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Background and Aims A hypothesis has been proposed that serum (s-) soluble urokinase receptor (suPAR) activates glomerular podocyte β3 integrin to cause podocyte injury and onset of proteinuria in primary nephrotic syndrome (pNS). However, s-suPAR has been questioned as a disease marker for pNS because it did not correlate with urinary protein (UP). Furthermore, there are a few reports that suggested a correlation between urinary (u-) suPAR and UP by univariate analysis, but the correlation between the two has not been studied by multivariate analysis taking confounding factors into account. In addition, it is unclear how u-suPAR is involved in the pathogenesis of pNS. Method In 36 patients with pNS including minimal change (n=18), focal segmental glomerulosclerosis (n=7), membranous nephropathy (n=9) and membranoproliferative glomerulonephritis (n=2), the relationship between u-suPAR (pg/mgCr) and UP (g/gCr) was examined by cross-sectional analysis of baseline values before treatment and longitudinal analysis of changes during the first 2 months of treatment (⊿). In addition, the localization and staining intensity of activated β3 integrin in renal tissue were examined by immuno-histochemistry methods. We also examined whether s-suPAR (pg/ml) or u-suPAR is useful for predicting renal prognosis (1.5-fold increase from baseline in s-Cr) using Cox proportional hazard analysis. Results In cross-sectional analysis, u-suPAR was a UP predictor independent of s-suPAR, eGFR and selectivity index (S.I.) [standardized partial regression coefficient (stdβ) = 0.879, p Conclusion In pNS, u-suPAR was a proteinuria predictor independent of s-suPAR, suggesting the possibility of the mechanisms of proteinuria through β3 integrin activation in PTBB by u-suPAR. In addition, s-suPAR was useful in predicting renal prognosis.

Background and Aims The impact of hepatitis C virus (HCV) infection on patient survival after renal transplantation was worse. Previously, we found that continuous HCV infection was a significant independent risk factor for actuarial survival (especially at ≥20 years after the transplant procedure) among Japanese renal allograft recipients. This study evaluates the impact of HCV and of the new direct acting antivirals (DAAs) on patient outcomes in renal allograft recipients. Method We studied 46 cases (28 males, 18 females; 37 living-donor cases, 9 deceased-donor cases; mean follow-up period 305 months ranging from 2 to 420 months) out of the 315 renal transplanted patients who underwent the first renal transplantation in Kanazawa Medical University since 1974. They had antibodies against HCV: 11 were positive for HCV RNA and received DAAs (Group A, all of them genotype 1b); 27 were HCV RNA positive and did not receive any treatment (Group B); 8 were negative for HCV RNA (Group C) (Fig.1). Results All Group A patients had HCV RNA negativity after 2-12 weeks of treatment started, and 11 (100%) achieved a sustained virological response (SVR) at 24 weeks. All of them had no adverse effects by the use of DAAs. In this cohort, no patients in Group A died. On the other hand, 15 (55.5％) of 27 in Group B and 3 (37.5%) of 8 in Group C died. Causes of death among Group B were liver cirrhosis (5 cases), hepatocellular carcinoma (2 case), infections complicated with chronic hepatitis (6 cases) in chronic phase, fibrosing cholestatic hepatitis due to HCV (1 case) after surgery, and cardiovascular disease (1 case). The patient survival rate was significantly higher in Group A patients who received DAAs by Kaplan- Meier life table method (Log Rank test, Kay-square 11.7, p=0.004) (Fig.2). Conclusion Our results support the notion that continuous HCV infection was a harmful and that new DAAs were efficient and safe to treat HCV infection after renal transplantation.

Background and Aims Collagen deposition is observed in various part of kidney tissue and is serious pathological damage in kidney. Nodular glomerulosclerosis is one of a phenotype of collagen deposition in glomerular lesion, which affects the prognosis of renal function, but there is no effective treatment at present. Recently, we identified that glomerular endothelial cells with DNA double-strand breaks (DSB) are involved in the long-term accumulation of ECM molecules, especially collagen type VI(COL6). However, the mechanism of glomerular COL6 accumulation is still unclear. Method We examined the phospho-histone H2AX (γ-H2AX) of the DSB marker and COL6 accumulation in biopsied human kidneys to investigate their association. In addition, we investigated in vitro the relationship between DSB and COL6 excretion and the intracellular signal pathways in human glomerular endothelial cells (HRGEc) using mitomycin C (MMc)-induced DNA damage. In this study, we focused on the expression of DSB response signal pathways, i.e. ATM, ATR and DNA-PK using their specific kinase inhibitors (KU55933, VE-821, Nu7441). Results COL6 deposits and γ-H2AX expression in nuclei were detected in human glomerular capillary loop and glomerular nodular lesions. The multiple regression analysis showed that γ-H2AX positive area is the most independent factor for COL6 accumulation in glomeruli (β: 0.539, t=2.668, p=0.014). Furthermore, COL6 was the independent factor of nodular lesion in various pathologic diseases such as diabetic nephropathy, hypertensive glomerulosclerosis and the long-term transplanted allografts (β: 0.373, t=2.268, p=0.032). In vitro study, COL6 excretion detected by the decrease of COL6 positive cells was suppressed only in the ATR-inhibited group (control vs. kinase inhibitors; 2 h, 40.1 ± 23.5 vs. 59.0 ± 23.2%, p Conclusion This study suggested that nodular glomerulosclerosis is induced by DNA damage and COL6 deposition through ATR pathway in glomerular capillary endothelial cells. These findings will provide great insights into the development of new therapies that would suppress glomerularsclerosis in various kidney diseases.

Background and Aims Although it is reported that chronic kidney disease participates some roles in progression of sarcopenia, mechanisms of the progression of sarcopenia are unclear so far. In this observational study, we focused on serum adiponectin levels, that is a marker of metabolic syndrome, cardiovascular disease, and skeletal muscle mass in patients with kidney transplantation. Method Fifty-one patients who underwent renal transplantation at our hospital in and after 1998 (31 males and 20 females; aged 29-52 years at the time of transplantation) were retrospectively examined the relationships between the psoas muscle index (PMI), intramuscular adipose tissue content (IMAC), serum adiponectin fractions (high-/low-molecular-weight), and new-onset diabetes after transplantation (NODAT). Results Age at kidney transplantation negatively correlated with PMI before transplantation and positively correlated with IMAC before transplantation (rS=-0.427, p Conclusion PMI increased associated with high-molecular-weight adiponectin levels after renal transplantation. In addition, PMI increased suppressed the development of NODAT.

Additional file 1: Figure S1. Flow diagram of the selection of study participants. Figure S2. Baseline systolic blood pressure and loss of kidney function according to age groups. Figure S3. Risk factors for loss of kidney function and differences from the mean estimated glomerular filtration rate slopes according to age (analysis using unadjusted systolic and diastolic blood pressure). Figure S4. Risk factors for loss of kidney function and differences from the mean estimated glomerular filtration rate slopes according to age (analysis of age 40–49 years merged with 50–59 years).