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Objective: To study the response of lupus nephritis (LN) patients with persistent proteinuria (≥ 1 g/day after ≥ 6 months corticosteroid and single immunosuppressant treatment, or ≥ 3 g/day after ≥ 3 months of corticosteroid and single immunosuppressant treatment) to corticosteroid combined with two immunosuppressants, and to evaluate associated factors of response within 1 year., Method: A retrospective study of proteinuria and renal function observed in LN patients with persistent proteinuria after adding a second immunosuppressant at 3, 6, 9 and 12 months., Result: Twenty-one LN patients (100.0% female) with persistent proteinuria were treated with corticosteroid and two immunosuppressants (mycophenolate mofetil [MMF] plus cyclosporine A [CSA]). Their mean age and duration from first immunosuppressant to initiating a combination therapy were 33.2 ± 10.2 years and 17.5 ± 15.7 months, respectively. Twelve (57.1%) patients had proteinuria levels ≥ 3 g/day. The renal pathology from 18 patients were Classes III or IV in 11 (61.1%). Fifteen patients (71.4%) responded to treatment (complete remission [CR], proteinuria ≤ 0.5 g/day, in seven patients and partial remission [PR], proteinuria reduced > 50%, in eight patients). Changing from a single immunosuppressant to combined immunosuppressants was associated with CR within 1 year (hazards ratio = 0.88; 95% CI = 0.78-0.99). Adverse events consisted of one patient with severe infection, two herpes zoster and one with transient increased serum creatinine level., Conclusion: Approximately 70% of LN patients with persistent proteinuria responded to MMF plus CSA. However, infection should be a concern with these patients., (© 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: A simple, convenient, and accurate method for detecting urine protein excretion in lupus nephritis is crucial., Objectives: The objectives of the study were to determine the sensitivity and the specificity of the qualitative urine dipstick test value to detect 0.50 g or greater of the quantitative 24-hour urine protein (24-hUP) in lupus patients, to evaluate an overall agreement of the dipstick test results and the magnitude of 24-hUP, and to examine the correlation between the spot urine protein creatinine index (S-UPCI) and the 24-hour UPCI with that of the 24-hUP., Methods: A prospective study was conducted in 92 patients with lupus. All dipstick test values from 5 dipstick assays (Bayer, Roche, Meditest USA, Standard Diagnostics, and Arkray) and the S-UPCI were obtained within 6 hours of the 24-hUP collection. Of 149 urine samples, only 39% were collected properly and were used for analysis., Results: The sensitivity and specificity of a ≥ 2+ dipstick test result to detect 0.50 g or greater 24-hUP were 56-% to 80% and 67% to 92%, respectively. The agreement of the urine dipstick test values and the magnitude of 24-hUP was fair (κ = 0.23-0.32). The correlation between the S-UPCI and the 24-hUP was 0.83 (P < 0.0001), and that of the 24-hour UPCI and the 24-hUP was 1 (P < 0.0001). Using 24-hUP 2 g/d or less, the bias ± 1.96 SD of the difference of S-UPCI and 24-hUP was 0.23 (SD, 0.96) g., Conclusions: A ≥ 2+ dipstick test is relatively sensitive to detect significant proteinuria, but it is poorly correlated with quantitative 24-hUP. The S-UPCI and the 24-hUP can be used interchangeably for follow-up in lupus nephritis patients with proteinuria of less than 2 g/d.

Objective: To develop a measure of renal activity in systemic lupus erythematosus and use it to develop a renal response index., Methods: Abstracted data from the medical records of 215 patients with lupus nephritis were sent to 8 nephrologists and 29 rheumatologists for rating. Seven nephrologists and 22 rheumatologists completed the ratings. Each physician rated each patient visit with respect to renal disease activity (none, mild, moderate, or severe). Using the most commonly selected rating for each patient as the gold standard, stepwise regression modeling was performed to identify the variables most related to renal disease activity, and these variables were then used to create an activity score. This activity score could then be applied to 2 consecutive visits to define a renal response index., Results: The renal activity score was computed as follows: proteinuria 0.5-1 gm/day (3 points), proteinuria 0.5-1 gm/day = 3 points, proteinuria >1-3 gm/day = 5 points, proteinuria >3 gm/day = 11 points, [corrected] urine red blood cell count > = 5/hpf = 3 points, [corrected] urine white blood cell count > or = 5/hpf = 1 point. [corrected] The chance-adjusted agreement between the renal response index derived from the activity score applied to the paired visits and the plurality physician response rating was 0.69 (95% confidence interval 0.59-0.79)., Conclusion: Ratings derived from this index for rating of renal response showed reasonable agreement with physician ratings in a pilot study. The index will require further refinement, testing, and validation. A data-driven approach to create renal activity and renal response indices will be useful in both clinical care and research settings.

Objective: To assess the degree to which physicians agree with each other and with ratings obtained with 3 existing responder indices, in rating the response to treatment of lupus nephritis., Methods: Lupus nephritis patient medical records from 125 pairs of visits (6 months apart) were used to create renal response scenarios. Seven nephrologists and 22 rheumatologists rated each scenario as demonstrating complete response, partial response, same, or worsening. The plurality (most frequent) rating of renal response by the physicians was compared with the calculated score from the renal component of the British Isles Lupus Assessment Group (BILAG) index (original and updated [2004] version) and of the Responder Index for Lupus Erythematosus (RIFLE). The degree of agreement among the physicians was assessed by calculating intraclass correlation coefficients (ICCs). The degree of agreement between the plurality physician rating and ratings obtained with the established response indices was assessed using the kappa statistic., Results: The ICC among all physicians was 0.64 (0.62 for nephrologists and 0.67 for rheumatologists). The chance-adjusted measure of agreement (kappa coefficient) between the plurality physician rating and the calculated score obtained using established indexes was 0.50 (95% confidence interval [95% CI] 0.38-0.61) for the RIFLE, 0.14 (95% CI 0.03-0.25) for the original BILAG, and 0.23 (95% CI 0.21-0.44) for the BILAG 2004., Conclusion: These findings indicate that rheumatologists as a group and nephrologists as a group have equal agreement in their rating of renal response. There was moderate agreement between plurality physician ratings and ratings obtained using the renal component of the RIFLE. Ratings of response using an index based on the original BILAG did not have good agreement with the plurality physician rating.

Studies of immunosuppressive therapy, particularly mycophenolate mofetil (MMF), in membranous lupus nephritis (MLN) are limited. We report on our experience with primary (first-line) MMF therapy to induce and sustain renal remission in MLN with and without a concurrent proliferative lesion. Systemic lupus erythematosus (SLE) patients were studied, retrospectively, if treated with MMF for newly diagnosed MLN. Complete remission was defined as proteinuria less than 0.5 g/24 h, inactive urine sediment and normal estimated glomerular filtration rate. Response in pure MLN (Group I, n=10) was compared with mixed MLN and proliferative lupus nephritis (Group II, n=19). By 12 months, 4 (40%) patients in Group I and 7 (36.8%) in Group II achieved complete remission (P=0.87). One (10%) patient in Group I and 2 (10.5%) in Group II had worsening renal disease (P=0.97). Mean time to remission was more than seven months in both groups. The remaining patients had stable disease without improvement or worsening. Only 2 of 11 achieving initial remission had a relapse with an average of 28 months of follow-up after remission. Self-limited gastrointestinal symptoms occurred in 12 patients, none requiring withdrawal of the drug. Mycophenolate mofetil as a primary therapy in MLN was successful in inducing complete remission in about 40% of MLN, particularly in patients with mild proteinuria. However, 12 months of therapy was necessary for best outcomes. Response rate was not different in the presence or absence of a proliferative lesion.

Estimates of renal function are widely used in clinical practice and research. We assessed the performance of the Cockcroft-Gault (CG) and the Modification of Diet in Renal Disease (MDRD) equations in lupus nephritis patients. Data from ninety-seven lupus nephritis patients in the Hopkins Lupus Cohort were reviewed. Two renal function estimates, the CG and the MDRD, were compared with the 24 h creatinine clearance (CrCl). In the entire group of patients, the CG and MDRD equations had good global agreement with CrCl (R-square = 0.91 and 0.69, respectively). On average the CG equation overestimated CrCl by 2.36 mL/min/1.73 m(2), whereas the MDRD equation underestimated CrCl by 5.85 mL/min/1.73 m(2), P = 0.0004. The CG equation had greater accuracy (mean squared error) than the MDRD equation (14.93 versus 28.47 mL/min/1.73 m(2), P = 0.002) when predicting CrCl. Although both equations lacked precision (standard deviation of the difference scores) in patients with CrCl > or = 60 mL/min/1.73 m(2), the CG equation was more precise than the MDRD equation in this group, (15.68 versus 29.58 mL/min/1.73 m(2), P = 0.003). In lupus nephritis patients, the CG equation was superior to the MDRD equation as an estimate of CrCl. However, both equations lacked precision in patients with CrCl > or = 60 mL/min/1.73 m(2).

The objective of this study was to identify clinical predictors of response to initial mycophenolate mofetil (MMF) therapy for membranous lupus nephritis (MLN). We observed the clinical outcomes of patients in the Hopkins Lupus Cohort within the first year of initiation of treatment with MMF therapy for newly diagnosed MLN, classified according to the new International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification. Complete renal remission was defined as proteinuria less than 500 mg/24 hours. Demographic, clinical, treatment and laboratory data were examined for their association with renal remission. Twenty-nine MLN patients treated with MMF were identified. Eleven (38%) patients achieved complete renal remission by 12 months. Of those taking hydroxychloroquine, 7/11 (64%) were in remission within 12 months compared to only 4/18 (22%) of those not on hyroxychloroquine (P = 0.036 based on a log-rank test). This association persisted after controlling for the presence of anti-ds-DNA (P = 0.026). Our results provide evidence that hydroxychloroquine has a benefit for renal remission when MMF is used as the initial therapy for MLN. Although hydroxychloroquine is frequently stopped in patients with lupus nephritis, this study suggests it should be started or maintained.