Sofia Pedroso

Oxidative stress in kidney transplantation: malondialdehyde is an early predictive marker of graft dysfunction.

Background Oxidative stress is one of the most important components of the ischemia-reperfusion process after kidney transplantation (KTx) and increases with graft dysfunction. Methods This prospective study was conducted on 40 consecutive KTx recipients to evaluate time-dependent changes in oxidative stress-related parameters within the first week after KTx and to assess their performance in predicting delayed graft function (DGF=dialysis requirement during initial posttransplant week) and graft function at 1 year. Blood samples were collected before (day 0) and after KTx (days 1, 2, 4, and 7). Total antioxidant capacity, plasma levels of malondialdehyde (MDA), and activities of glutathione peroxidase, glutathione reductase and superoxide dismutase were measured. Multivariable linear mixed and linear regression models, receiver-operating characteristic (ROC), and areas under ROC curves (AUC-ROC) were used. Results At all time points after KTx, mean MDA levels were significantly higher in patients developing DGF (n=18). Shortly after KTx (8–12 hr), MDA values were higher in DGF recipients (on average, +0.16 &mgr;mol/L) and increased further on following day, contrasting with prompt functioning recipients. Day 1 MDA levels accurately predicted DGF (AUC-ROC=0.90), with a performance higher than SCr (AUC-ROC=0.73) and similar to cystatin C (AUC-ROC=0.91). Multivariable analysis revealed that MDA levels on day 7 represented an independent predictor of 1-year graft function. Antioxidant enzyme activities were not significantly changed during the study period and were not predictors of 1-year graft function. Conclusions Increased MDA levels on day 1 after KTx might be an early prognostic indicator of DGF, and levels on day 7 might represent a useful predictor of 1-year graft function.

Weekly risedronate in kidney transplant patients with osteopenia

Daily bisphosphonate is effective in preventing and treating corticosteroid‐induced osteoporosis in renal transplant recipients, although it frequently has gastrointestinal side effects. The aim was to assess efficacy and side effect profile of weekly oral risedronate. Eighty‐four renal transplant patients, receiving either cyclosporin A or tacrolimus and steroids were prospectively included. The study group (39 patients) received 35 mg risedronate weekly, vitamin D and calcium, while control group (45 patients) only vitamin D and calcium. At baseline, 6 and 12 months, creatinine, calcium, phosphorus, alkaline phosphatase and iPTH were determined. Fractures and bone mineral densities were assessed by X‐rays and dual‐energy X‐ray absorptiometry, respectively. Pain was assessed by clinical interview. Mineral bone density score increased significantly in risedronate group after 1 year. There were no differences in the incidence of fractures, although, anamnestic pain assessment revealed that 3% of treatment group reported to have bone pain compared with 18% in nontreatment group (P < 0.05). Follow‐up calcium, phosphorus, alkaline phosphatases, and iPTH levels showed no differences from basal measures. Risedronate was well tolerated with no major side effects. Weekly oral risedronate in renal transplanted patients reduces bone mineral loss and bone pain and has an excellent side effect profile.

Pulmonary alveolar proteinosis: a rare pulmonary toxicity of sirolimus.

The aim of our paper is to describe an unusual pulmonary toxicity of sirolimus (SRL) in a kidney transplant recipient. We present a 34‐year‐old woman with a second renal transplantation, complicated with steroid‐resistant acute rejection and chronic allograft dysfunction. Two years after initiating SRL, she presented complaints of progressive dyspnoea, nonproductive cough, chest pain and low‐grade fever of 1 month duration. She had chronic allograft nephropathy and slight elevation of lactic dehydrogenase levels. After exclusion of common reasons of this condition, a computed tomography (CT) of the thorax and bronchoscopy was performed, revealing ground‐glass opacification with polygonal shapes on CT and an opaque appearance with numerous macrophages on bronchoalveolar lavage. The alveolar macrophages stained positive by Periodic acid‐Schiff. Diagnosis of pulmonary alveolar proteinosis (PAP) was made and drug‐induced toxicity was suspected. SRL was withdrawn with marked improvement in the patients’ clinical and radiological status. PAP resolved within 3 months without further therapy. PAP is a very rare complication of SRL therapy with only a few cases described. Withdrawal of SRL with conversion to another immunosuppressant seems to be an appropriate procedure in this condition.

Cost analysis of renal replacement therapy by transplant in a system of bundled payment of dialysis

Rocha MJ, Ferreira S, Martins LS, Almeida M, Dias L, Pedroso S, Henriques AC, Almeida R, Cabrita A. Cost analysis of renal replacement therapy by transplant in a system of bundled payment of dialysis.

Bone mineral density after simultaneous kidney-pancreas transplantation: four years follow-up of 57 recipients.

Bone disease and an high risk of fractures are major problems in transplantation. Among diabetic patients undergoing simultaneous kidney-pancreas (SKP) transplantation, there are few studies assessing long-term effects on bone mass. The aim of this study was to evaluate bone mineral density (BMD) over 4 years follow-up after SKP transplantation. Fifty-seven patients had 22.8 +/- 5.3 years of prior diabetes, 65% were female, and the overall mean age was 24.3 +/- 5.93 years. At the time of transplantation, the lumbar spine and femoral neck T-scores were -1.75 +/- 1.05 and -1.95 +/- 0.73, respectively; 28% of subjects had evidence of osteoporosis. One year after transplantation, 77.6% of patients displayed improved lumbar T-scores to -1.33 +/- 0.94 (P = .044) with stable femoral neck T-scores. Bone densitometry enhanced gradually through the 4 years follow-up: lumbar T-score to -1.04 +/- 0.67 (P = .004) and femoral neck T-score to -1.69 +/- 0.49 (P = .12). At year 4, no osteoporosis cases were detected but 86.7% of patients did not receive steroids in the immunosuppressive regimen. The graft function remained stable (serum creatinine, 1.2 mg/dL; fasting glucose, 87.7 mg/dL). During the follow-up, BMD improved more significantly at cortical sites. Our study reports a reduced prevalence of fractures (8.7%) compared with the literature, which could be related to a steroid-sparing protocol and/or aggressively treatment of osteoporosis.

Neutrophil Gelatinase-Associated Lipocalin in Kidney Transplantation Is an Early Marker of Graft Dysfunction and Is Associated with One-Year Renal Function

Urinary neutrophil gelatinase-associated lipocalin (uNGAL) has been suggested as potential early marker of delayed graft function (DGF) following kidney transplantation (KTx). We conducted a prospective study in 40 consecutive KTx recipients to evaluate serial changes of uNGAL within the first week after KTx and assess its performance in predicting DGF (dialysis requirement during initial posttransplant week) and graft function throughout first year. Urine samples were collected on post-KTx days 0, 1, 2, 4, and 7. Linear mixed and multivariable regression models, receiver-operating characteristic (ROC), and areas under ROC curves were used. At all-time points, mean uNGAL levels were significantly higher in patients developing DGF (n = 18). Shortly after KTx (3–6 h), uNGAL values were higher in DGF recipients (on average +242 ng/mL, considering mean dialysis time of 4.1 years) and rose further in following days, contrasting with prompt function recipients. Day-1 uNGAL levels accurately predicted DGF (AUC-ROC = 0.93), with a performance higher than serum creatinine (AUC-ROC = 0.76), and similar to cystatin C (AUC-ROC = 0.95). Multivariable analyses revealed that uNGAL levels at days 4 and 7 were strongly associated with one-year serum creatinine. Urinary NGAL is an early marker of graft injury and is independently associated with dialysis requirement within one week after KTx and one-year graft function.

Effect of Different Sensitization Events on HLA Alloimmunization in Kidney Transplantation Candidates

BACKGROUND HLA alloimmunization is caused by sensitization events (SEs), such as transfusion, pregnancy, or previous organ transplantation, and the effects of particular SEs have not been thoroughly studied. Our aim was to evaluate how each SE affected HLA alloimmunization by considering Luminex assays. METHODS Sera from 722 kidney transplantation candidates were screened per protocol by means of Luminex assays to determine the presence of anti-HLA class I/II antibodies; positive sera underwent single-antigen assay to determine the presence of specific antibodies against HLA A, B, C, DR, DQ, DP loci (positivity if median fluorescence intensity values were >1,000). The effect of each SE was analyzed considering only patients exposed to 1 kind of sensitization. RESULTS In the 453 candidates with ≥1 SE, anti-HLA class I positivity rates were significantly higher in patients with previous transfusion (18.9%; P = .014), pregnancy (38.3%; P < .001) or transplant (75%; P < .001) compared with those with no SE (similar results for class II). The strength (median fluorescence intensity) of specific antibodies was significantly higher in patients with previous transplantation than in those with previous transfusion for HLA-A (8,017 vs 2,302; P = .02), HLA-B (7,765 vs 2,901; P = .018), and HLA-DR (9,835 vs 2,060; P = .003). Other anti-HLA antibody strengths were similar between patients with previous pregnancy or transplantation. CONCLUSIONS Presence of any SE analyzed was associated with a higher prevalence of anti-HLA antibodies for class I ± II compared with nonsensitized patients. Transplantation had the strongest immunization effect on both classes, followed by pregnancy and then transfusion.

Over Ten-Year Kidney Graft Survival Determinants

Kidney graft survival has been mainly evaluated using an up to 10-year threshold. Instead, in this study our aim was to evaluate predictive variables that impact long-term kidney graft survival (≥10 years). We enrolled 892 patients in our analysis: 638 patients with functioning graft at 10 years PT and 254 patients with graft failure at 10 years PT (considering patient death with a functioning graft <10 years PT as graft failure). Between groups comparisons were done using Mann-Whitney and chi-square test. To determine independent predictive variables for long-term graft survival a multivariate-adjusted logistic regression was performed. Significant predictors of long term graft survival were lower 12-month PT creatinine (OR = 0.26, P < 0.001), lower donor age (OR = 0.98, P = 0.004), shorter time on dialysis (OR = 0.93, P = 0.044), recipient positive CMV IgG (OR = 1.59, P = 0.040), absence of AR episodes (OR = 1.57, P = 0.047), 0 to 1 (versus 2) HLA-B mismatch (OR = 1.80, P = 0.004), and recipients male gender (OR = 1.84, P = 0.005). Our results show that an early KT, younger donor age, and an optimal first year graft function are of paramount importance for long-term graft survival. Measures that address these issues (careful donor selection, preemptive KT, and effective immunosuppressive protocols) are still warranted.

Posttransplant Outcomes of Peritoneal Dialysis Versus Hemodialysis Patients

The impact of dialysis modality on posttransplant outcomes remains controversial. The authors have compared primary failure, delayed graft function (DGF), acute rejection episodes as well as patient and allograft survivals among patients undergoing renal transplantation between 2004 and 2009, according to the modality of hemodialysis (HD) versus peritoneal dialysis (PD). We studied 306 patients (268 HD and 38 PD) with a mean follow-up of 29 ± 16 months. The PD cohort included a predominance of females (68.4% vs 36.2%; P = .001), lower age at transplantation (38 ± 14 vs 46 ± 12 years; P = .004), shorter time on dialysis (33 ± 49 vs 59 ± 157 months; P = .043), and higher rate of living donor grafts (PD 31.6% vs HD 13.1%; P = .003). Donor age (PD 43 ± 13 vs HD 45 ± 14 years; P = .30), human leukocyte antigen mismatch (P = .17), panel reactive antibody values (HD 11 ± 22 vs PD 13 ± 26; P = .55), and hyperimmunized patients (HD 3.73%; PD 7.89%; P = .23) were not different. Primary graft failure (3.4% vs 0%; P = .025) and DGF (37.1% vs 13.1%; P = .037) were more frequent among HD patients, but incidences of acute rejection episodes were similar (HD 10.5% vs PD 5.3%; P = 0.19). Neither recipient survival at 1 (97% in PD and HD) or 3 years (HD 90% vs PD 94%; P = .657) nor allograft survival at 1 year (HD 94% vs PD 95%; P = .80) or 3 years: (HD 70%, vs PD 81%; P = .73) were different. Graft function was similar at 1 (HD 64.2 ± 25 vs PD 56.4 ± 24 mL/min; P = .17) and 3 years (HD 62.3 ± 21 vs PD 46 ± 23 mL/min; P = .16). In our study, HD patients showed an higher incidence of DGF and primary allograft failure, but there was no difference in acute rejection episodes, long-term survivals, or renal function.

Leptin and Adiponectin During the First Week After Kidney Transplantation: Biomarkers of Graft Dysfunction?

CONTEXT AND OBJECTIVE Based on evidence that leptin and adiponectin are removed from circulation primarily by the kidney, we designed a study to examine the longitudinal changes of these adipokines during the first week after kidney transplantation (KTx) and to test the hypothesis that higher levels of leptin and/or adiponectin could be early biomarkers of delayed graft function (DGF=dialysis requirement during the first post-transplant week) and acute rejection. STUDY DESIGN Repeated-measures prospective study. MATERIAL AND METHODS Forty consecutive adult patients with end-stage renal disease who were undergoing KTx. Leptin and adiponectin were measured in blood samples that were collected before (day-0) and after KTx (days-1, 2, 4 and 7). Linear mixed-models, receiver operating characteristic and area under curve (AUC-ROC) were used. RESULTS At post-transplant day-1, leptinemia and adiponectinemia declined 43% and 47%, respectively. At all times studied after KTx, the median leptin levels were significantly higher in patients developing DGF (n=18), but not adiponectin levels. Shortly after KTx (day-1), leptin values were significantly higher in DGF recipients in contrast to patients with promptly functioning kidneys, approximately two times higher when controlling for gender and BMI. The leptin reduction rate between pre-tranplant and one-day after KTx moderately predicted DGF (AUC=0.73). On day-1, serum leptin predicted DGF (AUC-ROC=0.76) with a performance slightly better than serum creatinine (AUC-ROC=0.72), even after correcting for BMI (AUC-ROC=0.73). Separating this analysis by gender showed that the performance of leptin in predicting DGF for male gender (AUC-ROC=0.86) improved. CONCLUSIONS Kidney graft function is an independent determinant of leptin levels, but not of adiponectin. Leptin levels at day-1 slightly outperformed serum creatinine in predicting the occurrence of DGF, and more accurately in male gender. No significant association was detected with acute rejection.