[New Mutation of CYP24A1 in a Case of Idiopathic Infantile Hypercalcemia Diagnosed in Adulthood].

Mutations in the 24-hydroxylase gene CYP24A1 have been recognized as causes of childhood idiopathic hypercalcemia (IIH), a rare disease (incidence <1:1,000,000 live births) characterized by increased vitamin D sensitivity, with symptomatic severe hypercalcemia. IIH was first described in Great Britain two years after the start of a program of vitamin D supplementation in milk for the prevention of rickets, manifesting in about 200 children with severe hypercalcemia, dehydration, growth failure, weight loss, muscle hypotonia, and nephrocalcinosis. The association between the epidemic occurrence of IIH and vitamin D administration was quickly attributed to intrinsic hypersensitivity to vitamin D, and the pathogenic mechanism was recognized in the inactivation of Cytochrome P450 family 24 subfamily A member 1 (CYP24A1), which was identified as the molecular basis of the pathology. The phenotypic spectrum of CYP24A1 mutation can be variable, manifesting predominantly with childhood onset and severe symptomatology (severe hypercalcemia, growth retardation, lethargy, muscle hypotonia, dehydration), but also with juvenile-adult onset forms with nephrolithiasis, nephrocalcinosis, and alterations in phosphocalcium homeostasis. We describe the case of a patient in whom the diagnosis of IIH was made in adulthood, presenting with finding of nephrocalcinosis in childhood, and with subsequent onset of severe hypercalcemia with hypercalciuria, hypoparathyroidism, hypervitaminosis D, and recurrent renal lithiasis. Genetic investigation revealed the presence in homozygosity of the c_428_430delAAG_p.Glu143del variant in the CYP24A1 gene with autosomal recessive transmission, a mutation not reported in the literature.

[Therapeutic Plasma Exchange in a Patient with Chronic Hemodialysis and a New Diagnosis of Myasthenia Gravis].

Case ReportC.S.T. (♂, 71 years old) is a patient with multiple and severe comorbidities, undergoing thrice-weekly chronic hemodialysis since 2008 due to the progression of post-lithiasic uropathy. Over the past 2 months, the patient had been experiencing progressive ptosis of the eyelids, muscle weakness, and ultimately dysphagia and dysarthria that emerged in the last few days. Urgently admitted to the Neurology department, electromyography (EMG) was performed, leading to a diagnosis of predominant cranial myasthenia gravis (with borderline anti-acetylcholine receptor antibody serology). Prompt treatment with pyridostigmine and steroids was initiated. Considering the high risk of acute myasthenic decompensation, therapeutic plasma exchange (TPE) with centrifugation technique was promptly undertaken after femoral CVC placement. TPE sessions were alternated with hemodialysis. The patient's condition complicated after the third TPE session, with septic shock caused by Methicillin-Sensitive Staphylococcus Aureus (MSSA). The patient was transferred to the Intensive Care Unit (ICU). Due to hemodynamic instability, continuous veno-venous hemodiafiltration (CVVHDF) with citrate anticoagulation was administered for 72 hours. After resolving the septic condition, intermittent treatment with Acetate-Free Biofiltration (AFB) technique was resumed. The patient completed the remaining three TPE sessions and, once the acute condition was resolved, was transferred back to Neurology. Here, the patient continued the treatment and underwent a rehabilitation program, showing significant motor and functional recovery until discharge. Conclusions. The multidisciplinary interaction among Nephrologists, Neurologists, Anesthesiologists, and experts from the Immunohematology and Transfusion Medicine Service enabled the management and treatment of a rare condition (MG) in a high-risk chronic hemodialysis patient.

[Pre-dialysis arteriovenous fistula results in better patency rate]. / Fistola artero venosa pre-dialisi = migliori risultati.

BACKGROUND: The timing of creation of the first permanent vascular access is crucial to the clinical history of haemodialysis patients. Our strategy is to create vascular access early enough to allow its maturation before the start of the treatment. METHODS: Aim of the study is to evaluate patency of primary A-V fistulas in patients treated between 1985 and 2000 in our dialysis unit. One hundred and thirty A-V fistulas created before haemodialysis treatment (range 10-540 days) and used at its beginning (pre-HD group) are compared with 74 A-V fistulas created and/or used after the start of the haemodialysis treatment (post-HD group). RESULTS: Pre-HD group fistulas resulted in higher patency rate than the post-HD group, immediately at the start of the treatment (94.6% vs. 86.5%, p<0.05), at 6 months (89.2% vs. 75.6%, p<0.025), at 12 months (84.5% vs. 64.6%, p< 0.005), at 24 months (77.2% vs. 54.8%, p< 0.005). CONCLUSIONS: A-V fistula is to be preferred in the choice of primary vascular access for chronic haemodialysis patients. It should be created early enough before the beginning of the treatment (when serum creatinine reaches 6 to 7 mg/dL). This planning avoids central venous catheter placement, preserves vessels and the choice of the best surgical option thus resulting in a better fistula survival.

A simple mathematical model of intradialytic sodium kinetics: "in vivo" validation during hemodialysis with constant or variable sodium.

A simple mathematical model of the intradialytic relationship between natraemia and dialysate sodium concentration is presented. The model includes a bicompartmental description of sodium, urea and fluid kinetics and an algebraic characterization of diffusive/convective mass-transfer across the dialysis membrane. Its ability to provide realistic responses has been validated comparing model predictions by a priori parameter tuning against quantities measured during in vivo sessions with both constant and variable dialysate sodium concentration. A quantitative analysis of model predictions indicates that the mean deviation between data calculated by the model and those measured in vivo is 1.32 mEq/l for sodium and 0.76 mmol/l for urea, values which do not greatly exceed the measurement errors of current instruments. The model's predictive capacity thus proves reliable. The ability of the model to calculate the amount of sodium removed and the time course of intra-extracellular volumes during the dialysis session makes it possible to forecast the patient's clinical tolerance to a given sodium dialysate concentration.

Posttraumatic chyluria due to lymphorenal fistula regressed after somatostatin therapy.

A sudden-onset chyluria after trauma was evaluated giving evidence of a lymphatic-urinary fistula in the right kidney. Treatment with somatostatin normalized the urinary pattern and the result was maintained even after the discontinuation of the therapy.

Alterations of exocrine pancreas in end-stage renal disease. Do they reflect a clinically relevant uremic pancreopathy?

Serum pancreatic enzyme behavior, exocrine function, and morphology of the pancreas were studied in 28 patients with end-stage renal disease undergoing regular hemodialysis, in order to better delineate and assess the clinical relevance of the pancreatic alterations that occur in these patients. Twenty-eight healthy subjects served as controls. Initial studies included serum amylase, isoamylase, and lipase assays; fecal chymotrypsin measurement; and abdominal ultrasonography. The amylase, lipase, and chymotrypsin determinations, as well as ultrasound examination, were repeated four years later. None of the patients had clinical evidence of pancreatic disease at entry into the study, but one had had previous attacks of pancreatitis and another developed mild acute pancreatitis one month after entry. Initial mean serum enzyme levels were significantly higher in patients than in controls (amylase, pancreatic isoamylase, and lipase, P < 0.001; salivary isoamylase P < 0.05). Serum amylase was raised in 16/28 patients; pancreatic isoamylase in 15/28, and lipase in 7/28; these elevations were generally mild. Mean fecal chymotrypsin was significantly lower (P < 0.001) in patients than in controls: abnormally low values were found in 9/28 patients. Amylase, lipase and chymotrypsin measurements repeated after four years showed no significant difference with respect to the first study. Ultrasonographic changes were rare and mild: one patient had a small cyst in the pancreas head, another, an increase in echogenicity of the gland not related to age; these findings were unchanged at repeat examination. The results demonstrate that the frequent elevations of serum pancreatic enzymes and the rare sonographic changes found in patients undergoing hemodialysis do not generally reflect a relevant pancreopathy. However, the finding of significantly decreased fecal chymotrypsin may indicate the presence of pancreatic dysfunction in end-stage renal disease.

Is Ace inhibitor treatment a possible cause of better cardiovascular remodelling in well functioning kidney transplant?

Diseases of the cardiovascular system are a common cause of death in renal transplanted patients. In this study we assessed the echocardiographic morphological and functional findings after renal transplantation of two homogenous groups of transplanted patients with normal renal function. The first (A) with spontaneously normotensive patients, the second (B) with moderate hypertension treated mainly with Ace inhibitors. Analysis of these data highlights two noteworthy results: the similar left ventricle hypertrophy found in both groups and the existence of better diastolic compliance among the hypertensive transplanted patients. If this is confirmed by studies currently in progress, the importance of Ace-inhibitors treatment in remodelling cardiac dysfunction after long term dialysis treatment might be seriously considered.