Post-Kidney Transplantation Results After Circulatory or Brain Death Without Pre-Mortem Heparin Administration.

BACKGROUND Kidney donation after circulatory death (DCD) follows confirmation of death using cardiorespiratory criteria, while donation after brain death (DBD) uses neurological criteria. DBD and DCD donors are the main sources of grafts for transplantation. This retrospective cohort study from a single center in the Czech Republic aimed to compare 5-year post-transplantation outcomes after DCD and DBD transplantation without pre-mortem heparin administration. MATERIAL AND METHODS A total of 227 recipients with matched donors enrolled in the transplantation program at our institution between 2015 and 2019 were analyzed. Following the application of the inclusion criteria, 99 recipients and 94 matched donors were finally included in the study. RESULTS The duration of cold ischemia (median 961 vs 1100 min, P=0.028) and the perfusion with the preservation solution (median 11 vs 22 min, P<0.001) was statistically significantly shorter in DBD than in DCD grafts. The 1-year survival rates were 97.5% (95% CI 94.1-100.0%) and 90.0% (95% CI: 77.8-100.0%) for DBD and DCD recipients, respectively. The 3-year survival rates were 91.9 (95% CI: 86.0-98.4) and 90.0 (95% CI: 77.8-100.0) for the DBD and DCD groups, respectively. The overall difference in survival between the 2 groups of patients was not statistically significant (P=0.750) nor was disease-free survival (P=0.370). CONCLUSIONS This retrospective study from a single center showed similar 5-year results after kidney transplantation for DCD and DBD donors without pre-mortem heparin administration, including the time to graft failure and patient survival.

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.

Rejection-associated Phenotype of De Novo Thrombotic Microangiopathy Represents a Risk for Premature Graft Loss.

BACKGROUND: Thrombotic microangiopathy (TMA) significantly affects kidney graft survival, but its pathophysiology remains poorly understood. METHODS: In this multicenter, retrospective, case-control paired study designed to control for donor-associated risks, we assessed the recipients' risk factors for de novo TMA development and its effects on graft survival. The study group consists of patients with TMA found in case biopsies from 2000 to 2019 (n = 93), and the control group consists of recipients of paired kidney grafts (n = 93). Graft follow-up was initiated at the time of TMA diagnosis and at the same time in the corresponding paired kidney graft. RESULTS: The TMA group displayed higher peak panel-reactive antibodies, more frequent retransplantation status, and longer cold ischemia time in univariable analysis. In the multivariable regression model, longer cold ischemia times (odds ratio, 1.18; 95% confidence interval [CI], 1.01-1.39; P = 0.043) and higher peak pretransplant panel-reactive antibodies (odds ratio, 1.03; 95% CI, 1.01-1.06; P = 0.005) were found to be associated with increased risk of de novo TMA. The risk of graft failure was higher in the TMA group at 5 y (hazard ratio [HR], 3.99; 95% CI, 2.04-7.84; P < 0.0001). Concomitant rejection significantly affected graft prognosis at 5 y (HR, 6.36; 95% CI, 2.92-13.87; P < 0.001). De novo TMA associated with the active antibody-mediated rejection was associated with higher risk of graft failure at 5 y (HR, 3.43; 95% CI, 1.69-6.98; P < 0.001) compared with other TMA. CONCLUSIONS: Longer cold ischemia and allosensitization play a role in de novo TMA development, whereas TMA as a part of active antibody-mediated rejection was associated with the highest risk for premature graft loss.

Mycophenolate mofetil substitution for cyclosporine a in renal transplant recipients with chronic progressive allograft dysfunction: the "creeping creatinine" study.

BACKGROUND: This study determined whether cyclosporine A (CsA)-treated renal allograft recipients with deteriorating renal function ("creeping creatinine") secondary to chronic allograft nephropathy (CAN) benefit from the addition of mycophenolate mofetil (MMF) to their immunosuppressive regimen, followed by withdrawal of CsA. METHODS: In a controlled, open, multicenter study, CsA-treated renal allograft recipients with progressively deteriorating renal function were randomized to have their CsA discontinued with the concomitant addition of MMF to their regimen (group A) or to continue treatment with CsA (group B). The primary endpoint was the response rate over the 6-month period after withdrawal of CsA in group A or the equivalent time in group B. Response was defined as a stabilization or reduction of serum creatinine (SCr), as evidenced by a flattening or positive slope of the 1/SCr plot and no graft loss. Secondary endpoints included the incidence of acute rejection, graft and patient survival, and changes in selected metabolic parameters. RESULTS: The response rate in the primary intent-to-treat population (n=122) was 58% (36/62) in group A versus 32% (19/60) in group B (P=0.0060). The corresponding percentages of responders in the per-protocol population (n=107) were 60% (36/60) and 26% (12/47), respectively (P=0.0008). There were no acute rejections in group A during the study period. Patients in this group also experienced a significant decrease in total cholesterol. CONCLUSIONS: In patients with progressively deteriorating renal function secondary to CAN, addition of MMF followed by withdrawal of CsA results in a significant improvement in transplant function without the risk of acute rejection.

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.

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.