Urine Biomarkers and Kidney Outcomes: Impact of Indexing Versus Adjusting for Urine Creatinine

BackgroundNovel urine biomarkers may improve identification of children at greater risk of rapid kidney function decline, and elucidate the pathophysiology of CKD progression.MethodsWe investigated the relationship between urine biomarkers of kidney tubular health (EGF and α-1 microglobulin), tubular injury (kidney injury molecule-1; KIM-1), and inflammation (monocyte chemoattractant protein-1 [MCP-1] and YKL-40) and CKD progression. The prospective CKD in Children Study enrolled children aged 6 months to 16 years with an eGFR of 30–90ml/min per 1.73m2. Urine biomarkers were assayed a median of 5 months [IQR: 4–7] after study enrollment. We indexed the biomarker to urine creatinine by dividing the urine biomarker concentration by the urine creatinine concentration to account for the concentration of the urine. The primary outcome was CKD progression (a composite of a 50% decline in eGFR or kidney failure) during the follow-up period.ResultsOverall, 252 of 665 children (38%) reached the composite outcome over a median follow-up of 6.5 years. After adjustment for covariates, children with urine EGF concentrations in the lowest quartile were at a seven-fold higher risk of CKD progression versus those with concentrations in the highest quartile (fully adjusted hazard ratio [aHR], 7.1; 95% confidence interval [95% CI], 3.9 to 20.0). Children with urine KIM-1, MCP-1, and α-1 microglobulin concentrations in the highest quartile were also at significantly higher risk of CKD progression versus those with biomarker concentrations in the lowest quartile. Addition of the five biomarkers to a clinical model increased the discrimination and reclassification for CKD progression.ConclusionsAfter multivariable adjustment, a lower urine EGF concentration and higher urine KIM-1, MCP-1, and α-1 microglobulin concentrations were each associated with CKD progression in children.

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Relationship between Urine Creatinine and Urine Osmolality in Spot Samples among Men and Women in the Danish Diet Cancer and Health Cohort

Toxics ◽

10.3390/toxics9110282 ◽

2021 ◽

Vol 9 (11) ◽

pp. 282

Author(s):

Selinay Ozdemir ◽

Clara G. Sears ◽

James M. Harrington ◽

Aslak Harbo Poulsen ◽

Jessie Buckley ◽

...

Keyword(s):

Linear Regression ◽

Correlation Coefficients ◽

Selection Procedure ◽

Urine Osmolality ◽

Strongly Correlated ◽

Spearman Correlation ◽

Urine Biomarkers ◽

Urine Creatinine ◽

Muscle Catabolism ◽

The Relationship

Assays of urine biomarkers often use urine creatinine to account for urinary dilution, even though creatinine levels are influenced by underlying physiology and muscle catabolism. Urine osmolality—a measure of dissolved particles including ions, glucose, and urea—is thought to provide a more robust marker of urinary dilution but is seldom measured. The relationship between urine osmolality and creatinine is not well understood. We calculated correlation coefficients between urine creatinine and osmolality among 1375 members of a subcohort of the Danish Diet, Cancer, and Health Cohort, and within different subgroups. We used linear regression to relate creatinine with osmolality, and a lasso selection procedure to identify other variables that explain remaining variability in osmolality. Spearman correlation between urine creatinine and osmolality was strong overall (ρ = 0.90; 95% CI: 0.89–0.91) and in most subgroups. Linear regression showed that urine creatinine explained 60% of the variability in urine osmolality, with another 9% explained by urine thallium (Tl), cesium (Cs), and strontium (Sr). Urinary creatinine and osmolality are strongly correlated, although urine Tl, Cs, and Sr might help supplement urine creatinine for purposes of urine dilution adjustment when osmolality is not available.

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Faculty Opinions recommendation of Systematic review of the clinical effectiveness and cost-effectiveness of photodynamic diagnosis and urine biomarkers (FISH, ImmunoCyt, NMP22) and cytology for the detection and follow-up of bladder cancer.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718020265.793478738 ◽

2013 ◽

Author(s):

Thomas Guzzo

Keyword(s):

Systematic Review ◽

Bladder Cancer ◽

Cost Effectiveness ◽

Clinical Effectiveness ◽

Photodynamic Diagnosis ◽

Urine Biomarkers

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Urine biomarkers of renal renin–angiotensin system activity: Exploratory analysis in humans with and without obstructive sleep apnea

Physiological Reports ◽

10.14814/phy2.14376 ◽

2020 ◽

Vol 8 (6) ◽

Cited By ~ 1

Author(s):

Patrick J. Hanly ◽

Sofia Ahmed ◽

Chris D. Fjell ◽

George B. Handley ◽

Darlene Sola ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Renin Angiotensin System ◽

Exploratory Analysis ◽

Angiotensin System ◽

System Activity ◽

Renin Angiotensin ◽

Urine Biomarkers ◽

Obstructive Sleep

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Proteinuria in COVID-19: prevalence, characterization and prognostic role

Journal of Nephrology ◽

10.1007/s40620-020-00931-w ◽

2021 ◽

Author(s):

Justine Huart ◽

Antoine Bouquegneau ◽

Laurence Lutteri ◽

Pauline Erpicum ◽

Stéphanie Grosch ◽

...

Keyword(s):

Urinary Catheter ◽

Single Center ◽

Tubular Injury ◽

Tubular Proteinuria ◽

Prognostic Role ◽

Urine Creatinine ◽

Single Center Study ◽

Center Study

Abstract Background Proteinuria has been commonly reported in patients with COVID-19. However, only dipstick tests have been frequently used thus far. Here, the quantification and characterization of proteinuria were investigated and their association with mortality was assessed. Methods This retrospective, observational, single center study included 153 patients, hospitalized with COVID-19 between March 28th and April 30th, 2020, in whom total proteinuria and urinary α1-microglobulin (a marker of tubular injury) were measured. Association with mortality was evaluated, with a follow-up until May 7th, 2020. Results According to the Kidney Disease Improving Global Outcomes staging, 14% (n = 21) of the patients had category 1 proteinuria (< 150 mg/g of urine creatinine), 42% (n = 64) had category 2 (between 150 and 500 mg/g) and 44% (n = 68) had category 3 proteinuria (over 500 mg/g). Urine α1-microglobulin concentration was higher than 15 mg/g in 89% of patients. After a median follow-up of 27 [14;30] days, the mortality rate reached 18%. Total proteinuria and urinary α1-microglobulin were associated with mortality in unadjusted and adjusted models. This association was stronger in subgroups of patients with normal renal function and without a urinary catheter. Conclusions Proteinuria is frequent in patients with COVID-19. Its characterization suggests a tubular origin, with increased urinary α1-microglobulin. Tubular proteinuria was associated with mortality in COVID-19 in our restropective, observational study.

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Validity and Cost-Effectiveness of Pediatric Home Respiratory Polygraphy for the Diagnosis of Obstructive Sleep Apnea in Children: Rationale, Study Design, and Methodology

Methods and Protocols ◽

10.3390/mps4010009 ◽

2021 ◽

Vol 4 (1) ◽

pp. 9

Author(s):

Esther Oceja ◽

Paula Rodríguez ◽

María Jurado ◽

Maria Luz Alonso ◽

Genoveva del Río ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Cost Effectiveness ◽

Sleep Apnea ◽

Therapeutic Interventions ◽

Diagnostic Process ◽

Urine Biomarkers ◽

Obstructive Sleep ◽

Respiratory Polygraphy ◽

The Cost ◽

The Impact

Obstructive sleep apnea (OSA) in children is a prevalent, albeit largely undiagnosed disease associated with a large spectrum of morbidities. Overnight in-lab polysomnography remains the gold standard diagnostic approach, but is time-consuming, inconvenient, and expensive, and not readily available in many places. Simplified Home Respiratory Polygraphy (HRP) approaches have been proposed to reduce costs and facilitate the diagnostic process. However, evidence supporting the validity of HRP is still scarce, hampering its implementation in routine clinical use. The objectives were: Primary; to establish the diagnostic and therapeutic decision validity of a simplified HRP approach compared to PSG among children at risk of OSA. Secondary: (a) Analyze the cost-effectiveness of the HRP versus in-lab PSG in evaluation and treatment of pediatric OSA; (b) Evaluate the impact of therapeutic interventions based on HRP versus PSG findings six months after treatment using sleep and health parameters and quality of life instruments; (c) Discovery and validity of the urine biomarkers to establish the diagnosis of OSA and changes after treatment.

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The Effect of Cadmium on GFR Is Clarified by Normalization of Excretion Rates to Creatinine Clearance

International Journal of Molecular Sciences ◽

10.3390/ijms22041762 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1762

Author(s):

Soisungwan Satarug ◽

David A. Vesey ◽

Muneko Nishijo ◽

Werawan Ruangyuttikarn ◽

Glenda C. Gobe ◽

...

Keyword(s):

Creatinine Clearance ◽

Tubular Injury ◽

Creatinine Concentration ◽

Thai Subjects ◽

Urine Creatinine ◽

Wide Range ◽

Nephron Loss ◽

Urine Cadmium ◽

Excretion Rates ◽

Cd Exposure

Erroneous conclusions may result from normalization of urine cadmium and N-acetyl-β-D-glucosaminidase concentrations ([Cd]u and [NAG]u) to the urine creatinine concentration ([cr]u). In theory, the sources of these errors are nullified by normalization of excretion rates (ECd and ENAG) to creatinine clearance (Ccr). We hypothesized that this alternate approach would clarify the contribution of Cd-induced tubular injury to nephron loss. We studied 931 Thai subjects with a wide range of environmental Cd exposure. For x = Cd or NAG, Ex/Ecr and Ex/Ccr were calculated as [x]u/[cr]u and [x]u[cr]p/[cr]u, respectively. Glomerular filtration rate (GFR) was estimated according to the Chronic Kidney Disease (CKD) Epidemiology Collaboration (eGFR), and CKD was defined as eGFR < 60 mL/min/1.73m2. In multivariable logistic regression analyses, prevalence odds ratios (PORs) for CKD were higher for log(ECd/Ccr) and log(ENAG/Ccr) than for log(ECd/Ecr) and log(ENAG/Ecr). Doubling of ECd/Ccr and ENAG/Ccr increased POR by 132% and 168%; doubling of ECd/Ecr and ENAG/Ecr increased POR by 64% and 54%. As log(ECd/Ccr) rose, associations of eGFR with log(ECd/Ccr) and log(ENAG/Ccr) became stronger, while associations of eGFR with log(ECd/Ecr) and log(ENAG/Ecr) became insignificant. In univariate regressions of eGFR on each of these logarithmic variables, R2 was consistently higher with normalization to Ccr. Our tabular and graphic analyses uniformly indicate that normalization to Ccr clarified relationships of ECd and ENAG to eGFR.

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Genetic variations of SCNA7 and blood pressure potassium interaction

European Heart Journal ◽

10.1093/ehjci/ehaa946.2702 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

C Delgado ◽

M Delgado-Lelievre ◽

D Lelievre ◽

A Delgado-Almeida

Keyword(s):

Blood Pressure ◽

Strong Correlation ◽

Genetic Variations ◽

Sodium Potassium ◽

Blood Institute ◽

Urine Creatinine ◽

National Heart Lung ◽

Gated Channel ◽

K Concentration ◽

The Relationship

Abstract Introduction The sodium voltage-gated channel alpha subunit 7 (SCN7A) has been associated to renal Na regulation and hypertension. This study explores the relationship between blood pressure (BP) and urinary overnight Na/K ratio (UONaK) in hypertensives (HT) and normotensive (NT) subjects from from National Heart, Lung and Blood Institute funded, Family Blood Pressure Program (FBPP) that were genotyped for 3 SNPs for SCN7A: CV2161217, CV 356958 and CV433036. Hypothesis Genetic variations in the SCNA7 are differently associated to BP and UONaK in HT and NT. Methods 1,749 subjects genotyped for SCN7A SNPs CV2161217, CV 356958 and CV433036 were analyzed from FBPP. Subjects with diastolic BP (DBP) ≥80 or systolic BP (SBP) ≥130 mmHg were classified HTN; subjects with SBP <130 and DBP <80 mmHg were classified as NT. UONAK was calculated by dividing overnight Na by K concentration. Correlation analysis done with partial variables (use of antihypertensive drug, use of diuretics, overnight urine creatinine). Results For the CV2161217, HTN group (n=1,030), 52% had C/C, 39% C/T and 9% T/T. In NT group (n=719), 52% had C/C, 38% C/T and 10% T/T. In the HT group, subjects with CC genotype showed strong correlation between DBP and UONaK (Fig 1a) while no significant correlation with SBP. Those with CT genotype maintained the correlation between SBP and UONaK (r=0.10, p=0.03) with no correlation with SBP. The TT showed no correlation between UONaK and SBP or DBP. In the NT, subjects with TT genotype showed strong correlation between DBP and UONaK (Fig 1b) and with SB (r=0.256, p=0.03). Those with CT or TT genotypes showed no correlation between UONaK and SBP or DBP. Similar finding were obtained for CV356958 SNP; no similar association was observed in the CV433036 SNP. Conclusions Subjects with the genetic variations in the SCNA7, such as CV2161217 and CV 356958 SNPs, showed significant correlation between blood pressure and overnight urinary sodium potassium. This finding could have important implications in non dipping status observed in some hypertensive patients. Funding Acknowledgement Type of funding source: None

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