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Background: Bisphosphonates are administered to post-transplantation patients with mineral and bone disorders; however, the association between bisphosphonate therapy and long-term renal graft survival remains unclear., Methods: This nested case-control study investigated the effects of bisphosphonates on long-term graft outcomes after kidney transplantation. We enrolled 3836 kidney transplant recipients treated from April 1979 to June 2016 and matched patients with graft failure to those without (controls). Annual post-transplant bone mineral density assessments were performed and recipients with osteopenia or osteoporosis received bisphosphonate therapy. The associations between bisphosphonate use and long-term graft outcomes and graft survival were analyzed using conditional logistic regression and landmark analyses, respectively., Results: A landmark analysis demonstrated that death-censored graft survival was significantly higher in bisphosphonate users than in non-users in the entire cohort (log-rank test, P < 0.001). In the nested case-control matched cohort, bisphosphonate users had a significantly reduced risk of graft failure than did non-users (odds ratio = 0.38; 95% confidence interval 0.30-0.48). Bisphosphonate use, increased cumulative duration of bisphosphonate use >1 year and increased cumulative bisphosphonate dose above the first quartile were associated with a reduced risk of graft failure, after adjustments., Conclusions: Bisphosphonates may improve long-term graft survival in kidney transplant recipients., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Some studies reported the correlations between renal parenchymal stiffness measured by transient elastography or acoustic radiation force impulse (ARFI) and the extent of interstitial fibrosis. This study was prospectively designed to evaluate the correlation between clinical, histological findings and the kidney shear wave velocity (SWV, m/s) assessed by ARFI elastography to identify factors affecting the kidney SWV in normal patients., Methods: Seventy-three adult living kidney transplantation donors were enrolled in our center between September 2010 and January 2013. Before transplantation, all donors were evaluated by ARFI elastography to identify the range of SWV in kidneys. Time-zero biopsies were performed on all graft kidneys before implantation., Results: Mean age of donors was 42.0 ± 11.3 years. The mean SWV and depth were 2.21 ± 0.58 m/s and 5.37 ± 1.06 cm. All histological findings showed mild degree of the Banff score, only grade I. In univariate analyses, the SWV was not associated with all histological parameters. Age (r = -0.274, P = .019) diastolic blood pressure (DBP, r = -0.255, P = .030) and depth for SWV measurement (r = -0.345, P = .003) were significantly correlated with the SWV. In multivariate linear regression analysis, age, gender, body mass index (BMI), and depth for SWV measurement were significantly correlated with the SWV (P = .003, .005, .002, and .004, respectively)., Conclusions: We demonstrated that all histological findings are not correlated with the SWV of donor kidney. Otherwise, factors influencing the kidney SWV assessed by ARFI elastography are age, gender, BMI, and depth for the SWV measurement in donors for kidney transplantation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Despite the obvious survival benefit compared to that among waitlist patients, outcomes of positive crossmatch kidney transplantation (KT) are generally inferior to those of human leukocyte antigen (HLA)-compatible KT. This study aimed to compare the outcomes of positive complement-dependent cytotoxicity (CDC) crossmatch (CDC + FC+) and positive flow cytometric crossmatch (CDC-FC+) with those of HLA-compatible KT (CDC-FC-) after successful desensitization., Methods: We retrospectively analyzed 330 eligible patients who underwent KTs between June 2011 and August 2017: CDC-FC- (n = 274), CDC-FC+ (n = 39), and CDC + FC+ (n = 17). Desensitization protocol targeting donor-specific antibody (DSA) involved plasmapheresis, intravenous immunoglobulin (IVIG), and rituximab with/without bortezomib for positive-crossmatch KT., Results: Death-censored graft survival and patient survival were not different among the three groups. The median estimated glomerular filtration rate was significantly lower in the CDC + FC+ group than in the compatible group at 6 months (P < 0.001) and 2 years (P = 0.020). Biopsy-proven rejection within 1 year of CDC-FC-, CDC-FC+, and CDC + FC+ were 15.3, 28.2, and 47.0%, respectively. Urinary tract infections (P < 0.001), Pneumocystis jirovecii pneumonia (P < 0.001), and cytomegalovirus viremia (P < 0.001) were more frequent in CDC-FC+ and CDC + FC+ than in CDC-FC-., Conclusions: This study showed that similar graft and patient survival was achieved in CDC-FC+ and CDC + FC+ KT compared with CDC-FC- through DSA-targeted desensitization despite the higher incidence of rejection and infection than that in compatible KT.

Background: The diagnostic criteria of antibody-mediated rejection (ABMR) has been significantly changed since Banff 2013. The most important revision was adopting microvascular inflammation (MVI) as immunopathologic evidence for ABMR even in C4d-negative cases. In this study, we retrospectively reviewed previous allograft biopsy results and evaluated the impact of this change., Methods: We reviewed results of 536 renal allograft biopsies at Severance Hospital during 2011 to 2013, which were diagnosed according to the Banff 2009 criteria. All biopsy results were reassessed according to the Banff 2017 criteria., Results: According to the Banff 2009 criteria, antibody-mediated changes were observed in 48 cases out of the 536 allograft biopsies (9.0%). According to the Banff 2017 criteria, 28 additional cases (5.2%) were reclassified as antibody-mediated changes. Twenty-six of these cases were C4d-negative ABMR. The most frequent diagnostic finding in these cases was MVI comprising glomerulitis and peritubular capillaritis. Donor-specific antibodies were investigated in 14 of these cases, which revealed positive results in 12 cases., Conclusion: The incidence rate of ABMR has increased after the recent revision of the Banff criteria. The MVI in C4d-negative ABMR cases is the major cause for this increase., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Several experimental studies implicate uric acid in renal injury and fibrosis. The objective of this study was to examine the association between uric acid level and allograft fibrosis after kidney transplantation. 241 adult patients who underwent kidney transplantation between 2003 and 2014 were divided into three groups according to the sex specific tertiles of mean uric acid level within the first post-transplant year. The renal biopsies performed during 1 to 5 post-transplant year were analyzed to compare the degree of interstitial fibrosis and tubular atrophy (IF/TA). Mean interval between kidney transplantation and biopsy was similar between groups (23.7 ± 15.3 vs. 30.0 ± 18.6 vs. 27.5 ± 18.5 months, P = 0.072). The higher tertile uric acid level was, the more advanced grade of IF/TA was shown (P = 0.001). Multivariate analysis identified uric acid tertile was independent risk factor for severe IF/TA (odds ratio [95% confidence interval] was 3.16 [1.13-8.82] for tertile 2 and 3.70 [1.25-10.93] for tertile 3, versus tertile 1, respectively). Other independent factors were estimated glomerular filtration rate at 1year post-transplant (0.80 [CI 0.65-0.98]) and biopsy-proven rejection (2.34 [1.05-5.21]). Graft survival over 10 years was significantly lower in tertile 3 (P = 0.041). The results showed that higher uric acid level after kidney transplantation was associated with more severe IF/TA.

Aims: ABO-incompatible (ABOi) kidney transplantation (KT) is being increasingly performed to overcome donor shortages. However, debate persists regarding the post-transplant outcomes of ABOi KT vs. that of ABO-compatible (ABOc) KT., Methods: A total 454 recipients who underwent living-donor KT (LDKT) between June 2010 and July 2014 at Severance Hospital (Seoul) were retrospectively reviewed. 100 ABOi and 354 ABOc KTs were compared. Recipients with a pretransplant positive crossmatch to their donors, pretransplant donor-specific anti-HLA antibody (DSA), or high panel reactive antibody (PRA ≥ 50%) were excluded from both the ABOi and ABOc KT groups. Finally, the authors compared the transplant outcomes of 95 of these ABOi KTs and 121 ABOc KTs performed over the same period., Results: No significant difference in incidence of biopsy-proven acute rejection was observed between the ABOi and ABOc KT groups (p = 0.230), and group glomerular filtration rate of ABOi KT was comparable to that of ABOc KT (p > 0.05 at all time points). 3-year death-censored graft survival rates were similar (96.8 vs. 96.6%, respectively; p = 0.801). However, the incidences of postoperative bleeding, cytomegalovirus infection, fungal infection, and serious infection rates were significantly higher after ABOi KT., Conclusions: In this study, graft renal function and survival after ABOi KT were excellent, and the incidence of acute rejection was similar to that of ABOc KT. However, efforts are needed to reduce hemorrhagic and infectious complications after ABOi KT. ABOi KT can be a good strategy to overcome ABO antibody barriers and relieve donor shortage.
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Rationale: Human leukocyte antigen (HLA) is the major immunologic barrier in kidney transplantation (KT). Various desensitization protocols to overcome the HLA barrier have increased the opportunity for transplantation in sensitized patients. In addition, technological advances in solid-phase assays have permitted more comprehensive assessment of donor-specific antibodies. Although various desensitization therapies and immunologic techniques have been developed, the final transplantation decision is still based on the classic complement-dependent cytotoxicity (CDC) crossmatch (XM) technique. Some patients who fail to achieve negative XM have lost their transplant opportunities, even after receiving sufficient desensitization therapies., Patient Concerns: A 57-year-old male with end-stage renal disease secondary to chronic glomerulonephritis was scheduled to have a second transplant from his son, but CDC XM was positive., Diagnoses: Initial CDC XM (Initial T-AHG 1:32) and flow-cytometry XM were positive. Anti-HLA-B59 donor specific antibody was detected by Luminex single antigen assay., Interventions: Herein, we report a successful case of KT across a positive CDC XM (T-AHG 1:8 at the time of transplantation) by using C1q assay-directed, bortezomib-assisted desensitization. After confirming a negative conversion in the C1q donor-specific antibody, we decided to perform KT accepting a positive AHG-CDC XM of 1:8 at the time of transplantation., Outcomes: The posttransplant course was uneventful and a protocol biopsy at 3 months showed no evidence of rejection. The patient had excellent graft function at 12 months posttransplant., Lessons: The results of XM test and solid-phase assay should be interpreted in the context of the individual patient.

Background: Tubuloreticular inclusions (TRIs) are anastomosing networks of microtubules that are frequently found in autoimmune diseases and viral infections. In renal allografts, TRIs have been reported in glomerular endothelial cells in association with viral infections and donor specific antibodies (DSAs), but their presence in peritubular capillaries has not been explored., Methods: We collected seven cases with TRIs out of 148 consecutive renal allograft biopsies taken from Dec. 2015 to Dec. 2016., Results: TRIs were present in peritubular capillaries in seven cases and were concomitantly present in glomerular endothelial cells in two cases. The diagnoses included polyomavirus nephropathy (n=2), acute T cell-mediated rejection (ACR) (n=1), combined ACR and antibody-mediated rejection (AMR) (n=1), suspicious for ACR (n=1), chronic active AMR (n=1), and moderate tubular atrophy and interstitial fibrosis (n=1). Six patients had recent or current viral infections (BK polyomavirus, hepatitis B virus, herpes simplex virus, and cytomegalovirus in two, two, one, and one case, respectively). DSA was positive in one case. Five cases had moderate to severe interstitial inflammation and four cases had peritubular capillaritis., Conclusion: TRIs are not rare in peritubular capillaries. They are associated with various viral infections and their appearance seems to be related to peritubular capillary injury., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

C3 glomerulonephritis (C3GN) is a recently described, rare glomerular disease characterized by predominant or sole glomerular C3 deposits. Morphologic features of C3GN are similar to those of dense deposit disease (DDD); however, ribbon-like intramembranous electron-dense deposits are absent in the former. We report a case of de novo C3GN in a renal allograft with morphologic transformation to DDD. A 6-year-old boy presented with congenital left renal agenesis and right ureteropelvic junction obstruction. The patient underwent pyeloplasty but experienced recurrent urinary tract infections. At the age of 22 years, he received a renal allograft from a living related donor. C3GN was diagnosed after 1 year of transplantation; initial histology showed minimal mesangiopathy and this progressed to mesangial proliferation and membranoproliferative features over the next 7 years. Serum creatinine levels were stabilized with anti-rejection treatments for combating repeated episodes of acute rejection; however, glomerular and tubular band-like electron-dense deposits became evident.

Purpose: Recently, bortezomib has been used to treat antibody-mediated rejection (AMR) refractory to conventional treatment such as plasmapheresis, intravenous immunoglobulin, and rituximab. The authors aimed to describe their experiences when bortezomib was used to treat refractory AMR., Materials and Methods: Eleven refractory AMR episodes treated with bortezomib were included in this study. The patients received one or two cycles of bortezomib (1.3 mg/m²) on days 1, 4, 8, and 11., Results: Bortezomib effectively reduced antibodies against various targets, including human leukocyte antigen (HLA) class I and II, ABO blood group antigen, and angiotensin II type 1 receptor. Antibodies were depleted or reduced significantly in eight AMR episodes. Overall, there was a significant improvement in the mean estimated glomerular filtration rate (eGFR) at 3 months after therapy (36.91±22.15 mL/min/1.73 m²) versus eGFR at time of AMR diagnosis (17.00±9.25 mL/min/1.73 m²; p=0.007). All six early-onset AMR episodes (within 6 months post-transplantation) showed full recovery of allograft function. Additionally, three of the five late-onset AMR episodes (>6 months post-transplantation) showed improved allograft function., Conclusion: Anti-humoral treatment based on bortezomib might be an effective strategy against refractory AMR caused by various types of antibodies. Notably, this treatment could be more effective in early-onset AMR than in late-onset AMR.

This study was designed to evaluate whether sirolimus (SRL) conversion effectively improves renal function and histopathology in calcineurin inhibitor (CNI)-treated renal recipients with mild to moderate renal insufficiency. SRL conversion from CNI was performed in patients who underwent kidney transplantation from 6 months to 5 yr prior to screening. Forty-five patients were enrolled. The effect of SRL conversion on graft function was evaluated, and protocol biopsies were performed preconversion and 1 yr after conversion. Overall graft function after SRL conversion gradually improved, and the improvement in renal function was closely associated with the shorter duration of CNI exposure. When we divided the patients by the duration of CNI exposure, the patients with less than 1 yr of CNI exposure demonstrated significant improvement, but patients with a greater than 1 yr CNI exposure did not exhibit significant improvement. In contrast, protocol biopsies demonstrated no significant improvements in the modified "ah" score or other Banff scores after SRL conversion. Furthermore, the duration of CNI treatment prior to SRL conversion was not associated with histological findings 1 yr after SRL conversion. SRL conversion improved graft function in renal recipients with mild to moderate renal insufficiency, but this effect is not accompanied by histological improvement.

Background: We explored the efficacy of the Oxford classification for assessing native immunoglobulin A nephropathy (IgAN) in posttransplantation patients compared with the glomerular injury score and Haas classification., Methods: A total of 125 renal allograft biopsies obtained from 114 patients diagnosed with IgAN regardless of original disease were assessed., Results: The average time to biopsy was 70.5±45.3 months after transplantation. Glomeruli showed normal histology in 18.4%. Mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), and tubulointerstitial fibrosis (T1-2) were present in 12.8%, 6.4%, 45.6%, and 20.8% of the samples, respectively. There was a significant correlation between Oxford-MEST scores and glomerular injury score or Haas subclass. S1 and T1-2 were correlated with elevated serum creatinine level, proteinuria, and decreased estimated glomerular filtration rate, and E1 was correlated with decreased estimated glomerular filtration rate at the time of biopsy. The 10- and 15-year graft survival rates were 62.9% and 34.3%, respectively. The graft survival rate was significantly lower in the presence of S1 and T1-2. Endocapillary hypercellularity, segmental sclerosis, and tubulointerstitial fibrosis predicted graft survival and endocapillary hypercellularity and tubulointerstitial fibrosis also predicted serum creatinine doubling., Conclusions: The Oxford classification scheme is useful for evaluating chronic graft dysfunction in patients with posttransplantation IgAN. In addition to tubulointerstitial fibrosis, the presence of endocapillary hypercellularity and segmental sclerosis should be included in the pathology report.

Little information is available regarding renal histology in cases of chronic allograft dysfunction and graft failure in patients with recurrent immunoglobulin A nephropathy. We compared 57 renal allograft biopsies of 44 patients with recurrent immunoglobulin A nephropathy to 43 biopsies of 33 patients without immunoglobulin A nephropathy recurrence. Clinical parameters such as patient demography and biopsy indications did not differ between the 2 groups, with the exception of time to biopsy. Renal allograft injury, which was assessed by semiquantitative scoring of glomerular, tubulointerstitial, and arteriolar changes, increased linearly over time after transplantation in both recurrent and nonrecurrent samples. Glomerular injuries were significantly correlated with tubulointerstitial injuries in both groups, but the correlation graph reflected an increasing gap in the degrees of tubulointerstitial injury between the 2 groups over time. The levels of glomerulosclerosis, mesangial proliferation, and crescent formation were significantly higher in recurrent samples, whereas the prevalence of chronic rejection was significantly higher in nonrecurrent samples. The presence of segmental sclerosis was associated with significant proteinuria in recurrent samples. Graft survival was better in recurrent immunoglobulin A nephropathy patients than in nonrecurrent patients (74.4% versus 51%) at 10 years after transplantation. In conclusion, slow and progressive glomerular injury is the major cause of long-term graft failure in patients with recurrent immunoglobulin A nephropathy. In contrast, rapidly increasing tubulointerstitial injury is responsible for graft failure in nonrecurrent patients.

Aims: We compared the relative efficacy of urine decoy cell (UDC) and polymerase chain reaction (PCR) to identify polyomavirus (PV) infection, and investigate the efficacy of reduction of immunosuppression for earlier-stage PV infection before irreversible graft injury., Methods: A total of 222 de novo renal transplant recipients from March 2003 to September 2005 were enrolled. Prospective UDC monitoring with supplementary PV-PCR was performed. Early reduction of immunosuppression was guided by the results of UDC and PV-PCR., Results: The positive predictive value of urine cytology for PV infection was 48.8%, and the negative predictive value was 74.1%. After reduction of immunosuppression, negative conversion or significant decrease of viral titer was achieved 100% in 15 PV-PCR positive recipients. Only 3 patients who were neglected or overlooked for PV screening or positive test results early after transplantation were diagnosed as having PV nephropathy, and resulted in graft dysfunction and failure. From January 2001 to December 2002, when we did not monitor the PV infection, there were 7 cases of PV nephropathy among 116 recipients., Conclusion: The combination of UDC and PV-PCR should be considered for screening of PV infection. Reduction of immunosuppression based on UDC monitoring and PV viral loads may reduce the incidence of PV nephropathy., ((c) 2008 S. Karger AG, Basel)

Background: Polyomavirus (PV) nephropathy may coexist with or follow acute renal transplant rejection. The aim of this study was to evaluate whether HLA-DR and CD54 are useful cellular markers for surveillance of acute rejection in PV-infected patients., Methods: A prospective study was conducted using 205 renal transplant patients. Urine samples were collected at a regular interval post-transplantation for routine cytology and immunocytochemistry. Urinary levels of tumour necrosis factor alpha, soluble interleukin-2 receptor and interleukin-6 were used as adjunctive markers for acute rejection., Results: Of the 699 total samples, decoy cells were identified in 100 samples of 50 patients. Patients with decoy cell-positive (DCP) samples had higher serum creatinine levels than decoy cell-negative (DCN) samples (1.55 vs 1.41 mg/dl, respectively; P = 0.006). DCP samples were also more likely to be HLA-DR positive (50.0 vs 32.4%; P = 0.029), as well as CD54 positive (17.4 vs 6.9%; P = 0.038). However, serum creatinine levels did not correlate with HLA-DR or CD54 positivity among DCP samples. Instead, CD54 positivity correlated with decoy cell grades. Immunosuppression decreased in 11 DCP patients, and HLA-DR was negatively converted in three of them. None of the patients developed acute clinical rejection. Urinary cytokine levels did not correlate with serum creatinine levels, nor did they correlate with HLA-DR or CD54 status among DCP patients., Conclusions: Urinary tubular HLA-DR and CD54 expression increased in decoy cell shedding patients but did not indicate a concomitant acute rejection. These markers may instead indicate renal inflammatory activity associated with viral reactivation, which has the potential to progress to PV interstitial nephritis.

With time after transplantation, the recurrence of IgA nephropathy (IgAN) becomes a relevant cause of graft dysfunction and failure. However, only limited information has been published regarding the related clinical and histological features. In this article, we review studies on recurrent IgAN in the English literature and describe our own clinical experience. The clinical and histological features related to recurrence are still indeterminate, but features associated with graft dysfunction include proteinuria, glomerulosclerosis, mesangial proliferation, glomerular crescents and interstitial fibrosis.

Maintenance of healthy endothelium is essential to vascular homeostasis, and preservation of endothelial cell function is critical for transplant allograft function. Damage of microvascular endothelial cells is now regarded as a characteristic feature of acute vascular rejection and chronic allograft nephropathy, which is an important predictor of graft loss and is often associated with transplant vasculopathy. In this review, we will discuss the role of microvascular endothelium, in renal allograft dysfunction, particularly as it relates to markers of endothelial dysfunction and endothelial repair mechanisms. We also discuss the potential for therapies targeting endothelial dysfunction and transplant graft vasculopathy.

Information is limited regarding the histological features related to chronic graft dysfunction and failure in patients with IgA nephropathy developing after renal transplantation. The prevalence and significance of glomerular crescents in post-transplant IgAN including recurrent, de novo and transmitted forms (TxIgAN), were studied. Renal morphology was evaluated in 71 patients of TxIgAN, obtained at more than 6 months post-transplant, and compared with regard to the presence (C-TxIgAN) or absence (N-TxIgAN) of glomerular crescents. Crescents were demonstrated in 12 samples of 10 patients (14.1%). The percentages of crescents were from 4.8% to 83.3% (median, 28.6%) in each sample. Ten samples of C-TxIgAN had cellular to fibrocellular crescents, and four of these were associated with diffuse mesangial proliferation. Serum creatinine levels and the frequency of nephrotic range proteinuria at the time of biopsy and the degree of interstitial inflammation were significantly different in the two groups. Graft survival after allograft biopsies was significantly lower in C-TxIgAN (P = 0.0017). Chronic rejection was a major cause of graft loss in N-TxIgAN (31.8%), whereas TxIgAN was the major cause in C-TxIgAN (66.7%). In conclusion, the current study suggests that glomerular crescents are not rare and that they are responsible for chronic graft dysfunction in TxIgAN patients.

Peritubular capillary (PTC) C4d staining represents a marker for acute humoral rejection, however, the impact of positive staining on chronic allograft dysfunction has received little attention. Ninety-three renal allograft biopsies from 93 patients were selected from a total of 174 renal allograft biopsies, which were obtained 6 months or more after transplantation (median: 89 months). Fresh frozen renal tissue was stained with monoclonal antibody against C4d. Sixteen of 93 biopsies showed C4d staining in PTC. C4d staining was positive in 40% of acute rejection cases (n=15) and 21% of chronic rejection cases (n=24). When the samples were divided according to C4d positivity, the C4d (+) group had a higher proportion of acute rejection than the C4d (-) group. However, no significant difference was observed between the two groups in terms of the prevalence of chronic rejection. Degrees of histological injury including tubulitis, interstitial inflammation and interstitial fibrosis were not significantly different between C4d (+) and C4d (-) groups. However, the 2-year graft survival rate after biopsy was lower in the C4d (+) group than in the C4d (-) group (24.8% versus 59.0%, p=0.1255). C4d staining in PTC is associated with late acute rejection, but not with chronic rejection based on conventional morphologic criteria in patients with chronic allograft dysfunction.

Polyomavirus (PV) nephropathy is a rare cause of graft dysfunction, but it may accompany acute rejection (AR), resulting in complications with respect to its diagnosis and treatment. To examine the validity of tubulitis and inflammatory phenotype in the diagnosis of concurrent AR, we reviewed the renal histology of ten biopsy samples from nine patients with PV nephropathy, and the immunohistochemistry from eight samples. Tubulitis was present in seven patients and was associated with AR in six. The degrees of tubulitis and interstitial inflammation were higher in biopsy samples with AR than in those without, but the degree of tubulitis was not related to the degree of interstitial inflammation. Virally infected cells were rare in the samples with no, or mild, tubulitis, but did not increase with the degree of interstitial inflammation. Immuno-phenotyping of inflammatory cells did not show any T-cell dominance in AR: T cells were dominant over B cells in three of six samples with AR and both samples without AR. Although the degrees of tubulitis and interstitial inflammation were higher in the AR subjects, the presence of tubulitis or inflammatory phenotype was not helpful in the diagnosis of concurrent AR. Further studies will be required to find a better marker for coexisting AR in patients with PV nephropathy and to establish strategies for treatment.

Introduction: Although graft dysfunction has been increasingly reported in post-transplant IgA nephropathy (Tx-IgAN), intragraft morphological changes have been largely overlooked. We evaluated glomerular changes in Tx-IgAN to identify the histological features pertaining to significant proteinuria and therapeutic response to enalapril., Materials and Methods: Fifty-four renal allograft biopsies, diagnosed as Tx-IgAN at a median of 46 months after transplantation, were the subject of the study. In 10 patients, glomerular morphometry was performed. In 14 patients who have been treated with enalapril for more than 12 months, we correlated the therapeutic response to enalapril with allograft histology., Results: No uniform pattern was found in the glomeruli of Tx-IgAN. The glomerular mesangium was mostly indistinct. Interstitial fibrosis was negative or mild in 88.9%. By morphometry, the glomerular tuft areas and mesangial areas were significantly larger in Tx-IgAN than those of the normal native kidney (p < 0.05), but were not different from transplant cases without glomerulonephritis. Proteinuria of >/=1 g/24 h was correlated with glomerulosclerosis, interstitial fibrosis and interstitial inflammation at time of biopsy (p < 0.005). The presence of segmental sclerosis (SS) correlated well with the amount of 24-h proteinuria (p < 0.001). After treatment with enalapril, the amount of proteinuria reduced in 64.3%. Therapeutic response to enalapril tended to be less effective in patients having SS (28.6 versus 71.4%), but this finding did not reach a statistical significance., Conclusions: Significant proteinuria was associated with advanced chronic injury, especially with the presence of SS in Tx-IgAN, but anti-proteinuric effect of enalapril was not affected by graft histology. It remains to be clarified whether glomerular mesangial expansion plays a role in graft dysfunction in a subset of Tx-IgAN showing prominent mesangial changes.

Diffuse glomerular basement membrane (GBM) lamellation, reminiscent of Alport's syndrome, has rarely, and exclusively, been reported in renal allografts from pediatric donors to adult recipients. We report on a similar lesion, identified in a 42-year-old male, who received a kidney from an unrelated 21-year-old living male donor. The disease of the recipient was unknown. Renal allograft biopsies were performed 3.5 and 4.8 years after the renal transplantation, due to massive proteinuria and serum creatinine elevation. The histological features of both biopsies were similar, but more advanced in the second biopsy. Glomerular mesangium was widened and had an IgA deposit in the first biopsy. In addition to the presence of mesangial electron dense deposits, the GBM showed diffuse lamellation and splintering on the subepithelial side, but no definite deposits. In the second biopsy, IgA deposits were extended to the peripheral capillary walls, but electron microscopic examination was not available. Two months after the second biopsy, the patient returned for hemodialysis.

SUMMARY: The long-term outcome was evaluated, in terms of recurrence and graft survival, after live donor renal transplantation in 90 grafts in 89 patients with biopsy-proven IgA nephropathy (IgAN) as a primary diagnosis of end-stage renal disease. Additionally, histological assessment including glomerular morphometry was performed in 19 grafts having recurrent IgAN. The 10-year graft survival for IgAN patients was 66%, which was comparable with that of 84% for 107 reference recipients having other kinds of glomerulonephritis (GN) or 69% for 90 other recipients having non-GN renal failure (P = 0.27). In 43 grafts, 54 event graft biopsies were performed, and mesangial IgA deposits were documented in 19 grafts. In eight grafts, lesions were accompanied by chronic rejection (CR). Ten-year cumulative recurrence was 44%. In total, 10 grafts were lost: this was due to CR (n = 3) or acute rejection (n = 1) in 24 recurrence-free recipients; CR (n = 2) or recurrence (n = 2) in 19 patients with recurrence; and patient death (n = 2) in 46 patients who did not have graft biopsy. No difference in 10-year graft survival between the patients with and without recurrence (63%vs 74%; P = 0.98), or the proportion of related donors was found (68%vs 83%; P = 0.25). In the grafts with recurrence, renal histological damage was relatively mild and had no uniform pattern. The percentage of global and segmental sclerosis were 11.9% and 3.7%, respectively. Non-sclerotic glomeruli were ischaemic or hypertrophied. Mesangium showed lysis or focal and mild expansion by matrix and cellular increase. Glomerular morphometry was performed in seven patients, in whom glomerular hypertrophy was found as demonstrated by increases of Bowman's and glomerular tuft areas (1.4 and 1.3 times the control, respectively) and concomitant decrease of total glomerular and mesangial cells per glomerular cross-section (71.2% and 84.9% of the control, respectively). In conclusion, recurrence increased to 44% with... [ABSTRACT FROM AUTHOR]