Publications by authors named "Lida Tartaglione"

21 Publications

  • Page 1 of 1

Focus on the Possible Role of Dietary Sodium, Potassium, Phosphate, Magnesium, and Calcium on CKD Progression.

J Clin Med 2021 Mar 1;10(5). Epub 2021 Mar 1.

Nephrology Unit Policlinico Umberto I Hospital, 00185 Rome, Italy.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10050958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957473PMC
March 2021

Oxygen extraction ratio to identify patients at increased risk of intradialytic hypotension.

Sci Rep 2021 Feb 26;11(1):4801. Epub 2021 Feb 26.

Department of Translational and Precision Medicine, Nephrology Unit at Policlinico Umberto I Hospital, "Sapienza" University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.

Intradialytic hypotension (IDH) is a hemodynamic phenomenon recently associated with decreased blood oxygen saturation (SO). The ratio between peripheral oxygen saturation (SpO) and central venous SO (ScvO) 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 ScvO measurement is at hand. OER ([(SpO - ScvO)/SpO] × 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 < 0.01), while OER values before HD were not different. Notably, in the high ΔOER group the OER increment was evident since after 15' and was significantly higher than in the low ∆OER group (∆OER-15' = 19 ± 3.0% vs. 9.0 ± 3.0%; p < 0.05). By comparison, blood volume changes overlapped in the two groups (average change - 9 ± 0.8%). Values of ∆OER > 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-84375-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910620PMC
February 2021

Inflammation, Oxidative Stress, and Bone in Chronic Kidney Disease in the Osteoimmunology Era.

Calcif Tissue Int 2021 Apr 2;108(4):452-460. Epub 2021 Jan 2.

Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00223-020-00794-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778498PMC
April 2021

A new technique for measuring fistula flow using venous blood gas oxygen saturation in patients with a central venous catheter.

Clin Kidney J 2020 Apr 1;13(2):184-187. Epub 2019 Jun 1.

Nephrology and Dialysis Unit, ICOT Hospital, Polo Pontino Sapienza University of Rome, Italy.

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 (ScvO) 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 ScvO 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. ScvO 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 ΔScvO ( 0.954, P < 0.0001).

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 ΔScvO. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ckj/sfz064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147307PMC
April 2020

Bone, inflammation and chronic kidney disease.

Clin Chim Acta 2020 Jul 8;506:236-240. Epub 2020 Apr 8.

Azienda Ospedaliero-Universitaria Policlinico Umberto I, Roma, Italy. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cca.2020.03.040DOI Listing
July 2020

On the role of skin biopsy in the diagnosis of calcific uremic arteriolopathy: a case-based discussion.

J Nephrol 2020 Aug 2;33(4):859-865. Epub 2019 Dec 2.

Dialysis Unit at ICOT Hospital, Latina, Italy.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40620-019-00678-zDOI Listing
August 2020

Effects of Sevelamer Carbonate in Patients With CKD and Proteinuria: The ANSWER Randomized Trial.

Am J Kidney Dis 2019 09 23;74(3):338-350. Epub 2019 Apr 23.

Division of Nephrology, University of Utah Health Sciences Center, Salt Lake City, UT.

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/1.73m 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.ajkd.2019.01.029DOI Listing
September 2019

Clinical impact of vitamin D hydroxylation efficiency.

Minerva Med 2019 Jun 22;110(3):259-262. Epub 2019 Feb 22.

Unit of Nephrology, Umberto I Polyclinic Hospital, Rome, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S0026-4806.19.06029-4DOI Listing
June 2019

Multicenter study on parathyroidectomy (PTX) in Italy: preliminary results.

J Nephrol 2018 Oct 28;31(5):767-773. Epub 2018 Aug 28.

Nephrology Unit, Azienda Policlinico Umberto I, Rome, Italy.

Background: 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.

Methods: 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.

Results: 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%, X = 21.52; p < 0.001), with non-significant regional differences (range 0.8-7.4%). PTX patients were younger (57.6 ± 12.5 vs. 67.1 ± 14.5 years; p < 0.001), more frequently female (56 vs. 38%, X = 68.05, p < 0.001) and had been on dialysis for a longer time (14.63 ± 8.37 vs. 4.8 ± 6.0 years, p < 0.001) compared to the 11,987 who did not undergo neck surgery. Median time since surgery was 6.0 years (3.0-9.0; 50%, IQR). The most frequent type of surgery was subtotal PTX (sPTX = 55.0%), significantly higher than total PTX (tPTX = 38.7%) or total PTX plus auto-transplantation (aPTX = 6.3%) (X = 5.18; Bonferroni post-hoc test, sPTX vs. tPTX + aPTX = p < 0.05). As for parathyroid hormone (PTH), calcium and phosphate control, cases targeting the KDOQI ranges were 18, 50.1 and 54.4%, respectively. The most prevalent biochemical condition was low PTH (62.7%).

Conclusion: PTX prevalence in Italy is stable compared to previous observations, is higher in hemodialysis than in peritoneal dialysis and results in a suboptimal biochemical control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40620-018-0527-xDOI Listing
October 2018

Bone, inflammation and the bone marrow niche in chronic kidney disease: what do we know?

Nephrol Dial Transplant 2018 12;33(12):2092-2100

Department of Experimental Diagnostic and Specialty Medicine (DIMES), Nephrology, Dialysis and Renal Transplant Unit, St Orsola Hospital, University of Bologna, Bologna, Italy.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfy115DOI Listing
December 2018

Oxygen Extraction Ratio (OER) as a Measurement of Hemodialysis (HD) Induced Tissue Hypoxia: A Pilot Study.

Sci Rep 2018 04 4;8(1):5655. Epub 2018 Apr 4.

Nephrology and Dialysis Unit, ICOT Hospital, Polo Pontino Sapienza University of Rome, Rome, Italy.

HD tissue hypoxia associates with organ dysfunctions. OER, the ratio between SaO 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 < 0.05) by 30' and to 47.4 ± 1.5% (M ± SE; p < 0.001) by end of treatment (delta 40%). During HD sessions of the long and short interdialytic intervals, OER values overlapped, suggesting no influence of patient's hydration status shifts. OER increased (p < 0.05) after 30' of isolated HD (zero ultrafiltration), but not during isolated ultrafiltration (zero dialysate flow), suggesting a role for blood-membrane-dialysate interaction, independent of volume reduction. In ten patients, individual variability of pre-HD OER was low and repeatable (maximum calculated difference over time 6.6%), and negatively correlated with HD-induced OER increments (r = 0.860; p < 0.005), suggesting a decline in the adaptive response along with resting OER increments. In 30 prevalent patients, adjusted multivariate analysis showed that pre-HD OER (HR = 0.88, CI 0.79-0.99, p = 0.028) and percent HD-induced OER (HR = 1.04, CI 1.01-1.08, p = 0.015) were both associated with mortality, with threshold values respectively <32% and >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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-24024-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884820PMC
April 2018

Interactions of sclerostin with FGF23, soluble klotho and vitamin D in renal transplantation.

PLoS One 2017 30;12(5):e0178637. Epub 2017 May 30.

Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, Sapienza University of Rome, Italy.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0178637PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5448809PMC
October 2017

Positioning novel biologicals in CKD-mineral and bone disorders.

J Nephrol 2017 Oct 24;30(5):689-699. Epub 2017 May 24.

Department of Cardiovascular, Respiratory, Nephrologic, Anesthetic and Geriatric Sciences, Sapienza University of Rome, Rome, Italy.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40620-017-0410-1DOI Listing
October 2017

[New biomarkers of CKD-MBD].

G Ital Nefrol 2016 Nov-Dec;33(6)

Chronic kidney failure involves abnormalities of mineral metabolism, skeletal and of cardiovascular system (so called CKD - MBD) that have a major impact on the survival of renal patient. Increasingly complex pathophysiological mechanisms have been discovered in recent years with evidence of new molecules involved in the development of CKD - MBD. Besides the classical PTH / Vitamin D axis, the most recent discovery of a new FGF23 / Klotho axis has expanded knowledge on the mechanisms of mineral homeostasis but also on the more complex mechanisms of cellular aging, vascular calcification and cardiac remodeling. The importance of bone as an endocrine organ has become even more evident following the discovery of molecules such as Sclerostin (involved in the regulation of osteoblastic proliferation and differentiation) and Sibling (a family of proteins that regulate both local and systemic mineral metabolism). The ability to characterize as biomarkers of CKD - MBD for these new molecules depends on their eventual ability to express a specific pathophysiological processes, identify patients at risk, highlight the response to a therapeutic treatment and to be easily identifiable and quantifiable on biological fluids. As of today, it seems that we can recognize FGF23 as a biomarker of CKD-MBD, while the remaining molecules as still waiting for a more definite settlement.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2017

Calcitriol/calcifediol ratio: An indicator of vitamin D hydroxylation efficiency?

BBA Clin 2015 Jun 14;3:251-6. Epub 2015 Mar 14.

Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, Sapienza University of Rome, Italy.

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 <0.001). Each clinical condition elicited a significant effect on 25D/1,25D (p < 0.0001) and adjusted multivariate analysis indicated levels of Cas, Ps, PTH, and 25D as predictors of 25D/1,25D. Both in vitamin D deficient and replete subjects (25D< or ≥20 ng/ml) 25D/1,25D associated with each clinical condition (p < 0.0001) and mean values increased progressively from HD to PHP (p-values for the trend <0.0001). Regression analysis between 25D (substrate) and 25D/1,25D (efficiency) revealed an exponential negative correlation in No-CKD (r(2)Exp = 0.53, p < 0.001) with sharp increments of 25D/1,25D when 25D values are <20 ng/ml. At variance, in CKD (r(2)lin = 0.19) and in TX (r(2)lin = 0.32) the regression was linear as if, in case of deficit, some inhibition of the system were operating.

Conclusion And General Significance: In conclusion 1,25D/25D can reflect the efficiency of vitamin D hydroxylases more than separate evaluation of 25D and 1,25D and can facilitate the therapeutic choices in different patient populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbacli.2015.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661572PMC
June 2015

Soluble α -Klotho Serum Levels in Chronic Kidney Disease.

Int J Endocrinol 2015 19;2015:872193. Epub 2015 Mar 19.

Department of Cardiovascular, Respiratory, Nephrology, Geriatric, and Anesthetic Sciences, "Sapienza" University, 5 Piazzale Aldo Moro, 00185 Rome, Italy.

Transmembrane α-Klotho (TM-Klotho), expressed in renal tubules, is a cofactor for FGF23-receptor. Circulating soluble-α-Klotho (s-Klotho) results from TM-Klotho shedding and acts on Phosphate (P) and Calcium (Ca) tubular transport. Decreased TM-Klotho, described in experimental chronic kidney disease (CKD), prevents actions of FGF23 and lessens circulating s-Klotho. Thus, levels of s-Klotho could represent a marker of CKD-MBD. To evaluate the clinical significance of s-Klotho in CKD we assayed serum s-Klotho and serum FGF23 in 68 patients (age 58 ± 15; eGFR 45 ± 21 mL/min). s-Klotho was lower than normal (519 ± 183 versus 845 ± 330 pg/mL, P < .0001) in renal patients and its reduction was detectable since CKD stage 2 (P < .01). s-Klotho correlated positively with eGFR and serum calcium (Cas) and negatively with serum phosphate (Ps), PTH and FGF23. FGF23 was higher than normal (73 ± 51 versus 36 ± 11, P < .0002) with significantly increased levels since CKD stage 2 (P < .001). Our data indicate a negative effect of renal disease on circulating s-Klotho starting very early in CKD. Assuming that s-Klotho mirrors TM-Klotho synthesis, low circulating s-Klotho seems to reflect the ensuing of tubular resistance to FGF23, which, accordingly, is increased. We endorse s-Klotho as an early marker of CKD-MBD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2015/872193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383388PMC
April 2015

News on biomarkers in CKD-MBD.

Semin Nephrol 2014 Nov;34(6):598-611

Department of Cardiovascular, Respiratory, Nephrologic and Geriatric Sciences, Sapienza University of Rome, Rome, Italy.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.semnephrol.2014.09.006DOI Listing
November 2014

Distinct impact of vitamin D insufficiency on calcitriol levels in chronic renal failure and renal transplant patients: a role for FGF23.

J Nephrol 2012 Nov-Dec;25(6):1108-18

Department of Cardiovascular, Respiratory, Nephrological and Geriatric Sciences, Sapienza University of Rome, Rome, Italy.

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<0.005), compared with those without insufficiency, had lower values of 1,25D in CRF (24.5 ± 17.4 vs 35.8 ± 17.8 pg/mL; p<0.01) but not in TX (42.7 ± 23.8 vs. 50.1 ± 25.4 pg/mL; p=n.s.). Serum 25D and 1,25D were correlated in both CRF (r=0.387, p<0.0001) and TX (r=0.240, p0<.005) groups, but 1,25D values were higher in the TX group in any of the 4 ranges for 25D considered. Serum calcitriol correlated with eGFR (CRF: r=0.641, p<0.0001; TX: r=0.426, p<0.0001), but again with higher values in the TX group, in any of the CKD stages considered, except stage 2. In both conditions, the most predictive parameter of 1,25D levels was eGFR, together with phosphate and 25D in the CRF group (r2=0.545; p<0.0001), and with Ca and 25D in the TX group (r2=0.345; p<0.0001). In 2 subgroups, comparable for eGFR and 25D, levels of FGF23 were lower in the TX group, in agreement with higher values of 1,25D.

Conclusions: A 25D deficit more significantly affects calcitriol concentrations in CRF as compared with TX. Efficiency of vitamin D hydroxylation should be considered when planning vitamin D replacement strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5301/jn.5000102DOI Listing
May 2013

[Update on the pathogenesis and possible therapeutic approach to vascular calcifications in patients with chronic renal failure].

G Ital Nefrol 2011 Sep-Oct;28(5):514-24

Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche e Geriatriche dell'Universita' Sapienza di Roma, Roma, Italy.

Chronic renal failure is a well-known risk condition for cardiovascular disease and in particular vascular calcifications. In fact, with respect to the normal population, where only ''classic'' risk factors have been described, kidney patients also have non-classic risk conditions. Among these, alterations in divalent ions, parathyroid hormone and vitamin D are of utmost importance. Further, several substances are recognized to have inhibitory or inductive effects in the pathogenesis of vascular calcifications, affecting either the calcium salts precipitation phenomenon or the phenotypic transformation of vascular smooth muscle cells into osteoblast-like cells (the latter phenomenon being regarded as a determinant of calcification of the tunica media). Given that vascular calcifications are irreversible, therapeutic strategies are aimed at preventing their formation or at blunting their progression (which is especially accelerated in renal patients). For this purpose it is essential to pursue optimal biochemical control of secondary hyperparathyroidism, but we must consider that in the individual patient the choice of drugs and their dosage can be essential for the development of calcifications. Given the physiological importance of inhibitory substances, we can hypothesize their future use in this setting. Finally, we must consider that by administering drugs known to interfere with inhibitors (like warfarin) or with the normal process of mineralization (like bisphosphonates), we can hypothetically favor or respectively prevent vascular calcifications.
View Article and Find Full Text PDF

Download full-text PDF

Source
January 2012

Does any therapy exist for vascular calcifications in uremia?

J Nephrol 2011 May-Jun;24 Suppl 18:S16-24

Department of Cardiovascular, Respiratory, Nephrologic and Geriatric Sciences, Sapienza University of Rome, Rome, Italy.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5301/JN.2011.7762DOI Listing
October 2011

The bone and the kidney.

Arch Biochem Biophys 2010 Nov 3;503(1):95-102. Epub 2010 Jul 3.

Department of Clinical Science, Sapienza University of Rome, Italy.

Renal tubular diseases may present with osteopenia, osteoporosis or osteomalacia, as a result of significant derangements in body electrolytes. In case of insufficient synthesis of calcitriol, as in renal failure, the more complex picture of renal osteodystrophy may develop. Hypothetically, also disturbed renal production of BMP-7 and Klotho could cause bone disease. However, the acknowledgment that osteocytes are capable of producing FGF23, a phosphaturic hormone at the same time modulating renal synthesis of calcitriol, indicates that it is also bone that can influence renal function. Importantly, a feed-back mechanism exists between FGF23 and calcitriol synthesis, while Klotho, produced by the kidney, determines activity and selectivity of FGF23. Identification of human diseases linked to disturbed production of FGF23 and Klotho underlines the importance of this new bone-kidney axis. Kidney and bone communicate reciprocally to regulate the sophisticated machinery responsible for divalent ions homeostasis and for osseous or extraosseous mineralisation processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.abb.2010.06.028DOI Listing
November 2010