Biomedical subjects

Dario Cattaneo

Publications and source records attributed to Dario Cattaneo.

22 records · Page 2Linked to original sources

PubMed2002

Glucocorticoids interfere with mycophenolate mofetil bioavailability in kidney transplantation.

BACKGROUND: Steroids have been shown to induce the hepatic glucuronyltransferase (GT) expression enhancing the activity of uridine diphosphate-GT, the enzyme responsible for mycophenolic acid (MPA) metabolism. The impact of steroids on MPA pharmacokinetics, however, has not been investigated to date. METHODS: As a part of a steroid-sparing clinical trial, we studied the effect of steroids on MPA bioavailability in 26 kidney transplant recipients. RESULTS: Despite that the MMF dose did not change significantly with time, dose-normalized MPA AUC0-12h was lower during the first month (triple therapy, high doses of steroids) than at month 6 post-surgery (triple therapy, low maintenance dose of steroids (32.94 +/- 10.98 vs. 50.87 +/- 22.37 microg/mL. h; P < 0.01). During the steroid tapering and withdrawal phase (from month 6 to 21 post-Tx), plasma MPA trough and peak concentration as well as AUC0-12h progressively increased, while plasma MPA clearance and MPAG (the major MPA metabolite) trough levels declined. Renal function was stable throughout. Since cyclosporine A (CsA) may interfere with MPA pharmacokinetics, MPA and CsA also were measured in an additional control group of 12 kidney transplant patients at month 21 post-Tx who were still on triple therapy (MMF, CsA and steroids). Despite a similar CsA exposure, the control group had a significantly lower MPA AUC0-12h and higher MPAG trough concentration than patients on dual therapy at month 21 post-Tx. CONCLUSION: These findings indicate that steroids interfere with MPA bioavailability, and that discontinuation of the drug results in higher MPA exposure, which may compensate at least in part for the lower immunosuppressive level achieved with the remaining dual therapy with CsA and MMF.

Creatinine↗

PubMed2002

Effect of acetate-free biofiltration and bicarbonate hemodialysis on neutrophil activation.

BACKGROUND: Activation of polymorphonuclear neutrophils (PMNs) and monocytes has been described during hemodialysis (HD), which results in the release of reactive oxygen species and cytokines. Acetate-free biofiltration (AFB) has been shown to cause less monocyte activation and cytokine release than bicarbonate HD (BHD). No data are available to date on the effect of AFB on PMN activation. METHODS: We studied ex vivo superoxide anion release by PMNs isolated from nine patients treated in random order with AFB or BHD (three sessions each). Plasma interleukin-1beta (IL-1beta) levels and the nitric oxide (NO) synthetic pathway also were evaluated. A polyacrylonitrile (AN69; Hospal, Bologna, Italy) dialyzer was used for both treatments. Fourteen healthy volunteers were used as controls. Blood samples were drawn predialysis and 5 and 15 minutes after starting dialysis to obtain plasma and PMNs. RESULTS: Neither ex vivo superoxide anion release nor blood PMN count was affected by AFB. Conversely, a peak in superoxide anion production associated with a decrease in PMN count was observed at 5 minutes during BHD. Results of superoxide anion production by control PMNs exposed in vitro to AFB or bicarbonate dialysis bath or Hank's balanced salt solution supplemented with bicarbonate or acetate indicated that BHD-induced PMN activation could be attributed to the amount of bicarbonate present in the dialysis bath. IL-1beta plasma levels did not change during dialysis with AFB and were numerically higher at 5 and 15 minutes with respect to predialysis values during BHD. Uremic plasma obtained during either AFB or BHD induced greater NO synthesis by human umbilical vein endothelial cells than control plasma. CONCLUSION: AFB, unlike BHD, does not cause PMN and monocyte activation, which could have a positive impact on dialysis-associated cardiovascular disease of dialyzed patients.

Aged↗

PubMed2002

How to fully protect the kidney in a severe model of progressive nephropathy: a multidrug approach.

The current therapy for chronic proteinuric nephropathies is angiotensin-converting enzyme inhibitors (ACEi), which slow, but may not halt, the progression of disease, and which may be not effective to the same degree in all patients. In accelerated passive Heymann nephritis (PHN), this study assessed the effect of combining ACEi with angiotensin II receptor antagonist (AIIRA) and with statin that, besides lowering cholesterol, influences inflammatory and fibrogenic processes. Uninephrectomized PHN rats were divided into four groups (n = 10 each) and daily given oral doses of the following: vehicle; 40 mg/L lisinopril; 100 mg/L lisinopril plus L-158,809; 0.3 mg/kg lisinopril plus L-158,809 plus cerivastatin. Treatments started at 2 mo when rats had massive proteinuria and signs of renal injury and lasted until 10 mo. Increases in BP were equally lowered by treatments. ACEi kept proteinuria at levels comparable to pretreatment and numerically lower than vehicle. The addition of AIIRA to lisinopril was more effective, being proteinuria reduced below pretreatment values and significantly lower than vehicle. When cerivastatin was added on top of ACE inhibition and AIIR blockade, urinary protein regressed to normal values and renal failure was prevented. Renal ACE activity was increased threefold in PHN, it was inhibited by more than 60% after ACEi, and decreased below control values with triple therapy. Cerivastatin inhibited ACE activity by 30%. Glomerulosclerosis, tubular damage and interstitial inflammation were ameliorated by ACEi alone or combined with AIIRA, and prevented by addition of statin. TGF-beta(1) mRNA upregulation in PHN kidney was partially reduced after ACEi or combined with AIIRA and almost normalized after adding statin. Cerivastatin inhibited TGF-beta(1) gene upregulation by 25%. These data suggest a possible future strategy to induce remission of proteinuria, lessen renal injury, and protect from loss of function in those patients who do not fully respond to ACEi therapy.

Angiotensin Receptor Antagonists↗

PubMedDate not supplied

Delayed graft function in kidney transplantation.

Delayed graft function is a form of acute renal failure resulting in post-transplantation oliguria, increased allograft immunogenicity and risk of acute rejection episodes, and decreased long-term survival. Factors related to the donor and prerenal, renal, or postrenal transplant factors related to the recipient can contribute to this condition. From experimental studies, we have learnt that both ischaemia and reinstitution of blood flow in ischaemically damaged kidneys after hypothermic preservation activate a complex sequence of events that sustain renal injury and play a pivotal part in the development of delayed graft function. Elucidation of the pathophysiology of renal ischaemia and reperfusion injury has contributed to the development of strategies to decrease the rate of delayed graft function, focusing on donor management, organ procurement and preservation techniques, recipient fluid management, and pharmacological agents (vasodilators, antioxidants, anti-inflammatory agents). Several new drugs show promise in animal studies in preventing or ameliorating ischaemia-reperfusion injury and possibly delayed graft function, but definitive clinical trials are lacking. The goal of monotherapy for the prevention or treatment of is perhaps unattainable, and multidrug approaches or single drug targeting multiple signals will be the next step to reduce post-transplantation injury and delayed graft function.

Animals↗