Abstract Background Advagraf, an extended release formulation of tacrolimus, is administered once daily during the morning fast. Tacrolimus can be safely converted from the twice daily formulation ...(Prograf) to the same dose (1 mg:1 mg) of once daily dosing tacrolimus (m-Tac). The adverse effects of tacrolimus play important roles in posttransplant cardiovascular risk factors (CVR): hyperglycemia, posttransplant diabetes mellitus, dyslipidemia and hypertension. It has been suggested that avoiding high tacrolimus peak levels minimizes its diabetogenic effects leading to better glycemic control. The aim of our study was to observe the effects of conversion to m-Tac therapy on graft function and CVR among stable transplant kidney recipients. Methods We selected 2 groups of 20 patients with stable kidney transplantation, who had been treated with Prograf for >6 months with a triple regimen. Group 1 were converted to once daily tacrolimus at the same dose (1 mg:1 mg); whereas in group 2, the therapy was maintained as a twice daily regimen. Blood pressure, creatinine and glomerular filtration rate levels evaluated by the Modification of Diet in Renal Disease formula, as well as urea, total, high- and low-density lipoprotein remained stable between the 2 groups as well as inside group 1 before and after conversion. Results After conversion, glycemia and triglyceride values showed significant reductions in group 1 and between the 2 groups. These results were significant, as they may be associated with better long-term graft and patient survivals.
Abstract Background Chronic renal dysfunction is present in about one quarter of kidney transplant patients at 1 year and in about 90% by 10 years. Nephrotoxicity caused by calcineurin inhibitors is ...among the most common factors. Elevated tacrolimus levels have been correlated with worse control of side effects including acute and/or chronic nephrotoxicity. The aim of this study was to observe the effects on graft function of conversion from the twice daily to the once daily extended release tacrolimus formulation in stable kidney transplant recipients within 5 years of grafting. Methods Thirty-one stable kidney transplant patients were converted at the same dosage (1 mg:1 mg). Patients served as their own controls based on results before versus after conversion. Results The trough levels of tacrolimus showed a slight albeit significant reduction after the conversion. Serum creatinine and glomerular filtration rate showed a significant improvement without an association with the tacrolimus trough levels. Conclusion We suggest that the immunosuppression with once daily tacrolimus may be a good option for kidney transplant patients.
Abstract Renal dysfunction in cirrhotic patients is primary related to disturbances of circulatory function, triggered by portal hypertension with chronic intrarenal vasoconstriction and ...hypoperfusion. Pretransplant renal function is an important factor implicated in the development of acute renal failure (ARF) after liver transplantation (OLT), but other factors mostly related to liver function seem to influence the development of ARF. The Acute Dialysis Quality Initiative workgroup developed the RIFLE classification to define ARF. We sought to evaluate the incidence of ARF among patients undergoing OLT, to evaluate the association of ARF with pre-OLT renal and hepatic functions, and to evaluate the influence of ARF on chronic kidney disease (CKD) at 1 month post-OLT. Clinical, renal, hepatic function, and donor risk index data of 24 patients who underwent deceased donor OLT were collected before transplantation, in the perioperative period and in the first month post-OLT. ARF occurred in 37.5% of patients with 56% developing the R grade and 44% the I grade; no patient showed the F grade. An association was observed between ARF and a higher Model for End-Stage Liver Disease (MELD) score and between ARF and a reduced pre-OLT serum albumin. No association was noted between ARF and other pre-OLT parameters. In cirrhotic patients serum creatinine is a bias for renal function assessment and the Modification of Diet in Renal Disease formula overestimates GFR. Post-OLT CKD was present in 6.7% of patients without ARF and in 44.4% of patients with ARF. The R grade developed more frequently among patients with viral cirrhosis. The association of ARF with MELD and hypoalbuminemia may be the result of a close relationship between renal and hepatic functions among cirrhotic patients. Post-OLT CKD may be the result of unrecognized, preexisting CKD and/or the effects of not fully resolved acute damage to an injured kidney.
Objectives. To determine whether tumour necrosis factor (TNF)-α blockers may reduce carotid intima-media thickness (cIMT) in patients with active rheumatoid arthritis (RA) steadily responsive to such ...therapy.
Methods. From 287 consecutive RA patients attending our out-patient clinic and diagnosed on the basis of the American College of Rheumatology (ACR) criteria, 49 without traditional cardiovascular risk factors and meeting the requirements for TNF-α blockers therapy were selected. Among them, 39 actually started TNF-α blockers, but only 30, who reached at least a response on the ACR 20% improvement criteria at 14 weeks, maintained during the whole year of treatment, were finally considered (group A). The remaining 10/49, homogeneous for age, sex, traditional cardiovascular risk factors, socioeconomic status, disease activity and duration, who did not consent to TNF-α-blocker administration, were used as controls (group B). Disease activity score in 44 joints (DAS44), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were evaluated before starting the study, and 3, 6, 12 months thereafter; cIMT was measured by ultrasound before and 12 months thereafter only.
Results. Patients in group A showed a very significant cIMT reduction (P < 0.0001 and P < 0.0001, on the right and left side, respectively), preceded by an early and lasting significant decrease in DAS44, ESR and CRP. Moreover, a significant correlation was found between cIMT and DAS44 (r = 0.435, P < 0.05).
Conclusions. These results demonstrate that TNF-α blockade is associated with cIMT reduction in RA patients steadily responsive to therapy, probably by lowering inflammation.
Close monitoring of estimated glomerular filtration rate (eGFR) is important for early recognition of worsening renal function to prevent further deterioration. Safe conversion from twice-daily ...tacrolimus (TD-Tac) to once-daily tacrolimus (OD-Tac) has been reported, but the effects on eGFR are contrasting.
The aim of our study is to evaluate long-term stability of eGFR after 1:1 conversion from TD-Tac to OD-Tac and the effects on serum cytokine blood levels. Forty-six consecutive kidney transplant recipients treated with TD-Tac 3 to 5 years post-transplant, with stable renal function, were enrolled in the study (2009–2011). Clinical and biochemical parameters were evaluated for 12 months before conversion up to 6 years after conversion. The patients served as their own controls. A panel of cytokines was evaluated repeatedly during the first year after conversion. Mean values of eGFR were not different long-term after conversion (P = .11) compared with baseline, and the majority of patients remained stable on Kidney Disease: Improving Global Outcomes stage during the study period; eGFR was stable in 30.0% after 5 years, decreased > 1 mL/min/1.73 m2/y in 13.3%, and improved > 1 mL/min/1.73 m2/y in 56.7%. Cytokine levels and C-reactive protein did not show any significant deterioration. Metabolic parameters were stable during the 6 years of follow-up. OD-Tac therapy can preserve an effective immunosuppressive state together with a safe profile of eGFR.
•Long-term estimated glomerular filtration rate (eGFR) monitoring after twice-daily tacrolimus (Tac) to once-daily Tac conversion in kidney transplantation.•Cytokines panel including interleukin (IL) 2, IL-4, IL-6, IL-8, IL-10, interferon-γ, tumor necrosis factor -α, and C-reactive protein.•eGFR and Kidney Disease: Improving Global Outcomes stage stability after 6 years of follow-up post-conversion.•Stability of metabolic parameters over 6 years of follow-up.•Tac therapy: effective immunosuppressive state together with a safer profile of eGFR.
Abstract Hepatic function and renal failure are closely related among patients with end-stage liver disease (ESLD) due to splanchnic hemodynamic mechanisms that characterize advanced decompensated ...cirrhosis. Acute renal failure (ARF) is a frequent complication that occurs immediately post–orthotopic liver transplantation (OLT). The Model for End-stage Liver Disease (MELD) score describes the survival of patients with ESLD awaiting OLT related to the severity of liver disease. The Simplified Acute Physiology Score (SAPS II) is a mortality prediction model that scores the severity of illness among intensive care unit patients. In a previous study we observed an association between ARF post-OLT and a higher MELD score, but it was not clear whether this association depends on the grade of ESLD or on the critical condition of liver transplant patients. The aim of this study was to evaluate the association of ARF with MELD score and/or SAPS II criteria among liver transplant patients. We analyzed 46 patients with ESLD who underwent deceased donor OLT. All patients were evaluated at baseline and in the first 7 days post-OLT. According to the RIFLE classification, the incidence of the worst grade of ARF post-OLT was 19.2%. These patients showed significantly higher MELD scores, while there was no association with systemic parameters related to the critical patient's condition or with the mortality score as evaluated by SAPS II criteria. We confirmed the association between renal failure and hepatic function among liver transplant patients. A more severe degree of hepatic dysfunction before OLT was associated with a greater incidence of ARF that can adversely affect patient survival.
Abstract The aim of our study was to evaluate the occurrence of middle and long-term chronic renal failure (CRF) after orthotopic liver transplantation (OLT) in relation to acute renal failure (ARF). ...We prospectively monitored 75 patients, studying renal function on the basis of serum creatinine and glomerular filtration rate as estimated using the Modification of Diet in Renal Disease formula before as well as 1,6, and 12 months after OLT. The prevalence of ARF was 56% classified by the Acute Kidney injury Network criteria (52% stage 1, 29% stage 2, and 19% stage 3). The occurrences of CRF were 18.6% (11/59), 11.5% (6/52), and 14% (6/43) at 1, 6, and 12 months after OLT, respectively. The occurrence of CRF before OLT was 14.7%. We did not find any association between ARF and post-OLT CRF. The most relevant result of our study was the association between CRF at 6 and 12 months after transplantation with pre-OLT CRF on univariate and multivariate analysis. We suggest that evaluation of pre-OLT renal function should always be considered in the follow-up of liver transplant patients. Pre-OLT renal dysfunction must be recognized to be a risk factor for post-OLT CRF, representing important criterion to define specific therapeutic interventions to reduce patient morbidity and mortality.
Fabry's disease (FD) is a genetic disorder of lysosomal storage characterized by the intralysosomal accumulation of globotriaosylceramide (Gb3). This genetic mutation causes a total or partial ...deficit of the α-galactosidase (GAL) enzyme activity. FD has an incidence of 1:40000-60000 born alive. Its prevalence is higher in specific pathological conditions like chronic kidney disease (CKD). The aim of this study was to evaluate the FD prevalence in Italian renal replacement therapy (RRT) patients from Lazio region.
485 patients in RRT (hemodialysis, peritoneal dialysis, and kidney transplantation) were recruited. The screening test was performed on venous blood sample. The latter was analyzed using specific FD diagnostic kit, based on the analysis of dried blood spots on filter paper.
We found 3 cases of positivity to FD (1 female and 2 males). In addition, 1 male patient was identified with biochemical alteration indicative of GAL enzyme deficiency with a genetic variant of the GLA gene of unknown clinical significance. The FD prevalence in our population was 0.60% (1 case out 163), it rises to 0.80% (1 case out of 122) if the genetic variant of unknown clinical significance is considered. Comparing the three subpopulations, we observed a statistically significant difference in GAL activity in transplanted patients compared to dialysis patients (p<0.001).
Considering the presence of an enzyme replacement therapy able to modify FD clinical history, it is essential to try to implement FD early diagnoses. However, the screening is too expensive to be extended on large scale, due to the low prevalence of the pathology. The screening should be performed on high-risk populations.
Abstract Chronic renal failure and acute renal failure (CRF and ARF) are common complications after orthotopic liver transplantation (OLT) that adversely affect patient survival. Many factors ...influence the development of ARF in the OLT setting. In a previous study we reported an association between ARF and the development of CRF at 1 month after OLT. The aims of our study were to evaluate the influence of ARF on short-, middle-, and long-term renal function after OLT and its influence on 1-year survival of patients and grafts. Fourty-four patients who underwent deceased donor OLT between August 2008 and August 2010 were evaluated pretransplantation, in the perioperative period, and at 1, 6, and 12 months posttransplantation. ARF was associated with CRF at 1 month post-OLT, whereas no association was observed at 6 and 12 months post-OLT. The development of CRF at 6 months post-OLT was associated with pre-OLT renal dysfunction and 1 month post-OLT CRF. Four patients died in the ARF group, whereas 3 patients died in the group without ARF. We confirmed ARF to be a predictive event for short-term renal dysfunction. The majority of patients recovered renal function after the first month. Although many pre-, peri-, and post-OLT factors may contribute to the development of posttransplantation CRF, pre-OLT CRF seemed to be the most important risk factor.
Abstract The development of early acute renal dysfunction (eARD) occurring in the first week after orthotopic liver transplantation (OLT) is mainly influenced by more severe degrees of pre-OLT ...hepatic insufficiency and liver graft dysfunction. The aim of our study was to evaluate the incidence of eARD post-OLT as well as its association with pre- and post-OLT hepatic dysfunction. We selected 54 end-stage liver disease patients who underwent OLT from 2008 to 2011. The prevalence of eARD was 53.7% (29/54) classified according to AKIN criteria in ARD-Risk (55.2%), ARD-Injury (27.6%) and ARD-Failure (17.2%). The worst stage of post-OLT eARD (eARD-Failure) seems to be influenced by the poor pre-OLT hepatic function as well as by early suboptimal recovery of graft function.
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