Kidney360最新文献

{"title":"nPOD-Kidney: A Heterogenous Donor Cohort for the Investigation of Diabetic Kidney Disease Pathogenesis and Progression.","authors":"Heather Hilary Ward, Florence Anquetil, Vivek Das, Claire Blanche Gibson, Tobias Højgaard Dovmark, Irina Kusmartseva, Mingder Yang, Maria Beery, Mark Alvin Atkinson, Xu Zeng, Charles Edward Alpers, Johnna Dane Wesley, Anil Karihaloo","doi":"10.34067/KID.0000000620","DOIUrl":"https://doi.org/10.34067/KID.0000000620","url":null,"abstract":"<p><strong>Background: </strong>The Network for Pancreatic Organ donors with Diabetes-Kidney (nPOD-K) project was initiated to assess the feasibility of using kidneys from organ donors to enhance understanding of diabetic kidney disease (DKD) progression.</p><p><strong>Methods: </strong>Traditional and digital pathology approaches were employed to characterize the nPOD-K cohort. Periodic acid-Schiff- and Hematoxylin and Eosin-stained sections were used to manually examine and score each nPOD-K case. Brightfield and fluorescently labelled whole slide images of nPOD-K sections were used to train, validate, and test deep learning compartment segmentation and machine learning image analysis tools within Visiopharm software. These digital pathology tools were subsequently employed to evaluate kidney cell-specific markers and pathological indicators.</p><p><strong>Results: </strong>Digital quantitation of mesangial expansion, tubular atrophy, kidney injury molecule (KIM)-1 expression, cellular infiltration, and fibrosis index aligned with histological DKD classification, as defined by pathologists' review. Histological quantification confirmed loss of podocyte, endothelial, and tubular markers, correlating with DKD progression. Altered expression patterns of prominin-1, protein-tyrosine phosphatase receptor type O, and coronin 2B were validated, in agreement with reported literature.</p><p><strong>Conclusions: </strong>The nPOD-K cohort provides a unique open resource opportunity to not only validate putative drug targets but also better understand DKD pathophysiology. A broad range of pathogenesis can be visualized in each case, providing a simulated timeline of DKD progression. We conclude that organ donor-derived tissues serve as high-quality samples, provide a comprehensive view of tissue pathology, and address the need for human kidney tissues available for research.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581500","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":"Building a Physician/Advanced Practice Provider Partnership for Inpatient Dialysis Care.","authors":"Rita L McGill, Tammy Poma, Arlene B Chapman","doi":"10.34067/KID.0000000633","DOIUrl":"https://doi.org/10.34067/KID.0000000633","url":null,"abstract":"","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522261","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":"Changes in Microbiome in Patients with Kidney Injury after Allogeneic Hematopoietic Stem Cell Transplantation.","authors":"Matthew H Abramson, Insara Jaffer Sathick, Andrea Knezevic, Miguel-Angel Perales, Edgar A Jaimes","doi":"10.34067/KID.0000000627","DOIUrl":"https://doi.org/10.34067/KID.0000000627","url":null,"abstract":"<p><strong>Background: </strong>Acute kidney injury (AKI) is a common complication of allogeneic hematopoietic cell transplantation (allo-HCT) that increases the risk of mortality. In contrast, higher diversity of intestinal microbiota at the time of neutrophil engraftment has been associated with lower mortality. We aimed to better understand kidney outcomes in relation to changes in gut diversity in this patient population, hypothesizing that patients with lower microbiome diversity at baseline and at engraftment were at higher risk of developing kidney complications.</p><p><strong>Methods: </strong>We performed a single-center retrospective study of 419 hematopoietic cell transplant recipients from 2014-2017 at our institution whose gut microbiota were analyzed. We defined AKI and CKD based on KDIGO criteria and estimated glomerular filtration rate (GFR) using the CKD Epidemiology Collaboration equation. We defined gut microbiome diversity using Shannon and Simpson reciprocal diversity indices, with higher levels indicating more diverse microbiota.</p><p><strong>Results: </strong>Simpson reciprocal DI and Shannon DI were 21.8 (IQR: 13.7, 35.2; range: 1.6, 102.5) and 3.7 (IQR: 3.2, 4.2; range: 0.7,5.2) in our cohort at baseline and 6.3 (IQR: 3.7, 10.4) and 2.3 (IQR: 1.7, 2.8) at peri-engraftment. Of the 419, 263 patients (63%) developed any grade AKI in 100 days post-HCT, and 114 (27%) developed Grade 2+ AKI. There were no significant differences in microbiome diversity at baseline or peri-engraftment in patients who developed post-transplant AKI or CKD, respectively, in comparison to those who did not develop kidney complications.</p><p><strong>Conclusions: </strong>Our findings do not support the existence of a link between baseline or peri-engraftment gut diversity and the risk for development of AKI or CKD in patients undergoing allo-HCT. This study highlights the complex and multifactorial etiology of AKI in allo-HCT recipients and the need for additional prospective and mechanistic studies.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503117","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":"Feasibility and Acceptability of a Palliative Care Intervention Among Older or Adults with Advanced CKD and their Caregivers.","authors":"Fahad Saeed, Robert K Horowitz, Rebecca J Allen, Peggy Auinger, Ronald M Epstein, Kevin A Fiscella, Peter J Veazie, Paul R Duberstein","doi":"10.34067/KID.0000000622","DOIUrl":"https://doi.org/10.34067/KID.0000000622","url":null,"abstract":"<p><strong>Background: </strong>In non-nephrology settings, specialty Palliative Care (PC) improves decision-making, patient's quality of life (QoL), advance care planning (ACP), and certain indicators of the quality of end-of-life (EoL) care. This pilot RCT explored the feasibility and acceptability of a PC intervention, CKD-EDU, for older adults ≥75 years with eGFR ≤25 ml/min and their caregivers.</p><p><strong>Methods: </strong>Participants randomized to the control group received standard nephrology care and routine kidney therapy (KT) education, while those randomized to CKD-EDU received a decision aid and met with a PC clinician up to three times to discuss KT decisions and EoL planning. Patients were assessed at baseline, 4-6, 12-14, and 24-26 weeks. Main outcomes included intervention feasibility and acceptability, decision-conflict, and patient QoL. The mediating effects of reduced decision conflict on improved QOL were explored, as were the effects of CKD-EDU on ACP, EoL treatment intensity and 6-month-hospitalization. Statistical analyses encompassed descriptive analyses, adjusted repeated-measure-models, mediation analyses and logistic-regression models.</p><p><strong>Results: </strong>Among the 127 eligible patients screened, 58 (44%) consented: 30 were randomized to CKD-EUD and 28 to the control arm. All patients completed baseline assessments, and 89% completed at least one intervention session (n=26/29), underscoring intervention adherence and feasibility. Similarly, assessments completion rates at 4 (83%, n=45/54) ), 12 (93%, n=42/45), and 24 (95%, n=40/42) weeks were high. The intervention received over 85% acceptability ratings for all questions. Patients exposed to CKD-EDU exhibited significant improvement in decisional conflict scale scores (P = 0.003) at 4-6 weeks and improvements in QoL at 24-26 weeks (P=0.02). Exploratory analyses were not statistically significant in this pilot, but all effect sizes were in the predicted direction.</p><p><strong>Conclusion: </strong>This study demonstrates the feasibility and acceptability of CKD-EDU. A larger scale trial is warranted to assess its effectiveness in improving key outcomes important to patients and families.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503120","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":"Risk of Postoperative Hypermagnesemia in Cardiopulmonary Bypass Assisted Cardiovascular Surgery.","authors":"Malak Ghaddar, Taha Hatab, Adel El-Kaakour, Hani Tamim, Maha Makki, Tasnim El-Halabi, Khalid Rifaii, Pierre Sfeir, Mayssaa Hoteit, Sahar H Koubar","doi":"10.34067/KID.0000000628","DOIUrl":"https://doi.org/10.34067/KID.0000000628","url":null,"abstract":"<p><strong>Background: </strong>Magnesium administration is a common practice in cardiovascular surgeries utilizing cardiopulmonary bypass (CPB). However, concerns persist regarding the risk of hypermagnesemia, particularly in patients with kidney dysfunction. This study aims to determine the incidence of postoperative hypermagnesemia in CPB-assisted cardiovascular surgeries and identify the associated risk factors.</p><p><strong>Methods: </strong>This was a retrospective cohort study conducted at a tertiary medical center. Data from adult patients undergoing open-heart surgery utilizing CPB between 2018 and 2020 were analyzed. Sociodemographic, perioperative, and clinical variables were collected from electronic medical records. Logistic regression was utilized to identify independent risk factors for hypermagnesemia.</p><p><strong>Results: </strong>Of 278 patients analyzed, 53.2% developed postoperative hypermagnesemia (Mg ≥2.5 mg/dL). Mild hypermagnesemia (Mg 2.5-3.9 mg/dL) was most common, with no significant impact on clinical outcomes observed. Patients with hypermagnesemia were older, with higher comorbidity burdens and lower baseline estimated glomerular filtration rate (eGFR). Cardioplegic solutions with higher magnesium content and lower baseline eGFR were independently associated with hypermagnesemia (OR 64.3; 95% CI 12.9-501.1 and OR 1.3; 95% CI, 1.1-1.5 respectively). Notably, ultrafiltration on CPB was associated with low risk of hypermagnesemia (OR 0.4, 95% CI 0.1-1.0, P value 0.048).</p><p><strong>Conclusions: </strong>This study highlights the importance of mindful magnesium supplementation strategies in those with advanced kidney disease. Future large-scale prospective multicenter studies should validate these findings and explore the extended effects of hypermagnesemia on clinical outcomes in patients with advanced CKD undergoing CPB surgeries.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503124","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":"Clinical and Humanistic Burden of IgAN in Adult Patients: A Global Real-World Survey.","authors":"Sydney C W Tang, Chen Wei, Carolina Aldworth, Aneesh T George, Julia Kattlun, Gisela R Tomas, Michel Kroes, Dario Roccatello, Raymond Przybysz, Serge Smeets, Keisha Golden, Jade Garratt-Wheeldon, Emma Chatterton, Jonathan de Courcy, Richard Lafayette","doi":"10.34067/KID.0000000613","DOIUrl":"https://doi.org/10.34067/KID.0000000613","url":null,"abstract":"<p><strong>Background: </strong>Immunoglobulin A nephropathy (IgAN) is a chronic, progressive kidney disease in which proteinuria, reduced estimated glomerular filtration rate (eGFR), pain and fatigue are common. How symptoms interact and impact patient quality of life (QoL) in real-world practice is poorly studied. This study investigated how patient and physician symptom perceptions differ and how proteinuria and eGFR correlate with pain, fatigue, and QoL in adult IgAN patients.</p><p><strong>Methods: </strong>Data were drawn from the Adelphi IgAN Disease Specific Programme™, a cross-sectional survey of physicians and their biopsy confirmed IgAN patients in China, France, Germany, Italy, Spain, the United Kingdom, United States, and Japan, from June-October 2021. Physicians provided demographics and clinical characteristics, including pain and fatigue severity. The same patients completed a self-completion form containing questions on symptom severity, the EQ-5D-5L, Kidney Disease Quality of Life, and Work Productivity and Activity Impairment questionnaires. Symptom scores were grouped by severity and patients grouped by proteinuria and eGFR. Analysis of variance, chi-squared or Fisher's exact tests were performed as appropriate and Dunn's multiple comparisons with Bonferroni adjustment for pair-wise comparisons.</p><p><strong>Results: </strong>Overall, 1515 patients were included (mean [standard deviation] age: 43 [15] years, 60% [n=903] male, 70% [n=1020/1459] diagnosed >1 year ago). Pain was reported by 46% (n=374) of physicians and 47% (n=384) of patients and fatigue by 65% (n=530) of physicians and 76% (n=620) of patients. Both pain and fatigue increased with increased proteinuria and reduced eGFR (all p<0.001). Finally, patients with increased proteinuria and reduced eGFR experienced worse (p<0.05) QoL and work productivity across all measures (except work absenteeism).</p><p><strong>Conclusions: </strong>Patients with higher proteinuria and lower eGFR face higher symptom burden and reduced QoL than their counterparts. Physicians underestimated fatigue levels faced by patients. In order to improve QoL, more effective treatments are needed to prevent high proteinuria and preserve eGFR.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503118","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":"Antimalarials in Lupus Nephritis: How Strong is the Evidence?","authors":"Fernando Caravaca-Fontán, Federico Yandian, Ladan Zand, Sanjeev Sethi, Fernando C Fervenza","doi":"10.34067/KID.0000000626","DOIUrl":"https://doi.org/10.34067/KID.0000000626","url":null,"abstract":"<p><p>Systemic lupus erythematosus is a chronic multisystem autoimmune disease that affects the kidneys in approximately 50% of patients, with prevalence rising to as high as 70% in certain populations, such as African Americans and Asians. Antimalarials -and particularly hydroxychloroquine- are currently considered a mainstay of therapy, together with immunosuppressants. Over the last decades, several studies have extensively investigated the mechanisms of action of antimalarial agents, and their potential beneficial properties in patients with SLE in general. However, the evidence for the therapeutic benefit of hydroxychloroquine in patients with lupus nephritis (LN) derives mainly from observational studies, conducted in an era prior to the refinement of induction and maintenance protocols for immunosuppressive therapy. Despite the paucity of high-quality evidence on its efficacy in LN, the nephrology community widely supports the universal use of hydroxychloroquine in LN patients, and recommendations for its use are firmly entrenched in various clinical practice guidelines. Nonetheless, the use of antimalarials may also carry inherent risks, underscoring the importance of personalized approaches in these patients. Herein, we comprehensively review the available literature on antimalarials in LN aiming to update the current evidence, limitations, and future perspectives for the use of antimalarials in adults.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503116","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":"The Occurrence of Senescence in the Arteriovenous Fistula in the Rat.","authors":"Karl A Nath, Luis A Juncos, Raman Deep Singh, Joseph P Grande, Anthony J Croatt, Allan W Ackerman, Karina S Kanamori, Christopher M Adams, Tamara Tchkonia, James L Kirkland, Zvonimir S Katusic","doi":"10.34067/KID.0000000605","DOIUrl":"https://doi.org/10.34067/KID.0000000605","url":null,"abstract":"<p><strong>Background: </strong>Maturational failure of dialysis arteriovenous fistulas (AVFs) not uncommonly occurs and is of considerable and timely importance. Our prior studies demonstrate that senescence, a phenotypic process that promotes vascular and other diseases, occurs in the murine AVF. In the present study, we examined whether senescence also occurs in the rat AVF model and the effect of compounds that inhibit or accelerate senescence.</p><p><strong>Methods: </strong>The rat AVF was created in the femoral vessels by an end vein-side artery anastomosis. We assessed in the AVF the expression of critical drivers of senescence, specifically, the cell cycle inhibitors p16Ink4a and p21Cip1, and such indices of a senescence phenotype as senescence-associated β-galactosidase (SA-β-gal) activity, SA-β-gal staining, and a senescence-associated secretory phenotype (SASP). We examined the effects of compounds that retard or accelerate senescence on AVF blood flow.</p><p><strong>Results: </strong>The AVF evinced upregulation of p16Ink4a and p21Cip1 when assessed 3 days after AVF creation. The AVF also demonstrated increased SA-β-gal activity in the artery and vein; staining for SA-β-gal in the AVF artery, anastomosis, and vein; and a prominent SASP. Fisetin, an established senolytic that is protective in other models of vascular injury, when administered for 3 weeks, increased AVF blood flow and outward remodeling. Hemin, when administered for 3 weeks, decreased AVF blood flow. We demonstrate that hemin is a novel inducer of a senescence phenotype in endothelial cells, as reflected by several senescence indices. However, when administered relatively acutely (for 5 days) hemin increased AVF blood flow via HO-dependent mechanisms, as the latter was entirely prevented by a competitive inhibitor of HO activity.</p><p><strong>Conclusions: </strong>The rat AVF exhibits senescence within 3 days of its creation. Chronic administration of a senolytic compound (fisetin) increases AVF blood flow, whereas chronic administration of a pro-senescence compound (hemin) decreases AVF blood flow.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468978","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":"Risk Score for Predicting AKI from Contrast-Enhanced CT (Pre-CT AKI score): Training and Validation from Retrospective Cohort.","authors":"Pattharawin Pattharanitima, Nutthaphol Bumrungsong, Bhapita Phoompho, Raksina Tanin, Suthiya Anumas","doi":"10.34067/KID.0000000623","DOIUrl":"https://doi.org/10.34067/KID.0000000623","url":null,"abstract":"<p><strong>Background: </strong>The lack of a recognized risk evaluation for Contrast-associated acute kidney injury (CA-AKI) after contrast-enhanced computed tomography (CECT) makes it challenging to counsel patients before the procedure. This study aims to identify the incidence of CA-AKI post CECT, assess the associated risk factors, develop and validate a predictive score.</p><p><strong>Methods: </strong>All adult patients who underwent CECT in 2018 to 2022 were included in the training cohort while those in 2023 formed the external validation cohort. Exclusions applied to patients with CKD stage 5, recent dialysis, or incomplete data. Multiple logistic regression was employed to identify risk factors. The area under the receiver operating characteristic curve (AUROC) was used to evaluate both internal and external validation.</p><p><strong>Results: </strong>From 21,878 enrolled patients, 6,042 and 2,463 met the inclusion criteria for the training and validation cohorts with a mean eGFR of 86.0 (26.4) and 81.4 (27.6) mL/min/1.73 m2, respectively. In the training cohort, 492 patients (8.1%) developed CA-AKI, and 49 (0.8%) required dialysis. Independent risk factors for CA-AKI included male gender, clinical setting, hemoglobin levels of <10 g/dL, and baseline eGFR less than 90 mL/min/1.73 m2. The model, using a weighted integer score derived from these factors, exhibited an AUROC of 0.715 (95% CI: 0.692-0.743) in the training cohort and 0.706 (95% CI: 0.663-0.748) in the validation cohort.</p><p><strong>Conclusions: </strong>CECT can lead to CA-AKI in specific populations. The Pre-CT AKI risk score for CA-AKI following CECT demonstrated good discriminative power and can be easily applied in clinical practice.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468977","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":"Familial Renal Glucosuria and Potential Pharmacogenetic Impact on SGLT2 Inhibitors.","authors":"Patrick Allaire, Jamie Fox, Terrie Kitchner, Rachel Gabor, Connie Folz, Shankar Bettadahalli, Scott Hebbring","doi":"10.34067/KID.0000000621","DOIUrl":"https://doi.org/10.34067/KID.0000000621","url":null,"abstract":"<p><strong>Background: </strong>Renal glucosuria is a rare inheritable trait caused by loss-of-function variants in the gene that encodes SGLT2 (i.e., SLC5A2). The genetics of renal glucosuria is poorly understood and even less is known on how loss-of-function variants in SLC5A2 may affect response to SGLT2 inhibitors, a new class of medication gaining popularity to treat diabetes by artificially inducing glucosuria.</p><p><strong>Methods: </strong>We used two biobanks that link genomic with electronic health record data to study the genetics of renal glucosuria. This included 245,394 participants enrolled in the All of Us (AoU) Research Program and 11,011 enrolled in Marshfield Clinic's Personalized Research Project (PMRP). Association studies in AoU and PMRP identified 10 variants that reached an experiment-wise Bonferroni threshold in either cohort, nine were novel. PMRP was further used as a recruitment source for a prospective SGLT2 pharmacogenetic trial. During a glucose tolerance test, the trial measured urine glucose concentrations in 15 SLC5A2 variant-positive individuals and 15 matched wild types with and without an SGLT2 inhibitor.</p><p><strong>Results: </strong>This trial demonstrated that carriers of SLC5A2 risk variants may be more sensitive to SGLT2 inhibitors compared to wild types (P=0.075). Based on population data, 2% of an ethnically diverse population carry rare variants in SLC5A2 and are at risk for renal glucosuria.</p><p><strong>Conclusions: </strong>As a result, 2% of individuals being treated with SGLT2 inhibitors may respond differently to this new class of medication compared to the general population suggesting a larger investigation into SLC5A2 variants and SGLT2 inhibitors is needed.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468979","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}