Non-renal Patients Research Articles

Safety and efficacy of total hip arthroplasty in patients with end stage renal disease

To evaluate the safety and efficacy of total hip arthroplasty (THA) in patients with end stage renal disease (ESRD). Between December 2009 and May 2016, 30 THAs were performed in 28 patients with dialysis-dependent renal failure (18 patients) or renal transplantation (10 patients). A retrospective case control study was carried out to compare these 28 ESRD patients (ESRD group) with a matched cohort of 28 nonrenal patients (control group). There was no significant difference in gender, age, hip side, American Society of Anesthesiology (ASA) classification, comorbidities, and preoperative Harris score and hemoglobin (Hb) level between 2 groups ( P>0.05). The complications during hospitalization, Hb level changes, perioperative transfusion rate, hospital stay, and hospitalization costs in 2 groups were evaluated; and the creatinine changes of dialysis patients in ESRD group were evaluated. During the follow-up period, 90 days readmissions, periprosthetic infection, prosthesis loosening, hip Harris score, and deaths were recorded. There was no loss of follow-up. The mean postoperative follow-up of ESRD group was 3.4 years (range, 1.0-7.4 years) and control group was 3.5 years (range, 1.0-7.4 years). Differences in hospital stay and the drop of Hb was not significant between 2 groups ( P>0.05). The hospitalization costs and perioperative transfusion rate were significantly higher in ESRD group than in control group ( P<0.05). There was no significant difference in creatinine value of dialysis patients in ESRD group between pre- and post-operation ( t=1.804, P=0.089). At last follow-up, the Harris score was significantly higher than preoperative score in both groups ( P<0.05); however, there was no significant difference in Harris score between groups ( t=1.278, P=0.207). In ESRD group, 5 patients presented complications, 1 patient was readmitted to hospital, and 2 patients died during the follow-up. In control group, 1 patient presented complications, and there was no 90 days readmission and no death. During the follow-up period, there was no loosening or revision in 2 groups and the prosthesis was in good position. THA can improve joint function and life quality of ESRD patients, but the risks of operation, perioperative complications, transfusion rate, and cost are high. Correct perioperative evaluation and management can help ESRD patients safely go through the perioperative period.

Vascular inflammation and media calcification are already present in early stages of chronic kidney disease.

While patients with chronic kidney disease (CKD) have a high prevalence of classical coronary risk factors, there is increasing evidence that atherosclerosis is different in renal compared to nonrenal patients. Therefore, the present study compares changes in different vessels obtained at cardiac surgery between patients with early and advanced CKD and nonrenal control patients. Fifty patients undergoing cardiac bypass surgery were divided into three groups: (i) 24 control patients with creatinine <1.3mg/dl, (ii) 14 patients with early CKD (creatinine 1.3-2.0mg/dl), and (iii) 12 patients with advanced CKD (creatinine >2.0mg/dl). Aorta, arteria mammaria interna, and vena saphena (V. saphena) were analyzed using morphometry, Kossa stain for vascular calcification, and immunohistochemistry for markers of inflammation and proosteogenic differentiation of vascular smooth muscle cells (VSMCs). Thereby, aortic wall thickness and calcification score of aortic intima and of V. saphena were significantly higher in advanced CKD patients than in nonrenal control patients, whereas significant vascular inflammation and proosteogenic dedifferentiation of VSMC and calcification of the aortic media were already present in early CKD. Interestingly, marked calcification of the V. saphena magna was seen in advanced CKD. Of note, calcium-phosphate product correlated well with markers of inflammation, but not with calcification itself. Early stages of CKD are already associated with local up-regulation of proinflammatory and proosteogenic molecules in the vascular wall and calcification of the aortic media. These findings point to the importance of local microinflammation in CKD and may shed new light on the potentially overestimated role of the calcium-phosphate product for vessel calcification.

Signal-intensity-ratio MRI accurately estimates hepatic iron load in hemodialysis patients.

BackgroundIron overload, diagnosed by means of magnetic resonance imaging (MRI), is an increasingly recognized disorder in hemodialysis patients. Specific MRI protocols have been shown to provide a reliable estimation of tissue iron content in non-renal patient populations but have not been validated in dialysis patients. Such validation studies require liver biopsy for histological comparison, but this invasive and risky procedure raises ethical concerns, especially regarding frail patients with end-stage renal disease.Materials and methodsWe compared in a pilot study Scheuer’s histological classification and Deugnier and Turlin’s histological classification of iron overload (Perls staining) with signal-intensity-ratio MRI values obtained with the Rennes University algorithm in 11 hemodialysis patients in whom liver biopsy was formally indicated for their medical follow-up.ResultsFor Scheuer’s histological classification, the Wilcoxon non-parametric matched-pairs test showed no significant difference in the ranking of iron overload by the two methods eg histology and MRI (sum of ranks = 1.5; p = 1). The MRI and Scheuer’s histological classifications were tightly correlated (rho = 0.866, p = 0.0035, Spearman’s coefficient), as were the absolute liver iron concentrations (LIC) at MRI (rho = 0.860, p = 0.0013, Spearman’s coefficient). The absolute liver iron concentrations at MRI were also highly correlated with Deugnier and Turlin’s histological scoring (rho = 0.841, p = 0.0033, Spearman’s coefficient).ConclusionsThis pilot study shows that liver iron determination based on signal-intensity-ratio MRI (Rennes University algorithm) very accurately identifies iron load in hemodialysis patients, by comparison with liver histology.

Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 2: Why to measure glomerular filtration rate with iohexol?

A reliable assessment of glomerular filtration rate (GFR) is of paramount importance in clinical practice as well as epidemiological and clinical research settings. It is recommended by Kidney Disease: Improving Global Outcomes guidelines in specific populations (anorectic, cirrhotic, obese, renal and non-renal transplant patients) where estimation equations are unreliable. Measured GFR is the only valuable test to confirm or confute the status of chronic kidney disease (CKD), to evaluate the slope of renal function decay over time, to assess the suitability of living kidney donors and for dosing of potentially toxic medication with a narrow therapeutic index. Abnormally elevated GFR or hyperfiltration in patients with diabetes or obesity can be correctly diagnosed only by measuring GFR. GFR measurement contributes to assessing the true CKD prevalence rate, avoiding discrepancies due to GFR estimation with different equations. Using measured GFR, successfully accomplished in large epidemiological studies, is the only way to study the potential link between decreased renal function and cardiovascular or total mortality, being sure that this association is not due to confounders, i.e. non-GFR determinants of biomarkers. In clinical research, it has been shown that measured GFR (or measured GFR slope) as a secondary endpoint as compared with estimated GFR detected subtle treatment effects and obtained these results with a comparatively smaller sample size than trials choosing estimated GFR. Measuring GFR by iohexol has several advantages: simplicity, low cost, stability and low interlaboratory variation. Iohexol plasma clearance represents the best chance for implementing a standardized GFR measurement protocol applicable worldwide both in clinical practice and in research.

The avidity of PR3-ANCA in patients with granulomatosis with polyangiitis during follow-up.

The objective of this study is to investigate whether the avidity of proteinase-3-anti-neutrophil cytoplasmic antibody (PR3-ANCA) changes during follow-up in different subgroups of patients with granulomatosis with polyangiitis (GPA). We selected 10 patients with renal relapsing GPA, 10 patients with renal non-relapsing GPA and 10 patients with non-renal relapsing GPA. In all patients, an ANCA rise occurred during remission. The avidity was measured using a chaotropic approach at the time of an ANCA rise and at the time of a relapse in relapsing patients or time-matched during remission in non-relapsing patients. No difference was observed in the avidity at the ANCA rise between renal relapsing patients [26·2% (15·5-47·5)], renal patients without a relapse [39·6% (21·2-63·4)] and non-renal relapsing patients [34·2% (21·6-59·5)]. In renal relapsing patients, the avidity increased significantly from the moment of the ANCA rise to the relapse [difference 6·4% (0·0-17·1), P=0·0273]. The avidity did not increase after an ANCA rise in renal non-relapsing patients [difference 3·5 (-6·0 to 10·1), P=0·6250] or in non-renal relapsing patients [difference -3·1% (-8·0 to 5·0), P=0·5703]. The avidity of PR3-ANCA increases after an ANCA rise during follow-up in renal relapsing patients, but not after an ANCA rise in renal patients who remain in remission or in non-renal relapsing patients.

Serum and Urinary Interferon-Gamma-Inducible Protein 10 in Lupus Nephritis.

Lupus nephritis is a serious manifestation of systemic lupus erythematosus (SLE). The objective of this study was to identify the sensitivity, specificity, and cut-off values of IP-10 in the serum and urine of patients with lupus nephritis compared to renal biopsy, albumin/creatinine ratio, and serum anti-dsDNA. Thirty female SLE patients were included. SLEDAI was calculated and blood and urine samples were collected. Patients were divided into 10 SLE patients with renal involvement (six active and four inactive), 10 active SLE, and 10 inactive SLE patients. Ten age-matched healthy (control) were included. Serum and urinary levels of IP-10 were measured by ELISA. Anti-dsDNA, urine albumin/creatinine ratio were performed. Serum and urinary IP-10 in active SLE patients had significantly increased levels as compared to inactive SLE patients (P = 0.015, P = 0.033, respectively). However, there was no difference in serum and urinary levels between active renal and active non-renal patients. Albumin/creatinine ratio is a better marker in differentiating between lupus nephritis and SLE with no renal involvement. Any of serum and urinary IP-10, albumin/creatinine ratio, and anti-dsDNA did not correlate with the class of lupus nephritis in renal biopsy. Urinary and serum IP-10 are useful markers of lupus activity, but not indicative of renal activity. Albumin/creatinine ratio is superior in identifying lupus nephritis and renal activity.

Heightened preclinical dysregulation of distinct adaptive and renal-associated mediators in patients who develop nephritis as they transition to systemic lupus erythematosus classification

Abstract Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease marked by immune dysregulation. Why some patients have only moderate symptoms and others develop organ-threatening manifestations is unclear. This study evaluates the temporal expression of autoantibodies and cytokines in sera from the Department of Defense Serum Repository during transition from preclinical lupus to SLE in patients (n=83) who do or do not present with nephritis. Patients who met renal criteria (n=30; 36%) did so within 5.2 (±5.5) months of SLE classification (range −5.2 to +12 months). Renal cases experienced earlier onset of autoantibody positivity vs. non-renal cases (mean −3.8 vs −2.6 years relative to SLE classification, p=0.0442). Prior to developing nephritis, renal cases exhibited elevated levels of distinct soluble mediators compared to matched non-renal cases and healthy controls, including adaptive mediators IL-4, IL-5, IL-12, and IFN-γ, chemokines IP-10 and MCP-3, and nephritis-associated mediators SCF and shed TNFRII (all p&amp;lt;0.05), increasing again at the time of nephritis (all p&amp;lt;0.02 compared to pre-nephritis levels). These same mediators were significantly increased at SLE classification in patients with nephritis vs. non-renal patients (all p&amp;lt;0.0001). These data indicate that perturbations in distinct immune mediated inflammatory processes may help identify individuals at high risk of renal involvement for early and continued monitoring and intervention.

Iatrogenic Iron Overload in Dialysis Patients at the Beginning of the 21st Century.

Iron overload used to be considered rare in hemodialysis patients but its clinical frequency is now increasingly realized. The liver is the main site of iron storage and the liver iron concentration (LIC) is closely correlated with total iron stores in patients with secondary hemosideroses and genetic hemochromatosis. Magnetic resonance imaging is now the gold standard method for LIC estimation and monitoring in non-renal patients. Studies of LIC in hemodialysis patients by quantitative magnetic resonance imaging and magnetic susceptometry have demonstrated a strong relation between the risk of iron overload and the use of intravenous (IV) iron products prescribed at doses determined by the iron biomarker cutoffs contained in current anemia management guidelines. These findings have challenged the validity of both iron biomarker cutoffs and current clinical guidelines, especially with respect to recommended IV iron doses. Three long-term observational studies have recently suggested that excessive IV iron doses may be associated with an increased risk of cardiovascular events and death in hemodialysis patients. We postulate that iatrogenic iron overload in the era of erythropoiesis-stimulating agents may silently increase complications in dialysis patients without creating frank clinical signs and symptoms. High hepcidin-25 levels were recently linked to fatal and nonfatal cardiovascular events in dialysis patients. It is therefore tempting to postulate that the main pathophysiological pathway leading to these events may involve the pleiotropic master hormone hepcidin (synergized by fibroblast growth factor 23), which regulates iron metabolism. Oxidative stress as a result of IV iron infusions and iron overload, by releasing labile non-transferrin-bound iron, might represent a ‘second hit’ on the vascular bed. Finally, iron deposition in the myocardium of patients with severe iron overload might also play a role in the pathogenesis of sudden death in some patients.

Clinical Trials in Vasculitis.

Opinion statementThe systemic vasculitides include a heterogenous group of diseases characterised by inflammation of blood vessels. Evidence for treatment in this group of patients is limited due to rarity of the diseases, incomplete understanding of the pathogenesis and lack of appropriate biomarkers. In the last 20 years, international collaboration and networking led to clinical trials in a select subgroup of patients with systemic vasculitis. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is the most studied subgroup. This article discusses the treatment options of AAV in light of evidence from clinical trials. Treatment of AAV, which includes an induction and a maintenance phase, is dependent on the severity of the disease. Oral or intravenous cyclophosphamide and high-dose glucocorticoids are considered to be standard of care for induction of remission in AAV patients with generalised disease. Latest evidence supports rituximab as an alternative to cyclophosphamide especially in relapsing patients and is increasingly being used in patients who cannot have cyclophosphamide. Plasma exchange and intravenous immunoglobulins (IVIGs) are used as adjunctive therapies for induction. Azathioprine or methotrexate (in non-renal patients) is considered to be the choice for remission maintenance, whilst mycophenolate mofetil is reserved for patients who cannot tolerate either of them. Rituximab is also being increasingly used for remission maintenance in relapsing patients. Even though an enormous progress has been made in the outlook of patients with AAV, a number of questions remain unanswered with regard to the optimal treatment strategy.

Elective Total Knee Arthroplasty in Patients With End-Stage Renal Disease: Is It a Safe Procedure?

BackgroundThe purpose of this study was to compare outcomes and complications after total knee arthroplasty (TKA) between end-stage renal disease (ESRD) patients and patients without renal insufficiency. MethodsA retrospective case–control study with prospectively collected data was carried out to compare 15 ESRD patients with a matched cohort of 30 nonrenal patients. Clinical evaluation was performed by the Knee Society Scores (KSS) and reduced Western Ontario MacMasters University (WOMAC) questionnaire. Radiologic evaluation was also performed. ResultsThe mean postoperative follow-up was 3.4 years (range, 2-6). In the ESRD, the mean hospital stay and transfusion rate were significantly higher than control group. Preoperatively and postoperatively, there were no significant differences in KSS-knee or WOMAC-pain scores, but KSS-function and WOMAC-function were significantly lower in the ESRD group. There was no significant difference between groups in mean gain of KSS-function (45.1 vs 43.2, P = .071), but there was a significant lower mean gain for WOMAC-function in the ESRD group (37.0 vs 44.0, P = .003). In the ESRD group, 3 patients presented medical complications which were treated successfully. There were 2 superficial infections and no deep infection. One patient died at 30 postoperative months. In the control group, there were no medical complications, infections, or deaths during the follow-up period. In ESRD group, there were 2 knees with radiolucent lines. In either group, there was no loosening or revision. ConclusionTKA was a successful procedure for knee osteoarthritis in most ESRD patients. Dialysis patients may expect improvement in function after TKA, but the patients need to be informed of the possible risk of postoperative severe medical complications due to nature of their renal disease.

Mycophenolate Mofetil in Nonrenal Manifestations of Systemic Lupus Erythematosus: An Observational Cohort Study.

Mycophenolate mofetil (MMF), along with corticosteroids, is considered as the standard of care in lupus nephritis (LN); however, little is known regarding its efficacy in extrarenal manifestations of systemic lupus erythematosus (SLE). We aimed to determine its effectiveness in nonrenal SLE. One hundred seventy-seven patients with SLE were enrolled; 105 for whom MMF was introduced for active LN (mean age 35.6 ± 10.7 yrs, mean disease duration 8.9 ± 7.8 yrs) and 72 for extrarenal manifestations (mean age 38.6 ± 11.7 yrs, mean disease duration 11.7 ± 9.2 yrs). The main indication for MMF initiation was based on the respective SLE Disease Activity Index element that was present at that time. Patients were subdivided according to the major nonrenal manifestation. Improvement was defined as the absence of the initial clinical or laboratory manifestation after 6 and 12 months. Cumulatively, the initial clinical manifestation or hematological abnormality was resolved in 42/72 nonrenal patients (58.3%) after 6 months and in 45/72 (62.5%) after 12 months. Corticosteroid dose was reduced in 44/72 patients (61.1%, p < 0.001, mean dose 18.4 ± 12.6 mg/day at baseline to 12.1 ± 9.0 mg/day after 12 mos, p < 0.05). In renal patients, 40 (38.1%) had complete resolution of the extrarenal manifestation after 6 months, while 53 (50.5%) achieved complete response after 12 months. Prednisone dose was reduced in 73/105 patients (69.5%) after 12 months (mean dose 29.2 ± 16.6 mg/day at baseline to 15.3 ± 9.7 mg/day, p < 0.001). MMF seems to be an efficacious alternative in refractory to standard of care nonrenal manifestations of SLE in the long term, allowing for disease activity control and significant reduction in corticosteroid dose.

Search for the presence of occult hepatitis C in patients with treatment-induced viral clearance using an ultrasensitive assay.

Occult hepatitis C is defined by the presence of virus in the peripheral blood mononuclear cells (PBMCs) and/or liver cells, in the absence of serum viremia. To detect the persistence of occult hepatitis C in hemodialysis (HD) patients and patients without renal disease (non-renal) with treatment-induced clearance of hepatitis C virus (HCV) infection, using assays with a very low detection limit of viremia. A group of 13 HD patients and a group of 43 non-renal patients, with treatment-induced HCV infection clearance were investigated in the study. The HD patients were treated with pegylated interferon alpha (PEG-IFN-α) only, while the non-renal patients were treated with a combination therapy of PEGIFN- α and ribavirin. Detection of a possible persistence of HCV RNA in the PBMCs and plasma samples was assessed by an ultrasensitive reverse transcription polymerase chain reaction (RT-PCR) assay (2 IU/ml). HCV RNA was not detected in the PBMCs and plasma samples of HD patients and of non-renal patients, when assessed by the ultrasensitive RT-PCR assay. When a sensitive RT-PCR assay was applied, to determine if treatment induced clearance of HCV infection had been successful, occult hepatitis C could not be detected by an ultrasensitive assay, neither in HD nor in non-renal patients.

Study of epidemiological features of hepatitis D virus infection in HBsAg-positive chronic hemodialysis patients

Objective Study the prevalence, clinical, and laboratory features of hepatitis D virus (HDV) infection in hepatitis B surface antigen positive chronic hemodialysis (HD) patients. Background Delta virus or HDV is a small RNA-containing virus requiring the concomitant presence of hepatitis B virus (HBV) for its survival and pathogenicity. Worldwide, 20 million of chronic HBV patients are thought to be infected with HDV. It is important to know that HDV infection is present in a HD patient with HBV infection, because it allows a more accurate determination of prognosis, and the response of HDV patients to antiviral therapy and needed dosage therapeutic regimens are different from those with chronic hepatitis B alone. Materials and methods The study included 50 chronic HBV-infected renal patients and 25 chronic HBV nonrenal patients collected from Shebin El-Kom Fever Hospital and Menoufiya University Hospital, Menoufiya, Egypt. The study was conducted from January 2013 to May 2014. Enzyme-linked immunosorbent an assay was used to detect hepatitis B surface antigen and HDV antibodies (total antibody). Results HDV antibody (total) was positive in 58% of the HBV renal patients and in 24% of the HBV nonrenal patients, with high significant statistical difference. Laboratory data showed significant statistical differences between the two groups regarding platelet concentration (higher in HBV renal patients), albumin and prothrombin (higher in HBV nonrenal patients), bilirubin levels, and renal functions (higher in HBV renal patients). Furthermore, the infection with hepatitis delta is more common in HBV renal patients in the HD group IA (72%) than HBV renal patients on conservative treatment group IB (44%), with significant statistical differences of laboratory data between the two groups regarding hemoglobin (higher in group IB) and platelet concentration (higher in group IA), albumin and prothrombin (higher in group IA), bilirubin levels (higher in group IB), and renal functions (higher in group IA). Conclusion It is concluded that HD may have a major role in widening the prevalence of delta infection among the studied HBV renal patients (72%).

Complement and Cardiovascular Disease - The Missing Link in Haemodialysis Patients?

Background: Patients on haemodialysis (HD) have high rates of cardiovascular (CV) disease and activation of the complement system. Despite evidence in non-renal patients that these may be linked, this association has received little attention in HD patients to date. In the setting of a randomised controlled trial we evaluated the relationships between baseline complement levels and subsequent CV events and mortality, in addition to the effects of HD with a vitamin E (VE)-coated dialysis membrane on circulating complement levels. Methods: A total of 260 HD patients were randomised to dialysis with a VE-coated dialysis membrane or non-VE coated equivalent for 12 months. Blood samples were taken at baseline, 6 and 12 months for measurement of C3, factor D, factor H and SC5b-9 levels. Data were collected prospectively on deaths and CV events. Results: Higher C3 levels at baseline were associated with subsequent CV events (hazard ratio 1.20 (1.01-1.42) per 0.1 mg/ml). Patients with intermediate SC5b-9 levels had significantly lower CV event rates and mortality than those with either high or low levels (p < 0.01). There were no effects of the VE-membranes on the complement components measured nor the clinical endpoints considered. Conclusions: The levels of C3 and SC5b-9 may have prognostic utility for predicting future CV events and/or mortality in HD patients - a relationship that requires further investigation. Dialysing prevalent HD patients with VE-bonded polysulfone membranes for a period of 12 months did not alter the circulating levels of the alternative complement pathway components considered here.

Down-regulation of expression of retinoid acid-related orphan receptor C (RORC) in systemic lupus erythematosus

Context: Retinoic acid-related orphan receptor C (RORC), the key factor orchestrating the transcription of genes encoding interleukin 17, plays a critical role in the regulation of inflammatory responses. Objective: The objective of this study was to analyze the expression of RORC in the peripheral blood of patients with systemic lupus erythematosus (SLE) for a better understanding of the pathogenesis of SLE especially in relation to disease activity and clinical and biochemical findings. Methods: The study included 24 patients with SLE and a control group of 18 healthy gender- and age-matched individuals. Evaluation of the level of expression of RORC mRNA was performed by real-time polymerase chain reaction. Results: The results showed that patients with SLE had lower RORC gene expression levels compared with healthy subjects that were not correlated with disease activity. The down-regulation of RORC was significantly lower in patients with lupus nephritis in remission than active lupus nephritis and nonrenal patients. Conclusions: The findings suggest that RORC plays a significant role in the dysregulated immune response associated with SLE. Deciphering the intricate regulatory network and the target genes of RORC will help unravel new specific treatments for SLE.

Co-Positivity for Anti-dsDNA, -Nucleosome and -Histone Antibodies in Lupus Nephritis Is Indicative of High Serum Levels and Severe Nephropathy.

ObjectiveTo characterize the significance of correlated autoantibodies in systemic lupus erythematosus (SLE) and its complication lupus nephritis (LN) in a large cohort of patients.MethodsClinical data were statistically analyzed in 1699 SLE patients with or without nephritis who were diagnosed and treated during 2002–2013 in the northeast region of China. Reactivity to a list of 16 autoantibodies was detected by the serum test Euroline ANA profile (IgG). Serum titers of the anti-nucleosome autoantibodies were measured by ELISA assays. Kidney biopsies were examined by pathologists. Immune complex deposition was identified by immunohistochemistry stain.ResultsSimultaneous positivity of anti-dsDNA, -nucleosome and -histone antibodies (3-pos) was prevalent in SLE patients with LN compared to Non-renal SLE patients (41% vs 11%, p< 0.001). Significant correlations were found between any two of the above three anti-nucleosome antibodies in LN patients. In comparison to non-3-pos cohorts, 3-pos patients with LN had significantly higher serum levels of the three antibodies and more active disease; was associated with type IV disease; suffered from more severe renal damages; received more intensive treatment and had worse disease outcome. The serum levels of these three autoantibodies in 3-pos LN patients were significantly decreased when they underwent clinical recovery.ConclusionsSimultaneous reactivity to anti-dsDNA, -nucleosome and -histone antibodies by Euroline ANA profile (IgG) may indicate severe nephropathy in patients with SLE.

Epicardial adipose tissue in long-term hemodialysis patients: its association with vascular calcification and long-term development.

Epicardial adipose tissue (EAT) is associated with coronary artery disease (CAD) in the general population. EAT is suggested to promote CAD by paracrine mechanisms and local inflammation. We evaluated whether in chronic hemodialysis (HD) patients EAT associates with CAD, how the amount of EAT develops over time, and if EAT independently predicts the mortality risk. Post-hoc analysis of a prospective study in 59 chronic HD patients who underwent non-enhanced multi-slice computed tomography (MSCT) at baseline. Thirty-seven patients underwent another MSCT after 24 ± 5 months. We measured EAT volume (cm³) and Agatston calcification scores of coronary arteries (CAC) and aortic valves (AVC). All-cause mortality was assessed after a follow-up of 88 months (IQR 52-105). Baseline EAT was 128.2 ± 60.8 cm³ and significantly higher than in a control group of non-renal patients (94 ± 46 cm³; p < 0.05). Median Agatston score for CAC was 329 (IQR 23-1181) and for AVC was 0 (IQR 0-25.3) in HD patients. We observed significant positive correlations between baseline EAT and age (r = 0.386; p = 0.003), BMI (r = 0.314; p = 0.016), CAC (r = 0.278; p = 0.03), and AVC (r = 0.282; p = 0.03). In multivariate analysis, age, BMI and AVC remained as significant predictors of EAT (p < 0.01). Calcification scores significantly increased over 2 years; in contrast EAT change was not significant (+11 %, IQR -10 to 24 %; p = 0.066). The limited patient number in the present study precludes analysis of the EAT impact upon survival. EAT correlated significantly with cardiovascular calcification in long-term HD patients. Mean EAT did not significantly change over 2 years.

MicroRNA Profiling of B Cell Subsets from Systemic Lupus Erythematosus Patients Reveals Promising Novel Biomarkers.

MicroRNAs control the differentiation and function of B cells, which are considered key elements in the pathogenesis of systemic lupus erythematosus (SLE). However, a common micro(mi)RNA signature has not emerged since published data includes patients of variable ethnic background, type of disease, and organ involvement, as well as heterogeneous cell populations. Here, we aimed at identifying a miRNA signature of purified B cells from renal and non-renal severe SLE patients of Latin American background, a population known to express severe disease. Genome-wide miRNA expression analyses were performed on naive and memory B cells and revealed two categories of miRNA signatures. The first signature represents B cell subset-specific miRNAs deregulated in SLE: 11 and six miRNAs discriminating naive and memory B cells of SLE patients from healthy controls (HC), respectively. Whether the miRNA was up or down-regulated in memory B cells as compared with naive B cells in HC, this difference was abolished in SLE patients, and vice versa. The second signature identifies six miRNAs associated with specific pathologic features affecting renal outcome, providing a further understanding for SLE pathogenesis. Overall, the present work provided promising biomarkers in molecular diagnostics for disease severity as well as potential new targets for therapeutic intervention in SLE.

High Titer Anti-Basement Membrane Antibodies in a Subset of Patients with Pediatric Systemic Lupus Erythematosus

Background/Aims: There is a critical need for more noninvasive biomarkers to identify nephritis in patients with systemic lupus erythematosus (SLE). Recent studies in a model mouse and an adult SLE patient cohort suggest that anti-basement membrane antibody levels correlate well with lupus activity and kidney injury. The purpose of this study was to assess the anti-basement membrane reactivity in pediatric SLE (pSLE) patients with or without nephritis. Methods: Auto-antibodies to basement membrane antigens were assessed using an anti-matrigel ELISA. Endpoint titers were measured in pSLE patients and healthy children, as well as in autoimmune and non-immune mice, with good reproducing capabilities. Findings were also analyzed with respect to the presence or absence of nephritis, dsDNA antibodies, and other manifestations of pSLE. Results: MRL/lpr mice developed high-titer anti-matrigel antibodies, whereas C57BL/6 mice did not. In a cohort of 21 pSLE patients and 22 pediatric controls, high-titer anti-matrigel IgG, IgM and IgA antibody levels were specific for pSLE. High-titer anti-matrigel IgG3 levels could distinguish with good sensitivity the 13 pSLE patients with a history of nephritis from the 8 non-renal pSLE patients. High-titer anti-matrigel IgG, IgA, IgM or IgG3 did not correlate with positive anti-double stranded DNA, but defined an overlapping subset of patients. Conclusion: The addition of anti-basement membrane antibody testing to serologic testing in pSLE may help to monitor disease activity or to define important subsets of patients with risks for specific disease manifestations.

A national study of practice patterns in UK renal units in the use of dialysis and conservative kidney management to treat people aged 75 years and over with chronic kidney failure

BackgroundConservative kidney management (CKM) is recognised as an alternative to dialysis for a significant number of older adults with multimorbid stage 5 chronic kidney disease (CKD5). However, little is known about the way CKM is delivered or how it is perceived.AimTo determine the practice patterns for the CKM of older patients with CKD5, to inform service development and future research.Objectives(1) To describe the differences between renal units in the extent and nature of CKM, (2) to explore how decisions are made about treatment options for older patients with CKD5, (3) to explore clinicians’ willingness to randomise patients with CKD5 to CKM versus dialysis, (4) to describe the interface between renal units and primary care in managing CKD5 and (5) to identify the resources involved and potential costs of CKM.MethodsMixed-methods study. Interviews with 42 patients aged &gt; 75 years with CKD5 and 60 renal unit staff in a purposive sample of nine UK renal units. Interviews informed the design of a survey to assess CKM practice, sent to all 71 UK units. Nineteen general practitioners (GPs) were interviewed concerning the referral of CKD patients to secondary care. We sought laboratory data on new CKD5 patients aged &gt; 75 years to link with the nine renal units’ records to assess referral patterns.ResultsSixty-seven of 71 renal units completed the survey. Although terminology varied, there was general acceptance of the role of CKM. Only 52% of units were able to quantify the number of CKM patients. A wide range reflected varied interpretation of the designation ‘CKM’ by both staff and patients. It is used to characterise a future treatment option as well as non-dialysis care for end-stage kidney failure (i.e. a disease state equivalent to being on dialysis). The number of patients in the latter group on CKM was relatively small (median 8, interquartile range 4.5–22). Patients’ expectations of CKM and dialysis were strongly influenced by renal staff. In a minority of units, CKM was not discussed. When discussed, often only limited information about illness progression was provided. Staff wanted more research into the relative benefits of CKM versus dialysis. There was almost universal support for an observational methodology and a quarter would definitely be willing to participate in a randomised clinical trial, indicating that clinicians placed value on high-quality evidence to inform decision-making. Linked data indicated that most CKD5 patients were known to renal units. GPs expressed a need for guidance on when to refer older multimorbid patients with CKD5 to nephrology care. There was large variation in the scale and model of CKM delivery. In most, the CKM service was integrated within the service for all non-renal replacement therapy CKD5 patients. A few units provided dedicated CKM clinics and some had dedicated, modest funding for CKM.ConclusionsConservative kidney management is accepted across UK renal units but there is much variation in the way it is described and delivered. For best practice, and for CKM to be developed and systematised across all renal units in the UK, we recommend (1) a standard definition and terminology for CKM, (2) research to measure the relative benefits of CKM and dialysis and (3) development of evidence-based staff training and patient education interventions.FundingThe National Institute for Health Research Health Services and Delivery Research programme.