Utility of Self-Reported Heat Stress Symptoms and NGAL Biomarker to Screen for Chronic Kidney Disease of Unknown Origin (CKDu) in Sri Lanka

Objective. We examined heat stress symptoms and urine markers of chronic kidney disease (CKDu) in Sri Lanka to assess differences between endemic vs. non-endemic regions and by occupation. Sample and Methods. We assessed a total of 475 villagers. In the endemic region, 293 were agricultural workers and 67 were not working primarily in agriculture. In the non-endemic region, 76 were agricultural workers. Of the residents, 218 were assessed for neutrophil gelatinase-associated lipocalin (NGAL), an early predictor of acute kidney injury, along with urine markers of chronic kidney disease. Results. The mean (sd) age of the sample was 45.2 (12.6), with males comprising 52.7%; 7.2% reported kidney disease (n = 34), and 5.7% reported diabetes (n = 27). The heat stress index (mean (sd)) was highest among agricultural workers in the endemic region (8.05 (5.9)), intermediate in non-agricultural workers in the endemic region (4.61 (4.5)), and lowest among agricultural workers in the non-endemic region (3.85 (3.3)); p < 0.0001. Correlations were higher between NGAL and serum microalbumin in the endemic agricultural worker sample than in the other two samples (Spearman’s r = 0.34 vs. 0.15 and 0.20). Conclusions. Both heat stress symptoms and NGAL values were higher among agricultural workers in endemic CKDu regions. Correlations between NGAL and microalbumin suggested a link between acute kidney injury and chronic kidney disease in the more-exposed sample.

Urine Sediment Findings and the Immune Response to Pathologies in Fungal Urinary Tract Infections Caused by Candida spp.

Fungi are pathogenic agents that can also cause disseminated infections involving the kidneys. Besides Candida, other agents like Cryptococcus spp. can cause urinary tract infection (UTI), as well as other non-yeast fungi, especially among immunocompromised patients. The detection and identification of fungi in urine samples (by microscopy and culture) plays an essential role in the diagnosis of fungal UTI. However, variable cutoff definitions and unreliable culture techniques may skew analysis of the incidence and outcome of candiduria. The sediment analysis plays a key role in the identification of fungal UTI because both yeasts and pseudohyphae are easily identified and can be used as a clinical sign of fungal UTI but should not be overinterpreted. Indeed, urine markers of the immune response (leukocytes), urine barriers of tissue protection (epithelial cells), and urine markers of kidney disease (urinary casts) can be found in urine samples. This work explores the manifestations associated with the fungal UTI from the urinalysis perspective, namely the urinary findings and clinical picture of patients with fungal UTI caused by Candida spp., aspects associated with the immune response, and the future perspectives of urinalysis in the diagnosis of this clinical condition.

Urinary-Based Markers for Bladder Cancer Detection

Background The use of urine markers for diagnosis and surveillance has been a topic of broad interest and ongoing controversies in the management of patients with bladder cancer. There has been a constant quest for markers that demonstrate clinical utility. Aim In the framework of the International Consultation on Urological Diseases 2019 on Molecular Biomarkers in Urologic Oncology, a comprehensive review of literature on urinary biomarkers for bladder cancer has been performed. Results Currently available urinary markers include protein-based markers, RNA-based markers, and DNA-based markers. The introduction of high-throughput analysis technologies provides the opportunity to assess multiple parameters within a short period of time, which is of interest for RNA-based, DNA-based, and protein-based marker systems. A comprehensive analysis of molecular alterations in urine samples of bladder cancer patients may be of interest not only for diagnosis and surveillance but also for non-invasive longitudinal assessment of molecular, potentially therapy-relevant, alterations. However, most systems lack prospective validation within well-designed trials and have not been broadly implemented in daily clinical practice. Conclusions Because of limited data from prospective trials, the routine use of any urine marker except cytology is not considered as standard of care in international guidelines. There is an urgent need for prospective trials of urine markers to answer specific clinical questions.

Timing of Turmeric Consumption and Oxidative Stress

Objectives The objective of this study was to compare the effects of morning vs. evening consumption of turmeric on urine markers of oxidative stress. The hypothesis stated that turmeric's action to modulate transcription of diurnally regulated genes coding for oxidative defense proteins would be influenced by the timing of turmeric consumption. Methods Participants prepared for each of four lab visits by consuming a low-antioxidant diet for two days and fasting for 12 hours. After providing a baseline urine sample, participants consumed one of two test meals (5 g turmeric + 180 ml egg white or egg white alone) at one of two clock times (morning or evening). A 1-week washout separated each visit. Urine was collected in the lab at 1 hour post-meal and at home for the following 5 hours. Urine biomarkers of oxidative stress were quantified using enzyme-linked immunosorbent assays; values were normalized to urine creatinine concentration. General Linear Models were used to predict biomarker levels over timepoints by turmeric intake and clock time. Results Participant (n = 4, 3 male) body mass index and age (median and range) were 33.3 (31.4–34.0) and 60.5 y (53–63). Urine 8-isoprostane concentration was significantly higher following consumption of the turmeric vs. control meal and after the 2-4-hour compared to 0-2-hour post-meal timepoint. The turmeric meal was not associated with urine malondialdehyde level. There was no significant interaction between turmeric consumption and clock time on either biomarker level. Conclusions Consuming turmeric at morning vs. evening did not differentially affect urine markers of oxidative stress. Studies of larger cohorts with measurements of oxidative stress markers over 24 hours would show whether these pilot results are generalizable. Funding Sources Academy of Nutrition and Dietetics Foundation, McCormick Science Institute Research Award; Academy of Nutrition and Dietetics Medical Nutrition Practice Group.

Urine Markers of Kidney Tubule Cell Injury and Kidney Function Decline in SPRINT Trial Participants with CKD

Background and objectiveseGFR and albuminuria primarily reflect glomerular function and injury, whereas tubule cell atrophy and interstitial fibrosis on kidney biopsy are important risk markers for CKD progression. Kidney tubule injury markers have primarily been studied in hospitalized AKI. Here, we examined the association between urinary kidney tubule injury markers at baseline with subsequent loss of kidney function in persons with nondiabetic CKD who participated in the Systolic Blood Pressure Intervention Trial (SPRINT).Design, setting, participants, & measurementsAmong 2428 SPRINT participants with CKD (eGFR<60 ml/min per 1.73 m2) at baseline, we measured urine markers of tubule injury (IL-18, kidney injury molecule-1 [KIM-1], neutrophil gelatinase-associated lipocalin [NGAL]), inflammation (monocyte chemoattractant protein-1 [MCP-1]), and repair (human cartilage glycoprotein-40 [YKL-40]). Cox proportional hazards models evaluated associations of these markers with the kidney composite outcome of 50% eGFR decline or ESKD requiring dialysis or kidney transplantation, and linear mixed models evaluated annualized change in eGFR.ResultsMean participant age was 73±9 (SD) years, 60% were men, 66% were white, and mean baseline eGFR was 46±11 ml/min per 1.73 m2. There were 87 kidney composite outcome events during a median follow-up of 3.8 years. Relative to the respective lowest quartiles, the highest quartiles of urinary KIM-1 (hazard ratio, 2.84; 95% confidence interval [95% CI], 1.31 to 6.17), MCP-1 (hazard ratio, 2.43; 95% CI, 1.13 to 5.23), and YKL-40 (hazard ratio, 1.95; 95% CI, 1.08 to 3.51) were associated with higher risk of the kidney composite outcome in fully adjusted models including baseline eGFR and urine albumin. In linear analysis, urinary IL-18 was the only marker associated with eGFR decline (−0.91 ml/min per 1.73 m2 per year for highest versus lowest quartile; 95% CI, −1.44 to −0.38), a finding that was stronger in the standard arm of SPRINT.ConclusionsUrine markers of tubule cell injury provide information about risk of subsequent loss of kidney function, beyond the eGFR and urine albumin.

Soluble TNF-R1, VEGF and other cytokines as markers of disease activity in systemic lupus erythematosus and lupus nephritis

Background Current non-invasive methods of assessing disease activity in systemic lupus erythematosus (SLE) are of limited sensitivity and specificity. Testing includes acute phase markers, autoantibodies and complement levels. Although measurements of dsDNA antibodies and complement C3/C4 levels are routine, they remain of limited value. Improved blood and urine markers may help in early detection of flare, distinction between flare and chronic damage, and monitoring response to therapy. Methods A total of 87 patients with SLE were tested for the following cytokines in serum and urine: monocyte chemoattractant protein 1 (MCP-1), regulated upon activation, normal T cell expressed and secreted (RANTES), soluble tumour necrosis factor receptor 1 (sTNF-R1), interferon-inducible protein 10 (IP-10), monocyte inhibitory protein 1α (MIP-1α) and vascular endothelial growth factor (VEGF). Patients attending the Lupus Unit at St Thomas’ Hospital, London, UK were divided into active lupus nephritis (LN), inactive LN and non-renal SLE groups based on their renal pathology and SLE disease activity index (SLEDAI). Cytokine testing was performed using the FIDIS multiplex bead assay. Results The mean level of serum sTNF-R1 was higher in the active LN group compared with both inactive LN and non-renal SLE groups ( p < 0.001). For urine measurements there were significant differences between active LN and non-renal SLE for VEGF ( p = 0.016), after statistical correction for multiple testing. Both urinary and serum sTNF-R1 and IP-10 levels correlated with SLEDAI scores ( p < 0.001), while serum VEGF correlated weakly with SLEDAI ( p = 0.025). The optimum combination for differentiating active from inactive LN patients was serum VEGF, sTNF-R1, MCP-1 and glomerular filtration rate plus urinary sTNF-R1 and protein-creatinine ratio. Conclusion These results indicate that for active LN, sTNF-R1 could be a useful serum cytokine marker, with potential for VEGF in the urine. This study has confirmed the ability of the multiplex bead technique to detect cytokines in a good analytical range, including very low and high levels, in both serum and urine. Combining serum and urine markers provided additional sensitivity in distinguishing active from inactive LN.