Lanthanum carbonate, like sevelamer-HCl, retards the progression of vascular calcification and atherosclerosis in uremic apolipoprotein E-deficient mice

Atherosclerosis and vascular calcification (VC) progression in chronic kidney disease is favored by disturbances of mineral metabolism. We compared the effect of phosphate binder lanthanum (La) carbonate with sevelamer-HCl on atherosclerosis, VC and bone structure and function in mice with chronic renal failure (CRF). Apolipoprotein E-deficient (apoE(-/-)) mice were randomized to one non-CRF and three CRF groups, fed with standard diet (one non-CRF and one CRF) or diet supplemented with either 3% lanthanum carbonate (La3%) or 3% sevelamer-HCl (Sev3%). Both La3% and Sev3% supplemented CRF mice displayed a decrease of serum phosphorus, calcification at both intimal and medial aortic sites and atherosclerosis. This was associated with a reduction of plaque Type I collagen expression by both binders and of positive nitrotyrosine staining in response to sevelamer-HCl only. Increased mineral apposition and bone formation rates in unsupplemented CRF mice were reduced by Sev3% but not by La3%. The beneficial effects of La carbonate and sevelamer-HCl on the progression of VC and atherosclerosis in CRF mice could be mainly due to a decrease in phosphate retention and likewise a reduction of arterial Type I collagen expression. The effect of La carbonate differed from that of sevelamer-HCl in that it did not appear to exert its vascular effects via changes in oxidative stress or bone remodeling in the present model.

Lupus nephritis is more severe in children and adolescents than in older adults

Objective: To evaluate clinicopathological features and treatment response in patients with lupus nephritis (LN), comparing the childhood- and late-onset forms of the disease. Methods: We retrospectively analyzed clinical presentation, treatment and evolution in patients diagnosed with LN by renal biopsy between 1999 and 2008. Patients were grouped by age-<= 18 years (n = 23); and >= 50 years (n = 13)-and were followed for the first year of treatment. Results: The baseline features of the childhood- and late-onset groups, respectively, were as follows: mean age, 15 +/- 2 and 54 +/- 5 years; female gender, 87% and 92%; hypertension, 87% and 77%; Systemic Lupus Erythematosus Disease Activity Index, 29 +/- 9 and 17 +/- 7 (p = 0.002); estimated glomerular filtration rate (eGFR), 86 +/- 66 and 70 +/- 18 ml/min; concurrent SLE/LN diagnosis, 90% and 15% (p < 0.001); crescents on biopsy, 74% and 30% (p = 0.02); activity index on biopsy, 4.8 +/- 2.6 and 3.3 +/- 1.9 (p = 0.10); and interstitial fibrosis (> 10%), 39% and 61% (p = 0.08). Treatment consisted mainly of methylprednisolone, prednisone and intravenous cyclophosphamide, average cumulative doses being similar between the groups. After 12 months of treatment, the eGFR in the younger and older patients was 116 +/- 62 and 78 +/- 20 ml/min, respectively (p = 0.005). Three of the younger patients progressed to dialysis at 12 months, compared with none of the older patients. Conclusion: Childhood-onset LN seems to be more severe than is late-onset LN. Lupus (2012) 21, 978-983.

The association between coronary artery calcification progression and loss of bone density in non-dialyzed CKD patients

Background: Coronary artery calcification (CAC) and low bone density are coexisting deleterious conditions commonly shared by chronic kidney disease (CKD) patients. In the present study, we aimed to investigate whether the progression of CAC was associated with overtime reduction in bone density in non-dialyzed CKD patients. Methods: This is a prospective study of 24 months including 72 non-dialyzed CKD patients Stages 2 - 4 (age 57.6 +/- 10.3 years, 62% male, 22% diabetics). CAC and vertebral bone density (VBD) were measured by computed tomography. Results: At baseline, 46% of the patients had CAC (calcified group) and calcification was not identified in 54% of the patients (non-calcified group). The calcified group was older, predominantly male, and had lower VBD in comparison to non-calcified group. CAC progression was observed only in the calcified group (91% of the patients increased calcium score). The multiple regression analysis revealed loss of VBD as the independent determinant of CAC progression in these patients. Conclusion: CAC progression was associated with loss of VBD in non-dialyzed CKD patients.

Hepatitis B virus infection in Haemodialysis Centres from Santa Catarina State, Southern Brazil. Predictive risk factors for infection and molecular epidemiology

Abstract Background Patients under haemodialysis are considered at high risk to acquire hepatitis B virus (HBV) infection. Since few data are reported from Brazil, our aim was to assess the frequency and risk factors for HBV infection in haemodialysis patients from 22 Dialysis Centres from Santa Catarina State, south of Brazil. Methods This study includes 813 patients, 149 haemodialysis workers and 772 healthy controls matched by sex and age. Serum samples were assayed for HBV markers and viraemia was detected by nested PCR. HBV was genotyped by partial S gene sequencing. Univariate and multivariate statistical analyses with stepwise logistic regression analysis were carried out to analyse the relationship between HBV infection and the characteristics of patients and their Dialysis Units. Results Frequency of HBV infection was 10.0%, 2.7% and 2.7% among patients, haemodialysis workers and controls, respectively. Amidst patients, the most frequent HBV genotypes were A (30.6%), D (57.1%) and F (12.2%). Univariate analysis showed association between HBV infection and total time in haemodialysis, type of dialysis equipment, hygiene and sterilization of equipment, number of times reusing the dialysis lines and filters, number of patients per care-worker and current HCV infection. The logistic regression model showed that total time in haemodialysis, number of times of reusing the dialysis lines and filters, and number of patients per worker were significantly related to HBV infection. Conclusions Frequency of HBV infection among haemodialysis patients at Santa Catarina state is very high. The most frequent HBV genotypes were A, D and F. The risk for a patient to become HBV positive increase 1.47 times each month of haemodialysis; 1.96 times if the dialysis unit reuses the lines and filters ≥ 10 times compared with haemodialysis units which reuse < 10 times; 3.42 times if the number of patients per worker is more than five. Sequence similarity among the HBV S gene from isolates of different patients pointed out to nosocomial transmission.

Acute hepatitis C virus infection assessment among chronic hemodialysis patients in the Southwest Parana State, Brazil

Abstract Background Chronic hemodialysis patients are at higher risk for acquiring hepatitis C virus (HCV). The prevalence varies among different countries and hemodialysis centers. Although guidelines for a comprehensive infection control program exist, the nosocomial transmission still accounts for the new cases of infection. The aim of this study was analyze the follow up of newly acquired acute hepatitis C cases, during the period from January 2002 to May 2005, in the Hemodialysis Center, located in the Southwest region of Parana State, Brazil and to analyze the effectiveness of the measures to restrain the appearance of new cases of acute hepatitis C. Methods Patients were analyzed monthly with anti-HCV tests and ALT measurements. Patients with ALT elevations were monitored for possible acute hepatitis C. Results During this period, 32 new cases were identified with acute hepatitis C virus infection. Blood screening showed variable ALT levels preceding the anti-HCV seroconversion. HCV RNA viremia by PCR analysis was intermittently and even negative in some cases. Ten out of 32 patients received 1 mcg/kg dose of pegylated interferon alfa-2b treatment for 24 weeks. All dialysis personnel were re-trained to strictly follow the regulations and recommendations regarding infection control, proper methods to clean and disinfect equipment were reviewed and HCV-positive patients were isolated. Conclusion Laboratory tests results showed variable ALT preceding anti-HCV seroconversion and intermittent viremia. The applied recommendations contributed importantly to restrain the appearance of new cases of acute hepatitis C in this center and the last case was diagnosed in May 2004.

Saphenofemoral arteriovenous fistula as hemodialysis access

Abstract Background An upper limb arteriovenous (AV) fistula is the access of choice for haemodialysis (HD). There have been few reports of saphenofemoral AV fistulas (SFAVF) over the last 10-20 years because of previous suggestions of poor patencies and needling difficulties. Here, we describe our clinical experience with SFAVF. Methods SFAVFs were evaluated using the following variables: immediate results, early and late complications, intraoperative and postoperative complications (up to day 30), efficiency of the fistula after the onset of needling and complications associated to its use. Results Fifty-six SFAVF fistulas were created in 48 patients. Eight patients had two fistulas: 8 patent (16%), 10 transplanted (20%), 12 deaths (24%), 1 low flow (2%) and 20 thrombosis (39%) (first two months of preparation). One patient had severe hypotension during surgery, which caused thrombosis of the fistula, which was successfully thrombectomised, four thrombosed fistulae were successfully thrombectomised and revised on the first postoperative day. After 59 months of follow-up, primary patency was 44%. Conclusion SFAVF is an adequate alternative for patients without the possibility for other access in the upper limbs, allowing efficient dialysis with good long-term patency with a low complication rate.

Physicochemical analysis of blood and urine in the course of acute kidney injury in critically ill patients: a prospective, observational study

Abstract Background Sequential physicochemical alterations in blood and urine in the course of acute kidney injury (AKI) development have not been previously described. We aimed to describe these alterations in parallel to traditional renal and acid–base parameters. Methods One hundred and sixty eight consecutive critically ill patients with no previous kidney disease, who had an indwelling urinary catheter at ICU admission and who remained with the catheter for at least two days without dialysis were included. A sample of blood and spot urine were collected simultaneously, once daily, until catheter removal or dialysis requirement. Traditional acid–base and renal parameters were sequentially evaluated in parallel to blood and urinary physicochemical parameters. Patients were classified during this period as having or not AKI and, for patients with AKI, duration (transient or persistent) and severity (creatinine-based AKIN stage) were evaluated. Results One hundred and thirteen patients (67.3%) had AKI: 92 at ICU admission and 21 during the observation period. AKI development was characterized in blood by increased values of phosphate and unmeasured anions (SIG), decreased albumin, and in urine by decreased values of sodium (NaU), chloride (ClU) as well as high urinary strong ion difference (SIDu). These alterations began to occur before AKI diagnosis, and they reverted in transient AKI but remained in persistent AKI. NaU, ClU and albumin decreased, and phosphate, SIG and SIDu increased with AKI severity progression. NaU and ClU values increased again when AKIN stage 3 was reached. Conclusions Simultaneous physicochemical analysis of blood and urine revealed standardized alterations that characterize AKI development in critically ill patients. These alterations paralleled AKI duration and severity. Future studies should consider including sequential evaluation of urine biochemistry as part of the armamentarium for AKI diagnosis and management.

Trabalho e qualidade de vida relacionada à saúde de pacientes em diálise peritoneal

OBJETIVO: Descrever e comparar a Qualidade de Vida Relacionada à Saúde (QVRS) de pacientes em Diálise Peritoneal (DP) que tinham ou não trabalho remunerado. MÉTODOS: Estudo seccional e populacional com 82 pacientes dos dois serviços de DP de Ribeirão Preto, (SP). A coleta de dados foi realizada por entrevistas entre dezembro/2009 e março/2010. Os questionário para caracterização dos pacientes, o Miniexame do Estado Mental e o Kidney Disease and Quality of Life-Short Form foram usados. Foram feitas as análises estatística exploratória uni e bivariada e a confirmatória bivariada entre variáveis independentes e as dimensões de QVRS. RESULTADOS: os pacientes com trabalho remunerado apresentavam maiores escores médios refletindo melhor QVRS para a maioria das dimensões do instrumento utilizado. CONCLUSÃO: o trabalho é uma faceta importante da vida desses pacientes e merece a atenção dos profissionais da saúde na busca de estratégias que favoreçam e incentivem sua manutenção e reinserção no mercado de trabalho.

Functional independence in patients with chronic kidney disease being treated with haemodialysis¹

PURPOSE: This study has described and analysed the functional independence of the patients served in the haemodialysis services of a countryside town in the State of São Paulo, Brazil, using the Functional Independence Measure (FIM). METHOD: The population considered was that of 214 patients being treated with haemodialysis, assessed in 2011, by means of a social, demographic and clinical report, a Mini-Mental State Examination (MMSE) and also the FIM. RESULTS: The mean age of the population under study was 58.01 years, while the mean FIM point score was 118.38 points, showing a level of complete or modified independence within this population. Even though the level of dependence found has been low, this can be highlighted, within the locomotion domain, in the activity of going up and down stairs (10.28%). Age, complications arising from haemodialysis, and comorbidities show a negative correlation with FIM. CONCLUSION: Awareness of the level of functional independence of the patients being subjected to treatment with haemodialysis is essential in order to back up intervention for the improvement of nursing assistance provided to this population.

Standard surgical treatment for benign prostatic hyperplasia is safe for patients over 75 years: analysis of 100 cases from a high-volume urologic center

OBJECTIVES: In this study, we aimed to determine the complications of standard surgical treatments among patients over 75 years in a high-volume urologic center. METHODS: We analyzed 100 consecutive patients older than 75 years who had undergone transurethral prostatic resection of the prostate or open prostatectomy for treatment of benign prostatic hyperplasia from January 2008 to March 2010. We analyzed patient age, prostate volume, prostate-specific antigen level, international prostatic symptom score, quality of life score, urinary retention, co-morbidities, surgical technique and satisfaction with treatment. RESULTS: Median age was 79 years. Forty-eight patients had undergone transurethral prostatic resection of the prostate, and 52 had undergone open prostatectomy. The median International Prostatic Symptom Score was 20, the median prostate volume was 83 g, 51% were using an indwelling bladder catheter, and the median prostatespecific antigen level was 5.0 ng/ml. The most common comorbidities were hypertension, diabetes and coronary disease. After a median follow-up period of 17 months, most patients were satisfied. Complications were present in 20% of cases. The most common urological complication was urethral stenosis, followed by bladder neck sclerosis, urinary fistula, late macroscopic hematuria and persistent urinary incontinence. The most common clinical complication was myocardial infarction, followed by acute renal failure requiring dialysis. Incidental carcinoma of the prostate was present in 6% of cases. One case had urothelial bladder cancer. CONCLUSIONS: Standard surgical treatments for benign prostatic hyperplasia are safe and satisfactory among the elderly. Complications are infrequent, and urethral stenosis is the most common. No clinical variable is associated with the occurrence of complications.

Facial lesions caused by renal osteodystrophy in a patient with chronic renal insufficiency: a case report

PURPOSE: Chronic renal insufficiency (CRI) is the last stage of a chronic renal condition in which the kidney loses its filtration and endocrine functions. Chronic endocrine hypofunction causes generalized damage to the body known as Uremic Syndrome, which affects the central nervous system as well as the cardiovascular, hematologic, dermatologic, ophthalmic, endocrine, respiratory, gastrointestinal and skeletal systems. The present study reports the case of a female patient with CRI who presented facial osteodystrophy of the osteitis fibrosa type, and highlights the main features of this condition. CASE DESCRIPTION: A 24-year old, female, Caucasian patient presented chronic glomerulonephritis recurrence and lost the transplanted kidney five years before, undergoing arteriovenous fistula hemodialysis three times a week. She presented swelling of the left masseter area with a hard consistency on palpation, covered by intact skin, swelling at the bottom of the left atrium, with a hard consistency on palpation, a mucosa-like color and absence of inflammation signs, suggesting expansive bone lesions on the face. These features were compatible with hyperparathyroidism brown tumor and/or osteodystrophy. The CT scan showed expansive bone lesions of heterogeneous appearance on the left jaw, maxilla/nasal floor, and right frontotemporal suture areas. The clinical and histopathological characteristics of the lesion, in association with PHT hormone high serum levels led to renal osteodystrophy diagnosis. The patient was referred to the nephrology services. CONCLUSION: Osteodystrophic bone alterations have a high prevalence in renal disease patients, and the dentist must take these alterations into consideration in bone lesion diagnosis for this specific group of patients.

La Restless Legs Syndrome aumenta il rischio cardiovascolare e la mortalità a breve termine nei pazienti emodializzati

Abstract Restless legs syndrome (RLS) is a sensori-motor neurological disorder characterzed by paraesthesia, dysaesthesia and irresistibile urge to move the legs especially at night. Its prevalence is much higher among dialysis patients at 12 to 62% compared to 3 to 9% in the general population. In our study we investigated the association between RLS and cardiovascular events risk and laboratory parameters in End-stage kidney disease (ESKD) patients on dialysis. We studied 100 ESKD patients undergoing hemodialysis that were enrolled in an 18-months prospective observational study. The main outcomes were the association of RLS with new cardiovascular events and cardiovascular mortality. RLS affected 31% of the study population. It was associated with female gender, gradual reduction in residual dieresis, lower albumin (P=0.039) and inflammation, but not the dialysis parameters spKt/V and URR. During observation, 47% of patients experienced new cardiovascular events (64.5% with and 39.1% without RLS; P=0.019). Mortality was 20.0% in all patients, 32.3% in those with and 14.5% in patients without RLS (P=0.04). This study confirmed the high prevalence of RLS among dialysis patients and the associations between the severity of RLS and the risk of new cardiovascular events and higher short-term mortality. Abstract Restless legs syndrome (RLS) is a sensori-motor neurological disorder characterzed by paraesthesia, dysaesthesia and irresistibile urge to move the legs especially at night. Its prevalence is much higher among dialysis patients at 12 to 62% compared to 3 to 9% in the general population. In our study we investigated the association between RLS and cardiovascular events risk and laboratory parameters in End-stage kidney disease (ESKD) patients on dialysis. We studied 100 ESKD patients undergoing hemodialysis that were enrolled in an 18-months prospective observational study. The main outcomes were the association of RLS with new cardiovascular events and cardiovascular mortality. RLS affected 31% of the study population. It was associated with female gender, gradual reduction in residual dieresis, lower albumin (P=0.039) and inflammation, but not the dialysis parameters spKt/V and URR. During observation, 47% of patients experienced new cardiovascular events (64.5% with and 39.1% without RLS; P=0.019). Mortality was 20.0% in all patients, 32.3% in those with and 14.5% in patients without RLS (P=0.04). This study confirmed the high prevalence of RLS among dialysis patients and the associations between the severity of RLS and the risk of new cardiovascular events and higher short-term mortality.

Identificazione dei fenotipi clinici dell’insufficienza renale cronica che predicono la progressione della malattia. Un’applicazione della tecnica degli alberi decisionali

The primary aim of this dissertation to identify subgroups of patients with chronic kidney disease (CKD) who have a differential risk of progression of illness and the secondary aim is compare 2 equations to estimate the glomerular filtration rate (GFR). To this purpose, the PIRP (Prevention of Progressive Kidney Disease) registry was linked with the dialysis and mortality registries. The outcome of interest is the mean annual variation of GFR, estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. A decision tree model was used to subtype CKD patients, based on the non-parametric procedure CHAID (Chi-squared Automatic Interaction Detector). The independent variables of the model include gender, age, diabetes, hypertension, cardiac diseases, body mass index, baseline serum creatinine, haemoglobin, proteinuria, LDL cholesterol, tryglycerides, serum phoshates, glycemia, parathyroid hormone and uricemia. The decision tree model classified patients into 10 terminal nodes using 6 variables (gender, age, proteinuria, diabetes, serum phosphates and ischemic cardiac disease) that predict a differential progression of kidney disease. Specifically, age <=53 year, male gender, proteinuria, diabetes and serum phosphates >3.70 mg/dl predict a faster decrease of GFR, while ischemic cardiac disease predicts a slower decrease. The comparison between GFR estimates obtained using MDRD4 and CKD-EPI equations shows a high percentage agreement (>90%), with modest discrepancies for high and low age and serum creatinine levels. The study results underscore the need for a tight follow-up schedule in patients with age <53, and of patients aged 54 to 67 with diabetes, to try to slow down the progression of the disease. The result also emphasize the effective management of patients aged>67, in whom the estimated decrease in glomerular filtration rate corresponds with the physiological decrease observed in the absence of kidney disease, except for the subgroup of patients with proteinuria, in whom the GFR decline is more pronounced.

Uremic Neuropathy: Epiemiological Study in Hemodialysis Patients

Background/Aims. Uremic Neuropathy (UN) highly limits the individual self-sufficiency causing near-continuous pain. An estimation of the actual UN prevalence among hemodialysis patients was the aim of the present work. Methods. We studied 225 prevalent dialysis patients from two Italian Centres. The Michigan Neuropathy Score Instrument (MNSI), already validated in diabetic neuropathy, was used for the diagnosis of UN. It consisted of a questionnaire (MNSI_Q) and a physical-clinical evaluation (MNSI_P). Patients without any disease possibly inducing secondary neuropathy and with MNSI score  3 have been diagnosed as affected by UN. Electroneurographic (ENG) lower limbs examination was performed in these patients to compare sensory conduction velocities (SCV) and sensory nerve action potentials (SNAP) with the MNSI results. Results. Thirtyseven patients (16.4%) were identified as being affected by UN, while 9 (4%) presented a score <3 in spite of neuropathic symptoms. In the 37 UN patients a significant correlation was found between MNSI_P and SCV (r2 = 0.1959; p<0.034) as well as SNAP (r2 = 0.3454; p=0.027) both measured by ENG. Conclusions. UN is an underestimated disease among the dialysis population even though it represents a huge problem in terms of pain and quality of life. MNSI could represent a valid and simple clinical-instrumental screening test for the early diagnosis of UN in view of an early therapeutic approach.

Utilizzo del Rituximab nel trattamento della vasculiti ANCA associate.

Introduzione. Recenti studi hanno dimostrato che il Rituximab (RTX) è un’alternativa sicura ed efficace alla ciclofosfamide nell’indurre la remissione in pazienti con severa vasculite ANCA-associata (AAV) di nuova diagnosi o recidiva. Scopo dello studio era valutare l’efficacia e la sicurezza del RTX nei nostri pazienti con AAV. Metodi. Studio retrospettivo delle caratteristiche cliniche, dei risultati e della tolleranza al RTX dei pazienti con AAV trattati presso il nostro centro da Gennaio 2006 a Dicembre 2011. Inizialmente veniva utilizzato lo schema convenzionale delle 4 somministrazioni settimanali da 375 mg/m2. Dal 2011 sulla base dell’esperienza maturata e dei nuovi dati della letteratura si decideva di non adottare uno schema fisso per le recidive, ma di somministrare una o due dosi secondo la severità della recidiva ed il rischio infettivo. Risultati. Venivano trattati 51 pazienti con AAV, 15/51 (29%) di nuova diagnosi e 36/51 (71%) ad una recidiva. La maggior parte dei pazienti con nuova diagnosi presentavano una micropoliangioite con severo interessamento renale, 5/15 (33%) erano in dialisi dall’esordio. 32/36 (89%) pazienti trattati ad una recidiva presentavano una recidiva granulomatosa di Granulomatosi di Wegener (WG). Tutti ottenevano una remissione, più rapidamente per le manifestazioni vasculitiche. 2/5 pazienti in dialisi dall’esordio recuperavano la funzione renale. Si osservavano 11 recidive in 9 pazienti con GW mediamente dopo 23.1 mesi, tutti ottenevano nuovamente la remissione. Ad un follow-up medio di 20.1 mesi si registravano 4 decessi, 3 (3/15, 20%) nel gruppo di pazienti con nuova diagnosi, uno (1/36, 3%) nel gruppo trattato ad una recidiva. Quattro pazienti sospendevano il RTX per infezioni. Conclusioni. Nella nostra casistica il RTX si è dimostrato efficace e sicuro nell’indurre la remissione in pazienti con severa AAV, sia all’esordio che alla recidiva. I pazienti con WG presentano maggior rischio di recidiva e dovrebbero pertanto essere mantenuti in terapia immunosoppressiva dopo RTX.