Coexistence of systemic sclerosis and cryopyrin-associated periodic syndrome.

Systemic sclerosis (SSc) and cryopyrin-associated periodic syndrome (CAPS) are distinct clinical entities belonging to the autoimmune and autoinflammatory diseases, respectively. The coexistence of the two entities has rarely been reported and is poorly characterized. Here, we described a case of a 38-year-old Japanese woman diagnosed with anti-centromere antibody-positive SSc and CAPS carrying the pathogenic mutation in the NLRP3 gene, with a detailed autoantibody profile by a high-throughput comprehensive protein array covering approximately 90% of the human transcriptome. The clinical manifestations of the patient were typical of both SSc and CAPS. Comprehensive autoantibody profiling identified 65 autoantibodies in the patient's serum and 78 autoantibodies in the serum of her daughter with CAPS, who carried the same NLRP3 mutation as the patient. SSc-associated autoantibodies (anti-DBT, anti- CENP-B, and anti-CENP-A) and anti-CD320 antibody were detected at high levels only in the patient's serum, while autoantibodies to the following four proteins were detected in the sera of both the patient and her daughter: TRIM21, LIMS1, CLIP4, and KAT2A. The TRRUST enrichment analysis identified NF-κB1 and RelA as overlapping key transcription factors that regulate the genes encoding proteins to which autoantibodies were detected in the patient and her daughter, therefore the autoantibody profile of the patient cannot be solely attributed to SSc, but may also be influenced by CAPS. Although autoimmune and autoinflammatory diseases are considered to be at opposite ends of the immunological spectrum, detailed autoantibody profiling may reveal a unique immunological landscape in an overlapping case of the two entities.

Outcomes of brachial artery transposition in hemodialysis patients.

OBJECTIVE: In hemodialysis patients with a difficult access extremity who are not suitable for an arteriovenous fistula or arteriovenous graft creation, the concept of cannulating a superficialized artery for arterial outflow in dialysis sessions has been adopted as a tertiary alternative. However, its long-term patency and complications have not been recognized widely. We report our 16-year experience with hemodialysis access creation using the brachial artery transposition (BAT) technique. METHODS: This single-center retrospective study included consecutive patients who underwent BAT for hemodialysis vascular access between June 1, 2006, and December 31, 2022. The patency of the whole access circuit and the transposed brachial artery itself was evaluated independently. RESULTS: In total, 193 surgical procedures were included. The success rate was 93.2%. The mean operative time was 128 minutes. The median interval from access placement to first cannulation was 21 days. The primary patency rates for BAT were 92.3%, 91.3%, 90.3%, 86.1%, and 71.9% at 1, 2, 3, 5, and 10 years, respectively. The secondary patency rates for BAT were 96.3%, 96.3%, 95.0%, 90.1%, and 74.9% at 1, 2, 3, 5, and 10 years, respectively. The primary patency rates for the whole access circuit were 61.4%, 49.2%, 45.8%, and 26.9% at 1, 2, 3, and 5 years, respectively. The secondary patency rates for the whole access circuit were 85.1%, 83.3%, 82.0%, and 68.6% at 1, 2, 3, and 5 years, respectively. The overall patient survival rates were 79.6%, 69.6%, 54.6%, 36.5%, and 13.4% at 1, 2, 3, 5 and 10 years, respectively. The abandonments of BAT were brachial artery thrombosis (n = 6), pseudoaneurysm (n = 2), aneurysmal change (n = 1), and other reasons (n = 1). The abandonments of the whole access circuit were exhaustion of venous return (n = 26), abandonment of BAT (n = 7), and other reasons (n = 2). Complications were exhaustion of venous return (n = 26), aneurysmal change (n = 12), pseudoaneurysm (n = 6), brachial artery thrombosis (n = 7), impaired wound healing (n = 19), lymphorrhea (n = 9), skin infection (n = 5), hematoma on cannulation (n = 3), and reduced peripheral blood flow (n = 2). CONCLUSIONS: The patency of BAT was excellent, and that of the whole access circuit was adequate, with a few complications. BAT is an effective alternative from a long-term perspective for patients who are unsuitable for conventional hemodialysis access creation.

Evidence of tosufloxacin deposition in the kidneys of a patient presenting with crystal nephropathy.

Tosufloxacin tosilate is classified as a new quinolone antibacterial agent, which has been reported to cause crystal nephropathy. However, the origin of these crystal deposits has not yet been elucidated. We encountered a case of renal failure that progressed slowly owing to crystal-forming interstitial nephritis after long-term exposure to tosufloxacin. Mass spectrometry of the renal specimens revealed that tosufloxacin was deposited in the kidneys. The patient's renal function improved slowly with the withdrawal of tosufloxacin and steroid therapy. This is the first case to demonstrate the presence of crystal deposits consisting of tosufloxacin.

Bioelectrical Impedance Phase Angle Value and Prolongations of PR and Corrected QT Intervals in Patients Undergoing Dialysis.

INTRODUCTION: Phase angle value, derived from bioelectrical impedance analysis, represents the body cell mass and nutritional status of patients undergoing hemodialysis. Although the phase angle value has clinical significance in these patients, its relationship with electrocardiogram (ECG), another clinically relevant bioelectrical examination, has not yet been well clarified. METHODS: Two hundred and twenty-four patients undergoing dialysis (80 females and 144 males; mean ± SD, 72.2 ± 12.0 years old; 117 diabetic and 107 nondiabetic patients) were studied retrospectively. Multifrequency bioelectrical impedance analysis was performed immediately after the end of dialysis therapy. The phase shift was geometrically converted into a phase angle value. The ECG was recorded simultaneously, and the upper limits of the PR interval, QRS width, and corrected QT interval (QTc) were set at 0.20, 0.12, and 0.44 s, respectively. The geriatric nutritional risk index (GNRI), a representative nutritional index, was also determined. In addition, we examined the incidence of cardiac events, including heart failure, myocardial infarction, cardiac revascularization procedure, cardiac arrhythmia, and cardiac death, or all-cause death. RESULTS: Of 224 patients undergoing dialysis, the prolongation of the PR interval, QRS width, and QTc was found in 30.7, 17.4, and 62.1%, respectively. The prevalence of QTc prolongation was higher in females and diabetic patients than in males and nondiabetic patients. An inverse relationship between phase angle value and QTc was observed only in males and nondiabetic patients. The relationships of GNRI both with phase angle value and QTc were stronger in males and nondiabetic patients. In addition, PR interval was inversely correlated with a phase angle value only in nondiabetic patients. No significant correlation was found between phase angle value and QRS width. Five-year survival probability for the composite endpoints was significantly worse in patients with lower phase angle values. QTc prolongation was associated with survival in males and nondiabetic patients. Prolonged PR was associated with survival in nondiabetic patients. DISCUSSION: Relationships between phase angle value and ECG findings were demonstrated in patients undergoing dialysis, especially in males and nondiabetic patients. Although the phase angle value has been considered as an index for evaluating nutritional status, another clinical application of phase angle value in predicting cardiac complications seems to be useful.

Comparison of peripheral cutting balloon angioplasty with conventional balloon angioplasty for recurrent hemodialysis vascular access stenosis: A prospective randomized controlled trial.

PURPOSE: This study aimed to compare the efficacy and safety of cutting balloon angioplasty (CBA) and conventional balloon angioplasty (control group) for recurrent vascular access stenosis in arteriovenous fistulas. MATERIALS AND METHODS: This prospective, randomized single-center clinical trial included patients with hemodynamically significant recurrent vascular access stenosis of an arteriovenous fistula. The Kaplan-Meier method was used to assess primary patency, whereas the log-rank test was used to evaluate differences in patency between groups. Functional evaluations were performed using Doppler ultrasonography. RESULTS: Patients (n = 122) were randomly assigned to undergo CBA or conventional balloon angioplasty between December 2012 and November 2017. The clinical success rate was 100% in both groups. The anatomical success rates were 65% and 56% in the CBA and control groups, respectively. The primary patency of the target lesion was significantly better in the CBA group (33.3%) than in the control group (16.1%) at 6 months (hazard ratio, 0.50; 95% confidence interval, 0.33-0.77; p = 0.00171). The stenosis percentage decreased significantly after angioplasty in the CBA group (Δ-50.7%) compared with the control group (Δ-41.9%) (p = 0.0008). Access flow, measured using duplex Doppler ultrasonography, improved after angioplasty in both groups (300-526 ml/min in the control group and, 268-546 ml/min in the CBA group). Change in access flow (Δ + 278 ± 162) in the CBA group tended to be greater than that in the control group (Δ + 226 ± 151) (p = 0.07). However, the difference was not statistically significant. CONCLUSION: In patients with recurrent vascular access stenosis of the arteriovenous fistula CBA is effective and superior to conventional angioplasty.

A case of unusual renal manifestation in a patient with neuronal intranuclear inclusion disease treated with steroids.

Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disorder characterized by intranuclear inclusions. Kidney injury involvement and successful treatment for NIID have rarely been reported. A NIID patient developed crescentic IgA nephropathy. Steroid therapy resolved digestive symptoms and recovered renal function. Steroids are considered for concomitant symptoms of NIID.

Sentinel lymph node biopsy in extramammary Paget disease: A 13-year institutional experience.

Whether sentinel lymph node biopsy status is a prognostic factor or effective in determining treatment strategies in extramammary Paget disease remains unclear. This study aimed to investigate the significance of sentinel lymph node biopsy in extramammary Paget disease. We retrospectively reviewed the clinical information of previously untreated patients with invasive extramammary Paget disease who underwent wide local excision of the primary tumor and sentinel lymph node biopsy at our hospital between April 2008 and March 2021. Clinical data including the baseline neutrophil-to-lymphocyte ratio and recurrence-free survival were analyzed. Sentinel lymph node metastases were classified as macrometastases and micrometastases, with a cut-off value for sentinel lymph node tumor burden of 2 mm. Univariate and multivariate analyses of factors affecting sentinel lymph node biopsy positivity and recurrence-free survival rates were performed. Overall, 85 patients were included in the analysis. Patients in the sentinel lymph node biopsy-positive group (n = 26) had a significantly higher invasion level and neutrophil-to-lymphocyte ratio. According to multivariate analyses, invasion level and a high neutrophil-to-lymphocyte ratio were independent predictive factors for sentinel lymph node biopsy positivity, and the sentinel lymph node biopsy status was an independent prognostic factor for recurrence-free survival. In conclusion, sentinel lymph node biopsy provides an accurate risk classification and clinical indication for postoperative follow-up in patients with invasive extramammary Paget disease.

Deep learning analysis of clinical course of primary nephrotic syndrome: Japan Nephrotic Syndrome Cohort Study (JNSCS).

BACKGROUND: Prognosis of nephrotic syndrome has been evaluated based on pathological diagnosis, whereas its clinical course is monitored using objective items and the treatment strategy is largely the same. We examined whether the entire natural history of nephrotic syndrome could be evaluated using objective common clinical items. METHODS: Machine learning clustering was performed on 205 cases from the Japan Nephrotic Syndrome Cohort Study, whose clinical parameters, serum creatinine, serum albumin, dipstick hematuria, and proteinuria were traceable after kidney biopsy at 5 measured points up to 2 years. The clinical patterns of time-series data were learned using long short-term memory (LSTM)-encoder-decoder architecture, an unsupervised machine learning classifier. Clinical clusters were defined as Gaussian mixture distributions in a two-dimensional scatter plot based on the highest log-likelihood. RESULTS: Time-series data of nephrotic syndrome were classified into four clusters. Patients in the fourth cluster showed the increase in serum creatinine in the later part of the follow-up period. Patients in both the third and fourth clusters were initially high in both hematuria and proteinuria, whereas a lack of decline in the urinary protein level preceded the worsening of kidney function in fourth cluster. The original diseases of fourth cluster included all the disease studied in this cohort. CONCLUSIONS: Four kinds of clinical courses were identified in nephrotic syndrome. This classified clinical course may help objectively grasp the actual condition or treatment resistance of individual patients with nephrotic syndrome.

Predictors of early remission of proteinuria in adult patients with minimal change disease: a retrospective cohort study.

Previous studies reported conflicting results regarding an association between serum albumin concentration and the cumulative incidence of remission of proteinuria in adult patients with minimal change disease (MCD). The present study aimed to clarify the clinical impact of serum albumin concentration and the cumulative incidence of remission and relapse of proteinuria in 108 adult patients with MCD at 40 hospitals in Japan, who were enrolled in a 5-year prospective cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study (JNSCS). The association between serum albumin concentration before initiation of immunosuppressive treatment (IST) and the cumulative incidence of remission and relapse were assessed using multivariable-adjusted Cox proportional hazards models. Remission defined as urinary protein < 0.3 g/day (or g/gCr) was observed in 104 (96.3%) patients. Of 97 patients with remission within 6 month of IST, 42 (43.3%) developed relapse defined as ≥ 1.0 g/day (or g/gCr) or dipstick urinary protein of ≥ 2+. Serum albumin concentration was significantly associated with remission (multivariable-adjusted hazard ratio [95% confidence interval] per 1.0 g/dL, 0.57 [0.37, 0.87]), along with eGFR (per 30 mL/min/1.73 m2: 1.43 [1.08, 1.90]), whereas they were not associated with relapse. A multivariable-adjusted model showed that patients with high eGFR level (≥ 60 mL/min/1.73 m2) and low albumin concentration (≤ 1.5 g/dL) achieved significantly early remission, whereas those with low eGFR (< 60 mL/min/1.73 m2) and high albumin concentration (> 1.5 g/dL) showed significantly slow remission. In conclusion, lower serum albumin concentration and higher eGFR were associated with earlier remission in MCD, but not with relapse.

Time to remission of proteinuria and incidence of relapse in patients with steroid-sensitive minimal change disease and focal segmental glomerulosclerosis: the Japan Nephrotic Syndrome Cohort Study.

BACKGROUND: Minimal change disease (MCD) is characterized by a nephrotic syndrome usually steroid-sensitive and a high incidence of relapse of proteinuria. Previous cohort studies have reported conflicting results regarding the association between the time to remission and incidence of relapse. METHODS: This multicenter prospective cohort study included 102 adult patients with steroid-sensitive MCD or focal segmental glomerulosclerosis from a 5-year cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study, who achieved remission of proteinuria within 2 months of immunosuppressive therapy (IST). The association between the time to remission of proteinuria after immunosuppressive therapy and incidence of relapse was assessed using Cox proportional hazards models adjusted for clinically relevant factors. RESULTS: Remission was observed at 3-7, 8-14, 15-21, 22-28, and 30-56 days after initiation of immunosuppressive therapy in 17 (16.7%), 37 (36.3%), 21 (20.6%), 13 (12.7%), and 14 (13.7%) patients, respectively. During a median observation period of 2.3 years after the end of the 2nd month after initiation of immunosuppressive therapy, 46 (45.1%) patients relapsed. The time to remission was associated with the incidence of relapse in an inverse U-shaped pattern (multivariable-adjusted hazard ratios [95% confidence intervals] of the time to remission of 3-7, 8-14, 15-21, 22-28, 30-56 days: 1.00 [reference], 1.76 [0.56, 5.51], 6.06 [1.85, 19.80], 5.46 [1.44, 20.64], and 2.19 [0.52, 9.30], respectively). CONCLUSION: The time to remission was identified as a significant predictor of relapse in steroid-sensitive patients.

Supportive Effects of Online Hemodiafiltration Therapy on the Nutritional State and Lipid Profile in Very Elderly Dialysis Patients.

INTRODUCTION: Online hemodiafiltration (HDF) therapy has been recognized as one of the potential dialysis modalities. However, the long-term effects of online HDF therapy on very elderly dialysis patients older than 75 years have yet to be fully elucidated. METHODS: Seventy-four very elderly patients older than 75 years undergoing maintenance dialysis therapy were studied retrospectively. Twenty-four (mean ± SE, 81.5 ± 1.0 years) were treated by predilution online HDF, and fifty (81.2 ± 0.6 years) were treated by conventional hemodialysis (HD) for 3 years. Laboratory data related to the nutritional state and lipid profile were collected. Body composition was measured by a bioelectrical impedance method. RESULTS: Dry weight and body mass index decreased in HD patients (2.9%, p = 0.003 and 3.1%, p = 0.001, respectively), while no significant changes were found in online HDF patients. Serum albumin levels reduced in both HD and online HDF groups (3.5%, p = 0.003 and 2.9%, p = 0.026, respectively). The geriatric nutritional risk index decreased in HD patients (3.0%, p < 0.001), while no significant change was shown in online HDF patients. Body composition analysis demonstrated a significant decrease in intracellular water and increases in extracellular water and edema ratio in both groups. Fat mass and %fat showed significant decreases in HD patients (8.1%, p = 0.003 and 7.3%, p = 0.003, respectively), but no significant changes in online HDF patients. Among laboratory data, serum high-density lipoprotein cholesterol levels did not change in HD patients. However, the levels elevated significantly (10.6%, p = 0.03) in online HDF patients. DISCUSSION/CONCLUSION: These results indicated that the time-dependent deterioration of the nutritional state in very elderly dialysis patients was inevitable; however, such deterioration was not prominent in online HDF patients. Moreover, the lipid profile showed unique changes in online HDF patients. In order to treat very elderly dialysis patients, online HDF should preferentially be taken into consideration because the maintenance of general condition seems to be a practical goal against the natural time-dependent deterioration.

Serum Cytokeratin 18 as a Metastatic and Therapeutic Marker for Extramammary Paget's Disease.

Extramammary Paget's disease (EMPD) is a rare cutaneous adenocarcinoma with unfavourable prognosis once it becomes invasive. A tumour marker that reflects disease progression is required for adequate management of EMPD. Cytokeratin 18 is highly expressed in many types of cancer and its soluble forms are detected by M30 (for caspase-cleaved form) and M65 (for both caspase-cleaved and intact forms) assays. We report here that tumour cells of EMPD in both lesional skin and lymph node metastasis are immunohistochemically positive for CK18, and the baseline serum M30 and M65 levels in patients with metastatic EMPD are significantly higher than those in non-metastatic patients. In addition, serial serum M30 and M65 levels might reflect recurrence of EMPD and response to chemotherapy. These results suggest that serum CK18 levels may be a useful tumour marker for advanced EMPD.

TGF-ß1 is involved in senescence-related pathways in glomerular endothelial cells via p16 translocation and p21 induction.

p16 inhibits cyclin-dependent kinases and regulates senescence-mediated arrest as well as p21. Nuclear p16 promotes G1 cell cycle arrest and cellular senescence. In various glomerular diseases, nuclear p16 expression is associated with disease progression. Therefore, the location of p16 is important. However, the mechanism of p16 trafficking between the nucleus and cytoplasm is yet to be fully investigated. TGF-ß1, a major cytokine involved in the development of kidney diseases, can upregulate p21 expression. However, the relationship between TGF-ß1 and p16 is poorly understood. Here, we report the role of podocyte TGF-ß1 in regulating the p16 behavior in glomerular endothelial cells. We analyzed podocyte-specific TGF-ß1 overexpression mice. Although p16 was found in the nuclei of glomerular endothelial cells and led to endothelial cellular senescence, the expression of p16 did not increase in glomeruli. In cultured endothelial cells, TGF-ß1 induced nuclear translocation of p16 without increasing its expression. Among human glomerular diseases, p16 was detected in the nuclei of glomerular endothelial cells. In summary, we demonstrated the novel role of podocyte TGF-ß1 in managing p16 behavior and cellular senescence in glomeruli, which has clinical relevance for the progression of human glomerular diseases.

One-year intradialytic leg exercises with resistance bands and fat mass increase in elderly hemodialysis patients: a retrospective study.

BACKGROUND: Intradialytic exercises are recommended to be available as a treatment for enhancing physical functioning. However, there have been few reports which evaluated the results of long-term mild intradialytic exercises in elderly patients. The purpose of this study is to investigate the changes in body weight, body composition, and laboratory data in elderly hemodialysis patients after 1-year intradialytic leg exercises with resistance bands. METHODS: A retrospective study. Twenty-one outpatients, aged 65 or older (mean ± SD, 75.2 ± 5.1 years), received intradialytic leg exercises with resistance bands for a year were analyzed. The values of dry weight, body composition, and laboratory data were collected from the year-ago period, at baseline and 1 year after baseline. Fat and muscle mass were evaluated by using a multi-frequency bioimpedance device. RESULTS: Physical performance changed and body weight increased after 1-year resistance band exercises. However, the participants gained fat mass, not muscle mass. Although the changes in biochemical data related to protein intake were equivocal, triglyceride levels increased significantly after 1-year exercises. An elevation in serum creatinine levels was observed, even if solute clearance increased significantly. CONCLUSIONS: One-year intradialytic leg exercises with resistance bands may have a potential clinical benefit for body mass index even in elderly hemodialysis patients. However, optimal dietary modification is needed to achieve a balanced increase of muscle and fat mass. An increase of serum creatinine levels does not always mean muscle mass hypertrophy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41100-021-00341-z.

Usefulness of presepsin / creatinine ratio as a new index that corrects for renal function.

Background : Presepsin (P-SEP) is a highly specific sepsis marker, and its fluctuation with respect to advanced renal impairment or sample agitation has not been fully investigated. We evaluated several renal function-corrected P-SEP indices to establish a simple index and its reference range. Methods : Blood samples for P-SEP measurement were collected with minimal agitation. P-SEP levels were measured using the rapid automated immunoanalyzer "PATHFAST." This study included 85 chronic kidney disease (CKD) patients, 65 healthy volunteers, and 4 sepsis patients. Results : Patients stratified by estimated glomerular filtration rate (GFR) had significantly higher P-SEP levels for CKD stage G3, especially the advanced GFR stage. We evaluated presepsin / creatinine (P-SEP / CRE) and P-SEP / eGFR ratios as possible indices for renal function. The P-SEP / CRE ratio exhibited no increase correlating with the GFR stage and was identical in the normal and CKD groups ;  P-SEP / eGFR decreased if GFR stage worsened. The P-SEP / CRE ratio became significantly higher in sepsis patients and was a more useful index with a reference range of 67-263. Conclusions : P-SEP levels were inversely correlated with renal function, indicating the necessity to consider the influence of renal impairment in CKD patients. The P-SEP / CRE ratio is helpful for sepsis diagnosis, even in patients with renal impairment. J. Med. Invest. 68 : 105-111, February, 2021.

Association between diabetes-related clinical indicators and oral health behavior among patients with type 2 diabetes.

Objective : The aim of this study was to evaluate the association between diabetes-related indicators and oral health behavior among patients with type 2 diabetes. Methods : Seventy-four outpatients were included. We administered a questionnaire and divided the patients into two groups according to oral health behavior and eating habits. We then compared diabetes-related clinical records between the groups and performed logistic regression analysis. Results : Participants who brushed their teeth before bedtime every night had lower BMIs than those who did not. Participants who reported eating slowly and chewing well every day had significantly lower HbA1c than their counterparts. Participants who reported gum bleeding had significantly higher LDL-cholesterol than their counterparts. Binominal logistic regression analysis revealed that BMI < 25 was associated with not brushing teeth before bedtime every night, HbA1c < 7.5 with not eating slowly or chewing well every day, and LDL-cholesterol < 120 with gum bleeding (odds ratio : 0.140, 95% confidence interval : 0.036-0.540 ; OR : 0.085, 95% CI : 0.010-0.736, OR : 0.275, 95% CI : 0.077-0.979, respectively). Conclusions : Our findings suggest that toothbrushing before bedtime every night is associated with reduced risk of obesity and that eating slowly and chewing well are advantageous for glycemic control in patients with type 2 diabetes.J. Med. Invest. 68 : 140-147, February, 2021.

Dual disruption of eNOS and ApoE gene accelerates kidney fibrosis and senescence after injury.

The relationship between cellular senescence and fibrosis in the kidney is being elucidated and we have identified it as therapeutic target in recent studies. Chronic kidney disease has also become a lifestyle disease, often developing on the background of hypertension and dyslipidemia. In this study, we clarify the effect of interaction between these two conditions on kidney fibrosis and senescence. Wild type mice (WT), apolipoprotein E-/- mice (ApoEKO), and endothelial nitric oxide synthase (eNOS)-/- ApoE-/- mice (DKO) were obtained by breeding. Unilateral ureteral obstruction (UUO) was performed on 8-10 week old male mice and the degree of renal tubular injury, fibrosis and kidney senescence were evaluated. DKO manifested elevated blood pressure, higher total cholesterol and lower HDL than WT. DKO showed sustained kidney injury molecule-1 protein expression. Kidney fibrosis was significantly higher in ApoEKO and DKO. mRNA expression of genes related to kidney fibrosis was the highest in DKO. The mRNA expression of Zinc-α2-Glycoprotein and heme oxygenase-1 were significantly decreased in DKO. Furthermore, mRNA expression of p53, p21 and p16 were increased both in ApoEKO and DKO, with DKO being the highest. Senescence associated ß-gal positive tubule area was significantly increased in DKO. Increased DNA damage and target of rapamycin-autophagy spatial coupling compartments (TASCCs) formation was found in DKO. Mice with endothelial dysfunction and dyslipidemia developed kidney fibrosis and accelerated senescence even in young mice after injury. These data highlight the fact managing lifestyle-related diseases from a young age is important for CKD prevention.

Glucocorticoid-dependent Tubulointerstitial Nephritis with IgM-positive Plasma Cells Presenting with Intracellular Crystalline Inclusions within the Rough Endoplasmic Reticulum.

Tubulointerstitial nephritis (TIN) with IgM-positive plasma cells (IgMPC-TIN) is an autoimmune kidney disease characterized by IgM/CD138-double-positive plasma cell infiltration in the tubulointerstitium. A 50-year-old man developed IgMPC-TIN and presented with crystalline inclusions in the rough endoplasmic reticulum. Intracellular crystal formation is a rare finding in paraprotein-related kidney diseases, but this case showed no pathogenic monoclonal immunoglobulin. Prednisolone (PSL, 30 mg) improved the TIN, but PSL tapering resulted in the recurrence of TIN. Combination therapy with 15 mg PSL and 150 mg mizoribine ultimately stabilized TIN. This case offers original evidence concerning the pathophysiology and treatment strategy of IgMPC-TIN.