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BACKGROUND: A renewed interest for activity and chronicity indices as predictors of lupus nephritis (LN) outcome has emerged. Revised National Institutes of Health activity and chronicity indices have been proposed to classify LN lesions, but they should be validated by future studies. The aims of this study were (1) to detect the histologic features associated with the development of kidney function impairment (KFI), and (2) to identify the best clinical-histologic model to predict KFI at time of kidney biopsy. METHODS: Patients with LN who had more than ten glomeruli per kidney biopsy specimen were admitted to the study. Univariate and multivariate logistic regression and Cox proportional hazards models were used to investigate whether activity and chronicity indices could predict KFI development. RESULTS: Among 203 participants with LN followed for 14 years, correlations were found between the activity index, and its components, and clinical-laboratory signs of active LN at baseline. The chronicity index was correlated with serum creatinine. Thus, serum creatinine was significantly and directly correlated with both activity and chronicity indices. In the multivariate analysis, glomerulosclerosis (OR, 3.05; 95% CI, 1.17 to 7.91; P=0.02) and fibrous crescents (OR, 6.84; 95% CI, 3.22 to 14.52; P

Mechanisms for the generation of anti-dsDNA autoantibodies are still not completely elucidated. One theory states that dsDNA interacts for mimicry with antibodies raised versus other antigens but molecular features for mimicry are unknown. Here we show that, at physiological acid-base balance, anti-Annexin A1 binds IgG2 dsDNA in a competitive and dose-dependent way with Annexin A1 and that the competition between the two molecules is null at pH 9. On the other hand, these findings also show that dsDNA and Annexin A1 interact with their respective antibodies on a strictly pH-dependent basis: in both cases, the binding was minimal at pH 4 and maximal at pH9-10. The anionic charge of dsDNA is mainly conferred by the numerous phosphatidic residues. The epitope binding site of Annexin A1 for anti-Annexin A1 IgG2 was here characterized as a string of 34 amino acids at the NH2 terminus, 10 of which are anionic. Circulating levels of anti-dsDNA and anti-Annexin A1 IgG2 antibodies were strongly correlated in patients with systemic lupus erythematosus (n 496) and lupus nephritis (n 425) stratified for age, sex, etc. These results show that dsDNA competes with Annexin A1 for the binding with anti-Annexin A1 IgG2 on a dose and charged mediated base, being able to display an inhibition up to 75%. This study provides the first demonstration that dsDNA may interact with antibodies raised versus other anionic molecules (anti-Annexin A1 IgG2) because of charge mimicry and this interaction may contribute to anti-dsDNA antibodies generation.

Lupus nephritis (LN) is a frequent and severe manifestation of SLE. Along the decades, the epidemiology of LN and its clinical presentation have been changing. However, even though retrospective cohort studies report a decreased mortality rate and an improvement in the disease prognosis, the percentage of patients progressing into end stage renal disease (ESRD) keeps steady despite the improvements in therapeutic strategies. Current in-use medications have been available for decades now, yet over the years, regimens for optimizing their efficacy and minimizing toxicity have been developed. Therapeutic research is now moving towards the direction of precision medicine and several new drugs, targeting selectively different pathogenetic pathways, are currently under evaluation with promising results. In this review, we address the main changes and persistent unmet needs in LN management throughout the past decades, with a focus on prognosis and upcoming treatments.

Background: Belimumab (Benlysta) is currently approved for the treatment of active Lupus despite standard therapy. Few data are available on the efficacy of this drug in lupus nephritis (LN). Methods: 17 LN female followed in two Nephrology Italian Unit received belimumab for a median period of 36 months (range 6–42 months). The indications were: arthralgia in 3 patients, cutaneous manifestations in 2, residual proteinuria in 8, and the need to reduce steroids for severe side effects in 4. Of interest, 1 patient started therapy during Peritoneal Dialysis and continued after kidney transplantation due to non-responsive arthralgias. Results: Arthralgia and skin manifestations resolved in all patients. Proteinuria normalized in three patients and stabilized in all but one of the others. Steroids were indefinitely stopped in six patients (35%) and reduced to around 40% of the basal dosage in the other patients. During belimumab therapy, three extrarenal and one renal SLE flares were diagnosed accounting for a rate of renal flares of 0.02/patient/year. No major adverse events leading to therapy withdrawal occurred. Clinical case: Arthralgia resolved, immunological parameters improved and prednisone could be reduced within few months in the patient who started belimumab during peritoneal dialysis. After kidney transplantation belimumab was stopped but due to arthralgias unresponsive to standard immunosuppressive therapy it was restarted with success. Conclusions: Belimumab allows the achievement of complete response together with the withdrawal or the reduction of corticosteroids in almost all our patients. Of interest its satisfactory use in a patient in peritoneal dialysis and after kidney transplantation.

We aimed to identify the rates and predictors of chronic damage accrual and mortality in lupus nephritis (LN).We retrospectively measured SLICC/ACR Damage Index (SDI) in biopsy proven active LN with at least 5 years follow-up. We searched for the predictors of first SDI increase and death at univariate and multivariate regression analysis. Then, we considered clinical/biochemical/histological features at diagnosis, corticosteroids dose and proportion of follow-up in complete renal remission.187 patients (91.4% females, age 28.1 years, 95.7% Caucasians) were included. After a median follow-up of 18.6 years, 26 patients (13.9%) died, 116 (62%) accrued damage. SDI annual rate has significantly reduced over the last decades (from a mean of 0.14±0.17 in 1970-1985, to 0.09±0.21 in 1986-2001, to 0.07±0.1 in 2002-2019; p=0.0032). SDI increases occurred more frequently in renal (22.5%), ocular (18.2%), cardiovascular, neuropsychiatric (13.4% both) and malignancy (12.8%) domains. First SDI increase free survival was 73.3%, 59.8%, 49.9% and 38% at 5,10,15 and 20 years. At multivariate analysis, hypertension (HR:1.699, CI:1.126-2.457, p=0.011), presentation with acute renal dysfunction (HR:1.587,CI:1.082-2.327, p=0.018) and average prednisone dose5mg/day (HR:3.378, CI:1.984-5.751, p0.0001) independently predicted damage. Achievement of complete renal remission (HR:0.993, CI:0.987-0.999, p0.039) reduced the risk of damage. Age (HR:1.063, CI:1.027-1.099, p=0.0004), hypertension (HR:3.096, CI:1.211-7.912, p=0.019), and no immunosuppressors as maintenance therapy (HR:4.168, CI:1.212-14.336, p=0.024) predicted mortality at multivariate analysis.Besides arterial hypertension, presentation with acute renal dysfunction and corticosteroids dose predict SDI increase in LN, while achieving renal remission prevents damage. Aggressive therapy to induce remission in the acute phases of LN and low corticosteroids dose in maintenance therapy may prevent the increase of chronic damage.

Objective: The long-term outcome of children born to SLE mothers still represents a controversial topic in literature, with some studies reporting a possible increased prevalence of different neurologic and psychiatric diseases (NPD), including neurodevelopmental disorders (ND), and in particular learning disorders (LD). Different risk factors have been advocated, such as the in utero exposure to auto-antibodies and drugs, particularly Azathioprine (AZA).Methods: A case-control study was designed to compare pregnancies treated with AZA (cases) with those not treated with AZA (controls). All the pregnancies had been prospectively followed in two Italian centers. The match was based upon renal involvement, antiphospholipid (aPL) status, maternal age at pregnancy (±5 years) and child’s age at the time of the study (±2 years). SLE mothers were interviewed by a telephone survey, particularly focused on the presence of a certified NPD in their children ≥6 years of age.Results: Twenty-seven cases and 65 controls were similar in terms of demographic, immunological and clinical features, except for a higher rate of SLE flares during pregnancy in cases (22.2% vs. 10.8%, p:0.191). The 92 children had a mean age of 14.0 years at the time of the survey; 11 had at least one NPD (12.0%). The frequency of each single NPD was similar to that of the general pediatric population and no association was found with either the in utero exposure to AZA, or other specific factors (auto-antibodies, disease activity, obstetric complications, prematurity).Conclusion: The long-term neuropsychiatric outcome of the children born to SLE mothers did not show neither an increased frequency of NPD as compared to the general pediatric population nor a specific pattern of NPD. The in utero exposure to AZA was not associated with the development of NPD in this case-control study of prospectively-followed pregnancies. NPD are complex conditions and large prospective studies are needed to capture the wide range of variables that may contribute to their development in the offspring of SLE women.

In 178-kidney transplanted patients (KTxp), the prevalence of hypovitaminosis-D, the presence and novel development of left ventricular hypertrophy(LVH) and the correlations between native Vitamin-D (25OHD) and LVH were evaluated during the 1st year of transplantation (KTx). Clinical and instrumental data were recorded at pre-KTx and at one (T1) and 12 (T12) months after KTx. 25OHD levels were considered sufficient (s25OHD, ≥ 30 ng/dL) or insufficient (i25OHD

Background CMV disease (CMVd) is a frequent complication in renal transplanted patients (RTxp), especially during the first year of transplantation (RTx). CMVd impacts on long term graft and patients outcomes is still debated. Our observational retrospective study aims to evaluate: 1) the prevalence of CMVd during the first year of RTx; 2) the factors related to CMVd; 3) the relationship between CMVd and early and long term graft and patients survival. Method In 505 RTxp (age: 50[41;58]yrs – 292 males), up to the 616 transplanted in our unit between 2004 and 2016, clinical, blood and urinary parameters were recorded after 1 (T1) and 12 (T12) months of RTx. eGFR was estimated by MDRD formula. Donor (D) and Recipient (R) CMV serology was tested at the moment of RTx. CMV IgG-D+/IgG-R- RTxp (12%) and high risk patients (second or more RTx, ATG induction therapy), received prophylaxis therapy until the 3rd month of RTx. CMVd, was defined by the presence either of CMVr (CMV replication without clinical signs of CMV disease) or CMVs (CMV replication with signs of disease and/or need of antiviral therapy/reduction of immunosuppressive therapy). Median follow up (FU) was 8[5-11]yrs. The following outcomes were investigated: 1) graft: reduction of eGFR >20% between T1 and T12; reduction of eGFR >50% between T1 and end of FU (eGFRr>50%); graft loss (GL); eGFRr>50% + GL.; 2) RTxp survival at the end of FU. Results Ninty percent of RTxp had a kidney from a deceased D; 73% and 21% received haemodialysis (HD+) and peritoneal dialysis before RTx. Dialysis vintage was 50[33-75] months. In 12% of RTxp, induction therapy included ATG. Cumulative steroids dose was 880[840-105]mg and 2272[2598-3223]mg at T1 and T12 respectively. During the first year of RTx, 45% of patients had CMVd (CMVd+). CMVd+ were older than CMV free RTxp (CMVd-). Female gender, HD+ and CMV IgG-D+/IgG-R- were more prevalent in CMVd+. In addition, at T1, CMVd+ had lower albumin, haemoglobin and higher PTH, uric acid and reactive C protein levels than CMVd- and, both at T1 and T12, received higher steroid dose. In multivariate analysis, albumin-T1 was the most significant modifiable factor in determining CMVd+ (p=0.009 OR 0.50 – IC 0.29-0.84). Albumin-T1 maintained its significance also after the addiction of CMV serology IgG-D+/IgG-R- to the model (albumin T1: p=0.008 OR 0.48 – IC 0.29-0.84; CMV serology IgG-D+/IgG-R-: p=0.01 OR 2.16 – IC 1,18 -3,95). Among CMVd, 19% and 25% had respectively CMVr and CMVs. CMVs were characterized by lower dialysis vintage and higher prevalence of CMV IgG-D+/IgG-R- than CMVr. GL and death were observed in 11% and 8% of RTxp respectively. In univariate and survival analyses, CMVd, CMVr and CMVs didn’t show any impact on the graft and patients outcomes examined. Conclusion Our retrospective study confirms the high prevalence of CMVd during the first year of RTx, and identifies albumin at T1 as the most impacting parameter in influence CMVd insurgence. This might reflect the importance of the pre-RTx status in CMVd development after RTx. Nevertheless, CMVd seems not impact significantly on early and long term outcomes, experienced however in a small part of the cohort studied. Future studies, possibly prospective and including higher number of patients might better elucidate this issue.

Background and Aims Tunneled central venous catheter (T CVC) use is rising among patients undergoing chronic hemodialysis (HD) and non-tunneled (NT) CVCs are often used for HD initiation in late referral chronic kidney disease (CKD) or acute kidney injury (AKI). Catheter-related bloodstream infections (CRBSI) are a major complication of CVC use. This study examines potential patient- and CVC- related factors associated with CRBSI incidence and its microbiological features. Method In this retrospective single-center study, 413 patients undergoing an extracorporeal treatment (HD or Plasma Exchange) between February 1st 2014 and January 31st 2017 with 561 CVCs were recruited. Clinical data at study entry and CVC type are summarized in table 1. All bloodstream infections (BSI) occurring during the observation period were recorded and classified into CRBSI or non-CRBSI (nCRBSI), and their infecting agents collected. An incidence rate ratio (IRR (95% CI)) was calculated to assess the association between CRBSI incidence rate (IR), expressed as events/1000 catheter-days, and each clinical variable or CVC type. Significant associations at the univariate analyses were investigated with multivariate cox models. Results During a cumulative follow-up time of 66686 catheter-days, 54 (IR: 0.81) CRBSI and 30 (IR: 0.45) nCRBSI events occurred. CRBSI had higher frequency of GRAM+ bacteria compared with nCRBSI (70% vs 33%, p At the univariate analysis, male sex, age Conclusion Patients affected by AKI and use of NT or Femoral CVCs are independently associated with CRBSI risk.

Background and aims Bone and mineral metabolism (MM) disorders are relevant problems in renal transplanted patients (RTxp). In our observational monocentric study, we evaluated the effects on femoral and lumbar bone mineral density (BMD) and on MM parameters, and the safety of one year-treatment with Denosumab (DB) in a cohort of RTxp. Method We recorded data about 32 RTxp treated with DB in our Center in the last year. RTxp were evaluated for BMD and T-score (Ts) before the start (T0) and after 12 months (T12) of treatment. Osteopenia was defined, at femoral (F-OPN) and lumbar (L-OPN) sites as Ts:-1>Ts>-2.5 whereas osteoporosis, in the same sites (F-OPS and L-OPS) as Ts9.0 mg/dL were the finding at T0 of: 1) F-OPS and/or V-OPS; 2) sVF. During the year of treatment, hypocalcemic (HpCa=Ca Results The cohort was composed mainly by females (n=21). The time of RTx was 144[59-232]mths. Steroid therapy was prescribed in 30 RTxp (93%), 22(68%) and in 2 (6%) RTxp were taking 25OHD and 1-25OH. Three RTxp (9%) were receiving Ca supplements. Bisphosphonate therapy was reported in 15 RTxp (46%) in the year before DB start. At T0, 25(78%) and 7 (22%) RTxp had F-OPS and F-OPN. Twenty-three (71%) and 6 (20%) RTxp had L-OPS and L-OPN. In 3 RTxp normal lumbar T-score was found. sVF were present in 17 RTxp (53%). Ca and P were 9.6±0.6 mg/dL and 3.1±0.6 mg/dL whereas PTH, ALP and 25OHD were 64±32 pg/mL, 80±37 U/L and 28±16 mg/dL. SCr and Prot-U were 1,32±0,4 mg/dL and 0,23±0,16 g/24h. At T12, F-Ts increased significantly (T0: -3.0[-3.5/-2.5] vs T12:-2.8[-3.5/-2.4) as like as V-Ts (T0: -3.0[-3.7/-1.9] vs T12:-2.8[-3.0/-1.6) both p Conclusions The preliminary results presented in our study, limited by the monocentric, not randomized design and by the smallness of the cohort, reported a good bone efficacy of DB in RTxp, especially at lumbar level. The therapy was characterized by a good general safety. Future longer and randomized studies, involving more RTxp might elucidate the possible primary role of DB in the treatment of bone disorders in RTxp.

COVID-19 is a life-threatening infection among elderly patients, comorbid patients, or transplanted patients. Lombardy (region of Italy), accounts for 786,324 cases as of 21 April 2021. We retrospectively describe our single Centre experience in 82 adult kidney-transplant patients with COVID-19 infection during two pandemic outbreaks: 27 (first outbreak) and 65 (second outbreak). Thirty-seven patients were hospitalized (HP) and sixty-five were home managed (HM). Infection presented with fever (80%), cough (51%), and dyspnea (33%). HP were older (60 ± 11 vs. 50 ± 14 years, p = 0.001), had more severe respiratory symptoms (dyspnea 62.1%, p &lt, 0.0001–cough 67% p = 0.008), and a longer length of disease (30 ± 28 vs. 21 ± 10, p = 0.04). The incidence of acute kidney injury (AKI) was 29.7% (p &lt, 0.0001). Steroid dosage was increased in 66% of patients (p = 0.0003), while calcineurin inhibitors were reduced by up to one third in 45% of cases, p &lt, 0.0001. Eleven patients died (13%). HM patients recovered completely without sequelae. In the overall cohort, AKI development (p = 0.006 OR 50.4 CI 95% 3.0–836) and age (p = 0.04 OR 1.1 CI 95% 1.0–1.2) were the most important factors influencing the probability of death during the infection. Although we report a relatively low incidence of infection (5.1%) the incidence of death is almost four times higher than it is in the general population.

Renal involvement is a frequent and severe complication of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV). It is generally characterized by a pauci-immune necrotizing and crescentic glomerulonephritis with a very rapid decline of renal function (rapidly progressive glomerulonephritis). Even though there are no qualitative differences in glomerular lesions in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), chronic damage is usually higher in MPA (and/or P-ANCA-positive patients) than in GPA (and/or CANCA-positive patients). If untreated, necrotizing and crescentic glomerulonephritis has an unfavorable course leading in a few weeks or months to end-stage renal disease (ESRD). Serum creatinine at diagnosis, sclerotic lesions, and the number of normal glomeruli at kidney biopsy are the best predictors of renal outcome. Corticosteroids and cyclophosphamide or rituximab (with the addition of plasma exchange in the most severe cases) are the cornerstone of induction treatment of ANCA-associated renal vasculitis, followed by azathioprine (or methotrexate, mycophenolate, rituximab) for maintenance. Despite significant improvement in patient outcomes over the past decades, AAV still results in ESRD in a quarter of patients over 5 years. Relapse rates are significantly lower in patients on chronic dialysis. Patient survival on regular replacement treatment (RRT) does not differ between AAV and matched nondiabetic patients, while it is lower than that of glomerulonephritis. Patients with AAV who undergo kidney transplantation have a mortality not different from the matched control group of primary glomerulonephritides, and favorable transplant survival is similar to that of the matched control groups.

Background The most effective drug for the maintenance therapy of severe forms of lupus nephritis (LN) is still a matter of debate. Objectives To compare efficacy and safety of cyclosporine (CYA) with mycophenolate mofetil (MMF) and with azathioprine (AZA) in the long-term maintenance therapy of LN. Methods Ninety-six patients (pts) (93 females, mean age 31.98±12.78 years) with SLE and biopsy proven LN (16 pts:class III; 64 pts:class IV; 16 pts:class V ISN/RPS). Fifty-six pts entered this study at diagnosis of LN and 40 during a course of a LN flare. Twenty-five pts (30%) had Glomerular Filtration Rate (eGFR) 60ml/min and proteinuria 60ml/min and proteinuria >0.5/die, no response: eGFR Results At the beginning of maintenance therapy, the mean serum creatinine and eGFR were similar in the 3 groups (0.92±0.26mg/dl, eGFR 109,9±49,5ml/min in CYA, 0.86±0.4mg/dl, eGFR 119±44,6 in MMF, 0.85±0.3mg/dl, eGFR 106,6±43,9ml/min in AZA). Proteinuria was higher in CYA group (CYA:2.03±1.7g/day; MMF:0.77±0.8g/day; AZA:1.2±1.1g/day). At the beginning of maintenance therapy, complete, partial and no response were 26.6%, 60%, and 13.4% in CYA, 53.1%, 43.8% and 3.1% in MMF and 38.2%, 58.8% and 3% in AZA group (Fig 1). At 1 year, after 6 months of maintenance therapy, in CYA group the percentage of pts in complete remission increased to 73% (vs 65.6% in MMF and 40% in AZA), at 5 years it was 80% (vs 83% in AZA and in MMF) and 88% at 10 years vs 70% in MMF and 68% in AZA (Fig 2,3,4). The percentage of non-responsive pts was stable from 1 to 10 years in the CYA group (around 13%), it slightly increased in MMF group (from 3.1 to 13,5%) and in AZA group (from 15 to 24%). During the study, SLE flares occurred in 30% of CYA group, 41% in MMF and 32% of the AZA. The average time from the beginning of the study and the first flare was 3.95±2.76years in CYA, 3.62±1.60 in MMF and 5.9±2.37 in AZA. No side effects were reported in 90% of pts treated with CYA, in 81.3% with MMF and in 85.3% with AZA group. Conclusion This is the first study comparing these 3 drugs as maintenance therapy in the long term. After 10 years of observation, CYA, AZA and MMF have proven to be effective in consolidating and maintaining the remission of LN. Of interest are the results achieved in the CYA group. Despite worse clinical conditions at the beginning of maintenance therapy, CYA allowed a rapid achievement of LN remission in the great majority of pts compared to AZA and MMF. Remission persisted over 10 years of observation. The number and type of flares and of side effects were not different between groups. Reference [1] Moroni G, et al. 2006 Disclosure of Interests Lorenza Maria Argolini: None declared, Elena Elefante: None declared, Francesca Saccon: None declared, Valentina Binda: None declared, Maria Gerosa: None declared, Luigi Sinigaglia Speakers bureau: Yes, I,ve been invited speaker by Amgen, Ely Lilly, UCB, Abbvie, Roche and BMS., Piergiorgio Messa: None declared, Andrea Doria: None declared, Marta Mosca Paid instructor for: GlaxoSmithKline, Lilly, UCB, Gabriella Moroni: None declared

There is little information about very long-term outcomes of kidney allograft recipients exposed to calcineurin inhibitors. In this single-centre retrospective study with 20-year follow-up, we analyzed data from 644 patients who underwent primary renal transplantation between 1983 and 1993. Participants were treated with a cyclosporine-based immunosuppressive scheme and had allograft function at 1 year. After 20 years, 15.2% patients died, 39.7% experienced allograft loss, 26.8% were alive with a functioning transplant, and 18.2% were lost to follow-up. Cardiovascular disease (30.8%), malignancy (26.6%) and infection (17.0%) were the main causes of death. Age, new-onset proteinuria > 1 g/day, major acute cardiovascular event (MACE), and malignancy were independent predictors of mortality at time-dependent multivariate analysis. Chronic rejection (63.3%), recurrent glomerulonephritis (14.0%), and nonspecific interstitial fibrosis/tubular atrophy (13.2%) were the leading cause of allograft loss. Basal disease, hepatitis C, difference between 1 year and nadir serum creatinine, new-onset proteinuria > 1 g/day, and MACE were independent predictors of transplant failure. Among patients with 20-year allograft function, we recorded the following complications: hypertension (85%), malignancy (13%), diabetes (9%), and cardiovascular disease (9%). Median serum creatinine and proteinuria were 1.4 mg/dL and 0.6 g/day, respectively. Prolonged use of cyclosporine may expose to several dose-related adverse events and may contribute to the development of allograft dysfunction but it does not necessarily cause relentless, progressive transplant failure if patients are carefully and consistently monitored during the follow-up.

Background:Indications to repeat renal biopsy (RB) in lupus nephritis (LN) are not unanimously acknowledged.Objectives:To evaluate the renal outcome of patients with LN undergoing a second RB.Methods:We retrospectively analyzed prospectively collected data of patients with LN followed up in four Italian referral centres for systemic lupus eryhtematosus. Serological and clinical information were retrieved according to a shared database. RB were classified according to ISN/RPS 2003 classification; chronicity (CI) and activity indexes (AI) were defined according to Austin et al. The primary renal outcome was renal failure, defined as serum creatinine (SCr)>1.0mg/dL with eGFRResults:Four-hundred and thirty-eight patients were recruited. One-hundred and three patients repeated RB after 6.1±4.7 (mean± SD) years from the first due to: protocol biopsy due to renal remission (Group 1, n=8); proteinuric flare (Group 2, n=51); worsened renal function (Group 3, n=26); partial renal response (Group 4 n=18). Patients undergoing a second RB were younger (pConclusion:Patients undergoing a repeated RB had more aggressive clinical and histological features already at first RB and developed renal failure more frequently. Among baseline features, uncontrolled hypertension had the strongest association with renal failure, thus suggesting that control of blood pressure since early stages is highly advisable.References:[1]Austin HA, et al. Predicting renal outcomes in severe lupus nephritis: contributions of clinical and histologic data. Kidney Int 1994;45:544–50.Table .Comparison of patients undergoing 2nd RB according to development of renal failureRenal failure (n=26)No renal failure (n=69)*pTotal FU (years), mean (SD)21 (10.4)16.5 (9.39)0.002SCr (mg/dl) at 2° RB, mean (SD)1.7 (1)0.98 (0.35)0.001Proteinuria (g/24h) at 2° RB, mean (SD)4.7 (3.9)2.99 (2.63)0.022Class IV and IV+V at 2° RB, %76.954.50.07Hypertension at onset, %84.632.4HCQ intake at 2° RB, %9.552Glucocorticoids at 2° RB %8487nsImmunosuppressants at 2° RB %4058nsAI at onset, mean (SD)7.14 (3.95)7.02 (3.86)nsAI at 2° RB, mean (SD)5.37 (4.12)4.02 (3.71)nsCI at onset, mean (SD)2.05 (1.88)1.56 (1.64)nsCI at 2° RB, mean (SD)3.87 (3.08)3.52 (2.16)nsYears between 2° RB and end of FU, mean (SD)14.1 (10.5)9.3 (8.84)ns*Group 1 excludedRB, renal biopsy; AI, activity index; CI, chronicity index; SCr serum creatinine; FU, follow-up; SD, standard deviation.Disclosure of Interests:Mariele Gatto Speakers bureau: GSK, Francesca Saccon: None declared, Francesca Radice: None declared, Paolo Gilles Vercelloni: None declared, Renato Alberto Sinico: None declared, Giulia Frontini: None declared, Valentina Binda: None declared, Piergiorgio Messa: None declared, Federico Alberici: None declared, Gabriella Moroni: None declared, Andrea Doria Consultant of: GSK, Pfizer, Abbvie, Novartis, Ely Lilly, Speakers bureau: UCB pharma, GSK, Pfizer, Janssen, Abbvie, Novartis, Ely Lilly, BMS

Lupus nephritis (LN) treatment requires an initial intensive period of therapy followed by a long-term maintenance treatment in order to stabilize disease control and eventually reach renal remission. In this section, Authors discuss the feasibility of safely lowering and even suspending maintenance therapy in LN patients having entered remission, highlighting hurdles in predicting the depth and durability of disease quiescence together with the need for minimizing potentially toxic therapies. Even though no firm conclusions can still be drawn, the treating physician has to find the wise balance between disease control and treatment-related drawbacks by following patients closely and recognizing as early as possible the ones who are likely to reach a deep and durable renal remission; there is consensus that is these are the only patients in whom a potential safe complete withdrawal can be foreseen so far.

Twenty-yr patient and death-censored graft survival of 348 kidney transplant recipients with primary glomerulonephritis (GN) and of 696 matched controls were 82.2% in GN patients and 75% in controls (p = 0.037) and 49.5% and 54%, respectively (p = 0.013). GN patients had a higher incidence of graft failure than controls even considering death as a competing risk (p = 0.004). In the GN group, graft survival of deceased and of living donor recipients was similar. At multivariate analysis, GN as primary disease (RR: 1.47), delayed graft function recovery (RR: 2.34), acute rejection (RR: 2.36), and any PRA positivity (RR: 1.01) were predictive of graft loss. GN recurred in 85 of 348 grafts (24.4%), and 43 were lost for recurrence. In non-recurrent patients, graft survival at 20 yr was significantly better than in recurrent patients (59.4% vs. 24.4%, p = 0.000), but not different from that of controls (59.4 vs. 54%, p = 0.9). At multivariate analysis, young age at transplantation (RR: 0.97), shorter duration of dialysis (RR: 1.05 per each dialysis year), and graft from living donors (RR: 1.668) were independent predictors of recurrence. Patients with primary GN have reduced graft survival in comparison with controls, and this is mainly due to recurrence of original disease. However, the most frequent recurrence in living recipients does not compromise graft survival.