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Urinary matrix metalloproteinase activity in diabetic kidney disease: a potential marker of disease progression. 尿基质金属蛋白酶在糖尿病肾病中的活性:疾病进展的潜在标志。
Nephron Extra Pub Date : 2012-01-01 Epub Date: 2012-08-09 DOI: 10.1159/000339645
Nagi Altemtam, Meguid El Nahas, Tim Johnson
{"title":"Urinary matrix metalloproteinase activity in diabetic kidney disease: a potential marker of disease progression.","authors":"Nagi Altemtam,&nbsp;Meguid El Nahas,&nbsp;Tim Johnson","doi":"10.1159/000339645","DOIUrl":"https://doi.org/10.1159/000339645","url":null,"abstract":"<p><strong>Background: </strong>Progressive kidney fibrosis, associated with chronic kidney disease (CKD), results from an imbalance in extracellular matrix (ECM) homeostasis. Reduced matrix metalloproteinases (MMP) activity causing lower clearance of ECM proteins has been implicated mainly through an overproduction of tissue inhibitors of metalloproteinases (TIMP), but also by reduced MMP synthesis. We tested the hypothesis that MMP activity can be measured in human urine and can be used as a potential biomarker of the progression of diabetic kidney disease (DKD).</p><p><strong>Methods: </strong>An observational prospective study was performed on 102 DKD patients using 21 diabetic patients without kidney disease and 21 healthy volunteers as controls. The Molecular Probes EnzChek Gelatinase/Collagenase Assay Kit were used to determine urinary MMP activity using DQ™ Gelatin (total MMPs), DQ™ Collagen I (interstitial collagenases) and DQ™ Collagen IV (gelatinises) substrates. A broad-spectrum synthetic inhibitor of all MMP, 1,10-phenanthroline, was used to confirm that the proteolytic activity is due to MMP activity. All MMP values were expressed per unit of urine creatinine.</p><p><strong>Results: </strong>Overall urinary MMP activity (DQ Gelatin substrate) was significantly elevated in DKD patients (14.76 ± 3.65 Δ fl/h/mmol creatinine) compared to diabetes mellitus controls (7.09 ± 2.12 Δ fl/h/mmol creatinine) and healthy volunteers (1.87 ± 0.74 Δ fl/h/mmol creatinine) (ANOVA p = 0.01). Within the DKD cohort, there was an approximate threefold higher urinary MMP activity in nonprogressive DKD patients compared to those with progressive disease (p = 0.002). The urinary MMP activity:creatinine ratio was significantly higher in normoalbuminuric and microalbuminuric DKD compared to macroalbuminuric DKD. Positive correlations were observed between the rate of total MMP activity and interstitial collagenases (r = 0.75, p < 0.0001) and gelatinases (r = 0.59, p = 0.0001). The accuracy of MMP activity to predict the rate of annual eGFR decline (ROC analysis) was 77% compared to 64% for albuminuria.</p><p><strong>Conclusions: </strong>Total MMP activity can be easily measured in human urine. Surprisingly and in contrast to MMP activity in the kidney, urine MMP activity is elevated in DKD. However, there is a significantly lower MMP activity in patients with progressive DKD. ROC analysis demonstrates that single urine MMP activity estimation is superior to albuminuria in predicting DKD patients with progressive disease.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 ","pages":"219-32"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000339645","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30881870","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}
引用次数: 27
Serum Beta 2-microglobulin/cystatin C index: a useful biomarker in lupus nephritis? 血清β 2微球蛋白/胱抑素C指数:狼疮性肾炎的有用生物标志物?
Nephron Extra Pub Date : 2012-01-01 Epub Date: 2012-06-22 DOI: 10.1159/000339643
Marcus Vinicius Madureira Silva, Grace T Moscoso-Solorzano, Sonia K Nishida, Gianna Mastroianni-Kirsztajn
{"title":"Serum Beta 2-microglobulin/cystatin C index: a useful biomarker in lupus nephritis?","authors":"Marcus Vinicius Madureira Silva,&nbsp;Grace T Moscoso-Solorzano,&nbsp;Sonia K Nishida,&nbsp;Gianna Mastroianni-Kirsztajn","doi":"10.1159/000339643","DOIUrl":"https://doi.org/10.1159/000339643","url":null,"abstract":"<p><strong>Background: </strong>Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease with frequent flares. Our aim was to evaluate the beta 2-microglobulin/cystatin C (β2M/CysC) index versus other markers as a predictor factor for assessment of SLE reactivation.</p><p><strong>Methods: </strong>We prospectively analyzed 42 patients with lupus nephritis. Disease activity was classified using SLEDAI-2K and BILAG. Routine renal function and laboratory markers of SLE activity were performed, as well as serum β2M (Sβ2M)/serum CysC (SCysC) and Sβ2M/serum creatinine (SCreat) indexes determinations.</p><p><strong>Results: </strong>The 42 enrolled patients had a mean age of 37.7 ± 13.1 years, 88% were female and 67% Caucasians; mean estimated glomerular filtration rate was 61.9 ± 20.0 ml/min/1.73 m(2). There was a strong correlation between SCreat versus SCysC (r = 0.887), SCreat versus Sβ2M (r = 0.865), and SCysC versus Sβ2M (r = 0.880). Multivariate analysis showed that the Sβ2M/SCreat index is a prognostic factor predicting active lupus nephritis.</p><p><strong>Conclusion: </strong>As SCysC is a good marker of renal function, it would be expected that the Sβ2M/SCysC index could be a better indicator of renal activity than Sβ2M/SCreat, but in the present study it did not add relevant clinical information in the assessment of renal activity in SLE.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"169-76"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000339643","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30774012","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}
引用次数: 24
Nephroprotective Effect of Echinodorus macrophyllus Micheli on Gentamicin-Induced Nephrotoxicity in Rats. 大叶棘虫对庆大霉素所致大鼠肾毒性的保护作用。
Nephron Extra Pub Date : 2012-01-01 Epub Date: 2012-06-28 DOI: 10.1159/000339181
Viviane Gomes Portella, Gustavo Pereira Cosenza, Lúcio Ricardo Leite Diniz, Lílian Fernanda Pacheco, Giovanni Dantas Cassali, Marcelo Vidigal Caliari, Maria das Graças Lins Brandão, Maria Aparecida Ribeiro Vieira
{"title":"Nephroprotective Effect of Echinodorus macrophyllus Micheli on Gentamicin-Induced Nephrotoxicity in Rats.","authors":"Viviane Gomes Portella,&nbsp;Gustavo Pereira Cosenza,&nbsp;Lúcio Ricardo Leite Diniz,&nbsp;Lílian Fernanda Pacheco,&nbsp;Giovanni Dantas Cassali,&nbsp;Marcelo Vidigal Caliari,&nbsp;Maria das Graças Lins Brandão,&nbsp;Maria Aparecida Ribeiro Vieira","doi":"10.1159/000339181","DOIUrl":"https://doi.org/10.1159/000339181","url":null,"abstract":"<p><strong>Background/aims: </strong>Leaves of Echinodorus macrophyllus (EM), from the Alismataceae family, have been used in Brazilian folk medicine for their anti-inflammatory and diuretic properties. In this work, the diuretic and nephroprotective activities of crude extracts of EM were evaluated.</p><p><strong>Methods: </strong>Normal Wistar rats were given 0.9% NaCl containing either EM (10-300 mg/kg), furosemide (13 mg/kg) or arginine vasopressin (0.2 mg/kg). Thereafter, the rats were individually housed in metabolic cages, and urine volume was measured every 30 min for a total of 3 h. Acute kidney injury was induced by gentamicin (GM, 80 mg·kg(-1)·day(-1), b.i.d., 5 days). Along with GM, 0.9% NaCl (control) or EM (30 mg/kg) was given to the rats by gavage.</p><p><strong>Results: </strong>EM produced a dose-dependent reduction in urine elimination. EM was effective in reversing all GM-induced alterations such as polyuria and glomerular filtration rate reduction. The GM-induced morphological alterations were not observed when EM was given concomitantly with GM.</p><p><strong>Conclusion: </strong>This study provides evidence that EM possesses nephroprotective effect which indicates that EM may have therapeutic applications in GM-induced acute kidney injury.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"177-83"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000339181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30774013","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}
引用次数: 18
Comparison of volume status in asymptomatic haemodialysis and peritoneal dialysis outpatients. 无症状血液透析与腹膜透析门诊患者血容量状况的比较。
Nephron Extra Pub Date : 2012-01-01 Epub Date: 2012-03-26 DOI: 10.1159/000337338
Eugenia Papakrivopoulou, John Booth, Jennifer Pinney, Andrew Davenport
{"title":"Comparison of volume status in asymptomatic haemodialysis and peritoneal dialysis outpatients.","authors":"Eugenia Papakrivopoulou,&nbsp;John Booth,&nbsp;Jennifer Pinney,&nbsp;Andrew Davenport","doi":"10.1159/000337338","DOIUrl":"https://doi.org/10.1159/000337338","url":null,"abstract":"<p><strong>Background: </strong>The majority of haemodialysis (HD) patients gain weight between dialysis sessions and thereby become volume overloaded, whereas peritoneal dialysis (PD) is a more continuous technique. Cardiovascular mortality and hypertension is increased with both treatment modalities. We therefore wished to compare volume status in PD and HD to determine whether PD patients are chronically volume overloaded, as a risk factor for cardiovascular mortality. Study Design, Setting and Participants:We retrospectively audited 72 healthy HD patients and 115 healthy PD patients attending a university hospital dialysis centre for routine outpatient treatment, who had multi-frequency bioimpedance measurements of extracellular water to total body water (ECW/TBW).</p><p><strong>Results: </strong>The groups were well matched for age, sex, weight and ethnicity, PD patients had greater urine output [1,075 (485-1,613) vs. 42.5 (0-1,020) ml/day, p < 0.001], but there was no difference in antihypertensive prescription (63.5 vs. 76.4%), mean arterial blood pressure (post-dialysis 101.6 ± 1.5 mm Hg vs. pre-dialysis 102 ± 2.4 mm Hg), although post-dialysis arterial blood pressure was lower than in PD patients (96.4 ± 3.1 mm Hg, p < 0.05). The ratio of ECW/TBW fell after HD (pre-dialysis 0.394 ± 0.001 vs. post-dialysis 0.389 ± 0.004, p < 0.001) and was similar in the PD group to the group before HD (0.393 ± 0.001), and greater than that in the group after HD (p < 0.001). ECW/TBW was greater than the normal reference range in 30% PD patients, 28% patients before HD and 20% patients after HD.</p><p><strong>Conclusions: </strong>Overhydration is common in healthy stable PD outpatients, and ECW volumes in PD patients are not dissimilar to those of pre-dialysis HD patients. The role of chronic volume overload as a risk factor for cardiovascular disease needs further investigation.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"48-54"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000337338","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30637726","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}
引用次数: 53
Association of HCV core antigen seropositivity with long-term mortality in patients on regular hemodialysis. HCV核心抗原血清阳性与定期血液透析患者长期死亡率的关系
Nephron Extra Pub Date : 2012-01-01 Epub Date: 2012-03-28 DOI: 10.1159/000337333
Akihiko Kato, Takako Takita, Mitsuyoshi Furuhashi, Taiki Fujimoto, Hiroo Suzuki, Yukitaka Maruyama, Yukitoshi Sakao, Hiroaki Miyajima
{"title":"Association of HCV core antigen seropositivity with long-term mortality in patients on regular hemodialysis.","authors":"Akihiko Kato,&nbsp;Takako Takita,&nbsp;Mitsuyoshi Furuhashi,&nbsp;Taiki Fujimoto,&nbsp;Hiroo Suzuki,&nbsp;Yukitaka Maruyama,&nbsp;Yukitoshi Sakao,&nbsp;Hiroaki Miyajima","doi":"10.1159/000337333","DOIUrl":"https://doi.org/10.1159/000337333","url":null,"abstract":"<p><p>Anti-hepatitis C virus (HCV) antibody seropositivity is independently associated with poor prognosis in hemodialysis (HD) patients. However, anti-HCV antibody cannot distinguish between patients with active infection and those who have recovered from infection. We therefore aimed in this study to examine the association of HCV core antigen (HCVcAg) seropositivity with mortality in HD patients. We first measured serum HCVcAg using an immunoradiometric assay and anti-HCV antibody in 405 patients on regular HD, and followed them for 104 months. There were 82 patients (20.2%) who had been positive for anti-HCV antibodies; 57 (69.5%) of these were positive for HCVcAg. During the follow-up, 29 patients were excluded, so we tested the association of HCVcAg seropositivity with all-cause, cardiovascular (CV) and non-CV mortalities in 376 patients. A total of 209 patients (55.6%) had expired during the observational period, 92 out of them due to CV causes. After adjusting for comorbid parameters, HCVcAg was independently associated with overall mortality (HR 1.61, 95% CI 1.05-2.47, p < 0.05). HCV infection was significantly related to liver disease-related mortality. Past HCV infection also contributed to CV mortality (HR 2.63, 95% CI 1.27-5.45, p < 0.01). In contrast, anti-HCV antibody and HCVcAg seropositivities did not associate with infectious disease-related and cancer-related (expect for hepatocellular carcinoma) mortality. It follows from these findings that HCVcAg serology is associated with all-cause and CV mortality in HD patients.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"76-86"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000337333","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30637729","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}
引用次数: 6
Relative Change in NT-proBNP Level: An Important Risk Predictor of Cardiovascular Congestion in Haemodialysis Patients. NT-proBNP水平的相对变化:血液透析患者心血管充血的重要风险预测因子。
Nephron Extra Pub Date : 2012-01-01 Epub Date: 2012-12-12 DOI: 10.1159/000343897
M Pastural-Thaunat, R Ecochard, N Boumendjel, E Abdullah, C Cardozo, A Lenz, I M'pio, J C Szelag, D Fouque, A Walid, M Laville
{"title":"Relative Change in NT-proBNP Level: An Important Risk Predictor of Cardiovascular Congestion in Haemodialysis Patients.","authors":"M Pastural-Thaunat,&nbsp;R Ecochard,&nbsp;N Boumendjel,&nbsp;E Abdullah,&nbsp;C Cardozo,&nbsp;A Lenz,&nbsp;I M'pio,&nbsp;J C Szelag,&nbsp;D Fouque,&nbsp;A Walid,&nbsp;M Laville","doi":"10.1159/000343897","DOIUrl":"https://doi.org/10.1159/000343897","url":null,"abstract":"<p><strong>Background: </strong>Cross-sectional studies have shown that B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP) are predictive of cardiovascular death in haemodialysis (HD) patients. In the present study, we tested the hypothesis that monitoring NT-proBNP measurements adds further prognostic information, i.e. predicts congestive heart failure (CHF) events.</p><p><strong>Methods: </strong>In a prospective cohort of 236 HD patients, NT-proBNP levels were measured monthly during 18 months. Patients were divided according to the occurrence of CHF events. In a nested case-control study, we assessed the evolution of NT-proBNP levels.</p><p><strong>Results: </strong>On average, the 236 HD patients were followed up for 12.5 months, a period during which 44 patients developed a CHF event (half requiring hospitalisation). At baseline, patients who developed a CHF event had significantly more dilated cardiomyopathy and/or altered left ventricular ejection fraction and higher NT-proBNP levels compared with patients who did not develop a CHF event. During follow-up, we observed a significant increase in NT-proBNP levels preceding the CHF event. At a 20% relative increase of NT-proBNP, the sensitivity of NT-proBNP as a predictor of CHF events was 0.57 and the specificity 0.77.</p><p><strong>Conclusion: </strong>The relative change in NT-proBNP levels is a significant risk predictor of a CHF event.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"311-8"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000343897","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31176987","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}
引用次数: 7
Mineralocorticoid Receptor Blocker Protects against Podocyte-Dependent Glomerulosclerosis. 矿皮质激素受体阻滞剂可预防足细胞依赖性肾小球硬化。
Nephron Extra Pub Date : 2012-01-01 Epub Date: 2012-01-31 DOI: 10.1159/000334961
Nobuaki Takagi, Takakuni Tanizawa, Valentina Kon, Agnes B Fogo, Iekuni Ichikawa, Ji Ma
{"title":"Mineralocorticoid Receptor Blocker Protects against Podocyte-Dependent Glomerulosclerosis.","authors":"Nobuaki Takagi,&nbsp;Takakuni Tanizawa,&nbsp;Valentina Kon,&nbsp;Agnes B Fogo,&nbsp;Iekuni Ichikawa,&nbsp;Ji Ma","doi":"10.1159/000334961","DOIUrl":"https://doi.org/10.1159/000334961","url":null,"abstract":"Background: We previously showed that angiotensin type 1 receptor (AT1) blocker (ARB) attenuates glomerular injury in Nphs1-hCD25 (NEP25) transgenic mice, a model of selective podocyte injury. However, subsequent studies in NEP25 mice with podocyte-specific deficiency of AT1 revealed that the protective effects of ARB are not through the podocyte AT1, thereby raising the possibility that the protective effects of ARB involve mineralocorticoids. Methods: NEP25 mice were treated with the mineralocorticoid receptor blocker (MRB) spironolactone (25 mg/kg/day, n = 10), the ARB losartan (250 mg/kg/day, n = 11), both (ARB+MRB, n = 8) or vehicle (Vehicle, n = 9) from day –7 to day 9 of induction of podocyte injury. Results: Although MRB did not reduce systolic blood pressure or proteinuria, addition of MRB to ARB significantly attenuated glomerulosclerosis (glomerulosclerosis index: ARB+MRB 1.67 ± 0.19 vs. MRB 2.01 ± 0.29, ARB 2.35 ± 0.19, and Vehicle 2.25 ± 0.26, p < 0.05) and preserved the number of WT1-positive podocytes (ARB+MRB 152.5 ± 9.7 vs. MRB 117.2 ± 9.0 or ARB 113.6 ± 7.4, and ARB+MRB vs. Vehicle 97.5 ± 4.0 per glomerulus; p < 0.05). Conclusion: These data suggest that, while MRB does not attenuate proteinuria caused by podocyte-specific injury, it provides protective effects against glomerulosclerosis that is independent of systemic blood pressure.","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"17-26"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000334961","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30554658","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}
引用次数: 9
Renoprotective action of a matrix metalloproteinase inhibitor in progressive mesangioproliferative nephritis. 基质金属蛋白酶抑制剂在进展性肾系血管增殖性肾炎中的肾保护作用。
Nephron Extra Pub Date : 2012-01-01 Epub Date: 2012-05-26 DOI: 10.1159/000338801
Takayuki Kuroda, Masao Masui, Mitsuru Notoya, Masashi Ito, Yoshinori Tamura, Hiroyuki Okamoto, Eri Kanaoka, Toshihiro Shinosaki
{"title":"Renoprotective action of a matrix metalloproteinase inhibitor in progressive mesangioproliferative nephritis.","authors":"Takayuki Kuroda,&nbsp;Masao Masui,&nbsp;Mitsuru Notoya,&nbsp;Masashi Ito,&nbsp;Yoshinori Tamura,&nbsp;Hiroyuki Okamoto,&nbsp;Eri Kanaoka,&nbsp;Toshihiro Shinosaki","doi":"10.1159/000338801","DOIUrl":"https://doi.org/10.1159/000338801","url":null,"abstract":"<p><strong>Background/aim: </strong>Matrix metalloproteinases (MMPs) play pivotal roles in extracellular matrix turnover and are involved in chronic kidney disease. The renoprotective action of a synthetic MMP inhibitor, compound A, was investigated in chronic nephritis.</p><p><strong>Methods: </strong>Nephritis was induced by a single injection of anti-Thy1.1 antibody to unilaterally nephrectomized rats. The effects of compound A on proteinuria, blood urea nitrogen, and matrix-related gene expressions were evaluated. Collagen accumulation, as assessed by periodic acid-Schiff staining and hydroxyproline content, was determined. The integrity of glomerular epithelial cells and glomerular basement membrane was evaluated with desmin immunohistochemistry and electron microscopic detection of anionic charge sites, respectively.</p><p><strong>Results: </strong>Treatment with compound A notably attenuated proteinuria, ameliorated blood urea nitrogen, and prevented glomerulosclerosis. Gene upregulation of collagen and transforming growth factor β1 in the cortex was prevented in the treated animals. Glomerular epithelial cell injury was milder, and glomerular basement membrane anionic sites were protected with the treatment.</p><p><strong>Conclusion: </strong>A novel MMP inhibitor, compound A, exerts protective effects in progressive glomerulonephritis. Compound A ameliorates various aspects of renal injuries and may have therapeutic potential toward kidney diseases.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"133-46"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000338801","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30723167","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}
引用次数: 2
Epidemiology of uromodulin-associated kidney disease - results from a nation-wide survey. 尿调素相关肾病的流行病学——来自一项全国性调查的结果
Nephron Extra Pub Date : 2012-01-01 Epub Date: 2012-06-01 DOI: 10.1159/000339102
Karl Lhotta, Sian E Piret, Reinhard Kramar, Rajesh V Thakker, Gere Sunder-Plassmann, Peter Kotanko
{"title":"Epidemiology of uromodulin-associated kidney disease - results from a nation-wide survey.","authors":"Karl Lhotta,&nbsp;Sian E Piret,&nbsp;Reinhard Kramar,&nbsp;Rajesh V Thakker,&nbsp;Gere Sunder-Plassmann,&nbsp;Peter Kotanko","doi":"10.1159/000339102","DOIUrl":"https://doi.org/10.1159/000339102","url":null,"abstract":"Background/Aims: Uromodulin-associated kidney disease (UAKD) is caused by uromodulin mutations and leads to end-stage renal disease. Our objective was to examine the epidemiology of UAKD. Methods: Data from all UAKD families in Austria were collected. Patients included in the Austrian Dialysis and Transplantation Registry (OEDTR) with unclear diagnoses or genetic diseases were asked whether they had (1) a family history of kidney disease or (2) had suffered from gout. Patients with gout and autosomal dominant renal disease underwent mutational analysis. Kaplan-Meier and Cox analysis was employed to estimate time to renal failure. Results: Of the 6,210 patients in the OEDTR, 541 were approached with a questionnaire; 353 patients answered the questionnaire. Nineteen of them gave two affirmative answers. In 7 patients, an autosomal dominant renal disease was found; in 1 patient a UMOD mutation was identified. One family was diagnosed through increased awareness as a consequence of the study. At present, 14 UAKD patients from 5 families are living in Austria (1.67 cases per million), and 6 of them require renal replacement therapy (0.73 per 1,000 patients). Progression to renal failure was significantly associated with UMOD genotype. Conclusion: UAKD patients can be identified by a simple questionnaire. UMOD genotype may affect disease progression.","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"147-58"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000339102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30725123","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}
引用次数: 23
Increased Prevalence and Severity of Coronary Artery Calcification in Patients with Chronic Kidney Disease Stage III and IV. 慢性肾脏疾病III期和IV期患者冠状动脉钙化的患病率和严重程度增加
Nephron Extra Pub Date : 2012-01-01 Epub Date: 2012-07-04 DOI: 10.1159/000339786
Maria Koukoulaki, Evangelos Papachristou, Christina Kalogeropoulou, Maria Papathanasiou, Petros Zampakis, Maria Vardoulaki, Dimitrios Alexopoulos, Dimitrios S Goumenos
{"title":"Increased Prevalence and Severity of Coronary Artery Calcification in Patients with Chronic Kidney Disease Stage III and IV.","authors":"Maria Koukoulaki,&nbsp;Evangelos Papachristou,&nbsp;Christina Kalogeropoulou,&nbsp;Maria Papathanasiou,&nbsp;Petros Zampakis,&nbsp;Maria Vardoulaki,&nbsp;Dimitrios Alexopoulos,&nbsp;Dimitrios S Goumenos","doi":"10.1159/000339786","DOIUrl":"https://doi.org/10.1159/000339786","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular disease (CVD) is the main cause of mortality in patients with chronic kidney disease (CKD). The pathophysiology of coronary artery disease in CKD is multifactorial including, in addition to traditional risk factors (hypertension, hyperlipidemia, diabetes mellitus), parameters related to uremia.</p><p><strong>Methods: </strong>The study consisted of measuring coronary artery calcification (CAC) score in patients with CKD stage III and IV without history of CVD and in a group of controls with normal renal function matched for age, gender and risk factors using multi-detector computed tomography.</p><p><strong>Results: </strong>The study included 49 patients and 49 controls. CAC was present in 79.6% in the CKD group versus 59.2% in the control group (p = 0.028). The median CAC score value in CKD patients was 139 (interquartile range (IQR): 23-321) versus 61 (IQR: 6-205) in controls (p = 0.007). CAC was associated with traditional risk factors such as older age, hypertension and baseline cardiovascular risk score, while CKD patients with severe calcification had marginally lower estimated glomerular filtration rate and increased levels of parathormone.</p><p><strong>Conclusions: </strong>CAC is more frequent and severe in patients with CKD stage III and IV compared to matched controls with normal renal function, even though kidney disease-related parameters are not directly correlated with intensity of calcification.</p>","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"192-204"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000339786","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30774015","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}
引用次数: 14
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