect of aminophylline in critically ill children with AKI. METHODS: A retrospective chart review of children admitted to the paediatric intensive care unit of the Red Cross War Memorial Children's Hospital (RCWMCH) with AKI who received aminophylline (from 2012 to June 2018) was carried out. Data captured and analyzed included demographics, underlying disease conditions, medications, urine output, fluid balance, and kidney function. RESULTS: Data from thirty-four children were analyzed. Urine output increased from a median of 0.4 mls/kg/hr [IQR: 0.1, 1.1] at six hours prior to aminophylline administration to 0.6 mls/kg/hr [IQR: 0.2, 1.9] at six hours and 1.6 mls/kg/hr [IQR:0.2, 4.2] at twenty-four hours post aminophylline therapy. The median urine output significantly varied across the age groups over the 24-h time period post-aminophylline, with the most response in the neonates. There was no significant change in serum creatinine levels six hours post-aminophylline administration [109(IQR: 77, 227)-125.5(IQR: 82, 200) micromole/l] P-value = 0.135. However, there were significant age-related changes in creatinine levels at six hours post-aminophylline therapy. CONCLUSIONS: Aminophylline increases urine output in critically ill children with AKI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Lessons learned from regional training of paediatric nephrology fellows in Africa.

BACKGROUND: Access to care for children with kidney disease is limited in less well-resourced regions of the world and paediatric nephrology (PN) workforce development with good practical skills is critical. METHODS: Retrospective review of a PN training program and trainee feedback from 1999 to 2021, based at Red Cross War Memorial Children's Hospital (RCWMCH), University of Cape Town. RESULTS: A regionally appropriate 1-2-year training program enrolled 38 fellows with an initial 100% return rate to their country of origin. Program funding included fellowships from the International Pediatric Nephrology Association (IPNA), International Society of Nephrology (ISN), International Society of Peritoneal Dialysis (ISPD), and the African Paediatric Fellowship Program (APFP). Fellows were trained on both in- and out-patient management of infants and children with kidney disorders. "Hands-on skills" training included examination, diagnosis and management skills, practical insertion of peritoneal dialysis catheters for management of acute kidney injury and kidney biopsies. Of 16 trainees who completed > 1 year of training, 14 (88%) successfully completed subspecialty exams and 9 (56%) completed a master's degree with a research component. PN fellows reported that their training was appropriate and enabled them to make a difference in their respective communities. CONCLUSIONS: This training program has successfully equipped African physicians with the requisite knowledge and skills to provide PN services in resource-constrained areas for children with kidney disease. The provision of funding from multiple organizations committed to paediatric kidney disease has contributed to the success of the program, along with the fellows' commitment to build PN healthcare capacity in Africa. A higher resolution version of the Graphical abstract is available as Supplementary information.

International Pediatric Transplant Association (IPTA) position statement supporting prioritizing pediatric recipients for deceased donor organ allocation.

A position statement of the International Pediatric Transplant Association endorsing prioritizing pediatric recipients for deceased donor organ allocation, examining the key ethical arguments that serve as the foundation for that position, and making specific policy recommendations to support prioritizing pediatric recipients for deceased donor organ allocation globally.

Allocation to pediatric recipients around the world: An IPTA global survey of current pediatric solid organ transplantation deceased donation allocation practices.

BACKGROUND: There has not been a comprehensive global survey of pediatric-deceased donor allocation practices across all organs since the advent of deceased donor transplantation at the end of the 20th century. As an international community that is responsible for transplanting children, we set out to survey the existing landscape of allocation. We aimed to summarize current practices and provide a snapshot overview of deceased donor allocation practices to children across the world. METHODS: The International Registry in Organ Donation and Transplantation (IRODAT, www.irodat.org) was utilized to generate a list of all countries in the world, divided by continent, that performed transplantation. We reviewed the published literature, published allocation policy, individual website references and associated links to publicly available listed allocation policies. Following this, we utilized tools of communication, relationships, and international fellowship to confirm deceased donation pediatric centers and survey pediatric allocation practices for liver, kidney, heart, and lung across the world. We summarize pediatric allocation practices by organ when available using source documents, and personal communication when no source documents were available. RESULTS: The majority of countries had either formal or informal policies directed toward minimizing organ distribution disparity among pediatric patients. CONCLUSION: Children have long-term life to gain from organ donation yet continue to die while awaiting transplantation. We summarize global strategies that have been employed to provide meaningful and sustained benefit to children on the waitlist.

Perspectives: Neonatal acute kidney injury (AKI) in low and middle income countries (LMIC).

Neonatal AKI (NAKI) remains a challenge in low- and middle-income countries (LMICs). In this perspective, we address issues of diagnosis and risk factors particular to less well-resourced regions. The conservative management pre-kidney replacement therapy (pre-KRT) is prioritized and challenges of KRT are described with improvised dialysis techniques also included. Special emphasis is placed on ethical and palliation principles.

Experience of ethical dilemmas among professionals working in pediatric transplantation: An international survey.

BACKGROUND: Professionals working in pediatric transplantation commonly encounter complex ethical dilemmas. Most ethical research in transplantation is related to adult practice. We aimed to gain insight into ethical issues faced by transplant professionals when dealing with pediatric transplant recipients. METHODS: A two-stage study was designed; the first part was a questionnaire completed by 190 (80%) members of the International Pediatric Transplant Association (IPTA) from over 30 different countries. This was followed by a multidisciplinary focus group that explored the preliminary data of the survey. RESULTS: A total of 38% (56 of 149) respondents of the questionnaire had experienced an ethical issue between 2016 and 2018. Surgeons were more likely to have encountered an ethical issue as compared with physicians (60% vs. 35.7%, p = .035). Clinicians from Europe were more likely to have experienced an ethical issue in living organ donation compared with those from North America (78.9% vs. 52.5%, p = .005), with common ethical concerns being psychosocial evaluation and follow-up care of donors. The focus group highlighted the importance of a multidisciplinary approach to ethical issues. CONCLUSION: The results of this study can direct future research into pediatric transplantation ethics with the aim of producing educational resources, policies, and ethical guidelines.

Update on COVID-19 vaccination in pediatric solid organ transplant recipients.

BACKGROUND: COVID-19 vaccination has been successful in decreasing rates of SARS-CoV-2 infection in areas with high vaccine uptake. Cases of breakthrough SARS-CoV-2 infection remain infrequent among immunocompetent vaccine recipients who are protected from severe COVID-19. Robust data demonstrate the safety, immunogenicity, and effectiveness of several COVID-19 vaccine formulations. Importantly, Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine studies have now included children as young as 5 years of age with safety, immunogenicity, and effectiveness data publicly available. In the United States, emergency use authorization by the Federal Drug Administration and approval from the Centers for Disease Control/Advisory Committee on Immunization Practices have been provided for the 5- to 11-year-old age group. METHODS: Members of the International Pediatric Transplant Association (IPTA) provide an updated review of current COVID-19 vaccine data with focus on pediatric solid organ transplant (SOT)-specific issues. RESULTS: This review provides an overview of current COVID-19 immunogenicity, safety, and efficacy data from key studies, with focus on data of importance to pediatric SOT recipients. Continued paucity of data in the setting of pediatric transplantation remains a challenge. CONCLUSIONS: Further studies of COVID-19 vaccination in pediatric SOT recipients are needed to better understand post-vaccine COVID-19 T-cell and antibody kinetics and determine the optimal vaccine schedule. Increased COVID-19 vaccine acceptability, uptake, and worldwide availability are needed to limit the risk that COVID-19 poses to pediatric solid organ transplant recipients.

Transplant: The Success of Renal Transplant Programs.

In the absence of malignancy or other severe comorbidity, kidney transplantation offers better survival rates and quality of life than dialysis. Despite this survival advantage, many lower- and upper-middle-income countries do not offer adequate kidney transplant services. This is particularly troubling because end-stage kidney disease often is more common in these countries than in high-income countries and overall is less costly in the life of a patient. We describe the contrasting levels of provision of kidney transplantation in Mexico, India, Nigeria, Ghana, and Zimbabwe, and kidney transplant services for children in Africa.

TB in paediatric kidney transplant recipients - A single-centre experience.

BACKGROUND: TB remains a major challenge in transplantation, particularly in endemic countries. This study aimed to describe the incidence, clinical presentation and outcomes of TB in paediatric kidney transplant recipients and to assess the impact of INH prophylaxis. METHODS: Single-centre retrospective descriptive analysis of children who received kidney transplants from 1995 to 2019 was carried out. The cohort was stratified according to receipt of INH prophylaxis which began in 2005. RESULTS: A total of 212 children received a kidney transplant during the study period. Median age at transplantation was 11.2 years (IQR: 2.2-17.9), and 56% were males. TB was diagnosed in 20 (9%) children, with almost two-thirds (n = 12) occurring within the first year. Most infections were pulmonary. The main presenting symptoms included fever (n = 13/20), weight loss (n = 12/20) and cough (n = 10/20). TST was positive in four of 20 children. Coinfection with EBV, CMV or Staph was found in five children. Due to drug interactions, an up to threefold increase in calcineurin inhibitor dose was required to maintain therapeutic blood levels. INH prophylaxis was protective against development of TB (p = .04). Gender, age and type of allograft were not significant risk factors. Graft and patient survival was 100% upon completion of TB treatment. CONCLUSION: Kidney transplant recipients in endemic countries have a high risk of developing TB. Diagnosis remains a challenge. Frequent and meticulous monitoring of immunosuppression drug levels during treatment of TB is required to avoid loss of patient or graft. INH prophylaxis protects against development of TB in this population.

Paediatric Nephrology in Africa.

PURPOSE OF REVIEW: We highlight the unique facets of paediatric nephrology in Africa in terms of the spectrum of kidney diseases, available diagnostic and treatment modalities, kidney healthcare financing options, paediatric nephrology manpower and the contribution of geography and demographics. RECENT FINDINGS: Paediatric acute kidney injury in Africa is now commonly due to sepsis rather than gastroenteritis. Steroid-sensitive form of nephrotic syndrome is far more common than was two decades ago. SUMMARY: The hot arid climate in North Africa and the tropical climate in most of sub-Saharan Africa, and the high rate of consanguinity, sickle cell disease and HIV drive the spectrum of paediatric kidney diseases in the continent. Kidney diseases are often precipitated by infectious triggers associated with poor living conditions and little access to medical care thus resulting in late presentation and often end-stage kidney disease. Although accessibility to kidney care has improved in the continent due to training opportunities provided by international professional organisations, most children still face significant barriers to kidney care because they live in rural areas, governments spend the least on healthcare and the continent has the least density of healthcare practitioners and nephrology trainees.

Use of locally prepared peritoneal dialysis (PD) fluid for acute PD in children and infants in Africa.

BACKGROUND: In less well-resourced countries, the high cost of commercially available peritoneal dialysis (PD) fluid limits its use. The major concerns regarding bedside-prepared PD fluid is peritonitis as well as electrolyte disorders. The aim of this study was to review our experience with the use of PD fluids prepared at the bedside using the intravenous infusion solution Balsol (Fresenius Kabi). METHODS: This was a retrospective review of all patients who received PD for acute kidney injury (AKI) using a bedside-prepared PD solution adapted from the intravenous solution Balsol in our intensive care unit. RESULTS: In total, 49 cases of acute PD were performed. Of the 49 children, 21 (43%) were male. The ages of the patients ranged from newborn to 10.2 years (median 0.33 years). The weight of children ranged from 1.3 kg to 50 kg (median 4.1 kg). The type of PD catheters used: Cook catheters, 41 patients; Kimal peel-away, 10 patients; and surgical inserted Tenckhoff type of catheter, 2 patients. The duration of PD was 1-17 days (median 3 days) Complications included peritonitis in 2 of 49 patients and blocked catheter in 6 of 49 patients. There were no electrolyte disturbances as a result of the PD. Overall survival was 43% of patients. CONCLUSIONS: Locally prepared PD solutions at the bedside adapted from intravenous solutions can be used safely and effectively. This has important relevance for centres in less well-resourced countries, where commercially produced PD fluid is not available for the management of AKI.

Global case studies for chronic kidney disease/end-stage kidney disease care.

The prevalence of chronic kidney disease and its risk factors is increasing worldwide, and the rapid rise in global need for end-stage kidney disease care is a major challenge for health systems, particularly in low- and middle-income countries. Countries are responding to the challenge of end-stage kidney disease in different ways, with variable provision of the components of a kidney care strategy, including effective prevention, detection, conservative care, kidney transplantation, and an appropriate mix of dialysis modalities. This collection of case studies is from 15 countries from around the world and offers valuable learning examples from a variety of contexts. The variability in approaches may be explained by country differences in burden of disease, available human or financial resources, income status, and cost structures. In addition, cultural considerations, political context, and competing interests from other stakeholders must be considered. Although the approaches taken have often varied substantially, a common theme is the potential benefits of multistakeholder engagement aimed at improving the availability and scope of integrated kidney care.

Challenges for sustainable end-stage kidney disease care in low-middle-income countries: the problem of the workforce.

Prevention and early detection of kidney diseases in adults and children should be a priority for any government health department. This is particularly pertinent in the low-middle-income countries, mostly in Asia, Africa, Latin America, and the Caribbean, where up to 7 million people die because of lack of end-stage kidney disease treatment. The nephrology workforce (nurses, technicians, and doctors) is limited in these countries and expanding the size and expertise of the workforce is essential to permit expansion of treatment for both chronic kidney disease and end-stage kidney disease. To achieve this will require sustained action and commitment from governments, academic medical centers, local nephrology societies, and the international nephrology community.

Supportive care for end-stage kidney disease: an integral part of kidney services across a range of income settings around the world.

A key component of treatment for all people with advanced kidney disease is supportive care, which aims to improve quality of life and can be provided alongside therapies intended to prolong life, such as dialysis. This article addresses the key considerations of supportive care as part of integrated end-stage kidney disease care, with particular attention paid to programs in low- and middle-income countries. Supportive care should be an integrated component of care for patients with advanced chronic kidney disease, patients receiving kidney replacement therapy (KRT), and patients receiving non-KRT conservative care. Five themes are identified: improving information on prognosis and support, developing context-specific evidence, establishing appropriate metrics for monitoring care, clearly communicating the role of supportive care, and integrating supportive care into existing health care infrastructures. This report explores some general aspects of these 5 domains, before exploring their consequences in 4 health care situations/settings: in people approaching end-stage kidney disease in high-income countries and in low- and middle-income countries, and in people discontinuing KRT in high-income countries and in low- and middle-income countries.

Increasing access to integrated ESKD care as part of universal health coverage.

The global nephrology community recognizes the need for a cohesive strategy to address the growing problem of end-stage kidney disease (ESKD). In March 2018, the International Society of Nephrology hosted a summit on integrated ESKD care, including 92 individuals from around the globe with diverse expertise and professional backgrounds. The attendees were from 41 countries, including 16 participants from 11 low- and lower-middle-income countries. The purpose was to develop a strategic plan to improve worldwide access to integrated ESKD care, by identifying and prioritizing key activities across 8 themes: (i) estimates of ESKD burden and treatment coverage, (ii) advocacy, (iii) education and training/workforce, (iv) financing/funding models, (v) ethics, (vi) dialysis, (vii) transplantation, and (viii) conservative care. Action plans with prioritized lists of goals, activities, and key deliverables, and an overarching performance framework were developed for each theme. Examples of these key deliverables include improved data availability, integration of core registry measures and analysis to inform development of health care policy; a framework for advocacy; improved and continued stakeholder engagement; improved workforce training; equitable, efficient, and cost-effective funding models; greater understanding and greater application of ethical principles in practice and policy; definition and application of standards for safe and sustainable dialysis treatment and a set of measurable quality parameters; and integration of dialysis, transplantation, and comprehensive conservative care as ESKD treatment options within the context of overall health priorities. Intended users of the action plans include clinicians, patients and their families, scientists, industry partners, government decision makers, and advocacy organizations. Implementation of this integrated and comprehensive plan is intended to improve quality and access to care and thereby reduce serious health-related suffering of adults and children affected by ESKD worldwide.

Teaching Pediatric Peritoneal Dialysis Globally through Virtual Simulation.

BACKGROUND AND OBJECTIVES: Despite the increasing prevalence of childhood kidney disease worldwide, there is a shortage of clinicians trained to provide peritoneal dialysis (PD). E-learning technologies may provide a solution to improve knowledge in PD. We describe the development of a virtual PD simulator and report the first 22 months of online usage. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The PD simulator was developed and released on OPENPediatrics in January of 2016. A prospective study of international, multidisciplinary healthcare providers was conducted from January of 2016 through October of 2017. User action data were analyzed with descriptive statistics and linear regression. Paired t tests compared user pre- and post-test scores. User satisfaction was assessed by survey. RESULTS: The simulator was accessed by 1066 users in 70 countries. Users spent a median of 35 minutes (interquartile range [IQR] 14-84) in the simulator. Users who completed the structured learning curriculum (n=300) spent a median of 85 minutes (IQR 46-95), and those who completed the entire simulator (n=63) spent a median of 122 minutes (IQR 69-195). Users who completed the simulator were more likely to scroll through text and access the simulator in multiple sessions. The 300 users that completed testing showed statistically significant increases in the post- versus pretest scores, with a mean increase of 36.4 of 100 points, SD 19.9 (95% confidence interval, 34.1 to 38.6, P<0.001). Eighty-seven percent (20 of 23) of survey respondents felt the simulator was relevant to their clinical practice, and 78% (18 of 23) would recommend it to others. CONCLUSIONS: This is the first reported virtual PD simulator. Increased test scores were observed between pre- and post-tests by clinicians who completed testing, across disciplines, training levels, and resource settings.

Renal transplantation in human immunodeficiency virus (HIV)-positive children.

Renal transplantation is being performed in adult human immunodeficiency virus (HIV)-positive patients and increasingly in paediatric patients as well. A multidisciplinary team involving an infectious disease professional is required to assist with HIV viral-load monitoring and in choosing the most appropriate highly active antiretroviral therapy (HAART). Drug interactions complicate immunosuppressant therapy and require careful management. The acute rejection rates appear to be similar in adults to those in noninfective transplant recipients. Induction with basiliximab and calcineurin-based immunosuppression appears to be safe and effective in these recipients. Prophylaxis is advised for a variety of infections and may need life-long administration, especially in children. Organ shortage remains a significant problem, and kidneys from deceased HIV-positive donors have been used successfully in a small study population. Overall, with careful planning and close follow-up, successful renal transplantation for paediatric HIV-infected recipients is possible.