Post-dilution hemodiafiltration with a heparin-grafted polyacrylonitrile membrane.

The aim of this multicenter, prospective study was to explore the possibility of carrying out routine sessions of post-dilution hemodiafiltration with a polyacrylonitrile membrane grafted with heparin (HeprAN) and reduced anticoagulation. Forty-four patients from eight centers were included in the study and treated by means of post-dilution on-line hemodiafiltration with automatic control of TMP, according to three different modalities tested consecutively: phase 1, polyethersulfone filter primed with heparinized saline and anticoagulated with continuous infusion of unfractionated heparin 1000/h; phase 2, HeprAN membrane filter primed with saline without heparin. Anticoagulation: a 1000-unit bolus of unfractionated heparin at the start of session followed by a second one at the end of the second dialysis hour; phase 3, same filter and priming procedure as in phase 2; anticoagulation with nadroparin calcium at the beginning of treatment. Partial or massive clotting of the dialyzer occurred in less than 1% of sessions in phase 1; 10% and 7% in phase 2; and 1% and 2% in phase 3. Clotting limited to the drip chambers was observed in 13%, 34% and 12%, respectively. The study of coagulation parameters showed a better profile when low-molecular weight heparin (LMWH) was used in association with HeprAN membrane, while the generation of TAT complexes did not differ from that observed with the standard anticoagulation modality used in phase 1. Our results suggest that the HeprAN membrane can be used safely in routine post-dilution hemodiafiltration with reduced doses of LMWH.

Effect of a plasma sodium biofeedback system applied to HFR on the intradialytic cardiovascular stability. Results from a randomized controlled study.

BACKGROUND: Intradialytic hypotension (IDH) is still a major clinical problem for haemodialysis (HD) patients. Haemodiafiltration (HDF) has been shown to be able to reduce the incidence of IDH. METHODS: Fifty patients were enrolled in a prospective, randomized, crossover international study focussed on a variant of traditional HDF, haemofiltration with endogenous reinfusion (HFR). After a 1-month run-in period on HFR, the patients were randomized to two treatments of 2 months duration: HFR (Period A) or HFR-Aequilibrium (Period B), followed by a 1-month HFR wash-out period and then switched to the other treatment. HFR-Aequilibrium (HFR-Aeq) is an evolution of the haemofiltration with endogenous reinfusion (HFR) dialysis therapy, with dialysate sodium concentration and ultrafiltration rate profiles elaborated by an automated procedure. The primary end point was the frequency of IDH. RESULTS: Symptomatic hypotension episodes were significantly lower on HFR-Aeq versus HFR (23 ± 3 versus 31 ± 4% of sessions, respectively, P l= l0.03), as was the per cent of clinical interventions (17 ± 3% of sessions with almost one intervention on HFR-Aeq versus 22 ± 2% on HFR, P <0.01). In a post-hoc analysis, the effect of HFR-Aeq was greater on more unstable patients (35 ± 3% of sessions with hypotension on HFR-Aeq versus 71 ± 3% on HFR, P <0.001). No clinical or biochemical signs of Na/water overload were registered during the treatment with HFR-Aeq. CONCLUSIONS: HFR-Aeq, a profiled dialysis supported by the Natrium sensor for the pre-dialysis Na(+) measure, can significantly reduce the burden of IDH. This could have an important impact in every day dialysis practice.

[Prevention of chronic allograft nephropathy]. / Prevenzione della nefropatia cronica del rene trapiantato.

Chronic allograft nephropathy, characterized by interstitial fibrosis and tubular atrophy, is one of the main causes of allograft failure in the long term. It may be induced by several factors, immunogical or not in nature, which nephrologists must recognize in order to establish the appropriate treatment strategy and prevent progressive loss of graft function. Extensive use of graft biopsy, whether carried out by protocol or suggested by the clinical setting, is recommended for an accurate diagnosis of renal lesions and prompt identification of calcineurin inhibitor-induced toxicity or signs of immunological activity (i.e., subclinical rejection or chronic antibody-mediated rejection) requiring changes of immunosuppressive strategy.

[Kidney transplant: a mere stage of CKD?]. / Il trapianto è uno stato di malattia renale?

At present, renal transplantation is the best treatment for end-stage renal disease but not the cure. The main factors limiting a full recovery after transplantation include the need for lifelong immunosuppressive therapy (which may lead to severe side effects in the long term), and only partial recovery of renal function after grafting. The latter event is not infrequent nowadays due to the increasing age of donors, who frequently die of cerebrovascular accidents and may have subclinical renal vascular lesions despite a GFR >60 mL/min, with increased susceptibility to calcineurin inhibitor toxicity. As a consequence, uremic alterations such as anemia, arterial hypertension and bone disease may persist at various degrees after surgery and affect the patients' outcome in the long term. The outcome of renal transplantation may be improved if, in addition to accurate tuning of immunosuppressive regimens, we take into account the prevention and treatment of all conditions that may impair the clinical course of transplant recipients.

Removal of linezolid by conventional intermittent hemodialysis, sustained low-efficiency dialysis, or continuous venovenous hemofiltration in patients with acute renal failure.

OBJECTIVE: To study the removal of linezolid, a new oxazolidinone antibiotic, by renal replacement therapy in patients with acute renal failure. DESIGN: Prospective, single-dose pharmacokinetic study. SETTING: Renal intensive care unit of a tertiary university hospital. PATIENTS: Fifteen critically ill patients with oliguric acute renal failure on renal replacement therapy (seven males, mean age 72.3 yrs, range 60-94; Acute Physiology and Chronic Health Evaluation II score 24.9, range 18-36; mechanical ventilation ten of 15). INTERVENTIONS: All patients received 600 mg of intravenous linezolid before starting renal replacement therapy, which consisted of intermittent hemodialysis lasting 3-4 hrs in eight patients, sustained low-efficiency dialysis lasting 8 hrs in five patients, and continuous venovenous hemofiltration lasting 10.5-12 hrs in two patients. MEASUREMENTS AND MAIN RESULTS: Linezolid concentrations were measured by liquid chromatography/mass spectrometry methods on serum and dialysate/ultrafiltrate samples. At the start of renal replacement therapy, serum levels averaged 11.91 mg/L (range 5.49-21.52) and dropped at the end to levels <4 mg/dL (90% minimum inhibitory concentration values for Staphylococcus aureus) in three of eight patients on hemodialysis, three of five patients on sustained low-efficiency dialysis, and two of two patients on continuous venovenous hemofiltration. Mean removal of the drug was 193.7 mg with hemodialysis (32.3% of the dose administered), 205 mg with sustained low-efficiency dialysis (33.9%), and 74.8 mg (12.4%) and 105 (17.5%) mg following a continuous venovenous hemofiltration session lasting 10.5 and 12 hrs, respectively. CONCLUSIONS: In patients with acute renal failure, serum levels of linezolid can be reduced to the subtherapeutic range following renal replacement therapy.

Plasma and urinary free 3-nitrotyrosine following cardiac angiography procedures with non-ionic radiocontrast media.

BACKGROUND: Radiocontrast media (RCM) administration is a common cause of hospital-acquired acute renal failure, especially in high-risk patients, but mechanisms of nephrotoxicity have not been fully elucidated. Reactive oxidant species recently have been shown to play a role in experimental RCM nephropathy, while there is clinical evidence that acetylcysteine, an antioxidant drug, has a protective effect against RCM nephropathy in humans. However, no study has been published showing that RCM administration elicits oxidative stress in humans. METHODS: In an unselected series of patients undergoing elective cardiac catheterization for coronary artery angiography and/or angioplasty, we monitored the time course of plasma and urinary levels of free 3-nitrotyrosine (3-NT), a stable marker of peroxynitrite generation resulting from the in vivo reaction of superoxide and nitric oxide. Urinary 3-NT levels were measured as the ratio of urinary 3-NT to urinary creatinine. Measurements were taken at baseline, immediately after the procedure and at 24, 48 and 72 h. RESULTS: Twenty-six patients were studied (median age 67.5 years, range 42-86; baseline serum creatinine 1.0 mg/dl, 0.6-1.5; RCM dose 215 ml, 100-580). Plasma 3-NT levels slightly increased over the 72 h following the procedure (P<0.001), while urinary 3-NT levels peaked at the end of the procedure (P<0.001). Urinary 3-NT levels reached at the end of the procedure were proportional to the RCM dose administered (P = 0.017). CONCLUSIONS: The present study provides indirect evidence that RCM administration in humans is associated with an increased production of 3-NT. Further studies are needed to ascertain whether oxygen- and nitrogen-derived radical species play a major role in the pathogenesis of RCM-associated nephrotoxicity in the clinical setting.

Enteral nutrition in patients with acute renal failure.

BACKGROUND: Systematic studies on safety and efficacy of enteral nutrition in patients with acute renal failure (ARF) are lacking. METHODS: We studied enteral nutrition-related complications and adequacy of nutrient administration during 2525 days of artificial nutrition in 247 consecutive patients fed exclusively by the enteral route: 65 had normal renal function, 68 had ARF not requiring renal replacement therapy, and 114 required renal replacement therapy. RESULTS: No difference was found in gastrointestinal or mechanical complications between ARF patients and patients with normal renal function, except for high gastric residual volumes, which occurred in 3.1% of patients with normal renal function, 7.3% of patients with ARF not requiring renal replacement therapy, 13.2% of patients with ARF on renal replacement therapy (P= 0.02 for trend), and for nasogastric tube obstruction: 0.0%, 5.9%, 14%, respectively (P < 0.001). Gastrointestinal complications were the most frequent cause of suboptimal delivery; the ratio of administered to prescribed daily volume was well above 90% in all the three groups. Definitive withdrawal of enteral nutrition due to complications was documented in 6.1%, 13.2%. and 14.9% of patients, respectively (P= 0.09 for trend). At regimen, mean delivered nonprotein calories were 19.8 kcal/kg (SD 4.6), 22.6 kcal/kg (8.4), 23.4 kcal/kg (6.5); protein intake was 0.92 g/kg (0.21), 0.87 g/kg (0.25), and 0.92 g/kg (0.21), the latter value being below that currently recommended for ARF patients on renal replacement therapy. Median fluid intake with enteral nutrition was 1440 mL (range 720 to 1960), 1200 (720 to 2400), and 960 (360 to 1920). CONCLUSION: Enteral nutrition is a safe and effective nutritional technique to deliver artificial nutrition in ARF patients. Parenteral amino acid supplementation may be required, especially in patients with ARF needing renal replacement therapy.