Paweł Stróżecki

PARATHORMON, CALCIUM, PHOSPHORUS, AND LEFT VENTRICULAR STRUCTURE AND FUNCTION IN NORMOTENSIVE HEMODIALYSIS PATIENTS

Clinical and experimental data suggest that Parathormon (PTH), calcium, and phosphorus participate in left ventricular hypertrophy (LVH) and affect myocardial contractility in end-stage renal disease. Cellular calcium overload and interstitial fibrosis induced by PTH may lead to impairment of left ventricular diastolic function. Hyperphosphatemia is an independent risk of cardiovascular mortality in dialysis patients. The aim of the study was to estimate the influence of PTH and calcium-phosphorus metabolism on left ventricular structure and function in hemodialysis patients, without hypertension and antihypertensive drug therapy (SBP = 126.2 ± 11.1 DBP = 75.8 ± 6.5 mmHg). Echocardiographic findings in a group of 22 normotensive HD patients had been compared to 43 hypertensive HD patients. Relationships between PTH, calcium-phosphorus metabolism and echocardiography in normotensive group were then evaluated. Left ventricular mass index (LVMI) was lower in normotensive patients: 128.3 ± 46.2 versus 165.8 ± 46.7 (p < 0.01). The prevalence of LVH was 55% in normotensive HD patients compared to 86% in hypertensive group (p < 0.01). In normotensive group we found correlation between PTH and LVMI (r = 0.44; p < 0.05). There were also significant relationships between calcium and posterior wall thickness (r = −0.44; p < 0.05), phosphorus and LVMI (r = 0.47; p < 0.05). A significant correlation was observed between both phosphorus, calcium × phosphorus product and E/A ratio: r = −0.47 and r = −0.43, respectively (p < 0.05 both). Disturbances of calcium-phosphorus metabolism and secondary hyperparathyroidism contributes to left ventricular hypertrophy, and impaired left ventricular diastolic function in normotensive hemodialysis patients.

25-hydroxyvitamin D, biomarkers of endothelial dysfunction and subclinical organ damage in adults with hypertension.

BACKGROUND The mechanism that underlies the association between low 25-hydroxyvitamin D [25(OH)D] and hypertension is not well understood; it seems to involve regulation of the renin-angiotensin-aldosterone system and the impact on endothelial function, cardiac remodeling, and subclinical organ damage. Vitamin D supplementation presents an ambiguous effect on endothelial function and arterial stiffness. We assess serum 25(OH)D3, biomarkers of endothelial dysfunction (soluble intercellular adhesion molecule [sICAM], C-reactive protein [CRP], homocysteine [Hcy]) and subclinical organ damage in adults with newly diagnosed untreated hypertension. METHODS Patients were classified based on ambulatory blood pressure monitoring: 98 had hypertension, whereas in 60 persons BP was normal. Laboratory assays including serum 25(OH)D3, hsCRP, Hcy, sICAM, glucose, insulin, lipids, echocardiography, pulse wave velocity (PWV), intima-media thickness (IMT), and left-ventricular mass (LVM) measurements were performed. RESULTS 25(OH)D3 was significantly lower in hypertensive patients. The logistic regression analysis indicated that 25(OH)D3 reduced the probability of hypertension occurrence after adjusting for body mass index (BMI). 25(OH)D3 in those with hypertension correlated significantly with systolic BP (SBP; r = -0.39), PWV, IMT (r = -0.33), and diastolic BP (r = -0.26). Multiple regression analysis in patients with hypertension revealed that 25(OH)D3 and sICAM accounted for up to 27% of SBP variation after adjusting for age, BMI, and smoking. 25(OH)D3 and either PWV or IMT accounted for 23% of SBP variation. The impact of 25(OH)D3 was 10%. CONCLUSION The impact of 25(OH)D3 on SBP variation, mediated by its effect on endothelial dysfunction and subclinical organ damage, is modest but significant.

Effect of parathormone on heart rate variability in hemodialysis patients.

INTRODUCTION Parathormone (PTH) is a very potent uraemic toxin, which affects heart structure and function. PTH also plays the role in uraemic autonomic neuropathy (AN). The aim of the study was to investigate the relationship between high PTH level and AN assessed with frequency domain measures of heart rate variability (HRV). MATERIALS AND METHODS A 24-h ECG was performed in 40 HD (F=19, M=21) patients aged 49+/-11 years, duration of HD therapy 37+/-30 months. Frequency domain measures of HRV were obtained according to European Society of Cardiology recommendations. Total spectral power (TP), high frequency band (HF) and low frequency band (LF) were computed as indexes of: total autonomic nervous system (ANS) activity, parasympathetic and sympathetic activities, respectively. LF/HF ratio was calculated. TP, HF, LF and LF/HF were expressed as natural logarithm. Patients were divided into two groups due to PTH level: PTH+ (PTH> or =275 pg/ml) and PTH- (PTH<275 pg/ml). RESULTS The values of lnTP and lnLF were lower in patients PTH+ than in patients PTH- (6,58+/-0,76 vs. 6,99+/-0,44 ms2, p<0,05, and 4,91+/-0,99 vs. 5,33+/-0,65 ms2, respectively, p=0,06). We also found negative correlation between lnPTH and lnTP (r=-0,47; p<0,005), lnPTH and lnLF (r=-0,35; p<0,05), lnPTH and lnHF (r=-0,34; p<0,05). On multiple regression analysis, lnTP, lnLF and lnHF were independently related to lnPTH. CONCLUSIONS Parathormone exerts effect on activity of both parts of autonomic nervous system: sympathetic and parasympathetic. High PTH level deteriorates total autonomic activity.

The influence of calcineurin inhibitors on pulse wave velocity in renal transplant recipients.

Background. Pulse wave velocity (PWV) is a marker of the arterial wall stiffness and independent cardiovascular risk factor in hemodialysis patients. Cyclosporine A (CyA) and tacrolimus (TAC) are known to differ in the influence on cardiovascular risk factors in renal transplant recipients. Recent studies suggest that CyA may decrease arterial compliance. The aim of the study was to assess the influence of CyA and TAC on the PWV and arterial wall stiffness in renal transplant recipients. Methods. The study population consisted of two groups of cadaveric renal transplant recipients, 76 patients each, matched for age, sex, blood pressure, body mass index, and length of the post-transplant follow-up. PWV between carotid and femoral artery was measured using a Complior device. Fasting blood was sampled for serum creatinine, lipid profile, uric acid, glucose, and C-reactive protein. Results. Aortic pulse wave velocity—a marker of increased arterial stiffness—was significantly higher in CyA group compared with TAC group (9.33 ± 2.10 vs. 8.54 ± 1.35, respectively; p < 0.01). Uric acid, total cholesterol, triglycerides, and LDL-cholesterol concentrations were significantly higher in CyA group. Significant correlations were found between PWV and age, systolic and diastolic blood pressure, and fasting glucose in the CyA group, but only between PWV and age in TAC group. Conclusion. CyA-based immunosuppressive therapy is associated with an unfavorable profile of cardiovascular risk factors and increased arterial stiffness in renal transplant recipients.

The Influence of Intravenous 1,25(OH)2D3 Therapy on Glucose Metabolism in Hemodialyzed Patients with Secondary Hyperparathyroidism

Glucose intolerance, insulin resistance and hyperinsulinemia are common findings in end‐stage renal disease patients. Parathormone (PTH) and vitamin D3 are linked with disturbances of glucose metabolism. Glycated hemoglobin (HbA1c) reflects long‐term glycemic control. HbA1c is a marker of increased risk of death in diabetic patients but also in general population. The aim of the study was to investigate the influence of 1,25(OH)2D3 therapy on long‐term control of glycemia in hemodialyzed (HD) patients with severe secondary hyperparathyroidism (SHP). Eight HD patients with SHP (PTH = 1088.6 ± 472.2) were given intravenous 1,25(OH)2D31–2 µg thrice a week, for 12 weeks (mean dose 4.5 µg/week). At baseline and after 12 weeks fasting blood was sampled for: glucose, insulin, HbA1c, PTH. Insulin/glucose ratio (I/G) was calculated as marker of insulin resistance. Results were compared with 14 healthy volunteers (controls) matched for age, sex and BMI. At baseline I/G was higher in HD vs controls 0.110 ± 0.045 vs 0.073 ± 0.021 (p = 0.02), and of borderline significance at follow‐up (0.106 ± 0.053, p = 0.05 vs controls). PTH decreased significantly to 506.1 ± 646.3 (p < 0.02) during therapy. Significant decrease of HbA1c in HD patients was observed (5.84 ± 0.40 vs 5.13 ± 0.51; p = 0.01), while fasting glucose, insulin and I/G did not change significantly. Intravenous 1,25(OH)2D3 therapy is successful, even in patients with severe secondary hyperparathyroidism. Significant decrease in HbA1c with stable insulin concentration may indicate positive impact of intravenous 1,25(OH)2D3 therapy on long‐term glucose metabolism.

Left ventricular remodeling and arterial remodeling in patients with chronic kidney disease stage 1–3

Abstract Introduction: Chronic kidney disease (CKD) is an independent factor for cardiovascular system complications, such as arterial hypertension, left ventricular hypertrophy (LVH), heart failure or accelerated atherosclerosis progression. The aim of the paper was to analyze left ventricular and arterial remodeling in patients with CKD stages 1–3 to identify the subclinical marker of cardiovascular system damage which changes first in the course of CKD. Methods: The examined group consisted of 90 patients with CKD stage 1–3 and 30 subjects constituting the control group. Left ventricular mass index (LVMI), left ventricular relative wall thickness (RWT) and ejection fraction (EF) were determined by echocardiographic examination. Pulse wave velocity (PWV) between the carotid and femoral arteries as well as common carotid artery intima–media thickness (IMT) was measured. 24-h ambulatory blood pressure monitoring was performed in all subjects. Results: No differences were found between blood pressure values in the examined groups of patients with CKD1, CKD2 and CKD3. Concentric remodeling was found in 20.0%, concentric hypertrophy in 22.2% and eccentric hypertrophy in 18.9% of patients. LVMI values in patients with CKD2 and 3 were higher than in the control group. IMT values in patients with CKD3 were higher than in patients with CKD2. PWV in patients with stage 3 CKD was significantly higher than in the control group (p < 0.05). Conclusions: In the course of CKD, the left ventricle undergoes remodeling earlier than large arterial vessels. Echocardiographic assessment of LVH in early stages of CKD may identify patients at increased cardiovascular risk.

Cardiac valve calcifications and left ventricular hypertrophy in hemodialysis patients.

Cardiac valve calcification (VC) is a common finding in end-stage renal disease patients. It was shown recently that VC is an independent predictor for all-cause and cardiovascular mortality in peritoneal dialysis patients. In hemodialysis (HD) patients, VC was associated with all-cause and cardiovascular mortality, but after adjusting for other cardiovascular risk factors and complications, as well as left ventricular mass index (LVMI), it lost significance. The aim of the study was to assess the relationship between VC and left ventricular hypertrophy in hemodialysis patients. Echocardiographic examination with mitral and aortic valves assessment and LVMI calculation was performed in 65 HD patients ages 49 ± 12, with duration of HD therapy 38 ± 32 months. VC were found in 32 of 65 patients (49%)—Group VC(+), mitral valve calcifications (MVC) in 10, aortic valve calcifications (AVC) in 9, and both valves calcifications (MVC + AVC) in 13 patients. Patients with VC were older, on HD therapy were longer, had higher systolic and pulse pressure, and had higher LVMI. Patients with both VCs had the highest LVMI. No significant differences were found with respect to Ca, P, PTH, and mean Ca × P product, but the incidence of Ca × P product above 4.43 mmol2/L2 was higher in VC(+) compared with those without VCs. VC coexists with left ventricular hypertrophy, particularly when both valves are calcified. Even short-lasting incidents of increased Ca × P product may lead to cardiac VC.

Long graft cold ischemia time is associated with increased arterial stiffness in renal transplant recipients.

BACKGROUND Increased pulse wave velocity (PWV), an indicator of arterial stiffness, is associated with greater cardiovascular risk among renal transplant recipients. PWV depends on recipient-related factors and, as shown in recent studies, also on donor age. There is a lack of information whether graft-related factors influence arterial function in recipients. Graft cold ischemia time (CIT) significantly influences renal transplant outcomes. It was shown in an experimental model of aortic grafting that increased CIT promoted arteriosclerosis. The aim of the present study was to evaluate the relationship between renal graft CIT and PWV. METHODS Carotid-femoral PWV were measured in 103 cadaveric kidney recipients of mean age 45 +/- 12 years. We analyzed clinical data of recipient and donor ages, genders, body mass index, blood pressure, CIT, delayed graft function, and type of immunosuppressive therapy to compare patients with CIT < 24 (n = 24) versus CIT > or = 24 hours (n = 79). RESULTS PWV was lower among patients with shorter CIT (8.3 +/- 1.6 vs 9.2 +/- 2.0 respectively; P < .05). No significant differences were observed between the groups regarding donor and recipient ages, blood pressure, glomerular filtration rate, or immunosuppressive and cardiovascular therapy. A significant positive correlation was noted between PWV and CIT (r = .23; P = .019). Multiple regression analysis demonstrated that recipient age, therapy with cyclosporine, fasting glucose, systolic blood pressure, and CIT were independently associated with PWV. CONCLUSIONS Long CIT was associated with increased arterial stiffness. Further studies are necessary to understand the cause effect relationship of this finding.

Factors associated with increased pulse wave velocity in peritoneal dialysis patients

Elevated pulse wave velocity (PWV) reflects increased arterial stiffness. Several studies have investigated PWV in peritoneal dialysis (PD) patients, but direct comparisons with healthy controls were not done. The potential influence of peritoneal transport characteristics on arterial stiffness in PD patients was suggested in recent studies. The aims of this study were to compare PWV in PD patients and healthy volunteers, and to investigate factors associated with increased PWV. The carotid-femoral PWV was measured in 28 PD patients and 28 healthy controls, matched for age and gender. A peritoneal equilibration test (PET) was performed in all PD patients. Based on the PET, patients were classified as: high transporters (H) (n=8), high-average (HA) (n=12), low-average (LA) (n=6), and low transporters (L) (n=2). Six of the PD patients were diabetic. PWV was significantly higher in the PD patients than in the controls (9,9±2,4 vs. 8,0±0,9; p=0,0004). In the PD group, PWV was higher in H/HA than in L/LA patients (10,4 ± 2,5 vs. 8,6 ± 1,0; p=0,008), but all the diabetic patients were in the H/HA group. PWV was significantly higher in diabetic than in non-diabetic PD patients (12,8 ± 2,0 vs. 9,1 ± 1,7; p=0,004). In the PD patients, significant positive correlations were found between PWV and: age, pulse pressure, Kt/V, and duration of PD therapy. In conclusion, the carotid-femoral PWV is elevated in peritoneal dialysis patients. Increased PWV in PD patients is associated with age, diabetic status, and longer duration of PD therapy, but not with this type of peritoneal transport.

Bilateral Nephrectomy as a Rescue Therapy for Hemodialyzed Patient with Malignant Hypertension – Case Report

We present the case of a 64-year-old male patient in whom malignant phase of hypertension developed during dialysis therapy. Hypertension was resistant to pharmacological therapy with seven antihypertensive drugs and dialysis therapy with ultrafiltration. In this patient bilateral nephrectomy was performed as a rescue therapy. It led to better control of blood pressure and allowed to reduce the number and dosage of antihypertensive medications.