M. Cozzolino

Cardiac and pulmonary calcification in a hemodialysis patient: partial regression 4 years after parathyroidectomy.

AIMSnThe reversibility of extraskeletal calcifications in dialysis patients is an important and unresolved issue. Although periarticular calcifications have been shown to be reversible, little data are available on vascular or parenchymal calcifications.nnnCASE HISTORYnA patient on maintenance hemodialysis with severe hyperparathyroidism, hypercalcemia and hyperphosphatemia was admitted to undergo parathyroidectomy. A preoperative total body bone scintigraphy was performed to better evaluate a lytic lesion in the pelvis, the histology of which proved to be a brown tumor. The scan showed the typical findings of renal osteodystrophy, but also a diffuse extra-skeletal uptake of bone tracer in the lungs, kidneys, femoral arteries and myocardium. After surgery, good control of serum calcium, phosphate (Ca x P product < 50 mg2/dl2) and PTH levels was maintained during 4 years of follow-up. Bone scans were repeated after 2 and 4 years, showing marked improvement of periarticular uptake at the ends of long bones. Extraosseous calcium deposition was still markedly evident, but progressively decreased (at 4 years: heart -36%, lungs -18%).nnnCONCLUSIONnIn this dialysis patient, extraskeletal calcification of visceral organs (particularly in the heart and the lungs) due to prolonged hypercalcemia and hyperphosphatemia was partially reversible by parathyroidectomy followed by good long-term control of serum phosphate and calcium.

Nonvitamin K-dependent oral anticoagulants (NOACs) in chronic kidney disease patients with atrial fibrillation

Atrial fibrillation (AF) represents the most common arrhythmia in patients with chronic kidney disease (CKD). As in the general population, in CKD patients AF is associated with an increased risk of thromboembolism and stroke. However, CKD patients, especially those on renal replacement therapy (RRT), also exhibit an increased risk of bleeding, especially from the gastrointestinal tract. Oral anticoagulation is the most effective form of thromboprophylaxis in patients with AF presenting increased risk of stroke. Limited evidence on efficacy, the increased risk of bleeding as well as some concern regarding the use of warfarin in CKD, has often resulted in the underuse of anticoagulation CKD patients. A large body of evidence suggests that non-vitamin K-dependent oral anticoagulant agents (NOACs) significantly reduce the risk of stroke, intracranial hemorrhage, and mortality, with lower to similar major bleeding rates compared with vitamin K antagonist such as warfarin in normal renal function subjects. Hence, they are currently recommended for patients with atrial fibrillation at risk for stroke. However, NOACs metabolism is largely dependent on the kidneys for elimination and little is known in patients with creatinine clearance <25ml/min who were excluded from all pivotal phase 3 NOACs trials. This review focuses on the current pharmacokinetic, observational, and prospective data on NOACs in patients with moderate to advanced chronic kidney disease (creatinine clearance 15-49ml/min) and those on dialysis.

Clinical significance of FGF-23 measurement in dialysis patients

AIMSnConsidering the growing relevance of fibroblast growth factor-23 (FGF-23) in the pathogenesis of chronic kidney disease bone and mineral disorder (CKD-MBD), an analysis was performed to determine the relative importance of C-terminal (cFGF-23) and intact (iFGF-23) assays in assessing CKD-MBD status in the first place and the relationship between FGF-23 and mortality as a secondary aim.nnnMETHODSnIn 77 patients (15 peritoneal dialysis and 62 hemodialysis), levels of calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin- D (25D), 1,25D, FGF-23 (C-terminal and intact molecule) were measured and their correlations were analyzed. The relationship between FGF-23 levels and patient survival was also analyzed.nnnRESULTSnA significant correlation was found between cFGF-23 and 1,25D, PTH and 25D while iFGF-23 was significantly correlated with phosphate, 25D and PTH. PTH and 1,25D were independent predictors of cFGF-23, while for iFGF-23 independent predictors were phosphate and 25D. No significant relationship was found between FGF-23 and mortality.nnnCONCLUSIONSnC-terminal or intact FGF-23 levels are weakly correlated and thus not clearly indicative of FGF-23 effects on PTH, P and vitamin D metabolism in dialysis patients. Assays for cFGF-23 and iFGF-23 showed a good correlation, but the intact molecule was not superior in defining interactions with CKD-MBD molecules. Measuring FGF-23 on a regular basis with the current assays in CKD and dialysis patients does not yet seem clinically useful.

Evaluation of renal function in elderly patients: performance of creatinine-based formulae versus the isotopic method using 99mTc-diethylene triamine pentaacetic acid.

IntroductionMeasurement of the glomerular filtration rate (GFR) is recognized worldwide as the most accurate way of assessing kidney function. The prevalence of impaired renal function increases with advancing age. In this study we compared the clinical formulae Cockcroft–Gault (CG), isotope dilution mass spectrometry-modification of diet in renal disease (IMDS-MDRD) and chronic kidney disease epidemiology collaboration (CKD-EPI) with 99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA) in elderly patients over and under the age of 70 years in an attempt to establish which formula produces the best measurement of renal function in this population. Materials and methodsPatients were randomly selected from two age groups [<70 years (n=37) and ≥70 years (n=39)]. Two plasma samples were collected at 60 and 180 min after injection of 99mTc-DTPA, and the GFR was calculated applying Charles D. Russell’s two-sample method. ResultsIn patients younger than 70 years, no statistically significant difference was found between GFR evaluated with 99mTc-DTPA and GFR obtained using the other methods.In patients aged at least 70 years, no statistically significant difference was found between GFR evaluated with 99mTc-DTPA and GFR evaluated using the CG real weight formula. Conversely, statistically significant differences were found between GFR evaluated with 99mTc-DTPA and GFR obtained using the CG normalized weight (P=0.002), IMDS-MDRD (P=0.024) and CKD-EPI (P=0.028) formulae. Discussion and conclusionIn patients older than 70 years, the use of the two ‘classical’ formulae (IMDS-MDRD and CKD-EPI) overestimated GFR in stage III CKD (GFR 30–59 ml/min) when compared with the gold standard 99mTc-DTPA method. Thus, in patients aged 70 years and above only the CG real weight formula provided unbiased results comparable to 99mTc-DTPA. In conclusion, in elderly patients, GFR measured using CKD-EPI and IMDS-MDRD serum creatinine-based formulae may be overestimated compared with that measured using 99mTc-DTPA GFR.

Unsuccessful application of taurolidine in the treatment of fungal peritonitis in peritoneal dialysis

Fungal peritonitis (FP) is a serious complication for peritoneal dialysis (PD) patients, determining hospitalization, technique failure, catheter loss and death. In the 2005 update, treatment recommendations for FP from the International Society of Peritoneal Dialysis (ISPD) advocate catheter removal immediately after fungi are identified by microscopy or culture. The availability of more effective medical treatments could therefore be of great importance. The aim of this report is to describe a case of a 43-year-old, diabetic, HIV positive PD patient with fluconazole resistant Candida peritonitis, who was treated with an i.p. taurolidine solution. Taurolidine is a non-antibiotic antimicrobial, with broad bactericidal and fungicidal properties. It has been used during surgery for lavage of the peritoneum in cases of peritonitis. Its mechanism of action is related to direct toxic action on micro-organisms, through a chemical reaction between active taurolidine derivatives and structures on the cell wall. Treatment failed because the patient had severe burning pain during i.p. administration of the drug, limiting its dose. PD catheter removal allowed complete recovery. It remains undetermined if, with different doses and methodology, taurolidine could be more effective in treating bacterial and/or fungal peritonitis. Currently, catheter removal remains the most effective therapy of fungal peritonitis.

Phosphate in Chronic Kidney Disease Progression

A direct and independent association between serum phosphate (P) levels and mortality has been reported. High circulating P concentrations, still within the normal range, was associated with unfavourable outcomes in normal subjects as well as in chronic kidney disease (CKD) patients. Experimental data support the notion that P overload may hamper survival expectancy, directly inducing vascular, skeletal, and renal ageing. The balance of P results from dietary intake, intestinal absorption, glomerular filtration, tubular resorption, and hormonal asset. However, the accurate estimation of P balance is hampered by several methodological weaknesses, becoming even critical when renal function declines. Increasing evidence in the physiology of P metabolism in humans counteracts with uncertainties on dietary P intake and P balance assessment from general population and CKD subjects.

Calcium and Phosphate Physiology

Abstract In healthy subjects, the calcium and phosphate balance may be positive, normal, or negative in the absence of any overt abnormality in either serum calcium or phosphate concentration. Therefore simply measuring serum calcium and phosphate concentrations is of poor help in predicting calcium and phosphate balance. Anyway, if treatment is initiated assuming an initial condition of low serum calcium or high serum phosphate levels, a subsequent increase in parathyroid hormone (PTH) synthesis and secretion, accompanied by a rapid parathyroid gland hyperplasia, occurs. Target tissues for PTH are bone, kidney, and gut. The effects on bone are to enhance bone resorption to increase serum calcium and phosphate levels. The effects on kidneys are to increase calcium reabsorption but produce phosphate excretion, with an enhancement in active vitamin D. Active vitamin D increases calcium and phosphate reabsorption from the gut. Finally, higher calcium levels suppress PTH secretion through negative feedback.

Non-vitamin-K-dependent oral anticoagulants in end-stage renal disease patients with non-valvular atrial fibrillation: an impossible wedding

Atrial fibrillation (AF) is the most common arrhythmia in patients with chronic kidney disease (CKD). In this population, AF is associated with an increased risk of thromboembolism and stroke as a result of a progressive decline in the glomerular filtration rate. However, CKD patients, in particular those on renal replacement therapy, also have an increased risk of bleeding, especially from the gastrointestinal tract. Oral anticoagulation is the most effective form of thromboprophylaxis in patients with AF presenting an increased risk of stroke. Limited evidence of its efficacy, the increased risk of bleeding as well as some concern regarding the use of warfarin in CKD have often resulted in the underuse of anticoagulation in CKD patients. A large body of evidence suggests that non-vitamin-K-dependent oral anticoagulants (NOACs) significantly reduce the risk of stroke, intracranial hemorrhage and mortality. Hence, they are currently recommended for patients with AF at risk of stroke. However, the metabolism of NOACs is largely dependent on the kidneys for elimination and little is known about their use in patients with creatinine clearance <25 mL/min, who have been excluded from all pivotal phase III NOAC trials. This review focuses on the current pharmacokinetic, observational and prospective data on NOACs in patients affected by moderate to advanced CKD (creatinine clearance 15–49 mL/min) and in those on dialysis.