Hypertension in chronic kidney disease: What lies behind the scene

Ameer, Omar Z.

doi:10.3389/fphar.2022.949260

Cited by 35 publications

(33 citation statements)

References 355 publications

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“…Renal damage is a common complication of primary hypertension (HTN) and generally occurs after 5–10 years of HTN. HTN-related renal injury accounts for 13% of end-stage renal disease cases [1], secondary to primary renal diseases such as glomerular disease and diabetic nephropathy [2]. However, the onset of hypertensive nephropathy is often insidious, and it is discovered at an advanced stage in most patients, resulting in the occurrence of several complications and a high mortality rate.…”

Section: Introductionmentioning

confidence: 99%

A classifier based on 273 urinary peptides predicts early renal damage in primary hypertension

Wang

Ren

et al. 2023

Journal of Hypertension

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Objectives: Renal diseases caused by primary hypertension (HTN) are often asymptomatic without sensitive markers for early diagnosis and prediction, easily progressing to severe and irreversible renal damage in patients with clinical manifestations. This study explored whether a classifier developed based on 273 urinary peptides (CKD273) could serve as a potential biomarker for early prediction of renal damage in HTN. Methods: Urinary CKD273 level of healthy individuals, HTN + normoalbuminuric and HTN + albuminuria patients were compared, and 22 baseline data including sex, age, renal function, and hypertensive fundus lesions were collected. Patients diagnosed with HTN, albuminuria, and normal renal function were followed up. According to the follow-up results, the cut-off value of CKD273 in predicting hypertensive renal injury was calculated and analyzed in the high-risk and low-risk groups of HTN patients for its performance in detecting early hypertensive renal injury. Results: Among a sum of 319 participants, average urinary CKD273 level was significantly higher in patients with HTN than in normal individuals. A total of 147 HTN patients with normal albuminuria were followed up for a mean of 3.8 years. Thirty-five patients showed urinary albumin-to-creatinine ratio (uACR) at least 30 mg/g for three consecutive times. The receiver-operating characteristic (ROC) curve showed that the urinary CKD273 cut-off value for evaluating new-onset proteinuria in patients with HTN was 0.097. Based on this cut-off value, 39 and 108 patients were included in the high-risk and low-risk groups, respectively. Specifically, compared with patients in the low-risk group, those in the high-risk group showed significantly longer duration of HTN, higher proportions of hypertensive fundus lesions and at least 30 mg/g uACR, and higher levels of homocysteine (Hcy), cystatin C (CysC), beta-2 microglobulin (β2-MG), and uACR. 76.9% of high-risk patients had significantly higher new-onset proteinuria than the low-risk group. Correlation analysis demonstrated a positive correlation between urinary CKD273 and UACR (r = 0.494, P = 0.000). The incidence of new-onset albuminuria was significantly higher in the high-risk group than in the low-risk group, as shown by Cox regression analysis. The areas under the curve of CKD273, Hcy, β2-MG, and CysC were 0.925, 0.753, 0.796, and 0.769, respectively. Conclusion: Urinary CKD273 is a predictor of new-onset proteinuria in patients with HTN, therefore, it can be used for diagnosing patients with early renal injury in patients with HTN, contributing to early prevention and treatment of hypertensive nephropathy.

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Section: Introductionmentioning

confidence: 99%

A classifier based on 273 urinary peptides predicts early renal damage in primary hypertension

Wang

Ren

et al. 2023

Journal of Hypertension

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“…Functional impairment of the kidneys is also a frequent disorder in the presence of high blood pressure, also known as hypertension. It has been thought that renal damage linked to hypertension is caused by oxidative stress [ 146 , 147 , 148 ]. In this regard, ALA has also been tested for its antioxidant role in hypertension-induced kidney injury.…”

Section: Miscellaneousmentioning

confidence: 99%

Renal-Protective Roles of Lipoic Acid in Kidney Disease

Kamt

Liu

2023

Nutrients

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The kidney is a crucial organ that eliminates metabolic waste and reabsorbs nutritious elements. It also participates in the regulation of blood pressure, maintenance of electrolyte balance and blood pH homeostasis, as well as erythropoiesis and vitamin D maturation. Due to such a heavy workload, the kidney is an energy-demanding organ and is constantly exposed to endogenous and exogenous insults, leading to the development of either acute kidney injury (AKI) or chronic kidney disease (CKD). Nevertheless, there are no therapeutic managements to treat AKI or CKD effectively. Therefore, novel therapeutic approaches for fighting kidney injury are urgently needed. This review article discusses the role of α-lipoic acid (ALA) in preventing and treating kidney diseases. We focus on various animal models of kidney injury by which the underlying renoprotective mechanisms of ALA have been unraveled. The animal models covered include diabetic nephropathy, sepsis-induced kidney injury, renal ischemic injury, unilateral ureteral obstruction, and kidney injuries induced by folic acid and metals such as cisplatin, cadmium, and iron. We highlight the common mechanisms of ALA’s renal protective actions that include decreasing oxidative damage, increasing antioxidant capacities, counteracting inflammation, mitigating renal fibrosis, and attenuating nephron cell death. It is by these mechanisms that ALA achieves its biological function of alleviating kidney injury and improving kidney function. Nevertheless, we also point out that more comprehensive, preclinical, and clinical studies will be needed to make ALA a better therapeutic agent for targeting kidney disorders.

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“…The relationship between CKD and hypertension is reciprocal since hypertension is a strong determinant of worse renal function and decline in renal function frequently causes or exacerbates hypertension. This close interconnection is the result of multiple factors, including reduced nephron mass, increased sodium retention, endothelial dysfunction, and activation of hormones [7,8,9]. Dopamine is a natriuretic and diuretic hormone with an important paracrine/autocrine role in the kidney, affecting water and electrolyte balance.…”

Section: Introductionmentioning

confidence: 99%

Evidence for a relationship between genetic polymorphisms of the L-DOPA transporter LAT2/4F2hc and risk of hypertension in the context of chronic kidney disease

Crocco,

Dato,

Grotta

et al. 2024

Preprint

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Background Chronic kidney disease (CKD) and hypertension are chronic diseases affecting a large portion of the population, frequently coexistent and interdependent. The inability to produce/use adequate renal dopamine may contribute to the development of hypertension and renal dysfunction. The heterodimeric amino acid transporter LAT2/4F2hc (SLC7A8/SLC3A2 genes) promotes the uptake of L-DOPA, the natural precursor of dopamine. We examined the plausibility that SLC7A8/SLC3A2 gene polymorphisms may contribute to hypertensive CKD by affecting the L-DOPA uptake. Methods 421 subjects (203 men and 218 women, mean age of 78.9 ± 9.6 years) were recruited and divided in four groups according to presence/absence of CKD, defined as reduced estimated glomerular filtration rate (eGFR < 60 ml/min/m2) calculated using the creatinine-based Berlin Initiative Study–1 (BIS1) equation, and to presence/absence of hypertension (systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mmHg). Subjects were analysed for selected SNPs spanning the SLC7A8 and SLC3A2 loci by Sequenom MassARRAY iPLEX platform. Results The most significant SNP at the SLC3A2 (4F2hc) locus was rs2282477-T/C, with carriers of the C-allele having a lower chance to develop hypertension among CKD affected individuals [OR = 0.33 (CI 0.14–0.82); p = 0.016]. A similar association with hypertensive CKD was found for the SLC7A8 (LAT2) rs3783436-T/C, whose C-allele resulted associated with decreased risk of hypertension among subjects affected by CKD [OR = 0.56 (95% CI 0.35–0.90; p = 0.017]. The two variants were predicted to be potentially functional. Conclusions The association between SLC3A2 and SLC7A8 variants to hypertension development in patients with renal failure could be linked to changes in L-DOPA uptake and consequently dopamine synthesis. Although additional research is needed, our study opens new avenues for future basic and translational research in the field of hypertensive CKD.

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Hypertension in chronic kidney disease: What lies behind the scene

Cited by 35 publications

References 355 publications

A classifier based on 273 urinary peptides predicts early renal damage in primary hypertension

A classifier based on 273 urinary peptides predicts early renal damage in primary hypertension

Renal-Protective Roles of Lipoic Acid in Kidney Disease

Evidence for a relationship between genetic polymorphisms of the L-DOPA transporter LAT2/4F2hc and risk of hypertension in the context of chronic kidney disease

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