Pub Date : 2025-12-02DOI: 10.1016/j.xkme.2025.101195
Thomas Remer , Seyedeh-Masomeh Derakhshandeh-Rishehri , Yifan Hua , Luciana Peixoto Franco , Hermann Kalhoff , Stefan A. Wudy
<div><h3>Rationale & Objective</h3><div>Metabolic acidosis and reduced serum bicarbonate levels are known to contribute to kidney disease progression. Whether habitual high net endogenous acid production early in life may have consequences for long-term kidney function is not known. To date, no longitudinal study has examined the relationships between regular net acid excretion (NAE) during childhood and adolescence and later adult albumin excretion, estimated glomerular filtration rate (eGFR), and creatinine clearance (CL<sub>Cr</sub>).</div></div><div><h3>Study Design</h3><div>Open cohort study examining healthy children from infancy to adulthood.</div></div><div><h3>Setting & Participants</h3><div>Study participants with multiple 24-hour urine collections between ages 3 and 17 years who provided a blood sample between ages 18 and 35 years.</div></div><div><h3>Exposure</h3><div>Pre-adulthood NAE and its components ammonium excretion, titratable acidity, and pH.</div></div><div><h3>Outcomes</h3><div>Adults’ eGFR, CL<sub>Cr</sub>, and albumin-creatinine ratio (ACR).</div></div><div><h3>Analytical Approach</h3><div>Sex- and age-stratified standard deviation scores calculated for anthropometric and urinary biomarkers were averaged for each individual, and the relationships between urinary exposures and adulthood eGFR, CL<sub>Cr</sub>, and ACR were examined using multiple linear regression analysis. Regression models were adjusted for pre-adulthood nutrition-related renal biomarker standard deviation scores and various adult parameters.</div></div><div><h3>Results</h3><div>In fully adjusted models, children’s and adolescents’ repeatedly measured renal NAE and titratable acidity had a strong inverse association and their 24-hour urinary pH had a highly significant positive association with eGFR in adulthood. Similar findings were seen for CL<sub>Cr</sub>. Pre-adulthood ammonium excretion had a significant positive relationship only with ACR in adulthood.</div></div><div><h3>Limitations</h3><div>Outcomes determined only once.</div></div><div><h3>Conclusions</h3><div>These exclusively biomarker-based findings strongly suggest that habitually increased NAE and corresponding low urinary pH values in the normal range in childhood and adolescence are already related to incipient signs of kidney function decline in adulthood. Hence, as an important kidney health prevention measure, habitual consumption of alkalizing fruit- and vegetable-rich diets with clear ammoniagenic and NAE-lowering efficiency should start early in childhood.</div></div><div><h3>Plain-Language Summary</h3><div>Metabolic acidosis negatively affects kidney function. Whether habitually high renal net acid excretion early in life may already negatively affect kidney function in the long run is not known. By examining healthy children’s and adolescents’ acid excretion and urinary pH values in 24-hour urine samples, repeatedly collected during ages 3-17 years, we demonstrated that hi
{"title":"Renal Net Acid Excretion During Growth and eGFR, Creatinine Clearance, and Albuminuria in Young Adulthood","authors":"Thomas Remer , Seyedeh-Masomeh Derakhshandeh-Rishehri , Yifan Hua , Luciana Peixoto Franco , Hermann Kalhoff , Stefan A. Wudy","doi":"10.1016/j.xkme.2025.101195","DOIUrl":"10.1016/j.xkme.2025.101195","url":null,"abstract":"<div><h3>Rationale & Objective</h3><div>Metabolic acidosis and reduced serum bicarbonate levels are known to contribute to kidney disease progression. Whether habitual high net endogenous acid production early in life may have consequences for long-term kidney function is not known. To date, no longitudinal study has examined the relationships between regular net acid excretion (NAE) during childhood and adolescence and later adult albumin excretion, estimated glomerular filtration rate (eGFR), and creatinine clearance (CL<sub>Cr</sub>).</div></div><div><h3>Study Design</h3><div>Open cohort study examining healthy children from infancy to adulthood.</div></div><div><h3>Setting & Participants</h3><div>Study participants with multiple 24-hour urine collections between ages 3 and 17 years who provided a blood sample between ages 18 and 35 years.</div></div><div><h3>Exposure</h3><div>Pre-adulthood NAE and its components ammonium excretion, titratable acidity, and pH.</div></div><div><h3>Outcomes</h3><div>Adults’ eGFR, CL<sub>Cr</sub>, and albumin-creatinine ratio (ACR).</div></div><div><h3>Analytical Approach</h3><div>Sex- and age-stratified standard deviation scores calculated for anthropometric and urinary biomarkers were averaged for each individual, and the relationships between urinary exposures and adulthood eGFR, CL<sub>Cr</sub>, and ACR were examined using multiple linear regression analysis. Regression models were adjusted for pre-adulthood nutrition-related renal biomarker standard deviation scores and various adult parameters.</div></div><div><h3>Results</h3><div>In fully adjusted models, children’s and adolescents’ repeatedly measured renal NAE and titratable acidity had a strong inverse association and their 24-hour urinary pH had a highly significant positive association with eGFR in adulthood. Similar findings were seen for CL<sub>Cr</sub>. Pre-adulthood ammonium excretion had a significant positive relationship only with ACR in adulthood.</div></div><div><h3>Limitations</h3><div>Outcomes determined only once.</div></div><div><h3>Conclusions</h3><div>These exclusively biomarker-based findings strongly suggest that habitually increased NAE and corresponding low urinary pH values in the normal range in childhood and adolescence are already related to incipient signs of kidney function decline in adulthood. Hence, as an important kidney health prevention measure, habitual consumption of alkalizing fruit- and vegetable-rich diets with clear ammoniagenic and NAE-lowering efficiency should start early in childhood.</div></div><div><h3>Plain-Language Summary</h3><div>Metabolic acidosis negatively affects kidney function. Whether habitually high renal net acid excretion early in life may already negatively affect kidney function in the long run is not known. By examining healthy children’s and adolescents’ acid excretion and urinary pH values in 24-hour urine samples, repeatedly collected during ages 3-17 years, we demonstrated that hi","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 2","pages":"Article 101195"},"PeriodicalIF":3.4,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978472","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}
Pub Date : 2025-12-02DOI: 10.1016/j.xkme.2025.101194
Hirokazu Marumoto , Takaya Sasaki , Emi Oishi , Satoko Sakata , Mao Shibata , Yoshihiko Furuta , Jun Hata , Yoshinao Oda , Takanari Kitazono , Nobuo Tsuboi , Takashi Yokoo , Toshiharu Ninomiya
<div><h3>Rationale & Objective</h3><div>Nephrosclerosis is a major cause of end-stage kidney disease. However, few studies have addressed the association between kidney function and nephrosclerosis-related histopathologic findings because most cases of nephrosclerosis are diagnosed based on clinical signs without a kidney biopsy.</div></div><div><h3>Study Design</h3><div>Cross-sectional study.</div></div><div><h3>Setting & Participants</h3><div>Autopsy specimens of kidneys were obtained from 181 individuals who died within 6 years of a community-wide health examination in 2007 and who had an autopsy at the time of death.</div></div><div><h3>Exposure</h3><div>Histopathologic findings, including glomerular, tubulointerstitial, and vascular lesions, were evaluated as outcome variables in relation to estimated glomerular filtration rate. The kidney cortex in each specimen was divided into 3 equally spaced cortical regions (superficial, middle, and juxtamedullary cortex) to assess depth-dependent lesion distribution.</div></div><div><h3>Outcomes</h3><div>Glomerular, tubulointerstitial, and vascular lesions were evaluated in cortical regions at different depths.</div></div><div><h3>Analytical Approach</h3><div>Associations between estimated glomerular filtration rate levels and the extent of histopathologic findings based on cortical region were tested using generalized linear mixed-effects models.</div></div><div><h3>Results</h3><div>The present study included 172 autopsied cases (mean age: 81 years; men: 50%). The extent of histopathologic lesions progressed significantly with worsening kidney function, and the association was similar in each cortical region. Analysis based on cortical region showed significant gradients in the extent/severity of nephrosclerotic lesions, with global glomerulosclerosis and interstitial fibrosis and tubular atrophy dominating in the superficial cortex and arterial intima-media thickness and arteriolar hyalinosis dominating in the juxtamedullary cortex. The cortical region specificity of histopathologic findings in nephrosclerosis became less prominent with worsening kidney function.</div></div><div><h3>Limitations</h3><div>Participants were elderly, and the causal relationship between pathologic findings and renal dysfunction could not be determined.</div></div><div><h3>Conclusions</h3><div>The present study confirms a cortical region--dependent gradient of nephrosclerotic lesions within the kidney and suggests that arterial and tubulointerstitial lesions may be more strongly linked with kidney dysfunction than glomerular lesions.</div></div><div><h3>Plain-Language Summary</h3><div>Although nephrosclerosis is a major cause of end-stage renal failure, few studies have addressed its histopathologic relationship with kidney function. In this study, kidney specimens from 172 Japanese community residents at the time of death were evaluated based on 6 histopathologic indices in 3 renal cortical regions. The extent of
{"title":"Nephrosclerosis-Related Histopathological Findings by Cortical Region From a Japanese Community-Based Study","authors":"Hirokazu Marumoto , Takaya Sasaki , Emi Oishi , Satoko Sakata , Mao Shibata , Yoshihiko Furuta , Jun Hata , Yoshinao Oda , Takanari Kitazono , Nobuo Tsuboi , Takashi Yokoo , Toshiharu Ninomiya","doi":"10.1016/j.xkme.2025.101194","DOIUrl":"10.1016/j.xkme.2025.101194","url":null,"abstract":"<div><h3>Rationale & Objective</h3><div>Nephrosclerosis is a major cause of end-stage kidney disease. However, few studies have addressed the association between kidney function and nephrosclerosis-related histopathologic findings because most cases of nephrosclerosis are diagnosed based on clinical signs without a kidney biopsy.</div></div><div><h3>Study Design</h3><div>Cross-sectional study.</div></div><div><h3>Setting & Participants</h3><div>Autopsy specimens of kidneys were obtained from 181 individuals who died within 6 years of a community-wide health examination in 2007 and who had an autopsy at the time of death.</div></div><div><h3>Exposure</h3><div>Histopathologic findings, including glomerular, tubulointerstitial, and vascular lesions, were evaluated as outcome variables in relation to estimated glomerular filtration rate. The kidney cortex in each specimen was divided into 3 equally spaced cortical regions (superficial, middle, and juxtamedullary cortex) to assess depth-dependent lesion distribution.</div></div><div><h3>Outcomes</h3><div>Glomerular, tubulointerstitial, and vascular lesions were evaluated in cortical regions at different depths.</div></div><div><h3>Analytical Approach</h3><div>Associations between estimated glomerular filtration rate levels and the extent of histopathologic findings based on cortical region were tested using generalized linear mixed-effects models.</div></div><div><h3>Results</h3><div>The present study included 172 autopsied cases (mean age: 81 years; men: 50%). The extent of histopathologic lesions progressed significantly with worsening kidney function, and the association was similar in each cortical region. Analysis based on cortical region showed significant gradients in the extent/severity of nephrosclerotic lesions, with global glomerulosclerosis and interstitial fibrosis and tubular atrophy dominating in the superficial cortex and arterial intima-media thickness and arteriolar hyalinosis dominating in the juxtamedullary cortex. The cortical region specificity of histopathologic findings in nephrosclerosis became less prominent with worsening kidney function.</div></div><div><h3>Limitations</h3><div>Participants were elderly, and the causal relationship between pathologic findings and renal dysfunction could not be determined.</div></div><div><h3>Conclusions</h3><div>The present study confirms a cortical region--dependent gradient of nephrosclerotic lesions within the kidney and suggests that arterial and tubulointerstitial lesions may be more strongly linked with kidney dysfunction than glomerular lesions.</div></div><div><h3>Plain-Language Summary</h3><div>Although nephrosclerosis is a major cause of end-stage renal failure, few studies have addressed its histopathologic relationship with kidney function. In this study, kidney specimens from 172 Japanese community residents at the time of death were evaluated based on 6 histopathologic indices in 3 renal cortical regions. The extent of","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 2","pages":"Article 101194"},"PeriodicalIF":3.4,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023166","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}
Pub Date : 2025-12-01DOI: 10.1016/j.xkme.2025.101133
Vladimir Mushailov, Jai Radhakrishnan
<div><div>Primary adult glomerular diseases (GDs), including immunoglobulin A nephropathy, membranous nephropathy, and focal segmental glomerulosclerosis, are important causes of chronic kidney disease and may progress to kidney failure. Nonimmunosuppressive foundation drug therapy for primary adult GD focuses on renin-angiotensin-aldosterone system inhibition to reduce proteinuria, alleviate hypertension, and reduce the risk of kidney disease progression. Additional agents with a distinct mechanism of action may be added or substituted in patients with a high progression risk or who are intolerant to renin-angiotensin-aldosterone system inhibitors. This review highlights the role of lifestyle optimization as well as summarizing the currently nonimmunosuppressive pharmacologic treatment options, for the management of primary adult GDs. We also provide an overview of the key pathophysiologic processes contributing to disease progression. Given the safety concerns associated with immunosuppressive therapies, we discuss the future role of newer nonimmunosuppressive agents including finerenone (a nonsteroidal mineralocorticoid receptor antagonist), sparsentan (a dual endothelin-angiotensin II receptor antagonist), atrasentan (an endothelin receptor antagonist), and iptacopan (complement inhibitor), which are currently Food and Drug Administration approved or are under investigation in clinical trials for primary GDs. These and other agents may expand the currently limited treatment landscape for patients with primary adult GD.</div></div><div><h3>Plain-Language Summary</h3><div>Each kidney contains about 1 million tiny functional units called nephrons, and each nephron has a filter called a glomerulus. The glomeruli filter waste products and remove excess fluids from the blood, which exit the body through urine. When the glomeruli are damaged, there is loss of protein through the urine. This can result in a condition called glomerular disease (GD). Treatments for GD include eating a diet that is low in sodium, potassium, and protein because eating these in excess can make GD worse. People with GD may also be advised to exercise, stop smoking, and aim for an ideal target weight. Drug medicines are also an important part of treatment for GD. A type of drug called a renin-angiotensin-aldosterone system (RAAS) inhibitor helps to reduce the amount of damage to the glomeruli and also helps to reduce blood pressure in people who also have high blood pressure (called hypertension). If a person is taking a RAAS inhibitor drug (or an appropriate alternative) but their GD does not improve, then they are at a high risk of kidney disease progression. In this scenario, the person will be offered an additional drug (to take alongside their RAAS inhibitor drug) or an alternative drug that targets their GD in a different way. Some of these work by inhibiting parts of the immune system (called immunosuppressive drugs), whereas others do not do this (called nonimmunosu
{"title":"New and Emerging Nonimmunosuppressive Drug Therapies for Primary Adult Glomerular Diseases","authors":"Vladimir Mushailov, Jai Radhakrishnan","doi":"10.1016/j.xkme.2025.101133","DOIUrl":"10.1016/j.xkme.2025.101133","url":null,"abstract":"<div><div>Primary adult glomerular diseases (GDs), including immunoglobulin A nephropathy, membranous nephropathy, and focal segmental glomerulosclerosis, are important causes of chronic kidney disease and may progress to kidney failure. Nonimmunosuppressive foundation drug therapy for primary adult GD focuses on renin-angiotensin-aldosterone system inhibition to reduce proteinuria, alleviate hypertension, and reduce the risk of kidney disease progression. Additional agents with a distinct mechanism of action may be added or substituted in patients with a high progression risk or who are intolerant to renin-angiotensin-aldosterone system inhibitors. This review highlights the role of lifestyle optimization as well as summarizing the currently nonimmunosuppressive pharmacologic treatment options, for the management of primary adult GDs. We also provide an overview of the key pathophysiologic processes contributing to disease progression. Given the safety concerns associated with immunosuppressive therapies, we discuss the future role of newer nonimmunosuppressive agents including finerenone (a nonsteroidal mineralocorticoid receptor antagonist), sparsentan (a dual endothelin-angiotensin II receptor antagonist), atrasentan (an endothelin receptor antagonist), and iptacopan (complement inhibitor), which are currently Food and Drug Administration approved or are under investigation in clinical trials for primary GDs. These and other agents may expand the currently limited treatment landscape for patients with primary adult GD.</div></div><div><h3>Plain-Language Summary</h3><div>Each kidney contains about 1 million tiny functional units called nephrons, and each nephron has a filter called a glomerulus. The glomeruli filter waste products and remove excess fluids from the blood, which exit the body through urine. When the glomeruli are damaged, there is loss of protein through the urine. This can result in a condition called glomerular disease (GD). Treatments for GD include eating a diet that is low in sodium, potassium, and protein because eating these in excess can make GD worse. People with GD may also be advised to exercise, stop smoking, and aim for an ideal target weight. Drug medicines are also an important part of treatment for GD. A type of drug called a renin-angiotensin-aldosterone system (RAAS) inhibitor helps to reduce the amount of damage to the glomeruli and also helps to reduce blood pressure in people who also have high blood pressure (called hypertension). If a person is taking a RAAS inhibitor drug (or an appropriate alternative) but their GD does not improve, then they are at a high risk of kidney disease progression. In this scenario, the person will be offered an additional drug (to take alongside their RAAS inhibitor drug) or an alternative drug that targets their GD in a different way. Some of these work by inhibiting parts of the immune system (called immunosuppressive drugs), whereas others do not do this (called nonimmunosu","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"7 12","pages":"Article 101133"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145620823","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}
Pub Date : 2025-11-26DOI: 10.1016/j.xkme.2025.101192
Yoshitsugu Obi , Yunxi Zhang , Maria Clarissa Tio , Timothy E. Yen , Catherine C. Wells , Michael E. Hall , Neville R. Dossabhoy , Saurabh Chandra , Tariq Shafi
<div><h3>Rationale & Objective</h3><div>Blood pressure (BP) control in dialysis patients is often inadequate, partly owing to a lack of standardized home BP monitoring. We aimed to implement and evaluate a remote BP monitoring (RBPM) program for incenter hemodialysis (HD) patients.</div></div><div><h3>Study Design</h3><div>An effectiveness-implementation hybrid study conducted as a quality improvement program.</div></div><div><h3>Setting & Participants</h3><div>We screened 79 patients with kidney failure receiving thrice-weekly incenter HD at a US academic medical center between February and September 2022.</div></div><div><h3>Exposure</h3><div>Initiation of an RBPM program integrated into the electronic medical record.</div></div><div><h3>Outcomes</h3><div>The primary outcome was patient use of home BP monitoring. Secondary outcomes included changes in BP, number of antihypertensive medications, and target weight.</div></div><div><h3>Analytical Approach</h3><div>We compared 30-day average pre-HD BP, home BP measured 1 day after midweek HD, number of BP medications, and target weight before and after RBPM initiation using paired <em>t</em> test or Wilcoxon rank sum test. In addition, mixed-effects models were used to assess changes over time.</div></div><div><h3>Results</h3><div>Among the 79 patients screened, 48 referred to RBPM, 30 started monitoring, and 27 completed the 3-month follow-up. The mean predialysis systolic BP before RBPM initiation was 145 (standard deviation, 20) mm Hg. During month 1, home systolic BP postmidweek HD was lower than pre-HD measurement by 14 mm Hg (<em>P</em> = 0.005). The median number of BP medication decreased from 2.5-2.0 in month 3 (<em>P</em> = 0.005). Median monthly home BP measurements decreased from 17 during month 1 to 6 during month 3 (<em>P</em> < 0.001). In month 3, 67% (18/27) of participants were actively monitoring their BP, with only 13 (48%) measuring BP postmidweek HD.</div></div><div><h3>Limitations</h3><div>A single-center, observational study without a standardized protocol for medication management.</div></div><div><h3>Conclusions</h3><div>Our RPBM program confirmed significant discrepancies between home and pre-HD BP measurements, underscoring its potential use. However, the observed decline in patient engagement highlights the challenge of maintaining long-term adherence.</div></div><div><h3>Plain-language Summary</h3><div>Blood pressure (BP) is often difficult to control in patients receiving dialysis, and BP readings taken at the dialysis clinic may not show the full picture. We wanted to see if using a home BP monitoring program, in which patients measure their own BP and the readings are sent to their doctors electronically, could be a practical and useful tool in a real-world setting. We provided bluetooth-enabled home BP monitors to patients receiving incenter hemodialysis at our hospital. We trained them how to use the devices and asked them to measure their BP twice daily
{"title":"Operationalizing Home Blood Pressure Monitoring for Dialysis Patients: An Effectiveness-Implementation Hybrid Study","authors":"Yoshitsugu Obi , Yunxi Zhang , Maria Clarissa Tio , Timothy E. Yen , Catherine C. Wells , Michael E. Hall , Neville R. Dossabhoy , Saurabh Chandra , Tariq Shafi","doi":"10.1016/j.xkme.2025.101192","DOIUrl":"10.1016/j.xkme.2025.101192","url":null,"abstract":"<div><h3>Rationale & Objective</h3><div>Blood pressure (BP) control in dialysis patients is often inadequate, partly owing to a lack of standardized home BP monitoring. We aimed to implement and evaluate a remote BP monitoring (RBPM) program for incenter hemodialysis (HD) patients.</div></div><div><h3>Study Design</h3><div>An effectiveness-implementation hybrid study conducted as a quality improvement program.</div></div><div><h3>Setting & Participants</h3><div>We screened 79 patients with kidney failure receiving thrice-weekly incenter HD at a US academic medical center between February and September 2022.</div></div><div><h3>Exposure</h3><div>Initiation of an RBPM program integrated into the electronic medical record.</div></div><div><h3>Outcomes</h3><div>The primary outcome was patient use of home BP monitoring. Secondary outcomes included changes in BP, number of antihypertensive medications, and target weight.</div></div><div><h3>Analytical Approach</h3><div>We compared 30-day average pre-HD BP, home BP measured 1 day after midweek HD, number of BP medications, and target weight before and after RBPM initiation using paired <em>t</em> test or Wilcoxon rank sum test. In addition, mixed-effects models were used to assess changes over time.</div></div><div><h3>Results</h3><div>Among the 79 patients screened, 48 referred to RBPM, 30 started monitoring, and 27 completed the 3-month follow-up. The mean predialysis systolic BP before RBPM initiation was 145 (standard deviation, 20) mm Hg. During month 1, home systolic BP postmidweek HD was lower than pre-HD measurement by 14 mm Hg (<em>P</em> = 0.005). The median number of BP medication decreased from 2.5-2.0 in month 3 (<em>P</em> = 0.005). Median monthly home BP measurements decreased from 17 during month 1 to 6 during month 3 (<em>P</em> < 0.001). In month 3, 67% (18/27) of participants were actively monitoring their BP, with only 13 (48%) measuring BP postmidweek HD.</div></div><div><h3>Limitations</h3><div>A single-center, observational study without a standardized protocol for medication management.</div></div><div><h3>Conclusions</h3><div>Our RPBM program confirmed significant discrepancies between home and pre-HD BP measurements, underscoring its potential use. However, the observed decline in patient engagement highlights the challenge of maintaining long-term adherence.</div></div><div><h3>Plain-language Summary</h3><div>Blood pressure (BP) is often difficult to control in patients receiving dialysis, and BP readings taken at the dialysis clinic may not show the full picture. We wanted to see if using a home BP monitoring program, in which patients measure their own BP and the readings are sent to their doctors electronically, could be a practical and useful tool in a real-world setting. We provided bluetooth-enabled home BP monitors to patients receiving incenter hemodialysis at our hospital. We trained them how to use the devices and asked them to measure their BP twice daily","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 1","pages":"Article 101192"},"PeriodicalIF":3.4,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786980","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}
Pub Date : 2025-11-24DOI: 10.1016/j.xkme.2025.101191
Mirela A. Dobre , Chenyu Liu , Scott E. Janus , Liangliang Zhang , Aparna Padiyar , Shruti Ahlawat , Robert J. Gaivin , Sudha K. Iyengar , Mahboob Rahman , Jordana Yahr , Sanjay Rajagopalan , Sadeer Al-Kindi , Anne M. Huml , Jeffrey R. Schelling
<div><h3>Rationale & Objective</h3><div>Kidney transplantation (KT) improves cardiovascular outcomes in patients with kidney failure, yet the biological mechanisms underlying post-KT myocardial recovery remain unclear.</div></div><div><h3>Study Design</h3><div>Prospective observational cohort study with matched controls.</div></div><div><h3>Setting & Participants</h3><div>Fifty participants were enrolled at 2 transplant centers: 28 received a living KT, and a cardiac magnetic resonance imaging (CMRI) scan assessment of interstitial myocardial fibrosis with T1 maps before and nine months post-KT; 22 matched waitlisted controls had baseline and 9-month CMRI scans. The groups were matched using baseline characteristics and T1 values.</div></div><div><h3>Exposure</h3><div>Receipt of kidney transplantation.</div></div><div><h3>Outcome</h3><div>Change in native T1 mapping CMRI scan, a surrogate marker of interstitial myocardial fibrosis.</div></div><div><h3>Analytical Approach</h3><div>Regression models were used to estimate the effect of KT versus no KT (the waitlisted control group) on interstitial myocardial fibrosis, adjusted for demographic characteristics, comorbidities, blood pressure, and medications. Plasma collected at baseline was analyzed using SomaScan v.4.1 (6,472 unique proteins). Regression models were used to identify proteins associated with baseline and longitudinal changes in T1, adjusted for clinical covariates and corrected for multiple testing.</div></div><div><h3>Results</h3><div>KT recipients had reduced interstitial myocardial fibrosis compared with waitlisted controls (−47.49 ± 81.63 vs +13.77 ± 62.13 ms, <em>P</em> = 0.01). Forty-three plasma proteins were significantly associated with baseline T1 values; macrophage colony-stimulating factor displayed the greatest retest reproducibility (80%) and positive association with T1 (<em>P</em> = 3.1 × 10<sup>-4</sup>). Pathway enrichment analyses identified 17 interconnected fibrosis-related proteins with biological relevance to cardiac remodeling.</div></div><div><h3>Limitations</h3><div>A modest sample size and a single time-point proteomic assessment. External validation is needed.</div></div><div><h3>Conclusions</h3><div>KT leads to regression of interstitial myocardial fibrosis within 9 months, supporting a structural cardiac benefit of transplantation. Pretransplant proteomic signatures, particularly macrophage colony-stimulating factor, reflect underlying fibrotic burden and may serve as a predictive biomarker to monitor post-KT cardiac recovery.</div></div><div><h3>Plain-language summary</h3><div>Kidney transplantation results in improved cardiovascular health, but how the 2 are connected is not fully understood. In this study, we followed people with kidney failure who received a kidney transplant and compared them to similar patients who remained on the waitlist. We examined heart imaging to measure changes in diffuse fibrosis (scarring) over 9 months and associat
目的肾移植（KT）可改善肾衰竭患者的心血管预后，但KT后心肌恢复的生物学机制尚不清楚。研究设计具有匹配对照的前瞻性观察队列研究。在2个移植中心招募了50名参与者：28人接受活体KT，并在KT前和KT后9个月用T1图进行心脏磁共振成像（CMRI）扫描评估间质性心肌纤维化；22名匹配的候补对照进行了基线和9个月的CMRI扫描。使用基线特征和T1值对两组进行匹配。暴露：接受肾移植。结果：原生T1定位CMRI扫描的改变，间质性心肌纤维化的替代标志物。分析方法回归模型用于估计KT与未KT（候补对照组）对间质性心肌纤维化的影响，并根据人口统计学特征、合并症、血压和药物进行调整。基线时收集的血浆使用SomaScan v.4.1（6,472种独特蛋白）进行分析。回归模型用于鉴定与T1基线和纵向变化相关的蛋白质，并根据临床协变量进行调整，并对多重检验进行校正。结果与等候组相比，skt受体间质性心肌纤维化减少（- 47.49±81.63 ms vs +13.77±62.13 ms, P = 0.01）。43种血浆蛋白与基线T1值显著相关；巨噬细胞集落刺激因子复测重复性最高（80%），与T1呈正相关（P = 3.1 × 10-4）。途径富集分析鉴定出17种相互关联的纤维化相关蛋白，它们与心脏重塑具有生物学相关性。限制适度的样本量和单时间点蛋白质组学评估。需要外部验证。结论skt在9个月内导致间质性心肌纤维化消退，支持移植对心脏的结构性益处。移植前的蛋白质组学特征，特别是巨噬细胞集落刺激因子，反映了潜在的纤维化负担，可以作为监测kt后心脏恢复的预测性生物标志物。肾移植可改善心血管健康，但两者之间的联系尚不完全清楚。在这项研究中，我们跟踪了接受肾移植的肾功能衰竭患者，并将他们与仍在等待名单上的类似患者进行了比较。我们检查了心脏成像来测量9个月以上弥漫性纤维化（瘢痕）的变化及其与循环血液蛋白的关系。我们发现移植与减少心脏纤维化有关，特别是1蛋白-巨噬细胞集落刺激因子与减少纤维化有关。这些发现表明，肾脏移植可能有助于改善心脏组织结构，识别关键蛋白，如巨噬细胞集落刺激因子，可能代表未来监测心脏恢复的工具。
{"title":"Kidney Transplantation–Induced Reduction in Myocardial Fibrosis and Modulation of Plasma Proteome: Results of a Pilot Study","authors":"Mirela A. Dobre , Chenyu Liu , Scott E. Janus , Liangliang Zhang , Aparna Padiyar , Shruti Ahlawat , Robert J. Gaivin , Sudha K. Iyengar , Mahboob Rahman , Jordana Yahr , Sanjay Rajagopalan , Sadeer Al-Kindi , Anne M. Huml , Jeffrey R. Schelling","doi":"10.1016/j.xkme.2025.101191","DOIUrl":"10.1016/j.xkme.2025.101191","url":null,"abstract":"<div><h3>Rationale & Objective</h3><div>Kidney transplantation (KT) improves cardiovascular outcomes in patients with kidney failure, yet the biological mechanisms underlying post-KT myocardial recovery remain unclear.</div></div><div><h3>Study Design</h3><div>Prospective observational cohort study with matched controls.</div></div><div><h3>Setting & Participants</h3><div>Fifty participants were enrolled at 2 transplant centers: 28 received a living KT, and a cardiac magnetic resonance imaging (CMRI) scan assessment of interstitial myocardial fibrosis with T1 maps before and nine months post-KT; 22 matched waitlisted controls had baseline and 9-month CMRI scans. The groups were matched using baseline characteristics and T1 values.</div></div><div><h3>Exposure</h3><div>Receipt of kidney transplantation.</div></div><div><h3>Outcome</h3><div>Change in native T1 mapping CMRI scan, a surrogate marker of interstitial myocardial fibrosis.</div></div><div><h3>Analytical Approach</h3><div>Regression models were used to estimate the effect of KT versus no KT (the waitlisted control group) on interstitial myocardial fibrosis, adjusted for demographic characteristics, comorbidities, blood pressure, and medications. Plasma collected at baseline was analyzed using SomaScan v.4.1 (6,472 unique proteins). Regression models were used to identify proteins associated with baseline and longitudinal changes in T1, adjusted for clinical covariates and corrected for multiple testing.</div></div><div><h3>Results</h3><div>KT recipients had reduced interstitial myocardial fibrosis compared with waitlisted controls (−47.49 ± 81.63 vs +13.77 ± 62.13 ms, <em>P</em> = 0.01). Forty-three plasma proteins were significantly associated with baseline T1 values; macrophage colony-stimulating factor displayed the greatest retest reproducibility (80%) and positive association with T1 (<em>P</em> = 3.1 × 10<sup>-4</sup>). Pathway enrichment analyses identified 17 interconnected fibrosis-related proteins with biological relevance to cardiac remodeling.</div></div><div><h3>Limitations</h3><div>A modest sample size and a single time-point proteomic assessment. External validation is needed.</div></div><div><h3>Conclusions</h3><div>KT leads to regression of interstitial myocardial fibrosis within 9 months, supporting a structural cardiac benefit of transplantation. Pretransplant proteomic signatures, particularly macrophage colony-stimulating factor, reflect underlying fibrotic burden and may serve as a predictive biomarker to monitor post-KT cardiac recovery.</div></div><div><h3>Plain-language summary</h3><div>Kidney transplantation results in improved cardiovascular health, but how the 2 are connected is not fully understood. In this study, we followed people with kidney failure who received a kidney transplant and compared them to similar patients who remained on the waitlist. We examined heart imaging to measure changes in diffuse fibrosis (scarring) over 9 months and associat","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 2","pages":"Article 101191"},"PeriodicalIF":3.4,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978471","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}
Pub Date : 2025-11-20DOI: 10.1016/j.xkme.2025.101190
Deborah H. Wilson , Avrey Hughes , Samantha Curriero , Sarah Szanton , Deidra C. Crews , Mara McAdams-DeMarco , Daniel C. Brennan , Melissa deCardi Hladek
<div><h3>Rationale & Objective</h3><div>There is a critical need for interventions that help improve outcomes for individuals requiring a kidney transplant but are waitlisted as inactive. We explored the perspectives of dialysis patients and clinicians to develop community aging in place-advancing better living for elders (CAPABLE)–transplant. CAPABLE utilizes a home-visiting registered nurse, occupational therapist, and handy worker who work with older adults to create action plans that change behaviors to improve safety, independence, and health.</div></div><div><h3>Study Design</h3><div>Qualitative semi-structured interviews.</div></div><div><h3>Setting & Participants</h3><div>Individuals treated with dialysis and inactive on the transplant list (n = 20) and transplant clinicians (n = 6) from an urban transplant center.</div></div><div><h3>Outcomes</h3><div>The adaptation of CAPABLE into CAPABLE-transplant.</div></div><div><h3>Analytical Approach</h3><div>Following Braun and Clark’s method of thematic analysis to inform intervention adaptation.</div></div><div><h3>Results</h3><div>Three major themes were identified: (1) mismatch of expectations with subthemes: communication keeps breaking down; high volume at center impedes follow-up; (2) agency: from fragmentation to functionality with subthemes: patient agency needs enhancing; digital literacy is key to improving communication capacity; preposttransplant education needs to be ongoing; (3) “You gotta keep climbing that mountain ‘till you reach the goal” with a subtheme of navigating compliance while struggling with symptom burden.</div></div><div><h3>Limitations</h3><div>A single-center perspective and small sample size.</div></div><div><h3>Conclusions</h3><div>By comparing the patient and clinician experience, specific adaptations for CAPABLE-transplant that address modifiable factors to decrease time inactive on the kidney transplant waitlist were identified. These included adding a digital literacy component to the home-visiting team to improve patient-clinician communication, ongoing education about the transplant process to improve health literacy, and activities to strengthen mental fortitude, self-efficacy, and agency. The core components of CAPABLE remain important to improve physical function, medication management, pain, and depressive symptoms. Patients and clinicians expressed support for CAPABLE-transplant to help improve self-efficacy, agency, and engagement along the transplant continuum.</div></div><div><h3>Plain-Language Summary</h3><div>People listed as inactive on the kidney transplant waitlist need interventions to decrease time listed as inactive. Qualitative interviews with dialysis patients and transplant clinicians identified areas of need that could be addressed by a home-based intervention. We used the data to adapt an existing intervention called community aging in place-advancing better living for elders (CAPABLE) into CAPABLE-transplant. Adding a digital l
{"title":"“You Gotta Keep Climbing That Mountain to Reach the Goal”: Perspectives of Transplant Waitlisted Dialysis Patients. A Qualitative Study","authors":"Deborah H. Wilson , Avrey Hughes , Samantha Curriero , Sarah Szanton , Deidra C. Crews , Mara McAdams-DeMarco , Daniel C. Brennan , Melissa deCardi Hladek","doi":"10.1016/j.xkme.2025.101190","DOIUrl":"10.1016/j.xkme.2025.101190","url":null,"abstract":"<div><h3>Rationale & Objective</h3><div>There is a critical need for interventions that help improve outcomes for individuals requiring a kidney transplant but are waitlisted as inactive. We explored the perspectives of dialysis patients and clinicians to develop community aging in place-advancing better living for elders (CAPABLE)–transplant. CAPABLE utilizes a home-visiting registered nurse, occupational therapist, and handy worker who work with older adults to create action plans that change behaviors to improve safety, independence, and health.</div></div><div><h3>Study Design</h3><div>Qualitative semi-structured interviews.</div></div><div><h3>Setting & Participants</h3><div>Individuals treated with dialysis and inactive on the transplant list (n = 20) and transplant clinicians (n = 6) from an urban transplant center.</div></div><div><h3>Outcomes</h3><div>The adaptation of CAPABLE into CAPABLE-transplant.</div></div><div><h3>Analytical Approach</h3><div>Following Braun and Clark’s method of thematic analysis to inform intervention adaptation.</div></div><div><h3>Results</h3><div>Three major themes were identified: (1) mismatch of expectations with subthemes: communication keeps breaking down; high volume at center impedes follow-up; (2) agency: from fragmentation to functionality with subthemes: patient agency needs enhancing; digital literacy is key to improving communication capacity; preposttransplant education needs to be ongoing; (3) “You gotta keep climbing that mountain ‘till you reach the goal” with a subtheme of navigating compliance while struggling with symptom burden.</div></div><div><h3>Limitations</h3><div>A single-center perspective and small sample size.</div></div><div><h3>Conclusions</h3><div>By comparing the patient and clinician experience, specific adaptations for CAPABLE-transplant that address modifiable factors to decrease time inactive on the kidney transplant waitlist were identified. These included adding a digital literacy component to the home-visiting team to improve patient-clinician communication, ongoing education about the transplant process to improve health literacy, and activities to strengthen mental fortitude, self-efficacy, and agency. The core components of CAPABLE remain important to improve physical function, medication management, pain, and depressive symptoms. Patients and clinicians expressed support for CAPABLE-transplant to help improve self-efficacy, agency, and engagement along the transplant continuum.</div></div><div><h3>Plain-Language Summary</h3><div>People listed as inactive on the kidney transplant waitlist need interventions to decrease time listed as inactive. Qualitative interviews with dialysis patients and transplant clinicians identified areas of need that could be addressed by a home-based intervention. We used the data to adapt an existing intervention called community aging in place-advancing better living for elders (CAPABLE) into CAPABLE-transplant. Adding a digital l","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 2","pages":"Article 101190"},"PeriodicalIF":3.4,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978473","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}
Pub Date : 2025-11-19DOI: 10.1016/j.xkme.2025.101189
Ayman Al Jurdi , Abraham Cohen Bucay , Pitchaphon Nissaisorakarn , Hannah Gilligan , Claire T. Avillach , Veronica E. Klepeis , Rex N. Smith , Ragnar Palsson , Kassem Safa , Leonardo V. Riella
Immunoglobulin A (IgA) nephropathy is a common cause of kidney failure and can recur after kidney transplantation, increasing the risk of allograft loss. Effective treatments for recurrent IgA nephropathy in kidney transplant recipients are urgently needed. Iptacopan is a complement factor B inhibitor that received accelerated approval by the US Food and Drug Administration in August 2024 for the treatment of high-risk native IgA nephropathy based on trials that excluded transplant recipients. In this case series, we report our early experience with iptacopan in three individuals with biopsy-confirmed recurrent IgA nephropathy after kidney transplant. All received iptacopan for ≥3 months in combination with a short course of systemic corticosteroids. Two individuals demonstrated significant reductions in proteinuria and resolution of microscopic hematuria. One individual developed progressive graft dysfunction; repeat biopsy showed persistent active glomerulonephritis with codeposition of IgG, suggesting a more aggressive or atypical disease phenotype. These early data suggest that iptacopan, in combination with short-term corticosteroids, may offer therapeutic benefit in selected kidney transplant recipients with recurrent IgA nephropathy, warranting further investigation.
{"title":"Early Experience With Iptacopan for Recurrent IgA Nephropathy After Kidney Transplantation","authors":"Ayman Al Jurdi , Abraham Cohen Bucay , Pitchaphon Nissaisorakarn , Hannah Gilligan , Claire T. Avillach , Veronica E. Klepeis , Rex N. Smith , Ragnar Palsson , Kassem Safa , Leonardo V. Riella","doi":"10.1016/j.xkme.2025.101189","DOIUrl":"10.1016/j.xkme.2025.101189","url":null,"abstract":"<div><div>Immunoglobulin A (IgA) nephropathy is a common cause of kidney failure and can recur after kidney transplantation, increasing the risk of allograft loss. Effective treatments for recurrent IgA nephropathy in kidney transplant recipients are urgently needed. Iptacopan is a complement factor B inhibitor that received accelerated approval by the US Food and Drug Administration in August 2024 for the treatment of high-risk native IgA nephropathy based on trials that excluded transplant recipients. In this case series, we report our early experience with iptacopan in three individuals with biopsy-confirmed recurrent IgA nephropathy after kidney transplant. All received iptacopan for ≥3 months in combination with a short course of systemic corticosteroids. Two individuals demonstrated significant reductions in proteinuria and resolution of microscopic hematuria. One individual developed progressive graft dysfunction; repeat biopsy showed persistent active glomerulonephritis with codeposition of IgG, suggesting a more aggressive or atypical disease phenotype. These early data suggest that iptacopan, in combination with short-term corticosteroids, may offer therapeutic benefit in selected kidney transplant recipients with recurrent IgA nephropathy, warranting further investigation.</div></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 2","pages":"Article 101189"},"PeriodicalIF":3.4,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978511","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}
Pub Date : 2025-11-17DOI: 10.1016/j.xkme.2025.101187
Octavio Rene García Flores , Mayra Eugenia Avilés Ramírez , Jose Carlos Gasca Aldama , Marco Vidals Sánchez , María Virgilia Soto Abraham , Martha Arisbeth Villanueva Pérez , Magdalena Madero , Enzo Vásquez Jiménez
In patients with mechanical ventilation or critically ill patients there are various mechanisms for kidney function impairment, ranging from systemic disease to intrinsic kidney etiology. Kidney biopsy is the study of choice for the diagnosis, treatment decision and prognosis of kidney disease. Ten critically ill patients on mechanical ventilation underwent kidney biopsy using 2 kidney biopsy techniques: the standard technique (prone position) in 5 patients and the lateral position (left lateral decubitus position) in 5 patients. Most of our patients had a kidney histological diagnosis secondary to autoimmune disease that required induction treatment. Despite the risk factors for complications, only one patient received a transfusion of packed red blood cells. The prone group had the highest number of deaths due to the severity of the patient’s disease and unrelated to the procedure. Kidney biopsy in patients with mechanical ventilation is a high-risk procedure that should be performed on selected patients who can benefit from a histological diagnosis.
{"title":"Kidney Biopsy in Patients With Mechanical Ventilation: A Report of Ten Cases","authors":"Octavio Rene García Flores , Mayra Eugenia Avilés Ramírez , Jose Carlos Gasca Aldama , Marco Vidals Sánchez , María Virgilia Soto Abraham , Martha Arisbeth Villanueva Pérez , Magdalena Madero , Enzo Vásquez Jiménez","doi":"10.1016/j.xkme.2025.101187","DOIUrl":"10.1016/j.xkme.2025.101187","url":null,"abstract":"<div><div>In patients with mechanical ventilation or critically ill patients there are various mechanisms for kidney function impairment, ranging from systemic disease to intrinsic kidney etiology. Kidney biopsy is the study of choice for the diagnosis, treatment decision and prognosis of kidney disease. Ten critically ill patients on mechanical ventilation underwent kidney biopsy using 2 kidney biopsy techniques: the standard technique (prone position) in 5 patients and the lateral position (left lateral decubitus position) in 5 patients. Most of our patients had a kidney histological diagnosis secondary to autoimmune disease that required induction treatment. Despite the risk factors for complications, only one patient received a transfusion of packed red blood cells. The prone group had the highest number of deaths due to the severity of the patient’s disease and unrelated to the procedure. Kidney biopsy in patients with mechanical ventilation is a high-risk procedure that should be performed on selected patients who can benefit from a histological diagnosis.</div></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 2","pages":"Article 101187"},"PeriodicalIF":3.4,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023168","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}
Pub Date : 2025-11-13DOI: 10.1016/j.xkme.2025.101186
Erin E. Tapper , Johanna M. Huusko , Alicia M. Scocchia , Kimberly Gall , Mary-Beth Roberts , Manuel Bernal-Quirós , Satu Valo , Inka Saarinen , Matias Rantanen , Tuuli Pietila , Massimiliano Gentile , Lotta Koskinen , Meenakshi Mahey Kumar , Samuel Myllykangas , Juha Koskenvuo
<div><h3>Rationale & Objective</h3><div>Mounting evidence supports that identifying the specific molecular etiology for individuals with cystic kidney disease (CyKD) is important for prognostication, surveillance, identifying related living donors, and defining familial risk, even in cases in which a clinical diagnosis appears straightforward. In this study, we aimed to investigate the yield of genetic findings and the unique variant characteristics using multigene panel testing (MGPT) in a referral laboratory setting for an unselected population of patients with an indication of CyKD.</div></div><div><h3>Study Design</h3><div>Cross-sectional study.</div></div><div><h3>Setting & Participants</h3><div>A retrospective analysis of 1,235 genetic testing reports from patients with suspected CyKD who pursued MGPT was performed.</div></div><div><h3>Findings</h3><div>A positive result in a gene associated with CyKD was identified in 49.4% (610/1235) of patient reports, identifying 468 unique variants classified as pathogenic or likely pathogenic in 20 unique genes. Variants in <em>PKD1</em>, a gene complicated by homology to 6 different pseudogenes, contributed to 65.6% (400/610) of positive results. Copy number variants (CNVs) were identified in 9.5% (58/610) of positive results, with 30.4% (17/56) of deletions consisting of 4 exons or less. Variants of uncertain significance that were suspicious for being pathogenic (susVUS) were identified in 57.0% (94/165) of patients with inconclusive results.</div></div><div><h3>Limitations</h3><div>Genetic analysis was targeted to the genes included on the panel at the time of testing. As new evidence emerges supporting additional gene-disease associations, there is potential for additional positive results.</div></div><div><h3>Conclusions</h3><div>Thoughtful selection of carefully curated MGPT optimized to detect technically challenging variants can identify the molecular etiology in individuals presenting with CyKD. Further investigation of susVUS through segregation analysis in families may contribute to additional positive results.</div></div><div><h3>Plain-Language Summary</h3><div>Data informing the yield of multigene panel testing (MGPT) for individuals with cystic kidney disease (CyKD) is increasing. In this study, we retrospectively reviewed MGPT results from 1,235 individuals with suspected CyKD. A positive result in one of 20 CyKD-associated genes, including <em>PKD1</em>, was identified in 49.4% (610/1235) of patient reports. Copy number variants (CNVs) accounted for 9.5% (58/610) of positive results, with 30.4% (17/56) of deletions consisting of 4 exons or less. Suspicious variants of uncertain significance were identified in 57.0% (94/165) of patients with inconclusive results. MGPT can identify the molecular etiology of CyKD and, prior to ordering, should be carefully evaluated for relevant gene content, capabilities for technically challenging genes like <em>PKD1,</em> sensitivity to detect
{"title":"Results of Multigene Panel Testing, Including PKD1, in >1,200 Patients With Cystic Kidney Disease: A Retrospective Analysis","authors":"Erin E. Tapper , Johanna M. Huusko , Alicia M. Scocchia , Kimberly Gall , Mary-Beth Roberts , Manuel Bernal-Quirós , Satu Valo , Inka Saarinen , Matias Rantanen , Tuuli Pietila , Massimiliano Gentile , Lotta Koskinen , Meenakshi Mahey Kumar , Samuel Myllykangas , Juha Koskenvuo","doi":"10.1016/j.xkme.2025.101186","DOIUrl":"10.1016/j.xkme.2025.101186","url":null,"abstract":"<div><h3>Rationale & Objective</h3><div>Mounting evidence supports that identifying the specific molecular etiology for individuals with cystic kidney disease (CyKD) is important for prognostication, surveillance, identifying related living donors, and defining familial risk, even in cases in which a clinical diagnosis appears straightforward. In this study, we aimed to investigate the yield of genetic findings and the unique variant characteristics using multigene panel testing (MGPT) in a referral laboratory setting for an unselected population of patients with an indication of CyKD.</div></div><div><h3>Study Design</h3><div>Cross-sectional study.</div></div><div><h3>Setting & Participants</h3><div>A retrospective analysis of 1,235 genetic testing reports from patients with suspected CyKD who pursued MGPT was performed.</div></div><div><h3>Findings</h3><div>A positive result in a gene associated with CyKD was identified in 49.4% (610/1235) of patient reports, identifying 468 unique variants classified as pathogenic or likely pathogenic in 20 unique genes. Variants in <em>PKD1</em>, a gene complicated by homology to 6 different pseudogenes, contributed to 65.6% (400/610) of positive results. Copy number variants (CNVs) were identified in 9.5% (58/610) of positive results, with 30.4% (17/56) of deletions consisting of 4 exons or less. Variants of uncertain significance that were suspicious for being pathogenic (susVUS) were identified in 57.0% (94/165) of patients with inconclusive results.</div></div><div><h3>Limitations</h3><div>Genetic analysis was targeted to the genes included on the panel at the time of testing. As new evidence emerges supporting additional gene-disease associations, there is potential for additional positive results.</div></div><div><h3>Conclusions</h3><div>Thoughtful selection of carefully curated MGPT optimized to detect technically challenging variants can identify the molecular etiology in individuals presenting with CyKD. Further investigation of susVUS through segregation analysis in families may contribute to additional positive results.</div></div><div><h3>Plain-Language Summary</h3><div>Data informing the yield of multigene panel testing (MGPT) for individuals with cystic kidney disease (CyKD) is increasing. In this study, we retrospectively reviewed MGPT results from 1,235 individuals with suspected CyKD. A positive result in one of 20 CyKD-associated genes, including <em>PKD1</em>, was identified in 49.4% (610/1235) of patient reports. Copy number variants (CNVs) accounted for 9.5% (58/610) of positive results, with 30.4% (17/56) of deletions consisting of 4 exons or less. Suspicious variants of uncertain significance were identified in 57.0% (94/165) of patients with inconclusive results. MGPT can identify the molecular etiology of CyKD and, prior to ordering, should be carefully evaluated for relevant gene content, capabilities for technically challenging genes like <em>PKD1,</em> sensitivity to detect","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 1","pages":"Article 101186"},"PeriodicalIF":3.4,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145787335","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}
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