Infectious complications in HIV-infected kidney transplant recipients.

Renal transplantation is now a viable alternative for dialysis in HIV-infected patients who achieve good immunovirological control with current antiretroviral therapy regimens available. However, there are few studies that analyze the incidence of post-transplant infections in this population. In this study, a retrospective analysis of data files of 24 HIV-infected kidney transplant (KT) recipients was undertaken, matched to 21 non-infected controls. All patients received induction with anti-interleukin-2 antibodies and were followed in the Pitié-Salpêtrière Hospital in Paris, France. The rate of incidence of post-transplant infections was 23.58 and 26.98/100 patient-years, in HIV-infected and HIV-negative groups (relative risk [RR]: 0.90; 95% confidence interval [CI]: 0.58-1.39; p = 0.63). In HIV-infected KT recipients, bacterial infections were the most frequent (67.7%), followed by viral (14.7%) and fungal and parasitic infections (8.8%). Similar trends were seen in the control group. Incidence of opportunistic infections was similar in HIV-infected KT recipients and controls (38.2 vs. 26.5%; p = 0.44). There were three post-transplant HIV reactivations in two patients, secondary to poor adherence to medication. HIV status did not influence survival, but infections increased the risk of unfavorable outcome. Incidence of post-transplant infections was similar in HIV-infected KT recipients and controls. Infections, but not HIV status, had adverse effects on patient and graft survival.

NUTRITIONAL OR ACTIVE VITAMIN D FOR THE CORRECTION OF MINERAL METABOLISM ABNORMALITIES IN NON-DIALYSIS CHRONIC KIDNEY DISEASE PATIENTS?

CONTEXT: Benefits of vitamin D therapies in chronic kidney disease (CKD) are debated. OBJECTIVE: To compare the effects of medium-term native (VitD) and active (VDRA) vitamin D on parameters of mineral metabolism and arterial function in non-dialysis CKD. DESIGN: Open-label, active comparator, randomized study. SUBJECTS AND METHODS: Forty-eight adult patients, vitamin D naïve, CKD stage 3 to 5 with increased parathyroid hormone (iPTH) were randomized to receive either oral cholecalciferol 1000UI/day (n=24) or paricalcitol 1mcg/day (n=24) for 6 months. Median changes at end of study vs. baseline in serum calcidiol, iPTH, total alkaline phosphatase (ALP), and cardio-ankle vascular index (CAVI) were the efficacy parameters. RESULTS: Higher increase in calcidiol (15.5 [95%CI 13.3; 17.2] vs. 0.4 [95%CI -6.1; 3.7]ng/mL, p<0.001) were found in VitD group. Conversely, the decline of iPTH (-35.2 [95%CI -83; 9] vs. 13.3 [95%CI -8.1; 35]pg/mL, p=0.008) and ALP (-34 [95%CI -58; -11] vs. -10 [95%CI -23; -2]U/L, p=0.02) were greater after paricalcitol. More subjects experienced iPTH decrease in VDRA group (71% vs. 39%, p=0.03). The variation in CAVI and the incidence of hypercalcemia and hyperphosphatemia were similar. CONCLUSIONS: It seems that secondary hyperparathyroidism was more efficiently treated by VDRA, whereas cholecalciferol better corrected the calcidiol deficiency in non-dialysis CKD.

THE PREVALENCE OF BIOCHEMICAL ABNORMALITIES OF CHRONIC KIDNEY DISEASE. MINERAL AND BONE DISORDERS IN UNTREATED NON-DIALYSIS PATIENTS - A MULTICENTER STUDY.

BACKGROUND: There are scarce data about prevalence of mineral metabolism (MM) disorders in Romanian predialysis patients, so we assessed their occurrence and relationships in mild to severe chronic kidney disease (CKD). METHODS: One hundred fifteen non-dialysis CKD (eGFR 31, 95% CI 29-35mL/min) and 33 matched non-CKD subjects entered this multicentric, cross-sectional study. Serum 25-hydroxyvitamin D (25OHD), intact parathyroid hormone (iPTH), phosphate (PO4), total calcium (tCa) and alkaline phosphatase (AP) were measured, along with demographic and past medical history data. RESULTS: Hypovitaminosis D was equally prevalent in Controls and CKD (91% vs. 96% had 25OHD<30ng/mL). Increasing proportions of hyperparathyroidism (33% - stage 2 to 100% - stage 5; p<0.001) and hyperphosphatemia (2% - stage 3 to 38% - stage 5; p<0.001) were found. Hypocalcemia was more prevalent in stage 5 (25% vs. 6% in stage 4, none in stage 3 and Controls, p<0.001). Mineral metabolism parameters correlated with eGFR. In addition, iPTH was directly associated with PO4, AP, and urinary albumin-to-creatinine ratio (ACR), but inversely with tCa and 25OHD, while negative correlation of 25OHD with age, AP, ACR, and C-reactive protein emerged. In multiple regression, eGFR was the only predictor of iPTH (Beta -0.68, 95%CI -1.35 to -0.90, R2 0.46, p<0.001), whereas age and ACR were the determinants of 25OHD (a model which explained 14% of its variation). CONCLUSIONS: Hypovitaminosis D was very common irrespective of CKD presence and severity, and it seems worsened by older age and higher albuminuria. Hyperparathyroidism preceded hyperphosphatemia and hypocalcemia, and it seems mostly dependent on kidney function decline.

Venous versus arterial iron administration in haemodialysis. Influence on erythrocytes antioxidant parameters.

Introduction Intravenous iron administration in patients treated by haemodialysis for end stage renal disease can exacerbate oxidative stress by increasing the level of free redox active iron. A way to reduce the impact of iron on oxidative stress in haemodialysis patients may be the administration of iron through arterial extracorporeal circuit. Objective The aim of our study was to compare the influence of iron route of administration (venous versus arterial extracorporeal circuit infusion) on antioxidant parameters in red blood cells of haemodialysis patients in order to clarify if arterial iron administration can have positive impacts related to iron induced oxidative stress. Method Twenty stable patients on regular haemodialysis treatment were selected for the study. They were investigated in a cross-over design at 3 mid-week HD sessions, one week apart, without iron [HD basal] and with either IV infusion of 100mg iron sucrose over the first 20 minutes of HD session, via venous line [HDvenous], or the same solution infused on the arterial extracorporeal circulation [HDarterial]. Blood samples were drawn at 0 min, 40 min and 270 min. Erythrocytes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) activity, non-protein thiol levels and total antioxidant capacity (TEAC) were analysed. Conclusion Haemodialysis significantly decreases the total antioxidant activity in erythrocytes. Iron supplementation, through venous or arterial extracorporeal route has no impact on the total antioxidant activity in red blood cells. Venous iron administration increases GPx activity in erythrocytes suggesting increased lipid peroxidation compared with arterial extracorporeal administration.

Histological diagnosis and risk of renal vein thrombosis, and other thrombotic complications in primitive nephrotic syndrome.

BACKGROUND: The risk of thromboembolic events is increased in patients with nephrotic syndrome (NS) as compared with other medical conditions and is a severe complication associated with significant morbidity and mortality. We aimed to assess the risk of renal vein thrombosis, and other venous thromboembolic events (VTE) in a large cohort of patients with NS and to identify the disease-specific risk for VTE. PATIENTS AND METHODS: We performed a prospective observational study including consecutive adult patients with primitive NS admitted to our department. Clinical and biological data were obtained every six months during follow-up. Occurrence of VTE confirmed by imaging techniques was the primary study outcome. RESULTS: We enrolled 191 patients (47±15 years, 53% men) with a median follow-up of 24 [IQR:12,36] months. During follow-up, 23 VTE occurred, of which 65.2% in the first six months. The disease-specific risk of VTE during the follow-up period was different across the histological groups, with the lowest risk in minimal change disease and IgA nephropathy and the highest in membranous nephropathy and membranoproliferative glomerulonephritis patients. In the subgroup of membranous, the severity of the subepithelial electron dense deposits did not correlate with the risk for VTE (p=0.5). CONCLUSIONS: In this prospective study, the risk of VTE was higher in the first six months of follow-up in NS patients. The histological pattern seems to influence the risk of VTE in this setting.

A rare case of digestive hemorrhage in an elderly patient: diagnosis and treatment difficulties.

Abdominal pain represents one of the most common clinical conditions. However, there are some challenging cases in which an extensive work-up is mandatory for the diagnosis. We present the case report of a 65-year-old man admitted to our department for diffuse abdominal pain, nausea, vomiting, diarrhea, painful joints and rectal tenesmus. He initially had an urticarial rash, followed by palpable purpura involving the lower extremities. The diarrheic stools evolved towards melena. Endoscopic examination of the upper gastrointestinal tract showed hiatal hernia, superficial erosions in the stomach and multiple areas of deep and superficial ulcerations disseminated from the second to the third portion of the duodenum. Terminal ileum intubation at colonoscopy showed redness, edema, swelling, petechiae and ecchymosis, irregular erosions and ulcers. Endoscopic biopsy specimens showed non-specific inflammation. Computed tomography showed moderate ascites, small pleural effusion, mesenteric lymphadenopathy and small bowel wall thickening at the level of the second duodenum, proximal jejunum and segments of ileum. The urine analysis revealed microscopic hematuria with nephrotic range proteinuria, red cells and cellular casts. Therapy with corticosteroids and pulses of cyclophosphamide was started with significant clinical improvement. Three weeks after the first admission, the patient developed an acute peritonitis due to an intestinal perforation and acute mesenteric ischemia of the small bowel. We concluded that the patient had a Henoch-Schönlein type vasculitis with acute mesenteric ischemia and perforation of the small bowel.

Myofibroblast involvement in tubular basement membrane remodeling in type II diabetic nephropathy.

Diabetic nephropathy is always accompanied by tubulointerstitial damage. The mechanisms and the cells involved are not entirely clarified. The damaged tubules may regenerate or undergo necrosis or apoptosis. The purpose of this work was to investigate the structural transformations of both interstitial cells and extracellular matrix of the kidney stromal area in patients with type II diabetes mellitus associated with diabetic nephropathy. Tubulointerstitial fibrosis is characterized by loss of renal tubules and interstitial capillaries and the accumulation of extracellular matrix proteins. Tubular basement membranes were found to be a target of the remodeling process of the stromal area. Thickening, splitting and duplication were the main lesions of these membranes. Much attention has been focused on the importance of myofibroblasts in the progression of renal fibrosis. The results represent strong arguments for a direct involvement of myofibroblasts in the process of renal interstitial remodeling, tubular basement membrane thickening, and stromal fibrosis in the late stages of diabetic nephropathy.

Oxidative stress parameters in hemodialysis patients with or without diabetes.

Oxidative stress (imbalance of antioxidant and prooxidants in favour of the later) is considered to be a feature of diabetes and chronic renal failure. Carbonyl stress defined as accumulation of reactive carbonyl compounds due to excess production or disturbed clearance from the body is thought to amplify oxidative stress in these conditions. The accumulation of carbonyl compounds can be also a consequence of oxidative stress. A vicious cycle can thus be formed. We have studied the association between carbonyl stress markers (dicarbonyl compounds, Amadori products) and oxidative stress markers (total plasmatic thiols and malondialdehyde level) in hemodialysed patients with or without diabetes taking into account the levels of possible excess substrates (glucose and triglycerides). We have concluded that hemodialysed diabetes patients are more susceptible to oxidative stress than hemodialysed patients without diabetes.

Comparison of genomic profiles of Escherichia coli isolates from urinary tract infections.

Formally included in the larger category of extraintestinal pathogenic Escherichia coli (ExPEC), the uropathogenic E. coli remains the most frequent cause of urinary tract infection (UTI), an important endemic health problem. The genomic DNA of E. coli urinary isolates from adults diagnosed with urinary tract infections and of E. coli fecal isolates from healthy subjects was analysed by PCR for the presence of virulence factor encoding genes pap, sfa/foc, afa, hly and cnf and by field inversion gel electrophoresis (FIGE) fingerprinting of XbaI DNA macrorestriction fragments. The aim was to obtain more detailed microbiological data regarding the community circulating strains in respect of their virulence potential and genetic relatedness. Almost 70% of the urinary strains carried at least one of the target virulence genes, and only 35.5% of the fecal E. coli strains were positive in the PCR screening. Taking into account the virulence genotypes exhibited, a part of the strains isolated from the urinary tract could be defined as belonging to the ExPEC pathotype. A unique FIGE profile was obtained for each of the selected isolates and the dendrogram generated by Taxotron software package analysis suggested a polyclonal population of potential uropathogenic strains clustered into 14 groups of only 60% similarity. For better understanding the epidemiology of UTIs, diseases commonly caused by such a heterogeneous species like E. coli, molecular analysis methods could be essential due to their increased power of identification and fingerprinting.

Nephrology and renal replacement therapy in Romania.

BACKGROUND: In the context of the transformation of the Health Systems of Central and Eastern European countries, the role of professional associations is increasing, especially as regards data collection, analysis, and implementation of programmes for development of nephrology and renal replacement therapy (RRT). METHODS: The Romanian Renal Registry sent questionnaires to the heads of Haemodialysis and Nephrology Centres. The need for renal replacement therapy was deduced from the annual incidence (127 patients p.m.p.) of chronic renal failure. RESULTS: Although the rates of increase in the numbers of Nephrology Departments (+82%), HD Centres (+142%), and total number of patients alive on RRT (+196%) from 1991 to 1995 were higher than the European mean, only 27-30% of the incident patients (459 of 1000-1200 patients) could be provided with RRT. Sixty-two percent of the need for RRT in the age group 25-44 years was met, while only 20% of children (age < 15 years) and people over 55 years requiring RRT received this treatment. Primary renal diseases in patients on RRT were glomerulonephritis (49%) or interstitial nephropathies (23%); diabetic nephropathies, nephroangiosclerosis and systemic diseases were rare (4, 2, and 1% respectively). Most of the CRF patients (88%) were treated by HD. Renal transplantation and peritoneal dialysis were seldom performed (8 and 4%). The cost of HD treatment in Romania (87 USD) is low, even though dialyser reuse is not common practice. CONCLUSIONS: The increase in renal replacement therapy in Romania was mainly due to the expansion of the number of haemodialysis centres. Although a significant progress was realized, only one-third of the patients needing RRT could be treated in Romania in 1995.

Effect of hemodialysis on lipid peroxidation and antioxidant system in patients with chronic renal failure.

Plasma and blood lipid peroxidation, activity of erythrocyte superoxide dismutase (SOD), and serum antioxidant activity (AOA) in uremic patients were examined before and 15 and 30 minutes after the start of dialysis. Hemodialysis was found to produce increased lipid peroxidation in plasma and blood and a simultaneous decrease of SOD activity. The extracellular antioxidant systems were evaluated by the assay of ceruloplasmin level, which did not modify significantly during the dialysis. Our data indicate that the time since the start of dialysis is an important, but not unique factor, influencing possible oxidative damage during hemodialysis.