Non-meningeal, non-pulmonary cryptococcosis with limited posterior uveitis in a kidney organ transplant recipient with antibody-mediated rejection: a case report.

BACKGROUND: Cryptococcosis is one of the most frequent fungal eye infections in patients with immunosuppression. Currently, treatment approaches for non-meningeal, non-pulmonary cryptococcosis are based on those used for cryptococcal meningitis or pneumonia. CASE PRESENTATION: We present a rare case of non-meningeal, non-pulmonary cryptococcosis with clinical manifestations limited to one eye of a cadaveric kidney transplant recipient with chronic-active antibody-mediated rejection. Typical manifestations, diagnosis, and treatments, including antifungal therapies, adjunctive therapies, and immunosuppression reduction, are discussed. After timely diagnosis and treatment, her visual acuity recovered to baseline without recurrence or sequelae of cryptococcosis. CONCLUSIONS: Clinicians should be aware of rare presentations of fungal infections, especially when a kidney transplant recipient with rejection has been treated with intensive immunosuppressants. Early diagnosis with individualized therapies may have a favorable prognosis.

Discovery of Novel Protein Biomarkers in Urine for Diagnosis of Urothelial Cancer Using iTRAQ Proteomics.

Urothelial carcinoma (UC) is the ninth most prevalent malignancy worldwide. Noninvasive and efficient biomarkers with high accuracy are imperative for the surveillance and diagnosis of UC. CKD patients were enrolled as a control group in this study for the discovery of highly specific urinary protein markers of UC. An iTRAQ-labeled quantitative proteomic approach was used to discover novel potential markers. These markers were further validated with 501 samples by ELISA assay, and their diagnostic accuracies were compared to those of other reported UC markers. BRDT, CYBP, GARS, and HDGF were identified as novel urinary UC biomarkers with a high discrimination ability in a population comprising CKD and healthy subjects. The diagnostic values of the four novel UC markers were better than that of a panel of well-known or FDA-approved urinary protein markers CYFR21.1, Midkine, and NUMA1. Three of our discovered markers (BRDT, HDGF, GARS) and one well-known marker (CYFR21.1) were finally selected and combined as a marker panel having AUC values of 0.962 (95% CI, 0.94-0.98) and 0.860 (95% CI, 0.83-0.89) for the discrimination between UC and normal groups and UC and control (healthy + CKD) groups, respectively.

Everolimus-facilitated calcineurin inhibitor reduction in Asian de novo kidney transplant recipients: 2-year results from the subgroup analysis of the TRANSFORM study.

OBJECTIVE: We analyzed the efficacy and safety of an everolimus with reduced-exposure calcineurin inhibitor (EVR+rCNI) versus mycophenolic acid with standard-exposure CNI (MPA+sCNI) regimen in Asian patients from the TRANSFORM study. METHODS: In this 24-month, open-label study, de novo kidney transplant recipients (KTxRs) were randomized (1:1) to receive EVR+rCNI or MPA+sCNI, along with induction therapy and corticosteroids. RESULTS: Of the 2037 patients randomized in the TRANSFORM study, 293 were Asian (EVR+rCNI, N = 136; MPA+sCNI, N = 157). At month 24, EVR+rCNI was noninferior to MPA+sCNI for the binary endpoint of estimated glomerular filtration rate (eGFR) < 50 ml/min/1.73 m2 or treated biopsy-proven acute rejection (27.0% vs. 29.2%, P = .011 for a noninferiority margin of 10%). Graft loss and death were reported for one patient each in both arms. Mean eGFR was higher in EVR+rCNI versus MPA+sCNI (72.2 vs. 66.3 ml/min/1.73 m2 , P = .0414) even after adjusting for donor type and donor age (64.3 vs. 59.3 ml/min/1.73 m2 , P = .0582). Overall incidence of adverse events was comparable. BK virus (4.4% vs. 12.1%) and cytomegalovirus (4.4% vs. 13.4%) infections were significantly lower in the EVR+rCNI arm. CONCLUSION: This subgroup analysis in Asian de novo KTxRs demonstrated that the EVR+rCNI versus MPA+sCNI regimen provides comparable antirejection efficacy, better renal function, and reduced viral infections (NCT01950819).

Treatment of chronic active antibody-mediated rejection in renal transplant recipients - a single center retrospective study.

BACKGROUND: Chronic active antibody-mediated rejection is a major etiology of graft loss in renal transplant recipients. However, there is no consensus on the optimal treatment strategies. METHODS: Computerized records from Taichung Veterans General Hospital were collected to identify renal transplant biopsies performed in the past 7 years with a diagnosis of chronic active antibody-mediated rejection. The patients were divided into two groups according to treatment strategy: Group 1 received aggressive treatment (double filtration plasmapheresis and one of the followings: rituximab, intravenous immunoglobulin, antithymogycte globulin, bortezomib, or methylprednisolone pulse therapy); and group 2 received supportive treatment. RESULTS: From February 2009 to December 2017, a total of 82 patients with biopsy-proven chronic antibody mediated rejection were identified. Kaplan-Meier analysis of death-censored graft survival showed a worse survival in group 2 (P = 0.015 by log-rank test). Adverse event-free survival was lower in group 1, whereas patient survival was not significantly different. Proteinuria and supportive treatment were independent risk factors for graft loss in multivariate analysis. CONCLUSIONS: Aggressive treatment was associated with better graft outcome. However, higher incidence of adverse events merit personalized treatment, especially for those with higher risk of infection. Appropriate prophylactic antibiotics are recommended for patients undergoing aggressive treatment.

Distribution of glomerular diseases in Taiwan: preliminary report of National Renal Biopsy Registry-publication on behalf of Taiwan Society of Nephrology.

BACKGROUND: Despite the development of biomarkers and noninvasive imaging tools, biopsy remains the only method for correctly diagnosing patients with unexplained hematuria, proteinuria and renal failure. Renal biopsy has been performed for several decades in Taiwan; however, a national data registry is still lacking until 2013. METHODS: The Renal Biopsy Registry Committee was established within the Taiwan Society of Nephrology in January 2013. A biopsy registry format, including basic demographic data, baseline clinical features, laboratory data, and clinical and pathological diagnosis was developed. Approval from the local institutional review board was obtained in each participating medical center. RESULTS: From January 2014 to September 2016, 1445 renal biopsies were identified from 17 medical centers. 53.8% cases were reported in men. After excluding renal transplantation, renal biopsies were commonly performed in patients with primary glomerulonephritis (48.1%), secondary glomerulonephritis (36.2%), followed by tubulointerstitial diseases (12.3%) and vascular nephropathy (3.4%). Among primary glomerulonephritis, IgA nephropathy (26.0%), focal segmental glomerulosclerosis (21.6%), and membranous nephropathy (20.6%) were most frequently diagnosed. Diabetic nephropathy (22.4%) and lupus nephritis (21.8%) were the most common among secondary glomerulonephritis. Patients with minimal change disease and membranous nephropathy had heavier proteinuria than those with focal segmental glomerulosclerosis and IgA nephropathy (P < 0.001). Patients with minimal change disease had higher serum IgM and IgE levels. The most common cause of nephrotic syndrome in primary glomerular disease was membranous nephropathy (28.8%), followed by minimal change disease (28.2%). IgA nephropathy was the leading cause of chronic nephritic syndrome, acute nephritic syndrome, and persistent hematuria. The incidence of primary glomerulonephritis was approximately 2.19 in 100,000/year. CONCLUSIONS: This is the first report of the National Renal Biopsy Registry in Taiwan. IgA nephropathy is the most common primary glomerulonephritis, while membranous nephropathy is the most common cause of nephrotic syndrome. Primary glomerulonephritis distribution in Taiwan is slightly different from that in other Asian countries.

Risk of cancer in patients with polycystic kidney disease: a propensity-score matched analysis of a nationwide, population-based cohort study.

BACKGROUND: Data for the risk of any solid cancer in patients with polycystic kidney disease are scarce. Therefore, we did a nationwide cohort study in Taiwan to establish the risk of cancer in patients with polycystic kidney disease without either chronic kidney disease or end-stage renal disease. METHODS: From inpatient claims of the Taiwan National Health Insurance Research Database, we included patients aged 20 years and older and diagnosed with polycystic kidney disease between January, 1998 and December, 2010, in the polycystic kidney disease cohort. Patients with a history of cancer, a history of chronic kidney disease or of end-stage renal disease (recorded from the Registry of Catastrophic Illness Patient Database) were excluded. For each patient with polycystic kidney disease, one patient aged older than 20 years with no history of polycystic kidney disease or cancer was randomly selected from the National Health Insurance Research Database, matched 1:1 on the basis of the propensity score calculated by logistic regression, and was included in the control non-polycystic kidney disease cohort. The follow-up period for each patient was estimated from the index date to the date of diagnosis of cancer, or the patient was censored due to withdrawal from the insurance programme (eg, death, immigration, or imprisonment) or on Dec 31, 2011. The primary outcome of interest was a diagnosis of cancer during a 14-year follow-up period. The risk of cancer was represented as a hazard ratio (HR) calculated in Cox proportional hazard regression models. FINDINGS: 4346 patients with polycystic kidney disease and 4346 without were enrolled in the study. The median follow-up period in the polycystic kidney disease cohort was 3·72 years (IQR 1·25-7·31) and in the non-polycystic kidney disease cohort was 4·96 years (2·29-8·38). The overall incidence of cancer was higher in the polycystic kidney disease cohort than in the control cohort (20·1 [95% CI 18·3-21·9] per 1000 person-years vs 10·9 [10·1-11·8] per 1000 person-years; crude hazard ratio (HR) 1·77 [95% CI 1·52-2·07]; HR adjusted for age, sex, frequency of medical visits, and comorbidities was 1·83 [1·57-2·15]). The specific risks (adjusted subhazard ratios) were significantly higher in the polycystic kidney disease cohort than that in the non-polycystic kidney disease cohort for liver cancer (1·49 [95% CI 1·04-2·13]; p=0·030), colon cancer (1·63 [1·15-2·30]; p=0·006), and kidney cancer (2·45 [1·29-4·65]; p=0·006). INTERPRETATION: To our knowledge, this is the first report of the association of polycystic kidney disease without end-stage renal disease with the risk of liver, colon, and kidney cancer. Health-care professionals should be aware of this risk, when treating patients with polycystic kidney disease. FUNDING: Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence, Academia Sinica Taiwan Biobank, Stroke Biosignature Project, NRPB Stroke Clinical Trial Consortium, Tseng-Lien Lin Foundation, Taiwan Brain Disease Foundation, Katsuzo and Kiyo Aoshima Memorial Funds, China Medical University Hospital, and Taiwan Ministry of Education.

Long-Term Follow-Up of a Homozygous Familial Hypercholesterolemic Patient Receiving Regular Double Filtration Plasmapheresis - Case Report and Literature Review.

Homozygous familial hypercholesterolemia (HoFH) is a very rare condition (1 case per 1 million people) with a dismal outcome due to inevitable coronary artery disease that occurs when left untreated. Lipoprotein apheresis (LA), previously known as low-density lipoprotein (LDL) apheresis, is very effective in reducing LDL-cholesterol (LDL-C) if HoFH is refractory to aggressive drug therapy and diet control. In this study, we report a case with HoFH, who presented with xanthomata over the 4 limbs when she was 3 years old. When she was 11 years old, she began treatment with semi-selective LA with double filtration plasmapheresis (DFPP) once per week because HoFH was refractory to high-dose statin and diet control. LDL-C was reduced from 8.2 ± 0.9 to 2.69 ± 0.75 mmol/l (reduction rate = 67.3 ± 6.1%). The xanthomata over the 4 limbs were nearly completely resolved after 2 years of DFPP. Two years later, after the initiation of DFPP, we performed coronary angiography and echocardiography for regular checkup in the absence of chest pain, and the result was negative. To date (11 years after initiation of DFPP), she has not complained of any chest pain, shown intolerance to exercise, or exhibited ST-T change on electrocardiography. At the age of 20, multidetector computed tomography showed no significant stenosis over the coronary arteries. At the most recent follow-up visit, she was found to have good heart function and no xanthomata. LA is effective in the treatment of HoFH when drug therapy and diet control fail. With this treatment, pre-existing xanthomata can regress and coronary artery disease can be prevented.

Successful treatment with sirolimus for an angiomyolipoma mimicking renal cell carcinoma in a transplanted kidney.

Angiomyolipoma (AML) is a benign mesenchymal tumor composed of blood vessels, smooth muscle, and mature adipose tissue. AMLs in the kidney allografts are rare. We report a case of AML that was incidentally found 1 year after transplantation. Abdominal computed tomography showed a 4-cm renal tumor with contrast enhancement and an early washout pattern, resembling a renal cell carcinoma. Tumor biopsy proved a lipid-poor AML. Tumor diameter decreased to 2.4 cm after 6 months of treatment with sirolimus. Sirolimus not only reduces tumor size, but also benefits a transplant patient who needs immunosuppression.

Pneumococcal pneumonia infection is associated with end-stage renal disease in adult hospitalized patients.

Pneumococcal disease leads to renal complications ranging from persistent proteinuria to end-stage renal disease (ESRD) in pediatric patients. However, long-term renal effects after pneumococcal pneumonia infection in adult patients remains largely unknown. To evaluate this we conducted a population-based retrospective cohort study consisting of 18,733 adult patients at the time of pneumococcal pneumonia diagnosis, using claims data from Taiwan's National Health Insurance Research Database (NHIRD) with a comparison cohort of 73,409 age- and gender-matched patients without pneumococcal pneumonia. The overall incidence rate ratio of ESRD was 23% higher in those with pneumococcal pneumonia than in those without pneumococcal pneumonia (5.26 vs. 3.10 per 1000 person-years), with an adjusted hazard ratio of 1.14 (95% confidence interval 1.01-1.29). In addition, the risk of developing ESRD was associated with covariates including age, gender, chronic kidney disease, diabetes mellitus, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, and heart failure. The ESRD cumulative incidence curve showed a considerably higher risk of ESRD in those with pneumococcal pneumonia than in those without pneumococcal pneumonia (significant by log-rank test). Thus, pneumococcal pneumonia may be associated with an increased risk of ESRD in adult patients. A long-term follow-up of renal function is recommended for adult hospitalized patients with pneumococcal pneumonia infection.

Expression of hypoxia-inducible factor-1α (HIF-1α) in infiltrating inflammatory cells is associated with chronic allograft dysfunction and predicts long-term graft survival.

BACKGROUND: In chronic kidney failure, a hypoxic state, infiltrating inflammatory cells play a crucial role in the progression to end-stage renal disease. No studies have evaluated the influence of hypoxia and infiltrating inflammatory cells on chronic allograft dysfunction. METHODS: Renal transplant recipients who underwent renal allograft biopsy with interstitial fibrosis/tubular atrophy (IF/TA) were enrolled and renal allograft tissue sections were processed for immunohistochemical staining including hypoxia-inducible factor-1α (HIF-1α), nitrotyrosine, α-smooth muscle actin and e-cadherin. Patients with total renal tissue HIF score ≥1 were defined as positive for HIF-1α. To assess the phenotype of the infiltrating cells, dual staining of HIF-1α with CD45, CD68 and CD3 was performed. The correlation between HIF-1α score and Banff's score was analysed. Clinical parameters including renal survival among patients with or without an expression of HIF-1α were compared. RESULTS: Out of 55 patients enrolled, 23 patients (41.8%) had an HIF-1α score ≥1 (Group B). Compared with Group A (total renal HIF score <1), Group B had a significantly higher Banff score of interstitial infiltrates (i) (P = 0.029), vascular fibrous intimal thickening (cv) (P = 0.007) and arteriolar hyaline thickening (ah) (P = 0.026). Clinically, patients with an HIF-1α score were associated with a poor graft survival. Significantly inferior allograft survival was noted in Group B. HIF scores had an adjusted hazard ratio of 3.25 (95% confidence inteval: 1.71-6.16, P = 0.0003) in allograft failure. CONCLUSIONS: We first demonstrated the expression of HIF-1α protein among infiltrating inflammatory cells in areas with IF/TA in patients with chronic allograft dysfunction.

A higher glomerular filtration rate predicts low risk of developing chronic kidney disease in living kidney donors.

BACKGROUND: The risk of developing chronic kidney disease (CKD) among living kidney donors (LKDs) is seldom included in evaluations of patients' outcomes. Potential risk factors and new criteria for estimating the glomerular filtration rate (eGFR) indexed for body surface area (BSA) were investigated with a view to prevent the development of CKD in LKDs. METHODS: We conducted a retrospective study of LKDs from May 1983 to March 2011. The Mann-Whitney U test and χ(2) test were used to analyze the male versus female groups. Survival analysis was plotted as CKD-free survival and analyzed separately by different eGFR index classifications. The Cox regression model was used to identify potential risk factors for development of CKD. RESULTS: A total of 105 LKDs with a mean age of 46.3 ± 12.5 years had a mean eGFR indexed for BSA of 88.9 ± 21.5 ml/min per 1.73 m(2). After a mean duration of 5.4 ± 4.9 years' follow-up, eGFR dropped to 61.4 ± 16.4 ml/min per 1.73 m(2) (p = 0.002). Median CKD-free survival was only 5.7 years. The difference between eGFR ≥ 80 ml/min per 1.73 m(2) and <80 ml/min per 1.73 m(2) was not statistically significant (p = 0.980). Multivariate Cox regression analysis showed that higher eGFR at donation (HR = 0.952, p = 0.0199) could be a protective factor. The receiver operating characteristic (ROC) curve for initial eGFR with best sensitivity of 52.78 % and specificity of 81.40 % was obtained with a cutoff value of 90.2 ml/min per 1.73 m(2) for preoperative eGFR. An eGFR of 90 ml/min per 1.73 m(2) yielded a significant survival curve (p = 0.0199) after 21 years of follow-up. Further classifications of eGFR >90 ml/min per 1.73 m(2) into 90-99 ml/min per 1.73 m(2), 100-109 ml/min per 1.73 m(2), and ≥110 ml/min per 1.73 m(2) were examined, but this survival curve was not statistically significant (p = 0.1247). CONCLUSIONS: Living kidney donors will develop CKD after a long duration of follow-up if there is insufficiently high eGFR at donation. An eGFR above 90 ml/min per 1.73 m(2) before donation is the only factor that predicts prevention of CKD. Larger studies with longer duration of follow-up are necessary to clarify the clinical outcome of this postoperative CKD group, especially for patients with eGFR between 80 and 90 ml/min per 1.73 m(2).

Effect of different hemodialyzers on serum levels of interleukin-6, interleukin-10 and interleukin-18.

BACKGROUND: The blood and membrane contact during dialysis may elicit an immune reaction. The current study looked at the impact of different dialyzers on blood levels of cytokines. METHODS: During the first month, randomly selected patients were treated with one dialyzer (PF-170H) and then crossed over to another dialyzer (FLX-18GW) during the next month. Pre- and postdialysis blood samples were assayed for interleukin (IL)-6, IL-10 and IL-18. RESULTS: A significant drop of postdialysis systolic blood pressure (pre vs. post 156.4 ± 31.8 vs. 143.1 ± 24.8 mm Hg, p = 0.014) and diastolic pressure (80.7 ± 12.7 vs. 73.4 ± 10.9 mm Hg, p = 0.002) were found when patients were dialyzed with PF-170H. A significant increase of postdialysis IL-18 levels was found in both groups (pre vs. post 605.5 ± 278.6 vs. 690.6 ± 315.3 pg/ml, p = 0.016, for PF-170H and 556.4 ± 231.0 vs. 647.3 ± 282.6 pg/ml, p = 0.067, for FLX-18GW). There was a positive correlation between IL-6 and IL-10 levels (p < 0.0001). CONCLUSION: We demonstrated a significant increase of postdialysis serum IL-18 level when either dialyzer was used. There is a strong correlation between serum levels of IL-6 and IL-10.

Clinical outcome of elderly peritoneal dialysis patients with assisted care in a single medical centre: a 25 year experience.

AIM: Peritoneal dialysis (PD) is an alternative treatment for elderly patients with end-stage renal disease (ESRD). In Taiwan, non-professional personnel are employed to provide assisted care for elderly patients. Whether assisted care is appropriate for elderly patients is unknown. The aim of this paper is to evaluate the outcomes of assisted care in a single centre. METHODS: This is a retrospective cohort study in a single medical centre. The outcomes were derived from the assessment of patient survival, technique survival and peritonitis incidence between self-care patients and assisted-care patients. RESULTS: From 1984 to 2010, there were 138 elderly PD patients at Taichung Veterans General Hospital, of which 70% were assisted-care patients and 30% self-care patients. The mean duration of PD survival was 49.2 months in self-care patients, which was significantly longer than the 17.0 months of assisted-care patients (P < 0.05). Using the multivariate Cox proportion regression model to adjust for risk factors, it was found that self-care patients had a lower risk in both patient survival (Hazard Ratio 0.15; 95% confidence interval (CI) 0.2-0.94, P < 0.05) and technique survival (Hazard ratio; 0.11, 95% CI 0.1-0.9, P < 0.05). Fluid overloading was the major cause of technique failure in assisted-care patients. Type of assistance was not a risk factor for PD-related peritonitis. CONCLUSION: Our elderly assisted care had patients had a poorer survival and technique survival rates than those of the self-care patients. We argue that this is because early recognition of medical deterioration and early medical intervention are necessary for a better outcome for elderly PD patients.

The impact of body weight management in chronic kidney disease patients with obesity.

OBJECTIVE: Chronic kidney disease (CKD) and obesity are important public health concerns. Because obesity may initiate and/or accelerate kidney damage, weight control may benefit CKD patients. DESIGN AND METHODS: We examined the influence of dietary management and physical exercise in 38 obese CKD patients with or without target reduction of body weight 3% or more from baseline. RESULTS: After a 2-month lifestyle intervention program, those with target body weight control had significant improvement of blood pressure control, as well as reduced lipid profiles, serum creatinine level (1.1 ± 0.3 vs. 0.8 ± 0.3; P < .001), estimated glomerular filtration rate (75.9 ± 21.2 vs. 104.9 ± 38.1; P < .001), and proteinuria (76.3% vs. 50.0%; P = .02). They had greater improvement in cardiorespiratory endurance in an 800-m running test (375.1 ± 64.7 vs. 327.1 ± 84.0 seconds; P = .001), better abdominal muscle strength and endurance in a timed sit-up test (13.6 ± 9.1 vs. 19.9 ± 9.2 number/minute; P = .005), and greater flexibility in a sit-and-reach test (18.8 ± 10.9 vs. 27.8 ± 10.9 cm; P < .001) comparing baseline and postintervention values. CONCLUSIONS: A combination of dietary management and exercise were associated with improvements in health-related physical fitness, cardiovascular risk factors (blood pressure and lipid control), and renal profiles in obese CKD patients. Supportive individualized programs for lifestyle change could exert beneficial effects, but long-term research with a larger patient population is needed to elucidate the optimal effective combination of dietary management and exercise.

In-hospital mortality risk estimation in patients with acute nonvariceal upper gastrointestinal bleeding undergoing hemodialysis: a retrospective cohort study.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a major cause of clinical bleeding among patients with end-stage renal disease (ESRD). This study aimed to investigate the association between mortality and UGIB in patients with uremia. METHODS: From 2004 to 2010, a tertiary hospital-based retrospective cohort comprising 322 patients undergoing hemodialysis was investigated. All the patients were diagnosed with UGIB according to the International Classification of Diseases, 9th Revision (ICD-9) that included peptic ulcer bleeding, duodenal ulcer bleeding, and other symptoms. UGIB was required to be one of the first three discharge diagnoses. Rehospitalization within 3 days after discharge was regarded as the same course. Exclusion criteria were age <20 years, previous gastric resection or vagotomy, esophageal and gastric variceal bleeding, or gastric cancer within the first 2 years of the index hospitalization. RESULTS: The all-cause in-hospital mortality rate of patients with UGIB undergoing hemodialysis was high, with the first-month mortality rate of 13.7%, sixth-month mortality rate of 26.7%, and first-year mortality rate of 27.0%. Using Cox regression models, we found that the high mortality rate of the UGIB group was significantly correlated with older age [adjusted hazard ratio (HR) = 1.02, 95% confidence interval (CI) = 1.01-1.04], female sex (adjusted HR = 1.62, 95% CI = 1.05-2.51), infection during hospitalization (adjusted HR = 1.85, 95% CI = 1.13-3.03), single episodic UGIB (adjusted HR = 2.00, 95% CI = 1.08-3.70), abnormal white blood cell (WBC) count (adjusted HR = 1.59, 95% CI = 1.03-2.45), and albumin level ≤3 g/dL (adjusted HR = 2.67, 95% CI = 1.51-4.72). CONCLUSION: In conclusion, patients with ESRD who are admitted with primary UGIB have a profoundly increased risk of all-cause in-hospital mortality during the follow-up period.

Recombined sequences between the non-coding control regions of JC and BK viruses found in the urine of a renal transplantation patient.

Kidney cells are the common host for JC virus (JCV) and BK virus (BKV). Reactivation of JCV and/or BKV in patients after organ transplantation, such as renal transplantation, may cause hemorrhagic cystitis and polyomavirus-associated nephropathy. Furthermore, JCV and BKV may be shed in the urine after reactivation in the kidney. Rearranged as well as archetypal non-coding control regions (NCCRs) of JCV and BKV have been frequently identified in human samples. In this study, three JC/BK recombined NCCR sequences were identified in the urine of a patient who had undergone renal transplantation. They were designated as JC-BK hybrids 1, 2, and 3. The three JC/BK recombinant NCCRs contain up-stream JCV as well as down-stream BKV sequences. Deletions of both JCV and BKV sequences were found in these recombined NCCRs. Recombination of DNA sequences between JCV and BKV may occur during co-infection due to the relatively high homology of the two viral genomes.

Cyclosporine-induced tubular vacuolization: the role of Bip/Grp78.

Cyclosporine (CsA) nephrotoxicity shows characteristic tubular vacuolization (TV) which is endoplasmic reticulum (ER) in origin. However, the cellular events of CsA-induced TV and CsA-induced ER remained unclear. The aim of the present study was to study the nature of TV and the correlation to ER stress. Using proximal tubule NRK-52E cells in vitro and an in vivo model of acute CsA nephrotoxicity, we confirmed that CsA-induced TV was ER in origin and potentially reversible. Our results showed that CsA-induced ER stress and involved ER integrated stress response-related proteins (Bip/Grp78, ATF6, IRE1 and CHOP) but not cytoplasmic ER stress-related chaperones (HSP70, HSP40, HSP27, HSP90 and HSP60). Importantly, Bip/Grp78 was overexpressed on the membrane of TV and suppression of Bip/Grp78 blocked TV formation. In addition, suppression of Bip/Grp78-enhanced CsA-induced cell death and CsA-induced TV formation and Bip/Grp78 overexpression had a characteristic striped pattern in the tubulointerstitium. In summary, we demonstrate that CsA-induced TV was a potentially reversible process in which Bip/Grp78 overexpression is essential for TV formation. It is possible that Bip/Grp78 expression and TV formation may be involved in cellular defense mechanism against CsA nephrotoxicity.

Impact of posttransplantation glomerulonephritis on long-term outcome of kidney transplants: single-center 20-year experience.

BACKGROUND: Successful renal transplantation has been performed in patients with end-stage renal disease and has been routine in patients with end-stage renal failure for more than two decades. Despite advances in the use of immunosuppressants, there has been only modest improvement in long-term allograft survival. Accumulating data have demonstrated that chronic rejection and recurrent glomerulonephritis are major causes of long-term allograft loss. However, data regarding the long-term impact of posttransplantation glomerulonephritis (PTGN) on ethnic Chinese populations are still unavailable. METHODS: From 1984 to 2010, a total of 268 patients who underwent renal allograft biopsies were reviewed retrospectively. Renal outcomes were compared by Kaplan-Meier analysis, and risk factors for renal survival and all-cause mortality were analyzed using the Cox proportional hazards model. RESULTS: In all, 85 patients (31.7%) had PTGN, and the mean time of disease onset was 5.32±5.18 years after transplantation. Among the 85 PTGN cases, 33 (39%) were immunoglobulin A (IgA) nephropathy, 24 (28%) were focal segmental glomerulosclerosis, and 8 (9.4%) were membranous GN. Significant risk was associated with posttransplant IgA GN in hepatitis B virus carriers (odds ratio 5.371, 95% confidence interval 1.68, 17.19; p=0.0064). A total of 45 PTGN patients had allograft loss, of whom 49% had IgA nephropathy. Patients with PTGN had inferior allograft survival rates compared to those with other pathologic findings (p<0.0003). CONCLUSIONS: Taken together, our results indicate that PTGN had a strong negative impact on long-term kidney graft survival. Posttransplant IgA nephropathy is a leading cause of allograft loss in Chinese kidney transplant patients with PTGN.

Higher serum levels of soluble intracellular cell adhesion molecule-1 and soluble vascular cell adhesion molecule predict peripheral artery disease in haemodialysis patients.

AIM: Serum levels of soluble intracellular cell adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM) and monocyte chemotactic protein 1 (MCP-1), are elevated in patients with peripheral artery disease (PAD). However, the levels of these cell adhesion molecules in patients undergoing haemodialysis (HD) are unclear. METHOD: A total of 112 HD patients were included and PAD was diagnosed using the ankle-brachial index and Doppler ultrasound. Serum levels of sICAM-1, sVCAM-1 and MCP-1 were assayed using enzyme linked immunosorbent assay. RESULTS: Out of 106 HD patients, 31 (27.7%) were diagnosed with PAD. After adjusting for risk factors, higher serum levels of sVCAM-1 and sICAM-1 were associated with PAD in HD patients, with an odds ratio of 5.3 (95% CI 3.3-65.5) and 2.7 (95% CI 1.2-21.8) respectively. Using sVCAM-1 and sICAM-1 for diagnosis of PAD in HD patients, sVCAM-1 had a sensitivity of 72.4% and specificity of 62.3% for sVCAM-1 and sICAM-1 had a sensitivity of 89.3% and a specificity of 40%. MCP-1 was not associated with PAD in HD patients. In addition, the fistula of HD patients with PAD had a lower A-V access flow. CONCLUSION: sVCAM-1 and sICAM-1 was associated with higher risk of PAD in HD patients. Moreover, HD patients with PAD had a lower blood flow and lower A-V access flow. Our results showed that sVCAM-1 and sICAM-1 may be used as screening markers for PAD in HD patients.

Interleukin-2 receptor antagonist does not decrease biopsy-proven acute rejection among adult Chinese kidney transplant recipients.

Induction therapy with interleukin-2 receptor antagonist (IL2RA) is widely used for renal transplant recipients and this study aimed to examine the impact of IL2RA among Chinese renal transplant recipients. Two hundred and thirty-eight Chinese renal transplant recipients aged 18-65 years at the Taichung Veterans General Hospital from January 2004 to July 2009 were retrospectively studied to assess the influence of IL2RA on biopsy-proven acute rejection (BPAR) within 1 year. Secondary outcomes included acute rejection rate in the first 3 months, delayed graft function, post-transplant diabetes mellitus, and malignancy. Cox proportional hazard analysis was used for multivariate analysis. Of all the patients, 116 received IL2RA (basiliximab, n = 44; daclizumab, n = 72) and 122 had no induction therapy. The mean follow-up duration was 43.3 months (range, 1-79 months). Overall, 227 (95.4%) patients completed the 12-month follow-up period with a functioning graft. No difference of BPAR was observed between the two groups and the secondary outcomes were also similar. After adjusting potential covariates with Cox regression, IL2RA use still provided no benefit on BPAR. In conclusion, there is no benefit of IL2RA in decreasing BPAR was observed in our study. Routine use of IL2RA for adult Chinese kidney transplant recipients may not be as effective as we thought before. More research is still needed to elucidate the effect of IL2RA among Chinese kidney transplant recipients.