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ObjectivesThe 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).MethodsSubjects 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.ResultsA 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.ConclusionThe 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

Introduction/objectivesAcute 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.MethodAll 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.ResultsAmong 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.ConclusionsApproximately 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.

Background Prognostication in glomerulonephritis with severe kidney function impairment is critical for evaluating the benefit-to-risk ratio of immunosuppression. We hypothesized that the urine biomarker epidermal growth factor (EGF) could have good discrimination power to identify subjects who might ultimately recover kidney function. Methods We included 82 subjects with glomerulonephritis and severe kidney function impairment at admission (estimated glomerular filtration rate [eGFR] ≤ 30 mL/min/1.73m 2 ): 58 with lupus nephritis (LN) and 24 with ANCA-associated vasculitis (AAV). Thirty-five subjects required kidney replacement therapy (KRT) at presentation. Urine epidermal growth factor was measured and corrected by urine creatinine (uEGF/Cr) and the population was analyzed by uEGF/Cr tertiles. The primary outcome was time to recovery of eGFR ≥ 30 mL/min/1.73m 2 and time to recovery of kidney function with dialysis independence in those with initial KRT. Results Forty-four (54%) participants met the primary outcome of recovery of eGFR ≥ 30 mL/min/1.73m 2 . The 6-month recovery rates were 93%, 57%, and 0% for participants in the highest, middle, and lowest uEGF/Cr tertile, respectively. Recovery of the kidney function was faster and led to a higher post-therapy eGFR in the highest uEGF/Cr tertile. In the ROC analysis, uEGF/Cr was a predictor of recovery with an area under the curve (AUC) of 0.92 (95% CI 0.87–0.98), and a cutoff of 2.60 ng/mg had 100% sensitivity to detect patients who recovered kidney function. In the subgroup of participants with initial KRT, the cut-off of uEGF/Cr of 2.0 ng/mg had 100% sensitivity to detect participants who recovered kidney function with dialysis independence by 6 months. Conclusions Urine EGF/Cr is a promising biomarker to aid in the prediction of recovery of kidney function in glomerulonephritis with severe kidney function impairment. Graphical abstract

Introduction/ObjectivesThe 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.MethodsThe 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.ResultsFourteen 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.ConclusionEXO-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.