Significant impact of COVID-19 on organ donation and transplantation in a low-prevalence country: Australia.
The incidence and impact of COVID-19 has varied enormously across the globe. The pandemic has negatively impacted organ donation and transplantation in countries that have experienced high rates of infection, including the USA, France and the UK, all reporting greater than 50% reductions in transplant activity1,2. Australia has experienced a significantly lower incidence of COVID-19 (Table 1). Despite this, the impact on organ transplantation has been significant. (Source: Kidney International)
Source: Kidney International - October 20, 2020 Category: Urology & Nephrology Authors: S.J. Chadban, M. McDonald, K. Wyburn, H. Opdam, L. Barry, P.T. Coates Tags: letters to the editor Source Type: research

A Kidney International “Journal of the COVID-19 Year” in Kidney Transplantation
The global COVID-19 pandemic ’s impact on kidney transplant recipients and transplantation programs in the calamitous months of February to June 2020, the Northern Hemisphere Spring to Summer, is represented in articles published in the December issue of Kidney International. Writing about another pandemic in the year of 1665 over 300 years ago the author Daniel Defoe describes the same period of time in London and gives a remarkably familiar description of how a pandemic affects populations, including the unproven treatments, epidemiology of infection and human response to restrictions on freedom of city lockdowns t...
Source: Kidney International - October 19, 2020 Category: Urology & Nephrology Authors: P. Toby Coates Tags: commentary Source Type: research

COVID-19 infection in kidney transplant recipients at the epicenter of pandemics
We investigated the prevalence and clinical outcomes of COVID-19 in recipients of kidney transplants in the Bronx, New York, one of the epicenters of the pandemic. Between March 16 and June 2, 2020, 132 kidney transplant recipients tested positive by SARS-CoV-2 RT-PCR. From May 3 to July 29, 2020, 912 kidney transplant recipients were screened for SARS-CoV-2 IgG antibodies during routine clinic visits, of which 16.6% tested positive. Fifty-five of the 152 patients had previously tested positive by RT-PCR, while the remaining 97 did not have significant symptoms and had not been previously tested by RT-PCR. (Source: Kidney International)
Source: Kidney International - October 15, 2020 Category: Urology & Nephrology Authors: Yorg Azzi, Michael Parides, Omar Alani, Pablo Loarte-Campos, Rachel Bartash, Stefanie Forest, Adriana Colovai, Maria Ajaimy, Luz Liriano-Ward, Cindy Pynadath, Jay Graham, Marie Le, Stuart Greenstein, Juan Rocca, Milan Kinkhabwala, Enver Akalin Tags: clinical investigation Source Type: research

Increase in phosphaturia by inhibition of renal sodium-dependent phosphate co-transporter NPT2a
Numerous mechanisms are involved in maintaining serum phosphate concentration in the normal range, mainly by regulating phosphate absorption in the gut and tubular phosphate reabsorption in the kidney. In the gut, phosphate is absorbed by passive paracellular diffusion and active transcellular transport, mainly via NPT2b, the major sodium phosphate co-transporter in the small intestine (1). Active phosphate absorption is enhanced by 1,25(OH)2 vitamin D. Intestinal phosphate absorption can be reduced by several approaches (1), including reduction of dietary phosphate intake, chelation of phosphate in the gut lumen (2), spec...
Source: Kidney International - October 14, 2020 Category: Urology & Nephrology Authors: Tilman B. Drueke Tags: nephrology digest Source Type: research

More reasons to use SGLT2 inhibitors: EMPEROR-Reduced and DAPA-CKD
Refers to: (Source: Kidney International)
Source: Kidney International - October 14, 2020 Category: Urology & Nephrology Authors: Masaomi Nangaku Tags: nephrology digest Source Type: research

Thrombomodulin ameliorates transforming growth factor- β1–mediated chronic kidney disease via the G-protein coupled receptor 15/Akt signal pathway
Kidney fibrosis is the common consequence of chronic kidney diseases that inexorably progresses to end-stage kidney disease with organ failure treatable only with replacement therapy. Since transforming growth factor- β1 is the main player in the pathogenesis of kidney fibrosis, we posed the hypothesis that recombinant thrombomodulin can ameliorate transforming growth factor-β1–mediated progressive kidney fibrosis and failure. To interrogate our hypothesis, we generated a novel glomerulus-specific human trans forming growth factor-β1 transgenic mouse to evaluate the therapeutic effect of recombinant th...
Source: Kidney International - October 13, 2020 Category: Urology & Nephrology Authors: Atsuro Takeshita, Taro Yasuma, Kota Nishihama, Corina N. D ’Alessandro-Gabazza, Masaaki Toda, Toshiaki Totoki, Yuko Okano, Akihiro Uchida, Ryo Inoue, Liqiang Qin, Shujie Wang, Valeria Fridman D’Alessandro, Tetsu Kobayashi, Yoshiyuki Takei, Akira Mizog Tags: Basic Research Source Type: research

Registry reports in COVID-19 patients: juggling with big data, poor data, and no data
We read with great interest the paper by Caillard et al. recently accepted in the Journal (1), which is an interesting addition to the burgeoning COVID-19 literature (2). However, we noted a discrepancy between the 426 kidney transplant patients reported to the registry and the 279 cases presented, which corresponds to a third of all patients. These available but unreported cases may have significantly impacted the results, but the authors neither explain this omission nor acknowledge it as a limitation. (Source: Kidney International)
Source: Kidney International - October 13, 2020 Category: Urology & Nephrology Authors: John S øfteland, Kristian Karason, Jesper Magnusson, Andreas Schult, Marie Felldin, Vanda Friman, Mihai Oltean Tags: letters to the editor Source Type: research

Response to “Registry reports in COVID-19 patients: juggling with big data, poor data, and no data”
We thank S øfteland and coworkers (1) for their interest in our registry based-study focusing on COVID-19 in kidney transplant recipients (2). First, the authors lament that a discrepancy exists in the number of patients reported in the “Introduction” section (n=426) and those included in the final analys is (n=279). However, the 147 excluded patients had (Source: Kidney International)
Source: Kidney International - October 13, 2020 Category: Urology & Nephrology Authors: Marc Hazzan, Sophie Caillard Tags: letters to the editor Source Type: research

COVID-19 in Dialysis Patients: Outlasting and Outsmarting a Pandemic
COVID-19 has affected dialysis patients and dialysis patient care worldwide. In this issue of Kidney International, three reports highlight the disproportionately severe impact of COVID-19 on dialysis patients, noting its high prevalence, particularly among in-center dialysis patients. This likely reflects patients ’ limited ability to physically distance as well as community exposures, including residence in areas with high rates of infection. Dialysis patients are at extremely high risk should they develop COVID-19, with short-term mortality of 20% or higher. (Source: Kidney International)
Source: Kidney International - October 13, 2020 Category: Urology & Nephrology Authors: Caroline M. Hsu, Daniel E. Weiner Tags: commentary Source Type: research

Neural cell adhesion molecule 1 is a novel autoantigen in membranous lupus nephritis.
Membranous lupus nephritis is a frequent cause of nephrotic syndrome in patients with systemic lupus erythematosus. It has been shown in phospholipase A2 receptor positive membranous; nephropathy that known antibodies can be detected within sera, determination of the target; autoantigen can have diagnostic significance, inform prognosis, and enable non-invasive; monitoring of disease activity. Here we utilized mass spectrometry for antigen discovery in laser; captured microdissected glomeruli from formalin-fixed paraffin embedded tissue and tissue; protein G immunoprecipitation studies to interrogate immune complexes from ...
Source: Kidney International - October 9, 2020 Category: Urology & Nephrology Authors: Tiffany Caza, Samar Hassen, Michael Kuperman, Shree Sharma, Zeljko Dvanajscak, John Arthur, Rick Edmondson, Aaron Storey, Christian Herzog, Daniel Kenan, Christopher Larsen Tags: clinical investigation Source Type: research

SARS-CoV-2 receptor networks in diabetic and COVID-19 associated kidney disease
COVID-19 morbidity and mortality are increased in patients with diabetes and kidney disease via unknown mechanisms. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) for entry into host cells. Since ACE2 is a susceptibility factor for infection, we investigated how diabetic kidney disease and medications alter ACE2 receptor expression in kidneys. Single cellRNA profiling of healthy living donor and kidney biopsies from patients with diabetic kidney disease revealed ACE2 expression primarily in proximal tubular epithelial cells. (Source: Kidney International)
Source: Kidney International - October 6, 2020 Category: Urology & Nephrology Authors: Rajasree Menon, Edgar A. Otto, Rachel Sealfon, Viji Nair, Aaron K. Wong, Chandra L. Theesfeld, Xi Chen, Yuan Wang, Avinash S. Boppana, Jinghui Luo, Yingbao Yang, Peter M. Kasson, Jennifer A. Schaub, Celine C. Berthier, Sean Eddy, Chrysta C. Lienczewski, B Tags: clinical investigation Source Type: research

Ethics of kidney care in the era of COVID-19
The COVID-19 pandemic presents significant challenges for health systems globally, including substantive ethical dilemmas that may pose specific concerns in the context of care for people with kidney disease. Ethical concerns may arise as changes to policy and practice impact on the ability of all health professionals to fulfil their ethical duties towards their patients in providing best practice care. In this paper we briefly describe such concerns and elaborate on issues of particular ethical complexity in kidney care: equitable access to dialysis during pandemic surges; balancing the risks and benefits of different kid...
Source: Kidney International - October 6, 2020 Category: Urology & Nephrology Authors: Dominique E. Martin, Jordan A. Parsons, Fergus Caskey, David C.H. Harris, Vivekanand Jha Tags: review Source Type: research

KDIGO 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease
The development and publication of this guideline were supported by KDIGO. The opinions or views expressed in this professional education supplement are those of the authors and do not necessarily reflect the opinions or recommendations of the International Society of Nephrology or Elsevier. Dosages, indications, and methods of use for products that are referred to in the supplement by the authors may reflect their clinical experience or may be derived from the professional literature or other clinical sources. (Source: Kidney International)
Source: Kidney International - September 30, 2020 Category: Urology & Nephrology Authors: Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group Tags: Practice Guideline Source Type: research

Editorial Board
(Source: Kidney International)
Source: Kidney International - September 30, 2020 Category: Urology & Nephrology Source Type: research

Subscription Information
(Source: Kidney International)
Source: Kidney International - September 30, 2020 Category: Urology & Nephrology Source Type: research

Title Page
(Source: Kidney International)
Source: Kidney International - September 30, 2020 Category: Urology & Nephrology Source Type: research

Table of Contents
(Source: Kidney International)
Source: Kidney International - September 30, 2020 Category: Urology & Nephrology Source Type: research

How mTORC1 makes sense of nutrients
Mammalian cells must sense and respond to fluctuations in environmental nutrient concentrations to preserve homeostasis.1 A key step in this process is the recruitment of an ancient protein kinase called the mammalian Target of Rapamycin (mTOR) and its associated regulatory complex 1 (mTORC1) to the surface of the endolysosome — an organelle that functions in the degradation and recycling of cellular macromolecules.1 There, the kinase activity of mTORC1 is initiated by its activator, the small GTPase Rheb, which conveys the second set of different stimuli2 (e.g., cellular energy status, oxygen levels and growth facto...
Source: Kidney International - September 29, 2020 Category: Urology & Nephrology Authors: Alessandro Luciani, Massimiliano Stagi Tags: nephrology digest Source Type: research

Results from the ERA-EDTA Registry indicate a high mortality due to COVID-19 in dialysis patients and kidney transplant recipients across Europe.
The aim of this study was to investigate 28-day mortality after COVID-19 diagnosis in the European kidney replacement therapy population. In addition, we determined the role of patient characteristics, treatment factors, and country on mortality risk using ERA-EDTA Registry data on patients receiving kidney replacement therapy in Europe between February 1, 2020 and April 30, 2020. Additional data on all patients with a diagnosis of COVID-19 were collected from seven European countries encompassing 4298 patients. (Source: Kidney International)
Source: Kidney International - September 21, 2020 Category: Urology & Nephrology Authors: Kitty J. Jager, Anneke Kramer, Nicholas C. Chesnaye, C écile Couchoud, J. Emilio Sánchez-Álvarez, Liliana Garneata, Fréderic Collart, Marc H. Hemmelder, Patrice Ambühl, Julia Kerschbaum, Camille Legeai, María Dolores del Pino y Pino, Gabriel Mircesc Tags: clinical investigation Source Type: research

Response to Thrombotic Microangiopathy: COVID-19 or Hydroxychloroquine?
We thank Dr Hasbal for the concern expressed (1) regarding hydroxychloroquine (HCQ) as the cause of the TMA in our published case titled “Thrombotic microangiopathy (TMA) in a patient with COVID-19”(2). An immune mediated thrombotic microangiopathy usually requires ongoing exposure to the drug. In our case, the patient mentioned was on HCQ for a duration of 5 days. The initial 2 doses were prior to the admission and the drug was continued during the initial 3 days of hospitalization. The findings of hemolysis and TMA developed on day 17 of the admission which was 2 weeks after the drug had been discontinued. (S...
Source: Kidney International - September 20, 2020 Category: Urology & Nephrology Authors: Rimda Wanchoo, Maria Louise Barilla-LaBarca, Kenar D. Jhaveri Tags: letters to the editor Source Type: research

Thrombotic microangiopathy: COVID-19 or Hydroxychloroquine?
To the Editor, I read with great interest the Letter to the Editor by Jhaveri et al. reporting the first published case report of thrombotic microangiopathy in a patient with COVID-19.1 While there was a clear temporal relationship between the presentation with COVID-19 and development of thrombotic microangiopathy, I wonder whether the authors considered the possibility of a drug-induced thrombotic microangiopathy in particular hydroxychloroquine which was introduced on Day 1 of admission. (Source: Kidney International)
Source: Kidney International - September 20, 2020 Category: Urology & Nephrology Authors: Nuri Baris Hasbal Tags: letters to the editor Source Type: research

The sodium/proton exchanger NHA2 regulates blood pressure through a WNK4-NCC dependent pathway in the kidney.
NHA2 is a sodium/proton exchanger associated with arterial hypertension in humans, but the role of NHA2 in kidney function and blood pressure homeostasis is currently unknown. Here we show that NHA2 localizes almost exclusively to distal convoluted tubules in the kidney. NHA2 knock-out mice displayed reduced blood pressure, normocalcemic hypocalciuria and an attenuated response to the thiazide diuretic hydrochlorothiazide. Phosphorylation of the thiazide-sensitive sodium/chloride cotransporter NCC and its upstream activating kinase Ste20/SPS1-related proline/alanine rich kinase (SPAK), as well as the abundance of with no l...
Source: Kidney International - September 17, 2020 Category: Urology & Nephrology Authors: Manuel A. Anderegg, Giuseppe Albano, Daniela Hanke, Christine Deisl, Dominik E. Uehlinger, Simone Brandt, Rajesh Bhardwaj, Matthias A. Hediger, Daniel G. Fuster Tags: basic research Source Type: research

Immune evasion in renal cell carcinoma: biology, clinical translation, future directions
This article reviews the current understanding of the different, yet coordinated, mechanisms adopted by RCC cells to evade immune killing; summarizes various aspects of clinical translation thus far, including the currently registered RCC clinical trials exploring agents in combination with checkpoint inhibitors; and provides perspectives on the current landscape and future directions for the field. (Source: Kidney International)
Source: Kidney International - September 15, 2020 Category: Urology & Nephrology Authors: Xiaoyang Wang, Robert Lopez, Rebecca A. Luchtel, Sassan Hafizi, Benjamin Gartrell, Niraj Shenoy Tags: review Source Type: research

Successful Simultaneous Pancreas and Kidney Transplant in a Patient Post-COVID-19 Infection
We present a patient who underwent a simultaneous pancreas and kidney transplantation (SPK) after recovering from COVID-19 and is doing well close to 2 months post-transplantation. A 66-year-old Caucasian female with end-stage renal disease (ESRD) secondary to insulin dependent type 2 diabetes mellitus was called in to undergo SPK. (Source: Kidney International)
Source: Kidney International - September 14, 2020 Category: Urology & Nephrology Authors: Neeraj Singh, Srijan Tandukar, Gazi Zibari, Muhammad Saad Naseer, Hosein S. Amiri, Millie Samaniego Tags: letters to the editor Source Type: research

Plasma cadmium is associated with increased risk of long-term kidney graft failure.
The kidney is one of the most sensitive organs to cadmium-induced toxicity, particularly in conditions of long-term oxidative stress. We hypothesized that, in kidney transplant recipients, nephrotoxic exposure to cadmium represents an overlooked hazard for optimal graft function. To test this, we performed a prospective cohort study and included 672 outpatient kidney transplant recipients with a functioning graft of beyond one year. The median plasma cadmium was 58 ng/L. During a median 4.9 years of follow-up, 78 kidney transplant recipients developed graft failure with a significantly different distribution across tertile...
Source: Kidney International - September 12, 2020 Category: Urology & Nephrology Authors: Camilo G. Sotomayor, Dion Groothof, Joppe J. Vodegel, Michele F. Eisenga, Tim J. Knobbe, Jan IJmker, Rosa G.M. Lammerts, Martin H. de Borst, Stefan P. Berger, Ilja M. Nolte, Ram ón Rodrigo, Riemer H.J.A. Slart, Gerjan J. Navis, Daan J. Touw, Stephan J.L. Tags: clinical investigation Source Type: research

Mineral bone disease in autosomal dominant polycystic kidney disease.
Mice with disruption of Pkd1 in osteoblasts demonstrate reduced bone mineral density, trabecular bone volume and cortical thickness. To date, the bone phenotype in adult patients with autosomal dominant polycystic kidney disease (ADPKD) with stage I and II chronic kidney disease has not been investigated. To examine this, we characterized biochemical markers of mineral metabolism, examined bone turnover and biology, and estimated risk of fracture in patients with ADPKD. Markers of mineral metabolism were measured in 944 patients with ADPKD and other causes of kidney disease. (Source: Kidney International)
Source: Kidney International - September 9, 2020 Category: Urology & Nephrology Authors: Berenice Gitomer, Renata Pereira, Isidro B. Salusky, Jason W. Stoneback, Tamara Isakova, Xuan Cai, Lorien S. Dalrymple, Norma Ofsthun, Zhiying You, Harmut H. Malluche, Franklin Maddux, Diana George, Vicente Torres, Arlene Chapman, Theodore I. Steinman, My Tags: clinical investigation Source Type: research

Subgroup analysis of the ASPirin in Reducing Events in the Elderly randomized clinical trial suggest aspirin did not improve outcomes in older adults with chronic kidney disease.
The role of aspirin for primary prevention in older adults with chronic kidney disease (CKD) is unclear. Therefore, post hoc analysis of the randomized controlled trial ASPirin in Reducing Events in the Elderly (ASPREE) was undertaken comparing 100 mg of enteric-coated aspirin daily against matching placebo. Participants were community dwelling adults aged 70 years and older in Australia, 65 years and older in the United States, all free of a history of dementia or cardiovascular disease and of any disease expected to lead to death within five years. (Source: Kidney International)
Source: Kidney International - September 9, 2020 Category: Urology & Nephrology Authors: Rory Wolfe, James B. Wetmore, Robyn L. Woods, John J. McNeil, Hugh Gallagher, Paul Roderick, Rowan Walker, Mark R. Nelson, Christopher M. Reid, Raj C. Shah, Michael E. Ernst, Jessica E. Lockery, Andrew M. Tonkin, Walter P. Abhayaratna, Peter Gibbs, Erica Tags: clinical trial Source Type: research

Sepsis-Associated Acute Kidney Injury: Is COVID-19 different?
Faced with a new disease, clinicians understandably resort to what they know. For example, we know severe viral pneumonia secondary to influenza, so when we began seeing COVID-19, our first impression was that it was a similar disease, so we felt we knew how to manage it. However, it soon became clear that COVID-19 was strikingly different. First, there was the high transmission rate including spread within hospitals and health care workers 1 —but this could simply have been due to a new disease in a naïve population. (Source: Kidney International)
Source: Kidney International - September 8, 2020 Category: Urology & Nephrology Authors: John A. Kellum, Mitra K. Nadim, Lui G. Forni Tags: editorial Source Type: research

Human kidney organoids produce functional renin
Renin production by the kidney is of vital importance for salt, volume, and blood pressure homeostasis. The lack of human models hampers investigation into the regulation of renin and its relevance for kidney physiology. To develop such a model, we used human induced pluripotent stem cell derived kidney organoids to study the role of renin and the renin-angiotensin system in the kidney. Extensive characterization of the kidney organoids revealed kidney-specific cell populations consisting of podocytes, proximal and distal tubular cells, stromal cells and endothelial cells. (Source: Kidney International)
Source: Kidney International - September 8, 2020 Category: Urology & Nephrology Authors: Anusha S. Shankar, Zhaoyu Du, Hector Tejeda Mora, Thierry P.P. van den Bosch, Sander S. Korevaar, Ingrid M. Van den Berg – Garrelds, Eric Bindels, Carmen Lopez-Iglesias, Marian Clahsen-van Groningen, Joost Gribnau, Carla C. Baan, A.H. Jan Danser, Ewout Tags: basic research Source Type: research

The phosphoinositide 3-kinase inhibitor alpelisib restores actin organization and improves proximal tubule dysfunction in  vitro and in a mouse model of Lowe syndrome and Dent disease
Loss-of-function mutations in the OCRL gene, which encodes the phosphatidylinositol [PI] 4,5-bisphosphate [PI(4,5)P2] 5-phosphatase OCRL, cause defective endocytosis and proximal tubule dysfunction in Lowe syndrome and Dent disease 2. The defect is due to increased levels of PI(4,5)P2 and aberrant actin polymerization, blocking endosomal trafficking. PI 3-phosphate [PI(3)P] has been recently identified as a coactivator with PI(4,5)P2 in the actin pathway. Here, we tested the hypothesis that phosphoinositide 3-kinase (PI3K) inhibitors may rescue the endocytic defect imparted by OCRL loss, by rebalancing phosphoinositide sig...
Source: Kidney International - September 8, 2020 Category: Urology & Nephrology Authors: Marine Berquez, Jonathan R. Gadsby, Beatrice Paola Festa, Richard Butler, Stephen P. Jackson, Valeria Berno, Alessandro Luciani, Olivier Devuyst, Jennifer L. Gallop Tags: Basic Research Source Type: research

Cystinuria: clinical practice recommendation
Cystinuria (OMIM 220100) is an autosomal recessive hereditary disorder in which high urinary cystine excretion leads to formation of cystine stones due to its low solubility at normal urinary pH. We developed clinical practice recommendation for diagnosis, surgical and medical treatment, and follow up of cystinuria patients. Elaboration of these Clinical Practice Recommendations spanned from June 2018 until December 2019 with a consensus conference in January 2019. Selected topic areas were chosen by the co-chairs of the conference. (Source: Kidney International)
Source: Kidney International - September 8, 2020 Category: Urology & Nephrology Authors: Aude Servais, Kay Thomas, Luca Dello Strologo, John A. Sayer, Soumeya Bekri, Aurelia Bertholet-Thomas, Matthew Bultitude, Giovanna Capolongo, Rimante Cerkauskiene, Michel Daudon, Steeve Doizi, Valentine Gillion, Silvia Gr àcia-Garcia, Jan Halbritter, Lau Tags: review Source Type: research

Magnetic resonance imaging accurately tracks kidney pathology and heterogeneity in the transition from acute kidney injury to chronic kidney disease.
Acute kidney injury is common in hospitalized patients. Many of the patients who experience AKI develop chronic kidney disease. However, using clinically available tools it is difficult to predict who and when CKD will develop. CFE-MRI provides several measurements of functional glomeruli in preclinical studies. CFE-MRI has the potential to be translated to use in humans, to detect changes in the kidney following acute kidney injury and predict which patients may develop CKD. The next steps toward translation will include in vivo tracking of glomerular fate in preclinical models of AKI to CKD and assessing the toxicity of ...
Source: Kidney International - September 7, 2020 Category: Urology & Nephrology Authors: Jennifer R. Charlton, Yanzhe Xu, Teresa Wu, Kim A. deRonde, Jillian L. Hughes, Shourik Dutta, Gavin T. Oxley, Aleksandra Cwiek, Helen P. Cathro, Nathan P. Charlton, Mark R. Conaway, Edwin J. Baldelomar, Neda Parvin, Kevin M. Bennett Tags: basic research Source Type: research

Renin-angiotensin aldosterone inhibitor use at hospital discharge among patients with moderate to severe acute kidney injury and its association with recurrent acute kidney injury and mortality.
Recurrent episodes of acute kidney injury (AKI) are common among AKI survivors. Renin-angiotensin aldosterone inhibitors (RAASi) are often indicated for these patients but may increase the risk for recurrent AKI. Here, we examined whether RAASi associates with a higher risk for recurrent AKI and mortality among survivors of moderate to severe AKI in a retrospective cohort of Veterans who survived Stage II or III AKI. The primary exposure was RAASi at hospital discharge and the primary endpoint was recurrent AKI within 12 months. (Source: Kidney International)
Source: Kidney International - September 7, 2020 Category: Urology & Nephrology Authors: Edward D. Siew, Sharidan K. Parr, Khaled Abdel-Kader, Amy M. Perkins, Robert A. Greevy, Andrew J. Vincz, Jason Denton, Otis D. Wilson, Adriana M. Hung, T. Alp Ikizler, Cassianne Robinson-Cohen, Michael E. Matheny Tags: clinical investigation Source Type: research

Proximal tubular dysfunction in patients with COVID-19: what have we learnt so far?
Recent studies have reported a variety of urine abnormalities in patients hospitalized due to SARS-CoV-2 infection. In a single center study from Belgium, Werion et al., now present a concise investigation of tubular dysfunction in COVID-19 patients identifying potential risk factors for increased disease severity. These data complement current evidence regarding SARS-CoV-2 presence and potential infection in the kidney. (Source: Kidney International)
Source: Kidney International - September 7, 2020 Category: Urology & Nephrology Authors: Fabian Braun, Tobias B. Huber, Victor G. Puelles Tags: commentary Source Type: research

Prediction modelling - Part 2 - Using machine learning strategies to improve transplantation outcomes
Kidney transplant recipients and transplant physicians face important clinical questions where machine learning methods may help improve the decision-making process. This mini-review explores potential applications of machine learning methods to key stages of a kidney transplant recipient ’s journey, from initial waitlisting and donor selection, to personalization of immunosuppression and prediction of post-transplantation events. Both unsupervised and supervised machine learning methods are presented, including k-means clustering, principal components analysis, k-nearest neighbors and random forests. (Source: Kidney International)
Source: Kidney International - September 6, 2020 Category: Urology & Nephrology Authors: Craig Peter Coorey, Ankit Sharma, Samuel Mueller, Jean Yang Tags: xyz of statistics Source Type: research

Preoperative Carfilzomib and Lulizumab based desensitization prolongs graft survival in a sensitized non-human primate model.
Sensitized patients are difficult to transplant due to pre-formed anti-donor immunity. We have previously reported successful desensitization using carfilzomib and belatacept in a non-human primate (NHP) model. Here we evaluated selective blockade of the co-stimulatory signal (CD28-B7) with Lulizumab, which preserves the co-inhibitory signal (CTLA4-B7). Five maximally MHC-mismatched pairs of NHPs were sensitized to each other with two sequential skin transplants. Individuals from each pair were randomized to either desensitization with once-weekly Carfilzomib (27mg/m2 IV) and Lulizumab (12.5mg/kg SC) over four weeks, or no...
Source: Kidney International - September 4, 2020 Category: Urology & Nephrology Authors: Paul M. Schroder, Robin Schmitz, Zachary W. Fitch, Brian Ezekian, Janghoon Yoon, Ashley Y. Choi, Miriam Manook, Andrew Barbas, Frank Leopardi, Mingqing Song, Alton B. Farris, Bradley Collins, Jean Kwun, Stuart J. Knechtle Tags: basic research Source Type: research

A cross sectional study of 502 patients found a diffuse hyperechoic kidney medulla pattern in patients with severe gout.
We have previously shown that ultrasonography can detect hyperechogenic crystal deposits in the kidney medulla of patients with gout. In this cross-sectional study we investigated the frequency and clinical correlates of hyperechogenic kidney medulla in 502 consecutive primary consultants for gout (ACR/EULAR criteria) at the Vien Gut medical center in Ho Chi Minh City, Vietnam. None of these patients received urate-lowering drugs. Kidney medulla echogenicity on B-mode ultrasonography was compared to that of the kidney cortex. (Source: Kidney International)
Source: Kidney International - September 4, 2020 Category: Urology & Nephrology Authors: Thomas Bardin, Quang D. Nguyen, Khoy M. Tran, Nghia H. Le, Minh D. Do, Pascal Richette, Emmanuel Letavernier, Jean-Michel Correas, Mathieu Resche-Rigon Tags: clinical investigation Source Type: research

Time-dependent lymphocyte count after transplantation is associated with higher risk of graft failure and death.
The transplantation field requires the identification of specific risk factors associated with the level of immunosuppression. Here, our aim was to analyze the association between the number of circulating lymphocytes, monitored routinely by complete blood cell counts during outpatient visits, and patient and graft survival. In total, 2,999 kidney or combined kidney-pancreas recipients transplanted between 2000 and 2016, from two University hospitals, were enrolled. We investigated the etiological relationship between time-dependent lymphocyte count beyond one year after transplantation and patient and graft survival, vira...
Source: Kidney International - September 2, 2020 Category: Urology & Nephrology Authors: Amaury Dujardin, Marine Lorent, Yohann Foucher, Christophe Legendre, Clarisse Kerleau, Sophie Brouard, Magali Giral, DIVAT consortium Tags: clinical investigation Source Type: research

Multifactorial intervention has a significant effect on diabetic kidney disease in patients with type 2 diabetes.
To evaluate the effect of multifactorial intervention on the onset and progression of diabetic kidney disease in the patients with type 2 diabetes, we analyzed the effects of intensified multifactorial intervention (intensive therapy treatment targets; HbA1c under 6.2%, blood pressure under 120/75 mmHg, low-density lipoprotein cholesterol under 80 mg/dL) comparing with step-wise intensification of medications and life-style modifications of guideline-based standard care (conventional therapy treatment targets: HbA1c under 6.9%, blood pressure under 130/80 mmHg, low-density lipoprotein cholesterol under 120 mg/dL) on diabet...
Source: Kidney International - September 2, 2020 Category: Urology & Nephrology Authors: Kohjiro Ueki, Takayoshi Sasako, Yukiko Okazaki, Kana Miyake, Masaomi Nangaku, Yasuo Ohashi, Mitsuhiko Noda, Takashi Kadowaki, J-DOIT3 Study Group Tags: clinical trial Source Type: research

HLA-D and PLA2R1 risk alleles associate with recurrent primary membranous nephropathy in kidney transplant recipients.
Recurrence of primary membranous nephropathy after transplantation occurs in up to 44% of patients and is driven by PLA2R antibody. Here, we asked whether genetic determinants could improve risk prediction. First, we sequenced PLA2R1 and HLA-D loci in 248 patients with primary membranous nephropathy and identified two independent single nucleotide polymorphisms (SNPs) at risk for primary membranous nephropathy at each locus. These were rs9271188 (intergenic between HLA-DRB1 and HLA-DQA1,) and rs9275086 (intergenic between HLA-DQB1 and HLA-DQA2) at the HLA-D locus along with rs6726925 and rs13018963 at the PLA2R1 locus. (So...
Source: Kidney International - August 31, 2020 Category: Urology & Nephrology Authors: Lena Berchtold, Eric Letouz é, Mariam Priya Alexander, Guillaume Canaud, Anne-Els van de Logt, Patrick Hamilton, Christiane Mousson, Vincent Vuiblet, Ann M. Moyer, Sylvain Guibert, Petra Mrázová, Charlène Levi, Valérie Dubois, Josep Maria Cruzado, Ar Tags: clinical investigation Source Type: research

Development and testing of an artificial intelligence tool for predicting end stage kidney disease in patients with immunoglobulin A nephropathy.
We have developed an artificial neural network prediction model for end-stage kidney disease (ESKD) in patients with primary immunoglobulin A nephropathy (IgAN) using a retrospective cohort of 948 patients with IgAN. Our tool is based on a two-step procedure of a classifier model that predicts ESRD, and a regression model that predicts development of ESKD over time. The classifier model showed a performance value of 0.82 (area under the receiver operating characteristic curve) in patients with a follow-up of five years, which improved to 0.89 at the ten-year follow-up. (Source: Kidney International)
Source: Kidney International - August 31, 2020 Category: Urology & Nephrology Authors: Francesco Paolo Schena, Vito Walter Anelli, Joseph Trotta, Tommaso Di Noia, Carlo Manno, Giovanni Tripepi, Graziella D ’Arrigo, Nicholas C. Chesnaye, Maria Luisa Russo, Maria Stangou, Aikaterini Papagianni, Carmine Zoccali, Vladimir Tesar, Rosanna Coppo Tags: clinical investigation Source Type: research

Impaired angiotensin II type 1 receptor signaling contributes to sepsis induced acute kidney injury.
In sepsis-induced acute kidney injury, kidney blood flow may increase despite decreased glomerular filtration. Normally, angiotensin-II reduces kidney blood flow to maintain filtration. We hypothesized that sepsis reduces angiotensin type-1 receptor (AT1R) expression to account for this observation and tested this hypothesis in a patient case-control study and studies in mice. Seventy-three mice underwent cecal ligation and puncture (a sepsis model) or sham operation. Additionally, 94 septic mice received losartan (selective AT1R antagonist), angiotensin II without or with losartan, or vehicle. (Source: Kidney International)
Source: Kidney International - August 30, 2020 Category: Urology & Nephrology Authors: Daniel E. Leisman, Tiago D. Fernandes, Vanesa Bijol, Mabel N. Abraham, Jake R. Lehman, Matthew D. Taylor, Christine Capone, Omar Yaipan, Rinaldo Bellomo, Clifford S. Deutschman Tags: basic research Source Type: research

Consensus Definitions for Glomerular Lesions by Light and Electron Microscopy: Recommendations from a Working Group of the Renal Pathology Society
Over the past two decades, scoring systems for multiple glomerular diseases have emerged, as have consortia of pathologists and nephrologists for the study of glomerular diseases, including correlation of pathologic findings with clinical features and outcomes. However, one important limitation faced by members of these consortia and other renal pathologists and nephrologists in both investigative work and routine practice remains a lack of uniformity and precision in clearly defining the morphologic lesions on which the scoring systems are based. (Source: Kidney International)
Source: Kidney International - August 27, 2020 Category: Urology & Nephrology Authors: Mark Haas, Surya V. Seshan, Laura Barisoni, Kerstin Amann, Ingeborg M. Bajema, Jan Ulrich Becker, Kensuke Joh, Danica Ljubanovic, Ian S.D. Roberts, Joris J. Roelofs, Sanjeev Sethi, Caihong Zeng, J. Charles Jennette Tags: meeting report Source Type: research

Management of idiopathic childhood nephrotic syndrome in Sub-Saharan Africa: Ibadan consensus statement
In sub-Saharan Africa, glomerular disease, specifically nephrotic syndrome (NS), is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) in children.1-3 Prevalence of NS is estimated at 2-7 per 100,000 children worldwide,1 and it is one of the more common causes of pediatric kidney disorders in Africa. Despite limited reports from Nigeria and Sudan, 2-4 the overall incidence of NS in Africa is unknown. Among the 54 African countries, only 17 have information on the burden of childhood NS indicating substantial underreporting. (Source: Kidney International)
Source: Kidney International - August 27, 2020 Category: Urology & Nephrology Authors: Christopher Esezobor, Adebowale D. Ademola, Adewale E. Adetunji, Emmanuel Ademola Anigilaje, Anthony Batte, Fatima Nma Jiya Bello, Francis Fredrick Furia, Uzoamaka Muoneke, Mignon McCulloch, Peter Nourse, Patience Obiagwu, Odutola Odetunde, Perditer Okyer Tags: policy forum Source Type: research

Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients.
The aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. (Source: Kidney International)
Source: Kidney International - August 23, 2020 Category: Urology & Nephrology Authors: Couchoud C écile, Bayer Florian, Ayav Carole, Béchade Clémence, Brunet Philippe, Chantrel François, Frimat Luc, Galland Roula, Hourmant Maryvonne, Laurain Emmanuelle, Lobbedez Thierry, Mercadal Lucile, Moranne Olivier, in the name of the French REIN r Tags: clinical investigation Source Type: research

A non-biodegradable scaffold-free cell sheet of genome-engineered mesenchymal stem cells inhibits development of acute kidney injury.
Cell therapy using genome-engineered stem cells has emerged as a novel strategy for the treatment of kidney diseases. By exploiting genome editing technology, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) secreting an angiogenic factors or an anti-inflammatory factor were generated for therapeutic application in acute kidney injury. Junction polymerase chain reaction analysis verified Zinc Finger Nucleases-assisted integration of the desired gene into the hUC-MSCs. Flow cytometry and differentiation assays indicated that genome editing did not affect the differentiation potential of these mesenchymal stem ...
Source: Kidney International - August 23, 2020 Category: Urology & Nephrology Authors: Hye-Jeong Park, Min Jung Kong, Hyo-Ju Jang, Jeong-In Cho, Eui-Jung Park, In-Kyu Lee, J ørgen Frøkiær, Rikke Norregaard, Kwon Moo Park, Tae-Hwan Kwon Tags: basic research Source Type: research

An initial report from the French SOT COVID Registry suggests high mortality due to Covid-19 in recipients of kidney transplants.
Notwithstanding the ongoing coronavirus disease-2019 (Covid-19) pandemic, information on its clinical presentation and prognosis in recipients of a kidney transplant remain scanty. The aim of this registry-based observational study was to explore characteristics and clinical outcomes of recipients of kidney transplants included in the French nationwide Registry of Solid Organ Transplant Recipients with Covid-19. Covid-19 was diagnosed in symptomatic patients who had a positive PCR assay for SARS-CoV-2 or having typical lung lesions on imaging. (Source: Kidney International)
Source: Kidney International - August 22, 2020 Category: Urology & Nephrology Authors: Sophie Caillard, Dany Anglicheau, Marie Matignon, Antoine Durrbach, Clarisse Greze, Luc Frimat, Olivier Thaunat, Tristan Legris, Valerie Moal, Pierre Francois Westeel, Nassim Kamar, Philippe Gatault, Renaud Snanoudj, Antoine Sicard, Dominique Bertrand, Ch Tags: clinical investigation Source Type: research

APOL1 variant associated kidney disease: From trypanosomes to podocyte cytoskeleton.
Expression of the C-terminal APOL1 variants G1 and G2 is strongly linked to chronic kidney disease. The recent analysis of podocytes genetically engineered to express either C-terminal truncated APOL1 or disrupted APOL3 allowed the conclusion that C-terminal APOL1 variants induce reorganization of actomyosin activities through inhibition of APOL3 functions. This editorial is not intended to review the literature in the field, but rather to discuss the proposal that podocyte dysfunctions linked to APOL3 inactivation can account for chronic kidney disease linked to expression of the APOL1 risk variants G1 and G2. (Source: Kidney International)
Source: Kidney International - August 20, 2020 Category: Urology & Nephrology Authors: Etienne Pays Tags: editorial Source Type: research

Development and evaluation of deep learning-based segmentation of histologic structures in the kidney cortex with multiple histologic stains.
The application of deep learning for automated segmentation (delineation of boundaries) of histologic primitives (structures) from whole slide images can facilitate the establishment of novel protocols for kidney biopsy assessment. Here, we developed and validated deep learning networks for the segmentation of histologic structures on kidney biopsies and nephrectomies. For development, we examined 125 biopsies for Minimal Change Disease collected across 29 NEPTUNE enrolling centers along with 459 whole slide images stained with Hematoxylin& Eosin (125), Periodic Acid Schiff (125), Silver (102), and Trichrome (107)] div...
Source: Kidney International - August 20, 2020 Category: Urology & Nephrology Authors: Catherine P. Jayapandian, Yijiang Chen, Andrew R. Janowczyk, Matthew B. Palmer, Clarissa A. Cassol, Miroslav Sekulic, Jeffrey B. Hodgin, Jarcy Zee, Stephen M. Hewitt, John O ’Toole, Paula Toro, John R. Sedor, Laura Barisoni, Anant Madabhushi Tags: basic research Source Type: research

Automated total kidney volume measurements in pre-clinical magnetic resonance imaging for resourcing imaging data, annotations, and source code
The objective of this study was to validate a fully automated total kidney volume measurement method for pre-clinical rodent trials that is fast, accurate, reproducible, and to provide these resources to the research community. Rodent studies that involve imaging are crucial for monitoring treatment efficacy in diseases such as polycystic kidney disease. Previous studies utilize manual or semi-automated segmentations, which are time consuming and potentially biased. To develop our automated system, a total of 150 axial magnetic resonance images (MRI) from a variety of mouse models were manually segmented and used to train/...
Source: Kidney International - August 19, 2020 Category: Urology & Nephrology Authors: Marie E. Edwards, Sigapriya Periyanan, Deema Anaam, Adriana V. Gregory, Timothy L. Kline Tags: technical notes Source Type: research