Panagiotis Pateinakis

Associations of fetuin-A and osteoprotegerin with arterial stiffness and early atherosclerosis in chronic hemodialysis patients

BackgroundCardiovascular morbidity and mortality remains excessive in patients with chronic kidney disease. The association of vascular changes with regulators of extraosseous calcification in this patient population is still under investigation. The aim of the present study was to investigate the associations of the calcification inhibitor fetuin-A, and the anti-osteoclastic factor osteoprotegerin (OPG) with vascular pathology in chronic hemodialysis patients.MethodsIn this cross-sectional study including 81 stable chronic hemodialysis patients, we measured carotid-to-femoral pulse wave velocity (cfPWV) with applanation tonometry, reflecting arterial stiffness, and common carotid intima-media thickness (ccIMT), a surrogate of early atherosclerosis, as well as serum levels of fetuin-A and OPG. Co-morbidities, traditional cardiovascular risk factors, inflammatory markers and mineral-bone disease serology parameters were also recorded.ResultscfPWV correlated inversely with fetuin-A (r=−0.355, p=0.001) and positively with OPG (r=0.584, p<0.001). In multilinear regression analysis including age, gender, diabetes, cardiovascular disease, hypertension, pulse pressure, LDL, logCRP, both fetuin-A and OPG were independently associated with cfPWV (p=0.024 and p=0.041 respectively). ccIMT was negatively associated with fetuin-A (r=−0.312, p=0.005) and positively with OPG (r=0.521, p<0.0001); however these associations lost statistical significance after adjustment for age.ConclusionIn chronic hemodialysis patients both fetuin-A and OPG levels are independently associated with arterial stiffness but not with early atherosclerotic vascular changes.

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.

Impact of Long-Term Cinacalcet, Ibandronate or Teriparatide Therapy on Bone Mineral Density of Hemodialysis Patients: A Pilot Study

Background: Insufficient evidenced-based information is available for the treatment of osteoporosis in hemodialysis (HD) patients. Methods: In 102 HD patients, bone mineral density (BMD) was measured twice 16 ± 3 months apart. In the second BMD measurement 66 of them had a femoral neck (FN) T-score <–2.5. Of these 66 patients, 38 consented to a bone biopsy. Depending on both the bone biopsy findings and parathyroid hormone levels, patients were assigned to treatment groups. Eleven patients with osteitis fibrosa and iPTH >300 pg/ml received cinacalcet, 11 with osteitis fibrosa and iPTH <300 pg/ml received ibandronate, 9 with adynamic bone disease received teriparatide, and 7 with mild abnormalities received no treatment. A third BMD measurement was done after an average treatment period of 13–16 months. We compared the annual percent change of FN and lumbar spine (LS) BMD before and during treatment. Results: FN and LS BMD decreased significantly in the cinacalcet group, with an annual change of 3.6 and 3.4% before treatment to –4.2% (p = 0.04) and –7.7% (p = 0.02) during treatment, respectively. In the teriparatide group, FN and LS BMD increased, although not significantly, with an annual change of –5.4 and –2.6% before treatment to 2.7 and 4.9% during treatment, respectively. In both the ibandronate and the no treatment groups, BMD change rate remained negative during the whole study. Conclusions: Teriparatide administration improved BMD in HD patients with adynamic bone disease, although these results did not reach statistical significance. In HD patients with osteitis fibrosa, ibandronate did not improve BMD while cinacalcet reduced BMD.

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.

Acute renal failure due to tumor lysis syndrome in a patient with non-Hodgkin’s lymphoma

Tumor lysis syndrome is characterized by multiple metabolic derangements resulting from the release of intracellular components into the bloodstream due to abrupt malignant cell death, spontaneously or following antineoplastic therapy. The syndrome is characterized by hyperkalemia, hyperuricemia, hyperphosphatemia, and hypocalcemia, while deposition of uric acid and calcium phosphate crystals may result in acute renal failure, which is often exacerbated by concomitant intravascular volume depletion. A case of tumor lysis syndrome complicated by acute renal failure in a patient with non-Hodgkin’s lymphoma is reported and the pathophysiology, the clinical features, and the treatment options are discussed.

Fabry disease due to D313Y and novel GLA mutations

Objectives Our aim is to report four novel α-gal A gene (GLA) mutations resulting in Fabry disease (FD) and provide evidence of pathogenicity of the D313Y mutation regarding which contradictory data have been presented in the literature. Setting and participants Twenty-five family members of nine unrelated patients with definite FD diagnosis, 10 clinically suspected cases and 18 members of their families were included in this polycentric cohort study. Primary and secondary outcome measures Genotyping and measurement of lyso-Gb3 was performed in all individuals. The α-Gal A activity was measured in all men as well as plasma and urine Gb3 concentration in selected cases. Optical and electron microscopy was performed in kidney biopsies of selected patients. All the above were evaluated in parallel with the clinical data of the patients. Results Fourteen new cases of FD were recognised, four of which were carrying already described GLA mutations. Four novel GLA mutations, namely c.835C>T, c.280T>A, c.924A>C and c.511G>A, resulting in a classic FD phenotype were identified. Moreover, FD was definitely diagnosed in five patients carrying the D313Y mutation. Eight D313Y carriers were presenting signs of FD despite not fulfilling the criteria of the disease, two had no FD signs and two others were apparently healthy. Conclusions Four novel GLA pathogenic mutations are reported and evidence of pathogenicity of the D313Y mutation is provided. It seems that the D313Y mutation is related to a later-onset milder phenotype than the typical phenotype with normal lysoGb3 concentration. Our study underlines the significance of family member genotyping and newborn screening to avoid misdiagnoses and crucial delays in diagnosis and treatment of the disease.

To intervene or not? A man with multidrug-resistant hypertension, endovascular abdominal aneurysm repair, bilateral renal artery stenosis and end-stage renal disease salvaged with renal artery stenting.

Abstract We report the case of a 69-year-old man with uncontrolled multidrug-resistant secondary hypertension following a 10 year history of endovascular abdominal aortic aneurysm repair, with suprarenal fixation and concurrent angioplasty with stenting of the left renal artery for atherosclerotic renal disease, and progressive chronic kidney disease. Renal scintigraphy revealed complete loss of the right kidney’s and severe reduction of the left kidney’s perfusion and function. Following recent evidence and consultation with vascular surgeons regarding the technical difficulties of any procedure, escalation of antihypertensive treatment was initially chosen. Careful drug adjustments significantly improved but did not fully control blood pressure (BP); further, the patient experienced an acute ischaemic stroke and renal function deterioration towards end-stage renal disease within a few months. At this point, revascularization of the left renal artery coupled with three haemodialysis sessions to remove contrast media was justified as rescue therapy against permanent renal replacement therapy. Successful intervention achieved an immediate BP reduction, with BP fully controlled, despite a  > 70% decrease in antihypertensive treatment, while renal function improved at 6 months from 11.5 to 22 ml/min/1.73 m2. Renal angioplasty confers undisputed benefits in BP control and nephroprotection, and should be offered without delay to patients with renovascular hypertension and/or ischaemic nephropathy.

Fever of unknown origin in a haemodialysis patient: a late diagnosis requiring a novel treatment

Fever in haemodialysis patients is usually attributed to infection, with less frequent causes including malignancy and autoimmune disorders [1]. Sometimes, fever persists despite empirical treatment, and investigations towards the above mentioned diagnoses fail to reveal the cause. Thus, rarer aetiologies need to be considered, which may appear rather unexpected, especially in patients under prolonged medical follow-up.

Can We Tackle with Vascular Calcification and Arterial Stiffness in Patients with Chronic Kidney Disease

Cardiovascular disease remains the leading cause of increased morbidity and mortality in patients with chronic kidney disease and is attributed to early and accelerated atherosclerosis and arteriosclerosis observed in this patient popu- lation. Vascular calcifications, particularly of the media, are commonly found in chronic uremia and are a major contribu- tor to arteriosclerosis and increased arterial stiffness. Epidemiologic data support the correlation of vascular calcification and arterial stiffness to adverse cardiovascular outcomes and mortality. Experimental evidence has shed light on the pathogenetic mechanisms of vascular calcification and arterial stiffness and their relation to impaired bone metabolism and imbalance between promoters and inhibitors of extra-osseous bone formation. However further research is needed to clarify their exact contribution and whether their targeting could significantly affect vascular calcification and arterial stiffening and could improve survival in chronic kidney disease patients.