1.
Glucose Metabolism in the Kidney: Neurohormonal Activation and Heart Failure Development.
Gronda, E, Jessup, M, Iacoviello, M, Palazzuoli, A, Napoli, C
Journal of the American Heart Association. 2020;(23):e018889
Abstract
The liver is not the exclusive site of glucose production in humans in the postabsorptive state. Robust data support that the kidney is capable of gluconeogenesis and studies have demonstrated that renal glucose production can increase systemic glucose production. The kidney has a role in maintaining glucose body balance, not only as an organ for gluconeogenesis but by using glucose as a metabolic substrate. The kidneys reabsorb filtered glucose through the sodium-glucose cotransporters sodium-glucose cotransporter (SGLT) 1 and SGLT2, which are localized on the brush border membrane of the early proximal tubule with immune detection of their expression in the tubularized Bowman capsule. In patients with diabetes mellitus, the renal maximum glucose reabsorptive capacity, and the threshold for glucose passage into the urine, are higher and contribute to the hyperglycemic state. The administration of SGLT2 inhibitors to patients with diabetes mellitus enhances sodium and glucose excretion, leading to a reduction of the glycosuria threshold and tubular maximal transport of glucose. The net effects of SGLT2 inhibition are to drive a reduction in plasma glucose levels, improving insulin secretion and sensitivity. The benefit of SGLT2 inhibitors goes beyond glycemic control, since inhibition of renal glucose reabsorption affects blood pressure and improves the hemodynamic profile and the tubule glomerular feedback. This action acts to rebalance the dense macula response by restoring adenosine production and restraining renin-angiotensin-aldosterone activation. By improving renal and cardiovascular function, we explain the impressive reduction in adverse outcomes associated with heart failure supporting the current clinical perspective.
2.
Association of glomerular hyperfiltration with serum chemokine levels and metabolic features in prepubertal children with overweight/obesity.
Muzzio, ML, Kabakian, ML, Morosán-Allo, Y, Ferrari, S, Fallahi, P, Fernández, J, Santucci, MP, Andrés-Lacueva, C, Antonelli, A, Brenta, G, et al
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2020;(7):1188-1195
Abstract
BACKGROUND AND AIMS Glomerular hyperfiltration (GH) is proposed as one of the earliest events in obesity (OB)-associated renal disease. Children with GH and type-1 diabetes showed increased chemokine levels. Chemokine associations with glomerular filtration rate (GFR) and metabolic features in prepubertal children with overweight (OW)/OB are unknown. METHODS AND RESULTS Cross-sectional study. 75 prepubertal children (aged: 9.0 ± 1.7 years) with OW/OB were studied. Clinical and metabolic characteristics (including non-esterified fatty acids, NEFA) and GFR (combined Zappitelli equation) were assessed. GH was defined as GFR >135 ml/min.1.73 m2. Serum levels of regulated on activation, normal T cell expressed and secreted (RANTES)/CCL5, interleukin-8 (IL-8)/CXCL8 and monokine-induced by interferon-γ (MIG)/CXCL9 were measured by ELISA. Age- and sex-adjusted correlations and differences were tested. 48% of the cohort was female and 13% were OW, 54% OB and 33% severe OB. Prepubertal children with GH showed lower z-BMI (-12%), NEFA (-26%) and uric acid (-22%) than those without GH (all p < 0.05). Similarly to high sensitivity C-reactive protein (hsCRP), there were no differences in serum chemokines between children with GH or not (all p > 0.05). Adjusted correlations were significant for RANTES and z-BMI (r = 0.26; p < 0.05) and for MIG with z-BMI (r = -0.26; p < 0.05) and with NEFA (r = 0.27; p < 0.05). CONCLUSION GH was not associated with higher chemokine levels in prepubertal children with OW/OB. Decreased rather than elevated GFR values were correlated with obesity and worse metabolic profiles. Chemokines levels in children with severe OB suggest a regulation of the immune response. Follow-up studies are needed to address the clinical implications of these findings.
3.
[Immunoglobulin A nephropathy].
Seikrit, C, Rauen, T, Floege, J
Der Internist. 2019;(5):432-439
Abstract
Immunoglobulin A nephropathy (IgAN) is the most prevalent primary form of glomerulopathy in the western world. The pathogenetic relevance of autoimmune mechanisms, genetics and environmental or nutritional factors is not fully established. The majority of IgAN patients present with mild symptoms; however, the exact prognosis of the individual IgAN course is often difficult to predict. In approximately one third of the patients the disease remains on a stable benign course, whereas approximately 30% may develop end-stage renal disease. Risk factors for disease progression are a persistent microhematuria and proteinuria >1 g/day, arterial hypertension and the extent of tubulointerstitial fibrosis at the time of diagnosis. Recent genome-wide association studies (GWAS) identified numerous risk alleles, which can contribute to the pathophysiology of IgAN. The so-called gut-kidney axis as well as the complement system and genes that are linked to mucosal immunity appear to be important for the manifestation of the disease. Intensive supportive care should be initiated as first-line treatment and only rare cases with progressive features require treatment with corticosteroids. Other immunosuppressive treatment strategies have currently no indications for IgAN. Future approaches might be the use of local budesonide or the inhibition of lymphocyte activation.
4.
Renal Effects of Cytokines in Hypertension.
Wen, Y, Crowley, SD
Advances in experimental medicine and biology. 2019;:443-454
Abstract
Preclinical studies point to a key role for immune cells in hypertension via augmenting renal injury and/or hypertensive responses. Blood pressure elevation in rheumatologic patients is attenuated by anti-inflammatory therapies. Both the innate and adaptive immune systems contribute to the pathogenesis of hypertension by modulating renal sodium balance, blood flow, and functions of the vasculature and epithelial cells in the kidney. Monocytes/macrophages and T lymphocytes are pivotal mediators of hypertensive responses, while dendritic cells and B lymphocytes can regulate blood pressure indirectly by promoting T lymphocytes activation. Pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF), interleukin-1 (IL-1), interleukin-17 (IL-17), and interferon-γ (IFN), amplify blood pressure elevation and/or renal injury. By contrast, interleukin-10 (IL-10) protects against renal and vascular function when produced by T helper 2 cells (Th2) and regulatory T cells (Treg). Thus, understanding the renal effects of cytokines in hypertension will provide targets for precise immunotherapies to inhibit targeted organ damage while preserving necessary immunity.