Population-wide long-term study of incidence, renal failure, and mortality rates for lupus nephritis.

OBJECTIVE: Given limited regional data, we investigate the state-wide epidemiology, renal and patient outcomes for lupus nephritis (LN) in Western Australia (WA). METHODS: Patients hospitalized with incident SLE (≥2 diagnostic codes in the state-wide WA Health Hospital Morbidity Data Collection) in the period 1985-2015 were included (n = 1480). LN was defined by the presence of glomerulonephritis and/or raised serum creatinine. Trends over three study decades for annual incidence rate (AIR)/100.000 population, mortality (MR), and end-stage renal disease (ESRD) rates/100 person years were analyzed by least square regression and compared with a matched control group (n = 12 840). RESULTS: Clinical evidence of LN developed in 366 SLE patients (25.9%) after a median disease duration of 10 months (IQR 0-101) with renal biopsy performed in 308 (84.2%). The AIR for LN (0.63/100.000) did not change significantly over time (R2 = .11, p = .85), while point prevalence reached 11.9/100.000 in 2015. ESRD developed in 14.1% (n = 54) of LN patients vs. 0.2% in non-LN SLE patients and 0.05% in controls (all p ≤ 0.01). ESRD rates increased over time in LN patients (0.4 to 0.7, R2 = .52, p = .26). The odds ratio for death was 8.81 (CI 3.78-22.9) for LN and 6.62 (CI 2.76-17.9) for non-LN SLE patients compared to controls and MR for LN patients increased over time (1.3 to 2.2, R2 = .84, p = .26). CONCLUSIONS: The incidence rate of LN in WA remained unchanged over 30 years. A lack of improvement in renal failure and mortality rates illustrates the pressing need for better long-term treatment options and/or strategies in LN.

Demographic distribution analysis of different glomerular diseases in Southwest China from 2008 to 2022.

BACKGROUND: Environmental and lifestyle factors play an etiological role in the pathogenesis of different glomerular diseases. Thus, exploring the epidemic characteristics of renal disease in different nationalities and regions is important. MATERIALS AND METHODS: Patients who underwent renal biopsy from October 2008 to October 2022 were included. The proportion and change tendency of glomerular diseases and the differences between the sexes and different ages and races were analyzed. RESULTS: There were 15,146 cases of glomerular diseases (98.5%), involving 7538 males (49.8%) and 7608 females (50.2%). The mean age was 37.0 years (range 0-80 years). The proportion of membranous nephropathy (MN) and diabetic nephropathy (DN) showed an increased trend. The most common primary glomerulonephritis (PGN) was IgA nephropathy (IgAN, 44.6%), followed by minimal-change disease (MCD, 24.3%) and MN (15.4%). Lupus nephritis (LN, 30%) accounted for the largest proportion of SGNs, followed by Henoch-Schonlein purpura nephritis (HSPN, 20.9%) and DN (19.8%). Compared with adults aged 18-60 years old, MCD and HSPN were more common in children and MN and DN in elderly individuals, statistically significant differences. Additionally, the sex and age distribution of PGN and SGN between the Tibetan and Han populations differed significantly, whereby LN was higher in the Han population and HSPN in the Tibetan population. CONCLUSION: The distribution of glomerular diseases showed age, sex and race differences. This research will be beneficial for providing epidemiological evidence for clinical diagnosis, disease prevention and public health decision-making.

Pregnancy Outcomes in a Diverse US Lupus Cohort.

OBJECTIVE: Although the population of patients with systemic lupus erythematosus (SLE) is racially and ethnically diverse, many study populations are homogeneous. Further, data are often lacking on critical factors, such as antiphospholipid antibodies (aPLs). We investigated live birth rates in patients with SLE at Kaiser Permanente Northern California, including race and ethnicity and aPL data. METHODS: Electronic health records of pregnancies with outcomes observed from 2011 to 2020 were identified among patients with SLE. Prevalent SLE was defined as two or more International Classification of Diseases-coded visits seven or more days apart before the last menstrual period. We summarized patient characteristics, medication orders, health care use, and medication use. Pregnancy outcomes (live birth, stillbirth, spontaneous abortion, ectopic pregnancy, and molar pregnancy) were presented overall and stratified by race and ethnicity, aPL status, and nephritis history. RESULTS: We identified 657 pregnancies among 453 patients with SLE. The cohort was diverse, reflecting the Northern California population (27% Asian, 26% Hispanic, 26% Non-Hispanic White, 13% Non-Hispanic Black, 5% multiracial, and approximately 2% Pacific Islander and Native American). Approximately 74% of observed pregnancies ended in live birth, 23% resulted in spontaneous abortion, 2% were ectopic or molar pregnancies, and <1% were stillbirths. There was limited variability in live births by race and ethnic group (72%-79%), aPL status (69.5%-77%), and nephritis history (71%-75%). CONCLUSION: Our findings are consistent with previous studies; however, some methodologic differences may yield a range of live birth rates. We found that approximately 74% of pregnancies in patients with SLE ended in live birth, with modest variability in spontaneous abortion by race and ethnicity, nephritis history, and aPL status.

Herpes zoster in lupus nephritis: experience on 292 patients followed up for 15 years.

Objectives: To evaluate the prevalence, incidence, and predictors of herpes zoster (HZ) development in lupus nephritis (LN). Methods: This retrospective study included 292 LN patients to determine HZ incidence during the last decades and its correlation with LN activity. LN patients with HZ were matched with LN patients without HZ in a 1:2 ratio based on sex, age, year of LN diagnosis, and LN histological class at kidney biopsy to assess HZ risk factors. Statistical tests included t-test, U-test, and Fisher's test. Univariate and multivariate logistic regression analyses were conducted to identify potential risk factors. Results: HZ occurred after LN diagnosis in 66 patients (prevalence 22.6%) with an average of 8.7 years (range 0.2-28.4 years). Although with the potential limitations of the retrospective nature and the extensive duration of the study, the incidence of HZ was 15.6/1,000 person-years, increasing from 6.9 before 1980 to 16.0 in the 1990s and 43.9 after 2010. HZ onset was unrelated to LN activity. LN was active in 43% of cases and quiescent in the other 57% of cases at HZ diagnosis. The percentage of patients who developed lupus flares during the year after HZ (18.9%) was not different from that which occurred during the year before HZ (17.2%, p = 0.804). After excluding confounding factors through matching, the univariate analysis suggested that cyclosporin during induction therapy (p = 0.011) and higher cumulative doses of glucocorticoids (GCs; >50 g, p = 0.004), cyclophosphamide (CYC; >5 g, p = 0.001), and mycophenolate mofetil (MMF > 1,000 g, p = 0.007) predisposed patients to HZ. Univariate and multivariate analyses revealed a protective role of azathioprine (p = 0.008) and methylprednisolone pulses (p = 0.010) during induction therapy. Conclusions: HZ occurs unpredictably throughout the course of LN, underscoring the importance of continuous monitoring for these patients. In addition, the incidence of HZ seems to have increased in recent decades. Induction therapy with azathioprine and methylprednisolone pulses appears to provide protection, while higher cumulative doses of GCs, CYC, and MMF increase susceptibility.

Anti-C1q como Marcador de Nefritis Lúpica / Anti-C1q as Lupus Nephritis Marker

Introducción: Los autoanticuerpos anti-C1q han sido propuestos como un marcador útil en el lupus eritematoso sistémico por su asociación con la nefritis lúpica. Objetivo: Determinar la prevalencia de anti-C1q en pacientes con lupus eritematoso sistémico y otras enfermedades reumáticas para la evaluar la asociación con la nefropatía lúpica. Métodos: Se incluyeron 179 pacientes con lupus eritematoso sistémico y 82 con otras enfermedades reumáticas. La nefritis lúpica fue diagnosticada en 70 (39 por ciento) de los pacientes con lupus eritematoso sistémico. Los anticuerpos anti-C1q IgG se determinaron por ELISA. Las asociaciones se evaluaron por análisis de regresión logística. Resultados: La prevalencia de anti-C1q fue de 37 poe ciento (66/179) en los pacientes con lupus eritematoso sistémico y de 9 por ciento (7/82) en controles (OR = 6,3; IC 95 por ciento 2,8-14,1; p < 0,001). El anti-C1q fue asociado con proteinuria (OR = 2,6; IC 95 por ciento 1,2-6,0; p < 0,022); eritrosedimentación elevada (OR = 3,2; IC 95 por ciento 1,5-6,7; p < 0,003) y anti-DNAdc (OR = 3,9; IC 95 por ciento 1,7-9,1; p < 0,002). En el modelo de regresión logística ajustado para demografía y anti-DNAdc, aunque la OR del anti-C1q para la nefritis fue 2 veces más alta que en ausencia del anti-C1q, solo se aproximó a la significación estadística. La positividad simultánea de anti-C1q y anti-DNAdc estuvo asociada a la nefritis lúpica (OR = 4,3; IC 95 por ciento 1,9-9,5; p < 0,001). Conclusiones: El anti-C1q se presentó con mayor frecuencia en pacientes con lupus eritematoso sistémico que en los controles. El anti-C1q combinado con anti-DNAdc resultó fuertemente asociado a la nefritis lúpica(AU)

Introducción: Anti-C1q autoantibodies have been proposed as useful marker in systemic lupus erythematosus due to their association with lupus nephritis. Objective: To determine the prevalence of anti-C1q in patients with systemic lupus erythematosus and other rheumatic diseases to evaluate the association with lupus nephropathy. Methods: One hundred seventy-nine patients with systemic lupus erythematosus and 82 with other rheumatic diseases were included. Lupus nephritis was diagnosed in 70 (39percent) of patients with systemic lupus erythematosus. Anti-C1q IgG antibodies were determined by ELISA. Associations were evaluated by logistic regression analysis. Results: The prevalence of anti-C1q was 37percent (66/179) in patients with systemic lupus erythematosus and 9percent (7/82) in controls (OR = 6.3; 95percent CI 2.8-14). .1; p < 0.001). Anti-C1q was associated with proteinuria (OR = 2.6; 95percent CI 1.2-6.0; p < 0.022); elevated erythrocyte sedimentation rate (OR = 3.2; 95percent CI 1.5-6.7; p < 0.003) and anti-dsDNA (OR = 3.9; 95percent CI 1.7-9.1; p < 0.002). In the logistic regression model adjusted for demographics and anti-dsDNA, although the OR of anti-C1q for nephritis was 2-fold higher than in the absence of anti-C1q, it only approached statistical significance. Simultaneous positivity of anti-C1q and anti-dsDNA was associated with lupus nephritis (OR = 4.3; 95percent CI 1.9-9.5; p < 0.001). Conclusions: Anti-C1q occurred more frequently in patients with systemic lupus erythematosus than in controls. Anti-C1q combined with anti-dsDNA was strongly associated with lupus nephritis(AU)

Years of life lost and long-term outcomes due to glomerular disease in a Southeast Asian Cohort.

Death and end-stage kidney disease (ESKD) are major outcomes of glomerular disease. (GD) The years of potential life lost (YLL) may provide additional insight into the disease burden beyond death rates. There is limited data on premature mortality in GD. In this retrospective observational cohort study, we evaluated the mortality, ESKD rates, and YLL in Thais with biopsy-proven GD. The mortality and combined outcome rates were determined by log-rank test and ESKD by using a competing risk model. YLL and premature life lost before age 60 were calculated for different GD based on the life expectancy of the Thai population. Patients with GD (n = 949) were followed for 5237 patient years. The death rate and ESKD rates (95%CI) were 4.2 (3.7-4.9) and 3.3 (2.9-3.9) per 100 patient-years, respectively. Paraprotein-related kidney disease had the highest death rate, and diabetic nephropathy had the highest ESKD rate. Despite not having the highest death rate, lupus nephritis (LN) had the highest YLL (41% of all GD) and premature loss of life before age 60. In conclusion, YLL provided a different disease burden assessment compared to mortality rates and identified LN as the major cause of premature death due to GD in a Southeast Asian cohort.

Presentation and outcome of pediatric lupus nephritis from a large single centre contemporary cohort in Eastern India.

BACKGROUND: We present clinical, biochemical, and histopathological characteristics and treatment outcomes of biopsy proven childhood lupus nephritis (LN) from a low/middle income setting treated in the current era of increased use of Mycophenolate Mofetil (MMF) and biologics. METHODS: Retrospective observational study of children (1-18 years) with biopsy proven LN treated from 01.01.2010 to 31.01.2020. RESULTS: 60 children met our inclusion criteria (80%, n = 48 were females). The median age at diagnosis was 11 (IQR: 9-12) years. The most common extra-renal manifestation was mucocutaneous (n = 54, 90%) and the most common kidney manifestation was edema (n = 50, 83.3%). The median 24-h urinary protein excretion was 1117.8 (IQR: 795.4-1941.7) mg/m2/day with 67% (n = 40) having nephrotic range proteinuria (>1000 mg/m2/day). 75% (n = 45) children had eGFR <90 mL/min/1.73 m2 (median eGFR = 71; IQR: 56-90 mL/min/1.73 m2). Anti-Nuclear Antibody was positive in all, both complement three and four were low in 82% (n = 49) and anti-double stranded DNA antibodies were positive in 63% (n = 38). 85% (n = 51) had proliferative LN with majority being class IV (57%, n = 34). All children received steroids for induction therapy. MMF was given as the sole induction agent in 48% (n = 29) and cyclophosphamide in 27% (n = 16). Rituximab was added in 17% (n = 10) as a rescue agent. Median follow up duration was 50 (IQR: 28-82) months. Six children (10%) died as a result of serious infections and none of them had shown complete response (CR). Out of the 52 children who had a follow up duration of at least 2 years, CR was achieved in 46 children (88%) and partial response (PR) or no response (NR) in three children (6%) each. Although children who were in CR/PR at last follow up had lower proteinuria, higher eGFR, and lower histopathology activity index at onset; low numbers in the NR group precluded us from subjecting them to any statistical correlation tests. 36% (n = 22) of children developed 36 episodes of renal flares with overall incidence of 0.14/person-year. CONCLUSION: Our study on a contemporary cohort of childhood LN highlights the importance of achieving CR and its feasibility.

Risk and Factors associated with disease manifestations in systemic lupus erythematosus - lupus nephritis (RIFLE-LN): a ten-year risk prediction strategy derived from a cohort of 1652 patients.

Objectives: Lupus nephritis (LN) remains one of the most severe manifestations in patients with systemic lupus erythematosus (SLE). Onset and overall LN risk among SLE patients remains considerably difficult to predict. Utilizing a territory-wide longitudinal cohort of over 10 years serial follow-up data, we developed and validated a risk stratification strategy to predict LN risk among Chinese SLE patients - Risk and Factors associated with disease manifestations in systemic Lupus Erythematosus - Lupus Nephritis (RIFLE-LN). Methods: Demographic and longitudinal data including autoantibody profiles, clinical manifestations, major organ involvement, LN biopsy results and outcomes were documented. Association analysis was performed to identify factors associated with LN. Regression modelling was used to develop a prediction model for 10-year risk of LN and thereafter validated. Results: A total of 1652 patients were recruited: 1382 patients were assigned for training and validation of the RIFLE-LN model; while 270 were assigned for testing. The median follow-up duration was 21 years. In the training and validation cohort, 845 (61%) of SLE patients developed LN. Cox regression and log rank test showed significant positive association between male sex, age of SLE onset and anti-dsDNA positivity. These factors were thereafter used to develop RIFLE-LN. The algorithm was tested in 270 independent patients and showed good performance (AUC = 0·70). Conclusion: By using male sex, anti-dsDNA positivity, age of SLE onset and SLE duration; RIFLE-LN can predict LN among Chinese SLE patients with good performance. We advocate its potential utility in guiding clinical management and disease monitoring. Further validation studies in independent cohorts are required.

Clinicopathologic characteristics and outcomes of late onset lupus nephritis: a single centre experience.

Systemic Lupus Erythematosus (SLE) occurs in the reproductive age group. Renal involvement occurs less frequently in late-onset SLE than in reproductive-age SLE patients. Here, we aimed to study the clinical, serological and histopathological characteristics of late-onset lupus nephritis (LN). Late-onset LN was defined as disease onset after 47 years of age, corresponding to the average menopausal age. Records of biopsy proven late-onset lupus nephritis patients diagnosed between June 2000 and June 2020 were reviewed. Late-onset LN constituted 53 of 4420 patients (1.2%) biopsied during the study period. Females represented 90.65% of the cohort. Mean age of the cohort was 49.5 ± 7.05 years at the time of SLE diagnosis while its renal presentation was delayed by median duration of 10 months (IQR 3-48 months). Renal failure was present in 28 patients (52.8%) with acute kidney injury (AKI) (28.3%, n = 15) as the most common presentation. On histopathological analysis, class IV was observed in 23 patients (43.5%), crescents were observed in one-third cases and lupus vasculopathy in 4 patients (7.5%). All patients received steroids. Majority of patients (43.3%; n = 23) received Euro lupus protocol for induction. On median follow up duration of 82 months, renal flares were noted in 9 patients (17%) and 8 patients (15.1%) became dialysis dependent. Among 11 patients (21%) with infectious complications, 7 patients (13.2%) suffered from tuberculosis. Infections caused three-fourth of the deaths. Late-onset lupus nephritis is rare and presents as renal failure in majority. Renal biopsy affects the clinical decision of judicious use of immunosuppression which is imperative due to high rate of infections in this cohort.

Usefulness of the lupus low disease activity state as a treatment target in childhood-onset SLE.

OBJECTIVE: Treat-to-target (T2T) strategies are advocated to improve prognosis in childhood-onset SLE (cSLE). Proposed T2T states include SLEDAI score of <4 (SLEDAI-LD), limited corticosteroid use (low-CS), and lupus low disease activity state (LLDAS). We sought to compare T2T states for their association with cSLE prognosis under consideration of relevant disease characteristics such as pre-existing damage, race and lupus nephritis (LN). METHODS: Longitudinal data from 165 patients enrolled in the Cincinnati Lupus Registry were included. LN presence was based on renal biopsy, and patients were followed up until 18 years of age. RESULTS: The 165 patients (LN: 45, white: 95) entered the registry within a median of 0 (IQR: 0-1) year post diagnosis and were followed up for a median of 4 (IQR: 2-5) years during which 80%, 92% and 94% achieved LLDAS, low-CS and SLEDAI-LD. Patients with LN were significantly less likely to achieve any T2T state (all p<0.03) and required a significantly longer time to reach them (all p<0.0001). Over the study period, patients maintained low-CS, SLEDAI-LD or LLDAS for a median of 76% (IQR: 48%-100%), 86% (IQR: 55%-100%) or 39% (IQR: 13%-64%) of their follow-up. Significant predictors of failure to maintain LLDAS included LN (p≤0.0062), pre-existing damage (p≤0.0271) and non-white race (p≤0.0013). There were 22%, 20% and 13% of patients who reached SLEDAI-LD, CS-low and LLDAS and nonetheless acquired new damage. Patients with LN had a higher risk of new damage than patients without LN even if achieving low-CS (p=0.009) or LLDAS (p=0.04). CONCLUSIONS: Patients with LN and pre-existing damage are at higher risk of increased future damage acquisition, even if achieving a T2T state such as LLDAS. Among proposed common T2T states, the LLDAS is the hardest to achieve and maintain. The LLDAS may be considered the preferred T2T measure as it conveys the highest protection from acquiring additional disease damage.

Prevalence and clinical significance of ANCA positivity in lupus nephritis: a case series of 116 patients and literature review.

The prevalence and clinical significance of anti-neutrophil cytoplasmic antibodies [ANCAs] in patients with lupus nephritis [LN] is not fully elucidated. Our aim was to determine whether LN patients with ANCA positivity had different clinicopathological features and outcomes compared to ANCA-negative patients. METHODS: Among our LN patients we retrospectively selected those who underwent ANCA testing the day of the kidney biopsy and before the start of induction treatment. Clinical/histopathological features at kidney biopsy and renal outcome of ANCA-positive patients were compared with those of ANCA-negative subjects. RESULTS: We included 116 Caucasian LN patients in the study; 16 patients [13.8%] were ANCA-positive. At kidney biopsy, ANCA-positive patients presented more frequently with an acute nephritic syndrome than ANCA-negative ones; the difference however does not reach statistical significance [44 vs. 25%, p = 0.13]. At histological evaluation, proliferative classes [100% vs 73%; p = 0.02], class IV [68.8% vs 33%; p < 0.01] and necrotizing tuft lesions [27 vs 7%, p = 0.04] were more frequent, and the activity index was higher [10 vs 7; p = 0.03] in ANCA-positive than in ANCA-negative patients. Despite worse histological features, after a 10-year observation period, there were no significant differences in the number of patients with chronic kidney function impairment (defined as eGFR < 60 mL/min per 1.73 m2) between the ANCA-positive and negative groups [24.2 vs 26.6%, p = 0.9]. This could be the result of the more aggressive therapy, with rituximab plus cyclophosphamide, that ANCA-positive patients received more frequently than ANCA-negative ones [25 vs. 1.3%, p < 0.01]. CONCLUSIONS: ANCA-positive LN patients frequently have histological markers of severe activity (proliferative classes and high activity index) that require timely diagnosis and aggressive therapy to limit the development of irreversible chronic kidney damage.

Childhood-Onset Lupus Nephritis in the Childhood Arthritis and Rheumatology Research Alliance Registry: Short-Term Kidney Status and Variation in Care.

OBJECTIVE: The goal was to characterize short-term kidney status and describe variation in early care utilization in a multicenter cohort of patients with childhood-onset systemic lupus erythematosus (cSLE) and nephritis. METHODS: We analyzed previously collected prospective data from North American patients with cSLE with kidney biopsy-proven nephritis enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry from March 2017 through December 2019. We determined the proportion of patients with abnormal kidney status at the most recent registry visit and applied generalized linear mixed models to identify associated factors. We also calculated frequency of medication use, both during induction and ever recorded. RESULTS: We identified 222 patients with kidney biopsy-proven nephritis, with 64% class III/IV nephritis on initial biopsy. At the most recent registry visit at median (interquartile range) of 17 (8-29) months from initial kidney biopsy, 58 of 106 patients (55%) with available data had abnormal kidney status. This finding was associated with male sex (odds ratio [OR] 3.88, 95% confidence interval [95% CI] 1.21-12.46) and age at cSLE diagnosis (OR 1.23, 95% CI 1.01-1.49). Patients with class IV nephritis were more likely than class III to receive cyclophosphamide and rituximab during induction. There was substantial variation in mycophenolate, cyclophosphamide, and rituximab ever use patterns across rheumatology centers. CONCLUSION: In this cohort with predominately class III/IV nephritis, male sex and older age at cSLE diagnosis were associated with abnormal short-term kidney status. We also observed substantial variation in contemporary medication use for pediatric lupus nephritis between pediatric rheumatology centers. Additional studies are needed to better understand the impact of this variation on long-term kidney outcomes.

Chronic kidney disease in patients with childhood-onset systemic lupus erythematosus.

BACKGROUND: Lupus nephritis (LN) is a frequent manifestation of childhood-onset systemic lupus erythematosus (cSLE) with a potential risk for kidney failure and poor outcomes. This study aimed to evaluate stages III, IV, and V of chronic kidney disease (CKD) and investigate risk factors for CKD in cSLE patients. METHODS: We performed a nationwide observational cohort study in 27 pediatric rheumatology centers, including medical charts of 1528 cSLE patients. Data were collected at cSLE diagnosis, during follow-up, and at last visit or death, between September 2016 and May 2019. RESULTS: Of 1077 patients with LN, 59 (5.4%) presented with CKD, 36/59 (61%) needed dialysis, and 7/59 (11.8%) were submitted for kidney transplantation. After Bonferroni's correction for multiple comparisons (p < 0.0013), determinants associated with CKD were higher age at last visit, urinary biomarker abnormalities, neuropsychiatric involvement, higher scores of disease activity at last visit and damage index, and more frequent use of methylprednisolone, cyclosporine, cyclophosphamide, and rituximab. In the regression model analysis, arterial hypertension (HR = 15.42, 95% CI = 6.12-38.83, p ≤ 0.001) and biopsy-proven proliferative nephritis (HR = 2.83, 95%CI = 1.70-4.72, p ≤ 0.001) increased the risk of CKD, while children using antimalarials had 71.0% lower CKD risk ((1.00-0.29) × 100%) than children not using them. The Kaplan-Meier comparison showed lower survival in cSLE patients with biopsy-proven proliferative nephritis (p = 0.02) and CKD (p ≤ 0.001). CONCLUSIONS: A small number of patients manifested CKD; however, frequencies of dialysis and kidney transplantation were relevant. This study reveals that patients with cSLE with hypertension, proliferative nephritis, and absence of use of antimalarials exhibited higher hazard rates of progression to CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Variations in clinical presentation and biomarkers among biopsy-proven lupus nephritis patients: a Top End retrospective cohort study.

BACKGROUND: Lupus nephritis (LN) is a common feature of systemic lupus erythematosus (SLE) and affects 50% of patients with SLE. Racial differences in incidence and prevalence have been well documented worldwide. In Australia, higher incidence and prevalence of SLE had been previously reported in Aboriginal and Torres Strait Australians compared with non-Indigenous Australians. AIM: To describe the differences in clinical features and lupus biomarkers between Aboriginal and Torres Strait Islander Australian and non-Indigenous Australian patients with LN. METHODS: We retrospectively identified all consecutive biopsy-proven LN patients in our institution and compared the clinical features and lupus biomarkers between Aboriginal and Torres Strait Islander Australians and non-Indigenous Australians. RESULTS: Of the 33 consecutive biopsy-proven LN patients, 26 self-identified as of Aboriginal and Torres Strait Islander descent. The estimated incidence of LN in Aboriginal and Torres Strait Islander Australian and non-Indigenous Australians were 5.08 and 0.47 per 100 000 patient-years respectively. Neurological manifestations (23.08% vs 0%), haematological manifestations (46.50% vs 16.67) and right-heart catheter proven pulmonary arterial hypertension (23.08% vs 0%) were more frequently observed among Indigenous Australian patients compared with non-Indigenous Australian patients. The incidence of positive extractable nuclear antigen was also higher among Indigenous Australian patients (84.62% vs 57.14%). CONCLUSION: The present study further supports the observation that lupus in Aboriginal and Torres Strait Islander Australians were of a 'distinct phenotype' compared with non-Indigenous Australians. Future research should be aimed at delineating the reason for this observed difference.

Clinical and Military Outcomes of Kidney Diseases Diagnosed in Active Duty Service Members.

INTRODUCTION: Renal biopsy is a valuable tool for determining diagnosis, management, and prognosis of intrinsic kidney diseases. Indications for biopsy depend on the clinical presentation. Within the military, renal biopsies also enable medical review boards to make military service fitness assessments after diagnosis of a kidney disease. There are no recent studies evaluating kidney disease diagnoses and clinical outcomes after renal biopsy at military treatment facilities. Additionally, no studies have examined overall healthcare and military career outcomes following renal biopsy. MATERIALS AND METHODS: We retrospectively reviewed all native renal biopsies performed on active duty beneficiaries at the Walter Reed National Military Medical Center from 2005 to 2020. We determined the prevalence of those who progressed to end-stage kidney disease (ESKD), kidney transplantation, doubling of serum creatinine, nephrotic-range proteinuria (NRP; proteinuria >3.5 g/day), medical evaluation board (MEB) outcomes, and death. The Armed Forces Health Longitudinal Technology Application and the Joint Legacy Viewer electronic medical record systems were used to access clinical and laboratory data at the time of biopsy and subsequent outcomes. Death data were collected using the Defense Suicide Prevention Office database. RESULTS: There were 169 patients in the cohort, with a mean follow-up of 7.3 years. Mean age was 32 years; 79% male; 48% white; and 37% black. Sixty-seven percentage of them were junior or senior enlisted. The most common indication for renal biopsy was concomitant hematuria and proteinuria (31%). The most common histologic diagnoses were immunoglobulin A (IgA) nephropathy (23%), followed by focal segmental glomerulosclerosis (FSGS; 17%) and lupus nephritis (12%). Eleven percentage of them progressed to ESKD, of whom 87% received a kidney transplant (10% overall). Thirty percentage of the patients progressed to NRP and 5% died. Forty-seven percentage of our patients underwent MEB after diagnosis, and of these, 84% were not retained for further military service. Although IgA nephropathy was the most commonly diagnosed condition, FSGS and lupus nephritis diagnoses were significantly more likely to result in MEB. CONCLUSIONS AND IMPLICATIONS: Immunoglobulin A nephropathy was the most frequent histologic diagnosis in active duty service members undergoing renal biopsy between 2005 and 2020. Despite being largely young and previously healthy, 11% progressed to ESKD and 5% died. A confirmed histologic diagnosis was associated with separation from the service and the end of military careers for 84% of the patients in the cohort who underwent MEB.

Practice Patterns and Approach to Childhood Lupus Nephritis in Saudi Arabia.

Renal involvement of systemic lupus erythematosus needs aggressive treatment. Despite the development of multiple international guidelines, differences in practices exist. This study aimed to explore the current practices of pediatric rheumatologists and nephrologists for the diagnosis, management, and monitoring of lupus nephritis (LN) in Saudi Arabia through a survey. Among the 61 respondents, 54.1% were pediatric nephrologists and 49.9% were pediatric rheumatologists. Predominantly, the participating physicians received training either nationally (57%) or in North America (45%). Most of the respondents (77%) did not have a combined rheumatology-nephrology clinic, primarily because of space or time limitations (75%), or a lack of the other specialty (13%). In terms of the decision to request a renal biopsy, the most common factors were nephrotic-range proteinuria (85%) and a lower level of proteinuria associated with hypocomplementemia or elevated anti-double-stranded (ds) DNA (73%). There was marginal agreement over monitoring the disease's activity and treatment response; Complements 3 and 4, anti-dsDNA, protein-creatinine ratio, and estimated glomerular filtration rate were the most popular parameters. The main reason for repeating a renal biopsy was a new renal manifestation that was inconsistent with the previous biopsy. There was considerable variability in the induction therapies used to initiate and taper corticosteroids and conventional immunosuppressive drugs. Most respondents (91%) used angiotensin-converting enzyme agents to control proteinuria. Considerable agreement exists among Saudi physicians managing children with LN but significant variations exist regarding the therapeutic strategies. Additional endeavors are needed to establish a unified national clinical approach for managing LN in children.

Worse long-term renal outcome of lupus nephritis patients of African descent living in Europe.

INTRODUCTION: Prognosis of lupus nephritis (LN) among patients of African descent living in Europe has been understudied. METHODS: In a retrospective study performed in two European university hospitals, we compared the prognosis of LN in patients of African descent or Caucasians. Remission was defined as a urine protein to creatinine (uP/C) ratio<0.5 g/g and a serum creatinine value<120% of baseline. Renal relapse was defined as the reappearance of a uP/C>1 g/g, leading to a repeat kidney biopsy and/or immunosuppressive treatment change. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate≤60 mL/min/1.73 m2. Adherence was retrospectively assessed through medical files and/or hydroxychloroquine level measurements. RESULTS: 52 patients of African descent and 85 Caucasian patients were included in this analysis. Class III and isolated class V LN were more common among patients of African descent. Time to first renal remission did not differ between ethnic subgroups. By contrast, patients of African descent suffered from earlier renal flares, CKD was more common and time to CKD was shorter after a flare. In a multivariate analysis, African ancestry was an independent risk factor for progression to CKD. We observed no significant difference in non-adherence to treatment between the two groups. CONCLUSION: LN patients of African descent have worse renal outcomes, mainly explained by a higher rate of renal flare.

The long-term outcome of New Zealand Maori and Pacific Island children diagnosed with childhood onset lupus nephritis.

OBJECTIVE: To determine the long-term outcome of Maori and Pacific Island children diagnosed with childhood onset lupus nephritis. METHOD: A chart review was conducted of children diagnosed with biopsy proven lupus nephritis seen by the Starship Hospital and Kidz First paediatric rheumatology and/or Starship renal services between January 1992 and January 2018. Baseline and follow-up kidney histology, adherence and response to therapy including partial or full renal remission, refractory disease, end-stage kidney disease (ESKD) and mortality were determined. RESULTS: In a New Zealand cohort of 42 with childhood onset lupus nephritis, Maori and Pacific Island children were significantly more likely to develop class 4 lupus nephritis (RR (95% CI), 11.3 (3.84-49.9), p < 0.0001), demonstrate medication nonadherence (RR (95% CI) 12.4 (3.48-85.7), p < 0.0001) and experience end stage kidney disease (RR (95% CI) 15.7 (2.97-389.3), p = 0.0003) and mortality (RR (95% CI) 11.1 (1.91-280.1), p = 0.005) compared to non-Maori and Pacific Island children. In addition, Maori children with childhood onset lupus nephritis developed chronic histological changes significantly more rapidly than Pacific or Asian children (p = 0.038). CONCLUSION: Lupus nephritis is more common among Maori and Pacific Island children in New Zealand associated with a significant incidence of end stage kidney disease and mortality, with some Maori children developing rapid histologic disease progression.

Induction therapy and outcome of proliferative lupus nephritis in the top end of Northern Australia - a single centre study retrospective study.

BACKGROUND: Lupus nephritis is a common manifestation of Systemic Lupus Erythematosus. Mycophenolate is recommended by guidelines for induction therapy in patients with proliferative lupus nephritis and nephrotic range proteinuria Class V lupus nephritis. Indigenous Australians suffer disproportionally from systemic lupus erythematosus compared to non-Indigenous Australians (Anstey et al., Aust N Z J Med 23:646-651, 1993; Segasothy et al., Lupus 10:439-444, 2001; Bossingham, Lupus 12:327-331, 2003; Grennan et al., Aust N Z J Med 25:182-183, 1995). METHODS: We retrospectively identified patients with newly diagnosed biopsy-proven class III lupus nephritis, class IV lupus nephritis and class V lupus nephritis with nephrotic range proteinuria from 1st Jan 2010 to 31st Dec 2019 in our institution and examined for the patterns of prescribed induction therapy and clinical outcome. The primary efficacy outcome of interest was the incidence of complete response (CR) and partial response (PR) at one-year post diagnosis as defined by the Kidney Disease: Improving Global Outcome (KDIGO) guideline. Secondary efficacy outcome was a composite of renal adverse outcome in the follow-up period. Adverse effect outcome of interest was any hospitalisations secondary to infections in the follow-up period. Continuous variables were compared using Student's t-test or Mann-Whitney U-test. Categorical variables were summarised using frequencies and percentages and assessed by Fisher's exact test. Time-to-event data was compared using the Kaplan-Meier method and Log-rank test. Count data were assessed using the Poisson's regression method and expressed as incident rate ratio. RESULTS: Twenty of the 23 patients included in the analysis were managed with mycophenolate induction upfront. Indigenous Australian patients (N = 15), compared to non-Indigenous patients (N = 5) received lower cumulative dose of mycophenolate mofetil over the 24 weeks (375 g vs. 256 g, p < 0.05), had a non-significant lower incidence of complete remission at 12 months (60% vs. 40%, p = 0.617), higher incidence of composite renal adverse outcome (0/5 patients vs. 5/15 patients, p = 0.20) and higher incidence of infection related hospitalisations, (incident rate ratio 3.66, 95% confidence interval 0.89-15.09, p = 0.073). CONCLUSION: Mycophenolate as upfront induction in Indigenous Australian patients were associated with lower incidence of remission and higher incidence of adverse outcomes. These observations bring the safety and efficacy profile of mycophenolate in Indigenous Australians into question.

Management practice and treatment outcomes of adult patients with Lupus Nephritis at the Renal Clinic of St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia.

BACKGROUND: Lupus nephritis (LN) is the most common severe complication of systemic lupus erythematosus (SLE) which results in high morbidity and mortality. Up to 60% of adult patients with SLE develop the renal disease with different severity. Even with potent anti-inflammatory and immunosuppressive therapies, many LN patients still progress to chronic kidney disease or end-stage renal disease. Thus, this study aimed to assess the management practice, treatment outcomes and to identify the associated factors of poor renal outcome in adult LN patients at the renal clinic of St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia. METHODS: A retrospective cross-sectional study design was used to collect the data using an abstraction tool from patients' records. The Kidney Disease Improving Global Outcomes (KDIGO) criteria were used to diagnose LN among SLE patients. Logistic regression was used to determine crude and adjusted odds ratio and a p-value of < 0.05 was considered statistically significant. Ethical approval was obtained from the ethical review committee of the School of Pharmacy, Addis Ababa University and institutional review board of St. Paul's Hospital Millennium Medical College. RESULTS: Out of 168 study participants enrolled from September 1, 2016 to October 30, 2020, a total of 114 adult LN patients were included for final analysis. The mean (± SD) age of the LN patients at onset was 29.10 ± 9.67 years and 99 (86.8%) of all the patients were females. More than three-fourths (78.9%) of the LN patients had a good prognosis. However, 24 (21.1%) of the patients who didn't achieve complete or partial remission had a poor prognosis. A kidney biopsy was done for 71 patients at initial presentation with class IV and III as the commonest class. The commonly prescribed immunosuppressive medications were cyclophosphamide as induction therapy in 67 (58.7%) and mycophenolate mofetil (MMF) as maintenance therapy in 76 (66.7%). Gastrointestinal intolerances like abdominal pain, nausea, or diarrhea from MMF were the most common 27(31.2%) treatment-related adverse events reported. Acute kidney injury (AKI) at onset (AOR = 4.83, P = 0.026), high serum creatinine (SCr) at six months (AOR = 0.12, P = 0.003), no response at six months to attain complete remission (AOR = 0.05, P = 0.041) and presence of flare (AOR = 0.04, P = 0.004) were predictors poor treatment outcomes. CONCLUSION: Despite good response with the present immunosuppressive regimens, relapse, treatment-related complications and adverse events are major problems that require close monitoring. The results and identified gaps of this study are used as an input to improve the management practice of LN in the study setting. Overall, this study is comparable with other findings and strengthen the present available literatures.