Andrea Stucchi

Impaired oxygen extraction in metabolic myopathies: Detection and quantification by near-infrared spectroscopy

Patients with mitochondrial myopathies (MM) or myophosphorylase deficiency (McArdles disease, McA) show impaired capacity for O2 extraction, low maximal aerobic power, and reduced exercise tolerance. Non‐invasive tools are needed to quantify the metabolic impairment. Six patients with MM, 6 with McA, 25 with symptoms of metabolic myopathy but negative biopsy (patient‐controls, P‐CTRL) and 20 controls (CTRL) underwent an incremental cycloergometric test. Pulmonary O2 uptake (V̇O2) and vastus lateralis oxygenation indices (by near‐infrared spectroscopy, NIRS) were determined. Concentration changes of deoxygenated hemoglobin and myoglobin (Δ[deoxy(Hb + Mb)]) were considered an index of O2 extraction. Δ[deoxy(Hb + Mb)] peak (percent limb ischemia) was lower in MM (25.3 ± 12.0%) and McA (18.7 ± 7.3) than in P‐CTRL (62.4 ± 3.9) and CTRL (71.3 ± 3.9) subjects. V̇O2 peak and Δ[deoxy(Hb + Mb)] peak were linearly related (r2 = 0.83). In these patients, NIRS is a tool to detect and quantify non‐invasively the metabolic impairment, which may be useful in the follow‐up of patients and in the assessment of therapies and interventions. Muscle Nerve, 2006

Sevelamer for hyperphosphataemia in kidney failure: Controversy and perspective

The term ‘chronic kidney disease–mineral and bone disorder’ (CKD–MBD), coined in 2006, was introduced in a position statement by the Kidney Disease: Improving Global Outcomes (KDIGO) organization. According to the KDIGO guidelines, CKD–MBD is a systemic disorder and patients with vascular or valvular calcifications should be included in the group with the greatest cardiovascular risk. Therefore, the presence or absence of calcification is a key factor in strategy decisions for such patients. In particular, it is recommended that the use of calcium-based phosphate binders should be restricted in patients with hypercalcaemia, vascular calcification, low levels of parathyroid hormone (PTH) or adynamic bone disease. In this respect, it should be underscored that treatment with phosphate-binding agents can normalise the levels of phosphate and PTH, but the use of calcium carbonate can favour the progression of vascular calcifications. There is evidence of reduced progression of vascular calcification in patients treated with sevelamer compared with high doses of calcium-based binders, but there is as yet no strong evidence regarding hard outcomes, such as mortality or hospitalization, to support the use of one treatment over another. Nevertheless, a number of experimental and observational findings seem to suggest that sevelamer should be preferred over calcium-based binders, in as much as these can increase cardiovascular mortality when used in high doses. A threshold dose below which calcium-based binders can be used safely in CKD patients with hyperphosphatemia has yet to be established.

Hemodialysis tunneled central venous catheters: five-year outcome analysis.

Background Tunneled central venous catheters (tCVCs) are considered inferior to arteriovenous fistulas (AVFs) and grafts in all nephrology guidelines. However, they are being increasingly used as hemodialysis vascular access. The purpose of this study was to document the natural history of tCVCs and determine the rate and type of catheter replacement. Methods This was a prospective study of 141 patients who underwent hemodialysis with tCVCs between January 2008 and December 2012. The patients used 154 tCVCs. Standard protocols about management of tCVCs, according to European Renal Best Practice, were well established. All catheters were inserted in the internal jugular vein. Criteria for catheter removal were persistent bloodstream infection, detection of an outbreak of catheter-related bloodstream (CRBS) infections, or catheter dysfunction. Event rates were calculated per 1,000 catheter days; tCVC cumulative survival was estimated by Kaplan-Meier analysis. Results Catheter replacement occurred in 15 patients (0.29 per 1,000 days); catheter dysfunction was the main cause of replacement (0.18 per 1,000 days), typically within 12 months of surgical insertion. A total of 53 CRBS events in 36 patients were identified (0.82 per 1,000 days); 17 organisms, most commonly Gram-positive pathogens, were isolated; 87% of CVC infections were treated by systemic antibiotics associated with lock therapy. tCVC cumulative survival was 91% at 1 year, 88% at 2 years and 85% at 4 years. Conclusions Our data show a high survival rate of tCVCs in hemodialysis patients, with low incidence of catheter dysfunction and CRBS events. These data justify tCVC use for hemodialysis vascular access, also as first choice, especially in patients with exhausted peripheral access and limited life expectancy.

The Effect of Paricalcitol on Vascular Calcification and Cardiovascular Disease in Uremia: Beyond PTH Control

Secondary hyperparathyroidism is a systemic disorder that associates with bone and cardiovascular disease, including arterial calcification. Treatment with calcitriol, the active form of vitamin D, reduces parathyroid hormone levels, but may result in elevations in serum calcium and phosphorus, increasing the risk of vascular calcification in dialysis patients. New vitamin D receptor activators (VDRAs) have been developed and investigated with the rationale to treat high serum PTH levels, with a reduced risk of hypercalcemia and hyperphosphatemia. Paricalcitol is a selective VDRA that suppresses PTH secretion with minimal increases on serum calcium and phosphate. Moreover, paricalcitol prevents vascular calcification in experimental models of renal failure, compared with calcitriol.

Role of Vitamin D Receptor Activators in Cardio-Renal Syndromes

The involvement of vitamin D deficiency in cardiovascular morbidity and mortality is attracting great interest. In patients with chronic kidney disease this association is stronger because vitamin D levels decrease as a result of renal progressive impairment. In chronic kidney disease secondary hyperparathyroidism commonly occurs in response to persistent hypocalcemia and hyperphosphatemia; moreover, parathyroid gland volume increases, vascular calcification is accelerated, and structural and functional modifications of the left ventricle are observed. These alterations entail both cardiac and renal involvement, resulting in cardio-renal syndrome. Recent studies concluded that vitamin D administration seems to have cardioprotective and renoprotective effects and improve peripheral vascular disease, vascular calcification, cardiac outcome, and blood pressure control. In clinical practice, therefore, the use of this hormone may play an important role in cardio-renal syndrome prevention.

Vitamin K plasma levels determination in human health.

Abstract Vitamin K (phylloquinone or vitamin K1 and menaquinones or vitamin K2) plays an important role as a cofactor in the synthesis of hepatic blood coagulation proteins, but recently has also aroused an increasing interest for its action in extra-hepatic tissues, in particular in the regulation of bone and vascular metabolism. The accurate measurement of vitamin K status in humans is still a critical issue. Along with indirect assays, such as the undercarboxylated fractions of vitamin K-dependent proteins [prothrombin, osteocalcin (OC), and matrix gla protein], the direct analysis of blood levels of phylloquinone and menaquinones forms might be considered a more informative and direct method for assessing vitamin K status. Different methods for direct quantification of vitamin K serum levels are available. High-performance liquid chromatography (HPLC) methods coupled with post-column reduction procedures and fluorimetric or electrochemical detection are commonly used for food and blood analysis of phylloquinone, but they show some limitations when applied to the analysis of serum menaquinones because of interferences from triglycerides. Recent advancements include liquid chromatography tandem mass spectrometry (LCMS/MS) detection, which assures higher specificity. The optimization and standardization of these methods requires specialized laboratories. The variability of results observed in the available studies suggests the need for further investigations to obtain more accurate analytical results.

Phosphate Control in Peritoneal Dialysis

Chronic kidney disease (CKD) is characterized by phosphorus retention and, in more advanced stages, by high serum phosphorus (P) levels. During the last decade, it has been elucidated the central role of P in the pathogenesis of CKD mineral bone disorder (CKD-MBD), determining both renal osteodystrophy and cardiovascular disease. Unfortunately, at least one third of patients on chronic dialysis have high serum P levels, with a consequent higher serum PTH levels, commonly associated with vitamin D deficiency, increased vascular calcification and the highest ratios of morbidity and mortality. In patients with CKD stage 5 on dialysis, therapeutic approaches to reduce serum P levels should include restriction of dietary phosphate intake, optimal dialysis treatment, and use of P binders. In this context, the use of P binders appears to be an essential treatment to control P overload in CKD patients. In this review, we analyzed the use of calcium-based and calcium-free P binders in peritoneal dialysis patients.

Reprint of: Vitamin D receptor activation and prevention of arterial ageing.

In chronic kidney disease (CKD) patients, cardiovascular (CV) morbidity and mortality rate is higher than in the general population, because of frequently concomitant hypertension, peripheral vascular disease, heart failure, vascular calcification (VC), diabetes and mineral bone disease. Recently, another important factor associated to CV risk in CKD has been deeply investigated: vitamin D deficiency. Vitamin D Receptors (VDRs) are present in several systems and tissues and VDR activation is associated to positive effects, resulting in better blood pressure control and prevention of diabetic nephropathy. Unfortunately, the natural, non-selective vitamin D receptor activator (VDRA), calcitriol, is associated to higher serum calcium and phosphate levels, thus worsening CV risk in CKD. Recent data showed that the selective VDRA paricalcitol might have ameliorative CV effects. The potential positive impact of the use of paricalcitol on diabetic nephropathy, cardiac disease, hypertension, and VC may open new paths in the fight against CV disease in CKD patients.

Cardiovascular disease in dialysis patients

Abstract Cardiovascular disease (CVD) is a highly common complication and the first cause of death in patients with end-stage renal disease (ESRD) on haemodialysis (HD). In this population, mortality due to CVD is 20 times higher than in the general population and the majority of maintenance HD patients have CVD. This is likely due to ventricular hypertrophy as well as non-traditional risk factors, such as chronic volume overload, anaemia, inflammation, oxidative stress, chronic kidney disease–mineral bone disorder and other aspects of the ‘uraemic milieu’. Better understanding the impact of these numerous factors on CVD would be an important step for prevention and treatment. In this review we focus non-traditional CVD risk factors in HD patients.

Incremental peritoneal dialysis: a non-marginal treatment, qualitatively and quantitatively

Incremental peritoneal dialysis has been proved feasible and safe in asymptomatic patients with a glomerular filtration rate (GFR) <6 mL/min. A second population is composed of asymptomatic, mostly older patients with GFR between 6 and 10 mL/min, in whom a low-dose start may preserve the residual renal function. Lastly, patients with severe, terminal, chronic cardiomyopathy who are not candidates for a heart transplant may experience beneficial effects on cardiac function and hospitalization with low-dose peritoneal dialysis treatment even when they have GFR >10 mL/min. In conclusion, incremental peritoneal dialysis is a feasible therapeutic option that the nephrologist should know and be able to perform in those patients who may benefit from it. Therefore, it is noted that peritoneal dialysis is not a treatment marginal.