[Adverse effects of long-term proton-pump inhibitor therapy on adults]. / A hosszú távú protonpumpagátló kezelés következményei felnotteken.

In the last few decades, proton-pump inhibitors have become the mainstay of the treatment of acid-related disorders. Despite their efficacy, these drugs are not without risks. Recently several articles have been published on their long-term adverse effects. Among these adverse effects, the higher risk of bone fractures, the vitamin B12 and magnesium deficiencies and the higher risk of Clostridium difficile infection may be relevant. As these drugs are prescribed more and more frequently all over the world, the knowledge of the long-term adverse effects is very important not only for the specialists but for the general practitioners as well. In this review, the authors discuss the recent findings in this field, emphasising that the long-term use of these drugs must be based on an adequate and strong indication. Orv Hetil. 2018; 159(19): 735-740.

Burden of Clostridium difficile infection between 2010 and 2013: Trends and outcomes from an academic center in Eastern Europe.

AIM: To analyze the incidence and possible risk factors in hospitalized patients treated with Clostridium difficile infection (CDI). METHODS: A total of 11751 patients were admitted to our clinic between 1 January 2010 and 1 May 2013. Two hundred and forty-seven inpatients were prospectively diagnosed with CDI. For the risk analysis a 1:3 matching was used. Data of 732 patients matched for age, sex, and inpatient care period and unit were compared to those of the CDI population. Inpatient records were collected from an electronic hospital database and comprehensively reviewed. RESULTS: Incidence of CDI was 21.0/1000 admissions (2.1% of all-cause hospitalizations and 4.45% of total inpatient days). The incidence of severe CDI was 12.6% (2.63/1000 of all-cause hospitalizations). Distribution of CDI cases was different according to the unit type, with highest incidence rates in hematology, gastroenterology and nephrology units (32.9, 25 and 24.6/1000 admissions, respectively) and lowest rates in 1.4% (33/2312) in endocrinology and general internal medicine (14.2 and 16.9/1000 admissions) units. Recurrence of CDI was 11.3% within 12 wk after discharge. Duration of hospital stay was longer in patients with CDI compared to controls (17.6 ± 10.8 d vs 12.4 ± 7.71 d). CDI accounted for 6.3% of all-inpatient deaths, and 30-d mortality rate was 21.9% (54/247 cases). Risk factors for CDI were antibiotic therapy [including third-generation cephalosporins or fluoroquinolones, odds ratio (OR) = 4.559; P < 0.001], use of proton pump inhibitors (OR = 2.082, P < 0.001), previous hospitalization within 12 mo (OR = 3.167, P < 0.001), previous CDI (OR = 15.32; P < 0.001), while presence of diabetes mellitus was associated with a decreased risk for CDI (OR = 0.484; P < 0.001). Treatment of recurrent cases was significantly different from primary infections with more frequent use of vancomycin alone or in combination (P < 0.001), and antibiotic therapy duration was longer (P < 0.02). Severity, mortality and outcome of primary infections and relapsing cases did not significantly differ. CONCLUSION: CDI was accounted for significant burden with longer hospitalization and adverse outcomes. Antibiotic, PPI therapy and previous hospitalization or CDI were risk factors for CDI.

Influence of local exposure to static magnetic field on pain perception and bone turnover of osteoporotic patients with vertebral deformity - a randomized controlled trial.

PURPOSE: Static magnetic field (SMF) could improve pain sensation and bone turnover. In a single-center randomized double-blind placebo-controlled study we investigated the effects of SMF exposure on subjective pain and bone turnover. MATERIALS AND METHODS: Postmenopausal osteoporotic women (aged 50-70 years) with bone deformity and back pain were randomized to 10 weekly visits of 30-min SMF (n = 6) or treatment with non-magnetized pads (n = 5) on the back. Primary and secondary outcomes were changes in pain sensation on a visual analogue scale (VAS) during each visit and over 10 weeks, respectively. Tertiary outcomes were changes in osteocalcin and ß-crosslaps. SMF was inhomogeneous with 192 millitesla peak-to-peak value by 19 tesla/meter gradient of the magnetic flux density at 3 mm. RESULTS: Participants randomized to sham had higher VAS at baseline (mean difference: 2.8, 95% confidence interval (CI) 0.47-5.2 cm). Both SMF and sham similarly reduced short term pain (sham-SMF: 0.59, 95% CI - 0.31-1.49 cm, p = 0.195). VAS did not change in SMF, while it decreased in the sham group (between-group difference 0.27, 95% CI 0.04-0.50 cm/visit). Bone turnover markers remained stable. CONCLUSIONS: SMF as used in this investigation is not recommended for pain relief in postmenopausal women with vertebral deformity. The finding on long-term pain relief may relate to unbalanced randomization.

Is current smoking still an important environmental factor in inflammatory bowel diseases? Results from a population-based incident cohort.

BACKGROUND: Previous studies suggest that smoking is an important environmental factor in inflammatory bowel diseases (IBDs), with dichotomous effects in ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study was to analyze the relationship between smoking and IBD risk in a population-based database from Veszprem Province, which included incident cases diagnosed between January 1, 1977, and December 31, 2008. METHODS: Data from 1420 incident patients were analyzed (UC: 914, age at diagnosis: 38.9 years; CD: 506, age at diagnosis: 31.5 years). Both inpatient and outpatient records were collected and comprehensively reviewed. Overall, smoking frequency in the adult general population was 36.1%. RESULTS: Of patients with CD, 47.2% were current smokers at diagnosis. Smoking was more frequent in male patients (P = 0.002) and was associated with an increased risk of CD (odds ratio, 1.96; 95% confidence interval, 1.63-2.37; P < 0.001). In contrast, current smoking was protective against UC (odds ratio, 0.33; 95% confidence interval, 0.27-0.41). The effect of smoking was linked to gender (in CD, more deleterious in male patients) and age at diagnosis and was most prominent in young adults, with a difference already being seen in 18- to 19-year-olds. In CD, a change in disease behavior (P = 0.02), location from ileal or colonic to ileocolonic (P = 0.003), arthritis/arthropathy (P = 0.002), need for steroids (P = 0.06), or AZA (P = 0.038) was more common in current smokers. Smoking in UC was associated with more extensive disease (P = 0.01) and a tendency for decreased need for colectomy (P = 0.06). CONCLUSIONS: Current smoking was associated with the risk of IBD. This effect was linked to gender and age at diagnosis and was most prominent in young adults. No association was observed in pediatric or elderly patients. The deleterious and protective effects of smoking on the course in CD and UC were partially confirmed.

The risk of lymphoma and immunomodulators in patients with inflammatory bowel diseases: results from a population-based cohort in Eastern Europe.

BACKGROUND AND AIMS: Prior studies suggest a small but significantly increased risk of lymphoma in adults with inflammatory bowel disease (IBD), especially in patients treated with thiopurines. No data was available from Eastern Europe. The aim of this study was to analyze the incidence of lymphomas as related to drug exposure, in a population-based Veszprem province database, which included incident cases diagnosed between January 1, 1977 and December 31, 2008. METHODS: Data from 1420 incident patients were analyzed (UC: 914, age at diagnosis: 36.5 years; CD: 506, age at diagnosis: 28.5.5 years). Both in- and outpatient records were collected and comprehensively reviewed. The rate of lymphoma was calculated as patient-years of exposure per medication class, of medications utilized in IBD. RESULTS: Of the 1420 patients, we identified three patients who developed lymphoma (one CLL, two low-grade B-cell NHL including one rectal case), during 19,293 patient-years of follow-up (median follow-up: 13 years). All three patients were male. None had received azathioprine or biologicals. The absolute incidence rate of lymphoma was 1.55 per 10,000 patient-years, with 3 cases observed vs. 2.18 expected, with a standardized incidence ratio (SIR) of 1.37 (95% confidence interval [CI]: 0.44-4.26). No cases have been exposed to either azathioprine or biologicals. CONCLUSIONS: The overall risk of lymphoma in IBD was not increased; only three cases were seen in this population-based incident cohort over a 30-year period. An association with thiopurine exposure was not found.

[The effect of early immunosuppressive therapy on the rate of resections performed in patients with Chron's disease, in Veszprém county, Hungary, a population-based cohort study]. / A korai immunszuppresszív kezelés hatása a reszekciós mutétek arányára Crohn-betegekben, Veszprém megyében, populációs alapú kohorszvizsgálat alapján.

UNLABELLED: Medical therapy for Crohn's disease has changed significantly over the past 20 years with the increasing use of immunosuppressants. In contrast, surgery rates are still high and evidence about the the changes in the outcome of Crohn's disease over the past decades is scarce. AIMS: The objective of this study was to analyze the evolution of the surgical rates and medical therapy in the population-based Veszprém county database. METHODS: Data of 506 Crohn's disease patients were analyzed (age at diagnosis: 31.5 years, SD: 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. The study population was divided into three groups based on the year of diagnosis (cohort A: 1977-1989, cohort B: 1990-1998 and cohort C: 1999-2008). RESULTS: Overall azathioprine, systemic steroid, and biological (only available after 1998) exposure was 45.8, 68.6, and 9.5%, respectively. The 1 and 5-year probabilities of azathioprine use were 3.2 and 6.2% in cohort A, 11.4 and 29.9% in cohort B, and 34.8 and 46.2% in cohort C. In multivariate analysis, decade of diagnosis (P<0.001), age at onset (P = 0.008), disease behavior at diagnosis (P<0.001), and need for systemic steroids (P<0.001) were significantly associated with the time to initiation of azathioprine therapy. Early azathioprine use was significantly associated with the time to intestinal surgery in Crohn's disease patients; in a multivariate Cox analysis (HR: 0.43, 95% confidence interval (CI): 0.28-0.65) and after matching on propensity scores for azathioprine use (HR: 0.42,95% CI:0.26-0.67). CONCLUSIONS: This population-based inception cohort showed that reduction in surgical rates was independently associated with increased and earlier azathioprine use.

Has there been a change in the natural history of Crohn's disease? Surgical rates and medical management in a population-based inception cohort from Western Hungary between 1977-2009.

OBJECTIVES: Medical therapy for Crohn's disease (CD) has changed significantly over the past 20 years with increasing use of immunosuppressives. In contrast, surgery rates are still high and there is little evidence that disease outcomes for CD have changed over the past decades. The objective of this study was to analyze the evolution of the surgical rates and medical therapy in the population-based Veszprem province database. METHODS: Data of 506 incident CD patients were analyzed (age at diagnosis: 31.5 years, s.d. 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. The study population was divided into three groups by the year of diagnosis (cohort A: 1977-1989, cohort B: 1990-1998 and cohort C: 1999-2008). RESULTS: Overall, azathioprine (AZA), systemic steroid, and biological (only available after 1998) exposure was 45.8, 68.6, and 9.5%, respectively. The 1- and 5-year probability of AZA use were 3.2 and 6.2% in cohort A, 11.4 and 29.9% in cohort B, and 34.8 and 46.2% in cohort C. In a multivariate Cox-regression analysis, decade of diagnosis (P < 0.001, hazard ratio (HR)(cohorts B-C): 2.88-6.53), age at onset (P = 0.008, HR: 1.76), disease behavior at diagnosis (P < 0.001, HR(complicated): 1.76-2.07), and need for systemic steroids (P < 0.001, HR: 2.71) were significantly associated with the time to initiation of AZA therapy. Early AZA use was significantly associated with the time to intestinal surgery in CD patients; in a multivariate Cox analysis (HR: 0.43, 95% confidence interval (CI): 0.28-0.65) and after matching on propensity scores for AZA use (HR: 0.42, 95% CI: 0.26-0.67). CONCLUSIONS: This population-based inception cohort has shown that the recent reduction in surgical rates was independently associated with increased and earlier AZA use.

High-sensitivity C-reactive protein for identification of disease phenotype, active disease, and clinical relapses in Crohn's disease: a marker for patient classification?

BACKGROUND: C-reactive protein (CRP) is a traditional nonspecific marker of inflammation, with Crohn's disease (CD) being associated with a strong CRP response. Thus far, no clear cutoff values have been determined. The authors' aim was to investigate whether high-sensitivity (hs)-CRP is useful for the identification disease phenotype, active disease, and relapse during follow-up, using a classification based on the hs-CRP value at diagnosis. METHODS: In all, 260 well-characterized, unrelated, consecutive CD patients (male/female: 120/140; duration: 7.0 ± 6.1 years), with a complete clinical follow-up, were included. Hs-CRP, clinical activity according to the Harvey-Bradshaw Index, and clinical data (disease phenotype according to the Montreal Classification, extraintestinal manifestations, smoking habits, medical therapy, and surgical events) were prospectively collected between January 1, 2008 and June 1, 2010. Medical records prior to the prospective follow-up period were analyzed retrospectively. RESULTS: In all, 32.3% of CD patients had normal hs-CRP at diagnosis. Elevated hs-CRP at diagnosis was associated with disease location (P = 0.002), noninflammatory disease behavior (P = 0.058), and a subsequent need for later azathioprine/biological therapy (P < 0.001 and P = 0.024), respectively. The accuracy of hs-CRP for identifying patients with active disease during prospective follow-up was good (area under the curve [AUC]: 0.82, cutoff: 10.7 mg/L). AUC was better in patients with an elevated hs-CRP at diagnosis (AUC: 0.92, cutoff: 10.3 mg/L). In Kaplan-Meier and Cox-regression analyses, hs-CRP was an independent predictor of 3- (P = 0.007) or 12-month (P = 0.001) clinical relapses for patients in remission who had elevated hs-CRP at diagnosis. In addition, perianal involvement (P = 0.01) was associated with the 12-month relapse frequency. CONCLUSIONS: Our data suggest that hs-CRP positivity at diagnosis is associated with disease location and behavior, and in patients who are hs-CRP positive at diagnosis, is an accurate marker of disease activity and a predictor of short- and medium-term clinical flare-ups during follow-up.

[Predictors of efficacy, mucosal healing and dose intensification during the first year of adalimumab therapy in patients with luminal and fistulizing Crohn's disease. National data from Hungary]. / A klinikai hatékonyság, a nyálkahártya-gyógyulás és a dózisemelés prediktorai az adalimumabkezelés elso évében Crohn-betegségben szenvedo betegekben Magyarországon.

UNLABELLED: Adalimumab is a fully human monoclonal antibody targeting tumor necrosis factor with proven efficacy in the treatment of Crohn's disease in clinical trials. The aim of the present study was to investigate the predictors of medium term clinical efficacy and mucosal healing during adalimumab therapy in patients with Crohn's disease in specialized centers approved for biological therapy in Hungary. METHODS: Data of 201 Crohn's disease patients were prospectively captured (male/female: 112/89, median age: 24 years, duration: 8 years). Previous infliximab therapy was given in 97 (48.3%) patients, concomitant steroids in 41.3% and azathioprine in 69.2% (combined: 26.4%) of patients. RESULTS: Overall clinical response and remission rates at 24 and 52 weeks were 78% and 52%, and 69.4% and 44.4%, respectively. Endoscopic improvement and healing was achieved in 43.1% and 23.6%, respectively. In a logistic regression model, clinical efficacy and normalized C-reactive protein at week 12, need for combined immunosuppression at induction, shorter disease duration and smoking were identified as independent predictors for 12-month clinical outcome, while normalized C-reactive protein at week 12, clinical remission at week 24, frequency of previous relapses and smoking were associated to endoscopic improvement/healing. Dose intensification to weekly dosing was needed in 16.4%. Parallel azathioprine therapy and clinical remission at week 12 was inversely associated to dose escalation to weekly dosing. CONCLUSION: Clinical efficacy and normalized C-reactive protein at week 12, need for combined immunosuppression, luminal disease and smoking are predictors for medium term clinical efficacy/mucosal healing during adalimumab therapy, while parallel azathioprine therapy may decrease the probability for dose escalation.

[Evaluation of fracture risk in osteoporosis]. / A csonttörés kockázatának megítélése osteoporosisban.

Osteoporotic fractures are associated with excess mortality. Effective treatment options are available, which reduce the risk of vertebral and non-vertebral fractures, but the identification of patients with high fracture risk is problematic. Low bone mineral density (BMD)--the basis for the diagnosis of osteoporosis--is an important, but not the only determinant of fracture risk. Several clinical risk factors are know that operate partially or completely independently of BMD, and affect the fracture risk. These include age, a prior fragility fracture, a parental history of hip fracture, use of corticosteroids, excess alcohol intake, rheumatoid arthritis, and different types of diseases which can cause secondary bone loss. The FRAX® tool integrates the weight of above mentioned clinical risk factors for fracture risk assessment with or without BMD value, and calculates the 10-year absolute risk of hip and major osteoporotic (hip, vertebral, humerus and forearm together) fracture probabilities. Although the use of data is not yet uniform, the FRAX® is a promising opportunity to identify individuals with high fracture risk. The accumulation of experience with FRAX® is going on and it can modify current diagnostic and therapeutic recommendations in Hungary as well.

Diagnostic accuracy of serum parathyroid hormone levels in kidney transplant recipients with moderate-to-advanced CKD.

BACKGROUND/AIMS: Elevated parathyroid hormone (PTH) is used to diagnose high turnover bone disease in chronic kidney disease (CKD). The diagnostic accuracy of PTH in kidney transplant recipients with CKD is unknown. METHODS: We examined kidney transplant recipients with CKD stages 3 (n = 498) and 4 (n = 141) to determine the sensitivity and specificity of the Kidney/Dialysis Outcome Quality Initiative (K/DOQI)-recommended PTH levels in detecting elevated serum ß-CrossLaps (CTX) or osteocalcin (OC) levels. We performed receiver-operator curve analyses to determine CKD stage-specific PTH levels that provide optimal diagnostic accuracy. RESULTS: PTH below the lower limits of the K/DOQI ranges (35 and 70 pg/ml in CKD stages 3 and 4, respectively) showed sensitivity of >90% in diagnosing increases in biochemical markers. The upper limits (70 and 110 pg/ml), however, showed poor specificity. A specificity of >90% for detecting increased biochemical markers was seen with PTH of >140 and >240 pg/ml in CKD stages 3 and 4, respectively. CONCLUSION: Currently applied cutoffs for PTH in kidney transplant recipients with CKD stages 3 and 4 do not appear to adequately detect increased biochemical markers of bone turnover. Diagnostic uncertainty exists in patients with CKD stage 3 and PTH between 35 and 140 pg/ml, and CKD stage 4 and PTH between 70 and 240 pg/ml.

The method of distance measurement and torso length influences the relationship of pulse wave velocity to cardiovascular mortality.

BACKGROUND: The method of estimating distance traveled by the pulse wave, used in the calculation of pulse wave velocity (PWV), is not standardized. Our objective was to assess whether different methods of distance measurement influenced the association of PWV to cardiovascular mortality in hemodialysis (HD) patients. METHODS: Ninety-eight chronic HD patients had their PWV measured using three methods for distance estimation; PWV1: suprasternal notch-to-femoral site minus suprasternal notch-to-carotid site, PWV2: carotid-to-femoral site, PWV3: carotid-to-femoral site minus suprasternal notch-to-carotid site. Carotid-to-femoral distance was used to approximate torso length. Patients were followed for a median of 30 months and the association of PWV and cardiovascular mortality was assessed using survival analysis before and after stratification for torso length. RESULTS: The three methods resulted in significantly different PWV values. During follow-up 50 patients died, 32 of cardiovascular causes. In log-rank tests, only tertiles of PWV1 was significantly related to outcome (P values 0.017, 0.257, 0.137, for PWV1, PWV2, and PWV3, respectively). In adjusted Cox, proportional hazards regression only PWV1 was related to cardiovascular mortality. In stratified analysis, however, among patients with below median torso length all PWV values were related to outcome, whereas in patients with above median torso length none of the PWV methods resulted in significant relationship to outcome. CONCLUSIONS: PWV calculated using suprasternal notch-to-femoral distance minus suprasternal notch-to-carotid distance provides the strongest relationship to cardiovascular mortality. Longer torso weakens the predictive value of PWV, possibly due to more tortuosity of the aorta hence, more error introduced when using surface tape measurements.

Associations between serum leptin level and bone turnover in kidney transplant recipients.

BACKGROUND AND OBJECTIVES: Obesity is associated with increased parathyroid hormone (PTH) in the general population and in patients with chronic kidney disease (CKD). A direct effect of adipose tissue on bone turnover through leptin production has been suggested, but such an association has not been explored in kidney transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study examined associations of serum leptin with PTH and with biomarkers of bone turnover (serum beta crosslaps [CTX, a marker of bone resorption] and osteocalcin [OC, a marker of bone formation]) in 978 kidney transplant recipients. Associations were examined in multivariable regression models. Path analyses were used to determine if the association of leptin with bone turnover is independent of PTH. RESULTS: Higher leptin levels were associated with higher PTH and lower vitamin D levels, and adjustment for vitamin D attenuated the association between leptin and PTH. However, higher leptin was also significantly associated with lower levels of the bone turnover markers: 1 SD higher leptin was associated with 0.13 lower log-OC (-0.17, -0.08, P < 0.001) and 0.030 lower log-CTX (-0.045, -0.016, P < 0.001) after multivariable adjustments. Path analysis indicated that the association of leptin with PTH was mostly mediated through vitamin D, and that the association between leptin and bone turnover was independent of PTH and vitamin D. CONCLUSIONS: Elevated leptin level is associated with lower bone turnover independent of its effects on serum PTH in kidney transplant recipients.

[Significance of arterial stiffness parameters for predicting cardiovascular mortality in hemodialysis patients: a prospective cohort study]. / A különbözô érfali tágulékonysági paraméterek jelentôsége a cardiovascularis mortalitás elôrejelzésében hemodializált betegek között: prospektív kohorszvizsgálat.

UNLABELLED: Previous studies demonstrated that different parameters of arterial stiffness are related to cardiovascular mortality in hemodialysis patients. The relative prognostic value of these parameters has not previously been evaluated in one cohort. PATIENTS AND METHODS: Carotid-femoral pulse wave velocity, carotid augmentation index, carotid pulse pressure and carotid-brachial pulse pressure amplification were measured in 98 patients before and after hemodialysis. Patients were followed for a median of 29 months (1-34) and the association of these parameters with cardiovascular mortality was assessed using log-rank tests and Cox proportional hazards regressions. RESULTS: During follow-up, 40 patients died (mortality rate 20.7/100 patient-year), of which 25 died of cardiovascular causes. Increasing pre- and postdialysis pulse wave velocity tertiles and decreasing predialysis pulse pressure amplification tertiles were significantly related to cardiovascular mortality (p-values are 0.012 and 0.011 for pre- and postdialysis pulse wave velocity, and <0.001 and 0,321 for pre- and postdialysis pulse pressure amplification, respectively). Neither the carotid augmentation index nor carotid pulse pressure was related to cardiovascular mortality. In the Cox-regression, the adjusted hazard ratios for 1 m/s higher pre- and postdialysis pulse wave velocity were 1.24 (1.07-1.44) and 1.17 (1.06-1.28), respectively. The hazard ratio for 10% lower predialysis pulse pressure amplification was 1.41 (1.03-1.92). When included in the same model, both predialysis pulse wave velocity and pulse pressure amplification remained significantly associated with cardiovascular mortality (relative risk: 1.23 [1.07-1.42] and 1.39 [1.02-1.89]). CONCLUSION: Among different stiffness parameters, pulse wave velocity is consistently related to cardiovascular mortality, irrespective of the timing of measurement. Predialysis pulse pressure amplification seems to provide additional prognostic information.

Arterial stiffness in hemodialysis: which parameter to measure to predict cardiovascular mortality?

In previous studies, different parameters of arterial stiffness were related to cardiovascular mortality in hemodialysis patients, but their relative prognostic value has not previously been evaluated in 1 cohort. Carotid-femoral pulse wave velocity (PWV), the carotid augmentation index, carotid pulse pressure (CPP) and carotid-brachial pulse pressure amplification (AMP) were measured in 98 patients before and after hemodialysis. Patients were followed for a median of 29 months (1-34) and the association of these parameters with cardiovascular mortality were assessed using log-rank tests and Cox proportional hazards regressions. During follow-up, 25 patients died of cardiovascular causes. Increasing pre- and postdialysis PWV tertiles and decreasing predialysis AMP tertiles were significantly related to cardiovascular mortality (p = 0.012 and 0.011 for PWV, respectively; < 0.001 for AMP). Neither the carotid augmentation index nor carotid pulse pressure were related to cardiovascular mortality. The adjusted hazard ratios for 1 m/s higher pre- and postdialysis PWV were 1.24 (1.07-1.44) and 1.17 (1.06-1.28), respectively. The hazard ratio for 10% lower predialysis AMP was 1.41 (1.03-1.92). When included in the same model, both predialysis PWV and AMP remained significantly associated with cardiovascular mortality. Among different stiffness parameters, PWV is consistently related to cardiovascular mortality, irrespective of the timing of measurement. Predialysis AMP seems to provide additional prognostic information.

Calcium, phosphate and parathyroid metabolism in kidney transplanted patients.

INTRODUCTION: Impaired kidney function is common in kidney-transplanted patients and complications of chronic kidney disease (CKD), such as mineral and bone disorders (MBD) are also prevalent in this population. Similarly to other stages of CKD, increasing evidence supports the association between MBD and cardiovascular risk after kidney transplantation as well. Still, little is known about the prevalence, clinical correlates of MBD and its management in transplanted patients. In this study, we aimed to examine the characteristics of MBD and its associations with clinical parameters in a large prevalent cohort of patients after kidney transplantation. METHODS: Nine hundred and ninety stable patients followed at a single kidney transplant outpatient clinic were included in the study. Detailed medical history, demographic data and routine laboratory results, including Ca, P and intact PTH were collected. Estimated GFR was calculated using the abbreviated MDRD formula, patients were stratified into three groups based on eGFR. Target levels for Ca, P and iPTH were based on CKD stages according to the NKF-K/DOQI guidelines. Standard statistical procedures, binomial and multinomial regressions were used in the analysis. RESULTS: The mean age was 51 years, 57% were males and 21% were diabetic, with 72 months (median) post-transplantation. Most of the patients were in CKD stage 3. Serum phosphorus showed strong negative correlation with graft function in CKD stages 4-5 (r = -0.633, P < 0.001). Hyperphosphatemia was independently associated with the time spent on dialysis before transplantation, serum iPTH and CKD stages 4-5. iPTH showed negative correlation with eGFR in CKD stages 3-5 (rho = -0.289, P < 0.001) and weak positive correlation with time spent on dialysis prior to transplant (rho = 0.114, P < 0.001). Both hyperparathyroidism (42%) and relative hypoparathyroidism (15%) were frequent. The prescription of P-binders (6%) and vitamin D analogs (33%) was sporadic. CONCLUSION: Disturbances of bone and mineral metabolism after transplantation are prevalent and are strongly correlated with the kidney function, similarly to non-transplanted CKD patients. MBD in this population is not adequately managed.

[Osteoprotegerin: regulator, protector and marker]. / Osteoprotegerin: a regulátor, a protektor és a marker. Osszefoglalás irodalmi adatok és saját eredményeink alapján.

Experimental and clinical trials in the field of bone biology helped to clarify the role of receptors, which belong to the tumor necrosis factor family, such as osteoprotegerin and receptor activator of nuclear factor kappaB (RANK), in the regulation of bone remodeling. The ligand of the receptor activator of nuclear factor kappaB (RANKL) is a stimulator of bone resorption, while osteoprotegerin is the soluble "decoy" receptor to RANKL, protecting thereby bone from resorption. Pathological states of bone remodeling (like osteoporosis) are associated with imbalance in the activity of osteoprotegerin and the receptor activator of nuclear factor kappaB. Recent studies, however, also indicate that the osteoprotegerin/RANKL/RANK system has important roles in the regulation of the immune and vascular system as well. In this review we summarize the function and regulation of osteoprotegerin, its role in pathological states--primarily in cardiovascular diseases--and its relevance as a marker of cardiovascular risk. Finally, we present our prospective trial performed among the chronic dialyzed patients, where we examined the association between the cardiovascular mortality, osteoprotegerin levels and the arterial stiffness.

Serum osteoprotegerin level, carotid-femoral pulse wave velocity and cardiovascular survival in haemodialysis patients.

BACKGROUND: Osteoprotegerin (OPG) is a marker and regulator of arterial calcification, and it is related to cardiovascular survival in haemodialysis patients. The link between OPG and aortic stiffening--a consequence of arterial calcification--has not been previously evaluated in this population, and it is not known whether OPG-related mortality risk is mediated by arterial stiffening. METHODS: At baseline, OPG and aortic pulse wave velocity (PWV) were measured in 98 chronic haemodialysis patients who were followed for a median of 24 months. The relationship between OPG and PWV was assessed by multivariate linear regression. The role of PWV in mediating OPG related cardiovascular mortality was evaluated by including both OPG and PWV in the same survival model. RESULTS: At baseline mean (standard deviation) PWV was 11.2 (3.3) m/s and median OPG (interquartile range) was 11.1 (7.5-15.9) pmol/L. There was a strong, positive, linear relationship between PWV and lnOPG (P = 0.009, model R(2) = 0.540) independent of covariates. During follow-up 23 patients died of cardiovascular causes. In separate univariate survival models both PWV and lnOPG were related to cardiovascular mortality [hazard ratios 1.31 (1.14-1.50) and 8.96 (3.07-26.16), respectively]. When both PWV and lnOPG were entered into the same model, only lnOPG remained significantly associated with cardiovascular mortality [hazard ratio 1.11 (0.93-1.33) and 7.18 (1.89-27.25), respectively). CONCLUSION: In haemodialysis patients OPG is strongly related to PWV and OPG related cardiovascular mortality risk is, in part, mediated by increased PWV.

Independent effect of endogenous dehydroepiandrosterone-sulphate levels and birth weight on bone turnover parameters in young adults.

Data indicate that bone turnover is higher in young adults born with a low birth weight (LBW). Moreover, several data support the presence of altered adrenal hormone production in this population. The aim of our study was to investigate whether there is any connection between altered bone homeostasis and adrenal hormone levels. Bone mineral density (BMD), serum osteocalcin (OC), and urinary deoxypyridinoline (DPD) excretion were related to dehydroepiandrosterone-sulphate (DHEAS), cortisol, estradiol, testosterone, and sex-hormone binding globulin (SHBG) levels in 47 healthy young women (of those, 33 were LBW) and 65 healthy young men (of those, 49 were LBW). The age of the subjects was 19-21 years. BMD values were normal and did not correlate with any of the factors investigated. Cortisol did not have any independent effect on bone turnover parameters in either men or women. In women, birth weight, DHEAS levels, and free estradiol index were responsible for almost 50% (corrected r2= 0.45) of serum OC variability. Independent positive associations were observed between DHEAS and OC, and between DHEAS and DPD excretion. In men, birth weight and DHEAS levels together were responsible for more than one-third (corrected r(2) = 0.36) of the variability of serum OC. In contrast with women, DHEAS and OC were inversely correlated in men. Our results suggest that bone turnover depends on the subjects' birth weight. Moreover, DHEAS is also an independent determinant. The effect of DHEAS on bone turnover is different in women and men. DHEAS increases bone turnover in fertile women, while it decreases this in men.

Bone mineral density and bone acquisition in children and young adults with cystic fibrosis: a follow-up study.

OBJECTIVE: To investigate bone mineral density and bone homeostasis in cystic fibrosis (CF) and to assess changes in a 2-year period. METHODS: Thirty-eight patients with clinically stable CF (11 children, 16 adolescents, 11 young adults) were enrolled. No patient was treated with corticosteroids before or during the study. Weight and height Z scores and bone mineral density (BMD) Z-score at the femoral neck and the lumbar spine were recorded at the beginning of the study and after 2 years. Osteocalcin and cross-link excretion, both measurements of bone turnover were also measured. Correlations between BMD, bone turnover parameters, disease severity, pubertal stage, and nutritional state were calculated. The maternal BMD was also determined and related to that of the child. RESULTS: Height and weight Z scores were normal in children and below normal in adolescents. Puberty was delayed in most patients. Bone age was lower than chronological age in adolescents. Lumbar spine and femoral neck BMD Z scores were below normal in each age group. Disease severity determined by Schwachman score correlated with lumbar BMD (r = 0.45, P < 0.02). BMD Z scores did not change during 2 year follow-up. Maternal and patient lumbar and femoral BMD correlated significantly (r = 0.51, P < 0.01, and r = 0.54, P < 0.01, respectively). CONCLUSIONS: Bone deficit is present in patients with CF who have never received steroid treatment. Delay of puberty, chronic inflammation, or genetic susceptibility might be responsible for this phenomenon which was found in patients who had never received steroids and who were in relatively good clinical state.