Efficacy of induction therapy with ATG and intravenous immunoglobulins in patients with low-level donor-specific HLA-antibodies.

Low-level donor-specific HLA-antibodies (HLA-DSA) (i.e. detectable by single-antigen flow beads, but negative by complement-dependent cytotoxicity crossmatch) represent a risk factor for early allograft rejection. The short-term efficacy of an induction regimen consisting of polyclonal anti-T-lymphocyte globulin (ATG) and intravenous immunoglobulins (IvIg) in patients with low-level HLA-DSA is unknown. In this study, we compared 67 patients with low-level HLA-DSA not having received ATG/IvIg induction (historic control) with 37 patients, who received ATG/IvIg induction. The two groups were equal regarding retransplants, HLA-matches, number and class of HLA-DSA. The overall incidence of clinical/subclinical antibody-mediated rejection (AMR) was lower in the ATG/IvIg than in the historic control group (38% vs. 55%; p = 0.03). This was driven by a significantly lower rate of clinical AMR (11% vs. 46%; p = 0.0002). Clinical T-cell-mediated rejection (TCR) was significantly lower in the ATG/IvIg than in the historic control group (0% vs. 50%; p < 0.0001). Within the first year, allograft loss due to AMR occurred in 7.5% in the historic control and in 0% in the ATG/IvIg group. We conclude that in patients with low-level HLA-DSA, ATG/IvIg induction significantly reduces TCR and the severity of AMR, but the high rate of subclinical AMR suggests an insufficient control of the humoral immune response.

Pretransplant risk assessment in renal allograft recipients using virtual crossmatching.

Preformed donor-specific HLA-antibodies antibodies (DSA) are a major risk for early antibody-mediated rejection (AMR). This prospective study evaluated the accuracy of pretransplant risk assessment using virtual crossmatching (virtualXM) (i.e. comparing HLA-typing of the donor with the recipient's HLA-antibody specificities determined by flow-beads). Sixty-five consecutive patients were stratified according to virtualXM results: patients without DSA (n= 56) were considered low risk and received standard immunosuppression; patients with DSA (n= 9) were considered high risk and received additional induction with anti-T-lymphocyte-globulin (ATG) and intravenous immunoglobulins. Despite induction therapy 4 of 9 patients with DSA (44%) had clinical/subclinical AMR, whereas only 2 of 56 patients without DSA (4%) (p = 0.002). Notably, one of these two patients had early AMR likely induced by non-HLA-antibodies; the other had subclinical AMR at month 6 consistent with de novo DSA. The results of virtualXM and retrospectively obtained flow-cytometric crossmatches (FCXM) (n= 59) were concordant in 51 patients (86%), four patients (7%) were virtualXM-/FCXM+ and none had AMR, four patients (7%) were virtualXM+/FCXM- and one had AMR. VirtualXM can accurately define absence or presence of DSA and may become an invaluable tool for organ allocation and pretransplant risk assessment. However, further studies need to address whether all HLA-antibodies detected by flow-beads are clinically relevant.

[Glomerular erythrocytes in urine. Identification and significance]. / Glomeruläre Erythrozyten im Urin: Erkennung und Bedeutung.

The glomerular origin of microhematuria can often be identified by typical changes in erythrocyte morphology when the urinary sediment is examined with a phase contrast microscope. The so-called "glomerular erythrocytes" appear in uneven annular shape (ring forms) or as fragmented, crushed and ruptured cells (destroyed forms). Non-glomerular erythrocytes originating from the urinary tract have different morphological characteristics. The occurrence of only a few glomerular erythrocytes (0-2 per high power field) is a normal finding. The morphological characteristics of the erythrocytes should be analyzed as the first step in the work up of microhematuria. In the case of clearcut glomerular microhematuria, unnecessary urological or radiographical investigation can thus be avoided.

Value of urinary sediment in the diagnosis of interstitial rejection in renal transplants.

The occurrence of lymphocyturia, or a sharp increase in preexisting lymphocyturia, has been found to correlate with immunological rejection. In most studies time-consuming staining techniques or counting chambers have been used. A new staining technique, with prestained slides, is investigated as a predictor of cellular rejection and to distinguish between cellular rejection and cyclosporine (CsA) toxicity, or other causes of renal function impairment. In 18 consecutive renal transplant recipients, treated with CsA, urinary sediments were analyzed almost daily for two months, and prediction of cellular rejection was related to renal biopsies and retrospective clinical evaluation. In addition 24 transplant biopsies were compared with urinary sediment prediction; in both parts of the study a lymphocyturia of more than 20% and polymorphs less than 55% (of 100 nucleated cells, excluding squamous epithelial cells) were considered to suggest interstitial rejection. Episodes of lymphocyturia (greater than 20%), with simultaneous increase of the number of epithelial cells, resulting in a relative decrease of polymorphs (less than 55%), were found 10 times. Of these, 9 corresponded well with biopsy or clinical evaluation and 1 was false-positive. Correlating urinary sediment analysis with biopsy histology (n = 24), 19 were accurate, 3 equivocal, and 2 false; this corresponds to a sensitivity of 77% and a specificity of 91%. In conclusion, the analysis of urinary sediments with prestained slides is a quick and simple method to diagnose cellular rejection and to distinguish it from toxic of ischemic renal damage. Results are comparable to those of the fine-needle aspiration technique without invasive insult to the patient.