O. N. Ray Bignall II, Matthew W. Harer, Keia R. Sanderson & Michelle C. Starr
doi : 10.1007/s00467-021-05062-3
Pediatric Nephrology volume 36, pages2587–2591 (2021)
Ruth Belostotsky & Yaacov Frishberg
doi : 10.1007/s00467-020-04817-8
Pediatric Nephrology volume 36, pages2593–2606 (2021)
Loss-of-function mutations in three genes, involved in the metabolic pathway of glyoxylate, result in increased oxalate production and its crystallization in the form of calcium oxalate. This leads to three forms of primary hyperoxaluria—an early-onset inherited kidney disease with wide phenotypic variability ranging from isolated kidney stone events to stage 5 chronic kidney disease in infancy. This review provides a description of metabolic processes resulting in oxalate overproduction and summarizes basic therapeutic approaches. Unfortunately, current treatment of primary hyperoxaluria does not allow the prevention of loss of kidney function or to substantially diminish other symptoms in most patients. However, latest breakthroughs in biotechnology provide new promising directions for drug development. Some of them have already progressed to the level of clinical trials; others are just at the stage of proof of concept. Here we review the most advanced technologies including those that have been harnessed as possible therapeutic modalities.
Sanja Sever
doi : 10.1007/s00467-020-04812-z
Pediatric Nephrology volume 36, pages2607–2614 (2021)
The selectivity of the glomerular filter is established by physical, chemical, and signaling interplay among its three core constituents: glomerular endothelial cells, the glomerular basement membrane, and podocytes. Functional impairment or injury of any of these three components can lead to proteinuria. Podocytes are injured in many forms of human and experimental glomerular disease, including minimal change disease, focal segmental glomerulosclerosis, and diabetes mellitus. One of the earliest signs of podocyte injury is loss of their distinct structure, which is driven by dysregulated dynamics of the actin cytoskeleton. The status of the actin cytoskeleton in podocytes depends on a set of actin binding proteins, nucleators and inhibitors of actin polymerization, and regulatory GTPases. Mutations that alter protein function in each category have been implicated in glomerular diseases in humans and animal models. In addition, a growing body of studies suggest that pharmacological modifications of the actin cytoskeleton have the potential to become novel therapeutics for podocyte-dependent chronic kidney diseases. This review presents an overview of the essential proteins that establish actin cytoskeleton in podocytes and studies demonstrating the feasibility of drugging actin cytoskeleton in kidney diseases.
Licia Peruzzi & Rosanna Coppo
doi : 10.1007/s00467-020-04818-7
Pediatric Nephrology volume 36, pages2615–2625 (2021)
The clinical features of the kidney involvement in immunoglobulin A (IgA) vasculitis (IgAVN) differ in children and adults for both clinical presentation and progression. IgAVN in children has mostly a self-limiting course and favorable resolution, while in adults the kidney involvement is frequently severe with unfavorable outcome. However, a subset of children is at risk of progression within the pediatric age or decades later in adulthood, particularly when the diagnosis and a prompt intervention are delayed. Factors predicting progression and outcome in the whole spectrum of age have been investigated in recent research, as well as the relationship between IgAVN and primary IgAN, which share the same pathology features, in the light of peculiar clinical differences and progression tendencies, and hence need for selective treatments. The search for a personalized treatment in children with IgAV and in different ages of life should rely on the identification of different risks for progression. This review will focus on recent studies which contribute to improve our knowledge in this still largely unclear area.
Rupesh Raina, Ronith Chakraborty, Isabelle Mawby, Nirav Agarwal, Sidharth Sethi & Michael Forbes
doi : 10.1007/s00467-021-05084-x
Pediatric Nephrology volume 36, pages2627–2638 (2021)
COVID-19 is responsible for the 2019 novel coronavirus disease pandemic. Despite the vast research about the adult population, there has been little data collected on acute kidney injury (AKI) epidemiology, associated risk factors, treatments, and mortality in pediatric COVID-19 patients admitted to the ICU. AKI is a severe complication of COVID-19 among children and adolescents.
Eric G. Benz & Erum A. Hartung
doi : 10.1007/s00467-020-04869-w
Pediatric Nephrology volume 36, pages2639–2658 (2021)
Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are characterized by bilateral cystic kidney disease leading to progressive kidney function decline. These diseases also have distinct liver manifestations. The range of clinical presentation and severity of both ADPKD and ARPKD is much wider than was once recognized. Pediatric and adult nephrologists are likely to care for individuals with both diseases in their lifetimes. This article will review genetic, clinical, and imaging predictors of kidney and liver disease progression in ADPKD and ARPKD and will briefly summarize pharmacologic therapies to prevent progression.
Gabriel Cara-Fuentes & William E. Smoyer
doi : 10.1007/s00467-020-04867-y
Pediatric Nephrology volume 36, pages2659–2673 (2021)
Glomerular diseases are often chronic or recurring and thus associated with a tremendous physical, psychological, and economic burden. Their etiologies are often unknown, and their pathogeneses are frequently poorly understood. The diagnoses and management of these diseases are therefore based on clinical features, traditional laboratory markers, and, often, kidney pathology. However, the clinical presentation can be highly variable, the kidney pathology may not establish a definitive diagnosis, and the therapeutic responses and resulting clinical outcomes are often unpredictable. To try to address these challenges, significant research efforts have been made over the last decade to identify potential biomarkers that can help clinicians optimize the diagnosis and prognosis at clinical presentation, as well as help predict long-term outcomes. Unfortunately, these efforts have to date only identified a single biomarker for glomerular disease that has been fully validated and developed for widespread clinical use (anti-PLA2R antibodies to diagnose membranous nephropathy). In this manuscript, we review the definitions and development of biomarkers, as well as the current knowledge on both historical and novel candidate biomarkers of glomerular disease, with an emphasis on those associated with idiopathic nephrotic syndrome.
Natalie L. Wu & Sangeeta Hingorani
doi : 10.1007/s00467-020-04842-7
Pediatric Nephrology volume 36, pages2675–2686 (2021)
Pediatric oncology and hematopoietic cell transplant (HCT) patients are susceptible to both acute kidney injury (AKI) and chronic kidney disease (CKD). The etiologies of AKI vary but include tumor infiltration, radiation, drug-induced toxicity, and fluid and electrolyte abnormalities including tumor lysis syndrome. HCT patients can also have additional complications such as sinusoidal obstructive syndrome, graft-versus-host disease, or thrombotic microangiopathy. For patients with severe AKI requiring dialysis, multiple modalities can be used successfully, although continuous kidney replacement therapy (CKRT) is often the principal modality for critically ill patients. While increasing numbers of pediatric cancer and HCT patients are now surviving long term, they remain at risk for a number of chronic medical conditions, including CKD. Certain high-risk patients, due to underlying risk factors or treatment-related complications, eventually develop kidney failure and may require kidney replacement therapies. Management of co-morbidities and complications associated with kidney failure, including use of erythropoietin for anemia and potential need for ongoing cancer-related treatment while on dialysis, is an additional consideration in this patient population. Kidney transplantation can be successfully performed in pediatric cancer survivors, although additional features such as specific cancer diagnosis and duration of remission should be considered.
Jean-Pierre Guignard & Silvia Iacobelli
doi : 10.1007/s00467-021-04921-3
Pediatric Nephrology volume 36, pages2687–2695 (2021)
The use of diuretics is extremely frequent in sick neonates, the more so in very premature newborn infants. The use of diuretics in patients whose kidney function is immature necessitates a thorough knowledge of renal developmental physiology and pathophysiology. This review presents the basic aspects of body fluid homeostasis in the neonate, discusses the development of kidney function, and describes the mechanisms involved in electrolyte and water reabsorption along the nephron. Diuretics are then classified according to the site of their action on sodium reabsorption. The use of diuretics in sodium-retaining states, in oliguric states, in electrolyte disorders, and in arterial hypertension, as well as in a few specific disorders, is presented. Common and specific adverse effects are discussed. Recommended dosages for the main diuretics used in the neonatal period are given. New developments in diuretic therapy are briefly mentioned.
Jessica L. Stahl, Russell S. Whelan & Jordan M. Symons
doi : 10.1007/s00467-021-05026-7
Pediatric Nephrology volume 36, pages2697–2702 (2021)
Current guidelines for initiation of kidney replacement do not include specific recommendations for prescription parameters and monitoring.
Adem Yasin Köksoy
doi : 10.1007/s00467-021-04993-1
Pediatric Nephrology volume 36, page2703 (2021)
Adem Yasin Köksoy
doi : 10.1007/s00467-021-05033-8
Pediatric Nephrology volume 36, pages2705–2707 (2021)
Eimear Kirby, Shiraz Elbashier, Clodagh Sweeney, Eilish Twomey, Kathleen Gorman, Michael Riordan & Atif Awan
doi : 10.1007/s00467-021-05032-9
Pediatric Nephrology volume 36, pages2709–2710 (2021)
Eimear Kirby, Shiraz Elbashier, Clodagh Sweeney, Eilish Twomey, Kathleen Gorman, Michael Riordan & Atif Awan
doi : 10.1007/s00467-021-05005-y
Pediatric Nephrology volume 36, pages2711–2714 (2021)
Luisa Cortellazzo Wiel, Giulia Gortani, Davide Zanon, Matteo Bramuzzo, Marco Pennesi & Egidio Barbi
doi : 10.1007/s00467-021-05028-5
Pediatric Nephrology volume 36, pages2715–2716 (2021)
Luisa Cortellazzo Wiel, Giulia Gortani, Davide Zanon, Matteo Bramuzzo, Marco Pennesi & Egidio Barbi
doi : 10.1007/s00467-021-05035-6
Pediatric Nephrology volume 36, pages2717–2718 (2021)
Yanqin Zhang, Jan Böckhaus, Fang Wang, Suxia Wang, Diana Rubel, Oliver Gross & Jie Ding
doi : 10.1007/s00467-021-05040-9
Pediatric Nephrology volume 36, pages2719–2730 (2021)
Autosomal recessive Alport syndrome (ARAS) is caused by pathogenic variants in both alleles of either COL4A3 or COL4A4 genes. Reports on ARAS are rare due to small patient numbers and there are no reports on renin-angiotensin-aldosterone system (RAAS) inhibition therapy in ARAS.
Daan H. H. M. Viering, Anneke P. Bech, Jeroen H. F. de Baaij, Eric J. Steenbergen, A. H. Jan Danser, Jack F. M. Wetzels, René J. M. Bindels & Jaap Deinum
doi : 10.1007/s00467-021-05018-7
Pediatric Nephrology volume 36, pages2731–2737 (2021)
Genetic loss of function of AGT (angiotensinogen), REN (renin), ACE (angiotensin-converting enzyme), or AGTR1 (type-1 angiotensin II receptor) leads to renal tubular dysgenesis (RTD). This syndrome is almost invariably lethal. Most surviving patients reach stage 5 chronic kidney disease at a young age.
Carlos J. Cobeñas, Laura L. Lombardi, Priscila Pereyra, Emanuel De Rose, María José Gogorza, Ana Paula Spizzirri, Javier D. Ruscasso, Soledad Luján Ferradas, Ángela del Carmen Suárez, Oscar R. Amoreo, Javier H. Zalba & Paula Risso
doi : 10.1007/s00467-021-05017-8
Pediatric Nephrology volume 36, pages2739–2746 (2021)
We aimed to determine the prevalence of hypoalbuminemia in STEC-HUS patients with hemorrhagic colitis (HC) and whether serum albumin level (SAL), leukocyte count, hematocrit and serum sodium level (SSL) are prognostic markers of HC, central nervous system disease (CNSd) and/or dialysis requirement and evaluate if hypoalbuminemia is associated with fecal protein losses.
Jarcy Zee, Michelle T. McNulty, Jeffrey B. Hodgin, Olga Zhdanova, Sangeeta Hingorani, Jonathan Ashley Jefferson, Keisha L. Gibson, Howard Trachtman, Alessia Fornoni, Katherine M. Dell, Heather N. Reich, Serena Bagnasco, Larry A. Greenbaum, Richard A. Lafayette, Debbie S. Gipson, Elizabeth Brown, Matthias Kretzler, Gerald Appel, Kamalanathan K. Sambandam, Katherine R. Tuttle, Dhruti Chen, Meredith A. Atkinson, Marie C. Hogan, Frederick J. Kaskel, Kevin E. Meyers, John O’Toole, Tarak Srivastava, Christine B. Sethna, Michelle A. Hladunewich, JJ Lin, Cynthia C. Nast, Vimal K. Derebail, Jiten Patel, Suzanne Vento, Lawrence B. Holzman, Ambarish M. Athavale, Sharon G. Adler, Kevin V. Lemley, John C. Lieske, Jonathan J. Hogan, Crystal A. Gadegbeku, Fernando C. Fervenza, Chia-Shi Wang, Raed Bou Matar, Pamela Singer, Jeffrey B. Kopp, Laura Barisoni & Matthew G. Sampson
doi : 10.1007/s00467-021-04990-4
Pediatric Nephrology volume 36, pages2747–2757 (2021)
The G1 and G2 alleles of apolipoprotein L1 (APOL1) are common in the Black population and associated with increased risk of focal segmental glomerulosclerosis (FSGS). The molecular mechanisms linking APOL1 risk variants with FSGS are not clearly understood, and APOL1’s natural absence in laboratory animals makes studying its pathobiology challenging.
Jasjeet Sandhu, Deepak Bhat, Gurdeep Singh Dhooria, Puneet A. Pooni, Siddharth Bhargava, Shruti Kakkar & Karambir S. Gill
doi : 10.1007/s00467-021-05052-5
Pediatric Nephrology volume 36, pages2759–2767 (2021)
Oral cyclophosphamide (CYP) is an important therapeutic agent in treatment of steroid-sensitive nephrotic syndrome having a steroid-dependent (SD) or frequent relapsing (FR) course. This retrospective observational study aimed to determine response to oral CYP and factors associated with positive response in these patients.
Gysella Muniz, Erica Kar, Serter Gumus, Hui Liu & Nader Shaikh
doi : 10.1007/s00467-021-04973-5
Pediatric Nephrology volume 36, pages2769–2775 (2021)
To compare clinical history and measurements of fecal load on abdominal radiography (AR) in the prediction of urinary tract infection (UTI) recurrence in children.
Anders Breinbjerg, Cecilie Siggaard Jørgensen, Jørgen Frøkiær, Kjell Tullus, Konstantinos Kamperis & Søren Rittig
doi : 10.1007/s00467-021-05042-7
Pediatric Nephrology volume 36, pages2777–2787 (2021)
Acute pyelonephritis (AP) is a common bacterial infection in childhood. Follow-up guidelines on these children are controversial. This study aimed to identify risk factors for kidney scarring and vesicoureteral reflux (VUR). Furthermore, international follow-up guidelines were used for simulation to evaluate sensitivity and specificity.
Marwa M. Elgendy, Hasan F. Othman, Mira Younis, Subhash Puthuraya, Raed Bou Matar & Hany Aly
doi : 10.1007/s00467-021-04998-w
Pediatric Nephrology volume 36, pages2789–2795 (2021)
To assess prevalence and outcomes of acute kidney injury (AKI) in very-low-birth-weight infants.
Yincent Tse, Anne-Sophie E. Darlington, Kay Tyerman, Dean Wallace, Tanya Pankhurst, Sofia Chantziara, David Culliford, Alejandra Recio-Saucedo & Arvind Nagra
doi : 10.1007/s00467-021-05041-8
Pediatric Nephrology volume 36, pages2797–2810 (2021)
During the initial COVID-19 pandemic, young United Kingdom (UK) kidney patients underwent lockdown and those with increased vulnerabilities socially isolated or ‘shielded’ at home. The experiences, information needs, decision-making and support needs of children and young adult (CYA) patients or their parents during this period is not well known.
Laura F. Alconcher, Alejandro Balestracci, Paula A. Coccia, Angela del C. Suarez, Flavia B. Ramírez, Marta L. Monteverde, María Graciela Perez y Gutiérrez, Paula M. Carlopio, Illiana Principi, Patricia Estrella, Susana Micelli, Daniela C. Leroy, Nahir E. Quijada, Claudia Seminara, Marta I. Giordano, Susana B. Hidalgo Solís, Mariana Saurit, Alejandra Caminitti, Andrea Arias, Miguel Liern & Marta Rivas
doi : 10.1007/s00467-021-04988-y
Pediatric Nephrology volume 36, pages2811–2817 (2021)
Shiga toxin-producing Escherichia coli (STEC) infection is the most common cause of hemolytic uremic syndrome (HUS). Only few studies correlated serotypes and stx genotypes with disease severity. This study aimed to update STEC serotypes, stx genotypes, and virulence factors (eae and ehxA) in a cohort of patients with STEC-HUS and investigate whether they influence the severity of disease.
Nonnie Polderman, Meredith Cushing, Kirsten McFadyen, Marisa Catapang, Robert Humphreys, Cherry Mammen & Douglas G. Matsell on behalf of the Pediatric Nephrology Clinical Pathway Development Team
doi : 10.1007/s00467-021-05055-2
Pediatric Nephrology volume 36, pages2819–2826 (2021)
Our multidisciplinary clinical pathway for treatment of childhood nephrotic syndrome (NS) was established with the goal of standardizing local clinical practice. This descriptive study aimed to assess nutrient intakes of children with newly diagnosed NS compared with nutrition goals defined by our pathway.
Isabel de Pádua Paz, Tulio Konstantyner, Ricardo de Castro Cintra Sesso, Cristine Campos de Xavier Pinto, Maria Fernanda Carvalho de Camargo & Paulo Cesar Koch Nogueira
doi : 10.1007/s00467-021-05009-8
Pediatric Nephrology volume 36, pages2827–2835 (2021)
This study aimed to identify main factors associated with child and adolescent access to chronic kidney disease (CKD) treatment in Brazil.
Hadas Alfandary, Orly Haskin, Ori Goldberg, Amit Dagan, Yael Borovitz, Shelly Levi, Miriam Davidovits, Tomer Erlich, Daniel Landau & Oren Pleniceanu
doi : 10.1007/s00467-021-04980-6
Pediatric Nephrology volume 36, pages2837–2845 (2021)
We investigated the risk of kidney injury among adolescents with and without a congenital single functioning kidney (SFK).
Tülin Güngör, Fatma Yaz?l?ta?, Evrim Karg?n Çak?c?, Ay?e Seçil Ek?io?lu, Evra Çelikkaya, Deniz Karakaya, Esra Ba?lan & Mehmet Bülbül
doi : 10.1007/s00467-021-05027-6
Pediatric Nephrology volume 36, pages2847–2855 (2021)
Children born with unilateral renal agenesis (URA) are thought to have a risk of developing hypertension, proteinuria, and progressive chronic kidney disease (CKD). The present study aimed to evaluate the long-term prognosis and clinical characteristics of children with URA.
Eujin Park, Hye Jin Lee, Hyun Jin Choi, Yo Han Ahn, Kyoung Hee Han, Seong Heon Kim, Heeyeon Cho, Jae Il Shin, Joo Hoon Lee, Young Seo Park, Il-Soo Ha, Min Hyun Cho & Hee Gyung Kang
doi : 10.1007/s00467-021-05054-3
Pediatric Nephrology volume 36, pages2857–2864 (2021)
Preserving optimal growth has long been a significant concern for children with chronic kidney disease (CKD). We aimed to examine the incidence of and risk factors for short stature in Asian pediatric patients with CKD.
Sophia Nunes, Erin Hessey, Marc Dorais, Sylvie Perreault, Philippe Jouvet, Véronique Phan, Jacques Lacroix, Jean-Philippe Lafrance, Susan Samuel & Michael Zappitelli
doi : 10.1007/s00467-021-04999-9
Pediatric Nephrology volume 36, pages2865–2874 (2021)
Acute kidney Injury (AKI) in children undergoing cardiac surgery (CS) is strongly associated with hospital morbidity. Post-discharge CS AKI outcomes are less clear. We evaluated associations between AKI and post-discharge (a) healthcare utilization, (b) chronic kidney disease (CKD) or hypertension and (c) mortality.
Dominic Zanaboni, Jungwon Min, Roopa Seshadri, J. William Gaynor, Molly Dreher & Joshua J. Blinder
doi : 10.1007/s00467-021-04976-2
Pediatric Nephrology volume 36, pages2875–2881 (2021)
Ultrafiltration (UF) is used for fluid removal during and after infant cardiopulmonary bypass (CPB) surgery to reduce fluid overload. Excessive UF may have the opposite of its intended effect, resulting in acute kidney injury (AKI), oliganuria, and fluid retention.
Pierluigi Marzuillo, Vincenza Pezzella, Stefano Guarino, Anna Di Sessa, Maria Baldascino, Cesare Polito, Emanuele Miraglia del Giudice & Felice Nunziata
doi : 10.1007/s00467-021-05022-x
Pediatric Nephrology volume 36, pages2883–2890 (2021)
Acute kidney injury (AKI) enhances the risk of later chronic kidney disease. Significant prevalence of AKI is reported in adults with community acquired pneumonia (CAP). We investigated prevalence of and prognostic factors for AKI in children hospitalized for CAP.
Gianluigi Ardissino, Antenore Giussani, Valentina Capone, Sara Testa, Cristiano Gandini & Giovanni Montini on behalf of the ItalKid-HUS Network
doi : 10.1007/s00467-021-05127-3
Pediatric Nephrology volume 36, pages2891–2894 (2021)
Fenoldopam, a vasodilating agent, may represent a potential therapeutic opportunity to increase renal perfusion in those conditions where renal hemodynamics are severely impaired by vascular sub-occlusion, as, indeed, is the case in thrombotic microangiopathies.
Eric G. Benz & Erum A. Hartung
doi : 10.1007/s00467-021-04971-7
Pediatric Nephrology volume 36, pages2895–2897 (2021)
doi : 10.1007/s00467-021-05079-8
Pediatric Nephrology volume 36, pages2899–2960 (2021)
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