Relationship between parathyroid hormone and renin–angiotensin–aldosterone system in hemodialysis patients with secondary hyperparathyroidism

Kono, Keiji; Fujii, Hideki; Watanabe, Kentaro; Goto, Shunsuke; Nishi, Shinichi

doi:10.1007/s00774-020-01139-5

Cited by 9 publications

(6 citation statements)

References 38 publications

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“…It can stimulate cytokine release from vascular smooth muscle cells and lymphocytes and thus affect the cardiovascular system via pro-inflammatory effects ( 35 ). IPTH is linked to the renin–angiotensin–aldosterone system (RAAS) as a probable mechanism of hypertension and ICH ( 36 , 37 ). IPTH levels are a risk factor for hypertension via vessel calcification so hypertension potentially remains the main direct risk factor for ICH.…”

Section: Discussionmentioning

confidence: 99%

Risk factors for intracerebral hemorrhage in patients undergoing maintenance hemodialysis

2023

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BackgroundIn patients undergoing hemodialysis, intracerebral hemorrhage (ICH) is the main cause of mortality among stroke subtypes. It is unclear whether, along with traditional cardiovascular risk factors, the risk factors unique to the uraemic environment, such as the abnormal metabolism of intact parathyroid hormone (iPTH), can contribute to the risk of ICH in these patients.MethodsThis retrospective case–control study included 25 patients undergoing hemodialysis with ICH at a single center between 30 June 2015 and 10 October 2022. The controls were 95 patients undergoing maintenance hemodialysis treated at the same dialysis center in July 2020. We compared the characteristics of patients with ICH with those of the control group to identify factors that contributed to the development of ICH.ResultsIntracerebral hemorrhage (ICH) was located in the basal ganglia (14/25), cerebellum (6/25), and brainstem (6/25) in 25 patients. A total of 17 patients died in the first 16 days due to neurological complications. Univariate analysis showed significant differences in systolic BP, diastolic BP, iPTH, and alkaline phosphatase between the two groups (p < 0.05). Multivariate logistic regression analysis showed that higher systolic BP (OR, 1.053; 95% CI, 1.018–1.090; p = 0.003) and higher iPTH (OR, 1.007; 95% CI, 1.003–1.012; p = 0.001) were associated with the onset of ICH. ICH was predicted by systolic BP and iPTH by receiver operating characteristic (ROC) curve analysis, with areas under the curve (AUCs) of 0.732 and 0.624, respectively. The optimal cutoffs for systolic BP and iPTH were 151.9 mmHg and 295.4 pg./ml, respectively. Restricted cubic spline showed that the shape of the association of iPTH with the risk of ICH was approximately J-shaped (P for non-linearity <0.05).ConclusionHigher systolic BP and abnormal iPTH metabolism might be associated with ICH in patients undergoing hemodialysis. Comprehensive control of hypertension and iPTH may be a fundamental preventive strategy for ICH in these patients.

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Section: Discussionmentioning

confidence: 99%

Risk factors for intracerebral hemorrhage in patients undergoing maintenance hemodialysis

2023

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“…We can therefore look back at the concept of PTH as a uremic toxin [ 23 ]. In fact, we are aware that PTH may have several extra-mineral negative effects in dialysis patients, spanning from increased left ventricular hypertrophy and higher blood pressure to erythropoietin-resistant anemia and poor nutrition and quality of life [ 24 – 26 ]. In our opinion, it is possible that PTX, by shortening exposure to high PTH levels, reduces the effects of extra-mineral damage.…”

Section: Discussionmentioning

confidence: 99%

Parathyroidectomy and survival in a cohort of Italian dialysis patients: results of a multicenter, observational, prospective study

et al. 2023

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Background Severe secondary hyperparathyroidism (SHPT) is associated with mortality in end stage kidney disease (ESKD). Parathyroidectomy (PTX) becomes necessary when medical therapy fails, thus highlighting the interest to compare biochemical and clinical outcomes of patients receiving either medical treatment or surgery. Methods We aimed to compare overall survival and biochemical control of hemodialysis patients with severe hyperparathyroidism, treated by surgery or medical therapy followed-up for 36 months. Inclusion criteria were age older than 18 years, renal failure requiring dialysis treatment (hemodialysis or peritoneal dialysis) and ability to sign the consent form. A control group of 418 patients treated in the same centers, who did not undergo parathyroidectomy was selected after matching for age, sex, and dialysis vintage. Results From 82 Dialysis units in Italy, we prospectively collected data of 257 prevalent patients who underwent parathyroidectomy (age 58.2 ± 12.8 years; M/F: 44%/56%, dialysis vintage: 15.5 ± 8.4 years) and of 418 control patients who did not undergo parathyroidectomy (age 60.3 ± 14.4 years; M/F 44%/56%; dialysis vintage 11.2 ± 7.6 y). The survival rate was higher in the group that underwent parathyroidectomy (Kaplan–Meier log rank test = 0.002). Univariable analysis (HR 0.556, CI: 0.387–0.800, p = 0.002) and multivariable analysis (HR 0.671, CI:0.465–0.970, p = 0.034), identified parathyroidectomy as a protective factor of overall survival. The prevalence of patients at KDOQI targets for PTH was lower in patients who underwent parathyroidectomy compared to controls (PTX vs non-PTX: PTH < 150 pg/ml: 59% vs 21%, p = 0.001; PTH at target: 18% vs 37% p = 0.001; PTH > 300 pg/ml 23% vs 42% p = 0.001). The control group received more intensive medical treatment with higher prevalence of vitamin D (65% vs 41%, p = 0.0001), calcimimetics (34% vs 14%, p = 0.0001) and phosphate binders (77% vs 66%, p = 0.002). Conclusions Our data suggest that parathyroidectomy is associated with survival rate at 36 months, independently of biochemical control. Lower exposure to high PTH levels could represent an advantage in the long term. Graphical abstract

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“…HPT is a complex and diverse condition that significantly impacts the quality of life for affected patients with various complications, including cardiovascular diseases 2 , kidney stones, and bone diseases 3 . In rare cases, prolonged hyperparathyroidism can ultimately induce end-stage parathyroid carcinoma—an aggressive malignancy with limited treatment options 4 , 5 .…”

Section: Introductionmentioning

confidence: 99%

Unveiling potential drug targets for hyperparathyroidism through genetic insights via Mendelian randomization and colocalization analyses

Chen,

Wang,

et al. 2024

Sci Rep

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Hyperparathyroidism (HPT) manifests as a complex condition with a substantial disease burden. While advances have been made in surgical interventions and non-surgical pharmacotherapy for the management of hyperparathyroidism, radical options to halt underlying disease progression remain lacking. Identifying putative genetic drivers and exploring novel drug targets that can impede HPT progression remain critical unmet needs. A Mendelian randomization (MR) analysis was performed to uncover putative therapeutic targets implicated in hyperparathyroidism pathology. Cis-expression quantitative trait loci (cis-eQTL) data serving as genetic instrumental variables were obtained from the eQTLGen Consortium and Genotype-Tissue Expression (GTEx) portal. Hyperparathyroidism summary statistics for single nucleotide polymorphism (SNP) associations were sourced from the FinnGen study (5590 cases; 361,988 controls). Colocalization analysis was performed to determine the probability of shared causal variants underlying SNP-hyperparathyroidism and SNP-eQTL links. Five drug targets (CMKLR1, FSTL1, IGSF11, PIK3C3 and SLC40A1) showed significant causation with hyperparathyroidism in both eQTLGen and GTEx cohorts by MR analysis. Specifically, phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) and solute carrier family 40 member 1 (SLC40A1) showed strong evidence of colocalization with HPT. Multivariable MR and Phenome-Wide Association Study analyses indicated these two targets were not associated with other traits. Additionally, drug prediction analysis implies the potential of these two targets for future clinical applications. This study identifies PIK3C3 and SLC40A1 as potential genetically proxied druggable genes and promising therapeutic targets for hyperparathyroidism. Targeting PIK3C3 and SLC40A1 may offer effective novel pharmacotherapies for impeding hyperparathyroidism progression and reducing disease risk. These findings provide preliminary genetic insight into underlying drivers amenable to therapeutic manipulation, though further investigation is imperative to validate translational potential from preclinical models through clinical applications.

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Relationship between parathyroid hormone and renin–angiotensin–aldosterone system in hemodialysis patients with secondary hyperparathyroidism

Cited by 9 publications

References 38 publications

Risk factors for intracerebral hemorrhage in patients undergoing maintenance hemodialysis

Risk factors for intracerebral hemorrhage in patients undergoing maintenance hemodialysis

Parathyroidectomy and survival in a cohort of Italian dialysis patients: results of a multicenter, observational, prospective study

Unveiling potential drug targets for hyperparathyroidism through genetic insights via Mendelian randomization and colocalization analyses

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