Catastrophic healthcare expenditure and caregiver burden in pediatric chronic kidney disease - a mixed methods study from a low resource setting.

BACKGROUND: Caregivers of children with chronic kidney disease (CKD) in low resource settings must provide complex medical care at home while being burdened by treatment costs often paid out-of-pocket. We hypothesize that caregiver burden in our low resource setting is greater than reported from high income countries and is associated with frequent catastrophic healthcare expenditure (CHE). METHODS: We conducted a mixed-methods study of primary caregivers of children with advanced CKD (stage 3b-5) in our private-sector referral hospital in a low resource setting. We assessed caregiver burden using the Pediatric Renal Caregiver Burden Scale (PRCBS) and measured financial burden by calculating the proportion of caregivers who experienced CHE (monthly out-of-pocket healthcare expenditure exceeding 10% of total household monthly expenditure). We performed a qualitative reflexive thematic analysis of caregiver interviews to explore sources of burden. RESULTS: Of the 45 caregivers included, 35 (78%) had children on maintenance dialysis (25 PD, 10 HD). Mean caregiver burden score was 141 (± 17), greater than previously reported. On comparative analysis, PRCBS scores were higher among caregivers of children with kidney failure (p = 0.005), recent hospitalization (p = 0.03), non-earning caregivers (p = 0.02), caring for > 2 dependents (p = 0.009), and with high medical expenditure (p = 0.006). CHE occurred in 43 (96%) caregivers of whom 37 (82%) paid out-of-pocket. The main themes derived relating to caregiver burden were severe financial burden, mental stress and isolation, and perpetual burden of concern. CONCLUSION: Parents of children with CKD experienced severe caregiver burden with frequent CHE and relentless financial stress indicating an imminent need for social support interventions.

Evidence-based clinical practice guideline for management of urinary tract infection and primary vesicoureteric reflux.

We present updated, evidence-based clinical practice guidelines from the Indian Society of Pediatric Nephrology (ISPN) for the management of urinary tract infection (UTI) and primary vesicoureteric reflux (VUR) in children. These guidelines conform to international standards; Institute of Medicine and AGREE checklists were used to ensure transparency, rigor, and thoroughness in the guideline development. In view of the robust methodology, these guidelines are applicable globally for the management of UTI and VUR. Seventeen recommendations and 18 clinical practice points have been formulated. Some of the key recommendations and practice points are as follows. Urine culture with > 104 colony forming units/mL is considered significant for the diagnosis of UTI in an infant if the clinical suspicion is strong. Urine leukocyte esterase and nitrite can be used as an alternative screening test to urine microscopy in a child with suspected UTI. Acute pyelonephritis can be treated with oral antibiotics in a non-toxic infant for 7-10 days. An acute-phase DMSA scan is not recommended in the evaluation of UTI. Micturating cystourethrography (MCU) is indicated in children with recurrent UTI, abnormal kidney ultrasound, and in patients below 2 years of age with non-E. coli UTI. Dimercaptosuccinic acid scan (DMSA scan) is indicated only in children with recurrent UTI and high-grade (3-5) VUR. Antibiotic prophylaxis is not indicated in children with a normal urinary tract after UTI. Prophylaxis is recommended to prevent UTI in children with bladder bowel dysfunction (BBD) and those with high-grade VUR. In children with VUR, prophylaxis should be stopped if the child is toilet trained, free of BBD, and has not had a UTI in the last 1 year. Surgical intervention in high-grade VUR can be considered for parental preference over antibiotic prophylaxis or in children developing recurrent breakthrough febrile UTIs on antibiotic prophylaxis.

Clinical features and outcomes of patients with diacylglycerol kinase epsilon nephropathy: a nationwide experience.

BACKGROUND: Thrombotic microangiopathy (TMA) is usually caused due to dysregulation of the alternative complement pathway. Rarely, thrombotic microangiopathy is caused by non-complement mediated mutations in diacylglycerol kinase epsilon (DGKE); information about therapy and outcome of these patients is limited. METHODS: Medical records of patients, younger than 18 years, diagnosed with TMA and variants in DGKE were reviewed to include 12 patients from seven centers. Genetic studies included targeted exome sequencing and multiplex-ligation dependent probe amplification of CFH-CFHR5. RESULTS: Patients presented at a median age of 11 (7.5, 12.3) months; all were younger than 2 years. All patients had an infectious prodrome; enteroinvasive, enteropathogenic, and enterotoxigenic Escherichia coli were detected in two patients with diarrhea. Chief features included those of microangiopathic hemolysis (n = 11), microscopic hematuria (n = 10), nephrotic range proteinuria (n = 10), hypoalbuminemia (n = 6), elevated total cholesterol (n = 6), and hypocomplementemia (n = 4). Histopathology showed thrombotic microangiopathy (n = 4), overlapping with membranoproliferative pattern of injury (n = 1). At median 3.3 years of follow-up, significant hypertension and/or proteinuria (40%), relapses (66.7%), and death or progression to CKD (60%) were common. Genetic sequencing showed 13 homozygous and compound heterozygous variants (7 pathogenic, 3 likely pathogenic) located throughout DGKE; 11 variants were novel. CONCLUSIONS: This case series highlights the need to suspect DGKE nephropathy in young patients with TMA, especially those with severe proteinuria. Medium-term outcomes are unsatisfactory with risk of relapses, progressive kidney failure, and death. A higher resolution version of the Graphical abstract is available as Supplementary information.

Low renal transplantation rates in children with end-stage kidney disease: A study of barriers in a low-resource setting.

After 2 decades as a low-cost transplant centre in India, our rates of kidney transplantation are low compared to the burden of end-stage kidney disease (ESKD). We performed this study to identify possible barriers inhibiting paediatric kidney transplant and to assess the outcomes of paediatric ESKD. A retrospective chart review of ESKD patients (2013 - 2018) at a tertiary paediatric nephrology centre was conducted. Medical/non-medical barriers to transplant were noted. Patient outcomes were classified as "continued treatment," "lost to follow-up (LTFU)" or "died." Of 155 ESKD patients (monthly income 218 USD [146, 365], 94% self-pay), only 30 (19%) were transplanted (28 living donor). Sixty-five (42%) were LTFU, 19 (12%) died, and 71 (46%) continued treatment. LTFU/death was associated with greater travel distance (300 km [60, 400] vs 110 km [20, 250] km, P < .0001) and lower monthly income (145 USD [101, 290] vs 290 USD [159, 681], P < .0001). Among those who continued treatment, 41 proceeded to transplant evaluation of whom 13 had no living donor and remained waitlisted for 27 months (15, 30). The remainder (n = 30) did not proceed to transplant due to unresolved medical issues (n = 10) or a lack of parental interest in pursuing transplant (n = 20). Barriers to transplantation in low-resource setting begin in ESKD. LTFU resulted in withdrawal of care and was associated with low socioeconomic status. Among those who continued treatment, transplant rates were higher but medical challenges and negative attitudes towards transplant and organ donation occurred.

Nocturnal hypertension and left ventricular hypertrophy in pediatric renal transplant recipients in South India.

HTN after renal transplantation is associated with cardiovascular morbidity. ABPM allows diagnosis of masked HTN and isolated nocturnal HTN. Longitudinal ABPM data in children post-transplant are limited. ABPM was performed in children post-transplant and repeated in 6-12 months. BP indices were used to determine the prevalence of masked HTN, masked uncontrolled HTN (masked HTN in patients on antihypertensive medications), and isolated nocturnal HTN. Linear regression determined the association between LVMI and ABPM indices. Thirty children underwent a baseline ABPM. Ambulatory HTN was present in 25 (83%). Masked HTN was present in 18 (60%) and isolated nocturnal HTN in 13 (43%). Nocturnal ambulatory BP was higher than corresponding daytime BPs (P < .001 for systolic and diastolic) and 25 (83%) had a blunted nocturnal dip. Prednisone dose predicted nocturnal DBP index and DBP load (r2  = .40, P = .024 and r2  = .178, P = .02). ABPM was repeated in 18 patients within 11 (±3) months. BP indices decreased with time, but nocturnal BPs remained higher than daytime (P < .001 for SBP and DBP). Blunted nocturnal dip did not improve. LVH was present in 12 (57%). LVMI was directly related to the nocturnal SBP index (r2  = .377, P = .003) and nocturnal DBP index (r2  = .493, P < .001). We found no association between LVMI and daytime BP indices. The prevalence of masked HTN, isolated nocturnal HTN, and blunted nocturnal dip was high in children with kidney transplants. Nocturnal BP predicted LVMI. Ambulatory BP improved on longitudinal follow-up, but the pattern of isolated nocturnal HTN persisted.

Clinical Ethics in Pediatrics: An International Perspective.

In this article, we first review the development of clinical ethics in pediatrics in the United States. We report that, over the last 40 years, most children's hospitals have ethics committees but that those committees are rarely consulted. We speculate that the reasons for the paucity of ethics consults might be because ethical dilemmas are aired in other venues. The role of the ethics consultant, then, might be to shape the institutional climate and create safe spaces for the discussion of difficult and sometimes contentious issues. Finally, we report how pediatric clinical ethics has evolved differently in a number of other countries around the world.

Responsiveness of the PROMIS® measures to changes in disease status among pediatric nephrotic syndrome patients: a Midwest pediatric nephrology consortium study.

BACKGROUND: Nephrotic syndrome represents a condition in pediatric nephrology typified by a relapsing and remitting course, proteinuria and the presence of edema. The PROMIS measures have previously been studied and validated in cross-sectional studies of children with nephrotic syndrome. This study was designed to longitudinally validate the PROMIS measures in pediatric nephrotic syndrome. METHODS: One hundred twenty seven children with nephrotic syndrome between the ages of 8 and 17 years participated in this prospective cohort study. Patients completed a baseline assessment while their nephrotic syndrome was active, a follow-up assessment at the time of their first complete proteinuria remission or study month 3 if no remission occurred, and a final assessment at study month 12. Participants completed six PROMIS measures (Mobility, Fatigue, Pain Interference, Depressive Symptoms, Anxiety, and Peer Relationships), the PedsQL version 4.0, and two global assessment of change items. RESULTS: Disease status was classified at each assessment: nephrotic syndrome active in 100% at baseline, 33% at month 3, and 46% at month 12. The PROMIS domains of Mobility, Fatigue, Pain Interference, Depressive Symptoms, and Anxiety each showed a significant overall improvement over time (p < 0.001). When the PROMIS measures were compared to the patients' global assessment of change, the domains of Mobility, Fatigue, Pain Interference, and Anxiety consistently changed in an expected fashion. With the exception of Pain Interference, change in PROMIS domain scores did not correlate with changes in disease activity. PROMIS domain scores were moderately correlated with analogous PedsQL domain scores. CONCLUSION: This study demonstrates that the PROMIS Mobility, Fatigue, Pain Interference, and Anxiety domains are sensitive to self-reported changes in disease and overall health status over time in children with nephrotic syndrome. The lack of significant anchoring to clinically defined nephrotic syndrome disease active and remission status may highlight an opportunity to improve the measurement of HRQOL in children with nephrotic syndrome through the development of a nephrotic syndrome disease-specific HRQOL measure.

Vitamin D in incident nephrotic syndrome: a Midwest Pediatric Nephrology Consortium study.

BACKGROUND: Cross-sectional studies of children with prevalent nephrotic syndrome (NS) have shown 25-vitamin D (25(OH)D) deficiency rates of 20-100 %. Information on 25(OH)D status in incident patients or following remission is limited. This study aimed to assess 25(OH)D status of incident idiopathic NS children at presentation and longitudinally with short-term observation. METHODS: Multicenter longitudinal study of children (2-18 years old) from 14 centers across the Midwest Pediatric Nephrology Consortium with incident idiopathic NS. 25(OH)D levels were assessed at diagnosis and 3 months later. RESULTS: Sixty-one children, median age 5 (3, 11) years, completed baseline visit and 51 completed second visit labs. All 61 (100 %) had 25(OH)D < 20 ng/ml at diagnosis. Twenty-seven (53 %) had 25(OH)D < 20 ng/ml at follow-up. Fourteen (28 %) children were steroid resistant. Univariate analysis showed that children prescribed vitamin D supplements were less likely to have 25(OH)D deficiency at follow-up (OR 0.2, 95 % CI 0.04, 0.6). Steroid response, age, and season did not predict 25(OH)D deficiency. Multivariable linear regression modeling showed higher 25(OH)D levels at follow-up by 13.2 ng/ml (SE 4.6, p < 0.01) in children supplemented with vitamin D. CONCLUSIONS: In this incident idiopathic NS cohort, all children at diagnosis had 25(OH)D deficiency and the majority continued to have a deficiency at 2-4 months. Supplemental vitamin D decreased the odds of 25(OH)D deficiency at follow-up, supporting a role for supplementation in incident NS.

The impact of disease duration on quality of life in children with nephrotic syndrome: a Midwest Pediatric Nephrology Consortium study.

BACKGROUND: The Patient Reported Outcomes Measurement Information System (PROMIS) II is a prospective study that evaluates patient reported outcomes in pediatric chronic diseases as a measure of health-related quality of life (HRQOL). We have evaluated the influence of disease duration on HRQOL and, for the first time, compared the findings of the PROMIS measures to those of the PedsQL™ 4.0 Generic Scales (PedsQL) from the PROMIS II nephrotic syndrome (NS) longitudinal cohort. METHODS: This was a prospective study in which 127 children (age range 8-17 years) with active NS from 14 centers were enrolled. Children with active NS defined as the presence of nephrotic range proteinuria (>2+ urinalysis and edema or urine protein/creatinine ratio >2 g/g) were eligible. Comparisons were made between children with prevalent (N = 67) and incident (N = 60) disease at the study enrollment visit. RESULTS: The PROMIS scores were worse in prevalent patients in the domains of peer relationship (p = 0.01) and pain interference (p < 0.01). The PedsQL showed worse scores in prevalent patients for social functioning (p < 0.01) and school functioning (p = 0.03). Multivariable analyses showed that prevalent patients had worse scores in PROMIS pain interference (p = 0.02) and PedsQL social functioning (p < 0.01). CONCLUSION: The PROMIS measures detected a significant impact of disease duration on HRQOL in children, such that peer relationships were worse and pain interfered with daily life to a greater degree among those with longer disease duration. These findings were in agreement with those for similar domains in the PedsQL legacy instrument.

Key ethical challenges in providing dialysis in low resource settings - A view from the trenches.

Maintenance dialysis is life-sustaining but poorly accessible in low- and middle-income countries (LMICs). There are not enough functional dialysis centres in the public sector, and in the private sector dialysis is prohibitively expensive. This results in the need for (de facto) rationing of public sector dialysis beds or catastrophic out-of-pocket expenditure. Death occurs in the majority of patients from lower socio-economic backgrounds because dialysis cannot be initiated or must be discontinued [1]. Kidney transplantation is even more inaccessible than dialysis due to inadequate transplant centres and high costs [2]. Conservative care is a continuation of medical care without dialysis that focuses on symptom control and end-of-life care. In high-income countries (HICs), conservative care is usually chosen by elderly, frail kidney failure patients or those with multiple serious comorbidities [3]. In LMICs, conservative care is the only treatment option when dialysis or kidney transplant is inaccessible. In high resource settings, shared decision making by patients and nephrologists regarding dialysis versus conservative care would ideally occur before kidney failure has occurred. Unfortunately, in LMICs, chronic kidney disease (CKD) is often diagnosed late when the patient becomes severely ill from advanced symptoms of kidney failure, requiring emergency initiation of dialysis [4]. Kidney failure in children is usually caused by congenital diseases that present differently from that in adults. Late diagnosis and urgent start dialysis is typical [5]. Paediatric dialysis is only provided in a few specialised centres in LMICs. Thus, parents/caregivers must shoulder the burden of medical caregiving and its associated costs. In these difficult circumstances, physicians face several ethical challenges in their struggle to provide the best possible care despite resource limitations [6].

Transition of Kidney Care at 18: Challenges and Practical Solutions for India.

Health-care transition (HCT) from pediatric-centered to adult-oriented health-care setting is more than a simple transfer of care. It is a carefully planned movement specially tailored for the needs of adolescents and young adults (AYAs). Similar to other chronic diseases, the need for HCT for AYAs with kidney disease has been well established by the International Society of Nephrology (ISN) and the International Pediatric Nephrology Association (IPNA) consensus statements since 2011. However, successful HCT in India and other low- and middle-income countries (LMICs) has been limited. Undertaking the HCT program in India requires involvement of many stakeholders, that is, AYAs, parents/caregivers, health-care providers, and the health-care system. In this article, we discuss the need for HCT, the challenges faced during the transition, and the recommended models for HCT in kidney care. We focus on the unique challenges faced in India and conclude with practical suggestions to implement HCT in our setting.

Obesity-related glomerulopathy in children: connecting pathophysiology to clinical care.

Obesity has continued to emerge as a worldwide pandemic and has been associated with a significant increase in associated comorbidities. These include well-known conditions such as hypertension and diabetes, as well as lesser-known conditions such as obesity-related glomerulopathy (ORG). The main etiology of ORG is podocyte damage, but contributing theories include dysfunctional renin-angiotensin-aldosterone system activation, hyperinsulinemia and lipid deposition. Recent advances have made strides in understanding the complex pathophysiology of ORG. The key to treating ORG is weight loss and proteinuria reduction. Lifestyle modification, pharmacological interventions and surgery are mainstays of management. A special focus on obese children is required, as childhood obesity tracks into adulthood and primary prevention is key. In this review we discuss the pathogenesis, clinical features and established and newer treatment modalities of ORG.

Inequities in kidney health and kidney care.

Health inequity refers to the existence of unnecessary and unfair differences in the ability of an individual or community to achieve optimal health and access appropriate care. Kidney diseases, including acute kidney injury and chronic kidney disease, are the epitome of health inequity. Kidney disease risk and outcomes are strongly associated with inequities that occur across the entire clinical course of disease. Insufficient investment across the spectrum of kidney health and kidney care is a fundamental source of inequity. In addition, social and structural inequities, including inequities in access to primary health care, education and preventative strategies, are major risk factors for, and contribute to, poorer outcomes for individuals living with kidney diseases. Access to affordable kidney care is also highly inequitable, resulting in financial hardship and catastrophic health expenditure for the most vulnerable. Solutions to these injustices require leadership and political will. The nephrology community has an important role in advocacy and in identifying and implementing solutions to dismantle inequities that affect kidney health.

Addressing the Ethical Challenges of Providing Kidney Failure Care for Children: A Global Stance.

Children with kidney failure require kidney replacement therapy (KRT), namely maintenance dialysis and kidney transplant. Adequate kidney failure care consists of KRT or conservative treatment with palliative care. In the context of kidney failure, children depend on parents who are their surrogate decision-makers, and the pediatric nephrology team for taking decisions about KRT or conservative care. In this paper, we discuss the ethical challenges that arise relating to such decision-making, from a global perspective, using the framework of pediatric bioethics. While many ethical dilemmas in the care of children with KRT are universal, the most significant ethical dilemma is the inequitable access to KRT in low & middle income countries (LMICs) where rates of morbidity and mortality depend on the family's ability to pay. Children with kidney failure in LMICs have inadequate access to maintenance dialysis, timely kidney transplant and palliative care compared to their counterparts in high income countries. Using case vignettes, we highlight how these disparities place severe burdens on caregivers, resulting in difficult decision-making, and lead to moral distress among pediatric nephrologists. We conclude with key action points to change this status-quo, the most important being advocacy by the global pediatric nephrology community for better access to affordable kidney failure care for children.

Psychological aspects in children and parents of children with chronic kidney disease and their families.

Pediatric chronic kidney disease (CKD) is a chronic illness that affects the overall quality of life of patients during childhood. This article highlights the psychological and social burden of CKD in patients and their families. Patients with CKD and their families require comprehensive treatment for psychosocial problems. Therefore, it is crucial for pediatricians to screen for these issues and refer patients and their families for therapy. Tools that are short, easy to administer, and easy to score, such as the Pediatric Quality of Life Inventory or the Childhood Depression Inventory, can be utilized during routine clinical appointments. Reducing the negative impact of CKD on the family will improve the well-being and coping skills of patients and their families.

Risk factors for renal scarring and clinical morbidity in children with high-grade and low-grade primary vesicoureteral reflux.

INTRODUCTION: Primary vesicoureteral reflux (VUR) is associated with urinary tract infections (UTIs) and renal damage. However, the importance of early diagnosis of VUR has been questioned. Moreover, most studies have few patients with high-grade VUR. Hence, we retrospectively analyzed a large cohort of patients with primary high-grade and low-grade VUR and assessed risk factors for renal damage and clinical morbidity. MATERIAL AND METHODS: We included patients (<18 years) at diagnosis with low-grade (1-3) or high-grade (4-5) primary VUR and noted their clinical history and presence of hypertension, low eGFR (<60ml/in/1.73 m2), renal scarring (focal or generalised) and reduced differential renal function (DRF; <45%). Risk factors were assessed (in patients and renal units) by logistic regression and generalised estimating equation. RESULTS: Of 399 primary VUR patients, 255 (64%) had high-grade VUR. Indications for voiding cystourethrogram were recurrent UTI (38%), first UTI (28%) and antenatal hydronephrosis (17%). At diagnosis, 252 (65%) had renal scars (focal in 170 [44%], generalised in 82 [21%]), and 188 (47%) had reduced DRF. High-grade VUR patients were more likely than low-grade VUR patients to have renal scarring (75% vs. 49%, p < 0.01), low eGFR (23% vs. 13%, p = 0.04) and significant hypertension (26% vs. 13%, p = 0.02). High-grade VUR was associated with generalised scars (odds ratio [OR] 11, p < 0.001), focal scars (OR 3.1, p < 0.001) and reduced DRF (OR 2.3, p < 0.001) shown in the table. Male sex was a risk factor for generalised scars (OR 2.3, p = 0.005). Focal scars were associated with recurrent UTIs (OR = 1.8, p = 0.004) and reduced DRF (OR 1.4, p = 0.027). Patients with multiple focal scars were diagnosed at an older age (2 years [1,4] than those with single scars (1.5 years [1,4] or no scars (1 year [0, 3]), p = 0.04). DISCUSSION: The prevalence of renal damage and clinical morbidity at VUR diagnosis was higher than other studies. High-grade VUR patients had a greater prevalence of renal damage, low eGFR and hypertension than low-grade VUR patients and was a risk factor for focal scars, generalised scars and reduced DRF. Focal scars were independently associated with recurrent UTI. Those with multiple scars were diagnosed later than those with single scars or no scars. CONCLUSIONS: High-grade VUR was associated with renal damage and clinical morbidity. Our study highlights the importance of diagnosing VUR early to identify patients who may warrant long-term follow-up and intervention to minimize morbidity.

Hepatoblastoma and prune belly syndrome: a potential association.

Prune belly syndrome (PBS) is a congenital anomaly characterized by the clinical triad of lax abdominal musculature, bilateral cryptorchidism, and abnormalities of the kidney and urinary tract. Previous reports of malignancy in patients with PBS have been limited to germ cell tumors. Hepatoblastoma (HBL) is the most common hepatic malignancy of childhood, affecting approximately 100 children each year in the USA. We describe a set of 4 pediatric patients with PBS and HBL. All individuals were born after 2002. These subjects lacked genetic, natal, or environmental factors known to confer risk of HBL. The occurrence of PBS and HBL in these patients constitutes a novel potential association.

Managing Children With Renal Diseases During the COVID-19 Pandemic.

The coronavirus outbreak is a rapidly evolving pandemic, placing unprecedented strain on health-care systems. COVID-19 presents challenges for management of children with renal diseases, especially those receiving long-term immunosuppressive medications, including renal transplant recipients and those with chronic kidney disease and acute kidney injury requiring dialysis. Our preparedness for managing this vulnerable group of children is the need of the hour. The purpose of this article is to provide guidance to caregivers and health care personnel involved in management of children with renal diseases and to ensure patient well-being, while protecting staff from infection.