Safety and efficiency of treatment with cinacalcet of haemodialysed patients with chronic kidney disease and secondary hyperparathyroidism

Introduction: Secondary hyperparathyroidism (sHPT) is a common disorder in haemodialysed patients with chronic kidney disease (CKD). Cinacalcet increases the sensitivity of calcium receptor to the serum calcium, thus reducing serum parathormone (PTH) concentration. The aim of this study was to assess the safety and efficacy of six-month treatment with cinacalcet in haemodialysed CKD patients with sHPT in upper Silesia. Material and methods: 71 haemodialysed CKD patients with sHPT (PTH > 300 pg/mL) were enrolled in this study. The target was to decrease PTH concentration below 300 pg/mL. PTH (ECL; Roche, Mannheim, Germany), calcium and phosphate concentration was assessed before the first dose of cinacalcet and then after three and six months of treatment, before haemodialysis session. The results are shown as means and 95% confidence index. Results: 58 patients completed the study. There was a significant decrease in serum PTH concentration from 1,138 pg/mL (931&#8211;1,345 pg/mL) to 772 pg/mL (551&#8211;992 pg/mL) after three months of treatment (p < 0.0001) and to 635 pg/mL (430-839 pg/mL; p < 0.0001) after six months. The target PTH concentration was reached in 25% of the patients after three months and in 45% after six months of treatment. Cinacalcet was ineffective in decreasing serum PTH in 16 (28%) patients. There were no significant differences in serum calcium and phosphate concentration during the observation period. Conclusions: 1. Cinacalcet decreases serum PTH concentration in most haemodialysed CKD patients with sHPT. 2. In 28% of patients, resistance to treatment with cinacalcet was observed. 3. Cinacalcet treatment was well tolerated and caused only a few side effects. (Endokrynol Pol 2013; 64 (2): 176&#8211;181)Wstęp: U hemodializowanych chorych na przewlekłą chorobą nerek (PChN) często występuje wtórna nadczynność przytarczyc. Cynakalcet zwiększa wrażliwość receptora wapniowego na wapń w surowicy krwi i powoduje obniżenie stężenia parathormonu (PTH) w surowicy. Celem badania była ocena bezpieczeństwa i skuteczności sześciomiesięcznego leczenia preparatem cynakalcet hemodializowanych chorych na PChN z sHPT w województwie śląskim. Materiał i metody: Badaniem objęto 71 hemodializowanych chorych na PChN z sHPT. Celem leczenia było zmniejszenie stężenia PTH w surowicy do wartości poniżej 300 pg/ml. U wszystkich chorych na początku badania, jak również po 3 i 6 miesiącach oznaczono stężenia PTH (ECL; Roche, Mannheim, Niemcy), wapnia i fosforanów w surowicy przed zabiegiem hemodializy. Wyniki przedstawiono jako średnie i 95% przedział ufności. Wyniki: Badanie ukończyło 58 osób. Leczenie cynakalcetem doprowadziło do znamiennego obniżenia stężenia PTH z 1138 pg/ml (931&#8211;1345 pg/ml) na początku badania do 772 pg/ml (551&#8211;992 pg/ml) po 3 miesiącach leczenia (p < 0, 0001), a po 6 miesiącach do 635 pg/ml (430&#8211;839 pg/ml; p < 0, 0001). Docelowe stężenie PTH w surowicy osiągnięto u 25% chorych po 3 miesiącach leczenia i u 45% chorych po 6 miesiącach leczenia. U 16 (28%) chorych leczenie cynakalcetem nie spowodowało zmniejszenia stężenia PTH w surowicy. Podczas leczenia preparatem cynakalcet nie obserwowano znamiennych zmian stężenia wapnia i fosforanów w surowicy. Wnioski: 1. Cynakalcet obniża stężenie PTH w surowicy u większości hemodializowanych chorych na PChN z wtórną nadczynnością przytarczyc. 2. U 28% chorych obserwuje się oporność na leczenie preparatem cynakalcet. 3. Leczenie preparatem cynakalcet było u większości chorych dobrze tolerowane i powodowało niewiele działań niepożądanych. (Endokrynol Pol 2013; 64 (2): 176&#8211;181

Multiorders in amenable group actions

The paper offers a thorough study of multiorders and their applications to measure-preserving actions of countable amenable groups. By a~{\em multiorder} on a~countable group we mean any probability measure $\nu$ on the collection $\tilde{\mathcal{O}}$ of linear orders of type $\mathbb Z$ on $G$, invariant under the natural action of $G$ on such orders. Every free measure-preserving $G$-action $(X,\mu,G)$ has a~multiorder $(\tilde{\mathcal{O}},\nu,G)$ as a factor and has the same orbits as the $\mathbb Z$-action $(X,\mu,S)$, where $S$ is the \emph{successor map} determined by the multiorder factor. Moreover, the sub-sigma-algebra $\Sigma_{\tilde{\mathcal{O}}}$ associated with the multiorder factor is invariant under $S$, which makes the corresponding $\mathbb Z$-action $(\tilde{\mathcal{O}},\nu,\tilde S)$ a factor of $(X,\mu,S)$. We prove that the entropy of any $G$-process generated by a finite partition of $X$, conditional with respect to $\Sigma_{\tilde{\mathcal{O}}}$, is preserved by the orbit equivalence with $(X,\mu,S)$. Furthermore, this entropy can be computed in terms of the so-called random past, by a formula analogous to $h(\mu,T,\mathcal P)=H(\mu,\mathcal P|\mathcal{P}^-)$ known for $\mathbb Z$-actions. The above fact is then applied to prove a variant of a result by Rudolph and Weiss. The original theorem states that orbit equivalence between free actions of countable amenable groups preserves conditional entropy with respect to a~sub-sigma-algebra $\Sigma$, as soon as the ``orbit change'' is measurable with respect to $\Sigma$. In our variant, we replace the measurability assumption by a~simpler one: $\Sigma$ should be invariant under both actions and the actions on the resulting factor should be free. In conclusion we provide a characterization of the Pinsker sigma-algebra of any $G$-process in terms of an appropriately defined remote past arising from a multiorder.Comment: 36 pages, 2 figures, Changes: slightly changed formulation and proof of Theorem 7.4, some remarks adde

Serum testosterone concentrations in male patients with end-stage kidney disease treated with haemodialysis

Introduction: Testosterone deficiency is frequently found in male patients with chronic kidney disease (CKD) and may participate in the pathogenesis of osteoporosis, sarcopaenia, anaemia, impotence, infertility, and other comorbidities observed in these patients. The aim of the study was the evaluation of the frequency of testosterone deficiency in male patients with CKD on maintenance haemodialysis (HD). Material and methods: In 79 male HD patients, serum total (TT), free (FT) testosterone, C-reactive protein (CRP), and interleukin 6 (IL-6) serum concentrations were assessed before an HD procedure. Patients were divided into three subgroups based on age categories: 19-39 years (18 patients), 40–59 years (34 patients), and ≥ 60 years (27 patients). TT insufficiency and deficiency were diagnosed when the serum TT concentration was below 4.0 ng/mL and 2.9 ng/mL, respectively. FT deficiency was diagnosed in patients with serum FT concentration below 8.9, 6.6, and 4.9 pg/mL in the abovementioned age subgroups, respectively. Results: In the abovementioned age subgroups the serum TT concentration was 5.9 (4.6–7.1), 4.8 (3.9–5.4), and 4.6 (3.9–5.3) ng/mL, respectively. The serum FT concentration was 7.9 (5.2–10.1), 6.1 (5.1–7.2), and 6.0 (5.0–7.1) pg/mL, respectively. In the whole group TT insufficiency was found in 40%, TT deficiency in 15% of patients, and FT deficiency in 50% of patients. Significant negative correlations were found between both serum TT and FT concentrations and age (r = –0.23, p = 0.05 and r = –0.27, p = 0.02, respectively). Additionally, negative correlations were found between both serum TT and FT and IL-6 concentrations (r = –0.43, p &lt; 0.05 and r = –0.29, p &lt; 0.05), respectively. Conclusions: 1. Testosterone deficiency is common in male patients with chronic kidney disease treated with HD. 2. In HD patients the serum testosterone concentration decreases with age. 3. Chronic inflammation may participate in the pathogenesis of testosterone deficiency in haemodialysis patients.

Wielowymiarowa analiza porównawcza korupcji w Europie w latach 2001–2011

The article presents the results of a multidimensional comparative analysis carried out on 29 European countries. The analysis aims at grouping these countries according to features including the level of Corruption Perception Index, time required to start a business, paid taxes, inflow of foreign direct investments, level of KOF Index of Globalization, PKB per capita and the level of Human Development Index. The analysis of time series of mentioned-above indicators in years 2001–2011 was used also in the article.Artykuł prezentuje wyniki wielowymiarowej analizy porównawczej przeprowadzonej na 29 krajach europejskich. Ma ona na celu pogrupować owe państwa z uwzględnieniem takich cech jak poziom wskaźnika postrzegania korupcji, czas potrzebny do rozpoczęcia biznesu, skala płaconych podatków, wielkość napływu bezpośrednich inwestycji zagranicznych, poziom indeksu globalizacji KOF, wielkość PKB per capita oraz poziom indeksu rozwoju ludzkiego. W niniejszej pracy posłużono się także analizą szeregów czasowych wskazanych wyżej wskaźników w okresie 2001–2011.

Stężenia parathormonu w surowicy oznaczane metodą chemiluminescencji i elektrochemiluminescencji — czy wyniki są porównywalne u hemodializowanych chorych na przewlekłą chorobę nerek?

  Introduction: Secondary hyperparathyroidism (sHPT) is one of the most common abnormalities found in patients with chronic kidney disease (CKD). Measurement of serum PTH concentrations is crucial in diagnosis and treatment of sHPT. Different methods of serum PTH measurement may provide diverse results. This may have a significant impact on the therapeutic approach if under- or over-diagnosis of sHPT occurs. The aim of this study was to compare the results of serum PTH concentrations measured with two commonly used methods — chemiluminescence (CHL) and electrochemiluminescence (ECL). Material and methods: Seventy-seven haemodialysis patients with CKD were enrolled into the study. Blood samples were collected before haemodialysis, in the middle of the week. In all patients, serum PTH concentrations were measured using two methods: CHL and ECL. Results: Serum PTH concentration measured with CHL was significantly higher than that assessed with ECL: 455 pg/mL (352–559) pg/mL vs. 383 pg/mL (243–523) pg/mL; p &lt; 0.0001. Six patients from the studied cohort were treated with cinacalcet. In these patients, the serum PTH concentration was also significantly higher when measured with CHL than with ECL: 755 pg/mL (294–1216) pg/mL and 607 pg/mL (199–1015 pg/mL); p = 0.027, respectively). In three cases serum PTH concentration assessed with CHL method exceeded 300 pg/mL, whereas when measured with ECL it was below 300 pg/mL. Lower serum PTH concentrations could give the rationale to lower cinacalcet dose or to stop such treatment. Conclusions: 1. Serum PTH concentrations in haemodialysis patients with CKD measured by CHL and ECL methods differ significantly. 2. The choice of method for measurement of serum PTH concentration in these patients may have important clinical implications. (Endokrynol Pol 2015; 66 (3): 219–223)    Wstęp: Wtórna nadczynność przytarczyc jest jednym z najczęstszych następstw przewlekłej choroby nerek (CKD). Pomiar stężenia PTH w surowicy jest niezbędny dla prawidłowego diagnozowania i leczenia wtórnej nadczynności przytarczyc. Poszczególne metody oznaczania stężenia PTH w surowicy mogą dawać zróżnicowane wyniki, co może mieć istotny wpływ na decyzje terapeutyczne, jak zbyt szybkie lub zbyt późne rozpoznanie choroby. Celem pracy było porównanie stężeń PTH w surowicy oznaczanych przy pomocy dwóch powszechnie wykorzystywanych metod — chemiluminescencji (CHL) i elektrochemiluminescencji (ECL). Materiał i metody: Badaniem objęto 77 hemodializowanych chorych z CKD. Krew do badań pobierano przed zabiegiem hemodializy, w środku tygodnia. Stężenie PTH w surowicy oznaczono w tej samej próbce metodą CHL i ECL. Wyniki: Stężenia PTH w surowicy oznaczane przy użyciu CHL były znamiennie wyższe niż, uzyskane przy pomocy ECL: 455 pg/ml (352–559) pg/ml wobec 383 (243–523) pg/ml; p &lt; 0,0001. Sześciu chorych leczono cynakalcetem. U tych chorych stężenia PTH w surowicy oznaczane przy użyciu CHL były także znamiennie wyższe, niż oznaczane metodą ECL: 755 pg/ml (294–1216) pg/ml i 607 pg/ml (199–1015 pg/ml); p = 0,027. U trzech z tych sześciu chorych stężenie PTH w surowicy oznaczane metodą CHL przekraczało 300 pg/ml, podczas gdy oznaczane metodą ECL było niższe niż 300 pg/ml. Niższe stężenie PTH w surowicy mogłoby być podstawą do podjęcia decyzji o obniżeniu dawki lub zaprzestaniu leczenia cynakalcetem. Wnioski: 1. Stężenia PTH w surowicy u hemodializowanych chorych na CKD oznaczane przy pomocy metody CHL lub ECL różnią się znamiennie. 2. Wybór metody oznaczenia stężenia PTH w surowicy u hemodializowanych chorych z CKD może mieć istotne implikacje kliniczne. (Endokrynol Pol 2015; 66 (3): 219–223)

Experimental model for acute kidney injury caused by uropathogenic Escherichia coli

Introduction: Acute kidney injury (AKI) is the rapid deterioration of renal function, diagnosed on the basis of an increase in serum creatinine and abnormal urinary parameters. AKI is associated with increased risk of mortality or chronic kidney disease (CKD).The aim of the study was to develop an experimental model for AKI resulting from Escherichia coli-induced pyelonephritis. E. coli was isolated from a patient with clinical symptoms of urinary tract infection (UTI).Material/Methods: The study included three groups of female Wistar rats (groups 1, 2 and 3), in which pyelonephritis was induced by transurethral inoculation with highly virulent E. coli (105, 107 and 109 cfu/ml, respectively). Urine and blood samples for analysis were obtained prior to the inoculation (day 0), as well as 7, 14 and 21 days thereafter.Results: Aside from a microbiological examination of urine samples, daily urine output, serum creatinine (CreaS), creatinine clearance (CrCl), interleukin 6 (IL-6), fractional excretion of sodium (FENa) and fractional excretion of urea (FEUrea) were determined. A histopathological examination of kidney and urinary bladder specimens was conducted as well. While UTI-related pyelonephritis developed irrespective of E. coli inoculum size, AKI was observed only following transurethral administration of E. coli at the intermediate and high dose, i.e. 107 and 109 cfu/ml, respectively (group 2 and 3). Discussion: An increase in CreaS and abnormal diuresis were accompanied by changes in parameters specific for various forms of AKI, i.e. FENa and FEUrea. Based on these changes, administration of E. coli at 107 cfu/ml was demonstrated to induce renal AKI, whereas inoculation with 109 cfu/ml seemed to cause not only ascending pyelonephritis, but perhaps also bacteremia and urosepsis (prerenal component of AKI)

Virulence factors of Enterococcus strains isolated from patients with inflammatory bowel disease

AIM: To determine the features of Enterococcus that contribute to the development and maintenance of the inflammatory process in patients with inflammatory bowel disease (IBD). METHODS: Multiplex polymerase chain reaction (PCR) was applied to assess the presence of genes that encode virulence factors [surface aggregating protein (asa1), gelatinase (gelE), cytolysin (cylA), extracellular surface protein (esp) and hyaluronidase (hyl)] in the genomic DNA of 28 strains of Enterococcus isolated from the intestinal tissues of children with IBD (n = 16) and of children without IBD (controls; n = 12). Additionally, strains with confirmed presence of the gelE gene were tested by PCR for the presence of quorum sensing genes (fsrA, fsrB, fsrC) that control the gelatinase production. Gelatinase activity was tested on agar plates containing 1.6% gelatin. We also analysed the ability of Enterococcus strains to release and decompose hydrogen peroxide (using Analytical Merckoquant peroxide test strips) and tested their ability to adhere to Caco-2 human gut epithelium cells and form biofilms in vitro. RESULTS: A comparison of the genomes of Enterococcus strains isolated from the inflamed mucosa of patients with IBD with those of the control group showed statistically significant differences in the frequency of the asa1 gene and the gelE gene. Furthermore, the cumulative occurrence of different virulence genes in the genome of a single strain of Enterococcus isolated from the IBD patient group is greater than in a strain from the control group, although no significant difference was found. Statistically significant differences in the decomposition of hydrogen peroxide and adherence to the Caco-2 epithelial cell line between the strains from the patient group and control group were demonstrated. The results also showed that profuse biofilm production was more frequent among Enterococcus strains isolated from children with IBD than in control strains. CONCLUSION: Enterococcus strains that adhere strongly to the intestinal epithelium, form biofilms and possess antioxidant defence mechanisms seem to have the greatest influence on the inflammatory process

Central blood pressure and nighttime blood pressure in patients with non-diabetic chronic kidney disease

Introduction. Arterial hypertension is a well-known risk factor of both cardiovascular complications and faster progression of chronic kidney disease (CKD). There is growing evidence that central blood pressure (BP) and nighttime BP may have an advantage in predicting the risk of cardiovascular complications and the progression of CKD in comparison with the traditional office BP measurements. The aim of this study was to evaluate the central BP and nighttime BP in non-diabetic CKD patients with no, or only mild proteinuria i.e. autosomal dominant polycystic kidney disease (ADPKD) or IgA nephropathy (IgAN). Material and methods. Forty patients with CKD stage 3 or 4 were enrolled into the study. In each patient the measurement of peripheral and central BP was conducted, as well as the assessment of pulse wave velocity (PWV) and the 24-hour blood pressure monitoring (ABPM). Results. Despite the lower office and central BP values in patients with IgAN in comparison to patients with ADPKD, both studied groups did not differ in the mean BP in the 24-hour ABPM. In the entire studied group a significant positive correlation was found between the augmentation pressure and age, as well as between the augmentation index - AIx% and age. Moreover, a significant positive correlation between the decrease of nighttime BP and eGFR was observed. Additionally, a significant positive correlation between PWV and age was found. Conclusions. 1. Patients with ADPKD and IgAN, despite the differences in office and central BP do not differ in respect of the mean BP in the 24-hour ABPM. 2. In both groups of patients vascular stiffness increases with age and deteriorating kidney function. 3. Lower decrease of nighttime blood pressure is related to the worse kidney function in patients with non-diabetic CKD.