Acute and chronic kidney injuries represent critical issues after liver transplantation (LTx), but whereas renal dysfunction in adult transplant patients is well documented, little is known about its prevalence in childhood. It is a challenge to accurately evaluate renal function in patients with liver disease, due to several confounding factors. Creatinine-based equations estimating glomerular filtration rate, validated in nephropathic patients without hepatic issues, are frequently inaccurate in end-stage liver disease, underestimating the real impact of renal disease. Moreover, whereas renal issues observed within 1 year from LTx were often related to acute injuries, kidney damage observed after 5-7 years from LTx, is due to chronic, irreversible mechanisms. Most immunosuppression protocols are based on calcineurin inhibitors (CNIs) and corticosteroids, but mycophenolate mofetil or sirolimus could play significant roles, also in children. Early diagnosis and personalized treatment represent the bases of kidney disease management, in order to minimize its close relation with increased mortality. This review analyzed acute and chronic kidney damage after pediatric LTx, also discussing the impact of pre-existent renal disease. The main immunosuppressant strategies have been reviewed, highlighting their impact on kidney function. Different methods assessing renal function were reported, with the potential application of new renal biomarkers.

Morbidity and mortality marginally decreased over the last three decades in hemodialyzed (HD) patients, despite the introduction of multiple pharmacological and technological advancement. 1 Several randomized controlled studies failed to demonstrate the superiority of one procedure, schedule, or pharmacological interventions on survival and, consequently, weak level of recommendations has been revealed by best practice guidelines. [2][3][4][5] These negative results are closely related to the complexity of uremia, characterized by several metabolic disorders, as well as hyperparathyroidism, metabolic acidosis, Lcarnitine deficiency, and risk factors, influencing all-cause mortality. [6][7][8] General dialysis-dependent population is in fact elderly and affected by multiple co-morbid conditions, while hemodialysis (HD) represents just one component of the overall outcome-based risk profile. In particular, diabetes as well as obesity, due to their increasing incidence, are directly involved in kidney disease onset and progression. 9 Moreover, global patient heterogeneity, related to genetic, environmental, and demographic factors, needs to be evaluated as a risk factor for renal disease. Large-scale meta-analyses of genome-wide association studies have identified a number of loci significantly associated with systolic and/or diastolic blood pressure, apolipoproteins, or polymorphisms of vitamin D receptor, closely involved in the development of kidney disease. [10][11][12] Other obstacle to apply personalized dialysis is the lack of resources in the current sanitary systems, considering that, due to the combination of high costs and widespread need, renal replacement therapy is one of the most expensive treatments. 13,14 The actual costs of dialysis are not uniformly defined, with significant differences between highly resourced countries, where the most important item is the cost of nursing and medical care, and emerging countries, where the cost of dialysis supplies represents the most relevant item. 15 Moreover, ecologic implication is closely related with each HD session, analyzing water, energy, and waste

Background: Ferric carboxymaltose (FCM) is a parenteral, dextran-free iron formulation designed to overcome the limitations of existing iron preparations. The main aim of this study was to retrospectively examine results obtained from a long period of FCM therapy in hemodialysis patients who have been previously treated with ferric gluconate (FX). Markers of iron metabolism, erythropoietin (EPO) doses, and effects on anemic status have been analysed. Methods: The study was performed with a follow up period of 4 years, when patients were treated before with FX and then switched to FCM. A total of 25 patients were included in the study. Results: FCM increased transferrin saturation (TSAT) levels by 11.9% (P < 0.001) with respect to FX. Events of TSAT less than 20% were reduced during FCM. The monthly dose of EPO was reduced in the FCM period (-6,404.1 international unit [IU]; 95% confidence interval,-10,643.5 IU;-2,164.6 IU; P = 0.003), as well as the erythropoietin resistance index (P = 0.004). During the period with FCM, ferritin levels were higher than during FX (P < 0.001), while transferrin was reduced (P = 0.001). Conclusion: During FCM treatment, minor doses of EPO were administered if compared to those delivered during FX therapy. Stable and on target levels of hemoglobin were maintained with better control of anemia through high levels of ferritin and TSAT.

Background and Objectives: Iron deficiency and anemia characterize patients on chronic hemodialysis (HD). Available intravenous iron agents, such as ferric gluconate (FG) and ferric carboxymaltose (FCM), vary in dosing regimens and safety profiles. The aim of the present study was to analyze the modification of the iron status, the correction of anemia, and the economic implications after the shift from FG to FCM therapy in chronic HD patients. We evaluated, during the study, the variations in iron metabolism, assessing ferritin and transferrin saturation, erythropoietin-stimulating agent (ESA) doses and the number of administrations, the effects on anemic status, and consequent costs. Materials and Methods: A retrospective study was performed with a follow-up period of 24 months, enrolling forty-two HD patients. The enrolment phase started in January 2015, when patients were treated with iv FG, and continued until December 2015, when FG was discontinued, and, after a wash-out period, the same patients were treated with FCM. Results: The iron switch reduced the administered dose of ESA by 1610.500 UI (31% of reduction; p < 0.001) during the entire study period and reduced the erythropoietin resistance index (ERI) (10.1 ± 0.4 vs. 14.8 ± 0.5; p < 0.0001). The FCM group had the highest percentage of patients who did not require ESA treatment during the study period. The FCM patients were characterized by higher levels of iron (p = 0.04), ferritin (p < 0.001), and TSAT levels (p < 0.001) compared to the FG patients. The annual cost during FG infusion was estimated at EUR 105,390.2, while one year of treatment with FCM had a total cost of EUR 84,180.7 (a difference of EUR 21,209.51 (20%), saving EUR 42.1 per patient/month (p < 0.0001). Conclusions: FCM was a more effective treatment option than FG, reducing ESA dose requirements, increasing Hb levels, and improving iron status. The reduced ESA doses and the decreased number of patients needing ESA were the main factors for reducing overall costs.

Background and Aims Uremic toxins, poor removed by conventional hemodialysis (HD), represent independent risk factors for mortality in end-stage renal disease (ESRD). Middle uremic toxin molecules were associated to pathological features of uremia, such as immune dysfunction and inflammation. These two entities are not mutually exclusive, but they could represent two sides of the same coin. ESRD-associated inflammation is closely related to the activation of innate immune system. Free light chain (FLC) may be a specific assessment of inflammation, representing a direct function of adaptive immunity through B-cell lineage production rather than a general marker of inflammation. While several studies have assessed the relation between FLCs and mortality risk in chronic kidney disease (CKD), FLCs, as uremic toxins in non-multiple myeloma dialyzed patients, were marginally analyzed. The aim of this prospective study was to evaluate the clinical impact of FLCs levels in HD patients, during a 2-years follow-up analysing the relations with biomarkers of inflammation, such as C-reactive protein (CRP) and procalcitonin (PCT), main lymphocytes subsets, such as CD4+ and CD8+ T cell count and high mobility group box (HMGB) -1 levels, as expression of the innate immune system. The potential link between FLCs levels and mortality risk was assessed. Method 190 patients on chronic hemodialysis at the Nephrology and Dialysis Unit of Papardo Hospital in Messina, Italy, were enrolled and followed for 2 years. Inclusion criteria were: age &gt;18 years, absence or &lt;200 ml/die residual diuresis, κ/λ ratio within the renal reference range (0.37–3.1). Receiver operating characteristics (ROC) analysis was performed to estimate the cut-off points of HMGB-1 and cFLC. Kaplan-Meier survival analysis and Cox proportional multivariate hazards model were used for clinical outcome. Results HD patients were characterized by high FLC levels. κFLC values were 182.3 (IQR: 140.2 – 216.1) mg/L, whereas λFLC levels were 108.2 (IQR: 72.7 – 143.2) mg/L. The median combined (c) FLC concentration was 182.9 mg/L (IQR = 207.8 – 330.2), which was extremely greater than the median reported in the general population (normal range = 9.3 – 43.3 mg/L) and in CKD patients [68.9 mg/L (IQR = 49.4 – 100.9)]. No differences in cFLC levels were revealed according to dialysis techniques. HD patients showed significant reduction of CD4+ and CD4+/CD8+ ratio. High HMGB1 levels were detected in HD patients (161.3 ± 39.7 ng/ml) and positively related to PCT and cFLC (r = - 0.38; p &lt; 0.001), with an inverse relation to CD4+/CD8+ ratio. cFLC positively correlated with β2 microglobulin, hemoglobin, and HMGB1. Conversely, an inverse correlation was revealed with surrogate markers of inflammation, such as CRP, procalcitonin, neutrophil counts. There were 49 deaths during the follow-up. The majority (23/49) of deaths were attributed to cardiovascular disease, the remainder to infection and malignancy. cFLCs and sHMGB-1 levels in this group were significantly elevated. By ROC analysis, HMGB-1 levels &gt; 100.9 ng/mL and cFLC &gt; 223.4 mg/l were associated with a significantly lower survival rate (p &lt; 0.02 by log-rank test) than for patients with lower levels when using Kaplan-Meier analysis. After adjusting for confounding factors, by Cox proportional hazards method, the difference remained statistically significant (p = 0.02) Conclusion Our study demonstrated an independent relation between high cFLC levels and mortality in HD patients. cFLCs represent a potential biomarker of “inflammunity”, a physiopathological process playing a pivotal role in ESRD, based on a vicious circle between inflammation and immune dysfunction. Further in-depth examinations should be verify our findings, determining whether therapeutic measures targeting cFLC balance, such as hemodiafiltration and expanded dialysis, would be helpful to reduce the “inflammunity” process, characterizing dialyzed patients.