ArticlePediatric nephrology (Berlin, Germany)2013
Over- or underfill: not all nephrotic states are created equal.
Article in Pediatric nephrology (Berlin, Germany), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.
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Who cites it
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 53 citations in OpenAlex.
- Management of congenital nephrotic syndrome: consensus recommendations of the ERKNet-ESPN Working Group.Nature reviews. Nephrology · 2021Guideline
- IPNA clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome.Pediatric nephrology (Berlin, Germany) · 2020Guideline
- Glomerular filtration rate estimation in nephrotic patients: creatinine and/or cystatin-C-based equations, or none of them?Clinical kidney journal · 2026Article
- Early detection of proteinuria to prevent kidney fibrosis and progression to kidney failure: lessons from the School Urine Screening Program in Japan.Pediatric nephrology (Berlin, Germany) · 2026Review
- Uncommon Factors Leading to Nephrotic Syndrome.Biomedicines · 2025Review
- Ascites: Under- and Overfill: Is Amiloride the Answer?Journal of the American Society of Nephrology : JASN · 2024Article
- Clinical relevance of proteinuria selectivity index and fractional excretion of sodium in patients with nephrotic syndrome.Scientific reports · 2024Article
- An Elderly Case of Minimal Change Nephrotic Syndrome: Correlation between Renal Tubular Dysfunction and the Onset of Oliguric Acute Kidney Injury Requiring Hemodialysis.Case reports in nephrology · 2024Article
- Nephrotic syndrome: pathophysiology and consequences.Journal of nephrology · 2023Review
- Oral Furosemide and Hydrochlorothiazide/Amiloride versus Intravenous Furosemide for the Treatment of Resistant Nephrotic Syndrome.Journal of clinical medicine · 2023Article
- Role of ion channels in the mechanism of proteinuria (Review).Experimental and therapeutic medicine · 2023Review
- Mechanisms and management of edema in pediatric nephrotic syndrome.Pediatric nephrology (Berlin, Germany) · 2021Review
- Podocytopathies.Nature reviews. Disease primers · 2020Review
- Genetics of Childhood Steroid Sensitive Nephrotic Syndrome: An Update.Frontiers in pediatrics · 2019Review
- Urinary Plasmin(ogen) as a Prognostic Factor for Hypertension.Kidney international reports · 2018Article
- Article
- Diuretic Resistance.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2017Review
- The influences of larger physical constitutions including obesity on the amount of urine protein excretion in primary glomerulonephritis: research of the Japan Renal Biopsy Registry.Clinical and experimental nephrology · 2015Article
- Pathophysiology, Evaluation, and Management of Edema in Childhood Nephrotic Syndrome.Frontiers in pediatrics · 2015Review
- Draining the edema: a new role for aquaretics?Pediatric nephrology (Berlin, Germany) · 2014Article
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Authors and funding
1 author at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Blessed were the days when it all made sense and the apparent mechanism for edema formation in nephrotic syndrome was straightforward: the kidneys lost protein in the urine, which lowered the plasma oncotic pressure. Thus, fluid leaked into the interstitium, depleting the intravascular volume with subsequent activation of renin/aldosterone and consequent avid renal sodium retention. As simple as that! Unfortunately, a number of clinical and laboratory observations have raised serious concerns about the accuracy of this "underfill" hypothesis. Instead, an "overfill" hypothesis was generated. Under this assumption, the nephrotic syndrome not only leads to urinary protein wasting, but also to primary sodium retention with consequent intravascular overfilling, with the excess fluid spilling into the flood plains of the interstitium, leading to edema. Recently, an attractive mechanism was proposed to explain this primary sodium retention: proteinuria includes plasma proteinases, such as plasmin, which activate the epithelial sodium channel in the collecting duct, ENaC. In this edition, further evidence for this hypothesis is being presented by confirming increased plasmin content in the urine of children with nephrotic syndrome and demonstrating ENaC activation. If correct, this hypothesis would provide a simple treatment for the edema: pharmacological blockade of ENaC, for instance, with amiloride. Yet, how come clinicians have not empirically discovered the presumed power of ENaC blockers in nephrotic syndrome? And why is it that some patients clearly show evidence of intravascular underfilling? The controversy of over- versus underfilling demonstrates how much we still have to learn about the pathophysiology of nephrotic syndrome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.