Targets of alloantibodies in Alport anti-glomerular basement membrane disease after renal transplantation

A minority of patients with Alport syndrome develop anti-GBM disease in their allografts after renal transplantation. Clinically, the renal disease appears indistinguishable from Goodpasture's disease of native kidneys, in which the target of autoantibodies had been identified as the NC1 domain of the alpha 3 chain of type IV collagen, alpha 3(IV)NC1. However, in the majority of cases, Alport syndrome is due to mutations in the gene encoding the alpha 5 chain of type IV collagen, located on the X chromosome. Neither chain is detectable in the glomerular basement membrane (GBM) of most patients with Alport syndrome. We investigated the targets of the alloantibodies of 12 Alport patients who developed post-transplant anti-GBM disease by Western blotting onto recombinant NC1 domains made in insect cells. Binding to these antigens, for both typical Goodpasture and Alport anti-GBM antibodies, was strong and conformation-sensitive. Nine antibodies showed selective binding to alpha 5(IV)NC1. This specificity was confirmed by the demonstration of binding to a 26 kDa band of collagenase-solubilized human GBM, and/or binding to normal epidermal as well as renal basement membranes by indirect immunofluorescence. One antibody showed binding to alpha 5 and alpha 3(IV)NC1, while two showed predominant binding to alpha 3(IV)NC1. All seven patients whose pedigree or mutation analysis showed X-linked inheritance had predominant anti-alpha 5 reactivity. One with predominant anti-alpha 3 reactivity had a COL4A3 mutation. These findings show that human anti-GBM disease can be associated with antibodies directed towards different molecular targets. Alpha 5(IV)NC1 is the primary target in most patients with X-linked Alport syndrome who develop post-transplant anti-GBM disease.     

Seasonal variations in T-lymphocyte response to grass pollen allergens from pollen-allergic patients and healthy controls

Recurrence of membranous nephropathy after renal transplantation has been reported either anecdotally or in a few series. In the present study, the potential risk factors as well as hitherto unreported actuarial risk for recurrence and graft loss due to recurrence were evaluated by combining data of a series of transplanted patients with MN at Louvain Medical School (n = 12) and at Lyon (n = 18; previously reported by Couchoud et al. 1995) giving a total of 30 patients. No risk factor for recurrence was identified as there was no statistical difference between the patients with and without recurrence for duration of MN in native kidneys or of pretransplant hemodialysis, presence of HLA-DR3, graft origin and use of cyclosporin. Actuarial risk for recurrence reached 29% at 3 years, plateauing up to 10 years. The outcome of recurrence was poor since the actual risk for graft loss among patients with recurrent MN was 38 and 52% at 5 and 10 years, respectively.     

Temporomandibular joint derangement after air bag deployment: report of two cases

BACKGROUND: The outcome of 60 renal transplantations in 53 patients with end-stage renal disease (ESRD) because of lupus nephritis was studied retrospectively and compared with 106 controls matched for age, sex, maximum panel-reactive antibody (PRA) level, and date of transplantation. METHODS: The patients received their transplants over a 260-month period (21.5 years) between October 1971 and August 1993. The population was predominantly women (90%), and the mean age at the time of the transplantation was 33.2 years (range: 21-54 years). Fifty-six transplants (93%) were from cadaveric donors, and 4 (7%) were from living-related donors; 46 patients (86%) had primary allografts, and 7 (14%) received a second allograft. The duration of disease before transplantation was 93.6+/-6.2 months, and the duration of dialysis before transplantation was 48+/-6 months. RESULTS: No patient had clinically active systemic lupus erythematosus (SLE) at the time of transplantation. The 1-year graft and patient survival rates were 83% and 98%, and the 5-year graft and patient survival rates were 69% and 96%. Actuarial graft and patient survival rates in SLE patients were not significantly different from those of the matched control group. Chronic rejection was the major risk factor for graft loss. Lupus nephritis recurred in the graft of one patient 3 months after transplantation, and there were extrarenal manifestations of SLE in four others. CONCLUSIONS: The present study confirms that patients with SLE can receive transplants with excellent graft and patient survival rates and a low rate of clinical recurrent lupus nephritis.     

Human esophageal epithelial cells possess an Na+/H+ exchanger for H+ extrusion

Chronic progressive renal function loss is a main cause of long-term graft loss after initially successful renal transplantation. Transplanted kidneys share some risk factors for renal function loss, such as hypertension or proteinuria, with diseased native kidneys. Recently, it has been shown that renal function loss is influenced by the angiotensin-converting enzyme (ACE) (insertion/deletion [I/D]) genotype in renal disease in diseased native kidneys. This study examines whether donor or recipient ACE (I/D) genotype is a risk factor for graft loss after renal transplantation. To avoid bias by acute events, graft survival was studied, with patients dying with a functioning graft censored, starting at 12 mo after transplantation in a cohort of 367 patients transplanted between 1987 and 1994 with at least 2 yr of follow-up. Mean follow-up was 58 mo. ACE (I/D) genotype was determined by PCR on stored donor and recipient lymphocytes. Neither donor nor recipient ACE (I/D) genotype was associated with graft survival. However, Cox proportional hazards analysis identified recipient, but not donor, ACE (I/D) genotype D-allele to be independently associated with a shorter time to graft loss in subgroups of patients at high risk for graft loss defined by a creatinine clearance <50 ml/min (n = 108, P = 0.017) or proteinuria > or =0.5 g/24 h at 12 mo (n = 97, P = 0.0051) after transplantation. In conclusion, recipient ACE (I/D) genotype was associated with time to graft loss in a specific high-risk subgroup of the study population. This suggests that the effect of ACE (I/D) genotype on graft survival only becomes apparent when other risk factors are simultaneously present.     

The prevalence of hepatitis A antibodies among Israeli travellers and the economic feasibility of screening before vaccination

BACKGROUND: Tuberculosis is a recognized complication following renal transplantation. Patients with autosomal dominant polycystic kidney disease are increasingly being offered renal transplantation as an alternative to chronic hemodialysis. These patients are uniquely susceptible to serious upper urinary tract infections that are associated with significant morbidity and mortality. While involvement with gram-negative organisms is well described, mycobacterial infection of native polycystic kidneys after transplantation has not been addressed. METHODS: A case report of a renal transplant recipient who suffered an isolated Mycobacterium tuberculosis infection of a native polycystic kidney and a literature review. RESULTS: Despite appropriate drug therapy, the infection proved refractory, and the patient required nephrectomy. CONCLUSIONS: Mycobacterial tuberculosis, though not common, must be recognized as a potential source of infection of native polycystic kidneys in immunocompromised transplant recipients. Similar to the pattern observed with more common pathogens, these infections may be difficult to eradicate with standard antimicrobial drug regimens.     

Association of crescentic glomerulonephritis with membranous glomerulonephropathy: a report of three cases

Association of membranous glomerulonephropathy with crescentic glomerulonephritis is apparently extremely rare. We report three patients who had this combination. One patient had biopsy-proven membranous glomerulonephropathy thirteen months prior to sudden and rapid decline in renal function necessitating hemodialysis. A repeat renal biopsy showed a superimposed crescentic nephritis and antiglomerular (GBM) antibodies were demonstrable in the serum. A second patient had proteinuria of unknown duration and then developed renal failure. Renal biopsy showed crescentic nephritis with a fine granular glomerular immunofluorescence for IgG typical of membranous glomerulonephropathy. Anti-GBM antibodies were present in this patient's serum. The third patient presented with acute renal failure of moderate severity. A renal biopsy revealed crescentic nephritis, granular deposits of immunoglobulins, and epimembranous electron-dense deposits typical of membranous glomerulonephropathy. Although his creatinine clearance improved spontaneously, nephrotic syndrome has persisted and a repeat renal biopsy showed a progression of the membranous glomerulonephropathy with the disappearance of the crescentic lesions. The reason for this peculiar association of membranous glomerulonephropathy and crescentic glomerulonephritis is unclear. It is possible that deposition of immune-complexes along glomerular basement membrane may render the glomerulus more susceptible to additional injury from a variety of other agents. Alternatively, depostis formed in one disease could initiate release of normal or altered basement membrane material and lead to formation of anti-GBM antibodies and subsequent development.     

Acute intracranial complications of temporal bone trauma

BACKGROUND: A total of 110 patients, in whom kidneys from 95 living related and 15 cadaver donor, had experienced renal transplantation between February 1985 and October 1996 in our clinic. This study was conducted to evaluate the influence of the various pre-operative factors to the graft survivals and clinical course of patients in living related renal transplantation. METHODS: In 95 recipients, 17 adult patients had long term graft survivals over 5 years including 6 recurrent or denovo nephritis without chronic allografts nephropathy. Eight failed to graft loss attributed to chronic allografts nephropathy diagnosed within 5 years. Retrospective analysis were performed to elucidate the differences of these recipients. RESULTS: Donors of long graft survival recipients were younger (49.1 +/- 12.1 v.s. 58.9 +/- 10. 2) and had a better renal function evaluated by preoperative creatinine clearance in living related donors (115.5 +/- 37.0 v.s. 79.7 +/- 22.0 1/day). Graft long survival recipients had experienced less frequencies of acute rejection within 6 months (0.53 +/- 0.62: 8 patients, 9 times) compared with chronic allografts nephropathy recipients (1.00 +/- 0.53: 7 patients, 8 times). Long graft survival recipients had better responses to the antirejection therapy. Additionally acute rejection over 6 months were experienced only in chronic allografts nephropathy recipients. Higher serum creatinine level was revealed in recipients with chronic allografts nephropathy at 1 year after transplantation (1.27 +/- 0.27 v.s. 1.88 +/- 0.42 mg/dl). CONCLUSIONS: We concluded that donor age and renal function are related to the graft long survival as background factors. Long graft survival recipients had less frequency of acute rejection and good response to the antirejection therapy. In recipients with of acute rejection and good response to the antirejection therapy. In recipients with chronic allografts nephropathy, serum cretine level had already increased gradually within 1 year.     

Intrarenal arterial Doppler sonography in the detection of renal vein thrombosis of the native kidney

OBJECTIVE: Previous studies of transplant kidneys and recent reports on native kidneys have suggested intrarenal arterial Doppler findings can be helpful in the noninvasive workup of renal vein thrombosis. We used arterial Doppler sonography to evaluate cases of possible acute renal vein thrombosis in native kidneys that had equivocal results on standard Doppler analysis of the renal vein. MATERIALS AND METHODS: Twenty native kidneys in 12 patients with clinical findings suggestive of acute renal vein thrombosis had Doppler studies of the main renal vein that failed to show normal flow. In all 20 kidneys, duplex Doppler study of arcuate/interlobar intrarenal arteries was done and the resistive index was determined. The Doppler findings were compared with subsequent findings on either renal venograms (n = 11) or MR images (n = 9), which served as the reference "gold" standards. RESULTS: The prevalence of renal vein thrombosis was 25% (5/20). Ten kidneys had very abnormal findings on arterial Doppler studies (absent or reversed end-diastolic flow), but only two of these were proved to have renal vein thrombosis. In six other kidneys, end-diastolic flow was identified but the resistive index was still elevated (> or = 0.70), and only one of these kidneys was proved to have renal vein thrombosis. Four kidneys had normal arterial Doppler studies, and 50% (two) of these were proved to have renal vein thrombosis. When absent or reversed end-diastolic flow was used as a sign of renal vein thrombosis, intrarenal arterial Doppler analysis had a sensitivity of 40% (2/5) and a specificity of 47% (7/15). CONCLUSION: Unlike the reported experience in transplanted kidneys, intrarenal arterial Doppler analysis is neither sensitive nor specific for renal vein thrombosis in native kidneys. An intrarenal arterial Doppler study with normal findings should not prevent further workup if Doppler findings in the renal vein are equivocal, nor should absent or reversed end-diastolic arterial signals be considered highly suggestive of renal vein thrombosis.     

Detection of anti-lipoarabinomannan antibodies for the diagnosis of active tuberculosis

Patients with acquired cystic kidney disease (ACKD) are at an increased risk of renal neoplasms. Frequent tumors are adenomas and renal cell carcinomas. However, renal oncocytomas may occur in patients with ACKD. Little is known about oncocytomas of the native kidney following renal transplantation. By means of B scan ultrasonography, a solid and echo-inhomogeneous renal mass was incidentically observed in the right native kidney of a 28-year-old female patient with ACKD 4 years following renal transplantation. A nephrectomy was performed. The histological examination revealed a renal oncocytoma. The increased prevalence of neoplasms in the case of ACKD and following renal transplantation requires careful monitoring of the patients concerned. In very rare cases a renal oncocytoma may develop in the native kidney after renal transplantation.     

Polymorphism in the microsatellite located in the promoters of the Tnfa and Tnfb genes of different mouse strains

BACKGROUND: Hyperparathyroidism is common in patients with renal disease. These patients may require operation for this disease if it cannot be controlled by medical therapy. Because these patients continue to have renal failure, the risk of recurrence and reoperation is high. METHODS: Sixty-nine patients with renal failure underwent operation for hyperparathyroidism. These patients were followed up on dialysis or after transplantation. RESULTS: Sixty-nine patients, aged 2 to 71 years old, with end-stage renal disease required parathyroidectomy for hyperparathyroidism 6.2 +/- 4.2 (standard deviation) years after beginning dialysis. Thirty-six patients had undergone renal transplantation (creatinine = 1.6 +/- 0.4 mg/dL). All patients had elevated parathyroid hormone (PTH) levels. Sixty-eight patients had hyperplasia; 1 patient had adenoma. Six patients required reoperation for recurrent hyperparathyroidism 30 to 123 months after their initial parathyroidectomy. CONCLUSION: Patients with end-stage renal disease are prone to abnormalities of calcium metabolism. They frequently develop parathyroid hyperplasia. Recurrence can occur following operation because of continuing renal failure.     

The kidney in children with tyrosinemia: sonographic, CT and biochemical findings

BACKGROUND: Tyrosinemia relates to a deficiency of fumarylacetoacetate hydrolase and presents early in life with central nervous system and liver abnormalities. Renal function is often impaired. Little is known about the architecture and function of the kidneys. OBJECTIVE: Imaging changes on US and CT are compared to the function of the kidneys in children with tyrosinemia, and followed after liver transplantation. MATERIALS AND METHODS: Renal sonography, CT and renal function tests in 32 children were reviewed. Renal length, volume, echogenicity and nephrocalcinosis were evaluated. Renal function was assessed by glomerular filtration rate, and the presence of aminoaciduria, acidosis and calciuria. Seventeen children had open renal biopsy during time of liver transplantation. Histology was reviewed. Statistical analyses relating renal structure to function were performed, and repeated after transplantation. RESULTS: The kidneys were enlarged (47 %), hyperechogenic (47 %) and showed nephrocalcinosis (16 %). There was delayed excretion of contrast medium at CT in 64 %. Aminoaciduria was present in 82 % of children, hypercalciuria in 67 %, tubular acidosis in 59 %, and low GFR in 48 %. Delayed excretion of contrast was associated with low GFR (P < 0.05). Renal biopsies showed dilated tubules (81 %), interstitial fibrosis (56 %), glomerulosclerosis (56 %) and tubular atrophy (56 %). During a mean observation period of 3 years following liver transplantation, GFR improved in 50 %, tubular acidosis in 50 % and hypercalciuria in 70 %. No change was noted in renal size or sonographic architecture. CONCLUSION: Renal architecture and function are abnormal in the majority of children with tyrosinemia. Liver transplantation improves renal function in about 50 % of patients, but abnormal renal size and architecture persist.     

Magnetic resonance imaging abnormalities of the brain in Goldberg-Shprintzen syndrome (Hirschsprung disease, microcephaly, and iris coloboma)

The effects of a low-casein diet fortified with methionine and threonine on renal cortical and glomerular transforming growth factor (TGF)-beta activity were studied in rats with nephritis induced by anti-rat kidney glomerular basement membrane antiserum. Both normal and nephritic rats were fed experimental diets for 10 days. An injection of nephrotoxic serum increased urinary protein excretion and renal TGF-beta activity. A methionine-threonine-supplemented 8.5% casein diet, compared with a basal 20% casein diet, decreased these two measurements without aggravating growth retardation in nephritic rats. These results suggest that aggravation and alleviation of symptoms incident to anti-GBM nephritis are relevant to elevation and reduction of TGF-beta activity, respectively. The results also suggest that amino acid-balanced low-protein diets would have beneficial effects on glomerulonephritis without causing severe protein malnutrition.     

Recurrent type III membranoproliferative glomerulonephritis after kidney transplantation

The first well-documented case of recurrent type III membranoproliferative glomerulonephritis after kidney transplantation is reported in this article. A 48-year-old man was admitted to the hospital because of nephrotic syndrome and moderate renal failure. The renal biopsy showed double-contour images at light microscopy. Electron microscopy revealed electron-dense deposits in the mesangium and in both the subepithelial and subendothelial sides of the basement membrane. Subepithelial deposits were sometimes hump-like and produced an irregular disruption of the lamina densa. A diagnosis of type III membranoproliferative glomerulonephritis was suggested. The patient had a rapid decrease in renal function and received dialysis in 3 months. Three years later, he received a cadaveric kidney transplant, and subsequently recovered normal renal function. Proteinuria appeared after 13 months, and a biopsy of the graft demonstrated recurrence of the original disease. Seven years after transplantation, he returned to hemodialysis.     

Renal transplantation in children less than two years old

Twenty-one infants, 2 years old or younger, received 21 renal transplants between 1983 and 1995. Six of the transplantations were performed from 1983 to 1989, and the remaining 15 were performed from 1990 to 1995. The median age at transplantation was 16.0 months and the median body weight was 9.0 kg. Living-related donor kidneys were used in 15 cases, an adult cadaveric donor kidney was used in one case, and pediatric cadaveric donor kidneys were used in five cases. All grafts were placed intra-abdominally. The immunosuppressive therapy consisted of cyclosporine, azathioprine, and prednisolone. No prophylactic antithymocyte globulins were used. Five infants have died, one with a functioning graft and four after loss of graft function. All graft losses and deaths occurred during the first 6 months after transplantation. The 5-year patient survival and graft survival rates were 87% for recipients of living donor grafts and 44% for recipients of cadaveric grafts. The median height SD score increased from -3.7 before operation to -1.9 at 1 year, -0.7 at 3 years, and -1.1 at 5 years. The glomerular filtration rate in absolute values remained stable in all infants, whereas a reduction in glomerular filtration rate related to body surface area was seen at follow-up, 5 years after transplantation. We conclude that renal transplantation can be performed with good long-term results in children less than 2 years old.     

Primate renal transplants using immunotoxin

BACKGROUND: T-lymphocyte depletion 7 days before transplantation with immunotoxin FN 18-CRM9 has resulted in tolerance to subsequent renal allografts. We tested the effect of giving immunotoxin on the day of the transplantation and evaluated its effect on rhesus monkey and allograft survival, on antibody production, and on T-cell recovery. METHODS: Major histocompatibility complex mismatched renal allografts were performed in rhesus monkeys. Immunotoxin was given starting on the day of transplantation, with and without prednisone and mycophenolate mofetil for 3 days. T-cell subsets and alloantibody levels were measured by flow cytometry. The ability of treated monkeys to develop antibody to tetanus, diphtheria, and xenoantibody was measured. Histology of renal transplants was read in a blinded manner. RESULTS: Immunotoxin started on the day of transplantation resulted in prolonged allograft survival in all treatment groups. Graft loss between days 50 and 135 was most often due to interstitial nephritis. Later graft loss was due to chronic rejection. Monkeys had intact antibody responses to alloantigen, tetanus, diphtheria, and xenoantibody. Their CD4 cells recovered gradually over 6 months. CONCLUSIONS: Immunotoxin reliably prolongs renal allograft survival when started on the day of transplantation, but interstitial nephritis and chronic rejection limit the development of long-term tolerance. T-cell-dependent B-cell responses remain intact after treatment.     

Treatment of end-stage renal disease by transplantation: clinical results with 111 cases

The efficacy of renal transplantation for patients with end-stage renal disease was reviewed in 108 patients receiving 111 transplants followed for an average of two and one-half years after transplantation. Overall patient survival decreased 10 per cent per year from 90 per cent after the first year to 70 per cent at three years. Kidney survival was slightly less, with a similar pattern. Patients with better tissue matches and living related donor allografts had fewer and less severe rejections and better ultimate function than did patients with poor tissue matches and cadaver allografts. However, a significant number of patients with poor tissue matches and cadaver allografts had excellent results. Eighty-six per cent of all survivors with functioning kidneys had serum creatinines of 2.0 mg./100 ml. or below. Mortality was associated primarily with sepsis from a variety of bacterial, fungal, viral and protozoan organisms often associated with other complications such as rejection or gastrointestinal bleeding. Recipients over the age of 40 were in a higher risk group. Rejection per se, however, played a minor role. Urological and skeletal complications were a major source of morbidity but were not associated with mortality.     

Treatment of two cases of perigraft seroma with fistulization to the skin

Goodpasture's syndrome rarely affects children. Therefore, we present our experience in a young boy whose pulmonary hemorrhage was dramatically resolved by three plasma exchanges. We believe the hemorrhage was caused primarily by acute capillaritis. He received cytoxan and steroids and a series of plasma exchanges which removed/suppressed his anti-glomerular basement membrane (anti-GBM) antibody production. However, after a year, his renal function did not return, and he required renal transplantation and continues to do well.     

Role of the peripheral renin profile in predicting blood pressure control after bilateral nephrectomy in renal-transplanted patients

BACKGROUND: The unregulated renin release by native kidneys is one of the factors responsible for the high incidence of hypertension after renal transplantation but, even after three decades of transplantation, there is still a lack of a method to identify it as the major cause of hypertension. METHODS: We investigated whether or not peripheral renin activity, before and 90 min after 25 mg of captopril, can play this role. One hundred and five consecutive patients with SCr less than 2 mg/dl were studied 18 +/- 8 months after renal transplantation. Forty-seven of them were considered hypertensive and 58 normotensive. All hypertensive patients were submitted to the captopril test to analyse the peripheral renin activity profile. RESULTS: In the hypertensive group, 17 patients (36%) were considered Renin-pos and 30 (64%) Renin-neg. All Renin-pos (stimulated renin = 19.1 +/- 6.4 ng/ml/h) patients were submitted to bilateral nephrectomy (bNx) and re-evaluated 6 months later. All of them normalized renin activity (4.4 +/- 3.0 ng/ml/h, P = 0.0001) and 10 of 17 (60%) became normotensive and off drugs. The remaining seven (40%) decreased the number of hypotensive drugs from 2.2 +/- 0.5 to 0.5 +/- 0.7/pt/day. There was a correlation between b-Renin and dBP (r = 0.47, P < 0.05) which was lost after bNx. An 'in situ' renal-cell carcinoma was found in two cases. Serum creatinine did not change. CONCLUSIONS: This study shows that the unregulated renin-angiotensin system from the native kidneys plays a major role in the maintenance of hypertension in some patients with normal graft function and that peripheral renin activity can identify those who will benefit from bilateral nephrectomy.     

Inhibition of intercellular adhesion molecule-1 with antisense deoxynucleotides prolongs renal isograft survival in the rat

BACKGROUND: Delayed graft function from ischemia-reperfusion injury has a negative impact on long-term renal graft survival. We tested the utility of antisense oligodeoxynucleotide (ODN) against intercellular adhesion molecule-1 (ICAM-1) in the pretransplant treatment of renal isografts in improving long-term graft survival. METHODS: Three groups of 16 inbred Lewis rats each underwent unilateral nephrectomy and were then transplanted with a kidney from a Lewis donor rat, which had received antisense ODN, reverse sense ODN, or saline vehicle six hours prior to nephrectomy. The kidneys were subjected to one hour of warm ischemia and 30 minutes of cold ischemia, which when untreated results in delayed graft function. The remaining native kidney was removed 10 days later. Serum creatinine and urinary protein excretion were measured in surviving rats at weeks 2, 4, 6, 8, 12, 16, and 20 after native nephrectomy. RESULTS: A Kaplan-Meier analysis revealed that by week 6 one half of the animals receiving reverse sense ODN and saline vehicle treatment had died, while all but 2 rats in the antisense ODN-treatment group survived to 20 weeks. Serum creatinine concentrations and urine protein excretion of surviving reverse sense and saline vehicle-treated rats were significantly higher than antisense treated rats at every time point. Histology at week 20 revealed marked interstitial fibrosis, focal glomerular sclerosis, vascular intimal and medial thickening and tubular atrophy in reverse sense and saline vehicle-treated kidneys, while antisense ODN-treated kidneys showed only modest changes. Immunohistochemistry showed macrophage and lymphocyte infiltration, as well as substantial up-regulation of MHC class II, in reverse sense and saline vehicle-treated kidneys compared to antisense ODN-treated kidneys. CONCLUSIONS: These results suggest that by ameliorating acute nonimmunological renal isograft injury, the long-term chronic nonimmunologic processes are improved as well. Furthermore, the data suggest that an antisense ODN strategy directed against ICAM-1 may have utility in human kidney transplantation.     

Clinical hepatitis after transplantation of hepatitis C virus-positive kidneys: HLA-DR3 as a risk factor for the development of posttransplant hepatitis

BACKGROUND: Exposure to hepatitis C virus (HCV) and subsequent infection after renal transplantation lead to significant clinical hepatitis in approximately 50% of graft recipients. METHODS: One hundred thirty-two consecutive renal allotransplant patients, who underwent transplantation of kidneys from HCV-positive cadaveric donors, were studied to investigate the relationship between donor and recipient HLA type and the risk of developing clinical hepatitis. Specific attention was directed toward the DR3 and DR4 alleles, as these had previously been associated with worse prognoses in autoimmune and viral hepatitis. RESULTS: Overall, 42% of patients receiving kidneys from donors seropositive for HCV developed clinical hepatitis. This was unrelated to preoperative recipient HCV serum reactivity (P=0.65). Patients receiving kidneys from seropositive donors with HCV RNA as detected by PCR were more likely to develop hepatitis than those receiving kidneys from PCR-negative donors (56% vs. 11%; P=0.005). The presence of the DR3 allele was associated with a significant risk of clinical hepatitis (P=0.025); 80% of DR3-positive recipients (n=34) progressed to hepatitis compared with 42% of DR3-negative patients. No other recipient HLA type was significantly related to prognosis. All patients receiving a donated kidney that expressed the B41 allele developed hepatitis, compared with 55% of recipients of non-B41 grafts (P=0.039). No association between the development of clinical hepatitis and HLA compatibility was found. CONCLUSIONS: These results suggest that both HLA type and viral presence as assayed by polymerase chain reaction, influence the risk of disease progression after transplantation of HCV-positive kidneys. Application of these associations may decrease the relative risk of a recipient contracting HCV hepatitis after cadaveric renal transplantation.