Experience of 70-cm-long femoral tunnelled twin Tesio catheters for chronic haemodialysis.

BACKGROUND: Tunnelled femoral catheters with their tip in the lower inferior vena cava (IVC) are proposed only in few cases, but they often provide less than optimal blood flows and frequently have complications. The aim of this prospective observational study is to evaluate the use of 70-cm-long tunnelled cuffed femoral twin Tesio catheters with their tip in the upper IVC for haemodialysis. METHODS: Between May 2007 and May 2009, 25 tunnelled femoral catheters (fCVC) have been placed in 25 patients (77.7 +/- 10.8 years) with exhausted thoracic venous accesses or old patients with several comorbidities. Two 10 Fr carbothane 70-cm-long Tesio catheters with a Dacron cuff at 45 cm from the tip were placed in the femoral vein of each patient and then tunnelled; tips were in the upper third of the IVC. fCVCs were removed for either malfunction (Qb < 200 ml/min) or infection that did not resolve with antibiotics. RESULTS: Technical success of placement was 100%. The 6- and 12-month assisted primary patency rate were respectively 67 +/- 13% and 54 +/- 17%. The mean session Kt/V was 1.45 +/- 0.19, and the blood flow was 270 +/- 17 ml/min. Six fCVCs have been removed: three for infection, one for accidental damaging and two for the making of a different vascular access. The main complications were 2 catheter tip thrombi, 3 tunnel infections and 11 fCVC-related bacteraemia (1.77 episodes per 1000 CVC-days). CONCLUSION: The placement of twin fCVCs with their tip in the high IVC can provide an adequate dialysis and can be considered for patients with no remaining thoracic accesses.

Reduced coronary flow reserve in young adults with renal transplant.

BACKGROUND: Some degree of cardiovascular disease should be suspected in young adults who have been paediatric renal transplant recipients also if no systematic data collection is routinely performed in clinical setting. The aim of our work was to evaluate the degree of cardiovascular damage in these young patients, using a minimally invasive technique. We then evaluated coronary flow reserve (CFR) and carotid intima-media thickness (IMT) in 25 patients (13 males, median age 23.7 years). METHODS: Coronary flow velocity on the left anterior descending coronary artery was assessed by transthoracic echocardiography, before and after dipyridamole, after standard echocardiography. CFR was compared with that of a small control group (n = 16; median age 25 yrs). RESULTS: In this relatively young sample, mean CFR was 2.8 +/- 0.6 (median 2.75), and half of the patients had reduced coronary reserve (P = 0.01). Mean IMT (0.48 +/- 0.08 mm) was only slightly, though significantly larger compared with the reference standard (P < 0.05) but was significantly thinner in normotensive than in hypertensive patients (0.42 +/- 0.06 vs 0.49 +/- 0.05 mm, P < 0.05). The time on dialysis prior to transplantation, hypertension and age at the time of CFR evaluation affect CFR. IMT did not correlate with CFR. CONCLUSIONS: CFR and IMT abnormalities are common in young transplant recipients, in spite of the fact that our paediatric population has much less of the atherosclerotic 'legacy' common to adult patients.

Mechanisms of disease: The role of aldosterone in kidney damage and clinical benefits of its blockade.

In the past 10 years, many widely accepted concepts relating to aldosterone production and its pathogenetic role have changed. We now know that aldosterone is produced not only by the zona glomerulosa of the adrenal cortex, but also in the heart, blood vessels, kidney and brain; such extra-epithelial production occurs mainly during tissue repair. Also, increased aldosterone levels contribute to vessel inflammation, oxidative stress, endothelial dysfunction and organ damage. As such, aldosterone has a key role in the development of myocardial fibrosis. Anti-aldosterone treatment has proven effective in patients with heart failure. Experimental evidence regarding the role of aldosterone in kidney damage has accumulated. Aldosterone infusion can counteract the beneficial effects of treatment with angiotensin-converting-enzyme inhibitors, causing more-severe proteinuria and an increased number of vascular and glomerular lesions; treatment with aldosterone antagonists can reverse these alterations. Preliminary observations in pilot studies in humans confirm the experimental findings, supporting the hypothesis that aldosterone antagonists are renoprotective in clinical practice. Studies in larger populations with longer follow-up are needed to confirm this theory.

Home peritoneal ultrafiltration in patients with severe congestive heart failure without end-stage renal disease.

Congestive heart failure (CHF), mainly because of ischemic heart disease, is becoming a common medical problem. As CHF worsens and reaches New York Heart Association (NYHA) class IV, many patients can become refractory to medical therapy, especially those who are elderly or who have pre-existing non uremic chronic renal failure. For such patients, quality of life, morbidity, and mortality are expected to be bad. Our objective in the present study was to make a preliminary assessment of the usefulness of icodextrin administered in a single nocturnal peritoneal exchange to patients nonrespondent to the maximal conventional medical therapy. We studied two patients (aged 80 and 87 years), who were affected by severe dilatative cardiomyopathy and moderate-to-severe chronic renal failure. After at least 12 months of treatment, we observed a significant improvement in quality of life and a reduction in morbidity and hospitalization in both patients. Both patients also significantly increased their creatinine clearance. One patient maintained ejection fraction stability (22%-->27%); the other experienced an increase in ejection fraction to 50%from 25%. These preliminary observations suggest that a single nocturnal exchange with icodextrin can be an effective treatment in patients affected by refractory CHF and moderate-to-severe chronic renal failure.

Proteinuria as a predictor of disease progression in children with hypodysplastic nephropathy. Data from the Ital Kid Project.

Little is known about the role of proteinuria in the progression of childhood renal diseases. We analyzed the decline in creatinine clearance ( C(Cr)) and kidney survival in 225 children (185 males) with chronic renal failure (CRF) due to isolated hypodysplasia or hypodysplasia associated with urological abnormalities. The data were based on the information available in the Italian Pediatric Registry of CRF (ItalKid Project), which includes patients from all of Italy aged <20 years with C(Cr )levels of <75 ml/min per 1.73 m(2). Patients aged <2 years and those with C(Cr )levels of <20 ml/min per 1.73 m(2) or a follow-up of <1 year were excluded from the analysis, as were those receiving angiotensin-converting enzyme inhibitors. At baseline, the patients had a mean age of 7.8+/-4.2 years, a mean C(Cr )of 50+/-16.3 ml/min per 1.73 m(2), a median urinary protein/urinary creatinine (uPr/uCr) ratio of 0.38 (range 0.02-7.21), and a mean duration of follow-up of 3.5+/-1.1 years. The patients were divided into three groups on the basis of their baseline proteinuria levels: group A normal (uPr/uCr <0.2) n=83; group B low (uPr/uCr 0.2-0.9) n=71; and group C mild (uPr/uCr >0.9) n=71. Patients in groups A and B showed a significantly slower decline in C(Cr )than those in group C (slope +0.16+/-3.64 and -0.54+/-3.67 vs. -3.61+/-5.47, P<0.0001) and a higher rate of kidney survival after 5 years (96.7% and 94.1% vs. 44.9%, P<0.01). By multivariate analysis, the baseline uPr/uCr ratio ( P<0.01) and age ( P<0.0001) correlated with a faster decline in C(Cr )irrespective of baseline C(Cr). There was no correlation with mean arterial blood pressure. We conclude that proteinuria is an independent predictor of progression to end-stage renal failure also in children whose renal impairment is due to congenital hypodysplasia.

Identification of fifteen novel mutations in the SLC12A3 gene encoding the Na-Cl Co-transporter in Italian patients with Gitelman syndrome.

The SLC12A3 gene encodes the thiazide-sensitive Na-Cl co-transporter (NCCT) expressed in the apical membrane of the distal convoluted tubule of the kidney. Inactivating mutations of this gene are responsible for Gitelman syndrome (GS), a disorder inherited as an autosomal recessive trait. We searched for SLC12A3 gene mutations in 21 Italian patients with the clinical and biochemical features of GS (hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria, and the absence of nephrocalcinosis). All coding regions with their intron-exon boundaries were analyzed using PCR and SSCP techniques followed by sequencing analysis. We identified 21 different mutations evenly distributed throughout the gene without any mutation hot-spot. Fifteen are novel variants, including 12 missense mutations, one deletion, one deletion-insertion and one splice site mutation: R158Q, T163M, W172R, G316V, G374V, G463E, A464T, S615W, V677M, R852S, R958G, C985Y, 2114-2120delACCAAGT, 2144-2158delGCCTTCTACTCGGATinsTG, and 531-2A>G.

Nephrogenic diabetes insipidus: functional analysis of new AVPR2 mutations identified in Italian families.

The aim of this study was to identify loss-of-function mutations of the V2 vasopressin receptor gene (AVPR2) in Italian patients affected by X-linked nephrogenic diabetes insipidus (NDI). Mutations were found in 15 of the 18 unrelated families investigated: nine of these mutations were previously unknown, including two affecting residues located in regions known to be important for determining the pharmacologic properties of the receptor, which were therefore functionally investigated. The first (A84D) involves a residue located near an aspartic acid (D85) that is highly conserved in all G protein-coupled receptors and that is believed to play a role in the process of their isomerization into functionally active and inactive states. The present study indicates that this mutation not only affects receptor folding in such a way as to lead to its retention inside the intracellular compartments but, as expected, also has profound effects on its binding and coupling properties. The second was a mutation of a tryptophan located at the beginning of the first extracellular loop (W99R) that greatly impaired the binding properties of the receptor and had a minor effect on its intracellular routing. Molecular analysis of the first extracellular loop bearing this mutation suggests that this residue plays a fundamental role in stabilizing the peptide/receptor interactions responsible for the high-affinity binding of agonists to the V2 receptor.