urinary biomarkers for nephrotic syndrome

AIM: Idiopathic membranous nephropathy (IMN) has a varied clinical course that requires accurate prediction as a prerequisite for treatment administration. Currently, its prognosis relies on proteinuria, a clinical parameter whose onset lags behind kidney injury. Increased urinary excretion of matrix metalloproteinase-9 (MMP-9) and nephrin has been reported in a number of IMN-like glomerular diseases in which they reflected disease severity. However, little or nothing is known of the importance of these biomarkers in IMN, a major cause of adult nephrotic syndrome...

BACKGROUND: Up to 70% of patients with ANCA-associated vasculitis (AAV) develop GN, with 26% progressing to ESKD. Diagnostic-grade and noninvasive tools to detect active renal inflammation are needed. Urinary soluble CD163 (usCD163) is a promising biomarker of active renal vasculitis, but a diagnostic-grade assay, assessment of its utility in prospective diagnosis of renal vasculitis flares, and evaluation of its utility in proteinuric states are needed. METHODS: We assessed a diagnostic-grade usCD163 assay in ( 1 ) a real-world cohort of 405 patients with AAV and 121 healthy and 488 non-AAV disease controls; ( 2 ) a prospective multicenter study of 84 patients with potential renal vasculitis flare; ( 3 ) a longitudinal multicenter cohort of 65 patients with podocytopathy; and ( 4 ) a cohort of 29 patients with AAV (with or without proteinuria) and ten controls...

The choice of treatment for primary nephrotic syndrome depends on the pathologic type of the disorder. Renal biopsy is necessary for a definitive diagnosis, but it is burdensome for the patients, and can be avoided if tests could be performed using urine or plasma. In this study, we analyzed 100 urinary proteins, 141 plasma proteins, and 57 urine/plasma ratios in cases of diabetic nephropathy (DN; n = 11), minimal change nephrotic syndrome (MCNS; n = 14), and membranous nephropathy (MN; n = 23). We found that the combination of urinary retinol-binding protein 4 and SH3 domain-binding glutamic acid-rich-like protein 3 could distinguish between MCNS and DN, with an area under the curve (AUC) of 0...

INTRODUCTIONS: Kidney injury molecule-1 (KIM-1) and periostin (POSTN) are proximal and distal tubule injury biomarkers. We tested whether baseline urine KIM-1/creatinine (uKIM-1/cr) and/or uPOSTN/cr correlated with disease severity or improved a remission prediction model. METHODS: Baseline uKIM1/cr and uPOSTN/cr were measured on spot urine samples from immunosuppression-free patients enrolled in Nephrotic Syndrome Study Network until December 15, 2014. Urine protein/creatinine (UPCR) and albumin/creatinine (UACR) were measured at baseline, 4 months, and until last follow-up...

Kidney diseases are conditions that increase the morbidity and mortality of those afflicted. Diagnosis of these conditions is based on parameters such as the glomerular filtration rate (GFR), measurement of serum and urinary creatinine levels and equations derived from these measurements (Wasung, Chawla, Madero. Clin Chim Acta 438:350-357, 2015). However, serum creatinine as a marker for measuring renal dysfunction has its limitations since it is altered in several other physiological situations, such as in patients with muscle loss, after intense physical exercise or in people on a high protein diet (Riley, Powers, Welch...

Tolvaptan (TLV) is a vasopressin V2 receptor antagonist that increases free water excretion. However, there are few reports of the use of TLV in pediatric patients with nephrotic syndrome (NS). The efficacy of TLV for the management of edema and hyponatremia in a 12-year-old boy with refractory NS is demonstrated. In this patient, refractory NS developed at 5 years of age, and remission was maintained with several immunosuppressive agents. He was admitted to hospital due to relapse with oliguria, edema, hypoalbuminemia, and hyponatremia...

The discovery of microRNAs (miRNAs) has opened up new avenues of research to understand the molecular basis of a number of diseases. Because of their conservative feature in evolution and important role in the physiological function, microRNAs could be treated as predictors for disease classification and clinical process based on the specific expression. The identification of novel miRNAs and their target genes can be considered as potential targets for novel drugs. Furthermore, currently, the circulatory and urinary exosomal miRNAs are gaining increasing attention as their expression profiles are often associated with specific diseases, and they exhibit great potential as noninvasive or minimally invasive biomarkers for the diagnosis of various diseases...

INTRODUCTION: Heterogeneity of nephrotic diseases and a lack of validated biomarkers limits interventions and reduces the ability to examine outcomes. Urinary CD80 is a potential biomarker for minimal change disease (MCD) steroid-sensitive nephrotic syndrome (NS). We investigated and validated a CD80 enzyme-linked immunosorbent assay (ELISA) in urine in a large cohort with a variety of nephrotic diseases. METHODS: A commercial CD80 ELISA was enhanced and analytically validated for urine...

Podocyte injury has recently been described as unifying feature in idiopathic nephrotic syndromes (INS). Puumala hantavirus (PUUV) infection represents a unique RNA virus-induced renal disease with significant proteinuria. The underlying pathomechanism is unclear. We hypothesized that PUUV infection results in podocyte injury, similar to findings in INS. We therefore analyzed standard markers of glomerular proteinuria (e.g. immunoglobulin G [IgG]), urinary nephrin excretion (podocyte injury) and serum levels of the soluble urokinase plasminogen activator receptor (suPAR), a proposed pathomechanically involved molecule in INS, in PUUV-infected patients...

BACKGROUND: Fatty acid-binding protein 4 (FABP4), but not FABP1 (liver-type FABP), is ectopically induced in injured glomerular endothelial cells, and urinary FABP4 (U-FABP4) level is associated with proteinuria and renal dysfunction in a general population. METHODS: The clinical significance of U-FABP4 was investigated in 81 patients (male/female: 43/38, age: 57 ± 17 years) who underwent kidney biopsy. RESULTS: U-FABP4 was negatively correlated with estimated glomerular filtration rate (eGFR) (r = - 0...

BACKGROUND: Proteinuria is a major marker of chronic kidney disease (CKD) progression and the predictor of cardiovascular mortality. The rapid development of renal failure is expected in those patients who have higher level of proteinuria however, some patients may have slow decline of renal function despite lower level of urinary protein excretion. The different mechanical (visco-elastic) and chemical properties, as well as the proteome profiles of urinary proteins might explain their tubular toxicity mechanism...

Dominant and recessive mutations in podocalyxin (PODXL) are associated with human kidney disease. Interestingly, some PODXL mutations manifest as anuria while others are associated with proteinuric kidney disease. PODXL heterozygosity is associated with adult-onset kidney disease and podocalyxin shedding into the urine is a common biomarker of a variety nephrotic syndromes. It is unknown, however, how various lesions in PODXL contribute to these disparate disease pathologies. Here we generated two mouse stains: one that deletes Podxl in developmentally mature podocytes (Podxl∆Pod ) and a second that is heterozygous for podocalyxin in all tissues (Podxl+/- )...

BACKGROUND: Glucocorticosteroid is used for patients with primary nephrotic syndrome. This study aims to identify and validate that biomarkers can be used to predict steroid resistance. METHODS: Our study contained two stages, discovery and validation stage. In discovery stage, we enrolled 51 minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS) patients treated with full dose steroid. Five urinary biomarkers including β2-microglobulin (β2-MG) and α1-microglobulin (α1-MG) were tested and candidates' biomarkers were selected based on their associations with steroid response...

BACKGROUND: Treatment with cyclosporine A (CsA), a calcineurin inhibitor, is effective in children with difficult idiopathic nephrotic syndrome (INS). Prolonged CsA treatment can result in several adverse effects, the most significant being nephrotoxicity (CsAN). The plasma and urine levels of the proteins annexin V (AnV) and uromodulin (UM) were investigated in order to assess their usefulness as indicators of early-stage CsAN. Uromodulin is considered a distal tubular damage marker...

Introduction: Childhood-onset nephrotic syndrome has a variable clinical course. Improved predictive markers of long-term outcomes in children with nephrotic syndrome are needed. This study tests the association between baseline urinary epidermal growth factor (uEGF) excretion and longitudinal kidney function in children with nephrotic syndrome. Methods: The study evaluated 191 participants younger than 18 years enrolled in the Nephrotic Syndrome Study Network, including 118 with their first clinically indicated kidney biopsy (68 minimal change disease; 50 focal segmental glomerulosclerosis) and 73 with incident nephrotic syndrome without a biopsy...

Vitamin D deficiency is frequent in pediatric nephrology. The 2017 European guidelines recommend keeping 25OH vitamin D (25-D) levels within the 75-120 nmol/L range, ideally with daily supplementation. Intermittent supplementation with D3 has also been proposed. We aimed to assess the influence of our local protocol of intermittent vitamin D supplementation on the evolution of 25-D levels between baseline and 2 months. VITATOL is a prospective single-center study performed in our tertiary unit in children and teenagers followed for chronic kidney disease (CKD), kidney transplantation, or stable chronic nephrotic syndrome with 25-D levels below 75 nmol/L...

BACKGROUND: Primary membranous glomerulonephritis (MGN) is a major cause of nephrotic syndrome in adults. Its diagnosis is based on invasive biopsy, and the current traditional serum or urinary biomarkers, such as the anti-phospholipase A2 receptor, are not adequately sensitive or specific. AIM OF THE STUDY: Our purpose is to identify a sensitive and specific noninvasive panel of biomarkers for the diagnosis of MGN by using metabolomic techniques and to explore the pathogenic pathways that are involved in disease development...

Renal Cysts and Diabetes Syndrome (RCAD) is an autosomal dominant disorder caused by mutations in the HNF1B gene encoding for the transcriptional factor hepatocyte nuclear factor-1B. RCAD is characterized as a multi-organ disease, with a broad spectrum of symptoms including kidney abnormalities (renal cysts, renal hypodysplasia, single kidney, horseshoe kidneys, hydronephrosis), early-onset diabetes mellitus, abnormal liver function, pancreatic hypoplasia and genital tract malformations. In the present study, using capillary electrophoresis coupled to mass spectrometry (CE-MS), we investigated the urinary proteome of a pediatric cohort of RCAD patients and different controls to identify peptide biomarkers and obtain further insights into the pathophysiology of this disorder...

Introduction: In last few years, several studies have revealed the remarkable stability of extracellular microRNAs (miRNAs) circulating in the blood or excreted in the urine and underscored their key importance as biomarkers of certain diseases. Since miRNA in urinary sediment is relatively stable and easily quantified, it has the potential to be developed as a biomarker for disease diagnosis and monitoring. Identification of serum and urinary levels of certain miRNAs may assist in the diagnosis and assessment of disease activity in patients with nephrotic syndrome (NS)...

BACKGROUND: Urinary exosomal miRNAs are gaining increasing attention for their potential as ideal non-invasive biomarkers for kidney diseases; however, little is known about their diagnostic ability for paediatric nephrotic syndrome (NS). This study explored the clinical value of urinary exosomal miRNAs for paediatric idiopathic NS. METHODS: Urine samples were collected from 129 NS children and 126 age-/sex-matched healthy controls. The miRNA profile of urinary exosomes was analysed by high-throughput Illumina sequencing via synthesis (SBS) technology followed by verification with a quantitative reverse-transcription polymerase chain reaction (RT-qPCR) assay arranged in two independent cohorts...