Frontiers in nephrology最新文献

{"title":"Bidirectional negative relationship between thyrotropin and kidney function during alcohol intoxication in males","authors":"Hayrunnisa Unlu, Asmaa Yehia, Khalid Manji, Noah Manji, Andrés M Treviño-Alvarez, Tommy Cabeza De Baca, Mark A. Frye, Leslie F. Thomas, Osama A. Abulseoud","doi":"10.3389/fneph.2024.1322791","DOIUrl":"https://doi.org/10.3389/fneph.2024.1322791","url":null,"abstract":"Despite a well-established direct toxic effect of alcohol on renal cells, there is a salutary dose-dependent effect of alcohol consumption on common laboratory parameters related to kidney performance. Alcohol also impacts thyroid hormones, while thyroid status modulates kidney function. The modulation of kidney parameters with thyrotropin (TSH) and thyroid status indicates a possible interaction between alcohol, kidney, and thyroid functions. This retrospective study was conducted to test the hypothesis that the positive effect of alcohol use on the estimated glomerular filtration rate (eGFR) is mediated by alcohol’s effect on thyroid hormones.We reviewed the electronic medical records of 767 hospitalized adult patients free of thyroid disorders who received medical care in the Mayo Clinic Health System from June 2019 through June 2022 and had blood alcohol concentration (BAC), serum TSH, and serum creatinine measured during the hospitalization. We calculated the eGFR using both the re-expressed Modification of Diet in Renal Disease (MDRD II) study equation and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine equation.We found a significant relationship of BAC with eGFR (CKD-EPI) and TSH in males only. BAC had a positive association with eGFR (b = 0.24, p = 0.0001) and negative with TSH (b=-0.17, p = 0.006). The covariance between the two outcomes (eGFR and TSH) was negative (b = -0.12, p = 0.049). The path analyses using the eGFR MDRD II equation were not significant in males, whereas females had no significant path analyses with either of the eGFR equations.We observed that BAC influences both eGFR and TSH, whereas eGFR and TSH influence each other. After considering important covariates (e.g., age, body mass index, diabetes mellitus, cardiovascular disease, chronic kidney disease, and chronic liver disease) and the negative bidirectional effect of TSH and eGFR, a positive impact of BAC on eGFR was observed in males.","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"8 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141926326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence based treatment for lupus nephritis: present perspectives and challenges.","authors":"Efstathios Xagas, Konstantinos Drouzas, George Liapis, Sophia Lionaki","doi":"10.3389/fneph.2024.1417026","DOIUrl":"10.3389/fneph.2024.1417026","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a complex autoimmune disease known for its high heterogeneity among individuals, which affects various organs including the kidneys. Lupus nephritis (LN) is a frequent and life-threatening manifestation of the disease, with up to 50% of patients developing kidney involvement. Classification of renal involvement in lupus is based on specific histopathological findings, guiding therapeutical decisions. Immunosuppressive therapy, particularly glucocorticoids combined with cyclophosphamide or mycophenolate mofetil, has been the mainstay of treatment for many years, while rates of complete remission have not changed dramatically. Despite advancements in therapy, in an important proportion of patients LN leads to end-stage kidney disease (ESKD). Emerging therapies including belimumab, voclosporin, and obinutuzumab offer promising results in improving renal outcomes, especially in refractory or relapsing disease. Maintenance therapy is crucial to prevent disease flares and preserve renal function. Supportive measures including lifestyle modifications and non-immunosuppressive pharmacological interventions are nowadays also essential in managing LN. This review emphasizes recent advances of therapy and challenges regarding treatment optimization with strategies to improve long-term outcomes.</p>","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"4 ","pages":"1417026"},"PeriodicalIF":0.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009999","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":"Short-term therapy with R568 ameliorated secondary hyperparathyroidism but does not prevent aortic valve calcification in uremic rats.","authors":"Asmahan Abu-Snieneh, Irina Gurt, Suzan Abedat, Chaim Lotan, Michael Glikson, Mony Shuvy","doi":"10.3389/fneph.2024.1385705","DOIUrl":"10.3389/fneph.2024.1385705","url":null,"abstract":"<p><strong>Introduction: </strong>Renal failure associated aortic valve calcification (AVC) is the result of hyperphosphatemia and hyperparathyroidism. Calcimimetics is an effective tool for management of secondary hyperparathyroidism. Our goal was to evaluate the effect of the medical intervention with calcimimetic R568 on the AVC process.</p><p><strong>Methods and results: </strong>The experimental design consisted of administering a uremia-inducing phosphate-enriched diet to rats for six weeks. Rats received a daily R568 injection at different times. Biochemical analysis demonstrated increased urea (34.72 ± 3.57 <i>vs</i>. 5.18 ± 0.15 mmol/L, <i>p</i><0.05) and creatinine (293.93 ± 79.6 <i>vs</i>. 12.82 ± 1.56 µmol/L, <i>p</i><0.05). R568 treatment markedly reduced parathyroid hormone (PTH) levels in both treated groups (192.63 ± 26.85, 301.23 ± 101.79 <i>vs</i>. 3570 ± 986.63 pg/mL, <i>p</i><0.05), with no impact on serum calcium and phosphate. von Kossa staining showed increase in AVC in uremic rats compared to control (1409 ± 159.5 <i>vs</i>. 27.33 ± 25.83, <i>p</i><0.05). AVC was not affected by R568 in both groups (3343 ± 2462, 1593 ± 792 <i>vs</i>. 1409 ± 159.5, NS). Similarly, the inflammatory marker CD68 was elevated in uremic rats (15592 ± 3792 <i>vs</i>. 181.8 ± 15.29, <i>p</i><0.01), and was not influenced by R568 treatment (8453 ± 818.5, 9318 ± 2232 <i>vs</i>. 15592 ± 3792, NS). Runt-related transcription factor 2 (Runx2), the regulator of osteoblast differentiation, was upregulated in uremic rats (23186 ± 9226 <i>vs</i>. 3184 ± 2495), that accompanied by elevated levels of Osteopontin (158395 ± 45911 <i>vs</i>. 237.7 ± 81.5, <i>p</i><0.05) and Osteocalcin (22203 ± 8525 <i>vs</i>. 489.7 ± 200.6, <i>p</i><0.05). R568 had no impact on osteoblastic markers (Runx2: 21743 ± 3193, 23004 ± 10871 <i>vs</i>. 23186 ± 9226, NS; osteopontin: 57680 ± 19522, 137116 ± 60103 <i>vs</i>. 158395 ± 45911, NS; osteocalcin: 10496 ± 5429, 8522 ± 5031 <i>vs</i>. 22203 ± 8525, NS).</p><p><strong>Conclusion: </strong>In an adenine-induced uremic rat model, we showed that short-term R568 therapy had no effect on AVC. Treatment with R568 decreased PTH levels but had no effect on high phosphate levels. Regression of AVC necessitates not only a decrease in PTH levels, but also a decline in phosphate levels. To achieve improved outcomes, it is advisable to consider administering a combination of R568 with other medications, such as calcium supplements or phosphate binders. Additional studies are required for further evaluation of the potential treatment of chronic kidney disease (CKD)-associated AVC.</p>","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"4 ","pages":"1385705"},"PeriodicalIF":0.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142010000","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":"Case report: Roxadustat overdose in an anemia patient of chronic kidney disease: insight beyond insignificant consequence.","authors":"Long-Guang Zhang, Xue-Juan Ma, Xiang-Yang Li","doi":"10.3389/fneph.2024.1413496","DOIUrl":"10.3389/fneph.2024.1413496","url":null,"abstract":"<p><p>A 71-year-old man with a 20-year history of grade 3 hypertension experienced kidney dysfunction 2 years earlier. His serum creatinine (SCr) at the time was 140 μmol/L [with estimated glomerular filtration rate (eGFR) of 43.9 ml/min per 1.73m²], for which he received irbesartan since. At initial presentation, the spot urine dipstick protein was 1+, with an albumin-to-creatinine ratio of 230 mg/g (0-30) and normal urine sediments. The SCr was 176 μmol/L (eGFR = 32.8 ml/min per 1.73m²). The hemoglobulin (Hb) level decreased from 102 to 96 g/L despite oral ferrous succinate 100 mg twice daily starting 2 months ago. Roxadustat (ROXA) 50 mg (body weight, 70 kg) three times weekly was then prescribed. Unfortunately, the patient mistakenly took the drug at 50 mg three times a day (i.e., 1,050 mg instead of the intended 150 mg per week), which was 3.5 times the recommended starting dose for non-dialysis-dependent chronic kidney disease (CKD) patients (100 mg three times weekly for body weight >60 kg) and two times the highest drug manual-recommended weekly dose (2.5 mg/kg three times weekly) approved in the country. When the attending nephrologist discovered the misuse 1 month later, the patient reported no apparent discomfort, and his home blood pressure was in the range 110-130/60-80 mmHg. Repeat blood tests showed that the Hb increased from 96 to 163 g/L and the SCr from 199 to 201 μmol/L in a month. The serum alanine transaminase (ALT) remained within the normal range (from 12 U/L at baseline to 20 U/L), while the serum total and indirect bilirubin levels were slightly elevated. ROXA was withheld immediately. In 30 days, the serum bilirubin returned to baseline, but the Hb decreased from 163 to 140 g/L, and then to 108 g/L after 3 months. On the other hand, the SCr increased from 179 to 203 μmol/L. At 9 months after the initial dosing, when the SCr increased to 256 μmol/L and the Hb decreased to 94 g/L again, ROXA 50 mg three times weekly was reinitiated uneventfully. Herein, by introducing a case who erroneously consumed twice the highest recommended dose of ROXA for a month, but had apparently no obvious discomfort or unfavorable consequence, we attempt to provide a brief overview of the mechanism of action, characteristics, drug metabolism, and side effect profile associated with this agent.</p>","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"4 ","pages":"1413496"},"PeriodicalIF":0.0,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11327132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001488","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":"Eicosapentaenoic acid supplementation alleviates pruritus, enhances skin moisture, and mitigates depression in maintenance hemodialysis patients.","authors":"Ya-Ling Lin, Chia-Liang Wang, Tsay-I Chiang","doi":"10.3389/fneph.2024.1365809","DOIUrl":"10.3389/fneph.2024.1365809","url":null,"abstract":"<p><strong>Background: </strong>The objective of this study is to investigate the effects of oral supplementation with eicosapentaenoic acid (EPA) on circulating inflammatory factors, cardiometabolic parameters, skin moisturization, and the consequent symptoms of pruritus and depression in maintenance hemodialysis patients.</p><p><strong>Materials and methods: </strong>A total of 60 maintenance hemodialysis patients with severe pruritus symptoms completed this randomized, placebo-controlled study. Subjects of treatment group (n = 30) were instructed to consume 1000 mg fish oil (>900 mg EPA) and subjects of placebo group (n = 30) were instructed to consume 1000 mg soybean oil twice daily for 3 months. 5-D pruritus scoring, the Beck Depression Inventory (BDI) scale, skin moisture, serum creatinine, inflammatory factors, and cardiometabolic parameters were examined at baseline, and at the first, second, and third month post-supplementation.</p><p><strong>Results: </strong>A significantly decreased pruritus level was observed in the treatment group, whereas an opposite result was observed in the placebo group. Increased skin moisture levels on both the face and arms were observed in the treatment group, but not in the placebo group. Supplementation of EPA significantly decreased serum CRP and IL-6 levels. Significant decreases in total cholesterol (CHO), and triglycerides (TG) levels were observed; however, a decrease in high-density lipoprotein (HDL) level was observed in the treatment group. There was no change in plasma creatinine (CR) observed in both groups. A significantly decreased BDI score was observed, whereas the opposite result was observed in the placebo group. A correlational study showed that the severity of pruritus was significantly associated with skin moisture and serum CRP. The severity of pruritus was also positively correlated with the BDI score.</p><p><strong>Conclusion: </strong>Supplementation of EPA may provide multiple benefits including alleviating pruritus symptoms, addressing skin dryness, and mitigating depression in maintenance hemodialysis patients.</p>","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"4 ","pages":"1365809"},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977402","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":"Lupus nephritis kidney biopsy characteristics and preterm birth.","authors":"Monica L Reynolds, Keisha L Gibson, Tracy A Manuck, Caroline J Poulton, Lauren Blazek, Alison M Stuebe, Susan L Hogan, Ronald J Falk, Vimal K Derebail","doi":"10.3389/fneph.2024.1402597","DOIUrl":"10.3389/fneph.2024.1402597","url":null,"abstract":"<p><p>Individuals with lupus nephritis (LN) are at high risk of adverse maternal and fetal outcomes in pregnancy. Outside of pregnancy, proliferative lesions on kidney biopsies are associated with disease progression, but these have not been consistently associated with increased risk in pregnancy. This retrospective, single-center study examines how histologic findings, the timing from kidney biopsy to pregnancy, and the clinical features in the first trimester are associated with preterm birth among individuals with LN. Among 35 deliveries in 31 women, the mean gestational age at delivery was 33.8 weeks. The presence of a urine protein-to-creatinine ratio >0.5 g/g in the first trimester was associated with preterm delivery (81% vs. 36%, <i>p</i> = 0.04). Preterm birth was more common in individuals with glomerular crescents on biopsy (89% in those with >20% crescents vs. 50% in those with <20%, <i>p</i> = 0.06). A pregnancy occurring within 2 years after a kidney biopsy was more likely to result in preterm birth than if the biopsy was performed more than 2 years prior to conception (82% vs. 23%, <i>p</i> = 0.01). The time from diagnostic biopsy may be a surrogate for disease activity, and a 2-year delay from biopsy might allow sufficient time to achieve disease remission. Overall, these data could aid family planning discussions and promote preconception disease optimization for patients and their providers.</p>","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"4 ","pages":"1402597"},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977403","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 case report of dipeptidyl peptidase 4 inhibitor-related kidney disease combined with renal cancer.","authors":"Shigekazu Kurihara, Naoki Sawa, Keiichi Sumida, Daisuke Ikuma, Yuki Oba, Hiroki Mizuno, Akinari Sekine, Masayuki Yamanouchi, Eiko Hasegawa, Tatsuya Suwabe, Shinji Urakami, Kei Kono, Keiichi Kinowaki, Kenichi Ohashi, Yutaka Yamaguchi, Yoshifumi Ubara","doi":"10.3389/fneph.2024.1409098","DOIUrl":"10.3389/fneph.2024.1409098","url":null,"abstract":"<p><p>A kidney biopsy was performed in a 64-year-old woman with type 2 diabetes mellitus and less than 1 g of proteinuria who rapidly progressed to end-stage renal failure after approximately 2 years of treatment with two dipeptidyl peptidase 4 (DPP-4) inhibitors for type 2 diabetes mellitus. The biopsy revealed not only a coincidental diagnosis of renal cell carcinoma, which was not evident on pre-biopsy computed tomography, but also severe thrombotic microangiopathy (TMA)-like glomerular endothelial cell damage in the noncancerous areas. These results suggest that DPP4 inhibitors may have been involved in two kidney diseases.</p>","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"4 ","pages":"1409098"},"PeriodicalIF":0.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11317433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972403","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":"Corrigendum: Case report: Unveiling a less severe congenital nephrotic syndrome in a Rapa Nui patient with a <i>NPHS1</i> Maori founder variant.","authors":"Paola Krall, Angélica Rojo, Anita Plaza, Sofia Canals, María Luisa Ceballos, Francisco Cano, José Luis Guerrero","doi":"10.3389/fneph.2024.1454138","DOIUrl":"https://doi.org/10.3389/fneph.2024.1454138","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fneph.2024.1379061.].</p>","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"4 ","pages":"1454138"},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636455","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":"Examining the role of patient-reported external factors and risk of relapse in anti-neutrophilic cytoplasmic autoantibody vasculitis.","authors":"Mary M Collie, Dhruti P Chen, Yichun Hu, Lauren N Blazek, Vimal K Derebail, Eveline Y Wu, Koyal Jain, Nicole Orzechowski, Caroline J Poulton, Candace D Henderson, Ronald J Falk, Susan L Hogan","doi":"10.3389/fneph.2024.1404451","DOIUrl":"10.3389/fneph.2024.1404451","url":null,"abstract":"<p><p>The role of stressors, insect bites, and infections on disease relapse of ANCA vasculitis has yet to be entirely explored, with limited retrospective studies focused on disease onset from small participant cohorts. Our study analyzes longitudinal survey data from 2011-2022 to evaluate this perspective from a large ANCA vasculitis cohort. We collected surveys every three to six months to obtain information on self-reported psychological stressors and significant life events, insect bites, and infections throughout clinical disease. We defined cohorts as those who relapsed (Relapse Cohort) and controls as those who did not relapse (Remission Cohort) during the study period. Survey responses were retrospectively reviewed during a 15-month timeframe prior to relapse or during 15 months of remission and categorized by type of stress event, insect bite, and infections at every available 3-month interval. There were no significant differences in stress and insect bites between the relapse and remission cohorts. Patients who relapsed reported more frequent upper respiratory infections and other infections, such as those affecting the skin and eyes, but there were no significant differences in the incidence of pulmonary or urinary infections compared to the remission cohort. There was a significant difference in reported upper respiratory infections 9 to 15 months prior to the relapse date, indicating a remote history of infections as a potentially significant physical stressor that may contribute to disease relapse. More frequent patient-reported infections, specifically upper respiratory infections, may contribute to patient vulnerability to relapse. Counseling and close monitoring of patients after infectious symptoms could aid in earlier detection of disease flares. Future studies are essential to further understand the importance of distal risk factors and how they impact relapse.</p>","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"4 ","pages":"1404451"},"PeriodicalIF":0.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11249541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629372","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":"Role of plasminogen activated inhibitor-1 in the pathogenesis of anticoagulant related nephropathy.","authors":"Ajay Medipally, Min Xiao, Laura Biederman, Alana Dasgupta, Anjali A Satoskar, Samir Parikh, Iouri Ivanov, Galina Mikhalina, Sergey V Brodsky","doi":"10.3389/fneph.2024.1406655","DOIUrl":"10.3389/fneph.2024.1406655","url":null,"abstract":"<p><p>Anticoagulant related nephropathy (ARN) is the result of glomerular hemorrhage in patients on systemic anticoagulation therapy or underlying coagulopathy. Red blood cells (RBC) that passed through the glomerular filtration barrier form RBC casts in the tubules, increase oxidative stress and result in acute tubular necrosis (ATN). The mechanisms of ARN still not completely discovered. Plasminogen activator inhibitor-1 (PAI-1) plays a significant role in the maintenance of coagulation homeostasis. We developed an animal model to study ARN in 5/6 nephrectomy (5/6NE) rats. The aim of this study was to elucidate the role of PAI-1 in the ARN pathogenesis. 5/6NE rats were treated per os with warfarin (0.75 mg/kg/day) or dabigatran (150 mg/kg/day) alone or in combination with PAI-1 antagonist TM5441 (2.5, 5.0 and 10 mg/kg/day). TM5441 in a dose dependent manner ameliorated anticoagulant-induced increase in serum creatinine in 5/6NE rats. Anticoagulant-associated increase in hematuria was no affected by TM5441. The levels of reactive oxygen species (ROS) in the kidneys were in a dose-dependent manner decreased in 5/6NE rats treated with an anticoagulant and TM5441. Our data demonstrates that PAI-1 may reduce ARN by decreasing ROS in the kidneys. Glomerular hemorrhage is not affected by anti-PAI-1 treatment. These findings indicate that while symptoms of ARN can be reduced by PAI-1 inhibition, the main pathogenesis of ARN - glomerular hemorrhage - cannot be prevented.</p>","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"4 ","pages":"1406655"},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11239567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617720","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}