Sharing kidneys across donor-service area boundaries with sensitized candidates can be influenced by HLA C.

The United Network for Organ Sharing (UNOS) implemented the virtual crossmatch system in UNet as a way to improve the likelihood of a negative crossmatch when kidneys are shared with HLA-sensitized candidates across donor service area (DSA) boundaries. The role of HLA C in that process is not universally appreciated. We recently experienced an unexpected positive flow T and B cell crossmatch for an imported, HLA zero-mismatched kidney because of donor-specific HLA C antibodies and transplanted it into the backup candidate. HLA C locus antigens were not typed by the OPO's laboratory that sent the kidney so the UNet virtual crossmatch could not "strike" our candidate from the UNOS match run. HLA C locus typing data of donors for kidneys our DSA imported from other DSAs revealed that C typing was not performed in 23% (14/60) and was discrepant with our molecular type for 10% (6/60) and was concordant in 67% (40/60) of cases. The rate of positive donor-specific crossmatches was higher (83%) for HLA C discrepantly typed donors than for concordantly typed donors (44%). Sensitization for HLA C (42%) is less frequent than for A (80%) or B (83%) locus antigens but the immunogenicity of C locus antigens in patients who make C locus antibodies is equivalent in black and white patients. Finally, the transplant rate of imported kidneys into class I-sensitized candidates was 24%, and C locus-sensitized candidates comprised 55% of those transplanted.

Successful treatment of Henoch-Schonlein purpura nephritis with plasma exchange in an adult male.

Henoch-Schonlein purpura (HSP) frequently occurs in children under 15 years of age but is quite rare in adults. Most children who develop HSP nephritis completely recover from the illness, whereas up to 40% of adults have persistent hematuria and 10% develop chronic renal failure. Plasma exchange alone has been shown to be beneficial in children who have HSP nephritis. Adults have been treated using immunosuppressive drugs such as cyclophosphamide but effects are not certain. Here, we present a case of a 59-year-old white male who developed HSP nephritis while undergoing treatment with steroids. The patient developed acute renal failure with proteinuria and hematuria ∼2 weeks after being initially diagnosed with HSP by skin biopsy. Renal biopsy showed proliferative, exudative glomerulonephritis involving all 20 glomeruli; some with early crescent formation. Immunofluorescence staining showed 3+ IgA deposits in mesangium suggesting HSP-induced GN. The patient's serum creatinine rose to 2.5 mg/dl with ∼5 g of proteinuria by dipstick. Steroids were continued and the patient received plasma exchange treatments. Due to a very low leukocyte count, immunosuppressive agents were not given. Subsequently, renal function improved and the creatinine level came down to 1.3 mg/dl and proteinuria to <1 g/24 h. Since then, 1 year after this event, his serum creatinine has continued to stay at 1.2 mg/dl and he has trace proteinuria while taking a low-dose ACE inhibitor. This case illustrates the usefulness of plasma exchange in adult onset HSP nephritis, even without concomitant use of cytotoxic agents.

Successful renal transplantation despite low levels of donor-specific HLA class I antibody without IVIg or plasmapheresis.

We prospectively transplanted 10 primary kidney recipients with deceased donor organs (nine kidney and one pancreas/kidney) when their flow cytometric T-cell IgG, HLA class I donor-specific crossmatch was positive but the AHG T-cell crossmatch was negative, with a median follow-up of 1.8 yr. No pre- or peri-operative IVIg or plasmapheresis was administered to any patient. All but one of the 11 organs transplanted into patients with a flow T(+)/AHG(-) crossmatch is currently functioning despite the continued presence of circulating low levels of HLA class I antibody. Flow HLA class I antigen-coated beads showed the presence of at least one donor-specific HLA class I antibody at transplantation in each of the 10 cases. No rejections were observed in seven of the 10 cases (70%). Six rejection episodes, four cellular and two humoral, occurred in three patients. Each rejection was successfully treated. The only graft loss occurred in a kidney recipient on day 667 secondary to ischemia to the kidney because of cardiac surgery. Thus, short-term (one to two years) graft survival in primary transplants was not influenced by low levels of donor-specific HLA class I antibody present at transplantation and no prophylactic treatment such as IVIg, plasmapheresis, anti-CD20 or splenectomy was needed peri-operatively.

Tetralogy of Fallot, hypertrophic cardiomyopathy, and Down's syndrome: a rare and challenging combination.

A case of the combination of tetralogy of Fallot, hypertrophic cardiomyopathy, and Down's syndrome is reported here and is the first report on the combination of the 3 entities. Tetralogy of Fallot is often associated with chromosomal aberration, while hypertrophic cardiomyopathy associates with certain gene loci. Our experience with treating this patient, although ultimately unsuccessful, may provide useful information in any future cases.

HLA points assigned in cadaveric kidney allocation should be revisited: an analysis of HLA class II molecularly typed patients and donors.

The points now assigned for the quality of HLA match have received significant scrutiny to be modified in an effort to help reduce disparity in access to kidneys of minority groups, and since differences in graft survival between groups of patients in each of the HLA matched groups is less now than in the past. We analyzed long-term (5-year) graft survival in 746 DR DNA typed recipients of cadaveric kidneys transplanted from 1994-2001 whose donors were also DR DNA typed, with allocation based on those DNA-based typings. Five-year graft survival was not significantly different for recipient groups irrespective of if they had zero (84%), one (92%), two (89%), or three to four B, DR mismatches (79%) (log-rank = 0.15; died with a functioning graft [DWFG] censored). Mismatching of three and four DR and DQ antigens in black but not white patients was associated with significantly worse survival (Relative Risk = 2.9) (p = 0.002). The incidence of minority transplants in the well-matched group (zero and one B, DR mismatch), 12.8% (20/156) was over half that of the less well-matched group, 27.1% (160/590) (p < 0.001). Our data indicate that the current HLA-B, DR-based point system used to allocate kidneys warrants re-evaluation. Our data, taken in the context of the UNOS data, which has recently been re-evaluated, suggest that the only HLA-DR remain as a component of the national kidney allocation algorithm so as to increase access of kidneys to minorities and minimize graft loss.

Flow cytometry beads rather than the antihuman globulin method should be used to detect HLA Class I IgG antibody (PRA) in cadaveric renal regraft candidates.

HLA Class I antibody screening can be performed by flow cytometry using a mixture of 30 distinct bead populations each coated with the Class I antigen phenotype derived from different cell lines. In this study we compared the efficacy of Class I antibody screens done by flow cytometry beads with the antihuman globulin (AHG) method for patients awaiting cadaveric renal retransplantation. Class I panel reactive antibody (PRA) screening by flow cytometric beads of 21 regraft serum samples that had all been found to be negative by AHG DTT Class I PRA, revealed that 57.1% (12 of 21) had a flow Class I PRA of > or = 10%. Furthermore, when five regraft sera with an intermediate PRA were screened (mean AHG DTT PRA = 33.2 +/- 13%) the mean flow Class I PRA almost doubled (mean flow PRA = 72.4 +/- 10.2%) (p < 0.01). When active UNOS waiting list regraft candidates, after several months of screening the Class I PRA by flow beads, were divided into the three PRA categories based on their peak flow Class I PRA value (0-20%, 21-79% and > or = 80%), the incidence of a positive flow cross-match was 0%, 72% and 85% and the incidence of retransplantation was 60%, 22% and 10%, in each of these groups, respectively. These data provided our histocompatibility laboratory with the rationale to stop performing the AHG PRA and perform only the flow Class I PRA method for regraft candidates.

Novel collagen glomerulopathy in a homotrimeric type I collagen mouse (oim).

BACKGROUND: Oim/oim mice [osteogenesis imperfecta model; homozygous null for the proalpha2(I) collagen gene] synthesize exclusively the homotrimeric type I collagen isotype, alpha1(I)3, and are unable to synthesize the normal heterotrimeric type I collagen isotype, alpha1(I)2alpha2(I). Previous studies of the oim/oim mouse have focused on the musculoskeletal system, with no systematic evaluation of other organ systems. METHODS: Multiple tissues from oim/oim, oim/+ (heterozygous) and +/+ (wild-type) mice were examined for gross and histological abnormalities. Tissues were stained with (1) hematoxylin and eosin (to assess lesion formation), (2) picrosirius red (collagen content), and (3) periodic acid methenamine silver (basement membrane). Kidneys were further evaluated ultrastructurally by electron microscopy and immunohistochemically with anti-alpha1(I) and anti-alpha1(III) collagen antibodies. RESULTS: Histological analyses revealed accumulations of picrosirius red-positive material, consistent with collagen, in glomeruli of 28/29 oim/oim mice, with no evidence of mesangial cell proliferation. Only the most severely affected animals had evidence of increased capillary basement membrane thickening or mild inflammation around the affected glomeruli. Electron microscopy confirmed the presence of fibrillar collagen. Immunohistochemistry with anti-alpha1(I) collagen antibodies confirmed accumulation of type I collagen in the oim/oim glomeruli. The +/+ and oim/+ kidneys had normal mesangium with no evidence of infiltration of collagenous material. CONCLUSIONS: This study demonstrates the first evidence, to our knowledge, of abnormal glomerular collagen deposition associated with a type I collagen defect. Further in vivo and in vitro studies are necessary to elucidate the mechanistic, functional, and pathological significance of the oim/oim collagen glomerulopathy.