Rationale & Objective: Growth failure is a common problem among children with chronic kidney disease (CKD). Reduced height is associated with psychosocial burden, social stigma, and impaired quality of life. This study describes the aspects of growth impairment that are most impactful from the perspectives of children with CKD, their parents, and health professionals. Study Design: Qualitative study. Settings & Participants: 120 children with CKD (aged 8-21 years), 250 parents, and 445 health professionals from 53 countries who participated in 16 focus groups, 2 consensus workshops, and a Delphi survey. Analytical Approach: A thematic analysis of all qualitative data concerning growth from the Standardized Outcomes in Nephrology-Children and Adolescents (SONG-Kids) initiative. Results: We identified 5 themes: diminishing psychological well-being (compared to and judged by peers, tired of explaining to others, damaging self-esteem), constrained life participation and enjoyment (deprived of normal school experiences, excluded from sports or competing at a disadvantage, impaired quality of life in adulthood); grappling with impacts of symptoms and treatment (difficulty understanding short stature and accessing help, lack of appetite, uncertainty regarding bone pains, medication side effects, burden of growth hormone treatment); facilitating timely interventions and optimizing outcomes (early indicator of disease, assessing management, maximizing transplant outcomes, minimizing morbidity); and keeping growth and health priorities in perspective (quality of life and survival of utmost priority, achieved adequate height). Limitations: Only English-speaking participants were included. Conclusions: Impaired growth may diminish psychological well-being, self-esteem, and participation in daily activities for children with CKD. Balancing different treatments that can affect growth complicates decision making. These fi ndings may inform the psychosocial support needed by children with CKD and their caregivers to address concerns about growth.

Rationale & Objective:Children and adolescents with chronic kidney disease (CKD) are at risk of depression and other mental health conditions, which can impair quality of life, the capacity for self-management and adherence to treatment, and overall health. This study aimed to describe the perspectives of patients and caregivers on mental health in children and adolescents across all stages of CKD. Study Design:Qualitative study. Settings & Participants:A secondary analysis of a consensus, multi-stage and inclusive process designed to establish core outcomes for children with CKD [Standardised Outcomes in Nephrology-Children and Adolescents (SONG-Kids)]. A total of 120 children and 250 caregivers, from 53 countries, who participated in 16 focus groups, two consensus workshops and an international Delphi survey were eligible for inclusion. Analytical Approach:We conducted a secondary thematic analysis of all qualitative data from the (SONG-Kids). Results:We identified five themes: struggling with a frail and sick identity (demoralized by a restricted lifestyle, shattered body image, victim of bullying, and descending into loneliness and isolation), worried by ongoing uncertainty about health (confronting own mortality and apprehension awaiting medical results), disappointed by narrowed vocational opportunities (unable to reach academic potential and thwarted career goals), distressed by medical trauma (traumatized by invasive procedures, and unrelenting demands of medication and treatment) and despair without adequate psychological support. Limitations:The transferability of the findings may be limited as the study was conducted in English. Conclusion:Children and adolescents with CKD may feel vulnerable, experience fear and anxiety about their prognosis and health, harbour a sense of failure with disappointment, and experience medical trauma. Improving ways to address fears and uncertainty about health, disruption to lifestyle and identity, and medical trauma in children with CKD are needed.

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. 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. A regionally appropriate 1–2-year training program enrolled 38 fellows with an initial 100

RATIONALE & OBJECTIVE:Clinical decision-making priorities may differ among children, their parents, and their clinicians. This study describes clinicians' perspectives on shared decision making in pediatric chronic kidney disease (CKD) and identifies opportunities to improve shared decision making and care for children with CKD and their families.STUDY DESIGN:Semistructured interviews.SETTING & PARTICIPANTS:Fifty clinicians participated, including pediatric nephrologists, nurses, social workers, surgeons, dietitians, and psychologists involved in providing care to children with CKD. They worked at 18 hospitals and 4 university research departments across 11 countries (United States of America, Canada, Australia, People's Republic of China, United Kingdom, Germany, France, Italy, Lithuania, New Zealand, and Singapore).ANALYTICAL APPROACH:Interview transcripts were analyzed thematically.RESULTS:We identified 4 themes: (1) striving to blend priorities (minimizing treatment burden, emphasizing clinical long-term risks, achieving common goals), (2) focusing on medical responsibilities (carrying decisional burden and pressure of expectations, working within system constraints, ensuring safety is foremost concern), (3) collaborating to achieve better long-term outcomes (individualizing care, creating partnerships, encouraging ownership and participation in shared decision making, sensitive to parental distress), and (4) forming cumulative knowledge (balancing reassurance and realistic expectations, building understanding around treatment, harnessing motivation for long-term goals).LIMITATIONS:Most clinicians were from high-income countries, so the transferability of the findings to other settings is uncertain.CONCLUSIONS:Clinicians reported striving to minimize treatment burden and working with children and their families to manage their expectations and support their decision making. However, they are challenged with system constraints and sometimes felt the pressure of being responsible for the child's long-term outcomes. Further studies are needed to test whether support for shared decision making would promote strategies to establish and improve the quality of care for children with CKD.

Children with chronic kidney disease (CKD) generally have worse educational and psychosocial outcomes compared with their healthy peers. This can impair their ability to manage their treatment, which in turn can have long-term health consequences through to adulthood. We attempted to capture the experiences of children with CKD and to describe the perspectives of their parents and caregivers on access to educational and psychosocial support.Children with CKD (n = 34) and their caregivers (n = 62) were sampled via focus groups from pediatric hospitals in Australia, Canada, and the USA. Sixteen focus groups were convened and the transcripts were analyzed thematically.We identified four themes: disruption to self-esteem and identity (emotional turmoil of adolescence, wrestling with the sick self, powerlessness to alleviate child's suffering, balancing normality and protection); disadvantaged by lack of empathy and acceptance (alienated by ignorance, bearing the burden alone); a hidden and inaccessible support system (excluded from formal psychological support, falling behind due to being denied special considerations); and building resilience (finding partners in the journey, moving towards acceptance of the illness, re-establishing childhood).Children with CKD and their caregivers encountered many barriers in accessing psychosocial and educational support and felt extremely disempowered and isolated as a consequence. Improved availability and access to psychosocial and educational interventions are needed to improve the wellbeing and educational advancement of children with CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Background More than 50% of children with chronic kidney disease (CKD) have uncontrolled hypertension, increasing their long-term risk of cardiovascular disease and progression to kidney failure. Children receiving medications or dialysis may also experience acute blood pressure fluctuations accompanied by debilitating symptoms. We aimed to describe the perspectives of children with CKD and their parental caregivers on blood pressure to inform patient-centered care. Methods Secondary thematic analysis was conducted on qualitative data from the Standardized Outcomes in Nephrology-Children and Adolescents initiative, encompassing 16 focus groups, an international Delphi survey and two consensus workshops. We analyzed responses from children with CKD (ages 8-21 years) and caregivers (of children ages 0-21 years) pertaining to blood pressure. Results Overall, 120 patients and 250 caregivers from 22 countries participated. We identified five themes: invisibility and normalization (reassured by apparent normotension, absence of symptoms and expected links with CKD), confused by ambiguity (hypertension indistinguishable from cardiovascular disease, questioning the need for prophylactic intervention, frustrated by inconsistent messages and struggling with technical skills in measurement), enabling monitoring and maintaining health (gaging well-being and preventing vascular complications), debilitating and constraining daily living (provoking anxiety and agitation, helpless and powerless and limiting life activities) and burden of medications (overwhelmed by the quantity of tablets and distress from unexpected side effects). Conclusions For children with CKD and their caregivers, blood pressure was an important heath indicator, but uncertainty around its implications and treatment hampered management. Providing educational resources to track blood pressure and minimizing symptoms and treatment burden may improve outcomes in children with CKD.

Physicians from developing countries do not have many opportunities to train in nephrology. The International Society of Nephrology (ISN) Fellowship program was established in 1985 to address workforce shortages,1 given that inadequate nephrology workforce2 remains a major hurdle to provision of equitable kidney care globally.3 The density of nephrologists in high-income countries is >90 times the density in low-income countries, whereas density of nephrology trainees is >30 times higher in high-income countries than in low-income countries,2 suggesting a disadvantage in care access for populations with low nephrologist densities.

To understand recent trends in orphan drug pricing between the US and Europe (France, Germany and the UK) and to assess whether launch pricing differentials between markets are narrowing with time. 10 orphan drugs, including hospital and non-hospital medicines spanning a variety of indications, were chosen. Prevalence rates for indications in the US and Europe ranged from <500 people to ∼230,000 people. FDA and EMA approval dates of each drug ranged from 2014–2018. Launch pricing data was gathered from a number of publicly available sources for each market and included ex-factory prices, hospital prices and pharmacy purchase prices. Prices were adjusted to USD using historic month-specific exchange rates and annual treatment costs were calculated using the defined daily dose. FDA, EMA and WHO websites and other publicly available sources were used to source launch dates, prevalence estimates and defined daily dose information (used to calculate annual treatment costs). Annual treatment costs at launch were higher in the US than in Europe in 8 out of 10 cases. On average, annual treatment costs were 22% higher for those treatments more expensive in the US, and 47% higher for those treatments (asfotase alfa and cerliponase alfa) more expensive in Europe. While pricing differentials showed no time-dependent correlation between markets, launch prices were more strongly correlated with disease prevalence in Europe (R2=0.2336) than in the US (R2=0.1722). In general, orphan drugs are priced higher in the US than in Europe. While we found no trend suggesting a narrowing in orphan drug pricing between markets since 2014, launch prices do appear more strongly correlated with disease prevalence in Europe than in the US.

More than 250 drugs carry a small but important dose-independent risk of initiating a delayed-type hypersensitivity reaction that leads to acute tubulointerstitial nephritis (TIN). Clinical manifestations are often non-specific, making epidemiological studies challenging. In severe cases, if cessation of the offending drug is not followed by a prompt improvement in renal function, corticosteroid therapy appears to enhance renal recovery rates. Other drugs, classified as potential nephrotoxins, may induce dose-dependent acute tubular necrosis. Studies over the past decade have identified a unique form of tubular cell death called "necroptosis" that is accompanied by a specific and significant interstitial inflammatory response to certain insults, including some nephrotoxins. Insights into the molecular basis of this necroinflammatory pathway have emerged. There is still a paucity of pediatric data on these two distinct types of drug-induced TIN. Early recognition is essential to minimize the risk of chronic kidney damage.

RATIONALE & OBJECTIVE The inconsistency in outcomes reported and lack of patient-reported outcomes across trials in children with chronic kidney disease (CKD) limits shared decision making. As part of the Standardized Outcomes in Nephrology (SONG)-Kids initiative, we aimed to generate a consensus-based prioritized list of critically important outcomes to be reported in all trials in children with CKD. STUDY DESIGN An online 2-round Delphi survey in English, French, and Hindi languages. SETTINGS & PARTICIPANTS Patients (aged 8-21 years), caregivers/family, and health care professionals (HCPs) rated the importance of outcomes using a 9-point Likert scale (7-9 indicating critical importance) and completed a Best-Worst Scale. ANALYTICAL APPROACH We assessed the absolute and relative importance of outcomes. Comments were analyzed thematically. RESULTS 557 participants (72 [13%] patients, 132 [24%] caregivers, and 353 [63%] HCPs) from 48 countries completed round 1 and 312 (56%) participants (28 [40%] patients, 64 [46%] caregivers, and 220 [56%] HCPs) completed round 2. Five outcomes were common in the top 10 for each group: mortality, kidney function, life participation, blood pressure, and infection. Caregivers and HCPs rated cardiovascular disease higher than patients. Patients gave lower ratings to all outcomes compared with caregivers/HCPs except they rated life participation (round 2 mean difference, 0.1), academic performance (0.1), mobility (0.4), and ability to travel (0.4) higher than caregivers and rated ability to travel (0.4) higher than HCPs. We identified 3 themes: alleviating disease and treatment burden, focusing on the whole child, and resolving fluctuating and conflicting goals. LIMITATIONS Most participants completed the survey in English. CONCLUSIONS Mortality, life participation, kidney function, and blood pressure were consistently highly prioritized by patients, caregivers, and HCPs. Patients gave higher priority to some lifestyle-related outcomes compared with caregivers/HCPs. Establishing critically important outcomes for all trials in children with CKD may improve consistent reporting of survival, kidney health, and clinical and life impact outcomes that are meaningful for decision making.

RATIONALE & OBJECTIVE:Chronic kidney disease (CKD) has wide-ranging and long-term consequences for young people and their families. The omission of outcomes that are important to young people with CKD and their caregivers limits knowledge to guide shared decision making. We aimed to identify the outcomes that are important to young people with CKD and their caregivers.STUDY DESIGN:We used the nominal group technique whereby participants identified and ranked outcomes and explained their priorities.SETTINGS & PARTICIPANTS:Young people with CKD (stages 1-5, dialysis, or transplantation) and their caregivers were purposively sampled from 6 centers across Australia, the United States, and Canada.ANALYTICAL APPROACH:Importance scores were calculated (scale of 0-1), and qualitative data were analyzed thematically.RESULTS:34 patients (aged 8-21 years) and 62 caregivers participated in 16 groups and identified 48 outcomes. The 5 highest ranked outcomes for patients were survival (importance score, 0.25), physical activity (0.24), fatigue (0.20), lifestyle restrictions (0.20), and growth (0.20); and for caregivers, kidney function (0.53), survival (0.28), infection (0.22), anemia (0.20), and growth (0.17). 12 themes were identified reflecting their immediate and current priorities (wanting to feel normal, strengthening resilience, minimizing intrusion into daily life, imminent threats to life, devastating family burdens, and seeking control over health) and considerations regarding future impacts (protecting health/development, remaining hopeful, concern for limited opportunities, prognostic uncertainty, dreading painful and invasive procedures, and managing expectations).LIMITATIONS:Only English-speaking participants were recruited.CONCLUSIONS:Kidney function, infection, survival, and growth were the highest priorities for patients with CKD and their caregivers. Young people with CKD also prioritized highly the outcomes that directly affected their lifestyle and sense of normality, while caregiver's highest priorities concerned the long-term health of their child, current health problems, and the financial and family burdens of caring for a child with CKD.

Human GWAS and Mendelian genetic studies have linked polymorphic variants and mutations in the human uromodulin gene (UMOD) with chronic kidney disease. The primary function of this kidney‐specific and secreted protein remains elusive. This study investigated whether UMOD deficiency modified responses to unilateral ureteral obstruction (UUO)‐induced kidney injury. Kidneys harvested from groups of wild‐type (UMOD+/+) and knockout (UMOD−/−) male mice (n = 7–10 each) were studied on days 7, 14, and 21. Compared to sham kidneys, UMOD protein levels increased 9–13x after UUO and were associated with increased urinary UMOD levels. Kidney KIM‐1 protein levels were higher in the UMOD−/− groups at all time‐points (4–14x). The UMOD−/− groups also had higher KIM‐1 kidney‐to‐urine relative ratios (5–35x). In vitro studies using KIM‐1 expressing 769‐P cells showed lower KIM‐1 levels in the presence of UMOD protein. Levels of proapoptotic genes and the epithelial cell apoptotic protein marker M30 were significantly lower in the UMOD−/− groups. Both M30 and KIM‐1 colocalized with intraluminal UMOD protein deposits. Interstitial inflammation was less intense in the UMOD−/− groups. Renal fibrosis severity (kidney collagen mRNA and protein) was similar in both genotypic groups on days 7, 14, and 21. Our findings suggest a role for UMOD‐dependent inhibition of KIM‐1 expression and its apoptotic cell scavenging responses during chronic obstruction‐associated tubular injury.

Background & Objectives: Effective communication and shared decision making improve quality of care and patient outcomes but can be particularly challenging in pediatric chronic disease because children depend on their parents and clinicians to manage complex health care and developmental needs. We aimed to describe the perspectives of children with chronic kidney disease (CKD) and their parents with regard to communication and decision making. Study Design: Qualitative study. Setting & Participants: Children with CKD (n = 34) and parents (n = 62) from 6 centers across 6 cities in Australia, Canada, and the United States participated in 16 focus groups. Analytical Approach: Transcripts were analyzed thematically. Results: We identified 4 themes: (1) dis-empowered by knowledge imbalance (unprepared and ill-informed, suspicion of censorship, and inadequacy as technicians), (2) recognizing own expertise (intuition and instinct unique to parental bond, emerging wisdom and confidence, identifying opportunities for control and inclusion, and empowering participation in children), (3) striving to assert own priorities (negotiating broader life impacts, choosing to defer decisional burden, overprotected and overruled, and struggling to voice own preferences), and (4) managing child's involvement (respecting child's expertise, attributing "risky" behaviors to rebellion, and protecting children from illness burden). Limitations: Only English-speaking participants were recruited, which may limit the transferability of the findings. We collected data from child and parent perspectives; however, clinician perspectives may provide further understanding of the difficulties of communication and decision making in pediatrics. Conclusions: Parents value partnership with clinicians and consider long-term and quality-of-life implications of their child's illness. Children with CKD want more involvement in treatment decision making but are limited by vulnerability, fear, and uncertainty. There is a need to support the child to better enable him or her to become a partner in decision making and prepare him or her for adulthood. Collaborative and informed decision making that addresses the priorities and concerns of both children and parents is needed.

Objective To determine the range and heterogeneity of outcomes reported in randomized controlled trials of interventions for children with chronic kidney disease (CKD).Study design The Cochrane Kidney and Transplant Specialized Register was searched to March 2016. Randomized trials involving children across all stages of CKD were selected. All outcome domains and measurements were extracted from included trials. The frequency and characteristics of the outcome domains and measures were evaluated.Results From 205 trials included, 6158 different measurements of 100 different outcome domains were reported, with a median of 22 domains per trial (IQR 13-41). Overall, 52 domains (52%) were surrogate, 38 (38%) were clinical, and 10 (10%) were patient-reported. The 5 most commonly reported domains were blood pressure (76 [37%] trials), relapse/remission (70 [34%]), kidney function (66 [32%]), infection (61 [ 30%]), and height/pubertal development (51 [25%]). Mortality (14%), cardiovascular disease (4%), and quality of life (1%) were reported infrequently. The 2 most frequently reported outcomes, blood pressure and relapse/ remission, had 56 and 81 different outcome measures, respectively.Conclusions The outcomes reported in clinical trials involving children with CKD are extremely heterogeneous and are most often surrogate outcomes, rather than clinical and patient-centered outcomes such as cardiovascular disease and quality of life. Efforts to ensure consistent reporting of outcomes that are important to patients and clinicians will improve the value of trials to guide clinical decision-making. In our study, non-English articles were excluded.

In sub-Saharan Africa (SSA), rapid urbanization and changing lifestyle have modified the profile and pattern of various medical disorders. Apart from high prevalence rates, recent trends with regard to hypertension in Africa include: low levels of awareness, treatment and control. Although a large number of studies provide data about hypertension in SSA, few studies focused on special populations such as urban slum dwellers. The WHO STEP-wise approach to surveillance of noncommunicable diseases was used to access the prevalence of hypertension among adults in one of the urban slums in Enugu. Out of the 811 individuals aged 20 years and above surveyed, 774 (95.4%) cases were analyzed. About 4.7% and 2.7% reported a past history of diabetes and stroke, respectively, whereas 15% had a positive family history of hypertension. The mean (95% confidence interval (CI)) body mass index (BMI) was 23.7 (23.2–24.2) kg m−2 among males and 26.6 (25.7–26.7) kg m−2 among females (P<0.0001). The prevalence of hypertension was 52.5% (95% CI: 48.9–56.0) and 55.4% (95% CI: 49.5–61.3) in males and 50.8% (95% CI: 46.4–55.1) in females (P=0.23). It increased with age peaking at 45–54 years in females and ⩾55 years in males. About 40.1% were aware of their hypertension and 28.8% of those aware had normal blood pressure. In regression analysis, systolic (R2=0.192) and diastolic (R2=0.129) blood pressures increased with age and BMI. The prevalence of high blood pressure among adults in Enugu slums is very high and a cause for concern, and calls for urgent attention.