A novel method for assessing the renal biopsy specimens using an activatable fluorescent probe.

Gamma-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) is an activatable fluorescent probe that can be activated by γ-glutamyltranspeptidase (GGT). The expression of GGT in the kidney, which is one of the major organs exhibiting enhanced GGT expression, is exclusively localised to the cortex. Here, we aimed to investigate the feasibility of gGlu-HMRG as a probe for the on-site assessment of renal biopsy specimens. gGlu-HMRG fluorescent probe was applied to the renal proximal tubular epithelial cells and cortical collecting duct cells in vitro, mouse kidneys ex vivo, and human biopsy specimens. In addition, the fluorescence intensities in the cortex and the medulla were comparatively evaluated in the biopsy specimens. The fluorescence signal was rapidly detected in the renal proximal tubular epithelial cells, whereas that in the cortical collecting duct cells was not detected. The fluorescence signal was detected in the mouse kidneys ex vivo without markedly affecting the tissue morphology. In the human biopsy specimens, the fluorescence signal in the cortex was significantly distinct from that in the medulla (p < 0.05). Thus, this fluorescent probe can be used to distinctly identify the renal cortex in the biopsy specimens.

Refractory Peritoneal Dialysis Peritonitis Due to Neisseria macacae: A Case Report and Review of the Literature.

The Gram-negative diplococcus Neisseria macacae is a commensal bacterium of the mucosal surfaces in humans. A 52-year-old woman receiving continuous ambulatory peritoneal dialysis was admitted because of abdominal pain and turbid peritoneal fluid. N. macacae was isolated from peritoneal fluid culture and showed susceptibility to ceftriaxone. Despite appropriate antibiotics, the peritonitis was refractory, leading to the removal of the peritoneal dialysis catheter. We herein report the first case of peritoneal dialysis peritonitis caused by Neisseria macacae and review previous case reports of N. macacae infection in humans.

Prognostic Value of Neutrophil-To-Lymphocyte Ratio and Platelet-To-Lymphocyte Ratio for Renal Outcomes in Patients with Rapidly Progressive Glomerulonephritis.

BACKGROUND: Rapidly progressive glomerulonephritis (RPGN) is a syndrome characterized by a rapid decline in renal function that often causes end-stage renal disease. Although it is important to predict renal outcome in RPGN before initiating immunosuppressive therapies, no simple prognostic indicator has been reported. The aim of this study was to investigate the associations of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) to renal outcomes in patients with RPGN. METHODS: Forty-four patients with a clinical diagnosis of RPGN who underwent renal biopsy were enrolled. The relationships between NLR and PLR and renal outcome after 1 year were investigated. RESULTS: NLR and PLR were significantly higher in patients with preserved renal function in comparison to patients who required maintenance hemodialysis (p < 0.05 and p < 0.01, respectively). An NLR of 4.0 and a PLR of 137.7 were the cutoff values for renal outcome (area under the curve, 0.782 and 0.819; sensitivity, 78.4% and 89.2%; specificity, 71.4% and 71.4%, respectively). Furthermore, an NLR of 5.0 could predict recovery from renal injury in patients requiring hemodialysis (area under the curve, 0.929; sensitivity, 83.3%; specificity, 85.7%). CONCLUSION: NLR and PLR could be candidates for predicting renal outcomes in patients with RPGN.

[Malignant Mesothelioma of the Tunica Vaginalis Testis : A Case Report].

A 56-year-old man presented with a painless swelling of the left scrotum. Cytologic examination of blood stained hydrocele fluid suggested malignancy. Left high orchiectomy was performed under the suspicion of malignant tumor of the tunica vaginalis testis. The final pathologic report revealed malignant mesothelioma of the tunica vaginalis testis. There is no evidence of recurrence after 114 months followup. It is important to perform en bloc resection for this disease to prevent recurrence.

Ipragliflozin Ameliorates Endoplasmic Reticulum Stress and Apoptosis through Preventing Ectopic Lipid Deposition in Renal Tubules.

BACKGROUND: Chronic kidney disease (CKD) and non-alcoholic steatohepatitis (NASH) are major health burdens closely related to metabolic syndrome. A link between CKD and NASH has been assumed; however, the underlying mechanism is still unknown. Ectopic lipid deposition (ELD) in the hepatocyte results in endoplasmic reticulum (ER) stress, which plays an important role in the development of steatohepatitis. ELD is also assumed to play a role in the development of kidney injury. We aimed to investigate the role of ELD and ER stress in the development of CKD, and evaluate the efficacy of a sodium glucose cotransporter-2 inhibitor, ipragliflozin. METHODS: Male FLS-ob/ob mice that closely imitate the pathophysiology of NASH were treated with vehicle or ipragliflozin. Metabolic characteristics, histology of the kidney, ER stress, and apoptotic signals were evaluated. RESULTS: The serum triglyceride was significantly lower in mice treated with ipragliflozin. Ipragliflozin reduced ELD in renal tubules. Ipragliflozin also reduced the expression levels of GRP78 and CHOP, apoptotic cells, and interstitial fibrosis. CONCLUSIONS: ELD induced kidney injury through ER stress. Ipragliflozin improved the pathogenesis of CKD by reducing ELD and ER stress in NASH-model mice. Our results suggest ipragliflozin has therapeutic effect on CKD in NASH.

Predictive Value of Cortical Thickness Measured by Ultrasonography for Renal Impairment: A Longitudinal Study in Chronic Kidney Disease.

BACKGROUND: Kidney size is associated with renal function, however it is not elucidated whether kidney size is a risk for the progression of chronic kidney disease. The aim of this study was to investigate the predictive value of morphological evaluation of kidney size by ultrasonography for the progression of renal dysfunction. METHODS: Morphological parameters including kidney length, volume, cortical thickness, and medullary thickness were measured by ultrasonography in 87 patients with chronic kidney disease, and adjusted by body size. Renal functions at baseline and after 2 years were measured and the associations of morphological parameters to decline in renal function over 2 years were analyzed. RESULTS: Height-adjusted cortical thickness was correlated to decline in renal function (r = 0.426, p < 0.001). Height-adjusted cortical thickness could predict renal dysfunction with the area under the curve of 0.786, and height-adjusted cortical thickness of 4.0 mm/cm was a cut off value with a sensitivity of 72.5% and a specificity of 80.0% for the risk of a more than 30% decline in renal function or initiation of dialysis. CONCLUSIONS: We provide new insights into the utility of measuring cortical thickness by ultrasonography for predict future renal impairment.

Renal shear wave elastography for the assessment of nephron hypertrophy: a cross-sectional study in chronic kidney disease.

PURPOSE: To investigate the association of renal elasticity to microscopic findings of nephron hypertrophy and nephrosclerosis. METHODS: Patients who underwent renal biopsy were enrolled. Renal elasticity was measured by acoustic radiation force impulse, and nephron size (glomerular volume, non-sclerotic glomerular density, and mean profile tubular area) and nephrosclerosis (globally sclerotic glomeruli and interstitial fibrosis) were estimated. Nephron hypertrophy was indicated by larger glomerular volume, larger tubular area, and lower non-sclerotic glomerular density. Nephrosclerosis was indicated by a higher percentage of globally sclerotic glomeruli and higher severity of fibrosis. RESULTS: Renal elasticity was negatively correlated with glomerular volume (r = - 0.480, P = 0.024) and mean tubular area (r = - 0.469, P = 0.028), but it was not correlated with non-sclerotic glomerular density (r = 0.205, P = 0.359), percentage of globally sclerotic glomeruli (r = 0.057, P = 0.800), and severity of fibrosis (r = 0.014, P = 0.950). In a multiple linear regression analysis, glomerular volume and mean tubular area were independently associated with renal elasticity (std ß = - 0.454, P = 0.015 and std ß = - 0.577, P = 0.007, respectively). CONCLUSION: Renal elasticity was correlated with microstructural findings of nephron hypertrophy. Measuring renal elasticity could help in detecting kidney disease.

[Early Diagnosis of Squamous Cell Carcinoma of the Urinary Bladder Reached by Routine Abdominal Ultrasonography in a Patient on Self-Catheterization : A Case Report].

A 69-year-old woman was referred to our department for refractory cystitis. Incomplete emptying of the bladder was observed, and symptoms did not improve after medication. Clean intermittent catheterization was initiated. Two years after introduction of catheterization, a mass in the bladder dome was detected by routine abdominal ultrasonography. She was diagnosed with malignant tumor of the bladder diverticulum based on cystoscopy, computed tomography, and magnetic resonance imaging. Partial cystectomy and lymph node dissection was performed following transurethral resection of the bladder tumor. Histopathology revealed squamous cell carcinoma and no signs of lymph node metastasis. She is alive and recurrence-free 28 months after surgery.

Shewanella algae Bacteremia in an End-stage Renal Disease Patient: A Case Report and Review of the Literature.

A 71-year-old man was admitted because of nausea and abdominal pain. He was receiving an erythropoiesis-stimulating agent for anemia and dysregulated iron metabolism due to stage G5 chronic kidney disease. He had a history of raw fish intake and was diagnosed with infectious enterocolitis, which worsened and led to septic shock. Shewanella putrefaciens grew in the blood culture, but Shewanella algae was identified in a 16S rRNA gene sequence analysis. We herein report a case of S. algae bacteremia believed to have been transmitted orally. We also reviewed previous case reports on Shewanella infection in end-stage renal disease patients.

Effects of Simvastatin on Alveolar Regeneration and Its Relationship to Exposure in Mice with Dexamethasone-Induced Emphysema.

In the present study, the relationship between systemic exposure of simvastatin (SV) hydroxy acid (SV-acid), an active form of SV, and its alveolar regeneration rates was investigated using emphysema model mice created by postnatal treatment of dexamethasone. In a model with young animals, the mice were treated with SV for 10 d from postnatal day 42. Similar alveolar regeneration with a % mean linear intercept (Lm) recovery of 60 to 70% by histochemical observation was observed in mice after intraperitoneal administration at dose in the range of 4-100 µg/mouse. The % Lm recovery after oral administration of 20 µg/mouse was comparable with that after intraperitoneal administration at a dose of 4 µg/mouse, when their exposure of SV-acid was almost similar in both treated groups. Regardless of the route of administration, the recovery can depend on the exposure level of SV-acid, and to the maximum was about 60-70%. On the other hand, in a model with adult animals, the mice were intraperitoneally administrated SV at a dose of 4 µg/mouse for 10 d from postnatal day 152. Compared to young animals, less % Lm recovery was observed in adult mice even their systemic exposures of SV-acid were similar.

Left Renal Cortical Thickness Measured by Ultrasound Can Predict Early Progression of Chronic Kidney Disease.

AIMS: The kidney becomes atrophic in advanced chronic kidney disease, and renal size and parenchymal volume correlate with renal function. However, alterations in renal parenchymal volume have not been adequately studied in terms of the renal cortex and medulla. We investigated the relationship between the changes in the renal cortex and medulla and renal function. METHODS: Renal ultrasound (US) parameters including renal length, parenchymal thickness, cortical thickness and medullary thickness were assessed in 176 subjects, who were categorized into 4 groups based on the estimated glomerular filtration rate (ml/min/1.73 m2): group 1, ≥ 90; group 2, ≥ 60 but < 90; group 3, ≥ 30 but < 60; and group 4, < 30. Renal US parameters in both kidneys were compared among the 4 groups. RESULTS: We found stepwise associations in renal length, cortical thickness and parenchymal thickness with decreased renal function. Medullary thickness showed no changes among groups 1-3. Multiple linear regression analysis including sex, age and renal US parameters showed that only renal length was an independent predictor of renal function. When analyzed in groups 1-3, cortical thickness was the strongest associated parameter. Lower cortical left/right ratio (left cortical thickness/right cortical thickness) showed a stepwise association with a decrease in renal function. CONCLUSION: Renal length and cortical thickness measured by US were correlated with renal function. In particular, left cortical thickness could help to detect early changes in renal function.

Renal shear wave velocity by acoustic radiation force impulse did not reflect advanced renal impairment.

AIM: Acoustic radiation force impulse is a noninvasive method for evaluating tissue elasticity on ultrasound. Renal shear wave velocity measured by this technique has not been fully investigated in patients with renal disease. The aim of the present study was to compare renal shear wave velocity in end-stage renal disease patients and that in patients without chronic kidney disease and to investigate influencing factors. METHODS: Renal shear wave velocities were measured in 59 healthy young subjects (control group), 31 subjects without chronic kidney disease (non-CKD group), and 39 end-stage renal disease patients (ESRD group). Each measurement was performed 10 times at both kidneys, and the mean value of eight of 10 measurements, excluding the maximum and minimum values, was compared. RESULTS: Renal shear wave velocity could be measured in all subjects. Renal shear wave velocity in the control group was higher than in the non-CKD group and in the ESRD group, and no difference was found between the non-CKD group and the ESRD group. Age and depth were negatively correlated to the renal shear wave velocity. In multiple regression analysis, age and depth were independent factors for renal shear wave velocity, while renal impairment was not. There was no difference between the non-CKD group and the ESRD group, even when ages were matched and depth was adjusted. CONCLUSION: Renal shear wave velocity was not associated with advanced renal impairment. However, it reflected alteration of renal aging, and this technique may be useful to detect renal impairment in the earlier stages.

[Two Cases of Intrapelvic Schwannoma].

A 67-year-old man (case 1) and 65-year-old man (case 2) were incidentally found to have a tumor in the retrovesical region. Computed tomography and magnetic resonance imaging demonstrated a solid tumor at the right side of the rectum. 2-Deoxy-2-[fluorine-18] fluoro-D-glucose (FDG) -positron emission tomography revealed uptake at the tumor. Both patients were cured by tumor resection. Histological diagnosis was benign schwannoma. In case 2, it was difficult to diagnose the tumor as schwannoma by imaging studies. We made a histological diagnosis by transrectal needle biopsy of the tumor before the operation. Schwannoma is located mostly in the limbs and the head and neck, but rarely in the intrapelvic cavity. We expect that the transrectal needle biopsy is valuable for diagnosing the retrovesical tumor.

Influence of Olmesartan on Sirtuin 1 mRNA Expression in 5/6 Nephrectomized Spontaneously Hypertensive Rats.

BACKGROUND: Recent studies revealed that sirtuin 1 (SIRT1) has a relation to the mechanism of transforming growth factor-beta (TGF-beta) mediated apoptosis in glomerular mesangial cells and plays an important role in blood pressure regulation. It has been suggested that SIRT1 contributes to the renoprotective effect of angiotensin receptor blocker (ARB), but this has not yet become clearly recognized. In this study, we examined the relationship between SIRT1 and the therapeutic effect of olmesartan on renal injury in nephrectomized spontaneously hypertensive rats (SHRs). METHODS: Male Wistar rats and 5/6 nephrectomized (5/6Nx) SHRs were assigned to 5 groups as follows: group A, Wistar rats; group B, Wistar rats administered high-dose olmesartan (15 mg/kg/day); group C, 5/6Nx SHRs; group D, 5/6Nx SHRs administered low-dose (3 mg/kg/day) olmesartan; and group E, 5/6Nx SHRs administered high-dose olmesartan. The drugs were administered for 12 weeks. Blood pressure and urinary protein excretion were measured every 4 weeks. Serum creatinine, glomerular sclerosis, SIRT1 mRNA level, TGF-beta mRNA level and klotho mRNA level were measured at the end of the examination. RESULTS: Systolic blood pressure, urinary protein excretion, serum creatinine and glomerular sclerosis in Wistar rats were significantly lower than that of 5/6Nx SHRs. Among 5/6Nx SHRs, high doses of olmesartan significantly decreased urinary protein excretion, serum creatinine and glomerular sclerosis compared to the non-treated and low-dose olmesartan groups. Expression of SIRT1 and klotho mRNA were significantly downregulated in 5/6Nx SHRs; however, olmesartan did not attribute to any change in gene expression. Expression of TGF-beta mRNA was significantly increased in 5/6Nx SHRs, and olmesartan did not affect the level of TGF-beta mRNA expression. CONCLUSION: Expression of SIRT1 is decreased in 5/6Nx SHRs compared to Wistar rats. Olmesartan suppressed glomerular sclerosis, but did not increase the expression of SIRT1, suggesting that the renoprotective effect of olmesartan is independent of the SIRT1 pathway.

[Stromal Tumors of Uncertain Malignant Potential (STUMP) of the Prostate : A Case Report].

A 77-year-old man was seen at our hospital with the chief complaint of pollakisuria. Magnetic resonance imaging (MRI) showed a 25 mm cystic tumor with solid components behind the prostate. A transrectal biopsy for the prostate showed no evidence of malignancy. Two years later, he complained of weak urinary stream, and the MRI diagnosis demonstrated an increase of the tumor size to 67 mm. Since prostatic sarcoma was diagnosed by the transrectal biopsy for the prostate, a tumor resection and prostatectomy were performed. At 19 months after the operation, there was no evidence of metastasis or recurrence, and he has had no dysuria. The final pathological diagnosis was of a prostatic STUMP.

Seminal vesicle metastasis of renal cell carcinoma.

We present an unusual magnetic resonance imaging finding of a 70-year-old man with the seminal vesicle tumor. The patient underwent radical nephrectomy for renal cell carcinoma 4 years ago. Laboratory data, including prostatic-specific antigen, ranged within normal limits. Transrectal needle biopsy disclosed a clear cell carcinoma, which was compatible with the original renal cell cancer. Vesiclectomy was performed. Pathohistologic examination confirmed a metastatic renal cell carcinoma of the seminal vesicle.

Prevalence of antibodies to hepatitis E virus among Japanese blood donors: identification of three blood donors infected with a genotype 3 hepatitis E virus.

Risk factors for acquiring hepatitis E among individuals in industrialized countries including Japan are not fully understood. We investigated whether Japanese blood donors with or without an elevated alanine aminotransferase (ALT) level are likely to have hepatitis E virus (HEV) infection. Serum samples were collected from 5,343 voluntary blood donors including 1,087 donors with elevated ALT of 61-966 IU/L and 4,256 donors with normal ALT (< or = 60 IU/L) at two Japanese Red Cross Blood Centers, and were tested for the presence of anti-HEV IgG by in-house enzyme-linked immunosorbent assay (ELISA). Overall, 200 donors (3.7%) were positive for anti-HEV IgG, including 32 (2.9%) with elevated ALT and 168 (3.9%) with normal ALT. Serum samples with anti-HEV IgG were further tested for the presence of anti-HEV IgM by in-house ELISA and for HEV RNA by reverse transcription (RT)-polymerase chain reaction (PCR). Three donors with ALT of 966, 62 or 61 IU/L were positive for anti-HEV IgM and HEV RNA. The HEV isolates obtained from the three viremic donors segregated into genotype 3, were 91.5-93.4% similar to each other in the 412 nucleotide sequence of open reading frame 2, and had the highest identity of 91.5-94.9% with the JRA1 isolate which was recovered from a Japanese patient with sporadic acute hepatitis E who had never been abroad, suggesting that these three HEV isolates are indigenous to Japan. This study suggests that a small but significant proportion of blood donors in Japan with or without elevated ALT are viremic and are potentially able to cause transfusion-associated hepatitis E.