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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 -
Pediatric Annals Jun 2020Although the American Academy of Pediatrics (AAP) removed the screening urinalysis from its health supervision guidelines in 2007, the use of the urinalysis remains an... (Review)
Review
Although the American Academy of Pediatrics (AAP) removed the screening urinalysis from its health supervision guidelines in 2007, the use of the urinalysis remains an important part of pediatric care. Thus, the incidental finding of proteinuria is still commonplace when a urine sample is collected for various complaints, such as fever and abdominal pain. Knowing when to reassure a patient with proteinuria versus when to perform additional testing is a situation that general practitioners face regularly, but also one that not all may be comfortable dealing with due to the possibility of missing a diagnosis. In addition, proteinuria in certain conditions can signify renal disease and worse outcomes, so general practitioners should know how to screen and interpret the results. Understanding the common benign and pathological causes of proteinuria helps medical providers to better inform and treat their patients, and possibly avoid unnecessary additional testing or subspecialty referrals. [Pediatr Ann. 2020;49(6):e268-e272.].
Topics: Child; Diagnosis, Differential; Humans; Incidental Findings; Kidney Diseases; Missed Diagnosis; Practice Guidelines as Topic; Proteinuria; Risk Factors
PubMed: 32520368
DOI: 10.3928/19382359-20200520-04 -
Primary Care Dec 2014The kidney has anatomic and physiologic features that prevent protein from reaching the urine. In disease processes, this natural mechanism is disrupted, causing protein... (Review)
Review
The kidney has anatomic and physiologic features that prevent protein from reaching the urine. In disease processes, this natural mechanism is disrupted, causing protein to leak into the urine. Proteinuria can be used as a marker for disease and disease progression. The general anatomy of the glomerulus along with preliminary workup to evaluate disease based on history, physical and urinalysis results are reviewed in this article. Examples of commonly encountered diseases in the outpatient setting and relevance of proteinuria in chronic kidney disease along with general complications and treatments are also reviewed.
Topics: Biomarkers; Diabetic Nephropathies; Diet; Dyslipidemias; Edema; Glomerulonephritis; Humans; Hypertension; Kidney Function Tests; Kidney Glomerulus; Primary Health Care; Proteinuria; Renal Insufficiency, Chronic; Sensitivity and Specificity
PubMed: 25439530
DOI: 10.1016/j.pop.2014.08.010 -
European Journal of Internal Medicine Dec 2023Cancer is the second leading cause of death among the adult population following cardiovascular diseases. Prevention and earlier diagnosis are among the cornerstones in... (Review)
Review
Cancer is the second leading cause of death among the adult population following cardiovascular diseases. Prevention and earlier diagnosis are among the cornerstones in the management of malignancies. Albuminuria is a diagnostic criterion for chronic kidney disease and has been associated with multiple conditions including cardiovascular diseases and systemic inflammation while the association between albuminuria and malignancy has been inadequately addressed. Large-scale observational studies with long follow-up periods demonstrate a statistically significant association between albuminuria and overall malignancy incidence, especially urothelial malignancy incidence. However, the underlying pathophysiology linking these two entities is not a straightforward causal relationship but most likely a multidirectional relationship including a causal link. In this narrative review, we evaluate the clinical studies investigating the association between albuminuria and malignancy along with potential underlying mechanisms linking them. We also summarize data on the impact of treatment modalities prescribed for albuminuria and/or proteinuria on the prevention or prognosis of malignancies.
Topics: Adult; Humans; Albuminuria; Cardiovascular Diseases; Proteinuria; Risk Factors; Neoplasms; Diabetes Mellitus, Type 2
PubMed: 37741791
DOI: 10.1016/j.ejim.2023.09.010 -
Journal of Nephrology Feb 2016The therapy of IgA nephropathy (IgAN) is cause for debate among nephrologists. Since the early 1980s, many therapeutic attempts have been proposed, but most of them did... (Review)
Review
The therapy of IgA nephropathy (IgAN) is cause for debate among nephrologists. Since the early 1980s, many therapeutic attempts have been proposed, but most of them did not prove efficacy. The recent KDIGO Clinical Practice Guideline for Glomerulonephritis recommend long-term ACE-I or ARB treatment when proteinuria is more than 1 g/day, with up-titration of the drug. For patients with GFR >50 ml/min and proteinuria persistently higher than 1 g/day, they suggest a 6-month course of corticosteroid therapy. Based on our experience and the results of the literature, we propose a progressive treatment, which takes into account the time the IgAN is recognized and the clinical conditions present at that time. The treatment can be summarize as follows: (1) in patients with macro-microscopic haematuria, in case with proteinuria less than 0.3 g/day, only annual controls; (2) in patients with proteinuria between 0.3 and 0.9 g/day, ACE-I and/or ARB, with titration of the drugs; (3) in patients with proteinuria higher than 1 g/day, in case with the presence of arterial hypertension and GFR up to 30 ml/min, 6 months course of corticosteroids, in addition to ACE-I and/or ARB; (4) in patients with GFR less than 30 ml/min, ACE-I/ARB, dialysis and kidney transplantation; corticosteroids should be in case considered for patients with persistently high or increasing proteinuria; (5) the immunosuppressants (cyclophosphamide and azathioprine) should be reserved for patients with progressive renal insufficiency or with vasculitic lesions on renal biopsy.
Topics: Adrenal Cortex Hormones; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Critical Pathways; Disease Progression; Glomerular Filtration Rate; Glomerulonephritis, IGA; Hematuria; Humans; Kidney; Kidney Transplantation; Proteinuria; Renal Dialysis; Treatment Outcome
PubMed: 26577268
DOI: 10.1007/s40620-015-0248-3 -
Clinical Journal of the American... Apr 2024IgA nephropathy is the most common primary GN. Clinical features of IgA nephropathy include proteinuria, which is the strongest known surrogate of progression to kidney... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
IgA nephropathy is the most common primary GN. Clinical features of IgA nephropathy include proteinuria, which is the strongest known surrogate of progression to kidney failure. Complement pathway activation is a critical driver of inflammation and tissue injury in IgA nephropathy. Cemdisiran is an investigational RNA interference therapeutic that suppresses hepatic production of complement component 5 (C5), thereby potentially reducing proteinuria in IgA nephropathy. We evaluated the efficacy and safety of cemdisiran in adult patients with IgA nephropathy at high risk of kidney disease progression.
METHODS
In this phase 2, 36-week, double-blind study, adult patients with IgA nephropathy and urine protein ≥1 g/24 hours were randomized (2:1) to subcutaneous cemdisiran 600 mg or placebo every 4 weeks in combination with the standard of care. The primary end point was percentage change from baseline at week 32 in urine protein-to-creatinine ratio (UPCR) measured by 24-hour urine collection. Additional end points included change from baseline in UPCR measured by spot urine, serum C5 level, and safety assessments.
RESULTS
Thirty-one patients were randomized (cemdisiran, N =22; placebo, N =9). Cemdisiran-treated patients had a placebo-adjusted geometric mean change in 24-hour UPCR of -37.4% (cemdisiran-adjusted geometric mean ratio to baseline [SEM], 0.69 [0.10]) at week 32. Spot UPCR was consistent with 24-hour UPCR placebo-adjusted change of -45.8% (cemdisiran-adjusted geometric mean ratio to baseline [SEM], 0.73 [0.11]). Mean (SD) change in serum C5 level from baseline at week 32 was -98.7% (1.2) with cemdisiran and 25.2% (57.7) with placebo. Over 36 weeks, most adverse events were mild or moderate and transient; the most common adverse event after cemdisiran treatment was injection-site reaction (41%).
CONCLUSIONS
These findings indicate that treatment with cemdisiran resulted in a reduction of proteinuria at week 32 and was well tolerated.
Topics: Adult; Humans; Glomerulonephritis, IGA; Glomerular Filtration Rate; Proteinuria; Kidney Function Tests; Double-Blind Method
PubMed: 38214599
DOI: 10.2215/CJN.0000000000000384 -
Proteomics. Clinical Applications Jun 2015Preeclampsia (PE) is a multisystem disorder of pregnancy that develops after 20 wk of gestation in previously normotensive women and complicates 5-8% of pregnancies.... (Review)
Review
Preeclampsia (PE) is a multisystem disorder of pregnancy that develops after 20 wk of gestation in previously normotensive women and complicates 5-8% of pregnancies. This rapidly progressive syndrome is usually diagnosed when the mother develops hypertension and proteinuria. The only effective treatment is delivery of the baby although early low-dose aspirin has been shown to significantly reduce the risk for PE. Recent advances in proteomic methods of protein separation, identification, and quantitation may allow for the identification of proteins and peptides that could facilitate early detection of disease, improve assessment of prognosis, and allow closer monitoring of women at risk for PE. This review summarizes all currently available markers for prediction and diagnosis of PE and presents urine proteomic studies performed for the identification of novel biomarkers.
Topics: Animals; Biomarkers; Female; Humans; Pre-Eclampsia; Pregnancy; Prognosis; Proteinuria; Proteome; Proteomics; Risk Factors
PubMed: 25644222
DOI: 10.1002/prca.201400092 -
Pediatric Clinics of North America Dec 2022Proteinuria and/or hematuria are common findings in ambulatory settings. Proteinuria can be glomerular and/or tubular in origin and it may be transient, orthostatic, or... (Review)
Review
Proteinuria and/or hematuria are common findings in ambulatory settings. Proteinuria can be glomerular and/or tubular in origin and it may be transient, orthostatic, or persistent. Persistent proteinuria may be indicative of a serious kidney pathology. Hematuria, which denotes the presence of an increased number of red blood cells in the urine, can be gross or microscopic. Hematuria can originate from the glomeruli or other sites of the urinary tract. Asymptomatic microscopic hematuria or mild proteinuria in an otherwise healthy child is less likely to be of clinical significance. However, the presence of both requires further workup and careful monitoring.
Topics: Child; Humans; Hematuria; Proteinuria; Ambulatory Care
PubMed: 36880921
DOI: 10.1016/j.pcl.2022.07.002