Risk factors for acute rejection in renal transplant recipients experiencing delayed graft function

Acute rejection (AR) superimposed upon delayed graft function (DGF) following renal transplantation worsens graft outcomes. However, risk factors for AR in patients displaying DGF remain unclear. In this study, 71 patients displaying DGF >/= 5 d were investigated. All received cyclosporine, adjunctive azathioprine or mycophenolate mofetil (MMF), and corticosteroids, with 43 receiving anti-CD25 monoclonal antibody induction. AR episodes were seen in 20 of 71 (28%) patients. Higher C2 levels at days 3 and 5 and the use of MMF were associated with a reduced incidence of AR, with increased HLA-DR mismatch associated with an increased risk for AR. C2 levels at days 3 and 5 below 885 and 1096 ng/mL, respectively, showed best discriminatory values for AR. C2 levels showed no correlation with DGF duration. This study suggests that optimizing immunosuppression in patients with DGF (by ensuring adequate calcineurin inhibitor exposure and the use of potent adjunctive immunosuppression) may reduce the incidence of AR without prolonging the duration of dialysis requirement.     

Suppurative bacterial pyelonephritis as a cause of acute renal failure

Acute oliguric renal failure associated with bacterial pyelonephritis is a rarely recognized clinical entity. We report a woman with an ectopic pregnancy who developed acute renal failure requiring dialytic support. The renal biopsy revealed focal microabscess formation and leukocyte interstitial infiltration compatible with suppurative pyelonephritis. Although her renal function improved gradually with antimicrobial treatment, the process was incomplete and renal dysfunction persisted at a 10-week follow-up, suggesting permanent renal damage.     

Acute antibody-mediated rejection in paediatric renal transplant recipients

Acute antibody-mediated rejections (aAMR) after renal transplantation are defined by rapidly deteriorating graft function, detection of donor-specific antibodies (DSA) and characteristic histological features. In adults, anti-rejection strategies comprise intravenous immunoglobulin (IVIG), steroid pulses, plasmapheresis and rituximab. Data of children with aAMR are scarce. We report four episodes of aAMR in three children (aged 10, 10 and 11 years respectively) occurring early after renal transplantation. Pre-transplant complement-dependent cytotoxicity crossmatches were negative; in the case of re-transplantation repeated antigens were excluded. Basic immunosuppression comprised cyclosporine A, MMF and steroids. All four rejection episodes were histologically proven and associated with acute renal failure. De novo DSAs were detected in two aAMRs; one patient was additionally tested positive for AT1-receptor antibodies. All aAMRs were treated with steroid pulses, tacrolimus, MMF, IVIG, plasmapheresis and one single dose of rituximab. Despite therapy one graft was lost; in the remaining three cases kidney function re-established within 1–8 weeks. At follow-up, 14, 15 and 22 months’ post-rejection their GFRs were 65, 88 and 105 ml/min/1.73 m² respectively. A combined therapy of steroid pulses, IVIG, plasmapheresis and rituximab is potentially effective in the treatment of aAMR in children.     

Acute torsion of a renal transplant: cause of organ loss

Acute torsion of a renal allograft has not been previously described as a cause of organ loss. We present a case of acute torsion of a transplanted kidney in a patient with prune-belly syndrome which led to renal necrosis, necessitating organ removal.     

Is graft irradiation of value in renal transplant rejection?

Thirty-six patients who received renal transplants and who subsequently underwent rejection episodes were randomized into two groups before undergoing treatment. One group received high doses of steroid drugs, and the other group received in addition 600 rads of radiotherapy to the graft. After 3 years (minimum follow-up 12 months) the groups were compared with respect to initial response to treatment, patient and graft survivals, and level of transplant function. No benefit was obtained by the group receiving radiotherapy.     

The relative influence of delayed graft function and acute rejection on renal transplant survival

Three hundred and eight cadaveric renal transplants were analysed to establish the effects of acute rejection in the first 90 days and delayed graft function (DGF) on graft outcome. There were 120 patients (39%) with no DGF and no rejection (group 1), 101 patients (33%) with rejection but no DGF (group 2), 41 patients (13%) with DGF but no rejection (group 3) and 46 patients (15%) with both rejection and DGF (group 4). The actuarial 4-year graft survival rates for groups 1,2,3 and 40.4%, respectively. The acute rejection rate was 101/221 (46%) in patients with initial graft function compared with 46/87 (53%) for those with DGF (²=1.02, P=0.31). Cox stepwise logistic regression analysis demonstrated that DGF was a more powerful predictive factor for poor graft survival (P=0.001) than acute rejection occurring in the first 90 days post-transplant (P=0.034). Further efforts at improving graft outcome should concentrate on reducing the incidence of DGF.     

Influence of hypercholesterolemia and acute graft rejection on chronic nephropathy development in renal transplant recipients

Graft endothelial lesions resulting from acute rejection may be sustained by concomitant hypercholesterolemia, thus increasing the risk of chronic graft failure. The present study was undertaken to examine the influence of hypercholesterolemia and acute graft rejection (AGR) episodes on graft function and graft loss due to chronic nephropathy. A cohort of 336 patients transplanted between 1993 and 2000 having graft function at 12 months after transplantation were examined. Immunosuppressive therapy consisted of CsA, azathioprine, and corticosteroids in 90% with 10% of patients receiving mycophenolate mofetil in place of azathioprine. During the first year after transplantation, AGR occurred in 134 (39.8%) and hypercholesterolemia (6.2 mmol/L) in 132 (39.2%) of patients. The population was divided into four groups according to AGR occurrence and cholesterol concentrations during the first year after transplantation for analysis of serum creatinine concentrations and graft loss at 5 years of follow-up. Patients with AGR irrespective of cholesterol levels displayed significantly higher creatinine concentrations. Graft loss in these patients increased over twofold compared to the remaining groups. Patients without hypercholesterolemia and AGR showed normal creatinine concentrations and low graft loss rates during 5 years of follow-up.     

Acute pyelonephritis causing acute renal allograft dysfunction

In renal transplant recipients, acute pyelonephritis may cause acute deterioration of renal function. We report a case with acute allograft failure due to acute pyelonephritis, which was confirmed by graft biopsy. After appropriate antimicrobial therapy, allograft function recovered.     

Acute renal failure due to acute pyelonephritis

We report a case of biopsy-proved acute pyelonephritis which caused acute renal failure. Despite appropriate antibiotic therapy, recovery of renal function was slow and incomplete. Renal papillary necrosis was an apparent complication, which the patient may have been predisposed to by alcoholism. Although rare, acute pyelonephritis is an important consideration in the differential diagnosis of acute renal failure because of the need for specific therapy.     

Low cyclosporin A blood levels and acute graft rejection in a renal transplant recipient during rifampin treatment

Cyclosporin A trough blood levels were unusually low during rifampin treatment in a kidney transplant patient. Simultaneously, acute graft rejection occurred. Pharmacokinetic investigation revealed a rapid turnover of cyclosporin A leading to low blood levels. Cessation of rifampin therapy reversed these changes. Rifampin substantially reduces the bioavailability of cyclosporin A and should not be used in transplant recipients on cyclosporin A.     

Acute renal failure due to acute pyelonephritis

We report a case of acute renal failure due to acute pyelonephritis with microabscess formation. Despite antibiotic therapy renal function deteriorated, necessitating peritoneal dialysis. Although rare, acute pyelonephritis is an important consideration in the differential diagnosis of acute renal failure, and prompt antibiotic therapy is crucial to insure a favourable outcome.     

Efficacy of local graft irradiation in preventing cadaveric renal transplant rejection: a prospective randomized trial

Successful renal transplantation depends on the modification of the normal immunologic response. The earliest attempts at such modification involved the use of ionizing irradiation. The significant morbidity and mortality of total body irradiation led to its abandonment in favor of the safer technique of local graft irradiation. While still commonly used, the efficacy of this technique has never been evaluated in a prospective, randomized fashion. The present study is a prospective, randomized, double blinded evaluation of the efficacy of the addition of local graft irradiation to our immunosuppressive protocol. One hundred consecutive cadaveric renal transplants were randomized to receive either conventional immunosuppression alone or conventional immunosuppression plus local graft irradiation delivered in doses of 150 rads on the 1st, 3rd and 5th post-operative days. Patients were followed for a period of 2 years. No significant difference was demonstrated between the groups among any measured parameter. In conclusion, the addition of local graft irradiation in doses of 150 rads on d 1, 3, and 5 does not appear to offer any advantage over standard immunosuppressive therapy and its use cannot be recommended.     

Virus infections and acute renal transplant rejection.

The date of onset of 360 acute renal transplant rejection episodes from 1969 to 1973 have been compared with the prevalence of various common viral infections and infections due to Mycoplasma pnuemoniae. A positive correlation was found for influenza B infections (r=0.43, p less than 0.01) up to 5 months before transplantation and for adenovirus infections (r=0.32, p less than 0.05) at 1 month before kidney grafting.     

Adenovirus pyelonephritis in a pediatric renal transplant patient

Gross hematuria, graft pain, and rising serum creatinine are classic signs of acute rejection, obstruction, or bacterial pyelonephritis for patients with renal transplants. This presentation often prompts percutaneous renal allograft biopsy. If subsequent evaluation fails to show evidence of acute rejection, obstruction, or bacterial infection, viral etiologies should be considered. We report a 14-year-old Hispanic female with a living-related renal transplant who had gross hematuria, graft tenderness, and increased serum creatinine, but did not have evidence of acute rejection, obstruction, or bacterial pyelonephritis. To our knowledge, this is the first report of adenovirus pyelonephritis in a transplanted kidney of a pediatric patient, with isolation of adenovirus in the urine and in the allograft using immunocytochemical techniques.     

Blood group Lewis alloantibodies cause antibody-mediated rejection in renal transplant recipients

Three patients with negative Lewis phenotypes who displayed anti-Lewis antibodies suffered severe kidney allograft dysfunction. One woman and two men (22-44 years) received ABO compatible kidney transplants with negative donor-recipient cross-match tests. Two patients had the phenotype Le(a-b-) with anti-Le(a) and anti-Le(b) complement binding antibodies. The third patient of phenotype Le(a+b-) developed anti-Lewis(b) antibody a few months after transplantation. One patient presented recurrence of worsened graft function from the day 6 to 4 months after transplantation; despite treatment there was not full recovery. The second patient had recurrences of acute graft dysfunction at 4 and 6 months after transplantation with nephrotic range proteinuria. The third patient showed progressive graft dysfunction at 7 months after transplantation. Biopsy specimens showed histological changes of antibody-mediated rejection. In the third patient, we observed fibrinoid necrosis and thrombosis of arterioles and glomerular capillaries. Immunofluorescence studies showed immunoglobulin IgG and IgM in glomerular capillaries and C4d and C3 on endothelial cells of peritubular capillaries. Posttransplantation cross-match tests with donor lymphocytes were negative. Anti-Lewis antibodies were observed during follow-up. All patients were treated with methylprednisolone boluses. In addition, one subject received antithymocyte globulin (ATG) and 1 received plasmapheresis. Two patients had moderate renal dysfunction (creatinine levels 1.8 and 1.9 mg/dL) after 8-17 months follow-up. The third patient lost her graft at 11 months after transplantation. Lewis antibodies may injure a renal allograft. C4d deposition and failure to show donor-specific anti-HLA antibodies suggested the participation of other antibodies.