Allograft Biopsy Findings Research Articles

Arterial spin labeling combined with T1 mapping for assessment of kidney function and histopathology in patients with long-term renal transplant survival after kidney transplantation.

The long-term survival of kidney transplants is often influenced by various factors, among which renal allograft rejection is the most notable factor. A noninvasive and reliable imaging biomarker correlating with kidney function and histopathology would facilitate longitudinal long-term follow-up of renal allografts. The aim of the study is to investigate the value of arterial spin labeling (ASL) combined with T1 mapping for assessing kidney function in patients with long-term renal transplant survival, and to establish radiological and histopathologic correlations between the magnetic resonance imaging (MRI) measurements and kidney allograft biopsy findings. Kidney transplant recipients who were admitted to the Department of Urology in First Affiliated Hospital of Soochow University between January and December 2022 were prospectively consecutively recruited [group A, estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2; group B, 30≤ eGFR <60 mL/min/1.73 m2; group C, eGFR <30 mL/min/1.73 m2], and part of them underwent biopsies. All patients underwent ASL and T1 mapping. MRI parameters were calculated and analyzed. A total of 63 patients (Group A, 30 cases; Group B, 20 cases; and Group C, 13 cases) were included in this cross-sectional study. Cortical T1 increased, whereas renal blood flow (RBF) and ΔT1 [100% × (cortical T1 - medullary T1)/cortical T1] decreased with the decrease of eGFR. The RBF, cortical T1, and ΔT1 values were moderately correlated with eGFR (r=0.569, -0.573, and 0.672, respectively). The MRI parameters were moderately correlated with Banff scores, which determined renal allograft rejection and chronicity. The area under the curve (AUC) for the discrimination of groups A versus B and groups A versus C were 0.740 [95% confidence interval (CI): 0.597-0.854, P=0.004] and 0.923 (95% CI: 0.800-0.982, P<0.001), respectively, using ASL; 0.873 (95% CI: 0.749-0.950, P<0.001) and 0.926 (95% CI: 0.803-0.983, P<0.001), respectively, using T1 mapping; and 0.892 (95% CI: 0.771-0.962, P<0.001) and 0.956 (95% CI: 0.846-0.995, P<0.001), respectively, using multi-parameter MRI. The AUC for discrimination between groups B and C was 0.729 (95% CI: 0.546-0.868, P=0.02) using ASL. The RBF, cortical T1, and ΔT1 can serve as new imaging biomarkers of kidney function and histopathological microstructure.

Impact of nonspecific allograft biopsy findings in symptomatic kidney transplant recipients

A for-cause biopsy is performed to diagnose the cause of allograft dysfunction in kidney transplantation. We occasionally encounter ambiguous biopsy results in symptomatic kidney transplant recipients. Yet, the allograft survival outcome in symptomatic recipients with nonspecific allograft biopsy findings remains unclear. The purpose of this study was to analyze the impact of nonspecific for-cause biopsy findings in symptomatic kidney transplant recipients. We retrospectively collected records from 773 kidney transplant recipients between January 2008 and October 2021. The characteristics of transplant recipients with nonspecific findings in the first for-cause biopsy were analyzed. Nonspecific allograft biopsy findings were defined as other biopsy findings excluding rejection, borderline rejection, calcineurin inhibitor toxicity, infection, glomerulonephritis, and diabetic nephropathy. The graft outcome was compared between recipients who had never undergone a for-cause biopsy and those who had a first for-cause biopsy with nonspecific findings. The graft survival in recipients with nonspecific for-cause biopsy findings was comparable to that in recipients who did not require the for-cause biopsy before and after propensity score matching. Even in symptomatic kidney transplant recipients, nonspecific allograft biopsy findings might not be a poor prognostic factor for allograft survival compared to recipients who did not require the for-cause biopsy.

The Molecular Diagnosis Might Be Clinically Useful in Discrepant Kidney Allograft Biopsy Findings: An Analysis of Clinical Outcomes.

The Molecular Microscope Diagnostic System (MMDx) may overcome histology shortcomings. Previous studies have simply examined discrepant findings but have not attempted to determine clinical endpoints. To measure performance, clinical outcomes are strongly required. This single-center cohort study described discrepancies between MMDx and histology from 51 kidney transplant recipients (KTRs) and analyzed 72 indication biopsies, including 21 follow-up biopsies. Clinical performance was assessed by a combined endpoint of graft failure, rejection on follow-up biopsy, de novo donor-specific antibody, and improvement of kidney allograft function upon antirejection treatment. MMDx agreed in 33 (65%) and differed in 18 (35%) of 51 KTRs. Most discrepancies occurred in biopsies called no rejection by MMDx and rejection by histology (15/24, 63%). In contrast, in biopsies called rejection by MMDx, 3 were classified as no rejection by histology (3/27, 11%). Discrepant findings between MMDx and histology occurred following delayed graft function and MMDx from biopsies with a low percentage of cortex. Among 15 biopsies classified as no rejection by MMDx but rejection by histology, the clinical course suggested no rejection in 9 cases. Six KTRs reached the endpoint, showing predominant t ≥ 2 lesions. The most often occurring discrepancy is rejection by histology but no rejection by MMDx. As more KTRs do not meet the combined endpoint for rejection, MMDx might be clinically useful in these discrepant cases. Although strong histological findings have priority in indicating the treatment, clinical implementation of MMDx could strengthen treatment strategies.

The Role of Lymphocyte Subset in Predicting Allograft Rejections in Kidney Transplant Recipients

Allograft rejection remains a significant challenge in managing post-transplant recipients despite the improvement in immunologic risk assessment and immunosuppressive therapy. Published literature including animal studies has demonstrated that the cells responsible for rejection are beyond the innate T and B cells, and other studies revealed evidence supporting natural killer (NK) cells' role in kidney allograft injury. This study aims to find the association between the peripheral blood lymphocyte subset counts, primarily NK cells, and the kidney allograft biopsy findings. This is a prospective cross-sectional study among a total of 100 kidney allograft biopsies in 61 kidney transplant recipients. The peripheral blood for the lymphocyte subset was sent just before the allograft biopsy. The patients' immunosuppression and other laboratory investigations were managed as per clinical practices by the attending nephrologist. Overall, the mean age of our patients was 43.72 ± 10.68 years old, and 55.7% of recipients were male. Higher counts of T cells (CD4+; 658.8 ± 441.4 cells/µL; P = .043) and NK cells (CD3-CD16+CD56+; 188 [interquartile range = 133.0-363.0 cells/µL]; P = .002) were associated with higher risk of allograft rejection in the initial analysis. Patients with an allograft age <12 months had significantly higher total T cells, CD4+ T cells, and NK cells in the rejection groups. However, after assessing factors associated with rejection in the multivariate analysis, we only found that being ABO-incompatible and having >497 CD4+ cells/µL had a higher odds of allograft rejection. Higher CD4± counts were associated with a higher risk of allograft rejection. However, there was no significant increase in CD8±, CD19±, and NK cells count in our cohort with allograft rejection.

Kidney allograft biopsy findings after COVID-19

COVID‐19 has been associated with acute kidney injury and published reports of native kidney biopsies have reported diverse pathologies. Case series directed specifically to kidney allograft biopsy findings in the setting of COVID‐19 are lacking. We evaluated 18 kidney transplant recipients who were infected with SARS‐CoV‐2 and underwent allograft biopsy. Patients had a median age of 55 years, six were female, and five were Black. Fifteen patients developed COVID‐19 pneumonia, of which five required mechanical ventilation. Notably, five of 11 (45%) biopsies obtained within 1 month of positive SARS‐CoV‐2 PCR showed acute rejection (four with arteritis, three of which were not associated with reduced immunosuppression). The remaining six biopsies revealed podocytopathy (n = 2, collapsing glomerulopathy and lupus podocytopathy), acute tubular injury (n = 2), infarction (n = 1), and transplant glomerulopathy (n = 1). Biopsies performed >1 month after positive SARS‐CoV‐2 PCR revealed collapsing glomerulopathy (n = 1), acute tubular injury (n = 1), and nonspecific histologic findings (n = 5). No direct viral infection of the kidney allograft was detected by immunohistochemistry, in situ hybridization, or electron microscopy. On follow‐up, two patients died and most patients showed persistent allograft dysfunction. In conclusion, we demonstrate diverse causes of kidney allograft dysfunction after COVID‐19, the most common being acute rejection with arteritis.

Renal Allograft Biopsy Findings in Live-related Renal Transplant Recipients.

To determine the pattern of histopathology in living-related, kidney transplant recipients (KTRs) from a transplant centre in Khyber Pakhtunkhwa (KPK), Pakistan. Descriptive, observational study. Institute of Kidney Diseases, Peshawar, from August 2008 to July 2018. A retrospective review of graft biopsy reports and clinical charts from living-related, kidney transplant recipients was carried out. Allograft biopsies were done for graft dysfunction with no apparent cause. The biopsy pathology was classified according to updated Banff classifications. The descriptive statistics were used to tabulate the results. Out of the 55 biopsies, 51 (92.73%) were from males with mean age of 34.35±9.40 years. Out of 52 percutaneous biopsies, 10 (19.23%) belonged to the normal category. Category 2 (borderline rejection) and 3 (acute/active cellular rejection) were seen in three (5.7%) and one (1.9%) cases, respectively. Interstitial fibrosis/tubular atrophy (Banff Category 5) was observed in 18 (34.62%) cases. Banff Category 6 (others) was seen in 19 (36.5%) cases, in which calcineurin inhibitors (CNI) toxicity was commonest (17 [89.4%] of 19 cases). Mixed lesions were found in 19 (36.5%) cases. Out of the 19 mixed category cases, 12 (63.16%) showed both Category 3 and Category 5 changes with most of the cases showing mild to moderate IF/TA; while one case had severe IF/TA. Three graft nephrectomies were done, one each for recurrent oxalosis, nephroblastoma and fungal infection. Among the studied specimens, mixed lesions were the predominant findings, followed by others (mostly CNI toxicity) and IFTA categories. The frequency of acute/active rejections was low and that of chronic changes higher, in keeping with delayed biopsies. Key Words: Allograft biopsy, Graft dysfunction, Rejection, Kidney.

Correspondence: The First Asian Kidney Transplantation Prediction Models for Long-term Patient and Allograft Survival.

We read the article by Udomkarnjananun et al and appreciate the author’s effort to establish the first Asian kidney transplant (KT) prediction model for long-term outcomes.1 As the authors mentioned in the article, most of the previous prediction models were derived from Caucasian cohorts. Considering the differences in ethnicity, insurance, and pharmacokinetics, this prediction model seems to be useful for predicting outcomes in Asian KT recipients. However, this model might not be fully applicable in current Asian recipients and for long-term outcomes because of two reasons. First, a prediction model is evaluated in terms of the abilities of discrimination and calibration. Regarding calibration, this model derived in Thailand would work well in other Asian countries. However, it might be difficult to discriminate the probability of outcome in each individual since most Asian countries, except China and Thailand, perform predominantly living-donor KTs (LDKTs) (Figure 1).2 Although this model includes donor type as a predictor, characteristics of LDKT in Asian countries might show a high level of collinearity except the recipient’s age, cause of end-stage kidney disease, and comorbidity. For instance, the proportion of positive hepatitis C virus antibodies in donors is <2%, and the use of tacrolimus as the maintenance immunosuppressive medication is over 85% in Japan. Furthermore, donor’s serum creatinine levels have very narrow SD (0.8 ± 0.1 mg/dL), and most patients have extremely low levels of panel-reactive antibody (Annual Progress Report from the Japanese Renal Transplant Registry. In Japanese). Thus, it would be difficult to discriminate the probability of outcomes in some Asian countries where LDKTs predominate DDKTs.FIGURE 1.: Proportion of donor types among Asian countries in 2019. This figure is referred to as Ref. 2.Second, prediction models in KT mainly have three purposes (decision making before transplantation, and short-term and long-term prognosis). If the decision making for the patients and their families whether KT is better than dialysis therapy in terms of prognosis is the main concern, only available information at the time of KT can be incorporated into the prediction model as in “iChoose Kidney.”3 The other US prediction score by Molnar et al4 (http://transplantscore.com/), which was referred as a comparison in the article by Udomkarnjananun et al, was created not only for shared decision-making purposes but also for short-term prediction.4 Therefore, it selected only pre-KT information. On the other hand, if the prediction of long-term outcomes (5 y and above) is the priority as in the model by Udomkarnjananun et al, the addition of relevant post-KT information as well as pre-KT variables such as allograft biopsy findings and rejection events would much improve the predictive accuracy. In fact, a recent prediction model for kidney allograft loss (long-term outcome) by Loupy et al,5 which consists of only post-KT information (such as kidney function, proteinuria, histologic findings, and human leukocyte antigen antibody profiling), has 0.8 of C-statistics for a 7-year prediction, which is regarded as a great discrimination ability. Albeit utility of using only post-KT information for predicting long-term outcomes, short-term prognosis (early death or graft loss) could not be taken into account, which corresponds to survivor bias. Thus, to develop the most appropriate and applicable prediction model in Asia, we suggest the model would take the type of donor and post-KT information into account, which would make the prediction ability much better.

Transplantation of Kidneys From Hepatitis C Virus-Infected Donors to Hepatitis C Virus-Negative Recipients: One-Year Kidney Allograft Outcomes

Transplant centers in the United States are increasingly willing to transplant kidneys from hepatitis C virus (HCV)-infected (HCV+) donors into HCV- recipients. We studied the association between donor HCV infection status and kidney allograft function and posttransplantation allograft biopsy findings. Retrospective cohort study. We examined 65 HCV- recipients who received a kidney from a HCV+ donor and 59 HCV- recipients who received a kidney from a HCV- donor during 2018 at a single transplant center. Predictor(s) of donor infection with HCV. Kidney allograft function and allograft biopsy findings during the first year following transplantation. We compared estimated glomerular filtration rate (eGFR), findings on for-cause and surveillance protocol biopsies, development of de novo donor-specific antibodies (DSAs), and patient and allograft outcomes during the first year following transplantation between recipients of HCV+ and HCV- kidneys. We used linear regression to estimate the independent association between allograft function and HCV viremic status of the kidney donor. The mean age of recipients was 52 ± 11 (SD) years, 43% were female, 19% and 80% of recipients were White and Black, respectively. Baseline characteristics were similar between the HCV+ and HCV- groups. There were no statistically significant differences between the HCV+ and HCV- groups in delayed graft function rates (12% vs 8%, respectively); eGFRs at 3, 6, 9, and 12 months post-transplantation; proportions of patients with cellular rejection (6% vs 7%, respectively); and proportions with antibody-mediated rejection (7% vs 10%, respectively) or de novo DSAs (31% vs 20%, respectively). HCV viremic status was not associated with eGFR at 3, 6, 9, or 12 months. Generalizability from a single-center study and small sample size was limited. Recipients of kidneys from donors infected with HCV had similar kidney allograft function and probability of rejection in the first year after transplantation compared to those who received kidneys from donors without HCV infection.

Liver Function Enzymes are Potential Predictive Markers for Kidney Allograft Dysfunction.

Biopsy of the allograft is the gold standard for assessing kidney allograft dysfunction. The aim of our pilot study was to identify serum biomarkers that could obviate the need for biopsy. We conducted a study to identify the biomarkers in the serum from different groups of chronic kidney disease (CKD) patients and kidney transplanted patients vs. healthy individuals. The four groups (n=25 in each group) were as follows: 1) Patients with unstable kidney allograft transplants requiring biopsy for cause, 2) Patients with stable kidney allograft transplants, 3) Patients with CKD not on immunosuppressive therapy and, 4) healthy subjects. We measured the activity and level of serum alkaline phosphatase (ALP) and other liver enzymes (alanine transaminase (ALT) and aspartate transaminase (AST)) as potential serum biomarkers in acute allograft dysfunction. We found that ALP correlated with allograft biopsy findings, liver function, and clinical outcomes and possibly graft survival. Additionally, AST and ALT were higher in patients with graft rejection compared to non-rejected and stable kidney transplants. Moreover, the low Pearson correlations (r- values) between ALP level with age (r=0.179), gender, body mass index (r=0.236), creatinine (r=0.044) or estimated glomerular filtration rate (r=0.048) suggest that ALP may be an independent biomarker which is relatively unaffected by other individual-level variables. ALP may be a putative biomarker to predict kidney allograft function and rejection. Data also indicated that liver function plays an important role for the overall success of kidney transplantation.

Early isolated V-lesion may not truly represent rejection of the kidney allograft.

Intimal arteritis is known to be a negative prognostic factor for kidney allograft survival. Isolated v-lesion (IV) is defined as intimal arteritis with minimal tubulointerstitial inflammation (TI). Although the Banff classification assesses IV as T cell-mediated rejection (TCMR), clinical, and prognostic significance of early IV (early IV, eIV) with negative C4d and donor-specific antibodies (DSA) remains unclear. To help resolve if such eIV truly represents acute rejection, a molecular study was performed. The transcriptome of eIV (n=6), T cell-mediated vascular rejection with rich TI (T cell-mediated vascular rejection, TCMRV, n=4) and non-rejection histologic findings (n=8) was compared using microarrays. A total of 310 genes were identified to be deregulated in TCMRV compared with eIV. Gene enrichment analysis categorized deregulated genes to be associated primarily with T-cells associated biological processes involved in an innate and adaptive immune and inflammatory response. Comparison of deregulated gene lists between the study groups and controls showed only a 1.7% gene overlap. Unsupervised hierarchical cluster analysis revealed clear distinction of eIV from TCMRV and showed similarity with a control group. Up-regulation of immune response genes in TCMRV was validated using RT-qPCR in a different set of eIV (n=12) and TCMRV (n=8) samples. The transcriptome of early IV (< 1 month) with negative C4d and DSA is associated with a weak immune signature compared with TCMRV and shows similarity with normal findings. Such eIV may feature non-rejection origin and reflect an injury distinct from an alloimmune response. The present study supports use of molecular methods when interpreting kidney allograft biopsy findings.

Renal Allograft Biopsy Findings in HLA Identical Renal Transplant Recipients

Renal Allograft Biopsy Findings in HLA Identical Renal Transplant Recipients

Association between Reperfusion Renal Allograft Biopsy Findings and Transplant Outcomes.

Biopsy findings at the time of procurement of deceased donor kidneys remain the most common reason cited for kidney discard. To determine the value of renal allograft histology in predicting outcomes, we evaluated the significance of histologic findings, read by experienced renal pathologists, in 975 postreperfusion biopsy specimens collected from 2005 to 2009 after living donor (n=427) or deceased donor (n=548) renal transplant. We evaluated specimens for the degree of glomerulosclerosis, interstitial fibrosis and tubular atrophy, and vascular disease; specimens with a score of 0 or 1 (scale, 0-3) for each parameter were considered optimal. Overall, 66.3% of living donor kidneys and 50.7% of deceased donor kidneys received an optimal histology score (P<0.001). Irrespective of donor status, suboptimal kidneys came from older donors with a higher incidence of diabetes mellitus, hypertension, and obesity and a higher mean kidney donor risk index (all P<0.001). Death-censored outcomes after transplant differed significantly between optimal and suboptimal kidneys only in the deceased donor transplants (P=0.02). Regardless of histologic classification, outcomes with deceased donor kidneys were inferior to outcomes with living donor kidneys. However, 73.2% of deceased donor kidneys with suboptimal histology remained functional at 5 years. Our findings suggest that histologic findings on postreperfusion biopsy associate with outcomes after deceased donor but not living donor renal transplants, thus donor death and organ preservation-related factors may be of greater prognostic importance. Discarding donated kidneys on the basis of histologic factors may be inappropriate and merits further study.

Allograft biopsy findings in patients with small bowel transplantation.

In this study, we sought to determine the incidence of post-transplant complications including acute cellular rejection (ACR), infection, and post-transplant lymphoproliferative disease (PTLD) in mucosal allograft biopsies in patients with small bowel transplant at our institution. We retrospectively reviewed pathology reports from 5675 small bowel allograft biopsies from 99 patients and analyzed the following: indications for biopsy, frequency and grade of ACR, the presence of infectious agents, results of workup for potential PTLD, results of C4d immunohistochemistry (IHC), features of chronic mucosal injury, and findings in concurrent native bowel biopsies. Findings from 42 allograft resection specimens were also correlated with prior biopsy findings. Indeterminate, mild, moderate, and severe ACR were seen in 276 (4.9%), 409 (7.2%), 100 (1.8%), and 207 (3.6%) of biopsies, respectively. Although ACR may show histologic overlap with mycophenolate mofetil toxicity, we found the analysis of concurrent native bowel biopsies to be helpful in this distinction. Adenovirus was the most common infectious agent seen (11%), and we routinely performed adenovirus IHC on biopsies. Eighteen patients (18%) developed PTLD, 83% of which were EBV associated, but only 28% of PTLD cases were diagnosed on mucosal allograft biopsies. C4d IHC did not correlate with the presence of donor-specific antibodies in limited cases.

The impact on graft survival of interstitial inflammation in borderline change of allograft kidneys.

In kidney transplantation cases, borderline change (BL) can lead to a progressive course. However, factors related to outcome and the progress of BL are not well defined. In this study, we focused specifically on interstitial inflammation as a factor influencing outcome after diagnosis of BL. We followed 252 recipients who underwent renal transplantation between 1998 to 2012 at our hospital. Of those, we retrospectively studied 40 diagnosed with BL from allograft biopsy findings, and then classified them as BL1 and BL2 according to the level of interstitial inflammation (i) (BL1: i < 10%, BL2: i ≥ 10%). There were 21 BL1 and 19 BL2 cases, of whom 7 developed rejection during the follow-up period. There were no significant differences for graft survival rate and the rate leading to acute rejection between the 2 groups (P = 0.44, P = 0.69). Univariate analysis showed that the grade of interstitial inflammation was not a significant risk factor for developing acute rejection (P = 0.816). Our results show that the level of interstitial inflammation does not have an effect on a progressive BL course.

Biopsy Findings in Renal Allograft Dysfunction in a Live Related Renal Transplant Program

Background: There is little information in literature on renal allograft biopsy findings in renal allograft dysfunction in live related renal transplant recipients. Material and Methods: A retrospective review of 1210 renal allograft biopsies from 575 renal transplant patients was carried out over a period of seven years from June 1997 till December 2004. The demographic, clinical, laboratory and biopsy findings were collected and analyzed. Results: A total of 1210 graft biopsies were performed on 575 patients. The mean age of recipients and donors was 29.2±9.7 years, and 35.7±10.5 years, respectively. The males were predominant among recipients (76.7 vs. 23.3%), while among donors they only slightly outnumbered females (51.8 vs. 48.2%). Regarding pathological lesions, acute rejection was seen in 292 (24%) cases, followed by acute tubular injury and cyclosporine A (CsA) toxicity, found in 281 (23.2%) and 134 (11%) cases respectively. Chronic allograft nephropathy (CAN) with variable degree of tubular atrophy was seen in 361 (29.8%) cases. Seventy nine cases (6.5%) of acute pyelonephritis were detected on graft biopsies. A number of rare lesions were also found, including 13 (1.07%) cases of recurrent/de novo renal disease, and 13 (1.07%) of polyoma virus infection. Five cases of CsA induced hemolytic uremic syndrome (HUS) were also noted. Conclusion: In conclusion, the incidence of acute rejection is low in our patients as compared to cadaveric renal transplant recipients as reported in Western studies and CsA toxicity is more common. Recurrent/de novo renal disease is uncommon in our patients.

Recurrent IgA nephropathy after renal transplantation despite immunosuppressive regimens with mycophenolate mofetil

Transplantation offers an excellent option for patients with immunoglobulin-A nephropathy (IgAN) with severe renal dysfunction. However, IgAN frequently recurs in allografts treated with azathioprine. We examined the impact of mycophenolate mofetil immunosuppression on recurrence of IgAN. We reviewed the charts of patients transplanted for IgAN at our institution in the cyclosporin era. Patients were excluded from further analysis if follow-up was <12 months or if immunosuppression at engraftment did not include azathioprine or mycophenolate mofetil. Laboratory data, medications and allograft biopsy findings were compiled. 152 kidney transplantations met the study criteria. At engraftment, 61 allografts were treated with azathioprine and 91 with mycophenolate mofetil. By 3 years post-transplant, IgAN developed in six of 60 (10.0%) azathioprine-treated allografts and five of 62 (8.1%) mycophenolate mofetil-treated allografts (P = 0.76). Overall, 13 azathioprine-treated and seven mycophenolate mofetil-treated allografts showed recurrence. As expected in this retrospective study, the duration of observation was longer in the azathioprine group. The interval between engraftment and diagnosis of recurrent disease was also longer. Survival of allografts with recurrent IgAN was similar in the two groups. Survival of allografts with recurrent IgAN was worse than for allografts without recurrence or allografts transplanted into patients with non-IgAN renal failure. Neither switching azathioprine to mycophenolate mofetil nor using an angiotensin-converting enzyme inhibitor or angiotensin-II type 1 receptor blocker ameliorated the clinical course after a biopsy documented recurrent IgAN. Mycophenolate mofetil, compared with azathioprine, did not lessen the recurrence of IgAN or its clinical impact.

THE CLINICAL USEFULNESS OF THE RENAL ALLOGRAFT BIOPSY IN THE CYCLOSPORINE ERA

The renal allograft biopsy is generally accepted as the gold standard for clarifying the cause of renal dysfunction. However, the clinical usefulness of this procedure has rarely been studied prospectively, nor have most studies included follow-up of patients to delineate the influence of the biopsy on clinical outcome. In this study, we evaluated prospectively the clinical usefulness of the allograft biopsy in renal transplant recipients receiving cyclosporine (CyA). During a 21-month period, 82 biopsies were performed. In 54 instances (47 patients), we outlined a presumed diagnosis and tentative treatment plan before the procedure. After the biopsy, a definitive diagnosis was made and an appropriate patient management approach was instituted. We analyzed the incidence of change in patient management that resulted from histological findings. All patients were followed to monitor their response to treatment and allograft survival. In cases of biopsy-proven acute cellular rejection (ACR) or cyclosporine (CyA) toxicity, clinical and laboratory data from the day of the biopsy were reviewed to determine their diagnostic value. One biopsy specimen was inadequate for definitive interpretation. The biopsy findings resulted in a change in patient management in 22 (41.5%) of the remaining 53 cases (change group). The incidence of altered patient management was 38.7% in biopsy specimens taken in the first month, 55.6% between 1 and 12 months, and 38.5% after 1 year posttransplantation. A change in management was required in 2 of 2 patients with chronic allograft dysfunction, in 44.4% of the 45 patients with acute allograft dysfunction, and in none of the patients with delayed graft function (n=6). Within the first week of treatment 19 of 22 (86.4%) in the change group and 25 of 31 (80.6%) in the no change group had a positive response to therapy. The 1-year allograft survival rate was also similar between the two groups. None of the clinical and laboratory data was useful in distinguishing ACR from CyA toxicity. Renal allograft biopsy findings alter patient management recommendations in approximately 40% of patients in whom a presumptive diagnosis had been made on the basis of clinical and laboratory findings. Patients who had a change in patient management because of biopsy findings demonstrated a response to therapy and allograft survival similar to those of patients who had no alteration in management plan after the biopsy.

Recurrence of haemolytic-uraemic syndrome in renal transplants: a single-centre report.

The incidence of recurrence of haemolytic-uraemic syndrome (HUS) in renal allografts appears to vary by centre, with the highest rates reported from the University of Minnesota. It is possible that the high rate of HUS recurrence at this institution reflects a transplant population skewed towards patients with a form of HUS that is more likely to recur in the allograft. This study examined whether the initial episode of HUS in the native kidneys was preceded by a diarrhoeal prodrome ('classical HUS') or not ('atypical HUS'), and evaluated transplant outcomes in 24 patients who received 36 transplants at the University of Minnesota between 31 May 1972 and 31 December 1994. Eighteen of the 24 patients had atypical HUS, three had classical HUS, and in three patients the presence or absence of a diarrhoeal prodrome could not be determined. Recurrent HUS, defined as microangiopathic haemolytic anaemia, thrombocytopenia, renal insufficiency, and allograft biopsy findings compatible with HUS, occurred 16 times in 14 grafts in 11 patients. Nine of these patients had atypical HUS, one had classical HUS, and in one the nature of the prodrome could not be determined. Eleven of the 14 initial recurrences took place within 2 months of transplant. Recurrence was not more frequent in patients who received cyclosporin or antilymphocyte preparations. Actuarial analysis using matched controls showed poorer graft survival in patients with a primary diagnosis of HUS (P = 0.007), due to the high frequency of graft loss in HUS patients with recurrence. Based upon these data and a review of the literature, it can be concluded that the risk of recurrence of HUS in the allograft is confined almost entirely to patients with atypical forms of HUS.