Kattah, Andrea G.

Abstract The incidence of hypertensive disorders of pregnancy is increasing, which may be due to several factors, including an increased age at pregnancy and more comorbid health conditions during reproductive years. Preeclampsia, the most severe hypertensive disorder of pregnancy, has been associated with an increased risk of future disease, including cardiovascular and kidney diseases. Cellular senescence, the process of cell cycle arrest in response to many physiologic and maladaptive stimuli, may play an important role in the pathogenesis of preeclampsia and provide a mechanistic link to future disease. In this article, we will discuss the pathophysiology of preeclampsia, the many mechanisms of cellular senescence, evidence for the involvement of senescence in the development of preeclampsia, as well as evidence that cellular senescence may link preeclampsia to the risk of future disease. Lastly, we will explore how a better understanding of the role of cellular senescence in preeclampsia may lead to therapeutic trials. © 2023 American Physiological Society. Compr Physiol 13:5077‐5114, 2023.

Abstract Preeclampsia and other hypertensive disorders of pregnancy are major contributors to maternal morbidity and mortality worldwide. This group of disorders includes chronic hypertension, gestational hypertension, preeclampsia, preeclampsia superimposed on chronic hypertension, and eclampsia. The body undergoes important physiological changes during pregnancy to allow for normal placental and fetal development. Several mechanisms have been proposed that may lead to preeclampsia, including abnormal placentation and placental hypoxia, impaired angiogenesis, excessive pro‐inflammatory response, immune system imbalance, abnormalities of cellular senescence, alterations in regulation and activity of angiotensin II, and oxidative stress, ultimately resulting in upregulation of multiple mediators of endothelial cell dysfunction leading to maternal disease. The clinical implications of preeclampsia are significant as there are important short‐term and long‐term health consequences for those affected. Preeclampsia leads to increased risk of preterm delivery and increased morbidity and mortality of both the developing fetus and mother. Preeclampsia also commonly leads to acute kidney injury, and women who experience preeclampsia or another hypertensive disorder of pregnancy are at increased lifetime risk of chronic kidney disease and cardiovascular disease. An understanding of normal pregnancy physiology and the pathophysiology of preeclampsia is essential to develop novel treatment approaches and manage patients with preeclampsia and hypertensive disorders of pregnancy. © 2023 American Physiological Society. Compr Physiol 13:4231‐4267, 2023.

Key Points Patient-centered care in an interdisciplinary CKD clinic addresses complex needs and supports comprehensive CKD management. Implementation of an interdisciplinary CKD clinic reduced hospital admissions by 26%, emergency department visits by 30%, and increased nephrology consultations. Comprehensive care models with integrated registries enhance tailored interventions, leading to improved CKD management outcomes. Background CKD is a significant public health issue globally. Its progressive nature calls for innovative care models to mitigate disease progression and enhance patient outcomes. An interdisciplinary clinic model may offer comprehensive care tailored to the needs of patients with CKD. The aim of this study was to evaluate the effect of an interdisciplinary CKD clinic on disease progression, health care utilization, and social determinants of health (SDOH). Methods We conducted a retrospective cohort study at the Mayo Clinic in Rochester, Minnesota. The study included 534 patients enrolled in the CKD clinic between March 5, 2021, and May 31, 2022, excluding those who opted out of research. The intervention involved a clinical registry and an interdisciplinary team delivering evidence-based care pathways, patient education, shared decision making, and care coordination. The primary outcomes assessed were CKD progression and health care utilization, while secondary outcomes examined the effect of SDOH. Results At entry, the median age was 73 (interquartile range, 64–79) years, with 60% at stage 4 or lower. Clinic implementation correlated with a 26% decrease in hospital admissions (incidence rate ratio [IRR], 0.74; 95% confidence interval [CI], 0.60 to 0.91; P = 0.004) and a 30% reduction in emergency visits (IRR, 0.70; 95% CI, 0.57 to 0.87; P = 0.001). Nephrology consultations increased by 46% (IRR, 1.46; 95% CI, 1.34 to 1.60; P < 0.001), reflecting enhanced specialized care. Lower exercise frequency and unemployment were linked to increased CKD progression and health care usage. Conclusions An interdisciplinary CKD clinic supported by a registry can potentially reduce health care utilization among patients with CKD, with SDOH playing a critical role in disease management.

Abstract Disclosure: L. Rahimi: None. J. Saini: None. E. Atkinson: None. S. Achenbach: None. A. Kattah: None. I. Bancos: None. Introduction: Patients with mild autonomous cortisol secretion (MACS) have higher prevalence of cardiovascular comorbidities including chronic kidney disease. However, considering that patients with MACS may have relative skeletal muscle atrophy, it is unclear whether the creatine-based assessment of kidney function is accurate in this population. Objective: To characterize the differences in assessing estimated glomerular filtration rate using cystatin (eGFRcys) versus creatinine (eGFRcre) in patients with MACS versus referent subjects. Methods: Cross-sectional single-center study, 2019-2022. MACS was defined as serum cortisol concentration &gt;1.8 mcg/dL after the 1 mg overnight dexamethasone suppression test (DST). For each patient, eGFRcre, eGFRcys and eGFRcre/eGFRcys ratio were measured and compared between the two groups. Body composition was measured by DXA scan. The Kruskal-Wallis test was used to compare measurements between groups. Result: A total of 37 patients with MACS (median age 59 years (interquartile range, IQR 47-67), 25 (68%) women) and 45 referent subjects (median age 57 years (IQR 51-66), 30 (67%) women) were included. The distribution of BMI, total body fat mass and total body lean mass were similar between the two groups. In the MACS cohort, the median cortisol following 1-mg DST was 3.0 ug/dL (IQR, 2.2-4.0). While assessment of kidney function with eGFRcre showed no differences between patients with MACS and referent subjects (median 85.1 vs 87.0 ml/min/1.73m2, P=0.431), kidney function using eGFRcys was lower in MACS (median 78.0 vs 89.3 ml/min/1.73m2 in referents, P&lt;0.014), resulting also in a higher eGFRcre/eGFRcys ratio (median 1.07 vs 0.97 in MACS vs referents, P=0.053). After adjusting for age, sex, and BMI, a higher 1 mg DST cortisol level in the MACS cohort was associated with a higher eGFRcre/eGFRcys ratio (Spearman correlation coefficient of 0.35, P = 0.042). Lower eGFRcys was associated with higher fat mass (Spearman correlation of -0.26, P = 0.023), and a higher eGFRcre/eGFRcys ratio showed a trend towards lower lean mass (Spearman correlation of -0.20, P = 0.081). Conclusion: Creatinine-based eGFR assessment in patients with MACS underestimates the degree of kidney dysfunction, likely due to underlying skeletal muscle atrophy. eGFRcys is a more accurate indicator of kidney function in patients with hypercortisolism. Presentation: 6/1/2024