Carboxylated and intact osteocalcin predict adiponectin concentration in hemodialyzed patients.

Purpose Disrupted bone metabolism in patients with chronic kidney disease (CKD) is associated with elevated concentrations of biochemical bone markers. Recently, animal studies show the role of osteocalcin in energy metabolism, which is partially confirmed in humans. The aim of our study was to evaluate the relationships between serum concentrations of bone markers and indices of energy metabolism in CKD patients on maintenance hemodialysis; in particular, the relationship between various forms of osteocalcin and adiponectin. Patients and methods The cross-sectional study included 155 hemodialyzed stage 5 CKD patients. Serum concentrations of glucose, insulin, adiponectin, bone alkaline phosphatase (bALP), tartrate resistant acid phosphatase (TRAP), carboxylated (cOC), undercarboxylated (ucOC), and intact osteocalcin (OC) were determined. Results In total cohort, bALP, TRAP, cOC, and ucOC negatively correlated with BMI. All analyzed bone markers positively correlated with adiponectin in total cohort and in men. In multiple linear regression analysis including all patients, log(cOC) and log(intact OC) were the only bone markers that predicted log(adiponectin) (beta = 0.22; p = 0.016 and beta = 0.26; p = 0.010) independently of sex, dialysis vintage, CRP, insulin, iPTH concentrations, BMI, and age. Conclusions Our data confirm the positive association between cOC, intact OC, and adiponectin concentrations in CKD patients on maintenance hemodialysis.

Prevalence of the stages of chronic kidney disease (CKD) according to simplified MDRD formula in patients from ambulatory settings.

BACKGROUND: The staging system of chronic kidney disease (CKD) classification plays an important role in patients stratification according to disease activity. The aim of the study was to evaluate the frequency of appearance of consecutive stages of chronic kidney disease based on simplified MDRD formula in patients with diagnosed CKD. Additionally, relationship between eGFR values and selected biochemical parameters and comorbidities were analyzed. METHODS: The study was performed retrospectively in the group of 1176 patients (636 males and 540 females) aged between 17-98 years (mean 64.7) with creatinine level > 120 µmol/l and/or creatinine clearance < 90 ml/min/1.73 m2. RESULTS: The highest percentage of patients were designated to the 3rd CKD stage. There were positive correlations between eGFR and Hb, Ht, Fe, LDL-Ch, AspAT, HbA1c and negative correlations between eGFR and age, mean and systolic blood pressure, as well as with P, K, iPTH, and uric acid concentration. Patients with cardiovascular diseases had significaintly lower eGFR values as compare with patients without such complications, respectively: atrial fibrillation, arterial hypertension, chronic heart failure, ischaemic heart disease (p < 0.01), and myocardial infarction (p < 0.04). CONCLUSIONS: The highest percentage of patients with diagnosed CKD belong to the 3rd stage of disease. Patients with cardiovascular complications have significantly lower eGFR as compared with those without such disturbances.

[Evaluation of immunosuppressive treatment on homocystein levels in patients after kidney transplantation during a 2 year observation period]. / Ocena wplywu rodzaju stosowanego leczenia immunosupresyjnego na stezenia homocysteiny u pacjentów po przeszczepieniu nerki w trakcie dwurocznej obserwacji.

UNLABELLED: The aim of the study was to evaluate the influence of the type of prescribed immunosuppression: cyclosporine A (CsA) vs. tacrolimus (Tac) on remote homocystein levels in patients (pts) after kidney transplantation (Ktx). PATIENTS AND METHODS: The study included 51 pts (17 F, 34 M) aged 15 to 62 years (mean 38.1) after cadaver Ktx. The mean observation period equaled 21.2 months (6 -24); while total observation period was 90 personlyears. Before Ktx, 46 pts were treated with maintenance hemodialysis (HD), while 5 by peritoneal dialysis (PD). After Ktx, patients had immunosuppression prescribed according to the following schemes: prednisone (P) + CsA + azathioprine (AZA) - 12 pts; P + CsA + mycophenolate mofetil (MMF) -26 pts; P + Tac + MMF - 11 pts; and P + Tac + AZA - 2 pts. Hcy level was measured using high performance liquid chromatography (HPLC). Serum creatinine level was measured by standard method using the Hitachi 917 analyzer. Creatinine clearance was calculated based on the Cockcroft-Gault formula. Patient's blood was drawn before Ktx and 3, 6, 9, 12,15, 18, 21 and 24 months post procedure. RESULTS: Delayed graft function (DGF) after Ktx was diagnosed in 29 pts (56.9%) and this group required from 4 to 28 HD sessions (mean 14 sessions). Hcy level did not significantly differ between pts requiring (29 pts) and not requiring (22 pts) HD treatment after Ktx. It was also noted that the number of performed HD sessions did not significantly correlate with Hcy levels 24 months after Ktx (R =0.04, p=0.81). No relationship was found (non-parametric Spearman test) between the drop in Hcy level 3 months after Ktx as compare with value before Ktx and ischemia time (R=0.09, p=0.49), number of compatible HLA A and B (R=0.07, p=0.63), and DR antigens (R=0.09, p=0.51). Decrease in Hcy level (before Ktx and 24 months after Ktx) did not significantly correlate with the above parameters, respectively: R=-0.14, p=0.40; R=0.06, p=0.73; R=0.12, p=0.45; R=0.11, p=0.50. Decrease in Hcy level (before Ktx and 3 months after) did not differ significantly when compared to pts receiving immunosuppressive therapy CsA vs. Tac (p=0.18). Even though notable differences were observed in the drop in Hcy level (immunosuppressive treatment scheme CsA vs. Tac) in measurements before Ktx and 24 months post (respectively: 27% and 57.6%), no statistical significance was noted (p=0.13). Using the Mann-Whitneys' Test, no statistical significance was noted (p=0.13) when comparing differences in creatinine clearance between the group of pts receiving CsA and Tac 24 months after Ktx. Patients treated with Tac achieved a higher creatinine clearance by 16.5% when compared with those receiving CsA. No significant differences were observed between these two groups (p=0.65) when serum creatinine levels were evaluated. CONCLUSIONS: Incidence of DGF, as well as prescribed immunosuppressive therapy does not have an influence on remote Hey levels in pts after Ktx. Graft function seems to be the main predictor that influences Hcy levels after Ktx in this group of pts.

Carpal tunnel syndrome in hemodialysis patients as a dialysis-related amyloidosis manifestation--incidence, risk factors and results of surgical treatment.

BACKGROUND: Carpal tunnel syndrome (CTS) is the most common complication of dialysis-related amyloidosis (DRA) developing in patients on long-term dialysis therapy. The aim of this study was to evaluate the incidence of CTS and identify factors influencing the development of CTS in patients on maintenance hemodialysis, as well as results of its surgical treatment. MATERIAL/METHODS: The study included 386 patients, among whom CTS was diagnosed in 40 patients (10.4%) on the basis of signs and physical symptoms, as well as by nerve conduction. The group of patients with CTS and the group of patients without CTS were compared according to age (mean 54.50 vs. 56.48 years) and duration of dialysis treatment. Initial analysis of CTS incidence by sex, presence of anti-HCV antibodies, and location of arterio-venous fistula (AV fistula) was undertaken. RESULTS: Duration of dialysis treatment was the statistically significant risk factor for the development of CTS (16.05 vs. 4.51 years; p<0.0001). Among patients treated for a long period on hemodialysis (20-30 years), 100% required surgical release procedures, while 66.66% of those treated for 15-19 years, 42.1% of those treated for 10-14 years, and 1.6% of those treated for less than 10 years. CTS was diagnosed more often in anti-HCV-positive patients as compared with anti-HCV-negative patients (47.5 vs. 6.9%; p<0.0001). No significant differences were found when comparing CTS incidence by sex or between the development of CTS requiring surgical release intervention and location of the AV fistula. CONCLUSIONS: Surgical release procedure of the carpal tunnel gave good treatment results in patients with CTS.

Hemodialysis vascular access infection and mortality in maintenance hemodialysis patients.

UNLABELLED: Infectious complications associated with vascular access are a well known cause of increased morbidity and mortality in hemodialysis patients. The aim of the study was to evaluate the incidence of hemodialysis vascular access infections and patients survival in the group of maintenance hemodialysis patients during a one year observation period. The study group consisted of 213 patients (126 male, 87 female; aged 57.4 +/- 14.9 years being on renal replacement therapy for 54 months; range: 2 to 384 months) treated by maintenance hemodialysis at the Nephrology Department of the University Hospital. From the study group 181 patients (84.9%) had created arterio-venous fistulas (AVF); 28 (13.2%) permanent central venous catheters (CVC) implanted and 4 (1.9%) arterio-venous grafts (AVG). Vascular access infectious complications were monitored during a one year observation period. Infections of CVC were observed in 4 (14.3%) of the patients with CVC; 4 (2.2%) of patients with AVF and 2 (50%) of AVG. In the group of patients with signs of AVF infection the following pathogens were found: S. epidermidis 50%, S. aureus 25% and negative culture in 25%. The common pathogens in the group of patients with AVG were as follows: S. aureus and S. hemoliticus. Patients that had infections of implanted CVCin 75% were found to have Gram-positive bacteria (50% S. aureus, 25% S. coagulazo-negative), while 25% had Gram-negative infections (E. coli). In the analyzed period 30 deaths (14.1%) were noted; 23 (12.7%) in patients with AVF and 7 (25%) with CVC. Mortality due to cardio-vascular events in dialyzed patients using permanent catheters came to 43%; death due to catheter infections 14%. In the group of patients with AVF from 23 deaths 83% were of cardio-vascular origin, and 4% due to infections. No deaths were occurred during the observation period in the group of patients with AVG. One should note that only 4 patients with AVG during the study period were evaluated. CONCLUSIONS: 1. Types of vascular access has some influence on infectious complications and survival in the group of hemodialized patients. 2. High rate of CVC infections and associated increased mortality and better patients outcome with AVF, indicate that fistula should be constructed in all cases where it is possible.

[Types of hemodialysis vascular access in patients on renal replacement therapy and its complications during a one year observation period]. / Rodzaje dostepu naczyniowego do hemodializy u chorych leczonych nerkozastepczo i ich powiklania w okresie jednorocznej obserwacji.

UNLABELLED: The type of vascular access is an important determinant of complications in the dialysis population. The aim of the study was to evaluate types of hemodialysis vascular access at hemodialysis start, in the course of treatment and complications during a one year observation period. The study group consisted of 213 patients [126 (59%) males; 87 (41%) females] treated for 54 months (range from 2 to 384 months) by maintenance hemodialysis at the Nephrology Department of the University Hospital. Mean age of the patients equaled 57.4 years and ranged from 21 to 91 years. The observation period began on June 1st, 2009 and finished on May 31st, 2010. At the start of the dialysis therapy - 99 (46.5%) patients had arterio-venous fistula (AVF), 81 (38.0%) temporary catheters (TC), and 33 (15.5%) permanent catheters (PC). At the beginning of the one-year observation period, 161 (75.6%) of the patients were treated using an AVF, 37 (17.4%) using a CP, 11 (5.1%) CT, and 4 (1.9%) using an artificial graft (AVG). At the end of the one year observation period - 179 (84%) patients were dialyzed using AVF, while 30 (14.1%) patients on PC, and 4 (1.9%) using a AVG. Statistically significant differences in possessing AVF were noted between start of renal replacement therapy and the start and finish of the one year observation period (p < 0.0001), as well as beginning and finish of the observation period (p < 0.002). During the observation period - 37 (20.7%) patients with an AVF required intervention due to complications associated with vascular access; where 4 from 11 (36.4%) patients in this group had AVF located on the arm and 33 from 150 (22.0%) on the forearm. The most common complications associated with AVF were thrombosis (23 = 14.3%), narrowing of the fistula (9 = 5.6%), too high output flow (HOF) 2 = 1.2% and the steal syndrome (SS) 3 (1.9%). Infectious complications were noted in 4 from 37 patients with PC (10.8%), and significantly less with AVF-4 from 161 (2.5%) (p < 0.0001). AVG infection occurred in 2 (50%) individuals of this group. CONCLUSIONS: AVF created using patients' own vessels of the forearm is characterized with decreased risk of complications in comparison to fistulas made of artificial materials or permanent catheters. However, fistula thrombosis of the AVF is still the most common complication requiring surgical intervention.

Dual, time-dependent deleterious and protective effect of anandamide on the course of cerulein-induced acute pancreatitis. Role of sensory nerves.

Some recent studies indicate that cannabis may induce acute pancreatitis in humans and administration of anandamide increases the severity of acute pancreatitis; whereas another study exhibits some therapeutic effects in acute pancreatitis. Aim of the present study was to discover what is the reason for these opposite confusing results and to determine the role of sensory nerves in this effect. Acute pancreatitis was induced in rats by cerulein. Anandamide, an endogenous cannabinoid, was administered i.p. (1.5 micromol/kg) before or 2 h after cerulein administration. Stimulation of sensory nerves was performed by capsaicin (0.5 mg/kg s.c.). In rats treated with combination of anandamide plus capsaicin, capsaicin was given 10 min after each dose of anandamide. After the last injection of cerulein or 4 h later, the study was terminated. In our study we observed that stimulation of sensory nerves by capsaicin, before administration of cerulein, reduced the severity of acute pancreatitis. Anandamide, administered alone before cerulein, increased pancreatic damage in acute pancreatitis. Anandamide administered in combination with capsaicin, before cerulein, abolished the capsaicin-induced protective effect on the pancreas. Opposite effects were observed when capsaicin and anandamide were administered after injection of cerulein. Capsaicin increased the severity of acute pancreatitis, whereas anandamide reduced pancreatic damage and reversed the deleterious effect of capsaicin. We conclude that the effect of anandamide on the severity of acute pancreatitis depends on the phase of this disease. Administration of anandamide, before induction of pancreatitis, aggravates pancreatic damage; whereas anandamide administered after induction of pancreatitis, reduces the severity of acute pancreatitis. Sensory nerves are involved in the mechanism of this biphasic effect of anandamide.

Hepatitis C virus infection in dialysis patients.

Hepatitis C virus (HCV) infection is a global health problem, common worldwide, leading to acute and chronic hepatitis and its consequences of hepatocirrhosis and hepatocellular carcinoma. Patients on hemodialysis belong to the high-risk group of HCV infection. The prevalence of HCV infection in dialysis patients ranges from 4% to more than 70% in some countries. The main reasons for such a high incidence of infections are a high prevalence of HCV infection in the general population, lack of standard infection precautions and effective vaccination, inadequate disinfection procedures of dialysis machines and other medical equipment, as well as spread of infection from patient to patient, especially in dialytic centers with a high percentage of infected patients. The diagnostic procedures useful in the evaluation of HCV infection are detection of anti-HCV antibodies, identification of HCV RNA, counts of virus copies, and identification of its genome. From the 6 major genotypes and multiple subtypes of the HCV, genotypes 1a and 1b are the most common in Europe and Japan, and 1b is responsible for more severe liver disease and aggressive course leading to liver fibrosis. Antiviral therapy of HCV+ dialysis patients with interferon-alpha (INF-alpha) gives slightly better results than in the general population, but is poorly tolerated and associated with side effects. Although ribavirin in not recommended for dialysis patients, the addition of small doses of this compound to pegylated INF is discussed, especially for patients in whom previous infection treatment failed.

The influence of sodium profiling on blood volume and intradialytic hypotension in patients on maintenance hemodialysis.

An accurate evaluation of water content in the body of hemodialyzed patients seems to be an important problem in chronic dialysotherapy. Acute intradialytic hypotension observed in 20-33% of hemodialysis patients is a very common complication of this kind of renal replacement therapy. The study was performed in 40 uremic patients, treated with hemodialysis at the Nephrology Clinic of the University Hospital in Cracow. In every patient, 3 model dialysis sessions were carried out. Total fluid removal was the same during every hemodialysis. The first model hemodialysis (HD1) was performed with constant dialysate sodium concentration (140 mmol/L), the second (HD2) with linear and the third (HD3) with expotential decrease of dialysate sodium concentration (from 144 to 136 mmol/L). Every hemodialysis was also monitored continuously with Crit-Line 2 R system (In-Line Diagnostics, Riverdale, UT). Before and after the first model hemodialysis (HD1), ultrasound examination of abdominal cavity was performed. The measurement of inferior vena cava diameter (mm), circumference (mm), area (mm2), at hepatic veins orifice-level, on expiration was performed. The fluid removal during the first model hemodialysis resulted in significant reduction of the vena cava inferior diameter, circumference and area, measured with ultrasound on expiration. The statistically significant lower fall of blood volume after the first and second hour of the second model hemodialysis session (HD2) was observed when compared to the first hemodialysis (HD1) - p<0.05 was observed. The statistically significant lower frequency of hypotension during the second hemo-dialysis session (HD2) as compared to HD1 (chi2=5.25 p<0.05). Differences among HD1 and HD3 and HD2 and HD3 did not reach statistical significance. The monitoring of hemodialysis with the Crit-Line instrument permits for optimalization of dry weight of dialyzed patients and allows reaching higher ultrafiltration rates during dialysis without hypotensive episodes. The changes in the blood volume, approximately 5% per one hour of dialysis session are an optimal value for these patients.

Osteoprotegerin as a marker of cardiovascular risk in patients on peritoneal dialysis.

INTRODUCTION: Arterial thickening contributes to elevated cardiovascular risk in patients on maintenance renal replacement therapy. The common carotid artery intima-media thickness (CCA-IMT) is an early atherosclerotic marker and may be used to assess the stratification of atherosclerotic advancement and resultant arterial calcification. OBJECTIVES: The aim of the study was to evaluate the associations between atherosclerotic changes in the common carotid arteries expressed as the CCA-IMT and the body mass index (BMI), serum lipid levels, C­reactive protein (CRP), and selected bone metabolism parameters including phosphorus, calcium, intact parathormone (iPTH), alkaline phosphatase, osteopontin, osteoprotegerin, osteocalcin, fetuin A, and fibroblast growth factor­23 (FGF­23) in patients treated with peritoneal dialysis. PATIENTS AND METHODS: The study included 67 patients with chronic kidney disease (36 men and 31 women) aged 53 ±13 years (range, 19-75 years) treated with peritoneal dialysis for 30 ±24 months. The CCA­IMT was assessed by ultrasonography using Acuson 128/10 XP. The BMI was calculated using the Quetelet formula. Serum lipid levels, phosphorus, calcium, iPTH, alkaline phosphatase, and CRP were measured using standard laboratory methods, while fetuin A, osteocalcin, osteoprotegerin, osteopontin, and FGF­23 using commercial enzyme­linked immunosorbent assay kits. RESULTS: Positive correlations were observed between CCA-IMT and age (r = 0.54, P <0.0001), BMI (r = 0.39, P = 0.003), and osteoprotegerin (r = 0.38, P = 0.004). In a multiple regression analysis, age (r = 0.41, P = 0.01), osteocalcin (r = 0.34, P = 0.04), and log­transformed osteoprotegerin values (r = 0.38, P = 0.02) remained independently associated with the CCA-IMT. The highest CCA­IMT values (0.85 ±0.21) were observed in patients with osteoprotegerin concentrations in the upper tertile. Osteoprotegerin concentrations strongly and positively correlated with the duration of dialysis treatment (r = 0.55, P <0.0001). CONCLUSIONS: The CCA­IMT has been shown to be a reliable noninvasive measure of subclinical atherosclerosis and, therefore, of associated increased vascular risk. Elevated serum osteoprotegerin levels may be useful as a prognostic marker of cardiovascular risk in dialyzed patients.