Alan M. Luger

Ten-year experience in transplantation of A2 kidneys into B and O recipients

BACKGROUND This article summarizes our 10-year multicenter experience with transplantation of 50 blood group A2 and A2B kidneys into B and O patients. METHODS Since 1986, we have transplanted kidneys from 46 cadaver donors and 4 living donors who were blood group A2 (47 donors) or A2B (3 donors) into 19 B and 31 O patients. In 1991, we began allocating these kidneys preferentially to B and O recipients who were selected based on a history of low (< or =4) anti-A IgG isoagglutinin titers. Immunosuppression was no different from that used in ABO-compatible grafts. RESULTS The 1-month function rate before thus selecting the patients was 68% (19/28), but is now 94% (17/18). Two-year cadaver-donor graft survival with this selection method is 94%, compared with 88% for 640 concurrent and consecutive ABO-compatible transplants (log-rank, 0.15). All four living-related transplants are still functioning, with a mean follow-up of 71 months. Since we began allocating A2 kidneys preferentially to B and O recipients, the percentage of the B patients who received A2 or A2B kidneys has increased from 29% (8/28) to 55% (10/18). CONCLUSIONS Transplantation of A2 or A2B kidneys into B and O patients is clinically equivalent to that of ABO-compatible transplantation when recipients are selected by low pretransplant anti-A titer histories. This approach increases access of blood group B recipients to kidneys.

Long-term graft survival is improved in cadaveric renal retransplantation by flow cytometric crossmatching.

BACKGROUND Cadaveric renal retransplantation is associated with a higher risk of early graft failure than primary grafts. A large proportion of those graft losses is likely attributable to donor-directed HLA class I antibodies, detectable by flow cytometry cross-matching but not by conventional crossmatching techniques. METHODS Long-term graft survival in a group of 106 recipients of consecutive cadaveric renal regrafts between 1990 and 1997, in whom a negative flow T-cell IgG crossmatch was required for transplantation, was compared with two other groups of cadaveric transplant recipients. The first group consisted of 174 cadaveric regrafts transplanted between 1985 and 1995 using only a negative anti-human globulin (AHG) T-cell IgG crossmatch. The second group was primary cadaveric transplants done concurrently with the flow group (1990 to 1997) using only the AHG T-cell IgG crossmatch. RESULTS The long-term (7 year) graft survival rate of flow crossmatch-selected regraft recipients (68%; n= 106) was significantly improved over that of regraft recipients who were selected for transplantation by only the AHG crossmatch technique (45%; n=174; log-rank=0.001; censored for patients dying with a functioning graft). Graft outcome for the flow cross-matched regraft recipients was not significantly different from that of primary cadaveric patients (72%; n=889; log-rank=0.2; censored for patients dying with a functioning graft). Finally, a positive B-cell IgG flow cytometric crossmatch had no influence on long-term regraft outcome. CONCLUSIONS The use of the flow T-cell IgG cross-match as the exclusion criterion for cadaveric renal retransplantation yields an improved long-term graft outcome over that obtained when only the AHG cross-match is used and has improved survival of regraft recipients to the level of our primary cadaveric renal transplant population.

Cold ischemia time: An independent predictor of increased HLA class I antibody production after rejection of a primary cadaveric renal allograft

Background. Cadaveric kidneys experiencing longer cold ischemia time (CIT) are associated with higher levels of delayed graft function, acute rejection, and early graft loss. One mechanism to explain these results is that ischemia/reperfusion (I/R) injury makes the allograft more immunogenic by upregulating molecules involved in the immune response (e.g., HLA Class I/II). Methods. We evaluated the influence of CIT on the production of HLA Class I antibody level, measured by an antihuman globulin panel reactive antibody (AHG PRA) level, in 90 unsensitized recipients of primary cadaveric renal transplants (from a total of 1442 between 1985 and 1997) who rejected their kidneys. Results. By multivariate analysis, a CIT of 15 hr or more (vs.<15 hr) independently increased the risk of the AHG Class I PRA level being ≥20% after unsensitized patients rejected their first kidneys (relative risk=3.57; 95% confidence interval=1.26 to 10.14;P =0.01), despite the same degree of Class I/II mismatch between the two CIT groups. The overall mean peak PRA level after primary kidney rejection was significantly lower for the CIT<15 hr group (25.9%±33.9; n=24) compared with the CIT≥15 hr group (46.3%±36.5; n=66) (P <0.001). Conclusion. Longer CIT induces a humorally more immunogenic kidney.

Are wedge biopsies of cadaveric kidneys obtained at procurement reliable

BACKGROUND Single wedge biopsy of cadaveric kidneys from donors older than 55 is currently the standard method of evaluating their viability for transplantation. The degree of glomerulosclerosis presently determines whether a kidney can be transplanted, but most biopsies sample only the subcapsular region and may not accurately represent the true renal architecture. Our study evaluated the accuracy of transplant suitability determinations based upon the single wedge biopsy of cadaveric kidneys. METHODS We took kidneys that were refused by UNOS centers on the basis of biopsy results, examined their histology in detail, and reviewed donor medical histories. Sections were taken from the upper, lower, and mid-portion of each kidney and stained with the periodic acid Schiff stain. Percentage and location of glomerulosclerosis and other relevant pathology were then determined in each section. We compared our findings with the results of the original wedge biopsies obtained at the time of procurement. RESULTS Nine kidneys were obtained and examined. The wedge biopsies at the time of procurement showed glomerulosclerosis ranging from 8 to 36% (median 17%). The multiple kidney sections we analyzed showed fewer sclerosed glomeruli, ranging from 3 to 15% (median 7%, P<0.001), with most of the sclerosed glomeruli identified located in the immediate subcapsular region (P<0.001). CONCLUSIONS Wedge biopsies of donor kidneys can overestimate the total amount of glomerulosclerosis, apparently because of a predominance of sclerosis in the kidneys subcapsular region, the area predominantly sampled by the usual wedge biopsy. These inappropriately high estimates of glomerulosclerosis can result in refusal of kidneys that might be suitable for transplantation.

Prediction of crossmatch outcome in highly sensitized dialysis patients based on the identification of serum HLA antibodies

High levels of allosensitization (greater than 50%), which often occur in dialysis patients awaiting renal transplant, make donor selection difficult. Such patients may be included in elaborate protocols in which they are crossmatched with all available ABO compatible donors, or crossmatching may be deferred until a very-well-matched donor becomes available. The former approach of random crossmatching is costly and inefficient, while the latter approach may overlook crossmatch-compatible donors. We believe that the identification of antibodies present in highly reactive sera and the use of this information in donor selection would increase the frequency of crossmatch-negative donors for these patients. In this study eleven sera, reactive with 70% to 100% of a random cell panel, were obtained from multiply transfused dialysis patients. Sera were analyzed by standard (CDC) and antiglobulin augmented (AHG-CDC) lymphocytotoxicity, and by differential absorption with HLA-typed platelets. All sera contained only one or two antibodies directed against the high frequency public HLA epitopes, accounting for 85% to 100% of each serums total reactivity. These characterized sera were crossmatched with 114 random normal donors. The frequency of negative crossmatches was 20.5%. However, if the serum antibody data had been used to preselect donors for crossmatch--that is, to exclude donors that were likely to be positive--the negative crossmatch frequency would have increased to 86.4%. The use of the serum analysis data in donor selection would have reduced the total number of required crossmatches by 78%. Serum analysis correctly predicted the outcome of 95.6% of crossmatches performed with an average of 3% false positives and 1.3% false negatives. This approach to donor selection reduces unnecessary crossmatching and increases the likelihood of finding crossmatch-compatible donors for highly reactive patients.

Familial unilateral renal agenesis and focal and segmental glomerulosclerosis.

Renal dysplasia and agenesis may be a familial disorder. We report the familial occurrence of unilateral renal agenesis and proteinuria that, at least in one case, was related to focal glomerulosclerosis. Whether these abnormalities are related to an intrinsic abnormality in the remaining kidney, hyperfiltration injury, systemic hypertension, or some other poorly defined factor is unclear at present. However, this report, along with previous case reports of familial renal agenesis, suggests that ultrasonographic screening of first-degree relatives of patients with renal agenesis is appropriate. Whether treatments such as dietary protein restriction, use of angiotensin-converting enzyme inhibitors, or other therapeutic interventions will have a beneficial effect in asymptomatic individuals with unilateral renal agenesis remains to be determined.

Nutrition in Renal Transplantation

This study was conducted to determine whether a high-nitrogen, low-carbohydrate diet in the immediate post-operative renal transplant period could result in a positive nitrogen balance and fewer cushingoid side effects. Twelve consecutive nondiabetic renal transplant recipients were randomly assigned to the isocaloric control or experimental diet group. The six patients ingesting the experimental diet achieved positive nitrogen balance whereas five of the six patients on the control diet had a negative nitrogen balance. The nitrogen balance varied directly and proportionately with the protein intake. Potassium balance mirrored the nitrogen balance data. Cushingoid side effects did not develop in any of the six experimental diet patients whereas four of the six control diet patients had evidence of severe cushingoid appearance and two had moderate cushingoid appearance (P = .01). Based upon the findings of this study, we suggest that the renal transplant recipients diet could be altered to provide more protein and less carbohydrate to improve nitrogen balance and prevent cushingoid features. It is possible that a high-protein, low-carbohydrate diet may be used by additional patients taking steroids for other disease states to prevent cushingoid side effects and improve nitrogen balance.

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.

Detection of HLA IgG antibodies by two enzyme-linked immunoassays, solubilized HLA class I and PRA-STAT : comparison with the AHG PRA

HLA class I-directed IgG antibodies have traditionally been detected with a complement-dependent lymphocytotoxicity (CDL) technique. We have evaluated two solid-phase enzyme-linked immunoassays (EIA) and compared them with the CDL antihuman globulin (AHG) dithiothreitol-treated (DTT) PRA in their ability to discriminate between the presence or absence of HLA class I-directed IgG antibodies in serum from patients awaiting transplantation. The EIA were: (1) an EIA that uses solubilized HLA class I antigens (sHLA-I) isolated from a 240-member platelet donor pool, and (2) the PRA-STAT ELISA kit. For the first comparison, we used 691 serum samples from 272 patients taken before they had been transplanted. The data show a significant (P < 0.0001) linear correlation (r = 0.77 between the AHG DTT PRA and the sHLA EIA. They also demonstrate that the mean sHLA-I EIA ratio significantly increases (P < 0.01) above background levels with each stepwise increase in AHG DTT PRA level. Discordant results were 1.0% (7/691) for sHLA-I EIA+ PRA- and 6.3% (44/691) for PRA+ sHLA-I EIA-. However, a lower correlation was noted between the AHG DTT PRA and the PRA-STAT (Nextran) PRA results (n = 230; r = 0.42). The sHLA-I EIA is able to determine whether or not HLA Class I IgG antibodies are present in serum from transplant candidates and is an appropriate adjunct to the traditional CDL PRA assay, whereas the PRA-STAT is not.

Poststreptococcal glomerulonephritis in the elderly: report of a case and review of the literature

Acute poststreptococcal glomerulonephritis (PSGN) is uncommonly seen in the elderly population and its diagnosis is not without some difficulty because clinical manifestations may mimic other diseases. Renal biopsy for diagnosis and early intervention, if indicated, is very valuable in such a situation. We present here a case of an elderly patient with PSGN and a review of the literature. In addition to the typical clinical manifestations of the disease, dyspnea and pulmonary congestion are commonly present in elderly patients, probably a result of excessive salt and water retention in the face of compromised cardiovascular function. Elderly patients with PSGN appear to have a remarkably poor prognosis, with significant incidences of acute mortality and chronic renal disease. Our patient had the unusual finding of a large number of glomerular crescents with near complete clinical recovery after short-term follow-up.