AimsDiagnosis of primary membranous nephropathy (PMN) is mainly based on immunofluorescence/immunohistochemistry findings. However, assessment of specific features on optical microscopy can help to estimate the severity of the disease, guide treatment and predict the response. The aim of this study was to identify, classify and grade the precise histological findings in PMN to predict renal function outcome and guide treatment.Methods and resultsHistological parameters, including focal segmental sclerosis (FSGS), tubular atrophy (TA), interstitial fibrosis (IF) and vascular hyalinosis (VH), were re‐evaluated in 752 patients with PMN. Their predictive value was estimated separately, and also in a combination score (FSTIV) graded from 0 to 4. Finally, the impact of histology was assessed in the response to immunosuppressive treatment. Mean age of patients was 53.3 (15–85) years and most presented with nephrotic syndrome. FSGS was present in 32% and VH in 51% of the patients, while TA and IF were graded as stage ≥1 in 52% and 51.4%, respectively. The follow‐up period was 122.3 (112–376) months. FSGS, TA and IF and VH were associated with impaired renal function at diagnosis (P = 0.02, P < 0.0001, P = 0.001 and P = 0.02, respectively) and at the end of follow‐up (P = 0.004, P < 0.0001, P < 0.0001 and P = 0.04, respectively). In multiple regression and binary logistic analysis, the presence of FSGS and degree of TA were the most significant parameters predicting renal function outcome, defined either by eGFR (end), FSGS (r = 0.6, P < 0.0001) and TA (r = 0.6, P < 0.0001), or by the endpoint of >50% eGFR reduction, FSGS (P = 0.001) and TA (P = 0.02). Also, patients presented with FSGS, IF, VH and/or with FSTIV > 1 could benefit from immunosuppression, regardless of clinical presentation.ConclusionsThe presence and degree of four histological indices, FSGS, VH, TA and IF, assessed separately or in combination, and FSTIV score not only predict renal function outcome after long‐term follow‐up, but can also help in the choice of appropriate treatment. Decisions concerning immunosuppressive treatment can be guided by pathology regardless of clinical findings.

3033 The adverse prognosis of renal impairment in patients with multiple myeloma (MM) has been reported in several series. However, the prognostic impact of renal dysfunction on the survival of MM patients who are treated upfront with novel agents has not been clearly defined. To address this question we studied 180 consecutive patients who received upfront novel agent (thalidomide, bortezomib or lenalidomide)-based regimens, in a single center in Athens, Greece. Many of these patients had been included in clinical trials; however, several patients who were ineligible because of poor performance status, significant renal impairment or comorbidities were also treated with novel agent-based regimens. Thus, these patients are more representative of the general myeloma population. Renal function, estimated by the glomelural filtration rate (eGFR) was assessed using the simplified Modification of Diet in Renal Disease (MDRD) formula (eGFR in mL/min/1.73 m2 = 186 × (Serum Creatinine)−1.154 × (Age)−0.203 × (0.742 if female) × (1.212 if African-American). Patients were divided into 5 groups according to the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI) chronic kidney disease (CKD) classification. According to this classification, stage 1 includes patients with eGFR ≥90 ml/min, while stage 2 includes patients with eGFR between 60–89 ml/min, stage 3 with eGFR between 30–59 ml/min, stage 4 with eGFR between 15–29 ml/min and stage 5 includes patients with eGFR below 15 ml/min or patients who undergo dialysis. Eighty-five patients (47%) had stage 3–5 CKD and 95 (53%) had stage 1 or 2 CKD. One half of our patients (51%) were 70 years of age or older. Advanced age (p=0.001), anemia (p<0.001), low serum albumin (p=0.017), hypercalcemia (p<0.001), elevated beta2-microglobulin (p<0.001) and Bence Jones proteinuria >2 g/day (p<0.001) were associated with stage 3–5 CKD. The majority of patients with International Scoring System (ISS)-3 myeloma had advanced renal disease (stage 3–5 CKD in 76%) in comparison with ISS-2 (33%) or ISS-1 (10.5%) patients (p<0.001). Eighty-one percent of our patients received upfront an IMiD-based therapy, while 19% received bortezomib-based regimens. The dose of lenalidomide was adjusted according to renal function. The frequency of advanced CKD was similar among patients treated with IMiDs- or bortezomib-based regimens (47% vs. 48.5%, p=0.843). Response to primary treatment was similar between patients with stage 3–5 CKD and patients with stage 1 or 2 CKD (72.6% vs. 78.7%, respectively; p=0.343). In the univariate analysis, variables associated with worse survival were: stage 3–5 CKD (median survival 39 months vs. not reached in stage 1 or 2 CKD; p=0.001), age ≥70 years (p<0.001), anemia (p=0.005), hypercalcemia (p=0.012), ISS stage (p<0.001) and LDH ≥300 IU/L (p=0.007). However, in the multivariate analysis, the presence of renal dysfunction (stage 3–5 CKD) or the degree of renal dysfunction (evaluating each CKD stage separately) was not independently associated with survival. Age >70 years (p<0.001), corrected serum calcium ≥11.5 mg/dl (p=0.04) and elevated LDH ≥300 IU/L (p=0.001) were the only independent factors associated with worse survival. The same results were obtained when we assessed renal function as a continuous variable. We also evaluated the effect of CKD staging on the survival of patients within each ISS stage and we did not find any statistically significant correlation. We conclude that the presence °r the degree of renal dysfunction has no independent prognostic impact on the survival of multiple myeloma patients who are treated upfront with novel agent-based regimens. Disclosures: No relevant conflicts of interest to declare.

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