Rapid direct identification of positive paediatric blood cultures by MALDI-TOF MS technology and its clinical impact in the paediatric hospital setting.

OBJECTIVE: Rapid diagnostic tools are imperative for timely clinical decision making, particularly in bacteraemic patients. This study evaluated the performance of a fast, inexpensive novel in house method for processing positive blood cultures for immediate identification of microorganisms by matrix-assisted laser desorption ionization-time of flight mass spectrometry (Vitek MS bioMérieux). We prospectively analyzed the clinical impact of such method on the management of pediatric patients. RESULT: In total, 360 positive blood cultures were included. Among 318 mono-microbial cultures, in-house method achieved correct identification in 270 (85%) cultures to the species level, whilst 43 (13.5%) gave no identification, and 7 (2.2%) gave discordant identifications. Identification of Gram-negative organisms was accurate to both species and genus level in 99% of isolates, and for Gram positives accuracy was 84% to genus and 81% to species level overall, with accuracy of 100% for Staphylococcus aureus and Enterococcus to the species level. Assessment of the potential impact of direct identification in sixty sequential cases revealed a clear clinical benefit in 35.5% of cases. Benefits included timely antibiotic rationalization, change of medical intervention, and early confirmation of contamination. This study demonstrates a highly accurate in-house method with considerable potential clinical benefits for paediatric care.

CYP3A5 and CYP3A7 genetic polymorphisms affect tacrolimus concentration in pediatric patients with nephrotic range proteinuria.

PURPOSE: The purpose of this study was to investigate the potential impact of CYP3A4, CYP3A5, and CYP3A7 polymorphisms on the concentration and efficacy of tacrolimus in a cohort of pediatric patients with nephrotic range proteinuria. METHODS: Genetic variants including CYP3A5*3 (rs776746), CYP3A4*1G (rs2242480), rs4646437, and CYP3A7 rs2257401 and rs10211 were detected in 70 pediatric patients with nephrotic range proteinuria. The relationships of dose-adjusted trough concentration (C0) of tacrolimus with corresponding genotypes were investigated. RESULTS: The tacrolimus concentration in patients without CYP3A5*3 A allele was 94% higher than those with A allele (90.7 vs 54.2, P = 0.00006). The CYP3A7 rs2257401 was also associated with the concentration of tacrolimus. The C allele carriers had an obviously lower C0 than the non-carriers (62.4 vs 90.7, P = 0.001). In addition, there were significant differences in tacrolimus concentration among CYP3A7 rs10211 G carriers and non-carriers; the latter had an almost twofold C0 of the former (101.8 vs 59.6, P = 0.0004). CONCLUSIONS: Our study demonstrated the associations between CYP3A5*3, CYP3A7 rs2257401 and rs10211, and tacrolimus concentration in pediatric patients with nephrotic range proteinuria. Children with CYP3A5*3 A, CYP3A7 rs2257401 C, and rs10211 G alleles might need a higher dose of tacrolimus.

Clinico-pathological findings in a striped dolphin (Stenella coeruleoalba) affected by rhabdomyolysis and myoglobinuric nephrosis (capture myopathy).

A striped dolphin (Stenella coeruleoalba) calf stranded alive because of a Salter-Harris fracture type 1 of a caudal vertebra and remained in a provisional rehabilitation facility for 3 days where the fracture stabilization was attempted, but he died the day after bandaging. Serum and urine samples were collected during hospitalization (days 1, 2 and 3 serum and day 2 urine). Serum analysis showed increased urea, alanine transaminase, aspartate transaminase, and serum amyloid A values, while creatinine was below the lower limit. Urine analysis showed urinary protein-to-creatinine ratio of 5.3 with glomerular proteinuria. Postmortem analyses demonstrated a severe rhabdomyolysis and myoglobinuric nephrosis, suggestive of capture myopathy syndrome. We report, for the first time, the clinico-pathological changes during this condition in a striped dolphin.

[Bile salt nephropathy/cholemic nephrosis]. / Néphropathie à cristaux biliaires/néphropathie cholémique.

Bile cast nephropathy is a tubulo-interstitial nephropathy. Its diagnosis may be under-estimated. It develops in patients who have cholestatic jaundice, with high bilirubinemia. Bile salts are freely filtered through glomerulus. Under certain circumstances, it forms casts into the tubule and cause an acute tubular necrosis. The diagnosis evidence is histologic, but fulfilment of renal biopsy is often made difficult, because of the hemostatic abnormalities that patients with hepatocellular injury develop. The treatment is supportive and etiological. We report here the case of a patient who presented a drug-induced hepatic jaundice, complicated with acute kidney failure secondary to bile cast nephropathy. We present the histological diagnosis evidence.

Reduced B lymphoid kinase (Blk) expression enhances proinflammatory cytokine production and induces nephrosis in C57BL/6-lpr/lpr mice.

BLK, which encodes B lymphoid kinase, was recently identified in genome wide association studies as a susceptibility gene for systemic lupus erythematosus (SLE), and risk alleles mapping to the BLK locus result in reduced gene expression. To determine whether BLK is indeed a bona fide susceptibility gene, we developed an experimental mouse model, namely the Blk+/-.lpr/lpr (Blk+/-.lpr) mouse, in which Blk expression levels are reduced to levels comparable to those in individuals carrying a risk allele. Here, we report that Blk is expressed not only in B cells, but also in IL-17-producing γδ and DN αß T cells and in plasmacytoid dendritic cells (pDCs). Moreover, we found that solely reducing Blk expression in C57BL/6-lpr/lpr mice enhanced proinflammatory cytokine production and accelerated the onset of lymphoproliferation, proteinuria, and kidney disease. Together, these findings suggest that BLK risk alleles confer susceptibility to SLE through the dysregulation of a proinflammatory cytokine network.

A patient with nephrotic-range proteinuria and focal global glomerulosclerosis.

A young male is evaluated for nephrotic-range proteinuria, hypercalciuria, and an elevated serum creatinine. A renal biopsy is performed and shows focal global glomerulosclerosis. The absence of nephrotic syndrome suggest that glomerulosclerosis was a secondary process. Further analysis of the proteinuria showed it to be due mainly to low-molecular weight proteins. The case illustrates the crucial role of electron microscopy as well as evaluation of the identity of the proteinuria that accompanies a biopsy finding of focal and global or focal and segmental glomerulosclerosis.

Low serum immunglobulin G (IgG) during nephrosis is a predictor of urinary tract infection (UTI) in children with nephrotic syndrome.

Low serum level of IgG, complement C3 and C4 in nephrotic syndrome children may cause increased susceptibility to infection. Serum level of IgG and complements in nephrotic children (NS) with UTI has been analyzed in this cross sectional study. It was carried out in the department of Pediatric nephrology, National Institute of Kidney Diseases & Urology (NIKDU), Dhaka, Bangladesh. The study subjects were followed up prospectively for one year to see and compare the frequency of relapse of NS and UTI. Patients were selected in a nonrandom purposive technique. Nephrotic syndrome children with initial attack between 1-12 year of age were included over a period of one year. The patients were grouped into Group I - UTI positive and Group II - UTI negative depending on urine culture positivity and colony count >105 CFU/ml. Serum IgG and complements C3, C4 levels were done in both groups during nephrosis and were compared. A total of 101 children M: F 1.7:1, mean age 5.96±3.2 years were included in this study. Group I, n=45 vs. Group II, n=56. The mean serum level of IgG was low in Group I (549.91±210.71 vs. 728.64±235.81mg/dl, p<0.001). Serum IgG level less than 700mg/dl was found in 37 vs. 23 children {x² (¹) 17.52 p<0.001, OR=6.63}. Mean serum complement C3 level was also low in Group I (123.09±40.52 vs. 143.38±37.06mg/dl, p<0.05). But complement C3 and C4 level do not carry any risk of developing UTI in nephrotic children. Higher number of children in Group II were at remission (n=24) during follow up, while frequent relapsers were high in Group I (n=22). Increased frequency of UTI attack (88 episodes) was found in Group I children compared to none in Group II during follow up. So low serum level of IgG in children with NS during nephrosis can predict UTI with an odds ratio of 6.63 as well as relapse. Serum level of C3, C4 do not associated with any risk of development of UTI in NS children.

Active proteases in nephrotic plasma lead to a podocin-dependent phosphorylation of VASP in podocytes via protease activated receptor-1.

Focal segmental glomerulosclerosis (FSGS) is associated with glomerular podocyte injury. Podocytes undergo dramatic changes in their actin structure, with little mechanistic insight to date into the human disease. Post-transplantation recurrence of FSGS is the archetypal form of the disease caused by unknown circulating plasma 'factors'. There is increasing indication that plasma protease activity could be central to this disease. Using clinical plasma exchange material, collected from patients in relapse and remission stages of disease, the effects of FSGS plasma on human conditionally immortalized podocytes (ciPods) were studied. We show that vasodilator stimulated phosphoprotein (VASP) is phosphorylated in response to relapse plasma from ten consecutively tested patients, and not in response to paired remission plasma or non-FSGS controls. The phosphorylation signal is absent in human podocytes carrying a pathological podocin mutation. To test for a plasma ligand, inhibition of proteases in relapse plasma leads to the loss of VASP phosphorylation. By the use of siRNA technology, we show that proteases in the plasma signal predominantly via protease activated receptor-1 (PAR1) to VASP. Mechanistically, FSGS plasma increases podocyte motility, which is dependent on VASP phosphorylation. These data suggest a specific biomarker for disease activity, as well as revealing a novel and highly specific receptor-mediated signalling pathway to the actin cytoskeleton.

Prednisolone-glucose derivative conjugate: synthesis, biodistribution and pharmacodynamics evaluation.

This study was aimed at synthesizing and evaluating a prednisolone-glucose derivative conjugate (PDG) that was expected to increase renal biodistribution without affecting pharmacological action and to decrease the systemic side effects of prednisolone. The PDG was designed and synthesized by tethering 6-amino-6-deoxy-D-glucose (a D-glucose derivative) to prednisolone and its chemical structure was confirmed by (1) H NMR, (13) C NMR, and LC-MS. This conjugate was then subjected to in vitro and in vivo evaluation like stability studies, biological distribution, pharmacodynamics, and systemic side effects studies. In these studies, PDG not only showed significant enhancement of renal target efficiency with high values of relative uptake efficiency (RE, 24.1), concentration efficiency (CE, 8.6), and kidney targeting index (KTI, 16.3), but retained the curative potency against minimal change nephrosis (MCN). In the systemic side effects study, no osteoporosis was observed in rats after the administration of PDG for 20 days, which exhibited limited side effects. Conclusively, our findings showed a pharmacologically active conjugate with the characteristics of renal targeting and limited systemic side effects. The results implied the potential of PDG as a promising therapeutic in the treatment of renal diseases.

The effect of omega-3 fatty acids on the atherogenic lipoprotein phenotype in patients with nephrotic range proteinuria.

AIMS: Patients with nephrotic range proteinuria are known to have an increased risk of cardiovascular disease partly due to possessing the atherogenic lipoprotein phenotype. The aim of this study was to examine the effect of high dose omega-3 fatty acids on atherogenic triglyceride rich lipoproteins in patients with nephrotic range proteinuria, comparing their effect on lipoprotein profiles in age and sex matched controls. METHODS: 17 patients with nephrotic range proteinuria and 17 age and sex matched controls were studied. Fasting lipids and lipoproteins were measured before and after 8 weeks treatment with 4 g daily of omega-3 fatty acids (Omacor®). RESULTS: In patients with proteinuria treatment reduced plasma triglyceride by a mean of 0.45 mmol/l (95%CI 0.16 - 0.74, p = 0.005) and plasma very low density lipoprotein cholesterol by a mean of 0.38 (95%CI 0.01 - 0.75, p = 0.04). LDL III concentration fell from 178.8 mg/dl (61.6 - 231.0) to 96.1 mg/dl (49.3 - 204.5), p = 0.05. In patients treatment altered the LDL profile so that LDLIII which was the major subfraction present at baseline was reduced from 49.9% to 29.8% (p = 0.01). Remnant lipoproteins (RLP) also fell with a mean reduction of 3.5 mg/dl in RLP-Cholesterol (95%CI 0.1 - 6.9, p = 0.05) and 12.4 mg/dl in RLP-triglyceride (95%CI 2.6 - 22.2, p = 0.03). There was however a 0.6 mmol/l rise in LDL-C (p = 0.06) in the patients. Treatment did not alter HDL-C. CONCLUSION: In patients with nephrotic range proteinuria, omega-3 fatty acids reduced triglyceride rich lipoproteins, LDL III and remnant lipoproteins. A tendency to an increase in LDL-C was observed but this was offset by an alteration in the distribution of the LDL profile towards lighter, larger LDL particles. We propose that treatment with omega-3 fatty acids in conjunction with a statin may be the ideal therapy in these patients.

Primary focal segmental glomerulosclerosis in nephrotic patients: common complications and risk factors.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) presents a range of potentially serious complications, including acute kidney injury (AKI), infection and thromboembolism. This study aimed to find out the incidence rates and risk factors for these complications in FSGS patients. METHODS: Patients with biopsy-proven primary FSGS and nephrotic-range proteinuria were included in this study. A short-term (16-week) follow-up was performed to observe the aforementioned complications. Clinical characteristics of patients were recorded upon enrollment. AKI was diagnosed as an absolute increase in serum creatinine of ≥0.3 mg/dL or a percentage increase of ≥50% within 48 hours; infection, by a combination of clinical manifestations, laboratory tests and imaging examinations; and thromboembolism, by imaging methods. Risk factors for complications were evaluated by logistic regression model. RESULTS: The study population included 90 FSGS patients (63 males, mean age 28.9 ± 12.9 years). The incidences of AKI, infection and thromboembolism were 44.4%, 25.6% and 12.2%, respectively. Patients with AKI were more likely to be male, with lower serum albumin, greater proteinuria and more severe acute tubulointerstitial damage. Patients with infection had higher proteinuria and lower serum albumin, globulin and IgG. Circulating endothelial cells (CECs) and von Willebrand factor were higher in patients with thromboembolism. Logistic regression showed that increased urine retinol-binding protein, decreased serum albumin and IgG, and increased CECs and hemoglobin were independent risk factors for AKI, infection and thromboembolism, respectively. CONCLUSIONS: AKI, infection and thromboembolism are common among FSGS patients. Awareness of risk factors and prevention of these complications are important for the prognosis of these patients.

Proinflammatory role of angiotensin II in a rat nephrosis model induced by adriamycin.

INTRODUCTION: Nephrotic syndrome induced by adriamycin (ADR) is an experimental model of glomerulosclerosis in humans. The AT(1) receptor for angiotensin II (Ang II) is involved in the renal expression of the nuclear factor-kappa B (NF-ΚB) during this nephrosis. NF-ΚB is a transcription factor for proinflammatory effects of Ang II; however, there is no information about the role of this receptor in the renal proinflammatory events in ADR nephrosis. MATERIALS AND METHODS: To determine the role of Ang II in ADR nephrosis, Sprague-Dawley rats were treated with ADR (6 mg/kg iv). One ADR group received oral losartan treatment (15 mg/kg gavage) 3 days before ADR injection and then daily for 4 weeks, and the other group water. Animals were sacrificed at week 4 and renal macrophage infiltration, ICAM-1, superoxide anion (O(2(-))) and Ang II expressions were analysed by indirect immunofluorescence and histochemical techniques. RESULTS: ADR rats showed increased expression of ICAM-1, Ang II, O(2(-)) and macrophage infiltration, events that were diminished by losartan treatment. Ang II expression remained unaltered after antagonist treatment. Proteinuria was reduced after 3 weeks of treatment. CONCLUSIONS: These data suggest that Ang II plays a role in the inflammatory events during ADR-induced nephrosis, probably mediated by AT(1) receptors.

Lipoprotein glomerulopathy.

PURPOSE OF REVIEW: Lipoprotein glomerulopathy is a rare disorder characterized by proteinuria, renal insufficiency and disturbances in lipoprotein metabolism closely related to those observed in type III hyperlipidemia. Rare mutations in apolipoprotein E (apoE) gene may contribute to the pathogenesis of the disease. This article reviews the clinical and laboratory features of lipoprotein glomerulopathy, discusses the mechanisms that may be implicated in its pathogenesis and summarizes the currently available therapeutic options. RECENT FINDINGS: During the past years two new apoE gene mutations were described in Caucasian patients, apoE Modena (Arg150→Cys) and apoE Las Vegas (Ala152→Asp), a finding indicating that the disease may be more common in white populations than initially thought. Results from case studies suggest that fibrates improve renal pathology and may result in the complete clinical remission of the disease. LDL-apheresis or immunoadsorption onto staphylococcal protein A may also have a role in refractory cases. SUMMARY: Lipid glomerulopathy is a rare, poorly understood disorder with potentially detrimental consequences. The determination of the effects of apoE mutations on the structural and functional characteristics of the mature protein may provide new insights in the pathogenesis of the disease. Meanwhile, intensive lipid-lowering may reduce proteinuria and preserve renal function in this patient group.

Intracellular nitric oxide assessment in whole blood leukocytes by flow cytometry: optimization and applicability to monitor patients with chronic graft nephropathy.

Flow cytometry has been proposed as an alternative method for direct determination of intracellular NO by using the 4,5-diaminofluorescein-diacetate (DAF-2DA) as a fluorescent probe. In the present study, the protocol for intracellular NO determination in peripheral blood monocytes and neutrophils of by flow cytometry was optimized and applied to monitor chronic graft nephropathy patients. The optimize method consists to incubate plasma-free whole blood samples with DAF-2DA at 2.0 microM for 180 min at 37 degrees C to determine the percentage of DAF-2T+ monocytes and neutrophils. Distinct intracellular NO profiles in monocytes and neutrophils from chronic graft nephropathy patients as compared to the healthy individuals. Although the pre-incubation with LPS was able to trigger higher percentages of DAF-2T+ monocytes and neutrophils in both groups, our data demonstrated that LPS had a greater impact on monocytes as compared to neutrophils, selectively in the group of healthy individuals. Moreover, our findings demonstrated that LPS had lower impact on monocytes from chronic graft nephropathy as compared to healthy individuals. Supplementary analysis revealed that the LPS impact tends to be resorted in those patients with longer post-transplant time, as demonstrated by a significant positive correlation index. Furthermore, our results demonstrated that AG had lower inhibitory impact on neutrophils as compared to monocytes, selectively in the group of chronic graft nephropathy patients. Taken together, this study showed a new approach to monitor the immunological status of patients with chronic graft nephropathy opening new perspectives of research regarding the monocyte and neutrophil functions in patient undergoing immunosuppressive therapy.

The relationship between adiponectin levels and degree of proteinuria in patients with nephrotic and non-nephrotic proteinuria.

Adipose tissue appears to be a modulator of vascular injury and systemic inflammation. The aim of this study was to establish the relationship between plasma adiponectin concentration and severity of proteinuria in patients with proteinuria. We enrolled 77 patients with nephrotic and non-nephrotic proteinuria with normal renal function along with 38 matched controls in a cross-sectional study. These patients were divided into group 1 (n = 44, non-nephrotic proteinuria, <3.5 g/day) and group 2 (n = 43, nephrotic proteinuria, >3.5 g/day) by severity of proteinuria. Circulating adiponectin and high-sensitivity C-reactive protein (hsCRP) levels were measured using commercial ELISA. HOMA index and hsCRP levels were all significantly higher in proteinuric patients than in control subjects, while plasma adiponectin levels were significantly lower (p < 0.001). When compared to patients with non-nephrotic proteinuria, patients with nephrotic proteinuria had significantly higher plasma hsCRP and HOMA index (p < 0.001). According to the multiple regression analysis, proteinuria levels were independently related to adiponectin levels. Decreases in adiponectin levels were more prominent in patients with nephrotic proteinuria than in patients with non-nephrotic proteinuria. These results show that the reduction of plasma adiponectin concentrations depend on insulin resistance and inflammation rather than directly severity of proteinuria in patients with proteinuria.

The ACTIVE Trial: comparison of the effects on renal function of iomeprol-400 and iodixanol-320 in patients with chronic kidney disease undergoing abdominal computed tomography.

BACKGROUND: We performed a multicenter, double-blind, randomized, parallel-group study to compare the renal effects of iomeprol-400 and iodixanol-320 in patients with preexisting chronic kidney disease undergoing contrast-enhanced multidetector computed tomography of the liver. METHODS: One hundred forty-eight patients with moderate-to-severe chronic kidney disease, ie, serum creatinine (SCr) > or =1.5 mg/dL (132.6 micromol/L) and/or calculated creatinine clearance (CrCl) <60 mL/min, undergoing contrast-enhanced multidetector computed tomography of the liver were randomized to equi-iodine doses (40 gI) of either the low-osmolar agent iomeprol-400 (400 mgI/mL, 726 mOsm/kg, N = 76) or the isotonic agent iodixanol-320 (320 mgI/mL, 290 mOsm/kg, N = 72), injected intravenously at 4 mL/S, followed by a bolus of 20 mL normal saline solution at the same rate. SCr was obtained at screening, baseline and at 48 to 72 hours postdose. SCr measurements and CrCl calculations were performed by a central laboratory. Contrast-induced nephropathy (CIN) was defined as an absolute SCr increase of > or =0.5 mg/dL (44.2 micromol/L) from baseline to 48 to 72 hours postdose. Mean SCr changes from baseline were also assessed. A Renal Safety Review Board comprised 3 medical experts reviewed the renal safety data, demographics, medical history, CIN risk factors, concomitant medications, and hydration status of each subject in a blinded manner. RESULTS: The 2 study groups were comparable with regard to age, gender distribution, concomitant nephrotoxins, hydration status, and total iodine dose; however, the iomeprol-400 group showed a significantly higher proportion of patients with diabetes mellitus (P = 0.02). Baseline SCr was 1.7 +/- 0.6 mg/dL (150.3 +/- 53.0 micromol/L) in the iomeprol-400 group and 1.7 +/- 0.7 mg/dL (150.3 +/- 61.9 micromol/L) in the iodixanol-320 group (P = 0.87). Predose CrCl was 41.5 +/- 13.1 mL/Min in the iomeprol-400 group and 43.0 +/- 13.3 mL/Min in the iodixanol-320 group (P = 0.49). Five of 72 patient receiving iodixanol-320 (6.9%) and none of the patients receiving iomeprol-400 showed an increase of > or =0.5 mg/dL (44.2 micromol/L) from baseline [P = 0.025, 95% CI (-12.8%, -1.1%)]. The mean SCr change from baseline was significantly higher (P = 0.017 ANCOVA) after iodixanol-320 (0.06 +/- 0.27) than after iomeprol-400 (-0.04 +/- 0.19). CONCLUSIONS: The incidence of CIN was significantly higher after IV administration of iodixanol-320 than iomeprol-400. The mean rise in SCr from baseline was also higher in patients receiving iodixanol.

Validation of an autotaxin enzyme immunoassay in human serum samples and its application to hypoalbuminemia differentiation.

BACKGROUND: Autotaxin (ATX), a tumor cell motility-stimulating factor, regulates the blood concentrations of lysophosphatidic acid (LPA), an important and multi-functional bioactive lipid, through its lysophospholipase D activity (lysoPLD). The introduction of ATX measurements into clinical laboratory testing is urgently needed. METHODS: Anti-human ATX monoclonal antibodies were produced by immunization of recombinant human ATX expressed in a baculovirus system. An immunoassay for the quantitative determination of ATX was established, and human serum samples were assayed. RESULTS: The within-run and between-run precision, interference, detection limit, and linearity studies were satisfactory. The central 95 percentile reference interval for the serum ATX antigen concentration in healthy subjects was 0.468-1.134 mg/l (n=120) and was strongly correlated with the serum lysoPLD activity. The ATX concentration was significantly (p<0.001) higher in women (0.625-1.323 mg/l) than in men (0.438-0.914 mg/l). The serum ATX concentrations were increased in patients with chronic liver diseases and decreased in postoperative prostate cancer patients but were not altered in nephrosis patients. Thus, serum ATX antigen concentrations could be used to discriminate these hypoalbuminemia conditions. CONCLUSIONS: The present ATX antigen assay may be useful for clinical laboratory testing.

[Lipids abnormalities in children with refractory nephrotic proteinuria]. / Zaburzenia lipidowe u dzieci z nawrotami bialkomoczu nerczycowego.

UNLABELLED: The aim of the study is to evaluate the lipids disorders in children with refractory proteinuria in acute phase and remission of the disease. The study group consist of 39 children, mean age 8.2 +/- 3.9 years with refractory nephrotic syndrome (RNS)/nephrotic proteinuria (RNP), wchich were divided in 3 groups according to RNS/RNP frequency: group A--17 children up to 3 times, group B--13 children 4-9 times, group C--9 children > or = 10 times. Total number of relapses was 53. In all children at the start and every 3 months, the total cholesterol concentration (TC), LDL, HDL cholesterol, triglicerydes (TG), apolipoprotein A1(apoA1), apoliporotein B100 (apoB100 ) were measured. The duration of the study was 12 months. RESULTS: Children with NS/NP in the acute phase of the disease show high levels of TC, TG, LDL-C and apolipoproteins: apo AI, apo B100, The level of HDL-C was normal. In the groups A, B, C a normalization of average levels of apo B100, was recorded after 3 month, apo AI after 3 to 6 months. With the increasing amount of relapses the time to normalization of average levels of TC and LDL-C was prolonged. Normal average levels of LDL-C were recorded in the group A after 3 months, in the group B after 9 months, in the group C was still high. TC normalization was recorded after 6 months only in the group A, in the groups B and C the level was high; TG was high during 12 months of observation in all groups. CONCLUSION: The persistance of high TC, LDL-C and TG levels during the remission phase in children with higher numbers of NS/NP relapses is a risk factor of atherosclerosis developement.

Bacterial superantigen TSST-1 attenuates suppressive efficacy of glucocorticoids and calcineurin inhibitors against blastogenesis of peripheral blood mononuclear cells from patients with antineutrophil cytoplasmic antibody-associated vasculitis and nephrosis.

Successful immunosuppressive therapy is critical for the treatment of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and nephrosis. However, a considerable number of patients have shown clinical resistance to therapy. Bacterial infection might influence the clinical response of patients to immunosuppressive drugs, but few studies have been carried out to investigate the effect of bacterial superantigens on the efficacy of the drugs in these patients. We evaluated the suppressive efficacy of prednisolone, methylprednisolone, cyclosporine, and tacrolimus on the blastogenesis of PBMCs obtained from 12 ANCA-associated vasculitis patients (ANCA patients), eight patients with nephrotic syndrome, and eight healthy subjects. PBMC-stimulation index was calculated from the formula: [3H]thymidine incorporated in the presence of stimulant (dpm)/[3H]thymidine incorporated in the absence of stimulant (dpm). In vitro drug concentrations giving 50% inhibition (IC50s) of PBMC blastogenesis stimulated with concanavalin A (con A) or toxic shock syndrome toxin 1 (TSST-1) derived from Staphylococcus aureus (S. aureus) were calculated. The IC50 values for the four drugs evaluated in TSST-1-stimulated PBMCs were significantly higher than those evaluated in con A-stimulated PBMCs in both ANCA patients and nephrosis patients (p<0.012-0.044). Whereas, the IC50 values for these immunosuppressive drugs, except methylprednisolone, were not significantly different between con A- and TSST-1-stimulated PBMCs in healthy subjects. The stimulation index was not significantly different between the con A- and TSST-1-stimulated PBMCs in either of the subject groups. These observations raise the possibility that TSST-1 induced by S. aureus infection attenuates the clinical efficacy of glucocorticoids and calcineurin inhibitors in ANCA patients and nephrosis patients.