Kidney injury molecule-1: potential biomarker of acute kidney injury and disease severity in patients with COVID-19

Aims The aim of the current study was to evaluate whether tubular markers kidney injury molecule-1 (KIM-1) and N-acetyl-ß-glucosaminidase (NAG) are related to acute kidney injury (AKI) and severe disease in patients with COVID-19. Methods and results In this prospective observational clinical trial we examined a cohort of 80 patients with proof of acute respiratory infection and divided them into a COVID-19 cohort (n = 54) and a control cohort (n = 26). KIM-1 and NAG were measured from urine samples collected in the emergency department. We assessed the development of AKI, admission to the intensive care unit (ICU) and intrahospital death as clinical endpoints. Urinary KIM-1 and NAG were not significantly different between patients with SARS-CoV-2 and those with other respiratory infections (each p = n.s.). Eight patients from the COVID-19 cohort and five of the non-COVID-19-patients suffered from acute kidney injury during their stay. Nine COVID-19 patients and two non-COVID-19 patients were admitted to the ICU. KIM-1 was significantly elevated in COVID-19 patients with, compared to those without AKI (p = 0.005), as opposed to NAG and creatinine (each p = n.s.). Furthermore, KIM-1 was significantly elevated in the patients with COVID-19 that had to be transferred to the ICU (p = 0.015), in contrast to NAG and creatinine (each p = n.s.). Conclusion Assessing KIM-1 in patients with COVID-19 might provide additional value in recognizing AKI at an early stage of disease. Further, KIM-1 might indicate higher risk for clinical deterioration as displayed by admission to the ICU. Graphical abstract

MO024THE ROLE AND MECHANISM OF DECOY RECEPTOR DCR2 IN EMBRYONIC KIDNEY DEVELOPMENT

Background and Aims Decoy receptor 2 (DcR2), a transmembrane receptor of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), has been regarded as a hallmark of cell senescence. This study aimed to explore the role and the potential mechanism of DcR2 in the embryonic kidney development. Method The 12.5d, 16.5d, 20.5d embryonic kidney and mature renal tissue (8w) form WT and DcR2-KO mice were obtained. The ureteric buds, S-shaped bodies, renal vesicles were observed by periodic Acid-Schiff staining. The expression of DcR2 were detected by IHC. The co-expression of DcR2 and proximal tubular markers (AQP-1, villin), distal tubular markers (AQP-2), senescent markers (P16, LaminB1), proliferation markers (Ki-67, PCNA, Edu) were analyzed by confocal. Results In WT kidneys, DcR2 were specifically expressed in the tubules and the percentage of DcR2 expression were higher than mature renal tissue. In addition, the expression of tubular DcR2 were significantly decreased in DcR2-KO kidney than WT. The number of ureteric buds, S-shaped bodies, renal vesicles were decreased in DcR2-KO kidney than WT. And the cortex of DcR2-KO kidney were thinner and medullar were enlarger than WT. DcR2 were co-expressed with proximal tubular markers AQP-1 and villin, but not with distal tubular markers AQP-2. Furthermore, DcR2 were co-expressed with senescent markers P16 and LaminB1, but not with proliferation markers Ki-67, PCNA, Edu. Conclusion DcR2 is specifically expressed in proximal tubular cells in embryonic kidney, and DcR2 is involved in early renal development. The potential mechanism is related to cell senescence participating in tissue remodeling and inhibiting cell proliferation.

Changes in Renal Function After Switching From TDF to TAF in HIV-Infected Individuals: A Prospective Cohort Study

Background Replacing tenofovir disoproxil fumarate (TDF) with tenofovir alafenamide (TAF) improves renal tubular markers in HIV-infected individuals but the impact on estimated glomerular filtration rate (eGFR) remains unclear. Methods In all participants from the Swiss HIV Cohort Study who switched from TDF to TAF-containing antiretroviral regimen or continued TDF, we estimated changes in eGFR and urine protein-to-creatinine ratio (UPCR) after 18 months using mixed-effect models. Results Of 3520 participants (26.6% women, median age 50 years), 2404 (68.5%) switched to TAF. Overall, 1664 (47.3%) had an eGFR <90 mL/min and 1087 (30.9%) an UPCR ≥15 mg/mmol. In patients with baseline eGFR ≥90 mL/min, eGFR decreased with the use of TDF and TAF (−1.7 mL/min). Switching to TAF was associated with increases in eGFR of 1.5 mL/min (95% confidence interval [CI], .5–2.5) if the baseline eGFR was 60–89 mL/min, and 4.1 mL/min (95% CI, 1.6–6.6) if <60 mL/min. In contrast, eGFR decreased by 5.8 mL/min (95% CI, 2.3–9.3) with continued use of TDF in individuals with baseline eGFR <60 mL/min. UPCR decreased after replacing TDF by TAF, independent of baseline eGFR. Conclusions Switching from TDF to TAF improves eGFR and proteinuria in patients with renal dysfunction.

Urinary Tubular Markers’ for Early Detection on Onset and Progression of Diabetic Nephropathy: Systematic Review

Diabetic nephropathy, a Diabetes Mellitus’ complication, leads to chronic renal failure. Previous studies found that proximal tubule of nephron, as the initial pathogenesis of DN, precedes state of albuminuria as the current biomarker of DN. This study aimed to propose the earliest and the most accurate tubular biomarkers in predicting onset of DN and assess progression of DN. Systematic review was performed to evaluate the validity and accuracy of tubular biomarkers based on available studies in EBSCO, PubMed, and Google Scholar. Validity was measured by scoring system including studies’ methodological quality assessment based on Standards for Reporting of Diagnostic Accuracy and adjustment score to DN conventional factors. Accuracy evaluation was reviewed based on accuracy value provided. From the total of 560 studies, 10 included studies were assessed and 5 biomarkers were compared. All studies were considered valid, except one study on NGAL marker. Based on their likelihood ratios for clinical application, N-acetyl-β-D-glucosaminidase (NAG) has the best accuracy in predicting onset of DN and Cystatin C in assessing progression of DN. Detection of these biomarkers could be applied clinically through quantitative and semi-quantitative method for potential use in all healthcare levels and locations. This review proposed the usage of NAG and Cystatin C as early and accurate diabetic nephropathy tubular biomarkers in all healthcare level.

Proteinuria-associated renal magnesium wasting leads to hypomagnesemia: a common electrolyte abnormality in chronic kidney disease

Background Hypomagnesemia (Hypo-Mg) predicts mortality and chronic kidney disease (CKD) progression. However, in CKD, its prevalence, kidney-intrinsic risk factors, and the effectiveness of oral magnesium (Mg) therapy on serum Mg levels is uncertain. Methods In a cross-sectional study enrolling pre-dialysis outpatients with CKD, the prevalence of electrolyte abnormalities (Mg, sodium, potassium, calcium and phosphorus) was compared. In an open-label randomized controlled trial (RCT), we randomly assigned CKD patients to either the magnesium oxide (MgO) or control arm. The outcome was serum Mg levels at 1 year. Results In 5126 patients, Hypo-Mg was the most common electrolyte abnormality (14.7%) with similar prevalence across stages of CKD. Positive proteinuria was a risk factor of Hypo-Mg (odds ratio 2.2; 95% confidence interval 1.2–4.0). However, stratifying the analyses by diabetes mellitus (DM), it was not significant in DM (Pinteraction = 0.04). We enrolled 114 patients in the RCT. Baseline analyses showed that higher proteinuria was associated with higher fractional excretion of Mg. This relationship between proteinuria and renal Mg wasting was mediated by urinary tubular markers in mediation analyses. In the MgO arm, higher proteinuria or tubular markers predicted a significantly lower 1-year increase in serum Mg. In patients with a urinary protein-to-creatinine ratio (uPCR) <0.3 g/gCre, serum Mg at 1 year was 2.4 and 2.0 mg/dL in the MgO and control arms, respectively (P < 0.001), with no significant between-group difference in patients whose uPCR was ≥0.3 g/gCre (Pinteraction=0.001). Conclusions Proteinuria leads to renal Mg wasting through tubular injuries, which explains the high prevalence of Hypo-Mg in CKD.