Piotr Kuczera

Cinacalcet treatment decreases plasma fibroblast growth factor 23 concentration in haemodialysed patients with chronic kidney disease and secondary hyperparathyroidism.

Recent clinical studies suggest that fibroblast growth factor 23 (FGF23) is important in the pathogenesis of calcium–phosphate abnormalities in patients with chronic kidney disease and that increased plasma FGF23 concentration is a cardiovascular risk factor in these patients. The aim of this prospective, single‐arm, open‐label clinical study was to assess the influence of 6‐month cinacalcet treatment on plasma FGF23 concentration in haemodialysed patients with secondary hyperparathyroidism (sHPT).

Extrarenal factors influencing resistance index in stable kidney transplant recipients.

Background Increased intrarenal resistance index (RI) has been associated with decreased long-term allograft and patient survival in kidney transplant recipients. Taking into account the potential role of endothelial dysfunction, systemic inflammation, arteriosclerotic lesions, and left ventricle remodeling, we performed a cross-sectional study that aimed to evaluate extrarenal factors that may have influence on kidney graft RI in a large cohort of stable kidney transplant recipients. Methods One hundred seventy-four kidney transplant recipients were enrolled into the study. Mean time after transplantation was 8.4±1.8 years. Echocardiography, carotid ultrasound (intima-media thickness), pulse wave velocity, and Doppler examination of kidney graft were performed. The inflammatory markers, adhesion molecules, and plasma N-terminal prohormone of brain natriuretic peptide concentrations were also measured. Patients were divided into quartile subgroups based on RI value (Q1: RI⩽0.68, Q2: RI=0.69–0.72, Q3: RI=0.73–0.76, and Q4: RI≥0.77). Results The analyzed subgroups were comparable with respect to demographics (except age) and anthropometric parameters as well as comorbidities. The values of age, serum phosphate, pulse wave velocity, left ventricular mass (LVM), and LVM index (LVMI) increased in subsequent RI quartile subgroups. The strongest correlation was found between RI and age, LVM, LVMI, and plasma parathormone concentration and was negative with estimated glomerular filtration rate. In backward stepwise multivariate regression analysis, the RI variability was explained by age, LVMI, and serum phosphate concentration. Conclusion Arterial stiffness and left ventricular hypertrophy may significantly influence the intrarenal vascular resistance measured using Doppler sonography in stable kidney transplant recipients.

Fibroblast Growth Factor-23—A Potential Uremic Toxin

Fibroblast growth factor-23 (FGF23) is a circulating member of the FGF family produced mainly by the osteocytes and osteoblasts that can act as a hormone. The main action of FGF23 is to lower phosphatemia via the reduction of urinary phosphate reabsorption and the decrease of 1,25(OH)2-D generation in the kidney. In the course of chronic kidney disease (CKD), plasma FGF23 concentration rises early, most probably to compensate the inability of the deteriorating kidneys to excrete an adequate amount of phosphate. However, this comes at the cost of FGF23-related target organ toxicity. Results of clinical studies suggest that elevated plasma FGF23 concentration is independently associated with the increased risk of CKD progression, occurrence of cardio-vascular complications, and mortality in different stages of CKD. FGF23 also contributes to cardiomyocyte hypertrophy, vascular calcification, and endothelial dysfunction. The impact of FGF23 on heart muscle is not dependent on Klotho, but rather on the PLCγ–calcineurin–NFAT (nuclear factor of activated T-cells) pathway. Among the factors increasing plasma FGF23 concentration, active vitamin D analogues play a significant role. Additionally, inflammation and iron deficiency can contribute to the increase of plasma FGF23. Among the factors decreasing plasma FGF23, dietary phosphate restriction, some intestinal phosphate binders, cinacalcet (and other calcimimetics), and nicotinamide can be enumerated. Anti-FGF23 antibodies have also recently been developed to inhibit the action of FGF23 in target organs. Still, the best way to normalize plasma FGF23 in maintenance hemodialysis patients is restoring kidney function by successful kidney transplantation.

The association of long-functioning hemodialysis vascular access with prevalence of left ventricular hypertrophy in kidney transplant recipients.

Left ventricular hypertrophy (LVH) is frequently observed in chronic dialysis patients and is also highly prevalent in kidney transplant recipients. This study evaluates the impact of long-functioning hemodialysis vascular access on LVH in single center cohort of kidney transplant recipients. 162 patients at 8.7 ± 1.8 years after kidney transplantation were enrolled. Echocardiography, carotid ultrasound, and assessment of pulse wave velocity were performed. LVH was defined based on left ventricular mass (LVM) indexed for body surface area (BSA) and height2.7. There were 67 patients with and 95 without patent vascular access. Both study groups were comparable with respect to gender, age, duration of dialysis therapy, and time after transplantation, kidney graft function, and cardiovascular comorbidities. Patients with patent vascular access were characterized by significantly elevated LVM and significantly greater percentage of LVH, based on LVMI/BSA (66.7 versus 48.4%, P = 0.02). OR for LVH in patients with patent vascular access was 2.39 (1.19–4.76), P = 0.01. Regression analyses confirmed an independent contribution of patent vascular access to higher LVM and increased prevalence of LVH. We concluded that long-lasting patent hemodialysis vascular access after kidney transplantation is associated with the increased prevalence of LVH in kidney transplant recipients.

The odontogenic-related microinflammation in patients with chronic kidney disease

Abstract Objectives: This study estimated plasma levels of interleukin IL-1β, IL-6, tumour necrosis factor-α (TNF-α), interferon-γ (INF-γ) in chronic kidney disease (CKD) patients with a single odontogenic pathology. Material and methods: Forty-nine selected adult CKD patients with single odontogenic pathology based on clinical and X-ray examination: patients after proper root canal treatment, without periapical lesions (n = 12), with pulp necrosis (n = 7), with asymptomatic periapical lesions (n = 22), with periodontal disease (n = 8), and 14 with healthy teeth were enrolled. Patients with coexisting different dental pathologies and the evidence of other infection were excluded. In all patients plasma concentrations of CRP, IL-1β, IL-6, TNF-α, and INF-γ were measured. Results: Patients with periodontitis were characterized by increased concentrations of IL-6 and TNF-α. Those with pulp necrosis had significantly more frequently serum CRP level over 2 mg/L and presented significantly elevated IL-6, but decreased TNF-α concentration than in the subjects with healthy teeth. In patients with periapical lesions and patients after root canal therapy, the concentrations of cytokines did not indicate for the systemic inflammation. Conclusions: Periodontitis and pulp necrosis are important sources of systemic microinflammation in CKD patients. Plasma concentrations of IL-6 and TNF-α appear to be more sensitive markers of odontogenic inflammation in CKD patients than CRP.

Serum Anti-Müllerian Hormone Concentration in Young Women with Chronic Kidney Disease on Hemodialysis, and After Successful Kidney Transplantation

Background/Aims: In women with chronic kidney disease (CKD) fertility abnormalities occur frequently. Anti-Müllerian hormone (AMH) inhibits excessive recruitment of primordial follicles. The aim of the study was to evaluate the serum AMH concentration in women on hemodialysis and after kidney transplantation (KTx). Methods: 46 hemodialysed women and 14 with CKD about to undergo kidney transplantation were enrolled into the study. The control group consisted of 40 healthy women. In all subjects serum concentration of AMH was determined (in chronic hemodialysis women and in control group once, and in women after KTx immediately before surgery, and 3 times after the transplantation). Results: Serum AMH concentration in hemodialysed women and in the control group did not differ significantly, while in hemodialysed women with regular menstrual cycles it was significantly lower than in the control group: 2.20 (1.08-3.55ng/ml) and 3.30 (1.80-6.10ng/ml) respectively, (p=0.02). In the KTx group, a significant decrease in serum AMH concentration was found from 3.30ng/ml (2.20-6.50ng/ml) at baseline to 1.90ng/ml (1.30-2.40ng/ml) at 6 months after KTx (p=0.007). Conclusions: 1. Significantly lower serum AMH concentration was found in the regularly menstruating CKD women on hemodialysis in comparison with the healthy controls. 2. Serum AMH decreased significantly after successful KTx.

Changes of Serum Total and Free Testosterone Concentrations in Male Chronic Hemodialysis Patients with Secondary Hyperparathyroidism in Response to Cinacalcet Treatment

Background/Aims: Calcium sensing receptor (CaSR) is expressed, among others also in testis. Cinacalcet binds to the CaSR, increases sensitivity of CaSR to serum calcium and is used in the treatment of secondary hyperparathyroidism (sHPT) in chronic hemodialysis patients (HDP). In most of male HDP, serum testosterone concentration is lower than in healthy males. The aim of this study was to assess the influence of six-month treatment with cinacalcet on the serum total and free testosterone concentration in male HDP with sHPT. Methods: 38 male, hemodialysed CKD patients with sHPT (PTH>300 pg/ml) were enrolled into the study. In each patient serum PTH, total testosterone (TT) and free testosterone (FT) concentrations were assessed before the first dose of cinacalcet and then after 3 and 6 months of treatment. The results are presented as means with 95% confidence interval. Results: In 33 patients who completed the study cinacalcet treatment caused significant decrease of serum PTH from 1143 pg/ml (828 - 1458 pg/ml) at the baseline, to 809 pg/ml (487 - 1132pg/ml) after 3 month of treatment (p = 0.002), and to 607 pg/ml (281 - 934pg/ml; p < 0.0001) after 6 months of treatment. Serum TT concentration also decreased from 4.95ng/ml (4.23 - 5.67 ng/ml) to 4.45 ng/ml (3.85 - 5.06ng/ml) and to 4.39 ng/ml (3.75 - 5.03ng/ml), respectively (p for trend = 0.009). Moreover, serum FT concentration decreased from 6.95 pg/ml (5.54 - 8.36pg/ml) to 5.98 pg/ml (5.00-6.94 pg/ml); p = 0.14 and to 5.60 pg/ml (4.63 - 6.57 pg/ml); p = 0.034, respectively (p for trend = 0.012). Conclusion: Treatment with cinacalcet decreases serum total and free testosterone concentration in male hemodialysed patients with chronic kidney disease and secondary hyperparathyroidism.

Endocrine Abnormalities in Patients with Chronic Kidney Disease

Abstract In patients with chronic kidney disease the alterations of the endocrine system may arise from several causes. The kidney is the site of degradation as well as synthesis of many different hormones. Moreover, a number of concomitant pathological conditions such as inflammation, metabolic acidosis and malnutrition may participate in the pathogenesis of endocrine abnormalities in this group of patients. The most pronounced endocrine abnormalities in patients with chronic kidney disease are the deficiencies of: calcitriol, testosterone, insulin-like growth factor and, erythropoietin (EPO). Additionally accumulation of several hormones, such as: prolactin, growth hormone and insulin frequently also occur. The clinical consequences of the abovementioned endocrine abnormalities are among others: anemia, infertility and bone diseases. Abstract Кај пациенти со хронична бубрежна бо- лест промените во ендокриниот систем можат да се јават од неколку причини. Бубрегот е мес- то на деградација, како и на синтеза на многу различни хормони. Покрај тоа, голем број прид- ружни патолошки состојби, како што се различ- ни воспаленија, метаболна ацидоза и неисхране- тост, може да учествуваат во патогенезата на ен- докрините абнормалности кај оваа група паци- енти. Најизразени ендокрини абнормалности кај пациентите со хронична бубрежна болест се не- достатоци на: калцитриол, тестостерон, фактор на раст сличен на инсулин и еритропоетин (ЕПО). Дополнителното акумулирање на неколку хормо- ни, како што се: пролактин, хормон за раст и инсулин, исто така, се случува доста често. Кли- ничките последици од гореспоменатите ендок- рини абнормалности, меѓу другите, се: анемија, неплодност и заболување на коските.

TREATMENT WITH CINACALCET INCREASES PLASMA ADIPONECTIN CONCENTRATION IN HEMODIALYZED PATIENTS WITH CHRONIC KIDNEY DISEASE AND SECONDARY HYPERPARATHYROIDISM

OBJECTIVE Cinacalcet increases calcium-sensing receptor (CaSR) sensitivity to serum calcium. CaSR is expressed by adipocytes, and adiponectin is an adipokine with antiatherogenic and insulin-sensitizing properties. The aim of this study was to assess the influence of a 3-month cinacalcet regimen on plasma adiponectin concentration in hemodialyzed patients (HDP) with chronic kidney disease (CKD) and secondary hyperparathyroidism (sHPT). METHODS Plasma adiponectin, advanced oxidation protein products (AOPP), serum interleukin-6 (IL-6) and C-reactive protein (CRP) concentrations were assessed in 65 HDP with sHPT treated with cinacalcet (30-120 mg/day) before the first dose and after 3 months of treatment. RESULTS There was a significant decrease in serum parathyroid hormone (PTH) concentration: from 1,089 (891-1,286) pg/mL to 775 (574-976) pg/mL after 3 months of treatment (P<.0001). The treatment was associated with a significant (P = .048) increase in plasma adiponectin concentration from 16.9 (14.4-19.5) μg/mL to 17.8 (15.0-20.6) μg/mL. Significant (P = .03) reduction of plasma AOPP concentration was observed from 186.7 (156.7-216.7) pg/mL to 162.6 (141.2-183.9) pg/mL. CONCLUSIONS A 3-month cinacalcet regimen increased plasma adiponectin concentrations in HDP with sHPT. Increased adiponectinemia in these patients may be related to reduced oxidative stress.

Treatment with cinacalcet decreases systolic blood pressure in haemodialysed patients with chronic kidney disease and secondary hyperparathyroidism

Background There are numerous evidences suggesting that parathyroid hormone (PTH) plays a role in the pathogenesis of arterial hypertension. Treatment with cinacalcet decreases serum PTH concentration in haemodialysed patients with chronic kidney disease (HDP) and secondary hyperparathyroidism (sHPT) Chronic kidney disease is a pro-inflammatory state. The aim of this study was therefore to assess the influence of 6-month treatment with cinacalcet on blood pressure (BP) and inflammation markers in HDP with sHPT. Material and methods In 58 HDP with sHPT serum PTH, interleukin-6, C-reactive protein, calcium and phosphate concentrations were assessed before the first dose of cinacalcet and after 3 and 6 months of treatment. BP was measured before haemodialysis sessions. Results Serum PTH concentration decreased significantly after 3 and 6 months of cinacalcet treatment from 1138 (931–1345) to 772 (551–992); p < 0.0001 and to 635 (430–839) pg/ml; p < 0.0001, respectively. Systolic BP decreased after 3 and 6 months of treatment from 128 (123–133), to 125 (120–131) and to 121 (115–127) mm Hg, respectively (p for trend = 0.014). Diastolic BP did not change significantly. There were no significant differences in the number of antihypertensive drugs, vitamin D analogues dose and patients’ body weight, nor the serum concentrations of IL-6 and CRP during the treatment period. Conclusions 1. Six-month treatment with cinacalcet decreases systolic BP in haemodialysed patients with chronic kidney disease and secondary hyperparathyroidism. 2. The elucidation of exact pathomechanism of such a BP decrease needs further clinical studies, but it seems not to be related to inflammatory status changes.