Novel strategies in nephrology: what to expect from the future?

Artificial kidney; Chronic kidney disease; XenotransplantationRonyó artificial; Malaltia renal crònica; XenotrasplantamentRiñón artificial; Enfermedad renal crónica; XenotrasplanteChronic kidney disease (CKD) will become the fifth global case of death by 2040. Its largest impact is on premature mortality but the number of persons with kidney failure requiring renal replacement therapy (RRT) is also increasing dramatically. Current RRT is suboptimal due to the shortage of kidney donors and dismal outcomes associated with both hemodialysis and peritoneal dialysis. Kidney care needs a revolution. In this review, we provide an update on emerging knowledge and technologies that will allow an earlier diagnosis of CKD, addressing the current so-called blind spot (e.g. imaging and biomarkers), and improve renal replacement therapies (wearable artificial kidneys, xenotransplantation, stem cell-derived therapies, bioengineered and bio-artificial kidneys).Research by A.O. is supported by IS/Fondos FEDER (PI18/01 366, PI19/00 588, PI19/00 815, DTS18/00 032, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00 064) and PERSTIGAN AC18/00 071, ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM, Instituto de Salud Carlos III (ISCIII) RICORS program to RICORS2040 (RD21/0005/0001) and SPACKDc PMP21/00 109, FEDER funds. RD16/0009

The Mitochondrion: A Promising Target for Kidney Disease

Acute kidney injury; Chronic kidney disease; Mitochondrial dysfunctionLesión renal aguda; Enfermedad renal crónica; Disfunción mitocondrialLesió renal aguda; Malaltia renal crònica; Disfunció mitocondrialMitochondrial dysfunction is important in the pathogenesis of various kidney diseases and the mitochondria potentially serve as therapeutic targets necessitating further investigation. Alterations in mitochondrial biogenesis, imbalance between fusion and fission processes leading to mitochondrial fragmentation, oxidative stress, release of cytochrome c and mitochondrial DNA resulting in apoptosis, mitophagy, and defects in energy metabolism are the key pathophysiological mechanisms underlying the role of mitochondrial dysfunction in kidney diseases. Currently, various strategies target the mitochondria to improve kidney function and kidney treatment. The agents used in these strategies can be classified as biogenesis activators, fission inhibitors, antioxidants, mPTP inhibitors, and agents which enhance mitophagy and cardiolipin-protective drugs. Several glucose-lowering drugs, such as glucagon-like peptide-1 receptor agonists (GLP-1-RA) and sodium glucose co-transporter-2 (SGLT-2) inhibitors are also known to have influences on these mechanisms. In this review, we delineate the role of mitochondrial dysfunction in kidney disease, the current mitochondria-targeting treatment options affecting the kidneys and the future role of mitochondria in kidney pathology

On the importance of the interplay of residual renal function with clinical outcomes in end-stage kidney disease.

Chronic kidney disease (CKD) is one of the most important public health concerns of the century, and is associated with high rates of morbidity, mortality and social costs. CKD evolving towards end-stage kidney disease (ESKD) is on the rise resulting in a greater number of patients requiring peritoneal dialysis (PD) and hemodialysis (HD). The aim of this manuscript is to review the current literature on the interplay of residual renal function (RRF) with clinical outcomes in ESKD. The persistence of RRF is one of the most important predictors of decreased morbidity, mortality, and better quality of life in both PD and HD patients. RRF contributes to the well-being of ESKD patients through various mechanisms including higher clearance of solutes, maintenance of fluid balance, removal of uremic toxins and control of electrolytes. Furthermore, RRF has beneficial effects on inflammation, anemia, malnutrition, diabetes mellitus, obesity, changes in the microbiota, and cardiac diseases. Several strategies have been proposed to preserve RRF, such as blockade of the renin-angiotensin-aldosterone system, better blood pressure control, incremental PD and HD. Several clinical trials investigating the issue of preservation of RRF are ongoing. They are needed to broaden our understanding of the interplay of RRF with clinical outcomes in ESKD

Tirzepatide and potential use for metabolically healthy obesity.

Metabolically healthy obesity or metabolically healthy overweight (MHO) is best described as being absent of any major metabolic disorder or cardiovascular diseases such as type 2 diabetes mellitus, dyslipidemia, hypertension, and atherosclerotic cardiovascular disease despite being obese or overweight. Nevertheless, MHO is being recognized as an important risk factor for the development of cardiovascular, cerebrovascular, and peripheral artery disease. In addition, these patients are at a high risk of conversion to the metabolically unhealthy phenotype. Tirzepatide is a newly developed glucose-lowering agent which acts on the glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. It has been shown to result in several highly beneficial outcomes including weight loss and a significant improvement in important metabolic parameters such as HbA1c, fasting serum glucose, and triglyceride/lipoprotein levels. These findings suggest that tirzepatide could potentially be beneficial to metabolically healthy obese or metabolically healthy overweight patients in reducing their risk of adverse cardiovascular outcomes and conversion to the metabolically unhealthy phenotype. In this review, we aim to discuss the potential benefits of using the novel anti-diabetic tirzepatide in the management of MHO to prevent the development of cardiovascular events and to decrease the likelihood of conversion to the unhealthy phenotype. We initially describe the clinical outcomes of MHO as well as the association of MHO with developing future cardiovascular events. We then delineate the currently available evidence behind the clinical effects of tirzepatide. We finally discuss the potential advantages of using tirzepatide in the management of MHO

Occult papillary thyroid carcinoma: prevalence at autopsy in Turkish people

The epidemiological features of occult papillary thyroid carcinoma (OPTC) at autopsy have not previously been reported in Turkish people. This study provides data on the prevalence of OPTC in people from the Marmara region in Turkey. The study includes thyroid glands from 93 male and 15 female cadavers between 18 and 80 years of age. The thyroid glands were removed, fixed and sectioned at 2-mm intervals. The sections were stained with hematoxylin and eosin, and were examined by a single pathologist. A total of 108 thyroid glands were examined. Macroscopic lesions were found in 36 (33.3%) glands (95% confidence interval = 24-42). OPTC was found in four (3.7%) cases (95% confidence interval = 1.0-7.5). It was concluded that in the Turkish people from the Marmara region, the prevalence of OPTC found at autopsy was relatively low. No age or sex predilection was detected. European Journal of Cancer Prevention 20:308-312 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

Xanthomatous hypophysitis

Xanthomatous hypophysitis (XH) is the rarely seen primary form of hypophysitis. The histological differential diagnosis includes other causes of hypophysitis, Erdheim-Chester disease (ECD), Langerhans cell histiocytosis, Rosai-Dorfman disease and plasma cell granulomas. We present a 39-year-old woman admitted to our department with headache, menstrual irregularity and galactorrhea. The MRI revealed a lesion with a central cystic/necrotic region and a diameter of almost 1 cm. Histologic examination showed an inflammatory infiltrate of numerous foamy histiocytes, surrounding the necrotic tissue. On immunohistochemical sections, infiltrating foamy cells stained strongly positive for CD68, and negative for CD1a and S100. After establishing the diagnosis of XH, the patient underwent glucocorticoid treatment. XH should be considered in the differential diagnosis of pituitary lesions. Since XH is rare, it is difficult to assess the efficacy of medical/surgical treatment of this entity accurately. (c) 2011 Elsevier Ltd. All rights reserved

Novel strategies in nephrology : what to expect from the future?

Chronic kidney disease (CKD) will become the fifth global case of death by 2040. Its largest impact is on premature mortality but the number of persons with kidney failure requiring renal replacement therapy (RRT) is also increasing dramatically. Current RRT is suboptimal due to the shortage of kidney donors and dismal outcomes associated with both hemodialysis and peritoneal dialysis. Kidney care needs a revolution. In this review, we provide an update on emerging knowledge and technologies that will allow an earlier diagnosis of CKD, addressing the current so-called blind spot (e.g. imaging and biomarkers), and improve renal replacement therapies (wearable artificial kidneys, xenotransplantation, stem cell-derived therapies, bioengineered and bio-artificial kidneys)

Metabolically healthy obesity: Misleading phrase or healthy phenotype?

Obesity is a heterogenous condition with multiple different phenotypes. Among these a particular subtype exists named as metabolically healthy obesity (MHO). MHO has multiple definitions and its prevalence varies according to study. The potential mechanisms underlying the pathophysiology of MHO include the different types of adipose tissue and their distribution, the role of hormones, inflammation, diet, the intestinal microbiota and genetic factors. In contrast to the negative metabolic profile associated with metabolically unhealthy obesity (MUO), MHO has relatively favorable metabolic characteristics. Nevertheless, MHO is still associated with many important chronic diseases including cardiovascular disease, hypertension, type 2 diabetes, chronic kidney disease as well as certain types of cancer and has the risk of progression into the unhealthy phenotype. Therefore, it should not be considered as a benign condition. The major therapeutic alternatives include dietary modifications, exercise, bariatric surgery and certain medications including glucagon-like peptide-1 (GLP-1) analogs, sodium-glucose cotransporter-2 (SGLT-2) inhibitors and tirzepatide. In this review, we discuss the significance of MHO while comparing this phenotype with MUO

Microsurgical and Tractographic Anatomy of the Supplementary Motor Area Complex in Humans

OBJECTIVE: To evaluate the microsurgical anatomy of the fiber tract connections of the supplementary motor area (SMA) and pre-SMA, and examine its potential functional role with reference to clinical trials in the literature

Acute kidney injury in hospitalized COVID-19 patients.

Background Acute kidney injury (AKI) in COVID-19 patients is associated with poor prognosis. However, the incidence, risk factors and potential outcomes of AKI in hospitalized patients are not well studied. Materials and methods This is a retrospective cohort study conducted in two major university hospitals. Electronic health records of the patients, 18 years or older, hospitalized between 13 April and 1 June 2020 with confirmed COVID-19 were reviewed. We described the incidence and the risk factors for AKI development in COVID-19 patients. Furthermore, we investigated the effects of AKI on the length of hospital and intensive care unit (ICU) stay, the admission rates to ICU, the percentage of patients with cytokine storm and in-hospital mortality rate. Results Among 770 hospitalized patients included in this study, 92 (11.9%) patients developed AKI. The length of hospitalized days (16 vs 9.9, p < 0.001) and days spent in the hospital until ICU admission (3.5 vs. 2.5, p = 0.003) were higher in the AKI group compared to patients without AKI. In addition, ICU admission rates were also significantly higher in patients with AKI (63% vs. 20.7%, p < 0.001). The percentage of patients with AKI who developed cytokine storm was significantly higher than patients without AKI (25.9% vs. 14%, p = 0.009). Furthermore, the in-hospital mortality rate was significantly higher in patients with AKI (47.2% vs. 4.7%, p < 0.001). Conclusions AKI is common in hospitalized COVID-19 patients. Furthermore, we show that AKI increases the admission rates to ICU and in-hospital mortality. Our findings suggest that AKI should be effectively managed to prevent the adverse outcomes in COVID-19 patients