Banff Histopathological Consensus Criteria for Preimplantation Kidney Biopsies.

The Banff working group on preimplantation biopsy was established to develop consensus criteria (best practice guidelines) for the interpretation of preimplantation kidney biopsies. Digitally scanned slides were used (i) to evaluate interobserver variability of histopathologic findings, comparing frozen sections with formalin-fixed, paraffin-embedded tissue of wedge and needle core biopsies, and (ii) to correlate consensus histopathologic findings with graft outcome in a cohort of biopsies from international medical centers. Intraclass correlations (ICCs) and univariable and multivariable statistical analyses were performed. Good to fair reproducibility was observed in semiquantitative scores for percentage of glomerulosclerosis, arterial intimal fibrosis and interstitial fibrosis on frozen wedge biopsies. Evaluation of frozen wedge and core biopsies was comparable for number of glomeruli, but needle biopsies showed worse ICCs for glomerulosclerosis, interstitial fibrosis and tubular atrophy. A consensus evaluation form is provided to help standardize the reporting of histopathologic lesions in donor biopsies. It should be recognized that histologic parameters may not correlate with graft outcome in studies based on organs deemed to be acceptable after careful clinical assessment. Significant limitations remain in the assessment of implantation biopsies.

Transplant glomerulopathy: clinical and pathological correlations.

OBJECTIVE: Chronic transplant glomerulopathy (TG) is one of the leading causes of severe posttransplantation proteinuria and graft loss. Our current knowledge about risk factors for the development of TG, as well as factors that affect its dynamics and prognosis, is poor. We sought to describe the pathological and clinical risk factors and correlations of TG as well as parameters that influenced the survival of grafts with that pathology. MATERIALS AND METHODS: We retrospectively reevaluated 86 kidney transplant cases with TG that have been recognized on the basis of an indication biopsy since 1997. All TG as well as all pre-TG (previous) biopsies were characterized for the presence of C4d deposits in the graft. RESULTS: Younger recipient age and minimal immunosuppression due to drug withdrawal or suboptimal drug doses/blood levels within 3 to 6 months preceding the biopsy were associated with C4d deposition in peritubular capillaries (PTC; P = .0053 and P = .0365, respectively). Diffuse PTC-itis (P = .029, RR [95% confidence interval] = 3.349 [1.131-9.919]) and total interstitial inflammation score (P = .015, RR [95% confidence interval] = 9.662 [1.784-52.329]) were observed to show a negative impact on graft survival. C4d deposition in PTC and glomeruli, the level of pretransplantation sensitization, episodes of acute rejection, and C4d in previous (pre-TG) biopsies did not influence the survival of grafts with TG. CONCLUSIONS: Younger recipient age and minimal immunosuppression were associated with C4d positivity in grafts with TG. The survival of kidney grafts with TG was significantly affected by the magnitude of inflammation in the interstitium and PTC, but not by C4d positivity in PTC and glomeruli.

Late conversion to everolimus complicated with necrotizing glomerulonephritis in a renal allograft recipient: case report.

Conversion from calcineurin inhibitors (CNI) to proliferation signal inhibitors (PSI), such as sirolimus or everolimus (EV), may improve the course of chronic allograft nephropathy. Herein we have presented a case of a kidney recipient with chronic cyclosporine (CsA) nephrotoxicity who was converted from CsA to EV at 5.5 years posttransplantation. There were no significant changes in immunofluorescence (IFL) or in electron microscopy (EM) in the preconversion biopsy. Two months after conversion, proteinuria and creatinine increased. The biopsy showed focal, segmental necrosis of the glomerular tuft with the formation of segmental cellular crescents and increased endocapillary cellularity. IFL showed granular deposits of IgG, IgM, and C3 mostly along the capillary walls; it was negative for C4d. EM revealed electron-dense deposits within the glomerular basement membrane (GBM) and in the subendothelial region with significant reduction in the capillary lumina due to GBM reduplication and widening of lamina rara interna with the formation of fibrillary structures therein: focal, segmental glomerulosclerosis. EV was withdrawn and we administered tacrolimus and steroid pulses with improvement. Five months after the withdrawal of EV, a third graft biopsy showed remission of the necrotizing glomerulonephritis. However, the patient demanded dialysis at 17 months after conversion to EV. We concluded that necrotizing glomerulonephritis with immune complex deposition in a renal allograft was possibly induced by late conversion from CNI to EV. Reconversion to CNI may be recommended in cases of PSI-associated posttransplantation glomerulonephritis but the long-term prognosis is uncertain.

Does Histopathology of Implanted Kidney According to Banff 07 Help Predict Long-term Transplantation Outcome?

Analyses of peritransplant biopsies of deceased-donor kidneys show high incidence of chronic abnormalities. The question arises whether chronic abnormalities present at implantation determine engrafted kidney fate regardless of other concomitant variables. The aim of this study was to identify risk factors of graft loss considering histopathological changes present at implantation scored according to Banff 07 criteria. PATIENTS AND METHODS: Inclusion criteria (n = 300) was engraftment between years 2000 and 2008 and availability of implantation biopsy. Analyzed abnormalities present in donor biopsy were arteriolar hyalinization, interstitial fibrosis, intimal sclerotization, tubular atrophy, total inflammation, and percentage of sclerotic glomeruli (Banff classification). Allograft function was estimated by abbreviated Modification of Diet in Renal Disease formula and proteinuria semi-quantitatively by standard dip-stick test. Kaplan-Meier estimate was used to assess graft survival. Searching for independent risk factors of graft survival was performed by means of Cox proportional hazards models (SAS System, SAS Institute Inc, Cary, NC, United States). RESULTS: In one-factor analyses, predictors of kidney allograft loss were donor age, donor history of diabetes, kidney allograft dysfunction within first posttransplant year, and recipient chronic hepatitis C. In terms of chronic abnormalities, arteriolar hyalinization of any intensity nearly doubled the risk of allograft loss. Independent risk factors of kidney allograft loss in multivariate analysis were donor age, posttransplant diabetes mellitus, proteinuria after engraftment, and recipient hepatitis C. CONCLUSION: The effect of arteriolar hyalinization on renal transplant survival is probably interwoven with other predictors of graft loss. Recognizing the negative impact of recipient chronic hepatitis C on graft survival, hepatitis C virus treatment should be provided to patients with advanced chronic kidney disease, patients on wait lists, or patients already transplanted.

Posttransplant Lymphoproliferative Disorder in Kidney and Liver Transplant Recipients: A Single-Center Experience.

INTRODUCTION: Posttransplant lymphoproliferative disorder (PTLD) is a heterogeneous group of lymphoid malignant neoplasms arising after solid organ transplantation or hematopoietic stem cell transplantation. The current World Health Organization classification identified 4 basic histologic types of PTLD: early, polymorphic variant, monomorphic variant, and classical Hodgkin lymphoma-type lesions. METHODS: Data of 12 PTLD cases of was retrospectively analyzed in terms of the transplanted organs, time to diagnosis of PTLD, type of immunosuppressive treatment in regard to the induction treatment and acute transplant rejection, and long-term survival. RESULTS: Most of the analyzed cases of PTLD occurred in men (n = 8, 67%); 83% of patients were renal transplant recipients and 17% were liver transplant recipients. Of the kidney recipients, 8% received induction of antithymocyte globulin and 17% received daclizumab. An episode of acute rejection occurred in 6 (50%) patients. All patients were treated with pulses of methylprednisolone and received triple immunosuppressive regimen. Histopathologic examination revealed polymorphic form of PTLD in 5 (42%) patients and classical Hodgkin lymphoma in 3 (25%) cases. Diffuse large B-cell lymphoma was diagnosed in 3 (25%) patients, and diffuse large B-cell lymphoma rich in T lymphocytes and histiocytes was diagnosed in 1 (8%) patient. ALK4- anaplastic lymphoma was diagnosed in 1 (8%) recipient. Four (25%) patients died as a result of PTLD progression (including all 3 patients with central nervous system involvement), and 8 survived with stable graft function. CONCLUSIONS: PTLD is a heterogeneous group of lymphoproliferative disorders occurring in organ recipients. The unusual location changes (especially central nervous system or intestine) can impede the proper diagnosis.

Outcomes of Prolonged Treatment With Intravenous Immunoglobulin Infusions for Acute Antibody-mediated Rejection in Kidney Transplant Recipients.

BACKGROUND: Treatment of antibody-mediated rejection (AMR) is one of the main problems after kidney transplantation (KTx). The results of intensive AMR treatment with plasmapheresis (PF) and repeated infusions of intravenous immunoglobulin (IVIg) are presented. METHODS: Diagnosis of AMR was based on graft biopsy and the presence of donor-specific antibodies (DSAs). AMR therapy consisted of 5 PF and IVIg infusions given after the last PF. Subsequent IVIg doses were given every 4 weeks for 6 months. Graft biopsy and DSA assessment were repeated at the end of the treatment (ET). RESULTS: Four women and 10 men were included in our study; mean time from KTx to AMR was 79 (range, 3-193) months. During the treatment, 4 patients had graft failure. Graft function at baseline was significantly worse (P = .02) in this group compared with patients who completed the therapy. At baseline, mean flourescence intensity (MFI) was 6574 (range, 852-15,917) in the whole group, 7088 (range, 1054-15,917) in patients who completed treatment, and 4828 (range, 852-11,797) in patients who restarted hemodialysis. At ET, DSA MFI decreased in 8 of 10 patients (80%) who completed the therapy. The MFI decrease was 3946 (range, 959-11,203). Control graft biopsies revealed decreased intensity of C4d deposits in peritubular capillaries in 7 patients (78%) and decreased peritubular capillaritis in 2 patients (22%). CONCLUSION: Intensive, prolonged AMR therapy with PF and IVIg resulted in a decrease in DSA titer and intensity of C4d deposits, but was not associated with reduction of microcirculation inflammation. Treatment was ineffective in patients with baseline advanced graft insufficiency.

Analysis of Distribution of Expanded- and Standard-Criteria Donors and Complications Among Polish Recipients by Kidney Donor Risk Index Value.

INTRODUCTION: The approach toward transplanting kidneys from expanded-criteria donors (ECDs) in Poland is largely site-dependent. The Kidney Donor Risk Index (KDRI) allows for obtaining a more precise characteristic of ECDs and further stratification into "better" and "worse" quality grafts. METHODS: Comparison of the incidence of delayed graft function (DGF) and biopsy-proven acute rejection (BPAR), median of hospitalization time and median of estimated glomerular filtration rate (eGFR) at 1 year after transplantation among kidney graft recipients (n = 468), divided by donor status (ECD/standard-criteria donor [SCD]) and KDRI value (I: 0.67-1.2, II: 1.21-1.6, III: 1.61-2.0, IV: 2.01-3.48). RESULTS: ECD kidneys have been transplanted to 32.47% of recipients. There were no ECD recipients in KDRI compartment I, 16.55% in compartment II, 79.22% in compartment III, and 100% in IV. In KDRI compartment II, DGF was diagnosed in 34.9% of SCDs and 56% of ECDs (P = .003), BPAR occurred in 7.8% of SCDs and 16% of ECDs (P = .073), median hospital stay was 12 days for SCDs and ECDs (P = 1), and eGFR was 50.7 mL/min for SCDs and 49.4 mL/min for ECDs (P = .734). In KDRI compartment III, DGF was diagnosed in 43.8% of SCDs and 49.2% of ECDs (P = .139), BPAR occurred in 6.3% of SCDs and 31.7% of ECDs (P = .001), median hospital stay was 10 days for SCDs and 12 days for ECDs (P = .634), and eGFR was 49.5 mL/min for SCDs and 45.2 mL/min for ECDs (P = .382). Among ECD recipients, DGF was diagnosed in 56.0%, 49.2%, and 47.7% of patients for KDRI compartments II, III, and IV respectively (P = .776); BPAR occurred in 16% (compartment II), 31.7% (compartment III), and 23.1% (compartment IV) (P = .273); the median hospital stay was 12 days (compartment II), 12 days (compartment III), and 12.5 days (compartment IV) (P = 1); and eGFR was 49.5 mL/min (compartment II), 45.4 mL/min (compartment III), and 36.1 mL/min (compartment IV) (P = .002). CONCLUSION: Assessment using both the ECD and KDRI systems allows for a more precise evaluation of prognosis and predicting complications among recipients.

Primary kidney allograft dysfunction due to myeloma-cast nephropathy: a case report.

Cast nephropathy is a rare event among renal transplants, usually associated with multiple myeloma or light chain nephropathy. Herein we have reported primary graft dysfunction early posttransplantation due to cast nephropathy, associated with thrombotic microangiopathy.

Posttransplantation glomerulonephritis: risk factors associated with kidney allograft loss.

AIM OF THE STUDY: Chronic glomerulonephritis (GN) is reported as a common cause of late kidney allograft loss. The aim of this study was to identify risk factors associated with kidney allograft loss in the course of posttransplantation GN. PATIENTS AND METHODS: The study analyzed 75 kidney allograft recipients with biopsy-confirmed posttransplantation GN, including 27 cases of immunoglobulin (Ig)A nephropathy (IgAN), 30 of membranous GN (MGN), 6 of mesangiocapillary GN (MCGN); and 12 of focal segmental GN (FSGS). The risk factors for kidney allograft loss, defined as dialysis reintroduction after GN onset, were identified through are historical cohort study. CLINICAL FINDINGS: After the onset of posttransplantation GN, the median time to dialysis introduction was 46 months. The risk factors for kidney allograft loss were as follows: male gender (hazard ratio [HR] = 1.92; 95% confidence intervall [CI] 1.0-3.70; P = .052), initial unsatisfactory kidney function (HR = 1.86 per 1 mg/dL serum creatinine increment; 95% CI 1.0-3.46; P < .05), graft dysfunction at diagnosis (HR = 1.65 per 1 mg/dL serum creatinine increment; 95% CI 1.32-2.07; P < .001), nephrotic syndrome (HR = 2.3; 95% CI 1.13-4.99; P < .05) late-onset GN (HR = 1.1 per each additional year of observation, 95% CI 1.0-1.21; P < .05), and MPGN as a type of GN. Enhanced immunosuppression increased and ACEI and/or statin treatment decreased the risk of return to dialysis, respectively: HR = 1.56, 95% CI 0.76-3.18, P = .22; HR = 0.39, 95% CI 0.16-0.98, P = .0037; and HR = 0.367, 95% CI 0.15-0.88, P = .025. CONCLUSIONS: Identification of risk factors can help discover patients who will have a faster progression to kidney allograft loss due to GN. In posttransplantation GN, statins and/or ACEI should be prescribed, if there are no contraindications.

Successful reversal of acute vascular rejection and cyclosporine-associated nephrotoxicity in renal allograft with combined sirolimus and mycophenolate mofetil as immunotherapy.

Cyclosporine (CsA) has substantially improved patient and graft survival rates in solid organ transplantation. In clinical studies, sirolimus has been shown to be as effective as CsA to maintain survival of renal and cardiac allografts without causing nephrotoxicity. Herein we describe a patient with biopsy-proven CsA-associated nephrotoxicity and refractory renal allograft rejection who was converted from steroids, CsA, and azathioprine to steroids, sirolimus (RAPA), and low-dose mycophenolate mofetil (MMF). The follow-up period was 60 months. We observed substantial improvement, even normalization in renal function. Our patient did not give consent to repeat biopsy after conversion. We also observed a beneficial effect of CsA withdrawal on blood pressure control. The spectrum of adverse events induced by sirolimus seemed to be mild relative to the potency of the immunosuppressive effect. The excellent response to combined RAPA and MMF in this patient was probably due to "concerted actions" of these agents on both B- and T-cell functions. The combination enhanced therapeutic efficacy while minimizing the toxicity of individual drugs used in the regimen. These findings suggest that sirolimus, when used as a base therapy in combination with low-dose MMF in a renal allograft recipient, may be an alternative to CsA-based therapy, providing potent immunosuppression of a renal allograft. Sirolimus administration facilitated steroids dose reduction.

Thrombotic nephropathy and pulmonary hypertension following autologous bone marrow transplantation in a patient with acute lymphoblastic leukemia: case report.

Thrombotic microangiopathy is a severe and life-threatening complication following allogeneic or autologous bone marrow transplantation (BMT). Herein we describe a case of microangiopathic hemolytic anemia with progressive renal failure and pulmonary hypertension subsequent to autologous BMT due to acute lymphoblastic leukemia.

Biliary complications following liver transplantation: single-center experience.

Biliary complications (BC) following orthotopic liver transplantation (OLT) remain one of the major causes of postoperative complications and treatment failures. The list of common BC consists of biliary stricture, fistula, ischemic type biliary lesions (ITBL), cholangitis, and bile leakage following T-drain removal. Between July 2000 and December 2004, 101 consecutive cadaveric OLTs were performed in our institution. All but three were first full-size grafts. Seventeen patients were transplanted from the urgent list, the remaining 84 (83.16%) from the elective list. All but three patients had a choledochocholedochostomy over a straight drain. Bile cultures were taken routinely. The bile drain was removed following cholangiography 6 weeks after OLT. All patients received antibiotic prophylaxis. Ursodeoxycholic acid was used in selected cases. During the first 6 weeks positive bile cultures in absence of clinical and biochemical symptoms of cholangitis were found in 61 (60.4%) cases. Symptomatic cholangitis requiring antibiotic treatment was observed in 19 (18.8%) patients during the first 6 weeks. Two patients required endoscopic sphincterotomy and temporary stenting due to anastomotic stricture (1) or papilla of Vater fibrosis (1). Bile leakage following drain removal was observed in 8 (7.9%) patients. Five of them were treated conservatively, the remaining 3 (2.9%) required surgery (lavage) and stenting. In one case extrahepatic bile duct necrosis was diagnosed requiring reconstruction of the biliary anastomosis. No case of ITBL, bile leak at the anastomostic site, or stricture requiring surgical repair was noted. Despite the high incidence of positive bile cultures most likely related to use of a drain, the overall number of BC was low.

Application of sulforaphane: histopathological study of intraportal transplanted pancreatic islets into livers of diabetic rats.

BACKGROUND: Islet cell transplantation is a promising method to restore insulin independence to patients with type 1 diabetes mellitus. A main problem in clinical islet transplantation is the fact that only a small percentage of allogeneic islet-transplanted type 1 diabetic patients can completely omit insulin injections after transplantation. One reason for the impaired survival of islet grafts is aberration of the function of islets due to toxic agents, including oxygen radicals and nitric oxide, which arise during warm or cold ischemic time. Therefore, in clinical islet transplantation, islets have been preserved with a mixture of antioxidants to reduce free radical-mediated damage of transplanted beta cells. Our aim was to examine hepatic tissue after metabolic normalization following intraportal islet transplantation after application of sulforaphane. MATERIALS AND METHODS: Islets were isolated from pancreata of WAG rats. Sulforaphane (24 mg/kg) was administered 24 hours before isolated islets were transplanted into the liver through the portal vein (1200 +/- 100 per rat). At 9 months after transplantation the animals were killed and liver tissue removed for morphological examination. RESULTS: This report indicated that the intrahepatic portal vein site was indeed an excellent locus for implantation of free pancreatic islets. The islet grafts developed rich vascularization derived from both venous and arterial sources. The islet cells maintained their structural and functional integrity after implantation. CONCLUSION: Our results showed that sulforaphane improved islet function in vivo, indicating that combination of a free radical scavenger and an antioxidant (sulforaphane) may be used to increase the effectiveness of islet transplantation.

Bacteriophages and transplantation tolerance.

Our recent findings suggest that bacteriophages (phages) may not only eliminate bacteria, but also modulate immune functions. In this communication, we demonstrate that phages may strongly inhibit human T-cell activation and proliferation as well as activation of the nuclear transcription factor NF-kappaB in response to a viral pathogen. Phage administration in vivo can diminish cellular infiltration of allogeneic skin allografts. Thus, phage treatment should be considered in antibiotic-resistant posttransplantation infections. Furthermore, phages could find a broader application in clinical transplantation.

IgA nephropathy in kidney allograft recipients-therapeutic perspective.

INTRODUCTION: A growing number of patients are losing their kidney allografts due to glomerulonephritis. Although posttransplant IgA nephropathy (IgAN) is regarded as benign, it may lead to late allograft loss in a substantial number of patients. The aim of this study was to evaluate the influence of posttransplant IgAN on long-term transplantation outcomes, risk factors for progression of graft dysfunction, and effectiveness of therapeutic interventions. PATIENTS AND METHODS: We evaluated, potential risk factors for accelerated graft loss among 27 kidney allograft recipients with posttransplant IgAN, comparing graft survival in a control group matched for population and transplantation-related parameters. We evaluated the effectiveness of therapeutic interventions regarding immunosuppressive regimen, and hypertension control including angiotensin converting enzyme inhibitor (ACEI) usage with Kaplan-Meier, Cox proportional hazard plots, and log-rank tests in statistical analyses. RESULTS: Compared with the control group, patients with IgAN experienced a 6.57 higher risk for dialysis dependence (P < .01, 95% CI 1.4 to 30.83). The risk for accelerated graft loss in the course of IgAN was associated with graft dysfunction (RR = 2.16 for additional 1 mg/dL of serum creatinine at glomerulonephritis presentation; P < .03, 95% CI 1.2 to 4.36) and intense proteinuria as evidenced by a RR = 4.67 for the presence of the nephrotic syndrome (P < .05, 95% CI 0.95 to 22.8). Immunosuppression enhancement resulted in a significantly decreased risk of dialysis dependence, namely, RR = 4.76 (95% CI 1.12 to 20, P < .04). With ACEI treatment there was a tendency for a 2.8-fold decreased risk of dialysis dependence, without reaching statistical significance (P = .14). CONCLUSIONS: Patients with posttransplant IgAN may benefit from intensifying maintenance immunosuppression, which slows progression to end-stage graft dysfunction.

Nephropathy Evolving Within the First Two Posttransplant Months With No Typical Cytopathic Lesions: Two Cases Presentation.

BACKGROUND: We report 2 cases of polyomavirus-associated nephropathy (PyVAN) emerging within the initial 8 posttransplant weeks. These cases were characterized by intraepithelial BK virus replication without typical nuclear inclusions in epithelial cells. METHODS AND RESULTS: A 70-year-old male recipient of a cadaveric kidney transplant had experienced unsatisfying graft function since the time of transplantation (Tx). One month after Tx, results of a graft biopsy revealed mild tubulointerstitial inflammation. No intraepithelial nuclear inclusions suggestive of viral infection were present at that time. The patient received intravenous methylprednisolone, and the dosage of tacrolimus was increased. Due to a further drop in the glomerular filtration rate, a subsequent kidney biopsy was performed during posttransplant week 10, which revealed lesions typical of PyVAN. Retrospectively performed SV40 staining revealed that intragraft polyomavirus replication was already present on posttransplant day 30. Basic immunosuppression reduction and ciprofloxacin administration were followed by BK viremia elimination, stabilization of graft function, and resolution of PyVAN. In another patient, a 62-year-old male recipient of a cadaveric renal graft, BK viremia was monitored from the time of Tx. Two months after Tx, the patient was found to have a BK viral load of 6 × 4 log(10)/mL. Results of the graft biopsy revealed fully preserved tubular epithelium, but SV40 staining was positive in some of these cells. After basic immunosuppression reduction and introduction of ciprofloxacin, the BK viral load dropped to 1 × log(10)/mL with graft function stabilization. CONCLUSIONS: PyVAN may emerge as early as 4 weeks after Tx, with near-normal or acute rejection-like graft morphology. The early monitoring of plasma BK viral load, as well as SV40 staining, avoids misdiagnosis of this severe posttransplant complication.

Dynamic Elastography in Diagnostics of Liver Fibrosis in Patients After Liver Transplantation Due to Cirrhosis in the Course of Hepatitis C.

BACKGROUND: Assessment of the dynamics and degree of liver fibrosis in patients after liver transplantation is a basic element in the process of determining transplant survival prognosis. It allows planning and early initiation of prophylaxis or treatment, which translates into increased chances of preventing cirrhosis and of long-term optimal function of the graft. The aim of this study was to compare the results of biopsy and dynamic elastography in diagnostics of transplanted liver fibrosis, as well as determination of the stiffness cut-off point for assessment of significant fibrosis. PATIENTS AND METHODS: The study included 36 patients who had undergone liver transplantation due to cirrhosis in the course of hepatitis C virus (HVC) infection. Fibrosis was assessed in bioptates according to the METAVIR score (F0-F4). Elastography was performed using FibroScan; receiver operating characteristic curve analysis was used to identify the cut-off point for significant fibrosis (≥F2). RESULTS: The median stiffness in kPa for the whole group F0-F4 was 6.3 (range 3.4-29.9); for ≥F2 it was 6.9 (3.4-29.9), whereas for F0-F1 it was 4.4 (3.5-8.0). It was demonstrated that the value of 4.7 kPa in elastography is a statistically significant cut-off point for differentiation between the groups F0-F1 and F2-F4 (sensitivity: 93%, specificity: 57%, positive predictive value: 90%, negative predictive value: 66%), area under the receiver operating characteristic curve: 0.746 (95% confidence interval: 0.53-0.95, P < .05). CONCLUSIONS: Elastography is a promising tool for noninvasive assessment of significant liver fibrosis in patients after transplantation due to cirrhosis in the course of hepatitis C; it allows reduction in the number of biopsies performed.

Human Pooled Immunoglobulin as Treatment of Active Antibody-Mediated Rejection of Transplanted Kidney.

BACKGROUND: Antibody-mediated rejection (ABMR) has emerged as the leading cause of renal graft loss. The optimal treatment protocol in ABMR remains unknown. This study aimed to assess the efficacy of intravenous immunoglobulin (IVIG) for treatment of ABMR in renal recipients. METHODS: Thirty-nine ABO-compatible cross-match-negative renal recipients with biopsy-proven ABMR composed the study group. Pulses of methylprednisolone (MP) and appropriate enhancement of net state of immunosuppression were applied in all individuals; 17/39 recipients were administered IVIG (IVIG group); the remaining 22/39 patients, identified to be nonadherent or unsatisfactorily immunosuppressed, were kept on the initial treatment (MP group). Serum creatinine concentration was obtained at each of 10 intended visits, and glomerular filtration rate (GFR) was estimated with the use of the standard Modification of Diet in Renal Disease (MDRD) formula. Generalized linear mixed model was used for statistical analysis. RESULTS: Renal function (modeled as linear slope of MDRD-based GFR change over time, separately for the pre- and post-intervention periods) improved significantly in IVIG-treated recipients. Pre-intervention slopes were -0.72 and -0.46 mL/min/mo for IVIG and MP groups, respectively (P = NS), whereas post-intervention the slopes changed to -0.03 and -0.47 mL/min/mo (IVIG and MP, respectively; P < .005). Within-group changes of slopes at the time of intervention were 0.69 and -0.01 mL/min/mo in IVIG (P < .01) and MP (P = NS) groups, respectively. The relative slope change (pre- to post-intervention) was 0.7 mL/min/mo in favor of the IVIG group (P < .033). None of the classic immunologic or nonimmunologic graft function predictors influenced GFR during 12 months of follow-up. CONCLUSIONS: IVIG improved graft function in renal recipients diagnosed with ABMR.

Association of MYH9 rs3752462 and rs5756168 Polymorphisms With Transplanted Kidney Artery Stenosis.

Allelic variants of the MYH9 gene, encoding myosin nonmuscle heavy chain type IIA, have been shown to correlate with diminished glomerular filtration rates and end-stage kidney disease in individuals of Caucasian ancestry. Myosin nonmuscle heavy chain type IIA is expressed during development as well as in injured vessels and kidney structures. We hypothesized that MYH9 risk variants may correlate with kidney artery injury and dysfunctional healing, such as transplant renal artery stenosis (TRAS). Our study aimed at evaluating the association of MYH9 risk allelic variants (rs4821480, rs4821481, rs3752462, rs11089788, rs136211, rs5756168, rs2032487, and rs2239784) with TRAS, defined as >50% renal artery lumen reduction. Genotyping was performed with the use of custom Taqman genotyping assays on DNA samples (n = 295) from white deceased-donor kidney transplant recipients and genomic DNA from the corresponding donors. Statistical analysis was performed with the use of Kaplan-Meier estimates, log-rank tests, and proportional hazard Cox models. Recipients carrying TT in rs5756168 experienced diminished risk of TRAS (hazard ratio [HR], 0.31; P < .009), whereas organs carrying CC in rs3752462 were exposed to excessive TRAS risk (HR, 2.54; P < .047). In multivariate stepwise analysis TRAS was 10.9-fold increased in kidneys originating from rs3752462 CC, whereas the risk was decreased 3.45-fold (adjusted HR, 0.29) in recipients carrying rs5756168 TT (P < .007 and P < .033, respectively). Intracranial bleeding or trauma compared with other mechanisms of donor death diminished TRAS risk by 87% and 91%, respectively (P < .030 and P < .017). Our study is the first to identify genetic predisposition to transplant renal artery stenosis.

Serum TGF-beta1 correlates with chronic histopathological lesions in protocol biopsies of kidney allograft recipients.

INTRODUCTION: Transforming growth factor-beta (TGF-beta) is a well-known profibrotic factor playing a role in chronic kidney allograft nephropathy. Cyclosporine (CsA)-sparing immunosuppressive regimens may improve long-term graft function. Our aim was to study the influence of immunosuppressive treatment with versus without calcineurin inhibitors on serum TGF-beta levels and histological changes in protocol biopsies of kidney allograft recipients. PATIENTS AND METHODS: In this prospective, randomized study of 42 low-rejection risk patients we randomized two groups: group A: mycophenolate mofetil (MMF), prednisone, daclizumab, and reduced CsA dose for 7 months (5 mg per kg per day) followed by complete withdrawal (n = 21); and group B: normal CsA dose (10 mg per kg per day adjusted according to C2 levels), MMF, prednisone, and no daclizumab (n = 21). METHODS: In both groups we performed histological assessments (Banff 97) and measured serum TFG-beta levels before as well as, at 3 and 12 months after transplantation. RESULTS: We found a relationship between immunosuppressive regimen and the TGF-beta concentration over 1 year of observation. Before transplant the TGF-beta1 levels did not differ between the groups (P = .29); at 3 months they were 33 +/- 9 vs 49 +/- 15 pg per mL, respectively, in groups A and B (P = .08), and at 12 months they were 39.5 +/- 4 versus 55.5 +/- 11 pg per mL, respectively, in groups A and B (P = .03). Protocol biopsies at 12 months in group B showed chronic tubular lesions more pronounced than in group A. TGF-beta1 concentrations were significantly higher among group B than A. We conclude that TGF-beta1 concentration may predict the development of kidney graft fibrosis; early CsA withdrawal may achieve a reduction in chronic tubular and interstitial injury of cadaveric kidney allografts.