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PubMed1986

Catalytic activities of alkaline phosphatase and N-acetyl-beta-D-glucosaminidase in human cortical nephron segments: heterogeneous changes in acute renal failure and acute rejection following kidney allotransplantation.

The catalytic activities of alkaline phosphatase and N-acetyl-beta-D-glucosaminidase, constituents of luminal brush-border membranes and lysosomes of kidney tubular cells, were measured in human kidney allografts in the maintenance and recovery phases of acute renal failure and in acute rejection crisis. The enzyme activities were fluorometrically determined in single microdissected cortical nephron segments of biopsies from 4 kidney allografts taken intraoperatively and postoperatively at different periods, which exhibited either good function or dysfunction. For comparison, the unaffected part of a human kidney nephrectomized due to hypernephroma as well as a biopsy of a morphologically normal human kidney were examined. Both enzymes displayed highest activities in the proximal part of the human nephron. In some intraoperative and postoperative biopsies with acute renal failure, alkaline phosphatase activity was reduced in proximal tubules, predominantly in the straight portion. This reduction could not be correlated with function. In acute rejection, very low alkaline phosphatase activities were uniformly found in proximal convoluted and straight tubules. Furthermore, intraoperative biopsies and biopsies of the functioning allograft have only approximately 50% of normal N-acetyl-beta-D-glucosaminidase activity in proximal convoluted tubules, but generally normal values in the straight portion. However, in acute renal failure, this enzyme activity was several-fold enhanced along the whole nephron, when compared with intraoperative values. In acute rejection, N-acetyl-beta-D-glucosaminidase activity was slightly reduced in proximal convoluted tubules, when compared with biopsies showing good function. It is suggested that the decrease of proximal tubular enzyme activities is the consequence of increased enzymuria and inadequate enzyme regeneration. On the other hand, the overshoot of N-acetyl-beta-D-glucosaminidase activity in the maintenance phase of acute renal failure appears to indicate increased degradative capacity, associated with cellular regeneration along the whole nephron.

Acetylglucosaminidase↗

PubMed1981

Growth acceleration following renal transplantation in children less than 7 years of age.

Of 110 consecutive renal allografts performed at Children's Hospital Medical Center 12 were in 11 patients aged 3 to 7 years. Patient and graft survival and linear growth were evaluated in these 11 children. All 11 are surviving, seven (64%) with functioning allografts 12 to 92 months after transplant. Six of these seven have normal renal function (on alternate day prednisone dose less than 0.7 mg/kg every two days plus daily azathioprine) and all seven have shown catch-up growth, reaching and maintaining normal height for age. An eighth patient, now returned to dialysis, grew from below the third percentile at age 3 years to the 25th percentile at age 8 years, after which renal function deteriorated. Three patients rapidly rejected allografts and have had decreased growth velocity for age. In contrast, although many of the remaining 76 patients who received 98 transplants after age 7 years are growing, none showed accelerated linear growth sufficient to catch up if below the third percentile for age or to cross centile lines if above. Neither the degree of pretransplant bone age retardation nor steroid dose per kilogram accounted for lack of growth acceleration of those more than 7 years of age. Despite small sample size, the growth of renal transplant recipients less than 7 years of age suggests that they are good, and in some ways, favored transplant candidates.

Adolescent↗

PubMed2005

Total femur replacement procedures in tumor treatment.

UNLABELLED: Replacement of bone segments after resection of a tumor-containing bone has a long history, and currently metallic implants and allografts have reasonable rates of success in terms of patient survival and restoration of useful function. Total femoral resections for extensive tumors are uncommon but clearly represent a major problem, which in the past has required hip disarticulations. In recent years, resection and replacement using custom metallic implants and more recently modular devices have allowed the patients to be restored to reasonable function. Allografts have not been used commonly for this purpose. During the past 23 years, we have done 15 total femoral replacements for osteosarcoma, chondrosarcoma, metastatic carcinoma, and an osteonecrotic fractured femur in a patient with rheumatoid arthritis and for a patient with severe deformity based on Paget's disease. Ten of these patients had allografts implanted with total hip replacement and total knee replacement implants and five patients had metallic implants. Eight of the patients died from disease, but the remaining seven have done reasonably well in terms of function and absence of complications such as fracture or infection. None of the patients required an amputation. The procedure is complex and metallic implant and allograft implantation require wide surgery and special systems of reconstruction. LEVEL OF EVIDENCE: Therapeutic study, Level IV-1 (case series). See the Guidelines for Authors for a complete description of levels of evidence.

Adolescent↗

PubMed1997

Effect of initial slow graft function on renal allograft rejection and survival.

Cadaver renal allografts with immediate excellent function have good long-term outcomes, while grafts with delayed function have been associated with an increased incidence of acute rejection (AR) and subsequent poor long-term graft survival. There is, however, an intermediate group with initial slow function whose outcome is not well defined. This group was examined by reviewing 510 patients that received primary cadaver transplants between 1/85 and 8/95. Recipients were grouped by initial function into: 1) those with immediate graft function (IGF), defined by serum creatinine (Cr) level < 3 mg/dl on post-operative day (POD) 5 (n = 237); 2) those with slow graft function (SGF), defined by serum Cr > 3 mg/dl on POD 5 but no need for dialysis (n = 160); and 3) those with delayed graft function (DGF), defined by the need for dialysis in the first week post-transplant (n = 113). Five-year graft survivals were determined for each group by Kaplan-Meier methods and compared by a generalized Wilcoxon test. The incidence of AR in the first 6 months was significantly higher in those with SGF (40%) vs. those with IGF (30%) (p < 0.05); both groups had a lower incidence than those with DGF (47%) (p < 0.05). In the absence of AR, 5-yr graft survival was similar between the 3 groups, 94%, 97% and 92% for IGF, SGF and DGF respectively. In the presence of AR, 5-yr graft survival was significantly reduced in all groups, but most notably in those with SGF (51%) or DGF (53%), as compared to those with IGF (80%), (p < 0.001). We conclude that recipients with SGF, but no AR, have excellent outcomes, comparable to those with IGF. However, there is an increased incidence of early AR associated with SGF. In recipients with SGF or DGF, AR has a more profound detrimental effect on long-term graft survival than in the IGF group. Thus, recipients with SGF are at increased risk for AR with resultant poor long-term graft survival, and may need modified immunosuppressive protocols.

Adult↗

PubMed1984

Membranous glomerulopathy following kidney transplantation. Association with renal vein thrombosis in two of nine cases.

The association of renal vein thrombosis and membranous glomerulopathy in native kidneys has been well documented. However, this association has only occasionally been described following renal transplantation. A review of 693 renal transplant recipients revealed 77 (11%) in whom persistent, heavy proteinuria (greater than 2 g/24 hr) developed. Renal histology was available in all 77 patients. A diagnosis of membranous glomerulopathy was made in 7 patients. Two further cases were added on the basis of biopsy findings--1 patient had a protein excretion of 1.7 g/24 hr, the other had microscopic hematuria and red cell casts in the urine. Renal venography was performed in 4 cases. The decision to perform venography was based on clinical criteria (thrombophlebitis or marked edema of the leg on the side of the allograft), and/or histological criteria (associated interstitial edema and venous congestion). Renal vein thrombosis was present in 2 patients. Three of the 9 patients had membranous glomerulopathy as the cause of their end-stage renal disease; 2 of these patients had received kidneys from living-related donors. Four of the patients were classified as having de novo membranous glomerulopathy on the basis of having a different cause for their end-stage renal disease. Two patients were classified as having unspecified membranous glomerulopathy; both of these patients had had chronic glomerulonephritis, but there was lack of characterization of the original glomerular disease. Seven of the 9 patients continued to have stable allograft function 1-12 months after the diagnosis of membranous glomerulopathy was made in the renal allograft. The remaining 2 patients both had associated renal vein thrombosis; 1 had progressive deterioration of renal function and returned to dialysis 24 months after the diagnosis of membranous glomerulopathy had been made, while the other died of unrelated causes 27 months after the diagnosis had been made.

Adult↗

PubMed1999

Hydroxyethyl starch does not impair immediate renal function in kidney transplant recipients: a retrospective, multicentre analysis.

BACKGROUND: The effect of hydroxyethyl starch (HES) on early allograft function was examined retrospectively in a cohort of 119 renal transplantations realized by local organ exchange between four cooperating centres. METHODS: After exclusions, 109 transplant procedures were subdivided in three groups according to donor colloid loading: (i) HS-group (Haes steril 6%, mean volume (SD): 979 (946) ml, n = 20); (ii) PS-group [Plasmasteril, mean volume (SD): 769 (411) ml, n = 16]; and (iii) control group (gelatin albumin, n=73). RESULTS: Delayed graft function (DGF), defined as the need for dialysis during the first post-transplant week, occurred in 3/20 (15%) cases in the HS-group, in 5/16 (31%) cases in the PS-group and in 14/73 (19%) cases in the control group (P = 0.450). Uni- and multivariate analysis revealed older donor age (P = 0.001) and kidney preservation with histidine-tryptophan-ketoglutarate (HTK) (P = 0.001) as the only factors associated with a higher incidence of DGF. CONCLUSIONS: Renal function as measured by daily serum creatinine concentration and 24 h urinary output up to 14 days post-transplantation in the HS-group was comparable with that of controls. The higher serum creatinine observed during the first seven post-transplant days in the PS-group could be related to higher donor age and haemodynamic instability, and recipient male preponderance, rather than to HES itself.

Adult↗

PubMed2004

Noninvasive detection of renal allograft inflammation by measurements of mRNA for IP-10 and CXCR3 in urine.

BACKGROUND: We explored the hypothesis that measurements of mRNA encoding interferon-inducible protein-10 (IP-10) or the chemokine receptor CXCR3 in urinary cells offer a noninvasive means of elucidating cellular traffic causing acute rejection of human renal allografts. METHODS: We obtained 63 urine specimens from 58 renal allograft recipients who underwent 63 allograft biopsies to resolve the basis for graft dysfunction, and 27 additional urine samples from 24 other patients with stable allograft function. Twenty-seven of the 63 biopsies were classified as acute rejection, 20 as other, and 16 as chronic allograft nephropathy. We measured the levels of transcripts for IP-10 and CXCR3, and a constitutively expressed gene 18S rRNA in the urine specimens and correlated transcript levels with renal allograft diagnosis. RESULTS: mRNA levels of IP-10 (P < 0.0001) or CXCR3 (P < 0.0001) but not the levels of 18S rRNA (P= 0.56) predicted intragraft cellular traffic causing acute rejection. Receiver-operating characteristic curve analysis demonstrated that acute rejection can be predicted with a sensitivity of 100% and a specificity of 78% using the (log-transformed) cutoff value of 9.11 copies of IP-10, and with a sensitivity of 63% and a specificity of 83% using the cutoff value of 11.59 copies of CXCR3. Immunohistologic analysis of allograft biopsies showed exuberant expression of IP-10 and CXCR3 during acute rejection whereas both were absent in grafts with stable function. CONCLUSION: Our investigation demonstrates that intragraft cellular events associated with acute rejection of human renal allografts can be noninvasively identified by measurements of mRNA for IP-10 and CXCR3 in urinary cells.

Adult↗

PubMed1985

In vitro allograft irradiation prevents graft-versus-host disease in small-bowel transplantation.

In small-bowel transplantation, the transfer of large numbers of donor lymphocytes with the intestinal allograft may provoke a lethal graft-versus-host reaction. The effectiveness of allograft irradiation in vitro as a method of preventing graft-versus-host disease (GVHD) was studied in a rat model of small-bowel transplantation, with the Lewis----Lewis X Brown Norway F1 hybrid strain combination. Cold harvested small-bowel allografts were irradiated immediately prior to heterotopic or orthotopic transplantation. Animals that had received heterotopic allografts irradiated with 0, 250, or 500 rad all died of GVHD after 14.4 +/- 3.0, 15.0 +/- 1.3, and 14.2 +/- 1.9 days, respectively. None of the animals that had received allografts treated with 1000 rad developed clinical or pathologic evidence of GVHD, however, and all survived for more than 6 months (P less than 0.001). Allograft function was studied in animals that underwent orthotopic transplantation. Recipients of nonirradiated orthotopic allografts all died of GVHD after 14.0 +/- 0.7 days, whereas recipients of allografts irradiated with 1000 rad all survived for more than 5 months (P less than 0.001). After 120 days, weight gain (51.8 +/- 11.7%), serum albumin (3.9 +/- 0.7 g/dl), serum triglycerides (67.0 +/- 24.3 mg/dl), CBC, and differential in these animals were not statistically different from those in either age-matched isograft recipients or normal animals, and when the rats were sacrificed, irradiated allografts showed no changes suggestive of radiation injury. These results indicate that irradiation of small-bowel allografts in vitro prevents development of GVHD, and that this can be achieved at a dose which does not cause injury to or malfunction of the allograft.

Animals↗

PubMed1975

Pediatric renal transplantation.

Thirty-one children received 38 kidney transplants from 22 live and 16 cadaver donors. Among the 31 patients, 25 received one transplant each, 5 received two transplants each and 1 received three transplants. Peritoneal or hemodialysis (or both) was carried out in 22 patients, with an average dialytic maintenance of 12 weeks before transplantation. Posttransplant immunosuppressive therapy included prednisone and azathioprine. Antilymphocyte globulin was administered to 33 recipients as adjunctive immunosuppressive therapy. At present, 23 patients have functioning allografts, 3 are on hemodialysis and 5 are dead. Of 22 live kidney transplants, 18 are presently functioning two months to 14 years after transplantation with an average of 36 months. Of 16 cadaver kidney transplants, 5 are presently functioning 9 to 57 months after transplantation with an average of 32 months. Actuarial live donor allograft survival for one year was 76 percent, for two years was 66 percent and for three years was 64 percent. Cadaver allograft survival was 50 percent, 40 percent and 40 percent, respectively. Complications were urologic and infection related. Of nine recipients with sustained hypertension, in six the condition was due to chronic rejection, while in one it was due to recurrence of the original disease in the allograft. Linear growth was measured in 15 children who were less than 14 years of age at the time of transplantation and in whom allografts survived more than one year. Maximum average linear growth velocity occurred during the first year after transplantation. Our experience indicates pediatric renal transplantation can be successfully used in the treatment of terminal renal failure.

Adolescent↗

PubMedDate not supplied

Hepatic artery angioplasty after liver transplantation: experience in 21 allografts.

PURPOSE: To assess whether percutaneous transluminal angioplasty (PTA) can help prolong allograft survival and improve allograft function in patients with hepatic artery stenosis after liver transplantation. PATIENTS AND METHODS: Hepatic artery PTA was attempted in 19 patients with 21 allografts over 12 years. The postangioplasty clinical course was retrospectively analyzed. Liver enzyme levels were measured before and after PTA to determine if changes in liver function occurred after successful PTA. RESULTS: Technical success was achieved in 17 allografts (81%). Retransplantation was required for four of 17 allografts (24%) in which PTA was successful and four of four allografts in which PTA was unsuccessful; this difference was significant (P = .03). Two major procedure-related complications occurred: an arterial leak that required surgical repair and an extensive dissection that necessitated retransplantation 14 months after PTA. Hepatic failure necessitated repeat transplantation in seven cases from 2 weeks to 27 months (mean, 8.4 months) after PTA. Six patients died during follow-up, three of whom had undergone repeat transplantation. Markedly elevated liver enzyme levels at presentation were associated with an increased risk of retransplantation or death regardless of the outcome of PTA. CONCLUSION: PTA of hepatic artery stenosis after liver transplantation is relatively safe and may help decrease allograft loss due to thrombosis. Marked allograft dysfunction at presentation is a poor prognostic sign; thus, timely intervention is important.

Aged↗

PubMed2001

An analysis of early renal transplant protocol biopsies--the high incidence of subclinical tubulitis.

To investigate the possibility that we have been underestimating the true incidence of acute rejection, we began to perform protocol biopsies after kidney transplantation. This analysis looks at the one-week biopsies. Between March 1 and October 1, 1999, 100 adult patients undergoing cadaveric kidney or kidney/pancreas transplantation, or living donor kidney transplantation, underwent 277 biopsies. We focused on the subset of biopsies in patients without delayed graft function (DGF) and with stable or improving renal function, who underwent a biopsy 8.2+/-2.6 d (range 3-18 d) after transplantation (n = 28). Six (21%) patients with no DGF and with stable or improving renal function had borderline histopathology, and 7 (25%) had acute tubulitis on the one-week biopsy. Of the 277 kidney biopsies, there was one (0.4%) serious hemorrhagic complication, in a patient receiving low molecular weight heparin; she ultimately recovered and has normal renal function. Her biopsy showed Banff 1B tubulitis. In patients with stable or improving renal allograft function early after transplantation, subclinical tubulitis may be present in a substantial number of patients. This suggests that the true incidence of rejection may be higher than is clinically appreciated.

Adult↗

PubMed1979

Alimentary tract complications after renal transplantation.

A computer analysis of post renal transplantation gastrointestinal problems was performed to identify important associated clinical factors. Thirty-seven per cent of all transplant recipients developed one or more significant problems. Hemorrhage, nondiverticular intestinal perforation, and esophagitis occurred most frequently in hospitalized patients. Pancreatitis, diverticulitis, and gastroduodenal perforation occurred characteristically in long-term survivors with well functioning allografts. Eleven of 32 HLA identical recipients treated with maintenance corticosteroids during stable kidney function developed gastrointestinal disease while only one of 13 HLA identical recipients not given maintenance steroids developed a problem, which strongly suggests a causal role for steroids in the development of late complications. The association of preexisting peptic ulcer and diverticular disease with hemorrhage and perforation supports previous recommendations that documented peptic ulcer disease or diverticulitis should be corrected surgically prior to transplantation.

Adolescent↗

PubMed2004

Preoperative renal volumes as a predictor of graft function in living donor transplantation.

BACKGROUND: Nephron underdosing and donor kidney-recipient body size mismatch can lead to poor allograft function. The purpose of this study is to examine the relationship between donor kidney volume and posttransplantation graft function by using magnetic resonance imaging (MRI) to obtain renal volumes. Previous investigators used donor body surface area as a surrogate for kidney size or measured renal volume by using ultrasonography; both these techniques are inaccurate measures of renal volume. Intraoperative weights are more accurate, but provide information only after the transplantation is underway. More recently, MRI has been used preoperatively to screen living donors; these novel MRI techniques also provide information regarding renal size. METHODS: We performed a retrospective analysis of 54 patients who underwent living donor transplantation at our institution from 2000 to 2002. All living donors underwent preoperative renovascular imaging using MRI, and renal volumes were obtained for each donor. A transplant kidney volume-recipient body weight (Vol/Wt) ratio was determined for each donor-recipient pair, and patients were divided into tertiles corresponding to 3 groups: high (>2.7), medium (2 to 2.7), and low (<2) "nephron dose" ratios. RESULTS: Glomerular filtration rate (GFR) correlated with Vol/Wt ratio at 6 and 12 months (r = 0.46; P = 0.0005 and r = 0.41; P = 0.003). At 6 months, mean GFRs in the low, medium, and high groups were 52.4 +/- 2.8 (SEM), 64.5 +/- 6.2, and 82.0 +/- 4.4 mL/min, respectively (P < 0.0005). At 12 months, GFRs in the low, medium, and high groups were 51.6 +/- 3.6, 63.3 +/- 3.8, and 83.9 +/- 5.4 mL/min, respectively (P < 0.0001). CONCLUSION: Transplantation of donor-recipient pairs with a Vol/Wt ratio less than 2 cm 3 /kg was associated with significantly worse graft function. Donor kidney volumes measured by means of preoperative MRI can be used to calculate Vol/Wt ratios before transplantation and identify patients at risk for a low GFR posttransplantation.

Adult↗

PubMed1996

Long-term results with single pediatric donor kidney transplants in adult recipients.

PURPOSE: We investigated whether transplantation of single pediatric donor kidneys into adults leads to an increased incidence of functional allograft impairment and complications, as previously reported. MATERIALS AND METHODS: To evaluate long-term functional outcome using single pediatric donor kidneys 60 adults (study group) who underwent transplantation between March 1973 and December 1988 using single pediatric donor kidneys 6 years old or younger (mean donor age plus or minus standard deviation 41.1 +/- 17.9 months) were compared to 58 matched adults (control group) who underwent transplantation with adult kidneys (mean donor age 29.7 +/- 10.8 years). The groups were identical for era of transplantation, recipient age, sex and followup (82 versus 83 months). RESULTS: There was no difference in patient survival between the study and control groups (p = 0.26). In the study group there were an increased requirement for early dialysis (45 versus 24%, p = 0.02), a higher incidence of proteinuria (greater than 0.8 gm./24 hours, 67 versus 48%, p = 0.04) and a higher incidence of rejection within the first 6 months (80 versus 64%, p = 0.05). There was also an increased incidence of graft failure from acute rejection in the study group. Early differences in serum creatinine levels in the 2 groups dissipated after 3 months. Renal allograft histopathology revealed no significant difference in the incidence of focal segmental glomerulosclerosis in the study versus control groups after transplantation (22.9 versus 13.3%, p = 0.70). However, focal segmental glomerulosclerosis manifested sooner after transplantation in study than control patients (mean 37 versus 82 months). After transplantation proteinuria developed in study patients with focal segmental glomerulosclerosis at a mean of 4.6 months compared to 31.8 months in controls with post-transplant focal segmental glomerulosclerosis. Graft survival in the study group was superior when cyclosporine was given rather than conventional noncyclosporine based immunosuppression. Five-year graft survival rates were 48 versus 44% for cyclosporine treated and 33 versus 44% for conventionally treated study versus control patients. CONCLUSIONS: These data suggest that with cyclosporine immunosuppression transplanting single pediatric kidneys into adults yields the same long-term functional graft outcome as adult donor kidneys.

Adult↗

PubMedDate not supplied

Intestinal and multivisceral transplantation: dynamics of nutritional management and functional autonomy.

OBJECTIVE: The objective of this study was to describe the dynamics of nutrition management of intestinal transplant recipients and allograft functional autonomy. METHODS: Intestinal absorptive functions and recipient nutritional status were monitored during the 12-month study period. Absorption was evaluated with D-xylose absorption and fecal fat excretion. Indices for nutrition were body weight, anthropometric measures, and serum albumin. RESULTS: Before transplant, all patients were total parenteral nutrition (TPN) dependent and well nourished. By the first postoperative month, all 22 recipients were tolerating enteral feeding. By 3 months, all recipients had begun oral feeding, with 13 off TPN and 7 off enteral feeds. By 6 months, 16 recipients were off TPN, and by the end of the 12th month, 17 (77%) were free of TPN. Although all 22 recipients were completely weaned off TPN during the first posttransplant year, 10 required temporary reinstitution of therapy at different points. Full nutritional autonomy was achieved at 3 months by 3 recipients, at 6 months by 8 recipients, and at 12 months by 12 (55%) recipients. CONCLUSIONS: These results reflect our early experience that led to surgical refinement of the operation and evolution of the recipient postoperative management. Nonetheless, even in this initial cohort, most of the engrafted intestines restored the recipient nutritional autonomy, and all survivors remained well nourished.

Adult↗

PubMed1988

Evidence that pretransplant donor blood transfusion prevents rat renal allograft dysfunction but not the in situ cellular alloimmune or morphologic manifestations of rejection.

The effects of preoperative donor-specific blood transfusion (DSBT) on the physiologic, morphologic, and immunologic aspects of allograft responsiveness were evaluated in a rat renal transplant model, using the ACI (RT1a) into PVG (RT1c) high-responder strain combination. Indefinite graft survival (mean greater than 63 days) could be induced by DSBT administration alone. In comparison, animals receiving autologous blood transfusion (ABT) all died within 7 days posttransplantation. As assessed by clearance of inulin and paraaminohippurate, renal allograft function in DSBT-pretreated recipients at 6 days was equivalent to that of isograft recipients, and in contrast to the significant reduction seen in ABT treated rats. Likewise, thromboxane B2 (TXB2) production by ex-vivo-perfused allografts from DSBT-treated recipients was comparable to that of isografts, and significantly lower than that of allografts from ABT-treated rats. A significant inverse correlation was found between renal TXB2 production and inulin clearance. Despite these substantial differences in renal function and eicosanoid metabolism, morphologic evaluation of renal allografts from DSBT-enhanced and ABT-rejecting recipients at comparable time points showed equivalent histologic manifestations of rejection. In addition, immunohistologic labeling of renal allograft sections and fluorescence-activated cell sorter analysis of cells eluted from allografts showed the same phenotype and pattern of infiltrating T cell subsets in both groups. Specific antidonor cytotoxic T lymphocyte precursor (pCTL) frequencies of cells eluted from kidney grafts were equivalent in DSBT and ABT-pretreated animals, and both groups expressed significantly higher (but equivalent) pCTL frequencies in the kidneys than spleens. Comparisons of the lysis of PVG.R1 (RT1.Aa on a PVG background) and ACI targets indicated that cytotoxic responses from effector cells freshly eluted from DSBT and ABT kidneys were primarily directed against allogeneic class I major histocompatibility complex (MHC) specificities, whereas several long term T cell lines generated from 6-day kidney transplants of both groups expressed a predominant W3/25+ (T helper) phenotype and cytotoxic activity against donor specificities other than RT1.Aa class I MHC. Specific antidonor proliferative T lymphocyte (pPTL) precursor frequencies of cells eluted from renal allografts were also equivalent for both DSBT- and ABT-treated recipients, and the range of pPTL frequencies for allograft cell eluates was similar to that in spleens, regardless of the source of the transfusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1997

Relationships between arterial hypertension and renal allograft survival in African-American patients.

In previous studies, we showed that in African-American patients arterial hypertension during the first 6 months after transplantation is associated with a high risk of renal allograft loss. In this study, we sought to examine the relationships between pretransplant blood pressure (preBP), blood pressure early after transplantation (postBP), and allograft function and survival. The study included 116 African-American recipients of first cadaveric renal allografts followed for 64 +/- 40 months. Prior to transplantation, 78% of the patients required antihypertensive medications and 59% had poorly controlled BP (average mean arterial pressure, > or =107 mm Hg). Blood pressure levels increased significantly during the first month posttransplant, particularly in patients with poorly controlled preBP. During the first 6 months posttransplant, 95% of patients required antihypertensive drugs; after the transplant, patients required significantly more and higher doses of antihypertensives compared with pretransplant. In 38% of the patients, postBP remained high despite therapy. The level of postBP correlated with the patient's weight pretransplant and with the level of preBP. Pretransplant BP correlated with postBP 1 month after transplantation (r = 0.4, P < 0.0001), and 70% of the patients with poorly controlled postBP had uncontrolled preBP. Patients with poorly controlled preBP had worse graft survival than patients with well-controlled preBP (P = 0.03 by Cox regression). Furthermore, compared with patients with well-controlled postBP, patients with high postBP had higher serum creatinine at 10 days (P = 0.04) and at 6 months (P = 0.0004) posttransplant; these patients had reduced graft survival (P = 0.0006 by Cox). We found no objective evidence of differences in patient compliance between individuals with high postBP and those with well-controlled postBP. This study confirms the association between high postBP and reduced renal allograft survival in African-American patients. In addition, these results show that the level of preBP can be used to identify patients at high risk of developing severe hypertension immediately after transplantation and those at risk for renal allograft failure.

Adult↗

PubMed2003

CD69 expression on peripheral CD8 T cells correlates with acute rejection in renal transplant recipients.

BACKGROUND: The development of a noninvasive method to diagnose renal allograft rejection could prevent the complications associated with graft biopsy and allow more accurate surveillance of allograft function. The present study determines whether expression of CD69 on peripheral T lymphocytes of renal allograft recipients correlates with the presence of acute graft rejection. METHODS: Peripheral blood T lymphocytes from healthy volunteers, renal allograft recipients with elevated creatinine but no evidence of rejection on biopsy, and renal allograft recipients with biopsy-proven rejection were analyzed by flow cytometry for the expression of CD69 and various intracellular cytokines (interleukin-2, interferon-gamma). Results were then compared with the degree of rejection on biopsy. RESULTS: CD69 expression on CD3+, CD4+, and CD8+ T-cell subsets was low in controls and transplant recipients without allograft rejection. In contrast, patients with renal allograft rejection showed significantly elevated percentages of CD69+ cells in the CD3+ (P<0.01) and CD8+ subsets (P<0.01). The fraction of CD69+ and CD8+ T cells was found to be a more clinically useful test based on receiver-operator characteristics. CD69 expression on CD4+ T cells did not correlate with rejection. Significant intracellular cytokine levels were not detected in unstimulated T cells from any of the groups; stimulation with mitogens increased expression equally among the three groups. CONCLUSIONS: We demonstrate that expression of CD69 on CD3+ and CD8+ peripheral blood T cells correlates closely with the presence of acute graft rejection in renal allograft recipients. Measurement of this surface marker may provide a rapid, noninvasive, and accurate means by which graft rejection can be identified.

Acute Disease↗