Allogeneic T cells cause acute renal injury after hematopoietic cell transplantation.

Acute kidney injury (AKI) is a frequent complication of allogeneic hematopoietic cell transplantation (allo-HCT). There are many causes of AKI after allo-HCT, but it is unknown whether renal acute graft-versus-host disease (aGVHD) caused by direct allogeneic donor T-cell-mediated renal damage contributes. Here, we tested whether allogeneic donor T cells attack kidneys in murine models of aGVHD. To avoid confounding effects of nephrotoxic agents, we did not administer immunosuppressants for GVHD prophylaxis. We found that urinary N-acetyl-ß-D-glucosaminidase, a marker of tubular injury, was elevated in allogeneic recipients on day 14 after allogeneic bone marrow transplantation. Donor major histocompatibility complex-positive cells were present and CD3+ T cells were increased in the glomerulus, peritubular capillaries, interstitium, and perivascular areas in the kidneys of allo-HCT recipient mice. These T cells included both CD4+ and CD8+ cells with elevated activation markers, increased exhaustion markers, and greater secretion of proinflammatory cytokines and cytotoxic proteins. Consistent with allo-T-cell-mediated renal damage, expression of neutrophil gelatinase-binding lipocalin, a marker of AKI, and elafin, a marker of aGVHD, were increased in renal tissue of allogeneic recipients. Because apoptosis of target cells is observed on histopathology of aGVHD target tissues, we confirmed that alloreactive T cells increased apoptosis of renal endothelial and tubular epithelial cells in cytotoxic T-lymphocyte assays. These data suggest that immune responses induced by donor T cells contribute to renal endothelial and tubular epithelial cell injury in allo-HCT recipients and that aGVHD may contribute to AKI after allo-HCT.

[Fecal metabolomic profiles in experimental murine bone marrow transplantation].

Graft-versus-host disease (GVHD) is a life-threating complication of allogeneic hematopoietic cell transplantation (allo-HCT). Prior studies have shown that gastrointestinal (GI) GVHD is associated with a reduction in intestinal microbiota diversity and a change in microbial metabolites. We conducted fecal metabolome analyses using a murine bone marrow transplantation. From this analysis, 290 metabolites were identified; of these, 18 metabolites were significantly or specifically higher and 12 were significantly or specifically lower in the allogeneic group than in the syngeneic one. Particularly, several metabolites in the choline metabolism and tryptophan metabolism were altered in the allogeneic group. Hierarchical clustering analysis demonstrated that the changed metabolites in the allogeneic group had similar profiles. Conclusively, we suggest that alloimmune responses are related to microbial metabolites in recipients receiving allo-HCT. The relationship between metabolites involved in GI GVHD and the intestinal microbiota and its physiological significance warrant further investigations.

Recent Advances of Acute Kidney Injury in Hematopoietic Cell Transplantation.

Acute kidney injury (AKI) is a common complication of allogeneic hematopoietic cell transplantation (allo-HCT) and is associated with non-relapse mortality (NRM) and quality of life (QOL). Multiple factors may contribute to AKI during allo-HCT and are often present at the same time making it difficult to determine the cause of AKI in each patient. Nephrotoxic drugs, infections, thrombotic microangiopathy (TMA), and sinusoidal obstruction syndrome (SOS) are well described causes of AKI during allo-HCT. Acute graft-versus-host disease (aGVHD) is a major complication of allo-HCT that mainly targets the intestines, liver, and skin. However, recent studies suggest aGVHD may also attack the kidney and contribute to AKI following allo-HCT. For example, severe aGVHD is associated with AKI, suggesting a link between the two. In addition, animal models have shown donor immune cell infiltration and increased expression of inflammatory cytokines in recipient kidneys after allo-HCT. Therefore, aGVHD may also target the kidney and contribute to AKI following allo-HCT. Herein, we describe the etiology, diagnosis, risk factors, pathophysiology, prevention, and treatment of renal injury after allo-HCT. In addition, we highlight emerging evidence that aGVHD may contribute to the development of AKI after allo-HCT.

A Case Demonstrating the Pathological Relationship between Granulomatous Vasculitis and Glomerular Lesion in Renal Sarcoidosis.

We experienced a rare case of tubulointerstitial angiocentric granulomatous vasculitis with focal segmental glomerulosclerosis (FSGS) and associated sarcoidosis. Our patient was an 18-year-old man who presented with exertional cough and dyspnea. He also had overt proteinuria (3.0 g/24 h), normal renal function (eGFR 95 mL/min/1.73 m2), heart failure, and hypertension. He had no previous episode of hypertension. These manifestations immediately improved after the administration of antihypertensive therapy that contained an angiotensin-converting enzyme inhibitor, calcium antagonists, beta antagonists, and diuretics. However, he, later on, developed renal dysfunction, with worsening of both proteinuria and hypertension. Renal biopsy was performed and showed epithelioid cells that were arranged concentrically around small blood vessels in tubulointerstitial granulomas. In the glomeruli, the segmental sclerotic lesions were classified as a perihilar variant of FSGS. There were no inflammatory changes, such as a mesangial lesion, inflammatory cell infiltration, fibrinoid necrosis, or crescent formation, and no glomerular granuloma. In the tubulointerstitial granulomas, the intimal elastic lamina of the interlobular arteries was reduplicated, and the intimal wall thickness of renal arterioles was remarkable. After receiving oral prednisolone therapy, the overt proteinuria resolved, the eGFR recovered from 39.4 to 60.6 mL/min/1.73 m2, and hypertension was managed more easily. Thereafter, he did not experience any recurrence. The concurrent improvement of renal function and proteinuria by steroid treatment suggested a relationship between the glomerular lesions and the tubulointerstitial granulomatous vasculitis with associated sarcoidosis.

Clinical outcomes of SeQuent Please paclitaxel-coated balloons for de novo small coronary artery lesion in a Japanese multicenter post-approval registry.

OBJECTIVE: Drug-coated balloon (DCB) angioplasty has emerged as an effective management strategy worldwide. In June 2016, DCB became available for the treatment of de novo small coronary lesions in Japan; however, there has been no multicenter analysis in a post-approval real-world clinical setting to date. The aim of this study was to evaluate the efficacy of DCB for de novo small coronary lesions based on a Japanese multicenter registry. METHODS AND RESULTS: From June 2016 to July 2017, a total of 111 lesions (102 patients) treated with DCB for de novo small coronary lesions were enrolled at six Japanese institutions. The primary endpoint was the rate of target lesion revascularization (TLR) at 12 months. Angiographic follow-up endpoints were binary restenosis and late lumen loss (LLL). Clinical follow-up data at 12 months were available for 106 lesions, excluding five lesions that required bailout stenting. The TLR rate was 5.7% (6/106 lesions). No cardiac death or target lesion thrombosis was observed. The binary restenosis rate was 14.4% and LLL was 0.0017 ± 0.37 mm. CONCLUSIONS: DCB angioplasty for de novo small coronary lesions in the real-world environment in Japan is effective with acceptable 12-month outcomes.

A 29-year-old Woman with Recurrent Pregnancy-induced Hypertension Based on Vascular Compression of the Medulla Oblongata.

We present a report of a 29-year-old woman with non-dipper type refractory hypertension due to the vascular compression of the medulla oblongata. The patient was diagnosed with hypertension at 17 years of age and underwent emergency Caesarean section at 26 weeks of gestation during 2 pregnancies due to severe high blood pressure. We suspected medullary compression by the curved posterior inferior cerebellar artery as the cause of her intractable hypertension, and she underwent Jannetta's decompression surgery. After the surgery, her blood pressure swiftly decreased to almost within the normal range, and her blood pressure pattern normalized to dipper type.

Real-Time Measurement of Polyvinylpyrrolidone Eluted from Polysulfone Membrane Dialyzers Based on the Ultraviolet Spectrum.

The objective of this study was to develop a new method for measuring polyvinylpyrrolidone (PVP) eluted from polysulfone (PSu) membrane dialyzers. The Müller method is generally used for the measurement of PVP, in which the PVP concentration is determined by measuring the absorbance after a red color is generated by the formation of PVP-iodine complexes when iodine is added to a sample. In contrast, our method does not require any reagents and allows real-time measurement of PVP by the ultraviolet absorption spectrum (UV-s method). In this study, the UV-s method and the Müller method were used to measure PVP eluted from two types of PSu membrane dialyzer (PS-1.6UW sterilized by autoclaving [n = 10] and APS-15SA sterilized by gamma radiation [n = 10]). Polyvinylpyrrolidone concentrations measured by the two methods showed a significant positive correlation (rs = 0.99, p = 0.0006). The PVP concentration (median [25th-75th percentiles]) in PS-1.6UW dialyzer washings obtained by rinsing with physiologic saline was 2.0 (1.18-4.85) mg/L with the Müller method and 3.35 (2.38-4.23) mg/L with the UV-s method, showing no significant difference. However, the PVP concentration in APS-15SA dialyzer washings was 0 (0-0.35) mg/L by the Müller method and 0.95 (0.45-2.58) mg/L by the UV-s method, and there was a significant difference between the two methods. In conclusion, the low concentration of PVP eluted from a PSu dialyzer sterilized by gamma radiation was hardly detected by the Müller method but could be clearly detected by the new UV-s method. These findings suggest that the UV-s method could be used for real-time measurement of PVP eluted from PSu membrane dialyzers.

Occurrence of internal browning in tuberous roots of sweetpotato and its related starch biosynthesis.

Although sweetpotato is an important crop worldwide, there has been almost no research on the occurrence of internal browning (IB) to date. In this study, we clarified the mechanism of occurrence of the disorder by using two types of cultivars with different IB susceptibility. In cells around the secondary vascular tissue, large size of starch grains accumulated in IB-susceptible cultivar compared with resistant one. Histochemical observation performed on cells around the secondary vascular tissues showed the presence of high levels of polyphenol oxidase activity, chlorogenic acid, and hydrogen peroxide in cells from the IB-affected regions in IB-susceptible cultivar. Likewise, high levels of starch content, hydrogen peroxide concentration, and polyphenol content were detected in the affected regions of IB-susceptible cultivar. In IB-susceptible cultivar, both the transcript levels of gens related starch and polyphenol biosynthesis were higher at an early stage of root maturation, while the levels in resistant cultivar were low at this stage and thereafter increased relatively more moderately. These observations suggest that the occurrence of IB disorder in sweetpotato largely depends on the morphology and timing of accumulated starch grain in cells around the secondary vascular tissues.

Histochemical observations and gene expression changes related to internal browning in tuberous roots of sweet potato (Ipomea batatas).

The mechanism underlying internal browning (IB), or brown discoloration, of the central region of tuberous roots of sweet potato (Ipomoea batatas) was examined. IB disorder begins in roots from approx. 90 days after transplanting, and the severity increases significantly with time. IB damage initially occurs in cells around the secondary vascular tissue, and the area per cell occupied by starch grains in this region was larger than in the unaffected region. High levels of reducing sugars, polyphenol oxidase (PPO) activities, chlorogenic acid, and hydrogen peroxide (H2O2) were detected in cells from the IB damaged regions. The content of sugar and polyphenols was higher in disks (transverse sections) with larger amounts of damaged tissues than in disks of sound root. The transcript levels of acid invertase (IbAIV) tended to be higher with greater IB severity, whereas fluctuation patterns of ADP-glucose pyrophosphorylase (IbAGPase), granule bound starch synthase (IbGBSS), and starch branching enzyme 1 (IbSBE1) were lower with higher IB severity. These observations suggest that the incidence of IB disorder in sweet potato is largely dependent on the excessive generation of reactive oxygen species (ROS) in cells around the secondary vascular tissues due to the abundant accumulation of sugar and/or starch grains during the root maturation period.

Influence of Sterilization and Storage Period on Elution of Polyvinylpyrrolidone from Wet-Type Polysulfone Membrane Dialyzers.

The objectives of this study were to investigate the influence of the sterilization and storage period on elution of polyvinylpyrrolidone (PVP) from wet-type polysulfone (PSu) membrane dialyzers. APS-15SA (APS) dialyzers sterilized by gamma-radiation and RENAK PS-1.6 (RENAK) dialyzers sterilized by autoclaving were compared in this study. Each dialyzer was washed with physiological saline and the amount of PVP eluted from the PSu membrane was measured. Then, experimental use of each dialyzer was performed by circulating physiological saline for 4 hours, after which the PVP eluted from the PSu membrane was measured. As the results, the amount of PVP eluted by washing was positively correlated with the storage period for both dialyzers (APS: rs = 0.958; RENAK: rs = 0.952). In the experimental circuit, the amount of PVP eluted from the RENAK dialyzer was positively correlated with the storage period (rs = 0.810), whereas the amount of PVP eluted from the APS dialyzer was negatively correlated with the storage period (rs = -0.833). We found that the amount of PVP eluted from PSu membrane is quite different by the sterilization and storage period of dialyzers.

Relationship between expression of onco-related miRNAs and the endoscopic appearance of colorectal tumors.

Accumulating data indicates that certain microRNAs (miRNAs or miRs) are differently expressed in samples of tumors and paired non-tumorous samples taken from the same patients with colorectal tumors. We examined the expression of onco-related miRNAs in 131 sporadic exophytic adenomas or early cancers and in 52 sporadic flat elevated adenomas or early cancers to clarify the relationship between the expression of the miRNAs and the endoscopic morphological appearance of the colorectal tumors. The expression levels of miR-143, -145, and -34a were significantly reduced in most of the exophytic tumors compared with those in the flat elevated ones. In type 2 cancers, the miRNA expression profile was very similar to that of the exophytic tumors. The expression levels of miR-7 and -21 were significantly up-regulated in some flat elevated adenomas compared with those in exophytic adenomas. In contrast, in most of the miR-143 and -145 down-regulated cases of the adenoma-carcinoma sequence and in some of the de novo types of carcinoma, the up-regulation of oncogenic miR-7 and/or -21 contributed to the triggering mechanism leading to the carcinogenetic process. These findings indicated that the expression of onco-related miRNA was associated with the morphological appearance of colorectal tumors.

Fusobacterium detected in colonic biopsy and clinicopathological features of ulcerative colitis in Japan.

BACKGROUND AND AIMS: Fusobacterium species are part of the gut microbiome in humans, but some species have been recognized as opportunistic pathogens implicated in inflammatory diseases including inflammatory bowel diseases. Here, we performed prevalence screening of Fusobacterium in ulcerative colitis (UC) in Japanese patients. METHODS: We examined Fusobacterium nucleatum (F. nucleatum) and whole Fusobacterium species (Pan-fusobacterium) by quantitative real-time PCR in 163 inflamed mucosae from 152 UC patients. Data were correlated with clinical subtypes of UC. RESULTS: In an initial prevalence screen, F. nucleatum and Pan-fusobacterium were detected in 6.3 % (4/64) and 53.1 % (34/64). For all 163 mucosae, the prevalence of Pan-fusobacterium was 54.6 % (89/163). Pan-fusobacterium status was concordant in inflamed and normal adjacent samples, and the matched cases during 1-year follow-up colonoscopy. The higher amount of Pan-fusobacterium was observed in chronic continuous type compared to one attack and relapse/remitting type (p = 0.039). The higher amount of Pan-fusobacterium was also associated with rather mild clinical course of disease, such as non-steroid dependency (p = 0.015), non-refractory phenotype (p = 0.013), and non-severe phenotype (p = 0.04). Based on the distribution of Pan-fusobacterium measurable cases, we identified 10 cases as having a high amount of Pan-fusobacterium (FB-high). The clinicopathological features of FB-high UC cases were also highlighted by chronic continuous type and mild phenotypes of disease. CONCLUSION: Whole Fusobacterium species, but not F. nucleatum, are common in UC patients and have a role in persistence of colonic inflammation in UC. However, Fusobacterium infection is associated with rather mild clinical phenotypes of UC.

Eluted substances from hemodialysis membranes elicit positive skin prick tests in bioincompatible patients.

Recently, hypotension and malaise during hemodialysis using polysulfone (PS) membranes have been reported. This study aimed to evaluate the bioincompatibility of eluted substances from PS hemodialysis membranes that can induce hypotension, malaise, and anaphylactic shock. Polyvinylpyrrolidone (PVP) elution from five hemodialysis membranes was measured in an in vitro experimental circulation. Skin prick tests (SPTs) with PVP or the priming fluid of hemodialysis membranes were carried out for seven PS membrane-incompatible patients and seven healthy volunteers. Skin reactivity for histamine was compared in patients and healthy volunteers. The symptoms of PS membrane-incompatible cases were hypotension, dyspnea, nausea, or vomiting. One patient had gone into shock. PVP was eluted from hemodialysis membranes, but the SPT for PVP was negative in all patients. SPTs with priming fluid (or priming fluid effluxed during priming) were positive in four out of six patients. However, the SPT with bisphenol A was positive in one patient. The area of the flare reaction against histamine in patients was smaller than that of healthy subjects. In conclusion, eluted substances apart from PVP from hemodialysis membranes could cause bioincompatibility with PS membranes.

Post-operative infection and prophylactic antibiotic administration after radical cystectomy with orthotopic neobladder urinary diversion.

The purpose of this study was to investigate the association between prophylactic antibiotic administration (PAA) and post-operative infection in radical cystectomy with orthotopic neobladder urinary diversion carried out for patients with bladder cancer. Fifty-seven consecutive cases were analyzed retrospectively. Post-operative infections were categorized as urinary tract, wound, and remote infections. We used the antibiotics tazobactam/piperacillin (TAZ/PIPC), sulbactam/ampicillin (SBT/ABPC), flomoxef (FMOX), cefazolin (CEZ), cefotiam (CTM), and cefmetazole (CMZ). Twenty-five (43.9%) patients had post-operative infections. Five of these (8.77%) patients had wound infections, 22 (38.6%) patients had urinary tract infections, and 2 (3.51%) had remote infections. Our statistical analysis demonstrated that the patients with TAZ/PIPC used for PAA (5/18: 27.8%) had a significantly lower post-operative infection rate than patients with other antibiotics (24/39: 61.5%) (p = 0.0442). In addition, the patients with a shorter-duration PAA (within 72 h after the operation (48-72 h)) had a significantly lower rate of post-operative infections (12/33: 36.4%) than those with longer-duration PAA (longer than 72-96 h after the operation) (16/24: 66.7%) (p = 0.0239). Taken together, these results suggest that TAZ/PIPC with shorter PAA duration (within 72 h) might lead to a lower rate of post-operative infections. In conclusion, our data showed that PAA with TAZ/PIPC with a shorter duration PAA (within 72 h) might be recommended for radical cystectomy with orthotopic neobladder reconstruction. A prospective study based on our data is desirable to establish or revise guidelines for prophylactic medication for preventing post-operative infection after radical cystectomy with orthotopic neobladder urinary diversion.

Different clinical outcomes for cardiovascular events and mortality in chronic kidney disease according to underlying renal disease: the Gonryo study.

PURPOSE: Chronic kidney disease (CKD) can result from a wide variety of diseases, but whether clinical outcomes differ in the same CKD stages according to the underlying renal disease remains unclear. Clarification of this issue is important for stratifying risk of cardiovascular disease (CVD) and death in patients before dialysis. PATIENTS AND METHODS: The study comprised 2,692 patients recruited from 11 outpatient nephrology clinics, classified by underlying disease of primary renal disease (PRD) (n = 1,306), hypertensive nephropathy (HN) (n = 458), diabetic nephropathy (DN) (n = 283), or other nephropathies (ON) (n = 645). Risks of events such as ischemic heart disease, congestive heart failure, stroke, and all-cause mortality within 12 months were examined by logistic regression analysis in each group. RESULT: During the 12-months' observation from recruitment, 200 cases were lost to follow-up, and 113 cases were introduced to chronic dialysis therapy. A total of 69 CVD events occurred (stroke in 27 cases), and 24 patients died. In total, increased odds ratios (OR) for the events by CKD stage (cf. CKD1 + 2: unadjusted) were CKD3, 1.29 [95% confidence interval (CI), 0.70-2.17]; CKD4, 2.73 (1.55-4.83); and CKD5, 4.66 (2.63-8.23). Regarding events in respective groups, no significant differences were seen by CKD stage except for the group with HN, but significant differences were seen by underlying diseases (cf. PRD: adjusted for confounding factors, including estimated glomerular filtration rate): HN, 2.57 (1.09-6.04); DN, 12.21 (3.90-38.20); and ON, 4.14 (1.93-8.89). CONCLUSION: Risk of CVD and mortality due to CKD needs to be stratified according to the underlying renal diseases.

A pilot study of quality of life of patients with hormone-refractory prostate cancer after gene therapy.

BACKGROUND: The effects on quality of life (QOL) after a Phase I/II clinical trial of a combination of osteocalcin promoter-driven herpes simplex virus thymidine kinase (Ad-OC-TK) gene therapy and valacyclovir (VAL) were investigated for patients with hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: The QOL of six patients was prospectively assessed after gene therapy on days 0, 14, and 28. A modified questionnaire was created based on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire's prostate cancer-specific module (EORTC QLQ-PR25). RESULTS: The scores of all items significantly improved along with the total score. Further, bodily pain was significantly reduced on day 28. Moreover, the rate of change in the serum prostate-specific antigen levels from day 0 to day 28 was significantly correlated with the rate of change in bodily pain. CONCLUSION: In this clinical trial, Ad-OC-TK plus VAL treatment significantly improved the short-term QOL and bodily pain of patients with localized recurrence or bone metastases of HRPC.

[Assessment of competence of predialysis chronic kidney disease stage 5 patients to make treatment decisions: preliminary report].

The competence to consent to treatment of 26 adults with stage 5 predialysis chronic kidney disease (CKD) (16 males, 10 females, age; 58 +/- 11 years, creatinine clearance; 10.1 +/- 3.9 mL/min)was assessed using two kinds of format: the MacArthur Competence Assessment Tool-Treatment (MacCAT-T) and mini-mental-state examination (MMSE). The MacCAT-T revealed poor ability for understanding(3.72 +/- 1.11 points; perfect score, 6 points), appreciating (2.88 +/- 0.88 points; perfect score, 4 points)and reasoning(4.30 +/- 2.11 points; perfect score, 8 points). The MMSE revealed poor performance on the attentional task. The level of attentional deficit was significantly related to both poor ability for understanding and reasoning (r = 0.432, p = 0.031 and r = 0.542, p = 0.014, respectively). These results suggest that the competence of predialysis CKD stage 5 patients to consent to treatment is impaired partly via an attentional deficit.

Effects of nafamostat mesilate on ADP-induced platelet aggregation and disaggregation in hemodialysis patients.

Nafamostat mesilate (NM), a synthetic protease inhibitor, is the most commonly used anticoagulant in the setting of extracorporeal circulation (ECC) in patients with bleeding tendency. It inhibits both platelet aggregation and activation of coagulation factors. Although it has been reported that NM disaggregates aggregated platelets, little is known about such an effect in the setting of hemodialysis therapy (HD). We examined the effects of NM on adenosine 5'-diphosphate (ADP)-induced platelet aggregation and disaggregation using platelet-rich plasma obtained from 6 HD patients. The platelet aggregation was stimulated by 3 microM ADP and change of aggregation was monitored by an aggregometer. NM adjusted to the final concentrations of 0.1 (1.9 x 10(-7)), 1.0 (1.9 x 10(-6)), 10, (1.9 x 10(-5)), and 100 (1.9 x 10(-4)) microg/ml (M) or veronal-buffered saline (VBS) as control was added before or after to the stimulation of ADP. NM not only inhibited platelet aggregation, but also disaggregated already aggregated platelets at concentrations of 1.0 microg/mln or higher. Moreover, NM almost completely disaggregated at 100 microg/ml. This NM concentration of 1.0 microg/ml was lower than the therapeutic concentration in ECC of HD (i.e., 10 M(-5)). Both inhibitory and disaggregatory effects of NM expressed a dose-related dependency. Our results suggest that NM can exert both aggregation inhibitory and disaggregatory effects on platelets of HD patients within the therapeutic concentration.

Polymorphism of the interleukin-4, interleukin-13, and signal transducer and activator of transcription 6 genes in Indonesian children with minimal change nephrotic syndrome.

BACKGROUND/AIMS: Minimal change nephrotic syndrome (MCNS) in children is frequently associated with allergy and immunoglobulin E (IgE) production. T-helper subtype 2 cytokines, such as interleukin (IL)-4 and IL-13, have been implicated in the regulation of IgE production. We investigated the associations of gene polymorphisms of IL-4, IL-13, and signal transducer and activator 6 (STAT6) in Indonesian children with MCNS (n = 84) and controls with neither allergic nor renal disease (n = 61). METHODS: Polymerase chain reaction-restriction fragment length polymorphism was used to determine the IL-4 promoter gene polymorphism (-590C/T) and IL-13 gene polymorphism (4257G/A), and direct sequencing was used for the STAT6 3S untranslated region (2964G/A) polymorphism. RESULTS: There was a significant difference between the MCNS group and the controls in the genotypic distribution of IL-4 and IL-13 gene polymorphism. In the case of the IL-4 promoter gene, the frequency of the CC homozygote was significantly lower in the MCNS group than in the controls, while, in the case of IL-13, the frequency of the GG homozygote was significantly lower in the MCNS group. However, there was no difference between the MCNS group and the controls in the STAT6 gene polymorphism. CONCLUSION: The genetic variations in the IL-4 and IL-13 genes may be associated with predisposition to MCNS.