Antithymocytes globulins: Time to revisit its use in kidney transplantation?

T cell depletion by polyclonal antithymocyte globulins (ATG) has been used for many years in both organ and hematopoietic cell transplantation as an induction and rejection therapy. Nevertheless, its use remains largely empirical and many clinical questions, such as the determination of an individualized dose, therapeutic relevance of nondepletive effects, or prediction of long-term effects, are still unresolved. This review evaluates the evidence-based knowledge and the uncertainties concerning ATG, and suggests perspectives and opportunities for modern use of this old drug.

[Role of percutaneous arterial embolization in renal pathology]. / Place de l'embolisation artérielle percutanée en pathologie rénale.

Therapeutic embolization in renal pathology is used for various conditions in cancerology, traumatology, urology, nephrology and for iatrogenic complications of percutaneous manoeuvers. Any department of vascular radiology may be requested to use this technique, especially in emergent traumatology or palliative cancerology. The authors study the various conditions that may benefit from these procedures and give the highlights of the main indications and the main types of embolic agents used. Complications, side effects and the major precautions are also reviewed.

Successful hepatorenal transplantation in hereditary amyloidosis caused by a frame-shift mutation in fibrinogen Aalpha-chain gene.

Hereditary systemic amyloidosis comprises several autosomal dominant diseases caused by mutations in a number of plasma proteins, including the fibrinogen Aalpha-chain. Four mutations in the fibrinogen Aalpha-chain that are able to induce amyloidosis have been identified so far, the most common being the Glu526Val mutation. We have observed a family in which the father and his son reached end-stage renal failure because of renal amyloidosis induced by a frame-shift mutation in the fibrinogen Aalpha-chain gene producing a novel amyloid protein. Two kidney transplantations in the father and one in the son resulted in fast graft loss caused by recurrence of amyloid deposition. We then performed hepatorenal transplantation in the son. Three years later, liver and kidney functions are normal without recurrence of amyloid deposition. This case, together with three others with the Glu526Val mutation in the extensive literature, suggests that liver transplantation can cure hereditary fibrinogen amyloidosis, whatever the mutation may be.

T-cell flow-cytometry crossmatch and long-term renal graft survival.

Flow cytometry crossmatch (FCXM) is a more sensitive technique than classical complement-dependent cytotoxicity (CDC) for the detection of donor-directed antibody before renal transplantation. Nevertheless, the role of FCXM in predicting long-term survival of kidney grafts is still unclear. The purpose of our study was to evaluate the impact of a positive T-cell FCXM (T-FCXM) on long-term kidney allografts outcome. Of the 184 consecutive kidney transplantations performed in our center between 1 January1991 and 15 November 1996 a FCXM, performed concurrently to the pre-transplant CDCXM, was available for 170 patients. The CDCXM was negative in all recipients. Among these recipients, 12 (7.1%) had a positive T-FCXM. These patients were not different from patients with a negative T-FCXM for donor and recipient age, sex, frequency of second transplantation, number of human leukocyte antigen matches or mismatches. Frequency of immunized patients was higher in kidney recipients with a positive FCXM (58.3% vs. 24.7%; p=0.02, chi-square test). Survival analysis revealed that kidney graft outcome was better in negative T-FCXM recipients (p=0.03), while patient survival was not statistically different. Our results suggest that a positive pre-transplant T-FCXM despite a negative CDCXM is associated with an impaired long-term graft survival in renal allotransplantation.

Hypertension in renal transplantation: donor and recipient risk factors.

AIMS: To determine the respective roles of donor and recipient factors in the subsequent development of hypertension after renal transplantation. PATIENTS AND METHODS: All the patients transplanted between January 1990 and December 1999 who still had a functioning graft 1 year post-transplant (n = 321) were retrospectively studied. Blood pressure was assessed at 1 year post-transplant. Hypertension was defined as a systolic BP > or equal 140 mmHg or diastolic BP > or equal 90 mmHg, or use of antihypertensive medication. Relevant donor and recipient characteristics were recorded. RESULTS: Two-hundred-and-sixty-three patients (82%) were hypertensive. In multivariate analysis, pretransplant hypertension (RR, 1.74, 95% CI, 1.07 to 2.87), anticalcineurin use (RR, 2.59, 95% CI, 1.13 to 5.92), urinary protein excretion (RR, 1.84, 95% CI, 1.06 to 3.18), BMI (RR, 1.08, 95% CI, 1.01 to 1.16), donor age (RR, 1.28,95% CI, 1.05 to 1.59, for each 10-year increase in donor age) and donor aortorenal atheroma (OR, 2.34; 95% CI, 1.24 to 4.46) were associated with hypertension. Among patients under calcineurin inhibitors, those receiving cyclosporine were more prone to have hypertension than those receiving tacrolimus (88.7% vs 78%; p = 0.04). CONCLUSION: Both recipient and donor factors contribute to hypertension in RTR.

Flow-PRA evaluation for antibody screening in patients awaiting kidney transplantation.

Flow-PRA is a flow cytometric method for both anti-HLA class I and class II antibody (Ab) detection. We evaluated this technique for Ab screening in patients awaiting kidney transplantation. After having established a rigorous threshold for positivity, a three-dilution difference in sensitivity between Flow-PRA and complement-dependent cytotoxicity (CDC) persisted. The sensitivity of the method was satisfactory since all CDC-positive sera were also found to be positive with the Flow-PRA method. Discrimination between anti-HLA class I and class II Abs was excellent. Furthermore, all sera responsible for a positive flow cytometry crossmatch (FCXM) and a negative CDC-crossmatch (CDCXM) at the time of a putative transplant were found to be positive with Flow-PRA beads. The specificity was excellent for anti-class I Ab detection since no false positive serum was found. On the other hand, the specificity was lower for anti-class II detection, since 8.3% (2/24) false positive results were detected among all the negative sera tested. Overall, our results suggested that Flow-PRA should be of value for anti-HLA Ab screening prior to kidney transplantation.

T-cell immune defect and B-cell activation in renal transplant recipients with monoclonal gammopathies.

Monoclonal immunoglobulins (molg) have repeatedly been described in organ and bone marrow transplantation. Although their exact significance is not known, their occurrence is often associated with intensive immunosuppression. We investigated whether molg reflect T-cell immune defect and B-cell activation in renal transplant recipients. Immunofixations and lymphocyte subset analysis (CD4, CD8, CD19) were performed in 182 renal transplant recipients. Soluble CD23 concentrations were measured in patients with molg and in control transplant patients without molg. Monoclonal immunoglobulins were identified in 54 patients (29.6 %). Transplant endurance was shorter (62 +/- 53 months vs 81 +/- 47 months; P < 0.02) and age was older (53 +/- 13 years vs 46 +/- 13 years; P < 0.005) in patients with molg. Maintenance immunosuppression did not differ between patients with and without molg. Mean CD4-cell count was significantly lower in patients with molg (387 +/- 286/mm(3) vs 538 +/- 341/mm(3); P < 0.005). Both CD8- and CD19-cell counts were similar for the 2 groups. Soluble CD23 concentrations were higher in patients with abnormal immunoglobulin values than in patients with normal immunofixation (12.8 +/- 8 vs 1.9 +/- 1.8 microg/l; P < 0. 005). Our study provides new evidence that molg reflect T-cell immune defect in renal transplant recipients. Further studies are required to determine whether CD4-cell count and sCD23 may help to predict the risk of lymphoma in transplant patients with molg.

Polycystic kidney disease as a risk factor for post-transplant diabetes mellitus.

BACKGROUND: Insulin resistance with compensatory hyperinsulinaemia has been reported in adult polycystic kidney disease (APKD) patients. Diabetes mellitus is a common complication following transplantation and previous studies have demonstrated that inadequate insulin secretion was a prerequisite for the development of post-transplant diabetes mellitus (PTDM). We conducted a retrospective study to determine whether APKD is a risk factor for PTDM. METHODS: Twenty-six consecutive patients transplanted because of end-stage renal disease due to APKD were studied. A control patient matched for age, gender, immunosuppressive therapy and transplant year was selected for each APKD patient. PTDM was defined by fasting glycaemia exceeding 7.8 mmol/l and the need for insulin or oral antidiabetic therapy. RESULTS: Age, renal function, immunosuppressive regimen, number of acute rejection, cumulative dose of steroids and haemodialysis duration before transplantation were similar in both groups. PTDM occured in 10 APKD patients and four controls (34.6% vs 15.3%; P < 0.005). Among diabetic patients, six APKD patients and two controls required insulin therapy (60% vs 50%; P = n.s.). Diabetic patients were significantly older (55.8 +/- 7 years vs 50.2 +/- 11 years; P < 0.05). CONCLUSION: Although retrospective, this study suggests that APKD confers an increased risk of PTDM.

Prevalence and clinical significance of antiphospholipid antibodies in renal transplant recipients.

BACKGROUND: The prevalence and clinical significance of antiphospholipid antibodies (APAs) have not been extensively studied in non-systemic lupus erythematosus (non-SLE) renal transplant recipients. METHODS: To further define the prevalence and clinical significance of APAs in non-SLE renal transplant recipients and the appearance of dialysis-related APAs after renal transplantation, we conducted a retrospective study on 178 renal transplant recipients. Documentation of anticardiolipin antibodies (ACAs) and lupus anticoagulant in non-SLE renal transplant recipients, retrospective documentation of ACAs on pretransplant frozen plasma and standardized collection of demographic characteristics and posttransplant history of thrombosis were assessed. RESULTS: Fifty of 178 patients (28.1%) had APAs. Transplant duration was shorter and hemodialysis duration was longer in patients with APAs. A posttransplant history of both venous and arterial thrombosis was more frequent in patients with posttransplant APAs (respectively, 18% vs. 6.2% [P<0.001] and 8% vs. 2.3% [P<0.001]). Pretransplant sera were available from 55 patients. Most of patients with posttransplant ACAs had ACAs in the pretransplant period (85%). Pretransplant ACAs were associated with a posttransplant history of venous thrombosis (P<0.001). CONCLUSIONS: Our study demonstrates a high prevalence of APAs in non-SLE renal transplant recipients. Most of them have been acquired in the pretransplant period. Both pretransplant ACAs and posttransplant APAs are associated with posttransplant episodes of thrombosis. Further studies are required to determine the interest of prophylactic measures.

Prevalence, determinants, and clinical significance of hyperhomocyst(e)inaemia in renal-transplant recipients.

BACKGROUND: Previous studies have demonstrated that hyperhomocyst(e)inaemia is present in patients with impaired renal function and is correlated with cardiovascular disease. Because conflicting data are available on the prevalence, determinants, and clinical significance of hyperhomocyst(e)inaemia in renal-transplant recipients, we conducted the largest cross-sectional study on homocysteine determinants and clinical correlates in renal transplant recipients. METHODS: Plasma homocyst(e)ine concentrations and factors known to influence homocysteine metabolism were analysed in 224 renal transplant recipients. Atherosclerotic complications were evaluated with respect to plasma homocysteine concentrations. RESULTS: Mean plasma homocyst(e)ine was 21.3+/-9.7 micromol/l. After adjusting for age, gender, transplant duration, and creatinine clearance, patients with and without cyclosporin A (CsA) had similar plasma homocyst(e)ine concentrations (16.9+/-5.9 micromol/l in CsA(+) patients vs 16.3+/-5.2 micromol/l in CsA(-) patients; P=0.3). We found a significant inverse relationship between plasma homocyst(e)ine and folate concentrations in both CsA(+) (r=-0.243; P<0.005) and CsA(-) (r=-0.396; P<0.05) patients. Patients with a past history of cardiovascular events had higher plasma homocyst(e)ine concentrations (25.2+/-11.7 mmol/l vs 20.5+/-8.9 mmol/l; P<0.005). CONCLUSION: Homocyst(e)inaemia is closely related to renal function and folate concentration in renal-transplant recipients. CsA does not seem to have direct effects on homocysteine metabolism. Hyperhomocyst(e)inaemia is associated with cardiovascular disease in renal-transplant recipients. Prospective placebo-controlled homocysteine-lowering therapy studies are required in this patient category.

Impaired renal graft survival after a positive B-cell flow-cytometry crossmatch.

BACKGROUND: The clinical and immunological relevance of a positive B-cell flow-cytometry (B-FCXM) crossmatch in renal transplantation is still controversial. METHODS: We retrospectively analysed 145 consecutive cadaveric renal transplantations performed from May 1991 to September 1995 in our institution. All grafts were transplanted following a negative IgG T-cell complement-dependent cytotoxicity crossmatch (T-CDCXM). Concomitantly to CDCXM, B-cell and T-cell FCXM were performed and results were expressed as a mean fluorescence index (FI). Two groups were compared: 116 recipients grafted with a negative B-FCXM vs a group of 19 patients grafted with a positive B-FCXM. RESULTS: The two groups were similar for length of cold ischaemia, donor and recipient's age and degree of HLA mismatching. The proportion of patients with pre-transplant anti-HLA class I antibodies or a retransplantation was significantly increased in the positive B-FCXM group vs the negative B-FCXM group. Recipient survival at 48 months was not significantly different in the two groups. However, graft survival at 12 and 48 months was significantly poorer in the positive B-FCXM than in negative B-FCXM (68% vs 90% at 12 months: P = 0.007, and 57% vs 79% at 48 months: P = 0.02). Within the positive B-FCXM group, no differences were found in pre-transplant anti-HLA class I or II alloimmunization as well as retransplantation frequency between the patients who lost their graft and the patients who did not. CONCLUSION: Our results suggest that a pretransplant positive B-FCXM is associated with an impaired long-term graft survival in renal allotransplantation.