Irreversible Graft Failure Research Articles

Update on human polyomavirus BK nephropathy

Polyomavirus BK (BKV) has ebeen identified as the main cause of polyomavirus-associated nephropathy, a major cause of renal allograft failure. Although BKV-associated nephropathy develops in only 2% to 5% of renal transplant recipients, its prognosis when present is very poor, with irreversible graft failure developing in 45% of affected patients. While the use of urine cytology for the detection of decoy cells has been in use for decades, other diagnostic modalities to detect BKV have emerged, including tissue biopsy, polymerase chain reaction, viral culture, and serology. Currently, there is no consensus regarding the laboratory technique best suited for clinical monitoring. This review article will discuss essential and clinical features of polyomavirus, followed by a discussion pertaining to the various diagnostic modalities that contribute to detecting polyomavirus-associated nephropathy.

Comparison of oral antiviral therapy with valacyclovir or acyclovir after penetrating keratoplasty for herpetic keratitis

Aims:To compare the outcome of prophylactic oral valacyclovir (VAL) or oral acyclovir treatment (ACV) in patients having undergone penetrating keratoplasty for herpetic keratitis (HK).Methods:All patients having received a penetrating keratoplasty...

Idoneidad del injerto corneal de donante neonato en la queratoplastia penetrante

The lower recommended age of the donor cornea is a controversial matter. Although newborn corneas have a high endothelial cell density, there are anatomical, refractive (myopic shift) and postoperative problems. Two cases are analyzed; one had an atypical refractive result and the other an unexpectedly severe immune response. We also review the use of pediatric donor corneas in penetrating keratoplasty. Two young patients with keratoconus, in whom a penetrating keratoplasty was done using a 4-month-old newborn corneal donor with high endothelial cell density (4.500 cell/mm2) are reported. In the early postoperative period, both had high hypermetropy with weak astigmatism that improved over the next few months. In one patient a marked increase in the astigmatism after removal of the continuous suture was observed. One and a half years after the penetrating keratoplasty there was V=1 corrected vision and the endothelial population was almost unchanged (4,300 cell/mm2). The other patient suffered an allograft reaction with corneal oedema in the seventh postoperative month, and subsequent rupture of the continuous suture made its early removal necessary. The oedema partially diminished with high doses of steroids, but still persisted eighteen months later. The newborn corneal graft might have led to an early strong hypermetropy as opposed to the supposed myopic shift referred to in the literature. The extremely rapid healing seen in young recipients may lead to early loosening of the continuous suture. High endothelial cell density increases the risk of irreversible graft failure probably due to a high antigenic response. The use of a newborn donor cornea is questionable due to unpredictable refractive and immunological responses.

Post-penetrating keratoplasty glaucoma

Post-penetrating keratoplasty (post-PK) glaucoma is an important cause of irreversible visual loss and graft failure. The etiology for this disorder is multifactorial, and with the use of new diagnostic equipment, it is now possible to elucidate the exact pathophysiology of this condition. A clear understanding of the various mechanisms that operate during different time frames following PK is essential to chalk out the appropriate management algorithms. The various issues with regard to its management, including the putative risk factors, intraocular pressure (IOP) assessment post-PK, difficulties in monitoring with regard to the visual fields and optic nerve evaluation, are discussed. A step-wise approach to management starting from the medical management to surgery with and without metabolites and the various cycloablative procedures in cases of failed filtering procedures and excessive perilimbal scarring is presented. Finally, the important issue of minimizing the incidence of glaucoma following PK, especially through the use of oversized grafts and iris tightening procedures in the form of concomitant iridoplasty are emphasized. It is important to weigh the risk-benefit ratio of any modality used in the treatment of this condition as procedures aimed at IOP reduction, namely trabeculectomy with antimetabolites, and glaucoma drainage devices can trigger graft rejection, whereas cyclodestructive procedures can not only cause graft failure but also precipitate phthisis bulbi. Watchful expectancy and optimal time of intervention can salvage both graft and vision in this challenging condition.

Die Prognose der Rekeratoplastik: Indikationsbezogene Analysen in einer großen monozentrischen Kohorte

Data from national graft registries suggests a limited prognosis in the group of all repeat keratoplasties. This group might rather consist mostly of cases already classified as high risk in the first place, however. Thus, repeat keratoplasties in normal risk indications might have a substantially better prognosis. In particular, any specific increase of immune reactions following repeat keratoplasty as compared to first keratoplasties is unknown at present. Furthermore, the contribution of chronic endothelial cell loss to graft failure following repeat keratoplasty has not yet been investigated. The aim of this analysis on a large retrospective cohort is to estimate the incidence of graft rejections and failures als well as chronic endothelial cell loss following repeat keratoplasty. All keratoplasties that had been performed from 1986 to 2006 at the University Eye Hospital Düsseldorf were selected for the 4 most relevant indications. A total of 2073 first keratoplasties and 236 repeat keratoplasties for keratoconus, Fuchs endothelial dystrophy, bullous keratopathy and herpetic corneal scars were included in the analysis. For each indication, the incidence of graft rejections and failures was compared between first and repeat keratoplasty using the Kaplan-Meier method and log-rank test. Endothelial cell loss was quantified by means of exponential regression analysis in the cases without immune reactions. Data of 65 repeat keratoplasties and 532 initial keratoplasties were available for analysis in a generalised linear model. After five years, the risk of graft rejections was not increased in repeat keratoplasties for keratoconus as compared to initial keratoplasties. In Fuchs endothelial dystrophy (p = 0.03) and herpetic corneal scars (n. s.) an increase of 11 % was observed. In bullous keratopathy the increase was as high as 24 % (p < or = 0.01). Irreversible graft failure increased by 4 % in keratoconus, 11 % in Fuchs endothelial dystrophy, 7 % in herpetic eye disease and by 31 % in bullous keratopathy. Only the latter difference reached statistical significance (p < or = 0.01), however. In this group, chronic endothelial cell loss was accelerated to a great extent as well: annual cell loss averaged 43 % in repeat keratoplasties whereas this rate was as low as 20 % for the initial surgery (p = 0.01). In the other indications, acceleration of cell loss in repeat keratoplasties as compared to the first transplantation did not exceed 12 % (p = 0.03). The prognosis of repeat keratoplasties for keratoconus does not seem to fall short of that of initial keratoplasty. A slight deterioration can be assumed in Fuchs endothelial and herpetic eye disease dystrophy. Repeat keratoplasties in initial bullous keratopathy, however, seem to have a substantially poorer prognosis with respect to immune reactions, graft survival and chronic endothelial cell loss.

Detection of Anti-HLA Antibodies with Flow Cytometry in Needle Core Biopsies of Renal Transplants Recipients with Chronic Allograft Nephropathy

The aim of this study was to assess the feasibility of detecting anti-HLA antibodies in eluates from needle core biopsies of renal transplants with chronic allograft nephropathy. Two methods of screening, the enzyme-linked immunosorbent assay (ELISA) and flow cytometry (FlowPRA) were compared. Twenty renal transplants with CAN were removed after irreversible graft failure. To assess the feasibility of detecting anti-HLA antibodies in small samples, needle core biopsies were sampled at the same place as surgical samples and at a second cortical area. Antibodies were eluted with an acid elution kit and anti-class I and class II IgG HLA antibodies detected using ELISA and flow cytometry. Flow cytometry was found to be more sensitive than ELISA for detecting anti-HLA antibodies in eluates from renal transplants with CAN (95% vs. 75% of positive cases). Detection of anti-HLA antibodies showed good agreement between surgical samples and needle core biopsies performed at the same place for anti-class I (80% vs. 65%, r=0.724 P<0.01) and anti-class II HLA antibodies (70% vs. 55%, r=0.827 P<0.01). In addition, differences in the detection of anti-class I HLA antibodies in needle core biopsies sampled at different sites suggests that immunization to class I donor antigen could be underestimated in needle core biopsy samples. These data indicate that anti-HLA antibodies can be detected in needle core biopsies from renal transplants. Provided further evaluation is done, elution might be a complementary method to detect anti-HLA antibodies when they are bound to the transplant.

Die ipsilaterale autologe Rotationskeratoplastik: Eine Möglichkeit der frühen Amblyopieprophylaxe bei Peters’scher Anomalie

It is a challenge to prevent irreversible amblyopia in infants suffering from Peters anomaly. In some cases of centrally located corneal opacifications an optical sector iridectomy can not lead to a clear optical axis. The homologous penetrating keratoplasty as early surgical procedure has shown an extremely poor outcome with a high risk of irreversible graft failure. We report on the autologous ipsilateral rotating penetrating keratoplasty in an eight-week-old infant suffering from Peters anomaly. An autologous ipsilateral rotating penetrating keratoplasty was performed in an eight-week-old infant suffering from Peters anomaly to prevent irreversible amblyopia. After a follow-up time of 8 months we saw a clear graft within the optical axis without any complications in wound healing. We removed the single sutures two months after keratoplasty. Postoperative astigmatism could be corrected first by fitting a special nursery contact lens and after reduction of astigmatism because of suture removal we fitted special nursery glasses. The intraocular pressure remained within the normal range during the follow-up period. The autologous ipsilateral rotating penetrating keratoplasty should be considered superior to homologous keratoplasty in infants with Peters anomaly if sector iridectomy is not advisable because of a central corneal opacification. Resulting high refractive errors can be successfully corrected by special contact lens fitting or by nursery glasses.

Topical FK506 as immunoprophylaxis after allogeneic penetrating normal-risk keratoplasty: a randomized clinical pilot study

The purpose of this study was to evaluate for the first time the efficacy and safety of topical FK506 in patients undergoing penetrating normal-risk keratoplasty in a prospectively randomized clinical trial. Twenty patients were treated with FK506 0.06% three times per day for 6 months postoperatively. An additional 20 patients received five drops of prednisolone acetate 1% tapered within 6 months. All patients received 1 mg/kg bodyweight/day of systemic fluocortolon tapered within 3 weeks postoperatively. Clear graft survival, ratio of immune reactions and side effects were the main outcome measures. One year postoperatively all patients of the FK 506 group were free from immune reactions, in contrast to 84% in the steroid group (Kaplan-Meier values; P = 0.9 in the log rank test). None of the patients developed irreversible graft failure so far. In eight patients of the FK506 group premature withdrawal of the drug was deemed appropriate because of local side effects. FK506 might turn out to become an effective immunoprophylaxis in subjects undergoing penetrating normal-risk keratoplasty. Local discomfort should be further reduced.

Penetrating keratoplasty for macular corneal dystrophy

To determine the prognosis of penetrating keratoplasty (PK) for macular corneal dystrophy (MCD). Single-center, retrospective, interventional, noncomparative case series. One hundred forty-one patients (229 eyes) with MCD. Retrospective review of the medical record of every patient who underwent primary PK for histopathologically confirmed MCD at the King Khaled Eye Specialist Hospital between January 1, 1983 and December 31, 2002 and for whom at least 12 months of follow-up is available. Visual acuity (VA), graft survival, and postoperative complications. After a mean follow-up period of 5.9+/-3.8 years (range, 1-17), the mean best-corrected VA was 20/50. At the most recent visit, 206 (90.0%) grafts were clear, and 23 (10.0%) had failed. Probabilities of graft survival were 98.1% at 1 year, 89.8% at 5 years, 82.1% at 10 years, and 74.1% at 15 years. There was a statistically significant increased likelihood of graft failure if the patient was older than 40 years at the time of surgery (P<0.00003). The differences in graft failure between patients older than 40 and those younger were not attributable to statistically significant differences in duration of follow-up, donor age, or donor endothelial cell counts. Corneal endothelial rejection episodes occurred in 47 (20.0%) grafts, but resulted in irreversible graft failure in only 8 (3.5%) eyes. Eighteen (27.3%) of 66 eyes with a recipient size of > or =7.5 mm developed a graft rejection episode, compared with 27 (16.6%) of 163 eyes with a recipient size of <7.5 mm (P = 0.04). Microbial keratitis occurred in 14 (6.1%) grafts and was more likely to occur in patients over 40 (14.0% vs. 3.0%, P = 0.01). Clinically significant recurrence was observed in 12 (5.2%) grafts, after a mean interval of 84+/-48.2 months, and was directly related to patient age (P = 0.04) and inversely related to donor graft size (P = 0.04). Good visual results and excellent graft survival can be achieved after PK for MCD. The risk of graft failure is higher in patients older than 40 years.

Funktionelle Ergebnisse der perforierenden Keratoplastik bei Pseudoexfoliationssyndrom (PEX)-Keratopathie

Keratopathy in pseudoexfoliation syndrome (PEX-keratopathy) is a particular form of corneal endothelial decompensation, which requires a penetrating keratoplasty (PK) for visual rehabilitation at advanced states. The aim of this study was to evaluate the functional outcome and the development of intraocular pressure (IOP) after PK in patients with PEX-keratopathy depending on the presence of pre-existing glaucoma. This retrospective study included 21 eyes of 21 patients (age 78.6 +/- 7.5 years) with a mean postoperative follow-up of 1.8 +/- 2.2 (median 2) years. The diagnosis of PEX-keratopathy was confirmed clinically as well as by electron microscopy. The recipient and donor trephinations were performed from the epithelial side using an 193 nm excimer laser (n = 11) or mechanically (n = 10). An iridotomy was performed routinely during PK. The postoperative treatment with topical steroid was standardized. Preoperatively, a secondary open-angle glaucoma (SOAG) with optic nerve damage was diagnosed in 11 patients (52 %). Topical antiglaucomatous treatment was needed in 81 % of patients with SOAG. Six weeks postoperatively, patients with SOAG showed a higher prevalence of increased intraocular pressure (IOP) and/or antiglaucomatous treatment compared to patients without SOAG (45 % vs. 20 %). Most of the mild-early intraocular pressure elevations were controlled in both groups during the follow-up. From one year post-PK, there was an increased need for topical antiglaucomatous treatment in both patient groups. In all eyes the IOP was controlled by topical antiglaucomatous treatment. Preoperatively, visual acuity was comparable in patients with and without SOAG (0.06 +/- 0.09 vs. 0.08 +/- 0.1, p = 0.7), but increased significantly more in patients without SOAG (0.38 +/- 0.1, median 0.4) than in patients with SOAG (0.2 +/- 0.1, median 0.2; p = 0.01) after PK. Visual acuity remained stable in both groups throughout the follow-up period. During follow-up only one eye developed an episode of reversible endothelial graft rejection 18 months postoperatively. An irreversible graft failure was seen in none of the patients. The functional outcome after PK in PEX-keratopathy seems to be strongly associated with pre-existing SOAG. Patients without SOAG may expect good visual rehabilitation without persistent postoperative IOP increases. However, patients should be followed-up for a prolonged period of time, because from 1 year following PK the need for topical antiglaucomatous treatment increased significantly.

HLA Mismatching Increases the Risk of BK Virus Nephropathy in Renal Transplant Recipients

BK virus (BKV)nephropathy is a serious complication in kidney transplant recipients that may lead to irreversible graft failure. We have analyzed the degree of donor/recipient HLA compatibility and HLA antigen association in 40 kidney transplant patients with BKV nephropathy in comparison with a control group of 404 unaffected transplant recipients who were on tacrolimus-based immunosuppression with no induction. HLA compatibility was assessed by determining the number of HLA-A, -B, -DR-mismatched antigens. BK virus nephropathy was diagnosed histologically and confirmed by immunochemistry. Univariate and multiple logistic regression statistical analyses have shown a significant association between BKV nephropathy and HLA mismatching. This analysis showed also that BKV nephritis is associated with a greater number of rejection episodes and a higher incidence of steroid-resistant rejection requiring antilymphocyte treatment. There was no association between BKV nephropathy and any specific HLA allele. We propose that HLA mismatching promotes the development of BKV nephropathy through rejection-related inflammatory processes and heavy immunosuppression which cause virus reactivation and injury of the tubular epithelium.

Liver retransplantation in children in Poland

An average of 15% of patients require retransplantation due to irreversible liver graft failure due to primary graft nonfunction, chronic rejection, vascular and biliary complications, or infections. The survival of patients and grafts after retransplantation is inferior to that after primary transplantation. The purpose of the present study was to examine the incidence, indications, and outcome of retransplantation in children. In our center 169 liver transplantations had been performed in 154 patients, and 14 patients (9%) required 15 retransplantations: nine in the early postoperative period, five late after primary transplantation, and one late after the second transplantation. One-year patient survival after primary transplantation was 82%, but after early retransplantation it was 55%.

Detection of donor-specific anti-HLA antibodies with flow cytometry in eluates and sera from renal transplant recipients with chronic allograft nephropathy.

Chronic allograft nephropathy (CAN), which remains the main cause of graft loss after kidney transplantation, is still poorly understood. Because anti-HLA antibodies may be involved in the pathogenesis of CAN, this study was performed to look for donor-specific antibodies (DSA) fixed onto renal transplants with CAN. DSA were identified after elution with flow cytometric assay and/or flow cytometric crossmatches in 20 transplants removed after irreversible graft failure caused by CAN and in control samples from 2 transplants with relapsing glomerulopathy, 2 transplants lost after vascular thrombosis, and 4 normal kidneys. The results were compared with those obtained in the serum samples 1 year after grafting, at the time of transplantectomy, and within 2 months after transplantectomy. IgG anti-class I, anti-class II, or both DSA were identified in 70.6% of eluates versus 73.6% of posttransplantectomy serum samples (NS), 42.1% of 1-year postgrafting serum samples (P<0.05), and 31.6% of serum samples at the time of transplantectomy (P<0.05). Our data show a good correlation between the target of anti-HLA antibodies found in both eluates and posttransplantectomy serum samples, but the precise specificity of anti-HLA antibodies is more often assigned in posttransplantectomy serum samples than in eluates. This problem needs further evaluation. This study shows that testing for anti-HLA DSA in eluates from removed kidney transplants using flow cytometry can be achieved and is highly efficient. It already suggests that both anti-class I and anti-class II HLA antibodies can be involved in CAN. Further studies are now needed to evaluate the possibility of identifying such antibodies in the eluates of transplant biopsy specimens from recipients experiencing CAN.

Risk factors for corneal allograft rejection: intermediate results of a prospective normal-risk keratoplasty study.

To analyze the incidence of and possible risk factors for endothelial corneal allograft rejection in a well-defined population following penetrating normal-risk keratoplasty. Since 1996 a longitudinal prospective study has been conducted to analyze the results of normal-risk penetrating keratoplasty. All patients underwent a standardized protocol of follow-up treatment and examinations in our institution. Diagnosis of corneal endothelial rejection was based on slit-lamp biomicroscopy and laser flare photometry. Data were analyzed using a proportional hazard model for censored data (Cox model), and Kaplan-Meier survival curves. The following parameters were analyzed: age, gender, atopic dermatitis, dry eye symptoms of the recipient; surgeon, graft diameter, post-mortem time, storage time and graft preservation method; and duration of postoperative epithelial defects. Between 1996 and May 2001, 397 patients were recruited and followed with a median follow-up of 18 months. Episodes of endothelial graft rejection were observed in 22 patients (5.5%; 18 eyes with acute diffuse episodes and 4 eyes with chronic focal rejection episodes). In addition, 12 eyes (3%) showed isolated small keratic precipitates ("graft rejection suspects"). All but one graft regained clarity after topical and systemic steroid treatment. Most episodes occurred 11-18 months postoperatively. The percentage of grafts without any episode of endothelial allograft rejection was 95% after 12 months, 89% after 18 months, and 86.5% after 24 months. The following factors were associated with graft rejection: atopic dermatitis (P=0.021), clinically manifest tear insufficiency (P=0.007), and short duration of graft storage (P=0.008). No significant correlation was detected for the remainder of the analyzed factors (P>0.05). The incidence of episodes of corneal endothelial allograft rejection following normal-risk keratoplasty was 13.5% within the first two postoperative years. However, the frequency of irreversible immunologic graft failure (3 per thousand) was lower than reported in the literature. Patients should be regularly followed up for at least 18 months postoperatively. Patients with underlying atopic dermatitis or dry eyes should receive special ophthalmological care.

Chronic endothelial cell loss of the graft after penetrating keratoplasty: influence of endothelial cell migration from graft to host

Chronic endothelial cell loss of the graft is common after penetrating keratoplasty. Some kind of subclinical immunological reaction that is not visible at the slitlamp has been suspected as main cause for this phenomenon. Furthermore, migration of graft endothelial cells towards the host cornea has been discussed to add to this loss in special cases. In this study, 3 homogenous patient groups with similar risk of immunological reactions were examined. Main difference between these groups was the potential of graft endothelial cells to migrate towards the host cornea. Patients with keratoconus without cataract surgery (group I with little migration potential, n = 273), patients with Fuchs endothelial dystrophy without/with cataract surgery (groups IIa/IIb with moderate migration potential, n = 89/n = 165) and patients with bullous keratopathy after cataract surgery (group III with potentially large migration tendency, n = 188) were included in the study. All patients had a first keratoplasty. Patients with glaucoma or further intraocular procedures after keratoplasty were excluded from the study. Clear graft survival and ratio of grafts without immune reactions were estimated according to Kaplan and Meier. Endothelial analysis concerned only patients without immune reactions and with at least 3 postoperative endothelial cell density values of the graft center (76 patients in I, 18 patients in IIa, 41 patients in IIb and 23 patients in III). Mean relative loss of endothelial cells per year was 14.0 +/- 19.0 % in group I, 17.0 +/- 19.1 % in group IIa, 20.8 +/- 18.2 % in group IIb and 29.4 +/- 17.6 % in group III (ANOVA, p < 0.01). Five years postoperatively in group I 99 %, in group IIa 98 %, in group IIb 93 % and in group III 69 % of the grafts were centrally clear (log rank test, p < 0.001). In the same period in group I 88 %, in group IIa 86 %, in group IIb 83 % and in group III 81 % of the grafts were free of immune reactions (log rank test, p < 0.05). Reasons for irreversible graft failure were immune reactions (0 in group I; 0 in group IIa; 1 in group IIb; 9 in group III, ), surface disorders (1 in group I; 0 in IIa; 1 in group IIb; 3 in group III) and endothelial failure (0 in group I; 1 in group IIa; 5 in group IIb; 6 in group III) (chi square test, p < 0.01). In patients with bullous keratopathy endothelial cell loss via migration seems to add significantly to the general chronic loss which is suspected to be immunological. Peripheral migration of endothelial cells, therefore, most probably contributes to limited prognosis of patients with bullous keratopathy in terms of clear graft survival. In consequence, corneal grafts for bullous keratopathy should be as large as immunologically tolerable, and endothelial cell density should be as high as possible in order to counteract this special endothelial loss factor.

Combined intravenous pulse methylprednisolone and oral cyclosporine A in the treatment of corneal graft rejection: 5-year experience.

To report the mid-term results of a treatment strategy using topical steroids, intravenous pulse methyl prednisolone and oral cyclosporine A (CSA) for the treatment of acute corneal graft rejection. Noncomparative, interventional case series. Treatment of corneal graft rejection included 1% prednisolone eye drops, intravenous infusion of 500 mg methyl prednisolone, and oral CSA in two regimens--standard dose was 15 mg/kg/day for 2 days, 7.5 mg/kg/day for 2 days, then adjusted to maintain trough blood levels of 100-200 microg/l; low dose was 2 mg/kg/day with no loading dose. Outcome in 34 eyes of 34 patients (21 M;13 F) aged 60 +/- 17.7 years (range 9-83 years), who presented after an average duration of 6.6 +/- 6.3 days (range 0-30 days) following acute corneal graft rejection, are reported. Twenty-five patients received standard dose CSA while nine patients received the low dose regimen. Mean duration of treatment before reversal of graft rejection was 13.6 +/- 12.1 days (range 3-54 days). Treatment was successful in reversing the graft rejection in 32/34 (94%) eyes. Irreversible graft failure occurred in one eye in each group. During a mean follow-up period of 19.2 +/- 16.7 months (range 1-55 months), further episodes of graft rejection were seen in 1/32 (3%) eyes. Complications due to treatment included: duodenal ulcer in one patient that responded to medical treatment, and transient elevation in serum creatinine levels in three patients, which returned to normal after decrease in dosage or cessation of oral CSA. Our 5-year experience with the use of oral CSA in the treatment of acute corneal graft rejection has shown this treatment approach to be safe and effective in reversing the rejection process. This approach may also protect the graft from subsequent episodes of allograft rejection. A randomised controlled trial to further delineate the role of CSA in reversing acute graft rejection seems warranted.

Visual rehabilitation and intraocular pressure elevation due to immunological graft rejection following penetrating keratoplasty

Endothelial graft rejection and intraocular pressure elevation are the most common causes of graft failure following penetrating keratoplasty (PK). Aim of this study was to evaluate the visual rehabilitation and the development of intraocular pressure during and after graft rejection. The study included 20 eyes of 20 patients (age 54.7 +/- 19.8 years) with endothelial graft rejection, that fulfilled the following inclusion criteria 1) graft rejection was diagnosed and treated in our department; 2) at least one year follow-up after graft rejection; 3) avascular corneal pathology. The mean follow-up was 23 +/- 14 months. According to the type of surgical procedure patients were classified in PK only (n = 15, one after cataract extraction), PK combined with extracapsular cataract extraction and intraocular lens (IOL) implantation (n = 1); PK combined with secondary IOL-implantation or IOL-exchange (n = 4). Standardized complete ophthalmological examinations were performed on a regular basis before, during the acute graft rejection und then regularly in a defined examination raster in an out-patient service with cornea specialization. The time interval between first symptom of 18 acute diffuse and 2 chronic focal graft rejection and start of treatment was 9 +/- 13 days. Best-corrected visual acuity (CVA) was 0.6 +/- 0.2 before graft rejection and decreased significantly at the time of diagnosis (0.2 +/- 0.2; p = 0.001). Six weeks after graft rejection CVA was 0.5 +/- 0.2 and remained almost stable until one year after rejection (0.6 +/- 0.3) in 16 patients with reversible graft rejection. Only 4 patients (20%) showed an irreversible graft failure requiring Re-PK. Intraocular pressure (IOP) was not elevated in 75% of the patients (n = 15) and did not need any antiglaucomatous treatment during and after the rejection phase. In 5 eyes (25%) (3 after PK combined with anterior chamber IOL-explantation and secondary posterior chamber IOL-implantation; 1 with secondary pseudoexfoliation glaucoma and 1 steroidal responder) IOP was elevated during graft rejection (26 +/- 7 mmHg), but was controlled by intensive topical antiglaucomatous treatment. Typically, the visual rehabilitation after graft rejection was good if the clinical signs were diagnosed just in time and treated adequately. There is no direct correlation between graft rejection and intraocular pressure elevation. However, the development of intraocular pressure elevation seems to be strongly associated with preexisting glaucoma, preexisting anterior synechiae and/or simultaneous anterior chamber lens implant removal. A careful patient management after PK plays an important role to prevent the development of irreversible graft failure due to graft rejection.

Polyoma virus infection after renal transplantation. Use of immunostaining as a guide to diagnosis.

Polyoma virus infection is characterized by lymphocytic interstitial infiltrate in the kidney, and it mimics acute rejection. The purpose of this study is to estimate renal allograft outcome with this infection and characterize the lymphocytic infiltrates in polyoma virus-infected renal allografts. Patients who had polyoma virus inclusions in renal allograft biopsies were identified. Other viral inclusions were excluded by immunohistochemistry. The lymphocytic infiltrates of six cases of polyoma virus infection were compared with six cases of definite acute rejection by immunostaining for T and B cells. There were 10 cases of polyoma virus infections in renal transplant recipients. Immunosuppressants consisted of mycophenolate mofetil with tacrolimus in eight cases and mycophenolate mofetil with cyclosporine in two. The median time of diagnosis of polyoma virus infection after transplantation was 9.5 months, and the time to graft failure after the diagnosis was 4 months. Reduced allograft survival was seen in patients who had polyoma virus infection. Immunostaining for T and B cells revealed marked increase in the B cells (CD20) in renal allografts with polyoma virus infection of 21% (range, 5-40%) compared with 6% (range, 0-10%) in those with acute rejection (P=0.039). Reduced cytotoxic T cells (TIA-1: median, 7%; range, 2-15%) were seen in polyoma virus-infected allografts compared with 24% (range, 15-30%) in those patients who had acute rejection (P=0.0159). Irreversible graft failure is more prevalent with polyoma virus infection. Enhanced immunosuppressants with mycophenolate mofetil with tacrolimus may play a role in the development of this infection. An increase in CD20 and a decrease in cytotoxic T cells in allografts is characteristic of polyoma virus infection.

Continuing improvement in cadaver donor graft survival in North American children: the 1998 annual report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

This report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) covers the years 1987-1997, and analyses data on 3,133 cadaver donor (CD) transplants performed in 2,736 patients. There has been a steady decline in the number of CD transplants in children since 1996. Kidneys recovered from donors under 10 years of age accounted for 35% of all transplants in 1987, whereas by 1996 they comprised less than 20%. Caucasian children received 54% of CD transplants, whereas African-American children received 21%. Children under 6 years of age received 17% of CD transplants. Approximately half (46%) of the patients were induced with a T-cell antibody, and at 7 years post-transplant triple therapy is used in 70% of those with a functioning graft. Cyclosporin A is the primary immunosuppressant, with 92% of the patients being maintained on it at 5 years post-transplant. Among patients receiving a transplant in 1997, 11% were initiated with another calcineurin inhibitor, tacrolimus. At 15 days post-transplant 20% of the patients have had a rejection episode and by day 45, 46% have had an acute rejection. The probability of developing a rejection within the first year was reduced from 71% in 1987-1988 to 47% in 1995-1996.

Single-lung retransplantation for late graft failure

In lung or heart-lung recipients, an irreversible graft-failure may develop in connection with chronic rejection, infection or bronchial complications. A limited number of transplant-recipients have undergone a retransplantation procedure in several centres. First results are discouraging, especially in the case of early retransplantation. We decided, 3 yrs ago, to evaluate the feasibility and benefits of single-lung retransplantation in lung-transplant recipients with late graft-failure. Eight consecutive single-lung retransplantations were performed in patients with previous single-lung (n = 7), or double-lung (n = 1) transplant. Primary graft and native lung were removed in 5 and 3 patients, respectively. The delay between the two surgical procedures was 16 +/- 10 months (range 6-37 months). Three patients died within 3 months. Long-term survivors experienced stable and satisfactory functional results (forced expiratory volume in one second (FEV1 63 +/- 21% predicted; range 40-103% predicted), with survival values ranging 8-20 months. One patient died of septic shock 16.5 months after retransplantation. The remaining four patients are alive. These data suggest that the retransplantation option could be considered in selected patients with late graft-failure. The final decision for retransplantation, however, is largely influenced by the current shortage of donor lungs.