Capacity for the management of kidney failure in the International Society of Nephrology South Asia region: report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA).

The South Asia region is facing a high burden of chronic kidney disease (CKD) with limited health resources and low expenditure on health care. In addition to the burden of CKD and kidney failure from traditional risk factors, CKD of unknown etiologies from India and Sri Lanka compounds the challenges of optimal management of CKD in the region. From the third edition of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA), we present the status of CKD burden, infrastructure, funding, resources, and health care personnel using the World Health Organization's building blocks for health systems in the ISN South Asia region. The poor status of the public health care system and low health care expenditure resulted in high out-of-pocket expenditures for people with kidney disease, which further compounded the situation. There is insufficient country capacity across the region to provide kidney replacement therapies to cover the burden. The infrastructure was also not uniformly distributed among the countries in the region. There were no chronic hemodialysis centers in Afghanistan, and peritoneal dialysis services were only available in Bangladesh, India, Nepal, Pakistan, and Sri Lanka. Kidney transplantation was not available in Afghanistan, Bhutan, and Maldives. Conservative kidney management was reported as available in 63% (n = 5) of the countries, yet no country reported availability of the core CKM care components. There was a high hospitalization rate and early mortality because of inadequate kidney care. The lack of national registries and actual disease burden estimates reported in the region prevent policymakers' attention to CKD as an important cause of morbidity and mortality. Data from the 2023 ISN-GKHA, although with some limitations, may be used for advocacy and improving CKD care in the region.

Assessment of Dietary Acid Load in Children with Chronic Kidney Disease: An Observational Study.

Introduction: Dietary acid load (DAL), which reflects the balance between acid- and alkaline-forming foods, is a modifiable risk factor for metabolic acidosis in CKD. Owing to the paucity of data in the Indian context, we undertook this cross-sectional study to estimate DAL and assess acid and alkaline food consumption in children with CKD2-5D (Chronic kidney disease stage 2 to 5 and 5D-those on hemodialysis). Methods: Clinical profile, dietary assessment of energy, protein intake/deficits, and macronutrients were noted and computed using software created by the division of nutrition, St John's research institute based on Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines in clinically stable children with CKD2-5D. DAL was estimated using potential renal acid load (PRAL in mEq/day) = (0.49 × protein intake in g/day) + (0.037 × phosphorus-intake in mg/day) - (0.02 × potassium intake in mg/day) - (0.013 × calcium intake in mg/day) - (0.027 × magnesium intake in mg/day). A positive dietary PRAL (>0) favors acidic content and negative (<0) favors alkaline content. PRAL was stratified into quartiles for analysis. The association of various clinical and dietary parameters were analysed across these quartiles. Results: Eighty-one children [of mean age 122 ± 47 months; 56 (69%) boys, 29 (36%) on dialysis, 62 (77%) non-vegetarians] were studied. Twenty-eight (34%) were on bicarbonate supplements. A positive PRAL (9.97 ± 7.7 mEq/day) was observed in 74/81 (91%) children with comparable proportions in those with CKD2-5 and 5D [47/52 (90%) vs. 27/29 (93%) respectively, P > 0.05]. Protein intake was significantly higher in the highest quartile compared to the lowest quartile of PRAL in CKD2-5 (55 ± 16 g/day vs. 40 ± 14 g/day, P < 0.001) and 5D groups (47 ± 15 g/day vs. 25 ± 11 g/day, P = 0.002). A majority of the participants 60/81 (74%) consumed highly acidic and minimal alkali foods. Conclusion: In children with CKD2-5D, PRAL estimation revealed high DAL in the majority with a high consumption of acidic foods. These findings provide implications for appropriate dietary counseling in children with CKD.

Pediatric AKI in the real world: changing outcomes through education and advocacy-a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference.

BACKGROUND: Acute kidney injury (AKI) is independently associated with increased morbidity and mortality across the life course, yet care for AKI remains mostly supportive. Raising awareness of this life-threatening clinical syndrome through education and advocacy efforts is the key to improving patient outcomes. Here, we describe the unique roles education and advocacy play in the care of children with AKI, discuss the importance of customizing educational outreach efforts to individual groups and contexts, and highlight the opportunities created through innovations and partnerships to optimize lifelong health outcomes. METHODS: During the 26th Acute Disease Quality Initiative (ADQI) consensus conference, a multidisciplinary group of experts discussed the evidence and used a modified Delphi process to achieve consensus on recommendations on AKI research, education, practice, and advocacy in children. RESULTS: The consensus statements developed in response to three critical questions about the role of education and advocacy in pediatric AKI care are presented here along with a summary of available evidence and recommendations for both clinical care and research. CONCLUSIONS: These consensus statements emphasize that high-quality care for patients with AKI begins in the community with education and awareness campaigns to identify those at risk for AKI. Education is the key across all healthcare and non-healthcare settings to enhance early diagnosis and develop mitigation strategies, thereby improving outcomes for children with AKI. Strong advocacy efforts are essential for implementing these programs and building critical collaborations across all stakeholders and settings.

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.

Epidemiology of acute kidney injury in children: a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference.

The nephrology and critical care communities have seen an increase in studies exploring acute kidney injury (AKI) epidemiology in children. As a result, we now know that AKI is highly prevalent in critically ill neonates, children, and young adults. Furthermore, children who develop AKI experience greater morbidity and higher mortality. Yet knowledge gaps still exist that suggest a more comprehensive understanding of AKI will form the foundation for future efforts designed to improve outcomes. In particular, the areas of community acquired AKI, AKI in non-critically ill children, and cohorts from low-middle income countries have not been well studied. Longer-term functional outcomes and patient-centric metrics including social determinants of health, quality of life, and healthcare utilization should be the foci of the next phase of scholarship. Current definitions identify AKI-based upon evidence of dysfunction which serves as a proxy for injury; biomarkers capable of identifying injury as it occurs are likely to more accurately define populations with AKI. Despite the strength of the association, the causal and mechanistic relationships between AKI and poorer outcomes remain inadequately examined. A more robust understanding of the relationship represents a potential to identify therapeutic targets. Once established, a more comprehensive understanding of AKI epidemiology in children will allow investigation of preventive, therapeutic, and quality improvement interventions more effectively.

Clinical characteristics, genetic profile and short-term outcomes of children with primary hyperoxaluria type 2: a nationwide experience.

BACKGROUND: Three types of primary hyperoxaluria (PH) are recognized. However, data on PH type 2 (PH2), caused by defects in the GRHPR gene, are limited. METHODS: We reviewed the medical records of patients < 18 years of age with genetically-proven PH2 from seven centres across India to identify the age of onset, patterns of clinical presentation, short-term outcomes and genetic profile, and to determine if genotype-phenotype correlation exists. RESULTS: We report 20 patients (all with nephrolithiasis or nephrocalcinosis) diagnosed to have PH2 at a median (IQR) age of 21.5 (7, 60) months. Consanguinity and family history of kidney stones were elicited in nine (45%) and eight (40%) patients, respectively. The median (IQR) serum creatinine at PH2 diagnosis was 0.45 (0.29, 0.56) mg/dL with the corresponding estimated glomerular filtration rate being 83 (60, 96) mL/1.73 m2/min. A mutational hotspot (c.494 G > A), rare in Caucasians, was identified in 12 (60%) patients. An intronic splice site variant (c.735-1G > A) was noted in five (25%) patients. Four (20%) patients required surgical intervention for stone removal. Major adverse kidney events (mortality or chronic kidney disease (CKD) stages 3-5) were noted in six (30%) patients at a median (IQR) follow-up of 12 (6, 27) months. Risk factors for CKD progression and genotype-phenotype correlation could not be established. CONCLUSIONS: PH2 should no longer be considered an innocuous disease, but rather a potentially aggressive disease with early age of presentation, and possible rapid progression to CKD stages 3-5 in childhood in some patients. A mutational hotspot (c.494 G > A variant) was identified in 60% of cases, but needs further exploration to decipher the genotype-phenotype correlation.

Nutrition Management for Chronic Kidney Disease: Differences and Special Needs for Children and Adults.

Common goals of nutritional therapy across the spectrum of pediatric and adult chronic kidney disease (CKD) include maintaining normal body mass and composition and reducing associated morbidity and mortality. Adult nephrologists caring for children and adolescents may be challenged by the existing complexities in identifying and interpreting the nutritional status and growth in children. Pediatric nephrologists may face situations that call for a sound knowledge of assessing nutritional status and providing nutrition therapy for adolescents and young adults. One important additional nutrition goal in children is to achieve normal growth and development. Children are growing and therefore need more calories and nutrients than just maintaining their body weight and composition. Lack of weight and height gain actually is considered failure to thrive in children. Some fundamental differences in approaches to nutritional therapy in CKD are necessitated based on the etiology of CKD. A large proportion of adults with CKD are diabetics, so the approach would be a low-carbohydrate diet. Children with CKD, especially young ones, often are anorexic, so calorie supplements that could include quite a lot of carbohydrates often are prescribed. More adults with CKD have hypertension and atherosclerotic comorbidities, which result in recommendations for low-salt and low-fat diets. Children with CKD often have salt and electrolyte wasting disease states and would require normal- or even high-salt diets, and fats often are included in supplements to bolster calorie intake. Low-protein diets often are recommended in adults with predialysis CKD to slow disease progression. Children are growing and have a higher protein daily requirement. Low-protein diets have not been found to be efficacious in children with CKD, in achieving normal growth, or in slowing disease progression. Adult nephrologists caring for children and adolescents may be challenged by the existing complexities in identifying and interpreting nutritional status and growth in children. Pediatric nephrologists may face situations that call for a sound knowledge of assessing nutritional status and providing nutrition therapy for adolescents and young adults. This article discusses the differences in the assessment of nutritional status between children and adults, as well as provides a comprehensive approach to nutritional management for CKD across the age spectrum. Semin Nephrol 43:x-xx © 2023 Elsevier Inc. All rights reserved.

Nutrition-Focused Physical Examination for Detecting Protein Energy Wasting in Children with Chronic Kidney Disease.

Introduction: There is a need to explore less laborious point-of-care assessment tools to diagnose protein energy wasting (PEW) in children with chronic kidney disease (CKD). This cross-sectional study was undertaken to assess the profile of specific nutrition-focused physical examination (NFPE) and mid-arm muscle area (MAMA) in children with CKD and determine their role in the diagnosis of PEW. Methods: PEW criterion was applied to all eligible children and MAMA was derived from mid-arm circumference and triceps skin fold thickness. NFPE signs examined were muscle wasting (MW) and subcutaneous fat loss (FL). Results: One hundred and twenty-six children with CKD (86 in CKD stages 2-4 and 40 on dialysis) were studied. PEW was prevalent in 41.8% children with CKD2-4 and in 72.5% on dialysis. In children with CKD 2-4, low MAMA, MW, and FL were significantly associated with PEW with an odd's ratio of 5.3 (1.55,18.30), 10.6 (3.8,29.8), and 10.5 (3.7,29.2) respectively (P = <0.001). Similarly, in children on dialysis, low MAMA, MW, and FL were more likely to be associated with PEW with an odd's ratio of 17 (2.2,127.7); P = 0.017, 16.6 (3,90.8); P = 0.001 and 19 (2.1,170.3); and P = 0.009, respectively. MW demonstrated high sensitivity and specificity [80.6 and 72%, respectively, with a positive predictive value (PPV) of 67.4%] to diagnose PEW in the CKD 2-4 group and in those on dialysis [86.2 and 72.1%, respectively, with PPV of 89.3%]. Conclusion: Clinical signs based on NFPE are useful in detecting PEW in children with CKD2-4 and in those on dialysis.

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.

Nutrition in Children With Chronic Kidney Disease: How to Thrive?

The nutritional status and management of children with chronic kidney disease (CKD) are complex and require a combined pediatric nephrology team work approach with physicians, nutritionists, nurses, and physical/occupational therapists. Prospective observational studies such as Children with CKD in the US, the 4C study in Europe and the International Pediatric Peritoneal Dialysis Network have advanced the field. However, most recommendations and guidelines from international task forces such as Kidney Diseases Improving Global Outcomes and Pediatric Renal Nutrition Taskforce are opinion-based rather than evidence-based. There is exciting ongoing research to improve nutrition in children with CKD to help them thrive.

Assessment of Dietary Phosphorus Intake and Implementation of Parental Phosphate Education in Pediatric Chronic Kidney Disease.

Introduction: Management of dietary phosphorus intake is a challenge in children with chronic kidney disease and is governed by regional food sources and culinary practices. The aim of this study was to evaluate dietary intake of phosphorus in these children and assess the utility of parental phosphate education for control of hyperphosphatemia. Methods: This prospective study included children aged 2-18 years with CKD stages 2-5D. Phosphorus intake was assessed by 24-hour dietary recall, analyzed using food processor software, and interpreted based on dietary reference intake (DRI) and suggested dietary intake (SDI). Parents of those with hyperphosphatemia were subjected to a structured phosphate education, and serum phosphate was monitored every 2 months for 6 months. Results: Seventy children were recruited (mean age 9.4 ± 3.4 years, CKD5/5D: 51% (n = 36)) with median duration of CKD being 3.8 (IQR2,6) years. In the overall cohort, 50% (35/70) had phosphorus intake exceeding DRI with no significant difference between groups [CKD 5/5D,52.7% (n = 19) vs CKD2-4 47% (n = 16), P = 0.63]. Mean daily phosphorus intake was comparable between children with and without hyperphosphatemia [908 ± 279 mg vs 814 ± 302 mg, P = 0.1]. Based on DRI, 44% of children with normal serum phosphate and 58% with hyperphosphatemia had increased dietary intake of phosphorus (P = 0.15). Based on SDI, 26% with normal serum phosphate and 94% with hyperphosphatemia had increased dietary phosphorus intake (P < 0.001). Hyperphosphatemia was observed in 51% (CKD 2-4); 33% CKD5-5D 66%, P = 0.6). Among 29 children completing 6 months of follow up, there was a significant reduction in mean serum phosphate levels (P = 0.001) which was independent of age, stage of CKD or intake of phosphate binders. At end of the study, hyperphosphatemia persisted in 34%. Conclusion: Compared to DRI, dietary assessment of phosphorus intake based on SDI was significantly associated with hyperphosphatemia in children with CKD 2-5D. In the majority, repeated parental structured phosphate education over 6 months was useful in managing hyperphosphatemia.

Early recognition and prevention of acute kidney injury in hospitalised children.

Acute kidney injury is common in hospitalised children and is associated with poor patient outcomes. Once acute kidney injury occurs, effective therapies to improve patient outcomes or kidney recovery are scarce. Early identification of children at risk of acute kidney injury or at an early injury stage is essential to prevent progression and mitigate complications. Paediatric acute kidney injury is under-recognised by clinicians, which is a barrier to optimisation of inpatient care and follow-up. Acute kidney injury definitions rely on functional biomarkers (ie, serum creatinine and urine output) that are inadequate, since they do not account for biological variability, analytical issues, or physiological responses to volume depletion. Improved predictive tools and diagnostic biomarkers of kidney injury are needed for earlier detection. Novel strategies, including biomarker-guided care algorithms, machine-learning methods, and electronic alerts tied to clinical decision support tools, could improve paediatric acute kidney injury care. Clinical prediction models should be studied in different paediatric populations and acute kidney injury phenotypes. Research is needed to develop and test prevention strategies for acute kidney injury in hospitalised children, including care bundles and therapeutics.

Changes in bone biomarkers in response to different dosing regimens of cholecalciferol supplementation in children with chronic kidney disease.

BACKGROUND: The effect of different dosing regimens of cholecalciferol supplementation on bone biomarkers has not been studied in children with chronic kidney disease (CKD). METHODS: This is a post hoc analysis of a multi-center randomized controlled trial which included children with CKD stages 2-4 with vitamin D deficiency (25-hydroxy vitamin D (25OHD) < 30 ng/ml) randomized 1:1:1 to receive an equivalent dose of oral cholecalciferol as daily, weekly or monthly treatment. Markers of bone formation (bone alkaline phosphatase (BAP), procollagen I N terminal peptide (PINP)), bone resorption (tartarate-resistant acid phosphatase 5b (TRAP), C terminal telopeptide (CTX)), and osteocyte markers (intact fibroblast growth factor 23 (iFGF23), sclerostin) and soluble klotho were measured at baseline and after 3 months of intensive replacement therapy. The change in biomarkers and ratio of markers of bone formation to resorption were compared between treatment arms. BAP and TRAP were expressed as age- and sex-specific z-scores. RESULTS: 25OHD levels increased with cholecalciferol supplementation, with 85% achieving normal levels. There was a significant increase in the BAP/TRAP ratio (p = 0.04), iFGF23 (p = 0.004), and klotho (p = 0.002) with cholecalciferol therapy, but this was comparable across all three therapy arms. The BAPz was significantly higher in the weekly arm (p = 0.01). The change in 25OHD (Δ25OHD) inversely correlated with ΔPTH (r = - 0.4, p < 0.001). CONCLUSIONS: Although cholecalciferol supplementation was associated with a significant increase in bone formation, the three dosing regimens of cholecalciferol supplementation have a comparable effect on the bone biomarker profile, suggesting that they can be used interchangeably to suit the patient's needs and optimize adherence to therapy. A higher resolution version of the Graphical abstract is available as Supplementary information.

Infection-Related Glomerulonephritis in Children and Adults.

Infection-related glomerulonephritis is an immunologically mediated glomerular injury after an infection. Glomerulonephritis may occur with the infection or after a variable latent period. Poststreptococcal glomerulonephritis (PSGN) is the prototype of infection-related glomerulonephritis. The streptococcal antigens, nephritis-associated plasmin-like receptor and streptococcal exotoxin B, have emerged as major players in the pathogenesis of PSGN. Although PSGN is the most common infection-related glomerulonephritis in children, in adults, glomerulonephritis is secondary to bacteria such as staphylococci, viruses such as hepatitis C, and human immunodeficiency virus, and, rarely, parasitic infections. Supportive therapy is the mainstay of treatment in most infection-related glomerulonephritis. Treatment of the underlying infection with specific antibiotics and antiviral medications is indicated in some infections. Parasitic infections, although rare, may be associated with significant morbidity. Poststreptococcal glomerulonephritis is a self-limiting condition with a good prognosis. However, bacterial, viral, and parasitic infections may be associated with significant morbidity and long-term consequences. Epidemiologic studies are required to assess the global burden of infection-related glomerulonephritis. A better understanding of the pathogenesis of infection-related glomerulonephritis may unravel more treatment options and preventive strategies.

Effects of Prematurity and Growth Restriction on Adult Blood Pressure and Kidney Volume.

Gaining insight into the complex cycle of renal programming and its early-life clinical associations is essential to understand the origins of kidney disease. Prematurity and intrauterine growth restriction are associated with low nephron endowment. This increases the risk of developing hypertension and chronic kidney disease later in life. There is appreciable evidence to support mechanistic links between low nephron endowment secondary to intrauterine events and kidney size, kidney function, and blood pressure in postnatal life. A clear understanding of the cycle of developmental programming and consequences of fetal insults on the kidney is critical. In addition, the impact of events in the early postnatal period (accelerated postnatal growth, development of obesity, exposure to nephrotoxins) on the cardiovascular system and blood pressure of individuals born prematurely or with low birth weight is discussed. In summary, this review draws attention to the concepts of renal programming and nephron endowment and underscores the associations between intrauterine growth restriction, prematurity, and its clinical consequences in adult life.

Consensus-Based Recommendations on Priority Activities to Address Acute Kidney Injury in Children: A Modified Delphi Consensus Statement.

Importance: Increasing evidence indicates that acute kidney injury (AKI) occurs frequently in children and young adults and is associated with poor short-term and long-term outcomes. Guidance is required to focus efforts related to expansion of pediatric AKI knowledge. Objective: To develop expert-driven pediatric specific recommendations on needed AKI research, education, practice, and advocacy. Evidence Review: At the 26th Acute Disease Quality Initiative meeting conducted in November 2021 by 47 multiprofessional international experts in general pediatrics, nephrology, and critical care, the panel focused on 6 areas: (1) epidemiology; (2) diagnostics; (3) fluid overload; (4) kidney support therapies; (5) biology, pharmacology, and nutrition; and (6) education and advocacy. An objective scientific review and distillation of literature through September 2021 was performed of (1) epidemiology, (2) risk assessment and diagnosis, (3) fluid assessment, (4) kidney support and extracorporeal therapies, (5) pathobiology, nutrition, and pharmacology, and (6) education and advocacy. Using an established modified Delphi process based on existing data, workgroups derived consensus statements with recommendations. Findings: The meeting developed 12 consensus statements and 29 research recommendations. Principal suggestions were to address gaps of knowledge by including data from varying socioeconomic groups, broadening definition of AKI phenotypes, adjudicating fluid balance by disease severity, integrating biopathology of child growth and development, and partnering with families and communities in AKI advocacy. Conclusions and Relevance: Existing evidence across observational study supports further efforts to increase knowledge related to AKI in childhood. Significant gaps of knowledge may be addressed by focused efforts.