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Biomedical subjects

J C Ruiz

Publications and source records attributed to J C Ruiz.

At least 19 recordsLinked to original sources
PubMed2006

Relevance of chronic kidney disease classification (K/DOQI) in renal transplant patients.

The National Kidney Foundation has developed guidelines for diagnosis and classification of chronic kidney disease (CKD) but it is not known whether they are applicable to renal transplant patients. This study analyzed the prevalence, the complications, and the influence of the CKD stage on the presence of complications in 506 stable transplant recipients. The mean age of the patients was 52.9 +/- 12 years, 34% were men, and the mean time after transplantation was 9.56 +/- 6.18 years. CKD was present in 90.3% with 9.9% were in CKD stages 4 or 5 with glomerular filtration rates lower than 30 mL/min per 1.73 m(2). The prevalence of anemia, phospho-calcium metabolism disorders, hypertriglyceridemia, and hypertension increased with the stage of CKD. We concluded that CKD and the complications of CKD were highly prevalent in renal transplant recipients. The classification of renal transplant patients by CKD stage may help clinicians to identify patients at increased risk and to target appropriate therapy to improve outcomes.

Adult↗
PubMed2006

Calcineurin inhibitors affect circulating regulatory T cells in stable renal transplant recipients.

INTRODUCTION: Immunosuppression, although crucial for short-term management, has been described in renal transplantation to be a major hurdle for long-term graft survival. Efforts have been directed at achieving a true state of allotolerance, thereby reducing the load of immunosuppression. Recently, increased frequencies of CD4(+)CD25(high) regulatory T cells (Tregs) have been described as an additional mechanism to induce alloimmune tolerance. MATERIALS AND METHODS: We assessed 64 renal transplant recipients with stable renal function for at least 1 year, divided into two groups: one composed of patients receiving rapamycin but not calcineurin inhibitors (CNIs), and another, of those receiving CNIs but not rapamycin. RESULTS: We demonstrated that T cells with a regulatory phenotype were decreased in peripheral blood of renal transplant recipients under CNI therapy compared to those who were CNI-free. The Tregs in our patients showed a modest association with renal function as measured by the delta serum creatinine, which was not significant. CONCLUSIONS: CNIs, but not rapamycin, reduce the frequencies of circulating Tregs in renal transplant recipients. The use of rapamycin might be further exploited in strategies reducing immunosuppression in renal transplantation. Furthermore, quantification of blood Tregs may be a suitable tool to identify those recipients who are candidates for reducing immunosuppression.

Adult↗
PubMed2006

Conversion to everolimus in kidney transplant recipients: a safe and simple procedure.

To date there is a substantial experience with rapamycin conversion in stable renal transplant recipients with respect to the procedure of conversion, initial doses, and target blood levels as well as adverse events, but in the case of Everolimus there is almost no experience with conversion and calcineurin inhibitor (CNI) withdrawal. We describe an initial experience among 32 renal transplant recipients who were converted to Everolimus with complete suspension of CNI in two Spanish transplant centers. Our results emphasised the procedure for conversion, the target levels, the adverse events, and the initial efficacy, over the first month after conversion. Our conclusions were that conversion from CNI to Everolimus was a simple, safe procedure with a predictable profile of adverse events, which were, in general, of mild intensity. There was a good correlation between initial dose and blood level. Initial doses of about 3 mg/d combined with rapid reduction in CNI exposure seemed to be adequate. The target range levels between 5 and 10 ng/mL seemed to be sufficient for complete CNI elimination, especially in patients also receiving antiproliferative drugs (such as mycophenolate mofetil or azathioprine) in whom levels near the lower end of the range might be adequate.

Calcineurin Inhibitors↗
PubMed2006

Acute renal failure associated with use of inhaled tobramycin for treatment of chronic airway colonization with Pseudomonas aeruginosa.

Aminoglycoside nephrotoxicity is a well-known clinical entity that complicates the course of infectious diseases treated under this antibiotic regime. Recently, a new administration form of tobramycin, inhaled tobramycin (TOBI), has been approved to improve the antibacterial activity and reduce nephrotoxicity. We describe the clinical case of a 73-year-old woman with chronic-obstructive pulmonary disease (COPD) who developed acute renal failure (ARF) after using TOBI. Clinical presentation and biochemical parameters were compatible with aminoglycoside-induced renal failure. Based on the clinical findings presented here, a surveillance program should be established to monitor the presence of factors predisposing to renal failure, and to measure serum levels of tobramycin.

Acute Kidney Injury↗
PubMed2005

Change in serum creatinine levels between 6 and 12 months and kidney graft survival: influence of proteinuria.

Renal function within the first year after transplantation has been shown to be an important parameter influencing long-term survival. In this study, we examined the relationship between long-term outcome in 365 renal transplants and renal function in the first year, expressed as serum creatinine (SCr) level at 6 months and at 1 year as well as namely deltaCr, the change in SCr between 6 months and 1 year. In addition, we examined the influence of the presence of proteinuria as a predictive factor for a worse evolution. Graft survival was worse among patients with higher deltaCr, especially among those who developed proteinuria. In a Cox regression analysis of long-term graft survival, both deltaCr and proteinuria were important predictors of half-life. The risk of graft loss when deltaCr >0.3 was 2.65 (1.8-3.8; P < .000), whereas the risk increased to 5.67 (3.3-9.4; P < .00) when proteinuria was present. In conclusion, deltaCr values predict long-term graft survival. Patients who developed proteinuria were at higher risk for graft loss compared with those without proteinuria. By using a combination of SCr and deltaCr with proteinuria, it is possible to identify a subset of transplant recipients with a predictably shortened half-life.

Adult↗
PubMed2005

Markers of fibrosis in early biopsies of renal transplants.

Many factors are involved in the development of chronic allograft nephropathy (CAN). Extracellular matrix turnover depends on the balance between fibrogenic and antifibrogenic cytokines. The aim of our study was to analyze the presence of transforming growth factor beta-1 (TGF-beta1), matrix metalloproteinase-2 (MMP-2), and mast cells in 53 early transplant biopsies using immunochemistry with specific monoclonal antibodies. We divided the patients into two groups depending on graft evolution (lost due to CAN versus functioning), renal function, presence of proteinuria, and graft survival. There were no differences in the demographic or immunological data. Renal function was worse and proteinuria greater among the group with CAN. The presence of mast cells was similar in both groups, but TGF-beta1 was expressed more and MMP-2 less in the CAN group. We observed a negative correlation between donor age and mast cells, and a positive correlation between TGF-beta1 and MMP-2. Grafts from younger donors showed better renal function, less proteinuria, greater graft survival, and less frequent development of CAN. According to our experience, cytokines involved in matrix turnover are expressed in early stages, correlating with donor age. The expressions of TGF-beta1 and MMP-2 seem to be important for the development of fibrosis in CAN.

Adult↗
PubMed2005

Similar impact of slow and delayed graft function on renal allograft outcome and function.

Kidney transplant patients can be divided into three groups, according to the initial graft function. First-week dialyzed patients form the delayed graft function (DGF) group. Nondialyzed patients are divided into slow graft function (SGF) or immediate graft function (IGF) according to whether the day 5 serum creatinine was higher versus lower than 3 mg/dL, respectively. SGF patients showed worse graft survival, above higher incidence of acute rejection and lower renal function than IGF patients, although few reports have analyzed outcomes in these groups. We analyzed the impact of SGF on graft survival, first-year renal function, and incidence of acute rejection in 291 renal transplant patients. Creatinine was significantly worse at 12 months for SGF and DGF than for IGF patients (1.9 +/- 0.8 mg/dL, 1.8 +/- 0.7 mg/dL, 1.5 +/- 0.5 mg/dL, respectively; P < .05). There was no difference in first-year renal function between SGF and DGF. The acute rejection rate was higher among the SGF than the IGF group (45% vs 21%, P < .05), but not different from DGF patients (42%, P < .05). Graft survival was better among IGF than SGF or DGF patients, with no significant difference between the last two groups (3-year graft survival, 82%, 71%, 70%, respectively; log-rank test, P < .05). Kidney transplant recipients who develop SGF have a worse outcome than patients with IGF, similar to DGF patients. SGF patients show worse graft survival, worse renal function, and higher acute rejection rates than IGF patients, despite not needing dialysis.

Adult↗
PubMed2005

High initial blood levels of tacrolimus in overweight renal transplant recipients.

For the purpose of both efficacy and safety, exposure to tacrolimus and other immunosuppressive drugs must be monitored, since initial levels influence the development of acute rejection episodes, nephrotoxicity, and posttransplantation diabetes mellitus. The aim of this study was to identify risk factors for developing high initial tacrolimus blood levels. We analyzed clinical and biochemical parameters of 85 renal transplant recipients receiving tacrolimus-based immunosuppressive therapy by stratifying into subgroups of patients who displayed first tacrolimus concentrations higher and lower than 15 ng/mL. Patients with a first level of tacrolimus higher than 15 ng/mL were older (52 +/- 13 vs 40 +/- 12 years, P < .05) and had a larger body mass index (27 +/- 4 vs 23 +/- 3 kg/m2, P < .05) than patients with lower levels, despite receiving a lower weight-adjusted cumulative steroid dose (8.2 +/- 2.2 vs 9.3 +/- 2.5 mg/kg, P < .05). Upon logistic regression, age (RR 1.047, 95% CI 1.007 to 1.08, P = .021) and body mass index (RR 1.176, 95% CI 1.009 to 1.371, P = .036) remained significant risk factors for high initial blood levels of tacrolimus. As these subgroups of patients are most prone to develop posttransplantation glycemic disorders, attention must be paid to avoid high tacrolimus blood levels by diminishing initial tacrolimus doses or estimating them from ideal body weight.

Area Under Curve↗
PubMed2005

Evolution of proteinuria after conversion from calcineurin inhibitors (CNI) to sirolimus (SRL) in renal transplant patients: a multicenter study.

Conversion from calcineurin inhibitors (CNI) to sirolimus (SRL) has become an option in patients with chronic allograft nephropathy or other conditions. However, in some cases an increase of proteinuria has been reported after such therapeutic intervention. The aim of this study was to characterize the clinical course of this so far unexplained proteinuria after conversion. We performed a retrospective analysis evaluating 94 renal transplant patients from various Spanish centers. Proteinuria (629 determinations) and clinical developments were analyzed between 6 months before and 6 months after conversion. Patients were divided into three groups according to mean proteinuria before conversion (group A: <300 mg/d; group B: 300 to 2000 mg/d; and group C: >2 g/d). The mean proteinuria level was 1.69 g/24 h (n = 312 determinations) before and 2.36 g/24 h after conversion (n = 317 determinations; P = .006), which corresponds to an overall increase of 25% (1.55 to 1.69 g/24 h considering only determinations of 1 month before and 1 month after conversion; P = NS). We could not detect any clear correlation between proteinuria and serum creatinine nor between changes of proteinuria and changes of serum creatinine. A variance analysis for repeated measures showed an increase in proteinuria compared to the preconversion values (P = .003), and when the three groups of preconversion proteinuria were evaluated separately it could be observed that this change in the evolution of proteinuria was almost completely dependent of an increase in the group C (preconversion proteinuria greater than 2 g/d; P = .03), whereas in the other two groups changes were almost irrelevant. Finally, the switch to SRL in renal transplant recipients is followed by an increase in the level of proteinuria predominantly dependent of an increase in patients with high levels of preconversion proteinuria, whereas it seems to be irrelevant in patients without or with light or moderate proteinuria. These results suggest that this might not be a direct effect of SRL.

Calcineurin Inhibitors↗
PubMed2005

Higher initial tacrolimus blood levels and concentration-dose ratios in kidney transplant recipients who develop diabetes mellitus.

Posttransplantation diabetes mellitus (PTDM) is a common complication of kidney transplantation, associated with poorer graft and patient outcomes. Tacrolimus is a strong immunosuppressive drug associated with low acute rejection rates, but a higher risk for PTDM. High trough levels of tacrolimus during the first month after transplantation have been found to be a significant risk factor for the development of PTDM. The aim of this single-center study was to identify the risk factors for the development of PTDM among kidney transplant recipients under tacrolimus therapy. We examined 73 cadaveric kidney transplant recipients receiving tacrolimus between 1994 and 2003. Age, donor and recipient gender, dialysis method, body mass index (BMI), first year weight gain, mismatches, incidence of acute rejection and delayed graft function, hepatitis C serology, first year cumulative steroid dose, first tacrolimus blood level, first tacrolimus blood level <15 ng/mL, and corresponding tacrolimus daily doses and concentration/dose ratios (CDR) were also collected. PTDM was defined as at least 2 fasting blood glucose values > or =126 mg/dL, according to the World Health Organization criteria. Incidence of first year PTDM was 27.4%. Patients with PTDM showed significantly higher age, BMI, first tacrolimus blood level, first tacrolimus CDR, and CDR with tacrolimus blood level <15 ng/mL as well as less 1-year weight gain. After logistic regression, age (relative risk [RR] 1.060, confidence interval [CI] 95%, 1.001-1.122; P = .043) and first tacrolimus blood level (RR 1.154; CI 95%, 1.038-1.283; P = .008) remain significant risk factors for developing PTDM. Older age and initial tacrolimus blood levels were the main risk factors for PTDM among our group of patients. Kidney transplant recipients who develop PTDM maintain a high CDR of tacrolimus.

Adult↗
PubMed2005

Clinical significance of antiphospholipid antibodies on allograft and patient outcome after kidney transplantation.

INTRODUCTION: Antiphospholipid antibodies (APA) have acquired great relevance as atherogenic factors. Kidney graft recipients have a higher prevalence of cardiovascular disease (CVD) than the general population, which is not fully explained by the classical vascular risk factors. The aim of this study was to assess the influence of APA on kidney graft and patient outcomes with special focus on CVD. MATERIALS AND METHODS: One hundred ninety seven cadaveric kidney graft recipients with functioning grafts for more than 1 year underwent determination of serum APA titres (anti-cardiolipin and anti-beta-2 glycoprotein I IgG and IgM antibodies) in one pretransplant serum and in second one obtained at least 1 year after transplantation. In the case of postransplant CVD, the postransplant serum was always chosen before the cardiovascular event. The enzyme linked immunosorbent assay (ELISA) for anti-cardiolipin antibodies was performed in the presence of cofactor. RESULTS: Twenty-seven percent of patients had pretransplant APA, whereas 15.7% developed postransplant APA de novo. The presence of pretransplant serum APA was not associated with a higher risk of postransplant CVD. The development of postransplant APA de novo showed a relationship to an acute rejection episode (ARE): the frequency of patients who had APA de novo was higher among patients who suffered ARE (18.8% vs 7%, P = .01). In addition, in patients who suffered any ARE, the production of postransplant APA was associated with a higher frequency of postransplant CVD. CONCLUSIONS: The detection of APA is not an independent risk factor for CVD after kidney transplantation. The inflammatory phenomena secondary to an ARE may be responsible for the de novo production of postransplant APA, which may be associated with the development of postransplant CVD. The control of cardiovascular risk factors should be intensified in this special group of patients.

Antibodies, Antiphospholipid↗
PubMed2005

Prevalence of anemia in renal transplant patients: results from MOST, an observational trial.

INTRODUCTION: Anemia is one of the most common complications of chronic renal disease. However, the incidence or prevalence of anemia in kidney transplant recipients has not been well studied. The aim of this study was to assess the prevalence of anemia in renal transplant in early and late posttransplant period and the influence of drugs (immunosuppressive and antihypertensive). METHODS: MOST is an observational, prospective trial of renal transplant receiving cyclosporine-based immunosuppressive regimen under condition of normal practice in de novo or maintenance recipients. We analyzed the Spanish data from 397 de novo recipients and 2102 maintenance recipients. RESULTS: In maintenance recipients mean hemoglobin levels were 12.8 +/- 1.6 g/dL (13.2 +/- 1.7 in men and 12 +/- 1.4 in women); 22.73% of men and 20.19% of women were found to be anemic. There was a significant correlation between hemoglobin and graft function (r = .14, P < .0001). The percentage of patients with anemia increased with the severity of chronic renal disease according to the KDOQI classification. Therapy with mycophenolate mofetil was also associated with a higher likehood of anemia as compared with other immunosuppressive therapies (azathioprine or sirolimus). There were no differences with angiotensin-converting enzyme inhibitors or ARB II. In de novo patients postransplant anemia was a frequent complication during the first 3 to 6 months. In patients with delayed graft function the recovery of anemia was slower. CONCLUSION: The prevalence of anemia in transplant recipients was remarkably high, especially in the early postransplant period, and appeared associated with impaired renal function and with immunosuppressive treatment.

Anemia↗
PubMed2005

Impact of HLA antibodies on transplant glomerulopathy.

The influence of humoral rejection on the development of chronic allograft nephropathy (CAN) is controversial, especially in relation to transplant glomerulopathy. The aim of our study was to analyse the influence of anti-HLA antibodies on the development of transplant glomerulopathy (cg0, cg1, cg2, and cg3; Banff'97). We selected all renal transplants patients from 1975 to 2003 who had a functioning graft for at least 6 months and a clinically indicated graft biopsy with CAN and chronic glomerular changes (case group). We studied the presence of anti-HLA antibodies (Ab) in the last serum taken while the graft was functioning and divided them into three groups according to the severity of glomerular lesions. We also selected 52 contemporary and comparable cases without transplant glomerulopathy (control group). A total of 77 case had transplant glomerulopathy: 39 cg1, 29 cg2, and 9 cg3. Pretransplant Ab titers and number of previous blood transfusions were higher among the subgroup with the most severe glomerulopathy. Patients who developed posttransplant anti-HLA Ab more frequently showed transplant glomerulopathy. Serum creatinine and proteinuria were higher among cases with chronic glomerulopathy, and more grafts were lost in that group. Thus, the presence of HLA-Ab is a key factor in the development of transplant glomerulopathy and chronic allograft rejection.

Follow-Up Studies↗
PubMed2004

The macrophage infiltration index and matrix metalloproteinase-II expression as a predictor of chronic allograft rejection.

The presence of macrophages on renal biopsy specimens is considered an important cofactor in the development of chronic allograft nephropathy (CAN). Macrophages can activate the expression of matrix metalloproteinases (MMP), which induce glomerulosclerosis, arteriosclerosis, and interstitial fibrosis. The aim of our study was to demonstrate if they were related to the development of CAN. We analyzed matrix metalloproteinase (MMP) expression with specific monoclonal antibodies on 53 kidney biopsies performed due to the suspicion of a first acute rejection (AR) episode: 24 of the grafts have been lost due to CAN and the rest are still functioning. The group with CAN showed worse graft function and greater proteinuria from the beginning. The macrophage infiltration index (MI) expression was significantly higher in that group also (18.8 +/- 12 vs 12.5 +/- 9.15; P < .05), with a more important presence of macrophages in the interstitium and tubules. We observed a positive correlation between MI and tubular infiltration (r(2) = 0.52; P < .001) and between MMP-II and MI in the interstitium (r(2) = 0.3; P < .05) and with the global MI (r(2) = 0.3; P < 0.05). The last correlation was more powerful in the group with CAN (r(2) = 0.4; P < .05). According to our experience, global MI and tubular infiltration during an AR episode are good markers of long-term graft survival. The correlation between MI and MMP-II supports the role of macrophages in the development of CAN, although further studies are needed to clarify the nature of this relationship.

Biomarkers↗
PubMed2004

[Current role of hormone replacement therapy in the prevention of postmenopausal osteoporosis: gynecologic point of view].

Hormonal Replacement Therapy (HRT) of the menopause has already proved to be effective in preventing bone loss and reducing the risk of fractures in postmenopausal women. Up until 2002, HRT was widely proposed and prescribed by French practitioners, in particular with regard to the prevention of osteoporosis. The results of two major studies, one American, the Women's Health Initiative (WHI) Study, and the other British, the Million Women Study (MWS), published in July 2002 and August 2003, have called into question the hitherto favourable benefits/risks ratio of HRT after finding an increased incidence of breast cancer and heart disease amongst women undergoing this treatment. Following these studies, the European and French health authorities have issued new recommendations regulating and restricting the use of HRT with a drastic restriction on the indications for its use in the prevention of osteoporosis. These new recommendations are the subject of controversy and pose new problems for practitioners.

Aged↗