Furthermore, testing of sera with individual peptides of each pro

Furthermore, testing of sera with individual peptides of each protein showed that rabbit antibodies recognized several linear epitopes that were scattered throughout the sequence of each protein. Interestingly, in previous studies using pools of synthetic peptides, all of these proteins have been shown as major T cell antigens in humans, and the linear T cell epitopes of Rv3874 and Rv3875 were found scattered throughout the sequence Alectinib ic50 of these proteins [10, 11]. A further

analysis of the sequence of each protein for B cell epitope prediction using ABCPred Prediction server, which is based on artificial neural network [37], also showed that B cell epitopes are scattered throughout the sequence of each protein (Fig. 5A, B and C for Rv3874, Rv3875 and Rv3619c, respectively).

Thus, both prediction and experimental results for B cell epitopes confirm the strong immunogenicity of Rv3874, Rv3875 and Rv3619c proteins for inducing polyclonal and antigen-specific antibody Selleck Birinapant reactivity in rabbits. In conclusion, the present study shows that pGES-TH-1 vector is useful in obtaining highly purified recombinant preparations of Rv3874, Rv3875 and Rv3619c proteins of M. tuberculosis. All of these recombinant proteins were immunogenic in rabbits, and antibody epitopes were scattered throughout the sequence of each protein. These results suggest that pGES-TH-1 vector could be useful in obtaining pure recombinant proteins, predicted to be encoded by hypothetical genes present in M. tuberculosis-specific genomic regions, for their immunological characterization. This work was supported by the Research Administration Grant YM 01/03 and the College of Graduate Studies, Kuwait University, Kuwait. We are thankful to Prof. Suhail Ahmed for providing pGES-TH-1 vector. Rabbits were immunized and handled according to established IACUC-approved protocols

at Kuwait University, Kuwait. “
“Sarcoidosis is an inflammatory disease. Epidemiological and treatment studies suggest that fungi play a part in the pathogenesis. The aim of this work was to study Bay 11-7085 the effect of fungal cell wall agents (FCWA) on the in vitro secretion of cytokines from peripheral blood monocytes from subjects with sarcoidosis and relate the results to fungal exposure at home and clinical findings. Subjects with sarcoidosis (n = 22) and controls (n = 20) participated. Peripheral blood mononuclear cells were stimulated with soluble or particulate β-glucan (S-glucan, P-glucan), chitin or lipopolysaccharide (LPS), whereafter tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and IL-12 were measured. The severity of sarcoidosis was determined using a chest X-ray-based score. Serum cytokines (IL-2R, IL-6, IL-10 and IL-12) were determined. To measure domestic fungal exposure, air in the bedrooms was sampled on filters.

003 and 0 006) For example, 1 kg increase in birth weight will l

003 and 0.006). For example, 1 kg increase in birth weight will lead to 4.7 and 4.2 capillaries/mm2 decrease in BCD and MCD, respectively. Within the twin infants, there were no significant differences SCH727965 concentration in BCD or MCD between infants with LBW or NBW (mean difference 3.3 capillaries/mm2; 95% CI: −1.8 to 8.5; p = 0.19, and mean difference 3.7 capillaries/mm2; 95% CI: −3.1 to 10.5; p = 0.27, respectively), whereas in the singleton infants both BCD and MCD were significantly higher in LBW infants (mean difference

10.5 capillaries/mm2; 95% CI: 6.6–14.4; p < 0.0001, and mean difference 11.1 capillaries/mm2; 95% CI: 7.4–14.7; p < 0.0001, respectively). We could not rule out for the possibility that the lack of significant difference in BCD and MCD between twin infants with LBW or NBW was due to the small number of infants. In the whole cohort, BCD Ku-0059436 cell line (r = −0.45, p < 0.0001) and MCD (r = −0.52, p < 0.0001) were inversely correlated with birth weight (Figure 2). This is consistent with the result in Table 2. The main finding of this study is that twin infants born to normotensive mothers tend to have higher functional and structural skin capillary densities at birth compared to singleton infants. To our knowledge, this is the first study to evaluate the capillary microcirculation in twin infants and shows that they do not have capillary rarefaction at birth contrary to studies

conducted when they are older children or adults which have shown significant microvascular structural alterations including narrower retinal arterioles [37]. We have recently reported, contrary to our expectations, that LBW singleton infants do not have capillary rarefaction at birth but rather higher capillary density [1, 14]. These results suggest that genetic

factors and Vorinostat supplier not birth weight per se may have a significant role in the predisposition to adult-life cardiovascular disease and hypertension [16, 31]. Of interest in our current study is that twin infants with NBW had capillary density similar to those with LBW, and there were no significant differences in BCD or MCD between the two groups. The significance of this finding is difficult to translate but one may postulate that the remodeling of the microcirculation in twin infants with LBW may be of distinctive functional significance than in LBW singleton infants; however, longitudinal studies are necessary to further examine assumption. Another possible explanation for the higher capillary density in twin infants is the recent finding that normotensive women carrying twins had approximately twofold higher circulating angiogenic factors than did normotensive women with singleton pregnancies [33]. Several studies in singleton infants have shown a strong relationship between LBW and retinal vasculature size in older children [12, 29, 38], adolescents [17], and adults [11, 19].

The mean length of right kidney (female) was 10 05 cm,

The mean length of right kidney (female) was 10.05 cm, GW-572016 manufacturer 9.63 cm, 9.63 cm by peroperative, USG & CT IVU measurement respectively. Mean of split GFR, (DTPA) of right kidney in male was 44.99 ml/min & in female it was 41.62 ml/min. Mean of total DTPA GFR in right kidney in male was 91.02 ml/min & in female was 89.12 ml/min. The mean length of left kidney in (male) was 10.68 cm, 10.08 cm, 10.35 cm by peroperative USG & CT IVU measurement respectively. Mean length of left kidney (female) was 10.40 cm, 9.72 &9.94 cm by peroperative USG & CT IVU measurement respectively. Mean of split

GFR (DTPA) left kidney in male was 46.36 ml/min & in female it was 43.57 ml/min. Mean of total DTPA GFR of left kidney in male was 96.12 ml/min and in female was 88.40 ml/min. Peroperative measured lengths of kidneys correlated with measurement by USG, CT IVU body weight, body surface area, split GFR (P = 0.015), eGFR (P = 0.43) and with DTPA total GFR (p = 0.019). Conclusion: This study shows that per operatively measured Everolimus datasheet kidney length correlates mostly with the USG measured lengths. PARK JI HYEON1, CHO AJIN2, JANG HYE RYOUN1, LEE JUNG EUN1, HUH WOOSEONG1, KIM YOON-GOO1, OH HA YOUNG1, KIM DAE JOONG1 1Division of Nephrology, Department of Internal Medicine, Samsung Medical center, Sungkyunkwan University

School of Medicine, Seoul, Republic of Korea; 2Department of Internal Medicine, Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Republic of Korea Introduction: Renal transplantation is the best treatment Megestrol Acetate modality for end-stage renal disease. We investigated the effects of donor source on renal allograft and patient survival in deceased donor transplants.

Methods: We retrospectively analyzed 190 cadaver kidney transplants that were performed in our center from January 2000 to December 2009. Of these, 136 kidneys were harvested in our transplantation center and 54 were from external donors. Primary outcome of graft survival was assessed with the Kaplan-Meier method and the significance of possible variables was determined with the Cox proportional hazard model. Results: There was no significant difference between groups in the age of donor and recipient, recipient body mass index, duration of dialysis, and panel reactive antibody >30%. Twenty recipients lost their grafts (14 from external donors and 6 from internal donors). Graft survival at 1, 3, and 5 years was 99.2%, 97.3%, and 95.5% for in-center donors and 98.1%, 88.9%, and 86.2% for external donor transplants (P = 0.01). There was no difference in patient survival rates between the groups. Acute rejection episodes (hazard ratio [HR] = 13.2; P < 0.001) and external hospital donor (HR = 9.3; P = 0.008) were independent factors associated with failure. Higher age of recipient was associated with increased patient death rate (HR = 1.2; P = 0.02).

The patient also developed macroscopic haematuria with clot reten

The patient also developed macroscopic haematuria with clot retention. CT abdomen revealed no haematoma. Empiric

antibiotics were commenced. Blood cultures subsequently grew both Enterobactor and E. coli species and both were also cultured on the urine sample taken the day prior to the biopsy. The patient required ICU admission with inotropic support. He was discharged home after one week with renal function slightly better than on admission. Histopathology revealed active pyelonephritis on a background of severe tubular atrophy and interstitial fibrosis, although rejection could not be excluded as cause of graft dysfunction. Conclusion: We report a case of asymptomatic renal allograft pyelonephritis which developed into septicaemia following an indication renal biopsy for worsening renal function. Obstruction

from haematuria may have contributed to the severity of the complication. Acute rejection as a cause SB203580 mouse of graft dysfunction was not able to be excluded. There are limited reports relating to the difficulties in differentiating pyelonephritis and cellular rejection in transplant recipients. 280 CEFEPIME RELATED INTERSTITIAL NEPHRITIS: A CASE REPORT K MAC, K HOWLIN, J WONG Department of Renal Medicine, Sydney South West Area Health Service, Australia Background: Cefepime is fourth-generation cephalosporin that is prescribed widely for severe infections varying from pyelonephritis to empirical Akt inhibition therapy for febrile neutropenia. It is well tolerated and severe adverse events are uncommon. Reversible neurotoxicity regardless of dose adjustment for renal impairment has been reported. Here we report a case of acute kidney injury (AKI) due to severe tubulointerstitial nephritis associated with long-term use of cefepime for treatment of temporal bone osteomyelitis. Case Report: A 62-year-old female with normal renal function (creatinine 70 μmol/L) received intravenous cefepime for chronic osteomyelitis of the right temporal bone. She developed dysgeusia after 2 weeks and AKI with creatinine rising up to 300 μmol/L after 6 weeks of therapy. Her medical

background included: diet controlled diabetic mellitus and well controlled hypertension. Urinalysis was bland. Autoimmune screen Endonuclease was negative. Renal biopsy confirmed tubulointerstitial nephritis. Corticosteroids were not administered given her diabetes, active infection, and prompt response to Cefepime discontinuation. She was continued on ciprofloxacin followed by oral amoxicillin. Her renal function improved but recovery remains incomplete at 6 months (creatinine 110 μmol/L). Conclusions: To our knowledge this is the first report of cefepime associated tubulointerstitial nephritis. Tubulointerstitial nephritis with cefepime neither relates to past or future beta lactam antibiotic exposure in spite of reported incidence of 10% cross sensitivity between penicillin-derivatives, cephalosporins and carbapenems.

The combination of rs2234711/rs1327474/rs7749390/rs41401746, whic

The combination of rs2234711/rs1327474/rs7749390/rs41401746, which was in strong linkage disequilibrium (D′ > 0.75), showed a significant association of ifngr1 with tuberculosis (P = 0.00079). Neither the single SNP nor the haplotype analysis showed a significant association between tuberculosis and the ifng gene markers. Our data implied the involvement of the ifngr1 gene in susceptibility to tuberculosis. Tuberculosis has been declared a global emergency by the World Health Organization. In 2008, there were an estimated 8.9–9.9 million incident cases of tuberculosis and KPT-330 purchase the 1.5–2.3 million deaths from

TB, mostly in developing countries [1]. Epidemiological data have revealed that only about one-tenth of the population that is infected by Mycobacterium tuberculosis will Cobimetinib develop clinical tuberculosis. Several twin studies have pointed

out significant differences in the development of tuberculosis between monozygotic and dizygotic twins [2], and there are significant racial differences in tuberculosis incidence. All these studies have indicated that genetic factors play an important role in the pathogenesis of tuberculosis [3]. Furthermore, the magnitude of the monozygotic to dizygotic difference has shown non-Mendelian inheritance, which implies that at least two and perhaps more interacting genes are involved [2]. Linkage-based, genome-wide screening of populations to determine the chromosomal location of genes involved in susceptibility to tuberculosis, as well as case–control association studies of candidate genes also have been carried out [4]. These results have indicated that polygenic factors contribute to the development of tuberculosis,

and ifng/ifngr1/ifngr2 stand out as some of main susceptibility genes for the disease [5, 6]. The Tau-protein kinase ifng gene is located on chromosome 12q24.1, and its protein product (interferon-γ; IFN-γ) is produced by lymphocytes activated by specific antigens or mitogens. IFN-γ shows antiviral activity and has important immunoregulatory functions. It is also a potent activator of macrophages and has antiproliferative effects on transformed cells. It can potentiate the antiviral and antitumor effects of the type I IFN [7]. A series of investigations has implicated ifng or IFN-γ in the pathological involvement of some infectious disorders, including hepatitis, AIDS and tuberculosis. Furthermore, the reeler mouse, a natural mutant that carries large deletions of the ifng gene, shows some alterations in its defence against M. tuberculosis [8]. These biochemical and in-vitro experimental data are supported by some association studies that have shown significant linkage between ifng gene polymorphism and tuberculosis.

In parallel,

even when increased level of insulin in the

In parallel,

even when increased level of insulin in the umbilical cord blood is found in GMD [71], confirming earlier observations [22, 51, 99], there is not information regarding the potential mechanism(s) associated with this specific response to insulin by the fetoplacental unit in GDM [5, 81, 83, 101]. Abnormal regulation of the insulin receptor splicing in key tissues responsive to insulin may occur in patients with insulin resistance, but its role is unclear in GDM [50, 81]. A recent study shows that IR-A activation by insulin activates a predominant mitogenic instead of a metabolic signaling selleck inhibitor pathway in HUVEC [98] (F Westermeier and L Sobrevia, unpublished observations), as described in response to IR-B activation in the R-cell line of mouse embryonic fibroblasts SCH772984 nmr [75]. These findings suggest differential cell signaling pathways activated by these insulin receptor subtypes in the human fetoplacental macrocirculation [35, 75]. Thus, modulation of the expression level of these isoforms will have a consequence in the metabolism of the endothelial cells of the fetoplacental unit in GDM. Other evidence suggests that decreased insulin response could result from increased IR-A over IR-B expression as reported in skeletal muscle of patients with type 2 diabetes

mellitus [63] and patients with myotonic dystrophy type 1 [73] or 2 [7, 73]. A potential insulin resistance in parallel with reduced insulin sensitivity and β-cell function in the human fetus from GDM pregnancies is reported [71]. Thus, differential expression of insulin receptor isoforms in fetoplacental tissues could be playing a

role in this Progesterone phenomenon. There is not available information regarding functionality of the l-arginine/NO pathway or the expression of hCATs and eNOS in placental microvascular endothelium from GDM pregnancies [39, 81]. However, in hPMEC from normal pregnancies l-arginine uptake has been reported as mediated by system y+/CATs with apparent Km ~ 90 μM and system y+L with apparent Km ~ 2 μM [26]. Based on the apparent Km values detected in these assays, it was suggested that hCAT-1 isoform instead of hCAT-2A or hCAT-2B isoforms were responsible of l-arginine transport in this cell type. Interestingly, since hCAT-2B transport activity occurs with an apparent Km in a similar range of that for hCAT-1 activity in hPMEC (E Guzmán-Gutiérrez and L Sobrevia, unpublished observations) and most mammalian cells [24, 53, 81], complementary assays such as trans-stimulation of transport, or the use of tools leading to knockdown or overexpression of these membrane transporters, are required for a better discrimination between these two potential transport mechanisms. We have found that l-arginine transport is mediated by hCAT-1 and hCAT-2B in hPMEC from normal pregnancies, a phenomenon most likely under modulation by insulin (E Guzmán-Gutiérrez and L Sobrevia, unpublished observations).

Others have suggested that Treg function can be modulated by the

Others have suggested that Treg function can be modulated by the local cytokine microenvironment, in murine models inhibition of suppression by lipopolysaccharide (LPS)-treated DCs can be reversed by the addition of HM781-36B IL-6 neutralizing antibody [25]. We did not observe a role for IL-6 in the biological effects of H. pylori on Tregs, which is at variance with both the publication of Pasare and descriptions of IL-6R expression by Tregs in inflammatory environments [49]. This can be explained by suggestions that IL-6 is incapable of blocking suppression on its own

and requires co-operative action with IL-1 to do so [26], whereas IL-1β has no obligate requirement for IL-6 and can break suppression of T cell proliferation on its own [24]. Alternatively, the variance could reflect differences

between murine and human cells. Others have also suggested that IL-12 (but not IL-23) may also be capable of reversing suppression [28], but this result may not be of significance in H. pylori infections, selleck chemicals llc as we have demonstrated previously that H. pylori-stimulated DCs are poor producers of IL-12 [10, 13]. We also failed to find a role for TNF-α in the effect of H. pylori on Tregs. Although there is evidence in patients with rheumatoid arthritis that anti-TNF therapy reverses a defect in Tregs [27, 50] we postulate that, in similar fashion to IL-6, this effect may be mediated through modification of other cytokines, such as IL-1, that may act in co-operation with TNF. Finally, it has often been assumed that the presence of Tregs in inflamed sites indicates active T cell suppression. Our observations that

H. pylori-stimulated DCs, as well as IL-1β, can subvert Treg suppression suggests that we should be cautious in this assumption. Equally, emerging data suggest that Tregs, or a subset of Tregs, retain the capacity to convert to the Th17 lineage when stimulated appropriately in the context of inflammation, in particular (for human Tregs) by IL-1β [51]. Such IL-17-producing, or ‘plastic’, Tregs have been described previously in lesional sites much of Crohn’s disease [52]. We have shown previously that DCs infected with H. pylori stimulate autologous CD4+ T cells to produce IL-17 and that this cytokine is expressed in gastric biopsies of patients with H. pylori infection [13]. Infection with H. pylori might not only inhibit Treg-mediated suppression but also differentiate subsets of Tregs to proinflammatory lineages, such as Th17. While, in this study, we looked for Th17 conversion of Tregs by HpDCs in vitro, we were unable to demonstrate Th17 conversion (data not shown), suggesting that Th17 conversion, if it occurs in response to H. pylori, is restricted to the in-vivo setting, where other components may be involved. Very recently, a different role for H. pylori infection of DCs has been published. Oertli et al. have demonstrated in a murine model that H.

7D) Thus, in vivo infusion with DC-FcγRIIb could protect MRL/lpr

7D). Thus, in vivo infusion with DC-FcγRIIb could protect MRL/lpr mice from obvious nephritis injuries. Finally, in vivo administration of DC-FcγRIIb, before (4-wk-old) or after (10-wk-old) the onset of clinic lupus, was found to be able to significantly prolong the survival of MRL/lpr mice, whereas MRL/lpr mice receiving DC-GFP or DCs all died by 40 wk (Fig. 7E). Thus, in vivo administration of DC-FcγRIIb check details could protect MRL/lpr mice from lupus progression, both preventively and therapeutically. SLE is a progressive systemic autoimmune disease, for which current therapy relies largely on long-term suppression of the immune system. We

here provide a short-term treatment regimen to attenuate lupus progression. Single infusion of DC-FcγRIIb, either before or after the onset of clinic lupus, into lupus-prone mice exerts a significant protection from lupus progression. The presence of large amounts of circulating IC in SLE may be potent stimulator for DCs. However, selleck kinase inhibitor for DC-FcγRIIb, these IC might become potent inhibitor of DC maturation through binding to the preferentially expressed FcγRIIb. FcγRIIb-mediated negative signal contributes to the maintenance of immature/tolerogenic property of DCs. The consequence of this event results in suppression of antigen-specific

T-cell responses and thereby inhibition of B-cell responses, furthermore reducing the generation of autoreactive T cells and autoantibodies. It has been previously reported that decreased FcγRIIb expression is associated with the progression of lupus;

it would therefore make sense that artificial enhancement of the inhibitory FcγRIIb expression on some cell types could possibly provide an efficient approach for the treatment of lupus. In addition to the maintenance of DC tolerogenecity, IC also induce massive PGE2 production from DCs and more PGE2 from DC-FcγRIIb. PGE2 might play a protective role in autoimmune responses via directly inhibiting both CD4+ and CD8+ T-cell responses, inducing Foxp3+ Treg differentiation, suppressing B-cell activation and Ig production 28–32. Moreover, PGE2 Thymidine kinase may be also responsible for the inhibition of TLR-induced DC maturation because PGE2-triggered signal is involved in the downregulation of TLR4 expression 27. It is worth investigating whether PGE2 also contributes to inhibition of TLR7 and TLR9 expression, because natural activators of TLR9 and TLR7 can be found in the blood of lupus patients. FcγRIIb seems to be a redundant receptor to mediate PGE2 production, because FcγRIIb−/− DCs can also produce certain amount of PGE2 although much less than that produced by WT DCs in response to stimuli. We found that DCs express more FcγRIIa than FcγRIIb (Supporting Information Fig. 5), suggesting that other activating FcγRs might contribute to the production of PGE2 by IC. Once pretreated with IC and then triggered with TLR-ligands, FcγRIIb−/− DCs could secrete certain level of PGE2.

These studies were encouraged by the seminal work by Pittock and<

These studies were encouraged by the seminal work by Pittock and

colleagues who showed that, contrary to previous thinking, the majority of NMO patients (up to 60%) exhibit (mostly unspecific) lesions on serial cranial MRI during the course of the disease. Some of these lesions are typical of MS and may even fulfill the so-called ‘Barkhof criteria’ [1, 225]. Similar findings have been reported by other groups, with approximately 15% of patients fulfilling the Barkhof criteria [1, 226]. Thus, it is widely accepted nowadays that, although many patients have normal cranial MRI findings at disease onset, brain lesions – including even those resembling typical MS lesions – do not rule out an NMO diagnosis [227]. However, ultrahigh-field imaging studies reported that, in contrast to MS, NMO lesions do not typically show central veins and a hypointense rim and lack visible cortical lesions [228, 229]. This is in line with other imaging and neuropathological selleck compound reports that indicate the absence of cortical demyelination in NMO [63, 230, 231]. Brain lesions tend to be located at sites of high aquaporin-4 expression,

such as the diencephalon, the hypothalamus and the aqueduct [232-234], and may also appear large and oedematous in the corpus callosum [235, 236]. Contrast enhancement Selleckchem Y-27632 on brain MRI with a cloudlike shape and pencil-thin ependymal enhancement were reported to be typical of NMO [237, 238]. Recent diffusion, perfusion and brain volume

studies, including voxel-based morphometry, revealed diffuse and widespread white matter and grey matter alterations in NMO [239-243]. Thus, brain damage is probably more severe than can be estimated from conventional MR images. While there is now compelling evidence that AQP4-Ab-positive ‘Asian opticospinal MS’ (OSMS) is identical to Western NMO, a small proportion of Asian patients still cannot be easily classified as NMO or MS, e.g. seronegative patients presenting with LETM and a secondary progressive course or OSMS patients with LETM and peripheral spinal cord Aspartate lesions [244, 245]. However, re-evaluation using more up-to-date assays, together with strict MRI criteria distinguishing between confluent (as sometimes seen in MS) and contiguous (as typically seen in NMO) longitudinal lesions, may help to clarify the nosological status of those patients. Optical coherence tomography (OCT) is a non-invasive technique by which unmyelinated retinal CNS axons (the so-called retinal nerve fibre layer RNFL) and their neurons, the retinal ganglion cells, can be visualized. Neuroaxonal retinal damage has been shown widely in MS and ON and is currently under investigation in many other neurological conditions [246-254]). In NMO, OCT studies have been consistent with the clinical experience of a more severe visual dysfunction and poorer visual outcome than for MS and more profound damage to the RNFL [246, 255-257].

The mean serum creatinine and urea at the initiation of dialysis

The mean serum creatinine and urea at the initiation of dialysis was 5.4 ± 0.6 mg/dL and 64.1 ± 6.1 mg/dL. The median number of haemodialysis sessions done was four. Renal biopsy was done in four patients. In three patients the urinalysis and serum chemistry was suggestive of Fanconi’s syndrome. Conclusion: Conclusion: In our patients, three renal manifestations of PNH were identified. They were acute renal failure, renal vessel thrombosis and Fanconi syndrome. Chronic renal failure was not identified in our patients. YAMAMOTO RYOHEI1,

SHINZAWA MAKI1, NAGASAWA YASUYUKI1, OSETO SUSUMU2, MORI DAISUKE3, TOMIDA KODO4, HAYASHI TERUMASA5, IZUMI MASAAKI4, FUKUNAGA MEGUMU2, YAMAUCHI ATSUSHI3, TSUBAKIHARA YOSHIHARU5,6, ISAKA YOSHITAKA1 1Department of Geriatric see more Medicine and Nephrology, Osaka Univeristy; 2Department of Internal Medicine, Toyonaka Municipal Hospital; 3Department of Internal Medicine, Osaka Rosai Hospital; 4Department of Internal

Medicine, Kansai Rosai Hospital; 5Department of Kidney Disease and Hypertension, Osaka General Medical Center; 6Department of Comprehensive Kidney Disease Research, Osaka University Introduction: Previous small trials suggested that intravenous methylprednisolone (mPSL) possibly accelerates remission of proteinuria in adult-onset minimal-change disease (MCD), its impact on relapse of proteinuria is unknown. Methods: This multicenter retrospective cohort study included 125 adult new-onset MCD patients diagnosed by kidney biopsy in 5 nephrology centers in Japan, which participated in the STudy Sorafenib mw of Outcomes and Practice patterns of Minimal-Change Disease (STOP-MCD). Times to first remission and first

relapse of proteinuria after initiating the first immunosuppressive therapy were compared between 65 patients with initial use of intravenous mPSL (0.5 g or 1.0 g for 3 consecutive days) followed by prednisolone (mPSL + PSL group) and 60 patients with initial use of prednisolone alone (PSL group) using multivariate Cox proportional hazards (CPH) models and propensity score (PS)-based models. Results: Median age (interquartile range) was 40 (25–59) and 41 (23–64) year in the mPSL + PSL group and the PSL group, respectively. During a median 3.6 years of observation (interquartile range 2.0−6.9), all 65 patients in the mPSL + PSL group achieved remission of proteinuria Interleukin-3 receptor within 11 (8−20) days of the corticosteroid initiation, while in the PSL group, 58 of 60 patients (96.6%) achieved remission within 19 (12−37) days (P < 0.001). After achieving the first remission, 32 (49.2%) patients in the mPSL + PSL group and 43 (71.7%) patients in the PSL group developed at least one relapse of proteinuria. Multivariate CPH models revealed that mPSL + PSL was significantly associated with early remission (multivariate-adjusted hazard ratio 1.54 [95% CI 1.05−2.26], P = 0.026) and lower incidence of relapse (0.50 [0.30−0.85], P = 0.009), compared with PSL alone. These results were ascertained in the PS-based models.