Takahiro Imaizumi

Urinary Podocalyxin as a Biomarker to Diagnose Membranous Nephropathy

Background A non-invasive diagnostic marker of membranous nephropathy (MN) is desirable. The urinary level of podocalyxin (PCX) is higher in various glomerular diseases, including MN. The aim of this study was to construct a diagnostic model of MN with the combination of urinary PCX and clinical parameters. Methods We performed this cross-sectional study to construct the diagnostic models for MN by using data and samples from the multicenter kidney biopsy registry of Nagoya University and its affiliated hospitals. Urinary (u-) PCX was measured by sandwich ELISA. We constructed 3 types of diagnostic models in 105 training samples: u-PCX univariate model, the combined model of clinical parameters other than u-PCX (clinical model), and the combined model of both u-PCX and clinical parameters (combined model). We assessed the clinical usefulness of the diagnostic models through the comparison of c-statistics and decision curve analysis (DCA) in 209 validation samples. Results The clinical model consisted of age, glomerular filtration rate, and diabetes mellitus. In the training cohort, the c-statistics were 0.868 [95% CI, 0.799–0.937] in the combined model. In the validation cohort, sensitivity was 80.5% and specificity was 73.5% on the cut-off value. The net benefit of the combined model was better between threshold probabilities of 40–80% in DCA. Conclusions In this study, we demonstrated the utility of u-PCX as a diagnostic marker for MN and the clinical usefulness of the diagnostic models, through the combination of u-PCX and clinical parameters including age, glomerular filtration rate, and diabetes mellitus.

Alleviation of Tail Boom with Staged Aft-body

In order to demonstrate a possibility of reducing a tail boom, the experimental model with staged aft-body was designed. The experimental model’s tail section was designed so that the expansion wave and the compression wave are generated one after the other. The generated pressure waves will interact to each other while propagating, resulting in reducing the pressure jump on the ground. The designed experimental model was launched using ballistic range to measure the pressure wave propagated from the experimental model at Mach 1.7. The obtained pressure wave and the Schlieren image indicated the propagating pressure wave was indeed separated into several steps at the near field. The ground pressure wave was simulated using the waveform parameter method. The separated pressure wave at the near field did not marge into N-wave after the 60,000 ft of propagation and maximum pressure jump was reduced. Thus, the alleviation effect of the tail boom with the staged aft-body was confirmed.

The Japanese Histologic Classification and T-score in the Oxford Classification system could predict renal outcome in Japanese IgA nephropathy patients

BackgroundThe Oxford Classification is utilized globally, but has not been fully validated. In this study, we conducted a comparative analysis between the Oxford Classification and Japanese Histologic Classification (JHC) to predict renal outcome in Japanese patients with IgA nephropathy (IgAN).MethodsA retrospective cohort study including 86 adult IgAN patients was conducted. The Oxford Classification and the JHC were evaluated by 7 independent specialists. The JHC, MEST score in the Oxford Classification, and crescents were analyzed in association with renal outcome, defined as a 50% increase in serum creatinine.ResultsIn multivariate analysis without the JHC, only the T score was significantly associated with renal outcome. While, a significant association was revealed only in the JHC on multivariate analysis with JHC.ConclusionsThe JHC and T score in the Oxford Classification were associated with renal outcome among Japanese patients with IgAN. Superiority of the JHC as a predictive index should be validated with larger study population and cohort studies in different ethnicities.

Association Between Staphylococcus aureus Bacteremia and Hospital Mortality in Hemodialysis Patients With Bloodstream Infection: A Multicenter Cohort From Japanese Tertiary Care Centers

Multiple studies have shown that Staphylococcus aureus bacteremia (SAB) has been a major cause of death in hemodialysis patients. We examined whether SAB is a risk for mortality among chronic hemodialysis patients in Japan where the standard vascular access is arteriovenous fistula (AVF). This was a multicenter, retrospective study of maintenance hemodialysis patients with bloodstream infection (BSI) from 2011 to 2013 at tertiary care centers in Japan. The endpoint was hospital mortality. Our cohort contained 32 SAB cases (14 MRSA and 18 MSSA) and 42 non‐SAB cases. Hospital mortality was higher among SAB cases than non‐SAB cases (46.9% vs. 23.8%, P = 0.038). In patients with BSI, SAB was significantly associated with hospital mortality after adjustment for potential confounders, including type of vascular access (OR 3.26). S. aureus was the leading cause of BSI and hospital mortality among this cohort. Therefore, initial empiric treatment should cover for S. aureus.

Development and Validation of a Clinical Prediction Rule for Bacteremia among Maintenance Hemodialysis Patients in Outpatient Settings

[This corrects the article DOI: 10.1371/journal.pone.0169975.].

Association between kidney function and genetic polymorphisms in atherosclerotic and chronic kidney diseases: A cross-sectional study in Japanese male workers.

Background Several single nucleotide polymorphisms (SNPs) have been implicated in the predisposition to chronic kidney disease (CKD). Atherosclerotic disease is deeply involved in the incidence of CKD; however, whether SNPs related to arteriosclerosis are involved in CKD remains unclear. This study aimed to identify SNPs associated with CKD and to examine whether risk allele accumulation is associated with CKD. Methods We conducted a cross-sectional study using data of 4814 male workers to examine the association between estimated glomerular filtration rate (eGFR) and 59 candidate polymorphisms (17 CKD, 42 atherosclerotic diseases). We defined the genetic risk score (GRS) as the total number of risk alleles that showed a significant association in this analysis and examined the relationship with CKD (eGFR < 60 ml/min/1.73m2). Multivariate logistic regression, discrimination by area under the receiver operating characteristic curve, integrated discrimination improvement (IDI), and category-free net reclassification improvement (cNRI) were evaluated. Results In total, 432 participants were categorized as having CKD. We found eight candidate SNPs with P value < 0.05 (CX3CR1 rs3732379, SHROOM3 rs17319721, MTP rs1800591, PIP5K1B rs4744712, APOA5 rs662799, BRAP rs3782886, SPATA5L1 rs2467853, and MCP1 rs1024611) in the multivariate linear regression adjusted for age, body mass index, systolic blood pressure, and fasting blood glucose. Among these eight SNPs, BRAP rs3782886 and SPATA5L1 rs2467853 were significantly associated with eGFR (false discovery rate < 0.05). GRS was significantly associated with CKD (odds ratio, 1.17; 95% confidence interval, 1.09–1.26). C-statisics improved from 0.775 to 0.780 but showed no statistical significance. However, adding GRS significantly improved IDI and cNRI (0.0057, P = 0.0028, and 0.212, P < 0.001, respectively). Conclusions After adjustment for clinical factors, kidney function was associated with BRAP rs3782886 and SPATA5L1 rs2467853 and the GRS for CKD that we developed was associated CKD.

Urinary and circulating levels of the anti-angiogenic isoform of vascular endothelial growth factor-A in patients with chronic kidney disease

INTRODUCTION The protective effects of vascular endothelial growth factor (VEGF)-A165b on kidney tissue have been suggested in animal studies. However, the relevance of urinary and circulating VEGF-A165b levels in chronic kidney disease patients remains unclear. Therefore, the present study aimed to investigate the urinary and circulating VEGF-A165b levels in patients with chronic kidney disease. METHODS This observational study enrolled a total of 92 Japanese patients with chronic kidney disease, who had undergone inulin renal clearance measurements for the accurate assessment of measured GFR. Urinary or circulating total VEGF-A and VEGF-A165b levels were measured using enzyme-linked immunosorbent assay. RESULTS Urinary VEGF-A165b levels were significantly lower in G3a, G3b, and G4+G5 category patients than in G1+G2 category patients. Correlation analysis found that serum creatinine levels, serum cystatin C levels, eGFRcre, eGFRcys, and mGFR were weakly but significantly correlated with urinary VEGF-A165b levels. Additionally, circulating VEGF-A165b levels were significantly higher in G4+G5 category patients than in G1+G2 category patients. CONCLUSION A low urinary VEGF-A165b level reflects renal dysfunction in the chronic kidney disease stage, while a high circulating VEGF-A165b level cannot be attributed to decreased renal clearance.

Effect of dietary energy and polymorphisms in BRAP and GHRL on obesity and metabolic traits

OBJECTIVE Obesity, a risk factor for all-cause and cardiovascular mortality, is a major health concerns among middle-aged men. The aim of this study was to investigate a possible association of dietary habits and obesity related single nucleotide polymorphisms (SNPs) with obesity and metabolic abnormalities. METHODS We conducted a retrospective cohort study using annual health examination data of 5112 male workers, obtained between 2007 and 2011. Average dietary energy was estimated using electronically collected meal purchase data from cafeteria. We examined 8 SNPs related to obesity: GHRL rs696217, PPARG rs1175544, ADIPOQ rs2241766, ADIPOQ rs1501299, PPARD rs2016520, APOA5 rs662799, BRAP rs3782886, and ITGB2 rs235326. We also examined whether SNPs that were shown to associate with obesity affect other metabolic abnormalities such as blood pressure (BP), glucose, and lipid profile. RESULTS Average dietary energy significantly associated with increased abdominal circumference (AC) and body mass index (BMI). The odds ratios (ORs) of overweight and obesity also increased. The major allele of rs696217 significantly increased BMI and an increased OR with obesity, while the minor allele of rs3782886 was associated with significantly decreased AC and the decreased ORs with overweight and obesity. The minor allele of rs3782886 was also associated with significantly decreased systolic BP (SBP), triglyceride (TG), high-density lipoprotein (HDL), and fasting blood sugar (FBS), while rs696217 was not associated with other metabolic abnormalities. CONCLUSIONS Average dietary energy in lunch, rs3782886, and rs696217 were associated with obesity, and rs3782886 was associated with other metabolic abnormalities.

Seasonal proteinuria changes in IgA nephropathy patients after proteinuria remission

Background Proteinuria is a powerful prognostic factor for end-stage renal disease in IgA nephropathy (IgAN) patients. However, it is not known whether proteinuria exacerbations are related to seasonal changes. Methods We retrospectively enrolled consecutive patients diagnosed with IgAN by kidney biopsy at our hospital between 2002 and 2014. Proteinuria remission was defined as urinary protein <0.3 g/gCr in two consecutive outpatient urinalyses and exacerbation as urinary protein ≥0.75 g/gCr. Four seasons were defined: spring (March–May), summer (June–August), autumn (September–November), and winter (December–February). We performed a multivariate analysis to identify factors associated with the second remission following a proteinuria exacerbation. Results We analyzed 116 patients. Proteinuria remission and exacerbation occurred in 77, and 43 patients, respectively. The incidence of proteinuria exacerbation was significantly higher in autumn and winter than in spring and summer (p = 0.040). The cumulative second remission rate was significantly higher in patients with autumn and winter proteinuria exacerbation than in patients with spring and summer exacerbations (p = 0.0091). In multivariate analyses, exacerbation onset in autumn and winter (hazard ratio [HR], 3.51; 95% confidence interval [CI], 1.41–8.74) and intensive therapy (HR, 2.26; 95% CI, 1.05–4.88) were significantly associated with a second proteinuria remission. Conclusion In IgAN patients in proteinuria remission, proteinuria exacerbation frequently occurred in autumn and winter. Exacerbations occurring in autumn and winter tended to remit early.

Acute Renal Failure with Severe Loin Pain and Patchy Renal Vasoconstriction in a Patient without Hypouricemia, Provoked by Epileptic Seizure

A 26-year-old Japanese man without hypouricemia and with 3 previous episodes of seizures concurrent with acute kidney injury (AKI) was admitted due to an epileptic seizure, lower back pain and AKI. His creatinine kinase levels were slightly elevated. Patchy renal ischemia on contrast-enhanced computed tomography and persistent residual contrast medium was observed, consistent with acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise (ALPE). Diffusion-weighted imaging (DWI) demonstrated signal changes in the corresponding area. ALPE should be considered a cause of AKI following seizures. We recommend DWI as an alternative diagnostic modality.