Effect of antimalarials on clinical outcomes in lupus nephritis.

OBJECTIVES: To evaluate the effect of antimalarial drugs in response to therapy, incidence of LN flares, and progression of kidney disease in a large LN cohort. METHODS: We retrospectively studied 424 biopsy-proven LN patients followed for >3 years. We obtained demographic, clinical, laboratory, histopathological, and treatment variables. Antimalarial use was approached as 1) users versus no users, 2) according to prevalent vs incident use regarding the LN flare, and 3) according to the type of antimalarial. All outcomes were evaluated by time-to-event analyses. Adjusted hazard ratios were obtained by Cox regression. RESULTS: The cohort included 424 patients, median age of 29 years (IQR 23-37), 96% female, with a median eGFR of 81 ml/min/1.73m2 (IQR 48-118) and proteinuria of 3.4 g/g (IQR 1.9-5.5). Antimalarial use was associated with higher complete response (aHR 1.57, 1.08-2.27), lower incidence of kidney flares (aHR 0.63, 0.43-0.92), and lower progression to kidney failure (aHR 0.37, 0.23-0.53). The effect on these outcomes was modified by the presentation eGFR, histological class, and/or concomitant initial immunosuppressor. These protective effects were observed in patients with prevalent or incident use regarding the LN flare and patients using hydroxychloroquine. The incidence of toxic retinopathy was 1.7%, 5.7%, and 8.8% by 3-, 5-, and 7 years of continued antimalarial use. CONCLUSION: The use of antimalarial drugs is associated with increased response to therapy, lower incidence of kidney flares, and lower progression to kidney failure in LN patients. Conversely, this population is at high risk of toxic maculopathy, and yearly ophthalmologic examination is recommended.

The influence of repeated flares in response to therapy and prognosis in lupus nephritis.

BACKGROUND: Repeated renal flares in lupus nephritis (LN) have been associated with worse long-term kidney function. This study aimed to assess the impact of repeated LN flares in response to therapy, kidney and patient prognosis. METHODS: All patients from a biopsy-proven LN cohort between 2008 and 2018 were segregated into three groups according to the number of LN flares when they entered our cohort: first LN flare, second LN flare or third LN flare. The following outcomes were evaluated by unadjusted and adjusted time-to-event analyses: complete and partial response, disease relapses, progression to decline of 30% of the estimated glomerular filtration rate (eGFR), doubling of serum creatinine, end-stage kidney disease and patient survival. RESULTS: A total of 441 patients were included: 257 (58%) in their first LN flare, 102 (23%) in their second LN flare and 82 (19%) in their third LN flare. There were significant differences in LN flare presentation in age, eGFR, serum albumin, pyuria and hematuria among groups. The National Institutes of Health chronicity indices and the percentage of patients with vascular lesions were higher in groups at progressive LN flares. In the adjusted analyses, complete and partial response rates decreased, as well as kidney and patient survival, at a progressive number of LN flares. No differences in the dynamic course of all surveillance laboratory parameters were observed in the first year after initial therapy among LN flare groups. CONCLUSIONS: A progressive number of LN flares is associated with a lower response to therapy and an adverse prognosis for kidney function and patient survival.

Exostosin-1/exostosin-2 expression and favorable kidney outcomes in lupus nephritis: a retrospective cohort study.

INTRODUCTION/OBJECTIVES: The heterodimer exostosin-1/exostosin-2 (EXO-1/2) is a novel antigen observed in membranous nephropathy associated with systemic lupus erythematosus. This study aimed to evaluate the association between EXO-1/2 positivity in kidney biopsy and kidney outcomes. METHODS: The kidney biopsy tissue from 50 class 5 lupus nephritis (LN) and 55 mixed class 3/4 + 5 LN patients was stained for EXO-1/2. Baseline clinical and histological characteristics were compared between EXO-1/2 positive and EXO-1/2 negative patients. Time-to-event analyses were performed to compare rates of response to therapy, kidney flares, and progression to a 40% decline of the glomerular filtration rate (eGFR), doubling of serum creatinine, and kidney failure. RESULTS: Fourteen out of 50 (28%) of class 5 and 5 out of 55 (9%) of mixed class 3/4 + 5 LN stained positive for EXO-1/2. Patients with class 5 LN and EXO-1/2 positive stain were younger, with better kidney function at presentation, and lower scarring in the kidney biopsy analysis. Over a median follow-up of 100 months, patients with positive EXO-1/2 staining had significantly lower rates of progression in the full cohort. When analyzed separately in class 5 and mixed class LN subgroups, there were significantly lower rates of progression to a 40% decline of the eGFR and non-statistically significant trends for doubling of serum creatinine and kidney failure. CONCLUSION: EXO-1/2 is a novel antigen detected in class 5 LN and associated with a good prognosis of kidney function. The incorporation of EXO-1/2 staining in clinical practice can potentially modify the management of LN due to its prognostic implications. Key Points • Exostosin-1/exostosin-2 antigen has been found in cases of membranous nephropathy associated with autoimmune diseases such as systemic lupus erythematosus. • Exostosin-1/exostosin-2 staining in the kidney biopsy of class 5 or mixed class 3/4 + 5 lupus nephritis is associated with a good long-term prognosis of kidney function. • The incorporation of exostosin-1/exostosin-2 staining into clinical practice can potentially modify management due to its prognostic implications.

The first-year course of urine MCP-1 and its association with response to treatment and long-term kidney prognosis in lupus nephritis.

OBJECTIVES: The present study aims to assess the course of uMCP-1 and its association with response to therapy and long-term kidney function in a prospective cohort of adults who received a kidney biopsy for suspicion of active lupus nephritis (LN). METHODS: Subjects were segregated into a histologically active LN group and a histologically chronic LN group. Both groups were followed for > = 36 months and urine were collected at flare, 3, 6, and 12 months of follow-up. The association between the course of uMCP-1, response to treatment, and progression to 30% loss of the eGFR was evaluated by linear mixed models for repeated measures. RESULTS: A kidney biopsy was performed on 125 subjects. In 114, the report was consistent with histologically active LN; in 11, with histologically chronic LN. Urine MCP-1 levels were significantly higher in the active LN than in the chronic LN group. Urine MCP-1 levels correlated with the histological findings of cellular crescents, endocapillary hypercellularity, interstitial inflammation, glomerular sclerosis, interstitial fibrosis, and tubular atrophy. The mean estimates of uMCP-1 at flare were higher in the non-response group than in the complete response group, and decreased in the complete/partial response groups by the third month, while they remained elevated in the non-response group. The mean estimates for uMCP-1 were higher at LN flare and remained elevated in patients who progressed to loss of 30% of the eGFR, while they decreased in patients with stable kidney function. CONCLUSION: The first-year course of uMCP-1 is associated with response to therapy and kidney survival in LN. Key Points •Urine MCP-1 levels differentiate histologically-active lupus nephritis from histologically-chronic lupus nephritis •Urine MCP-1 levels decrease by 3 months of therapy in subjects with a favorable response whose kidney function remains stable long-term •Urine MCP-1 levels remain elevated during the first year of therapy in subjects the will later lose kidney function.

Predictors of treatment outcomes in lupus nephritis with severe acute kidney injury and requirement of dialytic support.

INTRODUCTION/OBJECTIVES: Acute kidney injury (AKI) with the requirement of kidney replacement therapy (KRT) portends a poor prognosis for kidney function in lupus nephritis (LN). This study evaluated the kidney function recovery rates, the rates of reinitiation of KRT, and factors associated with these outcomes in LN. METHOD: All consecutive patients hospitalized for LN with KRT requirement between 2000 and 2020 were included. Their clinical and histopathologic characteristics were retrospectively registered. The outcomes and associated factors were evaluated by multivariable Cox regression analysis. RESULTS: Among 140 patients, 75 (54%) recovered kidney function, with recovery rates of 50.9% and 54.2% by 6 and 12 months of therapy. The factors associated with a lower probability of recovery included a previous history of LN flares, worse eGFR and higher proteinuria at presentation, immunosuppression with azathioprine, and hospitalizations within 6 months of therapy initiation. There was no difference in the kidney function recovery rates between mycophenolate and cyclophosphamide treatment schemes. Out of 75 patients who recovered kidney function, 37 (49%) reinitiated KRT, with KRT reinitiation rates of 27.2% and 46.5% by 3 and 5 years. Seventy-three (52%) patients had at least one hospitalization within 6 months of initial therapy, 52 (72%) of them secondary to infectious events. CONCLUSIONS: Approximately 50% of patients with LN and KRT requirement recover kidney function within 6 months. The risk-to-benefit ratio decisions may be aided by clinical and histological factors. These patients require close follow-up as ≈50% of those who recover kidney function will reinitiate dialysis in the long term. Key Points • Approximately 50% of patients with severe acute lupus nephritis with the need for kidney replacement therapy requirement recover their kidney function. • The factors associated with a lower probability of recovery of kidney function include a previous history of LN flares, worse eGFR and higher proteinuria at presentation, immunosuppression with azathioprine, and hospitalizations within 6 months of therapy initiation. • Patients who recover kidney function will require close follow-up as around 50% of them will eventually reinitiate kidney replacement therapy.

Validation of a renal risk score in a cohort of ANCA-associated vasculitis patients with severe kidney damage.

OBJECTIVE: To validate the renal risk score in a cohort of patients with advanced kidney damage. METHODS: A total of 72 patients with biopsy-proven ANCA glomerulonephritis with >12 months of follow-up were studied. The renal risk score was calculated and evaluated by survival analysis for time of renal survival. Cohort-specific clinical, histopathologic, and post-treatment factors associated with renal survival were determined by Cox regression analysis. RESULTS: Kidney biopsies were classified as focal, crescentic, mixed, and sclerotic classes in 6 (8%), 4 (6%), 25 (35%), and 37 (51%) patients, respectively. The 1-, 3-, and 5-year renal survival rates were 79%, 73%, and 68%, respectively. Patients were segregated by the risk score in low- (18%), medium- (47%), and high-risk (35%) groups. Patients in the low-risk group had 36-, 60-, and 84-month renal survival of 100%; those in the medium risk 85% (95% CI 72-92), 81% (95% CI 66-95), and 76% (95% CI 60-92), respectively; and those in the high risk 37% (95% CI 17-57), 26% (95% CI 7-45), and 18% (95% CI 1-36), respectively. Six (43%) of the 14 patients in the high-risk group recovered renal function after the initial episode, and 2 (14%) remained dialysis-free. Other parameters associated with renal survival included age, proteinuria, general symptoms, cellular crescents, glomerulosclerosis, tubulointerstitial lesions, best post-treatment eGFR, and renal relapses. CONCLUSIONS: We validated the renal risk score as a prognostic tool in a cohort with predominantly mixed and sclerotic histologic categories. Since patients in the high-risk group still benefited from immunosuppressive therapy, this score should be used in conjunction with other predictive parameters to aid therapeutic decisions.Key Points• The ANCA renal risk score is validated in a cohort with advanced kidney damage.• Patients in the high-risk group still benefited from immunosuppressive therapy.• Parameters not included in the risk score are associated with renal survival and may be useful.

Correction to: Validation of a renal risk score in a cohort of ANCA-associated vasculitis patients with severe kidney damage.

The footnote of Figure 2 in the published original version of the above article went missing and the correct figure is presented in this article.