Whole Exome Sequencing in CKD Hypertension

Hypertension;Nephropathy Clinical Trial

— WESCH  

Official title:

Whole Exome Sequencing Analysis Project in Chronic Kidney Disease Patients With Nocturnal Hypertension

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03718585
• Other study ID #: ZDWY.SNK.001
• Status: Recruiting
• Start date: June 1, 2018
• Est. completion date: October 2022

Study information

• Verified date: October 2018
• Source: Fifth Affiliated Hospital, Sun Yat-Sen University
• Contact: Jianting Ke, Doctor
• Phone: 0086 756 2528953
• Email: kjt1997[@]163.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The prevalence of hypertension in patients with CKD in China is high but the control rate is low. Compared with the single blood pressure measurement method of the blood pressure of the office, ambulatory blood pressure monitoring (ABPM) can reflect the overall situation of 24-hour blood pressure, dynamic fluctuation degree and circadian rhythm change more completely and objectively. Studies have shown that patients with CKD with hypertension have their own uniqueness through ABPM measurement, and nocturnal hypertension is the main cause of poor blood pressure control. Further studies have shown that nocturnal hypertension is an independent and more effective prognostic indicator of death and CVD in patients with hypertension. Evidence from European and American countries suggests that in the CKD population, elevated nighttime blood pressure is more predictive of CKD progression or CVD than daytime blood pressure. Compared with countries such as Europe and the United States, there are differences in the causes, genetic background and daily behaviors of kidney disease in our population. It is urgent to investigate the predictive value of nocturnal hypertension for renal end point and CVD in CKD population in China. To this end, our study found for the first time that CKD patients generally have changes in nocturnal blood pressure patterns, and the anti-dope type blood pressure pattern is closely related to the target organ damage. Our further study found that the incidence of nocturnal hypertension in Chinese patients with CKD is more than 50%, and compared with non-dipping blood pressure, patients with nocturnal hypertension have more serious target organ damage, which is independent risk factors for all-cause death, cardiovascular death, renal events, and cardiovascular events in patients with CKD. These preliminary results suggest the role of nocturnal hypertension in the prognosis of CKD patients in China, but there are still the following questions: Is the occurrence of nocturnal hypertension in CKD patients related to certain gene expression? This project intends to perform whole-genome exon sequencing and analysis on CKD patients with nocturnal hypertension to determine the genetic mechanism of CKD patients with nocturnal hypertension. The completion of the subject will reveal the genetic characteristics of CKD patients with nocturnal hypertension, and provide a basis for the precise prevention and treatment of chronic kidney disease hypertension.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4000
• Est. completion date: October 2022
• Est. primary completion date: October 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age over 14 years old and <75years.

2. The clinical data during the hospitalization period are detailed and complete.

3. Follow-up information is available.

4. Ambulatory blood pressure monitoring indicates nighttime blood pressure SBP=120mmHg and/or DBP=70mmHg.

5. Diagnosed as CKD according to the 2012 KDIGO guidelines, abnormalities of kidney structure or function, present for >3 months, with implications for health, including glomerular filtration rate (GFR) normal and abnormal pathological damage, blood (abnormal electrolyte or other components caused by renal tubular dysfunction) or urine components (proteinuria: ACR = 30mg / gCr; other abnormal urine components) abnormal, and imaging abnormalities; or unexplained GFR decline (< 60 ml/min/1.73 m2); and eGFR = 30 ml/min/1.73 m2.

Exclusion Criteria:

1. pregnancy.

2. combined tumors.

3. There is a history of drug abuse or alcohol abuse.

4. There are serious infections recently.

5. Life expectancy is less than half a year.

6. Renal replacement therapy has been performed.

7. Acquired immunodeficiency syndrome.

8. Those who are being treated with cortisol hormones.

9. Those who study or work at night for a long time and have irregular rest.

10. Those who cannot cooperate or are unable to tolerate ambulatory blood pressure monitors.

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Renal
• Hypertension;Nephropathy
• Nephritis
• Renal Insufficiency, Chronic

Intervention

Other:
• whole exome sequencing analysis
Collecting peripheral blood samples (2 ml) from subjects for whole exome sequencing

Locations

Country	Name	City	State
China	Fifth Affiliated Hospital, Sun Yat-Sen University	Zhuhai	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Fifth Affiliated Hospital, Sun Yat-Sen University	Third Affiliated Hospital, Sun Yat-Sen University

Country where clinical trial is conducted

China, 

References & Publications (25)

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Hermida RC, Ayala DE, Smolensky MH, Fernández JR, Mojón A, Portaluppi F. Chronotherapy with conventional blood pressure medications improves management of hypertension and reduces cardiovascular and stroke risks. Hypertens Res. 2016 May;39(5):277-92. doi: 10.1038/hr.2015.142. Epub 2015 Dec 10. Review. — View Citation

Hermida RC. Sleep-time ambulatory blood pressure as a prognostic marker of vascular and other risks and therapeutic target for prevention by hypertension chronotherapy: Rationale and design of the Hygia Project. Chronobiol Int. 2016;33(7):906-36. doi: 10.1080/07420528.2016.1181078. Epub 2016 May 24. — View Citation

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Mojón A, Ayala DE, Piñeiro L, Otero A, Crespo JJ, Moyá A, Bóveda J, de Lis JP, Fernández JR, Hermida RC; Hygia Project Investigators. Comparison of ambulatory blood pressure parameters of hypertensive patients with and without chronic kidney disease. Chronobiol Int. 2013 Mar;30(1-2):145-58. doi: 10.3109/07420528.2012.703083. Epub 2012 Oct 25. — View Citation

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Wang C, Deng WJ, Gong WY, Zhang J, Zhang QZ, Ye ZC, Lou T. Nocturnal Hypertension Correlates Better With Target Organ Damage in Patients With Chronic Kidney Disease than a Nondipping Pattern. J Clin Hypertens (Greenwich). 2015 Oct;17(10):792-801. doi: 10.1111/jch.12589. Epub 2015 Jun 4. — View Citation

Wang C, Ye Z, Li Y, Zhang J, Zhang Q, Ma X, Peng H, Lou T. Prognostic Value of Reverse Dipper Blood Pressure Pattern in Chronic Kidney Disease Patients not Undergoing Dialysis: Prospective Cohort Study. Sci Rep. 2016 Oct 7;6:34932. doi: 10.1038/srep34932. — View Citation

Wang C, Zhang J, Liu X, Li C, Ye Z, Peng H, Chen Z, Lou T. Reversed dipper blood-pressure pattern is closely related to severe renal and cardiovascular damage in patients with chronic kidney disease. PLoS One. 2013;8(2):e55419. doi: 10.1371/journal.pone.0055419. Epub 2013 Feb 5. — View Citation

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Zhang L, Wang F, Wang L, Wang W, Liu B, Liu J, Chen M, He Q, Liao Y, Yu X, Chen N, Zhang JE, Hu Z, Liu F, Hong D, Ma L, Liu H, Zhou X, Chen J, Pan L, Chen W, Wang W, Li X, Wang H. Prevalence of chronic kidney disease in China: a cross-sectional survey. Lancet. 2012 Mar 3;379(9818):815-22. doi: 10.1016/S0140-6736(12)60033-6. Erratum in: Lancet. 2012 Aug 18;380(9842):650. — View Citation

Zheng Y, Cai GY, Chen XM, Fu P, Chen JH, Ding XQ, Yu XQ, Lin HL, Liu J, Xie RJ, Wang LN, Ni ZH, Liu FY, Yin AP, Xing CY, Wang L, Shi W, Liu JS, He YN, Ding GH, Li WG, Wu GL, Miao LN, Chen N, Su Z, Mei CL, Zhao JY, Gu Y, Bai YK, Luo HM, Lin S, Chen MH, Gong L, Yang YB, Yang XP, Li Y, Wan JX, Wang NS, Li HY, Xi CS, Hao L, Xu Y, Fang JA, Liu BC, Li RS, Wang R, Zhang JH, Wang JQ, Lou TQ, Shao FM, Mei F, Liu ZH, Yuan WJ, Sun SR, Zhang L, Zhou CH, Chen QK, Jia SL, Gong ZF, Guan GJ, Xia T, Zhong LB; Prevalence, Awareness, and Treatment Rates in Chronic Kidney Disease Patients with Hypertension in China (PATRIOTIC) Collaborative Group. Prevalence, awareness, treatment, and control of hypertension in the non-dialysis chronic kidney disease patients. Chin Med J (Engl). 2013 Jun;126(12):2276-80. — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	whole exome sequencing analysis	Collecting peripheral blood samples (2 ml) from subjects for whole exome sequencing	4 years