-
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 -
Journal of Veterinary Internal Medicine Jul 2021Use of telmisartan for the treatment of proteinuria in dogs has not been thoroughly investigated.
BACKGROUND
Use of telmisartan for the treatment of proteinuria in dogs has not been thoroughly investigated.
HYPOTHESIS/OBJECTIVES
Telmisartan can be effective for the treatment of proteinuria in dogs.
ANIMALS
Forty-four client-owned dogs with proteinuria.
METHODS
Retrospective study. Dogs diagnosed with clinically relevant proteinuria (nonazotemic dogs with a urine protein-to-creatinine ratio [UPC] ≥2 and azotemic dogs with UPC ≥0.5) were separated into 3 groups: telmisartan alone, with benazepril, or with mycophenolate. The UPC was recorded before treatment and at subsequent follow-ups (1, 3, 6, and 12 months, as available). Response to treatment was categorized as complete (UPC ˂0.5), partial (UPC decreased by ≥50% but still ≥0.5), or no response (UPC decreased by <50%). Serum creatinine and potassium concentrations and arterial pressure also were recorded.
RESULTS
In the telmisartan group, treatment response (UPC ˂0.5 or decreased by ≥50%) was observed in 70%, 68%, 80%, and 60% of dogs at 1, 3, 6, and 12 months follow-up, respectively. No significant changes were noted in serum creatinine or potassium concentrations, or in arterial blood pressure at all follow-up times. Adverse effects consisted of mild self-limiting gastrointestinal signs in 5 dogs. Two dogs developed clinically relevant azotemia that required discontinuation of the treatment before the first follow-up.
CONCLUSIONS AND CLINICAL IMPORTANCE
Telmisartan can be considered for treatment of proteinuria in dogs, alone or in combination with other treatments for proteinuria.
Topics: Animals; Creatinine; Dog Diseases; Dogs; Proteinuria; Retrospective Studies; Telmisartan
PubMed: 33969924
DOI: 10.1111/jvim.16146 -
Journal of the American Society of... Mar 2020
Topics: Albumins; Albuminuria; Creatinine; Humans; Kidney Function Tests; Proteinuria
PubMed: 32024664
DOI: 10.1681/ASN.2020010049 -
International Journal of Molecular... Dec 2022Proteinuria is a broad term used to describe the pathological presence of proteins, including albumin, globulin, Bence-Jones protein, and mucoprotein in the urine. When... (Review)
Review
Proteinuria is a broad term used to describe the pathological presence of proteins, including albumin, globulin, Bence-Jones protein, and mucoprotein in the urine. When persistent, proteinuria is a marker of kidney damage and represents a reliable predictor of the risk of progression of renal failure. Medical nutrition therapy is imperative for patients with proteinuria because it may slow the progression of renal disease. The aim of this review is to explore different nutritional approaches in the management of proteinuria and their influence on pathophysiological processes. As such, protein restriction is the main dietary intervention. Indeed, other management approaches are frequently used to reduce it regarding micro and macronutrients, but also the dietary style. Among these, the nutritional approach represents one of the most used and controversial interventions and the studies rarely take the form of randomized and controlled trials. With this work we aspire to analyze current clinical knowledge of how nutrition could influence proteinuria, potentially representing a useful tool in the management of proteinuric nephropathy.
Topics: Humans; Proteinuria; Bence Jones Protein; Kidney Diseases; Diet
PubMed: 36613485
DOI: 10.3390/ijms24010044 -
Nutrients Oct 2023Nephrotic syndrome (NS) poses a number of nutritional and metabolic problems due to glomerulus injured podocytes, which are responsible for the loss of barrier function,...
Nephrotic syndrome (NS) poses a number of nutritional and metabolic problems due to glomerulus injured podocytes, which are responsible for the loss of barrier function, causing proteinuria, altered fluid and electrolyte balances, and hypoalbuminemia [...].
Topics: Humans; Nephrotic Syndrome; Podocytes; Proteinuria; Epithelial Cells
PubMed: 37960268
DOI: 10.3390/nu15214615 -
Cells Sep 2022Albuminuria, a hallmark of diabetic nephropathy, reflects not only injury and dysfunction of the filtration apparatus, but is also affected by altered glomerular... (Review)
Review
Albuminuria, a hallmark of diabetic nephropathy, reflects not only injury and dysfunction of the filtration apparatus, but is also affected by altered glomerular hemodynamics and hyperfiltration, as well as by the inability of renal tubular cells to fully retrieve filtered albumin. Albuminuria further plays a role in the progression of diabetic nephropathy, and the suppression of glomerular albumin leak is a key factor in its prevention. Although microalbuminuria is a classic manifestation of diabetic nephropathy, often progressing to macroalbuminuria or overt proteinuria over time, it does not always precede renal function loss in diabetes. The various components leading to diabetic albuminuria and their associations are herein reviewed, and the physiologic rationale and efficacy of therapeutic interventions that reduce glomerular hyperfiltration and proteinuria are discussed. With these perspectives, we propose that these measures should be initiated early, before microalbuminuria develops, as substantial renal injury may already be present in the absence of proteinuria. We further advocate that the inhibition of the renin-angiotensin axis or of sodium-glucose co-transport likely permits the administration of a normal recommended or even high-protein diet, highly desirable for sarcopenic diabetic patients.
Topics: Albumins; Albuminuria; Angiotensins; Diabetes Mellitus; Diabetic Nephropathies; Glucose; Humans; Proteinuria; Renin; Sodium
PubMed: 36139492
DOI: 10.3390/cells11182917 -
Ugeskrift For Laeger Nov 2022This is a case report of an observation of bradycardia and inverted T-waves anteroseptally on the electrocardiogram along with cardiac symptoms, in a previously healthy...
This is a case report of an observation of bradycardia and inverted T-waves anteroseptally on the electrocardiogram along with cardiac symptoms, in a previously healthy 35-year-old woman with post-partum pre-eclampsia. Initially, she had no hypertension or proteinuria, which delayed the time of diagnosis. A possible explanation of bradycardia is a baroreceptor-mediated response to hypertension and hypervolaemia. The changes on the electrocardiogram can be explained by pectus excavatum, an enlarged uterus and endothelial dysfunction. One should always consider peri-partum as well as post-partum pre-eclampsia.
Topics: Pregnancy; Female; Humans; Adult; Pre-Eclampsia; Bradycardia; Proteinuria; Hypertension; Chest Pain
PubMed: 36345902
DOI: No ID Found -
American Journal of Nephrology 2021Although diuretics are one of the most widely used drugs by nephrologists, their antiproteinuric properties are not generally taken into consideration. (Review)
Review
BACKGROUND
Although diuretics are one of the most widely used drugs by nephrologists, their antiproteinuric properties are not generally taken into consideration.
SUMMARY
Thiazide diuretics have been shown to reduce proteinuria by >35% in several prospective controlled studies, and these values are markedly increased when combined with a low-salt diet. Thiazide-like diuretics (indapamide and chlorthalidone) have shown similar effectiveness. The antiproteinuric effect of mineralocorticoid receptor antagonists (spironolactone, eplerenone, and finerenone) has been clearly established through prospective and controlled studies, and treatment with finerenone reduces the risk of chronic kidney disease progression in type-2 diabetic patients. The efficacy of other diuretics such as amiloride, triamterene, acetazolamide, or loop diuretics has been less explored, but different investigations suggest that they might share the same antiproteinuric properties of other diuretics that should be evaluated through controlled studies. Although the inclusion of sodium-glucose cotransporter-2 inhibitors (SGLT2i) among diuretics is a controversial issue, their renoprotective and cardioprotective properties, confirmed in various landmark trials, constitute a true revolution in the treatment of patients with kidney disease. Recent subanalyses of these trials have shown that the early antiproteinuric effect induced by SGLT2i predicts long-term preservation of kidney function. Key Message: Whether the early reduction in proteinuria induced by diuretics other than finerenone and SGLT2i, as summarized in this review, also translates into long-term renoprotection requires further prospective and observational studies. In any case, it is important for the clinician to be aware of the antiproteinuric properties of drugs so often used in daily clinical practice.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Chlorthalidone; Combined Modality Therapy; Diet, Sodium-Restricted; Diuresis; Diuretics; Humans; Hypertension; Indapamide; Mineralocorticoid Receptor Antagonists; Natriuresis; Proteinuria; Sodium Chloride Symporters; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Thiazides
PubMed: 34233330
DOI: 10.1159/000517020 -
International Journal of Molecular... May 2023Anti-PLA2R antibodies (Ab) are a diagnostic and prognostic biomarker in primary membranous nephropathy (PMN). We assessed the relationship between the levels of...
Anti-PLA2R antibodies (Ab) are a diagnostic and prognostic biomarker in primary membranous nephropathy (PMN). We assessed the relationship between the levels of anti-PLA2R Ab at diagnosis and different variables related to disease activity and prognosis in a western population of PMN patients. Forty-one patients with positive anti-PLA2R Ab from three nephrology departments in Israel were enrolled. Clinical and laboratory data were collected at diagnosis and after one year of follow-up, including serum anti-PLA2R Ab levels (ELISA) and glomerular PLA2R deposits on biopsy. Univariable statistical analysis and permutation-based ANOVA and ANCOVA tests were performed. The median [(interquartile range (IQR)) age of the patients was 63 [50-71], with 28 (68%) males. At the time of diagnosis, 38 (93%) of the patients had nephrotic range proteinuria, and 19 (46%) had heavy proteinuria (≥8 gr/24 h). The median [IQR] level of anti-PLA2R at diagnosis was 78 [35-183] RU/mL. Anti-PLA2R levels at diagnosis were correlated with 24 h proteinuria, hypoalbuminemia and remission after one year ( = 0.017, = 0.003 and = 0.034, respectively). The correlations for 24 h proteinuria and hypoalbuminemia remained significant after adjustment for immunosuppressive treatment ( = 0.003 and = 0.034, respectively). Higher levels of anti-PLA2R Ab at diagnosis in patients with active PMN from a western population are associated with higher proteinuria, lower serum albumin and remission one year after the diagnosis. This finding supports the prognostic value of anti-PLA2R Ab levels and their possible use in stratifying PMN patients.
Topics: Male; Humans; Female; Glomerulonephritis, Membranous; Prognosis; Hypoalbuminemia; Autoantibodies; Proteinuria
PubMed: 37240397
DOI: 10.3390/ijms24109051 -
Kidney & Blood Pressure Research 2021Proteinuria is a key biomarker in nephrology. It is central to diagnosis and risk assessment and the primary target of many important therapies. Etiologies resulting in... (Review)
Review
BACKGROUND
Proteinuria is a key biomarker in nephrology. It is central to diagnosis and risk assessment and the primary target of many important therapies. Etiologies resulting in pathological proteinuria include congenital and acquired disorders, as well as both glomerular (immune/non-immune mediated) and tubular defects.
SUMMARY
Untreated proteinuria is strongly linked to progressive loss of kidney function and kidney failure. Excess protein reaching the renal tubules is ordinarily resorbed by the tubular epithelium. However, when these mechanisms are overwhelmed, a variety of inflammatory and fibrotic pathways are activated, causing both interstitial fibrosis and glomerulosclerosis. Nevertheless, the specific mechanisms underlying this are complex and remain incompletely understood. Recently, a number of treatments, in addition to angiotensin system blockade, have been shown to effectively slow the progression of proteinuric chronic kidney disease. However, additional therapies are clearly needed. Key message: This review provides an update on the pathophysiology of proteinuria, the pathways leading to fibrosis, and an overview of current and emerging therapies.
Topics: Animals; Disease Management; Disease Progression; Fibrosis; Humans; Kidney; Proteinuria; Renal Insufficiency; Renal Insufficiency, Chronic
PubMed: 34130301
DOI: 10.1159/000516911