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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

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.

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.

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.

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.

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

Renal osteodystrophy (ROD), the histologic bone lesions of chronic kidney disease (CKD), is now included in a wider syndrome with laboratory abnormalities of mineral metabolism and extra-skeletal calcifications or CKD-mineral and bone disorders (CKD-MBD), to highlight the increased burden of mortality. Aging people, frequently identified as early CKD, could suffer from either the classical age-related osteoporosis (OP) or ROD. Distinguishing between these two bone diseases may not be easy without bone biopsy. In any case, besides classical therapies for ROD, nephrologists are now challenged by the possibility of using new drugs developed for OP. Importantly, while therapies for ROD mostly aim at controlling parathyroid secretion with bone effects regarded as indirect, new drugs for OP directly modulate bone cells activity. Thus, their action could be useful in specific types of ROD. Parathyroid hormone therapy, which is anabolic in OP, could be useful in renal patients with low turnover bone disease. Denosumab, the monoclonal antibody against receptor activator of NF-κB ligand (RANK-L) that inhibits osteoclast activity and proliferation, could be beneficial in cases with high turnover bone. Use of romosozumab, the monoclonal antibody against sclerostin, which both stimulates osteoblasts and inhibits osteoclasts, could allow both anabolic and anti-resorptive effects. However, we should not forget the systemic role now attributed to CKD-MBD. In fact, therapies targeting bone cells activity could also result in unpredicted extra-bone effects and affect cardiovascular outcomes. In conclusion, the new biologicals established for OP could be useful in renal patients with either OP or ROD. In addition, their potential non-bone effects warrant investigation.

Relationships of Sclerostin, a bone anti-anabolic protein, with biomarkers of mineral bone disorders in chronic kidney disease are still unsettled, in particular in kidney transplant (KTR). In 80 KTR patients (31F/49M, 54.7±10.3 years) we studied the relationships of serum Sclerostin with eGFR, Calcium, Phosphate, Alkaline Phosphatase (AP), intact Parathyroid hormone (iPTH), soluble alpha-Klotho (sKlotho), intact Fibroblast Growth Factor 23 (iFGF23), 25-hydroxyvitamin D(25D) and 1,25-dihydroxyvitamin D (1,25D). Thirty healthy subjects (35.0±12.4 years, eGFR 109.1±14.1 ml /min/1,73m2) served as control for Sclerostin, iFGF23 and sKlotho. With a median eGFR of 46.3 mL/min/1.73m2 (IQR, 36.2–58.3) our KTR had median Sclerostin levels of 23.7 pmol/L (IQR: 20.8–32.8), not different from controls (26.6 pmol/L, IQR: 22.0–32.2; p = n.s). Sclerostin correlated negatively with AP (r = -.251; p = 0.023) and positively with iFGF23 (r = .227; p = 0.017) and 25D (r = .214; p = 0.025). Age-adjusted multiple regression analysis identified AP and 1,25D as negative and 25D and sKlotho as positive best predictors of Sclerostin. No correlation was evident with eGFR. The negative correlation with AP confirms the direct anti-anabolic role of Sclerostin. The associations either negative or positive with iFGF23, sKlotho, and vitamin D metabolites suggest also a modulatory role in mineral homeostasis. In particular, the associations with iFGF23 (positive) and 1,25D (negative) underline the relevant inhibitory action of Sclerostin on vitamin D activation. In conclusion, Sclerostin levels in KTR are normal and influenced more by bone turnover than by eGFR. Its involvement with other hormones of mineral homeostasis (FGF23/Klotho and Vitamin D) is part of the sophisticated cross-talk between bone and the kidney.

INTRODUCTION Vitamin D insufficiency contributes to calcitriol (1,25D) reduction in chronic kidney disease (CKD). Since CKD patients on conservative therapy (CRF) mostly develop, whereas transplant (TX) patients possibly recover from, secondary hyperparathyroidism (SH), we hypothesized a different efficiency of vitamin D hydroxylation in these 2 clinical conditions. METHODS We compared the impact of reduced 25-hydroxyvitamin D (25D) on circulating 1,25D in 111 CRF (mean age 63 ± 15 years; estimated glomerular filtration rate [eGFR] 36.4 ± 22.0 ml/min) and in 136 TX patients (mean age 50 ± 11 years; eGFR 47 ± 19.0 ml/min). RESULTS Vitamin D insufficient patients (69.1% in TX vs. 82% in CRF; p

The increased awareness of the potential role played by mineral and bone disorder in the appearance of cardiovascular disease in renal patients has produced research efforts aimed at discovering possible pathogenic links. Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. In this article we include classic markers of bone metabolism and some of the noncollagenous bone proteins that are gaining experimental and clinical significance in CKD-MBD. Among classic markers of secondary hyperparathyroidism and of renal osteodystrophy, we analyzed parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides. We underlined, for each, the relevance of parent proteins (peptides or isoforms) that affect assay methods and, eventually, the diagnostic or prognostic significance. Also, we considered their relationship with cardiovascular mortality. Among the numerous noncollagenous bone proteins, we examined matrix Gla protein (MGP), osteocalcin (OC), osteoprotegerin, and the small integrin-binding ligand N-linked glycoprotein family. For MGP and OC we report the relevant involvement with the process of calcification (MGP) and with glucose and energy metabolism (OC). Both of these proteins require vitamin K to become active and this is a specific problem in renal patients who frequently are deficient of this vitamin. Finally, recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins are recapitulated briefly to underline their potential clinical interest and their complex involvement with all aspects of CKD-MBD. Their diagnostic role in clinical practice awaits further studies.

The pathogenesis of vascular calcifications in uremia is not completely understood, but is regarded as multifactorial, involving traditional and nontraditional risk factors. In particular, derangements in divalent ions are considered of outmost importance, but also the role of physiologic inhibitors of calcification is now claimed. The most powerful physiologic inhibitor of calcification is pyrophosphate, but its biochemical instability precludes its clinical use to date. The pharmacologic analogs of pyrophosphate, bisphosphonates, cannot be easily tested for this purpose in renal patients, given their renal clearance. The list of proteins involved in calcification is a growing one, and experimental models point to the potential clinical relevance of matrix Gla protein, fetuin, osteopontin, osteoprotegerin and bone morphogenetic protein-7. Induction of metabolic acidosis, although theoretically useful, is not recommended, while administration of sodium thiosulphate could be beneficial, but its safety awaits confirmation. Actually, the only available therapies for vascular calcifications are those directed toward achievement of the biochemical targets for calcium, phosphate and parathyroid hormone with the hope, but not the certainty, that this will be efficacious. However, to this purpose, selection of the most appropriate strategy in the individual patient seems essential.