scholarly journals ALCAM and VCAM-1 as urine biomarkers of activity and long-term renal outcome in systemic lupus erythematosus

Rheumatology ◽  
2019 ◽  
Vol 59 (9) ◽  
pp. 2237-2249 ◽  
Author(s):  
Ioannis Parodis ◽  
Sirisha Gokaraju ◽  
Agneta Zickert ◽  
Kamala Vanarsa ◽  
Ting Zhang ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Renal Involvement ◽  
Organ Damage ◽  
Population Based ◽  
Renal Outcome ◽  
Urine Biomarkers ◽  
Increased Risk ◽  
Function Loss

Abstract Objectives We investigated the cell adhesion molecules (CAMs) Vascular CAM 1 (VCAM-1) and Activated Leucocyte CAM (ALCAM) as urinary biomarkers in SLE patients with and without renal involvement. Methods Female SLE patients (n = 111) and non-SLE population-based controls (n = 99) were enrolled. We measured renal activity using the renal domain of the BILAG index and urine (U) and plasma (P) concentrations of soluble (s)VCAM 1 and U-sALCAM using ELISA. U-sCAM levels were next corrected by U-creatinine. Results U-sVCAM-1/creatinine and U-sALCAM/creatinine ratios were higher in SLE patients vs non-SLE controls (P < 0.001 for both), as well as in patients with active/low-active (BILAG A–C; n = 11) vs quiescent (BILAG D; n = 19) LN (P = 0.023 and P = 0.001, respectively). U-sALCAM/creatinine but not U-sVCAM-1/creatinine ratios were higher in patients with nephritis history (BILAG A–D; n = 30) vs non-renal SLE (BILAG E; n = 79) (P = 0.014). Patients with baseline U-sVCAM-1/creatinine ratios ≥75th percentile showed a 23-fold increased risk of a deterioration in estimated glomerular filtration rate by ≥25% during a 10-year follow-up (odds ratio: 22.9; 95% CI: 2.8, 189.2; P = 0.004); this association remained significant after adjustments for age, disease duration and organ damage. Traditional markers including anti-dsDNA antibodies did not predict this outcome. Conclusion While high U-sVCAM-1 levels appear to reflect SLE disease activity, sALCAM might have particular importance in renal SLE. Both U-sVCAM-1 and U-sALCAM showed ability to distinguish SLE patients with active renal involvement from patients with quiescent or no prior nephritis. High U-sVCAM-1 levels may indicate patients at increased risk for long-term renal function loss.

scholarly journals Organ damage in patients treated with belimumab versus standard of care: a propensity score-matched comparative analysis

2019 ◽  
Vol 78 (3) ◽  
pp. 372-379 ◽  
Author(s):  
Murray B Urowitz ◽  
Robert L Ohsfeldt ◽  
Ronald C Wielage ◽  
Kari A Kelton ◽  
Yumi Asukai ◽  
...  
Keyword(s):  
Propensity Score ◽  
Lupus Erythematosus ◽  
Damage Index ◽  
Standard Of Care ◽  
Organ Damage ◽  
Systemic Lupus ◽  
American College Of Rheumatology ◽  
Damage Progression

ObjectivesThe study (206347) compared organ damage progression in patients with systemic lupus erythematosus (SLE) who received belimumab in the BLISS long-term extension (LTE) study with propensity score (PS)-matched patients treated with standard of care (SoC) from the Toronto Lupus Cohort (TLC).MethodsA systematic literature review identified 17 known predictors of organ damage to calculate a PS for each patient. Patients from the BLISS LTE and the TLC were PS matched posthoc 1:1 based on their PS (±calliper). The primary endpoint was difference in change in Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score from baseline to 5 years.ResultsFor the 5- year analysis, of 567 (BLISS LTE n=195; TLC n=372) patients, 99 from each cohort were 1:1 PS matched. Change in SDI score at Year 5 was significantly lower for patients treated with belimumab compared with SoC (−0.434; 95% CI –0.667 to –0.201; p<0.001). For the time to organ damage progression analysis (≥1 year follow-up), the sample included 965 (BLISS LTE n=259; TLC n=706) patients, of whom 179 from each cohort were PS-matched. Patients receiving belimumab were 61% less likely to progress to a higher SDI score over any given year compared with patients treated with SoC (HR 0.391; 95% CI 0.253 to 0.605; p<0.001). Among the SDI score increases, the proportion of increases ≥2 was greater in the SoC group compared with the belimumab group.ConclusionsPS-matched patients receiving belimumab had significantly less organ damage progression compared with patients receiving SoC.

scholarly journals Kikuchi-Fujimoto disease: unusual presentation of rare disease

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Duy Vu ◽  
Srini Reddy ◽  
Lynn Day ◽  
Nail Aydin ◽  
Subhasis Misra
Keyword(s):  
Lupus Erythematosus ◽  
Unusual Presentation ◽  
Chronic Infections ◽  
Young Females ◽  
Inappropriate Treatment ◽  
Increased Risk ◽  
Long Term Follow Up ◽  
Autoimmune Processes

Kikuchi-Fujimoto disease (KFD) is a rare, benign disorder that typically follows a selflimiting natural course and was initially described in young females of Asian descent. Its clinical presentation may mimic lymphoproliferative disorders, connective tissue disorders, and chronic infections. This often leads to misdiagnosis and inappropriate treatment. The exact cause of this condition remains unknown although autoimmune processes and certain infectious agents have been associated with the disease. The diagnosis of KFD is made histopathologically. Treatment is supportive and long-term follow-up is recommended due to increased risk of future development of systemic lupus erythematosus. Here we are presenting a case of a patient with an unusual presentation of KFD.

scholarly journals Preeclampsia and the risk of chronic kidney disease: a national registry-based cohort study

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
P M Barrett ◽  
F P McCarthy ◽  
M Evans ◽  
M Kublickas ◽  
I J Perry ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Absolute Risk ◽  
Population Based ◽  
National Registry ◽  
Medical Birth Register ◽  
Increased Risk ◽  
History Of

Abstract Background Preeclampsia is associated with increased risk of future cardiovascular disease, but evidence for associations with chronic kidney disease (CKD) has been inconsistent to date. We aimed to measure associations between preeclampsia and long-term CKD in a population-based sample of parous women, and to identify whether the risk differs by CKD subtype. Methods Using data from the Swedish Medical Birth Register, singleton live births from 1973-2012 were identified and linked to data from the Swedish Renal Register and National Patient Register (up to 2013). Preeclampsia was the main exposure of interest and was treated as a time-dependent variable. The primary outcome was maternal CKD, and this was classified into 5 subtypes: hypertensive, diabetic, glomerular/proteinuric, tubulo-interstitial, other/non-specific CKD. Cox proportional hazard regression models were used for analysis. Women with pre-pregnancy comorbidities were excluded. Results The dataset included 1,924,591 unique women who had 3,726,819 singleton pregnancies. The median follow-up was 20.7 (interquartile range 9.9-30.0) years. Overall, 90,964 women (4.7%) experienced preeclampsia and 18,146 (0.9%) developed CKD. Women who had preeclampsia had higher risk of developing any CKD during follow-up (aHR 1.88, 95% CI 1.79-1.98). The risk differed by CKD subtype, and was higher for hypertensive CKD (aHR 3.76, aHR 3.09-4.57), diabetic CKD (aHR 3.45, 95% CI 2.83-4.21) and glomerular/proteinuric CKD (aHR 2.08, 95% CI 1.90-2.29). Women who had preterm preeclampsia, recurrent preeclampsia, or preeclampsia complicated by pre-pregnancy obesity were also at greater risk of any CKD. Conclusions Women with a history of preeclampsia are at increased risk of long-term CKD. The risk is most marked for hypertensive CKD, diabetic CKD, and glomerular/proteinuric CKD. The absolute risk of CKD related to preeclampsia is substantial, and these women may warrant systematic renal monitoring in the years following delivery. Key messages Preeclampsia is an independent predictor of long-term risk of chronic kidney disease in otherwise healthy parous women. Women with a history of preeclampsia may warrant systematic renal monitoring through additional blood pressure, blood glucose, and proteinuria checks.

Risk of cancer among sarcoidosis patients with biopsy-verified non-necrotizing granulomatous inflammation: Population-based cohort study

2021 ◽  
pp. jrheum.210588
Author(s):  
Mikkel Faurschou ◽  
Lars H. Omland ◽  
Niels Obel ◽  
Jesper Lindhardsen ◽  
Bo Baslund
Keyword(s):  
Solid Tumors ◽  
Granulomatous Inflammation ◽  
Population Based ◽  
Risk Difference ◽  
Increased Risk ◽  
Incidence Functions ◽  
Risk Of Cancer ◽  
Population Controls

Objective To assess the long-term risk of hematologic cancers, invasive solid tumors, and nonmelanoma skin cancer (NMSC) among sarcoidosis patients with biopsy-verified non-necrotizing granulomatous inflammation. Methods We used Danish administrative registers with nationwide coverage to construct a cohort of 3892 sarcoidosis patients and an age- and gender-matched comparison cohort of 38.920 population-controls. For all patients, a biopsy demonstrating non-necrotizing granulomatous inflammation had been obtained from the lower respiratory tract at time of diagnosis. Study outcome was time to diagnosis of cancer. Follow-up began at time of sarcoidosis diagnosis and continued for up to 10 years. We calculated hazard ratios (HRs) as estimates of the cancer risk among the sarcoidosis patients relative to that among the population-controls and used cumulative incidence functions to calculate absolute 10-year risk estimates. Results We observed an increased long-term risk of hematologic cancers (HR during the first 2 years of follow-up: 2.71 (95% CI: 1.18-6.25); HR after >2 years of follow-up: 2.12 (95% CI: 1.29-3.47)) and NMSC (HR after >2 years of follow-up: 1.82 (95% CI: 1.43-2.32)) among the sarcoidosis patients. An increased risk of invasive solid tumors was only observed during the first 2 years (HR: 1.55 (95% CI: 1.18-2.04)). Compared with the population-controls, the sarcoidosis patients had an increased absolute 10-year risk of hematologic cancers (risk difference: 0.56% (95% CI: 0.11%-1.01%)) and NMSC (risk difference: 1.58% (95% CI: 0.70%-2.47%)). Conclusion Sarcoidosis patients with biopsy-verified non-necrotizing granulomatous inflammation have an increased long-term risk of hematologic cancers and NMSC compared with the general population.

Maternal Hypothyroidism during Pregnancy and the Risk of Pediatric Endocrine Morbidity in the Offspring

2018 ◽  
Vol 36 (09) ◽  
pp. 975-980 ◽  
Author(s):  
Tamar Eshkoli ◽  
Tamar Wainstock ◽  
Eyal Sheiner ◽  
Ofer Beharier ◽  
Merav Fraenkel ◽  
...  
Keyword(s):  
Cox Regression ◽  
Survival Curve ◽  
Mode Of Delivery ◽  
Cumulative Risk ◽  
Maternal Diabetes ◽  
Population Based ◽  
Rank Test ◽  
Increased Risk

Objective Previous studies suggested maternal hypothyroidism during pregnancy to be associated with cognitive impairment of the offspring. Scarce data exist regarding long-term endocrine health of the offspring. This study was aimed to assess whether children born to mothers with hypothyroidism during pregnancy are at an increased risk for long-term endocrine morbidity. Study Design A retrospective population-based cohort study compared long-term endocrine morbidity of children born between the years 1991 and 2014 to mothers with and without hypothyroidism. Multiple gestations, fetuses with congenital malformations, and women lacking prenatal care were excluded. Hospitalizations of the offspring up to the age of 18 years involving endocrine morbidity were evaluated according to a predefined set of ICD-9 codes. Kaplan–Meier's survival curves were used to compare the cumulative risk and a Cox multivariable model was used to adjust for confounders. Results During the study period, 217,910 deliveries met the inclusion criteria; 1.1% of which were with maternal hypothyroidism (n = 2,403). During the follow-up period, the cumulative incidence of endocrine morbidity among children born to mothers with hypothyroidism was 27 per 1,000 person-years and 0.47 per 1,000 person-years in the comparison group (relative risk: 2.14; 95% confidence interval [CI]: 1.21–3.79). The Kaplan–Meier's survival curve demonstrated a significantly higher cumulative endocrine morbidity in children born to mothers with hypothyroidism (log-rank test, p = 0.007). In the Cox regression model controlled for maternal age, birth weight, preterm birth, maternal diabetes, hypertensive disorders of pregnancy, induction of labor, and mode of delivery, maternal hypothyroidism was found to be independently associated with pediatric endocrine morbidity in the offspring (adjusted hazard ratio = 1.92, 95% CI: 1.08–3.4, p = 0.025). Conclusion Maternal hypothyroidism appears to be independently associated with long-term pediatric endocrine morbidity of the offspring.

scholarly journals Long-term safety and limited organ damage in patients with systemic lupus erythematosus treated with belimumab: a Phase III study extension

Rheumatology ◽  
2019 ◽  
Vol 59 (2) ◽  
pp. 281-291 ◽  
Author(s):  
Ronald F van Vollenhoven ◽  
Sandra V Navarra ◽  
Roger A Levy ◽  
Mathew Thomas ◽  
Amy Heath ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Damage Index ◽  
Organ Damage ◽  
Index Score ◽  
Phase Iii ◽  
Extension Study ◽  
Laboratory Parameters ◽  
Damage Accrual

AbstractObjectiveThis extension study of the Phase III, randomized, placebo-controlled Belimumab International SLE Study (BLISS)-52 and BLISS-76 studies allowed non-US patients with SLE to continue belimumab treatment, in order to evaluate its long-term safety and tolerability including organ damage accrual.MethodsIn this multicentre, long-term extension study (GlaxoSmithKline Study BEL112234) patients received i.v. belimumab every 4 weeks plus standard therapy. Adverse events (AEs) were assessed monthly and safety-associated laboratory parameters were assessed at regular intervals. Organ damage (SLICC/ACR Damage Index) was assessed every 48 weeks. The study continued until belimumab was commercially available, with a subsequent 8-week follow-up period.ResultsA total of 738 patients entered the extension study and 735/738 (99.6%) received one or more doses of belimumab. Annual incidence of AEs, including serious and severe AEs, remained stable or declined over time. Sixty-nine (9.4%) patients experienced an AE resulting in discontinuation of belimumab or withdrawal from the study. Eleven deaths occurred (and two during post-treatment follow-up), including one (cardiogenic shock) considered possibly related to belimumab. Laboratory parameters generally remained stable. The mean (s.d.) SLICC/ACR Damage Index score was 0.6 (1.02) at baseline (prior to the first dose of belimumab) and remained stable. At study year 8, 57/65 (87.7%) patients had no change in SLICC/ACR Damage Index score from baseline, indicating low organ damage accrual.ConclusionBelimumab displayed a stable safety profile with no new safety signals. There was minimal organ damage progression over 8 years.Trial registrationClinicalTrials.gov, https://clinicaltrials.gov, NCT00424476 (BLISS-52), NCT00410384 (BLISS-76), NCT00732940 (BEL112232), NCT00712933 (BEL112234).

Autoantibodies persist in relatives to systemic lupus erythematosus patients during 12 years follow-up

Lupus ◽  
2016 ◽  
Vol 26 (7) ◽  
pp. 723-728 ◽  
Author(s):  
H Langkilde ◽  
A Voss ◽  
N Heegaard ◽  
H Laustrup
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Population Based ◽  
Systemic Lupus ◽  
Autoantibody Production ◽  
Increased Risk ◽  
Reported Health

Background Systemic lupus erythematosus (SLE) is an autoimmune disease with presence of autoantibodies and characteristic multi-organ involvement. Relatives of SLE patients have an increased risk of autoantibody production and autoimmune diseases. Methods In 2001, 226 first degree relatives (FDRs) of a population-based cohort of SLE patients were examined for the prevalence of autoantibodies and self-reported health complaints. In 2013, 143 FDRs were re-investigated and deceased’s medical records were examined. Results Participants and non-participants were comparable regarding baseline characteristics, while deceased FDRs were older than participants, but with comparable ANA status. ANA status at baseline correlated to ANA status at follow-up. At follow-up, two FDRs reported SLE and 15 FDRs other autoimmune diseases. No observation at baseline alone could predict self-reported health. During follow-up 33 died at median age 76 years. Three deceased FDRs were diagnosed with an autoimmune disease. Conclusion The study showed that FDRs of SLE patients have an increased prevalence of ANA compared to healthy controls. The prevalence increased during follow-up, and ANA positive FDRs at baseline were prone to be ANA positive at follow-up. ANA positive FDRs had more self-reported autoimmune diseases, including SLE and rheumatoid arthritis, than reported from other population-based investigations.

Childhood Systemic Lupus Erythematosus: Presentation, management and long-term outcomes in an Australian cohort

Lupus ◽  
2022 ◽  
pp. 096120332110697
Author(s):  
Megan P Cann ◽  
Anne M Sage ◽  
Elizabeth McKinnon ◽  
Senq-J Lee ◽  
Deborah Tunbridge ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Incidence Rate ◽  
Lupus Erythematosus ◽  
Renal Involvement ◽  
Damage Index ◽  
Organ Damage ◽  
Systemic Lupus ◽  
End Organ Damage ◽  
American College Of Rheumatology

Objectives Systemic Lupus Erythematosus (SLE) is a serious autoimmune disease often resulting in major end-organ damage and increased mortality. Currently, no data exists focussing on the presentation, long-term management and progression of SLE in the Australian paediatric population. We conducted the first Australian longitudinal review of childhood SLE, focussing on response to treatment and outcomes. Methods Detailed clinical and laboratory data of 42 children diagnosed with SLE before 16 years from 1998 to 2018 resident in Western Australia was collected. Data was collected at diagnosis and key clinical review time points and compared using the Systemic Lupus Collaborating Clinics (SLICC) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) criteria. End organ damage was assessed against Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Incidence rates of disease complications and end organ damage were determined. Results Of the 42 children, 88% were female with average age at diagnosis of 12.5 years. Indigenous Australians were over represented with an incidence rate 18-fold higher than non-Indigenous, although most children were Caucasian, reflecting the demographics of the Australian population. Median duration of follow-up was 4.25 years. On final review, 28.6% had developed cumulative organ damage as described by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (incidence rate: 0.08/PY (95% CI 0.04–0.14)), and one child died. Twenty-nine children had renal involvement (incidence rate: 0.38/PY (95% CI 0.26–0.56)). Of the 27 patients with biopsy proven lupus nephritis, 70% had Class III or IV disease. Average length of prednisolone use from diagnosis was 32.5 months. Hydroxychloroquine ( n = 36) and mycophenolate mofetil ( n =21) were the most widely used steroid sparing agents. 61.9% received rituximab and/or cyclophosphamide. Conclusion This is the first longitudinal retrospective review of Australian children with SLE, with a markedly higher incidence in Indigenous children. Although improving, rates of end organ complications remain high, similar to international cohort outcomes. Longitudinal multi-centre research is crucial to elucidate risk factors for poor outcomes, and identifying those warranting early more aggressive therapy.

scholarly journals Incidence, Risk Factors, and Outcomes of Neonatal Renal Vein Thrombosis in Ontario: Population-Based Cohort Study

Kidney360 ◽  
2020 ◽  
Vol 1 (7) ◽  
pp. 640-647 ◽  
Author(s):  
Allison C. Ouellette ◽  
Elizabeth K. Darling ◽  
Branavan Sivapathasundaram ◽  
Glenda Babe ◽  
Richard Perez ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Renal Vein Thrombosis ◽  
Population Based ◽  
Long Term Outcomes ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Neonatal Renal Vein Thrombosis

BackgroundThere are limited data at a population level on the burden, risk factors, and long-term outcomes of neonatal renal vein thrombosis (nRVT). We conducted a population-based cohort study to understand the epidemiology and outcomes of nRVT over a 25-year period in Ontario.MethodsUsing linked administrative health databases, all hospitalized neonates ≤28 days born in Ontario between 1992 and 2016 with nRVT were identified. The primary outcome was to calculate the incidence of nRVT and trend over time in Ontario. We also determined the risk factors associated with nRVT as well as the risk of long-term outcomes after nRVT, including CKD, ESKD, all-cause mortality, and hypertension (HTN) compared with the healthy neonatal population without nRVT.ResultsThe annual incidence rate of nRVT was 2.6 per 100,000 live births (n=85). Presence of respiratory distress syndrome (OR, 8.01; 95% CI, 4.90 to 13.1), congenital heart disease (OR, 9.1; 95% CI, 5.05 to 16.4), central venous catheterization (OR, 3.9; 95% CI, 1.89 to 7.93), maternal preeclampsia (OR, 2.8; 95% CI, 1.6 to 4.79), and maternal diabetes (OR, 2.36; 95% CI, 1.36 to 4.07) conferred the highest risk for nRVT. Over a median follow-up of 15 years and after adjusting for confounders, neonates with nRVT versus the comparator cohort had a 15.5-fold risk of CKD, HTN, or death (n=49 [58%] versus n=90,050 [3%]; 95% CI, 11.7 to 20.6); 12.3-fold increased risk of CKD or death (n=39 [46%] versus n=32,016 [1%]; 95% CI, 8.9 to 16.8); and a 15.7-fold increased risk of HTN (n=33 [39%] versus n=64,458 [2%]; 95% CI, 11.1 to 21.1). None of the nRVT cohort developed ESKD. The median time to composite outcome of CKD, HTN, or death was 11.1 years.ConclusionsPatients with a history of nRVT remain at higher risk than the general population for long-term morbidity or mortality, indicating the need for long-term follow-up.

Morbidity and mortality in adult-onset IgA vasculitis: a long-term population-based cohort study

Rheumatology ◽  
2021 ◽  
Author(s):  
Johannes Nossent ◽  
Warren Raymond ◽  
Helen Isobel Keen ◽  
David Preen ◽  
Charles Inderjeeth
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Premature Death ◽  
Population Based ◽  
Increased Risk ◽  
Serious Infections ◽  
Comorbidity Index ◽  
Independent Risk Factors

Abstract Objectives With sparse data available, we investigated mortality and risk factors in adults with IgAV. Methods Observational population-based cohort study using state-wide linked longitudinal health data for hospitalised adults with IgAV (n = 267) and matched comparators (n = 1080) between 1980-2015. Charlson comorbidity index (CCI) and serious infections (SI) were recorded over an extensive lookback period prior to diagnosis. Date and causes of death were extracted from WA Death Registry. Mortality rate (deaths/1000 person-years) ratios (MRR) and hazard ratio (HR) for survival were assessed. Results During 9.9 (±9.8) years lookback patients with IgAV accrued higher CCI scores (2.60 vs1.50 p &lt; 0.001) and had higher risk of SI (OR 8.4, p &lt; 0.001), not fully explained by CCI scores. During 19 years follow-up, the rate of death in Patients with IgAV (n = 137) was higher than in comparators (n = 397) (MRR 2.06, CI 1.70-2.50, p &lt; 0.01) and the general population (SMRR 5.64, CI 4.25, 7.53, p &lt; 0.001). Survival in IgAV was reduced at five (72.7 vs. 89.7%) and twenty years (45.2% vs. 65.6%) (both p &lt; 0.05). CCI (HR1.88, CI:1.25 - 2.73, p = 0.001), renal failure (HR 1.48, CI: 1.04 - 2.22, p = 0.03) and prior SI (HR 1.48, CI:1.01 – 2.16, p = 0.04) were independent risk factors. Death from infections (5.8 vs 1.8%, p = 0.02) was significantly more frequent in patients with IgAV. Conclusions Premorbid comorbidity accrual appears increased in hospitalized patients with IgAV and predicts premature death. As comorbidity does not fully explain the increased risk of premorbid infections or the increased mortality due to infections in IgAV, prospective studies are needed.

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