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Are Pax proteins potential therapeutic targets in kidney disease and cancer?
Pax genes encode developmental regulators that are expressed in a variety of tissues and control critical events in morphogenesis. In the kidney, Pax2 and Pax8 are expressed in embryonic development and in specific renal diseases associated with aberrant epithelial cell proliferation. Prior genetic and cell biological studies suggest that reducing the activity of Pax proteins in renal cancer or in polycystic kidney disease can slow the progression of these conditions. The Pax proteins may be critical for providing tissue and locus specificity to recruit epigenetic modifiers that control gene expression and chromatin struct...
Source: Kidney International - April 20, 2018 Category: Urology & Nephrology Authors: Edward Grimley, Gregory R. Dressler Tags: Review Source Type: research

Plasma biomarkers are associated with renal outcomes in individuals with APOL1 risk variants
G1/G2 variants in the Apolipoprotein L1 (APOL1) gene are associated with end-stage renal disease (ESRD) in people with African ancestry. Plasma biomarkers may have utility for risk stratification in APOL1 high-risk individuals of African ancestry. To evaluate this, we measured tumor necrosis factor receptor 1/2 (TNFR1/2) and kidney injury molecule-1 (KIM1) in baseline plasma specimens from individuals of African ancestry with high-risk APOL1 genotype. Biomarker association with a composite renal outcome of ESRD or 40% sustained decline in estimated glomerular filtration rate (eGFR) was then determined and then assessed as ...
Source: Kidney International - April 20, 2018 Category: Urology & Nephrology Authors: Girish N. Nadkarni, Kinsuk Chauhan, Divya A. Verghese, Chirag R. Parikh, Ron Do, Carol R. Horowitz, Erwin P. Bottinger, Steven G. Coca Tags: Clinical Investigation Source Type: research

The Case | Severe hypokalemia and metabolic acidosis
A 42-year-old man presented with altered mental status and severe respiratory distress at the emergency department. He was immediately intubated. On his admission, his family indicated that he had been sleepy and restless and had experienced difficulty standing and walking over the preceding 2 weeks. He developed flu-like symptoms 2 days before admission. His medical history revealed that he was taking ibuprofen (800 mg, 4 tablets per day) for headache, and he had increased the dose to 6 tablets per day because of his flu symptoms. (Source: Kidney International)
Source: Kidney International - April 19, 2018 Category: Urology & Nephrology Authors: Jonathan S. Ch ávez-Iñiguez, Francisco Espinosa-García, Alejandra Pacheco-Plascencia, Jorge Andrade-Sierra, Ricardo Rubio-Reynoso, Guillermo García-García Tags: Make Your Diagnosis Source Type: research

Delayed ileal perforation from sodium polystyrene  sulfonate
A 66-year-old man, without a significant medical history, was admitted to the hospital for polyarthralgia. He reported hemorrhagic diarrhea and having been treated with amoxicillin and metronidazole a month prior to admission. Reactive arthritis was first suspected. His serum creatinine level was 0.759 mg/dl. He received nonsteroidal anti-inflammatory drugs. After 3 days, he was admitted to our unit with acute kidney  failure. His serum creatinine level was 8.932 mg/dl. Proteinase-3 anti-neutrophil cytoplasmic antibodies were strongly positive, and granulomatosis with polyangiitis was confirmed by kidney biopsy. (Sour...
Source: Kidney International - April 19, 2018 Category: Urology & Nephrology Authors: Anne-Laure Faucon, Michel Daudon, Vincent Frochot, Dominique Bazin, Beno ît Terris, Valérie Caudwell Tags: Nephrology Image Source Type: research

Tumoral masses in failed kidneys
A 44-year-old male patient presented with recurrent urinary tract infections (urine cultures negative) for 2 years. He was diagnosed as having a urethral stricture, and he underwent dilatations. However, his renal functions deteriorated, and he developed chronic kidney disease (CKD) requiring dialysis and transplantation. Pretransplant workup revealed 4 –5 leukocytes on urine examination, proteinuria (0.2 g/d), and a serum creatinine level of 6.7 mg/dl. Magnetic resonance imaging of his kidneys showed multifocal hyperintense lesions in both. (Source: Kidney International)
Source: Kidney International - April 19, 2018 Category: Urology & Nephrology Authors: Ritambhra Nada, Raja Ramachandran, Ashwani Kumar, K.L. Gupta, Ashish Sharma Tags: Nephrology Image Source Type: research

Uncovering real mortality trends in ESRD patients
Major temporal changes in the case mix of patients accepted for renal replacement therapy impede analysis of long-term mortality trends in end-stage renal disease patients. A record linkage study of 2 large electronic hospital inpatient data sets with national mortality data used standardization by age, sex, and comorbidity to uncover a 50% decline in 3-year mortality in English patients starting renal replacement therapy between 1970 and 2008, a faster drop than that seen in the general population. (Source: Kidney International)
Source: Kidney International - April 19, 2018 Category: Urology & Nephrology Authors: B énédicte Stengel Tags: Commentary Source Type: research

The phosphate bucket list
As our understanding of phosphate homeostasis has expanded over the last 20 years, additional quandaries have surfaced. Though the phosphate bucket list remains full, we are confident that the next 20 years will lead to major fundamental discoveries. In this commentary, we provide an example of how findings from a basic study that examined the mechanisms for circadian rhythms of plasma and urinary phosphate sheds light on important pathways that can be harnessed for novel therapeutic approaches in the future. (Source: Kidney International)
Source: Kidney International - April 19, 2018 Category: Urology & Nephrology Authors: Tamara Isakova, Geoffrey Block Tags: Commentary Source Type: research

Unraveling the mechanisms of obesity-induced hyperoxaluria
Kidney stones is increasingly associated with obesity. With an increasing prevalence of obesity and metabolic syndrome in the past 30 years, urinary oxalate has significantly increased. However, its underlying pathophysiologic mechanisms of hyperoxaluria have not been fully explored. This preclinical study suggests that hyperoxaluria in obesity depends on a complex network of inflammatory responses linked to metabolic outcome. The future mechanistic and clinical investigations must be targeted at elucidating the pathogenetic role of inflammation in obesity induced hyperoxaluria. (Source: Kidney International)
Source: Kidney International - April 19, 2018 Category: Urology & Nephrology Authors: Khashayar Sakhaee Tags: Commentary Source Type: research

A more direct way to measure glomerular albumin permeability —even in human glomeruli!
Existing methods to measure glomerular permeability are limited to relative measures using changes in size of isolated glomeruli in response to changes in oncotic pressure. Further, these techniques are not easily adapted for use with human glomeruli. In the current issue, Desideri and colleagues validate a sophisticated new technique with great promise for future understanding of the glomerular filtration barrier. (Source: Kidney International)
Source: Kidney International - April 19, 2018 Category: Urology & Nephrology Authors: Malgorzata Kasztan, David M. Pollock Tags: Commentary Source Type: research

Fractures in CKD patients: action plans should not overlook the prevention of falls!
In their recent review concerning the diagnosis, treatment, and prevention of fractures in chronic kidney disease (CKD) patients, Pimentel et  al.1 point out that the incidence of fractures increases according to CKD stage, with the highest relative risk in patients receiving chronic hemodialysis. The authors underline the high mortality and costs related to fractures in CKD patients and review clinical, biochemical, histological, and st ructural parameters related to bone fragility in CKD. The authors briefly mention but regrettably omit to discuss the occurrence of falls as a crucial determinant for fractures in hem...
Source: Kidney International - April 19, 2018 Category: Urology & Nephrology Authors: Laura Labriola, Michel Jadoul Tags: Letter to the Editor Source Type: research

The Authors Reply
We thank Dr. Labriola and Dr. Jadoul for their comments.1 We fully agree with the relevance of falls as a major risk factor of fracture in such patients.2 Falls were mentioned and included in Figure  12 as an important determinant of fractures. However, this issue was not extensively discussed because of few relevant data available in chronic kidney disease (CKD) patients. CKD patients, including those treated by dialysis, may have a high propensity for falls. Several factors are probably invo lved, including accelerated aging with deleterious consequences such as impaired cognitive function, neurological disorders, v...
Source: Kidney International - April 19, 2018 Category: Urology & Nephrology Authors: Martine Cohen-Solal, Pablo Antonio Ure ña-Torres Tags: Letter to the Editor Source Type: research

Global glomerulosclerosis in primary nephrotic syndrome: including age as a variable to predict renal outcomes
With normal aging, there are increased numbers of globally sclerotic glomeruli. Global glomerulosclerosis is also a feature of chronic kidney disease. In this issue, Hommos and colleagues provide data on the fraction of globally sclerotic glomeruli in healthy kidney donor biopsies. This provides reference for evaluation of whether isolated global glomerulosclerosis is evidence of pathology. (Source: Kidney International)
Source: Kidney International - April 19, 2018 Category: Urology & Nephrology Authors: Jeffrey B. Kopp Tags: Commentary Source Type: research

International prevalence of hepatitis C positivity among hemodialysis patients awaiting transplantation
It is well recognized that the shortage of available kidneys has resulted in long wait times for dialysis patients seeking transplantation and that many patients die before receiving an allograft. Yet, the data presented by Reese et  al.,1 in their early, thoughtful proposal to begin considering transplanting hepatitis C virus (HCV)–positive kidneys, reveal that in the United States between 2005 and 2014, 4144 kidneys from 3273 deceased donors with hepatitis C antibody were discarded. With the recent development of highly ef fective, well-tolerated oral agents to treat HCV infection, it would seem desirable to t...
Source: Kidney International - April 19, 2018 Category: Urology & Nephrology Authors: David A. Goodkin, Brian Bieber Tags: Letter to the Editor Source Type: research

Age-adjusted global glomerulosclerosis in addition to Oxford histological classification of IgA nephropathy
We thank Hommos et  al. for their robust study that found that only globally sclerotic glomeruli (GSG) exceeding the age-specific 95th percentile for global glomerulosclerosis in healthy adults was associated with progressive chronic kidney disease in glomerulopathies presenting with nephrotic syndrome.1 Earlier, we demonstrated that extent of GSG was independently associated with end-stage renal disease at 30 years in a young cohort (median age, 25 years; interquartile range, 21–30 years) that did not receive immunosuppressants when diagnosed with IgA nephropathy (IgAN) in the 1970s and early 1980s. (Source: Kidney International)
Source: Kidney International - April 19, 2018 Category: Urology & Nephrology Authors: Cynthia C. Lim, Jason C.J. Choo, Choong Meng Chan, Keng Thye Woo Tags: Letter to the Editor Source Type: research

Clinical relevance and future perspective of fractures in  patients with chronic kidney disease
We read with great interest the article by Pimentel et  al.1 on diagnosis, treatment, and prevention of fractures in patients with chronic kidney disease (CKD). We support the message of the clinical relevance of fracture events in CKD, and we would like to add further comments on the issue, such as to stress the need to better study the likely underes timated prevalence of vertebral fractures in CKD. To do so, a systematic population-based screening with spine plain films and morphometric studies of vertebral deformity2 is needed. (Source: Kidney International)
Source: Kidney International - April 19, 2018 Category: Urology & Nephrology Authors: Maria Fusaro, Jorge B. Cannata-And ía, Thomas L. Nickolas, Mario Plebani, Maria Cristina Mereu, Andrea Aghi, Maurizio Gallieni Tags: Letter to the Editor Source Type: research

The Authors Reply
We thank Fusaro and her colleagues for their comments.1 We concur that there is a sound need for large, well-designed clinical studies to assess the prevalence, risk factors, treatment, and outcome of vertebral fractures in patients with chronic kidney disease (CKD). In our review,2 we did not include quantitative vertebral morphology as assessed by MorphoXpress software to quantify vertebral fractures in CKD. The assessment of vertebral fractures by quantitative vertebral morphology in patients on dialysis and renal transplant recipients resulted in the validation of the tool in osteoporotic patients of the general popula...
Source: Kidney International - April 19, 2018 Category: Urology & Nephrology Authors: Pablo Antonio Ure ña-Torres, Martine Cohen-Solal Tags: Letter to the Editor Source Type: research

In this issue
Patients with rheumatoid arthritis have a higher prevalence of chronic kidney disease than the general population. This is attributed to nephrotoxic drugs and systemic inflammation. Biologic agents have revolutionized the treatment of rheumatoid arthritis. Sumida and colleagues retrospectively examined a large rheumatoid arthritis cohort to determine whether treatment with biologics has improved kidney outcomes. Using propensity matched patients, the incidence of chronic kidney disease and change in estimated glomerular filtration rate was compared in 4000 patients treated with a biologic agent to 4000 patients who were no...
Source: Kidney International - April 19, 2018 Category: Urology & Nephrology Tags: In This Issue Source Type: research

Immune checkpoint inhibitors and the union of bugs against cancer
In 2011, the first immune checkpoint inhibitor (ICI) therapeutic antibody was approved by the US Food and Drug Administration for the treatment of advanced melanoma. Based on Phase III trials, 6 different ICI agents are now approved for the treatment of a range of tumors, including renal cell carcinoma, and, most recently, for any solid tumor with genetic instability (Table  1). These agents act by unleashing the power of the immune system via targeting of inhibitory T-cell immune checkpoint pathways, including the receptor programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) system, and the related CTLA-4 costimulati...
Source: Kidney International - April 19, 2018 Category: Urology & Nephrology Authors: Gregg J. Silverman, Doua F. Azzouz, Adam Mor Tags: Nephrology Digest Source Type: research

Journal Club
Purnell et  al. (JAMA. 2018;319:49–61; https://doi.org/10.1001/jama.2017.19152) (Source: Kidney International)
Source: Kidney International - April 19, 2018 Category: Urology & Nephrology Tags: Journal Club Source Type: research

Editorial Board
(Source: Kidney International)
Source: Kidney International - April 19, 2018 Category: Urology & Nephrology Source Type: research

Subscription Information
(Source: Kidney International)
Source: Kidney International - April 19, 2018 Category: Urology & Nephrology Source Type: research

Table of Contents
(Source: Kidney International)
Source: Kidney International - April 19, 2018 Category: Urology & Nephrology Source Type: research

Actin dynamics at focal adhesions: a common endpoint and putative therapeutic target for proteinuric kidney diseases
Proteinuria encompasses diverse causes including both genetic diseases and acquired forms such as diabetic and hypertensive nephropathy. The basis of proteinuria is a disturbance in size selectivity of the glomerular filtration barrier, which largely depends on the podocyte: a terminally differentiated epithelial cell type covering the outer surface of  the glomerulus. Compromised podocyte structure is one of the earliest signs of glomerular injury. The phenotype of diverse animal models and podocyte cell culture firmly established the essential role of the actin cytoskeleton in maintaining functional podocyte structu...
Source: Kidney International - April 17, 2018 Category: Urology & Nephrology Authors: Sanja Sever, Mario Schiffer Tags: Review Source Type: research

Renal cell carcinoma for the nephrologist
Renal cell carcinoma (RCC), a malignancy whose incidence is increasing, is frequently encountered in general nephrology practice when acute and chronic kidney disease occurs in the course of disease. Importantly, when kidney disease develops in the setting of RCC, mortality is significantly increased with patients often dying of a non-cancer-related complication of kidney disease. As such, practicing nephrologists need to have a working knowledge of this cancer ’s biology, treatment, and complications. (Source: Kidney International)
Source: Kidney International - April 14, 2018 Category: Urology & Nephrology Authors: Mark A. Perazella, Robert Dreicer, Mitchell H. Rosner Tags: Review Source Type: research

Different rates of progression and mortality in patients with chronic kidney disease at outpatient nephrology clinics across Europe
The incidence of renal replacement therapy varies across countries. However, little is known about the epidemiology of chronic kidney disease (CKD) outcomes. Here we describe progression and mortality risk of patients with CKD but not on renal replacement therapy at outpatient nephrology clinics across Europe using individual data from nine CKD cohorts participating in the European CKD Burden Consortium. A joint model assessed the mean change in estimated glomerular filtration rate (eGFR) and mortality risk simultaneously, thereby accounting for mortality risk when estimating eGFR decline and vice versa, while also correct...
Source: Kidney International - April 12, 2018 Category: Urology & Nephrology Authors: Katharina Br ück, Kitty J. Jager, Carmine Zoccali, Aminu K. Bello, Roberto Minutolo, Kyriakos Ioannou, Francis Verbeke, Henry Völzke, Johan Arnlöv, Daniela Leonardis, Pietro Manuel Ferraro, Hermann Brenner, Ben Caplin, Philip A. Kalra, Christoph Wanner Tags: Clinical Investigation Source Type: research

Legumain, an asparaginyl endopeptidase, mediates the effect of M2 macrophages on attenuating renal interstitial fibrosis in obstructive nephropathy
Two distinct macrophage phenotypes contribute to kidney injury and repair during the progression of renal interstitial fibrosis; proinflammatory (M1) and antiinflammatory (M2) macrophages. Legumain, an asparaginyl endopeptidase of the cysteine protease family, is overexpressed in macrophages in some pathological conditions. However, the macrophage subtype and function of macrophage-derived legumain remains unclear. To resolve this we tested whether M2 macrophages contribute to the accumulation of legumain in the unilateral ureteral obstruction model. (Source: Kidney International)
Source: Kidney International - April 12, 2018 Category: Urology & Nephrology Authors: Dekun Wang, Min Xiong, Chuan'ai Chen, Lingfang Du, Ze Liu, Yuzhi Shi, Mianzhi Zhang, Junbo Gong, Xiangrong Song, Rong Xiang, Ergang Liu, Xiaoyue Tan Tags: Basic Research Source Type: research

Donor-specific hypo-responsiveness occurs in simultaneous liver-kidney transplant recipients after the first year
Kidney allografts of patients who undergo simultaneous liver-kidney transplantation incur less immune-mediated injury, and retain better function compared to other kidney allografts. To characterize the host alloimmune responses in 28 of these patients, we measured the donor-specific alloresponsiveness and phenotypes of peripheral blood cells after the first year. These values were then compared to those of 61 similarly immunosuppressed recipients of a solitary kidney or 31 recipients of liver allografts. (Source: Kidney International)
Source: Kidney International - April 12, 2018 Category: Urology & Nephrology Authors: Timucin Taner, Michael P. Gustafson, Michael J. Hansen, Walter D. Park, Svetlana Bornschlegl, Allan B. Dietz, Mark D. Stegall Tags: Clinical Investigation Source Type: research

Improving the prognosis of patients with severely decreased glomerular filtration rate (CKD G4+): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference
Patients with severely decreased glomerular filtration rate (GFR) (i.e., chronic kidney disease [CKD] G4+) are at increased risk for kidney failure, cardiovascular disease (CVD) events (including heart failure), and death. However, little is known about the variability of outcomes and optimal therapeutic strategies, including initiation of kidney replacement therapy (KRT). Kidney Disease: Improving Global Outcomes (KDIGO) organized a Controversies Conference with an international expert group in December 2016 to address this gap in knowledge. (Source: Kidney International)
Source: Kidney International - April 12, 2018 Category: Urology & Nephrology Authors: Kai-Uwe Eckardt, Nisha Bansal, Josef Coresh, Marie Evans, Morgan E. Grams, Charles A. Herzog, Matthew T. James, Hiddo J.L. Heerspink, Carol A. Pollock, Paul E. Stevens, Manjula Kurella Tamura, Marcello A. Tonelli, David C. Wheeler, Wolfgang C. Winkelmayer Tags: KDIGO Executive Conclusions Source Type: research

Drug repurposing in kidney disease
Drug repurposing, is the re-tasking of known medications for new clinical indications. Advantages, compared to de novo drug development, include reduced cost and time to market plus the added benefit of a known pharmacokinetic and safety profiles. Suitable drug candidates are identified through serendipitous observations, data mining, or increased understanding of disease mechanisms. This review highlights drugs suited for repurposing in kidney disease. The main cause of mortality in patients with chronic kidney disease is cardiovascular disease. (Source: Kidney International)
Source: Kidney International - April 6, 2018 Category: Urology & Nephrology Authors: Usha Panchapakesan, Carol Pollock Tags: Review Source Type: research

Excessive neutrophil extracellular trap formation in ANCA-associated vasculitis is independent of ANCA
Neutrophil extracellular traps (NETs) are auto-antigenic strands of extracellular DNA covered with myeloperoxidase (MPO) and proteinase3 (PR3) that can be a source for the formation of anti-neutrophil cytoplasmic autoantibodies (ANCAs). The presence of NETs was recently demonstrated in renal tissue of patients with ANCA-associated vasculitis (AAV). NET formation was enhanced in AAV, suggesting that MPO-ANCA could trigger NET formation, supporting a  vicious circle placing NETs in the center of AAV pathogenesis. (Source: Kidney International)
Source: Kidney International - March 30, 2018 Category: Urology & Nephrology Authors: Tineke Kraaij, Sylvia W.A. Kamerling, Laura S. van Dam, Jaap A. Bakker, Ingeborg M. Bajema, Theresa Page, Francesca Brunini, Charles D. Pusey, Rene E.M. Toes, Hans U. Scherer, Ton J. Rabelink, Cees van Kooten, Y.K. Onno Teng Tags: Clinical Investigation Source Type: research

Intravital phosphorescence lifetime imaging of the renal cortex accurately measures renal hypoxia
Renal tubulointerstitial hypoxia is recognized as a final common pathway of chronic kidney disease and is considered a promising drug target. However, hypoxia in the tubules is not well examined because of limited detection methods. Here, we devised a method to visualize renal tubular oxygen tension with spatial resolution at a cellular level using the cell-penetrating phosphorescent probe, BTPDM1 (an iridium-based cationic lipophilic dye), and confocal phosphorescence lifetime imaging microscopy to precisely assess renal hypoxia. (Source: Kidney International)
Source: Kidney International - March 30, 2018 Category: Urology & Nephrology Authors: Yosuke Hirakawa, Kiichi Mizukami, Toshitada Yoshihara, Ippei Takahashi, Purevsuren Khulan, Tomoko Honda, Imari Mimura, Tetsuhiro Tanaka, Seiji Tobita, Masaomi Nangaku Tags: Technical Notes Source Type: research

Activated renal tubular Wnt/ β-catenin signaling triggers renal inflammation during overload proteinuria
Imbalance of Wnt/ β-catenin signaling in renal cells is associated with renal dysfunction, yet the precise mechanism is poorly understood. Previously we observed activated Wnt/β-catenin signaling in renal tubules during proteinuric nephropathy with an unknown net effect. Therefore, to identify the definitive role o f tubular Wnt/β-catenin, we generated a novel transgenic “Tubcat” mouse conditionally expressing stabilized β-catenin specifically in renal tubules following tamoxifen administration. Four weeks after tamoxifen injection, uninephrectomized Tubcat mice displayed proteinuria and ele...
Source: Kidney International - March 28, 2018 Category: Urology & Nephrology Authors: Dickson W.L. Wong, Wai Han Yiu, Kam Wa Chan, Ye Li, Bin Li, Sarah W.Y. Lok, Makoto M. Taketo, Peter Igarashi, Loretta Y.Y. Chan, Joseph C.K. Leung, Kar Neng Lai, Sydney C.W. Tang Tags: Basic Research Source Type: research

Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate
Patients with chronic kidney disease and severely decreased glomerular filtration rate (GFR) are at high risk for kidney failure, cardiovascular disease (CVD) and death. Accurate estimates of risk and timing of these clinical outcomes could guide patient counseling and therapy. Therefore, we developed models using data of 264,296 individuals in 30 countries participating in the international Chronic Kidney Disease Prognosis Consortium with estimated GFR (eGFR)s under 30 ml/min/1.73m2. Median participant eGFR and urine albumin-to-creatinine ratio were 24 ml/min/1.73m2 and 168 mg/g, respectively. (Source: Kidney International)
Source: Kidney International - March 28, 2018 Category: Urology & Nephrology Authors: Morgan E. Grams, Yingying Sang, Shoshana H. Ballew, Juan Jesus Carrero, Ognjenka Djurdjev, Hiddo J.L. Heerspink, Kevin Ho, Sadayoshi Ito, Angharad Marks, David Naimark, Danielle M. Nash, Sankar D. Navaneethan, Mark Sarnak, Benedicte Stengel, Frank L.J. Vi Tags: Clinical Investigation Source Type: research

Pyrophosphate deficiency in vascular calcification
Pathologic cardiovascular calcification is associated with a number of conditions and is a common complication of chronic kidney disease. Because ambient calcium and phosphate levels together with properties of the vascular matrix favor calcification even under normal conditions, endogenous inhibitors such as pyrophosphate play a key role in prevention. Genetic diseases and animal models have elucidated the metabolism of extracellular pyrophosphate and demonstrated the importance of pyrophosphate deficiency in vascular calcification. (Source: Kidney International)
Source: Kidney International - March 26, 2018 Category: Urology & Nephrology Authors: Ricardo Villa-Bellosta, W. Charles O ’Neill Tags: Review Source Type: research

Detection of renin lineage cell transdifferentiation to podocytes in the kidney glomerulus with dual lineage tracing
Understanding of cellular transdifferentiation is limited by the technical inability to track multiple lineages in  vivo. To overcome this we developed a new tool to simultaneously fate map two distinct cell types in the kidney, and genetically test whether cells of renin lineage (CoRL) can transdifferentiate to a podocyte fate. Ren1cCreER/tdTomato/Nphs1-FLPo/FRT-EGFP mice (CoRL-PODO mice) were generated by cro ssing Ren1c-CreER/tdTomato CoRL reporter mice with Nphs1-FLPo/FRT-EGFP podocyte reporter mice. (Source: Kidney International)
Source: Kidney International - March 24, 2018 Category: Urology & Nephrology Authors: Diana G. Eng, Natalya V. Kaverina, Remington R.S. Schneider, Benjamin S. Freedman, Kenneth W. Gross, Jeffrey H. Miner, Jeffrey W. Pippin, Stuart J. Shankland Tags: Technical Notes Source Type: research

Prevention and treatment of hyperphosphatemia in chronic kidney disease
Hyperphosphatemia has consistently been shown to be associated with dismal outcome in a wide variety of populations, particularly in chronic kidney disease (CKD). Compelling evidence from basic and animal studies elucidated a range of mechanisms by which phosphate may exert its pathological effects and motivated interventions to treat hyperphosphatemia. These interventions consisted of dietary modifications and phosphate binders. However, the beneficial effects of these treatment methods on hard clinical outcomes have not been convincingly demonstrated in prospective clinical trials. (Source: Kidney International)
Source: Kidney International - March 24, 2018 Category: Urology & Nephrology Authors: Marc G. Vervloet, Adriana J. van Ballegooijen Tags: Review Source Type: research

Disease burden and challenges of chronic kidney disease in North and East Asia
North and East Asia includes mainland China (including Hong Kong), Japan, Mongolia, North Korea, South Korea, and Taiwan (Figure  1). The region comprises a population of more than 1.6 billion, with considerable diversities in economy, living habits, climates, and environments. North Korea is classified as a low-income country by World Bank criteria, whereas China and Mongolia belong to the upper middle income group, and Jap an, Hong Kong, South Korea, and Taiwan to the high-income group with highly developed economies. (Source: Kidney International)
Source: Kidney International - March 22, 2018 Category: Urology & Nephrology Authors: Jinwei Wang, Luxia Zhang, Sydney Chi-wai Tang, Naoki Kashihara, Yong-Soo Kim, Ariunaa Togtokh, Chih-wei Yang, Ming-hui Zhao, ISN North and East Asia Regional Board Tags: Policy Forum Source Type: research

The Case | Shining a light on an unusual case of chronic kidney disease
A 65-year-old man of Afro-Caribbean origin was referred to the renal clinic for investigation of deteriorating renal function. His estimated glomerular filtration rate had fallen from 37 ml/min to 23 ml/min (creatinine 292 μmol/l) over 12 months. He had a past medical history of chronic back pain, Bell’s palsy, hypertension, and gout. He was noted to have a family history of chronic kidney disease in that his daughter had recently been diagnosed with renal sarcoidosis. Clinical examination was unremarkable. (Source: Kidney International)
Source: Kidney International - March 21, 2018 Category: Urology & Nephrology Authors: Amin Oomatia, Peter Dupont, Paul Bass, Shabir Moochhala Tags: Make Your Diagnosis Source Type: research

Uremic cranial neuropathy
A 22-year-old man with rapidly progressive chronic kidney disease secondary to Alport syndrome, lost to medical follow-up for more than 1 year, presented with a 1-day history of weakness, ataxia, dysarthria, dysphagia, headache, and blurry double vision. Physical examination was notable for left-sided ophthalmoplegia (partial cranial nerve III palsy with ptosis and upgaze paresis) and facial diplegia. He was also noted to have hyperreflexia and clonus. Laboratory investigations revealed blood urea nitrogen of 75 mmol/l and creatinine of 2340 umol/l. (Source: Kidney International)
Source: Kidney International - March 21, 2018 Category: Urology & Nephrology Authors: Januvi Jegatheswaran, Carlos Torres, Edward Clark Tags: Nephrology Image Source Type: research

Osteopetrosis with renal tubular acidosis and cerebral calcification
A 26-year-old Irish male with a history of developmental delay and multiple fractures presented with quadraparesis. There was a family history of consanguinity. His laboratory tests revealed the following: serum Na+, 139 mmol/l; K+, 1.7 mmol/l; Cl –, 114 mmol/l; HCO3, 15 mmol/l; urea, 4.1 mmol/l; creatinine, 103 μmol/l; Ca2+, 2.66 mmol/l; PO43–, 0.35 mmol/l; and Mg2+, 0.35 mmol/l. His arterial blood gas test showed a pH of 7.16, PaO2 at 14.4 kPa, and PaCO2 at 4.88 kPa. Urine chemistry results included the following: Na+, 173 mmol/l; K+, 21.5 mmol/l; Cl–, 169 mmol/l; and urine, pH 7. (Source: Kidney International)
Source: Kidney International - March 21, 2018 Category: Urology & Nephrology Authors: Dearbhla M. Kelly, Paul V. O ’Hara, Eoin M. Kelleher, Liam F. Casserly Tags: Nephrology Image Source Type: research

U-shaped dietary sodium –associated incidence of chronic kidney disease cautions against salt overrestriction in hypertension
In this population study salt intake is not associated with development of chronic kidney disease (CKD) in individuals with normal blood pressure, whereas in hypertensive individuals both low and high salt intakes are associated with increased incidence of CKD, similar to U-shaped associations between salt intake and mortality found in previous studies. The results contribute to the skepticism, which has questioned the present public health policy to reduce salt intake below 5.8 g. (Source: Kidney International)
Source: Kidney International - March 21, 2018 Category: Urology & Nephrology Authors: Niels Graudal Tags: Commentary Source Type: research

Increasing inclusion of patients with advanced chronic kidney disease in cardiovascular clinical trials
The inadequate inclusion of patients with reduced renal function in randomized clinical trials has become a topic of intense discussion in recent years. This limited representation has been most acutely witnessed in cardiovascular (CV) trials addressing the management of patients with advanced chronic kidney disease (CKD), especially those with end-stage renal disease (ESRD). Several investigators have highlighted the low inclusion of such patients in CV trials.1 The key question is why this occurs. (Source: Kidney International)
Source: Kidney International - March 21, 2018 Category: Urology & Nephrology Authors: Roy O. Mathew, Sripal Bangalore, Mandeep S. Sidhu, Jerome L. Fleg, Franklin W. Maddux Tags: Commentary: Opinion Source Type: research

Update on renal blood oxygenation level –dependent MRI to assess intrarenal oxygenation in chronic kidney disease
Identifying subjects with progressive chronic kidney disease will be important both in clinical practice and in conducting clinical trials. Pruijm et  al. (in this issue) demonstrate for the first time that cortical oxygenation as evaluated by blood oxygenation level–dependent magnetic resonance imaging can predict future loss of renal function. These observations provide the necessary stimulus to continue the development of renal blood oxygen ation level–dependent magnetic resonance imaging to further improve the sensitivity and specificity to renal oxygenation and hence the predictive power. (Source: Kidney International)
Source: Kidney International - March 21, 2018 Category: Urology & Nephrology Authors: Pottumarthi V. Prasad Tags: Commentary Source Type: research

Arrhythmia in hemodialysis patients and its relation to sudden death
Sudden death in patients on hemodialysis is believed to be due to arrhythmia, but the evidence for this is surprisingly limited. Five studies involving implantable loop recorders in patients on hemodialysis have now been published, and 4 have shown that bradyarrhythmia rather than tachyarrhythmia are the pre-eminent arrhythmic associations of fatal events. The Monitoring in Dialysis study, reported in this issue, sheds new light on the relationships of arrhythmia to the conventional 3-session weekly hemodialysis cycle. (Source: Kidney International)
Source: Kidney International - March 21, 2018 Category: Urology & Nephrology Authors: Philip A. Kalra, Darren Green, Dimitrios Poulikakos Tags: Commentary Source Type: research

Lipids, inflammation, and chronic kidney disease: a  SHARP perspective
Accumulating evidence indicates that inflammation plays a role in the initiation and progression of chronic kidney disease. In the Study of Heart and Renal Protection (SHARP) trial, higher baseline C-reactive protein and higher baseline low-density lipoprotein cholesterol levels were both associated with a higher risk of cardiovascular events, but higher baseline C-reactive protein levels were also associated with a higher risk of nonvascular events. Simvastatin/ezetimibe reduced cardiovascular events independent of baseline C-reactive protein levels. (Source: Kidney International)
Source: Kidney International - March 21, 2018 Category: Urology & Nephrology Authors: David D. Waters, Liffert Vogt Tags: Commentary Source Type: research

IL-17A –induced mesenchymal stem cells have promising therapeutic value for clinical translation
Interferon (IFN) gamma is the prototypic proinflammatory cytokine used to preactivate the immunomodulatory properties of mesenchymal stem cells (MSC). IFN-gamma, however, converts MSC into a cell therapy that can be immunogenic, detrimental, and hence nonfeasible for clinical application. The article by Bai et  al. is an in vivo proof-of-concept study that interleukin-17A (IL-17A) enhances the immunosuppressive, tolerance-promoting, and renoprotective properties of MSC. IL-17A is an alternative cytokine to preactivate MSC. (Source: Kidney International)
Source: Kidney International - March 21, 2018 Category: Urology & Nephrology Authors: Kisha Nandini Sivanathan, Patrick Toby Coates Tags: Commentary Source Type: research

The Authors Reply
In response to our paper,1 Dr. Comper argues that the megalin/cubilin receptor complex only has a minor role in the proximal tubular uptake of filtered albumin.2 This is based on the assumption that the normal glomerular filtration of albumin is as high as ∼225 g/d, and that a yet uncharacterized tubular retrieval pathway rescues the filtered albumin to maintain plasma albumin levels. From this notion, Dr. Comper infers that the calculated albumin glomerular sieving coefficient ( (Source: Kidney International)
Source: Kidney International - March 21, 2018 Category: Urology & Nephrology Authors: Kathrin Weyer, Henrik Birn, Rikke Nielsen, Erik Ils ø Christensen Tags: Letter to the Editor Source Type: research

Immunological remission in PLA2R-antibody –associated membranous nephropathy: cyclophosphamide versus rituximab
For the treatment of patients with idiopathic membranous nephropathy, rituximab is considered an alternative to alkylating agents. Still, the nonresponse rate to rituximab is approximately 35%,1,2 and partial remission rate is lower with rituximab compared with cyclophosphamide.3 The discovery of antibodies against PLA2R (aPLA2R) has positioned immunological remission as a major goal in the treatment of idiopathic membranous nephropathy. We questioned whether rituximab is less effective than cyclophosphamide in inducing an immunological remission in patients with idiopathic membranous nephropathy. (Source: Kidney International)
Source: Kidney International - March 21, 2018 Category: Urology & Nephrology Authors: Anne-Els van de Logt, Karine Dahan, Alexandra Rousseau, Renate van der Molen, Hanna Debiec, Pierre Ronco, Jack Wetzels Tags: Letter to the Editor Source Type: research

Megalin/cubilin has a minor  role in the proximal tubular cell uptake of filtered albumin
The claim by Weyer et  al.1 that the megalin/cubilin complex is the only way filtered albumin may enter the proximal tubule cell (PTC) has now been shown to be incorrect. The low capacity of the megalin/cubilin complex for albumin implies that the glomerular sieving coefficient (GSC) of albumin is very low ( (Source: Kidney International)
Source: Kidney International - March 21, 2018 Category: Urology & Nephrology Authors: Wayne D. Comper Tags: Letter to the Editor Source Type: research

Atypical chemokine receptors —“chemokine PACMANs” as new therapeutic targets in glomerulonephritis
Inflammatory cells are recruited to sites of inflammation by chemokines. Atypical chemokine receptors regulate chemokine gradients, thereby limiting inflammation. In this issue of Kidney International, atypical chemokine receptor 2 knockouts were described to be increasingly susceptible to immune complex –mediated glomerulonephritis. By degrading CCL2, atypical chemokine receptor 2 limited the recruitment of immune cells and myofibroblasts to the renal interstitial compartment. Therefore, not only inflammation, but also fibrosis, was effectively inhibited, making atypical chemokine receptor 2 an a ttractive therapeut...
Source: Kidney International - March 21, 2018 Category: Urology & Nephrology Authors: Kathrin Eller, Alexander R. Rosenkranz Tags: Commentary Source Type: research