An Elderly Case of Minimal Change Nephrotic Syndrome: Correlation between Renal Tubular Dysfunction and the Onset of Oliguric Acute Kidney Injury Requiring Hemodialysis.

Several theories have been proposed to explain the development of severe acute kidney injury (AKI) in patients with minimal change nephrotic syndrome (MCNS), but the exact mechanism remains unclear. We encountered an elderly patient with biopsy-proven MCNS who suffered from oliguric AKI, which required hemodialysis at the onset and during the first relapse of nephrotic syndrome. Throughout her relapse, we were able to monitor tubular injury markers, namely, urinary N-acetyl-ß-D-glucosaminidase and urinary alpha-1-microglobulin levels. This patient had hypertension. 8.5 years after achieving complete remission, she experienced a relapse of nephrotic syndrome accompanied by AKI, necessitating hemodialysis. The hemodialysis was discontinued after 7 weeks of corticosteroid therapy and cyclosporin A treatment. During this relapse, we observed a correlation between the sudden increase in renal tubular injury markers and proteinuria levels and the progression of severe AKI. Conversely, a reduction in renal tubular injury markers and proteinuria was associated with the resolution of AKI. The abrupt elevation of both tubular injury markers and proteinuria levels suggests a possible breakdown in protein endocytosis in proximal tubular cells. Moreover, it is less likely that the acute reduction in intra-glomerular pressure is the primary cause of tubular injury, as it might result in a decrease in both glomerular filtration rate and proteinuria levels. It is conceivable that massive proteinuria, in conjunction with the patient's clinical characteristics, may contribute to tubular injury, ultimately leading to severe AKI in this patient.

Self-Reported Sleep Duration and Bedtime Are Associated with Dementia Risk in Community-Dwelling People Aged 40-74 Years: The Murakami Cohort Study.

Background: Sleep is a potentially modifiable factor associated with dementia, including Alzheimer's disease, but current evidence supporting this is insufficient. Objective: This study aimed to determine whether sleep duration and bedtime patterns are associated with the risk of dementia among middle-aged and older people. Methods: This cohort study had an eight-year follow-up period. Participants were 13,601 community-dwelling people aged 40-74 years living in Murakami (Niigata, Japan). Data were collected using a self-administered questionnaire. Predictors were self-reported sleep duration and bedtime, and the outcome was newly-diagnosed dementia determined using the long-term care insurance database. Covariates were demographic characteristics, body mass index, smoking, alcohol consumption, total physical activity, insomnia symptoms, disease history, and either bedtime or sleep duration. Cox proportional hazard models were used to calculate hazard ratios (HRs). Results: The mean age of participants at baseline was 59.2 years. Over a mean follow-up period of 8.0 years, 319 cases of dementia were observed. A long self-reported sleep duration relative to the reference sleep duration (7 hours) was associated with increased dementia risk, with the "8 hours" group (adjusted HR = 1.30, 95% CI:0.99-1.73) and "≥9 hours" group (adjusted HR = 1.46, 95% CI:1.00-2.15) having an increased risk (marginally significant) relative to the reference group. Early bedtime was associated with increased dementia risk (adjusted p for trend = 0.0010), with the "21 : 00 or earlier" group (adjusted HR = 1.61, 95% CI:1.14-2.28) having an increased risk relative to the reference ("23 : 00"). Conclusions: A long self-reported sleep duration and early bedtime are both associated with increased dementia risk in middle-aged and older people.

Effective Management of Hypertensive Emergencies with Aliskiren Treatment in a Patient Before and After Introducing Hemodialysis Secondary to Scleroderma Renal Crisis-like Condition Under Corticosteroid Treatment for Sjögren Syndrome-associated Multiple Mononeuropathy.

A middle-aged woman presented with hypertensive emergency after corticosteroid treatment for Sjögren syndrome-associated multiple mononeuropathy with suspected systemic sclerosis. Hypertensive heart failure with hyperreninemia improved with antihypertensives, including aliskiren; however, she became hemodialysis-dependent. Clinical findings and biopsy-proven thrombotic microangiopathy indicated conditions resembling scleroderma renal crisis (SRC). Severe hypertension and heart failure with hyperreninemia occurred after stopping aliskiren for hypotension due to diverticular bleeding, which improved after the reintroduction of aliskiren. Aliskiren appears to be effective in managing hypertensive heart failure in patients with SRC. Nevertheless, hemodialysis remained necessary in our case, and whether or not aliskiren can restore the renal function is unclear.

Chronic Pain in the Lower Extremities and Low Back is Associated With Recurrent Falls in Community-Dwelling Japanese People Aged 40-74 Years.

OBJECTIVE: To determine the longitudinal association between chronic pain in the lower extremities and low back and the odds of recurrent falls in middle-aged and older people. DESIGN: A cohort study. SETTING: Communities in Japan. PARTICIPANTS: Participants were 7540 community-dwelling volunteers aged 40-74 years (N=7540). The baseline survey was a self-administered questionnaire conducted between 2011-2013. Predictors were presence of chronic pain in the knee, foot or ankle, and low back, with the degree of pain categorized as none, very mild/mild, moderate, or severe/very severe. Covariates in the multivariate model of chronic pain in a site were demographics, body mass index, physical activity level, disease history, and chronic pain in the other 2 sites. Logistic regression analysis was used to calculate odds ratios (ORs). INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Recurrent falls in the year before the 5-year follow-up survey. RESULTS: Mean participant age was 60.2 years. Higher degrees of chronic pain were associated with higher odds of recurrent falls for the knee (P=.0002) with a higher OR of 1.48 (95% CI: 1.11-1.97), for the foot or ankle (P=.0001) with a higher OR of 1.97 (95% CI: 1.36-2.86), and for the low back (P=.0470) with a higher OR of 1.45 (95% CI: 1.09-1.91) in those with any degree of pain relative to those without pain. Higher degrees of chronic knee pain were associated with higher odds of recurrent falls in women (P=.0005), but not in men (P=.0813). Meanwhile, higher degrees of chronic low back pain were associated with the odds of recurrent falls in men (P=.0065), but not in women (P=.8735). CONCLUSIONS: Chronic pain in the knee, foot or ankle, and lower back was independently and dose-dependently associated with a higher risk of recurrent falls. A marked sex-dependent difference was also noted in the association.

Body mass index, height, and osteoporotic fracture risk in community-dwelling Japanese people aged 40-74 years.

INTRODUCTION: The association between body size and fracture risk is complex and varies by sex and ethnicity. This study aimed to examine associations of body mass index (BMI) and height with osteoporotic fracture risk in middle-aged and older people. MATERIALS AND METHODS: This 10-year cohort study included 13,151 community-dwelling Japanese people aged 40-74 years. A self-administered questionnaire survey was conducted at baseline to obtain information on demographic characteristics, body size, lifestyle, and disease history. BMI (kg/m2) was categorized as underweight (< 18.5), low-normal (18.5-21.7), high-normal (21.8-24.9), overweight (25.0-29.9), and obese (≥ 30.0). Height was categorized into quartiles. All incident cases of major osteoporotic fractures, including fractures of the distal radius, neck of the humerus, neck or trochanter of the femur, and vertebrae, were obtained from medical records during follow-up. RESULTS: Mean participant age was 58.8 years. In men, the underweight group had a significantly higher hazard ratio (HR) for total fracture (adjusted HR = 2.46), and the obese group had significantly higher HRs for total (adjusted HR = 3.01) and vertebral (HR = 3.77) fractures relative to the reference (overweight) group. No significant associations were observed between BMI and risk of any fracture in women. Higher quartiles of height were associated with higher vertebral fracture risk (adjusted P for trend = 0.023) only in women. CONCLUSION: BMI and osteoporotic fracture risk showed a U-shaped association in men, whereas higher height was associated with higher vertebral fracture risk in women, suggesting sex-dependent differences in these associations.

Discontinuing Hemodialysis through Corticosteroid Treatment in a Patient with Cryofibrinogen-associated Glomerulonephritis.

Cryofibrinogen-associated glomerulonephritis (CryoFiGN) is rare, and its diagnosis is difficult while treatment is not established. We herein report an elderly woman with CryoFiGN who experienced recurrent purpura and nephritic features that subsequently progressed to nephrotic syndrome and required hemodialysis during the 18-month clinical course. The patient was treated with corticosteroids, which led to the discontinuation of hemodialysis. The diagnosis of CryoFiGN was based on the clinical presentation, characteristic glomerular deposits, and results of laser microdissection and liquid chromatography-tandem mass spectrometry of the glomeruli. This case highlights the potential utility of corticosteroids as a treatment option for patients with CryoFiGN, even after hemodialysis.

Slowly Progressive ANCA-associated Glomerulonephritis with Strong Mesangial MPO Deposits Following a Diagnosis of Interstitial Lung Disease: A Case Report.

An elderly woman showed positive conversion of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibodies (ANCAs) following the diagnosis of interstitial lung disease (ILD) and glomerular hematuria and subsequently experienced slowly progressive glomerulonephritis. A kidney biopsy revealed chronic damage and necrotizing crescentic glomerulonephritis with mesangial MPO deposits. After corticosteroid treatment, the patient's urinalysis results and MPO-ANCA titers almost normalized and her renal function stabilized. This case is similar to recently reported cases of slowly progressive ANCA-associated glomerulonephritis. ILD likely triggered the production of MPO-ANCAs, and the accumulation of MPO deposits in the glomeruli may have contributed to the progression of her renal disease.

Sex Differences in the Association Between Body Mass Index and Dementia Risk in Community-Dwelling Japanese People Aged 40-74 Years.

BACKGROUND: The association between body mass index (BMI) and dementia risk is heterogeneous across age groups and might be influenced by sex. OBJECTIVE: This study aimed to clarify sex differences in the association between BMI and dementia risk in community-dwelling people. METHODS: This cohort study with an 8-year follow-up targeted 13,802 participants aged 40-74 years at baseline in 2011-2013. A self-administered questionnaire requested information on body size, including height, weight, and waist circumference (the values of which were validated by direct measurement), socio-demographics, lifestyle, and disease history. BMI was calculated and categorized as < 18.5 (underweight), 18.5-20.6 (low-normal), 20.7-22.6 (mid-normal), 22.7-24.9 (high-normal), 25.0-29.9 (overweight), and≥30.0 kg/m2 (obese). Incident cases of dementia were obtained from the long-term care insurance database. A Cox proportional hazards model was used to calculate multivariable-adjusted hazard ratios (HRs). RESULTS: The mean age of participants was 59.0 years. In men, higher BMI was associated with lower dementia risk (fully-adjusted p for trend = 0.0086). In women, the association between BMI and dementia risk was U-shaped; the "underweight," "low-normal," and "overweight" groups had a significantly higher risk (fully-adjusted HR = 2.12, 2.08, and 1.78, respectively) than the reference ("high-normal" group). These findings did not change after excluding dementia cases which occurred within the first four years of the follow-up period. CONCLUSION: Overweight/obese women, but not men, had an increased risk of dementia, suggesting that sex differences in adiposity might be involved in the development of dementia.

Alcohol consumption, smoking, and risk of dementia in community-dwelling Japanese people aged 40-74 years: The Murakami cohort study.

OBJECTIVE: Alcohol drinking and tobacco smoking have impacts on lifestyle-related diseases, but their association with dementia remains a debated topic. This study aimed to examine longitudinal associations between alcohol consumption, smoking, and dementia risk in middle-aged and older Japanese people. METHODS: This study used a cohort design with an 8-year follow-up. Participants were community-dwelling Japanese people (N = 13,802) aged 40-74 years. The baseline survey, including a self-administered questionnaire, was conducted in 2011-2013. Predictors were alcohol consumption and tobacco smoking. The outcome was incident dementia obtained from a long-term care insurance database. Covariates were demographics, lifestyle factors, body mass index, general health status, and history of stroke, diabetes, and depression. RESULTS: Participant mean age was 59.0 years. The 1-149, 150-299, and 300-449 g ethanol/week groups had significantly lower adjusted hazard ratios (HRs) (0.62, 0.59, and 0.47, respectively) compared with the reference group, with no significant linear association. HRs increased toward 1 when past-drinkers and those with poor health status and a disease history were excluded (0.80, 0.66, and 0.82, respectively). Higher smoking levels were dose-dependently associated with a higher HR (adjusted P for trend = 0.0105), with the ≥20 cigarettes/day group having a significantly higher adjusted HR (1.80). Heavy drinkers (≥449 g ethanol/week) with smoking habits, but not those without smoking habits, had higher dementia risk (P for interaction = 0.0046). CONCLUSION: Light-to-moderate alcohol consumption is associated with decreased dementia risk, and smoking is dose-dependently associated with increased dementia risk, with an interaction between high alcohol consumption and smoking on dementia risk.

A Diagnostic and Therapeutic Dilemma Concerning Exostosin 1/Exostosin 2-associated Lupus-like Membranous Nephropathy with Positive Antinuclear Antibody in an Elderly Man with Various Immune Abnormalities.

Exostosin 1 (EXT1) and exostosin 2 (EXT2)-associated membranous nephropathy (MN) may be associated with active autoimmune disease. We encountered an elderly man who presented with EXT1/EXT2-associated lupus-like MN with full house immune deposits, monoclonal gammopathy of uncertain significance and Sjögren's syndrome. The patient exhibited various other immune abnormalities. Although he did not fulfill the criteria of clinical systemic lupus erythematosus (SLE), he met a stand-alone renal criterion of the Systemic Lupus International Collaborating Clinics (SLICC) 2012. Whether or not a stand-alone renal criterion with EXT1/EXT2 positivity, as in the present patient, can efficiently guide decisions regarding the diagnosis and treatment of SLE remains a clinical dilemma.

Tubulointerstitial B-cell infiltration and tertiary lymphoid tissue in adult-onset immunoglobulin A vasculitis with nephritis.

PURPOSE: This study aimed to examine tubulointerstitial B-cell infiltration in patients with adult-onset immunoglobulin A vasculitis (IgAV) and nephritis (IgAV-N), and to evaluate whether B-cell infiltration correlated with clinicopathological variables at kidney biopsy and with short-term renal outcomes. METHODS: Twenty patients with adult-onset IgAV-N and 10 control patients with thin basement membrane nephropathy (TBMN) were retrospectively examined. The lymphatic organization was graded based on B-cell infiltration and was classified into 4 groups: 0-T cells without B cells, 1-scattered B and T cells, 2-clustered B and T cells, and 3-nodular compartmentally arranged B- and T-cell aggregates, equivalent to tertiary lymphoid tissue (TLT). RESULTS: The B-cell infiltration grade was significantly higher in patients with IgAV-N than in patients with TBMN, and no age differences were observed. The B-cell infiltration grade in patients with IgAV-N was significantly correlated with age, serum IgA level, renal dysfunction, and tubulointerstitial injury parameters, but was not correlated with duration after purpura or glomerular injury parameters. Most patients with IgAV-N were treated with corticosteroids. The proteinuria level was significantly decreased, but renal function was not improved in 12 patients after the 24-month follow-up compared with the values at baseline. The B-cell infiltration grade was significantly correlated with renal dysfunction after 24 months of follow-up. CONCLUSIONS: The B-cell infiltration grade in patients with IgAV-N was associated with renal dysfunction and tubulointerstitial injuries but not with glomerular injury parameters. B-cell infiltration and TLT might have a pathologically significant role in irreversible renal dysfunction in patients with early phase adult-onset IgAV-N.

IgA vasculitis with transient glomerular hematuria, diarrhea, and pericarditis following COVID-19 mRNA vaccination in a young patient with possible pre-existing ulcerative colitis.

Exacerbations or de novo autoimmune/autoinflammatory disease have been reported after COVID-19 vaccination. A young male presented with cutaneous IgA vasculitis with glomerular hematuria, diarrhea and pericarditis following his second COVID-19 mRNA vaccination. He also showed positivity for proteinase 3 anti-neutrophil cytoplasmic antibody (PR3-ANCA) and anti-cardiolipin antibody. Skin biopsy was compatible to IgA vasculitis. His purpura subsided and hematuria spontaneously disappeared. Treatment with anti-inflammatory medications and prednisolone resolved the pericarditis. He had a history of persistent diarrhea, and colonic biopsies showed possible ulcerative colitis without vasculitis. Kidney biopsy after prednisolone therapy revealed minor glomerular abnormalities without any immune reactants and did not show vasculitis. After prednisolone treatment, PR3-ANCA decreased in a medium degree despite of improvement of symptoms and inflammatory data, suggesting that his PR3-ANCA may be associated with ulcerative colitis. The cause of the transient glomerular hematuria was unclear, however, it might be caused by focal glomerular active lesions (glomerular vasculitis) due to vaccine-induced IgA vasculitis with nephritis. This case highlights that COVID-19 mRNA vaccination can activate multiple autoimmune/autoinflammatory systems. The conditions might help us better understand the mutual mechanisms of the relevant disorders.

Physical activity and recurrent fall risk in community-dwelling Japanese people aged 40-74 years: the Murakami cohort study.

BACKGROUND: Falls are important causes of injury and mortality in older people, and associated medical costs can be enormous. Physical activity (PA) is a potential preventive factor for falls. However, few studies have examined the effect of different types of PA on fall prevention. This study aimed to evaluate the association between PA levels and the incidence of recurrent falls by type of PA in middle-aged and older people. METHODS: This cohort study targeted 7,561 community-dwelling individuals aged 40-74 years who did not experience recurrent falls in the year before baseline. Information on PA levels, demographics, body size, lifestyle, and fall/disease history was obtained using a self-administered questionnaire in the baseline survey. Levels of total PA, leisure-time PA, and non-leisure-time PA (occupation, commuting, and housework) were estimated using metabolic equivalent (MET) scores (MET-h/day; hours spent on a given activity per day multiplied by its MET intensity). PA levels were categorized into four groups. Falls were recorded as none, once, or twice or more (recurrent falls). The outcome of the study was the incidence of recurrent falls in the past year before a survey conducted 5 years after the baseline survey. Logistic regression analyses were performed to calculate odds ratios for recurrent falls. RESULTS: Higher total PA and non-leisure-time PA levels were associated with a higher risk of recurrent falls (P for trend = 0.0002 and 0.0001, respectively), with the highest total PA and non-leisure-time PA groups having a significantly higher adjusted OR (1.96 [95%CI:1.33-2.88] and 2.15 [95%CI:1.48-3.14], respectively) relative to the lowest group (reference). As for leisure-time PA, the medium group had a significantly lower adjusted OR (0.70 [95%CI:0.49-0.99]) relative to the reference group. By sex, the adjusted OR in the medium leisure-time PA group was significantly lower relative to the reference group in women (0.50 [95%CI: 0.29-0.85]) but not in men. CONCLUSIONS: Medium level leisure-time PA reduces the risk of recurrent falls in middle-aged and older people, whereas higher level non-leisure-time PA is associated with a higher risk of recurrent falls.

Selenium Associates With Response to Erythropoiesis-Stimulating Agents in Hemodialysis Patients.

Introduction: Impaired response to erythropoiesis-stimulating agents (ESAs) is associated with increased mortality in patients with end-stage kidney disease. However, the underlying mechanisms are not fully elucidated. Accumulating data reveal that selenium (Se), a trace element, plays a key role in stress erythropoiesis and erythrocyte homeostasis. We evaluated the relationship between serum Se levels and the response to ESAs in hemodialysis patients. Methods: In this cross-sectional study, we determined serum Se levels in 173 hemodialysis patients. We analyzed the association of serum Se with ESA responsiveness, as defined by ESA resistance index. Results: Of the study participants, 50% had lower Se levels than the population-based reference values. We found that serum Se levels were significantly and inversely correlated with erythropoiesis resistance index (ERI) but not transferrin saturation (TSAT) or ferritin levels. Multiple regression analyses confirmed the association between Se levels and ESA hyporesponsiveness, independently of other known factors, such as iron status, being female, and dialysis vintage (ß = -0.11, P < 0.001). When patients were divided according to Se levels and iron status, both low serum Se (<10.5 µg/dl) and iron deficiency significantly affected the response to ESA. Conversely, serum Se levels were significantly different among groups when patients were divided according to ERI quartiles. The association of low serum Se with ESA hyporesponsiveness persisted after adjustment of confounding variables. Conclusion: Serum Se levels are associated with the response to ESAs and can predict ESA resistance independently of iron status in Japanese hemodialysis patients. These data open the possibility to test whether Se supplementation reduces ESA demand.

A Patient with Acute Kidney Injury Associated with Massive Proteinuria and Acute Hyperuricemia after Epileptic Seizures.

A 25-year-old man presented with acute kidney injury (AKI), massive proteinuria and hyperuricemia after epileptic seizures. His AKI improved along with the disappearance of proteinuria after corticosteroid treatment. A kidney biopsy revealed no significant glomerular abnormalities, but varying degrees of tubular injury, such as proximal tubular simplification, mild distal tubular proliferation, and Tamm-Horsfall protein-like material accumulation with extravasation into the interstitium, were noted. A further analysis revealed the intratubular depositions of uric acid crystals, indicating the involvement of acute uric acid nephropathy associated with seizures. Our patient's condition is rare, and the clinicopathological aspects of the diagnostic challenges are discussed.