Radiolucent Pure Matrix Stones on Computed Tomography Scan, Arising in Patient with Type I Diabetes and Chronic Kidney Disease: A Case Report.

Kidney matrix stones are a rare form of calculi, which are challenging to diagnose. Matrix stones consist of a proteinaceous material which has a radiolucent appearance that might be overlooked on imaging. Recently, endourological intervention has been the standard treatment method for matrix stones. We report a case of urinary matrix stones in a patient with type 1 diabetes mellitus and chronic kidney disease, in whom the stones formed into a pure matrix and were not visualized in the computed tomography scan. The stones were found after additional work-up, and they were managed using a transureteral stone basket, not through endourological intervention.

Nrf2-Heme Oxygenase-1 Attenuates High-Glucose-Induced Epithelial-to-Mesenchymal Transition of Renal Tubule Cells by Inhibiting ROS-Mediated PI3K/Akt/GSK-3ß Signaling.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is thought to play a significant role in the advancement to chronic kidney disease and contributes to the deposition of extracellular matrix proteins and renal fibrosis relating to diabetic nephropathy. METHOD: We studied the effect of Nrf2-HO-1 signaling on high-glucose- (HG-) induced EMT in normal human tubular epithelial cells, that is, HK2 cells. In short, we treated HK2 cells with HG and sulforaphane (SFN) as an Nrf2 activator. EMT was evaluated by the expression activity of the epithelial marker E-cadherin and mesenchymal markers such as vimentin and fibronectin. RESULTS: Exposure of HK2 cells to HG (60 mM) activated the expression of vimentin and fibronectin but decreased E-cadherin. Treatment of HK2 cells with SFN caused HG-induced attenuation in EMT markers with activated Nrf2-HO-1. We found that SFN decreased HG-induced production of reactive oxygen species (ROS), phosphorylation of PI3K/Akt at serine 473, and inhibitory phosphorylation of serine/threonine kinase glycogen synthase kinase-3ß (GSK-3ß) at serine 9. Subsequently, these signaling led to the downregulation of the Snail-1 transcriptional factor and the recovery of E-cadherin. CONCLUSION: The present study suggests that Nrf2-HO-1 signaling has an inhibitory role in the regulation of EMT through the modulation of ROS-mediated PI3K/Akt/GSK-3ß activity, highlighting Nrf2-HO-1 and GSK-3ß as potential therapeutic targets in diabetic nephropathy.

Overhydration Negatively Affects Quality of Life in Peritoneal Dialysis Patients: Evidence from a Prospective Observational Study.

UNLABELLED: Backgound: This study evaluated whether the hydration status affected health-related quality of life (HRQOL) during 12 months in peritoneal dialysis (PD) patients. METHODS: The hydration status and the HRQOL were examined at baseline and after 12 months using a bioimpedance spectroscopy and Kidney Disease Quality of Life-Short Form, respectively in PD patients. Four hundred eighty-one patients were included and divided according to the baseline overhydration (OH) value; normohydration group (NH group, -2L≤ OH ≤+2L, n=266) and overhydration group (OH group, OH >+2L, n=215). Baseline HRQOL scores were compared between the two groups. The subjects were re-stratified into quartiles according to the OH difference (OH value at baseline - OH value at 12 months; <-1, -1 - -0.1, -0.1 - +1, and ≥+1L). The relations of OH difference with HRQOL scores at 12 months and the association of OH difference with the HRQOL score difference (HRQOL score at baseline - HRQOL score at 12 months) were assessed. RESULTS: The OH group showed significantly lower baseline physical and mental health scores (PCS and MCS), and kidney disease component scores (KDCS) compared with the NH group (all, P<0.01). At 12 months, the adjusted PCS, MCS, and KDCS significantly increased as the OH difference quartiles increased (P<0.001, P=0.002, P<0.001, respectively). In multivariate analysis, the OH difference was independently associated with higher PCS (ß = 2.04, P< .001), MCS (ß=1.02, P=0.002), and KDCS (ß=1.06, P<0.001) at 12 months. The OH difference was independently associated with the PCS difference (ß = -1.81, P<0.001), MCS difference (ß=-0.92, P=0.01), and KDCS difference (ß=-0.90, P=0.001). CONCLUSION: The hydration status was associated with HRQOL and increased hydration status negatively affected HRQOL after 12 months in PD patients.

Depressive Symptoms, Patient Satisfaction, and Quality of Life Over Time in Automated and Continuous Ambulatory Peritoneal Dialysis Patients: A Prospective Multicenter Propensity-Matched Study.

Health-related quality of life (HRQOL) is an important clinical outcome for dialysis patients. However, relative superiority in HRQOL between automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD) are not clearly known. We compared HRQOL over time between APD and CAPD patients and evaluated factors associated with HRQOL.All 260 incident patients initiating APD or CAPD at multiple centers throughout Korea were prospectively enrolled in this study between October 2010 and February 2013. HRQOL, depressive symptoms, and renal treatment satisfaction were assessed 1 and 12 months after the start of dialysis by the Kidney Disease Quality of Life Short Form 36 (KDQOL-36), the Beck Depression Inventory (BDI), and the Renal Treatment Satisfaction Questionnaire (RTSQ), respectively.Of 196 patients who completed all questionnaires and did not change the peritoneal dialysis (PD) modality during the 1-year follow-up period, 160 were matched. APD patients showed better baseline HRQOL than CAPD patients for the symptoms, patient satisfaction, pain, and social function domains. There were no differences in HRQOL between the 2 groups at 12 months, and CAPD patients had significantly greater improvements in symptoms (P = 0.02), the mental composite summary (P = 0.03), and health status domains (P = 0.03) than APD patients. There were similar improvements in depressive symptoms (P = 0.01) and patient satisfaction with treatment (P = 0.01) in CAPD and APD patients. Interestingly, depressive symptoms, not PD modality, was the most influential and consistent factor for HRQOL. Despite the spontaneous improvement of depressive symptoms, considerable PD patients still had depressive symptoms at the 1-year appointment.APD has no advantage over CAPD for HRQOL. Considering the substantial negative effect of depressive symptoms on HRQOL, it is important to evaluate PD patients for depression and to treat those with depression to improve their HRQOL.

Efficacy of hemocontrol biofeedback system in intradialytic hypotension-prone hemodialysis patients.

We conducted a study to determine whether the hemocontrol biofeedback system (HBS) can improve intradialytic hypotension (IDH) in hypotension-prone hemodialysis (HD) patients compared with conventional HD. In this multicenter prospective crossover study, 60 hypotension-prone patients were serially treated by conventional HD for 8 weeks (period A), by HD with hemoscan blood volume monitoring for 2 weeks (period B0), and by HBS HD for 8 weeks (period B1). The number of sessions complicated by symptomatic IDH during 24 HD sessions (14.9 ± 5.8 sessions, 62.1% in period A vs 9.2 ± 7.2 sessions, 38.4% in period B1, P<0.001) and the number of IDH-related nursing interventions in a session (0.96 ± 0.66 in period A vs 0.56 ± 0.54 in period B1, P<0.001) significantly decreased in period B1 than in period A. Recovery time from fatigue after dialysis was significantly shorter in period B1 than in period A. The patients with higher post-dialysis blood pressure, lower difference between pre- and post-dialysis blood pressure, less frequent IDH, and higher pre- and post-dialysis body weight in period A responded better to HBS in period B1 in regard to the reduction of IDH. In conclusion, HBS may improve the patient tolerability to HD by reducing the IDH frequency and promoting faster recovery from fatigue after dialysis.

Chronic asymptomatic pyuria precedes overt urinary tract infection and deterioration of renal function in autosomal dominant polycystic kidney disease.

BACKGROUND: Urinary tract infection (UTI) occurs in 30%-50% of individuals with autosomal dominant polycystic kidney disease (ADPKD). However, the clinical relevance of asymptomatic pyuria in ADPKD patients remains unknown. METHODS: We retrospectively reviewed medical records of 256 ADPKD patients who registered to the ADPKD clinic at Seoul National University Hospital from Aug 1999 to Aug 2010. We defined the asymptomatic pyuria as more than 5-9 white blood cells in high-power field with no related symptoms or signs of overt UTI. Patients were categorized into 2 groups depending on its duration and frequency: Group A included non-pyuria and transient pyuria patients; Group B included recurrent and persistent pyuria patients. The association between asymptomatic pyuria and both the development of overt UTI and the deterioration of renal function were examined. RESULTS: With a mean follow-up duration of 65.3 months, 176 (68.8%) out of 256 patients experienced 681 episodes of asymptomatic pyuria and 50 episodes of UTI. The annual incidence of asymptomatic pyuria was 0.492 episodes/patient/year. The patients in group B showed female predominance (58.5% vs. 42.0%, P=0.01) and experienced an upper UTI more frequently (hazard ratio: 4.612, 95% confidence interval: 1.735-12.258; P=0.002, adjusted for gender and hypertension). The annual change in estimated glomerular filtration rate (ΔeGFR) was significantly larger in magnitude in group B than in group A (-2.7±4.56 vs. -1.17±5.8, respectively; P=0.01). Age and Group B found to be the independent variables for ΔeGFR and developing end-stage renal disease (16.0% vs. 4.3%, respectively; P=0.001). CONCLUSIONS: Chronic asymptomatic pyuria may increase the risk of developing overt UTI and may contribute to declining renal function in ADPKD.

Heme oxygenase-1 attenuates epithelial-to-mesenchymal transition of human peritoneal mesothelial cells.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells has been regarded as an early mechanism of peritoneal fibrosis. A substantial and rapidly growing literature indicates that HO-1 provides the provenance for pathways that can interrupt virtually all major mechanisms of tissue injury. The effects of HO-1 expression on EMT, which plays a critical role in the development of peritoneal membrane (PM) fibrosis, are unknown and its roles in peritoneal fibrosis has not been studied, yet. METHODS: A piece of human omentum obtained from consenting patients undergoing elective abdominal surgery was used for study. We treated the human peritoneal mesothelial cells (HPMCs) with high glucose solution and HO-1 inducer (hemin, 10 µmol/L). To further investigate the pure effect of HO-1 on EMT of mesothelium, gene transfer of recombinant Adenovirus-harboring human HO-1 (Adv-HO-1 gene) to HPMCs was done. RESULTS: Exposure of HPMCs to HG solution resulted in an increase of the expression of mesenchymal markers such as α-smooth muscle actin (α-SMA) and was associated with a decrease in the expression of epithelial markers, E-cadherin. HO-1 protein expression was decreased in the same situation. Treatment of HPMCs with HO-1 inducer, hemin showed a dosage-dependent amelioration of HG induced changes in markers of EMT with increase of expression of HO-1. Human HO-1 gene transfection resulted in a significant increase in HO-1 expression and ameliorated HG-induced changes in expression of E-cadherin and α-SMA. CONCLUSION: Taken together, our results suggest that HO-1 has a critical role in the modulation of peritoneal fibrosis, and, more important, the suppression of EMT. This study is the first to show the beneficial effect of HO-1 on reversing EMT in MC.

Anti-proteinuric effect of sulodexide in immunoglobulin a nephropathy.

PURPOSE: We conducted a multi-center randomized double-blind study to determine the effects of 6-month therapy with sulodexide on urinary protein excretion in patients with idiopathic Immunoglobulin A (IgA) nephropathy. MATERIALS AND METHODS: A total of seventy-seven patients participated in the study. They were randomly allocated to one of three groups: sulodexide 75 mg or 150 mg daily or the placebo for 6 months. The primary end point was the achievement, at 6 months, of at least 50% reduction in urine protein/creatinine ratio (UPCR) from the baseline value. RESULTS: At 6 months, the primary end point was achieved by 12.5% of the patients assigned to the placebo, 4.0% of the patients assigned to sulodexide 75 mg daily and 21.4% of those assigned to 150 mg (p=0.308). Treatment with sulodexide 150 mg daily for 6 months significantly reduced log UPCR from 6.38±0.77 at baseline to 5.98±0.94 at 6 months (p=0.045), while treatment with sulodexide 75 mg daily and placebo did not. CONCLUSION: A 6-month treatment with sulodexide did not achieve 50% reduction of urinary protein excretion in IgA nephropathy patients, but showed a tendency to increase the time-dependent anti-proteinuric effect. Therefore, long-term clinical trials on a larger scale are warranted to elucidate the hypothesis that sulodexide affords renal protection in IgA nephropathy patients.

Assessment of deceased donor kidneys using a donor scoring system.

PURPOSE: Marginal grafts should be used more actively in Asian countries where deceased donor transplantation is unpopular. We modified a quantitative donor scoring system proposed by Nyberg and his colleagues and developed a donor scoring system in order to assess the quality of deceased donor grafts and their prognostic value as an initial effort to promote usage of marginal donors. MATERIALS AND METHODS: We retrospectively evaluated 337 patients. RESULTS: A scoring system was derived from six donor variables [age, 0-25; renal function, 0-4; history of hypertension, 0-4; Human Leukocyte Antigen (HLA) mismatch, 0-3; body weight, 0- 1; cause of death, 0-3 points]. Donor grafts were stratified by scores: grade A, 0-10; grade B, 11-20; grade C, 21-30; and grade D, 31-40 points. Donor grades significantly correlated with estimated glomerular filtration rate (eGFR) at 6 months (A, 64.0 mL/min/1.73 m(2); B, 57.0 mL/min/1.73 m(2); C, 46.8 mL/min/1.73 m(2); p < 0.001). The five-year graft survival rate was also lower in grade C than grade A (74% vs. 93%, p = 0.002). Donors in grade C and D were regarded as marginal donors. The proportion of marginal donors was much lower in Korea, compared with data from the United Network for Organ Sharing (15.2% vs. 29%). CONCLUSION: Considering the scarcity of deceased donor kidneys and the relatively better graft outcome with lower grade-donors in Korea, it is worth increasing the usage of marginal grafts.

Hydrogen peroxide-induced VCAM-1 expression in pancreatic islets and beta-cells through extracellular Ca2+ influx.

BACKGROUND: The use of porcine islets as alternatives to transplantable human islets is hampered by xenotransplant rejection. To identify molecular mechanisms that would allow subversion of xenoislet rejection, we investigated the role of H2O2 in vascular cell adhesion molecule-1 (VCAM-1) expression by porcine and mouse islets and beta-cell lines. METHODS: Porcine islets were treated with H2O2, tumor necrosis factor alpha, interferon-gamma, interleukin-1beta, and lipopolysaccharide, to assess the effects of inflammatory stimulators on VCAM-1 expression using flow cytometry. The role of Ca2+ in H2O2-induced VCAM-1 expression was investigated in beta-cell lines using an extracellular Ca2+ chelator and Ca2+-depleted media. Furthermore, H2O2-induced VCAM-1 expression was measured in beta-cells, pretreated with inhibitors of protein kinase C, phospholipase D, and phosphatidylinositol-3 kinase/Akt. Finally, H2O2-induced VCAM-1 expression was evaluated in porcine islets and rodent beta-cell lines infected with an adenovirus encoding catalase, a H2O2-removing enzyme. RESULTS: H2O2 was most potent inflammatory stimulator of VCAM-1 expression in porcine islets and had the greatest effect on VCAM-1 expression by beta-cells. Signaling pathway analysis demonstrated that extracellular Ca2+ influx was critical to H2O2-mediated VCAM-1 expression; however, protein kinase C, phospholipase D, and phosphatidylinositol-3 kinase/Akt activation were not required for VCAM-1 expression. Finally, catalase overexpression inhibited H2O2-induced VCAM-1 expression by islets and beta-cell lines. CONCLUSION: An extracellular calcium-dependent H2O2 pathway is the critical mediator of VCAM-1 expression by pancreatic islets and beta-cells. Inhibition of this pathway by catalase overexpression in donor islets can be exploited to protect against xenoislet immune responses.