A case of TAFRO syndrome after vaccination, successfully treated with cyclosporine.

BACKGROUND: TAFRO syndrome is a rare disorder that causes thrombocytopenia, generalized oedema, fever, organ enlargement, and renal impairment. Few reports have suggested an association with vaccines, and few cases have undergone renal biopsy. TAFRO syndrome is often severe and fatal, and its cause is unknown. We report a case of TAFRO syndrome that occurred after vaccination with the coronavirus disease 2019 (COVID-19) vaccine. CASE PRESENTATION: An 82-year-old woman received two doses of the BNT162b2 mRNA vaccine 3 weeks apart. Two weeks later, she was admitted to the hospital with oedema, accompanied with renal failure and thrombocytopenia. After close examination, she was diagnosed with TAFRO syndrome. She was treated with steroids, cyclosporine, and thrombopoietin receptor agonists. The patient was discharged after several months in remission. CONCLUSIONS: Although an incident of TAFRO syndrome after COVID-19 vaccination has been previously reported, this is a rare case in which the patient went into remission and was discharged. A renal biopsy was also performed in this case, which was consistent with previous reports. The favorable treatment course for TAFRO syndrome provides valuable insights.

Effect of iron administration on the aortic iron content and vascular calcification in phosphorus-loaded chronic kidney disease rats.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with chronic kidney disease (CKD) and could be related to oxidative stress. Vascular calcification (VC) has been established as a critical risk factor for accelerated CVD. In CKD, phosphorus (Pi), iron (Fe) and Nrf2 are modulators of VC and important agonists and antagonists of oxidative stress. The aim of this study was to determine whether Fe administration, which is commonly used to treat renal anemia, affects aortic Fe overload and VC, and whether Nrf2 and its related genes, ferritin H and HIF-1α, are involved in the development of VC. METHODS: A CKD model was created in rats by administering adenine and simultaneously feeding a high-Pi diet. In addition to control and CKD rats without Fe administration (No-Fe group), Fe was administered orally (PO-Fe group) or intraperitoneally (IP-Fe group) to CKD animals to clarify the effects of Fe administration on the aortic Fe and calcium (Ca) contents and the involvement of Nrf2 and its induced antioxidative proteins, ferritin H and HIF-1α, in VC. RESULTS: The aortic Fe content increased significantly in the IP-Fe group, which was closely correlated with liver HAMP (hepcidin) expression in all animals. Fe administration had no significant effect on the aortic Ca and Pi contents regardless of the route of Fe administration. The aortic mRNA level of Nrf2 was significantly increased in the IP-Fe group and correlated with serum Pi levels and aortic Fe contents, which could respond to oxidative stress. Notably, the mRNA level of Nrf2 was also significantly correlated with the mRNA levels of ferritin H and HIF-1α. Since we could not measure Nrf2 protein levels in this study, we confirmed the upregulation of HMOX1 and NQO1 mRNA expression in parallel with Nrf2 mRNA. CONCLUSION: Parenteral Fe administration increased aortic Fe in parallel with the liver HAMP mRNA level but did not affect VC. Aortic Nrf2 mRNA levels correlated significantly with aortic Fe and serum Pi levels and with aortic mRNA levels of ferritin H and HIF-1α as well as HMOX1 and NQO1.

Inhibition of urea transporter ameliorates uremic cardiomyopathy in chronic kidney disease.

Uremic cardiomyopathy, characterized by hypertension, cardiac hypertrophy, and fibrosis, is a complication of chronic kidney disease (CKD). Urea transporter (UT) inhibition increases the excretion of water and urea, but the effect on uremic cardiomyopathy has not been studied. We tested UT inhibition by dimethylthiourea (DMTU) in 5/6 nephrectomy mice. This treatment suppressed CKD-induced hypertension and cardiac hypertrophy. In CKD mice, cardiac fibrosis was associated with upregulation of UT and vimentin abundance. Inhibition of UT suppressed vimentin amount. Left ventricular mass index in DMTU-treated CKD was less compared with non-treated CKD mice as measured by echocardiography. Nephrectomy was performed in UT-A1/A3 knockout (UT-KO) to further confirm our finding. UT-A1/A3 deletion attenuates the CKD-induced increase in cardiac fibrosis and hypertension. The amount of α-smooth muscle actin and tgf-ß were significantly less in UT-KO with CKD than WT/CKD mice. To study the possibility that UT inhibition could benefit heart, we measured the mRNA of renin and angiotensin-converting enzyme (ACE), and found both were sharply increased in CKD heart; DMTU treatment and UT-KO significantly abolished these increases. Conclusion: Inhibition of UT reduced hypertension, cardiac fibrosis, and improved heart function. These changes are accompanied by inhibition of renin and ACE.

Significance of kidney biopsy in autosomal dominant tubulointerstitial kidney disease-UMOD: is kidney biopsy truly nonspecific?

BACKGROUND: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare hereditary disease caused by a variety of genetic mutations. Carriers of a mutation in the responsible genes are at risk of reaching end-stage kidney disease typically in middle age. The frequency of this disease is assumed to be underestimated because of a lack of disease-specific signs. Pathological findings obtained from kidney of uromodulin related ADTKD (ADTKD-UMOD) patients are regarded as non-specific and less-informative for its diagnosis. This research was undertaken to evaluate the significance of kidney biopsy in ADTKD-UMOD patients. METHODS: Thirteen patients from 10 families with nine identified uromodulin (UMOD) gene mutations who underwent kidney biopsy in the past were studied. Their kidney tissues were stained with anti-UMOD antibody in addition to conventional methods such as PAS staining. When positive, the numbers of tubules with visible UMOD protein accumulations were calculated based on the total numbers of UMOD expressing tubules. Pathological findings such as tubulointerstitial fibrosis, atrophy, inflammation and glomerulosclerosis were also evaluated and analyzed. RESULTS: Interstitial fibrosis and tubular atrophy were present in all 13 patients. Most atrophic tubules with thickening and lamellation of tubular basement membranes showed negative UMOD staining. In all but two patients with C94F mutations, massive accumulation of UMOD proteins was observed in the renal endoplasmic reticulum. UMOD accumulations were also detectable by PAS staining as polymorphic unstructured materials in the 11 patients at frequencies of 2.6-53.4%. 80.4% of the UMOD accumulations were surrounded by halos. The detection rate of UMOD accumulations positively correlated with eGFR. Glomerulosclerosis was detected in 11/13 patients, with a frequency of 20.0 to 61.1%, while no cystic dilatations of glomeruli were detected. CONCLUSIONS: Massively accumulated UMOD proteins in ADTKD-UMOD kidneys are detectable not only by immunostaining using anti-UMOD antibody but also by conventional methods such as PAS staining, although their detection is not easy. These findings can provide important clues to the diagnosis of ADTKD-UMOD. Kidney biopsy in ADTKD-UMOD may be more informative than assumed previously.

Alteration of normal level of serum urate may contribute to decrease in estimated glomerular filtration rate decline in healthy Japanese men.

INTRODUCTION: Serum uric acid (SUA) levels have a linear relationship with the estimated glomerular filtration rate (eGFR). It is unclear whether further changes, subsequent to normal level of SUA can attenuate eGFR decline in a healthy population, so we aimed to determine the normal level of SUA that can contribute to preventing kidney dysfunction. METHODS: In this retrospective cohort study from Japan, annual health checkup data from 2009 to 2014 was collected. After propensity score matching (1:1), data from 2,634 individuals with basal SUA ≤7.0 mg/dL (normal; mean age, 39 y; mean eGFR, 80.8 mL/min/1.73 m2) and 1,642 individuals with basal SUA >7.0 mg/dL (elevated; mean age, 42 y; mean eGFR, 75.0 mL/min/1.73 m2) were collected to determine the relationship between followed-up SUA level and the rate of change in eGFR. RESULTS: In individuals with normal level SUA at baseline, the elevation of SUA (>7.0 mg/dL) accelerated eGFR decline compared to those with normal SUA levels at 5-year follow-up (-4.1 ± 9.6% vs -9.9 ± 9.0%, p < .0001). Digression of SUA level (≤7.0 mg/dL) reduced eGFR decline compared with persistent SUA level over 7.0 mg/dL (-1.5 ± 11.5% vs -7.0 ± 10.1, p < .0001). In multiple linear regression analysis, there was strong association between the rate of change in SUA and eGFR in individuals with basal SUA ≤7.0 and >7.0 mg/dL (standardized coefficient; -0.3348, p < .001 and -.2523, p < .001, respectively). CONCLUSION: Subsequent to normal level of SUA (under 7.0 mg/dL) may contribute to a decrease in eGFR decline in apparently healthy men.

UT-A1/A3 knockout mice show reduced fibrosis following unilateral ureteral obstruction.

Renal fibrosis is a major contributor to the development and progression of chronic kidney disease. A low-protein diet can reduce the progression of chronic kidney disease and reduce the development of renal fibrosis, although the mechanism is not well understood. Urea reabsorption into the inner medulla is regulated by inner medullary urea transporter (UT)-A1 and UT-A3. Inhibition or knockout of UT-A1/A3 will reduce interstitial urea accumulation, which may be beneficial in reducing renal fibrosis. To test this hypothesis, the effect of unilateral ureteral obstruction (UUO) was compared in wild-type (WT) and UT-A1/A3 knockout mice. UUO causes increased extracellular matrix associated with increases in transforming growth factor-ß, vimentin, and α-smooth muscle actin (α-SMA). In WT mice, UUO increased the abundance of three markers of fibrosis: transforming growth factor-ß, vimentin, and α-SMA. In contrast, in UT-A1/A3 knockout mice, the increase following UUO was significantly reduced. Consistent with the Western blot results, immunohistochemical staining showed that the levels of vimentin and α-SMA were increased in WT mice with UUO and that the increase was reduced in UT-A1/A3 knockout mice with UUO. Masson's trichrome staining showed increased collagen in WT mice with UUO, which was reduced in UT-A1/A3 knockout mice with UUO. We conclude that reduced UT activity reduces the severity of renal fibrosis following UUO.

Relationship between abdominal adiposity and incident chronic kidney disease in young- to middle-aged working men: a retrospective cohort study.

BACKGROUND: Obesity is a risk factor for the development of chronic kidney disease (CKD). However, it remains to be fully examined whether fatness is more useful in predicting incident CKD. We aimed this study to determine the association of body fat, body mass index and waist circumference (WC) with subsequent changes in estimated glomerular filtration rate (eGFR) and incident CKD in young- to middle-aged working men. METHODS: We analyzed data from annual health check-up in male workers aged from 20 to 60 years with basal eGFR of 60-90 mL/min/1.73 m2. Cut-off values of parameters and odds ratio (OR) for the incident CKD were calculated by receiver operator characteristics analysis andχ2 test, respectively. We also tested trends of changes in eGFR according to changes in WC in each age decade. RESULTS: There were 8,015 men participants. During the 5-year follow-up, 11.0% of the participants (N = 878) had developed to incident CKD. When basal WC was greater than 80.0 cm, which was decided by Youden's Index, there was a significantly higher risk of incident CKD [OR 1.57 (95% confident interval 1.35-1.84)]. Changes in WC over 5 years were significantly related to eGFR decline in young men (< 40 years old) with normal blood pressures and normoglycemia. CONCLUSIONS: These findings suggest that WC > 80.0 cm is a risk factor for incident CKD and strongly associated with a decline in eGFR in the young- to middle-aged working healthy men.

Impact of low-density lipoprotein cholesterol on decline in estimated glomerular filtration rate in apparently healthy young to middle-aged working men.

BACKGROUND: It remains to be fully clarified whether there is a relationship between uncontrolled dyslipidemia and decline in estimated glomerular filtration rate (eGFR) in the general population. Therefore, this study's aim was to test the association of dyslipidemia with changes in eGFR in apparently healthy working men. METHODS: We retrospectively examined the annual medical check-up list of 14,510 male workers aged 20-60 years with eGFR ≥ 60 mL/min/1.73 m2 at baseline, and then evaluated the association of the changes in the check-up parameters with a decline in eGFR during the 5-year observation period. RESULTS: Mean age and eGFR were 38.5 years and 82.3 mL/min/1.73 m2 at baseline, respectively. Evaluated low-density lipoprotein cholesterol (LDL-C) (≥140 mg/dL) was a strong indicator of CKD development in participants (basal eGFR 60-90 mL/min/1.73 m2) without hypertension [odds ratio (95% confidence interval): 1.46 (1.12-1.90)] or diabetes mellitus (DM) [1.49 (1.23-1.82)]. When LDL-C normalized under 140 mg/dL during follow-up, the decline in eGFR was smaller in non-hypertensive participants [-5.9 (-14.4 to -0.9) vs -13.4 (-18.4 to -4.5) mL/min/1.73 m2, p < 0.05]. There was an inverse correlation between change of LDL-C and decline in eGFR (p for trend <0.001). CONCLUSION: Increased LDL-C levels are associated with the development of incident CKD and eGFR decline in young to middle-aged working men without hypertension and/or DM.

Strong expression of polypeptide N-acetylgalactosaminyltransferase 3 independently predicts shortened disease-free survival in patients with early stage oral squamous cell carcinoma.

The polypeptide N-acetylgalactosaminyltransferase (GalNAc-Ts) family of enzymes regulates the critical initial steps of mucin-type O-glycosylation. Among GalNAc-Ts that may significantly influence cancer biology, thus affecting cell differentiation, adhesion, invasion, and/or metastasis, GalNAc-T3 exhibits a high expression in several human cancers, closely associated with tumor progression and a poor prognosis. However, the expression pattern of GalNAc-T3 in oral squamous cell carcinoma (OSCC) remains obscure. Since postoperative recurrence of even early stage OSCC (ESOSCC) occurs at an early phase, significantly affecting their clinical course and worse outcome, the identification of clinically significant accurate biomarkers is needed. Therefore, we investigated the correlation between the immunohistochemical GalNAc-T3 expression and various clinicopathological characteristics and recurrence using 110 paraffin-embedded tumor samples obtained from patients with surgically resected ESOSCC (T1-2N0). Recurrence was recognized in 37 of 110 (33.6 %) patients. The GalNAc-T3 expression was considered to be strongly positive when 20 % or more of the cancer cells showed positive cytoplasmic staining. Consequently, a strong expression of GalNAc-T3 was observed in 40 patients (36.4 %), showing a close relationship to poor differentiation, the presence of lymphatic and vascular invasion, and recurrence. Univariate and multivariate analyses further demonstrated that the patients with a strong GalNAc-T3+ status had markedly lower disease-free survival (DFS) rates, especially within the first 2 years postoperatively. Therefore, GalNAc-T3 might play a role in the pathogenesis of ESOSCC recurrence, and its immunohistochemical detection potentially predicts a shorter DFS and may be a useful parameter for providing clinical management against ESOSCC in the early postoperative phase.

[Mechanism of and Therapy for Kidney Fibrosis].

Fibrosis occurs in systemic tissues other than the brain and finally induces dysfunction of the fibrotic organ. Kidney fibrosis is related to scarring after acute kidney injury and the progression of chronic kidney disease. Kidney function decreases with the progression of kidney fibrosis. As fibrotic tissue cannot return to its original status, advanced kidney fibrosis requires the administration of dialysis or kidney transplantation. Thus, elucidation the mechanism of kidney fibrosis is an important research theme. The proliferation and activation of (myo) fibroblasts and the excessive production of an extracellular matrix are common mechanisms in fibrosis in many organs, but it seems that kidney fibrosis has specific pathways. Tubular epithelial, mesangial cells, and erythropoietin producing cells, which exist only in the kidney, participate in forming kidney fibrosis. This review highlights an understanding of the cells and their underlying mechanisms, which are specific to kidney fibrosis process: transforming growth factor-ß (TGF-ß), epithelial-mesenchymal transition, wingless/int-1 (WNT) signaling, renal anemia, and uremia. Finally, we describe potential therapies that focus on the mechanisms of kidney fibrosis: anti-TGF-ß antibody and mammalian target of rapamycin (mTOR).

Mitochondrial Transcription Factor A and Mitochondrial Genome as Molecular Targets for Cisplatin-Based Cancer Chemotherapy.

Mitochondria are important cellular organelles that function as control centers of the energy supply for highly proliferative cancer cells and regulate apoptosis after cancer chemotherapy. Cisplatin is one of the most important chemotherapeutic agents and a key drug in therapeutic regimens for a broad range of solid tumors. Cisplatin may directly interact with mitochondria, which can induce apoptosis. The direct interactions between cisplatin and mitochondria may account for our understanding of the clinical activity of cisplatin and development of resistance. However, the basis for the roles of mitochondria under treatment with chemotherapy is poorly understood. In this review, we present novel aspects regarding the unique characteristics of the mitochondrial genome in relation to the use of platinum-based chemotherapy and describe our recent work demonstrating the importance of the mitochondrial transcription factor A (mtTFA) expression in cancer cells.

Lifestyle-Related Risk Factors for the Incidence and Progression of Chronic Kidney Disease in the Healthy Young and Middle-Aged Population.

The prevalence of chronic kidney disease (CKD) increased by 88% from 1990 to 2016. Age of onset of lifestyle-related diseases (such as hypertension, diabetes mellitus, obesity, dyslipidemia, and hyperuricemia), which are risk factors for incident CKD, is lower now compared with the past. Thus, we aimed to evaluate the risk factors for the incidence and progression of CKD in the young and middle-aged population. There are differences in the risk for CKD among the young, middle-aged, and elderly populations. We aimed to assess obesity (which is basic component of metabolic syndrome), waist circumference, and abdominal adiposity, which are predictive factors of CKD in the younger population. Furthermore, we described the management and clinical evidence of hypertension, diabetes mellitus, dyslipidemia, and hyperuricemia for young and middle-aged patients, along with diet management and nutrients associated with kidney function. Kidney function in the young and middle-aged population is mostly normal, and they are considered a low-risk group for incident CKD. Thus, we expect this review to be useful in reducing the prevalence of CKD.

Development of chronic kidney disease influenced by serum urate and body mass index based on young-to-middle-aged Japanese men: a propensity score-matched cohort study.

OBJECTIVE: To investigate the association between serum uric acid (SUA) level and body mass index (BMI) on the development of chronic kidney disease (CKD) in working men aged 20-60 years. DESIGN: Retrospective cohort study. SETTING: Data from employees' annual health check-ups were collected from two companies in 2009 and 2014. PARTICIPANTS: A total of 16 708 working men were recruited. We excluded participants with missing essential data (N=7801), who had basal estimated glomerular filtration rate (eGFR) <60.0 mL/min/1.73 m2 and/or proteinuria (N=698) or with the absence of follow-up data (N=2). PRIMARY OUTCOME: eGFR <60 mL/min/1.73 m2 and/or proteinuria (≥1+) in 2014 (defined as incident CKD). RESULTS: The cut-off values of SUA for incident CKD were 6.6 mg/dL in both young (20-39 years old) and middle-aged (40-60 years old) men analysed by receiver operator characteristics. ORs for incident CKD were assessed on propensity score-matched (1:1) cohorts. In young participants (N=1938), after propensity score matching, a coexistence of high-level SUA (≥6.6 mg/dL) and overweight (BMI ≥25 kg/m2) was a significant risk factor of incident CKD (OR=2.18, 95% CI 1.10 to 4.31, p=0.025), but high-level SUA was not an independent risk factor without overweight status (p=0.174). In middle-aged participants (N=2944) after propensity score matching, high-level SUA was a significant risk factor of incident CKD both with or without overweight (OR=1.44, 95% CI 1.02 to 2.04, p=0.037; OR=1.32, 95% CI 1.01 to 1.73, p=0.041, respectively). CONCLUSION: These findings suggest that high-level SUA is strongly associated with incident CKD in overweight young adult men.

Potential link between high FIB-4 score and chronic kidney disease in metabolically healthy men.

Although the association between non-alcoholic fatty liver disease and chronic kidney disease (CKD) has been well known, it is unclear whether Fibrosis-4 (FIB-4) score is a predictor of CKD development. We performed this retrospective cohort study, with a longitudinal analysis of 5-year follow-up data from Japanese annual health check-ups. Participants with CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2 and/or proteinuria) and a habit of alcohol consumption were excluded. The cut-off FIB-4 score was 1.30, indicating increased risk of liver fibrosis. Overall, 5353 participants (men only) were analyzed without exclusion criteria. After propensity score matching, high FIB-4 score (≥ 1.30) was not an independent risk factor for incident CKD (odds ratio [OR] 1.57; 95% confidence interval [CI] 0.97-2.56). However, high FIB-4 score was a significant risk factor for CKD in non-obese (OR 1.92; 95% CI 1.09-3.40), non-hypertensive (OR 2.15; 95% CI 1.16-3.95), or non-smoking (OR 1.88; 95% CI 1.09-3.23) participants. In these participants, FIB-4 score was strongly associated with eGFR decline in the multiple linear regression analysis (ß = - 2.8950, P = 0.011). Therefore, a high FIB-4 score may be significantly associated with CKD incidence after 5 years in metabolically healthy participants.

Downregulation of let-7 by Electrical Acupuncture Increases Protein Synthesis in Mice.

BACKGROUND: Our previous study found that acupuncture with low frequency electrical stimulation (Acu/LFES) prevents muscle atrophy by attenuation of protein degradation in mice. The current study examines the impact of Acu/LFES on protein synthesis. METHOD: C57/BL6 mice received Acu/LFES treatment on hindlimb for 30 min once. Acu/LFES points were selected by WHO Standard Acupuncture Nomenclature and electric stimulation applied using an SDZ-II Electronic acupuncture instrument. Muscle protein synthesis was measured by the surface-sensing of translation (SUnSET) assay. Exosomes were isolated using serial centrifugation and concentration and size of the collected exosomes were measured using a NanoSight instrument. The mature microRNA library in serum exosomes was validated using a High Sensitivity DNA chip. RESULTS: Protein synthesis was enhanced in the both hindlimb and forelimb muscles. Blocking exosome secretion with GW4869 decreased the Acu/LFES-induced increases in protein synthesis. MicroRNA-deep sequencing demonstrated that four members of the Let-7 miRNA family were significantly decreased in serum exosomes. Real time qPCR further verified Acu/LFES-mediated decreases of let-7c-5p in serum exosomes and skeletal muscles. In cultured C2C12 myotubes, inhibition of let-7c not only increased protein synthesis, but also enhanced protein abundance of Igf1 and Igf1 receptors. Using a luciferase reporter assay, we demonstrated that let-7 directly inhibits Igf1. CONCLUSION: Acu/LFES on hindlimb decreases let-7-5p leading to upregulation of the Igf1 signaling and increasing protein synthesis in both hindlimb and forelimb skeletal muscles. This provides a new understanding of how the electrical acupuncture treatment can positively influence muscle health.

Monocarboxylate Transporter-1 Mediates the Protective Effects of Neutral-pH Bicarbonate/Lactate-Buffered Peritoneal Dialysis Fluid on Cell Viability and Apoptosis.

We investigated the effects of bicarbonate/lactate-buffered peritoneal dialysis fluid (B/L-PDF) and lactate-buffered PDF (L-PDF) on cell viability and apoptosis, focusing on monocarboxylate transporters (MCTs). MCT-1 transports lactate into cells. Cell viability and apoptosis of human peritoneal mesothelial cells (HPMCs) were examined by water-soluble tetrazolium salt-1 and TUNEL assays, respectively. The relative number of viable HPMCs was significantly decreased by L-PDF at 48 h (8.8 ± 0.4%) compared with cells cultured in M199, but not by B/L-PDF (66.7 ± 1.1%). Apoptosis was markedly induced by L-PDF at 48 h (69.3 ± 16.2%), but not by B/L-PDF (2.6 ± 0.3%). Knockdown of MCT-1 by small interfering RNA (siRNA) attenuated the L-PDF-induced reduction of viable cells and increased apoptosis compared with control siRNA, but MCT-4 knockdown had no effect. B/L-PDF had lesser effects on cell viability and apoptosis of HPMCs compared with L-PDF. These results suggest that B/L-PDF biocompatibility occurs by avoiding the induction of apoptosis in HPMCs.

Corrigendum to "High glucose concentration-induced expression of pentraxin-3 in a rat model of continuous peritoneal dialysis".

This correct the article DOI: 10.14670/HH-11-756.

High glucose concentration-induced expression of pentraxin-3 in a rat model of continuous peritoneal dialysis.

BACKGROUND: Continuous exposure to peritoneal dialysis fluids (PDFs) is associated with pathological responses such as persistent micro-inflammation, which leads to ultrafiltration failure. Pentraxin-3 (PTX3), a multifunctional soluble pattern recognition receptor, is produced at sites of inflammation by a wide range of cell types. This study investigates the in vivo expression of PTX3 in the peritoneal membrane of a rat continuous peritoneal dialysis (PD) model, as well as the effect of high glucose on the in vitro expression of PTX3. METHODS: The expression of PTX3 was analyzed using RT-PCR, real-time PCR, immunohistochemistry and western blotting in a PD rat model receiving saline or conventional PDF containing 3.86% glucose for 8 weeks. The effects of high glucose on the expression of PTX3 were examined in cultured rat peritoneal mesothelial cells (RPMCs), mouse macrophage-like cells, and mouse fibroblasts. RESULTS: In a rat model of PD, eight-week instillation of the conventional PDF produced increased submesothelial thickening, followed by substantially enhanced PTX3 protein levels in the submesothelial layer of peritoneal membrane. PTX3 was detected in peritoneal mesothelial cells, macrophages and fibroblasts in the thickened submesothelial area. Glucose was found to induce PTX3 protein expression in RPMCs as well as macrophage-like cells and fibroblasts. CONCLUSION: Continuous exposure to conventional PDF induces PTX3 expression in the peritoneal membrane of rats. High glucose may be involved in the mechanism of PDF-induced local micro-inflammation in the peritoneum.

A novel UMOD gene mutation associated with uromodulin-associated kidney disease in a young woman with moderate kidney dysfunction.

Uromodulin-associated kidney disease (UAKD) is an autosomal dominant disease caused by a mutation in the uromodulin (UMOD) gene, leading to end-stage renal disease. We herein report the case of a family with UAKD caused by a novel mutation (C135G) in the UMOD gene. A 31-year-old woman had a low estimated glomerular filtration rate (59.7 mL/min per 1.73 m(2)). Her father, grandfather and paternal aunt had received maintenance hemodialysis therapy since their 40's. This case underscores the importance of performing genetic testing in young patients even in cases involving only moderate abnormalities in the kidney function.