Cardiac Device Therapy in Patients with Chronic Kidney Disease: An Update.

Cardiovascular diseases (CVDs) and chronic kidney disease (CKD) are frequently interconnected and their association leads to an exponential increase in the risk of both fatal and non-fatal events. In addition, the burden of arrhythmias in CKD patients is increased. On the other hand, the presence of CKD is an important factor that influences the decision to pursue cardiac device therapy. Data on CKD patients with device therapy are scarce and mostly derives from observational studies and case reports. Cardiac resynchronization therapy (CRT) is associated with decreased mortality, reduced heart failure symptoms, and improved renal function in early stages of CKD. Implantable cardioverter defibrillators (ICDs) are associated with a significant reduction in the mortality of CKD patients only for the secondary prevention of sudden cardiac death. Cardiac resynchronization therapy with defibrillator (CRT-D) is preferred in patients who meet the established criteria. The need for cardiac pacing is increased three-fold in dialysis patients. CKD is an independent risk factor for infections associated with cardiac devices.

[Recent advances in molecular pathogenesis and polycystic kidney disease treatment]. / Progrese recente în patogenia moleculara si în tratamentul bolilor renale polichistice.

Polycystic kidney diseases (PKD) are common genetic disorders characterized by formation and progressive enlargement of cysts kidney, liver and other organs, leading to end stage renal disease. Regardless of the genetic defect underlying PKD, cystic epithelia seem to display common abnormalities: increased proliferation and apoptosis, loss of cellular differentiation and polarity, hypersecretion. The localization of multiples proteins, whose function are disrupted in PKD, in the primary cilium or at basal body at the base of the cilium highlight this neglected organelle as a common trigger of cystic diseases. Significant progresses have been made over the last few years towards a greater understanding of the molecular pathogenesis of cysts formation, particularly in the signaling pathways involved in cytogenesis: cAMP, mTOR, Wnt, Ras/MAPK. These advances have already brought several potential therapies targeting several key pathways of cystogenesis.

[Recent advances in molecular pathogenesis and treatment of polycystic kidney disease]. / Progrese recente în patogenia moleculara si în tratamentul bolilor renale polichistice.

Polycystic kidney diseases (PKD) are common genetic disorders characterized by formation and progressive enlargement of cysts kidney, liver and other organs, leading to end stage renal disease. Regardless of the genetic defect underlying PKD, cystic epithelia seem to display common abnormalities: increased proliferation and apoptosis, loss of cellular differentiation and polarity, hypersecretion. The localization of multiples proteins, whose function are disrupted in PKD, in the primary cilium or at basal body at the base of the cilium highlight this neglected organelle as a common trigger of cystic diseases. Significant progresses have been made over the last few years towards a greater understanding of the molecular pathogenesis of cysts formation, particularly in the signaling pathways involved in cytogenesis: cAMP, mTOR, Wnt, Ras/MAPK. These advances have already brought several potential therapies targeting several key pathways of cystogenesis.

[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.

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.

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.

[Epidemiology of biopsy-proven renal disease in Romania: data from a regional registry in north-eastern Romania]. / Epidemiologia bolii renale în Romania trecere în revista a bazei de date regionale de biopsii renale din zona Moldovei (1995-2004).

Unlike Western European countries, data on the epidemiological biopsy-proven renal disease in Eastern Europe is scarce. We aimed to analyze retrospectively the main histological renal findings, over a 10-year (1995-2004) period, in a large tertiary nephrology referral center in North-Eastern (N-E) Romania, serving a population of 4.7 million inhabitants. Clinical and biological data were also collected and correlated with histological findings. 336 renal biopsies were finally analyzed. The distribution of major clinical syndromes was: nephrotic syndrome (52%), followed by acute renal failure (19%), mild-to-moderate chronic renal failure (17%), nephritic syndrome (8%) and asymptomatic urinary abnormalities. 56.6% and 32.2% were primary and secondary glomerulopathies (GN), respectively, whereas vascular nephropathies and tubulointerstitial nephritis accounted for only 3.6 and 2% of the diagnoses. Overall, membranoproliferative (MPGN) (38%) and mesangioproliferative (MesGN) GN's (19%) were the most common primary glomerulopathies. A progressive significant decrease in the incidence of MPGN and an increase in MesGN over time were seen in our center. Analyzing other Romanian regional data, also a geographical "shift" in the prevalence of the most common primitive GN's from Eastern (E) to Western (W) Romania, similar to the N to S gradients across Europe was noted: there is a high prevalence of MPGN in the E, and a high prevalence of MesGN (including IgA nephropathy) in W Romania. These important differences in the prevalence of the most common primary GN's in E Romania may be due to lower income, education, and infrastructure levels. This hypothesis is strengthening by the higher prevalence of post-infectious and, possible, vasculitis-related GN in E Romania.

[Five years of kidney transplantation in Iasi]. / Cinci ani de transplant renal în centrul universitar Iasi.

The activity of Renal Transplant Center Iasi started in November 2000, when we realized the first renal transplant from a live donor. Since then, 46 renal transplants were successfully realized in our center, to patients aged between 13-47 years (medium age = 30 +/- 5), M/F=27/19, 25 (56.8%) of them selected from HD, 17 (39.9%) from CAPD and 4 (8.7%) pre-emptive. Medium age of donors was 49.1 years (30-64), M/F=29/17. The donors were, in 78.3% of cases, first-degree relatives (parents, siblings). In 10 cases (21.7%) the grafts were donated by "emotionally related"donors (in most cases, spouses). An urologist-cardiovascular surgeon team, performed the transplant operations. There were no important complications during operation. We had one major vascular complication (graft artery thrombosis) in a 13 years recipient, successfully resolved after thrombectomy and stenting. Immunosuppressive therapy associated induction with monoclonal antibodies anti-Tac, cyclosporine, MMF and prednisone. Eight patients from 46 (17.39%) presented acute rejection episodes and all responded at corticosteroids. Medium values of serum creatinine were: 1.54 mg% at 1 month, 1.42 mg% at 6 months, 1.44 mg% at 1 year, 1.21 mg% at 2 years, 1.38 mg% at 3 years, 1.4 mg% at 4 years and 1.2 at 5 years. The survival of patients and donors is 100% and the survival of renal graft--97.1% (one case of chronic allograft nephropathy with lost of renal function). We also present the satisfactory evolution of the 51 renal transplanted patients addressed to our center from different other renal transplantation centers in Romania for management follow-up.

[Descriptive epidemiologic study of nosocomial infections in "C.I. Parhon" hospital of Iasi]. / Studiu epidemiologic descriptiv privind infectiile nosocomiale in spitalul "Dr. C.I. Parhon" Iasi.

Nosocomial infections (NI) represent a major public health problem. The descriptive study was carried out during one year, based on a lot of 12,731 in-patients from "C.I. Parhon" hospital. The objectives of the study were assessment of NI incidence and risk factors as well as monitoring resistance to antimicrobial drugs of bacterial pathogens from the hospital. The results of the study show lower NI incidence rates: 0.27%, most of them (91.5%) being urinary tract infections in the age group 65 y and over. 42.8% of cases were associated with risk factor of diabetes mellitus, neoplasm, skin or cardiovascular chronic conditions. The main etiological agent found for the NI was pseudomonas pyocyanea resistant to antibiotics. The antibiotic sensitivity analysis for the other gram negative rods illustrates gradually acquired resistance to the third or fourth generation of cephalosporins.

Nephrology and renal replacement therapy in Romania--transition still continues (Cinderella story revisited).

UNLABELLED: INTRODUCTION. This report describes the current status of nephrology and renal replacement therapy (RRT) in Romania, a country with previously limited facilities, highlighting national changes in the European context. METHODS: Trends in RRT development were analysed in 2003, on a national basis, using the same questionnaires as in previous surveys (1991, 1995). Survival data and prognostic risk factors were calculated retrospectively from a large representative sample of 2284 patients starting RRT between January 1, 1995 and December 31, 2001 (44% of the total RRT population investigated). RESULTS: In 2003, RRT incidence [128 per million population (p.m.p.)] and prevalence (250 p.m.p.) were six and five times higher, respectively, than in 1995. The annual rate of increase in the stock of RRT patients (11%) was supported mainly by an exponential development of the continuous ambulatory peritoneal dialysis (CAPD) population (+600%), while the haemodialysis (HD) growth rate was stable (+33%) and renal transplantation made a marginal contribution. Renal care infrastructure followed the same trend: nephrology departments (+100%) and nephrologists (+205%). The characteristics of RRT incident patients changed accordingly to current European epidemiology (increasing age and prevalence of diabetes and nephroangiosclerosis). 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). Patients' survival was negatively influenced (Cox regression analysis) by age >65 years (P < 0.001), lack of pre-dialysis monitoring by a nephrologist [P = 0.01, hazards ratio (HR) = 0.8], severe anaemia, lack of erythropoetin treatment (P < 0.001, HR = 0.6), and co-morbidity, e.g. cardiovascular diseases (P < 0.001, HR = 1.8) and diabetes mellitus (P < 0.001, HR = 2.2). CONCLUSIONS: Although the rate of increase in RRT patient stock in 1996-2003 in Romania was the highest in Europe, the prevalence remained below the European mean. As CAPD had the greatest expansion, followed by HD, an effective transplantation programme must be set up to overcome the imbalance. The quality of RRT appears to be good and survival was similar to that in other registries. Further evolution implies strategies of prevention, based on national surveys, supported by the Romanian Renal Registry.

The influence of dialytic modality on arterial stiffness, pulse wave reflections, and vasomotor function.

BACKGROUND: Measurements of aortic stiffness [aortic pulse wave velocity (PWV) and augmentation index (Alx)] have been established as powerful predictors of survival on hemodialysis (HD). Abnormal endothelial-dependent and endothelial-independent vascular reactivity and increased arterial stiffness are commonly described in HD patients. There is, however, a lack of information on the comparative impact of different renal replacement therapies (RRTs) on PWV and Alx, and how these different methods might influence endothelial-dependent abnormal vasodilatation. OBJECTIVE: To describe in a cross-sectional design arterial compliance and distensibility in continuous ambulatory peritoneal dialysis (CAPD) versus HD versus renal transplant (RTx) patients, compared with age- and blood pressure-matched essential hypertensive controls. The PWV and aortic Alx were determined from contour analysis of arterial waveforms recorded by applanation tonometry in 40 CAPD, 41 HD, 20 RTx patients (with normal serum creatinine), and 20 controls with essential hypertension (all normotensive under treatment). Endothelial-dependent and endothelial-independent vascular reactivities were assessed by changes in Alx following challenges with inhaled salbutamol and sublingual nitroglycerin respectively. RESULTS: CAPD patients had significantly stiffer arteries than all other categories. The PWV was 8.29 +/- 1.09 m/ second in CAPD patients, significantly higher (p < 0.05) compared to HD subjects (7.19 +/- 1.87 m/s). Both dialysis subgroups had significantly higher PWV values compared to RTx patients (6.59 +/- 1.62 m/s) and essential hypertensive controls (6.34 +/- 1.32 m/s), p < 0.05. The Alx had a profile similar to PWV in different RRTs. All groups with the exception of CAPD subjects had a significant decrease in Alx following salbutamol. Moreover, the vasodilatation induced by either nitroglycerin or salbutamol was significantly blunted compared to HD. Overall, both dialysis categories had more abnormal responses compared to RTx patients and essential hypertensive controls. CONCLUSION: CAPD is associated with stiffer arteries and more profoundly abnormal endothelial-dependent vasomotor function, compared to matched HD subjects. These differences in arterial physical properties might explain differences seen in cardiac structure and function between the RRTs.

A clinical description of rifampicin-induced acute renal failure in 170 consecutive cases.

Rifampicin re-administration may cause immunologically mediated acute tubulo-interstitial injury. Retrospectively, 170 consecutive cases with acute renal failure (ARF) following re-treatment with rifampicin (71% males, 29% females, age 21 to 68 years) were analysed, which accounted for 12% of all ARF patients treated by two large dialysis referral centres in Romania, Timisoara and Iasi, between 1974-2001 and 1988-2001, respectively. The most frequent clinical features of rifampicin-induced ARF were: Anuria, gastro-intestinal (abdominal pain, nausea, vomiting and diarrhoea) and "flu-like" symptoms. Urine analysis revealed sterile leucocyturia in 54%, proteinuria in 31%, haematuria in 26% and haemoglobinuria in 7% of cases. Haemolytic anaemia was frequent, found in 66% of the patients; half of these had Hct values of < 30%, thrombocytopenia and also more severe renal damage (a longer anuric phase and a slower recovery of the renal function), thus suggesting a severe multi-target autoimmune aggression. The association of hepatic injury--not explained by prior hepatic disease, B or C hepatitis virus infection or history of alcohol abuse--was encountered in 17% of the cases, without a significant influence on the renal and the general outcome. The outcome of rifampicin-induced ARF is generally favourable, with complete recovery of the renal function within 30 days in 52% of the cases and within 90 days in 92% of the cases. The mortality rate was 3.5%, compared to 21% for the overall ARF population treated during the same period (p < 0.05).

Haemodialysis acutely improves endothelium-independent vasomotor function without significantly influencing the endothelium-mediated abnormal response to a beta 2-agonist.

BACKGROUND: Increased aortic stiffness markers--aortic pulse wave velocity (PWV) and augmentation index (AIx)--have emerged as powerful predictors of survival in haemodialysis (HD). Various and often contradictory abnormalities of endothelium-dependent (ED) and endothelium-independent (EID) vasomotor function, have been described in dialysis subjects, pre- and post-dialysis, using methods that are difficult to export to the clinical setting or to large prospective trials assessing their relevance. Therefore, we determined the influence of a HD session on PWV and the ED and EID vascular reactivity, employing pulse wave analysis (PWA) of the aortic waveforms, combined with provocative pharmacological stimuli known to reduce wave reflection. METHODS: PWV and aortic AIx (difference between the first and second systolic peak on the aortic pressure waveform divided by the pulse wave height) were determined from PWA of arterial waveforms recorded by applanation tonometry using a SphygmoCor device in 41 HD (20 males, age 41.8 years) and in 20 controls with essential hypertension (10 males, age 43.6 years). ED and EID vascular reactivity were assessed by changes in AIx following inhaled salbutamol and sublingual nitroglycerin (GTN), respectively, pre- and post-dialysis session. Echocardiography was performed in all patients, pre-HD and before the PWV recordings. RESULTS: Pre-HD AIx (27.9+/-11.9%) was significantly higher compared with hypertensive patients with normal renal function (16.5+/-17%, P<0.05). Dialysis significantly reduced AIx to 18.2+/-18.3% (P<0.05 compared with pre-HD AIx), a level comparable with non-renal subjects (P = NS). Overall, PWV increased following HD to 7.89+/-2.09 m/s (P = 0.004 vs pre-HD, 6.34+/-1.32 m/s in essential hypertensive patients, P<0.05); however, a 19.1% increase was seen in 29 subjects and a 9.1% decrease in the remaining 12 subjects, both P<0.05. In HD patients, either pre- or post-HD, the EID vascular reactivity is significantly greater than the ED vasodilatation elicited by a beta 2-agonist. Moreover, when compared with hypertensive patients with normal renal function, the dialysis session only improved the EID abnormality (post-HD GTN AIx(HD) = -20.8+/-22.9% vs post-GTN AIx(hypertensive) = -14.2+/-5.7%, P = NS), while it had a non-additive effect on the ED response. A smaller response to a GTN challenge was associated with a greater left ventricular mass: r =-0.42, P = 0.007. In contrast, a diminished response to a beta 2-agonist did not represent a marker for cardiac abnormalities. CONCLUSIONS: The HD session acutely restores EID but not ED vasomotor function comparable with essential hypertensive patients. Pulse-wave analysis methodology, combined with provocative pharmacological testing may be used to unveil subsets of patients with more severe cardiac structural abnormalities.

[Biological and evolutive spectrum of patients ANCA present]. / Aspecte paraclinice si evolutive la pacientii cu ANCA pozitivi.

AIM: To analyse the immuno-biological profile of patients with antineutrophil cytoplasmic antibodies (ANCA) presents. This is a retrospective study of all ANCA positives cases from Nephrology Clinic Iasi during five years (1998-2003) on a cohort of 97 patients. RESULTS: pANCA was positive in 28, cANCA was positive in 60 and the others had pANCA and cANCA. The diseases ANCA associated were: systemic vasculitis, rapidly progressive glomerulonephritis (GNRP), chronic renal failure of an unknown etiology. ANCA presence was associated with inflammatory syndrome in 83.5%, anemic syndrome in 71.1%. From the patients with renal disfunction (71.1%), half of them presented an increased level of creatinine (>6 mg%). Renal biopsy proven especially crescentic glomerulonephritis. The complications and the diseases were more frequent in cANCA cases. CONCLUSIONS: cANCA presence is a negative prognosis factor in vasculitis; testing ANCA alone cannot be used to guide treatment.

[Risk of sudden death in patients with chronic renal failure and hemodialysis]. / Riscul mortii subite la pacientii cu insuficienta renala cronica hemodializati.

Cardiovascular mortality in uremic patients treated by hemodialysis overrates ten times cardiovascular mortality in general population. Approximatively 40% of patients on iterative hemodialysis die from cardiac diseases, half of cases by sudden death. Several risk factors for sudden death are well known: QTc interval prolongation, decrease of RR interval <750 msec, decrease of heart rate variability, presence of late ventricular potentials (LVP), presence of high risk ventricular extrasystoles, decrease of ejection fraction (EF) <40 %, presence of left ventricular hypertrophy. Our study evaluated the above-mentioned risk factors for sudden death in patients with chronic renal failure on hemodialysis. We studied 37 patients, 22 males and 15 females, with mean age of 42 years old, without diabetes, heart failure and arrhythmias, without myocardial ischemia on ECG, being on hemodialysis (HD) programme for minimum 1 year (HD parameters are: 4 h x 3/week, qB = 300 ml/min, buffer = bicarbonate, Ca dialysate = 1.75 mmol/l, K dialysate = 2.1 mmol/l, conductivity = 135 mS). The patients were evaluated by echocardiography, standard and Holter ECG. Statistics evaluation was performed in SPSS v.9.0. Program. The results proved that 80% of patients on HD have risk factors for sudden death, which are closely related with age and hyperhydration. Statistics proved that presence of high-risk arrhythmias is connected with heart rate variability and prolongation of QTc interval (favored by HD). 50% of our patients have 2 to 4 risk factors for sudden death, which increase incidence of sudden death in patients on HD.

[Retrospective study of 97 ANCA-positive patients: epidemiologic and clinical spectrum]. / Analiza retrospectiva a 97 de cazuri cu ANCA pozitivi: aspecte epidemiologice si clinice.

UNLABELLED: We analysed the clinical profile of antineutrophil cytoplasmic antibodies (ANCA) positive patients in a retrospective study including all cases of ANCA positivity (determined by ELISA) from the Nephrology Clinic, Parhon University Hospital Iasi during the interval 1998-2003. There were 97 ANCA positive patients (mean age 43.7 s18-75t years, female/male ratio 1.55), of whom almost two thirds had c-ANCA, almost one third p-ANCA, while 9 patients had both types of antibodies. The incidence was 22.5/pmp for the North-Eastern province of Romania. Just 19.3% from the suspected cases with ANCA-associated disease were positive for these antibodies. 47.7% had systemic vasculitis (10 with microscopic polyangiitis--MA, 6 with Wegener's granulomatosis--WG, 1 with Churg-Strauss angiitis, 29 with non-specific vasculitis--NSV). Twenty-seven (27.8%) had connective tissue disease--CTD (systemic lupus erythematosus, rheumatoid arthritis, polymyositis, systemic sclerosis, mixed connective tissue disease, and sarcoidosis), while in 5 cases ANCA were associated with other diseases. Nine cases presented with rapid progressive glomerulonephritis (RPGN) without signs of systemic involvement, and other ten with advanced chronic renal failure (CRF). The most frequent clinical manifestations involved the kidney (71%), the skin, the muscles and joints, and the cardiovascular system. CONCLUSIONS: ANCA positivity is associated with a wide spectrum of diseases, mostly with CTD and NSV. c-ANCA was predominantly seen in WG and advanced CRF, while p-ANCA was associated with MA. In nonspecific vasculitis and connective tissue diseases, both patterns were present. We recommend ANCA determination as a screening method in all cases with renal dysfunction and nephritic syndrome and/or with signs of systemic vasculitis and/or collagenosis.

A retrospective 5-year study in Moldova of acute renal failure due to leptospirosis: 58 cases and a review of the literature.

BACKGROUND: Renal involvement [as acute renal failure (ARF)] is a prominent feature of both mild and severe leptospirosis-a re-emerging infectious disease. Few large series describe in detail clinical and laboratory features of cases with ARF and their outcome. METHODS: We performed a retrospective analysis (1997-2001) of all consecutive, serological confirmed leptospirosis cases with ARF (n=58, 53 male, age 44+/-13 years, rural residents=31%, animal contact=88%. RESULTS: Clinical manifestations (>50% prevalence): oliguria 95%, fever and jaundice 93%, nausea and vomiting 83%, haemorrhagic diathesis 80%, headache, hepatomegaly 76%, myalgias, abdominal pain 70%, hypotension 62%, disturbed consciousness 50%. A pattern of multiple organ failure (MOF) was frequent: ARF together with hepatic failure in 72%, respiratory failure in 38%, circulatory failure in 33%, pancreatitis in 25% and rhabdomyolysis in 5% of cases. Renal dysfunction: 35% of cases had a renal K(+)-wasting defect and 43% a FE(Na)(+)>1% and low-osmolarity urine despite volume depletion. Haematuria was encountered in 12 and mild proteinuria in 10 subjects. OUTCOME: 26% deaths, 64% normal hepatic and renal function at 90 days from presentation (however 29% maintained the initial tubular defect), 10% persistent mild renal failure. All deceased patients had, beside ARF, at least two other organ failures, affected consciousness, and haemorrhagic diathesis vs a prevalence for the above features of only 34, 33, and 72%, respectively, in the survivors group (P<0.05). CONCLUSIONS: Leptospirosis presenting with ARF is a severe disease, frequently leading to MOF and to death in one-third of the patients. In particular, the haemorrhagic diathesis and cerebral involvement are markers for unfavourable patient and renal outcomes.

Haemodialysis increases QT(c) interval but not QT(c) dispersion in ESRD patients without manifest cardiac disease.

BACKGROUND: HD has been reported to determine an increase in QTc interval and QTc dispersion (QT(max)-QT(min))-risk factors that predispose to severe ventricular arrhythmias and sudden death. However, most studies have included end-stage renal disease (ESRD) patients with significant heart pathology. We therefore aimed to study the impact of a single HD session in subjects without manifest cardiac disease. METHODS: Sixty-eight stable, non-diabetic HD patients (47.1% males, age 40.2+/-12.7 years, HD duration 57+/-36 months and 37% hypertensive), with normal maximal ECG stress test and sub-endocardiac viability index and without ECG left ventricular hypertrophy were included. QT interval was calculated 10 min pre- and post-HD, as an average of three consecutive complexes, and corrected for heart rate using Bazett's formula (QTc=QT/(R-R)(1/2)). Na(+), K(+), Ca(2+), PO(4), pH and BP levels were also determined pre- and post-HD. RESULTS: The QTc interval increased significantly post-HD to 434+/-29 from 421+/-26 ms pre-HD (P=0.005); an abnormally prolonged QTc (>440 ms) was recorded in 34% cases pre-HD and in 46% post-HD, i.e. 1.5-2.3 times higher than in the high risk EURODIAB IDDM population. However, this effect was not homogeneous. Only 47 subjects had an increase in QTc duration after a dialysis session, while in 21 a decrease in QTc duration was recorded. The increase in QTc post-HD correlated with Ca(2+) homeostasis. Patients with greater increases in QTc after dialysis had higher baseline plasma calcium levels (r=0.47, P<0.001); also, a larger decrease in Ca(2+) post-HD correlated with higher increases in QTc interval (r=0.33, P<0.05). In contrast with QTc behaviour and with data from the literature, in this young HD population without manifest cardiac disease and with a low prevalence of HTA, post-HD QTc dispersion was similar to pre-HD values, increasing in only 39 patients. Furthermore, changes in QTc dispersion were not related to changes in electrolytes and BP following dialysis. However, changes in QTc dispersion and in QTc interval were directly correlated (r=0.37, P=0.42). There were no relationships between pre-HD measured echocardiographic variables, including: LV ejection fraction, internal diameters, wall thickness, mass and mass index and baseline or changes in QTc or QTc-d. CONCLUSIONS: Haemodialysis increases the QTc interval in ESRD patients, mainly related to rapid changes in electrolyte plasma concentrations. However, the impact on QTc dispersion is less important in the absence of significant coexisting cardiac disease.

[Cardiovascular risk after renal transplantation(II): ischemic heart disease, hypercholesterolemia, hyperhomocysteinemia and smoking]. / Riscul cardiovascular dupa transplantul de grefa renala (II): cardiopatia ischemica, hipercolesterolemia, hiperhomocisteinemia si fumatul.

Cardiovascular disease is the main cause of death in end-stage renal failure treated by hemodialysis or peritoneal dialysis. Though reduced in renal transplant recipients compared to the dialysis population, an excess cardiovascular mortality is still present after transplantation. The authors are reviewing the main data on mortality in the renal transplant population, focusing on major risk factors: ischaemic heart disease, hypercolesterolemia, smoking, hyperhomocysteinemia. The presence of these factors and the extent of cardiac and vascular abnormalities in the dialytic patient are closely related to outcomes in the post-transplant period. It is thus mandatory to approach and minimize all these in the dialytic and even predialytic period of chronic renal failure in order to reduce renal transplant mortality in patients with functioning grafts. Finally, an algorythm in managing cardiovascular disease pre- and post-transplantation is proposed.