Quality of Life and Energy Expenditure in Transplant Recipient Football Players

Football (soccer) is a highly motivating leisure activity with important potential as a health-promoting activity also for transplant recipients. The aim of this study was to assess the “on the field” energy expenditure during football games and the quality of life of transplant recipients practicing football. Twenty-two recipients of kidney (n = 11), bone marrow (n = 7), liver (n = 3) or corneal (n = 1) transplantations had an overall mean age of 37 ± 9 years, body mass index of 23.5 ± 2.4 kg/m², and time after transplantation of 9.3 ± 6.4 years. They were compared with 25 healthy football players of mean age 41 ± 10 years and body mass index of 26.3 ± 3.9 kg/m². There were no significant differences between transplant recipients and controls regarding mean energy expenditure (393 ± 113 vs 392 ± 132 kcal/h) number of steps (3.978 ± 1.317 vs 3.933 ± 1.563) during, and capillary blood lactate concentrations (4.8 ± 0.9 vs 5.2 ± 1.3 mmol/L) after the matches. The SF-36 questionnaire administered before the matches showed transplant recipient players to score significantly worse in the scales of general (P < .05) and mental health (P < .01). This study indicated that transplant recipients involved in football matches attained a level of energy expenditure and a quality of life consistent with a healthy lifestyle. Football has the potential to be implemented as a permanent health-promoting activity also for transplant recipients.     

Cholecalciferol supplements improve vitamin D deficiency in renal transplant recipients

Most renal transplant recipients display vitamin D deficiency or insufficiency. The KDIGO guidelines suggest that this deficit should be treated as in the general population. Since there are few studies about the effects of cholecalciferol in de novo renal transplant recipients, we sought to assess these effects in long-term kidney graft recipients. Among 37 renal transplant recipients (19 males, 18 females) at a mean of 105 ± 82 months posttransplantation, vitamin D insufficiency or deficiency was treated with cholecalciferol (400-800 IU/d) plus calcium supplements (600-1200 mg/d of elemental calcium). These subjects were compared with 37 untreated recipients for a period between 6 and 12 months. At baseline, there were no differences between the groups in age at transplantation, sex, length of follow-up after grafting, function measured by estimated glomerular filtration rate (44.4 ± 16.8 treated vs 42.0 ± 15.0 mL/min/1.73 m² untreated; P = .527); iPTH (157 ± 103 treated vs 176 ± 118 pg/mL untreated; P = .461); 25OHD (14.7 ± 4.7 treated vs 15.7 ± 9.7 ng/mL untreated; P = .584); or 1.25OHD (34.1 ± 26.0 treated vs 34.0 ± 13.0 pg/mL untreated; P = .950). When compared with baseline values, iPTH (157 ± 103 vs 144 ± 89 pg/mL; P = .11) and 1.25OHD levels at 6 months (34.1 ± 26.0 vs 35.9 ± 26.3 pg/mL; P = .282) showed no change but 25OHD levels (14.7 ± 4.7 vs 22.6 ± 7.4 ng/mL; P = .000) and phosphate tubular reabsorption (64% ± 17% baseline vs 69% ± 14% at 6 months; P = .030) were increased in the treated patients. There were no differences in the parameters studied in untreated patients. Among the 27 recipients followed at 12 months, iPTH was decreased compared with baseline values (157 ± 103 vs 124 ± 62 pg/mL; P = .024) and 25OHD remained stable with respect to the values at 6 months (21.1 ± 5.3 ng/mL). No adverse effects of cholecalciferol were observed such as those to increase urinary calcium excretion. Low doses of cholecalciferol improved vitamin D status and decreased iPTH levels at 12 months. Higher doses than those used in our study are needed to increase serum 25OHD concentrations above 30 ng/mL.     

Evaluation and significance of cytomegalovirus-specific cellular immune response in lung transplant recipients

In lung transplant recipients, cytomegalovirus (CMV) has been associated with direct ie, organ and systemic infection/disease, and indirect effects, including predisposition to develop acute rejection episodes and chronic allograft dysfunction. Cellular immune responses have been demonstrated to play a role in the control of CMV replication. We evaluated CMV-specific cellular responses among lung transplant recipients associated with the onset of organ infection/disease. Cellular responses were evaluated by an Elispot assay of 48 specimens from 24 patients. All samples were evaluated beyond 1 year after transplantation; CMV DNA was concomitantly detected in bronchoalveolar lavage (BAL) and whole blood specimens. Each patient received a combined prolonged antiviral prophylaxis with CMV Ig for 12 months and gancyclovir or valgancyclovir for 3 weeks after postoperative day 21. Nine patients (37.5%) showed transient or persistent CMV nonresponses including donor-recipient negative serologic matching in 2 cases. Positive CMV DNA results were observed in 18/48 BAL specimens (37.5%) from 12 patients (50%). A viral load of >10⁴ copies/mL was observed in only 3 cases, 2 of whom were positive also on whole blood. Among these 3 patients, 2 were responders and BAL (as well as whole blood) specimens collected subsequently were negative for CMV DNA; 1 nonresponder patient exhibited a viral load of 426,492 copies/mL BAL (DNAemia, <2,000 copies/mL), developed CMV pneumonia (confirmed by histopathology and immunohistochemistry) and died within 28 days. The prevalence of CMV DNA positivity on BAL did not differ in relation to the immune response; the mean viral load on BAL showed significantly higher results among nonresponders than responders, namely, 1.4 × 10⁵ ± 2.4 × 10⁵ copies/ml versus 7.9 × 10³ ± 1.4 × 10⁴ (P = .02). Evaluation of CMV-specific cellular immune responses by in vitro immunologic monitoring complements virologic monitoring, helping to identify lung transplant recipients at risk of developing organ infection/disease.     

N-Terminal Pro–B-type Natriuretic Peptide Is Inversely Related to Bone Mineral Density in Renal Transplant Recipients

IntroductionBone mineral density (BMD) was significantly lower in heart failure patients. Our aim was to evaluate the relationship between BMD and fasting serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration in renal transplant recipients.MethodsFasting blood samples were obtained from 69 renal transplant recipients. BMD was measured by dual energy x-ray absorptiometry in lumbar vertebrae (L2–L4). Serum NT-proBNP levels were measured by electrochemiluminescence immunoassay.ResultsAmong the renal transplant recipients, 8 patients (11.6%) had osteoporosis and 28 (40.6%) had osteopenia; 33 had a normal BMD. Increased serum NT-proBNP (P < .001) and decreased body mass index (P = .033) and body weight (P = .010) were significantly correlated with low lumbar T-score cutoff points between groups (normal, osteopenia, and osteoporosis). Women had lower lumbar BMD than did men (P = .013). Menopause in women (P = .005), use of tacrolimus (P = .020), and use of cyclosporine (P = .046) among renal transplant recipients were associated with lower lumbar BMD. Multivariate forward stepwise linear regression analysis of the significant variables revealed that log-transformed NT-proBNP (β, ?0.545; R² = 0.331; P < .001), and body weight (β, 0.273, R² = 0.104; P = .005) were independent predictors of lumbar BMD values among the renal transplant recipients.ConclusionsSerum NT-proBNP concentrations correlate negatively with lumbar BMD values among renal transplant recipients and may be an alternative to energy x-ray absorptiometry for identifying at risk of osteoporosis in renal transplant recipients.     

Human Cytomegalovirus Specific CD8 T Lymphocytes Display Interferon-γ Secretion Impairment in Kidney Transplant Recipients With pp65 Antigenemia

Our study sought to investigate the immune response of cytotoxic T lymphocytes to human cytomegalovirus (HCMV) in kidney transplant recipients with virus reactivation. Nine kidney transplant recipients with serum HCMV immunoglobulin G and HLA-A*0201 genotype displayed HCMV pp65 antigenemia and were compared with 29 control recipients who were free of antigenemia. The frequency of total HCMV-specific cytotoxic T cells was determined using HLA-A2-NLVPMVATV-pentamer staining. The frequency of HCMV specific interferon (INF)-γ secreting CD8⁺ T cells was determined using intracellular INF-γ staining after NLVPMVATV pulsing in vitro. The proportion of IFN-γ secreting pentamer-stained CD8⁺ T cells was calculated, representing the capacity for INF-γ secretion among HCMV-specific CD8⁺ T cells. We observed that the frequency of HCMV-specific pentamer-stained CD8⁺ T cells and HCMV-specific IFN-γ secreting CD8⁺ T cells both remained unchanged, yet the proportion of IFN-γ secreting CD8⁺ T cells showed a significant difference between the 2 groups (39.2% ± 17.2% vs 20.0% ± 13.3% respectively; P = .004), reflecting impaired IFN-γ secreting capacity of HCMV-specific CD8⁺ T cells among kidney transplant recipients displaying antigenemia, which may be a crucial reason for HCMV reactivation in immunosuppressed patients.     

Elevated serum gamma-glutamyltransferase and hypomagnesemia are not related with new-onset diabetes after transplantation

Background

New-onset diabetes mellitus after transplantation (NODAT) contributes to the risk of cardiovascular disease (CVD) and infection, reducing graft and patient survival in kidney transplant recipients. To reduce CVD and improve outcomes of kidney transplant recipients, it is of great interest to more precisely elucidate the risk factors that contribute to the development of NODAT. A previous study reported that hypomagnesemia is an independent predictor of NODAT. Elevated gamma-glutamyltransferase (GGT) activity increases the risk of incident type 2 diabetes in the general population. The objective of this study was to determine whether magnesium (Mg) and GGT were risk factors for NODAT among our population of kidney transplant recipients.

Methods

We retrospectively analyzed 205 non-previously diabetic kidney transplant recipients. GGT was measured before transplantation as well as at months 1, 2, and 12. Mg was measured at months 1, 2, and 12. NODAT was defined at month 12 and at the end of follow-up according to the “2003 international consensus guidelines.”

Results

Although 36 patients (17.5%) developed NODAT at month 12, 55 patients (26.8%) displayed it at the end of follow-up. We did not observe any significant difference, either in mean Mg (month 1, 1.73 ± 0.24 vs 1.75 ± 0.30 [P = .824]; month 2, 1.71 ± 0.22 vs 1.68 ± 0.26 [P = .565]; month 12, 1.77 ± 0.27 vs 1.80 ± 0.24 [P = .596]) or GGT values (pretransplantation, 32 ± 27 vs 33 ± 85 [P = .866]; month 1:39 ± 24 vs 48 ± 70 [P = .452]; month 2, 53 ± 96 vs 48 ± 83 [P = .739]; month 12, 40 ± 37 vs 38 ± 53 [P = .830]) between NODAT and non-NODAT patients at month 12 or at the end of follow-up.

Conclusion

Hypomagnesemia and high GGT activity were not risk factors for NODAT development in kidney transplant recipients.     

Nonverbal Communication and Psychopathology in Kidney Transplant Recipients

Transplant recipients have difficulty expressing, identifying, and describing their emotional experiences. The Machover human figure test allows us to bring out the deepest contents of a patient's personality, which are normally hidden and not explained to structured quantitative tests. The study analyzed possible situations of distress and possible symptoms of psychopathology in kidney transplant recipients, emerged from the projective test of the human figure and not easily verbalized to the common standardized tests.The sample included 80 kidney transplant patients (51 men and 29 women; mean age, 47.74 [SD, 12.39] years) during follow-up visits at 12 months after transplant. The Machover test was used to evaluate body image, affective aspects, and personality variables by projective method; the Symptom Checklist-90-R was used for the evaluation of possible psychopathology, and the 36-Item Short Form Health Survey was used for the assessment of perceived quality of life.Resultsshowed that the more anxiety there is in the human figure test, the less somatization dimensions (ANX/SOM R = ?331, P < .05), depression (ANX/DEP R = ?326, P < .05), and the global index of psychic symptomatology (ANX/GSI R = ?367, P < .05) of the Symptom Checklist-90-R are present.This research has confirmed the hypothesis that the spontaneous graphic production of the recipients, through the projective methods, allows them to identify and deepen their psychological contents and to activate and maintain a good psychophysical balance post transplant.     

Insulin resistance is a common denominator of post-transplant diabetes mellitus and impaired glucose tolerance in renal transplant recipients

Background. Post-transplant diabetes mellitus is a known complication of steroid therapy in renal transplant recipients. Both insulin resistance and insulin deficiency have been shown to be necessary for development of post-transplant diabetes mellitus. It is not known whether recipients with impaired glucose tolerance have similar degree of insulin resistance or deficient insulin response as recipients with post-transplant diabetes mellitus. Methods. To address this question, we used an oral glucose tolerance test to categorize 46 renal transplant recipients on triple immunosuppressive medication to groups with normal glucose tolerance, impaired glucose tolerance or post-transplant diabetes mellitus. Insulin sensitivity was measured using a hyperinsulinaemic euglycaemic clamp. Insulin response was calculated from the increase in serum insulin concentration during the oral glucose tolerance test. Results. Twenty-five were categorized to normal glucose tolerance, 15 to impaired glucose tolerance and six to post-transplant diabetes mellitus. There were no statistically significant differences between the groups regarding prednisolone dose, azathiprine dose, use of {beta}-blocker, age, gender, weight, waist-hip ratio, body mass index, donor source, smoking habits, or first-degree relatives with histories of diabetes mellitus. The impaired glucose tolerance and post-transplant diabetes mellitus groups showed a significant reduction in insulin-stimulated glucose disposal rate (mg/kg^.min) compared to the normal glucose tolerance group (4.6±1.6 and 3.4±1.3 respectively vs 7.1±2.4, P<0.05). The insulin response (picomol/l) was not different between the normal glucose tolerance and impaired glucose tolerance groups but was significantly reduced in the post-transplant diabetes mellitus group (448±310 and 450±291 respectively vs 170±128, P<0.05).Conclusion. Insulin resistance is a common denominator of post-transplant diabetes mellitus and impaired glucose tolerance in renal transplant recipients.     

Polymerase Chain Reaction Melting Profiles of Candida glabrata Clinical Isolates in Solid Organ Transplant Recipients in Comparison to the Other Group of Surgical Patients

The aim of the retrospective study were to estimate the prevalence of Candida glabrata in liver and kidney transplant recipients compared to patients with short bowel syndrome receiving chronic total parenteral nutrition and relevance of the polymerase chain reaction melting profile (PCR MP) method for Candida glabrata strains differentiation. C. glabrata clinical strains isolated from patients were identified by using standard mycological procedures. The analysis of genetic relatedness of the isolated strains was conducted using the PCR MP method. The prevalence of C. glabrata comprised 29% of all episodes of fungal colonization and infection in solid organ transplant recipients, and 54% of those in hospitalized patients receiving long-term total parenteral nutrition. Among 78 isolates obtained from 55 solid organ transplant recipients and 2 organ donors, 44 different C. glabrata PCR MP fingerprints were observed. Forty-seven organ recipients and one organ donor carried unique C. glabrata strains. Among 37 isolates obtained from 31 patients receiving long-term TPN, 8 different PCR MP profiles of C. glabrata strains were observed. Two patients carried unique C. glabrata strains. Most of the C. glabrata colonization and infections in solid-organ transplant recipients were caused by endogenic strains. Most of the C. glabrata colonization and infections in hospitalized patients receiving long-term total parenteral nutrition could result by patient-to-patient transmission. The results showed that the PCR MP technique is a good discriminatory method for genotyping for C. glabrata strains.     

Evolution of Anxious-Depressive Symptomatology in Liver and Kidney Transplant Recipients: Hospitalization and 12-Month Post-Transplantation Phases

ObjectiveThe objective of this study was to compare the evolution (hospitalization in the transplantation unit and at 12 months post-transplantation) of anxious and depressive symptomatology in cadaveric transplant recipients as a function of type of organ implanted (liver or kidney).MethodsUsing a 2 × 2 mixed factorial design, 2 groups were selected: 34 liver transplant recipients and 41 kidney transplant recipients. Both groups were assessed in 2 phases: (1) in the transplantation unit after discharge from the intensive care unit; and (2) 12 months after discharge from the hospital following implantation surgery. The Hospital Anxiety and Depression Scale and the Scale for the Assessment of Social Support were administered. A mixed analysis of covariance was used to assess the influence on transplant recipients' anxious-depressive symptomatology of 2 independent factors: phase (hospitalization in the transplantation unit and at 12 months post-transplantation) and organ (liver and kidney). Perceived social support and age were included as covariates in the analyses. We also calculated d and w as effect size indexes.ResultsInteractive effects of the factors phase and organ were found in the variable anxiety (P = .005). Specifically, the following simple effects were significant: (1) kidney transplant recipients presented more anxious symptomatology while hospitalized in the transplantation unit than at 12 months post-transplantation (P = .001; d = 0.52; medium effect size); and (2) kidney transplant recipients presented more anxious symptomatology than liver transplant recipients while hospitalized in the transplantation unit (P = .013; d = ?0.59; medium effect size). No statistically significant effect was obtained for the variable depression.ConclusionWorse mental health (anxious symptoms) was associated with kidney transplant recipients but not with liver recipients while recovering from the implantation surgery in the transplantation unit.     

Universal prophylaxis with gancyclovir preparation is not necessary in our kidney allograft recipients

Background

Cytomegalovirus (CMV) infection is a common cause of morbidity, graft loss, and mortality among kidney recipients due to its direct and indirect influences on organs and systems. In this study, we evaluated CMV infection in transplant recipients in Iran.

Materials and methods

We performed a retrospective study of 104 renal allograft recipients and their donors transplanted between January 2005 and January 2010. We included all patients (recipients and donors) with least one valid laboratory result for CMV immunoglobulin (Ig)G and CMV IgM. We evaluated the occurrence of CMV disease in allograft recipients in at least the first 3 years after renal transplantation.

Results

Fifty-seven renal allograft recipients (54.8%) were males and 47 (45.2%) were females. The overall mean (± standard error) age was 40.32 ± 13.30 years. CMV IgG was positive in 95 cases (91.3%), negative in 9 (8.7%). Serologically, 76.9% patients were D⁺/R⁺ 14.4% D⁻/R⁺, and 8.7% D⁺R⁻. Due to the proccurrence of rejection rendering them high-risk patients for CMV infection about 15% of subjects were treated with anti thymocyte globulin (ATG) followed by prophylactic intravenous gancyclovir for 2 weeks, at doses based on allograft function. Confirmed CMV infection and CMV disease occurred in less than 5% of recipients in the first year after transplantation. About 6% of renal allograft recipients died due to infections during the first 3 years posttransplantation but CMV disease was not confirmed in these patients.

Conclusion

Due to the living donor-based renal transplantation program, the selection of low-risk patients (panel-reactive antibodies 30%), the low percent of D⁺/R⁻ patients (8.7%) and the low use of ATG for induction therapy in the Iranian model, universal prophylaxis with gancyclovir is not routinely recommended for our cases.     

Usefulness of Monitoring Cell-Mediated Immunity for Predicting Post–Kidney Transplantation Viral Infection

Background

Monitoring cell-mediated immunity (CMI) can be used to estimate the risk of viral infections in kidney transplant recipients. The Immuknow (IMK) assay measures CD4⁺ T-cell adenosine triphosphate activity, assesses patient CMI status, and assists clinicians in determining the risk of viral infection.

Methods

We retrospectively analyzed 224 IMK values in 39 kidney transplant recipients at our institution from April 2012 to January 2013. We analyzed the relationship between IMK value and viral infection during the early and late post-transplantation periods. Multiple regression analyses were performed, to determine which factors impacted the results of the IMK assay.

Results

Eight patients developed viral infections, including BK virus, cytomegalovirus, herpes simplex, and shingles. Five infections occurred in the early post-transplantation period (<50 d) and 3 in the late period (>120 d). The IMK levels in patients who developed an infection in the early period were within normal limits; however, those in the late period were significantly lower than 200 ng/mL (421.0 ± 062.6 for early vs 153.7 ± 72.7 for late; P = .02).Our multiple regression analyses indicated that peripheral white blood cell and neutrophil counts affected IMK values (P = .03 and P = .02, respectively).

Conclusions

The IMK assay is a useful test for identifying patients at risk for post-transplantation viral infections in the late transplant period.     

Extracorporeal photopheresis as an antirejection prophylaxis in kidney transplant recipients: preliminary results

Extracorporeal photopheresis (ECP) is considered a promising immunomodulatory therapy of acute allograft rejection in organ transplantation and graft-versus-host disease. Our aim was to investigate the biological responses of 10 patients who underwent kidney transplantation with ECP as prophylactic treatment. They received conventional immunosuppressive therapy plus ECP immediately after transplantation: 12 to 16 applications over the course of 2.5 months. ECP procedures were performed using an automated system for leukocyte separation and photoactivation with methoxsalen. All recipients were followed by estimated glomerular filtration rate (eGFR) and peripheral T, B, natural killer, T-regulatory (Treg) and dendritic cells (DC) counts and phenotypes. An acute rejection episode appeared in one control group recipient. The ECP group showed a positive trend to an higher GFR at months 3 (53 ± 11 vs 47.1 ± 9; P = .17) and 6 (67.5 ± 10 vs 53.6 ± 3; P = .03, Wilcoxon test). An increased percentage of Treg (CD3⁺ CD4⁺ CD25⁺) among the total CD3 cell count (4.9% ± 1% to 9.4% ± 15%) as well as inducible Treg (CD3⁺ CD8⁺ CD28⁻) was observed among CD3 cells (3.3% ± 3% to 11.8% ± 8%, P = .025) within 3 months of ECP treatment. A significant difference in the percentage of Treg was noted at month 3 (completed ECP) between the ECP and the control groups (9.4% ± 15% vs 3% ± 1%; P = .01). Addition of ECP to standard immunosuppression was associated with a significantly higher GFR at 6 months and with a significant increase in natural Treg among CD3 cells.     

Conversion to Mycophenolate Mofetil From Azathioprine Shows Significant Positive Effect on Graft Function in Long-Term Past–Kidney Transplantation Stable-State Patients

Objectives

A number of reports have shown that the efficacy of mycophenolate mofetil (MMF) is superior to that of azathioprine (AZP) for long-term kidney allograft survival. We conducted a retrospective single-center study to evaluate renal function more than 2 years after conversion from AZP to MMF in kidney transplant recipients several years after transplantation.

Methods

AZP was converted to MMF in 51 recipients at 17.0 ± 0.8 years after kidney transplantation who were followed up for more than 2 years after conversion. Estimated glomerular filtration rate (eGFR) was determined using the Formula of the Japanese Society of Nephrology.

Results

The eGFR was significantly greater at 1 year before conversion (41.72 ± 1.91 mL/min/1.73 m²) as compared with the day of conversion (39.04 ± 1.82 mL/min/1.73 m²; P < .05). After conversion, eGFR plateaued to 39.30 ± 2.01 mL/min/1.73 m² at 1 year and 38.24 ± 2.42 mL/min/1.73 m² at 2 years after conversion. The average eGFR slopes were −2.96 ± 0.36 mL/min/1.73 m² per year for AZP and 1.22 ± 0.10 mL/min/1.73 m² per year for MMF (P < .0001). Cyclosporine (CSA) was reduced from 176 ± 9.3 to 165 ± 9.8 mg/d (P = .0394) after the switch, whereas the CSA trough level was increased from 77.3 ± 6.6 to 118 ± 9.8 ng/mL (P = .0017). Furthermore, the daily dose of tacrolimus (TAC) was decreased from 3.5 ± 0.3 to 3.1 ± 0.3 mg/d (P = .0083).

Conclusions

Our findings demonstrated the safety of conversion from AZP to MMF even in the patients who underwent renal transplantation several years prior. In addition, these short-term results indicated the improvement in allograft function following conversion.     

Fasting parameters for estimation of stimulated β cell function in islet transplant recipients with or without basal insulin treatment

In order to assess β cell secretory capacity after islet transplantation, standardized mixed meal stimulation tests are often used. But these tests are cumbersome and the effect of exogenous insulin on the test results is unclear. The aim of our study was to determine to what extent fasting glycemic indices can estimate stimulated β cell function in islet transplant recipients with and without basal insulin. In total 100 mixed meal stimulation tests, including 31 with concurrent basal insulin treatment, were performed in 36 islet transplant recipients. In a multivariate model, fasting C-peptide and fasting glucose together estimated peak C-peptide with R² = .87 and area under the curve (AUC) C-peptide with a R² = .93. There was a larger increase of glucose during tests in which exogenous insulin was used (+7.9 vs +5.3 mmol/L, P < .001) and exogenous insulin use was associated with a slightly lower estimated peak C-peptide (relative change: −15%, P = .02). In islet transplant recipients the combination of fasting C-peptide and glucose can be used to accurately estimate stimulated β cell function after a mixed meal stimulation test, whether exogenous basal insulin is present or not. These data indicate that graft function can be reliably determined during exogenous insulin treatment and that regular islet graft stimulation tests can be minimized.     

Evolution of left ventricular mass in renal transplant recipients: the influence of glucose homeostasis and oxidative stress

Background

Left ventricular hypertrophy, considered an independent factor for cardiovascular mortality, is frequent among renal transplant recipients (RTR), in whom we investigated changes in left ventricular mass (LVM) after grafting and associations with possible causal factors, especially glucose metabolism and oxidative stress.

Methods

We performed a prospective study of 37 RTR without prior diabetes mellitus who were evaluated at three times after transplantation (medians of 0.6, 16 and 28 months) by means of the LVM index (LVMI, echocardiographic measure of LVM related to body surface area, g/m²), oral glucose tolerance test and determinations of malondialdehyde and total glutathione (GSH), as well as glomerular filtration rate (GFR) estimate by the Modification of Diet in Renal Disease formula. We calculated the overall increment (DeltaLVMI) and percent change of LVMI. Patients were diagnosed to be prediabetic (PD) or new-onset diabetes after transplant (NODAT) according to ADA criteria.

Results

The mean LVMI decreased significantly over time among whole group baseline = 108.34 ± 27.71 g/m² versus middle: 100.03 ± 27.53 g/m² versus final: 90.62 ± 24.06 g/m² (P = .000). However, 13.5% of subjects showed an increased LVMI and 59.5%, a decrease less than 20%. Patients with NODAT at the end of the study showed a positive DeltaLVMI, which was negative in nondiabetics (0.24 ± 16.14 versus -19.86 ± 12.61 g/m², P = .018). Compared with DeltaLVMI(−) recipients, patients with DeltaLVMI(+) showed a greater proportion of PD and NODAT at baseline (60% and 40% versus 18.8% and 12.5%, P = .017), and significantly higher all-time fasting glycemia, lower estimated GFR, and greater increments of malondialdehyde and GSH over time. Those with a <20% LVMI decrease experienced progressive GFR impairment over time, as opposed to those with an LVMI decrease > 20%, who showed greater and improving GFR over the whole study.

Conclusions

LVMI does not always improve in RTR; the evolution of ventricular mass after renal transplantation is influenced by glucose metabolism disorders, oxidative stress, and graft function.     

Renal transplantation in old recipients from expanded criteria donors selected by kidney biopsy

Background

In Spain, the number of ideal kidney transplant donors has fallen, with at the same time an increase in the number of older recipients on the waiting list.

Aim

To analyze the results of expanded criteria cadaveric donor kidney transplants into older recipients using grafts selected by kidney biopsy.

Patients and methods

We studied 360 kidney transplant recipients who had been followed to December 2009: 180 in the study group and 180 in a control group composed of younger patients who received grafts from non-expanded criteria donors between 1999 and 2006. A paraffin-embedded kidney biopsy was evaluated by the percentages of sclerosed glomeruli, arteriolar hyalinosis, intimal wall thickening, interstitial fibrosis, and tubular atrophy.

Results

Significant differences were observed in donor age (63.50 ± 5.46 vs 31.90 ± 13.29 years; P < .001) and recipient age (58.40 ± 8.80 vs 40.71 ± 13.23 years; P < .001). Donor renal function was significantly worse among the expanded criteria group (90.80 vs 108.11 mL/min/1.73 m²; P = .006), remaining so over time in the recipient (at 1 year: 42.08 vs 63.71 [P < .001]; at 3 years: 41.25 vs 62.31 [P < .001], and at 7 years: 38.17 vs 64.18 [P < .001]). Censored 7-year graft survivals were 73% versus 87% (P < .001) with similar patient survivals (90.5% vs 95%; P = .39).

Conclusions

Selection of expanded criteria donors by kidney biopsy resulted in good renal function as well as graft and patient survivals at 7 years in older recipients.     

Clinical Courses of Renal Transplant Recipients with High BK Viremia

Objective

We sought to investigate the clinical courses of renal transplant recipients with plasma BK viral loads >10⁴ copies/mL.

Methods

A single-center retrospective review was performed of 88 kidney transplant patients in whom high BK viremia (defined as plasma BKV load >10⁴ copies/mL) was detected more than once from January 1, 2004, to December 31, 2011.

Results

At the time of transplantation, the mean recipient and donor ages were 44.5 ± 11.1 and 43.9 ± 11.3 years, respectively, and 59 subjects (67.0%) were male. The median times to first BK positivity and high BK viremia after transplantation were 44 and 136 days, respectively. Within 3 months after transplantation, we detected, 56 cases of high BK viremia (63.6%). The mean duration of high BK viremia was 8.2 ± 7.7 months. When plasma BKV load was first >4 logs, the mean log BKV load was 5.50 ± 1.11 log copies/mL, which rose to a maximum of 5.82 ± 1.11. At these times, mean serum creatinine concentrations were 1.67 ± 0.79 and 2.64 ± 2.78 mg/dL, respectively. There were 31 cases (35%) of biopsy-proven BK nephropathy patients among 51 (58%) biopsies. Treatment modalities included discontinuation or dose reduction of mycophenolic acid drugs (n = 68) and switch from tacrolimus to cyclosporine (n = 9), cidofovir (n = 9), and leflunomide (n = 3). Based on the serum creatinine elevation after high BK viremia, patients were divided into group 1 (n = 27; 30.1%), whose maximal creatinine change was <0.5 mg/dL, and group 2, with a greater alteration. On multivariate logistic regression analysis, the maximal plasma BK viral load was significantly associated with a greater serum creatinine elevation (P < .001).

Conclusions

High BK viremia mostly occurred within 3 months after kidney transplantation. About 30% of renal allograft recipients with high BK viremia maintained stable renal function. Maximal plasma BK viral load was the only independent risk factor for high serum creatinine elevation.     

Does Everolimus Associated With a Low Dose of Cyclosporine in Long-Term Cardiac Transplant Recipients Improve Renal Function? Initial Experience

Background

Cyclosporine (CsA) renal toxicity is a well-known side effect. Various immunosuppressive strategies have been developed to minimize renal insufficiency. The use of everolimus associated with low levels of CsA can be an alternative strategy.

Methods

From October 2007 to April 2008, everolimus was started with a lower dose of cyclosporine (trough levels from 109.3 ± 27.5 to 93.7 ± 30.1 ng/mL after 45 days) in 21 cardiac transplant recipients (18 male and 3 female patients, mean age 56.4 ± 10.7 years). Pre-everolimus therapy creatinine levels, creatinine clearances, and glomerular filtration rates were 1.9 ± 0.9 mg/dL, 54.2 ± 18.1 mL/mins and 44.3 ± 16.5 mL/min/m², respectively.

Results

We observed a significant reduction in creatinine levels (from 1.9 ± 0.9 to 1.4 ± 0.3 mg/dL, P = .022) as well as a significant improvement in creatinine clearances (from 54.2 ± 18.1 to 69.0 ± 19.0 mL/min, P = .020) and glomerular filtration rates (from 44.3 ± 16.5 to 57.1 ± 16.3 mL/min/m², P = .010) after 7 days of everolimus therapy. Upon univariate analysis patient age, pretransplantation creatinine clearance, creatinine clearance after everolimus introduction, glomerular filtration rate at 45 days, and time from transplantation were associated with renal improvement. Upon multivariate analysis, only creatinine clearance at 7 days was related to the renal improvement.

Conclusions

These preliminary data suggested that everolimus with a low dose of CsA may be safe and effective to reduce CsA-related renal insufficiency among selected, heart transplant patients.