The relationship between inflammation, blood pressure, and mean platelet volume in chronic kidney disease

Background: Neural precursor cell expressed developmentally down-regulated 4-like (NEDD4L) is a candidate gene for hypertension, and carriers of an intact NEDD4L C2-domain,encoded by the NEDD4L rs4149601 (G/A) GG genotype, together with the C-allele of the NEDD4L rs2288774 (C/T) polymorphism have been found be associated with hypertension both in African Americans and whites. However, there is no data on the relationship between polymorphism of NEDD4L rs4149601 and rs2288774 and hypertension in Chinese chronic kidney disease (CKD) patients. The purpose of the current study was to investigate the relationship between the variation of NEDD4L rs4149601, rs2288774 and hypertension in CKD patients. Methods: A total of 546 Chines Hans CKD patients were enrolled in our study. The SNPs were genotyped using PCR-based techniques. All patients underwent ambulatory blood pressure monitoring, and clinical data were also collected. Multivariate logistic regression analysis was used to identify the relationship between polymorphisms and hypertension. Results: 506 patients carried GG/GA genotype and 30 carried AA genotype. Rs4149601 AA genotype carriers had significantly higher rate of hypertension (68.3% vs 46.2%, P = 0.022) than GG/GA genotype carriers by Chi-squared test. AA genotype carriers also had a higher day-time and bedtime systolic blood pressure (142±16 vs 135±23, P=0.036; 137±18 vs 127±13, P=0.022, respectively) when compared with GG/GA genotype carriers. AA genotype [OR= 3.08, 95% CI (1.06-9.80)], lowever eGFR [OR=0.98, 95% CI (0.97-0.99)], older age [OR=1.03, 95% CI (1.01-1.05)] were independently associated with hypertension in CKD patients by multivariate logistic regression. However, No difference was found in blood pressure with rs2288774 TT/TC/CC genotypes, and no difference was found in the incidence of hypertension among patients with three genotypes. Conclusions: Our results suggested 4149601AA genotype of NEDD4L may be associated with hypertension in CKD patients, and further genetic and functional studies are required to understand its role in the manifestation of hypertension in Chinese CKD patients.

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Soluble Urokinase‐Type Plasminogen Activator Receptor, Changes of 24‐Hour Blood Pressure, and Progression of Chronic Kidney Disease

Journal of the American Heart Association ◽

10.1161/jaha.120.017225 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Jong Hyun Jhee ◽

Bo Young Nam ◽

Chan Joo Lee ◽

Jung Tak Park ◽

Seung Hyeok Han ◽

...

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Plasminogen Activator ◽

Interquartile Range ◽

Ckd Progression ◽

Type Plasminogen Activator ◽

Urokinase Type Plasminogen Activator ◽

Plasminogen Activator Receptor ◽

The Relationship

Background Soluble urokinase‐type plasminogen activator receptor (suPAR) is associated with cardiovascular risks and poor renal outcomes. However, whether elevated suPAR levels are associated with 24‐hour blood pressure patterns or kidney disease progression in patients with chronic kidney disease (CKD) is unclear. Methods and Results A total of 751 patients with CKD stage 1 to 5 were recruited from CMERC‐HI (Cardiovascular and Metabolic Disease Etiology Research Center–High Risk) cohort study (2013–2018). The relationship of serum suPAR levels to 24‐hour blood pressure parameters and CKD progression was analyzed. The median serum suPAR level was 1439.0 (interquartile range, 1026.2–2150.1) pg/mL, and the mean estimated glomerular filtration rate was 52.8±28.5 mL/min per 1.73 m 2 at baseline. Patients with higher suPAR levels had significantly higher levels of office, 24‐hour, daytime, and nighttime systolic blood pressure and nighttime diastolic blood pressure than those with lower suPAR levels. The highest suPAR tertile was associated with an increased risk of a reverse dipping pattern (odds ratio, 2.93; 95% CI, 1.27–6.76; P =0.01). During a follow‐up of 43.2 (interquartile range, 27.0–55.6) months, the CKD progression occurred in 271 (36.1%) patients. The highest suPAR tertile was significantly associated with higher risk of CKD progression than the lowest tertile (hazard ratio [HR], 2.09; 95% CI, 1.37–3.21; P =0.001). When the relationship was reevaluated with respect to each dipping pattern (dipper, extreme dipper, nondipper, and reverse dipper), this association was consistent only in reverse dippers in whom the risk of CKD progression increased (HR, 1.43; 95% CI, 1.02–2.01; P =0.03) with every 1‐unit increase in serum suPAR levels. Conclusions Elevated suPAR levels are independently associated with CKD progression, and this association is prominent in reverse dippers.

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