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1.
PLoS One ; 19(5): e0301715, 2024.
Article in English | MEDLINE | ID: mdl-38781188

ABSTRACT

INTRODUCTION: We examined whether the Clinical Frailty Scale (CFS), a widely adopted tool for stratifying the degree of frailty, and the Dementia Assessment Sheet for Community-based Integrated Care System 21-items (DASC-21), a simple tool for simultaneous assessment of impaired cognition and impaired ADL, at the time of initiation of hemodialysis is useful tool of older patients for the outcome and prognosis. METHODS: Data for 101 patients aged 75 years or older (mean age, 84.3 years) with ESRD who were initiated on hemodialysis and could be followed up for a period of 6 months were reviewed. RESULTS: The 6-month survival curves showed a significantly higher number of deaths in the frailty (CFS≥5) group than in the normal to vulnerable (CFS<5) group (p<0.01). The CFS level was also significantly higher (6.5±1.5) in patients who died within 6 months of dialysis initiation as compared with that (4.6±1.7) in patients who survived (p<0.01). On the other hand, the total score of DASC-21 was related to need for inpatient maintenance dialysis (p<0.01). The total score on the DASC-21 were found as showing significant correlations with the CFS level. The IADL outside the home was identified in the DASC-21 sub-analyses as being correlated with CFS. CONCLUSIONS: The CFS and the DASC-21 appeared to be a useful predictive tool of outcome and prognosis for older patients being initiated on hemodialysis. Assessment by the CFS or the DASC-21 might be useful for selecting the renal replacement therapy by shared decision-making and for advance care planning.


Subject(s)
Dementia , Frailty , Renal Dialysis , Renal Insufficiency, Chronic , Humans , Male , Female , Aged , Aged, 80 and over , Dementia/therapy , Dementia/mortality , Renal Insufficiency, Chronic/therapy , Renal Insufficiency, Chronic/mortality , Geriatric Assessment/methods , Prognosis , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/mortality , Delivery of Health Care, Integrated
2.
Nat Commun ; 14(1): 2885, 2023 May 20.
Article in English | MEDLINE | ID: mdl-37210396

ABSTRACT

Efficient ethylene (C2H4) removal below room temperatures, especially near 0 °C, is of great importance to suppress that the vegetables and fruits spoil during cold-chain transportation and storage. However, no catalysts have been developed to fulfill the longer-than-2-h C2H4 removal at this low temperature effectively. Here we prepare gold-platinum (Au-Pt) nanoalloy catalysts that show robust C2H4 (of 50 ppm) removal capacity at 0 °C for 15 days (360 h). We find, by virtue of operando Fourier transformed infrared spectroscopy and online temperature-programmed desorption equipped mass spectrometry, that the Au-Pt nanoalloys favor the formation of acetate from selective C2H4 oxidation. And this on-site-formed acetate intermediate would partially cover the catalyst surface at 0 °C, thus exposing active sites to prolong the continuous and effective C2H4 removal. We also demonstrate, by heat treatment, that the performance of the used catalysts will be fully recovered for at least two times.

3.
CEN Case Rep ; 12(3): 259-264, 2023 08.
Article in English | MEDLINE | ID: mdl-36456780

ABSTRACT

A 73-year-old Japanese woman, with a history of Sweet syndrome diagnosed 3 years earlier and anti-myeloperoxidase (MPO) antibody anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis diagnosed 1 year earlier, presented with an episode of rapidly progressive glomerulonephritis (RPGN) with anti-glomerular basement membrane (GBM) disease. At the time of diagnosis of the ANCA-associated vasculitis 1 year earlier, serological testing yielded a negative result for anti-GBM antibody. However, at the present visit, serology for anti-MPO antibody was negative, while that for anti-GBM antibody was positive. This is the first report of anti-GBM disease developing sequentially after Sweet syndrome and ANCA-associated vasculitis. This case may provide clues to the potential immunological links among these three distinct conditions.


Subject(s)
Anti-Glomerular Basement Membrane Disease , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Glomerulonephritis , Sweet Syndrome , Female , Humans , Aged , Anti-Glomerular Basement Membrane Disease/diagnosis , Anti-Glomerular Basement Membrane Disease/complications , Sweet Syndrome/diagnosis , Sweet Syndrome/complications , Antibodies, Antineutrophil Cytoplasmic , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications
4.
Hypertens Res ; 46(3): 556-564, 2023 03.
Article in English | MEDLINE | ID: mdl-36522425

ABSTRACT

The association between the urinary sodium (Na)/potassium (K) ratio and hypertension is well recognized. We investigated whether the urinary Na/K ratio might be associated with hypertension in community-dwelling older adults and whether the association was influenced by habitual dietary patterns. We enrolled a total of 684 older adults (mean age, 76.8 years) and conducted health examinations at Kusatsu, Japan, in 2021. The urinary Na/K ratio was found to be independently associated with systolic blood pressure (SBP) (p < 0.0001), years of education (p = 0.0027), number of cohabitants (p = 0.0175), estimated glomerular filtrate rate (eGFR) (p = 0.0244), and Geriatric Depression Scale short-version (GDS15) score (p = 0.0366). In addition, an unsupervised hierarchical clustering analysis revealed a spectrum of habitual dietary patterns for higher and lower values of the urinary Na/K ratio. The decision tree indicated that the urinary Na/K ratio was associated with the history of milk consumption. A positive history of daily milk consumption predicted a mean urinary Na/K ratio of 2.8, and a negative history of daily milk consumption predicted a mean urinary Na/K ratio of 3.3. Furthermore, the frequency of fruit and vegetable consumption also predicted the urinary Na/K ratio. The relationship between the urinary Na/K ratio and hypertension was influenced by the frequency of consumption of milk, fruits, and vegetables in the subjects. This finding might be due to the influence of education and/or depression. The results suggested the importance of nutritional education in the development of hypertension.


Subject(s)
Hypertension , Sodium, Dietary , Humans , Aged , Independent Living , Sodium , Diet , Blood Pressure , Potassium
5.
Nephrology (Carlton) ; 27(8): 701-711, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35436030

ABSTRACT

AIM: Diabetic kidney disease (DKD), a chronic kidney disease caused by diabetes and other comorbidities, is the leading cause of end-stage renal disease. The pathogenesis of DKD is diverse and influenced by various causes, some but not all of which cause proteinuria. Some factors such as hypertension can modify DKD. Therefore, the spectrum of DKD is difficult to elucidate and remains unsolved. This study aims to classify and characterize DKD. METHODS: We examined autopsy specimens from type 2 diabetes mellitus (DM) (n = 44) and non-DM (n = 21) groups. RESULTS: The frequency of interstitial fibrosis and tubular atrophy was higher in patients with proteinuric DKD than in those with non-proteinuric DKD. The presence of polar vasculosis was associated with hypertension in DKD. In addition, an unsupervised hierarchical clustering analysis revealed the spectrum of renal histopathology findings for more-proteinuric and less-proteinuric DKD. With changes in the diagnostic criteria for hypertension and advances in antihypertensive drugs, the pathogenesis of DKD may be changing. Furthermore, a decision tree model suggested how diabetes, hypertension, and dyslipidemia interacted in predicting the characteristics of DKD. CONCLUSION: Polar vasculosis is a good indicator of the presence of DM and hypertension. Furthermore, the histopathological and clinical spectrum of DKD were related to the interaction of diabetes, hypertension, and dyslipidemia. These histopathological and clinical results may help to show the range of patient characteristics when conducting clinical trials and could help to determine whether chronic kidney disease is caused by DM or some other cause.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Hypertension , Renal Insufficiency, Chronic , Aged , Autopsy , Cluster Analysis , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetic Nephropathies/diagnosis , Diabetic Nephropathies/etiology , Humans , Hypertension/complications , Hypertension/diagnosis , Renal Insufficiency, Chronic/complications
6.
Clin Exp Nephrol ; 26(6): 530-539, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35118548

ABSTRACT

BACKGROUND: The aim of this autopsy study was to clarify the differences of renal histopathology between non-chronic kidney disease (CKD) and CKD caused by hypertensive-nephrosclerosis in the elderly and during the aging process. METHODS: We examined autopsy specimens from 105 elderly patients (53 male subjects; mean age, 86.2 years) including 44 patients with CKD as a result of nephrosclerosis. The analysis was divided into two groups depending on whether they had CKD. RESULTS: The incidences of arterial intimal thickening (AIT), obsolescent-type global glomerulosclerosis (OB), and interstitial fibrosis and tubular atrophy (IF/TA) were higher in the CKD group than in the non-CKD group (all p < 0.01). These factors were all correlated with each other (AIT vs. OB, r = 0.43; AIT vs. IF/TA, r = 0.25; OB vs. IF/TA, r = 0.53). IF/TA had the strongest association with hypertension and decreased eGFR. In the non-CKD group, the frequency of OB was more than 20% in subjects aged 90 years or older. However, the individuals in the non-CKD group tended to have compensatory glomerular hypertrophy with increasing age and a retained eGFR, while the CKD group was unable to obtain compensatory hypertrophy and had a lower eGFR. We also found that AIT, OB and IF/TA occurred independently of systemic atherosclerosis. CONCLUSIONS: Non-CKD in the elderly refers to the so-called aging kidney. The progression from aging kidney to CKD caused by nephrosclerosis was influenced by increases in AIT, OB and IF/TA. IF/TA was thought to be the most important downstream factor in the progression of aging kidney to CKD.


Subject(s)
Hypertension, Renal , Nephrosclerosis , Renal Insufficiency, Chronic , Aged , Aged, 80 and over , Autopsy , Humans , Hypertension, Renal/complications , Hypertrophy/complications , Hypertrophy/pathology , Kidney , Male , Nephritis , Nephrosclerosis/complications , Renal Insufficiency, Chronic/complications
7.
Life (Basel) ; 11(10)2021 Sep 28.
Article in English | MEDLINE | ID: mdl-34685394

ABSTRACT

Ascorbate functions as an electron donor and scavenges free radicals. Dehydroascorbic acid (DHA), the oxidized form of ascorbate, is generated as a result of these reactions. While low plasma ascorbate levels have been reported in hemodialysis patients worldwide, no studies have measured DHA because it is not generalized. In this study, we aimed to clarify whether plasma ascorbate levels are low in dialysis patients and whether plasma ascorbate levels fluctuate before and after dialysis. Moreover, we applied our previously established method to measure the plasma ascorbate and DHA levels in chronic kidney disease (CKD) stage G3-G5 non-hemodialysis-dependent patients, and pre- and post-dialysis plasma ascorbate and DHA levels in CKD stage G5D hemodialysis patients. The sample size was calculated using G-power software. The pre-dialysis plasma total ascorbate levels, including DHA, were significantly (56%) lower in hemodialysis patients than in non-hemodialysis-dependent CKD patients. After dialysis, there was a 40% reduction in the plasma total ascorbate levels. Hemodialysis increased the post-dialysis plasma proportions of DHA from 37% to 55%. The study results demonstrated lower plasma total ascorbate levels in hemodialysis patients compared with in non-hemodialysis-dependent CKD patients; these low levels in hemodialysis patients were further reduced by hemodialysis and increased DHA proportion.

8.
BMJ Case Rep ; 14(6)2021 Jun 02.
Article in English | MEDLINE | ID: mdl-34083191

ABSTRACT

The diagnosis of elderly-onset IgA vasculitis (IgAV) and its prognosis can be difficult to ascertain because of its rarity and the frequent presence of comorbidities. Furthermore, the treatment of elderly-onset IgAV remains controversial. We report a case of IgAV in an 87-year-old patient. Renal involvement was detected early during the IgAV follow-up. He was treated with low-dose corticosteroid and azathioprine, which led to a complete remission without any adverse effects. This suggests that precise intervention with early diagnosis and careful renal follow-up may prevent renal failure and that low-dose steroids with azathioprine can be an effective treatment for elderly-onset IgAV with nephritis.


Subject(s)
IgA Vasculitis , Nephritis , Vasculitis , Adrenal Cortex Hormones , Aged , Aged, 80 and over , Azathioprine , Humans , Immunoglobulin A , Male , Vasculitis/drug therapy
9.
Langmuir ; 37(27): 8331-8338, 2021 Jul 13.
Article in English | MEDLINE | ID: mdl-34185523

ABSTRACT

Ordered anodic porous alumina with controlled-size holes on the order of a single-nanometer scale was obtained by the atomic layer deposition (ALD) of Al2O3 or TiO2. The thin metal oxide layers of uniform thickness were formed successfully on the inner wall of the hole of the ordered anodic porous alumina with high aspect ratios by ALD. The hole diameter of the ordered anodic porous alumina could be controlled precisely by adjusting the number of cycles of ALD. The obtained anodic porous alumina with an ordered hole arrangement of reduced holes will be applied to various application fields requiring uniform-sized holes on the order of a single-nanometer scale, such as the starting material for preparing various types of quantum effect devices.

10.
CEN Case Rep ; 10(1): 46-52, 2021 02.
Article in English | MEDLINE | ID: mdl-32754805

ABSTRACT

Both the diagnosis of elderly-onset IgA vasculitis (IgAV) and its prognosis can be difficult because of its rarity and the likely presence of comorbidities. Furthermore, the treatment of elderly-onset IgAV remains controversial: the ideal dosages of corticosteroid and/or immunosuppressants have not been determined. In the elderly, corticosteroid adverse effects can lead to severe outcomes, and a consensus regarding its benefit and risk balance has not been reached. We report a case of IgAV in an 89-year-old patient who was admitted to our hospital to investigate a 30-day history of palpable purpura and pitting edema on her leg. A renal biopsy showed membranoproliferative glomerulonephritis with IgA deposits (The International Study of Kidney Disease in Children (ISKDC) grade VI), which is a predictor of a poor prognosis; these findings led to early intervention with low-dose corticosteroid (15 mg/day) and mizoribine. As a result, a complete remission without obvious adverse effects was obtained. Early intervention with low-dose corticosteroid and mizoribine based on renal histopathology results might be an effective treatment for elderly-onset ISKDC grade VI IgAV.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Glomerulonephritis, Membranoproliferative/pathology , Immunoglobulin A/immunology , Ribonucleosides/therapeutic use , Vasculitis/drug therapy , Vasculitis/immunology , Adrenal Cortex Hormones/administration & dosage , Aged, 80 and over , Biopsy , Comorbidity , Drug Therapy, Combination , Edema/diagnosis , Edema/etiology , Female , Glomerulonephritis, Membranoproliferative/diagnosis , Glomerulonephritis, Membranoproliferative/immunology , Humans , IgA Vasculitis/diagnosis , IgA Vasculitis/etiology , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/therapeutic use , Kidney/pathology , Leg/pathology , Nephrotic Syndrome/diagnosis , Nephrotic Syndrome/etiology , Remission Induction , Ribonucleosides/administration & dosage , Vasculitis/pathology
11.
CEN Case Rep ; 9(3): 195-199, 2020 08.
Article in English | MEDLINE | ID: mdl-31997159

ABSTRACT

We present the case of a 29-year-old woman with focal segmental glomerulosclerosis (FSGS) who was treated with rituximab administration under different conditions for refractory nephrotic syndrome and posttransplant FSGS recurrence. At the age of 13 years, she developed FSGS, which followed a refractory clinical course, and eventually necessitated her to undergo plasmapheresis and receive rituximab at the age of 25 years. However, both therapies were ineffective, and she subsequently had progressive renal failure, for which dialysis was initiated at the age of 26 years. At the age of 28 years, she received a renal transplant from a living donor. However, nearly 1 year after the transplantation, nephrotic-range proteinuria was observed and FSGS recurrence was confirmed via biopsy of the transplanted kidney. Plasmapheresis resulted in complete remission, which was maintained by rituximab administration, and the patient followed a favorable course. To date, there have been no reports on the effect of rituximab on both the native kidney and post-transplant FSGS recurrence in the same patient. Interestingly, this case showed different responses to rituximab administration.


Subject(s)
Allografts/drug effects , Glomerulosclerosis, Focal Segmental/drug therapy , Kidney/drug effects , Rituximab/pharmacology , Adult , Biopsy , Combined Modality Therapy/methods , Female , Glomerulosclerosis, Focal Segmental/etiology , Humans , Immunologic Factors/administration & dosage , Immunologic Factors/pharmacology , Immunologic Factors/therapeutic use , Kidney Transplantation/adverse effects , Nephrotic Syndrome/complications , Nephrotic Syndrome/therapy , Plasmapheresis/methods , Proteinuria/diagnosis , Proteinuria/etiology , Recurrence , Remission Induction , Rituximab/administration & dosage , Rituximab/therapeutic use
12.
Clin Exp Nephrol ; 24(3): 216-224, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31617027

ABSTRACT

BACKGROUND: Estimated glomerular filtration rate (eGFR) is routinely calculated based on the serum creatinine level. However, the validity of such calculation in the geriatric population has not been sufficiently assessed. To examine whether the discrepancies between the eGFR determined based on the serum creatinine (eGFRcr) and that based on the serum cystatin C (eGFRcys) may be influenced to a lesser degree, by factors such as aging and muscle mass. METHODS: We measured the cystatin C and creatinine levels in 19,764 subjects (mean 77.0 years) and the eGFRcys and eGFRcr using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Japanese, and Berlin Invitation Study (BIS) equations were calculated. RESULTS: The mean measured eGFRcys and eGFRcr values by the CKD-EPI equation were 48.2 and 66.6 ml/min/1.73 m2 body surface area, respectively. The correlation between the eGFRcr (x) and eGFRcys (y) was y = 0.728x (r = 0.867; p < 0.001). Analysis of the slope among all ages could be shown by the relation, eGFRcys = (0.43 + 0.33/(1 + 10^((82-age)* - 0.046)))*eGFRcr. The correlation between the eGFRcr and eGFRcys by the Japanese equation were also similar. However, when it was calculated by the BIS equation, no drop of the slope of the linear regression line was observed with age. CONCLUSIONS: The eGFRcr was overestimated irrespective of whether the CKD-EPI or the Japanese equation was used. We could convert eGFRcr into eGFRcys by an equation using age. Estimation of eGFR including serum cystatin C was more accurate in elderly people.


Subject(s)
Creatinine/blood , Cystatin C/blood , Glomerular Filtration Rate , Renal Insufficiency, Chronic/blood , Adolescent , Adult , Aged , Aged, 80 and over , Asian People , Cross-Sectional Studies , Female , Geriatric Assessment , Humans , Male , Middle Aged , Young Adult
13.
Jpn J Infect Dis ; 72(5): 347-349, 2019 Sep 19.
Article in English | MEDLINE | ID: mdl-31155601

ABSTRACT

An 84-year-old man with chronic renal failure, anemia, and diabetes was admitted for hemodialysis initiation. His vital signs were stable until the eighteenth hospital day, before acquiring an influenza A virus infection. Three days later, he died of septic shock with severe liver impairment. His leukocyte count, prothrombin time (PT-INR), and liver enzyme levels such as aspartate transaminase and alanine aminotransferase, were significantly increased. Hypercytokinemia was also observed. Autopsy revealed bilateral diffuse pneumonia with neutrophil infiltration. The liver showed extensive centrilobular hepatocyte necrosis. Immunohistochemistry for influenza A nucleoprotein revealed positivity in the ciliated columnar epithelium of the bronchi and negativity in the trachea, lungs, and liver. Hypoxic hepatitis is characterized by an abrupt and massive increase in aminotransferase levels (> 20 times upper normal limit) due to anoxic centrilobular hepatocyte necrosis. The occurrence of hypoxic hepatitis requires a pre-existing, chronic condition, such as anemia, causing reduced oxygen supply to the liver, followed by an acute decrease in hepatic oxygen supply, such as septic shock. Therefore, this report suggests that hypoxic hepatitis can be an important causative factor for acute liver failure associated with influenza virus infection.


Subject(s)
Influenza, Human/complications , Liver Failure, Acute/diagnosis , Liver Failure, Acute/pathology , Shock, Septic/diagnosis , Shock, Septic/pathology , Aged, 80 and over , Anemia/complications , Autopsy , Diabetes Complications , Fatal Outcome , Humans , Influenza A virus , Kidney Failure, Chronic/complications , Male , Shock, Septic/complications
14.
Geriatr Gerontol Int ; 19(3): 259-264, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30623538

ABSTRACT

AIM: Neutrophil extracellular traps play key roles in the necrotizing vasculitis associated with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). However, the relationships between neutrophil extracellular traps formation and the distribution and phase of vasculitis are not well understood. In the present study, we clarified the clinicopathological characteristics of older AAV patients, as well as the expression of citrullinated histone H3 (citH3), a marker of neutrophil extracellular traps, in autopsied AAV patients. METHODS: We reviewed autopsy cases that were carried out at Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan, from 2001 to 2018. The expression of citH3 was determined by immunostaining. RESULTS: AAV patients (six cases) were elderly (aged 73-94 years; three men and three women; myeloperoxidase anti-neutrophil cytoplasmic antibody-positive, five cases; proteinase-3 anti-neutrophil cytoplasmic antibody-positive, one case; disease duration was 1.5-5.5 months; and patients were treated with steroids. All patients had necrotizing vasculitis in the medium-to-small-sized vessels in various organs, and also severe vasculitis-associated lesions including brain hemorrhage, alveolar bleeding, interstitial pneumonia, crescentic nephritis, acute pancreatitis and gastrointestinal bleeding. Expression of citH3 was associated with the activity of inflammation. CONCLUSIONS: We report severe clinicopathological characteristics of AAV in older patients. Expression of citH3 was a useful marker to evaluate vasculitis severity. Identification of these features might aid in the diagnosis of AAV. Geriatr Gerontol Int 2019; 19: 259-264.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/metabolism , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/pathology , Citrullination , Histones/metabolism , Aged , Aged, 80 and over , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/mortality , Autopsy , Female , Humans , Japan , Male , Retrospective Studies
15.
Contrib Nephrol ; 195: 12-19, 2018.
Article in English | MEDLINE | ID: mdl-29734146

ABSTRACT

Minimal change nephrotic syndrome (MCNS) usually responds to steroids but frequently relapses, requiring additional treatment with immunosuppressive agents. Rituximab is a chimeric murine/human monoclonal immunoglobulin G1 antibody that targets CD20, a B-cell differentiation marker. B-cell recovery begins at approximately 6 months following the completion of treatment. Rituximab has a beneficial effect, with the sustained remission or reduction of proteinuria in patients with steroid-dependent MCNS. Relapses are thought to be associated with an increase in CD19 cells. The mean serum half-life of rituximab was reported to be 10-15 days in patients with steroid-dependent MCNS. Only infusion reactions, such as rash and chills, occurred after single-dose rituximab infusion and can be managed by pre-medication or infusion rate adjustments. Even though severe adverse effects of rituximab are not expected, we must be aware of potentially life-threatening adverse effects. Controlled randomized trials that include adult patients with steroid-dependent MCNS are required to prove the efficacy and safety of rituximab and to evaluate the cost-effectiveness of rituximab treatment. In this review, we highlight recent studies and discuss the effects of these studies on the management of patients with MCNS in adults.


Subject(s)
Glucocorticoids/therapeutic use , Immunologic Factors/therapeutic use , Nephrosis, Lipoid/drug therapy , Nephrotic Syndrome/drug therapy , Rituximab/therapeutic use , Adult , Humans , Immunosuppressive Agents/therapeutic use , Recurrence
16.
Contrib Nephrol ; 195: 110-119, 2018.
Article in English | MEDLINE | ID: mdl-29734156

ABSTRACT

Nephrotic syndrome is a type of intractable disease caused by a disorder in the kidneys, which produces swelling. Although some patients show rapid improvement and recover completely with conventional treatment, many others experience frequent recurrence (frequently relapsing nephrotic syndrome) while some remain dependent on the same high dose of steroids they were initially prescribed at the start of treatment (steroid-dependent nephrotic syndrome). In the latter cases, side effects of prolonged steroid use are a major issue. Some reports show that administering rituximab is effective in treating patients with steroid resistance. However, drugs like rituximab, directed at specific molecular targets, are generally expensive and therefore need to be evaluated from a health economics perspective before being approved for widespread use. The research team compared the number of relapses and total medical costs in the 24-month period before and the same period after patients took rituximab. We found that relapse decreased from a mean of 4.30 (±2.76) times to 0.27 (±0.52) times, and the total medical costs shrank from USD 2,923 to 1,280 per month (mainly the result of lower inpatient costs). The study also identified a correlation between lower urinary protein levels and a reduction in total medical costs. Rituximab, therefore, proved beneficial in both clinical and cost-effective terms. While rising healthcare costs are becoming a major social problem, we should expect that the development of new drugs with high cost performance will be encouraged from the vantage of socioeconomics.


Subject(s)
Glucocorticoids/therapeutic use , Health Care Costs , Immunologic Factors/therapeutic use , Nephrotic Syndrome/drug therapy , Prednisolone/therapeutic use , Rituximab/therapeutic use , Adolescent , Adult , Cost-Benefit Analysis , Drug Costs , Female , Hospitalization/economics , Hospitalization/statistics & numerical data , Humans , Immunologic Factors/economics , Japan , Male , Nephrotic Syndrome/economics , Recurrence , Rituximab/economics , Young Adult
17.
Sci Rep ; 7: 46036, 2017 04 07.
Article in English | MEDLINE | ID: mdl-28387313

ABSTRACT

With regard to the use of rituximab for patients with steroid-dependent nephrotic syndrome and frequently relapsing nephrotic syndrome, not only has the regimen not been clinically verified but also there is a lack of health economics evidence. Therefore, we conducted a prospective clinical study on 30 patients before (with steroids and immunosuppressants) and after introducing rituximab therapy. Relapse rates and total invoiced medical expenses were selected as the primary endpoints for treatment effectiveness and treatment costs, respectively. As secondary endpoints, cost-effectiveness was compared before and after administering rituximab in relation to previous pharmacotherapy. The observation period was 24 months before and after the initiation of rituximab. We showed that there was a statistically significant improvement in the relapse rate from a mean of 4.30 events before administration to a mean of 0.27 events after administration and that there was a significantly better prognosis in the cumulative avoidance of relapse rate by Kaplan-Meier analysis (p < 0.01). Finally, the total medical costs decreased from 2,923 USD to 1,280 USD per month, and the pre-post cost-effectiveness was confirmed as dominant. We, therefore, conclude that treatment with rituximab was possibly superior to previous pharmacological treatments from a health economics perspective.


Subject(s)
Cost-Benefit Analysis , Nephrotic Syndrome/drug therapy , Rituximab/administration & dosage , Rituximab/economics , Steroids/therapeutic use , Adult , Female , Humans , Japan , Kaplan-Meier Estimate , Male , Nephrotic Syndrome/urine , Recurrence , Rituximab/therapeutic use
18.
Clin Exp Nephrol ; 21(5): 842-851, 2017 Oct.
Article in English | MEDLINE | ID: mdl-27999961

ABSTRACT

BACKGROUND: The objective of this study is to determine whether initial steroid therapy is actually effective for the treatment of iMN, and we examined a 40% reduction in estimated glomerular filtration rate (eGFR) and remission rates. METHODS: This was a retrospective study between 1993 and 2013. First, we divided patients with iMN having a urinary protein level of ≥1 g/gCre into two groups: those who had received steroid therapy (Group S1; n = 52) within 6 months of diagnosis and those who had received supportive therapy (Group H1; n = 31). Second, we compared 20 cases using propensity score matching (Group S2, Group H2). Third, we compared patients with a urinary protein level of 1-3.5 g/gCre (Group S3, n = 18; Group H3, n = 19) and those with a urinary protein level ≥3.5 g/gCre (Group S4, n = 34; Group H4, n = 12). The primary endpoint was a 40% reduction in eGFR, and the secondary endpoint was the achievement of complete remission (CR). RESULTS: In Group S1 and Group H1, a 40% reduction in the eGFR was observed at the end of 5 years in 18 and 17% of the patients, respectively (P = 0.93); at the end of 10 years, these rates had increased to 43% and 50%, respectively (P = 0.88). The CR rates at the end of 5 years were 58% and 32%, respectively (P = 0.02), while the rates at 10 years were 65 and 39%, respectively (P = 0.02). No difference in renal outcomes was observed between Group S1 and Group H1. No significant differences were observed between Group S2 and Group H2, between Group S3 and Group H3, or between Group S4 and Group H4. CONCLUSION: Initial steroid therapy is not superior to supportive care within the first 6 months after diagnosis in terms of a 40% reduction in eGFR.


Subject(s)
Glomerular Filtration Rate/drug effects , Glomerulonephritis, Membranous/drug therapy , Kidney/drug effects , Steroids/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Chi-Square Distribution , Disease Progression , Female , Glomerulonephritis, Membranous/diagnosis , Glomerulonephritis, Membranous/mortality , Glomerulonephritis, Membranous/physiopathology , Humans , Kaplan-Meier Estimate , Kidney/physiopathology , Male , Middle Aged , Propensity Score , Proportional Hazards Models , Proteinuria/drug therapy , Proteinuria/physiopathology , Remission Induction , Retrospective Studies , Steroids/adverse effects , Time Factors , Treatment Outcome , Young Adult
19.
Clin Exp Nephrol ; 21(4): 643-650, 2017 Aug.
Article in English | MEDLINE | ID: mdl-27830351

ABSTRACT

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis is commonly classified as pauci-immune glomerulonephritis; however, some cases have granular immunoglobulin deposition along the glomerular capillary. The pathogenesis of immune deposits is poorly studied. METHODS: Of 66 patients diagnosed with ANCA-associated glomerulonephritis on renal biopsy, cases with immunoglobulin deposition along the glomerular capillary were identified and their clinicopathological characteristics were analyzed. We also performed myeloperoxidase (MPO) and double immunofluorescence (IF) stainings to determine the presence of immune complex antigens. RESULTS: Granular IgG deposition, IgG plus IgM deposition, and IgM deposition were observed in 15 (22.1%), 8 (11.2%), and 17 (25.0%) cases, respectively. In cases with granular IgG deposition, MPO-IgG double IF staining revealed co-localization of MPO and IgG. In cases with granular IgM deposition, MPO-IgM double IF staining did not co-localize. By electron microscopy, subepithelial deposition as well as intramembranous, subendothelial, and mesangial deposition was detected in the patients with IgG deposition. In addition, renal survival curves were not significantly different between the immunoglobulin deposition and non-deposition groups. CONCLUSIONS: Granular IgG and/or IgM deposition was observed in 60.6% of patients with ANCA-associated glomerulonephritis. In cases with IgG deposition, electron-dense deposits (EDDs) were observed at various sites in the glomerulus, and MPO and IgG immunocomplex deposition was frequently observed along the glomerular capillary. With IgM deposition, EDDs were not obvious in the glomerular basement membrane, and MPO and IgM immunocomplex was not detected. These data suggest differential mechanism between IgG deposition and IgM deposition.


Subject(s)
Antibodies, Antineutrophil Cytoplasmic/analysis , Glomerulonephritis/immunology , Immunoglobulin G/analysis , Immunoglobulin M/analysis , Kidney Glomerulus/immunology , Adult , Aged , Biomarkers/analysis , Biopsy , Capillaries/immunology , Capillaries/pathology , Disease Progression , Female , Fluorescent Antibody Technique , Glomerular Basement Membrane/immunology , Glomerular Basement Membrane/pathology , Glomerulonephritis/classification , Glomerulonephritis/diagnosis , Glomerulonephritis/therapy , Glucocorticoids/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Kaplan-Meier Estimate , Kidney Glomerulus/drug effects , Kidney Glomerulus/ultrastructure , Male , Microscopy, Electron , Middle Aged , Peroxidase/analysis , Renal Replacement Therapy , Time Factors , Treatment Outcome
20.
J Nephropathol ; 5(2): 72-8, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27152293

ABSTRACT

BACKGROUND: The relationship between hematuria and histological lesions, the effect of hematuria on response to steroid therapy, and the outcome in patients with immunoglobulin A nephropathy (IgAN) remain undetermined. OBJECTIVES: The aim of this study was to clarify the effect of hematuria on histological findings, response to steroid treatment, and the outcome in IgA nephropathy. PATIENTS AND METHODS: Seventy-five patients with IgAN and proteinuria > 1 g/day and treated with prednisolone were divided into two groups: those with low (≤20/high-power field [HPF]) urinary red blood cell (U-RBC) counts (L-RBC group, n=55) and those with high (>20/HPF) U-RBC counts (H-RBC group, n=20). Their clinical and histological characteristics, the relationship between hematuria and histological lesions, renal outcomes, and risk factors for progression were compared. RESULTS: Except for U-RBC counts, the clinical and histological findings according to the Oxford classification of the two groups were similar. U-RBC counts were not correlated with active histological lesions. Median proteinuria in both groups decreased soon after starting steroid therapy. Median U-RBC also decreased after starting steroids, and it became similar between both groups at 2 years after treatment. The 20-year renal survival rate was also similar between the H-RBC and the L-RBC group (45.2% versus 58.0%, P=0.5577). Multivariate Cox regression analysis showed that the lower estimated glomerular filtration rate (eGFR) was an independent risk factor for progression. CONCLUSIONS: A higher degree of hematuria at renal biopsy in patients with IgAN was not associated with active pathological lesions, such as cellular and fibro-cellular crescents, resistance to steroid treatment and poor outcome.

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