Bone Morphogenetic Proteins (BMPs), Extracellular Matrix Metalloproteinases Inducer (EMMPRIN), and Macrophage Migration Inhibitory Factor (MIF): Usefulness in the Assessment of Tubular Dysfunction Related to Chronic Kidney Disease (CKD)

Bone morphogenetic proteins (BMP), extracellular matrix metalloproteinases inducer (EMMPRIN), and macrophage migration inhibitory factor (MIF) are known to be closely connected to renal tubule damage by experimental data; however, this has not been analyzed in children with chronic kidney disease (CKD). The aim of this study was to determine their usefulness in the assessment of CKD-related tubular dysfunction. The study group consisted of 61 children with CKD stages 1–5 and 23 controls. The serum and urine concentrations of BMP-2, BMP-6, EMMPRIN, and MIF were assessed by ELISA and their fractional excretion (FE) was calculated. The serum and urine concentrations of BMP-2, BMP-6, EMMPRIN, and MIF were significantly elevated in children with CKD vs. controls. The FE of BMP-2, FE BMP-6, and EMMPRIN increased significantly in CKD stages 1–2, but exceeded 1% in CKD stages 3–5. FE MIF became higher than in controls no sooner than in CKD 3–5, but remained below 1%. The FE values for BMP-2, BMP-6, and EMMPRIN of <1% may result from the tubular adaptive mechanisms, whereas those surpassing 1% suggest irreversible tubular damage. The analysis of serum/urinary concentrations and fractional excretion of examined parameters may allow the assessment of CKD-related tubular dysfunction.

Renal profile and urinary fractional excretion of calcium, phosphorus, and magnesium of lambs fed with different contents of phosphorus

Obstructive urolithiasis is common in confined sheep, and a predominant factor predisposing animals to this condition is nutritional management. The objective of this study was to evaluate the effect of different concentrations of phosphorus (P) on urinalysis, serum urea and creatinine, and serum and urine concentrations of calcium (Ca), P, and magnesium (Mg), as well as to establish the fractional excretion (FE) of these elements in confined lambs. Thirty male Santa Inês x Ile de France sheep at four months of age were divided into two groups according to the diet: Group 1 (G1, n = 15), with 0.43% P in their feed; and Group 2 (G2, n = 15) with 0.65% P. The diets consisting of 10% Coast-cross hay and 90% of a concentrate of soybean meal, wheat, and crushed corn were provided for 90 consecutive days, with water ad libitum. The time points (M) of blood and urine collection were determined as M0, immediately before the beginning of the diet, and at 15-day intervals: M1, M2, M3, M4, M5, and M6. Phosphorous-rich diets favored the appearance of triple phosphate crystals in both groups, causing calculogenesis in more than one third of the animals (11/30), emphasizing the relevance of conducting laboratory tests to aid in urolithiasis diagnosis. In addition, FE revealed an increased renal excretion of excess minerals in the diet, and therefore a greater predisposition for stone formation in relation to nutritional management.

The 5HTOL/5HIAA Ratio as a Biomarker of Alcohol Hangover

Assessment of the presence and severity of alcohol hangovers relies on the subjective method of self-report. Therefore, there is a need of adequate biomarkers that (1) correlate significantly with hangover severity, and (2) correspond to the level of hangover-related performance impairment objectively. In this naturalistic study, n = 35 social drinkers participated. Urine samples were obtained the morning after alcohol consumption and after an alcohol-free control day. Concentrations of 5-hydroxytryptophol (5-HTOL), 5-hydroxyindoleacetic acid (5-HIAA) and the 5-HTOL/5-HIAA ratio were determined. The results confirm previous findings that 5-HTOL and the 5HTOL/5-HIAA ratio are useful biomarkers of recent alcohol consumption. Significant correlations were found with the amount of alcohol consumed, total drink time, and estimated BAC. However, urine concentrations of 5-HTOL and 5-HIAA (and their ratio 5HTOL/5-HIAA) did not significantly correlate with hangover severity. In conclusion, urine 5-HTOL, 5-HIAA, and the 5HTOL/5-HIAA ratio cannot be considered to be suitable biomarkers of alcohol hangover.

Initial Evaluation of Uroplakins UPIIIa and UPII in Selected Benign Urological Diseases

BackgroundUroplakins (UPs) are glycoproteins that play a specific role in the structure and function of the urothelium. Disorders of normal expression of uroplakins are associated with the pathogenesis of infections and neoplasms of the urinary tract, primary vesicoureteral reflux, hydronephrosis and renal dysfunction. The appearance of uroplakins in the urine and/or plasma may be of potential importance in the detection of urinary tract dysfunction. The aim of the study was to investigate uroplakin IIIa (UPIIIa) and uroplakin II (UPII) expression in patients with selected urological diseases. Plasma and urine from patients with benign prostatic hyperplasia (BPH), urethral stricture (US), urinary tract infection (UTI) and urolithiasis, were compared to healthy people without urological disorders. MethodsA total 152 of human urine and plasma samples from normal and patients with selected benign urological diseases were analyzed. UPs concentration was measured by immunoenzymatic method. All calculations were done using the STATISTICA 13.3 (TIBCO software Inc.).ResultsIn patients with BPH and UTI, UPIIIa in urine and plasma also UPII in urine concentrations were statistically significantly higher than in the control groups. In the US group, only the plasma UPIIIa concentration differed significantly from the control. There were no significant differences between the concentrations of UPs compared to the controls in both the urine and plasma of patients with urolithiasis. ConclusionThe conducted research shows that benign urological diseases may affect the state of the urothelium, as manifested by an increased concentration of both UPs in patients’ urine and plasma, especially in BPH and UTI.

Associations of maternal bisphenol urine concentrations during pregnancy with neonatal metabolomic profiles

Background Fetal exposure to bisphenols is associated with altered fetal growth, adverse birth outcomes and childhood cardio-metabolic risk factors. Metabolomics may serve as a tool to identify the mechanisms underlying these associations. We examined the associations of maternal bisphenol urinary concentrations in pregnancy with neonatal metabolite profiles from cord blood. Methods In a population-based prospective cohort study among 225 mother–child pairs, maternal urinary bisphenol A, S and F concentrations in first, second and third trimester were measured. LC–MS/MS was used to determine neonatal concentrations of amino acids, non-esterified fatty acids (NEFA), phospholipids (PL), and carnitines in cord blood. Results No associations of maternal total bisphenol concentrations with neonatal metabolite profiles were present. Higher maternal average BPA concentrations were associated with higher neonatal mono-unsaturated alkyl-lysophosphatidylcholine concentrations, whereas higher maternal average BPS was associated with lower neonatal overall and saturated alkyl-lysophosphatidylcholine (p-values < 0.05).Trimester-specific analyses showed that higher maternal BPA, BPS and BPF were associated with alterations in neonatal NEFA, diacyl-phosphatidylcholines, acyl-alkyl-phosphatidylcholines, alkyl-lysophosphatidylcholine, sphingomyelines and acyl-carnitines, with the strongest effects for third trimester maternal bisphenol and neonatal diacyl-phosphatidylcholine, sphingomyeline and acyl-carnitine metabolites (p-values < 0.05). Associations were not explained by maternal socio-demographic and lifestyle characteristics or birth characteristics. Discussion Higher maternal bisphenol A, F and S concentrations in pregnancy are associated with alterations in neonatal metabolite profile, mainly in NEFA, PL and carnitines concentrations. These findings provide novel insight into potential mechanisms underlying associations of maternal bisphenol exposure during pregnancy with adverse offspring outcomes but need to be replicated among larger, diverse populations.

Low Urine Secretion of Semaphorin3A In Lupus Patients With Proteinuria

Background: Immune semaphorins are important players in controlling both innate and adaptive immune responses. The regulatory role of semaphorin3A (sema3A) in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and other autoimmune diseases is widely reported. Decreased levels of serum sema3A were shown to be associated with SLE disease activity. Objectives: To assess urine concentrations of sema3A in SLE patients and its correlation with renal involvement and disease activity. Methods: Urine levels of sema3A were analyzed in 38 SLE patients of whom 13 had renal involvement and were compared to 10 healthy controls and 8 RA patients (disease control group). Results: The secretion of urine sema3A was found to be significantly lower in SLE patients compared to healthy controls and RA patients (4.9±3.9 ng/ml, 8.5±2.7 ng/ml, 9.85±1.7 ng/ml, respectively, p = 0.0006). Urine sema3A was significantly lower in SLE patients with lupus nephritis than in patients without nephritis (4.0±3.4 ng/ml vs 6.5±3.8 ng/ml, p=0.03). Urine sema3A was inversely correlated with proteinuria and SLE disease activity. Conclusion: Urine sema3A is decreased in lupus patients and should be further evaluated as a possible biomarker for disease activity and renal involvement.

The validity urine color scoring at different light conditions to assess low versus high urine concentration

Context: Urine color (Uc) is used to asses urine concentration when lab techniques are not feasible. Objective: To compare the accuracy of Uc scoring using four different light conditions and two different scoring techniques with a 7-color Uc chart. Additionally to assess the results' generalizability, a subsample was compared to scores obtained from fresh samples. Design: Descriptive laboratory study. Samples: 178 previously frozen urine samples were scored and n=78 samples were compared to its own fresh outcomes. Main outcome measure: Urine color and accuracy for classifying urine samples were calculated using receiver operating characteristics (ROC) analysis, allowing to compare the diagnostic capacity against a 1.020 urine specific gravity (USG) cut-off and defining optimal Uc cut-off value. Results: Uc was significantly different between light conditions (P&lt;0.01), with the highest accuracy (80.3%) of correctly classifications of low or high urine concentrations occurring at the brightest light condition. Lower light intensity scored 1.5–2 shades darker on a 7-color Uc scale than bright conditions (P&lt;0.001), with urine color but no further practical differences for accuracy between scoring techniques. Frozen was 0.5–1 shade darker than freshly measured Uc (P&lt;0.004), but they were moderately correlated (r=0.64). A Bland-Altman plot showed that reporting bias mainly affects darker Uc without impacting the diagnostic ability of the method. Conclusions: Uc scoring, accuracy and Uc cut-off values are affected by lighting condition but not by scoring technique, with higher accuracy and a one-shade lower Uc cut-off value at the brightest light (i.e. LED flashlight).