Kidney Function, Albuminuria, and Risk of Incident Atrial Fibrillation
Lower eGFR and greater albuminuria were independently associated with increased risk of incident AF. CKD should be regarded as an independent risk factor for incident AF.
Summary
A Systematic Review and Meta-Analysis
[Posted 1/Mar/2024]
AUDIENCE: Nephrology, Internal Medicine
KEY FINDINGS: Lower eGFR and greater albuminuria were independently associated with increased risk of incident AF. CKD should be regarded as an independent risk factor for incident AF.
BACKGROUND: Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist. However, it is not known whether CKD is an independent risk factor for incident AF. Therefore, we evaluated the association between markers of CKD-estimated glomerular filtration rate (eGFR) and albuminuria-and incident AF.
DETAILS: Participants with measurement of eGFR and/or albuminuria who were not receiving dialysis.Selection Criteria for Studies: Cohort studies and randomized controlled trials were included that reported incident AF risk in adults according to eGFR and/or albuminuria. Age- or multivariate-adjusted risk ratios (RRs) for incident AF were extracted from cohort studies, and RRs for each trial were derived from event data. RRs for incident AF were pooled using random-effects models. 38 studies involving 28,470,249 participants with 530,041 incident AF cases were included. Adjusted risk of incident AF was greater among participants with lower eGFR than those with higher eGFR (eGFR <60 vs >=60 mL/min/1.73 m2: RR, 1.43; 95% CI, 1.30-1.57; and eGFR <90 vs >=90 mL/min/1.73 m2: RR, 1.42; 95% CI, 1.26-1.60). Adjusted incident AF risk was greater among participants with albuminuria (any albuminuria vs no albuminuria: RR, 1.43; 95% CI, 1.25-1.63; and moderately to severely increased albuminuria vs normal to mildly increased albuminuria: RR, 1.64; 95% CI, 1.31-2.06). Subgroup analyses showed an exposure-dependent association between CKD and incident AF, with the risk increasing progressively at lower eGFR and higher albuminuria
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Source: Ha, J. T., Freedman, S. B., Kelly, D. M., et al. (2024). Kidney Function, Albuminuria, and Risk of Incident Atrial Fibrillation: A Systematic Review and Meta-Analysis. American Journal of Kidney Diseases. Published: March, 2024. DOI: 10.1053/j.ajkd.2023.07.023.
Visceral Adiposity and Progression of ADPKD
Visceral abdominal adiposity quantified by MRI in the coronal plane using a deep learning segmentation model can be used as an index of axial segmentation in patients with ADPKD. Higher visceral abdominal adiposity was independently associated with faster kidney growth in patients with relatively early-stage ADPKD at high risk of rapid progression.
Summary
A Cohort Study of Patients From the TEMPO 3:4 Trial
[Posted 3/Sep/2024]
AUDIENCE: Nephrology, Internal Medicine
KEY FINDINGS: Visceral adiposity that can be quantified by MRI in the coronal plane using a deep learning segmentation model independently associates with more rapid kidney growth and improves classification of rapid progression in individuals with a normal BMI. Tolvaptan efficacy decreases with increasing visceral adiposity.
BACKGROUND: Body mass index (BMI) is an independent predictor of kidney disease progression in individuals with autosomal dominant polycystic kidney disease (ADPKD). Adipocytes do not simply act as a fat reservoir but are active endocrine organs. Authors hypothesized that greater visceral abdominal adiposity would associate with more rapid kidney growth in ADPKD and influence the efficacy of tolvaptan.
DETAILS: 1,053 patients enrolled in the TEMPO 3:4 tolvaptan trial with ADPKD and at high risk of rapid disease progression. In fully adjusted models, the highest tertile of visceral adiposity was associated with greater odds of annual change in TKV of >=7% versus v5% (odds ratio [OR], 4.78 [95% CI, 3.03-7.47]). The association was stronger in women than men (interaction P < 0.01). In linear mixed models with an outcome of percent change in TKV per year, tolvaptan efficacy (% change in TKV) was reduced with higher visceral adiposity (3-way interaction of treatment * time * visceral adiposity, P = 0.002). Visceral adiposity significantly improved classification performance of predicting rapid annual percent change in TKV for individuals with a normal BMI (DeLong's test z score: -2.03; P = 0.04). Greater visceral adiposity was not associated with estimated glomerular filtration rate (eGFR) slope in the overall cohort; however, visceral adiposity was associated with more rapid decline in eGFR slope (below the median) in women (fully adjusted OR, 1.06 [95% CI, 1.01-1.11] per 10 unit increase in visceral adiposity) but not men (OR, 0.98 [95% CI, 0.95-1.02]).
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Source: Nowak, K. L., Moretti, F., Bussola, N., et al. (2024). Visceral Adiposity and Progression of ADPKD: A Cohort Study of Patients From the TEMPO 3:4 Trial. Am J Kidney Dis. 2024; 84(3): 275-285. Published: September, 2024. DOI: XXXX.
Effect of Starting Dialysis Versus Continuing Medical Management on Survival and Home Time in Older Adults With Kidney Failure
Older adults starting dialysis when their eGFR fell below 12 mL/min/1.73 mm2 who were not referred for transplant had modest gains in life expectancy and less time at home.
KEY FINDINGS: Older adults starting dialysis when their eGFR fell below 12 mL/min/1.73 mm2 who were not referred for transplant had modest gains in life expectancy and less time at home.
BACKGROUND: Aim of the study is to compare survival and home time between older adults who started dialysis at an estimated glomerular filtration rate (eGFR) less than 12 mL/min/1.73 m2 and those who continued medical management.
DETAILS: Participants were adults aged 65 years or older with chronic kidney failure and eGFR below 12 mL/min/1.73 m2 who were not referred for transplant. Among 20,440 adults (mean age, 77.9 years [SD, 8.8]), the median time to dialysis start was 8.0 days in the group starting dialysis and 3.0 years in the group continuing medical management. Over a 3-year horizon, the group starting dialysis survived 770 days and the group continuing medical management survived 761 days (difference, 9.3 days [95% CI, -17.4 to 30.1 days]). Compared with the group continuing medical management, the group starting dialysis had 13.6 fewer days at home (CI, 7.7 to 20.5 fewer days at home). Compared with the group continuing medical management and forgoing dialysis completely, the group starting dialysis had longer survival by 77.6 days (CI, 62.8 to 91.1 days) and 14.7 fewer days at home (CI, 11.2 to 16.5 fewer days at home).
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Source: Montez-Rath, M. E., Thomas, I., Charu, V., et al. (2024). Effect of Starting Dialysis Versus Continuing Medical Management on Survival and Home Time in Older Adults With Kidney Failure: A Target Trial Emulation Study. Ann Intern Med.. 2024; Epub. Published: August 20, 2024. DOI: 10.7326/M23-302.
MASLD and MASH At the Crossroads of Hepatology Trials and Cardiorenal Metabolic Trials
The challenge is defining the optimal combination of biomarkers, imaging and morbidity/mortality outcomes and ensuring that they are included in future trials while minimizing the burden on patients, trialists and trial sponsors. This paper provides an overview of some of the wide array of CV, liver and kidney measurements that were discussed at the MOSAIC meeting.
KEY FINDINGS: The challenge is defining the optimal combination of biomarkers, imaging and morbidity/mortality outcomes and ensuring that they are included in future trials while minimizing the burden on patients, trialists and trial sponsors. This paper provides an overview of some of the wide array of CV, liver and kidney measurements that were discussed at the MOSAIC meeting.
BACKGROUND: Steatotic liver disease (SLD) is a worldwide public health problem, causing considerable morbidity and mortality. Patients with SLD are at increased risk for major adverse cardiovascular (CV) events, type 2 diabetes mellitus and chronic kidney disease.
DETAILS: Conversely, patients with cardiometabolic conditions have a high prevalence of SLD. In addition to epidemiological evidence linking many of these conditions, there is evidence of shared pathophysiological processes. In December 2022, a unique multi-stakeholder, multi-specialty meeting, called MOSAIC (Metabolic multi Organ Science Accelerating Innovation in Clinical Trials) was convened to foster collaboration across metabolic, hepatology, nephrology and CV disorders. One of the goals of the meeting was to consider approaches to drug development that would speed regulatory approval of treatments for multiple disorders by combining liver and cardiorenal endpoints within a single study. Non-invasive tests, including biomarkers and imaging, are needed in hepatic and cardiorenal trials. They can be used as trial endpoints, to enrich trial populations, to diagnose and risk stratify patients and to assess treatment efficacy and safety. Although they are used in proof of concept and phase 2 trials, they are often not acceptable for regulatory approval of therapies.
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Copyright © John Wiley & Sons, Inc. All rights reserved
Source: Zannad, F., Sanyal, A. J., Butler, J., et al. (2024). MASLD and MASH At the Crossroads of Hepatology Trials and Cardiorenal Metabolic Trials. Journal of Internal Medicine. 2024; 296(1): 24-38. Published: July, 2024. DOI: 10.1111/joim.13793.
Histologic and Clinical Factors Associated with Kidney Outcomes in IgA Vasculitis Nephritis
Kidney outcome in patients with biopsied IgA vasculitis nephritis treated with immunosuppression was determined by clinical risk factors and endocapillary hypercellularity (E1) and fibrous crescents, which are features that are not part of the International Study of Diseases of Children classification.
KEY FINDINGS: Kidney outcome in patients with biopsied IgA vasculitis nephritis treated with immunosuppression was determined by clinical risk factors and endocapillary hypercellularity (E1) and fibrous crescents, which are features that are not part of the International Study of Diseases of Children classification.
BACKGROUND: Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts.
DETAILS: Biopsies from 262 children and 99 adults with IgA vasculitis nephritis (N=361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists. MEST-C scores were assessed for correlation with eGFR/proteinuria at biopsy. Because most patients (N=309, 86%) received immunosuppression, risk factors for outcomes were evaluated in this group using latent class mixed models to identify classes of eGFR trajectories over a median follow-up of 2.7 years (interquartile range, 1.2-5.1). Clinical and histologic parameters associated with each class were determined using logistic regression. M, E, T, and C scores were correlated with either eGFR or proteinuria at biopsy. Two classes were identified by latent class mixed model, one with initial improvement in eGFR followed by a late decline (class 1, N=91) and another with stable eGFR (class 2, N=218). Class 1 was associated with a higher risk of an established kidney outcome (time to >= 30% decline in eGFR or kidney failure; hazard ratio, 5.84; 95% confidence interval, 2.37 to 14.4). Among MEST-C scores, only E1 was associated with class 1 by multivariable analysis. Other factors associated with class 1 were age 18 years and younger, male sex, lower eGFR at biopsy, and extrarenal noncutaneous disease. Fibrous crescents without active changes were associated with class 2.
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Source: Barbour, S., Coppo, R., Lee, E., et al. (2024). Histologic and Clinical Factors Associated with Kidney Outcomes in IgA Vasculitis Nephritis. Clinical Journal of the American Society of Nephrology . 2024; 19(4): 438-451. Published: May, 2024. DOI: 10.2215/CJN.0000000000000398.
High Incidence of Diabetes Mellitus After Distal Pancreatectomy and Its Predictors
Impaired glucose tolerance and reduced early-phase insulin response to glucose are involved in the development of new-onset diabetes after DP (Distal Pancreatectomy); the latter is an additional factor in the development of diabetes and becomes apparent when pancreatic beta cell mass is reduced after DP.
KEY FINDINGS: Impaired glucose tolerance and reduced early-phase insulin response to glucose are involved in the development of new-onset diabetes after DP; the latter is an additional factor in the development of diabetes and becomes apparent when pancreatic beta cell mass is reduced after DP.
BACKGROUND: Aim of this study is to investigate the changes in diabetes-related traits before and after DP and to clarify the incidence of diabetes and its predictors.
DETAILS: Among 493 registered patients, 117 underwent DP. Among these, 56 patients without diabetes before surgery were included in the study. Glucose and endocrine function were prospectively assessed using a 75-g oral glucose tolerance test preoperatively, 1 month after DP, and every 6 months thereafter for up to 36 months. Pancreatic volumetry was performed using multidetector row computed tomography before and after surgery. Insulin secretion decreased and blood glucose levels worsened after DP. Residual pancreatic volume was significantly associated with the reserve capacity of insulin secretion but not with blood glucose levels or the development of diabetes. Among 56 patients, 33 developed diabetes mellitus. The cumulative incidence of diabetes at 36 months after DP was 74.1%. Multivariate Cox regression analysis showed that impaired glucose tolerance as a preoperative factor as well as a decreased insulinogenic index and impaired glucose tolerance at 1 month postoperatively were identified as risk factors for diabetes following DP.
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Copyright © The Author(s). Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.
Source: Imamura, S., Niwano. F., Babaya, N., et al. (2024). High Incidence of Diabetes Mellitus After Distal Pancreatectomy and Its Predictors: A Long-term Follow-up Study. The Journal of Clinical Endocrinology & Metabolism. 2024; 109(3): 619-630. Published: March, 2024. DOI: 10.1210/clinem/dgad634.
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