Mixed lymphocyte cultures can predict TCR Vbeta repertoires of T cells infiltrating kidney transplants during acute rejection episodes.

Alloreactive T cell populations can show skewing of T-cell antigen receptor (TCR) Vbeta gene usage. The aims of the experiments were to compare in vivo and in vitro T cell alloresponses against donor alloantigens for TCR Vbeta gene usage. T-cell cultures from renal biopsies taken during acute rejection and pretransplant mixed lymphocyte cultures (MLC) were established from five renal transplant patients. TCR Vbeta gene usage, assessed with Vbeta family specific antibodies, showed that up to five different Vbeta families were significantly expanded. In four of five cases, there was close concordance between Vbeta families expanded from the biopsy and in MLC. T-cell clones from one renal biopsy were specific for the mismatched donor alloantigen and showed similar TCR Vbeta gene usage to the original T-cell line. The results show very similar patterns of TCR Vbeta gene usage in alloreactive T cells generated ex vivo or in vitro.

Calcineurin inhibitors and proximal renal tubular injury in renal transplant patients with proteinuria and chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN) is commonly associated with proteinuria. In native nephropathies, proteinuria is linked with proximal renal tubular damage. This study uses regression analysis to link proteinuria with urinary N-acetyl-beta-d-glucosaminidase (NAG) as a marker of tubular injury or hyperfunction in renal transplant patients. METHODS: Proteinuria and urinary NAG were measured and regression analysis applied in 105 transplant patients (42 with CAN). Most were receiving calcineurin inhibitor-based immunosuppression (cyclosporine, n=60; tacrolimus, n=26; and neither drug, n=19). Patients with native nephropathies (n=96) and volunteers (n=21) were also studied. RESULTS: Urinary NAG increased with increasing proteinuria. However, patients taking calcineurin inhibitors had higher urinary NAG at any level of urinary protein than those on alternative therapy, or in native nephropathies. CONCLUSIONS: In groups of transplant patients taking different immunosuppressive regimens, regression analysis of urinary NAG against urinary protein can identify the separate effects of drug-related tubular injury or hyperfunction from that of proteinuria.

Painful cutaneous lesions, renal failure and urgent parathyroidectomy.

We describe two patients with end stage renal failure who presented with painful skin lesions, which rapidly progressed to become necrotic and gangrenous. The diagnosis was calciphylaxis, a rare disorder due to calcification and luminal fibrosis of small and medium sized cutaneous and systemic vessels. Both patients had tertiary hyperparathyroidism. An urgent parathyroidectomy was performed on one patient, which relieved her symptoms; the other required local surgery but refused parathyroidectomy and died.

Clinical outcome of cadaveric renal allografts contaminated before transplantation.

This analysis was performed to define the incidence of pretransplant microbial contamination of donor kidneys, and to assess the resultant morbidity including infections requiring therapy, and graft loss. Case records of all 638 renal allograft recipients patients transplanted in our centre during the period June 1990 to October 2000 were studied. All the recipients were given a single dose of intravenous antibiotics at the time of induction of anaesthesia. A total of 775 microbiology reports on perfusion fluid, kidney swabs and ureteric tissue were retrieved. Fifty-eight of 638 (9.1%) patients were transplanted with a graft that showed preoperative contamination. 18 of these 58 patients (31%) subsequently required antibiotic treatment. Thirty of 32 patients who received kidney contaminated with skin flora had a benign course (i.e. no unexplained, no positive blood cultures or graft infection). By contrast, seven of nine recipients with grafts whose perfusion fluid yielded lactose fermenting coliforms (LFCs) required antibiotics and three of nine of them suffered graft loss as a result. Two of these patients had bacteraemia caused by LFC, and one died. Three of five patients with positive cultures due to yeast required treatment with antifungals. None of the four patients who had graft contaminated by Staphylococcus aureus became infected. One-year 49/58 (85%) of these patients survived with functioning graft. Overall 1-year patient survival was 53/55 (92%). These data suggest that contamination of renal allografts by LFCs or yeasts need to be treated preemptively before the onset of clinical manifestations. By contrast, contamination with skin contaminants does not pose a risk to the graft.

Utility of serial Doppler ultrasound scans for the diagnosis of acute rejection in renal allografts.

This study aims to explore the utility of serial duplex scanning and to compare its results with those of single time-point scans of renal allografts in the diagnosis of acute rejection (AR). A retrospective analysis of 6017 serial duplex scans (mean: 9.8 scans per patient, 5.7 of which were done during the first 10 days) was performed in 614 patients with 462 episodes of AR from 1992-2000. Even in the absence of AR (n=278), there were day-to-day fluctuations in pulsatility index (PI) and resistive index (RI). An increase of >10% in intra-renal indices was noted 0.95 days (mean) before the commencement of treatment for AR (SD 1.3, range 1-6 days). In patients with acute tubular necrosis (ATN), who have high base line indices, sensitivity of single value of PI and RI was 58% (cut-off level 1.8) and 68% (cut-off level 0.8), with specificity of 66% and 56%, respectively. By contrast, a >10% increase over the previous 'best' in PI and RI had a sensitivity of 78% and 60% respectively, and a specificity of 78% and 90%, respectively. Reversal of flow during diastole (n=50) was found to be associated with 22% graft loss within 3 months of transplantation. We can conclude that a considerable overlap between the indices of patients with AR and those with ATN greatly limits the diagnostic yield of duplex scanning. Nonetheless, serial scanning of renal allografts is more likely to herald the need for biopsy in the diagnosis of AR than one-time scanning.