OBJECTIVES:We aimed to identify the rates and predictors of chronic damage accrual and mortality in lupus nephritis (LN).METHODS: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.RESULTS: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 dose >5mg/day (HR:3.378, CI:1.984-5.751, p<0.0001) independently predicted damage. Achievement of complete renal remission (HR:0.993, CI:0.987-0.999, p<0.039) 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.CONCLUSIONS: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.

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, < 30 ng/dL). 25OHD correlated at T1 with parathormone(PTH), and at T12 with 25OHD-T1 and PTH-(T1,T12). At T12, s25OHD (15%) had higher 25OH and alkaline phosphatase (ALP), lower Ca, at T1, and lower PTH-(T1, T12) than i25OH-T12. At T1, KTxp with LVH (LVH-T1pos, 42%) were older and with longer dialysis vintage than LVH-T1neg. At T12, KTxp with LVH (LVH-T12pos, 53%) were older, with higher systolic blood pressure (SBP) at T12 than LVH-T12neg. No relation between 25OHD and LVH were found. Novel LVH was found in 14% of KTxp. They were older, had higher SBP-T12 and lower serum albumin-T12 than the others. LVH-modifications and 25OHD were not correlated. Hypovitaminosis-D is highly prevalent in KTxp. LVH correlates with different risk factors according to the time elapsed from KTx. However, during the 1st year of KTx, no relationship between LVH and 25OHD was observed.

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.

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 eGFR<60ml/min. Non-parametric tests were used for statistics. Patients repeating RB due to renal remission were excluded from the analysis. Results: 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 (p<0.001), had lower serum C3 at LN diagnosis (p<0.001) and displayed more frequently class IV and higher AI at first RB (p=0.0038 and p=0.043, respectively). At the end of follow-up, patients who repeated RB had more frequently renal failure (p=0.003). At the second RB, the histological class was unchanged in 55% of patients. CI increased at second RB compared to the first (3.6±2.4 vs.1.7±1.7; p<0.001). Overall, 26 out of 103 patients (25%) developed renal failure: 0 from group 1, 10 from group 2, 14 from group 3, 2 from group 4 (p<0.001). Uncontrolled hypertension at LN diagnosis, increased SCr and increased proteinuria at second RB predicted renal failure (Table). Conclusion: 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 failure Renal failure (n=26) No renal failure (n=69)* p Total FU (years), mean (SD) 21 (10.4) 16.5 (9.39) 0.002 SCr (mg/dl) at 2° RB, mean (SD) 1.7 (1) 0.98 (0.35) 0.001 Proteinuria (g/24h) at 2° RB, mean (SD) 4.7 (3.9) 2.99 (2.63) 0.022 Class IV and IV+V at 2° RB, % 76.9 54.5 0.07 Hypertension at onset, % 84.6 32.4 <0.001 HCQ intake at 2° RB, % 9.5 52 <0.001 Glucocorticoids at 2° RB % 84 87 ns Immunosuppressants at 2° RB % 40 58 ns AI at onset, mean (SD) 7.14 (3.95) 7.02 (3.86) ns AI at 2° RB, mean (SD) 5.37 (4.12) 4.02 (3.71) ns CI at onset, mean (SD) 2.05 (1.88) 1.56 (1.64) ns CI at 2° RB, mean (SD) 3.87 (3.08) 3.52 (2.16) ns Years between 2° RB and end of FU, mean (SD) 14.1 (10.5) 9.3 (8.84) ns *Group 1 excluded RB, 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

Abstract 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.

kidney disease were identified. Demographic characteristics of study group are shown in Table 1. 77 (%74) of patients were transplanted from living and 27 (%26) of patients from cadaveric donors. Mean duration of follow-up was 131667 months. Patient and graft survival rates did not differ significantly across varies genetic disease (p1⁄40.081 and p1⁄40.862 respectively). In subgroup analysis, patient who had monogenic kidney diseases had better survival rates compared to patients with polygenic kidney diseases (p1⁄40,04) (Figure 1). Pre-transplant HLA mismatch and biopsy confirmed rejections were significantly associated with graft loss. We did not find any significant effect of patient age, disease, and donor type (cadaveric or living) on allograft loss. In subgroup analysis, patients with hereditary glomerulonephritis had lower survival rates compared to other diseases (p1⁄40.042) (Figure 2). CONCLUSIONS: Patient with hereditary glomerulonephritis had lower survival rates compared to other diseases probably due to inflammation

BACKGROUND:Pemphigus foliaceus (PF) has both genetic and environmental susceptibility factors. Current data on human leucocyte antigen (HLA) in patients with sporadic PF are limited.AIM:To better define the distribution of HLA alleles in patients with PF in the UK.METHODS:We recruited 36 patients [26 of white British (WB) descent, 10 of Indo-Asian (IA) descent] with PF who were living in the UK and 159 ethnically matched normal controls, and analysed their class II HLA DRB1 and DQB1 allele distribution.RESULTS:There was an increased frequency of DRB1*1404 in association with DQB1*0503 in IA patients with PF. The DRB1*04 allele group as a whole had an increased frequency (P < 0.001) in the WB patient group compared with controls. The alleles contributing to this significance were DRB1*0401 (P = 0.03) and DRB1*0404 (P < 0.01).CONCLUSION:This is the largest HLA association study in sporadic PF from the UK to date. There appears to be a difference in PF susceptibility alleles between WB and IA patients, highlighting the importance of racial variation in genetic susceptibility to disease development.

Objective: Bone and cardiovascular disorders(CD) are relevant problems during kidney transplantation(KTx),especially during the 1styear. High interest in bone mineral density(BMD) in relation with vascular calcifications(VC)andCD is nowadays present. Our study wants to evaluate, in KTx pts:1)the prevalence of femoral osteopenia(OP)and osteoporosis(OS);2)the factors related to femoral BMD(F-BMD);3)the relationship between F-BMD and aortic calcifications(ACI);4)the role of F-BMD in predicting CD during the 1styear of KTx. Design and method: 293-KTx pts transplanted between2004 and 2013 were evaluated. Clinical parameters, fasting blood and urinary samples were collected at 1st(T0) and 12thmth(T12) after KTx. In addition, at the same time:1)in 170 FGF-23, Fetuin and 25OH-VitD were dosed;2)F-BMD(g/cm2), assessed by DEXA, was performed. T-score -1 > T>-2.5 was considered OP whereas T-score < -2.5 OS; 3)in 115 pts a Lumbar X-Ray for the ACI evaluation(Kauppila score)was performed. ACI progression(ACI-Prog) was determined by their simple increase. CD was defined by a major disease affecting heart (f.i. stroke, arrhythmia) or vascular (f.i. stenosis/thrombosis) system. Results: At T0 and T12 OP was present in 53%and52%of patients, OS in 15%and12%. At T0, F-BMD correlated directly with BMI, alkaline-phosphatase (ALP), fetuin, FGF-23 and 25OH-VitD (p = 0.003;p = 0.01;p = 0.02;p = 0.005)and inversely with the age, time of dialysis and s-P(p < 0.0001;p = 0.01;p = 0.03). At T12, a direct correlation with BMI,FGF-23 and fetuin (p = 0.001;p = 0.04,p = 0.003) and an inverse one with age and time of dialysis (p < 0.0001;p = 0.001) were found. In multivariate analysis age and fetuin resulted able in determining F-BMD, at T0 in addition to ALP and P. At T0 and T12,ACI were present in 55%and in61% of pts. Both at T0andT12 ACI were more in pts with abnormal F-BMD(p = 0.06–p = 0.01), without differences between OP and OS. During follow-up, in 26%of ptsACI-Prog was found. Their F-BMD was lower both at T0 and T12(p = 0.01;p = 0.03). Using ROC-curve, F-BMD showed a predictive role of ACI-Prog (T0:AUC0.65–p = 0.02;T12:AUC0.69-p = 0.005). During follow-up,8pts had a CD. Their T0-T12 F-BMD were not different with those of CD-free pts. Conclusions: 1) The prevalence of OPandOS is quite high in KTx. Fetuin and age influence independently F-BMD. 2) ACI are present approximately in half of patients. A small degree ofACI-progr was found. F-BMD could be a indirect indicator of ACI and of ACI-progr. 3)F-BMD seems not able to predict CV during the 1styear of KTx. Our results confirm a cross-link between bone mineralization and VC in KTx patients.

Objective: Bone and cardiovascular disorders(CD) are relevant problems during kidney transplantation(KTx),especially during the 1styear. High interest in bone mineral density(BMD) in relation with vascular calcifications(VC)andCD is nowadays present. Our study wants to evaluate, in KTx pts:1)the prevalence of femoral osteopenia(OP)and osteoporosis(OS);2)the factors related to femoral BMD(F-BMD);3)the relationship between F-BMD and aortic calcifications(ACI);4)the role of F-BMD in predicting CD during the 1styear of KTx. Design and method: 293-KTx pts transplanted between2004 and 2013 were evaluated. Clinical parameters, fasting blood and urinary samples were collected at 1st(T0) and 12thmth(T12) after KTx. In addition, at the same time:1)in 170 FGF-23, Fetuin and 25OH-VitD were dosed;2)F-BMD(g/cm2), assessed by DEXA, was performed. T-score -1 > T>-2.5 was considered OP whereas T-score < -2.5 OS; 3)in 115 pts a Lumbar X-Ray for the ACI evaluation(Kauppila score)was performed. ACI progression(ACI-Prog) was determined by their simple increase. CD was defined by a major disease affecting heart (f.i. stroke, arrhythmia) or vascular (f.i. stenosis/thrombosis) system. Results: At T0 and T12 OP was present in 53%and52%of patients, OS in 15%and12%. At T0, F-BMD correlated directly with BMI, alkaline-phosphatase (ALP), fetuin, FGF-23 and 25OH-VitD (p = 0.003;p = 0.01;p = 0.02;p = 0.005)and inversely with the age, time of dialysis and s-P(p < 0.0001;p = 0.01;p = 0.03). At T12, a direct correlation with BMI,FGF-23 and fetuin (p = 0.001;p = 0.04,p = 0.003) and an inverse one with age and time of dialysis (p < 0.0001;p = 0.001) were found. In multivariate analysis age and fetuin resulted able in determining F-BMD, at T0 in addition to ALP and P. At T0 and T12,ACI were present in 55%and in61% of pts. Both at T0andT12 ACI were more in pts with abnormal F-BMD(p = 0.06–p = 0.01), without differences between OP and OS. During follow-up, in 26%of ptsACI-Prog was found. Their F-BMD was lower both at T0 and T12(p = 0.01;p = 0.03). Using ROC-curve, F-BMD showed a predictive role of ACI-Prog (T0:AUC0.65–p = 0.02;T12:AUC0.69-p = 0.005). During follow-up,8pts had a CD. Their T0-T12 F-BMD were not different with those of CD-free pts. Conclusions: 1) The prevalence of OPandOS is quite high in KTx. Fetuin and age influence independently F-BMD. 2) ACI are present approximately in half of patients. A small degree ofACI-progr was found. F-BMD could be a indirect indicator of ACI and of ACI-progr. 3)F-BMD seems not able to predict CV during the 1styear of KTx. Our results confirm a cross-link between bone mineralization and VC in KTx patients.

OBJECTIVES:In 2010 a histopathological classification of ANCA-associated glomerulonephritis was proposed to predict the outcomes at diagnosis. Our aim was to validate the proposed classification in our cohort of patients and to compare the studies already published.METHODS:The data of 93 patients who underwent kidney biopsy in a single Italian centre within 15 years were retrospectively collected.RESULTS:The 10-year renal and patients' survival were 60% and 81%, respectively. Biopsies were classified as 21% focal, 30% crescentic, 39% mixed and 10% sclerotic. Survival without ESRD at 5 years was 82% in focal, 37% in crescentic, 81% in mixed and 51% in sclerotic group. The Kaplan-Meier analysis highlights that renal survival was not different between sclerotic and crescentic groups (p=0.9) but both had a significantly worse prognosis than focal (p=0.04 and 0.015 respectively) and mixed groups (p=0.05 and 0.03 respectively). Focal and mixed groups had the same renal survival (p=0.7). At multivariate analysis the independent predictors of end-stage renal disease were less than 20% of normal glomeruli at kidney biopsy (p=0.022), high serum creatinine (p=0.009) and arterial hypertension at presentation (p= 0.006).CONCLUSIONS:In our cohort, the proposed histological classification was not predictive of renal prognosis. The focal and the mixed classes had the same prognosis and a significantly better renal outcome than both the crescentic and the sclerotic classes. At multivariate analysis among the histological features only less than 20% of normal glomeruli defines the renal prognosis together with renal function and arterial hypertension at baseline.