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Renin-angiotensin system in mammalian kidney development
Ihor V. Yosypiv
doi : 10.1007/s00467-020-04496-5
Pediatric Nephrology volume 36, pages479–489(2021)
Mutations in the genes of the renin-angiotensin system result in congenital anomalies of the kidney and urinary tract (CAKUT), the main cause of end-stage renal disease in children. The molecular mechanisms that cause CAKUT are unclear in most cases. To improve the care of children with CAKUT, it is critical to determine the underlying mechanisms of CAKUT. In this review, we discuss recent advances that have helped to better understand how disruption of the renin-angiotensin system during kidney development contributes to CAKUT.
Treatment of IgA nephropathy in children: a land without KDIGO guidance
Rosanna Coppo
doi : 10.1007/s00467-020-04486-7
Pediatric Nephrology volume 36, pages491–496(2021)
IgA nephropathy (IgAN) in children is no longer considered a rare and benign disease but a nephritis with different presentations and various outcomes. The decision to initiate a treatment and the therapeutic choice depend on the individual risk of progression. The Kidney Disease: Improving Global Outcomes (KDIGO) clinical guidelines in 2012 considered that the risk factors for progression of IgAN were similar in both children and adults and suggested in some conditions to follow the adult schedules. In 2017 a KDIGO Controversies Conference on management and treatment of glomerular diseases decided not to include an update in children with IgAN since the level of evidence of treatments in children was too scarce. Children can follow the indications for adults as far as the disease is similar in the various ages. This review is aimed at discussing why the KDIGO guidelines are poorly suitable to treat children with IgAN, and there is a need to develop new prediction models for progression of IgAN in children to guide selection of the cases to be treated. The identification of different risk levels in children with IgAN may personalize the choice of available drugs and support the use of new targeted therapies.
New therapeutic perspectives for IgA nephropathy in children
Alexandra Cambier, Patrick J. Gleeson, Héloise Flament, Marie-Bénédicte Le Stang & Renato C. Monteiro
doi : 10.1007/s00467-020-04475-w
Pediatric Nephrology volume 36, pages497–506(2021)
Childhood IgA nephropathy (cIgAN) differs from the adult by having an abrupt clinical onset, often presenting as an acute attack that can progress to a chronic phase. No treatment guidelines have been established for the treatment of cIgAN. Given the severity of acute attack in children, and the number of life-years at stake, pediatricians prescribe immunosuppression in addition to renin–angiotensin system blockade. Non-specific immunosuppressors, such as corticosteroids, have systemic toxic effects, and given recent therapeutic advances in adult glomerulonephritis, new tailored strategies should be expected for children. The mucosal immune system has been highlighted as a key player in IgAN pathogenesis, and several biomarkers have been identified with a direct role in pathogenesis. In this review, we discuss current studies of conventional and novel therapeutic approaches for cIgAN.
Sex effects in pyelonephritis
Clayton D. Albracht, Teri N. Hreha & David A. Hunstad
doi : 10.1007/s00467-020-04492-9
Pediatric Nephrology volume 36, pages507–515(2021)
Urinary tract infections (UTIs) are generally considered a disease of women. However, UTIs affect females throughout the lifespan, and certain male populations (including infants and elderly men) are also susceptible. Epidemiologically, pyelonephritis is more common in women but carries increased morbidity when it does occur in men. Among children, high-grade vesicoureteral reflux is a primary risk factor for upper-tract UTI in both sexes. However, among young infants with UTI, girls are outnumbered by boys; risk factors include posterior urethral valves and lack of circumcision. Recent advances in mouse models of UTI reveal sex differences in innate responses to UTI, which vary somewhat depending on the system used. Moreover, male mice and androgenized female mice suffer worse outcomes in experimental pyelonephritis; evidence suggests that androgen exposure may suppress innate control of infection in the urinary tract, but additional androgen effects, as well as non-hormonal sex effects, may yet be specified. Among other intriguing directions, recent experiments raise the hypothesis that the postnatal testosterone surge that occurs in male infants may represent an additional factor driving the higher incidence of UTI in males under 6 months of age. Ongoing work in contemporary models will further illuminate sex- and sex-hormone-specific effects on UTI pathogenesis and immune responses.
The old becomes new: advances in imaging techniques to assess nephron mass in children
Marissa J. DeFreitas, Chryso P. Katsoufis, Juan C. Infante, Michael L. Granda, Carolyn L. Abitbol & Alessia Fornoni
doi : 10.1007/s00467-020-04477-8
Pediatric Nephrology volume 36, pages517–525(2021)
Renal imaging is widely used in the assessment of surrogate markers of nephron mass correlated to renal function. Autopsy studies have tested the validity of various imaging modalities in accurately estimating “true” nephron mass. However, in vivo assessment of nephron mass has been largely limited to kidney volume determination by ultrasonography (US) in pediatric populations. Practical limitations and risks create challenges in incorporating more precise 3D volumetric imaging, like magnetic resonance imaging (MRI), and computed tomography (CT) technologies, compared to US for routine kidney volume assessment in children. Additionally, accounting for structural anomalies such as hydronephrosis when estimating renal parenchymal area in congenital anomalies of the kidney and urinary tract (CAKUT) is important, as it correlates with chronic kidney disease (CKD) progression. 3D imaging using CT and MRI has been shown to be superior to US, which has traditionally relied on 2D measurements to estimate kidney volume using the ellipsoid calculation. Recent innovations using 3D and contrast-enhanced US (CEUS) provide improved accuracy with low risk. Indexing kidney volume to body surface area in children is an important standard that may allow early detection of CKD progression in high-risk populations. This review highlights current understanding of various imaging modalities in assessing nephron mass, discusses applications and limitations, and describes recent advances in the field of imaging and kidney disease. Although renal imaging has been a long-standing, essential tool in assessing kidney disease, innovation and new applications of established technologies provide important tools in the study and management of kidney disease in children.
The CKiD study: overview and summary of findings related to kidney disease progression
Meredith A. Atkinson, Derek K. Ng, Bradley A. Warady, Susan L. Furth & Joseph T. Flynn
doi : 10.1007/s00467-019-04458-6
Pediatric Nephrology volume 36, pages527–538(2021)
The Chronic Kidney Disease in Children (CKiD) cohort study is a North American (USA and Canada) multicenter, prospective study of children with chronic kidney disease (CKD). The original aims of the study were (1) to identify novel risk factors for CKD progression; (2) to measure the impact of kidney function decline on growth, cognition, and behavior; and (3) to characterize the evolution of cardiovascular disease risk factors. CKiD has developed into a national and international resource for the investigation of a variety of factors related to CKD in children. This review highlights notable findings in the area of CKD progression and outlines ongoing opportunities to enhance understanding of CKD progression in children. CKiD’s contributions to the clinical care of children with CKD include updated and more accurate glomerular filtration rate estimating equations for children and young adults, and resources designed to help estimate the CKD progression timeline. In addition, results from CKiD have strengthened the evidence that treatment of hypertension and proteinuria should continue as a primary strategy for slowing the rate of disease progression in children.
Should ACE inhibitors or calcium channel blockers be used for post-transplant hypertension?
Tom?? Seeman & Janusz Feber
doi : 10.1007/s00467-020-04485-8
Pediatric Nephrology volume 36, pages539–549(2021)
Arterial hypertension in renal transplant recipients warrants antihypertensive treatment. The preferable choice of antihypertensives that should be used in patients after kidney transplantation remains a matter of debate; however, calcium channel blockers (CCB) and angiotensin-converting enzyme inhibitors (ACEI) are currently the most commonly used antihypertensives. This educational review summarizes the current evidence about the effects of these two classes of medications in transplant recipients. Several studies have demonstrated that both classes of drugs can reduce blood pressure (BP) to similar extents. Meta-analyses of adult randomized controlled trials have shown that graft survival is improved in patients treated with ACEIs and CCBs, and that CCBs increase, yet ACEIs decrease, graft function. Proteinuria is usually decreased by ACEIs but remains unchanged with CCBs. In children, no randomized controlled study has ever been performed to compare BP or graft survival between CCBs and ACEIs. Post-transplant proteinuria could be reduced in children along with BP by ACEIs. The results of the most current meta-analyses recommend that due to their positive effects on graft function and survival, along with their lack of negative effects on serum potassium, CCBs could be the preferred first-line antihypertensive agent in renal transplant recipients. However, antihypertensive therapy should be individually tailored based on other factors, such as time after transplantation, presence of proteinuria/albuminuria, or hyperkalemia. Furthermore, due to the difficulty in controlling hypertension, combination therapy containing both CCBs and ACEIs could be a reasonable first-step therapy in treating children with severe post-transplantation hypertension.
Recurrent urinary tract infection and nephrocalcinosis: Questions
Robin Miller & Cheryl Sanchez-Kazi
doi : 10.1007/s00467-020-04643-y
Pediatric Nephrology volume 36, pages551–552(2021)
Recurrent urinary tract infection and nephrocalcinosis: Answers
Robin Miller & Cheryl Sanchez-Kazi
doi : 10.1007/s00467-020-04650-z
Pediatric Nephrology volume 36, pages553–554(2021)
A rare cause of postinfectious glomerulonephritis: Questions
Ozlem Yuksel Aksoy, Adem Yasin Koksoy, Saba Kiremitci, Nilgun Cakar & Fatma Semsa Cayci
doi : 10.1007/s00467-020-04671-8
Pediatric Nephrology volume 36, pages555–556(2021)
A rare cause of postinfectious glomerulonephritis: Answers
Ozlem Yuksel Aksoy, Adem Yasin Koksoy, Saba Kiremitci, Nilgun Cakar & Fatma Semsa Cayci
doi : 10.1007/s00467-020-04674-5
Pediatric Nephrology volume 36, pages557–559(2021)
An 8-month-old infant with hypercalcemia and hyperphosphatemia: Questions
O?uz ?zler, Gül Ye?iltepe Mutlu, Mehmet Ta?demir, ?ahin Avc?, Ilmay Bilge & ?ükrü Hatun
doi : 10.1007/s00467-020-04656-7
Pediatric Nephrology volume 36, pages561–562(2021)
An 8-month-old infant with hypercalcemia and hyperphosphatemia—Answers
O?uz ?zler, Gül Ye?iltepe Mutlu, Mehmet Ta?demir, ?ahin Avc?, Ilmay Bilge & ?ükrü Hatun
doi : 10.1007/s00467-020-04666-5
Pediatric Nephrology volume 36, pages563–566(2021)
A rare case of hyporeninemic hypertension: Questions
Ahmad Mashmoushi, Abha Choudhary, Christie P. Thomas & Matthias T. F. Wolf
doi : 10.1007/s00467-020-04658-5
Pediatric Nephrology volume 36, pages567–568(2021)
A rare case of hyporeninemic hypertension: Answers
Ahmad Mashmoushi, Abha Choudhary, Christie P. Thomas & Matthias T. F. Wolf
doi : 10.1007/s00467-020-04667-4
Pediatric Nephrology volume 36, pages569–573(2021)
A 6-year-old male with acute kidney injury and enlarged kidneys: Questions
Dunya Mohammad, Shannon Leikert, Melissa Gregory & Rossana Baracco
doi : 10.1007/s00467-020-04690-5
Pediatric Nephrology volume 36, pages575–576(2021)
A 6-year-old male with acute kidney injury and enlarged kidneys: Answers
Dunya Mohammad, Shannon Leikert, Melissa Gregory & Rossana Baracco
doi : 10.1007/s00467-020-04696-z
Pediatric Nephrology volume 36, pages577–580(2021)
Adherence to cysteamine in nephropathic cystinosis: A unique electronic monitoring experience for a better understanding. A prospective cohort study: CrYSTobs
Segolene Gaillard, Laurent Roche, Sandrine Lemoine, Georges Deschênes, Denis Morin, Christine Vianey-Saban, Cécile Acquaviva-Bourdain, Bruno Ranchin, Justine Bacchetta, Behrouz Kassai, Patrice Nony, Eurielle Bodénan, Valérie Laudy, Cécile Rouges, Setareh Zarrabian, Fabien Subtil, Catherine Mercier, Pierre Cochat & Aurélia Bertholet-Thomas
doi : 10.1007/s00467-020-04722-0
Pediatric Nephrology volume 36, pages581–589(2021)
In nephropathic cystinosis (NC), adherence to cysteamine remains challenging; poor adherence is worsening the disease progression with a decline of kidney function and increase of extrarenal morbidities. Our objective was to describe adherence to cysteamine in NC patients, using electronic monitoring systems.
Therapy and outcomes of C3 glomerulopathy and immune-complex membranoproliferative glomerulonephritis
Priyanka Khandelwal, Swati Bhardwaj, Geetika Singh, Aditi Sinha, Pankaj Hari & Arvind Bagga
doi : 10.1007/s00467-020-04736-8
Pediatric Nephrology volume 36, pages591–600(2021)
Data on therapy and outcome of dense deposit disease (DDD), C3 glomerulonephritis (C3GN), and immune-complex MPGN (IC-MPGN) in children are limited.
Pediatric C3 glomerulopathy: a 12-year single-center experience
Zafirah Zahir, Asif Sadiq Wani, Amit Gupta & Vinita Agrawal
doi : 10.1007/s00467-020-04768-0
Pediatric Nephrology volume 36, pages601–610(2021)
Complement component 3 glomerulopathy (C3G) is a disease with limited data in children. We aimed to compare childhood C3G cases with adults. We also studied subgroups of pediatric C3G and predictors of poor outcome.
Prophylactic rituximab administration in children with complicated nephrotic syndrome
Mika Okutsu, Koichi Kamei, Mai Sato, Toru Kanamori, Kentaro Nishi, Sho Ishiwa, Masao Ogura, Mayumi Sako, Shuichi Ito & Kenji Ishikura
doi : 10.1007/s00467-020-04771-5
Pediatric Nephrology volume 36, pages611–619(2021)
Rituximab is effective for maintaining remission in patients with complicated nephrotic syndrome, although a history of steroid-resistant nephrotic syndrome (SRNS) is a risk factor for early relapse. We investigated the efficacy of prophylactic rituximab treatment for maintaining remission after B cell recovery.
Therapeutic plasma exchange: single-center experience in children with kidney disorders
Catherine Joseph, Sahar Siddiqui, Shweta Shah, Catharina H. Solomon & Poyyapakkam R. Srivaths
doi : 10.1007/s00467-020-04744-8
Pediatric Nephrology volume 36, pages621–629(2021)
Therapeutic plasma exchange (TPE) is used in kidney diseases as an adjunct treatment. Little has been described as to its effectiveness in kidney disorders in children. This study aimed to assess the safety, efficacy, and outcomes of patients who underwent TPE for kidney indications.
Comparing predictive values of carbohydrate antigen 19-9, neutrophil gelatinase–associated lipocalin, and kidney injury molecule-1 in 161 patients with ureteropelvic junction obstruction
Kiarad Fendereski, Amirreza Nabighadim, Maryam Seyedtabib, Seyedeh Sima Daryabari, Mohammad Taghi Haghi-Ashtiani & Abdol-Mohammad Kajbafzadeh
doi : 10.1007/s00467-020-04750-w
Pediatric Nephrology volume 36, pages631–638(2021)
To evaluate and compare the efficacy of urinary carbohydrate antigen 19-9 (CA19-9), neutrophil gelatinase–associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) biomarkers as predictive factors to determine the surgery requirement in patients with ureteropelvic junction obstruction.
Resident foreign patients receive adequate dialysis but fewer preemptive transplantations: data from the Italian pediatric dialysis registry
Fabio Paglialonga, Silvia Consolo, Enrico Vidal, Mattia Parolin, Bruno Minale, Mario Giordano, Isabella Guzzo, Chiara Benevenuta, Rosa Roperto, Ciro Corrado, Francesca Mencarelli, Roberto Chimenz, Ilse-Maria Ratsch, Giovanni Pieri, Giovanni Montini, Alberto Edefonti & Enrico Verrina
doi : 10.1007/s00467-020-04730-0
Pediatric Nephrology volume 36, pages639–647(2021)
Sociocultural issues play a key role in children needing kidney replacement therapy (KRT).
Characterizing dynamics of serum creatinine and creatinine clearance in extremely low birth weight neonates during the first 6 weeks of life
Tamara van Donge, Karel Allegaert, Verena Gotta, Anne Smits, Elena Levtchenko, Djalila Mekahli, John van den Anker & Marc Pfister
doi : 10.1007/s00467-020-04749-3
Pediatric Nephrology volume 36, pages649–659(2021)
Characterizing the dynamics of serum creatinine concentrations (Scr) and associated creatinine clearance (CLcr) as a measure of kidney function in extremely low birth weight (??1000 g; ELBW) neonates remains challenging.
Evolution of bone mineral density in patients with idiopathic hypercalciuria: a 20-year longitudinal study
German Perez-Suarez, Ma Isabel Luis Yanes, Maria Cecilia Mart?n Fern?ndez de Basoa, Elena S?nchez Almeida & V?ctor M. Garc?a Nieto
doi : 10.1007/s00467-020-04754-6
Pediatric Nephrology volume 36, pages661–667(2021)
Several recent studies reported bone mineral density (BMD) reduction in pediatric patients with idiopathic hypercalciuria (IH). This longitudinal study aimed to evaluate BMD evolution in IH patients through three bone densitometry studies conducted over 20 years on average. A second objective was to evaluate urine calcium and citrate excretion during this period.
Estimated glomerular filtration rate in children: adapting existing equations for a specific population
Jennifer L. Holness, Anita Brink, M. Razeen Davids & James M. Warwick
doi : 10.1007/s00467-020-04770-6
Pediatric Nephrology volume 36, pages669–683(2021)
Creatinine-based glomerular filtration rate (GFR)-estimating equations frequently do not perform well in populations that differ from the development populations in terms of mean GFR, age, pathology, ethnicity, and diet. After first evaluating the performance of existing equations, the aim of this study was to demonstrate the utility of an in-house modification of the equations to better fit a specific population.
Pediatric kidney transplantation in China: an analysis from the IPNA Global Kidney Replacement Therapy Registry
Qian Shen, Xiaoyan Fang, Xinyue Man, Yihui Zhai, Longshan Liu, Changxi Wang, Wenjun Shang, Guiwen Feng, Lei Zhang, Li Zeng, Youhua Zhu, Jing Chen, Jia Rao, Bradley A Warady, Franz Schaefer & Hong Xu
doi : 10.1007/s00467-020-04745-7
Pediatric Nephrology volume 36, pages685–692(2021)
The International Pediatric Nephrology Association (IPNA) Global Kidney Replacement Therapy (KRT) Registry was established to evaluate the incidence and outcomes of kidney replacement therapy (dialysis and transplantation) provided to children worldwide. Analysis of registry data for separate regions is feasible.
The current status of kidney transplantation in Nigerian children: still awaiting light at the end of the tunnel
Felicia U. Eke, Taiwo A. Ladapo, Augustina N. Okpere, Olalekan Olatise, Ifeoma Anochie, Tochi Uchenwa, Henrietta Okafor, Paul Ibitoye, Uchenna Ononiwu, Ademola Adebowale, Rosamund Akuse & Seyi Oniyangi
doi : 10.1007/s00467-020-04753-7
Pediatric Nephrology volume 36, pages693–699(2021)
Kidney transplantation (KT) is the gold standard treatment for children with chronic kidney disease stage 5 (CKD5). It is easily accessible in well-resourced countries, but not in low/middle-income countries (LMICs). We present, a multicentre experience of paediatric KT of children domiciled in Nigeria. We aim to highlight the challenges and ethical dilemmas that children, their parents or guardians and health care staff face on a daily basis.
Lower albumin level and longer disease duration are risk factors of acute kidney injury in hospitalized children with nephrotic syndrome
Eun Mi Yang, Kee Hwan Yoo, Yo Han Ahn, Seong Heon Kim, Jung Won Lee, Woo Yeong Chung, Min Hyun Cho, Kee Hyuck Kim, Heeyeon Cho, Mee Jeong Lee, Jin-Soon Suh, Hye Sun Hyun, Jiwon M. Lee, Myung Hyun Cho, Ji Hyun Kim, Il-Soo Ha, Hae Il Cheong & Hee Gyung Kang
doi : 10.1007/s00467-020-04740-y
Pediatric Nephrology volume 36, pages701–709(2021)
Children with nephrotic syndrome (NS) are at an increased risk of acute kidney injury (AKI) and the incidence of AKI in this population is reportedly increasing. This study aimed to investigate the incidence, clinical profiles, and risk factors of AKI in hospitalized children with NS through a nationwide study.
Clinical practice recommendations for the diagnosis and management of Alport syndrome in children, adolescents, and young adults–an update for 2020
Clifford E. Kashtan & Oliver Gross
doi : 10.1007/s00467-020-04819-6
Pediatric Nephrology volume 36, pages711–719(2021)
In 2013, we published a set of clinical practice recommendations for the treatment of Alport syndrome in this journal. We recommended delaying the initiation of angiotensin-converting enzyme inhibition until the onset of overt proteinuria or, in some cases, microalbuminuria. Developments that have occurred over the past 7 years have prompted us to revise these recommendations. We now recommend the initiation of treatment at the time of diagnosis in males with X-linked Alport syndrome and in males and females with autosomal recessive Alport syndrome. We further recommend starting treatment at the onset of microalbuminuria in females with X-linked Alport syndrome and in males and females with autosomal dominant Alport syndrome. This article presents the rationale for these revisions as well as recommendations for diagnostic tactics intended to ensure the early diagnosis of Alport syndrome.
Glomerular involvement in children with H syndrome
Odeya David, Michael Geylis, Eyal Kristal, Galina Ling & Ruth Schreiber
doi : 10.1007/s00467-020-04860-5
Pediatric Nephrology volume 36, pages721–724(2021)
H syndrome is a multisystem inflammatory disease caused by mutations in the SLC29A3 gene (OMIM #602782). The protein product, hENT3, is a nucleoside transporter essential for DNA salvage synthesis. Clinical manifestations are hyperpigmentation, hypertrichosis, hepatosplenomegaly, hearing loss, heart anomalies, hypogonadism, short stature, skeletal deformities, and diabetes mellitus. Laboratory findings are consistent with inflammatory processes. Structural kidney anomalies have been described in 6% of patients.
Kidney re-transplantation in a child across the barrier of persisting angiotensin II type I receptor antibodies
Annika Gold, Alexander Fichtner, Daniela Choukair, Claus Peter Schmitt, Caner Süsal, Duska Dragun & Burkhard T?nshoff
doi : 10.1007/s00467-020-04879-8
Pediatric Nephrology volume 36, pages725–729(2021)
Approximately 20% of antibody-mediated rejection (ABMR) episodes in the absence of donor-specific antibodies against human leucocyte antigens (HLA-DSA) in pediatric and adult kidney transplant recipients are associated with, and presumably caused by, antibodies against the angiotensin type 1 receptor (AT1R-Ab). While the role of AT1R-Ab for ABMR and graft failure is increasingly recognized, there is little information available on the management of these patients for re-transplantation over the barrier of persisting AT1R-Ab.
Correction to: Clinical practice recommendations for the diagnosis and management of Alport syndrome in children, adolescents, and young adults–an update for 2020
Clifford E. Kashtan & Oliver Gross
doi : 10.1007/s00467-020-04892-x
Pediatric Nephrology volume 36, page731(2021)
