Novel techniques and newer markers for the evaluation of “proximal tubular dysfunction”

Ludwig, Michael; Sethi, Sidharth Kumar

doi:10.1007/s11255-011-9914-0

Cited by 7 publications

(6 citation statements)

References 59 publications

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“…These results suggest the importance of the process in diseases accompanied by altered permeability characteristics of the glomerular filter, some being very rare such as the Goodpasture's syndrome (see above), and some being very common such as the diabetic nephropathy (60). PT dysfunction is itself involved in various forms of the Fanconi syndrome, which is often associated with rare inherited diseases such as Dent's disease (61,62) or disease states accompanied by intraluminal pressure increases, such as obstructive uropathy (56,(63)(64)(65) or polycystic kidney disease (66). We therefore hope that our finding that radial stretch of the PT is sensed by basolateral TRPV4, which modifies albumin reabsorption, will help to treat patients with proteinuria.…”

Section: Discussionmentioning

confidence: 91%

Mechanical activation of TRPV4 channels controls albumin reabsorption by proximal tubule cells

et al. 2020

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Defects in protein reabsorption by the proximal tubule are toxic for epithelial cells in the nephron and may result in nephropathy. In this study, we showed that the ion channel TRPV4 modulated the endocytosis of albumin and low–molecular weight proteins in the proximal tubule. TRPV4 was found at the basolateral side of proximal tubule cells, and its mechanical activation by cell stretching induced Ca2+ entry into the cytosol, which promoted endocytosis. Trpv4−/− mice presented with mild proximal tubule dysfunction under basal conditions. To challenge endocytic function, the permeability of the glomerular filter was altered by systemic delivery of angiotensin II. The proteinuria induced by this treatment was more severe in Trpv4−/− than in Trpv4+/+ mice. Injecting antibodies against the glomerular basement membrane to induce glomerulonephritis is a more pathophysiologically relevant method of impairing glomerular filter permeability. Albuminuria was more severe in mice that lacked TRPV4 specifically in the proximal tubule than in control mice. These results emphasize the importance of TRPV4 in sensing pressure in the proximal tubule in response to variations in the amount of ultrafiltrate and unveil a mechanism that controls protein reabsorption.

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Section: Discussionmentioning

confidence: 91%

Mechanical activation of TRPV4 channels controls albumin reabsorption by proximal tubule cells

et al. 2020

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“…For the detection of tubular (low molecular weight proteinuria, single markers such as alpha-1-microglobulin, beta-2-microglobulin or retinol binding protein alone or in combination may be used [ 17 ] [ 18 ] [ 19 ] [ 20 ]. Beta-2-microglobulin, which is one of the first and most popular markers, is unstable in an acidic environment so that one can gain unreliable results by using it.…”

Section: Introductionmentioning

confidence: 99%

“…It is a method that was developed during the 90s of the last century. The advantage is that a panoramic view of all proteins is obtained, so a clear classification of the type of proteinuria is possible [ 1 ] [ 2 ] [ 3 ] [ 17 ] [ 18 ] [ 19 ] [ 20 ]. It is relatively fast and inexpensive method; it is possible to analyse multiple samples, especially using the Phast system [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

The Spectrum of Kidney Diseases in Children Associated with Low Molecular Weight Proteinuria

Salihu¹,

Tosheska²,

Aluloska³

et al. 2018

Open Access Maced J Med Sci

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BACKGROUND:Proteinuria, in addition to haematuria, is the most important laboratory parameter in patients with nephro-urological diseases. Low molecular weight proteinuria (LMWP) is of particular importance because some diseases genetic and tubulointerstitial are diagnosed based on its presence.AIM:The purpose of this study is to describe the clinical features, the course and outcome of pediatric patients with a renal disease associated with LMWP.MATERIAL AND METHODS:This retrospective observational study included 250 pediatric patients with various kidney diseases in which the type of proteinuria was defined by 4-20% gradient gel sodium dodecyl sulphate polyacrylamide gel (SDS-PAG) electrophoresis.RESULTS:Isolated LMWP was detected in 12% of patients, while mixed glomerulotubular proteinuria was detected in 18% of patients. It was detected in all patients with the Dent-1/2 disease, Lowe’s syndrome and secondary Fanconi syndrome. Transient LMWP was also detected in a series of 12 patients with distal renal tubular acidosis. In patients with nephrotic syndrome, it was associated with corticoresistence and unfavourable clinical course.CONCLUSION:This study contributes to the understanding of the clinical spectrum of various kidney diseases associated with LMWP, their natural course, and the effect of therapy.

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“…Fructose intake induces a secondary Fanconi syndrome, leading to dysfunction in the proximal renal tubule. There are clinical consequences (growth retardation; rickets; altered reabsorption of phosphate, amino acids, glucose, and uric acid [ 37 , 38 , 39 ]) that have been a cause for increased lactate and an acidification defect, characterized by a 15–30% reduction in tubular bicarbonate reabsorption [ 36 , 40 ].…”

Section: Resultsmentioning

confidence: 99%

Clinical Practice Guidelines for the Diagnosis and Management of Hereditary Fructose Intolerance

Úbeda,

Santander,

Luesma

2024

Diseases

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Introduction: Hereditary fructose intolerance or hereditary fructosemia is an autosomal recessive metabolic disorder caused by a loss of function in the aldolase B gene. This disorder affects 1 in 20,000 people, constituting a rare disease with a favorable prognosis through adherence to a fructose-free diet. Despite dietary management, chronic pathology may manifest, underscoring the importance of early diagnosis to mitigate adverse effects. However, early detection of the disease poses significant challenges. Aim: Our aim was to compile pertinent information on the differential diagnosis of this pathology based on patient symptoms, facilitating the development of a diagnostic algorithm for early identification. Methodology: A systematic review adhering to PRISMA guidelines was conducted on empirical studies from PubMed, encompassing a total of 35 studies. Results: Individuals with fructose intolerance may acutely experience postprandial symptoms such as hypoglycemia, vomiting, and abdominal distension. Despite proper treatment, chronic complications such as fatty liver, Fanconi syndrome, growth deficiency, and irritable bowel syndrome may arise. The proposed diagnostic algorithm aims to minimize these adverse processes. Conclusions: Understanding the pathogenesis enables prompt diagnosis and prevention of chronicity. Establishing continuity of care from pediatric to adult medicine is crucial, and disseminating information to non-pediatric endocrinologists is imperative for managing this rare disease.

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Novel techniques and newer markers for the evaluation of “proximal tubular dysfunction”

Cited by 7 publications

References 59 publications

Mechanical activation of TRPV4 channels controls albumin reabsorption by proximal tubule cells

Mechanical activation of TRPV4 channels controls albumin reabsorption by proximal tubule cells

The Spectrum of Kidney Diseases in Children Associated with Low Molecular Weight Proteinuria

Clinical Practice Guidelines for the Diagnosis and Management of Hereditary Fructose Intolerance

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