Muhammad Asim, Mohamad M Alkadi, Hania Asim, Adil Ghaffar
Dehydration and volume depletion describe two distinct body fluid deficit disorders with differing pathophysiology, clinical manifestations and treatment approaches. However, the two are often confused or equated with each other. Here, we address a number of commonly encountered misconceptions about body-fluid deficit disorders, analyse their origins and propose approaches to overcome them.
{"title":"Dehydration and volume depletion: How to handle the misconceptions.","authors":"Muhammad Asim, Mohamad M Alkadi, Hania Asim, Adil Ghaffar","doi":"10.5527/wjn.v8.i1.23","DOIUrl":"https://doi.org/10.5527/wjn.v8.i1.23","url":null,"abstract":"<p><p>Dehydration and volume depletion describe two distinct body fluid deficit disorders with differing pathophysiology, clinical manifestations and treatment approaches. However, the two are often confused or equated with each other. Here, we address a number of commonly encountered misconceptions about body-fluid deficit disorders, analyse their origins and propose approaches to overcome them.</p>","PeriodicalId":23745,"journal":{"name":"World Journal of Nephrology","volume":"8 1","pages":"23-32"},"PeriodicalIF":0.0,"publicationDate":"2019-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5527/wjn.v8.i1.23","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36966245","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}
Sung Han Kim, Whi-An Kwon, Jae Young Joung, Ho Kyung Seo, Kang Hyun Lee, Jinsoo Chung
Clear cell papillary renal cell carcinoma (ccpRCC) was recently established as a distinct type of epithelial neoplasm by the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia. Here, we report a case of partial nephrectomy for a ccpRCC detected during the routine follow-up of a previously treated liposarcoma in a 70-year-old male patient. The patient was referred to the urology department for a right-sided renal mass (size: 2 cm) detected during routine annual imaging follow-up for a malignant right inguinal fibrous histocytoma and liposarcoma that had been diagnosed 6 and 4 years earlier, respectively, and treated with surgery and adjuvant radiation therapy. Following partial nephrectomy, the renal mass was pathologically diagnosed as ccpRCC, and immunohistochemistry revealed carbonic anhydrase 9 (CA9) expression. No recurrences or metastases were detected on follow-up imaging for 6 months. This is the first report of partial nephrectomy for incidentally discovered CA9-positive ccpRCC.
{"title":"Clear cell papillary renal cell carcinoma: A case report and review of the literature.","authors":"Sung Han Kim, Whi-An Kwon, Jae Young Joung, Ho Kyung Seo, Kang Hyun Lee, Jinsoo Chung","doi":"10.5527/wjn.v7.i8.155","DOIUrl":"https://doi.org/10.5527/wjn.v7.i8.155","url":null,"abstract":"<p><p>Clear cell papillary renal cell carcinoma (ccpRCC) was recently established as a distinct type of epithelial neoplasm by the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia. Here, we report a case of partial nephrectomy for a ccpRCC detected during the routine follow-up of a previously treated liposarcoma in a 70-year-old male patient. The patient was referred to the urology department for a right-sided renal mass (size: 2 cm) detected during routine annual imaging follow-up for a malignant right inguinal fibrous histocytoma and liposarcoma that had been diagnosed 6 and 4 years earlier, respectively, and treated with surgery and adjuvant radiation therapy. Following partial nephrectomy, the renal mass was pathologically diagnosed as ccpRCC, and immunohistochemistry revealed carbonic anhydrase 9 (CA9) expression. No recurrences or metastases were detected on follow-up imaging for 6 months. This is the first report of partial nephrectomy for incidentally discovered CA9-positive ccpRCC.</p>","PeriodicalId":23745,"journal":{"name":"World Journal of Nephrology","volume":"7 8","pages":"155-160"},"PeriodicalIF":0.0,"publicationDate":"2018-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5527/wjn.v7.i8.155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36866141","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}
Vinod Krishnappa, William Hein, Daniel DelloStritto, Mona Gupta, Rupesh Raina
Patients with acute kidney injury (AKI) in the intensive care unit (ICU) are often suitable for palliative care due to the high symptom burden. The role of palliative medicine in this patient population is not well defined and there is a lack of established guidelines to address this issue. Because of this, patients in the ICU with AKI deprived of the most comprehensive or appropriate care. The reasons for this are multifactorial including lack of palliative care training among nephrologists. However, palliative care in these patients can help alleviate symptoms, improve quality of life, and decrease suffering. Palliative care physicians can determine the appropriateness and model of palliative care. In addition to shared decision-making, advance directives should be established with patients early on, with specific instructions regarding dialysis, and those advance directives should be respected.
{"title":"Palliative care for acute kidney injury patients in the intensive care unit.","authors":"Vinod Krishnappa, William Hein, Daniel DelloStritto, Mona Gupta, Rupesh Raina","doi":"10.5527/wjn.v7.i8.148","DOIUrl":"https://doi.org/10.5527/wjn.v7.i8.148","url":null,"abstract":"<p><p>Patients with acute kidney injury (AKI) in the intensive care unit (ICU) are often suitable for palliative care due to the high symptom burden. The role of palliative medicine in this patient population is not well defined and there is a lack of established guidelines to address this issue. Because of this, patients in the ICU with AKI deprived of the most comprehensive or appropriate care. The reasons for this are multifactorial including lack of palliative care training among nephrologists. However, palliative care in these patients can help alleviate symptoms, improve quality of life, and decrease suffering. Palliative care physicians can determine the appropriateness and model of palliative care. In addition to shared decision-making, advance directives should be established with patients early on, with specific instructions regarding dialysis, and those advance directives should be respected.</p>","PeriodicalId":23745,"journal":{"name":"World Journal of Nephrology","volume":"7 8","pages":"148-154"},"PeriodicalIF":0.0,"publicationDate":"2018-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4d/ad/WJN-7-148.PMC6305526.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36866140","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}
Renal artery stenosis is a common cause of secondary hypertension and chronic kidney disease. We present here a case of fibromuscular dysplasia that was treated with surgical revascularization, resulting in recovery of kidney function with eventual cessation of chronic dialysis. The case involves a 25-year-old female with coincidentally discovered hypertension, who underwent further investigations revealing a diagnosis of renal artery stenosis due to fibromuscular dysplasia. She subsequently developed two episodes of malignant hypertension, with flash pulmonary oedema and worsening renal failure that resulted in dialysis dependence. After evidence was obtained that the right kidney was still viable, a revascularization procedure was performed, improving blood pressure control and restoring kidney function, thereby allowing dialysis to be stopped. This case highlights the importance of evaluating patients with renal artery stenosis for revascularization before committing them to a life of chronic dialysis.
{"title":"Awakening the sleeping kidney in a dialysis-dependent patient with fibromuscular dysplasia: A case report and review of literature.","authors":"Mogamat-Yazied Chothia, Mogamat Razeen Davids, Raisa Bhikoo","doi":"10.5527/wjn.v7.i7.143","DOIUrl":"https://doi.org/10.5527/wjn.v7.i7.143","url":null,"abstract":"<p><p>Renal artery stenosis is a common cause of secondary hypertension and chronic kidney disease. We present here a case of fibromuscular dysplasia that was treated with surgical revascularization, resulting in recovery of kidney function with eventual cessation of chronic dialysis. The case involves a 25-year-old female with coincidentally discovered hypertension, who underwent further investigations revealing a diagnosis of renal artery stenosis due to fibromuscular dysplasia. She subsequently developed two episodes of malignant hypertension, with flash pulmonary oedema and worsening renal failure that resulted in dialysis dependence. After evidence was obtained that the right kidney was still viable, a revascularization procedure was performed, improving blood pressure control and restoring kidney function, thereby allowing dialysis to be stopped. This case highlights the importance of evaluating patients with renal artery stenosis for revascularization before committing them to a life of chronic dialysis.</p>","PeriodicalId":23745,"journal":{"name":"World Journal of Nephrology","volume":"7 7","pages":"143-147"},"PeriodicalIF":0.0,"publicationDate":"2018-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5527/wjn.v7.i7.143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36748538","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}
Samuel Shin, Aneil Srivastava, Nazira A Alli, Bidhan C Bandyopadhyay
Nephrolithiasis is increasing in developed and developing countries at an alarming rate. With the global spike in kidney stone diseases, it is crucial to determine what risk factors are influencing the current global landscape for kidney stones. Our aims for this review are: to identity and analyze the four categories of risk factors in contributing to the global scale of stone formation: lifestyle, genetics, diet, and environment; and discuss preventative measures for kidney stone formation. We also performed data search through the published scientific literature, i.e., PubMed® and found that there is a significant link between lifestyle and obesity with cases of calcium stones. Food and Agriculture Organization of the United Nations and World Health Organization factor indicators for dietary intake and obesity, along with climate data were used to create the projected total risk world map model for nephrolithiasis risk. Complete global analyses of nephrolithiasis deplete of generalizations is nearly insurmountable due to limited sources of medical and demographic information, but we hope this review can provide further elucidation into confounding risk factors and preventative measures for global nephrolithiasis analysis.
{"title":"Confounding risk factors and preventative measures driving nephrolithiasis global makeup.","authors":"Samuel Shin, Aneil Srivastava, Nazira A Alli, Bidhan C Bandyopadhyay","doi":"10.5527/wjn.v7.i7.129","DOIUrl":"https://doi.org/10.5527/wjn.v7.i7.129","url":null,"abstract":"<p><p>Nephrolithiasis is increasing in developed and developing countries at an alarming rate. With the global spike in kidney stone diseases, it is crucial to determine what risk factors are influencing the current global landscape for kidney stones. Our aims for this review are: to identity and analyze the four categories of risk factors in contributing to the global scale of stone formation: lifestyle, genetics, diet, and environment; and discuss preventative measures for kidney stone formation. We also performed data search through the published scientific literature, <i>i.e</i>., PubMed<sup>®</sup> and found that there is a significant link between lifestyle and obesity with cases of calcium stones. Food and Agriculture Organization of the United Nations and World Health Organization factor indicators for dietary intake and obesity, along with climate data were used to create the projected total risk world map model for nephrolithiasis risk. Complete global analyses of nephrolithiasis deplete of generalizations is nearly insurmountable due to limited sources of medical and demographic information, but we hope this review can provide further elucidation into confounding risk factors and preventative measures for global nephrolithiasis analysis.</p>","PeriodicalId":23745,"journal":{"name":"World Journal of Nephrology","volume":"7 7","pages":"129-142"},"PeriodicalIF":0.0,"publicationDate":"2018-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5527/wjn.v7.i7.129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36748537","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}
Chronic metabolic acidosis is a common complication seen in advanced chronic kidney disease (CKD). There is currently no consensus on its management in the Republic of Ireland. Recent trials have suggested that appropriate active management of metabolic acidosis through oral alkali therapy and modified diet can have a deterring impact on CKD progression. The potential benefits of treatment include preservation of bone health and improvement in muscle function; however, present data is limited. This review highlights the current evidence, available primarily from randomised control trials (RCTs) over the last decade, in managing the metabolic acidosis of CKD and outlines ongoing RCTs that are promising. An economic perspective is also briefly discussed to support decision-making.
{"title":"Oral alkali therapy and the management of metabolic acidosis of chronic kidney disease: A narrative literature review.","authors":"Adeel Rafi Ahmed, David Lappin","doi":"10.5527/wjn.v7.i6.117","DOIUrl":"https://doi.org/10.5527/wjn.v7.i6.117","url":null,"abstract":"<p><p>Chronic metabolic acidosis is a common complication seen in advanced chronic kidney disease (CKD). There is currently no consensus on its management in the Republic of Ireland. Recent trials have suggested that appropriate active management of metabolic acidosis through oral alkali therapy and modified diet can have a deterring impact on CKD progression. The potential benefits of treatment include preservation of bone health and improvement in muscle function; however, present data is limited. This review highlights the current evidence, available primarily from randomised control trials (RCTs) over the last decade, in managing the metabolic acidosis of CKD and outlines ongoing RCTs that are promising. An economic perspective is also briefly discussed to support decision-making.</p>","PeriodicalId":23745,"journal":{"name":"World Journal of Nephrology","volume":"7 6","pages":"117-122"},"PeriodicalIF":0.0,"publicationDate":"2018-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5527/wjn.v7.i6.117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36588163","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}
Aim: To examine possible alterations in acid-base parameters in patients switching from lanthanum carbonate (LanC) to sucroferric oxyhydroxide (SFOH).
Methods: Fifteen stable hemodialysis patients were switched from LanC to SFOH. Only nine continued on SFOH, three returned to LanC and the other three switched to sevelamer carbonate. The later six patients served as a control group to the SFOH group of nine patients. Blood was sampled on the 3-d and the last 2-d interval of the week prior to switching and six weeks after. Bicarbonate levels (HCO3-), pH, pO2, pCO2 were measured, and the mean of the two measurements (3-d and 2-d interval) was calculated.
Results: Comparing pre-switching to post-switching measurements in the SFOH group, no statistically significant differences were found in any of the parameters studied. The mean pre-switching HCO3- was 22.41 ± 1.66 mmol/L and the mean post-switching was 22.62 ± 2.25 mmol/L (P = 0.889). Respectively, the mean pH= 7.38 ± 0.03 vs 7.39 ± 0.03 (P = 0.635), mean pCO2= 38.41 ± 3.29 vs 38.37 ± 3.62 mmHg (P = 0.767), and Phosphate = 1.57 ± 0.27 vs 1.36 ± 0.38mmol/L (P = 0.214). There were not any significant differences when we performed the same analyses in the control group or between the SFOH group and control group. No correlations were found, either between pre-switching LanC daily dose or between post-switching daily dose of the new binder and the measured parameters.
Conclusion: In our small study, switching from LanC to SFOH did not have any significant effect on blood bicarbonate levels and gas analysis, indicating that there is no need to change hemodialysis prescription regarding these parameters.
目的:研究从碳酸镧(LanC)转向氢氧化铁(soh)的患者酸碱参数可能发生的变化。方法:将15例稳定血透患者由LanC转为SFOH。只有9个继续使用SFOH, 3个返回LanC,另外3个切换到七维拉姆碳酸。后6例患者作为SFOH组9例患者的对照组。在切换前一周和切换后六周的3-d和最后2-d间隔抽取血液。测量了碳酸氢盐(HCO3 -)、pH、pO2、pCO2水平,并计算了两者的平均值(三维和二维间隔)。结果:比较SFOH组切换前和切换后的测量结果,在研究的任何参数中均未发现统计学上的显著差异。切换前HCO3 -均值为22.41±1.66 mmol/L,切换后均值为22.62±2.25 mmol/L (P = 0.889)。平均pH= 7.38±0.03 vs 7.39±0.03 (P = 0.635),平均pCO2= 38.41±3.29 vs 38.37±3.62 mmHg (P = 0.767),平均磷酸盐= 1.57±0.27 vs 1.36±0.38mmol/L (P = 0.214)。当我们在对照组或SFOH组与对照组之间进行相同的分析时,没有任何显着差异。无论是切换前的LanC日剂量还是切换后的新粘合剂日剂量与测量参数之间都没有发现相关性。结论:在我们的小型研究中,从LanC切换到SFOH对血液碳酸氢盐水平和气体分析没有任何显著影响,表明无需改变血液透析处方的这些参数。
{"title":"Bicarbonate levels in hemodialysis patients switching from lanthanum carbonate to sucroferric oxyhydroxide.","authors":"Aristeidis Stavroulopoulos, Vasiliki Aresti, Christoforos Papadopoulos, Panagiotis Nennes, Polixeni Metaxaki, Anastasios Galinas","doi":"10.5527/wjn.v7.i6.123","DOIUrl":"https://doi.org/10.5527/wjn.v7.i6.123","url":null,"abstract":"<p><strong>Aim: </strong>To examine possible alterations in acid-base parameters in patients switching from lanthanum carbonate (LanC) to sucroferric oxyhydroxide (SFOH).</p><p><strong>Methods: </strong>Fifteen stable hemodialysis patients were switched from LanC to SFOH. Only nine continued on SFOH, three returned to LanC and the other three switched to sevelamer carbonate. The later six patients served as a control group to the SFOH group of nine patients. Blood was sampled on the 3-d and the last 2-d interval of the week prior to switching and six weeks after. Bicarbonate levels (HCO<sub>3</sub> <sup>-</sup>), pH, pO<sub>2</sub>, pCO<sub>2</sub> were measured, and the mean of the two measurements (3-d and 2-d interval) was calculated.</p><p><strong>Results: </strong>Comparing pre-switching to post-switching measurements in the SFOH group, no statistically significant differences were found in any of the parameters studied. The mean pre-switching HCO<sub>3</sub> <sup>-</sup> was 22.41 ± 1.66 mmol/L and the mean post-switching was 22.62 ± 2.25 mmol/L (<i>P</i> = 0.889). Respectively, the mean pH= 7.38 ± 0.03 <i>vs</i> 7.39 ± 0.03 (<i>P</i> = 0.635), mean pCO<sub>2</sub>= 38.41 ± 3.29 <i>vs</i> 38.37 ± 3.62 mmHg (<i>P</i> = 0.767), and Phosphate = 1.57 ± 0.27 <i>vs</i> 1.36 ± 0.38mmol/L (<i>P</i> = 0.214). There were not any significant differences when we performed the same analyses in the control group or between the SFOH group and control group. No correlations were found, either between pre-switching LanC daily dose or between post-switching daily dose of the new binder and the measured parameters.</p><p><strong>Conclusion: </strong>In our small study, switching from LanC to SFOH did not have any significant effect on blood bicarbonate levels and gas analysis, indicating that there is no need to change hemodialysis prescription regarding these parameters.</p>","PeriodicalId":23745,"journal":{"name":"World Journal of Nephrology","volume":"7 6","pages":"123-128"},"PeriodicalIF":0.0,"publicationDate":"2018-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5b/98/WJN-7-123.PMC6181871.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36588164","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}
Prani Paka, Brian Huang, Bin Duan, Jing-Song Li, Ping Zhou, Latha Paka, Michael A Yamin, Scott L Friedman, Itzhak D Goldberg, Prakash Narayan
Aim: To evaluate the novel platelet-derived growth factor receptor and vascular endothelial growth factor receptor dual kinase inhibitor ANG3070 in a polycystic kidney disease-congenital hepatic fibrosis model.
Methods: At 6 wk of age, PCK rats were randomized to vehicle or ANG3070 for 4 wk. At 10 wk, 24 h urine and left kidneys were collected and rats were continued on treatment for 4 wk. At 14 wk, 24 h urine was collected, rats were sacrificed, and liver and right kidneys were collected for histological evaluation. For Western blot studies, PCK rats were treated with vehicle or ANG3070 for 7 d and sacrificed approximately 30 min after the last treatments.
Results: Compared to the wild-type cohort, the PCK kidney (Vehicle cohort) exhibited a marked increase in kidney and liver mass, hepato-renal cystic volume, hepato-renal fibrosis and hepato-renal injury biomarkers. Intervention with ANG3070 in PCK rats decreased kidney weight, reduced renal cystic volume and reduced total kidney hydroxyproline, indicating significantly reduced rental interstitial fibrosis compared to the PCK-Vehicle cohort. ANG3070 treatment also mitigated several markers of kidney injury, including urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, cystatin C and interleukin-18 levels. In addition, this treatment attenuated key indices of renal dysfunction, including proteinuria, albuminuria and serum blood urea nitrogen and creatinine, and significantly improved renal function compared to the PCK-Vehicle cohort. ANG3070 treatment also significantly decreased liver enlargement, hepatic lesions, and liver fibrosis, and mitigated liver dysfunction compared to the PCK-Vehicle cohort.
Conclusion: These results suggest that ANG3070 has the potential to slow disease, and may serve as a bridge toward hepato-renal transplantation in patients with fibropolycystic disease.
{"title":"A small molecule fibrokinase inhibitor in a model of fibropolycystic hepatorenal disease.","authors":"Prani Paka, Brian Huang, Bin Duan, Jing-Song Li, Ping Zhou, Latha Paka, Michael A Yamin, Scott L Friedman, Itzhak D Goldberg, Prakash Narayan","doi":"10.5527/wjn.v7.i5.96","DOIUrl":"https://doi.org/10.5527/wjn.v7.i5.96","url":null,"abstract":"<p><strong>Aim: </strong>To evaluate the novel platelet-derived growth factor receptor and vascular endothelial growth factor receptor dual kinase inhibitor ANG3070 in a polycystic kidney disease-congenital hepatic fibrosis model.</p><p><strong>Methods: </strong>At 6 wk of age, PCK rats were randomized to vehicle or ANG3070 for 4 wk. At 10 wk, 24 h urine and left kidneys were collected and rats were continued on treatment for 4 wk. At 14 wk, 24 h urine was collected, rats were sacrificed, and liver and right kidneys were collected for histological evaluation. For Western blot studies, PCK rats were treated with vehicle or ANG3070 for 7 d and sacrificed approximately 30 min after the last treatments.</p><p><strong>Results: </strong>Compared to the wild-type cohort, the PCK kidney (Vehicle cohort) exhibited a marked increase in kidney and liver mass, hepato-renal cystic volume, hepato-renal fibrosis and hepato-renal injury biomarkers. Intervention with ANG3070 in PCK rats decreased kidney weight, reduced renal cystic volume and reduced total kidney hydroxyproline, indicating significantly reduced rental interstitial fibrosis compared to the PCK-Vehicle cohort. ANG3070 treatment also mitigated several markers of kidney injury, including urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, cystatin C and interleukin-18 levels. In addition, this treatment attenuated key indices of renal dysfunction, including proteinuria, albuminuria and serum blood urea nitrogen and creatinine, and significantly improved renal function compared to the PCK-Vehicle cohort. ANG3070 treatment also significantly decreased liver enlargement, hepatic lesions, and liver fibrosis, and mitigated liver dysfunction compared to the PCK-Vehicle cohort.</p><p><strong>Conclusion: </strong>These results suggest that ANG3070 has the potential to slow disease, and may serve as a bridge toward hepato-renal transplantation in patients with fibropolycystic disease.</p>","PeriodicalId":23745,"journal":{"name":"World Journal of Nephrology","volume":"7 5","pages":"96-107"},"PeriodicalIF":0.0,"publicationDate":"2018-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5527/wjn.v7.i5.96","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36488714","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}
Ameya Patil, William E Sweeney, Cynthia G Pan, Ellis D Avner
Aim: To delineate changes in miRNA expression localized to the peri-cystic local microenvironment (PLM) in an orthologous mouse model of autosomal dominant polycystic kidney disease (ADPKD) (mcwPkd1(nl/nl) ).
Methods: We profiled miRNA expression in the whole kidney and laser captured microdissection (LCM) samples from PLM in mcwPkd1(nl/nl) kidneys with Qiagen miScript 384 HC miRNA PCR arrays. The three times points used are: (1) post-natal (PN) day 21, before the development of trichrome-positive areas; (2) PN28, the earliest sign of trichrome staining; and (3) PN42 following the development of progressive fibrosis. PN21 served as appropriate controls and as the reference time point for comparison of miRNA expression profiles.
Results: LCM samples revealed three temporally upregulated miRNAs [2 to 2.75-fold at PN28 and 2.5 to 4-fold (P ≤ 0.05) at PN42] and four temporally downregulated miRNAs [2 to 2.75 fold at PN28 and 2.75 to 5-fold (P ≤ 0.05) at PN42]. Expression of twenty-six miRNAs showed no change until PN42 [six decreased (2.25 to 3.5-fold) (P ≤ 0.05) and 20 increased (2 to 4-fold) (P ≤ 0.05)]. Many critical miRNA changes seen in the LCM samples from PLM were not seen in the contralateral whole kidney.
Conclusion: Precise sampling with LCM identifies miRNA changes that occur with the initiation and progression of renal interstitial fibrosis (RIF). Identification of the target proteins regulated by these miRNAs will provide new insight into the process of fibrosis and identify unique therapeutic targets to prevent or slow the development and progression of RIF in ADPKD.
{"title":"Unique interstitial miRNA signature drives fibrosis in a murine model of autosomal dominant polycystic kidney disease.","authors":"Ameya Patil, William E Sweeney, Cynthia G Pan, Ellis D Avner","doi":"10.5527/wjn.v7.i5.108","DOIUrl":"https://doi.org/10.5527/wjn.v7.i5.108","url":null,"abstract":"<p><strong>Aim: </strong>To delineate changes in miRNA expression localized to the peri-cystic local microenvironment (PLM) in an orthologous mouse model of autosomal dominant polycystic kidney disease (ADPKD) (<i>mcwPkd1<sup>(nl/nl)</sup></i> ).</p><p><strong>Methods: </strong>We profiled miRNA expression in the whole kidney and laser captured microdissection (LCM) samples from PLM in <i>mcwPkd1<sup>(nl/nl)</sup></i> kidneys with Qiagen miScript 384 HC miRNA PCR arrays. The three times points used are: (1) post-natal (PN) day 21, before the development of trichrome-positive areas; (2) PN28, the earliest sign of trichrome staining; and (3) PN42 following the development of progressive fibrosis. PN21 served as appropriate controls and as the reference time point for comparison of miRNA expression profiles.</p><p><strong>Results: </strong>LCM samples revealed three temporally upregulated miRNAs [2 to 2.75-fold at PN28 and 2.5 to 4-fold (<i>P</i> ≤ 0.05) at PN42] and four temporally downregulated miRNAs [2 to 2.75 fold at PN28 and 2.75 to 5-fold (<i>P</i> ≤ 0.05) at PN42]. Expression of twenty-six miRNAs showed no change until PN42 [six decreased (2.25 to 3.5-fold) (<i>P</i> ≤ 0.05) and 20 increased (2 to 4-fold) (<i>P</i> ≤ 0.05)]. Many critical miRNA changes seen in the LCM samples from PLM were not seen in the contralateral whole kidney.</p><p><strong>Conclusion: </strong>Precise sampling with LCM identifies miRNA changes that occur with the initiation and progression of renal interstitial fibrosis (RIF). Identification of the target proteins regulated by these miRNAs will provide new insight into the process of fibrosis and identify unique therapeutic targets to prevent or slow the development and progression of RIF in ADPKD.</p>","PeriodicalId":23745,"journal":{"name":"World Journal of Nephrology","volume":"7 5","pages":"108-116"},"PeriodicalIF":0.0,"publicationDate":"2018-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5527/wjn.v7.i5.108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36488715","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}
The incidence of the collapsing variant of focal segmental glomerulosclerosis (FSGS) as a human immunodeficiency virus (HIV)-associated nephropathy has reduced since the introduction of antiretroviral therapy (ART). However, the incidence of other variants of FSGS, except for the collapsing variant, is increasing, and its therapeutic strategies remain uncertain. A 60-year-old HIV infected man in remission with ART was admitted for progressive renal insufficiency and nephrotic-ranged proteinuria. Renal biopsy revealed a tip variant of FSGS and his clinical manifestations resolved with corticosteroid therapy. HIV infected patients might develop non-collapsing FSGS, including tip variant of FSGS and corticosteroid therapy might be effective for them. A renal biopsy might be essential to determine the renal histology and to decide on corticosteroid therapy.
{"title":"Case of human immunodeficiency virus infection presenting as a tip variant of focal segmental glomerulosclerosis: A case report and review of the literature.","authors":"Daiki Goto, Naro Ohashi, Asumi Takeda, Yoshihide Fujigaki, Akira Shimizu, Hideo Yasuda, Kazuhisa Ohishi","doi":"10.5527/wjn.v7.i4.90","DOIUrl":"https://doi.org/10.5527/wjn.v7.i4.90","url":null,"abstract":"<p><p>The incidence of the collapsing variant of focal segmental glomerulosclerosis (FSGS) as a human immunodeficiency virus (HIV)-associated nephropathy has reduced since the introduction of antiretroviral therapy (ART). However, the incidence of other variants of FSGS, except for the collapsing variant, is increasing, and its therapeutic strategies remain uncertain. A 60-year-old HIV infected man in remission with ART was admitted for progressive renal insufficiency and nephrotic-ranged proteinuria. Renal biopsy revealed a tip variant of FSGS and his clinical manifestations resolved with corticosteroid therapy. HIV infected patients might develop non-collapsing FSGS, including tip variant of FSGS and corticosteroid therapy might be effective for them. A renal biopsy might be essential to determine the renal histology and to decide on corticosteroid therapy.</p>","PeriodicalId":23745,"journal":{"name":"World Journal of Nephrology","volume":"7 4","pages":"90-95"},"PeriodicalIF":0.0,"publicationDate":"2018-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5527/wjn.v7.i4.90","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36381335","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}