Cardiorenal Syndrome Type 4—Cardiovascular Disease in Patients with Chronic Kidney Disease: Epidemiology, Pathogenesis, and Management

The term cardiorenal syndrome refers to the interaction between the heart and the kidney in disease and encompasses five distinct types according to the initial site affected and the acute or chronic nature of the injury. Type 4, or chronic renocardiac syndrome, involves the features of chronic renal disease (CKD) leading to cardiovascular injury. There is sufficient epidemiologic evidence linking CKD with increased cardiovascular morbidity and mortality. The underlying pathophysiology goes beyond the highly prevalent traditional cardiovascular risk burden affecting renal patients. It involves CKD-related factors, which lead to cardiac and vascular pathology, mainly left ventricular hypertrophy, myocardial fibrosis, and vascular calcification. Risk management should consider both traditional and CKD-related factors, while therapeutic interventions, apart from appearing underutilized, still await further confirmation from large trials

FGF-23 Levels before and after Renal Transplantation

Phosphatonin fibroblast growth factor-23 (FGF-23) is involved in phosphate (P) excretion and vitamin D metabolism. Recently, FGF-23 has been suggested to be responsible for the hypophosphatemia and inappropriately low calcitriol levels observed after renal transplantation. We performed a prospective study to investigate FGF-23 levels in patients with end-stage renal disease before and after renal transplantation and their probable association with markers of bone and mineral metabolism. Intact FGF-23 levels were determined before and at 3, 6, and 12 months posttransplantation in 18 renal transplant recipients. Intact parathyroid hormone (iPTH), calcium (Ca), P, 25(OH)VitD, and 1,25(OH)2VitD levels were measured at the same time periods. Renal threshold phosphate concentration (TmPO4/GFR) was also calculated at 3, 6, and 12 months posttransplantation. The results showed that FGF-23 levels decreased by 89% 3 months posttransplantation (346 ± 146 versus 37 ± 9 pg/mL, P < .01) and remained stable throughout the study period. iPTH and P levels also decreased significantly after renal transplantation, while Ca and 1,25(OH)2VitD increased. Pretransplantation FGF-23 was significantly correlated with P levels at 3 months posttransplantation (P < .005). In conclusion, FGF-23 levels decrease dramatically after successful renal transplantation. Pre-transplantation FGF-23 correlate with P levels 3 months posttransplantation

Development of a rheumatology-specific patient concerns inventory and its use in the rheumatology outpatient clinic setting

Objective. Successful management of rheumatic conditions involves increasing complexity of care. Delivering this in a holistic way is a growing challenge. The aim of our study was to develop a Patient Concerns Inventory (PCI) and assess it in the rheumatology clinic setting. Methods. This observational exploratory study occurred with 2 phases. In phase I, the PCI was developed after a systematic literature search, expert opinion, and 3 patient focus group discussions. In phase II, the PCI was piloted in a general rheumatology clinic. Results. Fifty-four patients were assessed in the pre-PCI group and 51 in the post-PCI group. Median (IQR) duration of consultation was 8 min (5-14) without PCI and 15 min (10-20) with PCI. The pre-PCI group raised 335 concerns from 50 patients, median (IQR) of 5 (3-10) per patient, rising post-PCI to 521 concerns, median (IQR) of 9 (5-16) from 51 patients, p = 0.002. Additional concerns predominantly arose from "physical and functional well-being" and "social care and well-being" domains. Most patients rated their experience with their doctor in the consultation as excellent or outstanding across all 11 questions in the questionnaire, both before and after the introduction of the PCI to the clinic setting. Conclusion. The PCI is a useful holistic needs assessment tool for rheumatology clinics. Although its use may initially prolong the consultation slightly, patients can raise a significantly higher number of concerns, which does not occur at the expense of patient satisfaction. This may help in identifying areas of unmet needs that previously went unnoticed. The Journal of Rheumatology</p

Clinical Study FGF-23 Levels before and after Renal Transplantation

Recommended by Bruce Kaplan Phosphatonin fibroblast growth factor-23 (FGF-23) is involved in phosphate (P) excretion and vitamin D metabolism. Recently, FGF-23 has been suggested to be responsible for the hypophosphatemia and inappropriately low calcitriol levels observed after renal transplantation. We performed a prospective study to investigate FGF-23 levels in patients with end-stage renal disease before and after renal transplantation and their probable association with markers of bone and mineral metabolism. Intact FGF-23 levels were determined before and at 3, 6, and 12 months posttransplantation in 18 renal transplant recipients. Intact parathyroid hormone (iPTH), calcium (Ca), P, 25(OH)VitD, and 1,25(OH) 2 VitD levels were measured at the same time periods. Renal threshold phosphate concentration (TmPO 4 /GFR) was also calculated at 3, 6, and 12 months posttransplantation. The results showed that FGF-23 levels decreased by 89% 3 months posttransplantation (346 ± 146 versus 37 ± 9 pg/mL, P &lt; .01) and remained stable throughout the study period. iPTH and P levels also decreased significantly after renal transplantation, while Ca and 1,25(OH) 2 VitD increased. Pretransplantation FGF-23 was significantly correlated with P levels at 3 months posttransplantation (P &lt; .005). In conclusion, FGF-23 levels decrease dramatically after successful renal transplantation. Pre-transplantation FGF-23 correlate with P levels 3 months posttransplantation

Pregnancy in Systemic Lupus Erythematosus Patients with Nephritis

Pregnancy in patients with lupus nephritis is a challenging clinical situation. Although not absolutely contraindicated, it is associated with increased risk for foetal and maternal complications, including foetal loss, preterm delivery, intrauterine growth retardation, hypertension, pre-eclampsia, nephritis flare, and, rarely, maternal death. The complication rate is further increased in the presence of antiphospholipid antibodies or the antiphospholipid syndrome. Proliferative classes of nephritis (III and IV) also appear to confer excess risk for complications. Immunosuppressives such as cyclophosphamide and mycophenolate, and antihypertensives such as angiotensin-converting-enzyme (ACE) inhibitors and angiotensin receptor blockers need to be stopped due to teratogenic effects. Agents like corticosteroids, azathioprine, and probably calcineurin inhibitors are considered compatible with gestation. Lupus activity needs to be assessed and carefully monitored. Thrombotic risk due to antiphospholipid antibodies, thrombotic events, or nephrosis needs to be evaluated and managed accordingly, with the use of aspirin and/or unfractioned or low molecular weight heparin. Differentiating between severe pre-eclampsia and lupus nephritis flare might require a renal biopsy, which might not always be feasible, for example after the 32nd gestational week or in a setting of uncontrolled hypertension or thrombocytopaenia. A 6-month history of quiescent disease on non-teratogenic agents seems to be associated with best chance for favourable outcomes. Pregnancy is optimally managed by a multidisciplinary team of experienced specialists, and close monitoring for disease activity during gestation; additionally, follow-up for maternal flare postpartum is also advised.</jats:p

A study on the pathogenesis of vascular alterations and bone metabolism disorders in patients with end stage renal disease

The aim of the present study was to investigate the association between serum levels of the calcification inhibitor fetuin-A, the osteoclast inhibitor osteoprotegerin and the phosphatonin FGF-23, with arterial stiffness and with early atherosclerosis, in hemodialysis patients. The study enrolled 81stable chronic hemodialysis patients. Serum levels of fetuin-A, osteoprotegerin, intact FGF-23 (iFGF-23) and c-terminal FGF-23 (cFGF-23) were measured by enzyme-linked immunosorbent assay. Vascular stiffness was evaluated by measuring the carotid to femoral pulse wave velocity (PWV) with applanation tonometry and simultaneous electrocardiography. Early atherosclerosis was evaluated by measuring the common carotid intima-media thickness (IMT), which was visualized bilaterally by B-mode ultrasonography, in the far vessel wall at three points central to the carotid bulb. In univariate analysis PWV was positively associated with age (p=0,000), co-morbidities like diabetes mellitus (p=0,039), hypertension (p=0,024), cardiovascular disease (p=0,003) and coronary heart disease (p=0,016). There was also a positive association with SAP (p=0,006), PP (p=0,006), and LDL levels (p=0,037). PWV was negatively associated with fetuin-A (p=0,001), and positively with osteoprotegerin (p=0,000), while there was no linear correlation with either cFGF-23 or iFGF-23 levels. In multiple regression analysis both fetuin-A and osteoprotegerin displayed an independent association with PWV (p=0,032, standard beta=-0197 and p=0,041, standard beta=0,227 respectively). In a subgroup of patients without coronary heart disease (n=59) PWV values lower than 9,1m/sec and higher than 11,1m/sec were positively associated with iFGF-23 levels (p=0,032). In multiple regression this association was independent of age, diabetes, pulse pressure and levels of fetuin-A and osteoprotegerin (p=0.049). In univariate analysis IMT was positively associated with age (p=0,000), co-morbidities like diabetes, (p=0,005), cardiovascular disease (p=0,001) and coronary heart disease (p=0,001).There was a negative association with DAP (p=0,008) and MAP (p=0,032), as well as with six month average albumin levels (p=0,008), and a positive association with logCRP (p=0,01). Regarding the factors under investigation IMT was negatively associated with fetuin-A (p=0,005) and positively with osteoprotegerin (p=0,000). However, these associations were confounded by age. IMT did not show a linear correlation either with cFGF-23 or iFGF-23 levels. Nevertheless higher than the average iFGF-23 levels were associated with higher IMT values (p=0,035) and this was independent of age. In multiple regression analysis IMT was independently associated with age (p=0,000, standard beta=0,570), cardiovascular disease (p=0,031, standard beta=0,166), and higher than the mean iFGF-23 levels (p=0,028, standard beta=0,164). In a model including only the serum markers associated with IMT an independent association was displayed with osteoprotegerin (p=0,000, standard beta=0,420), iFGF-23 levels (p=0,016, standard beta=0,232) and fetuin-Α (p=0,032, standard beta=-0,223). In conclusion, in chronic hemodialysis patients arterial stiffness (PWV) exhibited a negative independent correlation with fetuin-A and a positive with osteoprotegerin. The negative association of fetuin-A and the positive of osteoprotegerin with early atherosclerosis (IMT) was confounded by age.Σκοπός της παρούσας μελέτης ήταν η διερεύνηση σε αιμοκαθαιρόμενους ασθενείς της συσχέτισης των επιπέδων στον ορό της φετουΐνης-Α, της οστεοπροτεγερίνης και του FGF-23, με τη σκλήρυνση του αρτηριακού τοιχώματος και την αρχόμενη αθηροσκλήρωση.Στη μελέτη εντάχθηκαν 81 ασθενείς υπό χρόνια αιμοκάθαρση. Τα επίπεδα φετουΐνης-Α, οστεοπροτεγερίνης, άθικτου μορίου FGF-23 (iFGF-23) και καρβοξυτελικού τμήματος (cFGF-23) προσδιορίστηκαν στον ορό με ανοσοενζυμική μέθοδο. Η σκλήρυνση του αρτηριακού τοιχώματος εκτιμήθηκε με τη μέτρηση της ταχύτητας αγωγής σφυγμικού κύματος (PWV) μεταξύ καρωτίδας και μηριαίας αρτηρίας. Η αρχόμενη αθηροσκλήρωση εκτιμήθηκε με την υπερηχογραφική μέτρηση του πάχους του έσω-μέσου χιτώνα (ΙΜΤ) της κοινής καρωτίδας. Η PWV παρουσίασε αρνητική συσχέτιση με την φετουΐνη-Α (p=0,001), και θετική με την οστεοπροτεγερίνη (p=0,000), ενώ δεν παρουσίασε γραμμική συσχέτιση με τα επίπεδα cFGF-23 και iFGF-23. Σε μοντέλο πολλαπλής γραμμικής παλινδρόμησης, τόσο η φετουΐνη-Α όσο και η οστεοπροτεγερίνη παρουσίασαν ανεξάρτητη συσχέτιση με την PWV (p=0,032, standard beta=-0197 και p=0,041, standard beta=0,227 αντίστοιχα). Σε υποομάδα 59 ασθενών χωρίς στεφανιαία νόσο ταχύτητες αγωγής σφυγμικού κύματος 11,1m/sec παρουσίασαν θετική συσχέτιση με τα επίπεδα iFGF-23 (p=0,032), η οποία στην πολυπαραγοντική ανάλυση ήταν ανεξάρτητη από την ηλικία, την παρουσία σακχαρώδους διαβήτου, την πίεση σφυγμού και τα επίπεδα φετουΐνης-Α, οστεοπροτεγερίνης (p=0.049). Στη μονοπαραγοντική ανάλυση το ΙΜΤ παρουσίασε αρνητική συσχέτιση με την φετουΐνη-Α (p=0,005), και θετική με την οστεοπροτεγερίνη (p=0,000). Οι συσχετίσεις όμως αυτές δεν ήταν ανεξάρτητες από την ηλικία. Το ΙΜΤ δεν παρουσίασε γραμμική συσχέτιση με τα επίπεδα cFGF-23 και iFGF-23. Όμως υψηλότερα από το μέσο όρο επίπεδα iFGF-23 συσχετίσθηκαν με υψηλότερες τιμές ΙΜΤ (p=0,035). Η συσχέτιση αυτή ήταν ανεξάρτητη από την ηλικία. Στην πολυπαραγοντική ανάλυση ανεξάρτητη συσχέτιση με το ΙΜΤ παρουσίασαν η ηλικία (p=0,000, standard beta=0,570), η παρουσία καρδιαγγειακής νόσου (p=0,031, standard beta=0,166), και τα υψηλότερα σε σχέση με το μέσο όρο επίπεδα iFGF-23 (p=0,028, standard beta=0,164). Σε μοντέλο που περιελάμβανε μόνο τους ορολογικούς δείκτες που συσχετίσθηκαν με το ΙΜΤ ανεξάρτητη συσχέτιση με το ΙΜΤ παρουσίασαν η οστεοπροτεγερίνη (p=0.000, standard beta=0,420), τα επίπεδα iFGF-23 (p=0.016, standard beta=0,232) και η φετουΐνη-Α (p=0.032, standard beta=-0,223). Συμπερασματικά σε ασθενείς υπό χρόνια αιμοκάθαρση η φετουΐνη-Α και η οστεοπροτεγερίνη παρουσίασαν ανεξάρτητη γραμμική συσχέτιση, αρνητική και θετική αντίστοιχα, με τη σκλήρυνση του αρτηριακού τοιχώματος, ως ταχύτητα αγωγής σφυγμικού κύματος (PWV). Η συσχέτισή τους με την αρχόμενη αθηροσκλήρωση ως πάχυνση του αρτηριακού τοιχώματος (IMT) δεν ήταν ανεξάρτητη από την ηλικία

Pregnancy in Systemic Lupus Erythematosus Patients with Nephritis

Pregnancy in patients with lupus nephritis is a challenging clinical situation. Although not absolutely contraindicated, it is associated with increased risk for foetal and maternal complications, including foetal loss, preterm delivery, intrauterine growth retardation, hypertension, pre-eclampsia, nephritis flare, and, rarely, maternal death. The complication rate is further increased in the presence of antiphospholipid antibodies or the antiphospholipid syndrome. Proliferative classes of nephritis (III and IV) also appear to confer excess risk for complications. Immunosuppressives such as cyclophosphamide and mycophenolate, and antihypertensives such as angiotensin-converting-enzyme (ACE) inhibitors and angiotensin receptor blockers need to be stopped due to teratogenic effects. Agents like corticosteroids, azathioprine, and probably calcineurin inhibitors are considered compatible with gestation. Lupus activity needs to be assessed and carefully monitored. Thrombotic risk due to antiphospholipid antibodies, thrombotic events, or nephrosis needs to be evaluated and managed accordingly, with the use of aspirin and/or unfractioned or low molecular weight heparin. Differentiating between severe pre-eclampsia and lupus nephritis flare might require a renal biopsy, which might not always be feasible, for example after the 32nd gestational week or in a setting of uncontrolled hypertension or thrombocytopaenia. A 6-month history of quiescent disease on non-teratogenic agents seems to be associated with best chance for favourable outcomes. Pregnancy is optimally managed by a multidisciplinary team of experienced specialists, and close monitoring for disease activity during gestation; additionally, follow-up for maternal flare postpartum is also advised