Nephron
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Here, we review the most recent findings on the effects of SARS-CoV-2 infection on kidney diseases, including acute kidney injury, and examine the potential effects of ARBs on the outcomes of patients with COVID-19. Lastly, we discuss the clinical management of COVID-19 patients with existing chronic renal disorders, particularly those in dialysis and with kidney transplants.
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Glomerular hyperfiltration (GH) is a hallmark of renal dysfunction in diabetes and obesity. Recent clinical trials demonstrated that SGLT2 inhibitors are renoprotective, possibly by abating hyperfiltration. The present review considers the current evidence for a cause-to-effect relationship between hyperfiltration-related physical forces and the development of chronic kidney disease (CKD). ⋯ Glomerular hyperfiltration is associated with glomerular and tubular hypertrophy. Hyperfiltration is mainly due to an increase in glomerular capillary pressure, which increases tensile stress applied to the capillary wall structures. In addition, the increased ultrafiltrate flow into Bowman's space heightens shear stress on the podocyte foot processes and body surface. These mechanical stresses lead to an increase in glomerular basement membrane (GBM) length and to podocyte hypertrophy. The ability of the podocyte to grow being limited, a mismatch develops between the GBM area and the GBM area covered by foot processes, leading to podocyte injury, detachment of viable podocytes, adherence of capillaries to parietal epithelium, synechia formation and segmental sclerosis. Mechanical stress is also applied to post-filtration structures, resulting in dilation of glomerular and tubular urinary spaces, increased proximal tubular sodium reabsorption by hypertrophied epithelial cells and activation of mediators leading to tubulointerstitial inflammation, hypoxia and fibrosis Key Messages: GH-related mechanical stress leads to both adaptive and maladaptive glomerular and tubular changes. These flow-related effects play a central role in the pathogenesis of glomerular disease. Attenuation of hyperfiltration is thus an important therapeutic target in diabetes and obesity-induced CKD.
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Although the epidemiology of acute kidney injury (AKI) has been well described, less is known about recurrent AKI (r-AKI). We undertook a systematic review to identify incidence, risk factors, and outcomes of r-AKI. ⋯ From 2,824 citations, 10 cohort studies met inclusion criteria (total patients n = 538,667). There were 2 distinct set of studies; 4 studies assessed r-AKI within the same hospital admission (most were intensive care unit [ICU] patients) and 6 studies assessed postdischarge r-AKI. The median percentage of people developing r-AKI within the same hospital admission was 23.4% (IQR 20.3-27.2%) and postdischarge r-AKI was 31.3% (IQR 26.4-33.7%). A higher Acute Physiology and Chronic Health Evaluation score was associated with increased risk of r-AKI within the same hospital admission in ICU patients. Cardiovascular disease and AKI severity were associated with increased risk of postdischarge r-AKI. R-AKI (within same admission and postdischarge) was associated with worse survival. It was not possible to pool results due to methodological differences across studies, such as varying definitions for AKI and r-AKI, varying length of follow-up and effect measures. Key messages: More representative population-based studies with robust assessment of predictors and consensus definition of r-AKI are needed to identify risk factors and develop risk stratification tools to reduce recurrence and improve outcomes. Systematic Review Registration: CRD42017082668.
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Review
Immunomodulatory and Kidney-Protective Effects of the Human Chorionic Gonadotropin Derivate EA-230.
The systemic inflammatory response following infectious or non-infectious insults is related to morbidity (including acute kidney injury) and mortality. Pregnancy is associated with immunotolerance and an increased glomerular filtration rate. ⋯ Furthermore, an excellent safety profile of EA-230 was observed in phase 1 studies in humans, and the immunomodulatory effects of EA-230 were recently demonstrated in a phase IIa study during human experimental endotoxemia. A prospective double-blind placebo-controlled randomized trial in 180 patients undergoing elective CABG-surgery with or without valve surgery is currently conducted to investigate the immunomodulatory and renoprotective properties of EA-230.
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Several cellular and molecular targets and mechanisms have been investigated in preclinical studies of acute kidney injury (AKI), but translation in successful clinical studies has failed to date. This article reviews many issues that have limited this and the potential future perspectives in AKI prevention and treatment. ⋯ Preclinical models of AKI should closely mimic the complexity of human AKI, considering the importance of several comorbidities in determining the clinical course and outcomes in the human disease. Moreover, studies should test novel interventions in models where AKI is already established, instead of focusing only at primary prevention. AKI definitions and endpoints in animal studies should be similar to those applied in clinical studies; in particular, AKI biomarkers should be implemented to guide patient selection for clinical trials and monitor intervention efficacy. In this scenario, cell-cycle arrest biomarkers have been widely investigated as AKI predictors in both preclinical and clinical studies and they serve as useful tools for future interventional studies. A better understanding of human AKI through a large collection of biological samples and kidney biopsies and omics applications, and an iterative relationship between preclinical and clinical studies are critical steps to improve future preclinical models and clinical trials. Finally, given the great variability in clinical manifestation of AKI, a strong collaboration between research centers and industry is recommended. Key messages: Several methodological issues have hampered the translation of basic research findings in clinical studies, and overcoming these obstacles is necessary to achieve success.