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Valeria Cernaro, Sebastiano Calimeri, Alfredo Laudani, Domenico Santoro Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Messina, ItalyCorrespondence: Valeria CernaroUnit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria N. 1, Messina 98124, ItalyTel/Fax +39.090.2212317Email valecern82@virgilio.itAbstract: Patients with progressive chronic kidney disease (CKD) commonly develop mineral and bone abnormalities and extraskeletal calcifications with following increased cardiovascular risk. A key pathophysiological role is played by hyperphosphatemia. Since diet and dialysis are often insufficient to control serum phosphorus levels, many patients require treatment with phosphate binders. Among them is lanthanum carbonate, an aluminum-free non-calcium-based compound. The present review summarizes the most recent literature data concerning the safety, efficacy and tolerability of lanthanum carbonate in patients with end-stage renal disease and hyperphosphatemia. The drug is taken orally as chewable tablets or powder with only minimal gastrointestinal absorption and resulting reduced risk of tissue deposition and systemic drug interactions. The dissociation of the drug in the acid environment of the upper gastrointestinal tract induces the release of lanthanum ions, which bind to dietary phosphate forming insoluble complexes then excreted in the feces. Even though there is no clear evidence that lowering serum phosphorus levels can improve patient-centered outcomes, a mortality benefit with all phosphate binders, especially non-calcium containing ones, is not excluded. Lanthanum carbonate has been suggested to decrease all-cause mortality but not cardiovascular event rate compared to other phosphate binders. It induces a lower suppression of bone turnover than calcium carbonate and calcium acetate and may improve systolic function and cardiac dimension compared to calcium carbonate. Moreover, the use of lanthanum carbonate has been associated with better nutritional status compared to other phosphate binders, lower risk for hypercalcemia than calcium-containing binders, and amelioration of mild metabolic acidosis contrary to sevelamer hydrochloride. Main adverse effects include nausea, alkaline gastric reflux, gastric deposition of lanthanum, gastrointestinal obstruction, subileus, ileus, perforation, fecal impaction, and reduction of gastrointestinal absorption of some drugs including statins, angiotensin-converting enzyme inhibitors and some antibiotics such as fluoroquinolones or tetracyclines.Keywords: adverse effects, chronic kidney disease-mineral bone disorder, CKD-MBD, hyperphosphatemia, lanthanum carbonate, phosphate binders

Background and Aims Lupus nephritis (LN) develops in about 50% of patients affected by Systemic Lupus Erythematosus (SLE) and it is associated with higher morbidity and mortality risk. Approximately 10 % of LN patients is expected to reach end stage renal disease (ESRD). Proteinuria at 1 year has been demonstrated as the best predictor factor of long-term renal outcome. We compared the effects of two different induction therapies (Euro Lupus protocol [EL] vs Mycophenolate [MMF]) in terms of eGFR, proteinuria, serum albumin and complement activation in LN patients related to our centre. Method We retrospectively reviewed the records of 34 adult patients with LN from 2011 to 2019. Patients were divided in two groups according to therapeutic strategy chosen: EL (n=21 patients, group 1) and MMF (n=13, group 2). Data with normal distribution are expressed as average ± standard deviation, while data with non normal distribution are referred to as median and interquartile range [IQR]. Basal values of eGFR, proteinuria, albumin and complement were compared to 1 year values with Student t-test for normal variables or with Wilcoxon test for non normal variables. Results The mean age of the patients was 41.27±17.43 years, there was a predominance of female (85,3%) LN was diagnosed at 32±16 years old. According to LN classification, 88.2% of them was affected by III, IV, V and mixed LN class Basal values of eGFR (estimated with CKD-EPI method) were similar between groups 1 and 2 (86.12±52.86 vs 73.75±30.35, P=0.4890) as well as proteinuria (2.00 [0.48-4.57] vs 0.71 [0.28-1.39] g/24h, P=0.3284). After one year of follow up, eGFR did not show significant differences between two groups, while proteinuria was significantly lower in group 1 (2.)). 00 [0.48-4.57] vs 0.44 [0.19-0.91] g/24h, P=0.0034) than in group 2 (0.71 [0.28-1.39] vs 0.15 [0.08-0.77] g/24h, P=0.4687) (fig.1). Moreover, we recorded in group 1 higher values of albumin after one year of follow up (3.20 [2.52-3.94] vs 4.33 [3.99-4.57] g/dl, P=0.0195) (fig.2) and C3 consumption (35.00 [1.00-81.25] vs 89.00 [2.00-112.50] mg/dl, P=0.0067) (fig.3), while group 2 did not show any statistically significant differences. Conclusion In patients affected by LN, EL protocol demonstrated to be more effective than MMF in reducing one year after proteinuria, thus improving albumin and C3 serum titer.

Background and Aims A real progress in treating patients more than diseases, would rest on tailored medicine and go beyond the hypothesis that “one size fits all”. Glomerular diseases are not an exception to this consideration, and deserve case-by-case evaluation for choosing both the most suitable therapeutic agent and its appropriate dose, because a standardized treatment may result in worse prognosis. We analyzed the role of body mass index (BMI) in modifying renal outcomes of patients with nephrotic syndrome due to membranous nephropathy (MN) treated with immunosuppressive drugs. Method We performed a retrospective analysis of 29 MN patients related to our center (M 19, F 10), checking their anti PLA2R status at kidney biopsy time and any change in proteinuria, serum creatinine (SCr) and body mass index (BMI) between diagnosis and at last follow-up visit, in search of a correlation with their response to immunosuppressive treatment. Data with non normal distribution are expressed as median and interquartile range [IQR]. Results The median follow-up of our patients lasted 49 months [IQR 14-80]. At biopsy time, almost half of them was anti-PLA2R positive (n=14 subjects) while the other resulted to be negative and were thus screened for secondary causes of MN (n=15). Irrespective either of anti-PLA2R status or the administration of Ponticelli regimen or Rituximab, complete remission was achieved in 31% of patients, while 34.5% experienced a partial remission and 34.5% resulted non responder to at least a therapeutic protocol. Median proteinuria reduction was of 3.732g/24h [IQR 7.636-1.77 g/24h]. Median rise in SCr was 0.140 mg/dl [IQR -0.11 – 0.4 mg/dl]. Direct association between the proteinuria/BMI ratio at diagnosis and remission of proteinuria at last follow up was statistically significant (r=-0.7506; P Conclusion Albeit remission is not directly correlated with basal BMI, our results appear to confirm that an appropriate drug posology, not only according to patients’ renal or hepatic function but also to their body mass, may result in more effective individualized therapies in MN; nevertheless, this recorded association must be confirmed by large scale randomized clinical trials.

Diabetes mellitus (DM) poses a major public health problem worldwide, with ever-increasing incidence and prevalence in recent years. The Institute for Alternative Futures (IAF) expects that the total number of people with type 1 and type 2 DM in the United States will increase by 54%, from 19,629,000 to 54,913,000 people, between 2015 and 2030. Diabetic Nephropathy (DN) affects about one-third of patients with DM and currently ranks as the first cause of end-stage kidney disease in the Western world. The complexity of interactions of Vitamin D is directly related with progressive long-term changes implicated in the worsening of renal function. These changes result in a dysregulation of the vitamin D-dependent pathways. Various studies demonstrated a pivotal role of Vitamin D supplementation in regression of albuminuria and glomerulosclerosis, contrasting the increase of glomerular basement membrane thickening and podocyte effacement, with better renal and cardiovascular outcomes. The homeostasis and regulation of the nephron’s function are absolutely dependent from the cross-talk between endothelium and podocytes. Even if growing evidence proves that vitamin D may have antiproteinuric, anti-inflammatory and renoprotective effects in patients with DN, it is still worth investigating these aspects with both more in vitro studies and randomized controlled trials in larger patient series and with adequate follow-up to confirm the effects of long-term vitamin D analogue supplementation in DN and to evaluate the effectiveness of this therapy and the appropriate dosage.