Protocol Renal Biopsies Research Articles

#2917 Desensitization techniques in ABO-incompatible renal transplantation: efficacy and analysis of complications

Abstract Background and Aims Living donor transplantation is the best optimal choice for the vast majority of patients with terminal renal insufficiency. However, it is limited by the AB0/ HLA incompatibility between donor and receptor. The resolution of this inconvenient relies on desensitization of isoagglutinins (anti-AB0 immunoglobulins depletion); thus transplantation could be performed safely. For desensitization there are two techniques: specific adsorption (S) and non-specific (NS) techniques, including centrifugal therapeutic plasma exchange (cTPE) and membrane-based therapeutic plasma exchange (mTPE). The aims are to evaluate the efficacy of apheresis techniques: specific versus non-specific, and identify their complications. Secondary objectives include analyzing the acute rejection rate (RR), graft survival, and complications of each technique. Method A retrospective cohort study was conducted on AB0-incompatible living donor transplantation patients at our center (Bellvitge's Hospital) from 2014 to 2022. All patients (except 1) received rituximab and induction treatment by Thymoglobulin or Basiliximab, followed by maintenance treatment (Steroids, Mycophenolate, and calcineurin inhibitors). During follow-up, protocol renal biopsies (RB) were taken at one month and between 3-6 months post-transplantation. Complications were defined as significant haematological alterations, bleeding, or major infections requiring hospitalization. According to the technique used, two cohorts were identified: specific (Glycosorb®/Vitrosorb® columns) and non-specific: mTPE (prismaflex TPE2000) and cTPE (Spectra/Optia®). Both were anticoagulated with heparin or citrate randomly. An expert nurse supervised the technique. To calculate the efficacy we considered the percentual reduction of isoagglutinins in the first session. T-student test was used to calculate the percentage of complication and compare the results. Results A total of 50 patients were selected with a mean age (MA) of 49.5 ± 11.8. Four of these did not require apheresis due to lower title isoagglutinins (<1/8). Each cohort included 23 patients: specific with MA 49.5 vs non-specific 48.4, with a mean isoagglutinin titles in specific of 61.65 vs non-specific 11.8 (p = 0.05). Isoagglutinin clearance were higher in specific techniques with 73% vs 59% non-specific (p < 0.03). Due to the dispersion in the number of sessions, results are expressed with the median (4 sessions in specific vs 3 non-specific). Total renal graft survival rate is 93.4%. At one month, it was diagnosed by biopsy an acute renal rejection rate of 16.7% in non-specific vs 18.2% specific (p > 0.05). Considering complications, they are higher with non-specific 41.7% vs specific 18% (p < 0.05). Regarding infectious issues, there are no differences in cytomegalovirus or polyomavirus infections, but there are differences in urinary infections observing in non-specific 79.2% vs specific 63% (p < 0.05). Conclusion Specific techniques are more effective in reducing isoagglutinins, show a lower rate of complications and post-transplant infections, providing greater benefit to the patient.

Expression of Rejection-Associated Transcripts in Early Protocol Renal Transplant Biopsies Is Associated with Tacrolimus Exposure and Graft Outcome.

Subclinical inflammation in protocol biopsies relates to tacrolimus exposure and human leukocyte antigen (HLA) matching. We aimed to characterize transcripts associated with rejection and tacrolimus exposure and the latter's association with transplant outcomes. We tested whether gene expression is associated with rejection using strictly normal protocol biopsies (n = 17) and biopsies with T cell-mediated rejection (TCMR) or antibody-mediated rejection (ABMR) according to Banff criteria (n = 12). Subsequently, we analyzed these transcripts in a set of 4-month protocol biopsies (n = 137) to assess their association with donor and recipient characteristics, the intensity of immunosuppression, and the graft outcome. Differential expression (false discovery rate (FDR) < 0.01, fold (change (FC) > 3) between normal and rejection biopsies yielded a set of 111 genes. In the protocol biopsy cohort (n = 137), 19 out of these 111 genes correlated with tacrolimus trough levels at the time of biopsy (TAC-C0), and unsupervised analysis split this cohort into two clusters. The two clusters differed in donor age and tacrolimus trough levels. Subclinical rejection, including borderline lesions, tended to occur in the same cluster. Logistic regression analysis indicated that TAC-C0 at the time of biopsy (OR: 0.83, 95%CI:0.72-0.06, p = 0.0117) was associated with cluster 2. In a follow-up averaging 70 ± 30 months, this patient group displayed a significant decline in renal function (p = 0.0135). The expression of rejection-associated transcripts in early protocol biopsies is associated with tacrolimus exposure and a faster decline in renal function.

Visual interstitial fibrosis assessment as continuous variable in protocol renal transplant biopsies.

In current renal transplant pathology practice interstitial fibrosis is visually assessed in categories according to the Banff classification. As this has a moderate reproducibility, which is little ameliorated by morphometric analysis, we investigated whether visual renal fibrosis assessment is feasible on a continuous scale, i.e. as percentage affected area of the cortex. Protocol renal biopsies taken at transplantation (n=125), three (n=73) and twelve months (n=88) after transplantation were visually scored in categories (Banff), and percentages for interstitial fibrosis (ci). Interobserver variation (ICC and weighted κ) was assessed, and morphometric analysis on Sirus Red stained sections was performed. Correlations between the different methods and their association with donor age and eGFR 1 year and 5 year post transplant were analyzed using Pearson's or Spearman's rho. Interobserver agreement was equivalent for Banffci and %ci (κ0.713 vs. ICC 0.792), and for BanffIF/TA and %IF/TA (κ0.615 vs. ICC 0.743). Both Banffci and %ci were associated with Sirius Red morphometry in three and twelve month. With all three methods, a significant correlation was found between donor age and fibrosis in the implantation biopsy, and between fibrosis in the 12 month biopsy and eGFR at 1 and 5 years (eGFR at 1 year: Sirius Red ρ-0.487, %ci ρ-0.393, Banffci ρ-0.413, all p<0.01, eGFR at 5 years: Sirius Red ρ-0.392, %ci ρ-0.333, Banffci ρ-0.435, all p<0.01. Interstitial fibrosis assessment on a continuous scale can be used next to scoring in categories according to the Banff classification in protocol renal transplant biopsies.

From the Wright Brothers to the A380: Developing Transplantation Takes Teams of Teams.

From the Wright Brothers to the A380: Developing Transplantation Takes Teams of Teams.

Calcineurin inhibitors and renal biopsy in children with idiopathic nephrotic syndrome.

Idiopathic nephrotic syndrome (NS) is common in children, and most patients respond to corticosteroid therapy. Patients who relapse may need additional immunosuppression with cyclophosphamide, mycophenolate mofetil, calcineurin inhibitors (CNI), or rituximab. Many such patients undergo protocol renal biopsies before and after the initiation of CNI therapy. The main objective of our study was to assess the role of protocol renal biopsies in the monitoring of CNI-induced nephrotoxicity in patients with steroid-dependent (SD)/frequent relapse (FR) NS. We did an Institutional Review Board (IRB)-approved retrospective chart review of patients who were diagnosed with NS at the Children's Hospital of Michigan from January 2000 to June 2019. Study inclusion criteria were a diagnosis of NS, age 1 - 21 years at initial diagnosis, SD/FR clinical course, patients with initial steroid resistance with renal biopsy showing minimal change disease, and renal biopsy before and after CNI initiation. The data is presented on 24 patients who met study inclusion criteria. Only 3 patients (12.5%) showed evidence of chronic CNI nephrotoxicity after a median treatment 66.5 months (range 12 - 153 months). Our study revealed that a baseline renal biopsy before starting CNI therapy for children with FR/SDNS is not necessary. A renal biopsy may be considered after 2 - 3 years of CNI administration in selected few cases in whom the diagnosis of CNI nephrotoxicity might help change the management.

Nephrotoxicity of calcineurin inhibitors as a risk factor for BK polyomavirus replication after kidney transplantation.

BK polyomavirus-associatednephropathy (PyVAN) is responsible for a significant percentage of transplanted kidneys prematurely terminating their function. Its occurrence is closely related to the intensity of immunosuppressive therapy. In a group of 161 newly transplanted patients, we prospectively evaluated 457 protocol renal biopsies performed within the first year after transplantation. Using the calcineurin inhibitors (CI) nephrotoxicity score, the incidence of nephrotoxicity was monitored as a manifestation of excessive immunosuppression. Findings were correlated with clinical evidence of active BK polyomavirus (BKPyV) replication and PyVAN. Compared to the normal histology, nephrotoxicity was associated with more frequent BKPyV viremia and viruria (p = .01 and p < .01, respectively) and more common occurrence of PyVAN. The persistence of toxicity in the subsequent biopsy proved to be a negative risk factor of viremia and viruria (p = .03 and p < .01, respectively), independently of the initial BKPyV status. Toxicity could also be used as a predictor of viremia and viruria (p = .04 and p < .01, respectively) even in the absence of viral replication at the time of initial biopsy. The early histological manifestation of CI nephrotoxicity was associated with significant BKPyV reactivation in the risky first posttransplant year.

P1663CLINICAL AND PATHOLOGICAL FACTORS INFLUENCING RESIDUAL RENAL FUNCTION AFTER LIVING DONOR NEPHRECTOMY

Abstract Background and Aims Renal function decreases with aging. Aging is associated with significant changes in structure and function of the kidney. On the macrostructural level, kidney cortical volume decreases, therefore total kidney volume (TKV) also decreases with aging. On the microstructural level, the number of glomerulosclerosis increases, therefore nephron number decreases with aging. Some reports show that the decline of TKV and nephron number is accompanied by a reduction in renal function. However, in the field of living kidney transplantation, TKV and glomerulosclerosis are not fully evaluated as factors influencing the donor’s post-transplant renal function. Living kidney transplantation is an established renal replacement therapy for end-stage renal disease patients. To predict living kidney recipient’s renal function, one-hour protocol biopsy is conducted during the operation. From one-hour protocol biopsy, donor’s pathophysiological findings such as glomerulosclerosis can be evaluated. In this study, we evaluated the correlation of potential influencing factors including TKV and glomerulosclerosis with pre- and post-transplant renal function in living kidney donors. Method This is a retrospective study including all 37 living related kidney donors seen at Kyoto University Hospital from January 2013 to April 2019. Estimated glomerular filtration rate (eGFR) was calculated using equation for Japanese population from serum creatinine levels at pre- and post-transplant. TKV was calculated from the 3D volume-rendered images of enhanced CT (=π/6×length×width×thickness), and adjusted to standard body surface area (BSA) by individual BSA. The ratio of number of non-glomerulosclerosis per that of whole glomeruli (non-GS) was evaluated by protocol renal biopsy at one hour after renal reperfusion. This study protocol was approved by the Ethics Committee on human research of the Graduate School of Medicine, Kyoto University. Results We evaluated 37 living kidney donors (35.1% male, mean age 58.2 ± 12.0 years). Mean pre-transplant eGFR was 75.7 ± 12.1 ml/min/1.73m2, mean post-transplant eGFR; 44.9 ± 7.75 ml/min/1.73m2, adjusted TKV (aTKV); 349.3 ± 58.4 ml, and non-GS; 0.892 ± 0.086. Pre-transplant eGFR was associated with aTKV and aTKV×nonGS (r=0.525, 0.569 respectively, p&amp;lt;0.01). Post-transplant eGFR was associated with age (≧65 years old, p&amp;lt;0.01), aTKV, non-GS, and aTKV×non-GS (r=0.527, 0.344, 0.626 respectively, p&amp;lt;0.05). The rate of eGFR decline was associated with age (≧65 years old, p=0.044), but not with aTKV and non-GS, aTKV×non-GS. Conclusion These results suggest that non-GS and age are correlated with post-transplant renal function but not pre-transplant renal function in living kidney donor, and the decline rate of eGFR are correlated with age.

P1759NEPHROTOXICITY OF CALCINEURIN INHIBITORS AS A RISK FACTOR FOR BK VIRUS REPLICATION AFTER KIDNEY TRANSPLANTATION

Abstract Background and Aims BK virus nephropathy (BKVN) represents a serious complication of kidney transplantation and is responsible for significant percentage of transplanted kidneys prematurely terminating their function. Its occurrence is considered a complication of immunosuppressive therapy and is closely related to its intensity. The aim of our prospective study was to evaluate the incidence of subclinical and clinically manifest nephrotoxicity of calcineurin inhibitors (CI) in repeated protocol kidney graft biopsies as a manifestation of excessive immunosuppression and to evaluate its relationship to the PCR confirmed active BKV replication and bioptically proven BKVN during the first year after transplantation. Method In a group of 161 newly transplanted patients we prospectively evaluated 457 consecutive protocol renal biopsies performed within the first year after transplantation. Using the CI nephrotoxicity score, the incidence of nephrotoxicity was monitored. Findings were correlated with laboratory (PCR) and histological evidence of active BK virus (BKV) replication and BKVN. Results When compared to the normal histology, nephrotoxicity was associated with more frequent significant BKV viraemia and viruria (P = 0.02 and P = 0.01, respectively) and more common occurrence of BKVN. The persistence of toxicity in the subsequent biopsy proved to be a negative risk factor of significant BKV viraemia and viruria (P = 0.03 and P = 0.01, respectively), independently of the initial BKV status of the monitored groups. Toxicity could also be used as a predictor of significant viraemia and viruria (P = 0.02 and P = 0.01, respectively) even in the absence of viral replication at the time of initial biopsy. Conclusion Early histological detection of CI nephrotoxicity followed by pre-emptive CI dose reduction might prevent significant BKV reactivation in the risky first posttransplant year. The evaluation whether a regression of histological signs of nephrotoxicity after a CI dose reduction leads to a reduction in BKV replication, and whether a more frequent occurrence of rejection does not complicate further posttransplant course, will be the subject of our further investigation. Supported by grant of Ministry of Health, Czech Republic DRO (FNOL 00098892) – 87-68.

High Tacrolimus Clearance – A Risk Factor for Development of Interstitial Fibrosis and Tubular Atrophy in the Transplanted Kidney

Background Patients showing high tacrolimus clearance eliminate the drug more rapidly, and in order to reach the same trough concentration they need higher daily doses compared to those with low clearance. The high clearance makes them more exposed to transient under-immunosuppression in case of a missed/delayed dose but the higher daily tacrolimus doses cause higher maximum concentrations (Cmax). Both are hypothesized to induce development of interstitial fibrosis and tubular atrophy (IFTA) in the transplanted graft. We wanted to investigate the association between estimated tacrolimus clearance and development of IFTA in the renal transplant during the first year post-engraftment. Methods Data from all patients transplanted between 2009 and 2013 at Oslo University Hospital, Rikshospitalet were included in the analysis. Association between estimated tacrolimus clearance (daily tacrolimus dose [mg]/trough concentration [μg/L]) and development of IFTA, (defined as i+t ≤ 1 and ci+ct ≥ 2) in renal protocol biopsies from 6 weeks to 12 months post-transplantation was investigated. Results In total, 510 patients were treated with tacrolimus and had paired protocol biopsies (6 weeks + 12 months) after transplantation, were included in the analysis. Patients were divided in four groups according to their estimated tacrolimus clearance. There were no differences in biopsy scores between the groups at 6 weeks. The high clearance group developed significantly more IFTA from 6 weeks to 12 months compared to the low clearance group (50% vs 22%, P<0.007). Of the 233 patients without IFTA in the 6-week biopsies a 1-unit increase in tacrolimus clearance was associated with an odds ratio of 1.88 (95% CI; 1.12-3.27) for development of IFTA after adjusting for donor age and deceased donor. Conclusion High tacrolimus clearance was significantly associated with development of IFTA within the first year following renal transplantation. The effect may be explained by higher peak concentrations and/or more severe transient under-immunosuppressive episodes in these patients.

Abnormalities in Protocol Graft Kidney Biopsy 6 Months Posttransplantation in a Tertiary Care Center Hospital of Nepal

BackgroundIncreasing graft survival is the prime focus of every transplantation program. Detection of subclinical abnormalities with the help of protocol renal graft biopsies performed at predetermined intervals after transplantation has been one of the approaches.The objective was to study the abnormalities in protocol renal graft biopsy specimens at 6 months posttransplantation. MethodsThis was a hospital-based observational descriptive study. It included the recipients who underwent kidney transplantation between October 2014 and September 2015. The recipients were followed up postoperatively on an outpatient basis, as per the institution protocol. At 6 months posttransplantation, protocol graft biopsy was performed in all patients with normal functioning allograft without proteinuria after obtaining informed written consent. ResultsA total of 57 patients with chronic kidney disease underwent renal transplantation during the study period. Protocol biopsy was performed in 47 recipients.Subclinical rejection was found in 4 (8.5%) recipients. Two recipients had significant tubulitis and interstitial inflammation. One of them showed features of Banff Type IA cellular rejection (t2, i2) and another showed Banff Type IB cellular rejection (t3, i2). Biopsy specimen of 1 recipient showed significant glomerulitis and peritubular capillaritis (g3, ptc1). Another recipient showed significant peritubular capillaritis (ptc2) with C4d positivity. IgA nephropathy was present in 6 (12.8%) recipients. BK virus nephropathy was found in 2 (4.3%) recipients. ConclusionThis study demonstrates that abnormal histologic findings occur in protocol graft biopsy specimens at 6 months post renal transplantation in patients without any clinical or laboratory abnormalities.

Immunoglobulin A (IgA) Nephropathy in Protocol Graft Kidney Biopsy done at six months Post Transplantation in a Tertiary Care Center Hospital of Nepal

Background: Renal transplantation is the treatment of choice for end stage renal disease. The focus of interest has been to increase the life of the transplanted graft. Recurrence of native kidney disease or occurrence of denovo glomerulonephritis has adverse effects in graft survival. Protocol graft biopsy done at fixed time interval after transplantation aids in early identification of post-transplant glomerulonephritis before development of clinical signs and symptoms. This study describes the incidence of post-transplant IgA Nephropathy in protocol renal graft biopsies done at six months post- transplantation.Materials and Methods: This is a hospital based observational descriptive study, done in Tribhuvan University Teaching Hospital, Kathmandu, Nepal, a tertiary medical referral center in the capital. Protocol biopsy of the graft kidney was performed at six months post-transplantation in all recipients who underwent kidney transplantation in this hospital between 2071 Kartik and 2072 Ashwin.Results: Protocol biopsy was performed in total 47 recipients. Mean age of the recipients was 33.7 years ±10.83 years. The study population consisted of 33 (70.2%) male and 14 (29.8%) female recipients. IgA Nephropathy was present in 6 (12.8%) recipients.Conclusion: Our study demonstrates that IgA Nephropathy does occur in patients with stable GFR and without any clinical or laboratory abnormalities. Protocol biopsy is valuable in detection of early histologic abnormalities before onset of clinical manifestations, thus helping in prompt management with aim to prolong the graft survival.Journal of Nobel Medical CollegeVolume 6, Number 1, Issue 10 (January-June, 2017)

Clinico-pathological features of repeat renal biopsies in patients with lupus nephritis at Groote Schuur Hospital, Cape Town.

Background Repeat renal biopsies in patients with lupus nephritis are usually done to guide treatment or to establish disease chronicity. Their value is not clear from available literature. There are also no available data in Africa to guide clinicians. Methods This was a retrospective study of patients undergoing a repeat renal biopsy between January 2003 and December 2014 from a single centre in Cape Town, South Africa. Relevant demographic, clinical and histological records of patients with repeat renal biopsies were documented. Comparison of data from first and second renal biopsy was performed. Results Forty-four patients had at least two biopsies done during the study period. Most patients were females (81.8%). The mean biopsy interval was 2.8 ± 1.8 (range 0.38-9.4) years. Proteinuria was the main indication for the repeat biopsy (36.1%). The glomerular filtration rate and proteinuria worsened between the two biopsies ( p = 0.001 and 0.019, respectively) suggesting disease progression. Most patients (65.4%) with a non-proliferative class of lupus nephritis at first biopsy progressed into a proliferative class, whereas patients with initial proliferative lupus nephritis at first biopsy (77.8%) remained as proliferative at repeat biopsy. Treatment was changed in 85% of patients at second biopsy. Conclusion Repeat renal biopsies in patients with lupus nephritis presents a useful means of assessing disease progression and provides guidance regarding modification of treatment. More studies are, however, required to evaluate the value of repeat biopsies and perhaps the need for protocol renal biopsies in patients with lupus nephritis.

Integrative Genomics Identifies Novel Associations with APOL1 Risk Genotypes in Black NEPTUNE Subjects.

APOL1 variants have been associated with renal phenotypes in blacks. To refine clinical outcomes and discover mechanisms of APOL1-associated kidney injury, we analyzed clinical and genomic datasets derived from 90 black subjects in the Nephrotic Syndrome Study Network (NEPTUNE), stratified by APOL1 risk genotype. Ninety subjects with proteinuria ≥0.5 g/d were enrolled at first biopsy for primary nephrotic syndrome and followed. Clinical outcomes were determined, and renal histomorphometry and sequencing of Mendelian nephrotic syndrome genes were performed. APOL1 variants were genotyped, and glomerular and tubulointerstitial transcriptomes from protocol renal biopsy cores were analyzed for differential and correlative gene expression. Analyses were performed under the recessive model (high-risk genotype defined by two risk alleles). APOL1 high-risk genotype was significantly associated with a 17 ml/min per 1.73 m(2) lower eGFR and a 69% reduction in the probability of complete remission at any time, independent of histologic diagnosis. Neither APOL1 risk group was enriched for Mendelian mutations. On renal biopsy, high-risk genotype was associated with increased fractional interstitial area, interstitial fibrosis, and tubular atrophy. Risk genotype was not associated with intrarenal APOL1 mRNA expression levels. Differential expression analysis demonstrated an increased steady-state level of five genes associated with the high-risk genotype (CXCL9, CXCL11, and UBD in glomerulus; SNOR14B and MUC13 in tubulointerstitium). APOL1 tubulointerstitial coexpression analysis showed coexpression of APOL1 mRNA levels with a group of intrarenal transcripts that together were associated with increased interstitial fibrosis and tubular atrophy. These data indicate the high-risk APOL1 genotype confers renal risk across histopathologic diagnoses.

M-RNA Expression of Renal Transporters and Drug Metabolizing Enzymes Changes With Time Following Living and Deceased Donor Renal Transplantation.

Introduction:A renal allograft undergoes cold ischemia(CI), warm-reperfusion injury, and calcineurin-inhibitor nephrotoxicity during its functional life-time. These abuses may alter the expression and activity of renal drug transporters(RDTs) and drug metabolizing enzymes(DMEs) which may inturn alter Transplant(Tx) medication disposition. Rodent data from our group suggests changes in mRNA expression of RDTs post-Tx. The objective of this study was to evaluate the effect of prolonged CI on longitudinal changes in RDTs and DMEs post-Tx in living donor(LD) and deceased donor(DD) renal-Tx recipients. Methods:GSE11166 microarray dataset (GPL570 Affymetrix-GeneChip) with baseline biopsies from 14DD and 14LD and 67 protocol renal biopsies obtained at 3, 6, 12 and 24months post-Tx was accessed through the NIH-Gene Expression Omnibus(GEO). Partek Genomic Suite® was used to analyze significant changes in mRNA expression of RDTs and DMEs deemed important for drug disposition by the FDA and EMA. Results:DD kidneys exhibited 1.5-5 fold decline in ABCB1, SLC22A1, CYP2B6, CYP3A4, and CYP3A7 and a 1.6-2.7 fold increase in SLCO4C1, SLC15A1, SLC22A1, CYP2C9 and UGT1A1 mRNA expression compared to LD.Table: No Caption available.ABCB4, SLC22A3, and CYP3A4 mRNA expression significantly and non-uniformly increased by 2 fold in DD kidney-Tx recipients, whereas ABCC4, SLC15A1, SLC22A5, SLCO4C1, CYP2C9 and UGT1A6 mRNA expression is significantly and non-uniformly decreased(ratio:0.32-0.54) in DD kidney-Tx recipients. Conclusion:Prolonged CI, Warm reperfusion injury, surgical stress associated with kidney-Tx and calcineurin-inhibitor nephrotoxicity significantly alters the mRNA expression of important RDTs and DMEs in DD transplant recipients compared to LD. GEO database combined with Partek Genomic Suite® is an invaluable tool to understand the changes in gene expression of target genes in publicly available NIH funded biosets.

Long-Term Renal Function After Size-Mismatched Renal Transplantation.

Aim: It is controversial whether incompatibility between donor kidney weight and recipient weight influences long-term function of renal allograft. We retrospectively assessed the association of the ratio of the kidney weight with the recipient weight (Kw/Rw) and long-term graft survival and function. Method: 292 patients who received living donor renal transplants in our hospital between 2002 and 2007 were included. Patients diagnosed with acute rejection, those aged <17 years, and those with inaccurate data collection were excluded. Patients were divided into two groups: those with Kw/Rw <2.7 (n=96) and those with Kw/Rw >2.7 group (n=126). The two groups were compared according to recipient/donor gender and age, recipient weight, allograft weight, immunosuppressant regimen, and eGFR at 1 month and 1, 3, 5, 7, and 9 years after transplantation. Using protocol renal biopsy samples obtained at 1 h and 1 year after transplantation, we also compared glomerular volume (GV), measured by the Weibel and Gomez method, between the two groups (<2.7: n=20, >2.7: n=28). Results: The mean eGFR at 1 month and at 1, 3, and 5 years after transplantation in the Kw/Rw <2.7 group was 46.2, 43.3, 41.7, and 40.4 ml/min/1.73 m2. These values were significantly lower than the corresponding values in the Kw/Rw >2.7 group: 54.2, 46.2, 44.2, and 41.2 ml/min/1.73 m2 (p <0.05).There were no significant differences between the two groups in eGFR or in graft survival at 7 years after transplantation (p =0.18). In multiple regression analysis, the factor most affecting eGFR during the follow-up period (72±34 months) was donor age. In addition, Kw/Rw affected eGFR only at 1 month and 1 year after transplantation. The median GV in the 1 h biopsy was 1.6±0.4 × 106 μm3 in the Kw/Rw <2.7 group and was 1.8±0.4 ×106 μ3 in the Kw/Rw >2.7 group (p =0.18). At the 1 year biopsy, median GV was 2.0±0.5×106 μm3 (<2.7) and 1.7±0.4×106μm3 (>2.7) (p =0.04). GV showed a trend to increase in the Kw/Rw <2.7 group at 1 year after transplantation. Conclusion: In the observation period, significant adverse effects on long-term allograft function caused by size-mismatched renal transplantation were not found. We conclude that glomerular enlargement, which was common in the Kw/Rw <2.7 group, allows for the effective maintenance allograft function.

Early Microchimerism in Peripheral Blood Following Kidney Transplantation

BackgroundThe role of microchimerism found in the peripheral blood of renal transplant recipients remains a matter of debate. We assessed the frequency of microchimerism after kidney transplantation and examined its influence on clinical courses over a 12-month follow-up period. Patients and MethodsTen single-kidney recipients underwent microchimerism detection at 2 days, 2 weeks, and 1, 3, 6, and 12 months after transplantation, with mismatch human leukocyte antigen (HLA)-A, -B, and -C used as markers. ResultsMicrochimerism was detected in 8 (80%) patients at 2 days after kidney transplantation. In 3 of those, microchimerism became negative within 3 months after transplantation, whereas it remained present for up to 12 months in 3 patients (33 %). There was 1 acute rejection episode in a patient in whom microchimerism became negative within 3 months. Protocol renal graft biopsy specimens obtained 3 months after transplantation revealed no acute cellular-mediated rejection (ACMR) or acute antibody-mediated rejection (AAMR) in the 5 patients positive for microchimerism at 3 months. ConclusionsMicrochimerism was frequently detected after kidney transplantation. Microchimerism that remained for more than 3 months post-transplantation might be correlated with a lower incidence of rejection, thus its monitoring may help identify recipients with a low rejection risk.

Protocol renal biopsy in patients with lupus nephritis: a single center experience.

Renal biopsy plays an indispensable role in the diagnosis and management of patients with lupus nephritis (LN). A number of studies have evaluated the role of a repeat biopsy in case of disease relapse or treatment unresponsiveness. We studied 40 patients with LN with renal biopsies performed at baseline and after six months of therapy. The baseline and protocol biopsies were compared with respect to histological class transformation, crescents, tubular atrophy, interstitial fibrosis and glomerulosclerosis. We also compared serum creatinine, hemoglobin, systemic lupus erythematosus disease activity index (SLEDAI) scores, 24-h urine protein excretion and C3levels as well as activity index (AI) and chronicity index (CI) at baseline and at six months. Comparison of means was made by paired t test, McNemar test and marginal homogeneity test (multinomial data). Histological class transformation was seen in 10 patients (25%). Intra-class progression to greater chronicity was seen in 10 other patients (25%).There was an increase in glomerulosclerosis, tubular atrophy, interstitial fibrosis and a reduction in cellularity, crescent formation and wire loop lesions in the protocol biopsy. A decline in AI (6.05 vs. 2.50, P <0.001) and SLEDAI scores (8.1 vs. 3.7, P <0.001) and an increase in CI (0.68 vs. 2.52, P <0.001) was observed at the time of protocol biopsy. Our study shows a trend toward greater chronicity in protocol biopsies in LN.

The Kidney as a Reservoir for HIV-1 after Renal Transplantation

Since the recent publication of data showing favorable outcomes for patients with HIV-1 and ESRD, kidney transplantation has become a therapeutic option in this population. However, reports have documented unexplained reduced allograft survival in these patients. We hypothesized that the unrecognized infection of the transplanted kidney by HIV-1 can compromise long-term allograft function. Using electron microscopy and molecular biology, we examined protocol renal transplant biopsies from 19 recipients with HIV-1 who did not have detectable levels of plasma HIV-1 RNA at transplantation. We found that HIV-1 infected the kidney allograft in 68% of these patients. Notably, HIV-1 infection was detected in either podocytes predominately (38% of recipients) or tubular cells only (62% of recipients). Podocyte infection associated with podocyte apoptosis and loss of differentiation markers as well as a faster decline in allograft function compared with tubular cell infection. In allografts with tubular cell infection, epithelial cells of the proximal convoluted tubules frequently contained abnormal mitochondria, and both patients who developed features of subclinical acute cellular rejection had allografts with tubular cell infection. Finally, we provide a novel noninvasive test for determining HIV-1 infection of the kidney allograft by measuring HIV-1 DNA and RNA levels in patients' urine. In conclusion, HIV-1 can infect kidney allografts after transplantation despite undetectable viremia, and this infection might influence graft outcome.

A case of chronic antibody-mediated rejection in the making

A kidney transplant recipient developed chronic antibody-mediated rejection (ABMR) with clinically significant transplant glomerulopathy while under careful clinical monitoring. The patient developed a de novo donor-specific antibody (DSA) posttransplantation, and a protocol renal biopsy showed C4d deposition with no histological evidence of rejection. Subsequently he developed peritubular capillary basement membrane multilayering, with negative C4d and DSA. Finally, he developed proteinuria and transplant glomerulopathy, with reappearance of DSA and C4d. Despite having a de novo antibody and progressive antibody-mediated damage, this patient under close histological and serological surveillance did not fulfill Banff criteria for acute or chronic ABMR until his disease was advanced. This case illustrates the limitations of current Banff criteria in this setting, due to the fluctuating nature of DSA and C4d staining.

AB0425 Silent lupus nephritis in protocol biopsy after complete remission

BackgroundRenal biopsy is an essential tool in lupus nephritis (LN) diagnose, It is also useful to establish prognosis. In general biological markers as complement, Anti ADN autoantibody are used to...