Acute infections in kidney transplant recipients.

Immunosuppressed kidney transplant recipients have a high risk of infectious complications. A variety of infections of viral, bacterial, or mycotic etiology, including opportunistic infections, occur in this group of patients, but bacterial infections are primarily responsible for the high infection-related mortality. Of the bacterial infections, urinary tract infections and pneumonia are the most common, often requiring hospitalization and temporary reduction of immunosuppressive therapy after consultation of the transplant center. In addition to symptoms due to the location of the infection, fever is often present. The differential diagnosis of fever and/or high inflammatory activity is specific to patients after kidney transplantation. In addition to infectious causes, we consider drug-related fever, a rejection episode, a relapse of systemic disease or in patients with graft failure in dialysis treatment graft intolerance syndrome (“symptomatic graft”). Saving the patients life, which often requires a significant reduction in immunosuppressive therapy, always takes precedence over preventing a rejection episode. Infection prevention is an integral part of the care of transplant patients, including the recommendation of vaccination where possible.

Phosphorus Removal in Low-Flux Hemodialysis, High-Flux Hemodialysis, and Hemodiafiltration.

Phosphorus removal by hemoelimination procedure is a important mechanism to maintain phosphorus level in acceptable level in patients on dialysis. Phosphorus is removed by both diffusion and convection, but in clinical practice, it is not possible to differentiate the contribution of this two transport modalities. We used Gutzwiller formula to quantify the amount of removed phosphorus and compared it in low-flux hemodialysis (LFHD), high-flux hemodialysis (HFHD), and on-line hemodiafiltration (HDF). There were no significant differences in phosphorus predialysis concentration, duration of procedure, processed blood volume and ultrafiltration, e.g., factors, which could possibly influence phosphorus elimination. All three tested dialysis modes also did not differ in urea dialysis dose (Kt/V) as a parameter of small molecular weight removal (LFHD, 1.50 ± 0.04 vs HFHD, 1.5 ± 0.06 vs HDF, 1.5 ± 0.05). The amount of removed phosphorus in LFHD, HFHD, and HDF was 34.0 ± 1.2, 37.8 ± 1.6, and 38.3 ± 1.4 mmol, respectively. Statistically significant increase in phosphorus removal was seen only with use of high-flux membrane (HFHD and HDF) when compared with the low-flux one. No difference was, however, found between HFHD and HDF. It can thus be concluded that phosphorus removal in all three dialysis modes is a predominantly diffusive issue and contribution of convection to it is minor to negligible.

Endothelial progenitor cells and asymmetric dimethylarginine after renal transplantation.

Levels of the endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) are elevated and endothelial progenitor cells (EPCs) decreased in patients undergoing renal transplantation (Tx) and may contribute to cardiovascular complications. In this study, we tested the hypothesis that elevated ADMA and decreased EPC can be positively influenced with regular physical exercise early after Tx. Blood samples for analysis of ADMA and EPC were obtained from randomly selected 64 patients after Tx who agreed to participate in a supervised aerobic exercise program for 6 months (group I). Samples were collected before the training began, 1 month after surgery (with stabilized renal function), and at 6 months after initiation. Sixty-two age, sex, human leukocyte antigens (HLA) typing, duration of previous dialysis, history of cardiovascular disease, and immunosupression regimen-matched transplant patients who did not exercise regularly were examined as controls (group II). There were no differences in ADMA levels and EPC count between both groups before the training program began. After 6 months of exercise, ADMA concentration in the group I decreased (3.50 ± 0.45 vs. 2.11 ± 0.35 µmol/L; P < .01) and was also lower comparing with group II (2.11 ± 0.23 vs. 3.25 ± 0.35 µmol/L; P < .01). In the same period, EPC cells increased from 2.085 ± 650 cells/mL versus 3.991 ± 560 cells/mL, P < .01 in group I; but in group II, changes were nonsignificant (P = .11). Blood lipids, HbA1c, insulin, and systolic blood pressure were also affected by the training program. Elevated ADMA level and decreased EPC count were significantly influenced by early regular exercise in patients after Tx.

Evaluation of biochemical markers and bone mineral density in patients with chronic kidney disease stage 5D at the start of hemodialysis treatment.

BACKGROUND: Patients with chronic kidney disease (CKD) have significant disorders of bone and mineral metabolism. In addition, they can also develop other bone disorders including osteoporosis. This study evaluated the bone mineral density (BMD) of patients at the start of hemodialysis treatment as well as the relationship between BMD and possible risk factors or biochemical markers. METHODS: The study was performed in 82 patients (28 females, 54 males). BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and the proximal femur. RESULTS: We found a high prevalence of 25-hydroxyvitamin D deficiency (96%; mean levels 30.0 ± 17.7 nmol/L) and a reduction of BMD in comparison with gender- and age-matched normal population values at the total hip (Z-score = -0.31 ± 1.11) and the femoral neck (Z-score = -0.48 ± 1.16), but not at the lumbar spine (Z-score = 0.68 ± 1.81). The prevalence of T-scores ≤ -2.5 SD in the group of patients over 50 years was 52.0% in females and 33.3% in males. BMD positively correlated: with male gender and calcium levels at all measured sites, with age at the lumbar spine and with weight or BMI at the proximal femur. CONCLUSION: CKD patients at the start of hemodialysis treatment had a high prevalence of low T-score values, corresponding to values for osteoporosis in the general population. BMD at the proximal femur was below the expected average for age and gender, but at the lumbar spine, BMD in hemodialysis patients was above average in persons without known CKD.

Early exercise training after renal transplantation and asymmetric dimethylarginine: the effect of obesity.

BACKGROUND/AIMS: To assess, in a prospective cohort study of 238 renal transplant patients, our hypothesis that elevated ADMA levels may be influenced by physical exercise and obesity. METHODS: Blood samples before and after six months were obtained from 116 transplant patients participating in an aerobic exercise (Group I). A control group consisted of 122 matched transplant patients who did not exercise regularly (Group II). RESULTS: There were no significant differences in ADMA levels between both groups before the training program (Group IB vs. Group IIB). After six months of exercise, ADMA levels in Group I decreased (Group IB vs. Group IA : 3.50 ± 0.45 vs. 2.11 ± 0.35 µmol/L; p< 0.01) and were lower compared to those in Group II (Group IA vs. Group IIA : 2 11 ± 0 23 vs 3 25 ± 0 34 µmol/L; p< 0 01) Analysis of our results in obese renal transplant recipients (BMI B 30 kg/m(2)) confirmed a smaller effect of exercise training (Group IBO vs Group IAO : 3 75 ± 0 52 vs 3 45 ± 0 45; p< 0 05 and Group IAO vs. Group IIAO : 3.45 ± 0.45 vs. 3.74 ± 0.62; p<0.05). Blood lipids, HbA1C, insulin, and systolic BP were also affected by the training program. CONCLUSION: Elevated ADMA levels were significantly decreased by early exercise after renal transplantation. The effect of exercise was smaller in obese patients.

HLA-G and HLA-E specific mRNAs connote opposite prognostic significance in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is characterized by its resistance to radiotherapy and/or chemotherapy. On the other hand, it is an immunogenic tumor - it is able to stimulate antitumor responses. A prognostic significance of HLA-G expression by neoplastic cells in RCC is not well characterized; significance HLA-E expression in RCC is not characterized at all. METHODS: In our study, we evaluated the expression of HLA-G and HLA-E specific mRNA transcripts produced by neoplastic cells in 38 cases of RCC and in 10 samples of normal kidney parenchyma. The results were statistically correlated with various clinico-pathological parameters. RESULTS: We confirmed that HLA-G is downregulated in normal kidney tissue; if it is up-regulated in RCC, then it is connected to worse prognosis. On the other hand, HLA-E mRNA transcripts were present in both normal kidney tissue and RCC and their increasing concentrations counterintuitively carried better prognosis, more favorable pT stage and lower nuclear Fuhrmann's grade. CONCLUSION: Considering the fact that there is known aberrant activation of HLA-G and HLA-E expression by interferons, identification of HLA-G and HLA-E status could contribute to better selection of RCC patients who could possibly benefit from more tailored neoadjuvant biological/immunological therapy. Thus, these molecules could represent useful prognostic biomarkers in RCC, and the expression of both these molecules in RCC deserves further study. THE VIRTUAL: Slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7383071387016614.

Improvement of cardiovascular risk factors and cosmetic side effects in kidney transplant recipients after conversion to tacrolimus.

AIMS: Tacrolimus and Cyclosporine A (CyA) are cornerstones in immunosuppressive therapy. Cyclosporine side eff ects include hypertension and hypercholesterolemia both of which may increase the risk of cardiovascular mortality, gingival hyperplasia and hirsutism are known to reduce quality of life. The aim of this prospective study was to evaluate changes in cardiovascular risk profile and cosmetic side eff ects after conversion from CyA to tacrolimus. METHODS: 25 stable kidney transplant recipients (9 male, 16 female) were converted from a CyA to a tacrolimus--based regimen. Mean age was 45.7 +/- 13.5 years. Time to switch following transplantation was 4.7+/-1.7 years. Reasons for conversion were multiple: arterial hypertension (9), hypertrichosis (3), gingival hyperplasia (3), hyperlipidemia (14). RESULTS: 19/25 patients completed the one year study period. One patient died, two returned to hemodialysis, two were switched back to CyA and one patient was lost to follow-up. There were statistically significant changes (p = < 0.05) in systolic and diastolic pressure and antihypertensive medication could be reduced in 13 patients. The dose of lipid-lowering agents could be reduced in the majority of the recipients and a complete withdrawal was achieved in 7 patients. Hypertrichosis and gingival hyperplasia resolved in all patients. Further, there was a significant improvement (p = <0.05) in urea and serum creatinine levels. Adverse events were consistent with the established safety profile for tacrolimus. CONCLUSIONS: Conversion to a tacrolimus-based regimen led to an improvement in the cardiovascular risk profile. Further, cosmetic side eff ects which may lead to non-compliance, resolved after the switch.

Nutritional consequences of renal transplantation.

Successful kidney transplantation leads to restoration of renal function. Some metabolic disorders from chronic renal failure may persist and new metabolic abnormalities can develop (obesity, diabetes, hypertension, bone disease, and anemia). Additionally, influence of immunosuppressive drugs (corticosteroids, cyclosporine A, tacrolimus, and rapamycin) may aggravate the course of diabetes, hypertension, and dyslipidemia. Nutritional management of renal transplantation is divided into the pretransplant period, transplant surgery, and early and late posttransplant period. Patients in the pretransplant period in dialysis treatment may develop protein-energy malnutrition and negative nitrogen balance, with loss of lean body mass and fat deposits. Nutritional management in the early posttransplant period with a functioning kidney graft necessitates fluid and electrolyte balance control with protein intake of 1,2/kg BW/day and 30-35 kcal/kg BW/day. In a nonfunctioning kidney graft, dialysis treatment continues and the therapeutic dose of immunosuppressive drugs must be reduced. The principal objective in the late posttransplant period is the maintenance of optimal nutritional status. Nutrition is important in managing obesity, insulin resistance, diabetes, hyperlipidemia, and hypertension. Other posttransplant conditions for which diet and/or nutritional supplements may be beneficial include hypomagnesemia, hypophosphatemia, hyperuricemia, hyperkalemia, hyperhomocysteinemia, chronic renal allograft failure, renal anemia, and renal bone disease.