methotrexate renal clearance by low dose dopamine in severe nephrotoxicity

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Loss of renal function in the elderly italians: a physiologic or pathologic process?

Abstract BACKGROUND: Nowadays it seems that chronic kidney disease (CKD) is outbreaking, mostly in the elderly participants. The aim of this study was to assess the progression of CKD in different ages. METHODS: We conducted a monocentric, retrospective, observational study enrolling 116 patients afferent to our outpatient clinic. INCLUSION CRITERIA: age >18 years, follow-up ≥5 years, estimated glomerular filtration rate (eGFR) <60mL/min/1.73 m(2), and/or diagnosed renal disease and/or presence of renal damage. Patients were divided into four groups according to their age: 25-55 years (n = 27), 56-65 (25), 66-75 (42), and 76-87 (22). eGFR was calculated using the modification of diet in renal disease and the CKD-epidemiology collaboration formulas. RESULTS: Younger patients had a significantly longer follow-up and less comorbidities, evaluated by the cumulative illness rating scale score, compared with the other groups. There was no difference between creatinine at baseline and at the end-of-follow-up period among the groups. Even though renal function significantly decreased in all groups, we noticed a slower progression as the age increased, and the difference between basal and end-of-follow-up eGFR was minimal in the group of patients aged 76-87 years. Analyzing the eGFR of every ambulatory control plotted against the year of follow-up, we showed a more rapid loss of filtrate in the younger group. Instead, loss of renal function decreased as the age of patients increased. CONCLUSIONS: This study demonstrates that, in elderly Italian participants, progression of CKD occurs more slowly than in younger patients. This implies that we may probably face an epidemic of CKD but that most of elderly patients diagnosed with CKD may not evolve to end-stage renal disease and require renal replacement therapy

Прототип автоматической системы экстренного торможения транспортного средства

Разработка, сборка и испытание прототипа автономной системы экстренного торможения транспортного средства на основе 8-битного микроконтроллера AVR типа ATmega16 и ультразвукового дальномера HC-SR04, срабатывающей при приближении к объекту на расстояние около 10 см. Программу микроконтроллера будет написана на языке Си с использованием программатора STK-500.Development, assembly and testing of the prototype of the autonomous emergency braking system of a vehicle based on the 8-bit AVR microcontroller type ATmega16 and ultrasonic rangefinder HC-SR04, triggered when approaching the object at a distance of about 10 cm. The program of the microcontroller will be written in C language using the programmer STK -500

RBP4: A Culprit for Insulin Resistance in End Stage Renal Disease That Can Be Cleared by Hemodiafiltration

Introduction. Retinol Binding Protein 4 (RBP4) is mainly excreted by the kidney and plays a pivotal role in insulin resistance (IR). In our study, we evaluated the association between RBP4 and IR in hemodialysis subjects (HD). We also assessed how circulating RBP4 could be influenced by kidney transplant or different dialytic techniques. Methods. RBP4 serum levels were evaluated in HD (n=16) and matched healthy controls (C; n=16). RBP4 and glucose transporter type 4 (GLUT4) mRNA expressions were also determined in adipose tissue. Circulating RBP4 was evaluated after kidney transplant (n=7) and in hemodialysis patients (n=10) enrolled in a cross-over study treated with standard bicarbonate dialysis (BD) or hemodiafiltration (HDF). Results. HOMA index (P<0.05) and serum RBP4 (P<0.005) were higher in HD compared to C. RBP4 levels positively correlated with fasting serum glucose (P<0.05). RBP4 mRNA was lower in HD compared to C (P<0.05) and positively correlated with kidney function (P<0.05) and GLUT4 mRNA (P<0.001). Transplant or HDF reduced circulating RBP4 (P<0.01 and P<0.05, resp.). Our results demonstrate that IR is associated with high circulating RBP4 and that suppressed RBP4 adipose tissue expression is accompanied by reduced GLUT4 expression in HD. Renal transplantation or HDF are effective in lowering serum RBP4 levels

Reversal of diabetic nephropathy by a ketogenic diet.

Intensive insulin therapy and protein restriction delay the development of nephropathy in a variety of conditions, but few interventions are known to reverse nephropathy. Having recently observed that the ketone 3-beta-hydroxybutyric acid (3-OHB) reduces molecular responses to glucose, we hypothesized that a ketogenic diet, which produces prolonged elevation of 3-OHB, may reverse pathological processes caused by diabetes. To address this hypothesis, we assessed if prolonged maintenance on a ketogenic diet would reverse nephropathy produced by diabetes. In mouse models for both Type 1 (Akita) and Type 2 (db/db) diabetes, diabetic nephropathy (as indicated by albuminuria) was allowed to develop, then half the mice were switched to a ketogenic diet. After 8 weeks on the diet, mice were sacrificed to assess gene expression and histology. Diabetic nephropathy, as indicated by albumin/creatinine ratios as well as expression of stress-induced genes, was completely reversed by 2 months maintenance on a ketogenic diet. However, histological evidence of nephropathy was only partly reversed. These studies demonstrate that diabetic nephropathy can be reversed by a relatively simple dietary intervention. Whether reduced glucose metabolism mediates the protective effects of the ketogenic diet remains to be determined

Combined anti-inflammatory and anti-AGE drug treatments have a protective effect on intervertebral discs in mice with diabetes.

Diabetes and low back pain are debilitating diseases and modern epidemics. Diabetes and obesity are also highly correlated with intervertebral disc (IVD) degeneration and back pain. Advanced-glycation-end-products (AGEs) increase reactive-oxygen-species (ROS) and inflammation, and are one cause for early development of diabetes mellitus. We hypothesize that diabetes results in accumulation of AGEs in spines and associated spinal pathology via increased catabolism. We present a mouse model showing that: 1) diabetes induces pathological changes to structure and composition of IVDs and vertebrae; 2) diabetes is associated with accumulation of AGEs, TNFα, and increased catabolism spinal structures; and 3) oral-treatments with a combination of anti-inflammatory and anti-AGE drugs mitigate these diabetes-induced degenerative changes to the spine.Three age-matched groups of ROP-Os mice were compared: non-diabetic, diabetic (streptozotocin (STZ)-induced), or diabetic mice treated with pentosan-polysulfate (anti-inflammatory) and pyridoxamine (AGE-inhibitor). Mice were euthanized and vertebra-IVD segments were analyzed by μCT, histology and Immunohistochemistry.Diabetic mice exhibited several pathological changes including loss in IVD height, decreased vertebral bone mass, decreased glycosaminoglycan content and morphologically altered IVDs with focal deposition of tissues highly expressing TNFα, MMP-13 and ADAMTS-5. Accumulation of larger amounts of methylglyoxal suggested that AGE accumulation was associated with these diabetic degenerative changes. However, treatment prevented or reduced these pathological effects on vertebrae and IVD.This is the first study to demonstrate specific degenerative changes to nucleus pulposus (NP) morphology and their association with AGE accumulation in a diabetic mouse model. Furthermore, this is the first study to demonstrate that oral-treatments can inhibit AGE-induced ROS and inflammation in spinal structures and provide a potential treatment to slow progression of degenerative spine changes in diabetes. Since diabetes, IVD degeneration, and accumulation of AGEs are frequent consequences of aging, early treatments to reduce AGE-induced ROS and Inflammation may have broad public-health implications

Safety and adequacy of percutaneous kidney biopsy performed by nephrology trainees

Abstract Background Recently there has been a progressive loss of specialty related skills for nephrologists. Among the skills we find the kidney biopsy that has a central role in diagnosis of renal parenchymal disease. One of the causes might be the belief that the kidney biopsy should be performed only in larger Centers which can rely on the presence of a renal pathologist and on nephrologists with a large experience. This trend may increase in the short term procedural safety but may limit the chance of in training nephrologists to become confident with the technique. Methods We evaluated renal biopsies performed from May 2002 to October 2016 in our Hospital, a mid-sized facility to determine whether the occurrence of complications would be comparable to those reported in literature and whether the increase in the number of biopsy performing physicians including nephrology fellows which took place since January 2012, after our Nephrology Unit became academic, would be associated to an increase of complications or a reduction of diagnostic power of renal biopsies. Three hundred thirty seven biopsies were evaluated. Patients underwent ultrasound guided percutaneous renal biopsy using a 14 G core needle loaded on a biopsy gun. Observation lasted for 24 h, we evaluated hemoglobin levels 6 and 24 h and kidney ultrasound 24 h after the biopsy. Results Complications occurred in 18.7% of patients, of these only 1,2% were major complications. Complications were more common in female (28%) compared to male patients (14,8%) (p = 0.004). We found no correlation between diagnosis, kidney function and complication rates; hypertension was not associated to a higher risk in complications. The increase of biopsy performing personnel was not associated to an increase in complication rates (18,7% both pre and post 2012) or with an increase of major complications (1.2% vs 1,2%). Conclusions Kidney biopsy can be safely performed in mid-sized hospitals. Safety and adequacy are guaranteed even if the procedure is performed by a larger number of less experienced nephrologists as long as under tutor supervision, thus kidney biopsy should become an integral part of a nephrology fellow training allowing more widespread diffusion of this technique

CHOP deficiency results in elevated lipopolysaccharide-induced inflammation and kidney injury

National Nature Science Foundation of China [81070272]; 973 Project [2012CB517601]; National Institute on Aging [5R01-AG-027628]; Genzyme Renal Innovation Grant; Italian Society of Nephrology (SIN)Esposito V, Grosjean F, Tan J, Huang L, Zhu L, Chen J, Xiong H, Striker GE, Zheng F. CHOP deficiency results in elevated lipopolysaccharide-induced inflammation and kidney injury. Am J Physiol Renal Physiol 304: F440-F450, 2013. First published December 12, 2012; doi:10.1152/ajprenal.00487.2011.-C/EBP homologous protein (CHOP) is an important mediator of endoplasmic reticulum (ER) stress-induced cell and organ injury. Here we show that lipopolysaccharide (LPS)-induced acute kidney injury (AKI) is associated with ER stress and elevated CHOP. We postulated that CHOP-/- mice would be protected against LPS-induced-AKI. Unexpectedly, while Toll-like receptor 4 (TLR4) expression levels were comparable in kidneys of CHOP-/- and wild-type (WT) mice, CHOP-/- mice developed more severe AKI after LPS injection. Furthermore, the severe kidney injury in CHOP-/- mice was associated with an exaggerated inflammatory response. Serum TNF-alpha levels were more elevated in LPS-treated CHOP-/- mice. There was a 3.5-fold higher amount of renal neutrophil infiltrates in LPS-treated CHOP-/- than in WT mice. Additionally, the kidneys of LPS-treated CHOP-/- mice had a more prominent increase in NF-kappa B activation and further upregulation of proinflammatory genes, i.e., c-x-c motif ligand 1 (CXCL-1), macrophage inflammatory protein-2 (MIP-2), and IL-6. Finally, proximal tubules, glomeruli, and podocytes isolated from CHOP-/- mice also had an exaggerated proinflammatory response to LPS. Since LPS directly increased CHOP in glomeruli and podocytes of WT mice, together these data suggest that the LPS-induced increase of CHOP in kidneys may inhibit inflammatory response in renal cells and provide protection against AKI