Predictors for early readmission in patients hospitalized with new onset pediatric lupus nephritis

Objective The objective is to determine the 30-day hospital readmission rate following a hospitalization due to pediatric lupus nephritis of recent onset and characterize the risk factors associated with these early readmissions. Methods The study included 76 children hospitalized from 01/01/2008 to 4/30/2017 due to a new diagnosis of lupus nephritis. We calculated the 30-day hospital readmission rate and compared the characteristics of the patients that were readmitted to patients that were not readmitted using univariable and multivariable analysis. Results The 30-day readmission rate was 17.1%. Factors that predicted hospital readmission in unavailable analysis were male gender (38.5 vs 14.3%, p = 0.04), not receiving pulse steroids (30.8 vs 3.2%, p = < .001), receiving diuretic treatment (69.2 vs 34.9%, p = .02), receiving albumin infusions (46.2 vs 12.7%, p = .004), stage 2 hypertension on day one of admission (76.9 vs 41.3%, p = .02), a higher white blood cell count on discharge (13.7 × 103/mm3 vs 8.8 × 103/mm 3 , p = .023), need for non-angiotensin converting enzyme (ACE) antihypertensive drugs (76.9 vs 46%, p = .042), and being discharged on nonsteroidal anti-inflammatory drugs (NSAIDs) (23.1 vs 4.8%, p = .025). Multivariable analysis demonstrated an increased risk of readmission for patients not treated with intravenous pulse methylprednisolone (IVMP) (OR = 17.5 (1.81–168.32) p = .013), and for those who required intravenous albumin assisted diuresis for hypervolemia (OR=6.25 (1.29–30.30) p = .022). Conclusion In all, 17% of children hospitalized due to new onset lupus nephritis were readmitted within 30 days of discharge. Absence of IVMP and receiving intravenous albumin assisted diuresis during initial hospitalization increase the risk of early readmission in new onset pediatric lupus nephritis.

Clinical manifestations, prognosis, and treat-to-target assessment of pediatric lupus nephritis

Background Pediatric lupus nephritis (pLN) is one of the most refractory secondary kidney diseases in childhood. The treat-to-target (T2T) strategy has become the standard treatment for systemic lupus erythematosus (SLE). This study reviewed clinical features, overall remission status, and factors affecting prognosis, to guide pLN management according to T2T strategy. Methods This single-center retrospective study studied 220 children diagnosed with LN from January 2012 to December 2018, with > 6-month follow-up data on 173 and complete data on 137 patients. Primary outcome was treatment failure (deterioration or no response) at the latest follow-up. Results The most common pLN manifestation was proteinuria (81.36%). Females presented more often with rash (P<0.001) and alopecia (P=0.026) than males. Class IV LN (33.33%) was the most common grade on kidney biopsy. Median follow-up was 27.20 months (IQR, 15.78–44.45 months). One-, 3-, and 5-year cumulative overall survival rates were 93.5%, 87.8%, and 86.5%, respectively. The 5-year cumulative kidney survival rate was 97.1%. Regarding initial therapy, efficacy of corticosteroids combined with immunosuppressive agents was significantly better than corticosteroids alone (P=0.010). Factors with P<0.05 in univariate analysis, including hypoalbuminemia, higher SCr at diagnosis, lower eGFR at diagnosis, anti-dsDNA positivity, heavy proteinuria, hypertension, nervous-system involvement, treatment non-compliance, and SLEDAI-2K score, were used for logistic regression analysis. Logistic regression analysis showed hypertension (OR=0.845, P=0.011), nervous-system involvement (OR=4.240, P=0.005), treatment non-compliance (OR=6.433, P=0.001), and lower estimated glomerular filtration rate at diagnosis (OR=1.020, P=0.021) affected prognosis. At end of follow-up, 34.31% achieved varying levels of remission, and 8.76% were in low disease activity state (LDAS). Conclusions pLN usually presented with proteinuria, and class IV LN was the dominant pathology. Hypertension, nervous-system involvement, treatment non-compliance, and lower eGFR at diagnosis were independent risk factors for poor prognosis of kidney outcomes. Compared with renal remission rate and cumulative overall survival rate, the proportion of targets achieved was not ideal, suggesting T2T strategy should be used to guide pLN management. Graphical abstract

Rituximab use in pediatric systemic lupus erythematosus: Indications, efficacy and safety in an Indian cohort

Introduction: Children with systemic lupus erythematosus have a more challenging and difficult course as compared to their adult counterparts. Today, the aim of therapy for any child with lupus is to keep the child in a state of sustained remission with minimal or no use of steroids. This laudable goal is often difficult to achieve for the child with lupus. In addition to the use of disease modifying agents, sometimes in combination, Rituximab (RTX) is also used as an off-label indication to manage such patients. Objectives: To study the use, efficacy and safety of RTX in a cohort of patients with pediatric lupus followed at a single tertiary level center in Northern India. Methods: This paper is a retrospective review looking at the use of RTX in children with systemic lupus at a tertiary level pediatric rheumatology center in North India over a period of seventeen years. This paper describes the indications, use, efficacy and safety of RTX in childhood systemic lupus erythematosus. Results: RTX was used in 17 of 225 pediatric lupus patients (7.5%), with the most common indication being resistant renal disease (53%). Significant improvement was seen in all domains studied: The mean SLEDAI was 16.25 prior to RTX and reduced to 1.43 six months after the RTX (p value 0.001), steroid use dropped from 100% pre- RTX to 33% at 2 years, there was a sustained reduction in proteinuria in the patients with nephritis from a mean urine spot protein creatinine ratio of 3.1 pre RTX to 0.4 at one year post RTX (p= .006). Finally, 82% of the children had no flare during the follow up (median 24 months). No patient had any adverse event. Conclusions: This study confirms that RTX is very effective in childhood lupus and can be safely used even in a country with a very high burden of infectious diseases. This data adds to the scarce literature in this area from the developing world.

Disease activity and health-care utilization among young adults with childhood-onset lupus transitioning to adult care: data from the Pediatric Lupus Outcomes Study

Background Individuals with childhood-onset systemic lupus erythematosus (cSLE) must transfer from pediatric to adult care. The goal of this study was to examine disease activity and health-care utilization among young adults with cSLE who are undergoing or have recently completed the transfer to adult care. Methods The Pediatric Lupus Outcomes Study (PLOS) is a prospective longitudinal cohort study of young adults aged 18–30 diagnosed with cSLE. We conducted a cross-sectional analysis comparing 47 participants under the care of pediatric rheumatologists to 38 who had completed transfer to adult care. Demographics, disease manifestations, health- care utilization and transition readiness were compared between groups. Results Those in the post-transfer group had significantly lower medication usage and were less likely to have seen a rheumatologist in the past year. Disease manifestations, flare rates, and hospitalizations were similar between groups. Nearly a quarter of patients who had transferred to adult care reported difficulties with the process. Conclusion Post-transfer patients had lower health-care utilization as evidenced by less medication usage and lack of rheumatology follow-up, in spite of the fact that disease activity was similar in both groups. Future studies will assess longitudinal changes in disease activity and damage in this population.

Understanding patient-provider discordance in adolescents with lupus: The role of pain and antidepressant medication use

The current study examines depression and pain as potential contributors to patient-provider discordance in the assessment of lupus disease activity. The study conducted a secondary analysis of data obtained from the Childhood Arthritis and Rheumatology Research Alliance registry, with N = 859 adolescent participants. Assessments of pain, disease activity, and antidepressant medication use were collected from the patient and provider. Results indicated that depression might be underdiagnosed in pediatric lupus patients. While psychotropic medication and pain scores were independently related to greater patient-provider discordance regarding health status, pain mediated this relationship. Implications for treatment outcomes are discussed.

Double negative T cells, a potential biomarker for systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease that is a challenge to diagnose and treat. There is an urgent need for biomarkers to help define organ involvement, and more effective therapies. A unique population of T cells, the CD3+CD4−CD8− (DNeg) cells, is significantly increased in lupus patients. Twenty-seven cases (53%) of pediatric SLE patients had elevated DNeg cells in their peripheral blood, which correlated with kidney function (R2 = 0.54). Significant infiltration of DNeg cells was observed in both adult and pediatric lupus kidneys by immunofluorescence. For the first time, this study provides direct evidence that DNeg cells facilitate kidney injury in preclinical 8-week-old MRL/lpr lupus mice. In lupus mice, the increase in DNeg cells tracked with worsening disease and correlated with kidney function (R2 = 0.85). Our results show that DNeg cells per se can cause kidney dysfunction, increase in number with increase in disease pathology, and could serve as a potential biomarker.

Pattern of Indirect Immunofluorescence Assay Antinuclear Antibody in Pediatric Lupus Nephritis

Objective: To determine the association between Anti-Nuclear Antibody (ANA) pattern in pediatric Systemic Lupus Erythematosus (SLE) patients and proteinuria as a sign of renal involvement in SLE. Methods: This was a cross-sectional study, using data from medical records involving 89 newly diagnosed with SLE (aged ≤ 18 years) in Department of Child Health Dr. Hasan Sadikin General Hospital, Bandung, from January 1st 2018 to June 30th 2019. Data of ANA pattern and proteinuria were collected from medical record. ANA pattern was examined by Immunofluorescence Assay (IFA) method. Chi-square was used to analyze the association between ANA pattern and proteinuria as a sign of renal involvement in pediatric SLE patients. Results: There were 89 patients, consisting of 7 male (7.9%) and 82 female (92.%) with median age of 14 (IQR=12-16). There were only 44 pattern of ANA as follow: homogenous 56.8%, speckled 36.4%, and nucleolar 6.8%. However, there is no significant association between homogenous pattern with proteinuria events (p=0.831). Conclusions: Homogenous pattern was the most frequent ANA pattern in children with SLE, and the pattern has no association with proteinuria events.