The detection of renal allograft rejection by fine-needle intrarenal manometry

The causes of early renal allograft malfunction include rejection, acute tubular necrosis, cyclosporin nephrotoxicity and vascular complications. Fine-needle intrarenal manometry is a potential method of distinguishing rejection from the other causes of malfunction and has been used by Salaman and Griffin in patients' treated with cyclosporin. The technique involves inserting a fine-needle, which is connected to a specially designed manometer, into the substance of the transplant kidney. One hundred and six measurements of intrarenal pressure have been made in 28 patients immunosuppressed with either azathioprine and prednisolone or cyclosporin. Thirteen rejection episodes were identified and confirmed by biopsy. These were treated by pulse steroid (methylprednisolone) therapy. Seven episodes of cyclosporin toxicity were identified and there were fifteen episodes of acute tubular necrosis. The mean intrarenal pressure in the rejecting group was 52.8 mmHg compared with 22.3, 24.1 and 24.3 mmHg for the normal function, acute tubular necrosis and cyclosporin nephrotoxicity groups, respectively (P less than 0.01; Wilcoxon unpaired test). There were no differences within these groups related to the type of immunosuppression used. There were no clinical complications associated with the procedure. Thus in newly transplanted patients, fine-needle intrarenal manometry accurately identified rejection and distinguished it from normal function, acute tubular necrosis and cyclosporin nephrotoxicity in all the patients regardless of the immunosuppressants used.     

An assessment of intrarenal hydrostatic pressure measurements in the diagnosis of acute renal allograft rejection

Postoperative intrarenal pressure measurements may be an aid to the diagnosis of acute renal transplant rejection, especially in patients treated with cyclosporine. Serial measurements of intrarenal pressure were made in 38 recipients using a fine-needle technique. Thirty-two intraoperative and 207 postoperative measurements were made, and 39 clinical rejection episodes (23 confirmed by biopsy) monitored. Intraoperative pressures in grafts with immediate function (37.4 +/- 4.0 mmHg, mean +/- SEM) were not significantly different from those with delayed function (30.9 +/- 4.8 mmHg), whereas postoperative pressures were greater (P less than 0.01) in kidneys with acute tubular necrosis (29.4 +/- 1.9 mmHg) than in functioning grafts (20.4 +/- 0.9 mmHg). Pressures recorded during clinical rejection episodes (44.3 +/- 2.3 mmHg) exceeded (P less than 0.001) those during quiescent periods (23.6 +/- 1.0 mmHg). During rejection episodes, higher pressures (P less than 0.01) were recorded from tender or palpably enlarged grafts (52.5 +/- 3.0 mmHg) than in the absence of these signs (36.3 +/- 3.1 mmHg), and patients whose transplants biopsies showed cellular rejection tended to have greater pressures (50.1 +/- 4.1 mmHg) than those with concomitant vasculopathy (36.4 +/- 3.9 mmHg), but the latter did not reach statistical significance. In 7 cases of cyclosporine toxicity the intrarenal pressure was 17.8 +/- 4.2 mmHg. Using a diagnostic cut off point of 40 mmHg, the investigation failed to recognize 26% of acute rejection episodes--and, in the presence of acute tubular necrosis, it wrongly categorized 21% of nonrejectors. While its predictive capacity was limited, the test may occasionally be helpful in the differentiation of cyclosporine toxicity and rejection in functioning kidneys.     

The use of fine-needle intrarenal manometry in the management of renal transplant patients receiving cyclosporine

The pressure inside a renal transplant can be measured by means of a fine (25-G) needle passed into the kidney, and we have shown previously that a rise in pressure to more than 40 mmHg commonly occurs during rejection episodes. A rise was not observed in patients with cyclosporine nephrotoxicity or acute tubular necrosis, so we have now used this test prospectively as part of our management of 37 patients undergoing renal transplantation. Fine needle intrarenal pressure was recorded weekly during the first three weeks after transplantation, with more frequent measures taken in patients with deteriorating or absent renal function. Treatment was dictated by the result of these tests. Deteriorating function in a kidney registering a normal pressure was diagnosed as cyclosporine nephrotoxicity and the dose of cyclosporine was reduced appropriately. A pressure reading in excess of 40 mmHg was regarded as rejection--and, after obtaining a conventional needle biopsy of the kidney, antirejection treatment was commenced immediately. Nineteen episodes of nephrotoxicity were confirmed and there was only one false-positive result. Twenty-eight of twenty-nine rejection episodes (observed in twenty-three patients) were associated with a significant rise in intrarenal pressure and were treated appropriately. In six patients who were oliguric at the time, as a result of posttransplant acute tubular necrosis, this rise in pressure was the first indication of rejection. A high pressure was recorded on the first day that the creatinine rose in two-thirds of the cases. In the remainder the pressure was seen to rise more slowly, particularly when the rejection was of the chronic vascular type and was occurring two months or more after transplantation. Fine-needle intrarenal manometry accurately identified rejection episodes in newly transplanted patients--and, because the results were unaffected by cyclosporine nephrotoxicity and acute tubular necrosis, the test was of most value in monitoring patients with these conditions.     

Combination fine-needle aspiration cytology and intrarenal manometry at the onset of renal dysfunction

Twenty-three consecutive cadaveric renal allograft recipients immunosuppressed with cyclosporin have been monitored three times a week by fine-needle aspiration cytology and intrarenal manometry until discharge from hospital or until 30 days post-transplant. Standard criteria were used to determine the cause of allograft dysfunction. The onset of allograft rejection was marked by an elevation of the total corrected increment score by fine-needle aspiration cytology in 80 per cent of rejection episodes whereas intrarenal pressure was raised in only 46.6 per cent. However, intrarenal pressure was greater than 40 mmHg on a single occasion in 16 measurements performed on allografts showing evidence of cyclosporin nephrotoxicity. By combining fine-needle aspiration cytology and intrarenal manometry the sensitivity of these tests for allograft rejection was increased to 93.3 per cent at the onset of renal dysfunction. Our results demonstrate that fine-needle aspiration cytology is more sensitive than intrarenal manometry as a single investigation. However, the combined test may have an important role in the differentiation of allograft rejection and cyclosporin nephrotoxicity in the early management of renal allograft recipients.     

Limited value of 111-indium platelet scintigraphy in renal transplant patients receiving cyclosporine

Since the differential diagnosis between cyclosporine (CyA) nephrotoxicity and acute graft rejection is still a problem in clinical routine, we studied retrospectively the value of 111-indium (In) platelet scintigraphy in 53 patients immunosuppressed with CyA and prednisolone. Autologous platelets were labeled once per week. After daily gamma camera imaging, the platelet deposition in the graft was expressed as platelet-uptake ratio (PUR). The patients were monitored during the first 4-6 weeks after surgery. PUR values measured during an episode of graft dysfunction were compared to the histological diagnosis. The PUR of well-functioning and stable grafts measured 1.07 +/- 0.11 (mean +/- SD). The 111-In platelet scintigraphy failed to register acute interstitial rejection. The PUR values in episodes of chronic vascular rejection, of acute tubular necrosis due to prolonged ischemia times, of tubular CyA nephrotoxicity and of cytomegalovirus (CMV) infection did not differ from the PUR of well-functioning and stable grafts as well. The PUR was significantly increased to 1.48 +/- 0.26 because of a marked platelet deposition in the graft in episodes of acute vascular rejection. In 4 cases of microvascular CyA nephrotoxicity the same phenomenon of significantly increased PUR (1.33 +/- 0.18), could be encountered, too. Two of these 4 cases resembled the hemolytic uremic syndrome (HUS). The value of PUR measurement for diagnosis of acute vascular rejection and microvascular CyA nephrotoxicity together, was: sensitivity 0.62, specificity 0.95, predictive value of positive result 0.64, predictive value of negative result 0.94.(ABSTRACT TRUNCATED AT 250 WORDS)     

骁悉和环孢素-A预防肾移植术后早期急性排斥反应

目的 探讨骁悉和环孢素－Ａ预防肾移植术后早期急性排斥反应的效果。方法 回顾性分析１９９７年１２月￣１９９９年１月临床资料完整肾移植患者１４６例,随访时间６￣１６个月。根据应用免疫抑制剂方案的不同分为硫唑嘌呤（Ａｚａ）组（环孢素－Ａ、泼尼松龙、Ａｚａ）和骁悉（ＭＭＦ）组（环孢素－Ａ、泼尼松、ＭＭＦ）。其中Ａｚａ组７８例,ＭＭＦ组６８例。所有受者术前行人类白细胞抗原（ＨＬＡ）配型,ＨＬＡ错配≤３个位点     

Urine macrophage migration inhibitory factor concentrations as a diagnostic tool in human renal allograft rejection.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that is a potent activator of macrophages and T cells. Previous studies have shown that local MIF production is increased in acute renal allograft rejection, suggesting that it may play an important role in the rejection process. AIMS: To determine if urine and serum MIF concentrations: (1) are increased in acute rejection, and (2) can be used as noninvasive tools to discriminate between acute rejection (AR) and cyclosporine nephrotoxicity (CyA toxicity). METHODS: In a prospective study of nine renal allograft patients (five acute rejection and four stable), serial urine MIF concentrations were measured by ELISA in the first 14 days after transplantation. In a retrospective study, MIF concentrations in urine and serum were measured in 24 patients who were biopsied for acute renal transplant dysfunction (11 AR, 13 CyA toxicity). Urine and serum MIF were also measured in 23 stable renal transplant patients and 10 normals. RESULTS: MIF was readily detected in the urine of normal healthy controls (106+/-61 pg/micromol creatinine). In the prospective study, the urinary MIF concentration was increased substantially on day 1 posttransplantation and subsequently fell in parallel with the serum creatinine. However, urine MIF increased before episodes of biopsy proven acute rejection. The retrospective study showed that urine MIF concentrations in patients with AR were increased 5-fold compared to normal controls (439+/-313 pg/micromol Cr; P<0.01). In contrast, urine MIF concentrations in CyA toxicity were not significantly different to normal controls (145+/-119 pg/micromol Cr; P=NS). A marked increase in MIF immunostaining was seen in biopsies of AR, but not in CyA toxicity. No significant differences were evident in serum MIF levels between normals and any transplant patient group. CONCLUSIONS: These results suggest that measurement of urine MIF concentration may be useful in monitoring renal transplant patients for acute rejection and as a discriminator from cyclosporine nephrotoxicity.     

The effect of cyclosporine on mortality and renal function in living related pediatric kidney transplant recipients

The outcome, incidence of acute rejection episodes, complications and cyclosporine (CyA) induced nephrotoxicity were studied in 10 pediatric kidney transplant recipients who were grafted from one-haplotype indentical parent with immunosuppression of CyA and prednisolone (Pred). Excellent patient and graft survival could be achieved in this population with low incidences of acute rejection or serious complications as when compared with the results of azathioprine (AZ) treated pediatric patients. With a mean follow-up of 12.9 months (range 1 to 50 months), the patient survival rate was 100 per cent and the graft survival rate was 100, 84, 84 and 84 per cent at 1, 2, 3 and 4 years post transplantation, respectively. Serum creatinine levels in the group were 0.97, 1.17, 1.14 and 1.2 mg/dl at 3, 6, 12 and 24 months post transplantation, respectively. The incidence of treated acute rejection episodes was 20 per cent (2 out of 10) in the CyA-treated children, whereas it was 53 per cent (9 of 17) in the Az-treated children. Five children who had undergone transplant surgery before they were 11 years old displayed linear growth in height after their transplantation. There have been no opportunistic infections, aseptic necrosis or peptic ulcers in this group and cyclosporine nephrotoxicity has not been a serious problem in the pediatric recipients. Only 10 per cent (1 out of 10) of the recipients displayed acute nephrotoxicity and only one recipient has converted from CyA+Pred to CyA+AZ+Pred (Three drug therapy) due to persistent nephrotoxicity. Cyclosporine and prednisolone have therefore constituted a relatively safe, effective immunosuppressive regimen for pediatric renal allograft recipients. This paper was presented at the 7th international congress of pediatric nephrology.     

The importance of urinary thromboxane B2 excretion in the diagnosis of acute renal rejection

To establish whether or not urinary excretion TxB2 is a useful parameter in the diagnosis of acute renal rejection, 45 renal transplant patients were studied and classified in four groups: Group A. Ten observations of satisfactory clinical outcome (without either acute rejection or tubular necrosis). Urinary TxB2 was initially increased but had settled to normal by the 3rd postoperative day. Two patients had subsequent increases. Group B. Twenty-five episodes of acute rejection on a previously satisfactorily functioning graft. Nineteen had increases in TxB2 values before serum creatinine increased. Group C. Five episodes of tubular necrosis without acute rejection. The evolution was similar to Group A. Group D. Nine acute episodes of rejection on kidneys with tubular necrosis. The urinary output of TxB2 was increased from the beginning. This increase was maintained until the rejection was treated. This group had the highest values of urine TxB2. The principal significance of this parameter lies in its precocity and in its utility for diagnosis of acute rejection in the graft with tubular necrosis, as the persistence of raised values of TxB2 in the urine beyond the 3rd postoperative day is highly suggestive of an acute rejection.     

The role of C-reactive protein in graft dysfunction after renal transplantation

PURPOSE: We investigated whether serial daily measurements of serum C-reactive protein could help differentiate episodes of transplant dysfunction due to rejection, infection, cyclosporin A nephrotoxicity or acute tubular necrosis in renal allograft recipients. MATERIALS AND METHODS: Morning serum was obtained daily from 134 patients during the first 30 days after renal transplantation. All episodes of graft dysfunction were recorded and compared to transplant biopsies. C-reactive protein concentrations were correlated with postoperative graft function and the various causes of graft dysfunction. RESULTS: All patients demonstrated an increase in C-reactive protein in response to surgery and a maximum level was reached on day 2 after transplantation. Mean C-reactive protein concentration was significantly increased for delayed (61.50 microg./ml.) compared to primary (mean 38.01) graft function (p = 0.001, Mann-Whitney U test). There were significant increases in C-reactive protein for bacterial infections other than asymptomatic bacteriuria (33.98 microg./ml), interstitial graft rejection (16.43) and acute tubular necrosis (30.50) compared to uneventful courses. C-reactive protein was unchanged for viral infections or cyclosporin A toxicity. CONCLUSIONS: Serial C-reactive protein measurements help to identify renal transplant dysfunction of different origins. However, rejection, infection and acute tubular necrosis show similar patterns of C-reactive protein increase. Thus, C-reactive protein is unable to discriminate the causes of renal graft dysfunction. Biopsy remains the gold standard for the differential diagnosis of renal allograft dysfunction.     

Serum C-reactive protein concentrations in cyclosporine-treated renal allograft recipients

Acute or persistent elevations in serum C-reactive protein (CRP) concentration have been shown to be of value in diagnosing acute rejection episodes in azathioprine (AZA)-treated renal transplant recipients. To assess whether changes in serum CRP level might assist in differentiating nephrotoxicity from acute rejection in cyclosporine (CsA)-treated renal transplant recipients, we measured changes occurring in serum CRP concentrations in 74 CsA patients in response to transplant operation, acute rejection, cyclosporine nephrotoxicity, and serious infection, and compared these values with changes in AZA patients. Serum CRP concentration rose in response to operation in virtually all patients, regardless of immunosuppressive regimen, from mean baselines of 5.9 +/- 2.7 mcg/ml (AZA) and 6.8 +/- 6.5 mcg/ml (CsA) to mean peak levels of 43.8 +/- 33.4 mcg/ml and 65.1 +/- 39.5 mcg/ml, respectively. CRP rose during 76% of acute rejection episodes in AZA patients by a mean of 29.7 +/- 37.4 mcg/ml. In contrast, in 80% of acute rejection episodes of CsA patients, CRP remained undetectable or failed to rise above a stable, minimally elevated baseline. Similarly, there was no elevation in CRP in 9 of 10 episodes of nephrotoxicity. In 14 CSA patients with serious infections (8 pulmonary, 3 intraabdominal, 3 genitourinary), CRP rose by a mean of 67.7 +/- 50.7 mcg/ml. Thus, although CRP rises significantly with operation or serious infection in CsA patients, CRP fails to rise with nephrotoxicity or acute rejection.     

Anti-CD25 monoclonal antibody sequential immunosuppressive induction therapy in renal transplants with high risk of delayed graft function

There is little experience on the use of monoclonal antibodies that block the high-affinity interleukin-2 receptor (basiliximab and daclizumab) in sequential therapy in renal transplants with risk of delayed graft function. This study sougth to test the efficacy and safety of the substitution of anticalcineurins with two doses of basiliximab or daclizumab in the immediate posttransplant period for recipients at risk of delayed renal graft function. Immunosuppression consisted of steroids, mycophenolate mofetil, and two doses of basiliximab (20 mg/day) on days 0 and 4 posttransplant or daclizumab (1 mg/kg per day) on days 0 and 15 posttransplant. Anticalcineurins were not administered until the beginning of graft function. Among 49 recipients (mean age 63.5 +/- 10.5 years), 40 received a kidney from a donor over 60 years of age, three from a non-heart-beating donor, and six from donors with an acute elevation of serum creatinine to 2.4 +/- 0.86 (1.7-3.7). At a mean follow-up of 14.2 +/- 8.4 months, five patients experienced acute rejection episodes. Only 15 patients needed posttransplant dialysis (2.7 +/- 1.6). In 11 patients, cyclosporine (CsA) was introduced at 6 +/- 2.9 days posttransplant and in 37, tacrolimus on 8.6 +/- 3.6 days posttransplant. The incidence of kidney graft loss was 16.3%. Patient survival was 96%. Thirty-nine recipients are alive with functioning grafts, with mean serum creatinine of 1.4 mg/dL. In conclusion, substitution for anticalcineurins with interleukin-2-receptor blockade in the immediate posttransplant period for patients at risk of delayed graft function minimizes nephrotoxicity and reduces tubular necrosis, without increasing the risk of an acute rejection episode.     

The influence of donor age on renal function in transplant recipients

To the extent that age-related declines in kidney function are caused by intrarenal alterations, donor age should affect glomerular filtration rate (GFR) after renal transplantation. Although some investigations have suggested that transplantation of aging kidneys may cause an increased incidence of primary allograft failure, the effects of donor age on GFR are unknown. In the present study, 201 patients who had allografts that survived for at least 24 months were investigated. The age range of the donors was 7 to 61 years. Multivariate regression analysis demonstrated that both donor and recipient age had significant, independent effects on creatinine clearance at 1 year, and at last follow-up, 5.0 +/- 1.9 years (mean +/- SD) after transplantation. The effect of donor age on renal function could not be attributed to differences in the number of rejection episodes, the frequency or duration of posttransplant acute tubular necrosis, age of the recipient, or other factors. Donor age had no effect on allograft survival, and did not affect the rate of decline in creatinine clearance between 1 year and last follow-up. Thus, these results suggest that donor age is associated with intrarenal alterations that lead to reductions in renal function after transplantation, but donor age may not affect long-term prognosis or allograft survival in the late posttransplant period.     

Prospective, Pilot, Open-Label, Short-Term Study of Conversion to Leflunomide Reverses Chronic Renal Allograft Dysfunction

Leflunomide (LEF) is a synthetic isoxazole derivative with anti-inflammatory and antiviral properties, which has been reported to prevent acute rejection and delay progression of chronic allograft nephropathy (CAN) in animal models. We performed a pilot, crossover trial in 22 renal transplant recipients who were converted from azathioprine (AZA) or mycophenolate mofetil (MMF) to LEF in an effort to slow progression of renal dysfunction [deteriorating renal function (n = 5), cyclosporine (CyA) nephrotoxicity (n = 4) or biopsy-proven CAN (n = 13)]. Baseline maintenance immunosuppression consisted of CyA, AZA or MMF and prednisone. Six-month postconversion patient and graft survival was 100% and 91%, respectively. Mean serum creatinine 6months preconversion was 2.2 +/- 0.6mg/dL, at initiation was 3.0 +/- 1.1 mg/dL, and 6 months postconversion was 2.8 +/- 1.3 mg/dL. The rate of change in serum creatinine was 35 +/- 39%/6 months preconversion and -5 +/- 21%/6 months postconversion to LEF (p = 0.003). Two patients discontinued LEF for diarrhea and myalgia. No readmissions, increase in liver function tests, infections or acute rejection episodes occurred. Mean CyA levels did not change, 146 +/- 72 ng/ mL pre-LEF vs. 132 +/- 51 ng/mL post-LEF, p = NS. Conversion to LEF reversed progression of chronic renal allograft dysfunction with minimal toxicity.     

Monitoring of renal allografts by Doppler ultrasound.

Cyclosporin (CyA) associated renal dysfunction may be due to an arteriolopathy which reduces graft perfusion. We have prospectively monitored 27 renal allograft recipients, within 30 days of transplantation, by continuous wave Doppler ultrasound. Changes in the frequency shift waveform should indicate alterations in renal blood flow. Objective analysis was made in 112 waveforms by determining the ratio of the area under the frequency shift/time curve of the first half and the second half of the cardiac cycle (AUC 1/2 ratio). The AUC of the first half of the cycle indicates systolic blood flow plus the first part of diastolic flow, whereas the AUC of the second half indicates the remainder of diastolic flow. The AUC 1/2 ratio during ATN was not significantly different from that during stable renal function. However the ratio was significantly higher during acute rejection episodes and CyA nephrotoxicity. Although a statistical difference was demonstrated between acute rejection and CyA nephrotoxicity, the AUC 1/2 ratio alone does not differentiate these 2 conditions. These preliminary findings suggest CyA nephrotoxicity does reduce renal allograft blood flow and that this non-invasive technique may have a useful role to play in monitoring of patients immunosuppressed with CyA.     

Reversible acute tubular necrosis following severe acute renal rejection

The clinical observation of 6 out of 250 renal transplant patients showed that acute renal rejection may lead to reversible acute tubular necrosis (ATN) necessitating intermittent haemodialysis treatment. Despite missing early response to high-dose (methyl-) prednisolone therapy (during a mean period of 4.7 days) all 6 patients developed spontaneous diuresis 14.5 days on average after onset of rejection while on maintenance immunosuppressive therapy. From the clinical course the conclusion was drawn that in severe cases of renal rejection with arteriographic and histological findings consistent with acute tubular necrosis, prolonged therapy with high doses of (methyl-) prednisolone is not desirable, since after reversal of immunological rejection the onset of spontaneous diuresis will be determined mainly by the duration of the healing and recovery phase of acute tubular necrosis.     

B lymphocyte response as an indicator of acute renal transplant rejection. I. Immunoglobulin-secreting cells in peripheral blood

Monitoring of immunoglobulin-secreting cells in peripheral blood was performed in 88 renal transplant recipients using a reverse hemolytic plaque-forming cell assay. Comparison with other in vitro tests for rejection (plasma neopterin, CD4/CD8 ratio) demonstrated that the number of immunoglobulin-secreting cells in peripheral blood provides a highly sensitive rejection marker. Evidence of rejection was obtained 1.7 +/- 0.4 (mean +/- SEM) days before a rise in creatinine, with a significant PFC rise in 95% (73/77) of rejection episodes. The PFC response was not influenced by HLA matching, number of preoperative blood transfusions, acute tubular necrosis, or uremia. A significant PFC rise in the absence of an ongoing rejection episode occurred in the presence of bacterial or viral infections, in case of posttransplant surgical complications, and regularly during the early posttransplant period (days 4-9). However, even early posttransplant the PFC peak was significantly higher in patients with an ongoing rejection episode than in patients without rejection (P less than 0.001).     

Lymphocyturia: an important diagnostic and prognostic marker in renal allograft rejection

We examined the urine for lymphocytes in 60 renal allograft recipients in the immediate posttransplant period using a simple staining technique with methylene blue. 37 acute rejection episodes associated with deterioration in renal function were observed. Other causes of decreased renal function, such as acute tubular necrosis, vascular occlusion or urologic obstruction were carefully excluded. 34 (92%) of the 37 acute rejection episodes were accompanied by significant lymphocyturia. Lymphocyturia was recognized concomitantly with the rise in serum creatinine in 20 of the 34, whereas in 14 it preceded the rise in serum creatinine by a period of 3.5 +/- 2.5 days. 24 (71%) of the 34 acute rejection episodes were reversed by high dose steroid administration and only 2 of them showed persistent lymphocyturia following treatment. On the other hand, 9 of the 10 nonresponders to steroid therapy showed persistent lymphocyturia. All the nonresponders eventually required maintenance dialysis. Detection of lymphocyturia is not only of value in the diagnosis of acute allograft rejection, but is also useful in determining allograft survival in the immediate posttransplant period.     

Association of donor TNFRSF6 (FAS) gene polymorphism with acute rejection in renal transplant patients: a case-control study.

BACKGROUND: Genetic factors other than HLA have been reported to be associated with the outcome of organ transplantations. Because binding of FasL to its receptor Fas could play an important role in tubulitis and in the death of graft tubular epithelial cells during kidney allograft rejection, a gene polymorphism recently identified in position -671 in the promoter of the TNFRSF6 gene coding for Fas was investigated in donors. METHODS: A case-control study was performed within a cohort of non-hyperimmunized adult patients who had received cadaveric kidney transplants based on the occurrence or absence of acute cellular rejection in the first 6 months after renal transplantation. Each recipient from the acute rejection group (n = 35) was matched for age (+/- 5 years) and number of HLA-DR mismatches with two recipients within the non-acute rejection group (n = 70). RESULTS: The TNFRSF6-GG genotype was more frequent in donors in the group without rejection episodes. In contrast, patients who received a kidney from a TNFRSF6-A carrier were more likely to experience acute rejection episodes (relative risk nearly 2.1). CONCLUSION: This study suggests that donor TNFRSF6 polymorphism directly or indirectly influences acute kidney rejection episodes.     

Differentiation between renal allograft rejection and cyclosporine toxicity: a clinicopathological study

The differentiation between cyclosporine nephrotoxicity (CyN) and acute rejection (AR) still remains a matter of intensive research. In a retrospective study over the last 2 years, we assessed the clinical and histopathological data of 43 episodes of renal dysfunction in 39 renal transplant recipients immunosuppressed with cyclosporine (CyA). Ten episodes (23.2%) were identified as AR and 10 (23.2%) as acute CyN; in six cases (13.9%), signs of both AR and CyN were found. Fever (80%), oliguria (50%), and edema (50%) were prominent features in AR, but not in CyN. Renal blood flow was higher in the nephrotoxicity group and for corresponding degree of renal dysfunction. Significant hyperuricemia (greater than 8 mg/dL) was a prominent finding in CyN (80%) and to a lesser extent in AR (20%). The helper to suppressor cell ratio in the peripheral blood remained stable or slightly decreased in all cases with CyN, but increased in 70% of the cases with AR. CyN was associated with significantly higher whole blood CyA levels (P less than 0.005) and there was a positive correlation between plasma creatinine and CyA levels during the nephrotoxicity episodes (P less than 0.02). Diffuse mononuclear cell infiltrate was observed in 90% of the biopsies with AR and only in 20% with CyN (P less than 0.005). Concerning the extent of the tubular lesions, no significant differences were observed between the two groups. In contrast, vascular lesions such as arterial endothelial proliferation (P less than 0.05), hyalinosis (P less than 0.05), and glomerular capillary thrombi (P less than 0.05) were more commonly seen in nephrotoxicity biopsies.(ABSTRACT TRUNCATED AT 250 WORDS)