Lipid profile changes during the first year after kidney transplantation: risk factors and influence of the immunosuppressive drug regimen.

AIM: This study analyzed the incidence, time course, and risk factors associated with dyslipidemia during the first year after kidney transplantation among patients receiving various immunosuppressive regimens. METHODS: The analysis included 474 kidney transplant recipients receiving cyclosporine (CSA) combined with sirolimus (SRL; n=137) or mycophenolate (MMF, n=58) or everolimus (EVR, n=47); or SRL combined with MMF (n=32); or tacrolimus (TAC) combined with SRL (n=86) or MMF (n=114). All patients received prednisone. We evaluated the influence of demographic features, clinical outcomes, and statin use on lipid profiles during the first year after transplantation. total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (hdl-C), low-density lipoprotein cholesterol (ldl-C), non-HDL-C, TC:HDL-C, LDL-C:HDL-C, TG:HDL-C. RESULTS: Lipid profiles were within the recommended ranges in 28% of patients pretransplantation and in 10% at 1 year; 27% of them received statins. At 1 year, LDL-C<100 mg/dL was observed in 31.8% of patients but more than 35% of these patients still showed other lipid fractions or ratios outside recommended target concentrations. Among all patients with LDL-C>100 mg/dL, almost 70% to 80% had other lipid fractions or ratios within target ranges. A logistic regression analysis showed age, gender, time on dialysis, diabetes, type of calcineurin inhibitor (CSA vs TAC), adjunctive therapy (SRL/EVR vs MMF) and prednisone dose to be associated with dyslipidemia. CONCLUSION: Dyslipidemia is frequent at 1 year after transplantation. The lack of agreement among changes observed in lipid fractions and ratios suggests that more studies are necessary to guide therapy besides targeting LDL-C concentrations as recommended by current guidelines.

Risk factors associated with graft loss and patient survival after kidney transplantation.

OBJECTIVE: To evaluate the influence of traditional risk factors on major kidney transplantation outcome. PATIENTS AND METHODS: Data from kidney transplantation procedures performed between 2003 and 2006 were retrospectively analyzed for the influence of traditional risk factors on transplantation outcome. Of 2364 transplants, 67% were from living donors, 27% were from donors who met standard criteria, and 6% were from donor who met expanded criteria. Two hundred thirty-nine procedures (10%) were performed in pediatric patients. Immunosuppression was selected on the basis of subgroup population. RESULTS: At 1 year posttransplantation, cumulative freedom from a treated acute rejection episode (ARE) was 76.7%, with no difference between black vs nonblack recipients (75.0% vs 73.4%; P = .79). At 2 years, survival for patients (95.3% vs 88.3% vs 82.1%; P < .001) and grafts 92.3% vs 80.3% vs 70.9%; P < .001) was better in recipients of living donor grafts compared with donors who met standard or expanded criteria, respectively. Moreover, graft survival was poorer in black vs nonblack patients (83.6% vs 88.7%; P < .05) because of high mortality (13% vs 7%; P<.001). Risk factors associated with death included cadaveric donor organ (odds ratio [OR], 2.4) and black race (OR, 1.8), and risk factors associated with graft loss included cadaveric donor organ (OR, 2.1), extended-criteria criteria donor organ (OR, 2.0), delayed graft function (OR, 1.8), and any ARE (OR, 3.5). At 6 months posttransplantation, risk factors associated with death included cadaveric donor organ (OR, 2.5) or ARE (OR, 2.4), and risk factors associated with graft loss included cadaveric donor organ (OR, 2.0), extended-criteria donor organ (OR, 2.6), ARE (OR, 9.5), and impaired graft function (creatinine concentration >1.5 mg/dL; OR, 2.1). CONCLUSION: Traditional risk factors are still associated with transplantation outcome. Poorer graft survival in black vs nonblack recipients was due to higher mortality rather than graft loss.

Clinical impact of polymorphisms of transport proteins and enzymes involved in the metabolism of immunosuppressive drugs.

Individualization of immunosuppressive therapy after solid organ transplantation is a goal that has been pursued for a long time. Nevertheless, in clinical practice, we are still stratifying patients in subgroups in which risk is assessed using demographic information and population analysis. Then, a combination of immunosuppressive drugs is chosen and doses are individualized to compensate for intra- and interindividual variabilities in drug pharmacokinetics, to obtain similar plasma/blood concentrations that are believed to be therapeutic, again based on data derived from population analysis. One step further in this strategy is to recognize, before initiation of immunotherapy, those patients at higher risk to be either under- or overexposed to currently used immunosuppressive drugs. Several studies have been undertaken to correlate single nucleotide polymorphisms in genes encoding transport proteins and metabolizing enzymes involved in the disposition of immunosuppressive drugs. Overall, the results from these studies have been mixed. The causes of these sometimes conflicting results include methodologic, genetic, or nongenetic factors. The degree of linkage disequilibrium, the measure of nonrandom associations between polymorphisms at different loci, not necessarily on the same chromosome, is perhaps the main genetic factor. The influence of the environment, physiology (such as kidney and liver functions), disease state, use of multidrug regimens, and inherent drug-to-drug interactions are present nongenetic factors. Moreover, it is also important to increase our knowledge of the genetic factors involved in the variabilities observed in drug responses of pharmacodynamics. True individualized therapy, with the ability to improve health outcomes of each transplant recipient, will depend on our knowledge of the genetic factors involved in immunological response and drug pharmacokinetics and pharmacodynamics.

Sobrevida de pacientes diabéticos em diálise / Survival of diabetic patients in dialysis

OBJETIVO. Diabetes melito é uma causa de insuficiência renal terminal de importância crescente. Nosso objetivo foi avaliar a sobrevida depacientes diabéticos e näo-diabéticos em tratamento dialítico. MATERIAL E MÉTODOS. Foram estudados 295 pacientes em programa de diálise em um centro de referência terciário na cidade de Säo Paulo, entre 1992 e 1994. Setenta e um paciente eram diabéticos (17 do tipo I e 54 do tipo II) e 224 tinham outros diagnósticos dedoença de base. Os dados foram coletados prospectivamente através de formuláriospadronizados, e também retrospectivamente, para pacientes que iniciaram tratamento entre 1992 e junho 1993. Análise de sobrevida foi realizada por meio do método do produto limite. RESULTADOS. Os pacientes diabéticos apresentavam média de idade mais elevada e uma maior proporçäo utilizava diálise peritoneal em relaçäo aos näo-diabéticos. Após um ano, a taxa de sobrevida foi 67 por cento e 86 por cento para pacientes diabéticos e näo-diabéticos (p<0,0001). A diferença de sobrevida se acentuou com a duraçäo do tratamento. Esta diferença foi observada tantoem pacientes mais jovens (ó50 anos) quanto nos mais idosos, embora tenha sido mais precoce nos primeiros. A sobrevida dos diabéticos permaneceu significantemente reduzida, ajustando-se para a idade dos pacientes. CONCLUSÖES. Pacientes diabéticos em diálise apresentam taxa de sobrevida inferior aos näo-diabéticos, independentemente da sua idade média mais elevada. Cuidados especiais devem ser dedicados a estes pacientes, tanto em relaçäo a fatores co-mórbidos pré-diálise quanto durante o tratamento dialítico, a fim de se melhorar a sua sobrevida.

[Survival of dialyzed diabetic patients]. / Sobrevida de pacientes diabéticos em diálise.

OBJECTIVE: Diabetes is a cause of end-stage renal failure of increasing importance. Our aim was to evaluate the survival of diabetic and non-diabetic patients on dialysis treatment. MATERIAL AND METHODS: Two hundred and ninety-five patients on dialysis program in a tertiary referral center of the São Paulo city, from 1992-94, were studied. Seventy-one patients were diabetics (17 type I and 54 type II) and 224 had other diagnoses of renal disease. Data were prospectively collected using standard questionnaires and also retrospectively for patients who started treatment between 1992 and June 1993. Survival analysis was done using the product-limit method. RESULTS: Diabetic patients had a greater mean age and a higher proportion on peritoneal dialysis than non-diabetics. After one year, survival rates were 67% and 86% for diabetics and non-diabetics (p < 0.0001). The difference in survival rates increased with the duration of treatment. This difference was observed both in young (< or = 50 years) and in elderly patients, although it has been noted earlier in the former. Survival of diabetics remained significantly reduced adjusting for the age of the patients. CONCLUSIONS: Diabetic patients on dialysis have lower survival rates than non-diabetics, independently of their greater mean age. Special attention should be given to these patients, both in relation to pre-dialysis comorbidity and during dialysis treatment, to improve their survival experience.