Serum osteoprotegerin is associated with pulse pressure in kidney transplant recipients.

Pulse pressure (PP) reflects increased large artery stiffness, which is caused, in part, by arterial calcification in patients with chronic kidney disease. PP has been shown to predict both cardiovascular and cerebrovascular events in various patient populations, including kidney transplant (KTX) recipients. Osteoprotegerin (OPG) is a marker and regulator of arterial calcification, and it is related to cardiovascular survival in hemodialysis patients. Here we tested the hypothesis that OPG is associated with increased pulse pressure. We cross-sectionally analyzed the association between serum OPG and PP in a prevalent cohort of 969 KTX patients (mean age: 51 +/- --13 years, 57% male, 21% diabetics, mean eGFR 51 +/- 20 ml/min/1.73 m2). Independent associations were tested in a linear regression model adjusted for multiple covariables. PP was positively correlated with serum OPG (rho = 0.284, p < 0.001). Additionally, a positive correlation was seen between PP versus age (r = 0.358, p < 0.001), the Charlson Comorbidity Index (r = 0.232, p < 0.001), serum glucose (r = 0.172, p < 0.001), BMI (r = 0.133, p = 0.001) and serum cholesterol (r = 0.094, p = 0.003). PP was negatively correlated with serum Ca, albumin and eGFR. The association between PP and OPG remained significant after adjusting for multiple potentially relevant covariables (beta = 0.143, p < 0.001). We conclude that serum OPG is independently associated with pulse pressure in kidney transplant recipients.

Randomized trial of bioelectrical impedance analysis versus clinical criteria for guiding ultrafiltration in hemodialysis patients: effects on blood pressure, hydration status, and arterial stiffness.

BACKGROUND: Chronic fluid overload is common in maintenance hemodialysis (HD) patients and is associated with severe cardiovascular complications, such as arterial hypertension, left ventricular hypertrophy, congestive heart failure, and arrhythmia. Therefore, a crucial target of HD is to achieve the so-called dry weight; however, the best way to assess fluid status and dry weight is still unclear. Dry weight is currently determined in most dialysis units on a clinical basis, and it is commonly defined as the lowest body weight a patient can tolerate without developing intra-dialytic or inter-dialytic hypotension or other symptoms of dehydration. One of the most promising methods that have emerged in recent years is bioelectrical impedance analysis (BIA), which estimates body composition, including hydration status, by measuring the body's resistance and reactance to electrical current. Our objective was to study the effect BIA-guided versus clinical-guided ultrafiltration on various cardiovascular disease risk factors and markers in HD patients. MATERIALS AND METHODS: We included 135 HD patients from a single center in a prospective study, aiming to compare the long-term (12 months) effect of BIA-based versus clinical-based assessment of dry weight on blood pressure (BP), pulse wave velocity (PWV), and serum N-terminal fragment of B-type natriuretic peptide (NT-proBNP). The body composition was measured using the portable whole-body multifrequency BIA device, Body Composition Monitor-BCM(®) (Fresenius Medical Care, Bad Homburg, Germany). RESULTS: In the "clinical" group there were no changes in BP, body mass index (BMI), and body fluids. The PWV increased from 7.9 ± 2.5 to 9.2 ± 3.6 m/s (P = 0.002), whereas serum NT-proBNP decreased from 5,238 to 3,883 pg/ml (P = 0.05). In the "BIA" group, BMI and body volumes also did not change; however, there was a significant decrease in both systolic BP, from 144.6 ± 14.7 to 135.3 ± 17.8 mmHg (P < 0.001), and diastolic BP, from 79.5 ± 9.7 to 73.2 ± 11.1 mmHg (P < 0.001). In this group, PWV also decreased from 8.2 ± 2.3 to 6.9 ± 2.3 m/s (P = 0.001) and NT-proBNP decreased from 7,552 to 4,561 pg/ml (P = 0.001). CONCLUSION: BIA is not inferior and possibly even better than clinical criteria for assessing dry weight and guiding ultrafiltration in HD patients.

Regression of left ventricular hypertrophy in hemodialyzed patients is possible: a follow-up study.

BACKGROUND: Few studies have addressed the description of serial changes in left ventricular mass (LVM) and relevant risk factors. The aims of our study were to describe trends in left ventricular (LV) structure and function derived from echocardiographic measurements over a 10-year period in Fresenius Nephrocare Dialysis Center in Iasi and to compare the results with those obtained on a smaller group 4 years ago. METHODS: Three hundred and thirty-four hemodialyzed patients were enrolled at baseline, between January 1999 and March 2009. Echocardiography was performed at inclusion and several times for each patient during this period, until the end of the study. Mean values of the biochemical parameters (hemoglobin, serum proteins, calcium, phosphate) at the time of the echocardiographic examination were calculated and included in the final analysis. RESULTS: Outcome in dialysis was 70.5% alive at the end of the study. The most important improvement was observed in LV mass index: at the 4th echocardiography, the mean LVMi was 144.8 vs. 156.0 g/m(2) at the 2nd echocardiographic examination vs. 167.2 g/m(2) at the first echocardiographic examination (mean decrease 3.34 ± 9.6 g/m(2)/month). Significant results were obtained by comparing LVMi only in patients with all 4 echocardiographies: left ventricular hypertrophy regression was statistically significant, from 172.7 g/m(2) at the 1st echocardiography to 146.0 g/m(2) at the 4th, i.e. 15.4% reduction of LVMi. Delta LVMi significantly correlated only with changes in hemoglobin (P < 0.05).There was a significant regression of the relative wall thickness from an average of 0.46 to 0.42 (P < 0.05). CONCLUSION: Our study proves that regression of LVH in hemodialyzed patients is possible and constitutes a must-achieve objective in dialysis centers.

Nutritional status evaluation and survival in haemodialysis patients in one centre from Romania.

BACKGROUND: Protein-energy wasting is a common complication and an important predictive factor for mortality in chronic dialysis patients. Therefore, nutritional status needs to be regularly assessed in these patients, by using several methods, and, if malnutrition is present, its possible causes should be thoroughly searched for and properly treated. MATERIAL AND METHODS: In 149 prevalent haemodialysis patients (82 men, mean age 53.9 +/- 13.7 years), we evaluated the nutritional status by anthropometrics [post-dialysis height (H), body weight (BW), body mass index (BMI), mid-arm circumference (MAC), tricipital skin-fold thickness (TST), mid-arm muscle circumference (MAMC), corrected mid-arm muscle area (cMAMA) and three-category subjective global assessment score (SGA)], biochemical tests [protein equivalent of nitrogen appearance (nPNA), and pre-dialysis serum albumin, creatinine, total cholesterol, bicarbonate and haemoglobin (Hb) levels] and bioelectrical impedance analysis (BIA) to estimate body composition [percent body fat (%BF), fat-free mass (%FFM), body cell mass (%BCM), extracellular mass (%ECM) and the phase angle (PhA)]. RESULTS: Age was found to be positively correlated with BMI (P = 0.001), and inversely correlated with %BCM (P = 0.013). Patients with A-category SGA were significantly younger (50.1 versus 63.7 years) than those with B-category SGA. Patients with diabetes had lower %BCM (32.9 versus 35.9%; P = 0.035) and PhA (5.5 versus 6.9 degrees ; P = 0.0007) than those without diabetes. The presence of heart failure was associated with significantly reduced nPNA (1.17 versus 1.34 g/kg day; P = 0.014), MAMC (22.0 versus 23.6 cm(2); P = 0.041), %BCM (33.0 versus 36.1; P = 0.021), PhA (5.8 versus 7.0 degrees ; P = 0.031), serum albumin (39.7 versus 42.4 g/l; P = 0.013) and serum creatinine (8.1 versus 9.4 mg/dl; P = 0.010), and with a higher percent of B-category SGA (47.8% versus 22.6%; P = 0.019). Eleven deaths (7.4%) occurred during the follow-up period. Among general factors, age >or= 55, the presence of diabetes, and dialysis vintage <2 years were associated with significantly reduced survival. Among nutritional factors, B-category SGA, nPNA <1.2 g/kg day, %BF <15% and PhA <6 degrees significantly predicted mortality in both Kaplan-Meier and Cox analyses. The most important risk factor appeared to be nPNA; for every 0.1 g/kg day increase in nPNA, death risk decreased by 15%. CONCLUSIONS: In our haemodialysis patients, advancing age, diabetes and heart failure were associated with worse nutritional status, as estimated by anthropometry, biochemical markers and BIA. Age >or=55 years, the presence of diabetes, nPNA <1.2 g/kg day, lower SGA score, %BF <15% and PhA <6 degrees were associated with significantly increased death risk.

[Persistent and recurrent skin infection with small-colony variant methicillin-resistant Staphylococcus aureus]. / Infectie cutanata persistenta si recurenta cu Staphylococcus aureus meticilino-rezistent, varianta cu colonii mici.

S. aureus is one of the problematic bacteria, capable to develop resistance mechanisms to all antibiotics that the bacteria are naturally susceptible. A particular phenotypic mechanism, especially against the antibiotics that repressed the synthesis of the cellular wall and aminoglycosides, was evidenced in subpopulations that grows in small-colonies and represents auxotrophic mutants for hemin, menadione or thymidine. This type of strains has been isolated most frequently from patients with osteomyelitis, septic arthritis or pulmonary infections after a long period of antibiotic treatment. The authors present the case of a patient with persistent and recurrent staphylococcal infection of the peritoneal dialysis exit site, treated with different antibiotics (ciprofloxacin, vancomycin, amoxicillin and clavulanic acid, cephalexin) from witch has been isolated a small-colony strain of methicillin-resistant S. aureus. Therapeutic failure can be explain by the slow multiplication of this strain in vivo, persistence into phagocytes and the protection offered by biofilm from the surface of the catheter. Bacteriologic diagnosis in these cases is difficult because of the culture, biochemical and susceptibility testing particularities of these strains. All these may lead failure to identification small colony variants of S. aureus and mis-evaluation of the frequency of infection with these strains in patients with long-term antibiotherapy.

[Nutritional status evaluation in maintenance hemodialysis patients]. / Evaluarea starii de nutritie la pacientii cu insuficienta renala cronica terminala tratati prin hemodializa.

UNLABELLED: Protein-calorie malnutrition is a common complication and an important predictive factor for mortality in patients with end-stage renal disease on maintenance dialysis. Therefore, nutritional status needs to be regularly assessed in these patients by using several methods. If malnutrition is diagnosed, its causes should be thoroughly searched for and properly treated. MATERIAL AND METHOD: This cross-section study aimed at evaluating the nutritional status and the possible risk factors for malnutrition in 149 (82 men) hemodialysis patients by anthropometry, biochemical tests and bioelectrical impedance analysis (BIA). The patients' height (H), post-dialysis body weight (BW), mid-arm circumference (MAC), tricipital skin-fold thickness (TST) were measured and a 3-category subjective global assessment (SGA) was performed. Body mass index (BMI), mid-arm muscle circumference (MAMC), corrected mid-arm muscle area (cMAMA) and anthropometry-estimated percent body muscle mass (% AMM) were calculated from the above measurements by using specific equations. Biochemical tests included protein equivalent of nitrogen appearance (nPNA), and predialysis serum albumin, creatinine, total cholesterol, bicarbonate, and hemoglobin (Hb) levels. We used BIA to estimate body composition - i.e. percent body fat (% BBF), fat-free mass (% FFM), body cell mass (% BCM), extracellular mass (% ECM), muscle mass (% BMM)--and the phase angle (PhA). T-test was used to make comparisons and Pearson coefficient to analyze the correlations. P < 0.05 was considered statistically significant. RESULTS: The male patients had a higher mean muscle mass--as estimated by serum creatinine (9.8 s 8.3 mg/dl; P < 0.0001) and by % BMM (41.7% vs 34.7%)--and a lower fat mass--as estimated by TST (0.95 cm vs 1.2 cm; P = 0.016) and by % FAT (16.7% vs 31.3%; P < 0.0001) than the female patients. Age was found to be positively correlated with BMI (P = 0.001), but inversely correlated with % BCM (P = 0.013) and with % AMM (P = 0.003). Patients with diabetes had lower % BCM than those without diabetes (32.9 vs 35.9%; P = 0.041). The presence of heart failure was associated with significantly reduced MAMC (22.0 vs 23.6 cm2; P = 0.045), % AMM (28.5 vs 32.1; P = 0.021), % BCM (33.0 vs 36.1% ; P = 0.034), BMM/H2 (8.6 vs 9.4 kg/m2; P = 0.013), nPNA (1.17 vs 1.34 g/kg-d ; P = 0.047), serum albumin (39.7 vs 42.4 g/l; P = 0.010), serum creatinine (8.1 vs 9.4 mg/dl; P = 0.008) and Hb (10.5 vs 11.2 g/dl; P = 0.017). The serum Hb level was positively correlated with BMI (P = 0.005), BMM/H2 (P = 0.009), serum albumin (P = 0.002) and serum creatinine (P = 0.011). Also, patients with category B-SGA were older (63.7 vs 50.1 y.o.; P < 0.0001) and had more heart failure (42% vs 13%; P = 0.013) than those with category A-SGA. In hemodialysis patients, advancing age, diabetes, heart failure and decreasing Hb levels are associated with worse nutritional status, as estimated by anthropometry, biochemical markers and BIA. Whether treatment of comorbidities such as heart disease and anemia may improve nutritional status in these patients is an important issue that deserves further research.

The impact of acute kidney injury on short-term survival in an Eastern European population with stroke.

BACKGROUND: Stroke is one of the leading causes of death and of serious disability with significant impact on patients' long-term survival. The short-term evolution following stroke can associate acute kidney injury (AKI) as a possible complication, frequently overlooked and underestimated in clinical trials. We aimed to describe in an East European cohort (i) the incidence of AKI and its risk factors; (ii) the 30-day mortality and its risk factors and (iii) the relationship between mortality, pre-existent renal function and subsequent AKI. METHODS: A total of 1090 consecutive cases hospitalized-during a 12-month period-with a CT-confirmed diagnosis of stroke, from a distinct administrative region were included. Demographic details, comorbidities, laboratory and outcome data were retrieved from the electronic hospital database. All patients included in the study were followed for 30 days or until death. RESULTS: The mean age of this population was 66.1 +/- 11.5 years, 49.3% were males, mean glomerular filtration rate (GFR) 68.9 +/- 22.6 ml/min/1.73 m(2). The 30-day mortality rate was 17.2%. One hundred and fifty-eight patients presented with haemorrhagic stroke and 932 patients had ischaemic stroke. Stroke mortality was-14% for ischaemic stroke and almost twice as high for haemorrhagic stroke-36.3%. One hundred fifty-eight (14.5%) patients were classified as developing AKI. The AKI patients were older, had a higher baseline serum creatinine, lower GFR, higher serum glucose, higher prevalence of chronic heart failure and ischaemic heart disease, were more likely to have suffered a haemorrhagic stroke, and had a significantly higher 30-day mortality rate (43.1 vs 12.8%) (P < 0.05 for all). Independent predictors for AKI development in the logistic regression analysis were age, GFR, presence of comorbidities (ischaemic heart disease and chronic heart failure) and type of stroke (Cox and Snell R(2) 0.244; Nagelkerke R(2) 0.431; P < 0.05). In our study, we demonstrated that the occurrence of AKI is not a rare finding in stroke patients. This is the first study to report the incidence of AKI in a distinct geographic population base, in patients with stroke. Baseline renal function emerged as both a significant independent marker for short-term survival after an acute stroke (even after adjustment for baseline comorbidities) and as a risk factor for subsequent AKI.

Serial echocardiographic changes in patients on hemodialysis: an evaluation of guideline implementation.

BACKGROUND: Few studies have addressed the description of serial changes in left ventricular mass (LVM) and relevant risk factors. All these studies were initiated before the implementation of EBPG or K/DOQI guidelines. The aims of our study were to prospectively describe trends in left ventricular (LV) structure and function, evaluate risk factors for progression of LVM derived from serial echocardiographic measurements starting January 2003, 6 months after full implementation of EBPG in our unit. METHODS: One hundred seventy-six patients were enrolled at baseline, between 1 January 2003 and 1 October 2004; 33 patients were excluded from analysis due to poor echocardiographic window, 14 patients died and 26 were transplanted or transferred during the follow-up period of minimum 12 months. One hundred and three patients were included in the final analysis (mean age 51 years, mean follow-up 24.1 +/- 14.4 months). Echocardiography was performed at inclusion and at the end of study. Biochemical, blood pressure (BP) and medication data were collected and the means of monthly values were used. RESULTS: At baseline, 86.4% of the patients had left ventricular hypertrophy (LVH) (56.3% concentric hypertrophy, 30.1% eccentric hypertrophy, 6.8% concentric remodeling and only 6.8% normal LV geometry), 25.6% had systolic dy-sfunction and 50.5% had abnormal LV volume index (LVVI). Similar data were recorded at follow-up (82.5%, 44.7%, 37.9%, 7.7%, 9.7%, and 19.5%, respectively). Baseline left ventricular mass index (LVMI) significantly correlated with hemoglobin (Hb) and total protein level. LVMI at follow-up correlated to Hb, SBP, PP, mean level of serum phosphate, calcium x phosphate product and cholesterol. Independent predictors for LVMI (multiple regressions) were anemia and mineral metabolism markers. In our population, 62.1% of the patients had a regression of LVMI, with a mean decrease in LVMI of 12 g/m 2 (1.7 +/- 11.7 g/m 2 /month) over more than 12 months of guideline implementation. Regressors had a significant improvement of anemia, serum phosphate level and calcium x phosphate product (p<0.05). CONCLUSION: Our study suggests that a holistic interventional approach, targeting various pathogenic mechanisms, as per guidelines, can elicit at least a partial regression in LV structural and functional abnormalities in hemodialysis patients.

Analysis of safety and efficacy of pegylated-interferon alpha-2a in hepatitis C virus positive hemodialysis patients: results from a large, multicenter audit.

BACKGROUND: Hepatitis C virus (HCV) infection rates are still high in hemodialysis (HD) centers in developing countries. Standard interferon (IFN) monotherapy is associated with good results in HCV-positive patients (more than 30% rate of sustained virological response) but with poor tolerance. Pegylated interferon (PEG-IFN) is better tolerated and has a more sustained antiviral effect in the general population. There have been no large trials to date with PEG-IFN in hemodialysis populations. METHODS: We report the largest series to date of HCV+ HD patients (n=78) treated with PEG-IFN alfa -2a 135 microg s.c. weekly monotherapy. The primary outcomes were (a) efficacy - assessed by the viral response at 12, 48 weeks and 6 months after completion of therapy, and (b) rate of serious adverse events. RESULTS: In 48/78 (61.5%) patients an early (12 weeks) viral response was obtained. Viral end-of-treatment response (ETR) was evaluated in the 21 patients (26.9%) who reached week 48 on therapy: only 15 subjects (19.2% of the initial population) had undetectable HCV-RNA levels. In these 15 patients, a sustained viral response (SVR) was recorded in 11 - i.e. 14.1% of the initial intention-to-treat (ITT) population. A high prevalence of noncompliance (32%) and of adverse events (83%) was recorded; minor adverse effects (flu-like syndrome, mild-to-moderate thrombocytopenia, leukopenia and anemia) responded to symptomatic therapy or dose reduction, but often caused lack of compliance. The incidence rate of serious adverse events was 0.19/patient-year (median time to event 20.5 weeks), and incidence of deaths was 0.11/patient-year. CONCLUSIONS: In dialysis patients, PEG-IFN alfa -2a is poorly tolerated and associated with a high number of serious adverse events, causing a significant lack of compliance/discontinuation of therapy. In this largest HCV-positive hemodialysis population survey, we report a low sustained viral response in an ITT analysis, compared with previously published historical data using non-PEG-IFN, a low compliance rate and an unsatisfactory overall safety profile, not supporting the superiority of PEG-IFN monotherapy.

Arterial wave reflections and mortality in haemodialysis patients--only relevant in elderly, cardiovascularly compromised?

BACKGROUND: Chronic kidney disease (CKD) patients have a 3-30-fold increased risk of death compared with the general population. This mortality difference is even more pronounced in younger subjects. Two markers of aortic stiffness--aortic pulse wave velocity (PWV) and augmentation index (AIx)--have been prospectively related to all-cause and cardiovascular (CV) mortality in end-stage renal disease (ESRD) populations. The aims of our study were first, to confirm the important deleterious effect of arterial stiffness in uraemia and second, to assess the impact on survival of increased AIx in a relatively young non-diabetic dialysis population, with minimal CV disease. METHODS: Ninety-two patients (mean age 42.6 +/- 11.2 years) were included in the study and followed for a period of 61 +/- 25 months. None of the patients had diabetes mellitus, and only 3.3% had prior history of CV disease. AIx was determined by applantation tonometry using a SphygmoCor device (AtCor, PWV Inc., Westmead, Sydney, Australia). RESULTS: Mean AIx in our study population was 19.9 +/- 13.7%; other significant haemodynamic parameters were: systolic blood pressure (SBP) 129 +/- 24 mmHg, pulse pressure 35.3 +/- 17.5 mmHg with 27.2% of the study population receiving angiotensin-converting enzyme inhibitors (ACE-I). On univariate analysis, in our group AIx correlated with: body weight (P < 0.001), radial SBP (P < 0.001) and haemoglobin levels (P < 0.05). There was no correlation between AIx and any of the echocardiographic parameters. In the stepwise multiple regression analysis, the only independent predictors for AIx were weight (P < 0.001), SBP (P < 0.001) and haemoglobin (P < 0.05) with the model explaining 33% of the AIx variability (adjusted R(2) = 0.33). During the follow-up period, 15 deaths were recorded. In the Cox analysis (P = 0.014; chi square 20.7 for the model) the only independent predictors for all-cause mortality were age (P = 0.001), left ventricular mass index (P = 0.032) and ACE-I therapy (P = 0.039) while AIx did not reach statistical significance. There was no difference in patients' survival when divided by AIx tertiles, assessed by the log rank test (P = 0.78). CONCLUSION: Our results fail to support the notion that an increased effect of wave reflections on central arteries is a strong and independent predictor of mortality in all ESRD patients on haemodialysis. The effect of arterial wave reflections might be in fact dependent on patient age and concurrent comorbidity status.

The success story of peritoneal dialysis in Romania: analysis of differences in mortality by dialysis modality and influence of risk factors in a national cohort.

BACKGROUND: This report describes the status of renal replacement therapy (RRT), particularly continuous ambulatory peritoneal dialysis (CAPD), in Romania (a country with previously limited facilities), outlines the fast development rate of CAPD, and presents national changes in a European context. METHODS: Trends in the development of RRT were analyzed in 2003 on a national basis using annual center questionnaires from 1995 to 2003. Survival data and prognostic risk factors were calculated retrospectively from a representative sample of 2284 patients starting RRT between 1 January 1995 and 31 December 2001 (44% of the total RRT population investigated). RESULTS: The annual rate of increase in the number of RRT patients (11%) was supported mainly by an exponential development of the CAPD population (+600%); the hemodialysis (HD) growth rate was stable (+33%) and renal transplantation had a marginal contribution. The characteristics of both HD and PD incident patients changed according to current European epidemiology (increasing age and prevalence of diabetes and nephroangiosclerosis). There were significant differences between PD and HD incident populations, PD patients being significantly older and having a higher prevalence of diabetic nephropathy and baseline comorbidities, probably reflecting different inclusion policies. The estimated overall survival of RRT patients in Romania was 90.6% at 1 year [confidence interval (CI) 89.4 - 91.8] and 62.2% at 5 years (CI 59.4 - 65.0). The initial treatment modality did not significantly influence patients' survival. There was no difference in unadjusted technique survival during the first 2 years; afterwards, there was a clear advantage for HD, with more patients being transferred from PD to HD. Several factors seemed to significantly and negatively influence PD patients' survival (Cox regression analysis): male gender, lack of predialysis erythropoietin treatment, and initial comorbidities. Stratified analysis to discover the influence of these factors on patients' survival revealed that HD was associated with an increased risk of death in the younger nondiabetic end-stage renal disease population, regardless of other coexisting comorbid conditions. However, in older patients (>65 years) and in diabetics, regardless of the presence or absence of associated comorbid conditions, there was no significant difference in death rates between HD and PD patients. CONCLUSIONS: We report an impressive quantitative and qualitative development of CAPD in one of the rapidly growing Central and Eastern Europe countries. CAPD should be the method of choice for young nondiabetic end-stage renal disease patients. Improvement in predialysis nephrologic care and in transplantation rates is required to further ensure the ultimate success of the Romanian PD program.

Increased arterial stiffness in children on haemodialysis.

BACKGROUND: Measures of aortic stiffness--aortic pulse wave velocity (PWV) and augmentation index (AIx)--have been shown to be powerful predictors of survival in adult haemodialysis (HD) patients. Very few data have been reported regarding arterial stiffness in paediatric renal populations. METHODS: PWV and aortic AIx were determined from contour analysis of arterial waveforms recorded by applanation tonometry using a SphygmoCor device in 14 children on HD (age = 14.1 years) and in 15 age, height matched children controls. RESULTS: Pre-HD AIx (29.7 +/- 15.4%) and PWV (6.6 +/- 1.0 m/s) were significantly higher compared with children controls (8.3 +/- 8.0% and 5.4 +/- 0.6 m/s, respectively, P < 0.0001). The only significant difference between normal and HD children was BP level: 103/61 vs 114/72 mmHg, P < 0.05. In children of HD patients, a multiple linear regression model including BP, age, height, weight, Ca and P levels as independent variables accounted for 57% of the variability in AIx. Dialysis had no impact on AIx (post-HD: 28.5 +/- 12.7%) or on PWV (post-HD: 6.7 +/- 0.8 m/s). CONCLUSIONS: We show, in this first-ever report of increased arterial stiffness in children on dialysis, that end-stage renal disease is associated with abnormalities in arterial wall elastic properties, comparable with adult levels, even in childhood. Most importantly, the absence of a discernible amelioration with dialysis implies that purely structural and not functional alterations lie behind the increased arterial stiffness.

[The first case of coronary artery by-pass grafting surgery (CABG) in a patient on maintenance dialysis in Iasi]. / Prima operatie de by-pass coronarian la un pacient dializat cronic în Iasi.

Coronary artery disease has a significantly higher prevalence in chronic dialysis patients compared to the general population, explained by a cluster of non-specific and specific (uremia-associated) cardiovascular risk factors, typical for these patients. Nephrologists and cardiovascular surgeons worldwide are rather reluctant to offer CABG to dialysis patients, because of concerns about higher risks associated with this procedure in this frail population. However, there is an increasing opinion supporting a more aggressive management of coronary artery disease in uremic individuals. To illustrate this "positive attitude", we report here the first dialysis patient ever treated by CABG in Iasi; his good outcome was both rewarding and encouraging for us all.

Dynamics of the circadian blood pressure profiles after renal transplantation.

BACKGROUND: Abnormalities of diurnal blood pressure (BP) rhythm ("nondipping") are well-described in dialysis patients, and have prognostic importance. It is controversial whether successful renal transplantation (RTx) improves diurnal BP rhythm. To date, no study has attempted to define and model the evolution of diurnal BP rhythm profiles from dialysis to engraftment, focusing on the immediate (4-6 weeks) and medium-term (>1 year) postengraftment periods. METHODS: To test if kidney transplantation normalizes the BP profile, ambulatory blood pressure monitoring (ABPM) was performed in 20 living related transplants (age, 30.3+/-5.1 years; 11 males, on dialysis for 25.6 months) 1 month preRTx and repeated 1 month and >1 year (ABPM3) after successful RTx. Dipping was defined as a sleep-to-awake ratio>0.92 (for systolic BP) and >0.90 (for diastolic BP). RESULTS: PreRTx only 15% patients were dippers. At 1 month postRTx (creatinine clearance, 65.8 ml/min), all patients were complete nondippers. However, after >1 year postRTx (creatinine clearance, 70.4 ml/min), 40% were now dippers. Most importantly, overall, 30% of the patients improved significantly their circadian rhythm (35.3% of the initial preRTx nondippers). Despite successful renal transplantation, 55% patients maintained unchanged their nondipping profile throughout all three ABPM recordings. The only determinants of "long-term" postRTx circadian rhythm are the contemporary level of the renal function and the baseline, dialysis dipping profile: SBP3 sleep-to-awake ratio is related with serum creatinine3 (r=0.58, P=0.001), creatinine clearance (r=-0.41, P=0.036) and SBP1 sleep-to-awake ratio (r=0.48, P=0.034); similarly DBP3 sleep-to-awake ratio is related with serum creatinine3 (r=0.63, P=0.001), creatinine clearance (r=-0.471, P=0.036) and SBP1 sleep-to-awake ratio (r=0.53, P=0.016). In all, 57% of the variance in dipping status can be attributed and explained by the contribution of renal function and initial circadian variability. CONCLUSIONS: Half of the nondipper dialysis patients maintain a permanently abnormal circadian rhythm, despite successful RTx. In the short term, RTx is associated with a highly abnormal diurnal profile, exclusively related to ciclosporin dose and levels. However, in the longer term, renal transplantation leads to a significant improvement of the circadian blood pressure profile, influenced by the renal function level and by the pretransplantation dipping profile.

Intradialytic changes in reflective properties of the arterial system during a single hemodialysis session.

Increased aortic stiffness-measured as aortic augmentation index (AIx), a global stiffness marker-has emerged as a powerful predictor of survival in hemodialysis (HD). A single HD session is known to produce considerable improvement in aortic stiffness. We set out, for the first time, to examine the relative contributions to the post-HD drastic improvement in aortic stiffness of ultrafiltration rate and volume, or blood pressure (BP) changes. Aortic AIx (difference between the first and the second systolic peak of the aortic pressure waveform divided by pulse wave height) was determined hourly and recorded by applanation tonometry using a SphygmoCor device in 20 chronic HD patients (9 males, age 55.1 years). The other parameters recorded were: weight pre- and post-HD, ultrafiltration volume (UFV), hemoglobin, albumin, creatinine, urea reduction rate (URR), calcium and PTH, and BP. The dialysis significantly decreased AIx from 24.2+/-11.27% to 15.57+/-12.58% (p<0.05). In a univariate analysis, the intradialytic decrease in AIx (AIx 0-4) did not correlate with UFV, URR or with any of the biochemical markers. Significant correlations for AIx 0-4 were age (p=0.018), systolic blood pressure (SBP) at the beginning of HD (p=0.049), the intradialytic decrease in the SBP (p=0.001), and in pulse pressure (PP) (p=0.009). Multivariate stepwise regression showed that the decrease in SBP, PP, and intradialytic percentage reduction in weight explained 64.9% of the total variation in AIx 0-4. The decrease in SBP was the most important factor influencing the AIx variation (b=1.54, p=0.007). The most significant reduction in AIx was from the beginning of HD to the third hour (p=0.039), and correlated with the reduction in SBP (p=0.006) and PP (p=0.025) between the same moments. A single HD session produces a drastic improvement in aortic stiffness. The effect is not explained by the UFV depletion but is highly correlated with the decrease in SBP and PP. Further work is now needed to explore a potential role for endothelin and nitric oxide metabolism.

Acute effect of CyA A (Neoral) on large artery hemodynamics in renal transplant patients.

BACKGROUND: CyA A (CyA) may induce intrarenal vasoconstriction, endothelial dysfunction, and hypertension. There are only two contradictory reports describing the acute effect of CyA on renal resistances measured by color Doppler flowmetry. Therefore, we studied the acute influence of oral CyA on arterial haemodynamics by assessing simultaneous changes in blood pressure, applanation tonometry-derived pulse wave analysis and duplex ultrasound-derived intrarenal resistance indices. METHODS: Augmentation index (AIx) (difference between the first and second systolic peak on the aortic pressure waveform divided by the pulse pressure = AIx) was determined from contour analysis of arterial waveforms recorded by applanation tonometry using the AtCor device in 18 live-related renal transplants (11 females/7 males, age = 32.0 +/- 8.1 years, transplantation duration = 17.5 +/- 16.1 months, and mean serum creatinine = 133 +/- 70 micromol/L). All studies were performed just before (C0), and 2 hours after (C2) the oral administration of CyA. At the same C0 and C2 moments the resistive index (RI) = (peak systolic frequency shift - minimum diastolic frequency shift)/peak systolic frequency shift, and pulsatility index (PI) = (peak systolic frequency shift - minimum diastolic frequency shift)/mean frequency shift were calculated from Doppler recorded waveforms. RESULTS: Blood pressure and heart rate did not differ significantly at C0 and at C2 serum levels: 134.3/82.9 vs. 128.1/80.0 mm Hg and 72.0 vs. 71.0 beats/min, respectively, despite a marked increase in whole blood concentration (CyA(C0)= 90.8 +/- 45.9 vs. CyA(C2)= 547.4 +/- 251.3 ng/mL) (P= 0.05). Mean AIx fell significantly from 17.2 +/- 13.8 to 12.9 +/- 14.2 (P < 0.0001). There was no correlation between the extent (expressed as absolute or relative change) of the measured alteration in AIx and total administered CyA dose, or increment in blood level between C0 and C2. In support, the intake of CyA did not induce a significant increase in Doppler resistance (RI(C0)= 0.68 +/- 0.08 vs. RI(C2)= 0.70 +/- 0.09) and pulsatility indices (PI(C0)= 1.32 +/- 0.31 vs. PI(C2)= 1.33 +/- 0.28). Finally, three patients were studied twice (>1 week): one under two levels of creatinine, one with no antihypertensives, and a third receiving verapamil initially. All these maintained a significant decrease in AIx at C2 from C0 supporting the reproducibility of the phenomenon. CONCLUSION: We demonstrate that Neoral CyA acutely improves large arterial compliance function and does not induce an acute rise in intrarenal resistance in stable renal transplant subjects with normal renal function. We speculate that there may be an effect of vitamin E, the diluent vehicle in which CyA is carried (1000 IU/100 mg CyA), shown to improve endothelial function.