Properdin binds independent of complement activation in an in vivo model of anti –glomerular basement membrane disease
Properdin is the only known positive regulator of complement activation by stabilizing the alternative pathway convertase through C3 binding, thus prolonging its half-life. Recent in  vitro studies suggest that properdin may act as a specific pattern recognition molecule. To better understand the role of properdin in vivo, we used an experimental model of acute anti-glomerular basement membrane disease with wild-type, C3- and properdin knockout mice. The model exhibited severe proteinuria, acute neutrophil infiltration and activation, classical and alternative pathway activation, and progressive glomerular deposi...
Source: Kidney International - October 12, 2018 Category: Urology & Nephrology Authors: Joseph O ’Flynn, Juha Kotimaa, Ria Faber-Krol, Karin Koekkoek, Ngaisah Klar-Mohamad, Angela Koudijs, Wilhelm J. Schwaeble, Cordula Stover, Mohamed R. Daha, Cees van Kooten Tags: Basic Research Source Type: research

Hydroxypropyl- β-cyclodextrin protects from kidney disease in experimental Alport syndrome and focal segmental glomerulosclerosis
Studies suggest that altered renal lipid metabolism plays a role in the pathogenesis of diabetic kidney disease and that genetic or pharmacological induction of cholesterol efflux protects from the development of diabetic kidney disease and focal segmental glomerulosclerosis (FSGS). Here we tested whether altered lipid metabolism contributes to renal failure in the Col4a3 knockout mouse model for Alport Syndrome. There was an eight-fold increase in the cholesterol content in renal cortexes of mice with Alport Syndrome. (Source: Kidney International)
Source: Kidney International - October 6, 2018 Category: Urology & Nephrology Authors: Alla Mitrofanova, Judith Molina, Javier Varona Santos, Johanna Guzman, Ximena A. Morales, G. Michelle Ducasa, Jonathan Bryn, Alexis Sloan, Ion Volosenco, Jin-Ju Kim, Mengyuan Ge, Shamroop K. Mallela, Matthias Kretzler, Sean Eddy, Sebastian Martini, Patric Tags: Basic Research Source Type: research

Donor APOL1 high-risk genotypes are associated with increased risk and inferior prognosis of de novo collapsing glomerulopathy in renal allografts
Collapsing focal segmental glomerulosclerosis (cFSGS) in the native kidney is associated with heavy proteinuria and accelerated renal failure. However, cFSGS in the renal allograft is less well characterized. Here we report clinico-pathologic features and APOL1 donor risk genotypes in 38 patients with de novo post-kidney transplant cFSGS. Recipients were 34% female and 26% African American. Concurrent viral infections and acute vaso-occlusion (including thrombotic microangiopathy, cortical necrosis, atheroembolization, and cardiac arrest with contralateral graft thrombosis) were present in 13% and 29% of recipients, respec...
Source: Kidney International - October 3, 2018 Category: Urology & Nephrology Authors: Dominick Santoriello, Syed A. Husain, Sacha A. De Serres, Andrew S. Bomback, Russell J. Crew, Elena-Rodica Vasilescu, Geo Serban, Eric S. Campenot, Krzysztof Kiryluk, Sumit Mohan, Gregory A. Hawkins, Pamela J. Hicks, David J. Cohen, Jai Radhakrishnan, Mic Tags: Clinical Investigation Source Type: research

Renal transplant recipients receiving loop diuretic therapy have increased urinary tract infection rate and altered medullary macrophage polarization marker expression
Loop diuretics deplete the renal cortico-medullary salt gradient that has recently been established as a major modulator of immune responses. Renal transplant recipients suffer from a markedly increased rate of urinary tract infections (UTIs). Whether diuretic therapy affects renal macrophage polarization in the human kidney graft and the incidence of UTI have not been reported. In a cohort of 112 adult renal allograft recipients, loop diuretic therapy significantly correlated with the rate of UTI during five years after transplantation in uni- and multivariable regression analysis. (Source: Kidney International)
Source: Kidney International - September 28, 2018 Category: Urology & Nephrology Authors: Janis Casper, Jessica Schmitz, Jan Hinrich Br äsen, Abedalrazag Khalifa, Bernhard M.W. Schmidt, Gunilla Einecke, Hermann Haller, Sibylle von Vietinghoff Tags: Clinical Investigation Source Type: research

CD8+ T cells modulate autosomal dominant polycystic kidney disease progression
Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent inherited nephropathy. To date, therapies alleviating the disease have largely focused on targeting abnormalities in renal epithelial cell signaling. ADPKD has many hallmarks of cancer, where targeting T  cells has brought novel therapeutic interventions. However, little is known about the role and therapeutic potential of T cells in ADPKD. Here, we used an orthologous ADPKD model, Pkd1 p.R3277C (RC), to begin to define the role of T cells in disease progression. (Source: Kidney International)
Source: Kidney International - September 21, 2018 Category: Urology & Nephrology Authors: Emily K. Kleczko, Kenneth H. Marsh, Logan C. Tyler, Seth B. Furgeson, Bonnie L. Bullock, Christopher J. Altmann, Makoto Miyazaki, Berenice Y. Gitomer, Peter C. Harris, Mary C.M. Weiser-Evans, Michel B. Chonchol, Eric T. Clambey, Raphael A. Nemenoff, Katha Tags: Basic Research Source Type: research

Iron attenuates erythropoietin production by decreasing hypoxia-inducible transcription factor 2 α concentrations in renal interstitial fibroblasts
Iron is an essential mineral for oxygen delivery and for a variety of enzymatic activities, but excessive iron results in oxidative cytotoxicity. Because iron is primarily used in red blood cells, defective erythropoiesis caused by loss of the erythroid growth factor erythropoietin (Epo) elevates iron storage levels in serum and tissues. Here, we investigated the effects of iron in a mouse model of Epo-deficiency anemia, in which serum iron concentration was significantly elevated. We found that intraperitoneal injection of iron-dextran caused severe iron deposition in renal interstitial fibroblasts, the site of Epo produc...
Source: Kidney International - September 20, 2018 Category: Urology & Nephrology Authors: Norio Suzuki, Yukari Matsuo-Tezuka, Yusuke Sasaki, Koji Sato, Kenichiro Miyauchi, Koichiro Kato, Sakae Saito, Yasushi Shimonaka, Michinori Hirata, Masayuki Yamamoto Tags: Basic Research Source Type: research

Electron microscopy of urinary sediments in Fabry  disease
A 60-year-old woman on peritoneal dialysis was found to have fatty bodies with whorl-like structures (called Mulberry bodies) in her urine, suggesting Fabry disease. Fabry disease is an X-linked hereditary disease, and  the phenotypes of female patients are often mild with a normal range of α-galactosidase activity. Her plasma globotriaosylceramide was increased, but renal biopsy samples showed a few ceramide deposits in the glomerular podocytes, renal tubular cells, and interstitial macrophages. (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Yoshiki Murayama, Mayu Uchida, Akihiro Tojo, Toshihiko Ishimitsu Tags: Nephrology Image Source Type: research

“Highlighting” an unusual case of discolored peritoneal dialysis effluent
A 34-year-old man with end-stage renal disease on continuous ambulatory peritoneal dialysis presented to home dialysis clinic for his monthly appointment. The patient ’s prescription consisted of 4 ambulatory exchanges of 2-liter dwell volume. He presented with peritoneal dialysis effluent bags from the prior day for measurement of dialysis adequacy. Two of the effluent bags (third and fourth exchange) were noted to be of fluorescent yellow discoloration (Figur e 1). Detailed questioning revealed that the patient had received i.v. (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Sana F. Khan, Mitchell H. Rosner Tags: Nephrology Image Source Type: research

A novel role of renin inhibitor in the complement cascade
Aberrant regulation of an alternative pathway of the complement system could be a therapeutic target of C3 glomerulopathy, including dense deposit disease. In the current issue, B ékássy and colleagues provide data on enzymatic conversion of C3 by renin in vitro and on the efficacy of a direct renin inhibitor, aliskiren, on systemic and renal complement activation in patients with dense deposit disease. (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Daisuke Nakano, Akira Nishiyama Tags: Commentary Source Type: research

Executive summary of the 2018 KDIGO Hepatitis C in CKD Guideline: welcoming advances in evaluation and management
Infection with the hepatitis C virus (HCV) has adverse liver, kidney, and cardiovascular consequences in patients with chronic kidney disease (CKD), including those on dialysis therapy and in those with a kidney transplant. Since the publication of the original Kidney Disease: Improving Global Outcomes (KDIGO) HCV Guideline in 2008, major advances in HCV management, particularly with the advent of direct-acting antiviral therapies, have now made the cure of HCV possible in CKD patients. In addition, diagnostic techniques have evolved to enable the noninvasive diagnosis of liver fibrosis. (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Michel Jadoul, Marina C. Berenguer, Wahid Doss, Fabrizio Fabrizi, Jacques Izopet, Vivekanand Jha, Nassim Kamar, Bertram L. Kasiske, Ching-Lung Lai, Jos é M. Morales, Priti R. Patel, Stanislas Pol, Marcelo O. Silva, Ethan M. Balk, Craig E. Gordon, Amy Ear Tags: Guideline Summary Source Type: research

Acute pseudogout after cinacalcet treatment
The EVOLVE trial showed that up to 58.3% of patients treated with cinacalcet developed hypocalcemia, albeit mostly asymptomatic and of minor clinical relevance.1 We treated an 80-year-old woman who had hypercalcemic primary hyperparathyroidism with cinacalcet, 30 mg/d. At baseline, her total serum calcium was 2.84 mmol/l. After 14 days of cinacalcet, she developed polyarthralgia and myalgia but no fever. Laboratory studies showed serum calcium of 2.05 mmol/l and C-reactive protein of 138 mg/l, but there was no leukocytosis. (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Elisa Grana, Alexandre Da Costa F. de Frias Pinto, Stefano Carda Tags: Letter to the Editor Source Type: research

Regarding ”Lipstick obsession and red urine”
We were very interested in the article by Mir and Nisar (2018) on lipstick obsession and red urine. A link has been established between the red coloring of a young woman ’s urine and lipstick, which she admits to reapplying around 20 times per day.1 The authors make it clear that this case is unique, and indeed no written trace of any previously published cases like this are to be found in the literature. We know, however, that there is a risk of absorption via in gestion of the ingredients in the lipstick formula. (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Laurence Coiffard, C éline Couteau Tags: Letter to the Editor Source Type: research

The author replies
Coiffard and Couteau have raised some pertinent queries.1 We are quite aware of the lipophilic nature of most lipstick pigments (not all, though),2 which is evident from the fact that our patient had been applying different brands of lipstick multiple times a day for many years without any change in the color of her urine.3 It was only with the introduction of a new brand of lipstick that her urine turned red, which she did not attribute to the change of lipstick because it had never happened before. (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Tajamul H. Mir Tags: Letter to the Editor Source Type: research

Are congenital anomalies of the kidney and urinary tract part of the SOX11 syndrome?
We reported that deletion or loss-of-function SOX11 variants result in a human neurodevelopmental disorder with features of Coffin-Siris syndrome.2 All of the pathogenic SOX11 variants so far reported in association with neurodevelopmental disorders have been either fra meshift or nonsense or have affected the DNA-binding domain. (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Alisdair McNeill Tags: Letter to the Editor Source Type: research

The author replies
We would like to thank Dr. McNeill for his reflections on “Are Congenital Anomalies of the Kidney and Urinary Tract Part of the of SOX11 Syndrome?”1 We agree that, similarly to the mouse,2,3 SOX11 is unlikely to be expressed in the adult human kidney. However, congenital anomalies of the kidney and urinary tract (CAKUT) syndrome is rooted in kidney for mation, and SOX11 has been recently shown to be dynamically expressed during human kidney development using single-cell RNA sequencing analysis.4 Although to date, patients with neurodevelopmental abnormalities that carry SOX11 mutations have not been reported to...
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Andreas Schedl Tags: Letter to the Editor Source Type: research

Regarding “Combination of pediatric and adult formulas yield valid glomerular filtration rate estimates in young adults with a history of pediatric chronic kidney disease”
Recently, Ng et  al.1 reported that the average of pediatric (serum creatinine–only equation from the Kidney Disease in Children study [CKiDSCr]) and adult (serum creatinine–only equation from the Chronic Kidney Disease Epidemiology Collaboration consortium [CKD-EPISCr]) creatinine-based estimate of the glomer ular filtration rate (GFR) yielded valid estimates in young adults. We analyzed the diagnostic performance of this “average” using a data set of 543 patients2 (273 women) aged 18 to 26 years with inulin-measured GFR from 5 to 135 ml/min per 1.73 m2. (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Luciano Selistre, Muriel Rabilloud, Vandr éa De Souza, Jean Iwaz, Mariana Bertoldo, Carlos Poli De Figueiredo, Sandrine Lemoine, Pierre Cochat, Laurence Dubourg Tags: Letter to the Editor Source Type: research

The authors reply
We read with interest the letter by Selistre et  al.1 and commend them for using an independent sample of young adults. They present several findings consistent with our article2: overestimation by the serum creatinine–only equation from the Chronic Kidney Disease Epidemiology Collaboration consortium (CKD-EPISCr), underestimation by the serum creatinine–only equation from the Kidney Disease in Children study (CKiDSCr), and their average yielding a higher proportion within 30% (P30) and concordance correlation coefficient than each one alone. (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Derek K. Ng, George J. Schwartz, Michael F. Schneider, Susan L. Furth, Bradley A. Warady Tags: Letter to the Editor Source Type: research

Antibodies to M-type phospholipase receptor and  immunological remission in treatment-resistant and relapsing membranous nephropathy
The report by van de Logt and colleagues1 adds to the expanding literature on the utility of measurement of antibodies against M-type phospholipase A2 receptor (aPLA2R) in diverse clinical circumstances in management of patients with membranous nephropathy. They show that rituximab is less effective than cyclophosphamide in effecting reduction in aPLA2R levels (immunological response), and that baseline antibody titers predict response to treatment, whether with rituximab or cyclic cyclophosphamide-glucocorticoid (cCTX-GC). (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Raja Ramachandran, Ashok K. Yadav, Jasmine Sethi, Krishan L. Gupta, Vivekanand Jha Tags: Letter to the Editor Source Type: research

The authors reply
Dr. Ramachandran and colleagues provide support for our finding that the level of anti-PLA2R antibodies (aPLA2Rab) may explain observed differences in efficacy of immunosuppressive agents.1,2 They studied patients with membranous nephropathy who were resistant to previous immunosuppressive therapy or had developed a relapse. In contrast, our study mainly included treatment-naive patients. (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Anne-Els van de Logt, Karine Dahan, Pierre Ronco, Jack Wetzels Tags: Letter to the Editor Source Type: research

The authors reply
We thank Eleftheriadis and colleagues for their comments in the letter titled “Xanthine Oxidase Inhibitors May Prevent or Slow Chronic Kidney Disease Even in the Absence of Hyperuricemia.”1 The authors refer to in vitro studies in endothelial cells that provide mechanistic data to support that xanthine oxidase (XO) inhibition reduces the generation of reactive oxygen spe cies. Confirmatory human clinical trials to demonstrate benefit independent of urate lowering with appropriate clinical renal endpoints are currently not available. (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Usha Panchapakesan, Carol Pollock Tags: Letter to the Editor Source Type: research

Xanthine oxidase inhibitors may prevent or slow chronic kidney disease even in the absence of hyperuricemia
In a recently published article, and based on the emerging evidence that suggests a causal link between hyperuricemia and the progression of chronic kidney disease (CKD), xanthine oxidase (XO) inhibitors were included in the list of promising medications for CKD.1 However, these drugs may also act independently of the serum urate levels by decreasing the generation of intracellular reactive oxygen species (ROS) in endothelial cells. (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Theodoros Eleftheriadis, Georgios Pissas, Vassilios Liakopoulos, Ioannis Stefanidis Tags: Letter to the Editor Source Type: research

Evocalcet in the management of secondary hyperparathyroidism in dialysis patients
Use of calcimimetics will be influenced not only by assessment of benefits and harms in individual patients but also by cost and by national guidelines. The Japanese Society for Dialysis Therapy has a lower PTH threshold for PTH control than other countries. The current RCT, despite its limitations, provides a rationale for use of evocalcet in the management of secondary hyperPTH. (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Patrick S. Parfrey Tags: Commentary Source Type: research

A novel role for Tamm-Horsfall protein (uromodulin) in the renal tubule
Tamm-Horsfall protein (THP)/uromodulin, the most abundant urinary protein, is produced in the thick ascending limb of the loop of Henle. Besides immunological functions, it has regulatory impact on ion transport and volume regulation. It had been debated whether the distal convoluted tubule is a source for THP as well. Novel results suggest that in its early portions, THP synthesis affects adaptive plasticity of the epithelium, stabilizes calcium homeostasis, and activates the thiazide-sensitive Na+,Cl--cotransporter. (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Sebastian Bachmann Tags: Commentary Source Type: research

The Case | A 33-year-old woman with gross hematuria
A 33-year-old woman presented with painless gross hematuria that began 10 days prior to admission. She denied any underlying disease and was on no medications. There were no abnormal findings in her physical examination. Urinalysis showed many red blood cells but no dysmorphic red blood cells or red blood cell casts. Computed tomography with contrast revealed no abnormal findings. Laboratory tests on admission are shown in Table  1. Renal biopsy revealed no morphologically specific findings in light microscopy, immunofluorescent staining for Igs, or electron microscopy. (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Hong Sang Choi, Sung Sun Kim, Hoon-In Choi, Ji Hong Song, Chang Seong Kim, Eun Hui Bae, Seong Kwon Ma, Soo Wan Kim Tags: Make Your Diagnosis Source Type: research

Repeat kidney biopsy for lupus nephritis: an important step forward
There is scant controlled data to guide the use of repeat kidney biopsies to guide therapy in glomerular disease. De Rosa et  al. assessed the value of a repeat biopsy during remission in estimating the risk of subsequent relapse of lupus nephritis. They demonstrated the feasibility of a per-protocol repeat biopsy study with prespecified subsequent therapy. Their results will inform the design of future studies of repeat biopsies in lupus nephritis and other kidney diseases. (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Patrick H. Nachman Tags: Commentary Source Type: research

Suzuki T, Abe T. Crossroads of metabolism and CKD. Kidney Int. 2018;94:242 –243
In the above-mentioned article, in the title, “Crossloads” was corrected to “Crossroads”. (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Tags: Corrigendum Source Type: research

Impact of cellular phosphate handling on vascular calcification
Cardiovascular calcification is still a major burden for patients with chronic kidney disease (CKD). The pathomechanism of vascular calcification is complex, involving numerous processes. In this issue, Yamada et  al. describe a protective role of Pit-2 within this context by using PiT-2 heterozygous mice with CKD fed a high-phosphate diet. The mechanisms still need to be elucidated. Pit-2 could become a potential therapeutic target. (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Georg Schlieper Tags: Commentary Source Type: research

C1q-binding donor-specific antibody assays help define risk  and prognosis in antibody-mediated rejection
Antibody-mediated rejection represents the first cause of graft loss in renal transplant recipients, and it is imperative to identify appropriate tools to enable risk stratification of such patients. Lately, the usefulness of measuring complement-binding anti –human leukocyte antigen (HLA) donor-specific antibodies (DSAs) in renal transplantation has been intensely debated. While the jury is still out, recent data suggest that monitoring complement-binding DSAs may help to recognize high-risk patients and possibly trigger more effective interventions i n selected patients. (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Emanuele Cozzi, Luigi Biancone Tags: Commentary Source Type: research

A new BEACON of hope for the treatment of inflammation? The endogenous metabolite itaconate as an alternative activator of the KEAP1-Nrf2 system
Intermediary metabolites are involved in maintaining organ homeostasis, and their signaling functions play important roles in the regulation of immunity. The endogenous metabolite itaconate was first identified as a product of citric acid distillation in 1836 and has been used extensively in the polymer industry for many years, but scientists only recently uncovered its function as a modulator of mammalian immunity through anti-inflammatory activity in activated macrophages.1 In a study published in Nature, Mills and colleagues2 furthered our understanding of the biological effect of itaconate (Figure  1), demonstrati...
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Authors: Luca Perico, Christina M. Wyatt, Ariela Benigni Tags: Nephrology Digest Source Type: research

In this issue
The enzyme renin is produced exclusively by juxtaglomerular cells in the kidney; until now, its only known substrate was angiotensinogen. B ékássy and colleagues showed that renin can cleave complement component C3 into C3a and C3b, thereby activating the alternative pathway. Renin cleaves C3 in the same place as the C3 convertase, and with similar activity. Renin-mediated complement activation was blocked by aliskiren, a renin inhibi tor approved for the treatment of hypertension. Békássy’s team then treated 3 patients who had dense deposit disease with aliskiren and showed that syst...
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Tags: In This Issue Source Type: research

Journal Club
Moroni et  al. (Ann Rheum Dis. 2018;77:1318–1325; https://doi.org/10.1136/annrheumdis-2017-212732) (Source: Kidney International)
Source: Kidney International - September 19, 2018 Category: Urology & Nephrology Tags: Journal Club Source Type: research

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

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

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

The angiotensin II type 2 receptors protect renal tubule mitochondria in early stages of diabetes mellitus
Diabetic nephropathy correlates more closely to defective mitochondria and increased oxidative stress in the kidney than to hyperglycemia. A key driving factor of diabetic nephropathy is angiotensin II acting via the G-protein –coupled cell membrane type 1 receptor. The present study aimed to investigate the role of the angiotensin II type 2 receptor (AT2R) at the early stages of diabetic nephropathy. Using receptor binding studies and immunohistochemistry we found that the mitochondria in renal tubules contain high-aff inity AT2Rs. (Source: Kidney International)
Source: Kidney International - September 3, 2018 Category: Urology & Nephrology Authors: Tamara Micakovic, Stamatia Papagiannarou, Euan Clark, Yalcin Kuzay, Katarina Abramovic, J örg Peters, Carsten Sticht, Nadine Volk, Thomas Fleming, Peter Nawroth, Hans-Peter Hammes, Natalia Alenina, Hermann-Josef Gröne, Sigrid Christa Hoffmann Tags: Basic Research Source Type: research

Rictor deficiency in dendritic cells exacerbates acute kidney injury
Dendritic cells (DCs) are critical initiators of innate immunity in the kidney and orchestrate inflammation following ischemia-reperfusion injury. The role of the mammalian/mechanistic target of rapamycin (mTOR) in the pathophysiology of renal ischemia-reperfusion injury has been characterized. However, the influence of DC-based alterations in mTOR signaling is unknown. To address this, bone marrow-derived mTORC2-deficient (Rictor-/-) DCs underwent hypoxia-reoxygenation and then analysis by flow cytometry. (Source: Kidney International)
Source: Kidney International - September 3, 2018 Category: Urology & Nephrology Authors: Helong Dai, Alicia R. Watson, Daniel Fantus, Longkai Peng, Angus W. Thomson, Natasha M. Rogers Tags: Basic Research Source Type: research

HLA class II alleles differing by a single amino acid associate with clinical phenotype and outcome in patients with primary membranous nephropathy
Genome-wide associations and HLA genotyping have revealed associations between HLA alleles and susceptibility to primary membranous nephropathy. However, associations with clinical phenotypes and kidney outcome are poorly defined. We previously identified DRB1*1501 and DRB1*0301 as independent risk alleles for primary membranous nephropathy. Here, we investigated HLA associations with demographic characteristics, anti-phospholipase A2 receptor (PLA2R) antibody, treatment response and kidney outcome after a median follow-up of 52 months in 258 patients. (Source: Kidney International)
Source: Kidney International - August 30, 2018 Category: Urology & Nephrology Authors: Huai-yu Wang, Zhao Cui, Li-jun Xie, Li-jie Zhang, Zhi-Yong Pei, Fang-jin Chen, Zhen Qu, Jing Huang, Yi-miao Zhang, Xin Wang, Fang Wang, Li-qiang Meng, Xu-yang Cheng, Gang Liu, Xu-jie Zhou, Hong Zhang, Hanna Debiec, Pierre Ronco, Ming-hui Zhao Tags: Clinical Investigation Source Type: research

HIF-1 α promotes cyst progression in a mouse model of autosomal dominant polycystic kidney disease
Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by mutations of the PKD1 gene and characterized by growth of bilateral renal cysts. Cyst growth is accompanied by regional hypoxia and induction of hypoxia-inducible factor (HIF)-1 α in cyst-lining epithelial cells. To determine the relevance of HIF-1α for cyst growth in vivo we used an inducible kidney epithelium-specific knockout mouse to delete Pkd1 at postnatal day 20 or 35 to induce polycystic kidney disease of different severity and analyzed the effects of Hif-1α co- deletion and HIF-1α stabilization using a prolyl-hydr...
Source: Kidney International - August 30, 2018 Category: Urology & Nephrology Authors: Andre Kraus, Dorien J.M. Peters, Bernd Klanke, Alexander Weidemann, Carsten Willam, Gunnar Schley, Karl Kunzelmann, Kai-Uwe Eckardt, Bjoern Buchholz Tags: Basic Research Source Type: research

Post-transplant lymphoproliferative disease may be an adverse risk factor for patient survival but not graft loss in kidney transplant recipients
Better prognostication of graft and patient outcomes among kidney transplant recipients with post-transplant lymphoproliferative disease (PTLD) in the rituximab era is needed to inform treatment decisions. Therefore, we sought to estimate the excess risks of death and graft loss in kidney transplant recipients with PTLD, and to determine risk factors for death. Using the ANZDATA registry, the risks of mortality and graft loss among recipients with and without PTLD were estimated using survival analysis. (Source: Kidney International)
Source: Kidney International - August 30, 2018 Category: Urology & Nephrology Authors: Anna Francis, David W. Johnson, Jonathan Craig, Armando Teixeira-Pinto, Germaine Wong Tags: Clinical Investigation Source Type: research

Alkylating histone deacetylase inhibitors may have therapeutic value in experimental myeloperoxidase-ANCA vasculitis
Current therapies for treating antineutrophil cytoplasm autoantibody (ANCA) –associated vasculitis include cyclophosphamide and corticosteroids. Unfortunately, these agents are associated with severe adverse effects, despite inducing remission in most patients. Histone deacetylase inhibitors are effective in rodent models of inflammation and act synergistically with many pharmacological agents, including alkylating agents like cyclophosphamide. EDO-S101 is an alkylating fusion histone deacetylase inhibitor molecule combining the DNA alkylating effect of Bendamustine with a pan-histone deacetylase inhibitor, Vorinosta...
Source: Kidney International - August 26, 2018 Category: Urology & Nephrology Authors: Dearbhaile Dooley, Mirjan M. van Timmeren, Vincent P. O ’Reilly, Gareth Brady, Eóin C. O’Brien, Barbara Fazekas, Fionnuala B. Hickey, Emma Leacy, Charles D. Pusey, Frederick W.K. Tam, Thomas Mehrling, Peter Heeringa, Mark A. Little Tags: Basic Research Source Type: research

Emerging evidence on renal denervation for the treatment of hypertension
The sympathetic nervous system plays a central role in the regulation of blood pressure and the pathogenesis of hypertension. In the first half of the 20th century, surgical sympathectomy was shown to reduce systolic blood pressure by more than 40 mm  Hg in approximately half of treated patients with severe symptomatic hypertension.1 This approach was abandoned because of intraoperative and long-term morbidity and the increased availability of effective antihypertensive medications. Experimental studies establishing multiple afferent and effere nt connections between the kidney and central nervous system have provided...
Source: Kidney International - August 26, 2018 Category: Urology & Nephrology Authors: Christina M. Wyatt, Stephen C. Textor Tags: Nephrology Digest Source Type: research

Hydroxychloroquine-induced mimic of renal Fabry  disease
A 27-year-old Asian woman was evaluated for a 15-year history of systemic lupus erythematosus treated with hydroxychloroquine, azathioprine, and intermittent prednisone. For the preceding 2 years, the urine protein/creatinine ratio fluctuated between 0.4 and 3.8 g/g with mild pyuria (5 –31 white blood cells/high power field). The estimated glomerular filtration rate was 119 ml/min per 1.73 m2. Kidney biopsy demonstrated mesangial proliferation and membranous glomerulopathy consistent with International Society of Nephrology/Renal Pathology Society Classification II + V. (Source: Kidney International)
Source: Kidney International - August 21, 2018 Category: Urology & Nephrology Authors: C. John Sperati, Avi Z. Rosenberg Tags: Nephrology Image Source Type: research

Do computers dream of electric glomeruli?
By training a convolutional neural network on more than 20,000 histological images of rat glomeruli, a computer can be taught to recognize them. After training the network using images with positive examples of glomeruli and negative examples of renal fields with no glomeruli present, new images of renal histology can be passed through the network to determine whether they contain glomeruli. Passing the image forward through the network predicts what objects may be present within the image. Passing images in reverse can be used to ascertain what features the network has been trained to find. (Source: Kidney International)
Source: Kidney International - August 21, 2018 Category: Urology & Nephrology Authors: John D. Bukowy, Alex Dayton, Dustin Cloutier, Julian H. Lombard, Leah C. Solberg Woods, Daniel A. Beard, Allen W. Cowley Tags: Nephrology Image Source Type: research

Utilization, costs, and outcomes for patients receiving publicly funded hemodialysis in  India
Lifestyle transitions are making chronic conditions such as chronic kidney disease increasingly common in low- and middle-income countries, including India. According to the 2016 Global Burden of Disease Study, chronic kidney disease was the ninth leading cause of death in India, having risen from 15th rank in 2005 (http://www.healthdata.org/india). In a recent analysis of deaths in 1.1 million Indian households, renal failure was responsible for 2.9% of all deaths among 15 –69-year-olds in 2010–2013, an increase of 50% from 2001–2003. (Source: Kidney International)
Source: Kidney International - August 21, 2018 Category: Urology & Nephrology Authors: Maaz Shaikh, Mark Woodward, Oommen John, Abhinav Bassi, Stephen Jan, Manisha Sahay, Gangadhar Taduri, Martin Gallagher, John Knight, Vivekanand Jha Tags: Nephrologists Sans Fronti ères Source Type: research

Energy sensor as a new regulator of FGF23 synthesis
Phosphate plays an important role in biological energy cycle, but the interaction of cellular energy metabolism with fibroblast growth factor 23 production has been less well characterized. Glosse and colleagues now demonstrate that AMP-activated protein kinase, a cellular energy sensor, regulates fibroblast growth factor 23 production. Interestingly, AMP-activated protein kinase –deficient mice show high fibroblast growth factor 23 levels, normal phosphate levels, and cardiac hypertrophy, which resemble those seen in patients with moderate chronic kidney disease. (Source: Kidney International)
Source: Kidney International - August 21, 2018 Category: Urology & Nephrology Authors: Hirotaka Komaba Tags: Commentary Source Type: research

The age-calibrated measured glomerular filtration  rate improves living kidney donation selection process
Recommendations on the glomerular filtration rate (GFR) threshold compatible with living kidney donation are not agreed upon. The recent KDIGO guidelines suggested a reset of the conventional cutoff value of 80 to 90 mL/min/1.73 m2. While GFR physiologically declines with age, it is unclear whether and how age should be taken into account for selecting acceptable pre-donation GFR. In this multicenter retrospective study encompassing 2007 kidney donors in France, we evaluated the impact of age using two threshold measured GFR (mGFR)s (80 and 90 mL/min/1.73 m2). (Source: Kidney International)
Source: Kidney International - August 21, 2018 Category: Urology & Nephrology Authors: Fran çois Gaillard, Marie Courbebaisse, Nassim Kamar, Lionel Rostaing, Arnaud Del Bello, Sophie Girerd, Michèle Kessler, Martin Flamant, Emmanuelle Vidal-Petiot, Marie-Noelle Peraldi, Lionel Couzi, Pierre Merville, Paolo Malvezzi, Benedicte Janbon, Brun Tags: Clinical Investigation Source Type: research

Modern field emission scanning electron microscopy provides new perspectives for imaging  kidney ultrastructure
Recent progress in electron microscopy (EM) techniques has opened new pathways to study renal tissue in research and pathology. Modern field emission scanning EM may be utilized to scan thin sections of resin-embedded tissue mounted on a conductive support. Here we sought to achieve automated imaging without the typical limitations of transmission EM with equivalent or superior quality. Extended areas of tissue were either imaged in two (nanotomy) or in three dimensions (volume EM) by serial-section-based array tomography. (Source: Kidney International)
Source: Kidney International - August 21, 2018 Category: Urology & Nephrology Authors: Carsten Dittmayer, Eckhard V ölcker, Irene Wacker, Rasmus R. Schröder, Sebastian Bachmann Tags: Technical Notes Source Type: research

Novel role for androgen signaling in pyelonephritis
Sex differences in urinary tract infection (UTI) susceptibility and severity are known, but have historically focused on anatomic differences between males and females. Until recently, experimental UTI has been limited to female animals due to ease of transurethral bladder catheterization. Olson and colleagues have developed a model of experimental UTI independent of sex that relies on direct bladder inoculation and thus permits investigation of sex differences in UTI susceptibility. They now build upon their prior work in this model by implicating androgens as drivers of tubular invasion by uropathogenic Escherichia coli,...
Source: Kidney International - August 21, 2018 Category: Urology & Nephrology Authors: Christina B. Ching, Brian Becknell Tags: Commentary Source Type: research

Pendred, pendrin, pseudohypoaldosteronism type II, and renal tubular  acidosis
The sodium chloride cotransporter is regulated by the with-no-lysine kinases 1 and 4. Mutations in these genes are responsible for Mendelian hypertension, increased sodium chloride cotransporter activity, metabolic acidosis, and hyperkalemia. Explaining metabolic acidosis and hyperkalemia has been difficult. We now learn that the versatile bicarbonate-chloride exchanger, pendrin, is important in the process. As a result, we are confronted with still another mechanism causing renal tubular acidosis. (Source: Kidney International)
Source: Kidney International - August 21, 2018 Category: Urology & Nephrology Authors: Friedrich C. Luft, Carsten A. Wagner Tags: Commentary Source Type: research

Sodium glucose cotransporter 2 inhibition and renal ischemia: implications for future clinical  trials
Sodium glucose cotransporter 2 inhibitors are increasingly being recognized for renal protective effects that are largely independent of hemoglobin A1c –lowering or glucosuria-related endpoints. Accordingly, there is growing interest in potential renal benefits with sodium glucose cotransporter 2 inhibitors in nondiabetic patients to take advantage of natriuresis-mediated effects on blood pressure, proteinuria, and renal function. In this issue o f Kidney International, Zhang et al. report renoprotective effects with the sodium glucose cotransporter 2 inhibitor lusogliflozin in an ischemia-reperfusion injury mod...
Source: Kidney International - August 21, 2018 Category: Urology & Nephrology Authors: Dani ël H. van Raalte, David Z.I. Cherney Tags: Commentary Source Type: research