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Cognitive impairment and malnutrition are prevalent in patients on hemodialysis (HD), and they negatively affect the outcomes of HD patients. Evidence suggests that cognitive impairment and malnutrition may be associated, but clinical studies to assess this association in HD patients are lacking. The aim of this study was to evaluate the association between cognitive impairment evaluated by the Montreal Cognitive Assessment (MoCA) score and nutritional status evaluated by the malnutrition inflammation score (MIS) in HD patients. We enrolled 84 HD patients (44 males and 40 females; age: 75.8 years (63.5–82.7); HD vintage: 46.0 months (22.1–66.9)). The MISs identified 34 patients (40%) as malnourished; the MoCa scores identified 67 patients (80%) with mild cognitive impairment (MCI). Malnourished patients had a higher prevalence of MCI compared to well-nourished patients (85% vs. 70%; p = 0.014). MoCa score and MIS were negatively correlated (rho:−0.317; p < 0.01). Our data showed a high prevalence of MCI and malnutrition in HD patients. Low MoCA scores characterized patients with high MISs, and malnutrition was a risk factor for MCI. In conclusion, it is plausible that MCI and malnutrition are linked by common sociodemographic, clinical, and biochemical risk factors rather than by a pathophysiological mechanism.

Routine systems for monitoring vascular access (VA) performance are lacking. We developed a vascular access triage system to evaluate the monthly performance of the access, developed a specific score and assessed the association between score improvement and clinical outcomes. Vascular access was triaged (Green, Yellow or Red) according to a score generated by dialytic and clinical parameters in all patients who, from 1/1/2014 to 31/03/2014, had been receiving haemodialysis treatment for at least 3 consecutive months in our Unit and who were then followed up for 4 years. We enrolled 130 patients, 78 with arteriovenous fistula (AVF) and 52 with tunnelled central venous catheter (CVC). During a median of 29 ± 11 months of follow up (range 3–46 months), 28 deaths and 303 hospitalizations (lasting 16 ± 30 days) were recorded. Vascular access triage scores improved over time (2014 vs 2015 vs 2016 vs 2017) in the population with an AVF (Green from 25% to 58% to 77% to 79%, Yellow from 65% to 39% to 18% to 20% and Red from 10% to 3% to 5% to 1%, respectively; χ2 p

Patients on haemodialysis (HD) suffer a high mortality rate linked to developing subclinical hypoxic parenchymal stress during HD sessions. The oxygen extraction ratio (OER), an estimate of the oxygen claimed by peripheral tissues, might represent a new prognostic factor in HD patients. This study evaluated whether the intradialytic change in OER (ΔOER) identified patients with higher mortality risks. We enrolled chronic HD patients with permanent central venous catheters with available central venous oxygen saturation (ScvO2) measurements; the arterial oxygen saturation was measured with peripheral oximeters (SpO2). We measured OER before and after HD at enrolment; deaths were recorded during two-years of follow-up. In 101 patients (age: 72.9 ± 13.6 years, HD vintage: 9.6 ± 16.6 years), 44 deaths were recorded during 11.6 ± 7.5 months of follow-up. Patients were divided into two groups according to a 40% ΔOER threshold (ΔOER < 40%, n = 56; ΔOER ≥ 40%, n = 45). The ΔOER ≥ 40% group showed a higher incidence of death (60% vs. 30%; p = 0.005). The survival curve (log-rank-test: p = 0.0001) and multivariate analysis (p = 0.0002) confirmed a ΔOER ≥ 40% as a mortality risk factor. This study showed the intradialytic ΔOER ≥ 40% was a mortality risk factor able to highlight critical hypoxic damage. Using a ΔOER ≥ 40% could be clinically applicable to characterise the most fragile patients.

BACKGROUND AND AIMS Routine systems for monitoring vascular access (VA) performance are lacking. We recently showed that with a VA triage system it is possible to improve the average value of a number of HD efficiency parameters and that the triage score was associated with clinical outcomes [1]. The triage categorization is generated monthly by a scoring system which is based on a number of parameters (blood flows, VA pressure values, end HD circuit clots and a dedicated score of the external VA examination) recorded at each session by the staff and by the KT/V value recorded once every month. According to threshold values, each VA is classified as Green (G), Yellow (Y) or Red (R), thus attracting the attention of the staff. In our open-label single centre study, with 3 years of follow-up, the average VA scores improved significantly and G VA associated with lower mortality, compared to the Y and R VA. To validate our triage system with a multicentre, blinded approach in a large number of patients. The primary outcome was to evaluate if the triage identifies VA with an increased rate of complications; the secondary outcome was to verify the association of G VA score with better clinical outcomes. METHOD In this interventional prospective multicentre study, each centre used the electronic spreadsheet without knowledge of the generated score and triage. After 6 months of system implementation, 2 years of follow-up (1 January 2020–1 December 2021) were planned to record VA-related events. Two external reviewers evaluated the records. A minimum of 3 months VA follow-up was necessary for patients’ enrolment. RESULTS From 18 HD centres we enrolled 757 patients, aged 64.5 ± 15.5 years; x/y M/F; 27% diabetics; HD since 24.4 ± 32.4 months; 369 (48.7%) with arteriovenous fistula (AVF) and 388 (51.3%) with permanent central venous catheter (CVC). During 11.4 ± 5.6 months of follow-up (range 3–23), 108 537 HD sessions were recorded on the triage electronic spreadsheet, with 214 total clinical events and an event-free time of 224.5 ± 172 days (range 4–713). The VA-related events were 150 (70.1%) with an event-free time of 230 ± 160 days (range 11–713). As of today, we have the association of VA triage with VA events in a subgroup of 300 patients (66.1 ± 11.7 years; HD vintage 28 ± 18; diabetes 27.6%; 180 with AVF and 120 had CVC) who are not different from the remaining 457. In this subgroup, 54% had G VA triage, 39% Y and 7% R. In the subgroups distinguished by VA type, AVF cases (64.5 ± 12.1 years; HD since 30.3 ± 27.2; 24.4% diabetics) were triaged as G in 54%, Y in 41% and R in 5%, while CVC cases (66.5 ± 11.7 years; HD since 28.8 ± 36.5 months; 34.3% diabetics) were G in 54%, Y in 34% and R in 11%. 83 patients had VA-related events VA during 16.3 ± 2.2 months of follow-up (range 3–23), with an event-free time of 237.8 ± 195.9 days. Figure 1 shows how both AVF and CVC patients, stratified into only two triage groups (G versus Y and R together) according to their average triage, had significantly different time-free from events, which was higher in both populations (AVF P = 0.04; CVC P = 0.001) in the green triage groups. CONCLUSION Our VA triage system identifies 40% of vascular accesses as yellow-red triage, thus deserving clinical surveillance. This score has increased the rate of clinical complications which, according to the time survival curve could be detectable roughly 237.8 days before the event developed.

BACKGROUND AND AIMS Chronic kidney disease (CKD) typically associates with mineral bone disorders (CKD-MBD), kidney damage progression and increased morbidity and mortality. CKD-MBD develops early in CKD and, if promptly detected, could receive therapeutic attention. However, early markers of CKD-MBD like fibroblast growth factor 23 (FGF23) and α-Klotho are not widely available in clinical practice. Recently, estimated proximal tubule fluid phosphate concentration (ePTFp) has been proposed as a novel early marker of MBD. In fact, in CKD patients, along with the progressive reduction of nephron number, FGF23 increments are necessary to reduce renal tubular phosphate reabsorption and to maintain phosphate balance. As a consequence, PTFp concentration per single nephron progressively increases, leading to renal tubular cells overload, interstitial inflammatory response and progression of kidney damage. For this reason, PTFp concentration could represent an early marker of CKD-MBD. OBJECTIVE To evaluate the relationship between ePTFp and early markers of MBD in patients with CKD stage G2–4. METHOD In CKD patients stage G2–4, we evaluated serum FGF23, α-Klotho, parathyroid hormone (PTH) and ePTFp [ePTFp = (phosphaturia/creatininuria) x creatininemia x 3,33]; 30 healthy subjects (age 40 ± 5 years) were the control group for normal value of ePTFp. RESULTS In 68 CKD patients (age 58.9 ± 15.6 years eGFR 45 ± 21 mL/min), ePTFp averaged 2.4 ± 1.3 mg/mg which was significantly higher than in the control group (ePTFp = 1.2 ± 0.5; P CONCLUSION Our data showed early and progressive increments of ePTFp in CKD patients since CKD stage 2. These increments are paralleled by increased FGF23 and PTH and decreased α-Klotho, suggesting reciprocal pathophysiologic dependence. Accordingly, ePTFp could represent a surrogate of renal tubular cells phosphate overload, indicative of CKD-MBD development. ePTFp can be easily obtained in everyday clinical routine and could represent a reference to make therapeutic choices (e.g. dietary phosphate control). In conclusion, ePTFp could identify patients at risk of developing the CKD-MBD maladaptive response with increased risk of kidney damage progression.

Aim To evaluate early, before the onset of cardiovascular events and of chronic renal insufficiency, the association between chronic kidney disease (CKD)-mineral bone disorder (MBD) biomarkers and vascular stiffness [Cardio Ankle Vascular Index (CAVI)] in the course of type 2 diabetes (T2DM). Method We evaluated 174 T2DM patients [median age 56 years; male/female (M/F) 100/74] with diabetes duration Results Albumin-to-creatinine ratio (ACR) averaged 8.5 mg/g (5.6-17.2) with 12.6% of the patients showing pathologic values, indicative of incipient diabetic nephropathy. Serum parathyroid hormone, fibroblast growth factor 23, and sclerostin were higher while 1,25-dihydroxyvitamin D and Klotho were lower than a control group. CAVI was normal ( Conclusion In the absence of overt cardiovascular disease and of chronic renal insufficiency, CAVI is frequently pathologic in T2DM. DBP and ACR are modifiable risk factors of vascular stiffness in T2DM, thus warranting optimal assessment.

Background and Aims Patients on haemodialysis (HD) suffer a very high rate of cardiovascular mortality with some evidence suggesting a possible association with decreasing blood oxygen saturation (SO2) during sessions. The ratio between arterial SO2 (SaO2) and central venous SO2 (ScvO2) or Oxygen Extraction Ratio (OER), which represents an estimate of the amount of oxygen claimed by peripheral tissues and of the haemodialysis related hypoxic stress, might represent a new prognostic factor. Method We evaluate the relationship between OER values and mortality risks in HD patients in a prospective multicentre observational study. We enrolled chronic HD patients with permanent central venous catheter (CVC) and no fistula, in whom ScvO2 measurement is at hand and SaO2 is available with a peripheral oxymeter. OER ([(SaO2−ScvO2)/SaO2]×100) was measured before and after HD at enrolment (HD OER sessions) in each patients, and a one-year follow-up was planned to record the number of deaths. Results In 101 patients (age 71.5 ± 14 years on dialysis for 47 ± 38 months), during 9 ± 6 months of follow up, we recorded 35 deaths. Patients were then divided into two groups, above or below the median value of pre-HD OER, which was 30%. In these groups, the average incidence of deaths was 12% (24 deaths) and 5,5% (11 deaths) respectively (p Conclusion Patients with pre-HD OER > 30% have a higher mortality risk, most probably secondary to reduced capability to respond to HD related oxygen requirements. OER is novel biomarker to identify patients at greatest clinical risk.

In Italy, starting from 2015, the date of publication of the guidelines on the 2014-2020 Digital Growth Strategy, technological evolution in medicine has provided encouraging results. The term telemedicine is now in common use, and it is also indicated at an encyclopedic level as “the set of technical and health care monitoring tools, created through systems designed to provide quick access to both medical specialists and patients, regardless of the place where they are respectively located”. Nowadays, in the COVID era, the need for social distancing has highlighted the contribution of digital technology to healthcare in terms of access to care and healthcare spending. With regard to chronic kidney disease, telemedicine has always proved essential in improving patients’ quality of life, as in the case of peritoneal dialysis. The remote management and monitoring of patients undergoing peritoneal dialysis has not only proved to radically change and improve patients’ quality of life in replacement therapy, but has also reduced costs. There are some situations in which telemonitoring can guarantee the maintenance of an adequate quality of life for patients in the different stages of the disease. Thanks to the constant commitment of some groups of professionals where the largest part is represented by the “pink quota”, it was possible to experiment and implement evaluation protocols for the renal patient in conservative and replacement treatment in some of the most central aspects of care: medical and dietary therapy.

Intradialytic hypotension (IDH) is a hemodynamic phenomenon recently associated with decreased blood oxygen saturation (SO2). The ratio between peripheral oxygen saturation (SpO2) and central venous SO2 (ScvO2) or Oxygen Extraction Ratio (OER), which represents a roughly estimate of the amount of oxygen claimed by peripheral tissues, might be used to estimate haemodialysis (HD) related hypoxic stress. Aim of this pilot study was to evaluate the relationship between OER increments during dialysis sessions (ΔOER) and episodes of IDH. We enrolled chronic HD patients with permanent central venous catheter (CVC) and no fistula, in whom ScvO2 measurement is at hand. OER ([(SpO2 − ScvO2)/SpO2] × 100) was measured in three consecutive HD sessions (HD OER sessions) before HD, after 15′, 30′ and 60′ min and at the end of HD. Then, a one-year follow-up was planned to record the number of IDH episodes. In the 28 enrolled patients (age 74 ± 2.6 years), during 12 ± 1.2 months of follow up, incidence of IDH was 3.6%. We divided patients into two groups, above or below the median value of ΔOER at the end of HD, which was 36%. In these groups, the average incidence of IDH was 7% and 2% respectively (p 19% after only 15′ of HD treatment or > 36% at the end of the session characterize patients with higher rates of hypotension. Intradialytic ∆OER, a parameter of tissue hypoxic stress, identifies more fragile patients at greater risk of IDH.

The impressive estimated number of chronic kidney disease (CKD) patients in the world justifies any possible effort at implementing preventive measures of disease progression. Renal insufficiency is associated with significant changes in the electrolyte handling and body balance of sodium, potassium, phosphate, magnesium, and calcium, all of which are biologically vital molecules. Dietary habits could contribute significantly to the optimal management of possible derangements. In this review, we examined the available evidence recommending dietary prescriptions for these five elements aiming at reducing CKD progression. Clear evidence that specific dietary prescriptions may halt or reduce CKD progression is lacking. However, some practical recommendations are possible to prescribe the best possible therapy to the individual CKD patient.

Bone is not only a mineralized and apparently non-vital structure that provides support for locomotion and protection to inner organs. An increasing number of studies are unveiling new biologic functions and connections to other systems, giving the rise to new fields of research, such as osteoimmunology. The bone marrow niche, a new entity in bone physiology, seems to represent the site where a complex crosstalk between bone and immune/inflammatory responses takes place. An impressive interplay with the immune system is realized in bone marrow, with reciprocal influences between bone cells and haematopoietic cells. In this way, systemic chronic inflammatory diseases realize a crosstalk with bone, resulting in bone disease. Thus, pathogenetic links between chronic kidney disease-mineral bone disorders and osteoporosis, cardiovascular disease, and ageing are common. The aim of this narrative review is to provide a general view of the progresses in the field of bone research and their potential clinical implications, with emphasis on the links with inflammation and the connections to osteoimmunology and chemokines.

Background and Aims Assuming that FGF23 levels correlate with phosphate excretion per nephron, nephron number can be estimated by measuring FGF23 levels and urinary phosphate excretion (FEP). Kuro-O proposed that the ratio of FEP to serum FGF23 levels should correlate with nephron number and is defined as the Nephron Index (NI). The aim of the study is calculating NI as nephron number estimation in patients affected by various degree of chronic kidney disease, both transplanted and not. Method In 147 CRF patients kidney function, mineral metabolism biomarkers and NI were evaluated. Nephron Index was calculated following Kuro-o’s equation (kuro-o 2019): NI=FEP·Ps·eGFRFGF23 Observed patients were divided into two groups: patients with CKD (noTX) and transplanted ones (TX). Results noTX group was made up of 67 patients (40 males and 27 females) affected by CKD stages from G1 to G5. TX group was composed by 80 patient (49 males and 31 females) with various degree of CKD (G1T-G4T) showing mean graft age of 83,2 ± 54,8 months (range: 10,3-268,0). The two groups differed for age (mean age 59 ± 15,6 years in CKD, 55± 10,3years in TX). Mean eGFR did not differ between TX and noTX but NI was higher in TX since FEP was higher despite lower FGF23 levels in TX. The difference in FGF23 levels does not appear to depend on Klotho and PTH whose serum levels were no different between Tx and noTx. (Table1). As far as correlations are concerned, NI correlated with eGFR, FGF23, PTH and 1,25D in both group, while NI correlated with FEP only in the TX group. It's interesting that no correlation existed between FGF23 and sP, FEP, eGFR and sKlotho in TX differently from noTX (Table2). Discussion. NI could not be properly defined as nephron number estimation in TX pts. However it may represent higher function of residual nephrons, since higher FEP did not correlate to FGF23 and could be determined by compensatory hyperfiltration (increased single nephron GFR) in transplanted patients. Conclusion After kidney transplantation, high NI value could have a functional meaning rather than represent residual number of nephrons.

Background and Aims DMT2 and its complications such as chronic kidney disease (CKD) lead to increase vascular stiffness, measurable with CAVI, and biochemical alterations in substances implicated in vascular damage like Klotho, FGF23, and Sclerostin. The aim of the study was to evaluate the role of CKD stage 1-2 and possible alterations of 25 (OH)Vitamin-D, FGF23, Klotho, and Sclerostin on early vascular damage in DMT2 patients Method Patients included: DMT2 from Results We enrolled 40 women and 60 men, average age 56 years (IQR: 52-59), 5-year DMT2 (IQR: 2.7-7), HbA1c 6.3% (5.8-6.7), eGFR of 95 ml/min/1.73m2. FGF23 (42±10 vs controls 29.8±11 pmol/l, p Conclusion In our DMT2 population, borderline and pathological CAVI is associated with increased ACR, elevated DBP and reduced 25(OH)Vitamin-D. Furthermore the alterations of FGF23, Sclerostin and Klotho, secondary to CKD, are an early sign of possible vascular damage. ACR, 25(OH)Vitamin-D and DBP can be modifiable risk factors for early vascular damage in DMT2

Background and Aims Intradialytic hypotension (IDH) involves a reduced tolerance to hemodialysis (HD), a poor quality of life and is associated with mortality. Intradialytic monitoring systems (blood pressure, heart rate, volemia) are not able to identify patients at greater risk of IDH. IDH is a hemodynamic phenomenon and attention has recently been given to the evaluation of oxygen saturation to evaluate its role in IDH. Oxygen Extraction Ratio (OER), the ratio between SaO2 and ScvO2, is a parameter used to monitor parenchyma oxygen consumption and stress. Recent evidence showed that HD patients with a greater delta OER (ΔOER) during HD (threshold 40%)had higher mortality risk. OER could be a new monitoring instrument to measure hemodialysis induced sub-clinical parenchyma hypoxia and stress, two elements included in the pathogenesis of IDH. The aim of the study was to evaluate the relationship between OER and IDH incidence. Method Inclusion criteria: age ≥18 years, chronic HD treatment by means of permanent jugular CVC, no evidence of acute underlying illness. We evaluated OER ([(SaO2 − ScvO2)/SaO2] × 100) before HD and at 15’, 30’, 60’ and post HD in three HD sessions (HD OER sessions). For the statistic analysis we considered for each patient the median OER value obtained from the three HD OER sessions. Then we started the follow-up study with a minimum follow-up of three months and end follow-up of two years, to record IDH (defined according to K/DOQI guidelines) for each patient. We divided the population in two groups using as a threshold the median percentage number of IDH in our population and evaluate the differences between the obtained two groups in pre HD OER, Delta OER and intradialytic OER trends. Results During the follow-up period (mean 12 ± 1.2 months), we enrolled 28 patients with permanent jugular CVC: 13 males and 15 females, aged 74±2.6 years, HD vintage 46 ± 6.5 months. The HD OER sessions for each patient were asymptomatic. Pre HD OER was 34 ± 1.4, post HD OER 46 ± 1.8, with a Delta OER of 39 ± 5 %. OER change during HD was evident since after 15 minutes (OER% 15’: 40 ± 1.2 p 3.6). The two groups were not different for age (76 ± 2.4 vs 73 ± 3.0 years; p 3.6 group had 159 IDH out of a total of 1911 sessions (9%), while IDH % ≤ 3.6 group had 27 IDH out of 2431 sessions (0.9%). Pre HD OER values were not different between the groups while the IDH % >3.6 group had greater delta OER% than the IDH % ≤ 3.6 group (43 ± 4.8 vs. 35 ± 3.0 %; p 3.6 group (ΔOER 20± 3.0 % vs. 8.0 ± 3.0 %; IDH % > 3.6 group vs. IDH % ≤ 3.6 group, p Conclusion Our data show that intradialytic ΔOER, representative of the extent of tissue hypoxic stress, identifies patients at greater risk of IDH. In particular, a ΔOER of 20% after the first 15 minutes of HD and of 43% at the end of the HD session characterizes the more hemodynamically fragile patients. The measurement of the OER can be a new and easy monitoring instrument to identify the most hemodynamically fragile patients already after the first 15 minutes of HD treatment.

The goal of the World Kidney Day 2020 (WKD) is “the promotion of public health by ensuring universal, equitable and sustainable access to care, making access to health for all people and social categories equitable”. Chronic Kidney Disease (CKD) is a complex and “demanding” health problem for patients and professionals, particularly in the more advanced stages of the disease. In addition to factors such as the so-called systemic conditions and risk factors, sex-related factors intervene in women, which can further complicate the CKD trend. For these reasons, one of the objectives of the World Kidney Day is that prevention and early treatment are included in the Universal Health Coverage (UHC) and that common strategies are implemented to promote awareness of this pathology. The woman has always played a central role in the “coordination” of family life and “taking care”, a role transversal to the different ethnic groups, as evidenced also by the data relating to living kidney donation. This article gives a reflection on some issues related to prevention and treatment of CKD from a female perspective, such as what strategies to identify to implement prevention in the family starting from nutrition, such as the advice for the preparation of a diet plan respectful of the traditions of the country of origin, the identification and treatment of risk factors in order to implement strategies aimed at prevention dedicated to the female world and which style distinguishes the female approach to care | (Gender_nephrology)

Recent improvements in our understanding of physiology have altered the way in which bone is perceived: no longer is it considered as simply the repository of divalent ions, but rather as a sophisticated endocrine organ with potential extraskeletal effects. Indeed, a number of pathologic conditions involving bone in different ways can now be reconsidered from a bone-centred perspective. For example, in metabolic bone diseases like osteoporosis (OP) and renal osteodystrophy (ROD), the association with a worse cardiovascular outcome can be tentatively explained by the possible derangements of three recently discovered bone hormones (osteocalcin, fibroblast growth factor 23 and sclerostin) and a bone-specific enzyme (alkaline phosphatase). Further, in recent years the close link between bone and inflammation has been better appreciated and a wide range of chronic inflammatory states (from rheumatoid arthritis to ageing) are being explored to discover the biochemical changes that ultimately lead to bone loss and OP. Also, it has been acknowledged that the concept of the bone-vascular axis may explain, for example, the relationship between bone metabolism and vessel wall diseases like atherosclerosis and arteriosclerosis, with potential involvement of a number of cytokines and metabolic pathways. A very important discovery in bone physiology is the bone marrow (BM) niche, the functional unit where stem cells interact, exchanging signals that impact on their fate as bone-forming cells or immune-competent haematopoietic elements. This new element of bone physiology has been recognized to be dysfunctional in diabetes (so-called diabetic mobilopathy), with possible clinical implications. In our opinion, ROD, the metabolic bone disease of renal patients, will in the future probably be identified as a cause of BM niche dysfunction. An integrated view of bone, which includes the BM niche, now seems necessary in order to understand the complex clinical entity of chronic kidney disease-mineral and bone disorders and its cardiovascular burden. Bone is thus becoming a recurrently considered paradigm for different inter-organ communications that needs to be considered in patients with complex diseases.

Chronic Kidney Disease (CKD) associates with disturbed modulation of hormones involved in calcium and phosphate homeostasis, with development of secondary hyperparathyroidism (SHPT). SHPT includes not only divalent ions derangements, but also renal bone disease (high turnover, low turnover and/or osteomalacia) and accelerated vascular and ectopic calcifications. In this way, SHPT resembles a true clinical syndrome named CKD-MBD, which is a recognized risk factor of all-cause and cardiovascular death. Long lasting stimulation of parathyroid hormone synthesis and secretion, as observed in CKD, causes specific and progressive histological changes responsible for the development of nodular hyperplastic glands unresponsive to physiologic inhibitors and thus characterized by hypercalcemia, elevated PTH levels and resistance to the available medical therapies. In these cases, surgical parathyroidectomy (PTX) becomes the only therapeutic option. In this chapter we review current evidence on indications, types and clinical outcomes of PTX from a practical and clinical point of view.

Increasing knowledge on inflammatory mediators and bone metabolism highlights the relationship between inflammation and bone disease. During acute illness, inflammatory cells and cytokines modulate bone cells activity so as to mobilize calcium seemingly to supply the metabolic requirements for immune response. In case of long lasting, chronic inflammatory states a condition of maladaptive, smouldering inflammation is realized and negatively affects calcium bone balance. Aging, now nicknamed inflammaging, is regarded as a chronic inflammatory condition, characterized by increased circulating inflammatory cytokines, that contributes to the development of osteoporosis, cardiovascular diseases and chronic kidney disease. In patients with renal insufficiency, the development of bone and mineral disorders (so called CKD-MBD "syndrome") is now a recognized pathogenic factor for the seemingly accelerated process of aging and for the increased risk of cardiovascular death in these patients. The adaptive changes in mineral and bone metabolism developing in the early stages of chronic kidney disease could represent a hypothetical model of accelerated aging, osteoporosis and cardiovascular disease.

Background and Aim: Chitotriosidase (Chit), a mammalian chitinases secreted by monocytes and epithelial cells, is increased in both cardiovascular disease (CVD) and type 2 diabetes (T2D). Arterial stiffness rises early in T2D and increases the risk of CVD. Aim of the study was to evaluate Chit activity as a precocious biomarker of arterial stiffness in T2D patients without overt vascular complications. Methods: Arterial stiffness was measured by Cardio-Ankle Vascular Index (CAVI) in 174 T2D patients (mean±SD age=55±4 years, 103 men) without established diabetic complications. For this cross-sectional study, we measured Chit activity by electrochemiluminescent assay in the sera from the 41 patients with the lowest (L_CAVI) and the 42 patients with the highest (H_CAVI) CAVI values. Results: Compared with L_CAVI, H_CAVI patients were older (57±4years vs. 52±4years, p Conclusion: Arterial stiffness raises with age, metabolic control, DBP and impaired kidney function. Chit is also associated with DBP, metabolic control and kidney damage but did not result as a direct marker of arterial stiffness in T2D patients without established complications. Disclosure L. D'Onofrio: None. C. Luordi: None. C. Mignogna: None. A. Carlone: None. C. Moretti: None. L. Tartaglione: None. E. Maddaloni: Speaker's Bureau; Self; Merck & Co., Inc., Pikdare. G. Leto: None. S. Mazzaferro: None. R. Buzzetti: None. Funding Sapienza University of Rome (“Avvio alla ricerca 2016”)

Chronic renal failure has an average prevalence of 10% in the general population and carries a significant burden of morbidity and mortality. Moreover, the recently appreciated cross-talk between b...

Calciphylaxis is a rare disease characterized by ectopic calcification of skin arterioles resulting in ischemia, thrombosis and necrosis. Since end stage renal disease patients are those mainly affected, the term calcific uremic arteriolopathy (CUA) is also suggested. Early clinical manifestations are subtle, while overt necrotic ulcers may quickly spread and become infected so as to result in ominous outcome. Diagnosis might not be easy due to the number of other ischemic and non-ischemic skin lesions observed in uraemia. Skin biopsy, has been proposed as the diagnostic test and is often considered, but not systematically performed due to the hypothetical risk of further spreading of the lesions. Such ambiguity could be responsible for misdiagnosis or underdiagnosis. We review here five consecutive cases recorded in our Unit, all submitted to skin biopsy but with inconsistent results which generated some clinical frustration. Thus, we decided to carefully re-evaluate all of them together with pathologists and dermatologists. However, even after this ex-post discussion, we could not reach a complete agreement on the final diagnosis. In the meanwhile, papers were published in the literature that started to shed some light on the role of skin biopsy in the diagnosis of CUA.

Background Doppler ultrasound (DU) monitoring early after arteriovenous fistula (AVF) creation allows the identification of low blood flow (Qa) requiring prompt revision, but it is costly (needs skilled operators and technical instruments) and is not available in all dialysis units. Therefore alternative first-line methods to measure Qa would be welcomed. We reasoned that once an AVF is created, an increment in central venous oxygen saturation (ScvO2) is predictable and proportional to Qa. Methods Accordingly, in patients receiving dialysis through a central venous catheter (CVC) in whom an AVF was created, we measured, by means of blood gas analysis, the ScvO2 increment before and after manual compression of the arteriovenous shunt and verified its correlation with DU-measured Qa. Results We sampled blood gas in 18 patients with CVC and AVF before and after 30 s manual compression of the AVF. ScvO2 averaged 70.5 ± 3% before and 65.2 ± 3% after AVF closure, with an average drop of 5.1 ± 3% (range 1–12). AVF Qa, which was measured within 24 h by means of DU, averaged 635 ± 349 mL/min (range 50–1300) and was strictly and positively correlated with ΔScvO2 (r = 0.954, P Conclusions Therefore we suggest that in patients with CVC and a newly created AVF, it is possible to monitor AVF Qa without DU by simply measuring blood gas and ΔScvO2. This technique is simple, cheap, repeatable, non-invasive and operator independent and represents a new useful screening test to detect delayed AVF access maturation deserving prompt DU measurement and surgical revision. It helps to quickly identify patients in urgent need of DU verification and possible surgical revision. Regrettably, it is applicable only in patients with CVC.

Rationale & Objective Hyperphosphatemia is associated with increased risk for chronic kidney disease (CKD) progression and reduced antiproteinuric effects of renin-angiotensin system (RAS) blockers. We investigated whether the phosphate binder sevelamer carbonate may enhance the antiproteinuric effect of RAS inhibitors in patients with CKD. Study Design Phase 2, randomized, controlled, open-label, crossover trial. Setting & Participants Between November 2013 and December 2014, we enrolled 53 patients with CKD with estimated glomerular filtration rates (eGFRs)>15mL/min/1.73m2 and residual proteinuria with protein excretion≥0.5g/24h despite maximal tolerated ramipril and/or irbesartan therapy from 2 nephrology units in Italy. Intervention After stratification by serum phosphate level, ≤4 or>4mg/dL, patients were randomly assigned to 3 months of sevelamer (1,600mg thrice daily) treatment followed by 3 months without sevelamer separated by a 1-month washout period or 3 months without sevelamer followed by 3 months with sevelamer, also separated by a 1-month washout period. Outcomes The primary outcome was 24-hour proteinuria (n=49patients). Secondary outcomes included measured GFR (using iohexol plasma clearance), office blood pressure (BP), serum lipid levels, levels of inflammation and bone metabolism biomarkers, urinary electrolyte levels, and arterial stiffness. Results Changes in proteinuria during the 3-month treatment with (from 1.36 [IQR, 0.77-2.51] to 1.36 [IQR, 0.77-2.60] g/24h) or without (from 1.36 [IQR, 0.99-2.38] to 1.48 [IQR, 0.81-2.77] g/24h) sevelamer were similar (P=0.1). Sevelamer reduced urinary phosphate excretion without affecting serum phosphate levels. Sevelamer reduced C-reactive protein (CRP), glycated hemoglobin, and total and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol levels without affecting levels of office BP, measured GFR, fibroblast growth factor 23, klotho, intact parathyroid hormone, serum vitamin D, or other urinary electrolytes. Results were similar in the low- and high-phosphate groups. Sevelamer was well tolerated. Adverse events were comparable between treatment periods. One case of transient hypophosphatemia was observed during treatment with sevelamer. Limitations Short treatment duration, lower pretreatment proteinuria than expected. Conclusions 3-month sevelamer treatment did not reduce proteinuria in patients with CKD on maximal RAS blockade. Amelioration of inflammation and dyslipidemia with sevelamer treatment raises the possibility that it may confer benefit in patients with CKD beyond reduction of proteinuria. Funding Sanofi (Milan, Italy). Trial Registration Registered at ClinicalTrials.gov with study number NCT01968759.

When medical therapy is unable to achieve biochemical control of secondary hyperparathyroidism, parathyroidectomy (PTX) is indicated, fortunately in a minority of patients. Thus, data on PTX prevalence and biochemical control are limited and, in particular in Italy, date back to 1999. We designed a prospective, observational and multicenter study to collect data from dialysis units distributed throughout the Italian regions. Clinical data were collected with a dedicated data sheet. From January to December 2010, 149 Centers serving a total of 12,515 patients provided data on 528 living PTX cases (PTX prevalence = 4.2%). Prevalence was higher in hemo- than in peritoneal dialysis (4.5 vs. 1.9%, X2 = 21.52; p

HD tissue hypoxia associates with organ dysfunctions. OER, the ratio between SaO2 and central-venous-oxygen-saturation, could estimate oxygen requirements during sessions, but no data are available. We evaluated OER behavior in 20 HD patients with permanent central venous catheter (CVC) as vascular access. Pre-HD OER (33.6 ± 1.4%; M ± SE) was higher than normal (range 20–30%). HD sessions increased OER to 39.2 ± 1.5% (M ± SE; p 40%. In HD patients with CVC as vascular access, OER is a cheap, easily measurable and repeatable parameter useful to assess intradialytic hypoxia, and a potential biomarker of HD related stress and morbidity, helpful to recognize patients at increased risk of mortality.

Background Calcifediol (25D) availability is crucial for calcitriol (1,25D) synthesis, but regulation of vitamin D hydroxylases is majorly responsible for 1,25D synthesis. The net efficiency of vitamin D hydroxylases might be informative. We assume that the ratio between calcitriol and calcifediol (25D/1,25D) serum concentrations could suggest the vitamin D hydroxylation efficiency. Methods We evaluated 25D/1,25D in different patient populations: hemodialysis (HD, n = 76), CKD stage 2–5 (n = 111), renal transplant (TX, n = 135), patients with no renal disease (No-CKD, n = 290), and primary hyperparathyroidism (PHP, n = 20). Results The geometric mean of 1,25D/25D (pg/ng) averaged 1.11 (HD), 1.36 (CKD), 1.77 (TX), 2.22 (No-CKD), and 4.11 (PHP), with a progressive increment from HD to PHP (p-value for the trend, Highlights • 1,25D/25D ratio could represent an index of vitamin D hydroxylation efficiency. • 1,25D/25D ratio progressively increases from HD to CKD, TX, No-CKD and PHP. • Each of these clinical conditions affected the value of the ratio. • In selected populations 1,25D/25D ratio could guide substitutive therapeutic choices.

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Recent clinical observations underline the link between bone disease and disturbances of mineral metabolism with increased morbidity and mortality of Chronic Renal Failure (CRF). Indeed, in patients with Chronic Kidney Disease (CKD), bone disease may occur either with normal glomerular filtration rate (renal tubular disorders involving pH, Calcium or Phosphate metabolism) or with reduced glomerular filtration rate (the complex endocrine disorder of secondary hyperparathyroidism of CRF). Recently, to underline the clinical burden of this type of secondary hyperparathyroidism, a new clinical term has been introduced: CKD-MBD (chronic kidney disease-mineral and bone disorder). Besides bone disease, the endocrine derangements of mineral metabolism and the accelerated calcification processes of vessel walls are considered together in this syndrome, to highlight the pathogenetic link with cardiovascular disease and the eventual morbidity and mortality. The gold standard technique to diagnose renal osteodystrophy still remains the invasive bone biopsy. The less invasive biomarkers and radiologic techniques are less reliable to evaluate bone histology but are necessary to study the hormonal condition and the mechanical performance of the skeleton, respectively. As for therapy, it has been mostly focused on the control of secondary hyperparathyroidism, but this does not impact significantly the high fracture rate of renal patients. New drugs employed for osteoporosis and targeting specific functions of bone cells promise to open new therapeutic frontiers for renal osteodystrophy and CKD-MBD.