Angiotensin Receptor-Neprilysin Inhibitors in Patients With Heart Failure With Reduced Ejection Fraction and Advanced Chronic Kidney Disease: A Retrospective Multi-Institutional Study.

Background: Data regarding using angiotensin receptor-neprilysin inhibitor (ARNI) in patients with both heart failure with reduced ejection fraction (HFrEF) and advanced chronic kidney disease (CKD) are limited. Methods and Results: Between January 2016 and December 2018, patients with HFrEF and advanced CKD (estimated glomerular filtration rate [eGFR] ≤ 30 mL/min/1.73 m2) were identified from a multi-institutional database in Taiwan. Patients who had never been prescribed with an ARNI, angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB) were excluded. We used inverse probability of treatment weighting (IPTW) to balance baseline covariates, and compared outcomes between ARNI and ACEI/ARB users. There were 206 patients in the ARNI group and 833 patients in the ACEI/ARB group. After IPTW adjustment, the mean ages (65.1 vs. 66.6 years), male patients (68.3 vs. 67.9%), left ventricular ejection fraction (30.5 vs.31.2%), eGFR (20.9 vs. 20.3 mL/min/1.73 m2) were comparable in the ARNI and ACEI/ARB groups. Over 85% of the patients had beta-blockers prescriptions in both groups (86.2 vs. 85.5%). After IPTW adjustment, the mean follow-up durations were 7.3 months and 6.6 months in the ARNI and ACEI/ARB groups, respectively. ARNI and ACEI/ARB users had a comparable risk of the composite clinical event (all-cause mortality or heart failure hospitalization) (hazard ratio [HR], 1.31; 95% confidence interval (CI) 0.91-1.88) and progression to dialysis (HR 1.04; 95% CI 0.54-2.03). In subgroup analysis, dialysis patients who used ARNIs were associated with higher incidence of heart failure hospitalization (subdistribution HR, 1.97; 95% CI 1.36-2.85). Conclusions: Compared with ACEIs or ARBs, ARNIs were associated with comparable clinical and renal outcomes in patients with HFrEF and advanced CKD (eGFR ≤ 30 mL/min/1.73 m2). In short-term, HF hospitalization may occur more frequently among ARNI users, especially in patients on dialysis.

Prognostic factors and complication rates for double-filtration plasmapheresis in patients with Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is an acute immune-mediated demyelinating polyradiculoneuropathy that could lead to disabilities if not properly treated. There are only limited data on the prognostic factors and complications when using double-filtration plasmapheresis in these patients. We reviewed the medical records of 60 GBS patients who underwent double-filtration plasmapheresis as the first-line therapy at a tertiary care teaching hospital. The severity of disease was evaluated at different time points using disability scores. Functional outcome was defined as good (GBS disability score 0 to 2) or poor (GBS disability score 3 to 6) at 28 days after admission. The cohort included 22 women and 38 men with a mean age of 50 ± 18 years. In univariate logistic regression analysis, potential factors associated with poor outcome include an older age (P = 0.101), the absence of preceding respiratory tract infection (P = 0.043), mechanical ventilation (P = 0.016), a lower hematocrit (p = 0.072), a lower serum sodium level (P = 0.153) and a higher disability score on admission (P < 0.001). In multivariate analysis, a higher disability score on admission was associated with a poorer outcome (OR, 5.61; 95% CI, 2.34 to 13.43; P < 0.001), whereas the presence of prodromal upper respiratory tract infection correlated with a better outcome (OR, 0.13; 95% CI, 0.03-0.59; P = 0.009). Among 60 patients, eleven (18.3%) have various complications attributed to plasmapheresis treatment. Six patients (10.0%) developed deep vein thrombosis and two experienced catheter-related infection (3.3%). Hypotension, allergy and hemolysis occurred in one patient each (1.7%). In conclusion, we describe our experiences of using DFPP in the treatment of GBS. The pretreatment severity score was the most significant predictor of treatment outcome, suggesting that early referral and timely treatment are important. Potential complications such as catheter-related infection and deep vein thrombosis should be monitored carefully.

Methicillin-resistant Staphylococcus aureus nasal carriage among patients receiving hemodialysis in Taiwan: prevalence rate, molecular characterization and de-colonization.

BACKGROUND: Staphylococcus aureus, particularly methicillin resistant (MRSA), is a common pathogen among patients receiving hemodialysis. To evaluate nasal carriage, molecular characterization and effectiveness of decolonization of MRSA among patients receiving hemodialysis in Taiwan, we conducted this study. METHODS: From January to June 2011, two nasal samplings with a 3-month interval were obtained from patients undergoing hemodialysis in a medical center (CGMH), and in a local hospital (YMH) and sent for detection of MRSA. For MRSA carriers, decolonization procedures were administered. All patients in CGMH were observed if MRSA infections occurred during the study period. RESULTS: A total of 529 nasal specimens (265 from CGMH and 264 from YMH) were collected from 296 patients (161 from CGMH and 135 from YMH). 233 patients participated in both surveys. Average one-time point MRSA carriage rate was 3.8%, and the rate was up to 6.9% for those with two-time point surveys. No additional significant factor for MRSA carriage was identified. Seventy percent of the 20 colonizing MRSA isolates, though categorized as healthcare-associated strains epidemiologically, shared common molecular characteristics of the local community-associated strains. Only one of the 20 MRSA-colonized patients failed decolonization and had persistent colonization, while without any intervention, 17 (61%) of 28 patients with methicillin-sensitive S. aureus colonization in the first survey had persistent colonization of a genetically indistinguishable strain. Within the study period, two patients (1.24%) in CGMH, one with MRSA colonization (9.1%), developed MRSA infection. CONCLUSION: A substantial proportion of patients receiving hemodialysis in Taiwan had MRSA colonization, mostly genetically community strains. Decolonization procedures may effectively eliminate MRSA colonization and might reduce subsequent MRSA infection in these patients.

Korean red ginseng improves blood pressure stability in patients with intradialytic hypotension.

Introduction. Intradialytic hypotension (IDH) is a common complication during hemodialysis which may increase mortality risks. Low dose of Korean red ginseng (KRG) has been reported to increase blood pressure. Whether KRG can improve hemodynamic stability during hemodialysis has not been examined. Methods. The 8-week study consisted of two phases: observation phase and active treatment phase. According to prehemodialysis blood pressure (BP), 38 patients with IDH were divided into group A (BP ≥ 140/90 mmHg, n = 18) and group B (BP < 140/90 mmHg, n = 20). Patients were instructed to chew 3.5 gm KRG slices at each hemodialysis session during the 4-week treatment phase. Blood pressure changes, number of sessions disturbed by symptomatic IDH, plasma levels of vasoconstrictors, blood biochemistry, and adverse effects were recorded. Results. KRG significantly reduced the degree of blood pressure drop during hemodialysis (P < 0.05) and the frequency of symptomatic IDH (P < 0.05). More activation of vasoconstrictors (endothelin-1 and angiotensin II) during hemodialysis was found. The postdialytic levels of endothelin-1 and angiotensin II increased significantly (P < 0.01). Conclusion. Chewing KRG renders IDH patients better resistance to acute BP reduction during hemodialysis via activation of vasoconstrictors. Our results suggest that KRG could be an adjuvant treatment for IDH.

Early identification of leptospirosis as an ignored cause of multiple organ dysfunction syndrome.

Leptospirosis is the most common zoonosis in the world but remains underreported, owing to protean manifestations and ignorance about the disease among health care providers in Taiwan. From September 2000 to March 2006, surveillance of 455 patients with multiple organ dysfunction syndrome with unclear cause or clinical suspicion of leptospirosis was performed. Diagnosis was further confirmed by microscopic agglutination test or isolation of Leptospira. Cases were classified as excluded based on confirmed etiology other than leptospirosis or negative paired serologic test. Forty-two patients were confirmed as having leptospirosis, which accounted for 9.2% of total patients with multiple organ dysfunction syndrome. Forty-nine excluded cases were identified for a case-control analysis for clinical distinction. The most common presentations of leptospirosis were fever (97.6%), acute kidney injury (85.7%), and jaundice (61.9%). The leptospirosis group showed lower urine specific gravity (cutoff value, 1.0145) and enlarged kidney size (cutoff value, 11.05 cm) as compared with the excluded cases by multivariate logistics regression. Delayed antibiotic administration prolongs the duration of hospitalization (R2 = 0.486, P < 0.01). No mortality has been found in the leptospirosis group after initiation in 2003 of rapid immunoglobulin M serology assay that showed considerably high sensitivity and specificity. Leptospirosis accounts for a salient cause of multiple organ dysfunctions in Taiwan. Early awareness of leptospirosis by distinct presentations, followed by prompt antibiotics therapy, can dramatically save the patients. The easily performed rapid immunoglobulin M serology assay is suitable as a rapid screening test for the diagnosis of leptospirosis.

Predictors of acquired perforating dermatosis in uremic patients on hemodialysis: a case-control study.

OBJECTIVES: The purpose of this study was to identify the predictors of acquired perforating dermatosis (APD) in patients on maintenance hemodialysis (HD). METHODS: A case-control study was performed at our outpatient HD center between January 1, 2000 and March 31, 2011. Patients on HD with APD were matched (1 : 2) for gender and age with controls on HD. Conditional logistic regression was used to identify factors associated with APD. RESULTS: A total of 19 patients with APD and 38 age and gender matched patients were enrolled in the study. Univariate logistic regression showed that APD was significantly associated with diabetes mellitus (DM), reduced levels of intact parathyroid hormone (iPTH) and albumin (Alb), reduced dialysis adequacy (Kt/V) and urea reduction rate (URR), and elevated levels of high-sensitivity C-reactive protein (hsCRP). Multivariate logistic regression identified reduced iPTH (hazard ratio (HR): 0.983; P = 0.026) and Alb (HR: 0.099; P = 0.047) and elevated hsCRP (HR: 1.210, P = 0.024) as risk factors for APD. CONCLUSIONS: iPTH, hsCRP, and Alb are predictors for APD in HD patients.

Immunoglobulin G levels can predict non-diabetic renal disease in patients with type 2 diabetes mellitus.

BACKGROUND: Proteinuria in patients with diabetes mellitus (DM) is sometimes caused by glomerular diseases other than diabetic nephropathy. In patients with type 2 DM (T2DM), specific predictors for non-diabetic renal disease (NDRD) are needed in addition to the traditional indicators for renal biopsy. METHODS: From 1 January 2000 to 31 March 2011, we retrospectively enrolled 54 T2DM patients with proteinuria who had undergone renal biopsies into the present study. Associations between NDRD and 20 potential biomarkers, including serum levels of Igs and proteins associated with kidney function, and urinary protein and red blood cell levels, and hepatitis virus carrier status, were analyzed by multivariate logistic regression. RESULTS: Multivariate logistic regression showed that reduced serum IgG (odds ratio [OR] 0.997; P = 0.006; 95% confidence interval [CI] 0.94-0.998) and creatinine (Cr; OR 0.587; P = 0.014; 95% CI 0.348-0.897) were predictors of NDRD. The area under the receiver operating characteristic curve (AUC(ROC) ) confirmed the good discriminatory power of IgG (AUC(ROC) 0.857 ± 0.058; 95% CI 0.744-0.970; P < 0.001) and Cr (AUC(ROC) 0.838 ± 0.054; 95% CI 0.732-0.943; P < 0.001). The IgG level below which the risk for NDRD increased, as calculated by obtaining the best Youden index, was 919.5 mg/dL (sensitivity 91.7%; specificity 83.3%), and the corresponding Cr level was 4.1 mg/dL (sensitivity 58.3%; specificity 96.7%). CONCLUSION: Serum IgG levels <919.5 mg/dL and serum Cr levels <4.1 mg/dL are associated with NDRD in T2DM patients.

The impact of type of assistance on characteristics of peritonitis in elderly peritoneal dialysis patients.

BACKGROUND: The elderly patients are the fastest-growing end-stage renal disease (ESRD) population in Taiwan. Assisted peritoneal dialysis (PD) has been employed to overcome the barriers to PD. The aim of this retrospective, single-center study was to describe the status of assisted PD and the impact of type of assistance on peritonitis in elderly patients in Taiwan. METHODS: One hundred and two patients initiated PD at the age of 65 or older between 2000 and 2008; 79 episodes of peritonitis occurred during the follow-ups. The patients and episodes of peritonitis were divided into three groups based on the type of assistance: (1) self-care: patients performing dialysis independently, (2) family: patients whose dialysis was performed by family, (3) caregiver: patients whose dialysis was performed by a private caregiver. Patient characteristics and incidence, etiology and outcomes of peritonitis were compared. RESULTS: There were 26 (25.5%), 44 (43.1%), and 32 (31.4%) patients in the self-care, family, and caregiver groups, respectively. The overall peritonitis rate was 1/33 patient-months. Patients in the caregiver group were older and had more comorbidities than the self-care group. They had a trend of higher overall peritonitis rate (1/24 patient-months, P = 0.077) and fungal peritonitis rate (P = 0.060) compared to the self-care and family groups, but this was statistically non-significant. CONCLUSIONS: Three-fourths of elderly PD patients in the present study required assistance from family members or private caregivers. Caregiver-assisted patients were significantly older and had more comorbidities. Also, a non-significant trend of higher peritonitis incidence was observed in these patients.

Short range magnetic correlations induced by La substitution in Ho(1-x)La(x)Mn(2)O(5).

Magnetic susceptibility, x-ray diffraction, neutron diffraction and Raman scattering measurements are employed to study the effects of La substitution on the magnetic properties of multiferroic HoMn(2)O(5). 9% and 18% La-substituted compounds crystallize into the same orthorhombic Pbam symmetry as the parent compound. The magnetic responses to an ac driving magnetic field between 40 and 140 K are greatly enhanced by 18% La substitution. The neutron magnetic diffraction patterns reveal the development of short range magnetic correlations below 140 K. In addition, two Raman peaks and a series of new x-ray diffraction peaks suddenly develop below this temperature. Incommensurate long range antiferromagnetic order appears below 38 K. Magnetic frustration could be the main mechanism governing the present observations.

Peritoneal dialysis and hemodialysis in systemic lupus erythematosus patients: comparison of clinical outcomes.

BACKGROUND: This study compared peritoneal dialysis (PD) and hemodialysis (HD) outcomes between female systemic lupus erythematosus (SLE) patients with end-stage renal disease (ESRD) due to lupus nephropathy. METHODS: 22 female SLE patients undergoing PD were compared with 14 female SLE patients receiving HD. Clinical outcomes and infective complications were reviewed. RESULTS: The overall mortality rate was much higher in the PD group (6/22) than in the HD group (1/14) (p = 0.027). PD patients had higher C-reactive protein level (37.1 +/- 41.4 vs. 6.7 +/- 9.5 mg/l, p = 0.037) and numbers of infectious episode (PD vs. HD: 1 episode per 33.16 patient-months vs. 1 episode per 118.26 patient-months, respectively, p = 0.046). Before the end of the observation period, HD patients had higher serum albumin (3.8 +/- 0.2 vs. 3.3 +/- 0.6 g/dl, p = 0.01). CONCLUSIONS: In female SLE patients with ESRD due to lupus nephropathy, clinical outcomes are better after undergoing HD than after undergoing PD.

Colchicine overdose-induced acute renal failure and electrolyte imbalance.

Colchicine has been used to control gouty arthritis for long time; colchicine overdose, however, causes multiple organ dysfunction. To date, no investigation has revealed the site of kidney lesion or dysfunction. This investigation describes the case of a male with a history of gout who ingested a large amount of colchicine and developed renal, hematopoietic, gastrointestinal, muscular, electrolytic, and hepatic disorder. Glucosuria was noted during hospital days. Colchicine intoxication is shown to induce proximal tubule damage. Severe electrolytes imbalance was noted, including hypomagnesemia, hypophosphatemia, and hypocalcemia. After management, the renal function and serum electrolyte of the patient recovered on the sixth day of hospitalization.

Culture-negative peritonitis: a fifteen-year review.

Peritonitis is a serious complication in peritoneal dialysis (PD) patients; however, the clinical outcome of culture-negative peritonitis (CNP) is controversial. This retrospective study of CNP attempts to resolve this controversy. In 813 episodes of peritonitis, 202 episodes of CNP in 152 PD patients were reviewed. Two different methods of effluent culture were utilized during the study period. The incidence of CNP was lower with 50 ml centrifugation culture than 10 ml direct inoculation culture (20.7% vs. 35.7%; p < 0.05). The overall cure rate of CNP was greater than 80% of patients receiving cefamezine and gentamicin as initial therapy. Relapse within 30 days after completion of treatment happened in 9.6% of cases, and antibiotic therapy failed in 8.1% of CNP cases. In comparison with cured patients, patients with relapse or treatment failure are older (62.0 +/- 15.0 years vs. 54.3 +/- 15.3 years; p = 0.007) and have a higher rate of abdominal pain (91.4% vs. 69.3%; p = 0.007) and greater need for salvage therapy (54.3 % vs. 11.0%; p < 0.001). A history of antibiotic use or peritonitis within 30 days before onset of CNP was noted in 23.3% and 12.5% of cases, respectively, but was not associated with clinical outcome. The clinical outcome of CNP was benign in this study. Older age, abdominal pain, and need for salvage therapy were associated with an increased risk for relapse and treatment failure in CNP cases. Moreover, 50 ml centrifugation culture method was better than 10 ml direct inoculation culture in reducing the incidence of CNP.

Enhancement of epithelial sodium channel expression in renal cortical collecting ducts cells by advanced glycation end products.

BACKGROUND: The epithelial sodium channel (ENaC) is a complex, and the alphaENaC subunit has a crucial role in sodium uptake induced by aldosterone in the distal nephron. Although experimental animal models of diabetes have demonstrated up-regulation of alphaENaC expression in renal cortical collecting duct (CCD) cells, the molecular mechanism remains unclear. Advanced glycation end products (AGEs) are by-products of long-term hyperglycaemia and comprise a significant pathogenic factor in diabetic nephropathy. We hypothesize that AGEs play a role in regulating alphaENaC gene expression. METHODS: Mouse CCD cells (mpkCCDcl(4)) were cultured with AGE to determine the effects of AGE on alphaENaC expression and sodium uptake. Gene expressions of ENaC were measured by real-time PCR and sodium uptake was measured with fluorescent dye as a sodium indicator (SBFI-AM). This study analysed mitogen-activated protein kinases signalling pathways by western blotting. Cells co-transfected with plasmids of the alphaENaC promoter carrying a luciferase reporter and plasmids expressing wild-type or mutant serum- and glucocorticoid-induced kinase 1 (Sgk1) mRNA were stimulated with AGE to identify the signalling pathway. RESULTS: The AGEs, stimulated in a time- and dose-dependent manner, enhanced alphaENaC mRNA expression and sodium uptake in mpkCCDcl(4) cells. The AGEs also significantly stimulated Sgk1 mRNA and Sgk1 activity in a time- and dose-dependent manner. Co-transfected with plasmid expressing mutant Sgk1 significantly limited stimulated alphaENaC promoter-driven luciferase activity by AGEs in mpkCCDcl(4) cells. CONCLUSION: Experimental results indicate that AGEs induced alphaENaC expression and increased sodium uptake in renal CCD cells. The mechanism through which AGEs activate alphaENaC expression may be via activation of Sgk1 in mpkCCDcl(4) cells.

A comparison of sevelamer hydrochloride with calcium acetate on biomarkers of bone turnover in hemodialysis patients.

OBJECTIVE: To evaluate the influence of sevelamer hydrochloride and calcium acetate on biomarkers of bone turnover in patients with hyperphosphatemia receiving hemodialysis. METHODS: In this prospective, open-label, randomized, active-controlled study, 70 patients (38 men and 32 women) with hyperphosphatemia (serum phosphorus level >6.0 mg/dL) underwent a two-week washout period and were randomly selected to receive sevelamer hydrochloride (n = 37) or calcium acetate (n = 33) for eight weeks. Changes in serum levels of intact parathyroid hormone (iPTH), alkaline phosphatase (Alk-P), phosphorus, and calcium were measured and compared. RESULTS: After eight weeks of treatment, calcium acetate lowered iPTH levels significantly more than sevelamer hydrochloride did (-178.0 vs. -69.0 pg/mL, p = 0.0019). Levels of Alk-P were significantly elevated in patients given sevelamer hydrochloride compared with levels in those given calcium acetate treatment (24.09 vs. 7.45 U/L, p = 0.0014). Changes in serum phosphorus levels did not differ between sevelamer hydrochloride (-1.93 mg/dL) and calcium acetate (-2.5 mg/dL) at the end of the study (p = 0.0514). Changes in the calcium and phosphorous product did not significantly differ between the sevelamer-hydrochloride group (-18.06 mg2/dL2) and the calcium-acetate group (-19.05 mg2/dL2, p = 0.6764). Fifteen patients (45.5%) treated with calcium acetate had hypercalcemia (serum-adjusted calcium level >10.5 mg/dL); the rate was significantly higher than that of patients treated with sevelamer (five [13.5%] of 37, p = 0.0039). CONCLUSION: Treatment with sevelamer hydrochloride had the advantage of maintaining stable iPTH levels and elevating Alk-P levels while lowering serum phosphorus levels and calcium-phosphorous product.

Xanthogranulomatous pyelonephritis and malacoplakia of the bladder in a middle aged female.

We describe the case of a female with xanthogranulomatous pyelonephritis and malacoplakia of the bladder, presenting with recurrent urinary tract infection and renal mass. The genitourinary tract should be explored to evaluate the coexistence of these two diseases. Nephrectomy and bladder mass resection is warranted to maintain sterile urine. This case represents an unusual instance of the synchronic appearance of xanthogranulomatous pyelonephritis and malacoplakia of the bladder, implying a common pathogenesis for two related diseases from a different histological spectrum, in which the urinary obstruction serves as a promoting factor for the stepwise transformation of morphogenesis.

Candida parapsilosis peritonitis has more complications than other Candida peritonitis in peritoneal dialysis patients.

Candida parapsilosis is the most prevalent pathogen of fungal peritonitis in peritoneal dialysis (PD). The difference between C. parapsilosis peritonitis and other C. species for clinical outcomes and treatment responses to fungal peritonitis remains unclear. This retrospective study of fungal peritonitis attempts to answer that question. A total 22 patients with fungal peritonitis in 762 PD patients were enrolled in this study. The mean age of the 22 patients, 9 males and 13 females, was 54.7 +/- 12.5 years with a mean PD duration of 39.7 +/- 33.4 months. Candida species accounted for 86% (19 cases) of fungal peritonitis and 41% (9 cases) were C. parapsilosis. Thirteen (59%) patients received fluconazole as monotherapy; others received either amphotericin B alone or in combination with fluconazole. Catheters were removed for all patients. The mean duration from peritonitis onset to catheter removal was 5.8 +/- 4.1 days. Eleven (50%) patients developed severe complications, with abscess formation or persistent peritonitis after catheter removal. C. parapsilosis peritonitis had a higher complication rate than other Candida species (78% versus 20%, p = 0.012). In patients who received fluconazole as monotherapy, the rate of severe complications of C. parapsilosis peritonitis was statistically higher than those of other Candida species (100% versus 29%, p = 0.013). Because of different severity and prognosis, C. parapsilosis peritonitis in PD patients should be treated more aggressively than other Candida species.

Aristolochic acid-related nephropathy associated with the popular Chinese herb Xi Xin.

Chinese herbs nephropathy is known as a subacute interstitial nephritis attributed to aristolochic acid. This work describes the case of a 49-year-old male who displayed subacute renal failure induced by ingestion of herbal powder containing Xi Xin, which includes aristolochic acid. Since Xi Xin is a common ingredient in traditional formulae, care needs to be taken in the future to identify the aristolochic acid concentration of different components of Xi Xin. Xi Xin containing aristolochic acid should be forbidden for use in remedies in order to prevent the harmful effects of aristolochic acid.

Does hepatitis C virus affect the reactivation of hepatitis B virus following renal transplantation?

BACKGROUND: Hepatitis B virus (HBV) is endemic in Taiwan. Transplantation followed by long-term immunosuppressive medications may precipitate HBV reactivation. Interference of hepatitis C virus (HCV) with HBV gene expression and replication has been confirmed in many studies involving non-transplant populations. This study investigates the incidence of HBV reactivation following renal transplantation and compares the clinical outcome, especially the liver outcome, of patients with or without HCV co-infection. METHODS: Fifty-one of 512 renal transplant recipients were positive for hepatitis B surface antigen before surgery, and were followed for 81.6+/-7.5 (4-120) months. Seventeen of 51 patients acquired HCV before transplantation and six patients acquired HCV after renal transplantation. RESULTS: At the end of this assessment, we had 28 patients who suffered HBV reactivation and another 23 patients who suffered no HBV reactivation. Initially, we found a significant difference of HCV carriage (P<0.05) between patients with (seven out of 28 or 25%) or without (21 out of 23 or 91.3%) HBV reactivation. Further inspection showed that 21 of the 28 patients without HCV co-infection and seven of the 23 patients with HCV co-infection suffered HBV reactivation. After comparison, we found a lower incidence of HBV reactivation in patients with HCV co-infection than in patients without HCV co-infection (P<0.05). In contrast to the latter, we found that patients with HCV co-infection suffering HBV reactivation tended to have a late onset of HBV reactivation (P<0.05). Otherwise, there was no difference in hepatitis severity, in terms of peak alanine aminotransferase, total bilirubin levels and hepatitis reactivation-related death, between these two groups of patients. Finally, a multivariable analysis also revealed that HCV carriage was indeed an independent variable leading to the reduced incidence of HBV reactivation in patients with HCV co-infection. CONCLUSION: HCV might affect the reactivation of HBV by decreasing the incidence or delaying the onset of HBV reactivation in renal transplant recipients carrying both HBV and HCV.

Leptospiral membrane proteins stimulate pro-inflammatory chemokines secretion by renal tubule epithelial cells through toll-like receptor 2 and p38 mitogen activated protein kinase.

BACKGROUND: Leptospiral membrane proteins extracted from pathogenic Leptospira santarosai serovar Shermani (LMPS) stimulated pro-inflammatory chemokines production in cultured mouse proximal tubule epithelial cells (PTECs) and implicated its role in the pathogenesis of leptospira-induced tubulointerstitial nephritis. PTECs express the functional TLR2 and TLR4, which have been shown to play essential roles in innate immunity. This study investigated the roles of Toll-like receptors (TLRs) and mitogen-activated protein kinases (MAPKs) signalling pathways in the pathogenesis of leptospira-induced tubulointerstitial nephritis. METHODS: The immortalized mouse PKSV-PR late PTECs were used as the model system. The genes expression and secretion of CCL2/monocyte chemoattractant protein-1 (CCL2/MCP-1) and CXCL2/macrophage inflammatory protein-2 (CXCL2/MIP-2) were measured by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA). We investigated MAPKs signalling pathways by Western blot and their reciprocal roles by specific inhibitors. A specific TLR2 neutralizing antibody was applied to evaluate the crosstalk between TLR2 and MAPKs. RESULTS: The LMPS stimulated extracellular signal-regulated kinases (ERK1/2), c-Jun N-terminal kinases (JNKs) and p38 mitogen-activated protein kinase (p38 MAPK), initiated the nuclear transcription factor kappaB (NF-kappaB), and enhanced the secretion of CCL2/MCP-1 and CXCL2/MIP-2. The LMPS also unregulated the level of TLR2 mRNA expression in PTECs through time- and dose-dependent effects. The LMPS enhanced the secretion of CCL2/MCP-1 and CXCL8/interleukin-8 (CXCL8/IL-8) in TLR-defective human embryonic kidney (HEK) 293 cells only when transfected with a TLR2 expressing plasmid. The secretions of CCL2/MCP-1 and CXCL2/MIP-2 stimulated by LMPS were significantly reduced by incubating PTECs with SB203580, an inhibitor of p38 MAPK. Furthermore, a neutralizing anti-mouse TLR2 antibody hindered the phosphorylation of p38 and LMPS-stimulated secretion of CCL2/MCP-1 and CXCL2/MIP-2. CONCLUSION: These findings demonstrate that activation of p38 MAPK and release of chemokines by LMPS are mediated by TLR2 in renal proximal tubule cells. These results also implicate the crucial role of innate immunity in leptospira-induced tubulointerstitial nephritis.

Acute renal failure induced by a Brazilian variety of propolis.

Propolis is a resinous substance collected by honeybees and used in hive construction and maintenance. Cumulative evidence suggests that propolis may have anti-inflammatory, antibiotic, antioxidant, antihepatotoxic, and antitumor properties. In addition to topical applications, products containing propolis have been used increasingly as dietary supplements. Although reports of allergic reactions are not uncommon, propolis is reputed to be relatively nontoxic. Its systemic toxicity is rarely reported and hence may be underestimated. This is the first report of propolis-induced acute renal failure. A 59-year-old man required hemodialysis for acute renal failure. The patient had cholangiocarcinoma and had ingested propolis for 2 weeks before presentation. Renal function improved after propolis withdrawal, deteriorated again after reexposure, and then returned to a normal level after the second propolis withdrawal. This case indicates that propolis can induce acute renal failure and emphasizes the need for vigilance and care when propolis is used as a medicine or dietary supplement.