Nephron ExtraPub Date : 2012-01-01Epub Date: 2012-10-10DOI: 10.1159/000342719
Carmen Vozmediano, Francisco Rivera, Juan Manuel López-Gómez, Domingo Hernández
{"title":"Risk factors for renal failure in patients with lupus nephritis: data from the spanish registry of glomerulonephritis.","authors":"Carmen Vozmediano, Francisco Rivera, Juan Manuel López-Gómez, Domingo Hernández","doi":"10.1159/000342719","DOIUrl":"https://doi.org/10.1159/000342719","url":null,"abstract":"<p><strong>Background: </strong>Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus. Data from national registries based on renal biopsies are scarce. The aim of our study was to analyze the demographic characteristics, clinicopathological correlations, and risk factors associated with renal failure in patients with LN at the time of renal biopsy.</p><p><strong>Methods: </strong>We performed a cross-sectional observational study based on data from the Spanish Registry of Glomerulonephritis for the years 1994-2009. The outcome measure was the presence of renal failure (eGFR <60 ml/min/1.73 m(2)). We also recorded age, gender, proteinuria levels, hypertension, and histological class.</p><p><strong>Results: </strong>We collected 17,525 native renal biopsies, of which 1,648 biopsies showed LN lesions. In total, 609 patients (37%) showed renal failure at the time of renal biopsy. The univariate analysis showed that these patients were older, had higher levels of proteinuria, and a higher prevalence of hypertension than the group with eGFR ≥60 ml/min/ 1.73 m(2). The histological class of LN was recorded for 566 patients, and multivariate logistic regression analysis showed that the independent risk factors for renal failure at the time of renal biopsy were age (OR 1.03; 95% CI 1.01-1.04), male gender (OR 1.94; 95% CI 1.12-3.10), hypertension (OR 3.18; 95% CI 2.16-4.67), proteinuria (OR 1.15; 95% CI 1.08-1.24), and histological classes III and IV (OR 1.82; 95% CI 1.16-2.87).</p><p><strong>Conclusions: </strong>Data from the Spanish Registry of Glomerulonephritis provide valuable information about risk factors for renal failure in patients with LN at the time of renal biopsy.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"269-77"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000342719","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31038381","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}
Nephron ExtraPub Date : 2012-01-01Epub Date: 2012-12-01DOI: 10.1159/000343899
Juliana A Zanocco, Sonia K Nishida, Michelle Tiveron Passos, Amélia Rodrigues Pereira, Marcelo S Silva, Aparecido B Pereira, Gianna Mastroianni Kirsztajn
{"title":"Race adjustment for estimating glomerular filtration rate is not always necessary.","authors":"Juliana A Zanocco, Sonia K Nishida, Michelle Tiveron Passos, Amélia Rodrigues Pereira, Marcelo S Silva, Aparecido B Pereira, Gianna Mastroianni Kirsztajn","doi":"10.1159/000343899","DOIUrl":"https://doi.org/10.1159/000343899","url":null,"abstract":"<p><strong>Background: </strong>Estimated glomerular filtration rate (eGFR) is very important in clinical practice, although it is not adequately tested in different populations. We aimed at establishing the best eGFR formulas for a Brazilian population with emphasis on the need for race correction.</p><p><strong>Methods: </strong>We evaluated 202 individuals with chronic kidney disease (CKD) and 42 without previously known renal lesions that were additionally screened by urinalysis. Serum creatinine and plasma clearance of iohexol were measured in all cases. GFR was estimated by the Mayo Clinic, abbreviated Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas, and creatinine clearance was estimated by the Cockcroft-Gault (CG) formula. Plasma clearance of iohexol was used as the gold standard for GFR determination and for the development of a Brazilian formula (BreGFR).</p><p><strong>Results: </strong>Measured and estimated GFR were compared in 244 individuals, 57% female, with a mean age of 41 years (range 18-82). Estimates of intraclass correlation coefficients among the plasma clearance of iohexol and eGFR formulas were all significant (p < 0.001) and corresponded to the following scores: CG 0.730; obesity-adjusted CG 0.789; Mayo Clinic 0.804; MDRD 0.848; MDRD1 (without race adjustment) 0.846; CKD-EPI 0.869; CKD-EPI1 (without race adjustment) 0.876, and BreGFR 0.844.</p><p><strong>Conclusions: </strong>All cited eGFR formulas showed a good correlation with the plasma clearance of iohexol in the healthy and diseased conditions. The formulas that best detected reduced eGFR were the BreGFR, CKD-EPI, and CKD-EPI1 formulas. Notably, the race correction included in the MDRD and CKD-EPI formulas was not necessary for this population, as it did not contribute to more accurate results.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"293-302"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000343899","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31127206","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}
Nephron ExtraPub Date : 2012-01-01Epub Date: 2012-01-26DOI: 10.1159/000335750
Peter E Westerweel, Jaap A Joles, Krista den Ouden, Roel Goldschmeding, Maarten B Rookmaaker, Marianne C Verhaar
{"title":"ACE Inhibition in Anti-Thy1 Glomerulonephritis Limits Proteinuria but Does Not Improve Renal Function and Structural Remodeling.","authors":"Peter E Westerweel, Jaap A Joles, Krista den Ouden, Roel Goldschmeding, Maarten B Rookmaaker, Marianne C Verhaar","doi":"10.1159/000335750","DOIUrl":"https://doi.org/10.1159/000335750","url":null,"abstract":"<p><strong>Background/aims: </strong>ACE inhibitor (ACE-I) treatment effectively inhibits proteinuria and ameliorates the course of various renal diseases. In experimental glomerulonephritis, however, angiotensin II (AngII) infusion has also been shown to be renoprotective. We evaluated the long-term (28 days) course of anti-Thy1 glomerulonephritis in animals with suppressed AngII formation by ACE-I treatment.</p><p><strong>Methods: </strong>Brown Norway rats received perindopril (2.8 mg/kg/day, n = 12), dihydropyridine calcium-antagonist amlodipine (Ca-A; 13 mg/kg/day, n = 6) or were left untreated (n = 14). All animals were monitored for blood pressure, proteinuria, and creatinine clearance after anti-Thy1 injection. Renal histology was assessed at day 7 and 28.</p><p><strong>Results: </strong>Systolic blood pressure was equally reduced by ACE-I and Ca-A treatment. AngII suppression prevented development of proteinuria, but did not protect against glomerular microaneurysm formation or reduction in creatinine clearance. After resolution of the microaneurysms, animals with suppressed AngII production showed a modest increase in glomerulosclerosis and vasculopathic thickening of intrarenal vessels.</p><p><strong>Conclusions: </strong>In anti-Thy1 glomerulonephritis, suppression of AngII formation does not protect against the induction of glomerular damage and is associated with mild aggravation of adverse renal fibrotic remodeling. Proteinuria, however, is effectively prevented by ACE-I treatment. Ca-A treatment did not affect the course of glomerulonephritis, indicating that ACE-I effects are blood pressure independent.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"9-16"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000335750","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30554657","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}
Nephron ExtraPub Date : 2012-01-01Epub Date: 2012-03-28DOI: 10.1159/000336482
Bergur V Stefánsson, Mats Abramson, Ulf Nilsson, Börje Haraldsson
{"title":"Hemodiafiltration improves plasma 25-hepcidin levels: a prospective, randomized, blinded, cross-over study comparing hemodialysis and hemodiafiltration.","authors":"Bergur V Stefánsson, Mats Abramson, Ulf Nilsson, Börje Haraldsson","doi":"10.1159/000336482","DOIUrl":"https://doi.org/10.1159/000336482","url":null,"abstract":"<p><strong>Background/aims: </strong>Data from studies comparing the effect of hemodiafiltration (HDF) and conventional hemodialysis (HD) on clinically important outcomes are insufficient to support superiority of HDF. None of these studies has been participant-blinded.</p><p><strong>Methods: </strong>We performed a prospective, randomized, and patient-blinded cross-over study. Twenty patients on chronic HD received either HD for 2 months followed by post-dilution HDF for 2 months or in opposite order. A range of clinical parameters, as well as markers of inflammation, oxidative stress and iron metabolism was measured.</p><p><strong>Results: </strong>The two treatments were similar with respect to dialysis-related complications, quality of life, and the biomarkers of oxidative stress and inflammation. Compared to HD, 25-hepcidin and β(2)-microglobulin were 38 and 32%, respectively, lower after 60 days of HDF (p < 0.001 and p < 0.01, respectively). The consumption of ESA (erythropoietin-stimulating agent) and LMWH (low-molecular-weight heparin) was significantly higher with HDF.</p><p><strong>Conclusion: </strong>In short term, HDF is not superior to HD regarding dialysis-related complications. The higher ESA consumption observed with HDF can be explained by blood clotting in tubing and dialyzers, as more anticoagulation was needed with post-dilution HDF. In a longer perspective, lowering serum hepcidin levels may improve pathological iron homeostasis.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"55-65"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000336482","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30637727","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}
Nephron ExtraPub Date : 2012-01-01Epub Date: 2012-07-04DOI: 10.1159/000339282
Esther G Gerrits, Helen L Lutgers, Gertie H W Smeets, Klaas H Groenier, Andries J Smit, Reinold O B Gans, Henk J G Bilo
{"title":"Skin autofluorescence: a pronounced marker of mortality in hemodialysis patients.","authors":"Esther G Gerrits, Helen L Lutgers, Gertie H W Smeets, Klaas H Groenier, Andries J Smit, Reinold O B Gans, Henk J G Bilo","doi":"10.1159/000339282","DOIUrl":"https://doi.org/10.1159/000339282","url":null,"abstract":"Background: Accelerated formation and tissue accumulation of advanced glycation endproducts (AGEs), reflecting cumulative glycemic and oxidative stress, occur in age-related and chronic diseases like diabetes mellitus (DM) and renal failure, and contribute to vascular damage. Skin autofluorescence (AF), a noninvasive measurement method, reflects tissue accumulation of AGEs. The aim of our study was to determine the predictive value of skin AF on overall and cardiovascular mortality in hemodialysis patients. Methods: Baseline skin AF was measured in 105 patients on hemodialysis, 23 had DM. Survival status was assessed after a mean follow-up period of 4.9 years (interquartile range 2.3–6.9 years). Results: Multivariate Cox regression analysis showed skin AF (hazard ratio (HR) 1.83; 95% confidence interval (CI) 1.32–2.54), preexisting cardiovascular disease (CVD) (HR 2.77; 95% CI 1.48–5.18), renal replacement therapy duration (HR 1.10; 95% CI 1.01–1.19), age (HR 1.03; 95% CI 1.01–1.06), serum albumin (HR 0.90; 95% CI 0.85–0.95), hematocrit (HR 0.92; 95% CI 0.86–0.98), phosphorus (HR 2.01; 95% CI 1.15–3.49), and parathyroid hormone (HR 0.99; 95% CI 0.98–0.996) to be predictors of mortality, whereas DM was not. Preexisting CVD and serum phosphorus were the only predictors of cardiovascular mortality. Conclusion: Skin AF showed to be an independent predictor of overall mortality in hemodialysis patients, but it had no predictive value for cardiovascular mortality.","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"184-91"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000339282","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30774014","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}
Nephron ExtraPub Date : 2012-01-01Epub Date: 2012-03-28DOI: 10.1159/000337339
Chung Hee Baek, Won Seok Yang, Kyung Sun Park, Duck Jong Han, Jae Berm Park, Su-Kil Park
{"title":"Infectious risks and optimal strength of maintenance immunosuppressants in rituximab-treated kidney transplantation.","authors":"Chung Hee Baek, Won Seok Yang, Kyung Sun Park, Duck Jong Han, Jae Berm Park, Su-Kil Park","doi":"10.1159/000337339","DOIUrl":"https://doi.org/10.1159/000337339","url":null,"abstract":"<p><strong>Background: </strong>Rituximab, an anti-CD20 antibody, effectively depletes B lymphocytes. It is not clear whether the use of conventional doses of mycophenolate mofetil (MMF), methylprednisolone and tacrolimus as maintenance immunosuppression in rituximab-treated kidney transplantation is associated with increased risk.</p><p><strong>Methods: </strong>We retrospectively evaluated 67 patients who underwent HLA-sensitized or ABO-incompatible living donor kidney transplantation after one dose of rituximab (200 or 500 mg) (group 1). Eighty-seven kidney transplant recipients who did not require rituximab served as a control (group 2).</p><p><strong>Results: </strong>Cytomegalovirus infection (16.4 vs. 5.7%, p = 0.031) and pneumonia (9.0 vs. 1.1%, p = 0.043) occurred more often in group 1, and 2 patients of group 1 died of infection. The doses of methylprednisolone and tacrolimus levels of the two groups were not different. MMF dose was reduced when serious infection occurred. The doses of MMF (in grams/day) at the following times postoperatively were lower in group 1 than in group 2: 1 month: 1.26 ± 0.42 vs. 1.40 ± 0.39, p = 0.033; 3 months: 1.14 ± 0.51 vs. 1.36 ± 0.39, p = 0.011; 6 months: 1.07 ± 0.50 vs. 1.30 ± 0.42, p = 0.012; 1 year: 0.88 ± 0.52 vs. 1.19 ± 0.44, p = 0.009; 2 years: 0.69 ± 0.55 vs. 1.25 ± 0.49, p = 0.059, but the reduction of MMF doses did not increase the incidence of acute rejection in group 1 (4.5% in group 1 vs. 9.2% in group 2, p = 0.351). If patients who died with functioning graft were excluded, graft survival was 98.5% in group 1 and 100% in group 2.</p><p><strong>Conclusions: </strong>Serious infectious complications were increased in rituximab-treated kidney transplant recipients and it might be adequate to reduce the MMF dose from the early postoperative period.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"66-75"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000337339","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30637728","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}
Nephron ExtraPub Date : 2012-01-01Epub Date: 2012-05-22DOI: 10.1159/000338271
T A Facca, G Mastroianni Kirsztajn, A R Pereira, S R Moreira, V P C Teixeira, S K Nishida, N Sass
{"title":"Renal evaluation in women with preeclampsia.","authors":"T A Facca, G Mastroianni Kirsztajn, A R Pereira, S R Moreira, V P C Teixeira, S K Nishida, N Sass","doi":"10.1159/000338271","DOIUrl":"10.1159/000338271","url":null,"abstract":"<p><strong>Background/aims: </strong>Preeclampsia (PE) is a cause of glomerulopathy worldwide. Urinary retinol-binding protein (RBP) is a marker of proximal tubular dysfunction, albuminuria is an endothelial injury marker, urine protein:creatinine ratio (PCR) may have a predictive value for renal disease later in life, and, recently, podocyturia has been proposed as a sensitive tool in pregnancy, but it needs to be tested. The aim of this study was to evaluate renal involvement in PE and healthy pregnancy.</p><p><strong>Methods: </strong>Case-control study with 39 pregnant women assessed after 20 weeks of gestation (25 in the control group, CG, and 14 in the PE group) by performing urinary tests.</p><p><strong>Results: </strong>Mean (±SD) age and gestational age of the CG were 26.9 ± 6.4 years and 37.1 ± 5.0 weeks, and of the PE group 26.4 ± 6.9 years and 30.6 ± 5.6 weeks, respectively (p = 0.001). Mean (±SD) urinary RBP (p = 0.017), albuminuria (p = 0.002), and urinary albumin concentration (UAC) ratio (p = 0.006) of the CG were 0.4 ± 0.7 mg/l, 7.3 ± 6.9 mg/l, and 8.2 ± 6.7 mg/g and of the PE group 2.0 ± 4.4 mg/l, 2,267.4 ± 2,130.8 mg/l (p = 0.002), and 3,778.9 ± 4,296.6 mg/g (p = 0.006), respectively. Mean (±SD) urine PCR in the PE group was 6.7 ± 6.1 g/g (p < 0.001). No statistical differences were found between podocyturia in the CG and PE group (p = 0.258).</p><p><strong>Conclusions: </strong>Urinary RBP, PCR, albuminuria, and UAC ratio were elevated in the PE group in comparison to the CG. Podocyturia did not predict PE.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"125-32"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ac/d8/nne-0002-0125.PMC3383241.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30723827","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 role of apelin on the alleviative effect of Angiotensin receptor blocker in unilateral ureteral obstruction-induced renal fibrosis.","authors":"Masashi Nishida, Yasuko Okumura, Tatsujiro Oka, Kentaro Toiyama, Seiichiro Ozawa, Toshiyuki Itoi, Kenji Hamaoka","doi":"10.1159/000337091","DOIUrl":"https://doi.org/10.1159/000337091","url":null,"abstract":"<p><strong>Background: </strong>Apelin is a selective endogenous ligand of the APJ receptor, which genetically has closest identity to the angiotensin II type 1 receptor (AT-1). The effects of the apelin/APJ system on renal fibrosis still remain unclear.</p><p><strong>Methods: </strong>We examined the effects of the apelin/APJ system on renal fibrosis during AT-1 blockade in a mouse unilateral ureteral obstruction (UUO) model.</p><p><strong>Results: </strong>WE OBTAINED THE FOLLOWING RESULTS: (1) At UUO day 7, mRNA expressions of apelin/APJ and phosphorylations of Akt/endothelial nitric oxide synthase (eNOS) in the UUO kidney were increased compared to those in the nonobstructed kidney. (2) AT-1 blockade by the treatment with losartan resulted in a further increase of apelin mRNA as well as phosphorylations of Akt/eNOS proteins, and this was accompanied by alleviated renal interstitial fibrosis, decreased myofibroblast accumulation, and a decreased number of interstitial macrophages. (3) Blockade of the APJ receptor by the treatment with F13A during losartan administration completely abrogated the effects of losartan in the activation of the Akt/eNOS pathway and the amelioration of renal fibrosis. (4) Inhibition of NOS by the treatment with L-NAME also resulted in a further increase in renal fibrosis compared to the control group.</p><p><strong>Conclusion: </strong>These results suggest that increased nitric oxide production through the apelin/APJ/Akt/eNOS pathway may, at least in part, contribute to the alleviative effect of losartan in UUO-induced renal fibrosis.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"39-47"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000337091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30637725","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}
Nephron ExtraPub Date : 2012-01-01Epub Date: 2012-07-06DOI: 10.1159/000339436
Elizabeth R Flynn, David C Marbury, R Taylor Sawyer, Jonathan Lee, Christine Teutsch, Katalin Kauser, Christine Maric-Bilkan
{"title":"Amlodipine Reduces Inflammation despite Promoting Albuminuria in the Streptozotocin-Induced Diabetic Rat.","authors":"Elizabeth R Flynn, David C Marbury, R Taylor Sawyer, Jonathan Lee, Christine Teutsch, Katalin Kauser, Christine Maric-Bilkan","doi":"10.1159/000339436","DOIUrl":"https://doi.org/10.1159/000339436","url":null,"abstract":"<p><p>Amlodipine reduces blood pressure; however, its effect in the diabetic kidney irrespective of its blood pressure-lowering effects is unclear. This study examined the effects of amlodipine (0, 5, 10 and 20 mg/kg; D(A0), D(A5), D(A10) and D(A20), respectively) for 12 weeks on renal functional and structural changes in the streptozotocin-induced diabetic rat, a nonhypertensive model of diabetes-associated hyperfiltration. Compared with nondiabetic rats, diabetes (D) was associated with increased urine albumin excretion (UAE, 12.6 ± 3.40 vs. 3.73 ± 1.14 mg/day), glomerular filtration rate (2.17 ± 0.09 vs. 1.64 ± 0.12 ml/min/g kidney weight), glomerulosclerosis (0.21 ± 0.03 vs. 0.05 ± 0.01 AU) and infiltration of inflammatory cells (18.5 ± 2.78 vs. 6.92 ± 0.70 cells/cm(2)), but did not affect mean arterial pressure (MAP, 110 ± 4.70 vs. 109 ± 5.33 mm Hg). While D(A20) abolished glomerular hyperfiltration (1.49 ± 0.05 ml/min/g kidney weight) and inflammatory cell abundance (6.0 ± 0.79 cells/cm(2)), it exacerbated UAE (43.5 ± 8.49 mg/day) and increased MAP (132 ± 3.76 mm Hg), but had no effect on renal pathology. These data suggest that amlodipine reduces renal inflammation and abolished glomerular hyperfiltration, but increases blood pressure and exacerbates albuminuria in the rat model of normotensive diabetic kidney disease. We conclude that amlodipine may have limited renoprotective effects in the face of hyperfiltration and absence of elevated blood pressure.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"205-18"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000339436","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30773932","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":"Thrombin stimulates synthesis of macrophage colony-stimulating factor, granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor by human proximal tubular epithelial cells in culture.","authors":"Yuko Shimaya, Michiko Shimada, Yoshiko Shutto, Takeshi Fujita, Reiichi Murakami, Norio Nakamura, Hideaki Yamabe, Ken Okumura","doi":"10.1159/000335751","DOIUrl":"https://doi.org/10.1159/000335751","url":null,"abstract":"<p><strong>Background/aims: </strong>Colony-stimulating factors (CSFs) are well-known hematopoietic growth factors. Although recent studies revealed that CSFs are involved in many inflammatory conditions, the local production of CSFs and its regulation in the kidney is not well elucidated. Therefore, using cultured human proximal tubular epithelial cells (PTEC), we examined the effect of thrombin on CSFs production, since thrombin has been suggested to play an important role in tubulointerstitial injury.</p><p><strong>Methods: </strong>PTEC were incubated with thrombin (0.5-5.0 U/ml) and the effects on the production of macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF) and granulocyte CSF (G-CSF) were measured in the cell supernatant by enzyme-linked immunosorbent assay, and the expressions of mRNA were analyzed by quantitative real-time reverse transcription polymerase chain reaction. Using argatroban, a direct thrombin inhibitor, we also examined the specific effect of thrombin.</p><p><strong>Results: </strong>Thrombin 5.0 U/ml significantly stimulated the production of M-CSF (p < 0.01) and G-CSF (p < 0.01), and 1.0 and 5.0 U/ml thrombin significantly stimulated GM-CSF (p < 0.02 and p < 0.01) in a dose-dependent manner. Thrombin 5.0 U/ml increased CSFs (M-CSF, p < 0.005; GM-CSF, p < 0.0005; G-CSF, p < 0.005) in a time-dependent manner. Thrombin also significantly enhanced the mRNA expressions of M-CSF (p < 0.01), GM-CSF (p < 0.05) and G-CSF (p < 0.01). These effects of thrombin were significantly reduced by the addition of argatroban (M-CSF, p < 0.01; GM-CSF, p < 0.01; G-CSF, p < 0.05).</p><p><strong>Conclusion: </strong>We demonstrated that thrombin significantly increased the production of CSFs by PTEC. These data suggest that the local production of CSFs in the tubulointerstitium may affect tubulointerstitial lesions in kidney injury.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000335751","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30554656","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}