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Living well with kidney disease
Florencio McCarthy, Pierre Cochat, Khalid Alhasan & Melvin Bonilla-Felix
doi : 10.1007/s00467-021-05011-0
Pediatric Nephrology volume 36, pages1035–1036(2021)
Infantile urolithiasis
Maria Goretti Moreira Guimar?es Penido & Uri Saggie Alon
doi : 10.1007/s00467-020-04888-7
Pediatric Nephrology volume 36, pages1037–1040(2021)
Neurophysiological control of urinary bladder storage and voiding—functional changes through development and pathology
Youko Ikeda
doi : 10.1007/s00467-020-04594-4
Pediatric Nephrology volume 36, pages1041–1052(2021)
The effective storage of urine and its expulsion relies upon the coordinated activity of parasympathetic, sympathetic, and somatic innervations to the lower urinary tract (LUT). At birth, all mammalian neonates lack the ability to voluntary regulate bladder storage or voiding. The ability to control urinary bladder activity is established as connections to the central nervous system (CNS) form through development. The neural regulation of the LUT has been predominantly investigated in adult animal models where comparatively less is known about the neonatal and postnatal neurophysiological development that facilitate urinary continence. Furthermore, congenital neurological or anatomical defects can adversely affect both storage and voiding functions through postnatal development and into adulthood, leading to secondary conditions including vesicoureteral reflux, chronic urinary tract infections, and end-stage renal disease. Therefore, the aim of the review is to provide the current knowledge available on neurophysiological regulation of the LUT through pre- to postnatal development of human and animal models and the consequences of congenital anomalies that can affect LUT neural function.
Targeting optimal PD management in children: what have we learned from the IPPN registry?
Dagmara Borzych-Du?a?ka, Franz Schaefer & Bradley A. Warady
doi : 10.1007/s00467-020-04598-0
Pediatric Nephrology volume 36, pages1053–1063(2021)
National and international registries have great potential for providing data that describe disease burden, treatments, and outcomes especially in rare diseases. In the setting of pediatric end-stage renal disease (ESRD), the available data are limited to highly developed countries, whereas the lack of data from emerging economies blurs the global perspective. In order to improve the pediatric dialysis care worldwide, provide global benchmarking of pediatric dialysis outcome, and assign useful tools and management algorithms based on evidence-based medicine, the International Pediatric Peritoneal Dialysis Network (IPPN) was established in 2007. In recent years, the Registry has provided comprehensive data on relevant clinical issues in pediatric peritoneal dialysis patients including nutritional status, growth, cardiovascular disease, anemia management, mineral and bone disorders, preservation of residual kidney function, access-related complications, and impact of associated comorbidities. A unique feature of the registry is the ability to compare practices and outcomes between countries and world regions. In the current review, we describe study design and collection methods, summarize the core IPPN findings based on its 12-year experience and 13 publications, and discuss the future perspective.
Fucose as a new therapeutic target in renal transplantation
Mark C Howard, Christopher L Nauser, Daniela A Vizitiu & Steven H Sacks
doi : 10.1007/s00467-020-04588-2
Pediatric Nephrology volume 36, pages1065–1073(2021)
Ischaemia/reperfusion injury (IRI) is an inevitable and damaging consequence of the process of kidney transplantation, ultimately leading to delayed graft function and increased risk of graft loss. A key driver of this adverse reaction in kidneys is activation of the complement system, an important part of the innate immune system. This activation causes deposition of complement C3 on renal tubules as well as infiltration of immune cells and ultimately damage to the tubules resulting in reduced kidney function. Collectin-11 (CL-11) is a pattern recognition molecule of the lectin pathway of complement. CL-11 binds to a ligand that is exposed on the renal tubules by the stress caused by IRI, and through attached proteases, CL-11 activates complement and this contributes to the consequences outlined above. Recent work in our lab has shown that this damage-associated ligand contains a fucose residue that aids CL-11 binding and promotes complement activation. In this review, we will discuss the clinical context of renal transplantation, the relevance of the complement system in IRI, and outline the evidence for the role of CL-11 binding to a fucosylated ligand in IRI as well as its downstream effects. Finally, we will detail the simple but elegant theory that increasing the level of free fucose in the kidney acts as a decoy molecule, greatly reducing the clinical consequences of IRI mediated by CL-11.
The application of omic technologies to research in sepsis-associated acute kidney injury
Denise Hasson, Stuart L. Goldstein & Stephen W. Standage
doi : 10.1007/s00467-020-04557-9
Pediatric Nephrology volume 36, pages1075–1086(2021)
Acute kidney injury (AKI) is common in critically ill children and adults, and sepsis-associated AKI (SA-AKI) is the most frequent cause of AKI in the ICU. To date, no mechanistically targeted therapeutic interventions have been identified. High-throughput “omic” technologies (e.g., genomics, proteomics, metabolomics, etc.) offer a new angle of approach to achieve this end. In this review, we provide an update on the current understanding of SA-AKI pathophysiology. Omic technologies themselves are briefly discussed to facilitate interpretation of studies using them. We next summarize the body of SA-AKI research to date that has employed omic technologies. Importantly, omic studies are helping to elucidate a pathophysiology of SA-AKI centered around cellular stress responses, metabolic changes, and dysregulation of energy production that underlie its clinical features. Finally, we propose opportunities for future research using clinically relevant animal models, integrating multiple omic technologies and ultimately progressing to translational human studies focusing therapeutic strategies on targeted disease mechanisms.
Racial differences of early vascular aging in children and adolescents
Ruan Kruger, Lebo Francina Gafane-Matemane & Juliana Kagura
doi : 10.1007/s00467-020-04593-5
Pediatric Nephrology volume 36, pages1087–1108(2021)
The prevalence of non-communicable disease (NCDs) is rising globally, with a large burden recorded in sub-Saharan countries and populations of black race/ethnicity. Accelerated vascular deterioration, otherwise known as early vascular aging (EVA), is the underlying factor for highly prevalent NCDs such as hypertension. The etiology of EVA is multifactorial with a central component being arterial stiffness with subsequent development of hypertension and cardiovascular complications. Although arterial stiffness develops with increasing age, many children and adolescents are subjected to the premature development of arterial stiffness, due to genetic or epigenetic predispositions, lifestyle and behavioral risk factors, and early life programming. Race/ethnic differences in pediatric populations have also been reported with higher aortic stiffness in black (African American) compared with age-matched white (European American) counterparts independent of blood pressure, body mass index, or socioeconomic status. With known evidence of race/ethnic differences in EVA, the pathophysiological mechanisms underlying graded differences in the programming of EVA are still sparse and rarely explored. This educational review aims to address the early life determinants of EVA in children and adolescents with a particular focus on racial or ethnic differences.
Kidney replacement therapy in pediatric patients on mechanical circulatory support: challenges for the pediatric nephrologist
Alexandra Idrovo, Natasha Afonso, Jack Price, Sebastian Tume & Ayse Akcan-Arikan
doi : 10.1007/s00467-020-04605-4
Pediatric Nephrology volume 36, pages1109–1117(2021)
The use of mechanical circulatory support (MCS) therapies in children with medically refractory cardiac failure has increased over the past two decades. With the growing experience and expertise, MCS is currently offered as a bridge to recovery or heart transplantation and in some cases even as destination therapy. Acute kidney injury (AKI) is common in patients with end-stage heart failure (ESHF). When severe AKI develops requiring kidney replacement therapy (KRT), these patients present unique challenges for the pediatric nephrology team. The use of KRT has not been adequately described in children with ESHF on the newer MCS. We also present original case series data from our center experience. The purpose of this review is to familiarize the reader with the current MCS technologies, approach to their selection, how they interact when combined with current KRT circuits, and distinguish similarities and differences. We will attempt to highlight the distinctive features of each technology, specifically focusing on growing trends in use of continuous-flow ventricular assist devices (CF-VAD) as it poses additional challenges to the pediatric nephrologist.
Extracorporeal renal and liver support in pediatric acute liver failure
Bogdana Sabina Zoica & Akash Deep
doi : 10.1007/s00467-020-04613-4
Pediatric Nephrology volume 36, pages1119–1128(2021)
The liver is the only organ which can regenerate and, thus, potentially negate the need for transplantation in acute liver failure (ALF). Cerebral edema and sepsis are leading causes of mortality in ALF. Both water-soluble and protein-bound toxins have been implicated in pathogenesis of various ALF complications. Ammonia is a surrogate marker of water-soluble toxin accumulation in ALF and high levels are associated with higher grades of hepatic encephalopathy, raised intracranial pressure, and mortality. Therefore, extracorporeal therapies aim to lower ammonia and maintain fluid balance and cytokine homeostasis. The most common and easily available modality is continuous kidney replacement therapy (CKRT). Early initiation of high-volume CKRT utilizing an anticoagulation regimen minimizing treatment downtime and delivering the prescribed dose is highly desirable. Ideally, extracorporeal liver-assist devices (ECLAD) should perform both synthetic and detoxification functions of the liver. ECLAD may temporarily replace lost liver function and serve as a bridge, either to spontaneous recovery or liver transplantation. Various bioartificial and biologic liver-assist devices are described in specialty literature, including molecular adsorbent recirculating system (MARS), single pass albumin dialysis (SPAD), and total plasma exchange (TPE); however, clinicians commonly use modalities easily available in intensive care units. There is a lack of standardization of indications for ECLAD, availability of different extracorporeal devices with varied technical approaches, and, of note, the differences in doses of ECLAD provided in clinical practice. We review the practicalities and evidence regarding these four artificial liver support devices in pediatric ALF.
When salt is needed to grow: Questions
Ester Conversano, Sara Romano, Andrea Taddio, Flavio Faletra, Davide Zanon, Egidio Barbi & Marco Pennesi
doi : 10.1007/s00467-020-04639-8
Pediatric Nephrology volume 36, page1129(2021)
A 50-day-old girl was referred for a history of recurrent vomiting, poor feeding and moderate failure to thrive. She was born by a caesarean section at 41 + 5 weeks of gestation, from non-consanguineous parents. Her birth weight was 3430 g and she was fed with breast milk and formula. Upon admission, her weight was 3700 g (3° percentile) and blood pressure was normal. Physical examination showed mild dystrophy with poor representation of subcutaneous fat, normal external genitalia and age-appropriate psychomotor development.
When salt is needed to grow: Answers
Ester Conversano, Sara Romano, Andrea Taddio, Flavio Faletra, Davide Zanon, Egidio Barbi & Marco Pennesi
doi : 10.1007/s00467-020-04647-8
Pediatric Nephrology volume 36, pages1131–1132(2021)
An uncommon cause of a common disorder: Questions
Sare Gülfem ?zlü, Sonay ?ncesoy ?zdemir, Dilek K?l?c & Ay?egül Ne?e Citak Kurt
doi : 10.1007/s00467-020-04642-z
Pediatric Nephrology volume 36, page1133(2021)
A 7-year-old girl who had been followed up with cerebral palsy and epilepsy was consulted to our pediatric nephrology outpatient clinic because of incidentally detected hyponatremia on routine follow-up. She had birth-adjusted cerebral palsy and received various antiepileptics since the newborn period.
An uncommon cause of a common disorder: Answers
Sare Gülfem ?zlü, Sonay ?ncesoy ?zdemir, Dilek K?l?c & Ay?egül Ne?e Citak Kurt
doi : 10.1007/s00467-020-04649-6
Pediatric Nephrology volume 36, pages1135–1136(2021)
Incidental hyperkalemia in an infant: Questions
Chung-Hsiang Yang, Ming-Chou Chiang, Jhao-Jhuang Ding, Shih-Hua Lin & Min-Hua Tseng
doi : 10.1007/s00467-020-04727-9
Pediatric Nephrology volume 36, pages1137–1138(2021)
Incidental hyperkalemia in an infant: Answers
Chung-Hsiang Yang, Ming-Chou Chiang, Jhao-Jhuang Ding, Shih-Hua Lin & Min-Hua Tseng
doi : 10.1007/s00467-020-04729-7
Pediatric Nephrology volume 36, pages1139–1141(2021)
A girl with kidney agenesis, uterine didelphys, and pelvic cyst: Questions
Furkan Ufuk & Ayse Ruksan Utebey
doi : 10.1007/s00467-020-04682-5
Pediatric Nephrology volume 36, pages1143–1145(2021)
A girl with kidney agenesis, uterine didelphys, and pelvic cyst: Answers
Furkan Ufuk & Ayse Ruksan Utebey
doi : 10.1007/s00467-020-04687-0
Pediatric Nephrology volume 36, pages1147–1148(2021)
An unusual kidney presentation of severe proteinuria in a 2-year-old girl: Questions
Aya Nawata, Takahiro Morishita, Satoshi Hisano, Kaneyasu Nakagawa, Koichi Kusuhara & Toshiyuki Nakayama
doi : 10.1007/s00467-020-04669-2
Pediatric Nephrology volume 36, pages1149–1151(2021)
An unusual kidney presentation of severe proteinuria in a 2-year-old girl: Answers
Aya Nawata, Takahiro Morishita, Satoshi Hisano, Kaneyasu Nakagawa, Koichi Kusuhara & Toshiyuki Nakayama
doi : 10.1007/s00467-020-04676-3
Pediatric Nephrology volume 36, pages1153–1157(2021)
Taking a multidisciplinary approach to maintaining haemodialysis vascular access: a challenging case in an infant: Questions
Rebecca Anderson, Brendan Cusack, Elhamy Bekhit, Bernadita Troncoso Solar, Cathy Quinlan & Joshua Kausman
doi : 10.1007/s00467-020-04726-w
Pediatric Nephrology volume 36, pages1159–1160(2021)
Taking a multidisciplinary approach to maintaining haemodialysis vascular access: a challenging case in an infant: Answers
Rebecca Anderson, Brendan Cusack, Elhamy Bekhit, Bernadita Troncoso Solar, Cathy Quinlan & Joshua Kausman
doi : 10.1007/s00467-020-04728-8
Pediatric Nephrology volume 36, pages1161–1163(2021)
Long-term kidney and liver outcome in 50 children with autosomal recessive polycystic kidney disease
Guillaume Dorval, Olivia Boyer, Anne Couderc, Jean-Daniel Delbet, Laurence Heidet, Dominique Debray, Pauline Krug, Muriel Girard, Brigitte Llanas, Marina Charbit, Saoussen Krid, Nathalie Biebuyck, Marc Fila, Cécile Courivaud, Frances Tilley, Nicolas Garcelon, Thomas Blanc, Christophe Chardot, Rémi Salomon & Florence Lacaille
doi : 10.1007/s00467-020-04808-9
Pediatric Nephrology volume 36, pages1165–1173(2021)
Autosomal recessive polycystic kidney disease (ARPKD) is a rare ciliopathy characterized by congenital hepatic fibrosis and cystic kidney disease. Lack of data about long-term follow-up makes it difficult to discuss timing and type of organ transplantation. Our objectives were to evaluate long-term evolution and indications for transplantation, from birth to adulthood.
A global antiB cell strategy combining obinutuzumab and daratumumab in severe pediatric nephrotic syndrome
Claire Dossier, Benjamin Prim, Christelle Moreau, Thérésa Kwon, Anne Maisin, Sylvie Nathanson, Christiane De Gennes, Katia Barsotti, Abdelmajid Bourrassi, Julien Hogan & Georges Deschênes
doi : 10.1007/s00467-020-04811-0
Pediatric Nephrology volume 36, pages1175–1182(2021)
Steroid-sensitive nephrotic syndrome (SSNS) is, in most patients, a chronic disease with 80% experiencing at least one relapse after first flare. B cell depletion using rituximab is effective in preventing relapse in steroid-dependent (SDNS) patients but fails to maintain long-term remission following B cell recovery, possibly due to development of autoreactive long-lived plasma cells. We investigated sequential combination of antiCD20 antibody targeting all B cell subsets, and antiCD38 antibody with high plasma cell cytotoxicity in patients with uncontrolled SDNS after failure of one or several attempts at B cell depletion.
Thromboprophylaxis in congenital nephrotic syndrome: 15-year experience from a national cohort
Laurence J. Dobbie, Angela Lamb, Lucy Eskell, Ian J. Ramage & Ben C. Reynolds
doi : 10.1007/s00467-020-04793-z
Pediatric Nephrology volume 36, pages1183–1194(2021)
Congenital nephrotic syndrome (CNS) is an ultra-rare disease associated with a pro-thrombotic state and venous thromboembolisms (VTE). There is very limited evidence evaluating thromboprophylaxis in patients with CNS. This study aimed to determine the doses and duration of treatment required to achieve adequate thromboprophylaxis in patients with CNS.
Predictors of poor kidney outcome in children with C3 glomerulopathy
Ay?e Seda P?narba??, Ismail Dursun, Ibrahim Gokce, Elif ?omak, Seha Sayg?l?, Meral Torun Bayram, Osman Donmez, Engin Melek, Demet Tekcan, Neslihan ?içek, Dilek Y?lmaz, Y?lmaz Tabel, Zeynep Y. Y?ld?r?m, Elif Bahat, Mustafa Koyun, Alper Soylu, Nur Canpolat, Ba?dagül Aksu, Mehtap Ezel ?elak?l, Mehmet Ta?demir, Meryem Benzer, Gül ?zçelik, Sevcan A. Bakkalo?lu & Ruhan Dü?ünsel
doi : 10.1007/s00467-020-04799-7
Pediatric Nephrology volume 36, pages1195–1205(2021)
C3 glomerulopathy (C3G) is characterized by heterogeneous clinical presentation, outcome, and predominant C3 accumulation in glomeruli without significant IgG. There is scarce outcome data regarding childhood C3G. We describe clinical and pathological features, treatment and outcomes, and risk factors for progression to chronic kidney disease stage 5 (CKD5) in the largest pediatric series with biopsy-proven C3G.
Biopsy-proven Henoch-Sch?nlein purpura nephritis: a single center experience
Eda Didem Kurt-?ükür, Thivya Sekar & Kjell Tullus
doi : 10.1007/s00467-020-04809-8
Pediatric Nephrology volume 36, pages1207–1215(2021)
Knowledge on normal progress and treatment of Henoch-Sch?nlein purpura nephritis (HSPN) is limited. This study reviews outcome, clinical, pathological, and therapeutic factors affecting the prognosis of HSPN patients.
Primary membranous nephropathy in children and adolescents: a single-centre report from South Asia
Raja Ramachandran, Saurabh Nayak, Vinod Kumar, Ashwani Kumar, Neha Agrawal, Ritika Bansal, Karalanglin Tiewsoh, Ritambhra Nada, Manish Rathi & Harbir Singh Kohli
doi : 10.1007/s00467-020-04798-8
Pediatric Nephrology volume 36, pages1217–1226(2021)
Unlike adults, primary membranous nephropathy (PMN) comprises only 1–2% of childhood nephrotic syndrome. The clinical behaviour of PMN in children is not explicit and we report upon clinical presentation and outcome.
Nephrolithiasis during the first 6 months of life in exclusively breastfed infants
Neslihan Y?lmaz, Selçuk Yüksel, Fatih Alt?nta? & Ali Koçyi?it
doi : 10.1007/s00467-020-04815-w
Pediatric Nephrology volume 36, pages1227–1231(2021)
We investigated etiology and prognosis of infantile nephrolithiasis, including whether lithogenic and anti-lithogenic content of breast milk affects its formation.
Safety and efficacy of sucroferric oxyhydroxide in pediatric patients with chronic kidney disease
Larry A. Greenbaum, Nikola Jeck, Günter Klaus, Marc Fila, Cristina Stoica, Sahar Fathallah-Shaykh, Ana Paredes, Larysa Wickman, Raoul Nelson, Rita D. Swinford, Carolyn Larkins Abitbol, Mihaela Balgradean, Augustina Jankauskiene, Amandine Perrin, Milica Enoiu & Sun-Young Ahn
doi : 10.1007/s00467-020-04805-y
Pediatric Nephrology volume 36, pages1233–1244(2021)
Pediatric patients with advanced chronic kidney disease (CKD) are often prescribed oral phosphate binders (PBs) for the management of hyperphosphatemia. However, available PBs have limitations, including unfavorable tolerability and safety.
Silent and dangerous: catheter-associated right atrial thrombus (CRAT) in children on chronic haemodialysis
Martin Garcia-Nicoletti, Manish D. Sinha, Alexandra Savis, Shazia Adalat, Narayan Karunanithy & Francis Calder
doi : 10.1007/s00467-020-04743-9
Pediatric Nephrology volume 36, pages1245–1254(2021)
Catheter-associated right atrial thrombus (CRAT) is a recognised complication of central venous catheter (CVC) use for haemodialysis (HD) patients.
Evolution and change in paradigm of hemodialysis in children: a systematic review
Rahul Chanchlani, Claire Young, Aisha Farooq, Stephanie Sanger, Sidharth Sethi, Ronith Chakraborty, Abhishek Tibrewal & Rupesh Raina
doi : 10.1007/s00467-020-04821-y
Pediatric Nephrology volume 36, pages1255–1271(2021)
There are similarities in hemodialysis (HD) between adults and children and also unique pediatric aspects. In this systematic review, we evaluated the existing HD literature, including vascular access, indications, parameters, and outcomes as a reflection on real-life HD practices.
Tandem plasmapheresis and continuous kidney replacement treatment in pediatric patients
Naile Tufan Pekkucuksen, Katie E. Sigler, Ayse Akcan Arikan & Poyyapakkam Srivaths
doi : 10.1007/s00467-020-04769-z
Pediatric Nephrology volume 36, pages1273–1278(2021)
The objectives of the study are to describe tandem therapeutic plasma exchange (TPE) and continuous kidney replacement therapy (CKRT) patients’ outcomes in a large institution.
Acute kidney injury in children with chronic kidney disease is associated with faster decline in kidney function
Nabil Melhem, Pernille Rasmussen, Triona Joyce, Joanna Clothier, Christopher J. D. Reid, Caroline Booth & Manish D. Sinha
doi : 10.1007/s00467-020-04777-z
Pediatric Nephrology volume 36, pages1279–1288(2021)
This study aimed to investigate the association of acute kidney injury (AKI) with change in estimated glomerular filtration rate (eGFR) in children with advanced chronic kidney disease (CKD).
Baseline creatinine determination method impacts association between acute kidney injury and clinical outcomes
W. Alton Russell, David Scheinker & Scott M. Sutherland
doi : 10.1007/s00467-020-04789-9
Pediatric Nephrology volume 36, pages1289–1297(2021)
Current consensus definition for acute kidney injury (AKI) does not specify how baseline serum creatinine should be determined. We assessed how baseline determination impacted AKI incidence and association between AKI and clinical outcomes.
Baseline kidney function is associated with vancomycin-induced acute kidney injury in children: a prospective nested case-control study
Huanian Zhang, Ping Gao, Yang Wang, Jianzhong Chen, Guangwei Jia, Furong Zhang, Fang Tao & Shiying Yuan
doi : 10.1007/s00467-020-04820-z
Pediatric Nephrology volume 36, pages1299–1306(2021)
Children with kidney insufficiency are susceptible to vancomycin-induced acute kidney injury (VIAKI), but there is a lack of compelling clinical data. We conducted a nested case-control study to evaluate the relationship between kidney insufficiency and incidence of VIAKI in children.
Health-related quality of life in children with chronic kidney disease is affected by the number of medications
Maria E. D?az-Gonz?lez de Ferris, Chris B. Pierce, Debbie S. Gipson, Susan L. Furth, Bradley A. Warady, Stephen R. Hooper & Authoring group for the CKiD Study
doi : 10.1007/s00467-021-04919-x
Pediatric Nephrology volume 36, pages1307–1310(2021)
The number of medications could serve as a surrogate for burden of care at home and may affect health-related quality of life (HRQoL) in children with chronic kidney disease (CKD).
Complement activation in children with Streptococcus pneumoniae associated hemolytic uremic syndrome
Johannes Holle, Sandra Habbig, Alexander Gratopp, Anna Mauritsch, Dominik Müller & Julia Thumfart
doi : 10.1007/s00467-021-04952-w
Pediatric Nephrology volume 36, pages1311–1315(2021)
Hemolytic uremic syndrome caused by invasive pneumococcal disease (P-HUS) is rare in children and adolescents, but accompanied by high mortality in the acute phase and complicated by long-term renal sequelae. Abnormalities in the alternative complement pathway may additionally be contributing to the course of the disease but also to putative treatment options.
Correction to: Incidental hyperkalemia in an infant: Questions
Chung-Hsiang Yang, Ming-Chou Chiang, Jhao-Jhuang Ding, Shih-Hua Lin & Min-Hua Tseng
doi : 10.1007/s00467-020-04827-6
Pediatric Nephrology volume 36, page1317(2021)
Correction to: Incidental hyperkalemia in an infant: Answers
Chung-Hsiang Yang, Ming-Chou Chiang, Jhao-Jhuang Ding, Shih-Hua Lin & Min-Hua Tseng
doi : 10.1007/s00467-020-04826-7
Pediatric Nephrology volume 36, page1319(2021)
