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Background: Despite marked improvement in short-term renal allograft survival rates (GSR) in recent years, improvement in long-term GSR remained elusive., Methods: We analysed the kidney transplant experience at our centre accrued over four decades to evaluate how short-term and long-term GSR had changed and to identify risk factors affecting graft survival. The study included 1476 adult recipients of a deceased-donor kidney transplant who were transplanted between 1963 and 2006 and who had received one of five distinct immunosuppressive protocols., Results: Five-year actual GSR steadily improved over the years as immunosuppressive therapy evolved (22-86%, P < 0.001) in spite of an increasing trend in the transplantation of higher-risk donor-recipient pairings. For those whose grafts functioned for the first year, subsequent 4-year GSR (5-year conditional GSR) also improved significantly (63-92%, P < 0.001). Acute rejection and delayed graft function (DGF) were the most significant risk factors for actual graft survival, while acute rejection was the only significant risk factor for conditional GSR. Use of kidneys from expanded-criteria donors (ECD) was not a risk factor, compared to the use of standard-criteria donor kidneys for either 5-year actual or conditional GSR. There was an impressive decline in the incidence of acute rejection events (77.4-5.8%, P < 0.001). While the DGF rate had decreased, it still remained high (68.7-38.5%, P < 0.001)., Conclusions: We found a significant improvement in both short-term and long-term GSR of deceased-donor kidney transplants over the last four decades. These improvements are most likely related to the decreased incidence of acute rejection episodes. Minimizing acute rejection events and preventing DGF could result in further improvement in the GSR. Our experience in the judicious use of ECD kidneys suggests that this source of kidneys could be expanded further.

We previously reported that a calcium channel blocker supplemented immunosuppression produced excellent patient and graft survival rates in cadaveric kidney transplantation. We report here the long term outcome of patients treated with nifedipine-supplemented triple immunosuppression as compared with those of historical controls who were treated similarly without nifedipine. Study subjects included 111 patients transplanted in 1990-1994, treated with nifedipine and triple immunosuppression and with functioning grafts for more than one year (Nifedipine group). The results of cyclosporine (CyA) dose, blood pressure (BP), serum creatinine (Cr), and actuarial graft survival rate (GSR) up to 5 years posttransplant in these patients were compared with those of 52 patients transplanted in 1985-1990, treated similarly without calcium channel blockers (Control group). Donor sources, gender ratio, age distribution, causes of end stage renal disease, incidence of hypertension prior to transplantation and incidence of rejection in the first year between the groups were comparable. Throughout the study period the Nifedipine group had significantly lower serum Cr (1.5 +/- 0.7 vs. 1.8 +/- 0.7 mg/dl) and higher GSR (93.8% vs. 88% at 5 years) than the Control group. BP was comparable despite higher CyA doses in the Nifedipine group (4.3 +/- 1.1 vs. 3.3 +/- 1.1 mg/kg/day). We conclude that nifedipine is beneficial in improving long-term graft function and survival in kidney transplant recipients by mitigating CyA associated renal injury.

A major conceptual advance is the formulation that type I cytokines (such as IL-2 and IFN-gamma) enhance cellular immunity and are host-protective, and that type II cytokines (such as IL-4 and IL-10) dampen cellular immunity and facilitate the progression of infection. We have explored the intragraft expression of type I and type II cytokines during human renal allograft rejection. RNA was isolated from 98 allograft biopsies, and reverse transcription-PCR was used to amplify and identify intragraft expression of mRNA encoding IL-2, IFN-gamma, IL-4, or IL-10. Intragraft expression of IL-7 mRNA and TGF-beta 1 mRNA was also investigated. Our investigation demonstrated that: (a) intragraft expression of IL-10 mRNA and IL-2 mRNA are significant correlates of acute rejection; (b) IL-4, IL-7, IFN-gamma and TGF-beta 1 mRNA expression do not correlate with acute rejection; and (c) IL-10 does not prevent in vivo expression of IFN-gamma, IL-2, IL-7, or TGF-beta 1. Our studies identify, for the first time, a significant association between intragraft IL-10 mRNA expression and acute rejection, and suggest that treatment strategies capable of constraining IL-10 expression might be of value in the prevention of acute rejection.

The progression of lupus nephritis severe enough to require dialysis does not necessarily indicate that it is "end-stage." Ten percent to 28% of patients with lupus nephritis who develop renal failure requiring dialysis will recover enough function to come off dialysis. The clinical activity of systemic lupus erythematosus (SLE) is quiescent in most patients with end-stage lupus nephritis, regardless of the modality of dialysis treatment. Clinical and serologic remission of SLE permits judicious withdrawal of immunosuppressive therapy, as well as a favorable long-term outcome for patients that is comparable to that of nonlupus patients. The great majority of deaths in patients with end-stage lupus nephritis occur in the first 3 months of dialysis and most often result from infection. Later, infection and cardiovascular complications are common causes of death. Patients with lupus nephritis should wait at least 3 months on dialysis before receiving a kidney transplantation. Immunosuppressive therapy and graft survival rates for lupus patients are not different from those of nonlupus patients. Recurrence of lupus nephritis in the allograft is exceedingly rare.

This is a study of the incidence and clinicopathological significance of focal segmental glomerulosclerosis (FSG) in 154 renal allografts (22 biopsies, 128 nephrectomies and four necropsies) from 137 cadaveric and 17 living-related donors. FSG was identified in 18 grafts (11.7%) from 16 patients: six as recurrent FSG in four patients (two developed FSG in two consecutive transplants) and 12 as de novo FSG. The incidence of recurrent FSG in patients who had FSG as their original kidney disease was 30.8% whereas that of de novo FSG in patients who had renal diseases other than FSG was 8.7%. Histologically, recurrent FSG was characterized by mild degrees of obliterative arteriopathy of rejection and preferential involvement of the juxtamedullary glomeruli. Whereas, in de novo FSG, the occlusive vascular changes of rejection were severe and the glomeruli in the outer cortical region were mostly involved. Clinically, however, the differences between them were less clear, although nephrotic syndrome tends to occur more often and earlier in patients with recurrent FSG. Obliterative arteriopathy of chronic rejection and consequent glomerular ischemia appeared to be of major importance in the pathogenesis of de novo FSG in renal allografts.

The effect on cadaver-kidney transplant survival-rates of a gamma-globulin concentrate, prepared from clotted blood centrifugally expressed from placental tissue recovered from postpartum women, was evaluated in a prospective controlled trial in 195 patients who were also given a standard immunosuppressive regimen. Allograft-survival rates were analysed according to whether or not the recipient had lymphocytotoxic antibodies before transplantation (responders) and whether the graft was a first or second transplant. The graft-survival rate was improved in responder-type recipients of first transplants who had received the gamma-globulin concentrate as adjunctive therapy (control group 28.8+/-10.1% vs. gamma-globulin 55.5 + 9.7% at 2 years, p less than 0.05). The survival-rate of grafts in non-responders was not affected by administration of gamma-globulin and data on its use in recipients of a second graft were insufficient for analysis. These results suggest that the gamma-globulin concentrate was suppressing immunological responses associated with humoral-type rejection.

The ability of the monoclonal antibody directed at the T3 antigen (anti-T3) to induce cytolytic activity was investigated since several agents that can activate T cells induce the acquisition of cytolytic activity in a variety of test systems. Pretreatment of human alloimmune memory cells, generated in primary long-term mixed lymphocyte cultures, with anti-T3 resulted in the induction of statistically significant specific secondary cytolytic activity and natural killer (NK) cell-like activity. No such augmentation or induction of cytolytic activity was found with anti-T3 pretreatment when syngeneic cells or inappropriate allogeneic cells (HLA-A, B antigens different from the original priming stimulus) were used as target cells and pretreatment of memory cells with anti-T4 or anti-T8 did not induce cytolytic activity to allogeneic or syngeneic target cells. Differential effects were observed when anti-T3 was added to the cytotoxicity assay in which anti-T3 pretreated alloimmune memory cells were effectors. The addition of anti-T3 to the assay prior to the introduction of target cells resulted in 39 +/- 8% inhibition of specific secondary cytolytic activity and only 5 +/- 8% inhibition of NK cell activity. NK cell activity mediated by large granular lymphocyte-enriched fraction of peripheral blood mononuclear cells (PBM) obtained from normal individuals was significantly augmented by anti-T3 when NK-sensitive cell lines MOLT-4 or K-562 were used as target cells. This augmentation in NK cell activity was not associated with nonspecific cytotoxicity to syngeneic or allogeneic PBM, and anti-T3 failed to activate the LGL fraction depleted of T cells. The monoclonal antibodies, anti-T4 or anti-T8, did not increase NK cell activity. NK cell activity mediated by PBM from eight immunodeficient individuals (four with acquired immunodeficiency syndrome and four with renal allografts) was also significantly augmented by anti-T3 pretreatment. Our findings, in addition to providing a rationale for the frequent occurrence of re-rejection episodes in renal graft recipients treated with anti-T3, suggest that anti-T3 might be utilized to enhance the cytotoxic armamentarium of immunodeficient patients.

Urinary tract infection is the most frequent complication following renal transplantation and is important in the etiology of post-transplantation sepsis. The 87 renal homografts done in 1974 at The New York Hospital-Cornell Medical Center were reviewed retrospectively, with at least one year follow-up, in all cases, with particular attention to factors relating urinary tract infection to ultimate success or failure of the renal graft. The over-all incidence of urinary tract infection was 61%. Early infection was associated with a particularly poor prognosis for graft survival. Most patients with urinary infections after successful transplantation experience a combination of both early and late infections. Anatomic factors constitute a remediable cause of urinary infections after transplantation and should be searched for in cases of multiple, recurrent infections, de novo hypertension, or deterioration of previously stable graft function. There were significant differences in the bacteriologic spectrum of urinary tract infections associated with successful transplants as opposed to unsuccessful transplants.

Patient and graft survival were reviewed in a series of 249 kidney transplants done from 1963 to March 1973. Patient survival was calculated by the life table method for the periods 1963-1970, and 1970-1973, since in 1970 a formal Kidney Center was established and mortality rates changed. Graft survival was analyzed in terms of donor source, HL-A matching and immune responsiveness to HL-A antigens. Three-year predicted mortality for cadaver kidney recipients was 62% between 1963 and 1969 (42 patients) and 8% between 1970 anid 1973 (67 patients). Similar predicted mortality for related living donors was 30% between 1963 and 1969 (52 patients) and 14% between 1970 and 1973 (85 patients). Mortality has continued to decrease and there has been only one death in the last 87 consecutive transplants, including 57 consecutive cadaver transplants. Oneyear predicted kidney survival for the 10-year period is 44% for cadaveric, 60% for non HL-A identical related living and 90% for HL-A identical sibling donors. In the cadaver group, those sharing 2 or more HL-A antigens had the same kidney survival as the non HL-A identical related living donor grafts. Since cadaver graft recipients are on dialysis for a longer period of time, immune responsiveness can be detected by their response to blood transfusions, whereas this determination could not be made in our related living donor group. Non-responsive cadaver kidney recipients had 80% one year kidney survival. We conclude that transplant mortality can be reduced to less than 10% by the Center approach to treatment of renal disease, dialysis does not adversely affect future transplantation, and excellent (80%) kidney survival can be expected in properly selected cadaver graft recipients.

The foremost goal in organ transplantation is to achieve normal graft function without rejection. 31 (8.7%) of 357 cadaveric kidney transplant had no evidence of rejection for the first 3 months. Among these, 2 patients died with a functioning graft and four grafts failed during the 1- to 7-year follow-up period. Actuarial graft survival rates of these patients were 96.8 and 79.0% at 2 and 5 years, respectively, as compared with 64.6 and 51.2%, respectively, for the controls (p less than 0.01). Multiple preoperative blood transfusions and the adjunctive immunosuppressive therapy with retroplacental gamma globulin appeared to be playing a role for the induction of the 'no-rejection' state. However, continuous immunosuppressive therapy is necessary to maintain graft function.

1. One hundred milliliters of stored whole blood DST, three times at weekly intervals is a practical, less immunizing and effective approach to enhance graft survival in recipients of a living-related donor kidney. 2. This protocol could also be used in sibling donor/recipient pairs who do not share a haplotype as well as in those who share two haplotypes to enhance graft survival. 3. The use of a short course of Cs (6 mg/kg/d for three weeks) along with DST appears to reduce the sensitization rate even lower. The dose of Cs used in this study produced no clinically significant adverse reactions, whereas Aza (1 mg/kg/d) often produces leukopenia. 4. DST produces significantly suppressed donor specific MLC responses in the early post-DST period; however, it increases the response at a later time. DST modulates immune responses in such a way that secondary responses upon grafting are more readily reversible by immunosuppressive agents.

In the first month after transplantation 50% of 193 consecutive renal transplant recipients had bacteriuria. The most common organisms isolated were Streptococcus faecalis (34), Escherichia coli (28), Pseudomonas spp. (11), and staphylococcus (9). There was a significant correlation between infection with Str. faecalis and graft failure at one, three, and twelve months. This observation suggests that urinary infection with Str. faecalis may be associated with graft failure which is probably the result of immunological factors.

Forty-six renal donors who responded to a questionnaire and two additional donors with nephrotic syndrome and renal insufficiency were studied. The mean age was 46 +/- 2.0 years (mean +/- SE). Duration of follow-up was 6 +/- 0.5 years. Serum creatinine levels increased from 1.0 +/- 0.03 mg/dl before donation to 1.2 +/- 0.04 mg/dl at follow-up. The incidence of proteinuria (more than 150 mg over 24 hours) was 39 percent. The serum creatinine level was 1.0 +/- 0.08 mg/dl and 1.2 +/- 0.06 mg/dl in the proteinuric and nonproteinuric groups, respectively. The incidence of hypertension was 31 percent with a serum creatinine level of 1.1 +/- 0.11 mg/dl and 1.2 +/- 0.07 mg/dl in the hypertensive and normotensive groups, respectively. One patient with nephrotic syndrome had proliferative glomerulonephritis. It is concluded that renal donation is associated with a minimal but statistically significant increment in serum creatinine levels. The incidence of mild hypertension and proteinuria is increased, but impact on renal function is minimal as assessed by serum creatinine determination.

Our results concur with earlier published work, by other groups, showing that LRD-recipient pairs with low MLC stimulation usually have better and more prolonged graft success than do those with higher stimulation. Specific HL-A compatibilities or incompatibilities did not seem to affect these results, nor did the presence of an increased number of common loci, short of increasing the apparent chromosome compatibility. The presence of pre-transplant cytotoxic antibodies, in patients with a high MI, however, may unfavorably affect the LRD transplant. The overall results of our LRD transplant experience is shown in Figure 1, and superimposed upon Figure 2, is the current extrapolation of data showing MLC stimulation and haplotype success. Thus, it appears that graft survival may be improved and more closely approach the levels seen in a full-house, diplotype match, by using the MLC results in considering patients for transplantation. Not all patients with a high MLC, however, (see table) reject their grafts and it is impossible to predict pre-transplant who will develop specific allograft enhancement. Before the MI becomes a specific criteria for transplant selection, additional studies of patient stimulation in MLC should be done. Suppression of stimulation by donor cells in autologous serum, as compared to the response to unrelated controls, might provide pre-transplant clues to the presence of enhancing factors. Such studies could provide an index that would be more meaningful than the MI in AB sera alone. Since overall results from both our series and from the Transplant Registry continue to indicate better long term graft survival for LRD than for cadaver transplants, and since the evidence suggests that a successful transplant offers a patient a better quality of life, as well as decreased morbidity and mortality compared to concomitant time spent on hemodialysis, continued LRD transplants with high MI is warranted in some circumstances with the patient's understanding of the overall outcome and backgrouns. Until in vitro tests can be more predictive of individual rather than statistical graft success, the patient with an LRD and a high MI should be given a complete explanation of the probabilities for success or failure, and he and the donor allowed to make an informed decision. The following are guidelines that we proposed for the selection of LRD transplants: 1. Availability and willingness. 2. Medical and psycho-social clearance. 3. ABO compatibility. 4. Negative direct crossmatch. 5. HL-A diplotype or haplotype. 6. MI less than 10 if possible, with or without HL-A antibodies. 7. MI greater than 10 with no HL-A antibodies, if possible. 8. MI greater than 10, with HL-A antibodies, if both donor and recipient clearly understand the enhanced chance for failure.

We observed an epidemic of parainfluenza type 3 viral infection in a renal transplantation service among 16 recent transplant recipients. To assess the effect of infection on transplant function, we retrospectively compared the infected patients with a matched, uninfected control group. In addition to symptoms of a mild upper respiratory tract infection associated with the epidemic, there was an increase in the frequency of acute rejection episodes during the period of infection in the infected group. Nevertheless, outcome in terms of patient and graft survival at six months was not affected when compared with the survival rates of the control group.

Experience with renal allograft fracture occurring in 21 of 246 transplants performed over a 29-month period is reviewed. Clinical manifestations included pain and tenderness at the graft site, fever, and falling hematocrit. The fracture occurred without exception in the course of an acute rejection episode. Diagnosis was made from two days to seven weeks following transplantation; in 13 patients (62%) diagnosis was made within two weeks of surgery. Severe damage to the kidney necessitated nephrectomy in all but two transplants. Of those not removed at initial exploration only one regained function to permit a dialysis-free existance for several months. Histologic examination of the fractured kidneys revealed the pathogenesis to be acute rejection in 13 (62%), accelerated acute rejection in four (19%), and a combination of these processes in four (19%). Conclusions from this study are that fractures of renal allografts: (1) are more frequent than commonly realized; (2) are primarily due to the swelling of acute rejection; (3) are often characterized by sudden onset of pain in the region of the graft accompanied by fever and falling hematocrit; (4) should be treated by prompt surgical intervention to control hemorrhage, to perform nephrectomy if indicated, and to evacuate the hematoma in order to reduce the possibility of secondary infection.

Ninety seven transplant recipients participated in a controlled, clinical trial measuring the graft-enhancing property of a human gamma globulin preparation. The latter was prepared from the blood of pregnant women (RPGG) and contained antibodies with specificities for HLA locus products. Data analysis indicated that RPGG treated recipients had enhanced survival rates of their grafts if they had received one or more blood transfusions prior to transplantation.

We developed a new and simplified donor-specific blood transfusion (DSBT) protocol for prospective kidney transplant recipients from one-haplotype-mismatched related donors. Prospective kidney donors gave 450 ml of blood in a quad-pack unit, and the blood was stored in a blood bank. Twenty-five patients were transfused with 100 ml of the respective donor's whole blood at 1, 8, and 15 days after its storage. After DSBT, only three (12%) developed donor-specific lymphocytotoxic antibodies. Following DSBT, donor-specific mixed lymphocyte culture (MLC) was significantly suppressed, without any accelerated (secondary-type) response in early MLC. In addition, sera obtained after DSBT also suppressed donor-specific MLC significantly. Sixteen recipients subsequently received a kidney transplant from the donor, and all had functioning grafts at three months, but one lost the graft thereafter (graft survival rate: 94% at 12 months). This study indicates that (1) 100 ml of stored whole-blood DSBT three times at weekly intervals is a practical, less immunizing, and effective approach to enhance graft survival in recipients of a one-haplotype-mismatched graft; and (2) immune consequences of DSBT include induction of donor-specific cellular and humoral adaptive responses that might be conducive to successful graft outcome.

We compared 26 HLA-A, B identical sibling kidney-transplant recipients followed for one to 10 years, with 104 HLA-A, B semi-identical kidney recipients from living, related donors to determine clinical differences. Graft-survival rates were significantly better in the HLA identical group at two years (85 per cent identical versus 53 per cent in semi-identical, P less than 0.005); patient-survival rates were high for both (96 per cent in identical and 87 per cent in semi-identical at two years, P less than 0.005). The incidence of complications was similar in HLA identical and semi-identical recipients. Nine of the 26 grafts in HLA identical recipients failed one week to eight years after transplantation. Rejection caused most of the graft failures. Recipients of HLA identical-sibling kidney transplants have a high patient and graft survival, but they also encounter many complications. Immunologic rejection occurs, even with negative mixed lymphocyte culture, suggesting the importance of donor determinants other than the HLAA, B and D other than the HLA-A, B and D.

We analyzed clinical and pathologic data from 36 recipients of 38 renal allografts who developed nephrotic syndrome following transplantation. Three groups were identified on the basis of histologic changes in the graft, and each group had a distinct clinical course. Nine grafts (23.7%) had recurrent glomerulonephritis (GN) (5 membrano-proliferative, 4 focal glomerulosclerosis) and developed nephrotic syndrome at 5.1 months (mean) posttransplant. Renal function deteriorated rapidly, with a 2-year graft survival of 29.7%. Four grafts (10.5%) with de novo GN (3 epimembranous, 1 minimal change) developed nephrotic syndrome at 32 months posttransplant, and all functioned for more than 3 years. Twenty-five grafts (65.8%) had allograft glomerulopathy with the onset of nephrotic syndrome at 9.1 months posttransplant and a 2-year graft survival of 66.6%. The differences in duratin of graft function between grafts with allograft glomerulopathy and recurrent GN (P < 0.01) and in graft survival rates at 2 years among the three groups (P < 0.05) are statistically significant. This analysis indicates that allograft glomerulopathy is the most common cause of kidney transplant nephrotic syndrome. Membranoproliferative GN and focal glomerulosclerosis may recur soon after transplantation and rapidly progress to renal failure in marked contrast to grafts with either de novo epimembranous nephropathy or minimal glomerular change, lesions that are compatible with prolonged graft function.

To examine the effects of hypertension on renal graft function, we studied the clinical course of 144 kidney transplant recipients who had functioning grafts for three to 13 years. The patients were divided into three groups: normotensive (n = 32), controlled hypertensive (n = 49) and uncontrolled hypertensive group (n = 63). In addition to the difference in their blood pressure status, the three groups had significantly different levels of serum creatinine at entry to the study (mean +/- SE in mg/dL: 1.41 +/- 0.02, 8.89 +/- 0.02 and 2.30 +/- 0.03, respectively, P = .0002). Cumulative graft survival (CGS) at ten years for normotensive patients was 81%, whereas it was 58% for controlled hypertensive patients and 50% for uncontrolled hypertensive patients. The difference of CGS between normotensive and hypertensive patients was significant (P = .01), whereas the difference between the two hypertensive groups, controlled v. uncontrolled, was not. If serum creatinine levels at entry to the study were adjusted and the CGS of hypertensive patients was compared to normotensive patients with comparable levels of serum creatinine, the differences in CGS between the two groups were no longer significant. Regression analyses for potential prognostic factors revealed that serum creatinine levels were of more primary importance as a prognostic variable than blood pressure status. We conclude that hypertension is an important risk factor for renal graft survival, but control of hypertension alone does not appear to improve it. Graft survival appears to be influenced more by the severity of graft dysfunction at entry to the study irrespective of blood pressure control.

Delayed hyperacute rejection, with its characteristic clinical course and histopathologic findings, occurred within one month after transplantation in five recipients of kidney transplants from HLA-A, B and D identical sibling donors. In all cases, unidirectional mixed lymphocyte cultures and immunologic studies to detect cytotoxic antibodies in the recipients against their respective donors, before kidney transplantation and after transplant nephrectomy, were unresponsive or negative. Onset of delayed hyperacute rejection was preceded by bacteremia in two of these patients. Two of these received second kidney transplants, three to six months later, from HLA-A, B and D identical sibling donors again. Although both have had an episode of acute rejection in the early postoperative period, the grafts have maintained excellent function for 21 and 25 months, respectively. Irreversible forms of transplant rejection, such as delayed hyperacute rejection, do occur even in recipients of kidney transplants from HLA-A, B and D identical sibling pairs, indicating that genetic determinants other than HLA-A, B and D loci, and perhaps other nongenetic immune mechanisms, play an important role in the ultimate results of kidney transplantation.

Unlabelled: Urinary calculi are an uncommon complication in renal transplant recipients. During a 15-year period, in 544 cases of kidney transplantation with a functioning allograft for more than 3 months, and a long-term follow-up, we have observed 9 cases (1.7%) of urinary calculi. Calculi occurred in 6 male and 3 female patients, 6 patients were recipients of living related and 3 of cadaveric kidneys. Calculi were diagnosed as early as 3 months and as late as 3.5 years after transplantation, but most were detected within the first year. The location of the calculi was the bladder in 4 cases, the transplant in 3, and indeterminant in 2. Crystallographic analysis of retrieved stones revealed calcium oxalate and/or phosphate in 4 cases, triple phosphate in 2, and uric acid in 1. All patients had one or more stone-predisposing factors, such as obstructive uropathy and recurrent urinary tract infection (4 cases), hyperoxaluria (3), or hypercalciuria (2). During long-term follow-up (mean 60 months), only one patient lost the renal graft, 14.5 years after transplantation, primarily from causes unrelated to urinary calculi. One instance of stone recurrence was noted., In Conclusion: (1) urinary calculi after renal transplantation are relatively uncommon; (2) predisposing factors and crystallographic composition of the calculi are identical in type, but not frequency, to those of nontransplant patients; and (3) with proper medical and surgical management, post-transplant urolithiasis does not appear to affect graft prognosis.

Between July 1971 and March 1977, steroid-induced diabetes (SD) developed postoperatively in 31 (10.8%) of 286 nondiabetic adult kidney transplant recipients who were observed for a total of 410 patient transplant years. There was a highly significant association between HLA-A28 and SD. There was no significant association between SD and BB or Bw 15. Age was also associated with SD. However, A28 was associated with SD even when corrected for age. A28 occurred more frequently in blacks than whites, 25.4% and 6.3%, respectively, and accounted for the higher incidence of SD in black adults. There were no significant associations between SD and patients' sex, donor source, number of short-term rejection treatments, or maintenance dose of corticosteroids. Steroid-induced diabetes had no adverse effects on graft or patient survival.

High-dose steroids administered to renal allograft recipients for treatment of acute graft rejection episodes may affect cell cycle progression of peripheral blood mononuclear (PBM) cells. DNA synthesis and cellular DNA and RNA contents of PBM cells were measured in 8 patients during clinically stable periods, and in another 10 patients both during acute rejection episodes and during 7 days of administration of high-dose steroids. Improved renal function documented successful reversal of the rejection episodes in the 10 patients. Compared with the stable patients, the rejecting patients had higher numbers of cells undergoing clonal expansion--namely, higher proportions of G1-cells and of proliferating, or S, G2, and M (SG2M) cells. Steroid treatment had no acute effects on proportions of G1 or SG2M cells in vivo or on incorporation of 3H thymidine by PBM cells in vitro. However, cells in the prereplicative compartment of the cell cycle (G0/1 cells) had significantly lower RNA content within 7 days of treatment with high doses of steroids. The results suggest that steroids do not acutely influence the posttranscriptional synthesis and the contents of nucleic acids of cells undergoing clonal expansion in vivo. The prereplicative phase of allogeneically stimulated PBM cells of renal allograft recipients may therefore be the cell cycle phase most sensitive to steroids in vivo.