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.

Intravoxel Incoherent Motion-Diffusion-Weighted MRI for Investigation of Delayed Graft Function Immediately after Kidney Transplantation.

Purpose: A non-invasive way of assessing post-transplant renal graft function has been needed. This study aimed to assess the micro-structural and micro-functional status of graft kidneys by using intravoxel incoherent motion- (IVIM-) diffusion-weighted imaging (DWI) to investigate delayed graft function (DGF) immediately after transplantation. Method: A prospective study was conducted on 37 patients, 14 with early graft function (EGF) and 23 with DGF (9 with complication, 14 without) who underwent IVIM-DWI, most often within 1-7 days after kidney transplantation. A total of 37 cases were collected and all the participants have been well-informed and signed their consents. In addition, the study conducted in this paper was approved by the Ethics Committee of Clinical Research, Taichung Veterans General Hospital (IRB number: CE14065). Using biexponential analysis of slow diffusion coefficient (D slow), fast diffusion coefficient (D fast), and perfusion fraction was performed. The apparent diffusion coefficient (ADC) was calculated by use of a monoexponential model. All parameters were measured from three different regions-of-interest (ROI), covering the entire renal parenchyma, cortex, and medulla. Results: D slow, perfusion fraction, and ADC were significantly higher in patients with EGF than DGF (all p values values <0.001). Especially, ADC measured from ROI covering the entire kidney parenchyma had the best cut-off value (1.93µm2/msec) with the highest area under the receiver operating characteristic curve (AUC 0.943) in differentiating EGF from DGF. For analysis of pair-wise differences, only the perfusion fraction values, measured from the ROI covering the renal cortex, were significantly higher in 14 DGF patients with no complications than in the 9 DGF patients with complications, with the best cut-off value of 12.3% and the AUC of 0.844. Conclusion: Noninvasive IVIM-DWI reliably differentiates DGF from EGF after kidney transplantation, and it may aid in identifying posttransplant complications and indications for renal biopsy.

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).

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.

Urine phthalate metabolites are associated with urothelial cancer in chronic kidney disease patients.

BACKGROUND: Di(2-ethylhexyl) phthalate (DEHP) is one of the most widely used phthalates and is associated with breast cancer. Ths association between DEHP and other types of cancer is not clear. DEHP may increase matrix metalloproteinase-9 that is critical for the development of urothelial cancer (UC). We examined the association between urinary phthalate metabolites and UC. CKD patients were selected as a control group because CKD patients are more at risk of UC than the general population. METHODS: In this cross-sectional study, we measured seven urinary phthalate metabolites that are abundant and can be measured using HPLC-MS/MS in Taiwan CKD patients between Jul 2013 and Dec 2015. MiBP (a urinary metabolite of Dibutyl phthalates[DBP]) and MEHHP (a urinary metabolite of DEHP) were described because they are the most abundant phthalate metabolites. The association of phthalate (log-transformed) and UC were analyzed using logistic regression with adjustments for age, gender, renal function, use of traditional Chinese medicine, toxins (dye, organic solvent), and non-steroidal anti-inflammatory drugs. RESULTS: We measured the urinary MEHHP and MiBP of 496 patients (224 UC and 272 CKD patients). The urinary MEHHP was associated with UC but MiBP was not. Medical history including the use of non-steroid anti-inflammatory drugs, exposure to environmental toxins (dye, paint, and organic solvent), and the use of traditional Chinese medicine was independently associated with UC. The adjusted odds ratio of MEHHP was 1.42 (95% confidence interval: 1.21-1.68). CONCLUSION: Phthalate urinary metabolite(MEHHP) may be associated with UC in CKD patients and the association is independent of well-known risk factors of UC.

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.

Effects of Sustained-Release Beraprost in Patients With Primary Glomerular Disease or Nephrosclerosis: CASSIOPEIR Study Results.

TRK-100STP, a sustained-release preparation of the orally active prostacyclin analogue beraprost sodium, targets renal hypoxia. This study aimed to show the superiority of TRK-100STP over placebos in patients with chronic kidney disease (with either primary glomerular disease or nephrosclerosis) to determine the recommended dose. CASSIOPEIR (Chronic Renal Failure Asian Study with Oral PGI2 Derivative for Evaluating Improvement of Renal Function) was a randomized, double-blind, placebo-controlled study conducted at 160 sites in seven Asia-Pacific countries and regions. Eligible patients (n = 892) were randomized to TRK-100STP 120, 240 µg, or placebo for a treatment period of up to 4 years. The primary efficacy endpoint was time to first occurrence of a renal composite: doubling of serum creatinine or occurrence of end-stage renal disease. No significant differences were observed in composite endpoints between TRK-100STP and placebo (P = 0.5674). Hazard ratios (95% CI) in the TRK-100STP 120 and 240 µg vs. placebo groups were 0.98 (0.78, 1.22) and 0.91 (0.72, 1.14), respectively. The overall incidence of adverse events and adverse drug reactions was comparable between treatment arms.

Development and validation of a nomogram for urothelial cancer in patients with chronic kidney disease.

Urothelial cancer (UC) is a common kidney cancer in Taiwan and patients with chronic kidney disease (CKD) are more at risk for UC than the general population. The diagnostic value of urine analysis and urine cytology is limited, especially in CKD patients. The aim of the study is to develop a nomogram to predict the risk of UC in CKD patients. We enrolled 169 UC patients and 1383 CKD patients from 9 hospitals in Taiwan between 2012 and 2015. CA125, HE4, clinical characteristics, and medical history were analyzed using multivariable logistic regression for its association with UC. A nomogram was developed to predict the risk of UC and was validated using Bootstrap. CA125 was associated with UC in CKD patients (OR: 5.91, 95% CI: 3.24-10.77) but HE4 was not (OR: 1.29, 95% CI: 0.67-2.35). A nomogram based on patients' age, estimated glomerular filtration rate, CA125 (log transformed), smoking, exposure of environmental toxin, use of nonsteroid anti-inflammatory drugs, and use of traditional Chinese medicine was conducted. The AUC of the nomogram was 0.90 (95% CI: 0.86-0.92, p < 0.01). Serum CA125 may identify UC patients from CKD patients but has limited diagnostic value due to low sensitivity. The diagnostic value of serum CA125 level can be improved by the combination with clinical characteristics including age, renal function, and medical history.

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.

Hyponatremia and increased risk of dementia: A population-based retrospective cohort study.

Hyponatremia is the most common electrolyte disorder and also a predictor of mild cognition impairment. However, the association between hyponatremia and dementia in long follow up periods is rarely investigated. A retrospective cohort study was performed using the claims data of all insured residents who were covered by Taiwan's universal health insurance from 2000 to 2011. A total of 4900 hyponatremia patients and 19545 matched comparisons were recruited for the analysis. The incidences of hyponatremia and dementia were diagnosed with clinical protocol and defined using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM). Cox proportional hazard regression and Kaplan-Meier curves were used for the analyses. Independent of adjusting factors, hyponatremia patients had 2.36-fold higher chances of suffering dementia, including Alzheimer's disease (AD) and non-AD dementia, than the comparisons. Severe hyponatremia patients had higher risks of suffering dementia than the non-severe hyponatremia patients (adjusted hazard ratio: 4.29 (95% CI: 3.47-5.31) versus 2.08 (95% CI: 1.83-2.37)). A dose response relationship was observed between hyponatremia and dementia. Those hyponatremia patients with baseline or incident stroke had significantly higher chances of suffering dementia compared with those patients without hyponatremia and stroke. Stroke is a significant modifier of the relationship between hyponatremia and dementia. Cerebrovascular disease after incident hyponatremia must be prevented to reduce the incidence of dementia.

Spironolactone and the risk of urinary tract cancer in patients with hypertension: a nationwide population-based retrospective case-control study.

AIM: This was a nationwide study by National Health Insurance Research Database to investigate the risk of urinary tract cancers (UTCs) for renin-angiotensin-aldosterone system inhibitors including spironolactone. METHODS: A total of 32 167 UTC patients with hypertension were enrolled in the National Health Insurance program between 2005 and 2011. RESULTS: Among different subclasses of renin-angiotensin-aldosterone system inhibitors, the adjusted odds ratio (OR) for UTC risk was 1.00 [95% confidence interval (CI) = 0.96-1.04] in angiotensin-converting enzyme inhibitors, 1.22 (95% CI = 1.18-1.26) in patients who received angiotensin II receptor blockers, 0.91 (95% CI = 0.87-0.96) in spironolactone. Spironolactone is associated with a significantly lower risk of prostate cancer (adjusted OR = 0.88, 95% CI = 0.82-0.94) in the male patients. A similar trend was observed in the female patients for the risk of bladder cancer (adjusted OR = 0.81, 95% CI = 0.72-0.92). CONCLUSION: Our findings show that a lower risk of UTCs significantly associated with spironolactone in patients.

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.

Current Safety of Renal Allograft Biopsy With Indication in Adult Recipients: An Observational Study.

Renal biopsy remains the golden standard diagnosis of renal function deterioration. The safety in native kidney biopsy is well defined. However, it is a different story in allograft kidney biopsy. We conduct this retrospective study to clarify the safety of allograft kidney biopsy with indication.All variables were grouped by the year of biopsy and they were compared by Mann-Whitney U test (for continuous variables) or Chi-square test (for categorical variables). We collected possible factors associated with complications, including age, gender, body weight, renal function, cause of uremia, status of coagulation, hepatitis, size of needle, and immunosuppressants.We recruited all renal transplant recipients undergoing allograft biopsy between January of 2009 and December of 2014. This is the largest database for allograft kidney biopsy with indication. Of all the 269 biopsies, there was no difference in occurrence among the total 14 complications (5.2%) over these 6 years. There were only 3 cases of hematomas (1.11%), 6 gross hematuria (2.23%), 1 hydronephrosis (0.37%), and 2 hemoglobin decline (0.74%). The outcome of this cohort is the best compared to all other studies, and it is even better than the allograft protocol kidney biopsy. Among all possible factors, patients with pathological report containing "medullary tissue only" were susceptible to complications (P < 0.001, 1.8 of relative risk).In modern era, this study demonstrates the safety of allograft kidney biopsy with indication. Identifying the renal capsule before biopsy to avoid puncture into medulla is the most important element to prevent complications.

Increased risk of hepatic complications in kidney transplantation with chronic virus hepatitis infection: A nationwide population-based cohort study.

Data regarding the risk of various liver diseases among different hepatitis viruses in kidney transplantation have not yet been identified.We selected individuals with kidney transplantation (ICD-9-CM V420 or 996.81) from 2000-2009 from the catastrophic illness registry of National Health Insurance Research Database (NHIRD)as the study cohort. The two end-points in the study included overall death, and post-transplant occurrence of hepatic disease. After adjustment for other risk factors, the risk of mortality was increased in patients with HBV infection (N = 352) and with HCV infection (N = 275) compared to those with neither HBV nor HCV infection (N = 3485). In addition,renal transplant recipients with HBV alone,HCV alone, and both with HBV and HCVinfectionrespectively had an approximately 10-fold hazard ratio (HR) = 9.84, 95% confidence interval (CI): 4.61-21.0, 4-fold increased risk (HR = 4.40, 95% CI: 1.85-10.5)and 5-fold increased risk (HR = 4.63, 95% CI: 1.06-20.2)of hepatocellular carcinoma (HCC)compared to those with neither HBV nor HCV infection. Our findings showed a significant risk of de novo liver disease in recipients with hepatitis virus infection. Based on our findings, we reinforce the importance and impact of hepatitis virus in renal transplantation.

RANTES mediates kidney ischemia reperfusion injury through a possible role of HIF-1α and LncRNA PRINS.

RANTES (Regulated on activation, normal T-cell expressed and secreted), recruits circulating leukocytes and augments inflammatory responses in many clinical conditions. Inflammatory responses in ischemia-reperfusion injury (IRI) significantly affect the unfavorable outcomes of acute kidney injury (AKI), and that infiltrating immune cells are important mediators of AKI. However, the significance of RANTES in AKI and whether hypoxia-induced LncRNAs are involved in the regulatory process of AKI are not known. Here we show that, in the kidney IRI mice model, significant RANTES expression was observed in renal tubular cells of wild type mice. RANTES deficient (RANTES(-/-)) mice showed better renal function by reducing the acute tubular necrosis, serum creatinine levels, infiltration of inflammatory cells and cytokine expressions compared to wild type. In vitro, we found that RANTES expression was regulated by NF-κB. Further, renal tubular cells showed deregulated LncRNA expression under hypoxia. Among HIF-1α dependent LncRNAs, PRINS (Psoriasis susceptibility-related RNA Gene Induced by Stress) was significantly up regulated in hypoxic conditions and had specific interaction with RANTES as confirmed through reporter assay. These observations show first evidence for RANTES produced by renal tubular cells act as a key chemokine in AKI and HIF-1α regulated LncRNA-PRINS might be involved in RANTES production.

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.

Risk of peripheral arterial occlusive disease in patients with rheumatoid arthritis. A nationwide population-based cohort study.

Rheumatoid arthritis (RA) is associated with atherosclerosis. However, the relationship between RA and peripheral arterial occlusive disease (PAOD) remains unclear. We used a national health insurance database to identify a cohort of 30,812 patients diagnosed with RA between 2000 and 2011. Each RA patient was frequency-matched according to age and sex with a patient without RA from a control cohort. A multivariate Cox proportional hazards model was used to analyse the adjusted risk of PAOD. The incidence of PAOD was 1.73-fold higher (95% confidence interval [CI] = 1.57-1.91) in the RA cohort than in the non-RA cohort. The adjusted risk of PAOD was the highest in the patients with RA aged ≤ 49 years (hazard ratio [HR] = 3.39, 95% CI = 2.66-4.32). Patients with RA and various comorbidities showed a significantly higher risk of PAOD (HR = 9.62, 95% CI = 4.86-19.1) compared with control patients without comorbidity. The risk of PAOD increased during the first year of follow-up. In conclusion, patients with RA have an independently higher risk of PAOD compared with the general population. Patients with RA and various comorbidities and those at a young age and early stage of the disease have an increased risk of PAOD.

Risk of Peripheral Arterial Occlusive Disease in Patients With Systemic Lupus Erythematosus: A Nationwide Population-Based Cohort Study.

Systemic lupus erythematosus (SLE) is associated with atherosclerosis, but the relationship between SLE and peripheral arterial occlusive disease (PAOD) remains unclear. We sought to investigate this relationship by comparing cardiovascular complications in patients with and without SLE.Data on patients from 2000 to 2011 were collected from the National Health Insurance Research Database of Taiwan. The SLE cohort was frequency-matched according to age, sex, and history of diabetes mellitus (DM) with patients without SLE (control cohort). We evaluated the risk of cardiovascular complications, including hypertension, DM, stroke, chronic obstructive pulmonary disease, heart failure, coronary artery disease, and hyperlipidemia.The study included 10,144 patients with SLE and 10,144 control patients. The incidence of PAOD was 9.39-fold higher (95% confidence interval [CI] = 7.70-11.15) in the SLE cohort than in the non-SLE cohort. Moreover, SLE was an independent risk factor for PAOD. The adjusted risk of PAOD was highest in patients with SLE who were aged ≤34 years (hazard ratio = 47.6, 95% CI = 26.8-84.4). The risk of PAOD was highest during the first year of follow-up and decreased over time.Patients with SLE exhibit a higher incidence and an independently higher risk of PAOD compared with the general population. The PAOD risk is markedly elevated in patients with SLE who are young and in whom the disease is at an early stage.

Expression of decoy receptor 3 in kidneys is associated with allograft survival after kidney transplant rejection.

Decoy receptor 3 (DcR3) expression in kidneys has been shown to predict progression of chronic kidney disease. We prospectively investigated a cohort comprising 96 renal transplant recipients (RTRs) undergoing graft kidney biopsies. Computer-assisted quantitative immunohistochemical staining value of DcR3 in renal tubular epithelial cells (RTECs) was used to determine the predictive role of DcR3 in kidney disease progression. The primary end point was doubling of serum creatinine and/or graft failure. A multivariate Cox proportional hazards model was used to assess the risk of DcR3 expression in rejected kidney grafts toward the renal end point. In total, RTRs with kidney allograft rejection were evaluated and the median follow-up was 30.9 months. The greater expression of DcR3 immunoreactivity in RTECs was correlated with a higher rate of the histopathological concordance of acute T cell-mediated rejection. Compared with 65 non-progressors, 31 progressors had higher DcR3 expression (HDE) regardless of the traditional risk factors. Cox regression analysis showed HDE was significantly associated with the risk of renal end point with a hazard ratio of 3.19 (95% confidence interval, 1.40 to 7.27; P = 0.006) after adjusting for other variables. In repetitive biopsies, HDE in tissue showed rapid kidney disease progression due to persistent inflammation.