bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 083: γ/δ T Cells Play a Role in Development of Hypertension
Authors: Caillon Antoine , Mian Muhammad O , Fraulob-Aquino Julio C , Huo Ku-Geng , Barhoumi Tlili , Sinnaeve Peter R , Granger Christopher B , Paradis Pierre , Schiffrin Ernesto L
Published: June 2021

Objective:
Both innate antigen-presenting cells and the adaptive immune system have been shown to play a role in the development of hypertension. Nevertheless, the T cell subsets involved in the pathophysiology of hypertension remains unclear. There is a small subset of “innate-like” T cells expressing the γ/δ T cell receptor (TCR) rather than the α/β TCR that could play a role bridging the innate and adaptive immune systems. We previously observed that angiotensin (Ang) II caused an increase in number and activation of γ/δ T cells and Ang II-induced systolic blood pressure (SBP) rise and vascular injury were blunted in
Tcr
δ

-/-

mice, which are devoid of γ/δ T cells. In order to further characterize the role of γ/δ T cells in hypertension, we determined whether Ang II-effects would be blunted by antibody-induced depletion of γ/δ T cells. In addition, we tested whether SBP in human could be predicted by combining the expression of genes encoding TCRGC (TCR gamma constant region) and pro-inflammatory markers of γ/δ T cells in peripheral blood mononuclear cells (PBMC).

Method and Results:
Thirteen to 15-week old male C57BL/6 wild-type (WT) mice were infused with Ang II (490 ng/kg/min, SC) for 14 days and injected IP with anti-γ/δ TCR or control isotype antibodies 1 day before and at day 6 of Ang II infusion. Depletion of γ/δ T cells decreased SBP (147±2
vs
167
±
3 mm Hg,
P
<0.05) and restored mesenteric artery relaxation responses to acetylcholine (E
max
: 90±4
vs
62
±
8%,
P
<0.05) compared to isotype antibody-treated mice. Using the SBP data and the PBMC gene expression profile (GSE12288) of 222 human subjects, we predicted with a supervised machine learning approach SBP by combining the gene expression of TCRGC and pro-inflammatory makers including interleukin-17A, interferon-γ and their receptors (R=0.23,
P
<0.001).

Conclusion:
Antibody-induced depletion further demonstrates the role of γ/δ T cells in Ang II-induced SBP elevation and vascular injury. Prediction of SBP using PBMC gene expression of γ/δ T cells and pro-inflammatory markers suggests that γ/δ T cells contribute to the development of human hypertension.
Abstract 086: The Angiotensin-(1-7) Mas Receptor Protects Heart and Lung Against Lps-induced Shock in Mice
Authors: Motta-Santos Daisy , Oliveira-Lima Onésia Cristina , Magalhães Giselle Santos , Rocha-Resende Cibele , Scalzo Sergio , Melo Marcos Barrouim , Carvalho-Tavares Juliana , Alenina Natalia , Bader Michael , Campagnole-Santos Maria José , Guatimosim Silvia Cristina Fonseca , Santos Robson Augusto Souza dos
Published: June 2021

The renin-angiotensin system (RAS) plays a key role inthe modulation of multiple functions in many organs. It has been demonstrated that the protective axis Ang-(1-7)/ACE2/Mas exerts anti-inflammatory effects in different disorders. Along this line, we have shown that Mas receptor deficiency exacerbates lipopolysaccharide(LPS)-induced cerebral and systemic inflammation in mice. In this study, we investigate the effects of LPS-induced shock in a mouse model for global increases in Mas receptor expression (UB8 mice). Mice were injected intraperitoneally (i.p.) with LPS, and experiments were performed 1h (RT-qPCR and ELISA) and 6 h (Echocardiography, NAG activity, and Lung histological analysis) after injection (except for the survival curve experiment). Cytokine gene expression was significantly attenuated in the left ventricle (LV) of UB8 vs. FVBN mice (p<0.05) the 1 hour after LPS (5mg/kg) administration: IL6 (119.7 ± 26.9 vs.199.6 ± 31.9 a.u), TNFα (59.3 ± 5.8 vs.89.2 ± 5.9 a.u), IL1β(56.6 ± 11,5 vs.122.8 ± 20.4 a.u) and IL10 (33.8 ± 3.5 vs.72.6 ± 5.8 a.u). Similar results were observed in serum protein levels: IL6 (6,651 ± 946.4 vs.3,203 ± 904.1 pg/ml), TNFα (925.5 ± 56.6 vs. 1,380 ± 114.1 pg/ml), IL1β (2,844 ± 462.2 vs. 5,876 ± 841.5 pg/ml) and IL10 (8.8 ± 6.4 vs.230.6 ± 54.4 pg/ml). In FVBN mice, LPS (15 mg/kg) significantly decreased stroke volume (before: 31.92 ± 2.44 after LPS: 17.50 ± 1.61 ul), cardiac output (before: 30.92 ± 2.35 after LPS: 16.83 ± 1.56 ml/min) but in the LPS-treated UB8 mice, no changes were observed in cardiac function. Additionally, Increases in NAG activity in the LV and lung and in Alveolar Wall Thickening (AWT) were seen only in FVBN mice after LPS administration (LV NAG FVBN sham vs. FVBN LPS: 0.051 ± 0.008 vs. 0.096 ± 0.004 U/L and lung: 0.030 ± 0.034 vs. 0.673 ± 0.093; AWT FVBN sham: 0.794 ± 0.160 vs FVBN LPS 1.781 ± 0.118 m2). Finally, we found a significant increase in survival of UB8 mice (60.32 %) vs. FVBN (48.3%) after LPS administration (30mg/kg). Taken together, these results indicate that global increase in receptor Mas expression in mice exerts protective actions in heart and lung against LPS challenge, highlighting the therapeutic potential of Mas axis during inflammatory processes.
Abstract 087: Mitochondrial Fission Inducer, Dynamin-Related Protein 1 (DRP1), is Required for Endothelial Inflammatory Responses
Authors: Forrester Steven J , Kawai Tatsuo , Elliott Katherine J , Eguchi Kunie , Rizzo Victor , Eguchi Satoru
Published: June 2021

Among various cardiovascular diseases, hypertension (HTN) is considered to be a disease plagued by chronic low-grade inflammation associated with endothelial dysfunction. Interestingly, recent studies have identified mitochondrial adaptation and/or dysfunction as components to hypertensive vascular dysfunction. While mitochondria are indispensable to maintain cellular metabolism, they also participate in adaptive and maladaptive cell/tissue responses via several retro grade signaling pathways. DRP1 plays a major role in mitochondrial quality control. However, whether DRP1 is involved in mitochondrial dysfunction and endothelial inflammation during development of HTN remains unknown. In the present study, we tested the hypothesis that inflammatory stimuli, through DRP1-dependent mitochondrial alteration, enhance endothelial inflammation. In cultured rat aortic endothelial cells (RAECs), TNFα (10 μg/mL) transiently induced mitochondrial fission maximally at 3h which was inhibited using a mitochondrial fission inhibitor, Mdivi1 (10 μM) (0.16±0.04 vs 0.10±0.02 mitochondria fragmentation count with MitoTracker,
p<.01
). TNFα and FCCP (a fission agonist, 10 μM) increased THP-1 monocyte adhesion to RAECs, which was also inhibited with Mdivi1 (256±17 vs 139±16 for TNFα, 238±30 vs 156±14 for FCCP, attached cells per field scanned,
p<.01
). Likewise, mdivi1 and adenoviruses encoding siRNA for DRP1 or dominant-negative K38A DRP1 (50 moi) attenuated TNFα-induced VCAM-1 induction in RAECs. TNFα increased aerobic respiration, which was prevented by mdivi1 or ER stress inhibitor PBA (10 mM). Inhibition of ER stress, glycolysis or mitochondrial respiration using PBA, 2-DG (1 mg/mL) or oligomycin (1 μM) prevented VCAM-1 induction. However, suppression of TNFα-induced mitochondrial ROS production by mito-Tempo (25 nM) was unable to prevent VCAM-1 induction. In C57BL6 mice receiving AngII (1000 ng/kg/min, 2 weeks) infusion, treatment with Mdivi-1 (25 mg/kg ip every other day) or PBA (1g/kg/day) prevented vascular VCAM-1 induction. In conclusion, our data suggests a critical role for ER stress and subsequent functional and structural remodeling of mitochondria induced by DRP1 in mediating endothelial inflammatory activation in HTN.
Abstract 091: High Salt Promotes Conversion of Human Monocytes Into Dendritic Cells via Formation of Immunogenic Isoketals
Authors: Barbaro Natalia R , Foss Jason D , Montaniel Kim R , Chen Wei , Harrison David G , Kirabo Annet
Published: June 2021

High salt intake and inflammation are implicated in the genesis of hypertension. Recently it has become clear that sodium can accumulate in the interstitial space in concentrations exceeding that of the plasma, and that these high salt (HS) concentrations can be pro-inflammatory. Our laboratory recently published a new pathway in which increased oxidative stress in dendritic cells (DCs) leads to formation of isoketal-modified proteins which act as neo-antigens to activate T cells. We hypothesized that increasing sodium chloride (NaCl) in excess activates antigen presenting cells via formation of immunogenic isoketals. We exposed monocytes from human volunteers to normal physiological NaCl (NS: 150 mM/L), elevated NaCl concentrations (HS: 190 mM/L), or an equiosmoloar concentration of mannitol. We found that exposure of human monocytes to high salt, but not mannitol, caused a 2-fold increase in formation of isoketal-modified proteins. This was associated with an increase in activation marker CD86 (NS: 466 ± 192 vs HS: 596 ± 324 MFI p<0.05) and production of inflammatory cytokines IL-6, IL-β and TNF-α. Interestingly, these cells expressed surface markers indicative of transformation to DCs, as evidenced by their acquisition of surface marker CD83. In additional immunofluorescence studies, we found that monocytes exposed to HS for 7 days acquire a DC like morphology. Moreover, using flow cytometry, we confirmed that high salt exposure causes these cells to lose the monocyte marker CD14 (NS: 41.1 ± 15.4 vs HS: 19.9 ± 6.4 MFI; p<0.05), and gain the DC marker CD209 (NS: 24.2 ± 1.0 vs HS: 49.3 ± 0.7 MFI; p<0.001). None to these effects were mimicked by mannitol and scavenging of isoketals during high salt exposure. High salt dramatically increased mRNA expression of GM-CSF (NS: 758 ± 440.8 vs HS: 5476 ± 2268 MFI; p<0.05), IL-4 NS: 1868 ± 560.6 vs HS: 4867 ± 1152 MFI; p<0.05) and Flt3 (NS: 2526 ± 636.8 vs HS: 10014 ± 2370 MFI; p<0.05), which are known to mediate monocyte conversion to DCs. Thus, we have defined a novel pathway whereby high NaCl concentrations lead to transformation of monocytes to DCs due to increased formation of immunogenic isoketals. These observations provide insight into how elevated sodium environments lead to an inflammatory state.
Abstract 093: Salt-sensitivity, Salt-resistance, and Incidence of Hypertension
Authors: He Jiang , Chen Jing , Huang Jianfeng , Chen Jichun , He Hua , Li Jianxin , Cao Jie , Chen Chung-Shiuan , Gu Dongfeng
Published: June 2021

It is well known that blood pressure (BP) responses to dietary sodium intake vary among individuals (salt-sensitivity and salt-resistance). However, it is unknown whether salt-sensitivity and salt-resistance predict the risk of hypertension. We conducted a dietary sodium intervention study among 1,906 Han Chinese in 2003-05 and followed the study participants in 2008-09 and 2011-12. The dietary intervention included a 7-day low-sodium feeding (51.3 mmol/day) and a 7-day high-sodium feeding (307.8 mmol/day). Three BP measurements were obtained during each of the 3 days of baseline observation and on days 5, 6, and 7 of each intervention period. We used latent class models to identify subgroups that share a similar underlying trajectory in BP responses to sodium intervention. Over an average of 7.4 years of follow-up, we identified 514 incident hypertension cases. The mean (standard deviation) change in systolic BP during low-sodium and high-sodium interventions according to salt-sensitive and -resistant groups are shown in the following table. In addition, age, sex, and baseline BP-adjusted and multiple-adjusted odds ratios (95% CI) of incident hypertension are shown in the following table. These data indicate that high responses or non-responses to dietary sodium intervention are related to the risk of hypertension. Furthermore, this is the first prospective cohort study to indicate that individuals with either salt-sensitivity or salt-resistance are at an increased risk for hypertension and should be targeted for dietary intervention.
Abstract 101: Alms1 (Alstrom Syndrome 1), a Novel Gene Involved in Blood Pressure Regulation, Renal Na Handling and Thick Ascending Limb (TAL) Function
Authors: Jaykumar Ankita Bachhawat , Caceres Paulo , Ares Gustavo , Beierwaltes William H , Ortiz Pablo A
Published: June 2021

Single nucleotide polymorphisms in the Alstrom syndrome 1 (ALMS1) gene are associated to hypertension, renal dysfunction, and obesity in the general population. The role of ALMS1 in regulating blood pressure or renal Na handling is unknown. In a proteomics screen, we identified ALMS1 as an interacting protein with the Na/K/2Cl cotransporter NKCC2. NKCC2 mediates NaCl reabsorption by the TAL. Thus, we hypothesized that ALMS1 regulates NKCC2 endocytosis and activity as well as blood pressure. First, we confirmed the expression of ALMS1 in isolated perfused TALs. To study ALMS1 function, we generated ALMS1 knockout (KO) rats in collaboration with the rat genome editing consortium at MCW and confirmed deletion of the ALMS1 gene. We found that 3 month old ALMS1 KO rats are hypertensive compared to wild type littermates (ALMS1 MAP: 141 ± 5 mmHg vs WT: 99 ± 6 mmHg, p< 0.005) fed a normal Na diet. We measured surface and intracellular NKCC2 and found a higher percentage of NKCC2 at the surface in TALs from ALMS1 KO (ALMS1: 13.8 ± 1.2% vs WT: 9.1 ± 1.0%, p<0.05, n=6). The increase in surface NKCC2 is due to lower endocytosis because the rate of NKCC2 internalization was lower in TALs from ALMS1 KO (ALMS1: 13.1 ± 1.2% vs WT: 28.2 ± 2.8% over 20 min, p<0.01, n=6). To study NKCC2-mediated Na transport
in vivo
, we measured bumetanide-induced natriuresis and diuresis. ALMS1 KO rats exhibited higher bumetanide-induced natriuresis (ALMS1: 1292 ± 65 vs WT: 564 ± 31 μmoles, p<0.01, n=5) and diuresis (ALMS1: 3.1 ± 0.32 vs WT: 1.6 ± 0.13 ml, p<0.05), indicative of higher TAL Na reabsorption. To study if this decreases the ability to excrete a volume and Na load in ALMS1 KO, we instrumented anesthetized rats and measured sodium excretion (U
Na
V) and urine volume (UV) over 150 min after an acute saline load. We found that the cumulative U
Na
V was lower in ALMS1 KO rats (ALMS1: 72 ± 38 vs WT: 219 ± 55 μmoles, p<0.05, n=8) as was the UV (ALMS1: 0.70 ± 0.24 vs WT: 1.78 ± 0.39 ml, p<0.05). We conclude that deletion of ALMS1 decreases NKCC2 endocytosis and increases TAL Na reabsorption. Thus, the hypertension observed in ALMS1 KO rats may be in part due to higher renal Na reabsorption. It is not known whether the expression of ALMS1 protein is decreased in hypertensive patients or lowered by dietary factors that increase BP in humans.
Abstract 105: Maternal Diet Leads to Nephron Count Differences After Postnatal Day 14 and Time-dependent Differences in Apoptosis and Unfolded Protein Response in Dahl Salt-sensitive Rats
Authors: Cabacungan Erwin T , Geurts Aron M , Mattson David L , Mingyu Liang
Published: June 2021

We have shown that maternal exposure to Casein-based AIN-76A diet [SS/JrHsdMcwi (SS/Mcw) rats] compared to grain-based 5L2F diet [SS/JrHsdMcwiCrl (SS/Crl) rats] during the gestational-lactational period exacerbates the development of salt-induced hypertension and renal injury in adult SS rats. We hypothesized that SS/Mcw rats will have significantly fewer glomeruli than SS/Crl rats, and determined its potential mechanisms. At different time points during development [embryonic day 20 (E 20), day of life (DOL) 14, 21, 56]: glomerular counts were determined by maceration method and by glomerular density (total glomerular number/renal cortex area); apoptosis was measured by TUNEL assay; RT-PCR, Western Blot and immunostaining were used to examine the expression level of genes involved in the apoptotic pathway and unfolded protein response (UPR). We found lower glomerular counts in SS/Mcw compared to SS/Crl rats at DOL 21 [26048±1423 per kidney vs. 34766±1821 (p<0.001] and DOL 56 [15717±2052 vs. 27999±3362 (p <0.001)], and lower glomerular densities [DOL 21, 10.8±1.0/mm2 vs. 13.2±1.6 (p<0.001); DOL 56, 2.4±0.1 vs. 3.6±0.2 (p < 0.001)]. Glomerular density was not different between SS/Mcw and SS/Crl at DOL 14 when nephrogenesis is complete. We found higher glomerular apoptosis in SS/Mcw compared to SS/Crl rats at DOL 14 [9.5±1.4 per 100 glomeruli vs. 5.1±1.8 (p<0.01)] and DOL 21 [5.2±0.7 vs. 3.6±0.5 (p <0.01)]. mRNA levels of several genes involved in intrinsic apoptotic pathway and UPR were significantly upregulated in SS/Mcw rats compared to SS/Crl rats at different time points. Significantly lower UPR-related protein expression in SS/Mcw compared to SS/Crl rats was detected for JNK and GRP78 (DOL 14 and 56) and CHOP (DOL 56). Significantly higher UPR-related protein expression in SS/Mcw compared to SS/Crl rats were detected for GRP78 (E 20), JNK (DOL 21) and Caspase 12 (DOL 14, 21 and 56). Caspase 12 was located in the glomeruli in DOL 21 and 56 kidneys. Our results show marked decrease of glomerular counts with age in SS/Mcw compared to SS/Crl after DOL 14. The time-dependent differences in the expression of apoptosis and UPR-related genes leading to glomerular apoptosis may be a potential mechanism for the nephron count differences between SS/Mcw and SS/Crl.
Abstract 106: Signaling Mechanisms Affecting Nitric Oxide Production in Glomerular Podocytes
Authors: Palygin Oleg , Ilatovskaya Daria V , Levchenko Vladislav , Endres Bradley T , Geurts Aron M , Staruschenko Alexander
Published: June 2021

While Nitric Oxide (NO), a potent vasodilator and vital signaling molecule, has been shown to contribute to the regulation of glomerular ultrafiltration, its role in podocytes during the pathogenesis of salt-sensitive hypertension has not yet been thoroughly examined. Recent studies have demonstrated that the deficiency of eNOS (the enzyme responsible for synthesizing NO) exacerbates renal injury and accelerates development of proteinuria and glomerulosclerosis. Considering this, we hypothesized that the podocytes of hypertensive animals would exhibit reduced NO production in response to various paracrine factors and this directly contributes to proteinuria. To test this, we isolated glomeruli from the kidneys of Dahl salt-sensitive (SS) rats fed either a high salt (HS; 4% NaCl, 3 weeks) or low salt (LS; 0.4% NaCl) diet and loaded podocytes with a combination of NO and Ca
2+
ionophores (DAF-FM and Fura Red, respectively). Changes in fluorescence were observed with the use of confocal microscopy in response to adenosine triphosphate (ATP), angiotensin II (Ang II), and H
2
O
2
. Application of Ang II or H
2
O
2
resulted in activation of both NO and [Ca
2+
]
i
; fluorescent transients which were significantly elevated in the soma and foot processes of podocytes of LS fed rats. In contrast, ATP specifically activated only changes in [Ca
2+
]
i
, but did not have any effects on NO production. Ang II treatment also caused hypertrophy of the podocytes, whereas ATP had no effect on cell volume (41.1±7.7 vs. 0.1±3.6% increase for Ang II and ATP, respectively;
P
<0.05). Collectively, our results show that in contrast to [Ca
2+
]
i
, which is modulated by all studied paracrine molecules, NO is produced by podocytes only in response to Ang II and H
2
O
2
, but not ATP. SS rats fed a HS diet for 3 weeks demonstrated impaired NO production; the response to Ang II or H
2
O
2
on HS contained only 23.7±6.6 and 43.4±28.4% of total effects on LS, respectively (
P
<0.05). Therefore, when fed a HS diet, SS podocytes had an impaired NO response to Ang II or oxidative stress, suggesting that NO signaling is dysfunctional and likely contributes to the development of kidney injury.
Abstract 107: Mir-431 as a Potential Master Regulator in Angiotensin Ii-induced Vascular Injury
Authors: Huo Kugeng , Barhoumi Tlili , Fraulob-Aquino Julio C , Richer Chantal , Lajoie Mathieu , Sinnett Daniel , Paradis Pierre , Schiffrin Ernesto L
Published: June 2021

Objective:
Vascular injury is an early manifestation and a cause of end-organ damage in hypertension. microRNAs (miRNAs) play an important role in cardiovascular disease, but their implication in vascular injury is remains unclear. We aim to use RNA sequencing (seq) and a systems biology approach to identify master regulators that mediate global gene expression changes in the course of vascular injury.

Methods and Results:
Ten week-old male C57BL/6 mice were infused or not with angiotensin (Ang) II (1 μg/kg/min, SC) for 14 days. Blood pressure (BP) was measured by telemetry. Total RNA was extracted from the mesenteric vasculature for total RNA and small RNA-seq. Differentially expressed (DE) miRNAs (23 up and 12 down) and mRNAs (550 up and 256 down) were identified (1.5-fold,
q
<0.05). Molecular networks were constructed to integrate predicted interactions between DE miRNAs and inversely expressed DE mRNAs and between DE transcription factors (TF) and DE genes. Gene enrichment analysis revealed DE mRNAs involved in extracellular matrix (ECM) and developmental processes regulated by DE miRNAs (
q
<1.5E-11). Seventeen upregulated miRNAs are located in the miRNA cluster of the Dlk1-Dio3 region that is highly conserved in humans, 9 of which had expression levels correlated with BP (
P
<0.05). Among those 9, miR-431 that ranked first as DE miRNA (
q
<0.0005) and is 100% conserved in humans, and a conserved putative DE target, a BP-correlated (
P
<0.05) TF ETS homologous factor (
Ehf
), which regulates numerous ECM genes including collagen type I α1 (
Col1a1
), were selected for functional studies. Transfection of a miR-431 mimic in human aortic smooth muscle cells (HASMCs) decreased
Ehf
(0.1±0.1-fold,
P
<0.001) and increased
Ehf
-suppressing target
Col1a1
(1.7±0.5-fold,
P
<0.001) mRNA levels. Transfection of a miR-431 inhibitor caused reciprocal effects (
P
<0.05).
Ehf
siRNA knockdown increased
Col1a1
(1.2±0.1-fold,
P
<0.001) mRNA levels.

Conclusions:
Ang II infusion altered expression of miRNAs in the Dlk1-Dio3 cluster and genes involved in ECM and developmental processes. miR-431 targets TF
Ehf
, which leads to increased
Col1a1
in HASMCs. miR-431 may act as a master regulator for vascular injury and could be a potential therapeutic target.
Abstract 116: The Effect of a Practice-based Multi-component Intervention That Includes Health Coaching on Medication Adherence and Blood Pressure Control in Rural Primary Care
Authors: Wu Jia-Rong , Cummings Doyle M , Li Quefeng , Halladay Jacquie , Donahue Katrina , Cene Crystal , Hinderliter Alan , Bosworth Hayden , Miller Cassandra , Garcia Beverly , Tillman Jim , DeWalt Darren
Published: June 2021

Background:
Lower adherence to anti-hypertensive medications contributes to sub-optimal patient outcomes, yet there are few successful interventions in rural primary care that target improved adherence. The purpose of this study was to determine whether a multi-component quality improvement intervention that included literacy-sensitive health coaching with motivational interviewing was associated with improved medication adherence and reductions in blood pressure (BP) in patients with a history of uncontrolled hypertension (HTN).

Methods:
Adult patients in six rural primary care settings with one or more visits in the last year with a systolic BP > 150 mmHg were recruited. Project faculty facilitated systematic changes in care delivery in local practices. Patients also received monthly phone-based literacy-sensitive health coaching including a focus on medication adherence, and a BP cuff for home monitoring. Data regarding medication adherence (Morisky Medication Adherence Scale-8) and BP were collected at baseline, 6, 12, 18, and 24 months. Linear mixed effects modeling was used to determine the effects of the multi-component intervention on medication adherence and whether changes in medication adherence were associated with changes in systolic and diastolic BP.

Results:
There were 477 patients enrolled; the majority were female, black, and reported an annual household income of < $40,000. At baseline, 39% of the patients had low medication adherence (MMAS-8 score < 6). In linear mixed effects models, the intervention resulted in modest increases in medication adherence [5.75 ± 1.37 at baseline to 5.94 ± 1.33 at 24 months (p = .04)]. Corresponding changes in BP were: from 138.6 ± 21.8/81.6 ± 12.9 mmHg at baseline to 132.7 ± 19.5/76.1 ± 14.5 mmHg at 24 months follow-up [mean 0.22-0.25/0.24-0.26 mmHg per month before and after adjustment for covariates (p < .001)]. Changes in medication adherence were significantly associated with reductions in diastolic BP longitudinally (p = .047).

Conclusion:
A practice-based quality improvement intervention that includes health coaching is associated with improvements in medication adherence and BP, and offers promise as a clinically applicable intervention in rural primary care.
Abstract 117: Preclinical Target Organ Damage Changes in Patients with Resistant Hypertension Randomized to Renal Denervation or Spironolactone as Add-on Therapy. Results From the DENERVHTA Study
Authors: Oliveras Anna , Armario Pedro , Sans Laia , Clarà Albert , Vázquez Susana , Molina Lluis , Pareja Júlia , Pascual Julio , de la Sierra Alejandro
Published: June 2021

Objective:
To compare the effect of renal denervation (RDN) and spironolactone, two proposed therapeutic strategies for the treatment of patients with resistant hypertension (RH), on preclinical target organ damage (pTOD).

Methods:
Patients with office systolic blood pressure (SBP) ≥150 mmHg and 24h-SBP ≥140 mmHg despite receiving ≥3 full-dose antihypertensive drugs, one a diuretic, but none aldosterone antagonist, were randomized to receive RDN or spironolactone (50mg), as add-on therapy. Changes (Δ) in 24h-BP, as well as Δ in urinary albumin excretion (ΔUAE), carotid-femoral pulse-wave velocity (ΔcfPWV), carotid intima-media thickness (ΔIMT), left ventricular mass index (ΔLVMI) and E/e’ (ΔE/e’), a marker of hypertension-induced diastolic dysfunction, were evaluated at 6 months. Between-group comparisons of ΔUAE (after log transformation), ΔcfPWV, ΔIMT, ΔLVMI and ΔE/e’ were carried out by generalized linear models before and after adjusting by Δ24h-SBP and the corresponding baseline value.

Results:
Twenty-four patients (mean age 64±8 yr) were included. Mean baseline-adjusted difference (95% CI) between the two groups (Spironolactone vs.RDN) at 6 months in 24h-SBP (mmHg) was of-17.9 (-30.9 to -4.9), p=0.01. As shown in the table, there were no statistically significant between-group differences in Δ on pTOD.

Conclusion:
Changes at 6 months on pTOD as assessed by UAE, cfPWV, IMT, LVMI and E/e’, were not associated with the therapeutic add-on strategy used to reduce high blood pressure in RH patients. We cannot discard that the high variability of some of these markers, especially UAE, could account for this lack of statistically significant between-group differences.
Abstract 119: Anti-hypertensive Effect of Thiazides Shifts From Salt Excretion to Vasorelaxation During Salt Restriction or Volume Depletion
Authors: Alshahrani Saeed , Zahedi Kamyar , Jiang Min , Nieman Michelle , Barone Sharon , Lorenz John , Rubinstein Jack , Soleimani Manoocher
Published: June 2021

Thiazide derivatives, including hydrochlorothiazide (HCTZ), are specific inhibitors of the Na+-Cl- Co-transporter (NCC) in the kidney distal tubules, and the most commonly used diuretic for the treatment of mild to moderate hypertension. Both renal (natriuretis) and extra renal (vasorelaxation) mechanisms have been proposed as major mediators of blood pressure reduction by HCTZ but the circumstances under which the renal or extra renal mechanism predominates remain unknown . To address these issues, systemic blood pressure was monitored by intra-arterial catheter and computerized tail cuff in transgenic mice lacking NCC under varying conditions. For comparison, mice with pendrin ablation or double deletion of pendrin and NCC were used to ascertain the compensatory role of pendrin in salt reabsorption in response to HCTZ. Pendrin KO mice were the only group which showed enhanced salt excretion in response to HCTZ, with salt excretion increasing by ~30% in pendrin KO vs. WT mice (p<0.05). In mice lacking NCC, HCTZ significantly reduced the systemic blood pressure only during salt restriction and without enhancing salt excretion. In volume depleted but not in volume resuscitated NCC/pendrin dKO mice, HCTZ caused dramatic reduction in systemic blood pressure, with systolic blood pressure decreasing from 72.13± 5.1 at baseline to 51.06 ± 6.6 mm Hg in dKO mice within 20 minutes of HCTZ administration (p<0.01 vs. baseline) with no significant effect in WT mice (p>0.5 vs. baseline) or in salt resuscitated NCC/pendrin dKO mice. There was no enhancement in salt excretion and no reduction in echocardiography-monitored cardiac output in pendrin/NCC dKO mice in response to HCTZ. The antihypertensive effects of HCTZ were abrogated in the presence of paxilline, a specific blocker of BK channel, which is upregulated in arterial vasculature of volume depleted mutant mice. We propose that thiazides reduce blood pressure predominantly via vasorelaxation during salt restriction/volume depletion; whereas, they enhance salt excretion during salt replete state and specifically in conditions associated with pendrin downregulation/inactivation.
Abstract 124: Soluble (Pro)Renin Receptor Regulation of ENaC in Angiotensin II Signaling in the Collecting Duct
Authors: Wang Fei , Lu Xiaohan , Xu Chuanming , Peng Kexin , Yang Tianxin
Published: June 2021

We have shown that activation of (pro)renin receptor (PRR) and local renin response in the collecting duct (CD) contributes to AngII-induced hypertension. Moreover, the 28 kDa soluble (pro)renin receptor (sPRR) derived from cleavage of the extracellular domain of PRR is elevated by AngII and stimulated AQP2 expression via activation of frizzled-8/β-catenin pathway. Here we examined sPRR regulation of ENaC and further explored its implication in AngII signaling. In cultured mpkCCD cells, a recombinant histidine-tagged rat sPRR, sPRR-His, at 10 nM for 24 h induced a 3-fold increase in α-ENaC protein abundance. The native sPRR generated by immunoprecipitation with anti-sPRR antibody from either mouse or human urine exhibited a similar stimulatory effect on α-ENaC expression. The sPRR-His-induced α-ENaC expression was nearly completely abolished by a frizzled-8 inhibitor OMP54F03 (OMP). Similarly, amiloride-sensitive Na
+
transport as assessed by epithelial volt-ohmmeter was elevated by exposure to sPRR-His within minutes, which was abolished by OMP. In mpkCCD cells expressing a β-catenin-driven luciferase construct, the reporter activity was increased by 2.5-fold which was sensitive to OMP. In these cells, ENaC activity was transiently stimulated by exposure to 100 nM AngII within minutes, which was abolished by a sPRR neutralizing antibody. ELISA demonstrated that 24-h AngII treatment induced a 7-fold increase in medium sPRR concentrations. In floxed mice, urinary sPRR excretion was increased by AngII infusion whereas CD-specific PRR KO mice exhibited a reduced bassline level of urinary sPRR excretion which was not responsive to AngII infusion (300 ng/kg/min). Radiotelemetry demonstrated that the null mice were largely resistant to AngII-induced hypertension (MAP: Floxed/CTR: 105.9±1.6; Floxed/AngII: 136.3±3.1; KO/CTR:106.3±3.6; KO/AngII: 118.7±3.1 mmHg) which was fully restored after sPRR-His infusion via catheterization of jugular vein at 30 μg/kg/d (MAP: KO/AngII+sPRR-His: 135±7.5 mmHg). The MAP returned to normal when sPRR-His was terminated. Together, the present study reveals frizzled-8/β-catenin-dependent activation of α-ENaC in response to sPRR that at least in part contributes to AngII-induced hypertension.
Abstract 132: Adrenergic Receptor Blockade Prevents Placental Ischemia-induced Hypertension
Authors: Spradley Frank T , Granger Joey P
Published: June 2021

Hypertensive disorders of pregnancy are the number one cause of pregnancy-related deaths in the United States. Preeclampsia is a disorder of maternal hypertension and cardiovascular dysfunction typically presenting in the second half of pregnancy along with fetal growth restriction. There are no steadfast therapies besides early delivery of the fetus and ischemic placenta, which releases factors into the maternal circulation promoting hypertension. Although sympathetic nervous activity was found to be increased in preeclamptic versus normal pregnant women, it is unknown if sympathetic nervous system plays a role in placental ischemia-induced hypertension. To address this question, we tested the hypothesis that adrenergic receptor blockade prevents placental ischemia-induced hypertension. Wistar rats were randomized to receive reduced uterine perfusion pressure, (RUPP, n=6) or Sham (n=5) surgeries on gestational day 14 and examined at day 19. In RUPP vs Sham rats, respectively, mean arterial blood pressure (115 ± 4 vs 103 ±2 mmHg, P<0.05) and the number of absorbed fetuses (6 ± 1 vs 1 ± 1, P<0.05) were greater whereas average fetal weight was lower (1.7 ± 0.1 vs 2.0 ± 0.2, P<0.05) with similar placental weights (0.49 ± 0.03 vs 0.52 ± 0.03). In RUPP vs Sham rats, renal cortical norepinephrine content (HPLC) was higher (183 ± 15 vs 150 ± 8 pg/mg wet weight, P<0.05) and vasoconstriction to phenylephrine was greater in small, third order mesenteric arteries (Emax: 262 ± 19 vs 160 ± 26% of KCl response). A subset of RUPP rats (n=3) received terazosin and propranolol (3 mg/kg per day each, subcutaneous osmotic minipump) to block alpha- and beta-adrenergic receptors, respectively, beginning the day of RUPP surgery. At day 19, adrenergic blockade prevented the development of hypertension (100 ± 4 mmHg, P<0.05) and did not alter number of fetal absorptions (8 ± 1). Average fetal weight was higher (2 ± 0.1, P<0.05) and placental weight lower (0.41 ± 0.03, P<0.05) compared to the untreated RUPP rats. In conclusion, placental ischemia-induced hypertension depends on activation of the sympathetic nervous system. The mechanism for this enhanced sympathetic nerve activity is unknown but may involve factors released from the ischemic placenta.
Abstract 133: Depletion of Natural Killer Cell Activation in Response to Placental Ischemia Improves Hypertension and Intrauterine Growth Restriction During Pregnancy
Authors: Cornelius Denise C , Elfarra Jamil , Amaral Lorena M , McCalmon Maggie , Cunningham Mark W , Ibrahim Tarek , Scott Jeremy D , LaMarca Babbette
Published: June 2021

Women with preeclampsia (PE), newly developed hypertension and renal dysfunction during pregnancy, have small-for-gestational-age babies and demonstrate an increase in the cytolytic natural killer (NK) cell activation. The specific role of cytolytic NK cells in the pathophysiology of PE has not been clearly defined. The reduced uterine perfusion pressure (RUPP) model of placental ischemia (PI) exhibits many of the characteristics of PE including hypertension, renal dysfunction, chronic inflammation and intrauterine growth restriction (IUGR). In this study, we tested the hypothesis that PI results in cytolytic activation of NK cells, and examined a role for a reduction in NK cells in RUPP to attenuate PE-like characteristics in response to PI. In this study NK cells were depleted in RUPP rats by intraperitoneal administration of the Anti-asialo GM1 antibody on gestation days 15 and 17. PBMCs and placental lymphocytes were examined via flow cytometry to quantify cytolytic NK cells and to verify NK cell depletion, blood pressure (MAP) and pup weight were measured. While total
placental
NK cells numbers did not change in response to PI (NP: 14±4.5%; RUPP: 14.3±3.8%), cytolytic activation of
placental
NK cells significantly increased in response to PI (NP: 3.4±1.1% vs RUPP 10.0±3.4%; p<0.05). Moreover, depletion of NK cells in RUPP (total NK: RUPP: 14.3±3.8% vs RUPP+NKD: 3.5±0.9%) significantly improved blood pressure and intrauterine growth restriction (IUGR): MAP significantly increased in response to PI from 109.5±2.3 mmHg in NP (n=10) to 125.4±2.7 mmHg (n=9) in RUPP rats (p<0.001). Depletion of NK cells with the cell specific depleting antibody significantly lowered blood pressure to 114.4.±1.9 mmHg in RUPP+NKD rats (n=11, p<0.01). Additionally, NK cell depletion in RUPP significantly reduced IUGR in response to PI (1.85±0.06g in RUPP vs. 2.0±0.4g in RUPP+NKD; p<0.05). Depletion of NK cells in RUPP rats was positively associated with lowering blood pressure and blunting IUGR in response to PI. These results suggest a role for cytolytic NK in contributing to hypertension and IUGR in response to PI, potentially identifying previously unknown mechanisms of PE pathophysiology and new therapeutic targets to improve maternal and fetal outcomes of PE.
Abstract P105: Greater 24 Hour Blood Pressure Variability is Associated With Higher 24 Hour Systolic Blood Pressure and Glucose Independent of Age and Large Elastic Artery Stiffness in Normotensive Adults
Authors: DuBose Lyndsey E , Holwerda Seth W , Stroud Amy K , Wooldridge Nealy A , Myers Janie E , Dubishar Kaitlyn M , Pierce Gary L
Published: June 2021

Older age is associated with elevated large elastic artery stiffness, a strong predictor of cardiovascular (CVD) risk in middle-age/older (MA/O) adults independent of blood pressure (BP). Greater 24-hour systolic BP variability (BPV) is also an independent risk factor for CVD and is linked to large artery stiffness in MA/O adults with hypertension and diabetes. However, its relation to age-related arterial stiffness in adults with low risk factor burden is unclear. We hypothesized that higher systolic BPV would be: 1) associated with advancing age, and 2) related to elevated aortic and carotid artery stiffness among healthy MA/O adults. To determine this, 98 healthy adults (ages 19-70 yrs) with measurements of systolic BPV (standard deviation of 24 hr systolic BP) via ambulatory BP monitoring, aortic stiffness (carotid-femoral pulse wave velocity, cfPWV), carotid artery stiffness (β-stiffness via carotid tonometry/B mode ultrasound) and circulating metabolic factors were included. In the entire cohort, greater systolic BPV was not associated with age, cfPWV, carotid β stiffness or circulating lipids/glucose (all P>0.05), but was correlated (age-adjusted) with 24 hr systolic BP (r= 0.41, P<0.001) and BMI (r= 0.21, P<0.05). In stepwise linear regression analyses that included age, sex, BMI, only 24 hr systolic BP was associated with systolic BPV (β= 0.14 ± 0.03, Model R
2
= 0.20, P< 0.001). Interestingly, there was no difference in 24 hr systolic BPV (11.4 ± 0.4 vs 11.4 ± 0.5 SD mmHg, P=0.99) in young (n=55; 29.0 ± 0.7 yrs) vs. MA/O (n= 43; 53.0 ± 1.2 yrs) adults despite higher cfPWV (594 ± 12 vs 913 ± 39 cm/sec, P<0.001), carotid β-stiffness (6.8 ± 0.6 vs 9.3 ±0.9 U, P=0.001) and 24 hr systolic BP (121 ± 1 vs 125 ± 2 mmHg, P<0.05). Systolic BPV was associated with BMI (r= 0.42, p< 0.01) and fasting blood glucose (r= 0.54, P= 0.001) in MA/O but not young adults. In a stepwise linear regression model among MA/O, 24 hr systolic BP (β= 0.18 ± 0.04, R
2
= 0.36, P<0.001) and fasting glucose (β= 0.10 ± 0.05, R
2
change= 0.07, P<0.001) were the only significant correlates of systolic BPV (Model R
2
= 0.43, P<0.001). In conclusion, 24 hr systolic BP and fasting blood glucose, but not age or large elastic artery stiffness, were the strongest determinants of higher systolic BPV in normotensive MA/O adults.
Abstract P108: Circulating Matrix Metalloproteinase-2 Invades the Heart and Causes Heart Failure
Authors: Prado Alejandro F , Azevedo Aline , Prado Cibele M , Pernomian Larissa , Pernomian Laena , Rizzi Elen , Castro Myrella L , Ramos Simone G , Tanus-Santos Jose E , Gerlach Raquel F
Published: June 2021

Background:
An increase in MMP-2 levels is reported in heart failure (HF). However the role of MMP-2 in the pathogenesis of HF remains unclear. The aim of the present study was to determine the effect of increased circulating levels of MMP-2 on heart morphology and function.

Methods and Results:
Purified MMP-2 catalytic domain fused to GFP (catMMP-2/GFP) or saline (control) was injected into 11-wk-old male C57BL/6 mice for four weeks. The fluorescent active protein was tracked in vivo and homed in the heart. Cardiomyocyte diameter not changed between groups (catMMP-2/GFP: 11.37 ± 0.25 μm, n=7; Control: 11.38 ± 0.13 μm, n=7;
P
=0.97). On the other hand, fibrosis increased in the hearts of catMMP-2/GFP mice (0.82 ± 0.05% area/field, n=7 vs Control: 0.58 ± 0.02% area/field, n=7;
P<
0.05). Apoptotic stained nuclei in the left ventricle (LV) of catMMP-2/GFP injected-mice amounted to 7.24%, n=4, P<0,05, whilst the LV of control animals only exhibited 0.27%, n=4. catMMP-2/GFP localized in the heart interstitium, where increased proteolytic activity (15.13 ± 1.33 U, n=5 vs Control: 9.70 ± 0.42 U, n=5;
P
<0.05). Hearts of catMMP-2/GFP mice showed 25% decrease in cardiac output (13 ± 1 mL/min, n=9 vs Control: 17 ± 1 mL/min, n=9), 30% decrease in ejection fraction (40 ± 2 %, n=9 vs Control: 56 ± 2 %, n=9) and stroke volume (28 ± 2 μL, n=9 vs Control: 40 ± 2 μL, n=9), and 34% decrease in fractional shortening (18 ± 1 %, n=9 vs Control: 28 ± 1 %, n=9) (
P
<0.05 for all data).Western blotting showed 40% decrease in N-cadherin in animals that received catMMP-2/GFP (0.53 ± 0.08 U, n=6 vs control: 0.89 ± 0.11 U, n=6;
P
<0.05). Expression of signaling proteins also changed in LV of catMMP-2/GFP mice: TGF-β1 expression increased by 30% (0.60 ± 0.07 U, n=7 vs control: 0.40 ± 0.05 U, n=7, P<0,05), pAkt/Akt decreased by 40% (0.46 ± 0.05 U, n=7 vs control: 0.76 ± 0.11 U, n=7;
P
<0.05), pSMAD2/total SMAD2 ratio increased (1.88 ± 0.22 U, n=6 vs control: 0.93±0.12 U, n=6, P<0,05), and pSMAD3/total SMAD3 ratio increased (1.24 ± 0.22 U, n=7 vs control: 0.33 ± 0.07 U, n=7;
P
<0.05).

Conclusions:
Circulating active MMP-2 homing to the heart interstitium degrades N-cadherin and induces TGF-β1 overexpression, leading to apoptosis, and fibrosis. This mechanism may account for heart function loss when plasma levels of MMP-2 increase.
Abstract P112: Decreased α-Myosin Expression is Associated with Left Ventricular Hypertrophy in Hypertensive Caribbean Vervets
Authors: Weaver Chelsea C , Gutierrez Anthony , Osborn Jeffrey L
Published: June 2021

Caribbean vervets (
Chlorocebus aethiops sabeus
) develop hypertension (HT; Systolic Blood Pressure ≥ 140 mmHg) in over 30% (125/345) of the outbred population. Elevated total peripheral resistance in HT increases cardiac afterload, which may lead to left ventricular hypertrophy (LVH) and cardiac remodeling. We hypothesize that prolonged spontaneous HT is associated with LVH, cardiac and aortic fibrosis, as well as differential transcription of myocardial contractile proteins. Vervets were characterized as HT (SBP = 170 ± 25.3 mmHg; n=125) or normotensive (NT, SBP = 99 ± 14.5 mmHg; n=148) using forearm plethysmography (ketamine sedated;15 mg/kg i.m.). Cardiomyocyte cross-sectional area was greater in HT compared to NT animals (HT 283 ± 52 μm
2
, n=9 vs NT 114 ± 8 μm
2
, n=10; p<0.01). Average collagen stained as a function of tissue area was similar in left ventricular myocardium of HT and NT animals (HT 14.17 ± 3.13% or 0.17/1.21 mm
2
, n=9 vs NT 12.22 ± 0.80% or 0.16/1.27 mm
2
, n=10; p>0.05). Aortic adventia collagen area was greater in HT compared to NT vervets (HT 66.12 ± 4.22% or 0.60/0.90 mm
2
, n=6 vs NT 54.53 ± 2.21% or 0.56/1.02 mm
2
, n=10; p<0.05). Total tissue collagen was estimated using a hydroxyproline assay. Collagen content was not different between HT and NT vervets for left ventricular myocardium (HT 194.02 ± 8.61 μg/mL, n=11 vs NT 201.70 ± 18.89 μg/mL, n=10; p=0.71) or aorta (HT 745.64 ± 44.49 μg/mL, n=11 vs NT 668.39 ± 31.06 μg/mL, n=11; p=0.17). Myosin gene expression (α and β) was estimated using RT-PCR of mRNA in left ventricular myocardium of NT (SBP = 98.91 ±10.89 mmHg; n=20) and HT (SBP = 171.51 ± 30.28 mmHg; n=17) vervets. α-myosin was downregulated in HT compared to NT vervets (HT RQ = 0.10 ± 0.03 vs. NT RQ = 0.22 ± 0.04; p<0.05), while β-myosin expression was not different (HT RQ = 0.22 ± 0.17 vs. NT RQ = 0.20 ± 0.16; p=0.83). Thus, spontaneous HT in outbred vervets induces LVH in response to factors other than cardiac fibrosis. Myosin gene expression may shift from α-myosin to other contractile protein isoforms, characteristic of human heart failure. In this nonhuman primate model, HT does not induce significant aortic fibrosis that may occur in aged animals. Future studies will further characterize contractile and pro-inflammatory proteins in LVH of spontaneous HT vervets.
Abstract P118: The Complexity of the Albuminuria Development in Salt-sensitive Hypertension
Authors: Endres Bradley T , Sandoval Ruben M , Rhodes George J , Campos-Bilderback Silvia B , Kamocka Malgorzata M , McDermott-Roe Christopher , Staruschenko Alexander , Molitoris Bruce A , Geurts Aron M , Palygin Oleg
Published: June 2021

Hypertension is one of the most prevalent diseases worldwide, and is a major risk factor for developing albuminuria, renal failure and cardiovascular diseases. The goal of this study was to investigate the mechanisms leading to albuminuria in the kidney of a canonical rat model of hypertension, the Dahl salt-sensitive (SS) rat. To determine the relative contributions of the glomerulus and proximal tubule (PT) to albuminuria, we applied intravital two-photon-based imaging to investigate complex changes in renal function that occur during salt-induced hypertension. Following a high salt (HS) diet, SS rats exhibited elevated blood pressure, accompanied by increased glomerular sieving of albumin (GSC
alb
=0.0686) and decreased serum albumin (-Δ0.54 g/dL), which corresponded to increased daily filtered albumin up to 3.7 vs 0.8 g at normal diet. Pathologically, hypertensive animals had significant tubular damage as indicated by increased prevalence of granular casts (+Δ2.20 casts/image), dilation/expansion and necrosis of PT epithelial cells, increased vascular injury (+Δ0.61 leakage/image), and progressive inflammation. HS diet significantly reduced total PT uptake of albumin, which also coincided with reduced transcellular transport of albumin back into circulation. Collectively, these results indicate that both the glomerulus and the proximal tubule contribute to albuminuria and dual treatment of glomerular filtration and albumin reabsorption may represent an effective treatment of salt-sensitive hypertension.
Abstract P121: Antenatal Corticosteroids and Alterations in Renal Function in Adolescents Born Preterm
Authors: South Andrew M , Nixon Patricia A , Chappell Mark C , Diz Debra I , Russell Gregory B , Snively Beverly M , Shaltout Hossam A , Rose James C , O’Shea T. M , Washburn Lisa K
Published: June 2021

Background:
Treatment with antenatal corticosteroids (ANCS) hastens fetal lung development and improves survival of infants born preterm, but the long-term effects of ANCS are not well described. Animal models suggest ANCS causes programmed alterations in renal maturation, including a decreased number of functional nephrons. Data in humans suggests that prematurity is associated with subsequent development of glomerular hyperfiltration and albuminuria as precursors of chronic kidney disease. We hypothesized that ANCS exposure alters renal function in adolescents born preterm.

Methods:
A cohort of 169 adolescents born prematurely, 91 of whom were exposed to ANCS, was evaluated at age 14. We measured plasma and urine creatinine (Cr) and urine albumin and calculated the estimated glomerular filtration rate (eGFR) and urine albumin-to-Cr ratio (ACR). The outcomes were albuminuria (urine ACR >30 mg/g Cr) and hyperfiltration (eGFR ≥147.5 mL/min/1.73 m
2
, the upper quintile of the cohort’s eGFR). We used multivariable logistic regression models to evaluate the association of ANCS exposure with renal outcomes, adjusting for confounding variables.

Results:
In unadjusted analyses and after adjustment for race, sex, and maternal hypertension, ANCS exposure was associated with a decreased likelihood of albuminuria (adjusted OR 0.33, 95% CI 0.12 to 0.91,
p
= 0.03). In unadjusted analysis ANCS was associated with an increased likelihood of hyperfiltration (unadjusted OR 3.17, 1.1 to 9.15,
p
= 0.03), and this relationship was only slightly attenuated after adjustment for confounding variables (
p
= 0.12).

Conclusions:
Adolescents born prematurely who were exposed to ANCS were less likely to exhibit albuminuria, but were more likely to have hyperfiltration. ANCS could affect renal function among adolescents born prematurely.