Patricia Campbell

High risk of sensitization after failed islet transplantation.

Human Leukocyte Antigen (HLA) antibodies posttransplant have been associated with an increased risk of early graft failure in kidney transplants. Whether this also applies to islet transplantation is not clear. To achieve insulin independence after islet transplants multiple donor infusions may be required. Hence, islet transplant recipients are at risk of sensitization after transplantation. Islet transplant recipients were screened for HLA antibodies posttransplant by flow‐based methods. A total of 98 patients were studied. Twenty‐nine patients (31%) developed de novo donor specific antibodies (DSA) posttransplant. Twenty‐three patients developed DSA while on immunosuppression (IS). Among recipients who have discontinued IS, 10/14 (71%) are broadly sensitized with panel reactive antibody (PRA) ≥50%. The risk of becoming broadly sensitized after transplant was 11/69 (16%) if the recipient was unsensitized prior to transplant. The majority of these antibodies have persisted over time. Appearance of HLA antibodies posttransplant is concerning, and the incidence rises abruptly in subjects weaned completely from IS. This may negatively impact the ability of these individuals to undergo further islet, pancreas or kidney transplantation and should be discussed upfront during evaluation of candidates for islet transplantation.

Pretransplant HLA antibodies are associated with reduced graft survival after clinical islet transplantation.

Despite significant improvements in islet transplantation, long‐term graft function is still not optimal. It is likely that both immune and nonimmune factors are involved in the deterioration of islet function over time. Historically, the pretransplant T‐cell crossmatch and antibody screening were done by anti‐human globulin—complement‐dependent cytotoxicity (AHG‐CDC). Class II antibodies were not evaluated. In 2003, we introduced solid‐phase antibody screening using flow‐based beads and flow crossmatching. We were interested to know whether pretransplant human leukocyte antigen (HLA) antibodies or a positive flow crossmatch impacted islet function post‐transplant. A total of 152 islet transplants was performed in 81 patients. Islet function was determined by a positive C‐peptide. Results were analyzed by procedure. Class I and class II panel reactive antibody (PRA) > 15% and donor‐specific antibodies (DSA) were associated with a reduced C‐peptide survival (p < 0.0001 and p < 0.0001, respectively). A positive T‐ and or B‐cell crossmatch alone was not. Pretransplant HLA antibodies detectable by flow beads are associated with reduced graft survival. This suggests that the sirolimus and low‐dose tacrolimus‐based immunosuppression may not control the alloimmune response in this presensitized population and individuals with a PRA > 15% may require more aggressive inductive and maintenance immunosuppression, or represent a group that may not benefit from islet transplantation.

Cytodiagnostic Urinalysis Is Very Useful in the Differential Diagnosis of Acute Renal Failure and Can Predict the Severity

Cytodiagnostic urinalysis was tested to determine its utility in the differential diagnosis of acute renal failure (ARF). Fifty-one patients with acute renal failure were included and evaluated clinically with regard to the etiology of the renal failure, whether underlying chronic renal failure was present, and if dialysis was required. Urine specimens were macroscopically examined and subjected to a multiparameter reagent-strip analysis. Papanicolaou stain was done on cytocentrifuge preparations and the number of blood cells, renal cells, and casts examined in a standardized fashion. The results showed that the 34 patients with acute tubular necrosis (ATN) of either ischemic or toxic origin had a higher number of collecting duct cells, and a higher total number of casts than the 17 non-ATN patients. Twelve patients requiring dialysis had a higher number of different types of casts (granular, waxy, leukocytic, broad casts) as well as more renal cells (mainly necrotic) than the 39 patients who did not require dialysis. A significant positive correlation was found between the magnitude of rise of serum creatinine and a number of cytodiagnostic parameters. We conclude that cytodiagnostic urinalysis may be valuable in addition to other tests in the evaluation of patients with acute renal failure.