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Mario Cozzolino, Piergiorgio Bolasco, Claudio Ronco, Giuseppe Conte, Paolo Menè, Maria Cristina Mereu, Marina Di Luca, Dario Roccatello, Alberto Rosati, Claudio Jommi, Anna Maria Costanzo, Giuliana Gualberti, Umberto di Luzio Paparatti, Giuseppe Remuzzi
BACKGROUND: Lack of adequate management of chronic kidney disease (CKD) often results in delayed diagnosis and inadequate treatment. This study assessed the clinical management and outcome of stages 1-5 CKD patients. METHODS: Patients were prospectively followed for 3 years in 25 nephrology centers across Italy. Clinical characteristics were measured at baseline and every 6 months. Outcome measures included CKD staging, presence of comorbidities, treatment, mineral bone disorder (MBD) parameters, and patient outcomes...
July 17, 2018: Nephron
Roslyn B Mannon
With the growing wait list of individuals waiting for kidney transplantation, there has been renewed interest in the quality and function of donor organs. In particular, concern about the development of delayed allograft function (DGF) after transplantation continues to lead to the avoidance of donor organs offered to a transplant center. DGF is associated with worse short-and long-term outcomes and associated with higher rejection rates. There are no FDA-approved therapies to mitigate the ischemic injury that occurs...
July 13, 2018: Nephron
Mark L Hepokoski, Atul Malhotra, Prabhleen Singh, Laura E Crotty Alexander
Mechanical ventilation is associated with significant increases in the risk of acute kidney injury (AKI). The rate of AKI due to mechanical ventilation and the associated mortality remain unacceptably high. Preventative and therapeutic strategies are clearly lacking. Ventilator-induced kidney injury is believed to occur due to changes in hemodynamics that impair renal perfusion, neurohumoral-mediated alterations in intra-renal blood flow, and systemic inflammatory mediators generated by ventilator-induced lung injury...
July 11, 2018: Nephron
Tomoyasu Otsuki, Kei Utsunomiya, Masari Moriuchi, Shu Horikoshi, Masahiro Okamura, Hiroko Suzuki, Makiyo Okamura, Noriaki Maruyama, Nami Shibahara, Masanori Abe
OBJECTIVE: This study investigated the effects of sucroferric oxyhydroxide on fibroblast growth factor (FGF)-23 and dose reduction of erythropoiesis-stimulating agents (ESA) and intravenous saccharated ferric oxide in hemodialysis patients. METHODS: In this prospective, open-label, parallel-group, multicenter trial involving patients receiving lanthanum carbonate hydrate, eligible patients were randomized to a sucroferric oxyhydroxide group or a control group. Hemoglobin, serum phosphate, FGF-23, iron, and ferritin levels, as well as transferrin saturation, doses of intravenous saccharated ferric oxide and ESA administered, and the erythropoietin responsiveness index (ERI) were monitored for 24 weeks...
July 10, 2018: Nephron
Takahisa Kawaguchi, Tadashi Yoshida, Junichi Hirahashi, Tomoko Uehara, Toshiki Takenouchi, Kenjiro Kosaki, Hiroshi Itoh, Matsuhiko Hayashi
Nephronophthisis-related ciliopathies (NPHP-RC) are autosomal recessive disorders characterized by renal corticomedullary cysts with the extrarenal symptoms. Typically, patients with NPHP-RC reach end-stage kidney disease (ESKD) before the age of 30 years. We herein report a Japanese woman with NPHP-RC who had unusually delayed progression to ESKD after 6 decades. She exhibited liver dysfunction at the age of 23 years. She also showed mild renal dysfunction at the age of 43 years. Ultrasonography revealed bilateral multiple renal cysts with loss of corticomedullary differentiation...
July 10, 2018: Nephron
Jin Ju Song, Kyu-Beck Lee, Young Youl Hyun, Hyang Kim
BACKGROUND/AIMS: Albuminuria is a risk factor for coronary artery calcification (CAC) and cardiovascular disease (CVD). Although the urine dipstick test is widely used to screen albuminuria, little is known about the association between low-grade urine dipstick albumin and CAC. The aim of this study is to investigate the relationship between the trace of urine dipstick albumin and CAC in Korean adults. METHODS: This cross-sectional study analyzed 45,006 participants without previous CVD, who underwent coronary computed tomography and urine dipstick test from 2012 to 2014 as part of a health examination program in Korea...
July 10, 2018: Nephron
Shinji Tanaka, Mark D Okusa
BACKGROUND: No approved pharmacological agents are available for the treatment and prevention of acute kidney injury (AKI). The nervous system has been reported to play an important role, directly or indirectly via the immune system, in the pathophysiology of AKI. Neuromodulation, such as vagus nerve stimulation and pulsed ultrasound, is emerging as an innovative therapeutic treatment for various diseases including AKI. However, lack of effective methods to selectively stimulate or inhibit neurons has hampered the complete understanding of the roles of the nervous system in AKI because electrical stimulation is nonspecific for cell types...
July 10, 2018: Nephron
John M Arthur, Nithin Karakala, Ricky D Edmondson
The search for acute kidney injury (AKI) biomarkers has identified a number of urine proteins that can be used to predict the presence of AKI but has struggled to identify proteins that are prognostic for severe AKI. In this review, we discuss 2 currently available biomarkers and the designs of the studies in which they were identified and relate this to the AKI characteristics they predict clinically. We discuss recent advances in mass spectrometry and sample preparation, which have improved the ability to identify low abundance proteins as well as the ability to characterize more of the protein by mass spectrometry...
July 10, 2018: Nephron
Wim Musch, Guy Decaux
BACKGROUND/AIMS: Hyponatremia secondary to distal diuretics intake could have a biochemical picture similar to the one observed in the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). In these patients, water retention is considered to be the main causal factor and solute depletion a secondary one. METHODS: We compared the level of cation (Na + K) depletion and water balance in patients with high or low uric acid levels (< 4 mg/dL or 238 µmol/L) or with high or low (< 30 mg/dL or 5 mmol/L) urea levels...
July 10, 2018: Nephron
Sundararaman Swaminathan
BACKGROUND: Iron is critical for fundamental biologic functions such as cell division and mitochondrial electron transport. However, by the virtue of its ability to donate electrons, iron is probably the most effective oxidant in biologic systems. SUMMARY: To avoid damage from iron-mediated oxidative injury or ferroptosis, multiple defense mechanisms exist including iron binding proteins and robust glutathione-dependent intracellular pathways. Hepcidin, through its ability to sequester iron within macrophages and induce H-ferritin, serves as an endogenous protective molecule against ferroptosis...
July 6, 2018: Nephron
Roger van Groenendael, Matthijs Kox, Lucas T van Eijk, Peter Pickkers
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. EA-230, a linear tetrapeptide (Alanine-Glutamine-Glycine-Valine), derived from the β-chain of the human chorionic gonadotropin hormone, has shown immunomodulatory and renoprotective properties in several pre-clinical animal models of systemic inflammation. 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...
July 6, 2018: Nephron
Srijan Tandukar, Linda F Fried
The widespread use of diuretics, potassium supplements, and medications that block renin angiotensin system puts the chronic kidney disease (CKD) population at high risk for dyskalemia, both hyperkalemia and hypokalemia. The optimal potassium level in a CKD patient is unknown. Subject of review: Two recent studies found conflicting results on the association of dyskalemia with outcomes. The Renal Research Institute CKD study [Clin J Am Soc Nephrol 2010; 5: 762-769] found increased mortality and incidence of end-stage renal disease (ESRD) with mild to moderate hypokalemia, whereas hyperkalemia was not significantly associated, compared to eukalemia...
July 4, 2018: Nephron
Anne von Mässenhausen, Wulf Tonnus, Andreas Linkermann
Renal tubules represent an intercellular unit and function as a syncytium. When acute tubular necrosis was first visualized to occur through a process of synchronized regulated necrosis (SRN) in handpicked primary renal tubules, it became obvious that SRN actually promotes nephron loss. This realization adds to our current understanding of acute kidney injury (AKI)-chronic kidney disease (CKD) transition and argues for the prevention of AKI episodes to prevent CKD progression. Because SRN is triggered by necroptosis and executed by ferroptosis, 2 recently identified signaling pathways of regulated necrosis, a combination therapy employing necrostatins and ferrostatins may be beneficial for protection against nephron loss...
June 29, 2018: Nephron
Martin Gritter, Liffert Vogt, Stanley M H Yeung, Rosa D Wouda, Christian R B Ramakers, Martin H de Borst, Joris I Rotmans, Ewout J Hoorn
BACKGROUND/AIMS: Dietary potassium (K+) has beneficial effects on blood pressure and cardiovascular (CV) outcomes. Recently, several epidemiological studies have revealed an association between urinary K+ excretion (as proxy for dietary intake) and better renal outcomes in subjects with chronic kidney disease (CKD). To address causality, we designed the "K+ in CKD" study. METHODS: The K+ in CKD study is a multicenter, randomized, double blind, placebo-controlled clinical trial aiming to include 399 patients with hypertension, CKD stage 3b or 4 (estimated glomerular filtration rate [eGFR] 15-44 mL/min/1...
June 29, 2018: Nephron
Hamid Rabb, Jennifer Pluznick, Sanjeev Noel
Acute kidney injury (AKI) is a major clinical problem in native and transplanted kidneys. Bidirectional interaction between gut microbiota and kidney tissue or the "colo-renal" system is being recognized as an important modulating factor in AKI. Gut microbes appear to have a complex but yet poorly understood communication with renal cellular and molecular processes that affect normal kidney function and response to injury. There have been major recent advances in the study of the microbiome that provide an opportunity to apply this knowledge to improve our understanding and treatment of patients with AKI...
June 29, 2018: Nephron
Stefano Romagnoli, Zaccaria Ricci, Claudio Ronco
BACKGROUND: Acute kidney injury (AKI) is a frequent complication of both cardiac and major non-cardiac surgery. AKI is independently associated with morbidity, mortality, and long-term adverse events including chronic kidney disease in postsurgical patients. Since specific treatment options for kidney failure are very limited, early identification, diagnosis, and renal support strategies are key steps to improve patients' outcome. SUMMARY: According to current Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, AKI diagnosis is based on 2 functional markers, serum creatinine increase and urine output decrease, that are not renal-specific and have important limitations...
June 26, 2018: Nephron
Douglas S Fuller, Bruce M Robinson, Francesco Locatelli, Ronald L Pisoni
BACKGROUND: Clinicians providing dialysis care have numerous erythropoiesis-stimulating agents (ESAs) available for treating anemia. We sought to provide a contemporary description of ESA types used in hemodialysis (HD) settings in nine European countries. METHODS: Our study uses Dialysis Outcomes and Practice Patterns Study phase 5 (2012-2015) data from nine European countries (Belgium, France, -Germany, Italy, Russia, Spain, Sweden, Turkey, and the United Kingdom)...
June 26, 2018: Nephron
Marieke Demeulenaere, Katrien Devreese, Hilde Vanbelleghem, Julie De Zaeytijd, Johan Vande Walle, Wim Van Biesen, Steven Van Laecke
Thrombomodulin (TM) is an endothelial glycoprotein that is present in all blood vessels. Five percent of all patients with atypical hemolytic uremic syndrome (aHUS) have mutations in the gene coding for TM, with a peak presentation in young children. Mutations often translate into quantitative and qualitative abnormalities of this endothelial glycoprotein. Outcome of the TM-associated aHUS is relatively poor with frequent relapses after transplantation despite its membrane-bound character. We observed a woman presenting with malignant hypertension (MHT) and associated kidney, brain, cardiac, and hematological involvement with thrombotic microangiopathy on kidney biopsy...
June 25, 2018: Nephron
Moin A Saleem
Soluble urokinase-type plasminogen activator -(suPAR) is an inflammatory signal with pleiotropic biological effects depending on context and post-translational modifications. Recently, [Hayek, et al: Nat Med 2017; 23: 945-953] it has been found that there is a link between suPAR and renal disease in several guises, and a key question is whether it is a driver or a marker of renal disease, and if so of which types of kidney damage. Subject of Review: Circulating suPAR has been postulated to cause acute proteinuric kidney disease, specifically focal segmental glomerulosclerosis (FSGS), though both the animal models and clinical data in the original reports have been challenged...
June 15, 2018: Nephron
Kazuya Matsumura, Kyoko Sugii, Midori Awazu
BACKGROUND/AIMS: Children with a solitary functioning kidney have a risk of renal injury caused by hyperfiltration. Timely intervention with renin-angiotensin inhibitors may be beneficial. We examined whether trajectory of estimated glomerular filtration rate (eGFR) would predict renal injury, defined as microalbuminuria/proteinuria, hypertension, and/or a decline in eGFR. METHODS: Seventeen patients (male 7, female 10) with multicystic dysplastic kidney (MCDK; median age 13 years, range 6-19 years) followed in our clinic were examined retrospectively...
June 7, 2018: Nephron
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