Autopsy study examining non-chronic kidney disease versus chronic kidney disease caused by hypertensive-nephrosclerosis in elderly subjects.

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.

Identification of histopathological and clinical spectrum of diabetic kidney disease based on an unsupervised hierarchical clustering analysis of elderly autopsy specimens.

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.

Preparation of Ordered Anodic Porous Alumina with Single-Nanometer-Order-Size Holes by Atomic Layer Deposition.

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.

Geriatric assessment of estimated glomerular filtration rate: a cross-sectional study.

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.

Long-term outcomes of initial therapy for idiopathic membranous nephropathy.

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.

Antineutrophil cytoplasmic antibody-associated glomerulonephritis with immunoglobulin deposition.

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.

Estimation of the 24-h urinary protein excretion based on the estimated urinary creatinine output.

BACKGROUND: The urinary protein/creatinine ratio [Up/Ucr (g/gCr)] has been used in the clinical management of patients with chronic kidney disease (CKD). However, a discrepancy is often noted between the Up/Ucr and 24-h urinary protein excretion [24hUp (g/day)] in patients with extremes of muscle mass. We examined devised a method for precise estimation of the 24-h urinary protein excretion (E-24hUp) based on estimation of 24-h urinary creatinine output (E-24hCr). METHODS: Three parameters, spot Up/Ucr, 24hUP and E-24hUp (=Up/Ucr × E-24hCr), were determined in 116 adult patients with CKD. The correlations among the groups were analyzed. RESULTS: There was a significant correlation between the Up/Ucr and 24hUp (p < 0.001). We divided the patients into three groups according to the 24hUp; the low urinary protein group (<1.0 g/day), the intermediate urinary protein group (1.0-3.5 g/day), and the high urinary protein group (>3.5 g/day). There was a significant correlation between the Up/Ucr and 24hUp in the low (p = 0.04) and high urinary protein (p = 0.01) groups, whereas the correlation coefficient was lower in the intermediate urinary protein (p = 0.07) group. Thus, we found a significant correlation between 24hUp and E-24hUp in the study population overall (p < 0.001), in the low (p = 0.01), in the intermediate (p < 0.001), and in the high urinary protein group (p < 0.001). CONCLUSION: We conclude that a poor correlation exists between the Up/Ucr and 24hUp in patients with intermediate urinary protein excretion levels. The recommended parameter for monitoring proteinuria in such patients may be the E-24hUp, which is calculated using the E-24hCr.

Amelioration of the adverse effects of prednisolone by rituximab treatment in adults with steroid-dependent minimal-change nephrotic syndrome.

BACKGROUND: We previously demonstrated the efficacy of single-dose 6-monthly rituximab infusions in 25 adults with steroid-dependent minimal-change nephrotic syndrome. Herein, we assessed the safety of rituximab treatment and its effect in ameliorating the adverse effects of prednisolone (PRED) in a larger study sample. METHODS: We treated 54 adult patients with four single-dose 6-monthly infusions of rituximab (375 mg/m(2) BSA per dose). We compared the adverse effects of PRED (osteoporosis, hypertension, and diabetes mellitus) between the first rituximab infusion (baseline) and the end of the 24-month observation period. In addition, we examined the adverse effects of rituximab during the same period. RESULTS: The PRED dose was significantly lower at 24 months than at the baseline. The bone density was significantly higher at 24 months as compared to the baseline value (Z score -1.8 vs. -1.1; p < 0.05). Blood pressure at 24 months was significantly lower than that at the baseline (120.9/74.4 vs. 111.8/70.3 mm Hg; p < 0.05). Eight patients with diabetes mellitus showed improved glycemic control at 24 months as compared to that at the baseline. There were no severe adverse effects of rituximab. However, mild infusion reactions occurred in 31 patients (57%). The frequency of the infusion reactions decreased significantly with every successive infusion. CONCLUSION: Rituximab treatment was effective and safe in patients with steroid-dependent nephrotic syndrome, allowed reduction of the PRED dose, and ameliorated the adverse effects of PRED. It may be preferentially used in patients at a risk of the adverse effect of PRED.

Alport syndrome and pregnancy: Good obstetric and nephrological outcomes in a pregnant woman with homozygous autosomal recessive Alport syndrome.

We describe the course of pregnancy in a 27-year-old woman with homozygous autosomal recessive Alport syndrome. Genetic analysis revealed a homozygous COL4A4 mutation in exon 36 (c.3307G > A) with p.G1102R inherited from her parents (who were parallel cousins) 1 year before conception. Before pregnancy, the patient's renal function and blood pressure were normal, and her urinary protein excretion was below 2 g/day. The pregnancy course was uneventful in the first and second trimesters. She was detected to have nephrotic-range proteinuria during the third trimester, but was observed closely on an outpatient basis without any medications, as her general condition was good, her renal function and blood pressure remained stable, and the fetal well-being was maintained. At 39(+0) weeks of pregnancy, she vaginally gave birth to an appropriate-birthweight infant and her urinary protein excretion returned to pre-pregnancy level. This is the first report of pregnancy in a patient with autosomal recessive Alport syndrome with good obstetric and nephrological outcomes in the absence of any treatment or hospitalization.

[Rituximab therapy in the treatment of anti-neutrophil cytoplasmic antibody (ANCA) -positive interstitial pneumonia: case report].

We report a patient treated with rituximab for interstitial pneumonia (IP) associated with microscopic polyangiitis (MPA) and who was undergoing hemodialysis. A 59-year-old woman who had been treated with tacrolimus for 1 year for rheumatic arthritis was referred to the Department of Nephrology for fatigue, fever, weight loss, and rapidly developing renal dysfunction. On the first admission, severe renal dysfunction, proteinuria, hematuria, and an elevated titer of MPO-ANCA were observed, and the woman was diagnosed with rapidly progressive glomerulonephritis because of MPA. At that point, IP was found to be present but not active. Although steroid semipulse therapy following an initial prednisolone (PSL) administration of 40 mg/day, IVCY, and plasma exchange were administered, renal dysfunction did not recover, and the patient required maintenance hemodialysis. Upon discharge, a high titer of MPO-ANCA was continuously observed. Nine months after the initiation of hemodialysis, respiratory discomfort and desaturation developed. Interstitial shadow and ground glass opacity were seen on a CT scan, and the patient was diagnosed with exacerbation of interstitial pneumonia caused by MPA recurrence. At the second admission, acute findings identified by imaging techniques had improved. However, the high titer of MPO-ANCA continued in spite of the steroid semi-pulse therapy following PSL administration, and rituximab corresponding to 200 mg/weekly for 1 month was also administered. The dose of rituximab was decreased subsequently because the patient was judged to be compromised by the hemodialysis. At the same time, internal administration of sulfamethoxazole/trimethoprim was initiated. After the rituximab treatment, MPO-ANCA antibodies gradually decreased, and the respiratory condition improved. Five months after the rituximab treatment, respiratory dysfunction recurred. Based on the CT findings and a high level of ß-D-glycan, the patient was diagnosed with ARDS due to pneumocystis pneumonia. In this case, rituximab was effective for IP due to MPA, but pneumocystis pneumonia could not be prevented in spite of prophylactic antibiotics. This case suggests that deliberative dose adjustments, careful patient observation, and prophylactic measures for infection are critical in rituximab treatment.

A case of medullary cystic kidney disease with rapid progressive renal dysfunction and kidney enlargement.

Medullary cystic kidney disease (MCKD) is usually associated with slowly progressive kidney injury. However, we encountered a case of MCKD with rapidly progressive kidney injury and irreversible renal dysfunction. A 63-year-old woman presented with a 4-month history of hypertension and rapidly progressive renal dysfunction. On admission, her blood pressure was slightly elevated (158/85 mmHg). The scrum creatinine (11.57 mg/dL) was markedly elevated. Urinalysis showed occult hematuria and proteinuria(1.06 g/gCr). /ß2- microglobulin 45,000 µg/ L, N-acetyl-/ß-D-glucosaminidase 5.6 U/L. Neither ultrasonography nor computed tomography revealed any evidence of renal medullary cysts. Both kidneys showed an irregular surface and enlargement. Microscopic evaluation of the renal biopsy revealed extensive tubular dilatation and atrophy with interstitial fibrosis. Often glomeruli, one had global sclerosis and the others were normal. The tubular dilatation was more marked in the distal than in the proximal tubules, according to the immunohistochemical findings of positivity for epithelial membrane antigen (EMA), a marker of distal tubules, and negativity for CD 10, a marker of proximal tubules. No immunoglobulin or complement deposition was detected in either the glomeruli or the tubules. Electron microscopy revealed disintegration of the tubular basement membrane with fragile thinning and lamination of the membrane. These pathological findings were compatible with MCKD. This was a case of MCKD diagnosed incidentally in an elderly patient who presented with rapidly progressive kidney injury accompanied by hypertension. Renal biopsy was necessary for the diagnosis.

Caveolae may enable albumin to enter human renal glomerular endothelial cells.

Caveolae on human renal glomerular endothelial cells (HRGECs) are increased in glomerular disease and correlate with the degree of albuminuria. To assess the mechanism by which caveolae contribute to albuminuria, we investigated whether albumin enters into HRGECs through caveolae. HRGECs were incubated with Alexa Fluor 488 labeled BSA or transferrin, followed by immunofluorescence localization with antibody to caveolin-1 (Cav-1), the main structural protein of caveolae, or clathrin, the major structural protein of clathrin coated pits, to assess whether BSA colocalized with Cav-1. HRGECs were also incubated with albumin and caveolae disrupting agents, including methyl beta cyclodextrin (MBCD) and nystatin, to determine whether disrupting caveolae interfered with albumin endocytosis into HRGECs. HRGECs were also incubated with albumin after transfection with Cav-1 small interfering RNAs (siRNAs). Labeled BSA colocalized with Cav-1, but not with clathrin. In contrast, labeled transferrin colocalized with clathrin, but not with Cav-1. Incubation of HRGECs with MBCD or nystatin, or transfection with Cav-1 siRNA, significantly reduced the intracellular amounts of albumin and Cav-1, relative to normal HRGECs, as shown by western blotting and immunofluorescence. These findings indicate that albumin enters HRGECs through the caveolae, suggesting that caveolae play an important role in the pathogenesis of albuminuria by providing a pathway through which albumin can enter glomerular endothelial cells.

Effect of hematuria on the outcome of IgA nephropathy with mild proteinuria.

BACKGROUND: The effects of hematuria on the outcome of IgA nephropathy (IgAN) remain unknown and treatment of IgAN with severe hematuria is controversial. METHODS: Eighty-eight IgAN patients with proteinuria <0.5 g/day and who had not received corticosteroids, immunosuppressive agents, or undergone a tonsillectomy were divided into two groups: (1) patients with low (<20/high-power field [HPF]) urinary red blood cell (U-RBC) counts (L-RBC group, n = 48); and (2) patients with high (≥20/HPF) U-RBC counts (H-RBC group, n = 40). Clinical and histological findings, renal survival rate and risk factors for progression were analyzed. RESULTS: The male ratio and blood pressure were significantly higher in the L-RBC group. Median proteinuria, mean estimated glomerular filtration rate and histological findings according to Oxford classifications were similar. During the 5 years after renal biopsy, the median amount of proteinuria remained at <0.5 g/day or g/g creatinine in both groups, and the median U-RBC decreased to <10/HPF in both groups without any intensive therapy. The 15-year renal survival rate, estimated using the Kaplan-Meier method, was 100 % in the H-RBC group, but decreased to 83.4 % in the L-RBC group, although it was not significant. The treatment of inhibitors of renin-angiotensin system (RAS inhibitors) decreased the risk for progression by Cox regression analysis (hazard ratio: 0.14, p = 0.027). CONCLUSION: Severe hematuria at the time of biopsy naturally improved without any intensive therapy, and there were no negative effects of hematuria on the outcome of IgAN with mild proteinuria. Its prognosis was relatively good, and the treatment of RAS inhibitors might prevent from progression.

Serum Thiamine Values in End-Stage Renal Disease Patients under Maintenance Hemodialysis.

OBJECTIVE: Hemodialysis patients are prone to malnutrition because of diet or many uremic complications. The objective of this study is to determine whether thiamine deficiency is associated with regular dialysis patients. METHODS: To determine whether thiamine deficiency is associated with regular dialysis patients, we measured thiamine in 100 patients undergoing consecutive dialysis. RESULTS: Average thiamine levels were not low in both pre-hemodialysis (50.1 ± 75.9 ng/mL; normal range 24 - 66 ng/mL) and post-hemodialysis (56.4 ± 61.7 ng/mL). In 18 patients, post-hemodialysis levels of thiamine were lower than pre-hemodialysis levels. We divided the patients into two groups, the decrease (Δthiamine/pre thiamine < 0; - 0.13 ± 0.11) group (n = 18) and the increase (Δthiamine/pre thiamine> 0; 0.32 ± 0.21)) group (n = 82). However, there was no significance between the two groups in Kt/V or type of dialyzer. Patients were dichotomized according to median serum thiamine level in pre-hemodialysis into a high-thiamine group (≥ 35.5 ng/mL) and a low-thiamine group (< 35.4 ng/mL), and clinical characteristics were compared between the two groups. The low-thiamine value group (< 35.4 ng/ml; 26.8 ± 5.3 ng/ml) exhibited lower levels of serum aspartate aminotransferase and alanine aminotransferase than the high-thiamine value group (≥ 35.4 ng/ml; 73.5 ± 102.5 ng/ml) although there was no significance in nutritional marker, Alb, geriatric nutritional risk index , protein catabolic rate and creatinine generation rate. CONCLUSION: In our regular dialysis patients, excluding a few patients, we did not recognize thiamine deficiency and no significant difference in thiamine value between pre and post hemodialysis.

Comparison of a novel chemiluminescence enzyme immunoassay (CLEIA) with enzyme-linked immunosorbent assay (ELISA) for the determination of MPO-ANCA in patients with ANCA-associated vasculitis.

BACKGROUND: Myeloperoxidase (MPO) anti-neutrophil cytoplasmic antibody (ANCA) represents the serological hallmark of ANCA-associated vasculitis (AAV). We evaluated the analytical and diagnostic accuracy of chemiluminescence enzyme immunoassay (CLEIA) versus enzyme-linked immunosorbent assay (ELISA) for the detection of MPO-ANCA. METHODS: A total of 242 sera obtained from 51 patients with AAV and 103 patients without AAV were tested for MPO-ANCA by ELISA (NephroScholor MPOANC II) and CLEIA (the STACIA MEBLux test). Disease activity in the patients with AAV was determined based on the Birmingham Vasculitis Activity Score. We analyzed the correlations between the MPO-ANCA titers determined by the CLEIA and those determined by the ELISA, and also between the MPO-ANCA titers and the disease activity. RESULTS: The MPO-ANCA titers determined by the CLEIA (x) were strongly correlated with those determined by the ELISA (y). The correlation could be expressed by the following equation in this study: y = 1.8x + 7.7 (r = 0.96; p < 0.0001). At the cutoff value of 3.5 U/ml, the CLEIA yielded positive test results for MPO-ANCA in 73 of the 242 sera (30.2%), while at the cutoff value of 20 U/ml, ELISA yielded positive test results in 57 of the 242 sera (23.6%). The CLEIA yielded false-positive test results in 4 of the 120 sera obtained from the non-AAV patients (3.3%), whereas the ELISA yielded a false-positive result in only 1 of the 120 sera obtained from the non-AAV patients (0.8%). The sensitivity and specificity of the CLEIA for the diagnosis of AAV were 100% and 96.7%, respectively, while those of the ELISA were 94.3% and 99.2%, respectively. The sensitivity and specificity of the CLEIA for the prediction of active disease were 100% and 64.4%, respectively, while those of the ELISA were 94.3% and 73.6%, respectively. CONCLUSION: The false positivity rate of the CLEIA for MPO-ANCA tended to be high as compared with that of the ELISA. Also, according to the correlation coefficient between the results of the CLEIA and the ELISA calculated in this study, it is necessary to pay attention to the differences in the sensitivity and specificity between CLEIA and ELISA.

Serum uric acid levels and long-term outcomes in chronic kidney disease.

Hyperuricemia is common in chronic kidney disease (CKD), but data regarding the relationship between serum uric acid levels and the long-term outcomes of CKD patients have been limited. The present study evaluated the associations between baseline serum uric acid levels with mortality and end-stage renal disease (ESRD). The subjects of this study were 551 stage 2-4 CKD patients. Cox proportional hazards models were used to evaluate the relationship between serum uric acid tertiles and all-cause mortality, cardiovascular disease (CVD) mortality, 50 % reduction in estimated glomerular filtration rate (eGFR), and development of ESRD, initially without adjustment, and then after adjusting for several groups of covariates. The mean age of the study subjects was 58.5 years, 59.3 % were men, and 10.0 % had diabetes. The mean eGFR was 42.02 ± 18.52 ml/min/1.73 m(2). In all subjects, the mean serum uric acid level was 6.57 ± 1.35 mg/dl, and 52.2 % of study subjects were on hypouricemic therapy (allopurinol; 48.3 %) at baseline. Thirty-one patients (6.1 %) died during a follow-up period of approximately 6 years. There was no significant association between serum uric acid level and all-cause mortality, CVD mortality, development of ESRD and 50 % reduction in eGFR in the unadjusted Cox models. In the adjusted models, hyperuricemia was found to be associated with all-cause mortality and CVD mortality after adjustment with CVD risk factors, kidney disease factors, and allopurinol, but not associated with development of ESRD and 50 % reduction in eGFR. The results of this study showed that hyperuricemia but not serum uric acid levels were associated with all-cause mortality, CVD mortality after adjustments with CVD risk factors, kidney disease factors, and allopurinol in stage 2-4 CKD patients.

Comparison between consecutive and intermittent steroid pulse therapy combined with tonsillectomy for clinical remission of IgA nephropathy.

BACKGROUND: In recent years, tonsillectomy and steroid pulse (TSP) therapy have been widely performed in Japan. However, there is no consensus about the treatment protocol and indication. METHODS: In this retrospective analysis, we compared patients who received tonsillectomy plus intermittent steroid pulse (SP) therapy three times in 6 months (ISP group, n = 44) with patients who received tonsillectomy plus 3 weeks of consecutive SP therapy (CSP group, n = 46) within 1 year after renal biopsy. These two different protocols were performed at two different institutions. We analyzed the clinical and histological background and clinical remission (CR), defined as disappearance of urine abnormalities at 18 months after starting treatment. RESULTS: Before treatment, there was no significant difference in the clinical findings except for sex between the two groups. In ISP group and CSP group, mean estimated glomerular filtration rate was 82.1 ± 20.9 and 85.9 ± 19.1 ml/min/1.73 m(2), median proteinuria was 0.55 and 0.56 g/day, and median urinary red blood cells were 20 (10-20) and 20 (6-30)/high power filed. The histological (H) grade was lower in the CSP than the ISP group (p = 0.022). The remission rate of proteinuria, hematuria, and rate of CR by the Kaplan-Meier method and logrank test were significantly higher in the CSP group than in the ISP group (CSP vs. ISP group; proteinuria: 97.8 vs. 77.3 %, p < 0.001, hematuria: 97.8 vs. 75.0 %, p = 0.005, CR: 95.6 vs. 63.6 %, p < 0.001). In the Cox proportional hazard model (forced entry), SP protocol and proteinuria before treatment were significantly associated with CR [SP protocol: hazard ratio (HR) 2.50, 95 % confidence interval (CI) 1.46-4.30, p = 0.001, proteinuria: HR 0.81, 95 % CI 0.68-0.96, p = 0.013)]. However H-grade was associated with remission of proteinuria (H-grade: hazard ratio (HR) 0.56, 95 % confidence interval (CI) 0.37-0.85, p = 0.006), and this result meant histological bias affected the remission of proteinuria. CONCLUSIONS: The difference of the protocol of TSP therapy may have some effect on the CR of IgAN, though the histological bias was observed in this study. The appropriate protocol and indication of TSP therapy must be analyzed and determined in the randomized controlled trial.

Statins stabilize the renal function of IgA nephropathy.

BACKGROUND: The renoprotective pleiotropic effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has recently been reported by several investigators. However, the effect of statins on IgA nephropathy (IgAN) is still unknown. METHODS: We selected 24 IgAN patients who had newly started statin therapy and were not treated with steroids and immunosuppressive agents during the observation period. We analyzed and compared clinical findings 1 year before and after treatment. RESULTS: Mean age was 50.5 ± 9.91 years and mean blood pressure was 90.9 ± 10.8 mmHg. Renal function was slightly deteriorated, serum creatinine was 1.03 (0.71-1.24) mg/dL and estimated glomerular filtration rate (eGFR) was 55.8 ± 22.8 mL/min. Lipid metabolism was poorly controlled [total cholesterol 247.7 ± 35.7 mg/dL, low-density lipoprotein cholesterol 151.5 (140.8-172.8) mg/dL, and triglyceride 163.0 (126.3-243.8) mg/dL]. Mild urinary abnormality was observed [proteinuria: 0.50 (0.22-1.29) g/g creatinine, urinary red blood cells 1.0 (0.2-5.0) per high power field]. After 1 year of statin treatment, lipid control was significantly better than at baseline. Proteinuria was not significantly decreased but renal function was improved. eGFR changed from a -5.9% decrease to a 2.4% increase (p = 0.0098). CONCLUSION: Our results indicated that statins stabilized the renal function of IgAN patients independent of their reduction of proteinuria.

Long-term damage assessment in patients with microscopic polyangiitis and renal-limited vasculitis using the Vasculitis Damage Index.

OBJECTIVES: The Vasculitis Damage Index (VDI) is used to define the degree of damage occurring in patients with systemic vasculitis. We conducted a retrospective study of 30 patients with microscopic polyangiitis (MPA) and renal-limited vasculitis (RLV). METHODS: The clinical data and VDI of the 30 patients enrolled in the study were collected and assessed for a period of 5 years. RESULT: The VDI score, which was 2.5 at 1 year after the initial diagnosis, increased gradually to 4.3 at 5 years post-diagnosis. The degrees of musculoskeletal and ocular damage significantly increased during the 5-year period (p = 0.001 and p = 0.002, respectively). The most frequent damage items in the VDI were cataract (13 %), hypertension (12 %), diabetes mellitus (9 %), and osteoporosis (6 %). The VDI score was significantly higher in the groups of patients who showed relapse or MPA than in the groups of patients who did not show relapse or RLV at 5 years (p = 0.02 and p = 0.03, respectively). In addition, a significant correlation was found between the VDI score at 5 years and the Birmingham Vasculitis Activity Score at diagnosis (p = 0.04, r = 0.4). CONCLUSION: The VDI was found to be a useful tool for determining the severity of damage caused by disease and the effects of treatment. The individual contributions of the VDI items may also be applied to treatment decisions.

Usefulness of assessment of the Clinical Frailty Scale and the Dementia Assessment Sheet for Community-based Integrated Care System 21-items at the time of initiation of maintenance hemodialysis in older patients with chronic kidney disease.

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.