A mathematical estimation of the physical forces driving podocyte detachment
Loss of podocytes, possibly through the detachment of viable cells, is a hallmark of progressive glomerular disease. Podocytes are exposed to considerable physical forces due to pressure and flow resulting in circumferential wall stress and tangential shear stress exerted on the podocyte cell body, which have been proposed to contribute to podocyte depletion. However, estimations of in vivo alterations of physical forces in glomerular disease have been hampered by a lack of quantitative functional and morphological data. (Source: Kidney International)
Source: Kidney International - July 29, 2021 Category: Urology & Nephrology Authors: Linus Butt, David Unnersj ö-Jess, Martin Höhne, Bernhard Schermer, Aurelie Edwards, Thomas Benzing Tags: basic research Source Type: research

The circadian clock regulates rhythmic erythropoietin expression in the murine kidney
Generation of circadian rhythms is cell-autonomous and relies on a transcription/translation feedback loop controlled by a family of circadian clock transcription factor activators including CLOCK, BMAL1 and repressors such as CRY1 and CRY2. The aim of the present study was to examine both the molecular mechanism and the hemopoietic implication of circadian erythropoietin expression. Mutant mice with homozygous deletion of the core circadian clock genes cryptochromes 1 and 2 (Cry-null) were used to elucidate circadian erythropoietin regulation. (Source: Kidney International)
Source: Kidney International - July 29, 2021 Category: Urology & Nephrology Authors: Lina K. Sciesielski, Matthias Felten, Laura Michalick, Karin M. Kirschner, Georgia Lattanzi, Charlotte LJ. Jacobi, Thomas Wallach, Veronika Lang, Dominic Landgraf, Achim Kramer, Christof Dame Tags: basic research Source Type: research

A Case of Membranous Nephropathy Following Pfizer-BioNTech mRNA vaccine against Coronavirus 2019
We read recent report describing the relapse of membranous nephropathy (MN) following inactivated vaccine against Coronavirus 2019 (COVID-19)1. Here, we describe a case of new onset MN following Pfizer-BioNTech mRNA based COVID-19 vaccine. (Source: Kidney International)
Source: Kidney International - July 29, 2021 Category: Urology & Nephrology Authors: Yi Da, Giap Hean Goh, Priyanka Khatri Tags: letters to the editor Source Type: research

Vitamin K and cardiovascular complications in CKD patients
Vitamin K, well known for its role in coagulation, encompasses two major subgroups: Vitamin K1 is exclusively synthesized by plants, whereas vitamin K2 mostly originates from bacterial synthesis. Vitamin K serves as a cofactor for the enzyme γ-glutamyl carboxylase, which carboxylates and thereby activates various vitamin K dependent proteins. Several vitamin K–dependent proteins are synthesized in bone but the role of vitamin K for bone health in CKD patients, in particular the prevention of osteoporosis is still not firmly establish ed. (Source: Kidney International)
Source: Kidney International - July 23, 2021 Category: Urology & Nephrology Authors: N. Kaesler, L.J. Schurgers, J. Floege Tags: review Source Type: research

Chronic Kidney Disease Rescuing kidney patients from early demise: Role of anti-cytokine therapies
Biomarkers of the inflammatory state are elevated in individuals with chronic kidney disease (CKD) and are also robust predictors of cardiovascular disease (CVD) and mortality in this population. In addition to its predictive ability, inflammation has been implicated in the pathogenesis of atherosclerotic CVD, primarily through NLRP3 inflammasome and interleukin-1 (IL-1) and interleukin-6 (IL-6) signaling pathways 1. Based on these data, it has been suggested that ameliorating the inflammatory response through anti-cytokine therapies could improve CVD risk factors and potentially survival in CKD. (Source: Kidney International)
Source: Kidney International - July 21, 2021 Category: Urology & Nephrology Authors: T. Alp Ikizler, Jonathan Himmelfarb Tags: nephrology digest Source Type: research

Skimming the fat in diabetic kidney disease: KIM-1 and tubular fatty acid uptake
Diabetic kidney disease (DKD) accounts for over 40% of incident ESKD cases. The clinical hallmarks of DKD include reduced glomerular filtration rate (GFR) and increased urinary albumin excretion. Although DKD is traditionally considered a glomerular disease, tubulointerstitial injury is recognized as an important predictor of chronic kidney disease progression in diabetes. Tubular atrophy and interstitial fibrosis are strongly correlated with the progression of diabetic nephropathy to ESKD. Further supporting the role of tubules in DKD progression, the sodium/glucose cotransporter 2 (SGLT2) expressed in proximal tubules ha...
Source: Kidney International - July 20, 2021 Category: Urology & Nephrology Authors: Huihui Huang, Samir M. Parikh Tags: nephrology digest Source Type: research

Bilious  peritoneal dialysate in a peritoneal dialysis patient
A 71-year-old man on peritoneal dialysis for end-stage kidney disease secondary to hypertensive nephropathy presented with vague right upper quadrant abdominal pain and fever. The initial peritoneal dialysate was mildly cloudy but with a slight brownish hue; he was treated for peritoneal dialysis –related peritonitis with intraperitoneal cefazolin and ceftazidime. However, the peritoneal effluent become dark a few hours after admission (Figure 1). The surgical team was consulted immediately for suspected perforated viscus. (Source: Kidney International)
Source: Kidney International - July 19, 2021 Category: Urology & Nephrology Authors: Winston Wing Shing Fung, Kai Ming Chow, Cheuk Chun Szeto Tags: Nephrology Image Source Type: research

Unilateral polycystic kidney disease
A 30-year-old man was diagnosed with polycystic kidney disease (PKD) at the age of 14 when he was found to be hypertensive. Initial abdominal imaging showed markedly enlarged kidney cysts on the left kidney and a solitary cyst on the right kidney, without hepatic cysts. Neither his father nor his mother had kidney cysts on ultrasound. He developed worsening abdominal fullness, left flank discomfort, and back pain. Repeat abdomen magnetic resonance imaging (Figure  1) showed that the total kidney volume was 7531 ml, with 7160 ml attributed to the left kidney. (Source: Kidney International)
Source: Kidney International - July 19, 2021 Category: Urology & Nephrology Authors: Carissa Y. Dumancas, Fouad T. Chebib Tags: Nephrology Image Source Type: research

Peritoneal calcification in a patient on peritoneal dialysis
A 51-year-old nondiabetic woman with end-stage kidney disease on peritoneal dialysis for 18 years presented with diarrhea. Her medical history was notable for an episode of Staphylococcus warneri peritonitis, which was successfully treated with i.p. vancomycin and amikacin. She also had a past episode of mycobacterium tuberculous peritonitis 15 years ago, which was treated with antitubercular agents. The patient was anuric for the last 10 years and was dialyzing with 2 L into 4 exchanges of Dianeal solution (Tamil Nadu; sodium chloride with dextrose). (Source: Kidney International)
Source: Kidney International - July 19, 2021 Category: Urology & Nephrology Authors: Maithrayie Kumaresan, Milly Matthew, Rajeevalochana Parthasarathy, Gerogi Abraham Tags: Nephrology Image Source Type: research

The Case | Cardiac tamponade in a kidney transplant recipient with chronic inflammation
A 45-year-old woman presented with Denys-Drash syndrome who had received a kidney transplant at the age of 12 years. The maintenance immunosuppressive regimen included cyclosporine, azathioprine, and steroids. Her basal creatinine level was 100 μmol/l. The patient was born in France. She was not working, and she had traveled to Australia and Tahiti 25 years prior and to Italy and Canada in 2019. (Source: Kidney International)
Source: Kidney International - July 19, 2021 Category: Urology & Nephrology Authors: Nathalie Chavarot, Perrine Parize, Isabelle Podglajen, Rebecca Sberro-Soussan, Carole Burger, Lucile Amrouche, Frank Martinez, Christophe Legendre, Julien Zuber, Anne Scemla, Geltrude Giura, Patrick Bruneval, Dany Anglicheau Tags: Make Your Diagnosis Source Type: research

Do we need to treat chronic active T cell –mediated rejection?
Chronic active T cell –mediated rejection, demonstrated by the presence of inflammation in areas of fibrosis, is associated with long-term allograft loss. Kung et al., in this issue of Kidney International, describe a series of cases of CA TCMR and analyze their clinical, molecular, and pathologic features as well as their response to therapy. Their translational study aids in understanding this diverse phenotype and provides future direction for managing these patients. (Source: Kidney International)
Source: Kidney International - July 19, 2021 Category: Urology & Nephrology Authors: Michael Mengel, Michelle Lubetzky Tags: Commentary Source Type: research

Establishing a nephrology genetic clinic
Nephrology practices currently are amidst a genetics/genomics revolution where clinical molecular screening has transitioned from analysis of single genes (Sanger sequencing) to global approaches (next-generation sequencing). Two approaches are now generally employed in nephrology, exome sequencing (screening the coding regions of all genes) followed by analysis of genes known to be associated with monogenic kidney disease, or just screening those genes or a phenotypically distinct subset (e.g., cystic kidney disease or nephrolithiasis) via targeted gene panels (Table  1). (Source: Kidney International)
Source: Kidney International - July 19, 2021 Category: Urology & Nephrology Authors: Filippo Pinto e Vairo, Jennifer L. Kemppainen, John C. Lieske, Peter C. Harris, Marie C. Hogan Tags: Editorial Source Type: research

Targeting TMEM16A-encoded Ca2+-activated Cl − channels: a new paradigm for antihypertensive therapy?
Hypertension is the leading risk factor for the development of heart diseases and stroke. Many hypertensive patients experience undesirable side effects to conventional antihypertensive pharmacotherapy. Cil et  al. documented the antihypertensive profile of a novel molecule, TMinh-23 (2-bromodifluoroacetylamino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylic acid o-tolylamide), in the spontaneously hypertensive rat model of systemic hypertension. They showed that this agent reduces blood pressu re by inhibiting transmembrane member 16A–encoded calcium-activated chloride channels in vascular myocytes fr...
Source: Kidney International - July 19, 2021 Category: Urology & Nephrology Authors: Normand Leblanc Tags: Commentary Source Type: research

Paclitaxel-coated balloon angioplasty for recurrent arteriovenous fistula stenosis
We read with interest the investigator-led Paclitaxel-assisted balloon Angioplasty of Venous stenosis in hEmodialysis access (PAVE) trial by Karunanithy et  al., evaluating the efficacy of paclitaxel-coated balloons (PCBs) in arteriovenous fistula (AVF).1 In contrast to a recently published large-scale randomized controlled trial by Lookstein et al.,2 the PAVE trial failed to demonstrate a difference in the treatment effect of PCBs versus standard ba lloons for AVF stenosis. The authors attributed this observation to the different PCB used in the study, which has a different excipient and paclitaxel dose, and a p...
Source: Kidney International - July 19, 2021 Category: Urology & Nephrology Authors: Ru Yu Tan, Suh Chien Pang, Alvin Ren Kwang Tng, Chieh Suai Tan Tags: Letter to the Editor Source Type: research

The authors reply:
We presented these as possible explanations in addition to a number of other possibilities. (Source: Kidney International)
Source: Kidney International - July 19, 2021 Category: Urology & Nephrology Authors: Narayan Karunanithy, Emily J. Robinson, Michael G. Robson Tags: Letter to the Editor Source Type: research

Salbutamol and salt-sensitive hypertension
Salbutamol activates the NaCl cotransporter of the distal convoluted tubule. Salbutamol, in conjunction with high salt intake, induced hypertension in mice, rescued by thiazide therapy. Phosphoproteomics identified protein phosphatase 1/inhibitor 1 as a distinct regulatory node for NaCl cotransporter activation by salbutamol, which did not activate the transporter in inhibitor 1 knockout mice. Salbutamol is widely used in respiratory medicine, and the acquisition of salt sensitivity may be relevant to understanding cardiovascular risk in certain patients. (Source: Kidney International)
Source: Kidney International - July 19, 2021 Category: Urology & Nephrology Authors: Matthew A. Bailey Tags: Commentary Source Type: research

In this issue
Chronic active T cell –mediated rejection (CA TCMR) is a relatively newly described rejection pathology found in some kidney allografts. CA TCMR is characterized by interstitial fibrosis and tubular atrophy in the presence of features of acute T cell–mediated rejection. To determine the responsiveness of this lesion to immunosuppressive therapy, Kung et al. did a retrospective analysis of 48 cases of isolated CA TCMR. About 92% of the patients were treated with pulse glucocorticoids, antithymocyte globulin, or both. (Source: Kidney International)
Source: Kidney International - July 19, 2021 Category: Urology & Nephrology Tags: In This Issue Source Type: research

Journal Club
Rovin et  al. (Lancet. 2021; 397: 2070–2080.) (Source: Kidney International)
Source: Kidney International - July 19, 2021 Category: Urology & Nephrology Tags: Journal Club Source Type: research

Drug-coated balloons and dialysis vascular access: is there light at the end of the tunnel . . .
This commentary uses the negative results of the PAVE (Paclitaxel-coated Balloons and Angioplasty of Arteriovenous Fistulas) study to (i) discuss the role of drug-coated balloons in the armamentarium of therapies for dialysis vascular access stenosis and (ii) suggest a more patient centered, individualized, and precision medicine –based approach for the future care of patients with dialysis vascular access dysfunction. (Source: Kidney International)
Source: Kidney International - July 19, 2021 Category: Urology & Nephrology Authors: Prabir Roy-Chaudhury, Theodore F. Saad, Scott Trerotola Tags: Commentary Source Type: research

Corrigendum to Flemming J, Marczenke M, Rudolph I-M, et  al. Induced pluripotent stem cell-based disease modeling identifies ligand-induced decay of megalin as a cause of Donnai-Barrow syndrome. Kidney Int. 2020;98:159–167
In the above-stated article, the given name and surname one of the authors, Erik Ilsoe Christensen, was presented inaccurately. The given name is Erik and the surname is Ilsoe Christensen. In addition, an additional affiliation of Maike Marczenke was omitted. The additional affiliation is the Department of Biology, Chemistry and Pharmacy, Freie Universitaet Berlin, Berlin, Germany. (Source: Kidney International)
Source: Kidney International - July 19, 2021 Category: Urology & Nephrology Authors: Julia Flemming, Maike Marczenke, Ina-Maria Rudolph, Rikke Nielsen, Tina Storm, Erik Ilsoe Christensen, Sebastian Diecke, Francesco Emma, Thomas E. Willnow Tags: Corrigendum Source Type: research

Editorial Board
(Source: Kidney International)
Source: Kidney International - July 19, 2021 Category: Urology & Nephrology Source Type: research

Subscription Information
(Source: Kidney International)
Source: Kidney International - July 19, 2021 Category: Urology & Nephrology Source Type: research

Table of Contents
(Source: Kidney International)
Source: Kidney International - July 19, 2021 Category: Urology & Nephrology Source Type: research

The ROMANOV study found impaired humoral and cellular immune responses to SARSCov-2 mRNA vaccine in virus unexposed patients receiving maintenance hemodialysis.
Patients on maintenance hemodialysis (MHD), which are at high risk of infection by SARS-CoV-2 virus and death due to COVID-19, have been prioritized for vaccination. However, because they were excluded from pivotal studies and have weakened immune responses, it is not known whether these patients are protected after the “standard” two doses of mRNA vaccines. To answer this, anti-spike receptor binding domain (RBD) IgG and interferon gamma-producing CD4+ and CD8+ specific-T cells were measured in the circulation 10-14 days after the second injection of BNT162b2 vaccine in 106 patients receiving MHD (14 with hist...
Source: Kidney International - July 17, 2021 Category: Urology & Nephrology Authors: Maxime Espi, Xavier Charmetant, Thomas Barba, Laetitia Koppe, Caroline Pelletier, Emilie Kalbacher, Elodie Chalencon, Virginie Mathias, Anne Ovize, Emmanuelle Cart-Tanneur, Christine Bouz, Laurence Pellegrina, Emmanuel Morelon, Denis Fouque, Laurent Juill Tags: clinical investigation Source Type: research

How cyclosporin reduces mycophenolic acid exposure by 40% while other calcineurin inhibitors do not.
The most frequently used immunosuppressive treatment in kidney transplant recipients is the combination therapy of a calcineurin inhibitor and mycophenolate mofetil (MMF), with or without corticosteroids. Cyclosporin and tacrolimus are the two calcineurin inhibitors registered for this indication.Also in the treatment of glomerular diseases calcineurin inhibitors and mycophenolic acid are being used on a worldwide scale, either alone or as combined treatment. In January 2021 the U.S. Food and Drug Administration (FDA) has approved voclosporin, a novel calcineurin inhibitor for the treatment of adult patients with active lu...
Source: Kidney International - July 17, 2021 Category: Urology & Nephrology Authors: Teun van Gelder Tags: mini review Source Type: research

A Team-Based Approach for Testing Biomarkers of Kidney Disease Progression
Acute kidney injury (AKI) is an important public health concern given its high incidence, paucity of effective therapies, and strong association with mortality. Survivors of hospitalized AKI are at increased risk of cardiovascular disease, de novo chronic kidney disease (CKD), and progression of prevalent CKD. Therefore, risk-classification is critical to guide surveillance and interventions after AKI. Specialized post-discharge care focused on high-risk AKI survivors has been implemented in multiple centers, and interventions to improve clinical and patient-centered outcomes are being investigated. (Source: Kidney International)
Source: Kidney International - July 16, 2021 Category: Urology & Nephrology Authors: Javier A. Neyra Tags: nephrology digest Source Type: research

Superior cellular and humoral immunity toward SARS-CoV-2 reference and alpha and beta VOC strains in COVID-19 convalescent as compared to the prime boost BNT162b2 vaccinated dialysis patients
Patients undergoing maintenance dialysis (DP) have a high risk of fatal coronavirus disease 2019 (COVID-19).1 Recent epidemiological data raise apprehension with respect to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) for DP.2,3 Therefore, ensuring cellular and humoral immunity directed to SARS-CoV-2 including VOC isolates is essential for this population. There are no data on vaccine-induced nor on natural SARS-CoV-2 infection –induced long-term immunity and its responsiveness to VOC isolates in DP. (Source: Kidney International)
Source: Kidney International - July 13, 2021 Category: Urology & Nephrology Authors: Arturo Blazquez-Navarro, Lema Safi, Toni L. Meister, Constantin J. Thieme, Sviatlana Kaliszczyk, Krystallenia Paniskaki, Mara Stockhausen, Jan H örstrup, Okan Cinkilic, Linus Flitsch-Kiefner, Corinna Marheinecke, Eike Steinmann, Felix S. Seibert, Ulrik S Tags: Letter to the Editor Source Type: research

Superior cellular and humoral immunity towards SARS-CoV-2 reference and alpha and beta VOC strains in COVID-19 convalescent as compared to the prime boost BNT162b2 vaccinated dialysis patients
Patients undergoing maintenance dialysis (DP) have a high risk of fatal COVID-19.1 Recent epidemiological data raise apprehension with respect to SARS-CoV-2 variants of concern (VOC) for DP.2,3 Therefore, assurance of cellular and humoral immunity directed to SARS-CoV-2 including VOC isolates is essential for this population. There are neither data on vaccine-induced, nor on natural SARS-CoV-2 infection-induced long-term immunity and its responsiveness to VOC isolates in DP. (Source: Kidney International)
Source: Kidney International - July 13, 2021 Category: Urology & Nephrology Authors: Arturo Blazquez-Navarro, Lema Safi, Toni L. Meister, Constantin J. Thieme, Sviatlana Kaliszczyk, Krystallenia Paniskaki, Mara Stockhausen, Jan H örstrup, Okan Cinkilic, Linus Flitsch-Kiefner, Corinna Marheinecke, Eike Steinmann, Felix S. Seibert, Ulrik S Tags: letters to the editor Source Type: research

Comparison of BNT162b2 (Biontech/Pfizer) and mRNA-1273 (Moderna) SARS-CoV-2 mRNA Vaccine Immunogenicity in Dialysis Patients
Patients with end-stage renal disease undergoing dialysis are at very high risk of death in case of COVID-191. Growing evidence suggests that a relatively high proportion of dialysis patients develops anti-SARS-Cov2-antibodies after vaccination, albeit to a lesser extent than healthy controls2. Here, we investigated whether there are differences in anti-SARS-CoV2 antibody levels (directed against the receptor binding domain (RBD) of the S1 subunit of the Spike (S) protein, measured with the SARS-CoV-2 IgG II Quant assay, Abbott) in hemodialysis patients without a history of SARS-CoV2-infection after full vaccination (2 dos...
Source: Kidney International - July 13, 2021 Category: Urology & Nephrology Authors: Robert A. Kaiser, Maria C. Haller, Petra Apfalter, Heidrun Kerschner, Daniel Cejka Tags: letters to the editor Source Type: research

Neutralizing antibody response against variants of concern after vaccination of dialysis patients with BNT162b2
We and others showed high seroconversion rates after BNT162b2 mRNA vaccination in patients on hemodialysis, but still significantly lower rates as compared to healthy controls (1 –3). Variants of concern (VOCs) such as B.1.351 (beta variant) or B.1.617.2 (delta variant) partially escape from neutralizing antibodies (NAbs) and will probably replace wildtype SARS-CoV-2 or the B.1.1.7 (alpha) variant with increasing immunity in the population, induced by natural infection or vaccination. Wall et al. (Source: Kidney International)
Source: Kidney International - July 11, 2021 Category: Urology & Nephrology Authors: Claudius Speer, Louise Benning, Maximilian T öllner, Christian Nusshag, Florian Kälble, Paula Reichel, Matthias Schaier, Marie Bartenschlager, Paul Schnitzler, Martin Zeier, Caner Süsal, Christian Morath, Ralf Bartenschlager Tags: letters to the editor Source Type: research

Reasons for COVID-19 vaccination hesitancy in hemodialysis patients
We read the excellent series of reports and editorial on the effectiveness of vaccination in dialysis patients (1). We would concur that although vaccination is less effective in these high-risk patients it remains critical to ensure our at-risk population remains as protected as possible. We would draw attention to the other significant challenge in such a population, namely hesitancy towards vaccination in maintenance dialysis patients. Vaccine hesitancy is defined by the World Health Organization as a delay in acceptance or refusal of safe vaccines despite availability of vaccine services. (Source: Kidney International)
Source: Kidney International - July 10, 2021 Category: Urology & Nephrology Authors: Sunil Bhandari Tags: letters to the editor Source Type: research

Specific disruption of calcineurin-signaling in the distal convoluted tubule impacts the transcriptome and proteome, and causes hypomagnesemia and metabolic acidosis
Adverse effects of calcineurin inhibitors (CNI), such as hypertension, hyperkalemia, acidosis, hypomagnesemia and hypercalciuria, have been linked to dysfunction of the distal convoluted tubule (DCT). To test this, we generated a mouse model with an inducible DCT-specific deletion of the calcineurin regulatory subunit B alpha (CnB1-KO). Three weeks after CnB1 deletion, these mice exhibited hypomagnesemia and acidosis, but no hypertension, hyperkalemia or hypercalciuria. Consistent with the hypomagnesemia, CnB1-KO mice showed a downregulation of proteins implicated in DCT magnesium transport, including TRPM6, CNNM2, SLC41A3...
Source: Kidney International - July 9, 2021 Category: Urology & Nephrology Authors: Eszter Banki, Viktoria Fisi, Sandra Moser, Agnieszka Wengi, Monique Carrel, Dominique Loffing-Cueni, David Penton, Denise V. Kratschmar, Ludovica Rizzo, Soeren Lienkamp, Alex Odermatt, Markus M. Rinschen, Johannes Loffing Tags: basic research Source Type: research

Harmonizing Acute and Chronic Kidney Disease Definition and Classification: report of a Kidney Disease: Improving Global Outcomes (KDIGO) Consensus Conference
Kidney disease is an important public health problem. Both acute kidney injury (AKI) and chronic kidney disease (CKD) have been well defined and classified leading to improved research efforts and subsequent management strategies and recommendations. For those patients with abnormalities in kidney function and/or structure who meet neither the definition of AKI nor CKD, there remains a gap in research, care and guidance. The term Acute Kidney Diseases and Disorders, abbreviated to Acute Kidney Disease (AKD), has been introduced as an important construct to address this. (Source: Kidney International)
Source: Kidney International - July 9, 2021 Category: Urology & Nephrology Authors: Norbert Lameire, Adeera Levin, John A. Kellum, Michael Cheung, Michel Jadoul, Wolfgang C. Winkelmayer, Paul E. Stevens, Conference Participants Tags: KDIGO executive conclusions Source Type: research

The ketone body β-hydroxybutyrate mitigates the senescence response of glomerular podocytes to diabetic insults.
Diabetic kidney disease (DKD) is one of the most common complications of diabetes and clinically featured by progressive albuminuria, consequent to glomerular destruction that involves podocyte senescence. Burgeoning evidence suggests that ketosis, in particular β-hydroxybutyrate, exerts a beneficial effect on aging and on myriad metabolic or chronic diseases, including obesity, diabetes and chronic kidney diseases. Its effect on DKD is largely unknown. In vitro in podocytes exposed to a diabetic milieu, β-hydroxybutyrate treatment substantially mitigated cellular senescence and injury, as evidenced by reduced fo...
Source: Kidney International - July 8, 2021 Category: Urology & Nephrology Authors: Yudong Fang, Bohan Chen, Athena Y. Gong, Deepak Malhotra, Rajesh Gupta, Lance D. Dworkin, Rujun Gong Tags: basic research Source Type: research

Shared-decision making in hemodialysis vascular access practice
Shared decision making (SDM) is a process of collaborative deliberation in the dyadic patient-physician interaction whereby physicians inform the patients about the pros and cons of all available treatment options and reach an agreement with the patients on their preferred treatment plan. In hemodialysis vascular access practice, SDM advocates a deliberative approach based on the existence of reasonable alternatives —i.e., arteriovenous fistula, arteriovenous graft, and central venous catheter—so that patients are able to form and share preferences about access options. (Source: Kidney International)
Source: Kidney International - July 8, 2021 Category: Urology & Nephrology Authors: Mariana Murea, Carl R. Grey, Charmaine E. Lok Tags: review Source Type: research

Significance of HLA-DQ in kidney transplantation - Time to re-evaluate HLA matching priorities to improve transplant outcomes? An expert review and recommendations
The weight of HLA matching in kidney allocation algorithms, especially in the US, has been devalued in a stepwise fashion, supported by the introduction of modern immunosuppression. The intent was further to reduce the observed ethnic/racial disparity, as data emerged associating HLA matching with decreased access to transplantation for African American patients. In recent years, it has been increasingly recognized that a leading cause of graft loss is chronic antibody mediated rejection attributed to the development of de novo antibodies against mismatched donor HLA expressed on the graft. (Source: Kidney International)
Source: Kidney International - July 7, 2021 Category: Urology & Nephrology Authors: Anat R. Tambur, Vasilis Kosmoliaptsis, Frans HJ. Claas, Roslyn B. Mannon, Peter Nickerson, Maarten Naesens Tags: review Source Type: research

An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis.
Nephropathic cystinosis is a rare disease secondary to recessive mutations of the CTNS gene encoding the lysosomal cystine transporter cystinosin, causing accumulation of cystine in multiple organs. Over the years, the disease has evolved from being a fatal condition during early childhood into a treatable condition, with patients surviving into adulthood. Data on cystinosis are limited by the rarity of the disease. Here, we have investigated factors associated with kidney and growth outcome in a very large cohort of 453 patients born between 1964 and 2016 and followed in Belgium, Germany, Austria, France, Italy, Spain, Th...
Source: Kidney International - July 5, 2021 Category: Urology & Nephrology Authors: Francesco Emma, William van ’t Hoff, Katharina Hohenfellner, Rezan Topaloglu, Marcella Greco, Gema Ariceta, Chiara Bettini, Detlef Bockenhauer, Koenraad Veys, Lars Pape, Sally Hulton, Suzanne Collin, Fatih Ozaltin, Aude Servais, Georges Deschênes, Robe Tags: clinical investigation Source Type: research

Measurement of urinary Dickkopf-3 uncovered silent progressive kidney injury in patients with chronic obstructive pulmonary disease.
Chronic kidney disease (CKD) represents a global public health problem with high disease related morbidity and mortality. Since CKD etiology is heterogeneous, early recognition of patients at risk for progressive kidney injury is important. Here, we evaluated the tubular epithelial derived glycoprotein dickkopf-3 (DKK3) as a urinary marker for the identification of progressive kidney injury in a non-CKD cohort of patients with chronic obstructive pulmonary disease (COPD) and in an experimental model. (Source: Kidney International)
Source: Kidney International - July 5, 2021 Category: Urology & Nephrology Authors: Stefan J. Schunk, Christoph Beisswenger, Felix Ritzmann, Christian Herr, Martina Wagner, Sarah Triem, Gregor H ütter, David Schmit, Stephen Zewinger, Tamim Sarakpi, Anja Honecker, Peer Mahadevan, Peter Boor, Stefan Wagenpfeil, Rudolf Jörres, Henrik Watz Tags: clinical investigation Source Type: research

A Review of kidney transplantation from HCV-Viremic Donors into Negative Recipients
The safety and efficacy of direct acting antiviral therapies have allowed the transplantation of organs from hepatitis C virus (HCV)-viremic donors into uninfected recipients. This novel strategy contrasts with the previous standard-of-care practice of limiting the transplantation of HCV infected donor organs to HCV infected recipients, or all too often, discarding viable organs. In this review, we summarize the published literature about the safety and feasibility of transplanting organs from HCV-viremic donors, the challenges that hinder wider adoption of this strategy, and future research needs. (Source: Kidney International)
Source: Kidney International - July 5, 2021 Category: Urology & Nephrology Authors: Reem Daloul, Todd Pesavento, David S. Goldberg, Peter P. Reese Tags: review Source Type: research

Granulomatous vasculitis after the AstraZeneca anti –SARS-CoV-2 vaccine
Several reports of newly diagnosed or relapses of immune-mediated renal diseases following vaccination with anti –severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA and AstraZeneca vaccines recently emerged in the litterature.1,2 (Source: Kidney International)
Source: Kidney International - July 4, 2021 Category: Urology & Nephrology Authors: Valentine Gillion, Michel Jadoul, Nathalie Demoulin, Selda Aydin, Arnaud Devresse Tags: Letter to the Editor Source Type: research

IgA Nephropathy presenting as macroscopic hematuria in 2 pediatric patients after receiving the Pfizer COVID-19 vaccine
To the editor: (Source: Kidney International)
Source: Kidney International - July 4, 2021 Category: Urology & Nephrology Authors: Christian Hanna, Loren P. Herrera Hernandez, Lihong Bu, Sarah Kizilbash, Lydia Najera, Michelle N. Rheault, Jan Czyzyk, Anne M. Kouri Tags: letters to the editor Source Type: research

Granulomatous vasculitis after the Astra-Zeneca anti-SARS-CoV-2 vaccine.
Several reports of newly diagnosed or relapses of immune-mediated renal diseases following vaccination with anti-SARS-CoV-2 mRNA and Astra-Zeneca vaccines recently emerged in the litterature.1,2 (Source: Kidney International)
Source: Kidney International - July 4, 2021 Category: Urology & Nephrology Authors: Valentine Gillion, Michel Jadoul, Nathalie Demoulin, Selda Aydin, Arnaud Devresse Tags: letters to the editor Source Type: research

Development of a photoacoustic microscopy technique to assess peritubular capillary function and oxygen metabolism in the mouse kidney
Microcirculatory changes and oxidative stress have long been associated with acute kidney injury. Despite substantial progress made by two-photon microscopy of microvascular responses to acute kidney injury in rodent models, little is known about the underlying changes in blood oxygen delivery and tissue oxygen metabolism. To fill this gap, we developed a label-free kidney imaging technique based on photoacoustic microscopy, which enables simultaneous quantification of hemoglobin concentration, oxygen saturation of hemoglobin, and blood flow in peritubular capillaries in vivo. (Source: Kidney International)
Source: Kidney International - July 1, 2021 Category: Urology & Nephrology Authors: Naidi Sun, Shuqiu Zheng, Diane L. Rosin, Nabin Poudel, Junlan Yao, Heather Perry, Rui Cao, Mark D. Okusa, Song Hu Tags: technical notes Source Type: research

Recent advances in lineage tracing for the kidney
Lineage tracing was originally developed by developmental biologists to identify all progeny of a single cell during morphogenesis. More recently this approach has been applied to other fields, including organ homeostasis and recovery from injury. Modern lineage tracing techniques typically rely on reporter gene expression induced by cell-specific DNA recombination. There have been important scientific advances in the last ten years that have impacted lineage tracing approaches, including intersectional genetics, optical clearing techniques and the use of sequencing-based genomic lineage tracing. (Source: Kidney International)
Source: Kidney International - July 1, 2021 Category: Urology & Nephrology Authors: Yoshiharu Muto, Benjamin D. Humphreys Tags: mini review Source Type: research

Humoral response after 3 doses of the BNT162b2 mRNA COVID-19 vaccine in patients on hemodialysis
Dialysis patients are at increased risk of severe coronavirus disease 2019 (COVID-19) infections.1 Therefore, they are considered as being a priority population for COVID-19 vaccination. Because immune responses against vaccines are considerably reduced in this population,2 a vaccination strategy including 3 doses of vaccine has been recommended for dialysis patients. However, few data exist concerning humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination with 3 doses of BNT162b2 (Pfizer-BioNTech) in patients on hemodialysis (HD). (Source: Kidney International)
Source: Kidney International - June 30, 2021 Category: Urology & Nephrology Authors: Didier Ducloux, M. Colladant, M. Chabannes, M. Yannaraki, C. Courivaud Tags: Letter to the Editor Source Type: research

Humoral response after three doses of BNT162b2 mRNA COVID-19 vaccine in patients on hemodialysis
Dialysis patients are at increased risk of severe COVID-19 infections (1). Therefore, there are considered as being a priority population for COVID-19 vaccination. Because immune responses against vaccines are considerably reduced in this population (2), a vaccination strategy including three doses of vaccine has been recommended for dialysis patients. However, few data exist concerning humoral response to SARS-coV-2 vaccination with three doses of BNT162b2 (Pfizer-BioNTech) in patients on hemodialysis (HD). (Source: Kidney International)
Source: Kidney International - June 30, 2021 Category: Urology & Nephrology Authors: D. Ducloux, M. Colladant, M. Chabannes, M. Yannaraki, C. Courivaud Tags: letters to the editor Source Type: research

A toggle switch linking coagulation and innate immunity in antiphospholipid antibody syndrome
The antiphospholipid syndrome (APS) is defined by the occurrence of thrombotic events or adverse pregnancy outcomes in individuals who persistentlytest positive for antiphospholipid antibodies (aPLs), including anticardiolipin antibodies, lupus anticoagulant, and anti- β2-glycoprotein 1 antibodies. A range of clinical features can occur in the context of APS, with thrombotic manifestations potentially occurring in any vessels, arterial or venous, large vessels or microvasculature (1).Previous studies have shown that aPLs induce translocation of toll-like receptor s (TLR) 7 and 8 to the endosome, promoting proinflammat...
Source: Kidney International - June 30, 2021 Category: Urology & Nephrology Authors: Dario Roccatello, Savino Sciascia Tags: nephrology digest Source Type: research

A genome-wide association study suggests correlations of common genetic variants with peritoneal solute transfer rates in patients with kidney failure receiving peritoneal dialysis.
Movement of solutes across the peritoneum allows for the use of peritoneal dialysis to treat kidney failure. However, there is a large inter-individual variability in the peritoneal solute transfer rate (PSTR). Here, we tested the hypothesis that common genetic variants are associated with variability in PSTR. Of the 3561 participants from 69 centers in six countries, 2850 with complete data were included in a genome-wide association study. PSTR was defined as the four-hour dialysate/plasma creatinine ratio from the first peritoneal equilibration test after starting PD. (Source: Kidney International)
Source: Kidney International - June 28, 2021 Category: Urology & Nephrology Authors: Rajnish Mehrotra, Ian B. Stanaway, Gail P. Jarvik, Mark Lambie, Johann Morelle, Jeffrey Perl, Jonathan Himmelfarb, Olof Heimburger, David W. Johnson, Talha H. Imam, Bruce Robinson, Peter Stenvinkel, Olivier Devuyst, Simon J. Davies, the Bio-PD Consortium Tags: clinical investigation Source Type: research

Primary results of the randomized trial of metformin administration in polycystic kidney disease (TAME PKD).
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by growth of kidney cysts and glomerular filtration rate (GFR) decline. Metformin was found to impact cystogenesis in preclinical models of polycystic disease, is generally considered safe and may be a promising candidate for clinical investigation in ADPKD. In this phase 2 two-year trial, we randomly assigned 97 patients, 18-60 years of age, with ADPKD and estimated GFR over 50 ml/min/1.73 m2, in a 1:1 ratio to receive metformin or placebo twice daily. (Source: Kidney International)
Source: Kidney International - June 26, 2021 Category: Urology & Nephrology Authors: Ronald D. Perrone, Kaleab Z. Abebe, Terry Watnick, Andrew Althouse, Kenneth R. Hallows, Christina M. Lalama, Dana C. Miskulin, Stephen L. Seliger, Cheng Tao, Peter C. Harris, Kyongtae Ty Bae Tags: clinical trial Source Type: research

The emerging field of non-HLA-antibodies in transplant medicine and beyond
The major medical advances in our knowledge of the human leukocyte antigen (HLA) system have allowed to uncover several gaps in our understanding of alloimmunity. Although the non-HLA system has long sparked the interest of the transplant community, recognition of the role of immunity to non-HLA antigenic targets has only emerged recently. In this review, we will provide a comprehensive summary of the paradigm changing concept of immunity to the non-HLA angiotensin II type 1 receptor (AT1R) discovered by Duska Dragun and colleagues, that began from careful bedside clinical observations, to validated detection of anti-AT1R ...
Source: Kidney International - June 26, 2021 Category: Urology & Nephrology Authors: Carmen Lefaucheur, Kevin Louis, Aur élie Philippe, Alexandre Loupy, P. Toby Coates Tags: review Source Type: research