Nephron Extra最新文献

{"title":"The Association between Fibroblast Growth Factor-23 and Vascular Calcification Is Mitigated by Inflammation Markers.","authors":"Mohamed M Nasrallah,&nbsp;Amal R El-Shehaby,&nbsp;Noha A Osman,&nbsp;Tarek Fayad,&nbsp;Amr Nassef,&nbsp;Mona M Salem,&nbsp;Usama A A Sharaf El Din","doi":"10.1159/000356118","DOIUrl":"https://doi.org/10.1159/000356118","url":null,"abstract":"<p><strong>Background: </strong>Fibroblast growth factor-23 (FGF-23) has been linked to vascular calcification, ventricular hypertrophy and mortality in chronic kidney disease (CKD), although these links may not be direct and independent. Similar grave outcomes are associated with inflammation and oxidative stress in CKD. Recently, accumulating evidence has linked components of phosphate homeostasis to inflammation and oxidative stress. The interaction between the triad of inflammation, FGF-23 and cardiovascular outcomes is underinvestigated.</p><p><strong>Methods: </strong>We studied 65 patients with stage 5 CKD on hemodialysis. Serum levels of FGF-23, high-sensitivity C-reactive protein (hsCRP), endogenous soluble receptor of advanced glycation end products (esRAGE), advanced oxidation protein products (AOPP), parathormone, lipids, calcium and phosphorous were measured. The aortic calcification index (ACI) was determined using non-contrast CT scans of the abdominal aorta.</p><p><strong>Results: </strong>FGF-23 was elevated (mean: 4,681 pg/ml, SD: 3,906) and correlated with hsCRP, esRAGE, AOPP, dialysis vintage and phosphorus in univariate analysis. In multiple regression analysis, hsCRP, AOPP and phosphorus but not esRAGE were all significantly correlated to FGF-23 (R² = 0.7, p < 0.001). In univariate analysis, ACI correlated with hsCRP, esRAGE, FGF-23, dialysis vintage, systolic blood pressure (BP) and serum cholesterol. In multiple regression analysis not including inflammation markers, ACI was associated with FGF-23. However, inclusion of inflammation markers in another multiple regression analyses showed that ACI correlated with hsCRP, BP, dialysis vintage and esRAGE but not with FGF-23 (R² = 0.65, p < 0.001).</p><p><strong>Conclusion: </strong>FGF-23 is strongly correlated to various markers of inflammation and oxidative stress in hemodialysis patients. The association between FGF-23 and vascular calcification was mitigated when corrected for inflammation markers.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":" ","pages":"106-112"},"PeriodicalIF":0.0,"publicationDate":"2013-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000356118","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31963967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil Gelatinase-Associated Lipocalin as a Biomarker of Acute Kidney Injury in Patients with Morbid Obesity Who Underwent Bariatric Surgery.","authors":"Maria Koukoulaki,&nbsp;Charalampos Spyropoulos,&nbsp;Panagiotis Hondrogiannis,&nbsp;Evangelos Papachristou,&nbsp;Eleni Mitsi,&nbsp;Fotios Kalfarentzos,&nbsp;Dimitrios S Goumenos","doi":"10.1159/000354892","DOIUrl":"https://doi.org/10.1159/000354892","url":null,"abstract":"<p><strong>Introduction: </strong>Neutrophil gelatinase-associated lipocalin (NGAL) has been identified as a biomarker of acute kidney injury (AKI) that could contribute to early diagnosis and effective management of AKI. The purpose of this study was to evaluate NGAL as a predictive marker of AKI in patients with clinically severe obesity (BMI >50) who underwent biliopancreatic diversion surgery.</p><p><strong>Patients and methods: </strong>We prospectively studied 23 patients with clinically severe obesity who underwent biliopancreatic bypass surgery. NGAL was measured using chemiluminescent microparticle immunoassay in three urine samples collected from each patient before surgery (first sample), 2-6 h after surgery (second sample) and on the first postoperative day (third sample).</p><p><strong>Results: </strong>Renal function was evaluated using serum creatinine values, which were 0.91 ± 0.26 mg/dl before surgery, 0.87 ± 0.31 mg/dl immediately after surgery and 0.92 ± 0.62 mg/dl on the fifth postoperative day. During the immediate postoperative period, AKI was observed in 2 patients, one of whom required renal replacement therapy with hemodialysis. In both patients, urine NGAL increased within the first postoperative hours before the values of serum creatinine increased.</p><p><strong>Conclusion: </strong>Urine NGAL in patients with clinically severe obesity, which was surgically treated, might be a potential biomarker of early AKI detection. Further research is required in order to confirm these results observed in a small number of patients who developed postoperative AKI and make recommendations for predictive NGAL values in patients who underwent bariatric surgery.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":" ","pages":"101-105"},"PeriodicalIF":0.0,"publicationDate":"2013-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000354892","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31963965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comparison of systemic inflammation-based prognostic scores in patients on regular hemodialysis.","authors":"Akihiko Kato,&nbsp;Takayuki Tsuji,&nbsp;Yukitoshi Sakao,&nbsp;Naro Ohashi,&nbsp;Hideo Yasuda,&nbsp;Taiki Fujimoto,&nbsp;Takako Takita,&nbsp;Mitsuyoshi Furuhashi,&nbsp;Hiromichi Kumagai","doi":"10.1159/000355148","DOIUrl":"https://doi.org/10.1159/000355148","url":null,"abstract":"<p><strong>Background/aims: </strong>Systemic inflammation-based prognostic scores have prognostic power in patients with cancer, independently of tumor stage and site. Although inflammatory status is associated with mortality in hemodialysis (HD) patients, it remains to be determined as to whether these composite scores are useful in predicting clinical outcomes.</p><p><strong>Methods: </strong>We calculated the 6 prognostic scores [Glasgow prognostic score (GPS), modified GPS (mGPS), neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), prognostic index (PI) and prognostic nutritional index (PNI), which have been established as a useful scoring system in cancer patients. We enrolled 339 patients on regular HD (age: 64 ± 13 years; time on HD: 129 ± 114 months; males/females = 253/85) and followed them for 42 months. The area under the receiver-operating characteristics curve was used to determine which scoring system was more predictive of mortality.</p><p><strong>Results: </strong>Elevated GPS, mGPS, NLR, PLR, PI and PNI were all associated with total mortality, independent of covariates. If GPS was raised, mGPS, NLR, PLR and PI were also predictive of all-cause mortality and/or hospitalization. GPS and PNI were associated with poor nutritional status. Using overall mortality as an endpoint, the area under the curve (AUC) was significant for a GPS of 0.701 (95% CI: 0.637-0.765; p < 0.01) and for a PNI of 0.616 (95% CI: 0.553-0.768; p = 0.01). However, AUC for hypoalbuminemia (<3.5 g/dl) was comparable to that of GPS (0.695, 95% CI: 0.632-0.759; p < 0.01).</p><p><strong>Conclusion: </strong>GPS, based on serum albumin and highly sensitive C-reactive protein, has the most prognostic power for mortality prediction among the prognostic scores in HD patients. However, as the determination of serum albumin reflects mortality similarly to GPS, other composite combinations are needed to provide additional clinical utility beyond that of albumin alone in HD patients.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":" ","pages":"91-100"},"PeriodicalIF":0.0,"publicationDate":"2013-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000355148","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32011959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence in the General Population of a CFH Sequence Variant Associated with Atypical Haemolytic Uraemic Syndrome in an Extensive Family from Southwest England.","authors":"Alexander J Hamilton,&nbsp;Carl B A Lyons,&nbsp;Timothy H J Goodship,&nbsp;Coralie Bingham","doi":"10.1159/000354667","DOIUrl":"https://doi.org/10.1159/000354667","url":null,"abstract":"<p><strong>Background/aims: </strong>Twenty-five members of a family from the county of Devon in England have been affected by atypical haemolytic uraemic syndrome (aHUS) associated with a CFH mutation (c.3643C>G; p.Arg1215Gly). A 65-year-old male was diagnosed with aHUS after losing a renal transplant to a thrombotic microangiopathy. Subsequent mutation screening revealed the same CFH mutation without him being knowingly related to the local kindred. We designed a study to investigate the prevalence of this mutation in the local area. In addition, we examined the diagnoses of pre-existing haemodialysis patients to determine whether other patients might unknowingly be at risk of carrying the same CFH mutation.</p><p><strong>Methods: </strong>The Exeter Ten Thousand (EXTEND) study aims to recruit 10,000 healthy volunteers over the age of 18 years living within 25 miles of Exeter in Devon. We genotyped DNA from 4,000 EXTEND subjects for CFH c.3643C>G; p.Arg1215Gly. We reviewed the diagnoses of 294 haemodialysis patients in the Devon area and genotyped 7 patients with either end-stage renal disease of unknown aetiology, malignant hypertension or renovascular disease.</p><p><strong>Results: </strong>CFH c.3643C>G; p.Arg1215Gly was not detected in any of the 7 haemodialysis patients or the 4,000 individuals within the EXTEND study.</p><p><strong>Conclusions: </strong>We conclude that CFH c.3643C>G; p.Arg1215Gly is not endemic in Devon. This reinforces our existing practice of genotyping only patients with kidney disease and evidence of a thrombotic microangiopathy for this mutation. This is the first study looking at the prevalence of CFH mutations in the general population.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":" ","pages":"86-90"},"PeriodicalIF":0.0,"publicationDate":"2013-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000354667","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40269461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variation of urate transport in the nephrons in subtypes of hyperuricemia.","authors":"Toru Nakamura, Rie Nishi, Tuneo Tanaka, Kazutaka Takagi, Katsuya Sakai, Mihoko Takai, Shigeru Morishima, Takahiro Yamauchi, Takanori Ueda","doi":"10.1159/000354029","DOIUrl":"10.1159/000354029","url":null,"abstract":"<p><strong>Background: </strong>Hyperuricemia cases (HU) can be classified into four subgroups by combining the two main causes of hyperuricemia, i.e. urate underexcretion and overproduction. These subgroups are as follows: underexcretion-type cases (UE); overproduction-type cases (OP); combined-type cases, and normal-type cases. Since urinary urate excretion (Uua) and urate clearance differ significantly between UE and OP, urate transport in the nephrons and the intratubular urate contents might also differ. Such differences might help clarify the pathophysiology of urate underexcretion in subgroups of hyperuricemia, and thus reveal its underlying mechanisms.</p><p><strong>Methods: </strong>Urate transport coefficients in each subtype of HU were determined employing the previously reported benzbromarone-loading urate clearance tests. The subtype cases of HU were plotted on a graph of urate transport coefficients versus Uua as coordinates. The characteristic features in the distribution of subtype cases on graphs were analyzed in relation to Uua.</p><p><strong>Results: </strong>The mean (±standard error) tubular secretion rate (TSR) in the UE (48.7 ± 1.7 ml/min) was significantly lower and the postsecretory urate reabsorption rate (R2) in the UE (0.904 ± 0.004) was significantly higher than those in the normal controls (78.0 ± 2.1 ml/min and 0.877 ± 0.003) or the OP (61.1 ± 3.2 ml/min and 0.861 ± 0.009). Decrements of TSR and increments of R2 in the UE were largest in the subtypes of the HU, in terms of case numbers and the deviation rate of the group. Conversely, decrements of TSR and increments of R2 were smallest in the OP. A significant correlation was identified between TSR and Uua (r = 0.345, p < 0.0001), and a significant negative correlation was also found between R2 and Uua (r = -0.393, p < 0.0001).</p><p><strong>Conclusion: </strong>IN THE UE, HYPERURICEMIA IS INDUCED MAINLY BY URATE UNDEREXCRETION, WHICH RESULTS FROM THE COMBINATION OF TWO MAIN CAUSES IN URATE TRANSPORTERS OF THE NEPHRON: significantly lower TSR and significantly higher R2. Neither of these was observed in OP. Differences in urate transporters in subtypes of the HU might be important not only for understanding the pathophysiology and mechanisms of urate underexcretion and hyperuricemia, but also for providing a strategic therapy for hyperuricemia.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":" ","pages":"73-85"},"PeriodicalIF":0.0,"publicationDate":"2013-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/58/57/nne-0003-0073.PMC3776396.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31747544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Prevalence of the Risk Factors for Atherosclerosis among Type 2 Diabetic Patients Is Greater in the Progressive Stages of Chronic Kidney Disease.","authors":"Hiroyuki Ito, Shinichi Antoku, Masahide Furusho, Masahiro Shinozaki, Mariko Abe, Mizuo Mifune, Michiko Togane, Kiyoko Ito, Tsutomu Sanaka","doi":"10.1159/000353592","DOIUrl":"10.1159/000353592","url":null,"abstract":"<p><strong>Background/aims: </strong>The prevalence of the risk factors for atherosclerosis, other than diabetes mellitus, among type 2 diabetic patients with different stages of chronic kidney disease (CKD) determined by glomerular filtration rate (GFR) was investigated.</p><p><strong>Methods: </strong>The prevalence of ten risk factors (age ≥65 years, history of smoking, male gender, obesity, albuminuria, hypertension, hypercholesterolemia, hypo-HDL-cholesterolemia, hyperuricemia and anemia) was determined in 2,107 Japanese type 2 diabetic patients with different stages of CKD (six stages according to GFR).</p><p><strong>Results: </strong>The risk factors for age ≥65 years and male gender were found in 49 and 62% of the study subjects, respectively. The percentages of subjects with a current history of smoking, obesity, albuminuria, hypertension, hypercholesterolemia, hypo-HDL-cholesterolemia, hyperuricemia and anemia were 35, 44, 47, 70, 61, 13, 21 and 26%, respectively. The prevalence of age ≥65 years, male gender, albuminuria, hypertension, hypo-HDL-cholesterolemia, hyperuricemia and anemia was greater in the later stages of GFR, whereas the prevalence of hypercholesterolemia and obesity did not differ between stages. The prevalence of a current history of smoking was lower in the later stages of GFR. The cumulative number of risk factors increased from 3.1 to 6.8 in the later stages of GFR.</p><p><strong>Conclusion: </strong>Among type 2 diabetic patients with CKD, the total number of risk factors increases with the progression of renal dysfunction. It is important to pay attention to newly recognized risk factors for hyperuricemia and anemia, in addition to hypertension, albuminuria and hypo-HDL-cholesterolemia, in monitoring diabetic patients with later stages of CKD.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":" ","pages":"66-72"},"PeriodicalIF":0.0,"publicationDate":"2013-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3f/ba/nne-0003-0066.PMC3728600.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31266918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of different administration protocols on the plasma concentration of donepezil hydrochloride in dementia patients with stage 5 chronic kidney disease.","authors":"Chika Amano,&nbsp;Takafumi Ito,&nbsp;Masahiro Egawa,&nbsp;Tomohiro Oka,&nbsp;Ken Hanada,&nbsp;Kosuke Matsui,&nbsp;Toru Nabika,&nbsp;Kazuaki Tanabe","doi":"10.1159/000351434","DOIUrl":"https://doi.org/10.1159/000351434","url":null,"abstract":"<p><p>The prevalence of chronic kidney disease (CKD) as well as Alzheimer's disease (AD) increases with age. With the aging of the population in Japan, there is an increasing likelihood that patients with CKD will receive donepezil hydrochloride (DPZ), an antidementia drug, in the near future. Nevertheless, there have been few reports on how to use DPZ in patients with severe CKD. We report on 2 CKD stage 5 patients who received DPZ under different prescriptions. In case 1, 3 mg/day of DPZ was initially administered for 4 months, after which the dose was increased to 5 mg/day. In case 2, 5 mg was administered twice a week. The plasma concentration of DPZ was measured and the effectiveness was assessed using the Mini-Mental Health State Examination and the Hasegawa Dementia Rating Scale. We found that (1) only a slight increase in the plasma concentration of DPZ was observed with a dose of 3 mg daily, (2) there was a significant increase in the plasma concentration with a dose of 5 mg daily, and (3) when 5 mg of DPZ was administered twice a week, the plasma concentration did not differ significantly from healthy controls who had received 5 mg daily. Although cognitive function was improved best when the 5-mg dose was administered daily with no apparent side effects, the plasma concentration came close to reaching a toxic level at this dose. Careful follow-up may be essential when DPZ is used at 5 mg/day or greater in severe CKD patients. </p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":" ","pages":"59-65"},"PeriodicalIF":0.0,"publicationDate":"2013-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000351434","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31618034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia Induces Mesenchymal Gene Expression in Renal Tubular Epithelial Cells: An in vitro Model of Kidney Transplant Fibrosis.","authors":"Stephanie Zell,&nbsp;Roland Schmitt,&nbsp;Sandra Witting,&nbsp;Hans H Kreipe,&nbsp;Kais Hussein,&nbsp;Jan U Becker","doi":"10.1159/000351046","DOIUrl":"https://doi.org/10.1159/000351046","url":null,"abstract":"<p><strong>Background: </strong>The development of interstitial fibrosis and tubular atrophy is a common complication after kidney transplantation and is associated with reduced long-term outcome. The hallmark of tubulointerstitial fibrosis is an increase in extracellular matrix resulting from exaggerated activation of fibroblasts/myofibroblasts, and tubular atrophy is characterized by a decrease in tubular diameter and loss of function. Atrophic epithelial cells may undergo epithelial-to-mesenchymal transition (EMT) with potential differentiation into interstitial fibroblasts. One potential driver of EMT in developing interstitial fibrosis and tubular atrophy is chronic hypoxia.</p><p><strong>Methods: </strong>The expression of 46 EMT-related genes was analyzed in an in vitro hypoxia model in renal proximal tubular epithelial cells (RPTEC). Furthermore, the expression of 342 microRNAs (miR) was evaluated in hypoxic culture conditions.</p><p><strong>Results: </strong>Hypoxic RPTEC expressed markers of a more mesenchymal phenotype and showed an increased expression of matrix metalloproteinase-2 (MMP2). MMP2 expression in RPTEC correlated inversely with a decreased expression of miR-124, which was found to have a putative binding site for the MMP2 transcript. Overexpression of miR-124 inhibited MMP2 protein translation. Hypoxia was associated with increased migration/proliferation of RPTEC which was reversed by miR-124.</p><p><strong>Conclusions: </strong>These results indicate that hypoxia promotes a mesenchymal and migratory phenotype in renal epithelial cells, which is associated with increased MMP2 expression. Hypoxia-dependent MMP2 expression is regulated via a reduced transcription of miR-124. Overexpression of miR-124 antagonizes hypoxia-induced cell migration. Further research is needed to elucidate the functional role of miR-124 and MMP2 in the development of fibrosis in renal transplant degeneration.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":" ","pages":"50-8"},"PeriodicalIF":0.0,"publicationDate":"2013-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000351046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31618033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renoprotection and the Bardoxolone Methyl Story - Is This the Right Way Forward? A Novel View of Renoprotection in CKD Trials: A New Classification Scheme for Renoprotective Agents.","authors":"Macaulay Onuigbo","doi":"10.1159/000351044","DOIUrl":"10.1159/000351044","url":null,"abstract":"<p><p>In the June 2011 issue of the New England Journal of Medicine, the BEAM (Bardoxolone Methyl Treatment: Renal Function in CKD/Type 2 Diabetes) trial investigators rekindled new interest and also some controversy regarding the concept of renoprotection and the role of renoprotective agents, when they reported significant increases in the mean estimated glomerular filtration rate (eGFR) in diabetic chronic kidney disease (CKD) patients with an eGFR of 20-45 ml/min/1.73 m(2) of body surface area at enrollment who received the trial drug bardoxolone methyl versus placebo. Unfortunately, subsequent phase IIIb trials failed to show that the drug is a safe alternative renoprotective agent. Current renoprotection paradigms depend wholly and entirely on angiotensin blockade; however, these agents [angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs)] have proved to be imperfect renoprotective agents. In this review, we examine the mechanistic limitations of the various previous randomized controlled trials on CKD renoprotection, including the paucity of veritable, elaborate and systematic assessment methods for the documentation and reporting of individual patient-level, drug-related adverse events. We review the evidence base for the presence of putative, multiple independent and unrelated pathogenetic mechanisms that drive (diabetic and non-diabetic) CKD progression. Furthermore, we examine the validity, or lack thereof, of the hyped notion that the blockade of a single molecule (angiotensin II), which can only antagonize the angiotensin cascade, would veritably successfully, consistently and unfailingly deliver adequate and qualitative renoprotection results in (diabetic and non-diabetic) CKD patients. We clearly posit that there is this overarching impetus to arrive at the inference that multiple, disparately diverse and independent pathways, including any veritable combination of the mechanisms that we examine in this review, and many more others yet to be identified, do concurrently and asymmetrically contribute to CKD initiation and propagation to end-stage renal disease (ESRD) in our CKD patients. We conclude that current knowledge of CKD initiation and progression to ESRD, the natural history of CKD and the impacts of acute kidney injury on this continuum remain in their infancy and call for more research. Finally, we suggest a new classification scheme for renoprotective agents: (1) the single-pathway blockers that block a single putative pathogenetic pathway involved in CKD progression, as typified by ACE inhibitors and/or ARBs, and (2) the multiple-pathway blockers that are able to block or antagonize the effects of multiple pathogenetic pathways through their ability to simultaneously block, downstream, the effects of several pathways or mechanisms of CKD to ESRD progression and could therefore concurrently interfere with several unrelated upstream pathways or mechanisms. We surmise that maybe the ideal","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":" ","pages":"36-49"},"PeriodicalIF":0.0,"publicationDate":"2013-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/57/67/nne-0003-0036.PMC3656681.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31443503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eosinophilic cystitis presented as a manifestation of hypereosinophilic syndrome: a case report and review of the literature.","authors":"Katsuaki Kojima,&nbsp;Jun Maeda,&nbsp;Shuji Mikami,&nbsp;Hiroyuki Yamagishi,&nbsp;Hiroki Ide,&nbsp;Seiya Hattori,&nbsp;Takao Takahashi,&nbsp;Midori Awazu","doi":"10.1159/000346713","DOIUrl":"https://doi.org/10.1159/000346713","url":null,"abstract":"<p><strong>Background: </strong>Hypereosinophilic syndrome (HES) is a group of disorders marked by the sustained overproduction of eosinophils, in which eosinophilic infiltration and inflammatory substance release cause damage to multiple organs. Eosinophilic cystitis (EC) is an inflammatory disorder caused by eosinophilic infiltration of the bladder wall. Although EC is often associated with eosinophilia, it has been rarely reported as a manifestation of HES. We report a case of EC as a primary manifestation of HES. The patient was a 27-year-old male with a history of complete intracardiac repair of tetralogy of Fallot who presented with an acute onset of dysuria accompanied by eosinophilia (7.5 × 10(3)/μl, 60% of white blood cells). Ultrasonography and MRI of the bladder showed a bladder mass, a biopsy of which revealed eosinophilic infiltration and degranulation.</p><p><strong>Methods: </strong>We performed a literature search in PubMed from 2001 to 2012 to find patients with EC who may have had HES.</p><p><strong>Results: </strong>There were 4 patients with HES who had EC including the present case. Of 14 patients reported as EC in whom the eosinophil count was described, 5 had eosinophils of ≥1,500/μl. None of the 5 patients had secondary causes for eosinophilia. Of the 9 patients with definite or probable HES, 7 patients (78%) were male and 5 patients (56%) showed a concomitant eosinophilic gastrointestinal disorder.</p><p><strong>Conclusion: </strong>HES may not be uncommon as the cause of EC. Thorough evaluation and close monitoring are warranted in EC patients with elevated eosinophils.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":" ","pages":"30-5"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000346713","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31348487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}