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Annales de Biologie Clinique Feb 2019The typing of proteinuria is one of the complementary examinations carried out during the exploration of proteinuria. It aims to separate and identify the different... (Review)
Review
The typing of proteinuria is one of the complementary examinations carried out during the exploration of proteinuria. It aims to separate and identify the different proteins, or fractions of proteins, that make up proteinuria. The nature and relative importance of the proteins present reflect the location of the renal involvement and help to determine the etiology. The typing of a proteinuria also allows the detection of a monoclonal component in urine and its quantification. Finally, it allows highlighting the existence of a proteinuria of overload that can occur in the absence of kidney damage. Many methods allow the typing of proteinuria, and these have benefited in recent years from technological advances. The purpose of this review is to summarize typing methods currently used, their benefits and limitations, and the help that these diagnostic tools can provide to the management of patients.
Topics: Diagnosis, Differential; Glomerular Filtration Rate; Humans; Kidney Diseases; Kidney Function Tests; Patient Selection; Proteinuria; Urinalysis
PubMed: 30799294
DOI: 10.1684/abc.2018.1401 -
Pediatrics in Review Dec 2018Pediatricians must be aware of screening indications and the evaluation and management of a child with hematuria and/or proteinuria. (Review)
Review
PRACTICE GAP
Pediatricians must be aware of screening indications and the evaluation and management of a child with hematuria and/or proteinuria.
OBJECTIVES
After completing this article, readers should be able to: 1. Understand the common causes of proteinuria and hematuria and be able to differentiate between benign and serious causes. 2. Describe screening techniques for initial evaluation of hematuria and proteinuria. 3. Recognize the criteria for diagnosis of proteinuria and hematuria. 4. Plan the appropriate initial evaluation for hematuria and proteinuria and interpret laboratory findings essential for diagnosis. 5. Recognize serious causes of hematuria and proteinuria that warrant immediate referral.
Topics: Adolescent; Child; Child, Preschool; Hematuria; Humans; Proteinuria; Urinalysis
PubMed: 30504250
DOI: 10.1542/pir.2017-0300 -
Journal of Veterinary Internal Medicine 2005Emerging data indicate that more attention should be given to the detection, evaluation, monitoring, and treatment of dogs and cats with proteinuria. The purposes of... (Review)
Review
Emerging data indicate that more attention should be given to the detection, evaluation, monitoring, and treatment of dogs and cats with proteinuria. The purposes of this consensus statement are to describe an appropriate approach for accomplishing these tasks and to provide specific recommendations for assessing and managing dogs and cats with proteinuria based on data that are currently available. Because proteinuria and albuminuria have numerous possible causes, they must be assessed appropriately to determine their implications for the patient. This assessment involves localization of the origin of the proteinuria as well as determination of its persistence and magnitude. Because persistent renal proteinuria usually indicates presence of chronic kidney disease, which sometimes is a progressive disorder, its detection identifies dogs and cats that have increased risk for adverse health outcomes. Thus, urine testing that will detect proteinuria should be a component of the clinical evaluations of dogs and cats under all circumstances that prompt their veterinarians to also perform comprehensive hematologic and serum biochemical evaluations. At a minimum, this testing should consist of a complete urinalysis that includes a satisfactorily accurate semiquantitative test for protein, and positive reactions should be properly followed with further testing. The appropriate response to persistent renal proteinuria depends on the magnitude of proteinuria and the status of the patient. The recommended response generally involves continued monitoring, further investigation, and therapeutic intervention, which should be implemented as an escalating series of inclusive, stepwise responses.
Topics: Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Kidney Diseases; Proteinuria
PubMed: 15954557
DOI: 10.1892/0891-6640(2005)19[377:aamopi]2.0.co;2 -
Journal of Reproductive Immunology Sep 2019Early-onset preeclampsia has been linked to poor placentation and fetal growth restriction, whereas late-onset preeclampsia was suggested to result from maternal... (Review)
Review
Early-onset preeclampsia has been linked to poor placentation and fetal growth restriction, whereas late-onset preeclampsia was suggested to result from maternal factors. We have proposed an alternative model, suggesting that both early- and late-onset preeclampsia result from placental syncytiotrophoblast stress. This stress represents a common endpoint of several Stage 1 processes, promoting the clinical stage 2 of preeclampsia (new-onset hypertension and proteinuria or other signs of end-organ dysfunction), but the causes and timing of placental malperfusion differ. We have suggested that late-onset preeclampsia, without evidence of poor spiral artery remodelling, may be secondary to intraplacental (intervillous) malperfusion due to mechanical restrictions. As the growing placenta reaches its size limit, malperfusion and hypoxia occurs. This latter pathway reflects what is observed in postmature or multiple pregnancies. Our revised two-stage model accommodates most risk factors for preeclampsia including primiparity, chronic pre-pregnancy disease (e.g. obesity, diabetic-, chronic hypertensive-, and some autoimmune diseases), and pregnancy risk factors (e.g. multiple or molar pregnancies, gestational diabetes or hypertension, and low circulating Placental Growth Factor). These factors may increase the risk of progressing to the second stage of preeclampsia (both early- and late-onset) by affecting one of or both pathways leading to Stage 1, as well as potentially accelerating the steps towards Stage 2, including priming the maternal cardiovascular susceptibility to inflammatory factors shed by the placenta. This paper reviews previous preeclampsia findings and concepts, which fit with the revised two-stage model, and argues that "maternal" preeclampsia does not exist, as all preeclampsia requires a placenta.
Topics: Female; Humans; Models, Biological; Pre-Eclampsia; Pregnancy; Proteinuria; Trophoblasts
PubMed: 31301487
DOI: 10.1016/j.jri.2019.07.004 -
Kidney International Mar 2003Proteinuria is consequence of two mechanisms: the abnormal transglomerular passage of proteins due to increased permeability of glomerular capillary wall and their... (Review)
Review
Proteinuria is consequence of two mechanisms: the abnormal transglomerular passage of proteins due to increased permeability of glomerular capillary wall and their subsequent impaired reabsorption by the epithelial cells of the proximal tubuli. In the various glomerular diseases, the severity of disruption of the structural integrity of the glomerular capillary wall correlates with the area of the glomerular barrier being permeated by "large" pores, permitting the passage in the tubular lumen of high-molecular-weight (HMW) proteins, to which the barrier is normally impermeable. The increased load of such proteins in the tubular lumen leads to the saturation of the reabsorptive mechanism by the tubular cells, and, in the most severe or chronic conditions, to their toxic damage, that favors the increased urinary excretion of all proteins, including low-molecular-weight (LMW) proteins, which are completely reabsorbed in physiologic conditions. Recent clinical studies showed that in patients with glomerular diseases the urinary excretion of some HMW proteins [immunoglobulins G and M (IgG and IgM)] and of some LMW proteins, alpha1-microglobulin, beta2-microglobulin, correlates with the severity of the histologic lesions, and may predict, better than the quantity of proteinuria, the natural course, the outcome, and the response to treatment. It is suggested that some patients have already, at the time of clinical presentation, a structural damage of the glomerular capillary wall (injury of podocytes) and of the tubulointerstitium, the severity and scarce reversibility of which are reliably indicated by an elevated urinary excretion of HMW and LMW proteins.
Topics: Animals; Humans; Kidney Glomerulus; Proteinuria
PubMed: 12631062
DOI: 10.1046/j.1523-1755.2003.00840.x -
Journal of the American Society of... Sep 2022The complement system is highly activated in primary membranous nephropathy (MN). Identifying the complement components that damage podocytes has important therapeutic...
BACKGROUND
The complement system is highly activated in primary membranous nephropathy (MN). Identifying the complement components that damage podocytes has important therapeutic implications. This study investigated the role of C3a and the C3a receptor (C3aR) in the pathogenesis of MN.
METHODS
C3aR expression in kidneys and circulating levels of C3a of MN patients were examined. Human podocyte damage was assessed after exposure to MN plasma +/- C3aR blockade (SB290157, JR14a). C3aR antagonists were administered to rats with Heymann nephritis on day 0 or after proteinuria. Clinical and pathologic parameters, specific IgG and complement activation, and podocyte injuries were then assessed.
RESULTS
In the glomeruli, C3aR staining merged well with podocin. Overexpression of C3aR correlated positively with proteinuria, serum creatinine, and no response to treatments. Human podocytes exposed to MN plasma showed increased expression of PLA2R, C3aR, and Wnt3/-catenin, reduced expression of synaptopodin and migration function, downregulated Bcl-2, and decreased cell viability. C3aR antagonists could block these effects. In Heymann nephritis rats, C3aR blockade attenuated proteinuria, electron-dense deposition, foot process width, and glomerular basement membrane thickening in glomeruli. The increased plasma C3a levels and overexpression of C3aR were also alleviated. Specific, but not total, IgG levels decreased, with less deposition of rat IgG in glomeruli and subsequent reduction of C1q, factor B, and C5b-9.
CONCLUSION
C3a anaphylatoxin is a crucial effector of complement-mediated podocyte damage in MN. The C3aR antagonist may be a potentially viable treatment for this disease.
Topics: Rats; Humans; Animals; Glomerulonephritis, Membranous; Complement C3a; Podocytes; Proteinuria; Immunoglobulin G; Complement Activation
PubMed: 35777783
DOI: 10.1681/ASN.2021101384 -
BMJ (Clinical Research Ed.) Feb 2006
Review
Topics: Family Practice; Humans; Medical History Taking; Proteinuria; Referral and Consultation
PubMed: 16455729
DOI: 10.1136/bmj.332.7536.284 -
Talanta Feb 2021Extensive medical research showed that patients, with high protein concentration in urine, have various kinds of kidney diseases, referred to as proteinuria. Urinary... (Review)
Review
Extensive medical research showed that patients, with high protein concentration in urine, have various kinds of kidney diseases, referred to as proteinuria. Urinary protein biomarkers are useful for diagnosis of many health conditions - kidney and cardio vascular diseases, cancers, diabetes, infections. This review focuses on the instrumental quantification (electrophoresis, chromatography, immunoassays, mass spectrometry, fluorescence spectroscopy, the infrared spectroscopy, and Raman spectroscopy) of proteins (the most of all albumin) in human urine matrix. Different techniques provide unique information on what constituents of the urine are. Due to complex nature of urine, a separation step by electrophoresis or chromatography are often used for proteomics study of urine. Mass spectrometry is a powerful tool for the discovery and the analysis of biomarkers in urine, however, costs of the analysis are high, especially for quantitative analysis. Immunoassays, which often come with fluorescence detection, are major qualitative and quantitative tools in clinical analysis. While Infrared and Raman spectroscopies do not give extensive information about urine, they could become important tools for the routine clinical diagnostics of kidney problems, due to rapidness and low-cost. Thus, it is important to review all the applicable techniques and methods related to urine analysis. In this review, a brief overview of each technique's principle is introduced. Where applicable, research papers about protein determination in urine are summarized with the main figures of merits, such as the limit of detection, the detectable range, recovery and accuracy, when available.
Topics: Biomarkers; Humans; Mass Spectrometry; Proteins; Proteinuria; Proteomics; Urinalysis
PubMed: 33303164
DOI: 10.1016/j.talanta.2020.121718 -
The Journal of Clinical Investigation Jan 2020BACKGROUNDProteinuria is considered an unfavorable clinical condition that accelerates renal and cardiovascular disease. However, it is not clear whether all forms of... (Clinical Trial)
Clinical Trial
BACKGROUNDProteinuria is considered an unfavorable clinical condition that accelerates renal and cardiovascular disease. However, it is not clear whether all forms of proteinuria are damaging. Mutations in CUBN cause Imerslund-Gräsbeck syndrome (IGS), which is characterized by intestinal malabsorption of vitamin B12 and in some cases proteinuria. CUBN encodes for cubilin, an intestinal and proximal tubular uptake receptor containing 27 CUB domains for ligand binding.METHODSWe used next-generation sequencing for renal disease genes to genotype cohorts of patients with suspected hereditary renal disease and chronic proteinuria. CUBN variants were analyzed using bioinformatics, structural modeling, and epidemiological methods.RESULTSWe identified 39 patients, in whom biallelic pathogenic variants in the CUBN gene were associated with chronic isolated proteinuria and early childhood onset. Since the proteinuria in these patients had a high proportion of albuminuria, glomerular diseases such as steroid-resistant nephrotic syndrome or Alport syndrome were often the primary clinical diagnosis, motivating renal biopsies and the use of proteinuria-lowering treatments. However, renal function was normal in all cases. By contrast, we did not found any biallelic CUBN variants in proteinuric patients with reduced renal function or focal segmental glomerulosclerosis. Unlike the more N-terminal IGS mutations, 37 of the 41 proteinuria-associated CUBN variants led to modifications or truncations after the vitamin B12-binding domain. Finally, we show that 4 C-terminal CUBN variants are associated with albuminuria and slightly increased GFR in meta-analyses of large population-based cohorts.CONCLUSIONCollectively, our data suggest an important role for the C-terminal half of cubilin in renal albumin reabsorption. Albuminuria due to reduced cubilin function could be an unexpectedly common benign condition in humans that may not require any proteinuria-lowering treatment or renal biopsy.FUNDINGATIP-Avenir program, Fondation Bettencourt-Schueller (Liliane Bettencourt Chair of Developmental Biology), Agence Nationale de la Recherche (ANR) Investissements d'avenir program (ANR-10-IAHU-01) and NEPHROFLY (ANR-14-ACHN-0013, to MS), Steno Collaborative Grant 2018 (NNF18OC0052457, to TSA and MS), Heisenberg Professorship of the German Research Foundation (KO 3598/5-1, to AK), Deutsche Forschungsgemeinschaft (DFG) Collaborative Research Centre (SFB) KIDGEM 1140 (project 246781735, to CB), and Federal Ministry of Education and Research (BMB) (01GM1515C, to CB).
Topics: Albuminuria; Anemia, Megaloblastic; Female; Humans; Kidney Tubules, Proximal; Malabsorption Syndromes; Male; Mutation; Proteinuria; Receptors, Cell Surface; Vitamin B 12 Deficiency
PubMed: 31613795
DOI: 10.1172/JCI129937 -
Clinical Journal of the American... Mar 2019IgA nephropathy (IgAN) is an important cause of ESKD for which there are no approved therapies. A challenge for evaluating treatments for IgAN is the usual long time...
IgA nephropathy (IgAN) is an important cause of ESKD for which there are no approved therapies. A challenge for evaluating treatments for IgAN is the usual long time course for progression to ESKD. The aim of this Kidney Health Initiative project was to identify surrogate end points that could serve as reliable predictors of a treatment's effect on long-term kidney outcomes in IgAN and be used as a basis for approval. Proteinuria was identified as the most widely recognized and well studied risk factor for progression to ESKD in IgAN. The workgroup performed a critical review of the data on proteinuria reduction as a surrogate end point for a treatment's effect on progression to ESKD in IgAN. Epidemiologic data indicate a strong and consistent relationship between the level and duration of proteinuria and loss of kidney function. Trial-level analyses of data from 13 controlled trials also show an association between treatment effects on percent reduction of proteinuria and treatment effects on a composite of time to doubling of serum creatinine, ESKD, or death. We conclude that data support the use of proteinuria reduction as a reasonably likely surrogate end point for a treatment's effect on progression to ESKD in IgAN. In the United States, reasonably likely surrogate end points can be used as a basis for accelerated approval of therapies intended to treat serious or life-threatening conditions, such as IgAN. The clinical benefit of products approved under this program would need to be verified in a postmarketing confirmatory trial.
Topics: Controlled Clinical Trials as Topic; Disease Progression; Endpoint Determination; Glomerulonephritis, IGA; Humans; Kidney Failure, Chronic; Proteinuria; Research Design; Risk Factors; Time Factors; Treatment Outcome
PubMed: 30635299
DOI: 10.2215/CJN.08600718