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Experimental analysis of the suppression of leucine-induced insulin release and cellular disorganization during chronic renal failure (CRF) shows that islets from CRF animals exhibit decreased leucine-induced insulin release and that secondary CRF hyperparathyroidism mediates the decreases. Parathyroidectomy of the animals with CRF or treatment with parathyroid hormone inhibitor results in the correction of cellular disorganization and decrease of insulin release. Defects in leucine metabolism and disruption of leucine-GLDH-alpha-ketoglutarate-glutaminase pathways also accompany cellular disorganization during CRF.

Background. Contrast-induced nephropathy (CIN) is a major cause of acute kidney injury in chronic kidney disease. Many cancer patients have risk factors for CIN and frequently undergo contrast-enhanced computed tomography (CECT). We aimed to develop a risk prediction model for CIN in cancer patients undergoing CECT. Methods. Between 2009 and 2017, 2,240 cancer patients with estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 who underwent CECT with CIN preventive measures were included in a development cohort. Primary outcome was development of CIN, defined as 25% increase in serum creatinine within 2-6 days after contrast exposure. A prediction model was developed using logistic regression analysis. The model was evaluated for prognostic utility in an independent cohort (N = 555). Results. Overall incidence of CIN was 2.5% (55/2,240). In multivariable analysis, eGFR, diabetes mellitus, and serum albumin level were identified as independent predictors of CIN. A prediction model including eGFR, serum albumin level, and diabetes mellitus was developed, and risk scores ranged from 0 to 6 points. The model demonstrated fair discriminative power (C statistic = 0.733, 95% confidence interval [CI] 0.656-0.810) and good calibration (calibration slope 0.867, 95% Cl 0.719-1.015). In the validation cohort, the model also demonstrated fair discriminative power (C statistic = 0.749, 95% CI 0.648-0.849) and good calibration (calibration slope 0.974, 95% CI 0.634-1.315). Conclusions. The proposed model has good predictive ability for risk of CIN in cancer patients with chronic kidney disease. This model can aid in risk stratification for CIN in patients undergoing CECT. [ABSTRACT FROM AUTHOR]

Objectives: Arteriovenous graft for hemodialysis shows poorer outcomes than arteriovenous fistula, due to frequent stenosis and thrombosis. We investigated arteriovenous graft patency outcomes and prognostic factors for these outcomes.Methods: We included a single-center cohort of patients receiving arteriovenous graft for hemodialysis access from 2010 to 2014. Demographics, laboratory data, comorbidities, and medications were collected from medical records. Surgical factors related to graft operation including the type and diameter of connected vessels, graft location, and type of operation (elective or emergency) were also recorded. Outcomes included primary and secondary patency. Survival analysis was conducted using the Kaplan-Meier method; univariate and multivariate analyses were used to evaluate the prognostic factors.Results: Data from 225 grafts were analyzed. During the follow-up period (mean: 583 days, range: 1-1717 days), 138 (61%) grafts required intervention and 46 (20%) permanently failed. Primary patency at one, two, and three years was 42%, 20%, and 16%, respectively. Secondary patency at one, two, and three years was 85%, 72%, and 64%, respectively. Multivariate analysis showed that primary patency was negatively associated with increasing age and location of vessel anastomosis (reference-brachiobrachial anastomosis; brachiobasilic - HR, 0.569; 95% CI, 0.376-0.860; p = 0.007; brachioaxillary anastomosis - HR 0.407; 95% CI, 0.263-0.631; p < 0.0001); secondary patency was positively associated with diastolic blood pressure, serum albumin level, and hemoglobin over 10 g/dL. Adverse events other than stenosis or thrombosis, such as infection/inflammation or pseudoaneurysm were observed in approximately 20% of grafts.Conclusions: Factors associated with diminished primary arteriovenous graft patency included increased patient age and location of vessel anastomosis (brachiobrachial type compared to brachiobasilic or brachioaxillary type); diminished secondary patency was associated with low diastolic blood pressure, low serum albumin, and hemoglobin level under 10 g/dL. Among these factors, diastolic blood pressure, serum albumin, and hemoglobin level may be modifiable and could improve arteriovenous graft patency outcomes. [ABSTRACT FROM AUTHOR]

A production capacity analysis considering market demand and raw materials is very important to design a new plant. However, in the food processing industry, the supply uncertainty of raw materials is very high, depending on the production site and the harvest season, and further, it is not straightforward to analyze too complex food production systems by using an analytical optimization model. For these reasons, this study presents a simulation-based decision support model to select the right location for a new food processing plant. We first define three supply vulnerability factors from the standpoint of regional as well as seasonal instability and present an assessment method for supply vulnerability based on fuzzy quantification. The evaluated vulnerability scores are then converted into raw material supply variations for food production simulation to predict the quarterly production volume of a new food processing plant. The proposed selection procedure is illustrated using a case study of semiprocessed kimchi production. The best plant location is proposed where we can reduce and mitigate risks when supplying raw material, thereby producing a target production volume steadily. [ABSTRACT FROM AUTHOR]

Abstract: Although various strategies for steroid withdrawal after transplantation have been attempted, there are few reports of the long‐term results of steroid withdrawal regimens in kidney transplantation. Earlier, we reported on a 5‐year prospective, randomized, single‐center trial comparing the safety and efficacy of cyclosporine (CsA) plus mycophenolate mofetil (MMF) with that of tacrolimus (TAC) plus MMF, when steroids were withdrawn 6 months after kidney transplantation in low‐risk patients. We now report the 10‐year observational data on the study population. We collected data from the database of the Organ Transplantation Center, Samsung Medical Center for 5 years after completion of the original study (TAC group n = 62; CsA group n = 55). The 10‐year patient survival, death‐censored graft survival, and acute rejection‐free survival did not differ between groups (98% vs 96%; P = 0.49, 78% vs 85%; P = 0.75 and 84% vs 76%; P = 0.14 in the TAC group vs CsA group, respectively). In low‐risk patients, there was no difference in long‐term patient and graft survival between TAC‐ and CsA‐based late steroid withdrawal regimens that included MMF treatment. More long‐term randomized clinical trials are needed to clarify the benefits of late steroid withdrawal in kidney transplantation. [ABSTRACT FROM AUTHOR]

The paper reports the solid-liquid phase equilibria (SLE), excess molar volume (VE), and molar refraction deviation (ΔR) for binary systems of ethanoic acid with the C3 to C5 carboxylic acids, propanoic, butanoic, and pentanoic acid, which are the main constituents of bio-butanol fermentation broth. The SLE was determined via a synthetic method using a custom-built glass tube at atmospheric pressure, whereas the thermodynamic mixture properties, VE and ΔR were obtained from directly measured density and refractive index using a precision densitometer and refractometer, respectively. All of the SLE that were determined for binary mixtures of ethanoic acid+C3-C5 carboxylic acids showed a single eutectic point and regressed well with the NRTL activity model within 0.6 K of RMSD. The VE values for the same binaries were positive for the entire composition ranges of all the systems, whereas the ΔR values were negative for all the systems. The VE and ΔR were well regressed by polynomial equations, namely Redlich-Kister within 0.006 cm3·mol−1 of the standard deviation for VE and 0.02 cm3·mol−1 for ΔR. [ABSTRACT FROM AUTHOR]

Abstract: Background: IgA nephropathy (IgAN) is the most frequent primary glomerular disease and the leading cause of end‐stage renal disease. We investigated clinicopathologic predictors of renal survival in patients with IgAN with a focus on glomerular filtration rate (GFR) decline slope. Materials and methods: We screened all patients with primary IgAN between 1995 and 2012. Renal progression was defined as doubling of serum creatinine. Using serial serum creatinine levels during the first‐year, we calculated the GFR decline slopes. Further, we defined patients in the steepest GFR slope quartile as rapid decliners and those in the second steepest GFR slope quartile as slow decliners. Others were defined as nondecliners. Results: Of 214 participants, baseline GFR was 81 (62, 100) mL/min/1.73 m2, which was not different among the 3 groups. Rapid decliners and slow decliners had higher levels of urinary protein/creatinine ratio (0.88, 0.89 and 0.58 g/gCr, respectively, P < .001). Five‐year renal survival was 76% in rapid decliners, 91% in slow decliners and 100% in nondecliners (P < .001, rapid or slow decliners vs nondecliners). After adjustment for clinicopathologic variables, slow decliners were associated with an 8.8‐fold higher risk of progression (P = .011), and rapid decliners were associated with a 10.2‐fold increased risk of progression (P = .007) compared with nondecliners. Conclusions: First‐year GFR slope was associated with increased risk of renal progression, independent of proteinuria and histologic findings. Further studies are needed to investigate whether early GFR change can identify high‐risk patients who benefit from immunosuppressive treatment in IgAN. [ABSTRACT FROM AUTHOR]

Background: IgA nephropathy (IgAN) is not always benign, and some patients at high risk of end-stage renal disease (ESRD) experience a rapid decline in renal function. This study retrospectively examined the beneficial effects of cytotoxic therapy.Methods: We identified 102 patients with progressive IgAN despite optimal conservative management. Of these, 31 who received cytotoxic therapy and 55 who were managed conservatively were included.Results: Median eGFR and urinary protein-to-creatinine ratio (uPCR) at baseline did not differ between the groups (p = 0.475 and 0.259, respectively). Median GFR slope was also similar (p = 0.896). Cumulative renal survival was better in the cytotoxic therapy group than in the control group (p = 0.009). Cytotoxic therapy was associated with lower risk of progression to ESRD, independent of eGFR, uPCR, GFR slope and kidney histologic findings (HR 0.13, 95% CI 0.03–0.66). In the cytotoxic therapy group, the median GFR slope decreased from −7.8 (−10.5, −5.0) mL/min/1.73 m2per year to −3.4 (−5.1, −1.8) mL/min/1.73 m2per year after treatment (p < 0.001). Mortality was not observed, but infection requiring hospitalization occurred at similar rates in both groups (p = 0.886).Conclusions: Cytotoxic therapy attenuated the rate of GFR decline and was associated with a favorable renal outcome in patients with progressive IgAN.Key messagesCytotoxic therapy was associated with a favorable renal outcome in IgA nephropathy patients whose glomerular filtration rate progressively declined despite optimal conservative management.Cytotoxic therapy significantly attenuated the rate of glomerular filtration rate decline as well as the amount of proteinuria in patients with progressive IgA nephropathy.Adverse events following cytotoxic therapy were comparable to conservative management. [ABSTRACT FROM PUBLISHER]

Warfarin skin necrosis (WSN) is an infrequent complication of warfarin treatment and is characterized by painful ulcerative skin lesions that appear a few days after the start of warfarin treatment. Calciphylaxis also appears as painful skin lesions caused by tissue injury resulting from localized ischemia caused by calcification of small- to medium-sized vessels in patients with end-stage renal disease. We report on a patient who presented with painful skin ulcers on the lower extremities after the administration of warfarin after a valve operation. Calciphylaxis was considered first because of the host factors; eventually, the skin lesions were diagnosed as WSN by biopsy. The skin lesions improved after warfarin discontinuation and short-term steroid therapy. Most patients with end-stage renal disease have some form of cardiovascular disease and some require temporary or continual warfarin treatment. It is important to differentiate between WSN and calciphylaxis in patients with painful skin lesions. [ABSTRACT FROM AUTHOR]

Background Advances in immunosuppression after kidney transplantation have decreased the influence of early acute rejection (EAR) on graft survival. Several studies have suggested that late acute rejection (LAR) has a poorer effect on long-term graft survival than EAR. We investigated whether the timing of acute rejection (AR) influences graft survival, and analyzed the risk factors for EAR and LAR. Methods We performed a retrospective cohort study involving 709 patients who underwent kidney transplantation between 2000 and 2009 at the Samsung Medical Center, Seoul, Korea. Patients were divided into three groups: no AR, EAR, and LAR. EAR and LAR were defined as rejection before 1 year and after 1 year, respectively. Differences in graft survival between the three groups and risk factors of graft failure were analyzed. Results Of the 709 patients, 198 (30%) had biopsy-proven AR [EAR=152 patients (77%); LAR=46 patients (23%)]. A total of 65 transplants were lost. The 5-year graft survival rates were 97%, 89%, and 85% for patients with no AR, EAR, and LAR, respectively. These differences were significant ( P <0.001 for both by log-rank test). In time-dependent Cox regression analysis, EAR (hazards ratio, 3.37; 95% confidence interval, 1.90–5.99) and LAR (hazards ratio, 5.32; 95% confidence interval, 2.65–10.69) were significantly related to graft failure. When we set LAR as standard and compared it with EAR, there was no statistical difference between EAR and LAR ( P =0.21). Conclusion AR, regardless of its timing, significantly worsened graft survival. Treatments to reduce the incidence of AR and improve prognosis are needed. [ABSTRACT FROM AUTHOR]

Fanconi syndrome (FS) is a rare condition that is characterized by defects in the proximal tubular function. A 48-year-old woman was admitted for evaluation of proteinuria. The patient showed normal anion gap acidosis, normoglycemic glycosuria, hypophosphatemia, and hypouricemia. Thus, her condition was compatible with FS. The M peak was found behind the beta globulin region in urine protein electrophoresis. Upon bone marrow examination, we found that 24% of cells were CD138+ plasma cells with kappa restriction. From a kidney biopsy, we found crystalline inclusions within proximal tubular epithelial cells. Thereafter, she was diagnosed with FS accompanied by multiple myeloma. The patient received chemotherapy and autologous stem cell transplantation, and obtained very good partial hematologic response. However, proximal tubular dysfunction was persistent until 1 year after autologous stem cell transplantation. In short, we report a case of FS accompanied by multiple myeloma, demonstrating crystalline inclusion in proximal tubular cells on kidney biopsy. [ABSTRACT FROM AUTHOR]

Background: Occult hepatitis B infection (OBI) is the presence of hepatitis B virus (HBV) DNA in serum or hepatic tissue without detectable hepatitis B surface antigen (HBsAg) in serum. Kidney disease patients in the post-renal transplantation period are in a specific situation as a result of the high pre-transplantational risk of HBV infection and post-transplantational immunosuppression. We studied the pre-transplantational prevalence and post-transplantational influence of OBI on kidney transplantation patients. Methods: We investigated pre-transplantational serum samples of 217 HBsAg-negative patients of post-renal transplant status for the presence of HBV DNA by real-time quantitative polymerase chain reaction. Serologic markers for HBV and hepatitis C virus (HCV) infection as well as liver enzymes were analyzed. Results: We detected HBV DNA in 2.3% (5/217) of HBsAg-negative patients, and the median HBV DNA titer was 33.15 copies/ml (range 30.6-144.6 copies/ml). Among the 5 OBI patients, 2 had hepatitis B surface antibodies (anti-HBs) and 1 had hepatitis B core antibodies (anti-HBc IgG). None of the patients with OBI were co-infected with HCV. There was no evidence of reactivation of OBI during the 36-month (range 27-63 months) follow-up monitoring period after transplantation, in spite of immune suppression to prevent rejection. Conclusions: The prevalence of occult HBV in the setting of renal transplantation was higher than that in the general population of Korea, and no reactivation of hepatitis B was observed in patients with OBI in the post-renal transplantation period. [ABSTRACT FROM AUTHOR]

Background. Urinary angiotensinogen (AGT) was reported as a marker of renal injury in chronic kidney disease patients. However, the main source of urinary AGT is unknown in proteinuric patients because the disrupted filtration barrier might cause AGT filtration. We investigated the origin and the clinical importance of urinary AGT in proteinuric IgA nephropathy (IgAN) patients. Methods. In patients with biopsy-proven IgAN, urinary and plasma AGT was measured using a sandwich ELISA and compared with intrarenal AGT expression. The patients were followed up for 3 years. Results. Natural logarithm of the urinary AGT/creatinine (ln (urinary AGT/Cr)) was positively correlated with intrarenal expression of AGT (ln (urinary AGT/Cr) versus AGT/β-actin, r = 0.620, P < 0.0001; ln (urinary AGT/Cr) versus AGT density, r = 0.452, P = 0.007). Ln (urinary AGT/Cr) showed a positive correlation with urinary protein/creatinine ratio (PCR) but a negative correlation with estimated glomerular filtration rate (eGFR). Regression analyses showed that ln (urinary AGT/Cr) was a significant determinant of urinary PCR and eGFR 3 years after biopsy. Conclusions. Urinary AGT reflects intrarenal AGT expression and correlates with the extent of proteinuria and renal function. Our study indicates the intrarenal compartment as the main source of urinary AGT, suggesting its clinical implication as an important biomarker in proteinuric IgAN patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: The purpose of this study was to evaluate the incidence of contrast-induced nephropathy (CIN), and the effect of intravenous albumin for prophylaxis of CIN in patients with liver cirrhosis (LC) and chronic kidney disease (CKD). Methods: We conducted a retrospective study of 81 subjects with LC and CKD (estimated glomerular filtration rate (eGFR)<60mL/min/1.73m2) who underwent contrast-enhanced computed tomography (CT). Patients received either isotonic sodium bicarbonate solution (3mL/kg for 1h before CT and 1mL/kg/h for 6h after CT) or albumin (20% albumin, 25mL for 1h before CT and 75mL for 6h after CT). CIN was defined as an increase of ≥25% or ≥0.5mg/dL in serum creatinine level. Results: Overall, CIN developed in three patients (3.7%). Of the 81 subjects, 43 received sodium bicarbonate solution and 38 received albumin. Both groups were comparable with regard to age, sex, diabetes mellitus, and baseline eGFR. The albumin group showed a significantly poorer liver function profile. CIN incidence did not differ significantly between the groups: it occurred in one (2.3%) of the 43 subjects receiving sodium bicarbonate and two (5.3%) of the 38 subjects receiving albumin (P=0.6). However, the albumin group showed a significantly smaller increase in body weight (P=0.03). Conclusion: The incidence of CIN in patients with LC and CKD undergoing contrast-enhanced CT after preventive measures was relatively low. The incidence of CIN was not significantly different between sodium bicarbonate and albumin groups. [Copyright &y& Elsevier]

Continuous renal replacement therapy (CRRT) has emerged as the preferred dialysis modality for critically ill patients with acute kidney injury. The objectives of this retrospective study were to assess the effect of nafamostat on circuit patency of CRRT and the safety regarding bleeding complications in patients at high risk of bleeding. We conducted a retrospective study of 243 CRRT patients at high risk of bleeding. We started CRRT without anticoagulation, and nafamostat was used if hemofilter lifespan was less than 12 h. The average hemofilter lifespan was measured before and after drug infusion to evaluate the efficacy of nafamostat. The frequency and number of red blood cell (RBC) transfusions were measured to assess the safety of nafamostat. Of the 243 patients, 62 (25.5%%) received nafamostat. In nafamostat group, the hemofilter lifespan was lengthened from 10.2 (7.5-13.0) h to 19.8 (12.6-26.6) h after drug infusion ( p < 0.001). The hemofilter lifespan was 27.5 (17.5-38.2) h in anticoagulation-free group. The frequency of RBC transfusion during CRRT did not differ between the nafamostat group and the anticoagulation-free group (71%% vs. 70%%, p == NS). The median number of RBC units transfused per CRRT day was also not different between the two groups [0.7 (0.5-1.0) units/day vs. 0.7 (0.4-1.1) units/day; p == NS]. The use of nafamostat in patients at high risk of bleeding who require CRRT effectively lengthened the filter survival time without an increase in RBC transfusion. However, 74.5%% of patients at high risk of bleeding maintained an acceptable CRRT hemofilter lifespan without circuit anticoagulation. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a serious complication after coronary artery bypass grafting and is closely associated with high mortality. The objective of the present study was to identify the incidence and risk factors for AKI after off-pump coronary artery bypass grafting (OPCAB) and to construct a risk model for prediction of AKI after OPCAB. Methods: We retrospectively studied 448 adult patients who underwent isolated OPCAB between April 2006 and July 2007. AKI was defined as an increase in serum creatinine of 0.3 mg//dL or 50%% within 48 h after surgery. Multivariate analysis was used to evaluate risk factors for AKI after OPCAB and a risk model was developed with a weighted score based on the odds ratio. Results: The incidence of AKI was 7.6%% ( n == 34). Most patients (97%%) had mild AKI. Independent preoperative risk factors of postoperative AKI were identified as high systolic blood pressure, decreased glomerular filtration rate, and coronary angiography (CAG) less than 7 days prior to OPCAB. The incidence of AKI across each increasing score level increased from 2.2%% to 60%%. Conclusion: AKI after OPCAB was common. High systolic blood pressure, renal dysfunction, and CAG less than 7 days prior to cardiac surgery were associated with AKI after OPCAB. Our risk model may provide information to clinicians and patients about the risk of postoperative AKI. [ABSTRACT FROM AUTHOR]

Culture-negative peritonitis, which results from a variety of etiologies, such as problems in culture techniques, prior use of antibiotics, infection caused by unusual organisms, and noninfectious causes, accounts for up to 20% of cases of peritonitis in peritoneal dialysis patients and sometimes poses diagnostic and therapeutic dilemmas. A 62-year-old woman on continuous ambulatory peritoneal dialysis (CAPD) presented with minimal abdominal pain and a turbid dialysate. Under the impression of infectious peritonitis, empirical intraperitoneal (IP) antibiotic treatment was administered. All cultures from the effluent were negative, although the white blood cell count in the effluent was elevated. Despite initial clinical improvement and resolution of abdominal pain, mild fever persisted, even after removal of the CAPD catheter. The first CT scan before removal of the catheter demonstrated no evidence of intra-abdominal pathology, except for the possibility of peritonitis, but a follow-up CT scan after removal of the catheter demonstrated a perforated appendix with a peri-appendiceal abscess. The patient recovered completely after removal of the appendix and the abscess. This case suggests that a follow-up CT scan and/or surgical exploration should be considered to identify the intra-abdominal pathology in patients with culture-negative refractory peritonitis, even after removal of CAPD catheter. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome has been suggested as a risk factor for chronic kidney disease (CKD). Inflammation is associated with both metabolic syndrome and CKD. We investigated inter-relationships between C-reactive protein (CRP), metabolic syndrome, and CKD among 9586 subjects without diabetes or hypertension. Methods: Metabolic syndrome was defined according to the criteria of the revised Adult Treatment Panel III. CKD was defined as a glomerular filtration rate <60 mL/min/1.73 m2 or as albuminuria. A CRP cutpoint of 3 mg/L was used to differentiate high and low CRP groups. Results: Chronic kidney disease was present in 6.2% of subjects without metabolic syndrome and in 13.1% of subjects with the syndrome (P < .001). In a multivariate model, high blood pressure (BP) (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.24–1.95), high fasting glucose (OR, 1.47; 95% CI, 1.19–1.81), abdominal obesity (OR, 1.52; 95% CI, 1.22–1.81), and high CRP (OR, 1.53; 95% CI, 1.18–1.98) were independently associated with prevalent CKD. Compared with low CRP/without metabolic syndrome, the multivariate-adjusted odds for CKD of high CRP/without metabolic syndrome and low CRP/with metabolic syndrome were 1.48 (95% CI, 1.10–2.0) and 1.90 (95% CI, 1.47–2.45), respectively. Subjects with high CRP and metabolic syndrome had a 3.26-fold greater odds of having CKD (95% CI, 2.00–5.31). Conclusions: Metabolic syndrome and high CRP were independently associated with increased prevalence of CKD. The odds of CKD increased in the setting of high CRP and metabolic syndrome. [Copyright &y& Elsevier]

Background. Hypokalaemic periodic paralysis (hypoPP) is an autosomal dominant disorder involving the abnormal function of ion channels and it is characterized by paralysis attacks of varying severity, accompanied by a fall in blood potassium levels. Linkage analysis showed that the candidate locus responsible for hypoPP was localized to chromosome 1q31‐32, and this locus encoded the muscle dihydropyridine‐sensitive calcium channel α1‐subunit (CACNA1S). So far, three different mutations in CACNA1S gene have been identified in patients with hypoPP: Arg528His, Arg1239His and Arg1239Gly in Caucasian patients. However, there are few reports about the mutations of CACNA1S gene in other races. [ABSTRACT FROM PUBLISHER]

Kidney biopsy is an indispensible procedure for making a pathologic diagnosis of renal diseases by fixing and staining the biopsy specimen. However, it is not a routine procedure to culture the cells from a renal biopsy specimen directly, or to utilize the cultured cells for any kind of diagnostic or functional evaluation. In this study, primary culture of the renal tubular epithelial cells was tried from a piece of percutaneous kidney biopsy specimen. Successive passages of the cells were possible until fourth passage. With these cells, morphologic characteristics of the cultured cells and integrin expression profiles were investigated. On light and electron microscopy, these cells were characterized by the cobblestone-like growth, presence of microvilli and tight junction, and the preservation of polarity. Immunohistochemical studies demonstrated the epithelial nature of these cells and particularly their differentiation from renal tubular epithelial cells, of either proximal or distal nephronic segment. The integrin profile confirms the epithelial nature of the cell. We hope that our results facilitate the understanding of pathophysiology of renal tubular cells from the patient directly. [ABSTRACT FROM AUTHOR]

Background/Aims: Since heparin can bind to Hemophan, hemodialysis using heparin-bound Hemophan (HBH-HD) could be a useful modality in patients at risk of bleeding. We designed a simplified heparin binding technique and assessed the safety and efficiency of HBH-HD. Methods: To bind heparin to Hemophan, heparin solution (1 liter, 20 IU/ml saline) was recirculated through Hemophan (GFS plus 11, Gambro) for 1 h while the saline solution (700 ml/h) was removed. In 28 maintenance dialysis patients at risk of bleeding, we evaluated the heparin concentration (HC) and activated partial thromboplastin time (aPTT) during HBH-HD to assess the increased risk of bleeding. We compared the safety and efficiency of HBH-HD with that of routine hemodialysis with low-dose heparinization (R-HD) in a prospective cross-over study, and then analyzed the outcomes of 1,057 HBH-HD in 159 patients. Results: During HBH-HD, there was a slight increase in both HC (0.15 ± 0.03 IU/ml, p < 0.01) and aPTT (43.7 ± 5.7 s, p < 0.01) at 15 min after the initiation of dialysis compared to predialysis levels (0.11 ± 0.03 IU/ml and 37.5 ± 6.3 s). However, there was no increase in HC and aPTT at 60 min, 120 min and at the end of dialysis. In a cross-over study, aPTT during dialysis was markedly lower in HBH-HD than in R-HD (p < 0.01). The Kt/V (1.22 ± 0.31, p > 0.05) and urea clearance (136 ± 17 ml/min, p > 0.05) of HBH-HD did not significantly differ from those of R-HD (1.29 ± 0.57 and 136 ± 13 ml/min). However, the loss of total blood compartment volume of the dialyzer was greater in HBH-HD (17.5 ± 9.2%, p < 0.01) than in R-HD (2.9 ± 1.2%). Out of 1,057 HBH-HD, 982 HBH-HD (93%) were successfully completed while 75 HBH-HD (7%) resulted in severe clotting. Conclusion: We conclude that the HBH-HD could minimize the bleeding risk and be an efficient HD technique in patients at high risk of bleeding. Careful observation for extracorporeal clotting is, however, required during HBH-HD. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims: The pathogenesis of diabetic kidney disease (DKD) is complex and multifactorial; increasing evidence suggests that tubular injury and inflammatory process are involved in disease progression. We investigated the potential association of renal expression of tubular injury markers, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and inflammatory markers, tumor necrosis factor receptor (TNFR) 1 and 2 with renal progression in pathologically proven diabetic nephropathy (DN).Methods: We identified 122 patients with confirmed DN. After excluding patients with other coexisting renal disease or estimated glomerular filtration rate (eGFR) <30mL/min/1.73m2, 35 patients were included. Annual decline of (GFR decline slope) was calculated using linear regression analysis. Tissue tubular and glomerular expressions of NGAL, KIM-1, TNFR1, and TNFR2 were assessed using immunohistochemistry.Results: Median baseline urinary protein to creatinine ratio (uPCR) was 6.76 (2.18-7.61) mg/mg Cr, median baseline eGFR was 50 (43-66) mL/min per 1.73m2, and median GFR decline slope was 15.6 (4.4-35.1) mL/min per 1.73m2 per year. Positive correlations were observed between tubular expressions of NGAL and KIM-1, and GFR decline slopes (r=0.601, p<0.001; r=0.516, p=0.001, respectively), and between tubular expressions of KIM-1 and uPCR (r=0.596, p<0.001), and between NGAL and interstitial fibrosis and tubular atrophy (IFTA) score (r=0.391, p=0.024). No correlations were found between glomerular or tubular expressions of TNFRs, and clinical parameters including GFR decline slopes. On multivariate analysis, the association between tubular expressions of KIM-1 and GFR decline slopes was dependent on uPCR. Tubular expressions of NGAL were independently associated with GFR decline slopes, with an adjusted coefficient factor of 0.290 (95% confidence interval, 0.009-0.202, p=0.038).Conclusions: These findings suggest that tubular injury plays a key role in the pathogenesis of DKD in high-risk patients. Further studies are warranted to determine whether tubular injury could be a therapeutic target in DKD. [ABSTRACT FROM AUTHOR]

Background Screening for monoclonal immunoglobulin (MIg) is critical in patients with kidney disease. Methods We identified 943 subjects who underwent kidney biopsy and at least one of monoclonal (M)-protein tests (serum and urine electrophoresis [EP], serum and urine immunofixation [IF], and serum free light chain [FLC] ratio). The sensitivities of several combinations of the 5 tests were examined by clinical presentations of kidney disease. Results The sensitivities of serum EP, urine EP, and the serum FLC ratio were 65%, 68%, and 71%, respectively, which were lower than those of serum IF (79%) and urine IF (87%) to detect MIg. In the nephrotic syndrome (NS) group, the panel including serum IF, urine IF, and the serum FLC ratio exhibited 100% sensitivity to identify MIg in patients with multiple myeloma (MM) or with monoclonal gammopathy of renal significance (MGRS). In subjects without NS, the panel of serum EP and serum FLC ratio detected MIg in all cases of MM, and the serum IF plus serum FLC ratio detected MIg in all cases of MGRS. Conclusion This study demonstrated that the sensitivity of screening panels differed by the presenting features of kidney disease. The M-protein tests had lower sensitivity for detection of MIg in subjects with NS compared to those with other clinical presentation. [ABSTRACT FROM AUTHOR]