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Article ; Online: A Step Ahead toward Measuring Pain in Autosomal Dominant Polycystic Kidney Disease (ADPKD).

Steele, Cortney N / Nowak, Kristen L

Clinical journal of the American Society of Nephrology : CJASN

2023 Volume 18, Issue 2, Page(s) 160–162

MeSH term(s)	Humans ; Polycystic Kidney, Autosomal Dominant/complications ; Polycystic Kidney, Autosomal Dominant/diagnosis ; Kidney ; Pain
Language	English
Publishing date	2023-01-17
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2226665-3
ISSN	1555-905X ; 1555-9041
ISSN (online)	1555-905X
ISSN	1555-9041
DOI	10.2215/CJN.0000000000000042
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Article ; Online: Nonpharmacological Management of Autosomal Dominant Polycystic Kidney Disease.

Steele, Cortney N / Nowak, Kristen L

Advances in kidney disease and health

2023 Volume 30, Issue 3, Page(s) 220–227

Abstract: Autosomal dominant polycystic kidney disease is a slowly progressive, lifelong disease characterized by continuous development and enlargement of kidney cysts. Thus, nonpharmacological interventions are crucial in disease management and have the ... ...

Abstract	Autosomal dominant polycystic kidney disease is a slowly progressive, lifelong disease characterized by continuous development and enlargement of kidney cysts. Thus, nonpharmacological interventions are crucial in disease management and have the potential for a large clinical impact as standalone interventions or in conjunction with pharmacological therapies. Current potential strategies regarding nonpharmacological management of autosomal dominant polycystic kidney disease include nonpharmacological management of blood pressure, calorie restriction, weight loss or weight management, enhanced hydration, limiting caffeine, dietary sodium restriction, protein restriction or altering the type of protein intake, phosphorus restriction, and reducing net acid load. This brief review discusses the available evidence, including cell culture, animal, epidemiological, and clinical studies, regarding the utility of such strategies in the nonpharmacological management of autosomal dominant polycystic kidney disease. We assert that lifestyle modification strategies should be a critical aspect of the treatment of autosomal dominant polycystic kidney disease, while further trial and mechanistic evidence continue to become available.
MeSH term(s)	Animals ; Polycystic Kidney, Autosomal Dominant/diagnosis ; Sodium, Dietary ; Sodium Chloride, Dietary ; Blood Pressure ; Kidney Neoplasms
Chemical Substances	Sodium, Dietary ; Sodium Chloride, Dietary
Language	English
Publishing date	2023-04-01
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3156601-7
ISSN	2949-8139
ISSN (online)	2949-8139
DOI	10.1053/j.akdh.2022.12.008
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Zs.A 4627: Show issues

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Article ; Online: Targeting Glycosphingolipid Metabolism in ADPKD: Another Roadblock for Treatment.

Steele, Cortney N / Nowak, Kristen L

American journal of kidney diseases : the official journal of the National Kidney Foundation

2023 Volume 81, Issue 5, Page(s) 504–506

MeSH term(s)	Humans ; Polycystic Kidney, Autosomal Dominant/therapy ; Kidney/metabolism ; Glycosphingolipids/metabolism
Chemical Substances	Glycosphingolipids
Language	English
Publishing date	2023-02-28
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	604539-x
ISSN	1523-6838 ; 0272-6386
ISSN (online)	1523-6838
ISSN	0272-6386
DOI	10.1053/j.ajkd.2022.12.010
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Zs.A 1669: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Obesity, Weight Loss, Lifestyle Interventions, and Autosomal Dominant Polycystic Kidney Disease.

Steele, Cortney / Nowak, Kristen

Kidney and dialysis

2022 Volume 2, Issue 1, Page(s) 106–122

Abstract: Obesity remains a growing public health concern in industrialized countries around the world. The prevalence of obesity has also continued to rise in those with chronic kidney disease. Epidemiological data suggests those with overweight and obesity, ... ...

Abstract	Obesity remains a growing public health concern in industrialized countries around the world. The prevalence of obesity has also continued to rise in those with chronic kidney disease. Epidemiological data suggests those with overweight and obesity, measured by body mass index, have an increased risk for rapid kidney disease progression. Autosomal dominant polycystic kidney disease causes growth and proliferation of kidney cysts resulting in a reduction in kidney function in the majority of adults. An accumulation of adipose tissue may further exacerbate the metabolic defects that have been associated with ADPKD by affecting various cell signaling pathways. Lifestyle interventions inducing weight loss might help delay disease progression by reducing adipose tissue and systematic inflammation. Further research is needed to determine the mechanistic influence of adipose tissue on disease progression.
Language	English
Publishing date	2022-03-04
Publishing country	Switzerland
Document type	Journal Article
ISSN	2673-8236
ISSN	2673-8236
DOI	10.3390/kidneydial2010013
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Article ; Online: Sex hormones and the risk of cardiovascular disease and mortality in male and female patients with chronic kidney disease: A systematic review and meta-analysis.

Oh, Ester S / Steele, Cortney N / You, Zhiying / Nowak, Kristen L / Jovanovich, Anna J

Physiological reports

2022 Volume 10, Issue 22, Page(s) e15490

Abstract: Patients with chronic kidney disease (CKD) commonly experience sex hormone disturbances, which may be associated with the risk of cardiovascular disease (CVD) and mortality. This review aimed to systematically evaluate current findings on the association ...

Abstract	Patients with chronic kidney disease (CKD) commonly experience sex hormone disturbances, which may be associated with the risk of cardiovascular disease (CVD) and mortality. This review aimed to systematically evaluate current findings on the association of sex hormone levels with the risk of CVD events and mortality (CVD and all-cause) in the CKD population. Articles were systematically searched in CINAHL, Cochrane, and PubMed. A total of 1739 articles were independently screened by two reviewers and 17 prospective cohort studies were included. The clinical conditions of the patients were those with non-dialysis CKD [mean/median estimated glomerular filtration rate (eGFR) between 15-51 ml/min/1.73 m
MeSH term(s)	Humans ; Male ; Female ; Middle Aged ; Aged ; Cardiovascular Diseases/etiology ; Prospective Studies ; Risk Factors ; Renal Insufficiency, Chronic/complications ; Gonadal Steroid Hormones ; Testosterone
Chemical Substances	Gonadal Steroid Hormones ; Testosterone (3XMK78S47O)
Language	English
Publishing date	2022-11-17
Publishing country	United States
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2724325-4
ISSN	2051-817X ; 2051-817X
ISSN (online)	2051-817X
ISSN	2051-817X
DOI	10.14814/phy2.15490
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Article ; Online: Cerebrovascular Pulsatility Index Is Reduced in Autosomal Dominant Polycystic Kidney Disease.

Steele, Cortney N / Oh, Ester S / Wang, Wei / Farmer-Bailey, Heather / Gitomer, Berenice Y / Chonchol, Michel / Nowak, Kristen L

American journal of nephrology

2023 Volume 54, Issue 5-6, Page(s) 165–174

Abstract: Introduction: Cerebrovascular dysfunction, characterized by increased brain pulsatile flow, reduced cerebrovascular reactivity, and cerebral hypoperfusion precedes the onset of dementia and is linked to cognitive dysfunction. Autosomal dominant ... ...

Abstract	Introduction: Cerebrovascular dysfunction, characterized by increased brain pulsatile flow, reduced cerebrovascular reactivity, and cerebral hypoperfusion precedes the onset of dementia and is linked to cognitive dysfunction. Autosomal dominant polycystic kidney disease (ADPKD) may increase the risk of dementia, and intracranial aneurysms are more prevalent in ADPKD patients. However, cerebrovascular function has not been previously characterized in patients with ADPKD. Methods: Using transcranial Doppler, we compared middle cerebral artery (MCA) pulsatility index (PI, cerebrovascular stiffness) and MCA blood velocity response to hypercapnia (normalized for blood pressure and end-tidal CO2, cerebrovascular reactivity) in patients with early-stage ADPKD versus age-matched healthy controls. We also administered the NIH cognitive toolbox (cognitive function) and measured carotid-femoral pulse-wave velocity (PWV, aortic stiffness). Results: Fifteen participants with ADPKD (9F, 27 ± 4 yrs, eGFR: 106 ± 22 mL/min/1.73 m2) were compared to 15 healthy controls (8F, 29 ± 4 yrs, eGFR: 109 ± 14 mL/min/1.73 m2). MCA PI was unexpectedly lower in ADPKD (0.71 ± 0.07) versus controls (0.82 ± 0.09 AU; p < 0.001); however, normalized MCA blood velocity in response to hypercapnia did not differ between groups (2.0 ± 1.2 vs. 2.1 ± 0.8 %Δ/mm Hg; p = 0.85). Lower MCA PI was associated with a lower crystalized composite score (cognition), which persisted after adjustment for age, sex, eGFR, and education (β = 0.58, p = 0.007). There was no association of MCA PI with carotid-femoral PWV (r = 0.01, p = 0.96), despite greater carotid-femoral PWV in ADPKD, suggesting MCA PI reflects vascular properties other than arterial stiffness (such as low wall shear stress) in ADPKD. Discussion/conclusion: MCA PI is lower in patients with ADPKD. Follow-up research on this observation is merited as low PI has been associated with intracranial aneurysm in other populations.
MeSH term(s)	Humans ; Polycystic Kidney, Autosomal Dominant/complications ; Hypercapnia ; Blood Pressure/physiology ; Cognition/physiology ; Vascular Stiffness ; Dementia ; Blood Flow Velocity/physiology
Language	English
Publishing date	2023-05-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	604540-6
ISSN	1421-9670 ; 0250-8095
ISSN (online)	1421-9670
ISSN	0250-8095
DOI	10.1159/000530583
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Zs.A 1635: Show issues

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Article ; Online: Visceral Adiposity and Progression of ADPKD: A Cohort Study of Patients From the TEMPO 3:4 Trial.

Nowak, Kristen L / Moretti, Federica / Bussola, Nicole / Steele, Cortney / Gregory, Adriana V / Kline, Timothy L / Ramanathan, Sumana / Trapletti, Giovanni / Furlanello, Cesare / McCormick, Linda / Chonchol, Michel

American journal of kidney diseases : the official journal of the National Kidney Foundation

2024

Abstract: Rationale & objective: 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 ... ...

Abstract	Rationale & objective: 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. We hypothesized that greater visceral abdominal adiposity would associate with more rapid kidney growth in ADPKD and influence the efficacy of tolvaptan. Study design: A retrospective cohort study. Setting & participants: 1053 patients enrolled in the TEMPO 3:4 tolvaptan trial with ADPKD and high risk of rapid disease progression. Predictor: Estimates of visceral adiposity extracted from coronal plane MRIs using deep learning. Outcome: Annual change in total kidney volume (TKV) and effect of tolvaptan on kidney growth. Analytical approach: Multinomial logistic regression and linear mixed models. Results: In fully adjusted models, the highest tertile of visceral adiposity was associated with greater odds of annual change in TKV of ≥7% vs. <5% (OR: 4.78 [3.03, 7.47]). The association was stronger in females than males (interaction p<0.01). In linear mixed models with an outcome of % change in TKV per year, tolvaptan efficacy (% change in TKV) was reduced with higher visceral adiposity (three-way interaction of treatmenttimevisceral adiposity p=0.002). Visceral adiposity significantly improved classification performance of predicting rapid annual % change in TKV for individuals with a normal BMI (De-Long'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 females (fully adjusted OR 1.06 [1.01, 1.11] per 10 unit increase in visceral adiposity) but not males (0.98 [0.95, 1.02]). Limitations: Retrospective; rapid progressors; computational demand of deep learning. Conclusions: 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.
Language	English
Publishing date	2024-04-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	604539-x
ISSN	1523-6838 ; 0272-6386
ISSN (online)	1523-6838
ISSN	0272-6386
DOI	10.1053/j.ajkd.2024.02.014
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Article ; Online: Overweight and Obesity and Progression of ADPKD.

Nowak, Kristen L / Steele, Cortney / Gitomer, Berenice / Wang, Wenchyi / Ouyang, John / Chonchol, Michel B

Clinical journal of the American Society of Nephrology : CJASN

2021 Volume 16, Issue 6, Page(s) 908–915

Abstract: Background and objectives: On the basis of earlier observations, we evaluated the association between overweight and obesity and rapid progression of autosomal dominant polycystic kidney disease in participants in the Tolvaptan Efficacy and Safety in ... ...

Abstract	Background and objectives: On the basis of earlier observations, we evaluated the association between overweight and obesity and rapid progression of autosomal dominant polycystic kidney disease in participants in the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4 trial. More importantly, we also determined whether efficacy of tolvaptan was attenuated in individuals with baseline overweight or obesity. Design, setting, participants, & measurements: A total of 1312 study participants with relatively early-stage autosomal dominant polycystic kidney disease (mean eGFR 78±22 ml/min per 1.73 m Results: In fully adjusted models, higher BMI was associated with greater annual percent change in TKV (difference of 1.20 [95% confidence interval (95% CI), 0.85 to 1.55] per five-unit higher BMI). Overweight and obesity were associated with higher odds of annual percent change in TKV of ≥7% versus <5% (overweight: odds ratio, 2.04 [95% CI, 1.45 to 2.87]; obese: odds ratio, 4.31 [95% CI, 2.83 to 6.57] versus normal weight). eGFR decline did not differ according to BMI (fully adjusted difference in decline of -0.95 [95% CI, -2.32 to 0.40] ml/min per 1.73 m Conclusions: Overweight and particularly obesity are strongly and independently associated with kidney growth, but not eGFR slope, in the TEMPO 3:4 trial, and tolvaptan efficacy is irrespective of BMI categorization. Clinical trial registry name and registration number: Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4, NCT00428948.
MeSH term(s)	Adult ; Cohort Studies ; Disease Progression ; Female ; Humans ; Male ; Middle Aged ; Obesity/complications ; Overweight/complications ; Polycystic Kidney, Autosomal Dominant/drug therapy ; Polycystic Kidney, Autosomal Dominant/etiology ; Time Factors ; Tolvaptan/therapeutic use
Chemical Substances	Tolvaptan (21G72T1950)
Language	English
Publishing date	2021-06-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2226665-3
ISSN	1555-905X ; 1555-9041
ISSN (online)	1555-905X
ISSN	1555-9041
DOI	10.2215/CJN.16871020
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Zs.A 6584: Show issues

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Article ; Online: Sodium Bicarbonate Treatment and Vascular Function in CKD: A Randomized, Double-Blind, Placebo-Controlled Trial.

Kendrick, Jessica / You, Zhiying / Andrews, Emily / Farmer-Bailey, Heather / Moreau, Kerrie / Chonchol, Michel / Steele, Cortney / Wang, Wei / Nowak, Kristen L / Patel, Nayana

Journal of the American Society of Nephrology : JASN

2023 Volume 34, Issue 8, Page(s) 1433–1444

Abstract: Significance statement: Lower serum bicarbonate levels, even within the normal range, are strongly linked to risks of cardiovascular disease in CKD, possibly by modifying vascular function. In this randomized, controlled trial, treatment with sodium ... ...

Abstract	Significance statement: Lower serum bicarbonate levels, even within the normal range, are strongly linked to risks of cardiovascular disease in CKD, possibly by modifying vascular function. In this randomized, controlled trial, treatment with sodium bicarbonate (NaHCO 3 ) did not improve vascular endothelial function or reduce arterial stiffness in participants with CKD stage 3b-4 with normal serum bicarbonate levels. In addition, NaHCO 3 treatment did not reduce left ventricular mass index. NaHCO 3 did increase plasma bicarbonate levels and urinary citrate excretion and reduce urinary ammonium excretion, indicating that the intervention was indeed effective. NaHCO 3 therapy was safe with no significant changes in BP, weight, or edema. These results do not support the use of NaHCO 3 for vascular dysfunction in participants with CKD. Background: Lower serum bicarbonate levels, even within the normal range, are strongly linked to risks of cardiovascular disease in CKD, possibly by modifying vascular function. Prospective interventional trials with sodium bicarbonate (NaHCO 3 ) are lacking. Methods: We conducted a randomized, double-blind, placebo-controlled trial examining the effect of NaHCO 3 on vascular function in 109 patients with CKD stage 3b-4 (eGFR 15-44 ml/min per 1.73 m 2 ) with normal serum bicarbonate levels (22-27 mEq/L). Participants were randomized 1:1 to NaHCO 3 or placebo at a dose of 0.5 mEq/lean body weight-kg per day for 12 months. The coprimary end points were change in brachial artery flow-mediated dilation (FMD) and change in aortic pulse wave velocity over 12 months. Results: Ninety patients completed this study. After 12 months, plasma bicarbonate levels increased significantly in the NaHCO 3 group compared with placebo (mean [SD] difference between groups 1.35±2.1, P = 0.003). NaHCO 3 treatment did not result in a significant improvement in aortic pulse wave velocity from baseline. NaHCO 3 did result in a significant increase in flow-mediated dilation after 1 month; however, this effect disappeared at 6 and 12 months. NaHCO 3 resulted in a significant increase in 24-hour urine citrate and pH and a significant decrease in 24-hour urine ammonia. There was no significant change in left ventricular mass index, ejection fraction, or eGFR with NaHCO 3 . NaHCO 3 treatment was safe and well-tolerated with no significant changes in BP, antihypertensive medication, weight, plasma calcium, or potassium levels. Conclusion: Our results do not support the use of NaHCO 3 for vascular dysfunction in participants with CKD and normal serum bicarbonate levels.
MeSH term(s)	Humans ; Sodium Bicarbonate/therapeutic use ; Bicarbonates ; Cardiovascular Diseases/etiology ; Cardiovascular Diseases/prevention & control ; Pulse Wave Analysis ; Prospective Studies ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/drug therapy ; Double-Blind Method
Chemical Substances	Sodium Bicarbonate (8MDF5V39QO) ; Bicarbonates
Language	English
Publishing date	2023-05-25
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.0000000000000161
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Article ; Online: Fasting and postprandial trimethylamine N-oxide in sedentary and endurance-trained males following a short-term high-fat diet.

Steele, Cortney N / Baugh, Mary Elizabeth / Griffin, Laura E / Neilson, Andrew P / Davy, Brenda M / Hulver, Matthew W / Davy, Kevin P

Physiological reports

2021 Volume 9, Issue 16, Page(s) e14970

Abstract: Gut bacteria release trimethylamine (TMA) from dietary substrates. TMA is absorbed and is subsequently oxidized in the liver to produce trimethylamine N-oxide (TMAO). Plasma TMAO levels are positively correlated with risk for type 2 diabetes (T2D) and ... ...

Abstract	Gut bacteria release trimethylamine (TMA) from dietary substrates. TMA is absorbed and is subsequently oxidized in the liver to produce trimethylamine N-oxide (TMAO). Plasma TMAO levels are positively correlated with risk for type 2 diabetes (T2D) and cardiovascular disease (CVD). High-fat diet (HFD) consumption has been reported to increase fasting and postprandial TMAO in sedentary individuals. However, whether the increase in TMAO with consumption of an HFD is observed in endurance-trained males is unknown. Healthy, sedentary (n = 17), and endurance-trained (n = 7) males consumed a 10-day eucaloric diet comprised of 55% carbohydrate, 30% total fat, and <10% saturated fat prior to baseline testing. Blood samples were obtained in a fasted state and for a 4-hour high-fat challenge (HFC) meal at baseline and then again following 5-day HFD (30% carbohydrate, 55% total fat, and 25% saturated fat). Plasma TMAO and TMA-moiety (choline, betaine, L-carnitine) concentrations were measured using isocratic ultraperformance liquid chromatography-tandem mass spectrometry. Age (23 ±3 vs. 22 ± 2 years) and body mass index (23.0 ± 3.0 vs. 23.5 ± 2.1 kg/m
MeSH term(s)	Adolescent ; Adult ; Cardiometabolic Risk Factors ; Diet, High-Fat/adverse effects ; Dietary Fats/metabolism ; Endurance Training ; Fasting/metabolism ; Humans ; Male ; Methylamines/blood ; Postprandial Period ; Sedentary Behavior
Chemical Substances	Dietary Fats ; Methylamines ; trimethyloxamine (FLD0K1SJ1A)
Language	English
Publishing date	2021-06-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2724325-4
ISSN	2051-817X ; 2051-817X
ISSN (online)	2051-817X
ISSN	2051-817X
DOI	10.14814/phy2.14970
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