scholarly journals Pharmacogenomics of hypertension in chronic kidney disease: the CKD-PGX study

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0005362021
Author(s):  
Michael T. Eadon ◽  
Judith Maddatu ◽  
Sharon M. Moe ◽  
Arjun D. Sinha ◽  
Ricardo Melo Ferreira ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Antihypertensive Agents ◽  
Pressure Control ◽  
Safety Net ◽  
Uncontrolled Hypertension ◽  
Cross Sectional ◽  
Significant Difference ◽  
Safety Net Hospital

Background: Patients with chronic kidney disease (CKD) often have uncontrolled hypertension despite polypharmacy. Pharmacogenomic drug-gene interactions (DGIs) may impact the metabolism or efficacy of antihypertensive agents. We report changes in hypertension control after providing a panel of 11 pharmacogenomic predictors of antihypertensive response. Methods: A prospective cohort with CKD and hypertension was followed to assess feasibility of pharmacogenomic testing implementation, self-reported provider utilization, and blood pressure control. The analysis population included 382 hypertensive subjects genotyped for cross-sectional assessment of DGIs and 335 subjects followed for 1 year to assess systolic (SBP) and diastolic blood pressure (DBP). Results: Most participants (58.2%) with uncontrolled hypertension had a DGI reducing the efficacy of > 1 antihypertensive agent. Subjects with a DGI had 1.85-fold (95% CI 1.2-2.8) higher odds of uncontrolled hypertension as compared to those without a DGI, adjusted for race, health system (safety net hospital versus other locations) and advanced CKD (eGFR < 30 ml/min). CYP2C9 reduced metabolism genotypes were associated with losartan response and uncontrolled hypertension (Odds Ratio 5.2, CI 1.9 -14.7). CYP2D6 intermediate or poor metabolizers had less frequent uncontrolled hypertension compared to normal metabolizers taking metoprolol or carvedilol (OR 0.55, CI 0.3-0.95). In 335 subjects completing 1 year follow-up, SBP (-4.0 mmHg, CI 1.6- 6.5) and DBP (-3.3 mmHg, CI 2.0-4.6) were improved. No significant difference in SBP or DBP change were found between individuals with and without a DGI. Conclusions: There is a potential role for the addition of pharmacogenomic testing to optimize antihypertensive regimens in patients with CKD.

scholarly journals Pharmacogenomics of hypertension in chronic kidney disease: the CKD-PGX study

2021 ◽  
Author(s):  
Michael T. Eadon ◽  
Judith Maddatu ◽  
Sharon M. Moe ◽  
Arjun D. Sinha ◽  
Ricardo Melo Ferreira ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Antihypertensive Agents ◽  
Pressure Control ◽  
Uncontrolled Hypertension ◽  
Gene Interactions ◽  
Cross Sectional ◽  
Antihypertensive Response

ABSTRACTBackgroundPatients with chronic kidney disease (CKD) often have uncontrolled hypertension despite polypharmacy. Pharmacogenomic drug-gene interactions (DGIs) may impact the metabolism or efficacy of antihypertensive agents. We hypothesized that providing a panel of 11 pharmacogenomic predictors of antihypertensive response would improve hypertension control.MethodsA prospective cohort with CKD and hypertension was followed to assess the effect of pharmacogenomic testing on blood pressure control. The analysis population included 382 hypertensive subjects genotyped for cross-sectional assessment of drug-gene interactions and 335 subjects followed for 1 year to assess systolic (SBP) and diastolic blood pressure (DBP).ResultsMost participants (58.2%) with uncontrolled hypertension had a DGI reducing the efficacy of one or more antihypertensive agents. Subjects with a DGI had 1.88-fold (95% CI 1.2-2.8) higher odds of uncontrolled hypertension as compared to those without a DGI, adjusted for race and CKD grade. CYP2C9 reduced metabolism genotypes were associated with losartan response and uncontrolled hypertension (Odds Ratio 5.2, CI 1.9 -14.7). CYP2D6 intermediate or poor metabolizers had less frequent uncontrolled hypertension compared to normal metabolizers taking metoprolol or carvedilol (OR 0.55, CI 0.3-0.95). In 335 subjects completing 1 year follow-up, SBP (−4.0 mmHg, CI 1.6-6.5) and DBP (−3.3 mmHg, CI 2.0-4.6) were improved. The magnitude of reductions in SBP (−14.8 mmHg, CI 10.3-19.3) and DBP (−8.4 mmHg, CI 5.9-10.9) were greatest in the 90 individuals with uncontrolled hypertension and an actionable genotype.ConclusionsThere is a potential role for the addition of pharmacogenomic testing to optimize antihypertensive regimens in patients with CKD.

scholarly journals Association between MR-proADM concentration and treatment intensity of antihypertensive agents in chronic kidney disease patients with insufficient blood pressure control

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Motoshi Iwao ◽  
Ryota Tanaka ◽  
Yosuke Suzuki ◽  
Takeshi Nakata ◽  
Kohei Aoki ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Antihypertensive Drugs ◽  
Antihypertensive Agents ◽  
Pressure Control ◽  
Ultra Performance Liquid Chromatography ◽  
Treatment Intensity ◽  
Cross Sectional ◽  
Intensity Score

AbstractResponse to antihypertensive drugs in patients with chronic kidney disease (CKD) has great interindividual variability. Adrenomedullin (ADM) is produced abundantly in hypertension, but clearance is very rapid. Mid-regional proADM (MR-proADM) produced from an ADM precursor is considered a surrogate biomarker for quantification of ADM. We investigated the association of MR-proADM with antihypertensive resistance in CKD patients with poor blood pressure (BP) control. This cross-sectional study analyzed 33 CKD patients with poor BP control defined as failure to achieve target BP despite at least two classes of antihypertensive drugs. Treatment intensity score was calculated to facilitate comparability of antihypertensive regimens across subjects taking different drugs. Plasma MR-proADM concentration was measured using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Plasma MR-proADM concentration correlated with estimated glomerular filtration rate (eGFR) (r =  − 0.777, p < 0.001). Treatment intensity score correlated positively with plasma MR-proADM concentration (r = 0.355, p = 0.043), and the correlation was further enhanced after correction by weight (r = 0.538, p = 0.001). Single and multiple regression analysis identified MR-proADM concentration (p = 0.005) as independently associated with weight-corrected treatment intensity score. MR-proADM may be useful as a biomarker to determine the therapeutic intensity of antihypertensive drugs in CKD patients with poor BP control.

scholarly journals Blood pressure control in chronic kidney disease: A cross-sectional analysis from the German Chronic Kidney Disease (GCKD) study

PLoS ONE ◽  
2018 ◽  
Vol 13 (8) ◽  
pp. e0202604 ◽  
Author(s):  
Markus P. Schneider ◽  
Karl F. Hilgers ◽  
Matthias Schmid ◽  
Silvia Hübner ◽  
Jennifer Nadal ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Blood Pressure Control ◽  
Pressure Control ◽  
Cross Sectional ◽  
Cross Sectional Analysis ◽  
Sectional Analysis

scholarly journals Correction: Blood pressure control in chronic kidney disease: A cross-sectional analysis from the German Chronic Kidney Disease (GCKD) study

PLoS ONE ◽  
2018 ◽  
Vol 13 (9) ◽  
pp. e0204340 ◽  
Author(s):  
Markus P. Schneider ◽  
Karl F. Hilgers ◽  
Matthias Schmid ◽  
Silvia Hübner ◽  
Jennifer Nadal ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Blood Pressure Control ◽  
Pressure Control ◽  
Cross Sectional ◽  
Cross Sectional Analysis ◽  
Sectional Analysis

Adherence to Antihypertensive Agents and Blood Pressure Control in Chronic Kidney Disease

2010 ◽  
Vol 32 (6) ◽  
pp. 541-548 ◽  
Author(s):  
Kristen E. Schmitt ◽  
Christine F. Edie ◽  
Paul Laflam ◽  
Loretta A. Simbartl ◽  
Charuhas V. Thakar
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Blood Pressure Control ◽  
Antihypertensive Agents ◽  
Pressure Control

scholarly journals The Copenhagen chronic kidney disease echo study (COInCYDE)

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Landler ◽  
S Bro ◽  
B Feldt-Rasmussen ◽  
D Hansen ◽  
A.L Kamper ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Cohort Study ◽  
Kidney Disease ◽  
Cardiac Function ◽  
Left Ventricular ◽  
Funding Source ◽  
Ckd Stage ◽  
Significant Difference ◽  
Stage 1

Abstract Background The cardiovascular mortality of patients with chronic kidney disease (CKD) is 2–10 times higher than in the average population. Purpose To estimate the prevalence of abnormal cardiac function or structure across the stages CKD 1 to 5nonD. Method Prospective cohort study. Patients with CKD stage 1 to 5 not on dialysis, aged 30 to 75 (n=875) and age-/sex-matched controls (n=173) were enrolled consecutively. All participants underwent a health questionnaire, ECG, morphometric and blood pressure measurements. Blood and urine were analyzed. Echocardiography was performed. Left ventricle (LV) hypertrophy, dilatation, diastolic and systolic dysfunction were defined according to current ESC guidelines. Results 63% of participants were men. Mean age was 58 years (SD 12.6 years). Mean eGFR was 46.7 mL/min/1,73 m (SD 25.8) for patients and 82.3 mL/min/1,73 m (SD 13.4) for controls. The prevalence of elevated blood pressure at physical exam was 89% in patients vs. 53% in controls. Patients were more often smokers and obese. Left ventricular mass index (LVMI) was slightly, albeit insignificantly elevated at CKD stages 1 & 2 vs. in kontrols: 3.1 g/m2, CI: −0.4 to 6.75, p-value 0.08. There was no significant difference in LV-dilatation between patients and controls. Decreasing diastolic and systolic function was observed at CKD stage 3a and later: LVEF decreased 0.95% (CI: −1.5 to −0.2), GLS increased 0.5 (CI: 0.3 to 0.8), and OR for diastolic dysfunction increased 3.2 (CI 1.4 to 7.3) pr. increment CKD stage group. Conclusion In accordance to previous studies, we observe in the CPHCKD cohort study signs of early increase of LVMI in patients with CKD stage 1 & 2. Significant decline in systolic and diastolic cardiac function is apparent already at stage 3 CKD. Figure 1. Estimated GFR vs. GLS & histogram of GLS Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): The Capital Region of Denmark

scholarly journals Optimal blood pressure for patients with chronic kidney disease: a nationwide population-based cohort study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
You-Bin Lee ◽  
Ji Sung Lee ◽  
So-hyeon Hong ◽  
Jung A. Kim ◽  
Eun Roh ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiovascular Events ◽  
Antihypertensive Treatment ◽  
Antihypertensive Agents ◽  
Population Based ◽  
Adverse Outcomes ◽  
Optimal Blood Pressure ◽  
Stage Renal Disease

AbstractThe effect of blood pressure (BP) on the incident cardiovascular events, progression to end-stage renal disease (ESRD) and mortality were evaluated among chronic kidney disease (CKD) patients with and without antihypertensive treatment. This nationwide study used the Korean National Health Insurance Service-Health Screening Cohort data. The hazards of outcomes were analysed according to the systolic BP (SBP) or diastolic BP (DBP) among adults (aged ≥ 40 years) with CKD and without previous cardiovascular disease or ESRD (n = 22,278). The SBP and DBP were ≥ 130 mmHg and ≥ 80 mmHg in 10,809 (48.52%) and 11,583 (51.99%) participants, respectively. During a median 6.2 years, 1271 cardiovascular events, 201 ESRD incidents, and 1061 deaths were noted. Individuals with SBP ≥ 130 mmHg and DBP ≥ 80 mmHg had higher hazards of hypertension-related adverse outcomes compared to the references (SBP 120–129 mmHg and DBP 70–79 mmHg). SBP < 100 mmHg was associated with hazards of all-cause death, and composite of ESRD and all-cause death during follow-up only among the antihypertensive medication users suggesting that the BP should be < 130/80 mmHg and the SBP should not be < 100 mmHg with antihypertensive agents to prevent the adverse outcome risk of insufficient and excessive antihypertensive treatment in CKD patients.

The Relationship Between Blood Pressure Variability And Renal Progression In Hypertensive Patients With Chronic Kidney Disease

2021 ◽  
Vol 6 (14) ◽  
pp. 80-88
Author(s):  
Huseyin Duru ◽  
Ekrem KARA
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Blood Pressure Measurement ◽  
Rapid Progression ◽  
Night Time ◽  
Hypertensive Patients ◽  
Significant Difference ◽  
Renal Progression

Objective: To evaluate the effect of 24 hour systolic blood pressure (SBP) and diastolic blood pressure (DBP) variability (BPV) on renal progression in hypertensive patients with chronic kidney disease (CKD) Methods: A total 59 hypertensive patients (mean age: 54.2±14.6 years, 50.8% male) with CKD who underwent 24 hours ambulatory blood pressure measurement (ABPM) were included. Data on SBP, DBP, BPV coefficients (VC) for SBP (SBP-CV) and DBP (DBP-CV) were recorded. A decrease in e-GFR of <5 ml/min/year was considered as normal renal progression and a decrease in ≥5 ml/min/year was considered as rapid renal progression. Results: Overall, 40.6% of the patients had uncontrolled HT, while 45.8% had non-dipper pattern. Mean±SD daytime and night-time SBP and SBP-VC values were 135.3±17.9 mmHg, 128.6±23.0 mmHg, 11.7±2.8 and 9.5±3.6, respectively. Mean±SD daytime and nigh-time DBP and DBP-VC values were 84.5±13.4 mmHg, 77.2±16.1 mmHg, 13.8±3.8 and 12.0±3.7, respectively. Rapid renal progression was detected in 25.4% of patients with no significant difference in daytime, night-time and total SBP, SBP-VC, DBP and DBP-VC values between patients with rapid vs. natural renal progression. The regression analysis adjusted for age, gender, presence of DM, baseline e-GFR and dipping status revealed no significant impact of SBP-VC and DBP-VC in predicting rapid progression (p> 0.05). Conclusion: In conclusion, our finding revealed no significant association between BPV and renal progression in hypertensive patients with CKD. Larger scale prospective, randomized controlled trials with longer follow-up are needed to clarify this issue.

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