Murine cytomegalovirus dissemination but not reactivation in donor-positive/recipient-negative allogeneic kidney transplantation can be effectively prevented by transplant immune tolerance.
Cytomegalovirus (CMV) reactivation from latently-infected donor organs post-transplantation and its dissemination cause significant comorbidities in transplant recipients. Transplant-induced inflammation combined with chronic immunosuppression has been thought to provoke CMV reactivation and dissemination, although sequential events in this process have not been studied. Here, we investigated this process in a high-risk donor CMV-positive to recipient CMV-negative allogeneic murine kidney transplantation model. (Source: Kidney International)
Source: Kidney International - February 20, 2020 Category: Urology & Nephrology Authors: Anil Dangi, Shuangjin Yu, Frances T. Lee, Melanie Burnette, Jiao-Jing Wang, Yashpal S. Kanwar M, Zheng J. Zhang, Michael Abecassis, Edward B. Thorp, Xunrong Luo Tags: Basic Research Source Type: research

The Case | A neoplastic cause of acute kidney injury
A 40-year-old male patient was admitted to the emergency department for persistent severe headache unrelieved by paracetamol. He had no medical history but reported asthenia and weight loss (2 kg) over the previous 3 weeks. At admission, blood pressure was 120/80 mm  Hg and physical examination was unremarkable. Laboratory blood tests showed: serum creatinine 1.7 mg/dl, sodium 141 mmol/l, calcium 9.2 mg/dl, C-reactive protein 6 mg/l, leucocytes 11520/mm3, neutrophils 9230/mm3, lymphocytes 1090/mm3, and hemoglobin 13.6 g/dl. (Source: Kidney International)
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Authors: Claire Garandeau, Lucile Figueres, Karine Renaudin, Fadi Fakhouri Tags: Make Your Diagnosis Source Type: research

The Case | Severe acute hypocalcemia in a patient on hemodialysis
A 56-year-old Caucasian man on maintenance hemodialysis for 5 years for end-stage kidney disease secondary to lithium-induced chronic interstitial nephropathy presented with acute and severe weakness of the 4 limbs. (Source: Kidney International)
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Authors: Christian Maalouly, Benjamin Seront, Johann Morelle, Michel Jadoul, Laura Labriola Tags: Make Your Diagnosis Source Type: research

Pseudoaneurysm-induced renal artery stenosis
A 66-year-old obese Hispanic female with IgA nephropathy and a previous failed kidney transplant received a left kidney transplant 4 months ago. She was hospitalized for recurrent pyelonephritis. Serial non –contrasted computed tomography over the prior 4 weeks reported a persistent hematoma and focal fluid collection of unclear etiology at the surgical site of the transplant kidney. Brightness-mode ultrasound showed mild hydronephrosis, initially thought to be secondary to pyelonephritis. A percutan eous nephrostomy tube was placed without improvement in urine output. (Source: Kidney International)
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Authors: Ayaz Aghayev, Jessica Cruz Whitley, Paul Salem, Jamil Azzi, Matthew Menard, Andrew M. Siedlecki Tags: Nephrology Image Source Type: research

Multicellular vacuoles in hypokalemic nephropathy
A 61-year-old morbidly obese Caucasian woman with hypertension, hyperlipidemia, and 6-month history of hypokalemia presented with generalized muscle weakness and nonoliguric acute kidney injury. After cholecystectomy in 2006, she underwent lysis of adhesions, partial ileal and rectosigmoid resection, and permanent end colostomy in 2011. Outpatient medications included Nexium (AstraZeneca, Wilmington, DE), pravastatin, furosemide (20 mg daily), and potassium chloride (10 mEq daily). She presented in July 2019 with serum creatinine 9.8 mg/dL (increased from baseline 1.0 mg/dL 1 year prior), serum sodium 133 mmol/l, chloride ...
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Authors: Satoru Kudose, Harry Dounis, Vivette D. D ’Agati Tags: Nephrology Image Source Type: research

The scar that never felt a wound
Chronic kidney disease is inevitably associated with the proliferation of fibroblasts following injury of the tubular system and collagen deposition in the interstitial tissue. To date, renal fibrosis has been hard to detect without histologic tissue examination. In this issue of Kidney International, Baues et  al. introduce a novel technology for noninvasive detection of renal fibrosis using a multimodal optical approach with the fluorescent-labelled collagen-binding agent CNA35-Cy7. (Source: Kidney International)
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Authors: Julian Stumpf, Christian Hugo Tags: Commentary Source Type: research

Dysfunctional HDL takes its  Toll on the endothelial glycocalyx
Patients with end-stage renal disease have a high risk of dying from cardiovascular disease that cannot be explained solely by traditional cardiovascular disease risk factors. Hesse et  al. suggest that dysfunctional high-density lipoprotein cholesterol generated in patients with end-stage renal disease causes endothelial glycocalyx degradation. Glycocalyx degradation may represent one of the earliest insults leading to atheroma formation, and so this work suggests a novel link b etween renal failure and cardiovascular disease. (Source: Kidney International)
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Authors: Matthew J. Butler Tags: Commentary Source Type: research

Danger in the jungle: sensible care to reduce avoidable acute kidney injury in hospitalized children
When children require hospital admission, many receive medications with nephrotoxic potential. As such, this can translate into an increased risk of acute kidney injury. In this context, acute kidney injury is hospital acquired, often iatrogenic, and portends risk of adverse outcomes. The Nephrotoxic Injury Negated by Just-in-Time Action study implemented a multicenter hospital-wide quality improvement initiative to detect and reduce nephrotoxin exposure in children aimed at decreasing the rates of potentially avoidable acute kidney injury. (Source: Kidney International)
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Authors: Samira Bell, Nicholas M. Selby, Sean M. Bagshaw Tags: Commentary Source Type: research

Visualizing fibrosis —hope for ideal markers beyond imaging
How do nephrologists, or physicians, evaluate chronic kidney disease (CKD) progression? Clinically, the progression of CKD is routinely assessed by the decrease in estimated glomerular filtration rate and histologically by expansion of the fibrotic area. Unfortunately, the level of estimated glomerular filtration rate does not always precisely reflect the extent of kidney fibrosis. The gap between the estimated glomerular filtration rate (the clinical indicator of the renal function of toxin excretion) and the interstitial fibrosis and tubular atrophy index (the histological index of collagen accumulation) complicates the ...
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Authors: Yosuke Hirakawa, Masaomi Nangaku Tags: Editorial Source Type: research

The authors reply
We thank Huang and Yu1 for their clarification on the role of daclatasvir and asunaprevir in hepatitis C virus (HCV) –infected patients with chronic kidney disease. As they note, this regimen is most appropriate for patients infected with HCV genotype 1b as it is less efficacious in HCV genotype 1a.2 This postmarketing study, published after the last update in May 2017 of the Kidney Disease: Improving Global Out comes evidence review search, does provide useful additional information on the use of this regimen. (Source: Kidney International)
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Authors: Paul Martin, Michel Jadoul Tags: Letter to the Editor Source Type: research

Daclatasvir plus asunaprevir in the treatment of uremic patients with chronic hepatitis C genotype 1b infection
We read and appreciate the report of the executive summary of the 2018 KDIGO Hepatitis C in CKD Guideline in Kidney International.1 Direct-acting antivirals are now the standard of care for chronic hepatitis C either in the general population or in patients with chronic kidney disease. A sustained virological response rate of>95% could be achieved with novel direct-acting antivirals. We acknowledge that the statement regarding the treatment recommendations should refer to the latest American Association for the Study of Liver Diseases (AASLD) or European Association for the Study of the Liver (EASL) guidelines. (Source:...
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Authors: Chung-Feng Huang, Ming-Lung Yu Tags: Letter to the Editor Source Type: research

Measuring glomerular filtration rate with iohexol plasma disappearance: blood collection duration is essential for accurate glomerular filtration rate determinations
Recently, Rowe et  al. reported the biological variation of measured glomerular filtration rate (mGFR) and estimated glomerular filtration rate (eGFR) for chronic kidney disease in 20 patients.1 An examination of their iohexol plasma disappearance mGFR protocol shows that the authors administered 5 ml of Omnipaque 2 40 (518 g/l of iohexol; GE Healthcare [Little Chalfont, Buckinghamshire, UK]) and acquired blood specimens at 3 time points with the longest collection time duration of 240 minutes. We acknowledge that there is currently no standardized protocol for an iohexol plasma disappearance procedure for the purpose...
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Authors: Jesse C. Seegmiller, Natalie Ebert Tags: Letter to the Editor Source Type: research

The authors reply
Seegmiller and Ebert1 comment on the potential for inaccuracy of the measured glomerular filtration rate (GFR), especially at low levels of kidney function, when a 240-minute sampling protocol is used. We are aware of the significant debate in this area. However, the focus of this aspect of our study2 was the biological variation of measured and estimated GFR, not the accuracy of the estimated GFR compared with the measured GFR. We do not believe that individual biological variation would be affected by the sampling protocol, provided that a consistent protocol is used within and between patients. (Source: Kidney International)
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Authors: Edmund J. Lamb, R. Neil Dalton, Paul E. Stevens, Maarten W. Taal Tags: Letter to the Editor Source Type: research

Treatment of glomerular diseases: pioneering clinical trials
Thtis year will be the 60th anniversary of the International Society of Nephrology ’s flagship journal, Kidney International (KI). KI has published articles that have advanced clinical nephrology since its inception. The selection of articles included below has led to significant changes in patient management in the editor’s opinion. (Source: Kidney International)
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Authors: Jai Radhakrishnan Tags: Editorial: Milestones in Nephrology Source Type: research

In memoriam: Marilyn Gist Farquhar, 1928 –2019
Marilyn Gist Farquhar passed away on Saturday, November 23, 2019, in La Jolla, California. She served as a Professor of Cellular and Molecular Medicine and Pathology at the University of California, San Diego School of Medicine. Dr. Farquhar ’s major scientific contributions included basic cell biology, particularly membrane trafficking in the Golgi apparatus and structure, and molecular composition and function of the kidney glomerulus. She was married to Nobel Laureate George Emil Palade from 1970 until his passing in 2008. (Source: Kidney International)
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Authors: Dontscho Kerjaschki, Yashpal Kanwar, Robert A. Orlando, Sanna Lehtonen, Aaro Miettinen Tags: Obituary Source Type: research

Diagnosis of uncertain significance: can next-generation sequencing replace the clinician?
New sequencing technologies are revolutionizing disease gene discovery and testing with tremendous benefits for the diagnosis of rare diseases. However, the more we sequence, the more we discover, and the challenge is to assess the numerous variants in the clinical and genetic context carefully to establish the correct diagnosis. Clinicians and geneticists must work together for this because failure to do so can result in incorrect advice with potentially serious consequences. (Source: Kidney International)
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Authors: Emma Ashton, Detlef Bockenhauer Tags: Commentary Source Type: research

Identification of ATP6V1C2 as a novel candidate gene for distal tubular acidosis
Young onset distal tubular acidosis is a rare genetic disorder that can lead, if untreated, to many complications. Mutations in few genes account for almost half of the cases, whereas the molecular mechanisms accounting for the remaining cases are still unknown. The present study reports the use of whole-exome sequencing to identify new dRTA –causing genes and demonstrates that inactivating mutations in the ATP6V1C2 gene impair renal proton pump function. (Source: Kidney International)
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Authors: Nicolas Corni ère, Dominique Eladari Tags: Commentary Source Type: research

Magnesium as a Janus-faced inhibitor of calcification
Vascular calcification is a life-threatening complication in patients with chronic kidney disease. Magnesium is a potent inhibitor of calcification and attracting attention as a new therapeutic candidate. ter Braake and colleagues demonstrate that magnesium supplementation strikingly prevents vascular calcification in Klotho knockout mice. However, these mice also show osteomalacia, indicating that magnesium has a Janus face. Maximizing the beneficial effects of magnesium without causing bone mineralization defects is an important next challenge. (Source: Kidney International)
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Authors: Yosuke Nakagawa, Hirotaka Komaba, Masafumi Fukagawa Tags: Commentary Source Type: research

Journal Club
Koenig et  al. (Nat Commun. 2019;10:5350; https://doi.org/10.1038/s41467-019-13113-5.) (Source: Kidney International)
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Tags: Journal Club Source Type: research

In this issue
Progressive kidney diseases result in interstitial fibrosis, and successful therapies must abrogate this accumulation of scar. However, because clinical markers of progression change slowly, and frequently repeated histologic investigation is not practical, success has been difficult to assess in clinical trials and practice. Baues et  al. addressed this, describing the results of optical imaging for collagen types I and III (scar collagen) using a fluorescently tagged molecular probe (collagen-binding adhesion protein CNA35). (Source: Kidney International)
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Tags: In This Issue Source Type: research

Editorial Board
(Source: Kidney International)
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Source Type: research

Subscription Information
(Source: Kidney International)
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Source Type: research

Table of Contents
(Source: Kidney International)
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Source Type: research

A deletion in the N-terminal polymerizing domain of laminin β2 is a new mouse model of chronic nephrotic syndrome.
The importance of the glomerular basement membrane (GBM) in glomerular filtration is underscored by the manifestations of Alport and Pierson syndromes, caused by defects in type IV collagen α3α4α5 and the laminin β2 chain, respectively. Lamb2 null mice, which model the most severe form of Pierson syndrome, exhibit proteinuria prior to podocyte foot process effacement and are therefore useful for studying GBM permselectivity. We hypothesize that some LAMB2 missense mutations that ca use mild forms of Pierson syndrome induce GBM destabilization with delayed effects on podocytes. (Source: Kidney International)
Source: Kidney International - February 19, 2020 Category: Urology & Nephrology Authors: Steven D. Funk, Raymond H. Bayer, Karen K. McKee, Kazushi Okada, Hiroshi Nishimune, Peter D. Yurchenco, Jeffrey H. Miner Tags: Basic Research Source Type: research

Connectivity mapping of a chronic kidney disease progression signature identified lysine deacetylases as novel therapeutic targets
Tubulointerstitial injury is an important determinant of chronic kidney disease progression, yet treatment is limited. Accordingly, we derived a chronic kidney disease progression signature based on aging and disease in Col4a3 –/– mice, a model associated with proteinuria and progressive loss of kidney function. Computational drug repurposing with the Connectivity Map identified vorinostat, a lysine deacetylase inhibitor, as a candidate treatment to reverse progression signature gene expression. Vorinostat administrat ion significantly increased the lifespan of Col4a3–/– mice and attenuated tubuloin...
Source: Kidney International - February 18, 2020 Category: Urology & Nephrology Authors: Vanessa R. Williams, Ana Konvalinka, Xuewen Song, Xiaohua Zhou, Rohan John, York Pei, James W. Scholey Tags: Basic Research Source Type: research

Modulation of iron homeostasis with hepcidin ameliorates spontaneous murine lupus nephritis.
Lupus nephritis is the end organ manifestation of systemic lupus erythematosus. Iron metabolism and its master regulator, hepcidin, are known to regulate cell proliferation and inflammation, but their direct role in the pathophysiology of lupus nephritis remains under-investigated. Exogenous hepcidin reduced the severity of lupus nephritis in MRL/lpr mice, a preclinical model of spontaneous systemic lupus erythematosus without worsening anemia of inflammation. Hepcidin treatment reduced renal iron accumulation, systemic and intrarenal cytokines, and renal immune cell infiltration, independent of glomerular immune complex d...
Source: Kidney International - February 18, 2020 Category: Urology & Nephrology Authors: Yogesh Scindia, Ewa Wlazlo, E. Ghias, S. Cechova, Valentina Loi, Joseph Leeds, Jonathan Ledesma, Cathro Helen, Sundararaman Swaminathan Tags: Basic Research Source Type: research

Tenascin-C promotes acute kidney injury to chronic kidney disease progression by impairing tubular integrity via αvβ6 integrin signaling.
Tenascin-C is an extracellular matrix glycoprotein that plays a critical role in kidney fibrosis by orchestrating a fibrogenic niche. Here, we demonstrate that tenascin-C is a biomarker and a mediator of kidney fibrogenesis by impairing tubular integrity. Tenascin-C was found to be increased in kidney biopsies from patients with chronic kidney disease (CKD). In a cohort of 225 patients with CKD, the urinary tenascin-C level was markedly elevated, compared to 39 healthy individuals. Moreover, the level of urinary tenascin-C in CKD was correlated with the severity of kidney dysfunction and fibrosis. (Source: Kidney International)
Source: Kidney International - February 18, 2020 Category: Urology & Nephrology Authors: Haili Zhu, Jinlin Liao, Xianke Zhou, Xue Hong, Dongyan Song, Fan Fan Hou, Youhua Liu, Haiyan Fu Tags: Clinical Investigation Source Type: research

Phenome-wide association analysis suggests the APOL1 linked disease spectrum primarily drives kidney specific pathways.
The relationship between commonly occurring genetic variants (G1 and G2) in the APOL1 gene in African Americans and different disease traits, such as kidney disease, cardiovascular disease, and pre-eclampsia, remains the subject of controversy. Here we took a genotype-first approach, a phenome-wide association study, to define the spectrum of phenotypes associated with APOL1 high-risk variants in 1,837 African American participants of Penn Medicine Biobank and 4,742 African American participants of Vanderbilt BioVU. (Source: Kidney International)
Source: Kidney International - February 18, 2020 Category: Urology & Nephrology Authors: Archna Bajaj, Andrea Ihegword, Chengxiang Qiu, Aeron M. Small, Wei-Qi Wei, Lisa Bastarache, QiPing Feng, Rachel L. Kember, Marjorie Risman, Roy D. Bloom, David L. Birtwell, Heather Williams, Christian M. Shaffer, Jinbo Chen, Regeneron Genetics Center, Jos Tags: Clinical Investigation Source Type: research

Gut microbiota generation of protein-bound uremic toxins and related metabolites is not altered at different stages of chronic kidney disease.
Chronic kidney disease (CKD) is characterized by accumulation of protein-bound uremic toxins such as p-cresyl sulfate, p-cresyl glucuronide, indoxyl sulfate and indole-3-acetic acid, which originate in the gut. Intestinal bacteria metabolize aromatic amino acids into p-cresol and indole, (further conjugated in the colon mucosa and liver) and indole-3-acetic acid. Here we measured fecal, plasma and urine metabolite concentrations; the contribution of gut bacterial generation to plasma protein-bound uremic toxins accumulation; and influx into the gut of circulating protein-bound uremic toxins at different stages of CKD. (Sou...
Source: Kidney International - February 18, 2020 Category: Urology & Nephrology Authors: Tessa Gryp, Kim De Paepe, Raymond Vanholder, Frederiek-Maarten Kerckhof, Wim Van Biesen, Tom Van de Wiele, Francis Verbeke, Marijn Speeckaert, Marie Joossens, Marie Madeleine Couttenye, Mario Vaneechoutte, Griet Glorieux Tags: Clinical Investigation Source Type: research

Renal TNF α activates the WNK phosphorylation cascade and contributes to salt-sensitive hypertension in chronic kidney disease
The inappropriate over-activation of the with-no-lysine kinase (WNK) –STE20/SPS1–related proline/alanine-rich kinase (SPAK)–sodium chloride cotransporter (NCC) phosphorylation cascade increases sodium reabsorption in distal kidney nephrons, resulting in salt-sensitive hypertension. Although chronic kidney disease (CKD) is a common cause of salt-sensitive hypert ension, the involvement of the WNK phosphorylation cascade is unknown. Moreover, the effect of immune systems on WNK kinases has not been investigated despite the fact that immune systems are important for salt sensitivity. (Source: Kidney International)
Source: Kidney International - February 11, 2020 Category: Urology & Nephrology Authors: Taisuke Furusho, Eisei Sohara, Shintaro Mandai, Hiroaki Kikuchi, Naohiro Takahashi, Takuya Fujimaru, Hiroko Hashimoto, Yohei Arai, Fumiaki Ando, Moko Zeniya, Takayasu Mori, Koichiro Susa, Kiyoshi Isobe, Naohiro Nomura, Kohei Yamamoto, Tomokazu Okado, Tate Tags: Basic Research Source Type: research

IL-17C has a pathogenic role in kidney ischemia/reperfusion Injury
Cytokines are necessary to trigger the inflammatory response in kidney ischemia/reperfusion injury. Interleukin-17C (IL-17C), a unique member of the IL-17 family, is a cytokine produced by epithelial cells implicated in host defense and autoimmune diseases. However, little is known about the role of IL-17C in acute kidney injury. We investigated this and found that IL-17C was significantly increased kidney biopsies of patients and mice with acute kidney injury. Exposure to hypoxia induced upregulation of IL-17C in kidney tubular epithelial cells. (Source: Kidney International)
Source: Kidney International - February 3, 2020 Category: Urology & Nephrology Authors: Feng Wang, Jianyong Yin, Yingying Lin, Fangfei Zhang, Xuanchen Liu, Guangyuan Zhang, Yiwei Kong, Zeyuan Lu, Rui Wu, Niansong Wang, Tao Xing, Youcun Qian Tags: Basic Research Source Type: research

Five year kidney outcomes of bariatric surgery differ in severely obese adolescents and adults with and without type 2 diabetes.
Bariatric surgery improves markers of kidney health in severe obesity, yet it is unclear if kidneydisease outcomes differ according to age at surgery. Therefore, we examined health effects of Roux-en-Y gastric bypass between 161 adolescents and 396 adults participating in two related but distinct studies. Primary outcomes were elevated urine albumin-to-creatinine ratio (UACR) of 30mg/g or more and hyperfiltration (an estimated glomerular filtration rate of 135 ml/min/1.73m2 or more). Analyses were stratified by the presence of pre-operative type 2 diabetes. (Source: Kidney International)
Source: Kidney International - February 3, 2020 Category: Urology & Nephrology Authors: P. Bjornstad, E. Nehus, T. Jenkins, M. Mitsnefes, M. Moxey-Mims, J.B. Dixon, T. Inge Tags: Clinical Investigation Source Type: research

A prospective controlled study of metabolic and physiologic effects of kidney donation suggests that donors retain stable kidney function over the first nine years.
While there have been numerous studies of living kidney donors, most have been retrospective without suitable controls and have yielded conflicting results. To clarify this we studied 205 living donor candidates and 203 controls having no medical conditions precluding donation. Before and at six months, one, two, three, six, and nine years after donation we measured iohexol glomerular filtration rate, clinic blood pressure, urine protein excretion and metabolic parameters reported to be affected by kidney function. (Source: Kidney International)
Source: Kidney International - February 3, 2020 Category: Urology & Nephrology Authors: Bertram L. Kasiske, Tracy L. Anderson-Haag, Daniel A. Duprez, Roberto S. Kalil, Paul L. Kimmel, Todd E. Pesavento, Jon J. Snyder, Matthew R. Weir Tags: Clinical Investigation Source Type: research

The spectrum of kidney biopsy findings in HIV-infected patients in the modern era
HIV-associated kidney disease is evolving rapidly. Few North American studies have addressedmodern trends and none has applied the 2018 Kidney Disease Improving Global Outcomes (KDIGO) pathologic classification. Therefore we performed a retrospective clinical-pathologic analysis of all HIV-positive patients with kidney biopsy interpreted at Columbia University from 2010-2018 using the KDIGO classification. The biopsy cohort of 437 HIV-positive patients had median age 53 years, including 66% males, 80% on anti-retroviral therapy, 57% with hypertension, 31% with diabetes, 27% with hepatitis C and 6% with hepatitis B co-infec...
Source: Kidney International - February 3, 2020 Category: Urology & Nephrology Authors: Satoru Kudose, Dominick Santoriello, Andrew S. Bomback, M. Barry Stokes, Ibrahim Batal, Glen S. Markowitz, Christina M. Wyatt, Vivette D. D ’Agati Tags: Clinical Investigation Source Type: research

Anti-CD20-mediated B-cell depletion in auto-immune diseases: successes, failures and future perspectives.
B-cell depletion with anti-CD20 monoclonal antibodies is widely used for the treatment of auto-immune diseases. In this review, we will discuss mechanisms contributing to success or failure of B-cell depletion therapy in antibody-mediated auto-immune diseases. We will also explain how key informations about disease pathogeny can be provided by the different outcomes observed after B-cell depletion therapy. These findings provide the basis for future innovative therapeutic strategies aiming at an optimized B cell and/or plasma cell depletion to increase long-term disease remission. (Source: Kidney International)
Source: Kidney International - January 30, 2020 Category: Urology & Nephrology Authors: Etienne Crickx, Jean-Claude Weill, Claude-Agn ès Reynaud, Matthieu Mahévas Tags: Review Source Type: research

How to assess kidney function in oncology patients
Assessment of kidney function in oncology patients is a fundamental factor in profiling the survival risk, determining the appropriate dose of chemotherapeutic drugs and defining a patient eligibility for clinical trials with novel agents. Both overestimation and underestimation of kidney function may affect the treatment efficacy and outcomes. Overestimation may lead to overdosing or inappropriate agent selection and corresponding toxicity, while underestimation may be responsible for underdosing or inappropriate agent exclusion and subsequent treatment failure. (Source: Kidney International)
Source: Kidney International - January 29, 2020 Category: Urology & Nephrology Authors: Jolanta Malyszko, Michael W. Lee, Giovambattista Capasso, Pawel Kulicki, Joanna Matuszkiewicz-Rowinska, Pierre Ronco, Paul Stevens, Petra Tesarova, Davide Viggiano, Anna Capasso Tags: Review Source Type: research

Mesenchymal Stromal Cell-Based Therapies for Acute Kidney Injury: Progress in the Last Decade
A little over 10 years ago, the therapeutic potential of mesenchymal stromal cells (MSC) for the treatment of acute kidney injury (AKI) was becoming widely recognized. Since then, there has been further intensive study of this topic with a clear translational intent. Over the past decade, many more animal model studies have strengthened the evidence that systemically or locally-delivered MSC ameliorate renal injury in sterile and sepsis-associated AKI (SA-AKI). Some of these pre-clinical studies have also provided a range of compelling new insights into the in vivo fate and mechanisms of action of MSC in the setting of AKI...
Source: Kidney International - January 28, 2020 Category: Urology & Nephrology Authors: Barbara Fazekas, Matthew D. Griffin Tags: Review Source Type: research

The Case | Knee pain and allograft dysfunction in a kidney transplant recipient
A 72-year-old man was admitted to the hospital with diabetic ketoacidosis and acute kidney injury 3 months after receiving a deceased-donor kidney transplant. He had undergone induction immunosuppression with rabbit-antithymocyte globulin and took tacrolimus and mycophenolic acid for maintenance immunosuppression. Twelve days prior to admission to the hospital, right knee pain and swelling developed. Synovial fluid was aspirated and showed a white blood cell count of 1825, 61% polymorphonuclear neutrophils, and monosodium urate crystals visualized by polarizing light microscopy. (Source: Kidney International)
Source: Kidney International - January 21, 2020 Category: Urology & Nephrology Authors: Samantha E. Jacobs, Kyriakos A. Kirou, Surya V. Seshan, Thomas J. Walsh, Choli Hartono Tags: Make Your Diagnosis Source Type: research

The Case | Glomerulonephritis with prolonged recurrent fever
A 52-year-old farmer was admitted with recurrent fever for>1 year, hematuria, proteinuria, renal insufficiency, and anemia for 4 months. He lost 15 kg over 1 year. He was employed in the animal husbandry industry including breeding of cattle and sheep and slaughtering cattle. On admission, the patient was afebrile and his blood pressure was 110/70 mm  Hg. Physical examination revealed 3 enlarged lymph nodes bilaterally in the inguinal area and was otherwise normal. (Source: Kidney International)
Source: Kidney International - January 21, 2020 Category: Urology & Nephrology Authors: Jiale Tang, Zhonghua Liao, Ting Meng, Jianping Ning, Xiangcheng Xiao, Qiaoling Zhou, Xiaozhao Li Tags: Make Your Diagnosis Source Type: research

X-linked Alport syndrome with “empty capsule sign”
A 4-year-old white boy with a 10-month history of microhematuria presented with episodes of gross hematuria. The patient ’s mother had a history of “chronic glomerulonephritis” diagnosed on renal biopsy many years earlier. The patient had serum creatinine of 0.3 mg/dl, 24-hour urine protein of 0.6 g, serum albumin of 3.9 g/dl, no edema, normal blood pressure, negative antinuclear antibodies, and normal serum co mplements. (Source: Kidney International)
Source: Kidney International - January 21, 2020 Category: Urology & Nephrology Authors: Satoru Kudose, Ibrahim Batal, Cynthia D ’Alessandri-Silva, Fangming Lin, Vivette D. D’Agati, Glen S. Markowitz Tags: Nephrology Image Source Type: research

Air embolism from pericatheter air leak
A 25-year-old male with end-stage kidney disease from obstructive uropathy and neurogenic bladder presented to the emergency room with generalized tonic-clonic seizures. Two weeks before this presentation, the patient was started on hemodialysis via nontunneled precurved hemodialysis catheter, which was inserted into the right internal jugular vein. A cranial computed tomography obtained for the seizures revealed subcutaneous emphysema of the scalp and air bubbles within the dural venous sinuses (Figure  1a). (Source: Kidney International)
Source: Kidney International - January 21, 2020 Category: Urology & Nephrology Authors: Tuncay Sahutoglu Tags: Nephrology Image Source Type: research

Statistics and data analyses —a new educational series for nephrologists
Evidence-based medicine has been the backbone of modern health care. Careful evaluation and synthesis of high-quality evidence may provide robust information that can be applied to policy and patient-level decision making, while accounting for patient preferences and needs and local contextual factors, with transformational effects on provision and delivery of care.1 Traditionally, evidence from randomized controlled trials (RCTs) has been considered the pinnacle of the hierarchy of clinical evidence because of the methodological rigor and robustness in RCT design and because RCTs are conducted in controlled settings with ...
Source: Kidney International - January 21, 2020 Category: Urology & Nephrology Authors: Valeria Saglimbene, Giovanni Strippoli, Jonathan C. Craig, Germaine Wong Tags: Editorial Source Type: research

Uncovering the etiology of  CINAC, a complex and mysterious renal syndrome: the invaluable role of histopathology and electron microscopy
Chronic interstitial nephritis in agricultural communities (CINAC) is a progressive form of tubulointerstitial nephritis affecting agricultural workers in different parts of the world. Its underlying etiology is not known, although a study by Vervaet and coworkers in this issue of Kidney International provides strong evidence that CINAC is a lysosomal tubulopathy induced by toxin exposure. Key to this important discovery is a thorough morphologic analysis of kidney tissue, including ultrastructural as well as histopathologic examination. (Source: Kidney International)
Source: Kidney International - January 21, 2020 Category: Urology & Nephrology Authors: Mark Haas Tags: Commentary Source Type: research

Notch notches lupus
The multifaceted Notch signaling pathway appears to tame the autoimmune response and protect lupus-prone mice from inflammation and damage. (Source: Kidney International)
Source: Kidney International - January 21, 2020 Category: Urology & Nephrology Authors: George C. Tsokos Tags: Commentary Source Type: research

The CKDGen Consortium: ten years of insights into the genetic basis of kidney function
With increasing incidence and a prevalence of>10% among adults worldwide, chronic kidney disease (CKD) represents a major public health issue.1 CKD can lead to metabolic disorders and progress to end-stage kidney disease, and it increases the risk for cardiovascular disease and mortality. Our limited understanding of CKD pathophysiology and the mechanisms influencing kidney function in the healthy range represents a major barrier to the development of treatments targeting the causes rather than the symptoms of CKD. (Source: Kidney International)
Source: Kidney International - January 21, 2020 Category: Urology & Nephrology Authors: Anna K öttgen, Cristian Pattaro Tags: Editorial Source Type: research

Systemic autoimmune diseases and the kidney
Since its inception, Kidney International has published seminal articles describing the effects of systemic autoimmune diseases on the kidney. These manuscripts have characterized the pathology and clinical course of these diseases and perhaps most importantly have provided guidance to the nephrology community about how to treat these complex conditions using the best possible evidence available at the time. To illustrate the wealth of information contained within the Kidney International archives, consider the following papers. (Source: Kidney International)
Source: Kidney International - January 21, 2020 Category: Urology & Nephrology Authors: Brad H. Rovin Tags: Editorial: milestones in nephrology Source Type: research

Potassium channels in control of renal function
Potassium channels are important to control membrane potential and drive epithelial transport processes. In this issue of Kidney International, Bignon et  al. report the role of the Kir4.2 K+-channel, localized at the basolateral membrane of proximal tubules, in the reabsorption of bicarbonate and the modulation of renal ammoniagenesis. The findings have implications for our understanding of how the kidney reacts to hypokalemia, an acid load, and th e metabolic acidosis of patients with advanced stages of chronic kidney disease. (Source: Kidney International)
Source: Kidney International - January 21, 2020 Category: Urology & Nephrology Authors: Pedro H. Imenez Silva, Carsten A. Wagner Tags: Commentary Source Type: research

Patient-centered outreach treatment toward micro-elimination of hepatitis C virus infection in hemodialysis patients
We read the report by Jadoul et  al.1 with great interest in a recent issue in Kidney International. The World Health Organization has set ambitious goals for hepatitis C virus (HCV) eradication using the “micro-elimination” approach.2 Taiwan has one of the highest prevalence and incidence of end-stage kidney disease worldwid e. HCV infection is an important complication among our hemodialysis patients.3 With the advent of the new direct-acting antivirals, complete eradication of HCV infection is one of our key priorities. (Source: Kidney International)
Source: Kidney International - January 21, 2020 Category: Urology & Nephrology Authors: Chung-Feng Huang, Yi-Wen Chiu, Ming-Lung Yu Tags: Letter to the Editor Source Type: research

The authors reply
Although our Dialysis Outcomes and Practice Patterns Study reported a relatively slow international decrease of hepatitis C virus (HCV) prevalence and incidence in hemodialysis (HD) units from 1996 to 20121 (before the direct-acting antiviral era), Huang et  al. now report their direct-acting antiviral–based elimination of HCV from a single HD unit in Taiwan.2 Such eradication of HCV will reduce the clinical burden associated with HCV infection. In addition, HCV eradication should prevent HCV nosocomial transmission. (Source: Kidney International)
Source: Kidney International - January 21, 2020 Category: Urology & Nephrology Authors: Michel Jadoul, Brian A. Bieber, David A. Goodkin, Ronald L. Pisoni Tags: Letter to the Editor Source Type: research

Erratum to “Wu K-Y, Zhang T, Zhao G-X, et al. The C3a/C3aR axis mediates anti-inflammatory activity and protects against uropathogenic E coli–induced kidney injury in mice.” Kidney Int. 2019;96:612–627
In the above-stated article, the publisher regrets that a Western blot was not included in a portion of Figure  4b. The figure in its entirety is below. (Source: Kidney International)
Source: Kidney International - January 21, 2020 Category: Urology & Nephrology Tags: Erratum Source Type: research