COVID-19 and its impact on the kidney and the nephrology community

COVID-19; NephrologyCOVID-19; NefrologiaCOVID-19; NefrologíaThis article is part of a supplement supported by Fresenius Medical Care without any influence on its content

Anti-phospholipase A2 receptor antibody and spontaneous remission in membranous nephropathy

Anti-phospholipase A2 receptor antibody; Membranous nephropathy; Spontaneous remissionAnticòs del receptor anti-fosfolipasa A2; Nefropatia membranosa; Remissió espontàniaAnticuerpo del receptor anti-fosfolipasa A2; Nefropatía membranosa; Remisión espontáneaMembranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in native kidney biopsies from adults. In 2009, antibodies to the M-type receptor of phospholipase A2 (anti-PLA2R) were identified in idiopathic MN patients, both within the kidney and in the circulation. The clinical course of idiopathic MN is variable and ranges from spontaneous remission to end-stage renal disease. Clinical variables such as proteinuria levels, patient sex, age and renal function at diagnosis have been associated with renal MN progression. In this editorial, we update the importance of anti-PLA2R levels as a prognostic marker in idiopathic MN at the diagnosis of the diseas

Sodium-glucose cotransporter inhibitors: beyond glycaemic control

SGLT2; Chronic kidney disease; Diabetic nephropathySGLT2; Malaltia renal crònica; Nefropatia diabèticaSGLT2; Enfermedad renal crónica; Nefropatía diabéticaDiabetes increases the risk of adverse cardiovascular and renal events. Recently, sodium-glucose co-transporter 2 (SGLT2) inhibitors have been demonstrated to reduce cardiovascular complications and slow diabetic kidney disease progression in patients with type 2 diabetes. The glycaemic control exerted by these drugs is not greater than the one achieved with other classical glucose-lowering medications such as sulphonylureas. For that reason, plausible renoprotective mechanisms independent from glycaemic control have been proposed such as blood pressure control, body weight loss, intraglomerular pressure reduction and a decrease in urinary proximal tubular injury biomarkers. Interestingly, the hypothesis that SGLT2 inhibitors have a direct renoprotective effect has been addressed in diabetic and non-diabetic models. In this editorial, we update the different postulated mechanisms involved in the cardiorenal protection afforded by SGLT2 inhibition in chronic kidney disease.The authors are current recipients of research grants from the FONDO DE INVESTIGACIÓN SANITARIA-FEDER, ISCIII, PI17/00257 and REDINREN, RD16/0009/0030

Transjugular Kidney Biopsy as a Safe Method to Increase the Etiological Diagnosis in Kidney Disease

Biopsia renal transyugular; Diagnóstico etiológico; Enfermedad renalBiòpsia renal transjugular; Diagnòstic etiològic; Malaltia renalTransjugular Kidney Biopsy; Etiological Diagnosis; Kidney Diseas

Immunotherapy and the Spectrum of Kidney Disease: Should We Individualize the Treatment?

Chronic kidney disease; Dialysis; ImmunotherapyEnfermedad renal cronica; Diálisis; InmunoterapiaMalaltia renal crònica; Diàlisi; ImmunoteràpiaThe new targeted cancer therapies including immune checkpoint inhibitors (ICIs) have been demonstrated to improve the survival of oncological patients, even in cases of metastatic cancer. In the past 5 years, several studies have revealed that ICI can produce several immune-mediated toxicities involving different organs, such as the skin, the gastrointestinal tract, the liver, and, of course, the kidney. The most frequent lesion of immunotoxicity in the kidney is acute interstitial nephritis (AIN), although other nephropathies have also been described as a consequence of the use of ICI, such as glomerulonephritis and acute thrombotic microangiopathy, among others. In addition, kidney rejection has also been reported in kidney transplant patients treated with ICI. Normally randomized clinical trials with ICI exclude patients with end-stage kidney disease, namely, patients undergoing dialysis and kidney transplant patients. Several important questions need to be addressed in relation to immunotherapy and patients with kidney disease: (a) when to start corticosteroid therapy in a patient with suspected acute kidney injury (AKI) related to ICI, (b) the moment of nephrologist referral and kidney biopsy indication, (c) management of ICI in patients undergoing dialysis, and (d) the effect of ICI in kidney transplantation, immunosuppressive personalized treatment, and risk of allograft rejection in kidney transplant patients. The objective of this review was to summarize the recently published literature on a wide spectrum of kidney disease patients with cancer and ICI. This review will address three main important groups of individuals with kidney disease and cancer immunotherapy, AKI associated with ICI, patients undergoing dialysis, and kidney transplant recipients. We believe that the information provided in this review will enlighten the personalized ICI treatment in individuals with a broader spectrum of kidney diseases.This research was funded by ISCIIII-FEDER and ISCIII-RETICS REDinREN, Grant Numbers PI17/00257, PI21/01292, RD16/0009/0030, and RICORS RD21/0005/0016. Enfermedad Glomerular Compleja del Sistema Nacional de Salud (CSUR), enfermedades glomerulares complejas

Intravenous fluid therapy in accordance with kidney injury risk: when to prescribe what volume of which solution

Acute kidney injury; Colloid solution; Intravenous fluid therapyLesión renal aguda; Solución coloidal; Fluidoterapia intravenosaLesió renal aguda; Solució col·loïdal; Fluidoteràpia intravenosaAcute kidney injury (AKI) is common in hospitalized patients while common risk factors for the development of AKI include postoperative settings, patients with baseline chronic kidney disease (CKD) or congestive heart failure. Intravenous (IV) fluid therapy is a crucial component of care for prevention and treatment of AKI. In this narrative review, we update the approach to IV fluid therapy in hospitalized patients including the timing of fluid prescription, and the choice of fluid type, amount and infusion rate along with the potential adverse effects of various crystalloid and colloid solutions, addressing specifically their use in patients with acute kidney disease, CKD or heart failure, and their potential impact on the risk of hospital-acquired AKI

Cardiorenal benefits of finerenone: protecting kidney and heart

Albuminuria; Enfermedad renal crónica; FinerenonaAlbuminúria; Malaltia renal crònica; FinerenonaAlbuminuria; Chronic kidney disease; FinerenonePersons with diabetes and chronic kidney disease (CKD) have a high residual risk of developing cardiovascular (CV) complications despite treatment with renin-angiotensin system blockers and sodium-glucose cotransporter type 2 inhibitors. Overactivation of mineralocorticoid receptors plays a key role in the progression of renal and CV disease, mainly by promoting inflammation and fibrosis. Finerenone is a nonsteroidal selective mineralocorticoid antagonist. Recent clinical trials, such as FIDELIO-DKD and FIGARO-DKD and the combined analysis FIDELITY have demonstrated that finerenone decreases albuminuria, risk of CKD progression, and CV risk in subjects with type 2 diabetes (T2D) and CKD. As a result, finerenone should thus be considered as part of a holistic approach to kidney and CV risk in persons with T2D and CKD. In this narrative review, the impact of finerenone treatment on the CV system in persons with type 2 diabetes and CKD is analyzed from a practical point of view

Exploring Renal Changes after Bariatric Surgery in Patients with Severe Obesity

Albuminuria; Aldosterone; Glucose metabolismAlbuminuria; Aldosterona; Metabolismo de la glucosaAlbuminúria; Aldosterona; Metabolisme de la glucosaObesity-related hyperfiltration leads to an increased glomerular filtration rate (GFR) and hyperalbuminuria. These changes are reversible after bariatric surgery (BS). We aimed to explore obesity-related renal changes post-BS and to seek potential mechanisms. Sixty-two individuals with severe obesity were prospectively examined before and 3, 6 and 12 months post-BS. Anthropometric and laboratory data, 24 h-blood pressure, renin-angiotensin-aldosterone system (RAS) components, adipokines and inflammatory markers were determined. Both estimated GFR (eGFR) and albuminuria decreased from the baseline at all follow-up times (p-for-trend <0.001 for both). There was a median (IQR) of 30.5% (26.2–34.4) reduction in body weight. Plasma glucose, glycosylated hemoglobin, fasting insulin and HOMA-index decreased at 3, 6 and 12 months of follow-up (p-for-trend <0.001 for all). The plasma aldosterone concentration (median (IQR)) also decreased at 12 months (from 87.8 ng/dL (56.8; 154) to 65.4 (56.8; 84.6), p = 0.003). Both leptin and hs-CRP decreased (p < 0.001) and adiponectine levels increased at 12 months post-BS (p = 0.017). Linear mixed-models showed that body weight (coef. 0.62, 95% CI: 0.32 to 0.93, p < 0.001) and plasma aldosterone (coef. −0.07, 95% CI: −0.13 to −0.02, p = 0.005) were the independent variables for changes in eGFR. Conversely, glycosylated hemoglobin was the only independent variable for changes in albuminuria (coef. 0.24, 95% CI: 0.06 to 0.42, p = 0.009). In conclusion, body weight and aldosterone are the main factors that mediate eGFR changes in obesity and BS, while albuminuria is associated with glucose homeostasis.The research reported in this publication was supported by the Spanish Society of Nephrology (Grant for Clinical Investigation. 2014) and by the Spanish Ministry of Health ISCIII RedinRen RD16/0009/0013

Endothelial ADAM17 Expression in the Progression of Kidney Injury in an Obese Mouse Model of Pre-Diabetes

Endothelial cells; Obesity; Pre-diabetesCélulas endoteliales; Obesidad; PrediabetesCèl·lules endotelials; Obesitat; Pre-diabetisDisintegrin and metalloproteinase domain 17 (ADAM17) activates inflammatory and fibrotic processes through the shedding of various molecules such as Tumor Necrosis Factor-α (TNF-α) or Transforming Growht Factor-α (TGF-α). There is a well-recognised link between TNF-α, obesity, inflammation, and diabetes. In physiological situations, ADAM17 is expressed mainly in the distal tubular cell while, in renal damage, its expression increases throughout the kidney including the endothelium. The aim of this study was to characterize, for the first time, an experimental mouse model fed a high-fat diet (HFD) with a specific deletion of Adam17 in endothelial cells and to analyse the effects on different renal structures. Endothelial Adam17 knockout male mice and their controls were fed a high-fat diet, to induce obesity, or standard rodent chow, for 22 weeks. Glucose tolerance, urinary albumin-to-creatinine ratio, renal histology, macrophage infiltration, and galectin-3 levels were evaluated. Results showed that obese mice presented higher blood glucose levels, dysregulated glucose homeostasis, and higher body weight compared to control mice. In addition, obese wild-type mice presented an increased albumin-to-creatinine ratio; greater glomerular size and mesangial matrix expansion; and tubular fibrosis with increased galectin-3 expression. Adam17 deletion decreased the albumin-to-creatinine ratio, glomerular mesangial index, and tubular galectin-3 expression. Moreover, macrophage infiltration in the glomeruli of obese Adam17 knockout mice was reduced as compared to obese wild-type mice. In conclusion, the expression of ADAM17 in endothelial cells impacted renal inflammation, modulating the renal function and histology in an obese pre-diabetic mouse model.This research was funded by ISCIIII-FEDER and ISCIII-RETICS REDinREN, grant number PI16/00620, PI17/00257, RD16/0009/0013, and RICORS RD21/0005. Additionally, C.B. is funded by the Catalan Health Department (Generalitat de Catalunya) contract PERIS STL008/18/00018 to develop clinical and epidemiological studies mainly focused in diabetes and its associations with new biomarkers. V.P. is a research fellow of ISCIII-FSE project FI17/00025

Redefining the Role of ADAM17 in Renal Proximal Tubular Cells and Its Implications in an Obese Mouse Model of Pre-Diabetes

ADAM17; Obesidad; Células tubulares proximales renalesADAM17; Obesity; Renal proximal tubular cellsADAM17; Obesitat; Cèl·lules tubulars proximals renalsAcute and chronic kidney lesions induce an increase in A Disintegrin And Metalloproteinase domain 17 (ADAM17) that cleaves several transmembrane proteins related to inflammatory and fibrotic pathways. Our group has demonstrated that renal ADAM17 is upregulated in diabetic mice and its inhibition decreases renal inflammation and fibrosis. The purpose of the present study was to analyze how Adam17 deletion in proximal tubules affects different renal structures in an obese mice model. Tubular Adam17 knockout male mice and their controls were fed a high-fat diet (HFD) for 22 weeks. Glucose tolerance, urinary albumin-to-creatinine ratio, renal histology, and pro-inflammatory and pro-fibrotic markers were evaluated. Results showed that wild-type mice fed an HFD became obese with glucose intolerance and renal histological alterations mimicking a pre-diabetic condition; consequently, greater glomerular size and mesangial expansion were observed. Adam17 tubular deletion improved glucose tolerance and protected animals against glomerular injury and prevented podocyte loss in HFD mice. In addition, HFD mice showed more glomerular macrophages and collagen accumulation, which was prevented by Adam17 deletion. Galectin-3 expression increased in the proximal tubules and glomeruli of HFD mice and ameliorated with Adam17 deletion. In conclusion, Adam17 in proximal tubules influences glucose tolerance and participates in the kidney injury in an obese pre-diabetic murine model. The role of ADAM17 in the tubule impacts on glomerular inflammation and fibrosis.This research was funded by ISCIIII-FEDER grant numbers PI16/00620 and PI17/00257; ISCIII-RETICS REDinREN RD16/0009/0013, and ISCIII-RICORS RD21/0005. C.B. is also funded by the Catalan Health Department (Generalitat de Catalunya) contract PERIS STL008/18/00018 to develop clinical and epidemiological studies mainly focused on diabetes and its associations with new biomarkers. V.P. is a research fellow of ISCIII-FSE project FI17/00025