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ObjectivesShort-term predictive endpoints of chronic kidney disease (CKD) are needed in lupus nephritis (LN). We tested response to therapy at 1 year.MethodsWe considered patients with LN who underwent renal biopsy followed by induction therapy between January 1970 and December 2016. LN was assessed using the International Society of Nephrology/Renal Pathology Society (2003) criteria and the National Institute of Health (NIH) activity and chronicity index. The renal outcome was CKD. Response was defined according to EULAR/European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations: complete: proteinuria <0.5 g/24 hours, (near) normal estimated glomerular filtration rate (eGFR); partial: ≥50% proteinuria reduction to subnephrotic levels, (near) normal eGFR; and no response: all the other cases. Logistic regression analysis was employed for 12-month response and Cox regression for CKD prediction.ResultsWe studied 381 patients (90.5% Caucasians). After 12-month therapy, 58%, 26% and 16% of patients achieved complete, partial and no response, respectively, according to EULAR/ERA-EDTA. During a median follow-up of 10.7 (IQR: 4.97–18.80) years, 53 patients developed CKD. At 15 years, CKD-free survival rate was 95.2%, 87.6% and 55.4% in patients with complete, partial and no response at 12 months, respectively (p<0.0001). CKD-free survival rates did not differ between complete and partial responders (p=0.067). Serum creatinine (HR: 1.485, 95% CI 1.276 to 1.625), eGFR (HR 0.967, 95% CI 0.957 to 0.977) and proteinuria at 12 months (HR 1.234, 95% CI 1.111 to 1.379) were associated with CKD, yet no reliable cut-offs were identified on the receiver operating characteristic curve. In multivariable analysis, no EULAR/ERA-EDTA response at 12 months (HR 5.165, 95% CI 2.770 to 7.628), low C4 (HR 1.053, 95% CI 1.019 to 1.089) and persistent arterial hypertension (HR 3.154, 95% CI 1.500 to 4.547) independently predicted CKD.ConclusionsLack of EULAR/ERA-EDTA response at 12 months predicts CKD.

IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. The disease generally runs an indolent course but may lead to ESRD in 20–30% of patients in 20 years or more after diagnosis. Patients with IgA nephropathy are ideal candidates for renal transplant because they are generally relatively young and with few comorbidities. Their graft survival is better or comparable to that of controls at 10 years, though few data are available after 10 years of follow-up. Recurrence of the original disease in the graft is a well-known complication of transplant in IgAN and is a significant cause of deterioration of graft function. Recurrent IgAN rarely manifests clinically before 3 years post transplantation. Recurrence rate is estimated to be around 30% with considerable differences among different series. Despite these factors there is no certain recurrence predictor, young age at renal transplant, rapid progression of the original disease and higher levels of circulating galactose-deficient IgA1 and IgA-IgG immune complexes are all associated with a higher rate of recurrence. Which pathogenetic mechanisms are responsible for the progression of the recurrence to graft function deterioration, and what therapy can prevent or slow down the progression of the disease in the graft, are open questions. The aim of this review is to describe the clinical outcome of renal transplantation in IgA patients with attention to the rate and the predictors of recurrence and to discuss the available therapeutic options for the management of recurrence.

ObjectivesRemission in systemic lupus erythematosus (SLE) is defined through a combination of ‘clinical SLE Disease Activity Index (cSLEDAI)=0’, ‘physician's global assessment (PGA) <0.5’ and ‘prednisone (PDN) ≤5 mg/day’. We investigated the performance of these items, alone or in combination, in defining remission and in predicting SLICC/ACR Damage Index.MethodsWe tested seven potential definitions of remission in SLE patients followed-up for ≥5 years: PDN ≤5 mg/day; PGA <0.5; cSLEDAI=0; PGA <0.5 plus PDN ≤5 mg/day; cSLEDAI=0 plus PGA <0.5; cSLEDAI=0 plus PDN ≤5 mg/day; cSLEDAI=0 plus PDN ≤5 mg/day plus PGA <0.5. The effect of these definitions on damage was evaluated by Poisson regression analysis; the best performance was identified as the lowest Akaike and Bayesian information criterion (AIC and BIC). Positive and negative predictive values in identifying no damage increase were calculated.ResultsWe included 646 patients (mean±SD disease duration 9.2±6.9 years). At multivariate analysis, ≥2 consecutive year remission according to all definitions protected against damage (OR, 95% CI: PGA <0.5 0.631, 0.444 to 0.896; cSLEDAI=0 0.531, 0.371 to 0.759; PGA <0.5 plus PDN ≤5 mg/day 0.554, 0.381 to 0.805; cSLEDAI=0 plus PGA <0.5 0.574, 0.400 to 0.826; cSLEDAI=0 plus PDN ≤5 mg/day 0.543, 0.376 to 0.785; cSLEDAI=0 plus PDN ≤5 mg/day plus PGA <0.5 0.532, 0.363 to 0.781, p<0.01 for all), except PDN ≤5 mg/day, which required four consecutive years (OR 0.534, 95% CI 0.325 to 0.877, p=0.013). Positive and negative predictive values were similar; however, cSLEDAI=0 showed the best performance (AIC 1082.90, BIC 1109.72, p<0.0001). Adding PGA <0.5 and/or PDN ≤5 mg/day to cSLEDAI=0 decreased remission duration (−1.8 and −1.5 year/patient, respectively) without increasing cSLEDAI=0 performance in predicting damage accrual.ConclusionscSLEDAI=0 is the most attainable definition of remission, while displaying the best performance in predicting damage progression in the short-to-mid-term follow-up.

Background. A renewed interest for activity and chronicity indices as predictors of lupus nephritis (LN) outcome has emerged. Revised National Institutes of Health (NIH) activity and chronicity indices have been proposed to classify LN lesions but should be validated by future studies. Aims of this study: i) to detect the histological features associated with the development of Kidney Function Impairment (KFI); ii) to identify the best clinical-histological model to predict KFI at time of kidney biopsy. Methods. LN patients with kidney biopsy containing >10 glomeruli per specimen were admitted to the study. Univariate and multivariate logistic regression and Cox proportional hazards model were used to investigate whether activity and chronicity indices could predict KFI development. Results. Among 203 LN participants followed for 14 years, correlations were found between activity index and its components and clinical-laboratory signs of active LN at baseline. Chronicity index was correlated with serum creatinine. Thus, serum creatinine was significantly and directly correlated with both activity and chronicity indexes. At multivariate analysis glomerular sclerosis (OR:3.0478, CI:1.173-7.91, P=0.022) and fibrous crescents (OR:6.8352, CI:3.218-14.519, P<0.001) associated with either moderate/severe tubular atrophy (OR:3.1697, CI:1.042-9.643, P=0.0421), or with interstitial fibrosis (OR:2.361, CI:1.047-5.322, P=0.0383) predicted KFI. Considering both clinical and histological features, serum creatinine (OR:1.677; 1.311-2.145; P<0.001), arterial hypertension (OR:4.641, CI: 1.902-11.324, P<0.001), glomerular sclerosis (OR:2.123, CI:1.001-4.503, P=0.049), and fibrous crescents (OR:5.182, CI: 2.433-11.037, P<0.001) independently predicted KFI. Older age (P<0.001) and longer delay between clinical onset of LN and kidney biopsy (P<0.001) were significantly correlated with baseline chronicity index. Conclusions. Chronicity index and its components, but not activity index, were significantly associated with an impairment of kidney function. The Cox model showed that serum creatinine, arterial hypertension, chronic glomerular lesions and delay in kidney biopsy predicted KFI. These data reinforce the importance of timely kidney biopsy in LN.

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Glucocorticoids and other immunosuppressants still represent the cornerstone drugs for the management of SLE (Systemic Lupus Erythematosus) and lupus nephritis. The refined use of these drugs over the years has allowed to obtain stable disease remission and improvement of the long-term kidney and patient survival. Nevertheless, a prolonged use of immunosuppressive agents may be accompanied by severe and even life-threatening side effects. Theoretically, a transient or even definitive withdrawal of immunosuppression could be useful to prevent iatrogenic morbidities. For many years, however, the risk of SLE reactivation has held clinicians back from trying to interrupt therapy. In this review we report the results of the attempts to interrupt glucocorticoids and other immunosuppressive agents in lupus nephritis and in SLE. The available data suggest that the therapy withdrawal is feasible at least in patients enjoying a complete clinical remission after a prolonged therapy. A slow and gradual reduction of treatment under medical surveillance is needed to prevent flares of activity. After therapy withdrawal around one quarter of patients may have kidney or systemic flares. However, most flares may respond to therapy if rapidly diagnosed. The other patients can enter stable remission even for 20 years or more. The use of antimalarials can help in maintaining the remission after the withdrawal of the immunosuppressive therapy. A repeated kidney biopsy could be of help in deciding to stop therapy, but given the few available data, it cannot be considered essential.

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