[Show abstract][Hide abstract] ABSTRACT: The literature is inconclusive as to whether the percentage of the lepidic component of an invasive adenocarcinoma (AC) of the lung influences prognosis. We studied a population-based series of selected, resected invasive pulmonary ACs to determine if incremental increases in the lepidic component were an independent, prognostic variable.
Patients undergoing resection for lung cancer reported to the Cancer Registry of Norway and diagnosed in the period 1993-2002 with a bronchioloalveolar carcinoma (BAC) (old terminology) (adenocarcinoma in situ, AIS in the new terminology) in the lung were selected. A pulmonary pathologist reviewed all sections and estimated the percentage of the lepidic component. Follow-up of survival was to the end of 2013.
One hundred thirty-one patients were identified, 102 had AC with lepidic growth. Of these, 44 had AC with a component of lepidic growth less than 50 % and seven had AC with 95 % lepidic component or more. One of the latter cases was considered to be AIS. In regression analyses, superior survival was associated with a greater lepidic component (p = 0.041). Mucinous tumors had a worse prognosis than non-mucinous (p = 0.012) in regression analyses, as did increasing age and stage. The five-year observed survival was 69.0 % for non-mucinous cases and 66.7 % for the group with a lepidic component of 80 % or greater.
The percentage of the lepidic component appears to be an independent, significant prognostic factor in a selection of pulmonary AC.
[Show abstract][Hide abstract] ABSTRACT: Recurrence of glomerulonephritis after kidney transplantation is especially in the long term an important cause of renal allograft failure. The exact frequency depends on the one hand how the diagnosis of recurrence was established, either on clinical grounds or histologically via a kidney transplant biopsy, and on the other hand on the type of the underlying or primary glomerular disease. The consequences of a relapse on allograft function and survival vary, depending on the primary disease. For example, recurrences after IgA nephropathy occur depending on the length of the observation period in over 50 % of the allografts with often relatively slow progression. However, focal segmental glomerulosclerosis and membranoproliferative glomerulonephritis recurrence generally have a much more rapid progression and poorer prognosi. The recent findings on the pathogenesis of certain glomerulopathies have led to new therapies, which have shown quite positive results in studies of smaller patient groups. New therapeutical approaches have been reported in particular for the following diseases: focal segmental glomerulosclerosis, idiopathic membranous nephropathy, membranoproliferative glomerulonephritis type 2 (dense deposit disease), IgA nephropathy and atypical hemolytic uremic syndrome (aHUS). In particular, rituximab or eculizumab represent interesting therapeutic options in some of these entities. Recurrence of glomerulonephritis - after allograft rejection and death with a functioning organ - is the third most common cause of kidney transplant failure. Overall, patients transplanted because of glomerular diseases have a longterm allograft survival comparable to patients suffering from other primary renal disorders. Nevertheless, a recent investigation showed a slightly worse long-term renal transplant survival in patients with a glomerulonephritis as the primary kidney disease. It is important to state that glomerulonephritis as the primary renal disorder does not represent a contraindication for kidney transplantation, including living kidney donation.
No preview · Article · Mar 2015 · Therapeutische Umschau
[Show abstract][Hide abstract] ABSTRACT: AimEarly acute antibody-mediated rejection (ABMR) occurs more frequently in ABO incompatible (ABOi) than in ABO compatible (ABOc) kidney transplantation. This could lead to increased inflammation/scarring in the ABOi grafts. Protocol biopsy data in ABOi kidney recipients are scarce.MethodsA single-centre retrospective matched cohort study was conducted. Eighty adult living donor (LD) renal transplant recipients without HLA donor-specific antibodies (DSA) transplanted between 2009 and 2012 were included; Twenty ABOi and 60 ABOc controls matched for donor age and transplantation year. Protocol biopsies at 1 year were scored according to the Banff classification. Three sums of scores were constructed: tubulointerstitial inflammation (t+i=0 vs.>0), microvascular inflammation (g+ptc=0 vs.>0), scarring/hyalinosis (ci+ct+cv+ah≤1 vs.>1. Scores and presence of subclinical rejection at 1 year were compared.ResultsProtocol biopsy findings at 1 year in the ABOi vs. ABOc matched control group were not statistically different: (t+i) >0, 30% vs. 20%; (g+ptc) >0, 5% vs. 8%; (ci+ct+cv+ah) >1, 85% vs. 60 respectively. No transplant glomerulopathy occurred. Subclinical rejection rate at 1 year was 30% vs. 18%, subclinical ABMR 5% vs. 7% (all with de novo HLA DSA).Conclusion
One year protocol biopsies of ABOi and ABOc LD recipients do not differ in chronic changes, inflammation or subclinical rejections.This article is protected by copyright. All rights reserved.
Full-text · Article · Jan 2015 · Clinical Transplantation
[Show abstract][Hide abstract] ABSTRACT: Recurrence of glomerulonephritis after kidney transplantation is especially in the long term an important cause of renal allograft failure. The exact frequency depends on the one hand how the diagnosis of recurrence was established, either on clinical grounds or histologically via a kidney transplant biopsy, and on the other hand on the type of the underlying or primary glomerular disease. The consequences of a relapse on allograft function and survival vary, depending on the primary disease. For example, recurrences after IgA nephropathy occur depending on the length of the observation period in over 50 [%] of the allografts with often relatively slow progression. However, focal segmental glomerulosclerosis and membranoproliferative glomerulonephritis recurrence generally have a much more rapid progression and poorer prognosi. The recent findings on the pathogenesis of certain glomerulopathies have led to new therapies, which have shown quite positive results in studies of smaller patient groups. New therapeutical approaches have been reported in particular for the following diseases: focal segmental glomerulosclerosis, idiopathic membranous nephropathy, membranoproliferative glomerulonephritis type 2 (dense deposit disease), IgA nephropathy and atypical hemolytic uremic syndrome (aHUS). In particular, rituximab or eculizumab represent interesting therapeutic options in some of these entities. Recurrence of glomerulonephritis - after allograft rejection and death with a functioning organ - is the third most common cause of kidney transplant failure. Overall, patients transplanted because of glomerular diseases have a longterm allograft survival comparable to patients suffering from other primary renal disorders. Nevertheless, a recent investigation showed a slightly worse long-term renal transplant survival in patients with a glomerulonephritis as the primary kidney disease. It is important to state that glomerulonephritis as the primary renal disorder does not represent a contraindication for kidney transplantation, including living kidney donation.
[Show abstract][Hide abstract] ABSTRACT: Objective To characterise a globotriaosylceramide (Gb3) storage cardiomyopathy mimicking Fabry.
Methods We investigated five patients from two unrelated families with early adult onset unexplained left ventricular hypertrophy. Endomyocardial biopsy was performed in all patients and diagnostic kidney biopsies in two of them. We measured α-galactosidase A activity in all patients. Three patients were checked for LAMP1 or LAMP2 deficiency and screened for congenital disorders of glycosylation. Gb3 concentration was quantified in plasma, urinary sediment and cardiac muscle. We sequenced the Fabry and Danon genes and looked for other genetic causes by single-nucleotide polymorphism array haplotyping and whole exome sequencing.
Results Three patients had a striking fat distribution around the buttocks and upper thighs. All patients developed bradyarrhythmias and needed pacemakers. Cardiac transplantation was performed in three patients due to end-stage heart failure, one patient died before transplantation. The cardiomyocytes contained lysosomal vacuoles with lamellar myelin-like deposits. Interstitial cells had vacuoles containing granular material. Deposits were found in the kidneys without renal dysfunction. The histological pattern was atypical for Fabry disease. Biochemical studies revealed normal activity of α-galactosidase A and other relevant enzymes. There was a selective accumulation of Gb3 in cardiomyocytes, at levels found in patients with Fabry disease, but no mutations in the Fabry gene, and Fabry disease was excluded. Other known lysosomal storage diseases were also excluded. Single-nucleotide polymorphism array haplotyping and whole exome sequencing could not identify the genetic cause.
Conclusions We describe a novel familial Gb3-assoociated cardiomyopathy. Autosomal recessive inheritance is likely, but the genetic and metabolic cause remains to be identified.
[Show abstract][Hide abstract] ABSTRACT: Background / Purpose:
The increased risk in ABO incompatble transplantation for early acute antibody mediated rejection could theoretically lead to increased subclinical inflammation, rejection and chronic changes at 1 year. Their are small numbers of published protocoll biopsy data in ABO incompatible transplantation in general.The aim of the study was to compare protocoll findings at 1 year in ABO incompatible allografts to ABO compatible allografts of living donors, matched for donor age and transplantation year to controll the main confounders for chronic changes.
We did not find any significant statistical difference in the protocol biopsies of ABO incompatible compared to a matched cohort of ABO compatible grafts for tubulo interstitial inflammation, microinflammation, chronic changes and subclinical rejection at 1 year. In both groups, development of HLA donor specific antibodies (DSA) was found in the patients with subclincal antibody-mediated rejection at 1 year. De novo DSA is a risk factor for graft loss and strategies for preventing the development of HLA DSA are warrented in both groups.
[Show abstract][Hide abstract] ABSTRACT: Background / Purpose:
Eculizumab, an anti-C5 complement antibody, emerged as a treatment option for C3-glomerulonephritis, in the absence of a disease specific therapy. Our patient showed subclinical recurrence of C3 glomerulonephritis, with elevated MAC and low circulating C3, but without proteinurea or inflammation in his 6 week and 1 year protocol biopsies. When he developed nephrotic proteinurea 3,5 years post-transplantation, and later crescentic changes in the transplant biopsy, we decided to treat him with Eculizumab.
In our patient complement factor H and I levels were normal, no Factor H antibodies or mutations in CFH, CFI, CFB; MCP, C3 or CFHR5 could be established. No improvement clinically or in the biopsy 3 months after initiation, led to Eculizumab being discontinued. We speculate that the patient might have benefited from Eculizumab if started earlier, but better criteria is needed to decide whom and when to treat with complement inhibition in C3 glomerulonehritis.
[Show abstract][Hide abstract] ABSTRACT: Introduction and Aims: Quantification of BKV-load and BKV-specific immunity have been evaluated to monitor BKV-replication. Particular risk factors,
long-term outcome, and markers characterizing kidney transplant recipients (KTRs) at increased risk of BK viremia, however,
remain poorly described.
Methods: We analyzed all adult KTRs at our single transplant center transplanted between 2004 and 2012. 103 (11.9%) of 862 KTRs were
diagnosed with BK viremia, among which 24 KTRs (23.3%) showed progression to BKV-associated nephropathy with allograft loss
in 3 cases (12.5%). An age-, gender, and maintenance immunosuppression-matched control group of 235 KTRs was used for comparison.
Samples were collected before transplantation and at +1, +2, and +3 months posttransplantation. BKV-specific, CMV-specific,
and alloreactive T-cells were measured using an interferon-γ Elispot assay. The extent of immunosuppression was quantified
by measures of immune function including lymphocyte subpopulations and serum cytokine levels.
Results: Upon multivariate analysis CMV reactivation, lymphocyte depletion induction, and acute rejection were more frequent in KTRs
developing BK viremia (p<0.05). Seven-year graft survival and estimated GFR were significantly lower in KTRs with BK viremia
(p=0.005). KTRs developing early BKV-replication showed significantly increased frequencies of BKV-specific T-cells directed
to Large T-antigen prior to transplantation (p<0.001). Shortly after transplantation, however, BKV-specific T-cells were significantly
decreased or undetectable (p<0.001). In addition CD3+, CD4+, and CD8+ T-cell counts, and interferon-γ serum levels were significantly
lower in KTRs with BK viremia at +1 month after transplantation (p<0.05). KTRs with BK viremia showed significantly higher
alloreactive T-cells (p=0.018).
Conclusions: Our results suggest that BKV-specific cellular immunity is triggered by subclinical activation of BKV infection prior to
transplantation. In KTRs developing BK viremia identified risk factors and overimmunosuppression result in a decline of BKV-specific
T-cells insufficient to further regulate BKV-replication. BKV infection may have significant effects on augmentation of alloreactive
T cells. Both cross-reactivity of alloreactive T-cells with viral antigens and bystander activation may contribute to allograft
Full-text · Article · May 2014 · Nephrology Dialysis Transplantation
[Show abstract][Hide abstract] ABSTRACT: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging is the reference standard for non-invasive assessment of fibrosis. In hypertrophic cardiomyopathy (HCM) patients the histological substrate for LGE is still unknown. The aim of this study was to assess the ability of LGE and strain echocardiography to detect type and extent of myocardial fibrosis in obstructive HCM patients undergoing septal myectomy.
Thirty-two HCM patients (age 60±10) were included in this cross-sectional study and preoperatively examined by speckle-tracking strain echocardiography and LGE-CMR (n=21). Histological fibrosis was classified as interstitial, replacement and total.
Histological fibrosis was present in 31 patients. The percentage of total, interstitial and replacement fibrosis was 15(7, 31)%, 11(5, 24)% and 3(1, 6)%, respectively. Reduced longitudinal septal strain correlated with total (r=0.50, p=0.01) and interstitial (r=0.40, p=0.03), but not with replacement fibrosis (r=0.28, p=0.14). Septal LGE was detected in 13/21 (62%), but percentage LGE did not correlate with total fibrosis (r=0.25, p=0.28). Extent of fibrosis did not differ between patients with and without septal LGE (20(9, 58)% versus 14(5, 19)% p=0.41). Patients with ventricular arrhythmias (n=8) had lower septal longitudinal strain and increased extent total and interstitial fibrosis in myectomy specimens, but no differences were demonstrated in LGE. Reduced longitudinal septal strain and increased extent of interstitial fibrosis predicted ventricular arrhythmias independently of age and gender.
In myectomised HCM patients, reduced longitudinal septal strain correlated better with interstitial and total fibrosis in myectomy specimens, and was a more powerful tool to predict arrhythmias than LGE.
[Show abstract][Hide abstract] ABSTRACT: Pemetrexed is effective in the treatment of non-small-cell lung cancer, mainly in nonsquamous cell carcinomas. Inhibition of thymidylate synthase (TS) is considered the key mechanism of action. Folate receptor-α facilitates uptake of pemetrexed. Polyglutamation by folylpolyglutamate synthetase enhances activity and prolongs cellular retention of pemetrexed. Thyroid transcription factor-1 (TTF-1) is mainly positive in nonsquamous cell carcinoma and has been proposed as a marker for sensitivity to pemetrexed. The aim was to investigate associations between these biomarkers and survival in patients who participated in a phase III trial comparing pemetrexed plus carboplatin with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer (n = 436). In this study, there was no difference in overall survival between the two regimens.
Formalin-fixed, paraffin-embedded biopsies were collected. Percentages of tumor cells positive and highly positive for the biomarkers were assessed using immunohistochemistry (IHC) and an IHC score was calculated (range, 0-200).
Two hundred thirty-six biopsies were analyzed (pemetrexed plus carboplatin: n = 114, gemcitabine plus carboplatin: n = 122). There was a significant difference in overall survival between those with TTF-1-positive and -negative tumors (10.4 versus 6.0 months; p < 0.001) and those with a low and a high TS IHC score (9.7 versus 6.2 months; p < 0.001). Folate receptor-α and folylpolyglutamate synthetase were not significant prognostic factors. In multivariate analyses adjusting for established prognostic characteristics, TS (p = 0.002) and TTF-1 (p = 0.003) remained significant. There were no differences in survival between the treatment arms depending on biomarker scores.
TTF-1 positivity and low TS level were associated with prolonged survival. The associations between the biomarkers and overall survival were similar for both chemotherapy regimens.
No preview · Article · Oct 2013 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer
[Show abstract][Hide abstract] ABSTRACT: Background:
Over the last decade, the diagnostic precision for acute antibody-mediated rejection (aABMR) in kidney transplant recipients has improved significantly. The phenotypes of early and late aABMR may differ. We assessed the characteristics and outcomes of early versus late aABMR.
Between January 1, 2005 and December 31, 2010, aABMR was diagnosed in 67 grafts in 65 kidney recipients, with a median follow-up of 3.6 years (range, 61 days-7.3 years). Recipients were stratified by early aABMR (<3 months after transplantation; n=40) and late aABMR (>3 months after transplantation; n=27). The main outcome was kidney allograft loss. Outcome of aABMR was compared with recipients with acute early (n=276) or late (n=100) non-ABMR during the same period.
Recipients with late aABMR had significantly reduced graft survival compared with recipients with early aABMR (P<0.001, log-rank test; 40% vs. 75% at 4 years; hazard ratio, 3.72; 95% confidence interval, 1.65-8.42). Graft survival in late aABMR was also inferior to late non-ABMR acute rejections (P=0.008). At transplantation, more patients were presensitized to human leukocyte antigens (22 [55%] vs. 4 [15%] in the early vs. late aABMR group). The late aABMR group was characterized by younger recipient age (37.9 ± 12.9 vs. 50.9 ± 11.6 years; P<0.001), increased occurrence of de novo donor-specific antibodies (52% vs. 13%; P=0.001), and nonadherence/suboptimal immunosuppression (56% vs. 0%; P<0.001).
Compared with early aABMR, late aABMR had inferior graft survival and was characterized by young age, frequent nonadherence, or suboptimal immunosuppression and de novo donor-specific antibodies.
[Show abstract][Hide abstract] ABSTRACT: Aims Reduced echocardiographic strain is associated with ventricular arrhythmias in hypertrophic cardiomyopathy (HCM) patients. The aim of this cross-sectional study was to investigate which type of histological fibrosis contributes to ventricular arrhythmias and reduced septal longitudinal strain, in obstructive HCM-patients with or without additional coronary artery disease (CAD) and/or hypertension (HT).Methods and resultsSixty-three HCM-patients (mean age 57 ± 13 years) were included. Strain by speckle tracking echocardiography was performed prior to either percutaneous transluminal septal ablation (n = 37) or septal myectomy (n = 26). In 24 patients myectomy specimens were available (histology population) and allowed determination of %area of interstitial and replacement fibrosis. Twenty-nine (46%) patients had concomitant CAD and/or HT, and 15 (24%) experienced ventricular arrhythmias defined as documented ventricular tachycardia or arrhythmogenic suspected syncope. The patients with ventricular arrhythmias had lower septal longitudinal strain compared with those without arrhythmias (-9.0 ± 4.0 vs.-13.6 ± 5.6%, P = 0.006). In the histology population reduced septal longitudinal strain correlated to interstitial (R2 = 0.36 P = 0.003), but not to replacement fibrosis (R2 = 0.03 P = 0.43). By logistic regression analyses, interstitial fibrosis predicted ventricular arrhythmias (OR 1.16, 95% CI 1.02-1.32, P = 0.03), while replacement fibrosis did not (OR 1.22, 95% CI 0.93-1.59, P = 0.15).Conclusion
Total amount of fibrosis was a marker of ventricular arrhythmias in obstructive HCM-patients. Interstitial fibrosis seemed to be more important compared with replacement fibrosis in arrhythmogenesis, and was related to reduced septal myocardial function. These findings suggest that interstitial fibrosis may play an important role as the arrhythmogenic substrate, and that strain echocardiography can help detection of patients at risk.
[Show abstract][Hide abstract] ABSTRACT: Acoustic radiation force impulse (ARFI) quantification estimates tissue elasticity by measuring shear-wave velocity (SWV) and has been applied to various organs. We evaluated the impact of variations in the transducer force applied to the skin on the SWV ultrasound measurements in kidney transplant cortex and ARFI's ability to detect fibrosis in kidney transplants.
SWV measurements were performed in the cortex of 31 patients with kidney allografts referred for surveillance biopsies. A mechanical device held the transducer and applied forces were equal to a compression weight of 22, 275, 490, 975, 2,040 and 2,990 g.
SWV group means were significantly different by repeat measures ANOVA [F(2.85,85.91) = 84.75, P < 0.0005 for 22, 275, 490, 975 and 2,040 g compression weight] and also by pairwise comparisons. Biopsy specimens were sufficient for histological evaluation in 29 of 31 patients. Twelve had grade 0, 11 grade 1, five grade 2 and one grade 3 fibrosis. One-way ANOVA showed no difference in SWV performed with any of the applied transducer forces between grafts with various degrees of fibrosis.
SWV measurements in kidney transplants are dependent on the applied transducer force and do not differ in grafts with different grades of fibrosis.
• Acoustic radiation force impulses (ARFI) can quantify tissue elasticity during ultrasound examinations. • Elasticity estimated by ARFI in kidney transplants depends on applied transducer force. • ARFI quantification cannot detect renal allograft fibrosis. • ARFI elasticity estimates may in general vary with applied transducer force.
No preview · Article · May 2012 · European Radiology
[Show abstract][Hide abstract] ABSTRACT: The relative clinical benefit of histopathology and computed tomography (CT) in patients with idiopathic interstitial pneumonia (IIP) is under debate.
To analyze thin-section CT features and histopathologic findings in patients with usual interstitial pneumonia (UIP) in the clinical context of idiopathic pulmonary fibrosis (IPF), and to evaluate and compare diagnostic accuracy of the two methods among patients with an appropriate spectrum of IIP.
The study included 91 patients (49 men; mean age 53.2 years; median follow-up 7.2 years) with clinically suspected interstitial lung disease. All underwent surgical lung biopsy and thin-section CT. Two independent readers retrospectively assessed the CT images for the extent and pattern of abnormality and made a first-choice diagnosis. Two pathologists retrospectively assessed the histopathologic slides. In 64 patients with IIP, a retrospective composite reference standard identified 41 patients with UIP. CT characteristics of UIP and IIPs other than UIP were compared with univariate and multivariate analyses.
There was good agreement between the readers for the correct first-choice CT diagnosis of UIP (κ = 0.79). The sensitivity, specificity, and positive predictive value of the CT diagnosis of UIP were 63%, 96%, and 96%, respectively. The sensitivity, specificity, and positive predictive value of the histological diagnosis of UIP were 73%, 74%, and 83%, respectively. The CT feature that best differentiated UIP from IIPs other than UIP was the extent of reticular pattern (odds ratio, 5.1).
Surgical lung biopsy may not be warranted in patients with thin-section CT diagnosis of UIP.
No preview · Article · Feb 2012 · Acta Radiologica
[Show abstract][Hide abstract] ABSTRACT: Chronic allograft nephropathy (CAN) characterized by interstitial fibrosis and tubular atrophy is a major cause of renal transplant failure. The diagnosis can currently only be verified by a graft biopsy.
To evaluate whether non-invasive dynamic color Doppler sonographic parenchymal perfusion measurements are different in grafts with various degrees of biopsy proven renal transplant fibrosis.
Forty-nine adult patients were prospectively included. Four patients were excluded. Color Doppler videos from the renal cortex were recorded. Perfusion in the renal cortex was evaluated using a software package which calculates color pixel area and flow velocity, encoded by each pixel inside a region of interest of a video sequence. The software calculates parameters that describe tissue perfusion numerically. Two of these, the perfusion intensity and tissue pulsatility index, were compared to grade of interstitial fibrosis (0-3) in biopsies. Observer agreement was evaluated in a subset of 12 patients.
Of the 45 patients analyzed, 18 patients had grade 0, 18 had grade 1, seven had grade 2 and two had grade 3 fibrosis. The mean perfusion intensity of grade 0 was significantly higher than that of grade 2 and 3 fibrosis in the proximal cortical layer (1.65 m/s vs. 0.84 m/s, P = 0.008). No significant difference was found between grade 0 and grade 1 fibrosis. Perfusion intensity was correlated to estimated glomerular filtration rate (Pearson r 0.51, P = 0.001, R(2) = 0.26 and 0.46, P = 0.001, R(2) = 0.22 in the distal and proximal cortex, respectively). Inter-observer agreement of the perfusion intensity, expressed as intraclass correlation coefficient was 0.69 in the proximal part of the cortex. Intra-observer agreement was 0.85 for observer 1 and 0.82 for observer 2.
Perfusion intensity assessed by dynamic color Doppler measurements is significantly reduced in allografts with grade 2 and 3 fibrosis compared to allografts without fibrosis. Further studies involving longitudinal assessment of allografts undergoing protocol biopsies would be of interest.
No preview · Article · Aug 2011 · Acta Radiologica
[Show abstract][Hide abstract] ABSTRACT: Benefits of conversion from calcineurin inhibitor (CNI) to mammalian target of rapamycin inhibitor-based immunosuppression in long-term kidney transplant patients remain uncertain.
ASCERTAIN was a 24-month, open-label, multicenter study. Kidney transplant patients more than 6 months posttransplant receiving CNI (baseline glomerular filtration rate [GFR] 30-70 mL/min/1.73 m) were randomized to everolimus with CNI elimination (n=127) or CNI minimization (n=144), or continued CNI unchanged (controls, n=123) to assess the effect on measured GFR at month 24 after randomization.
Renal function was stable in all groups to month 24. Mean measured GFR at month 24, the primary endpoint, was 48.0±22.0 mL/min/1.73 m, 46.6±21.1 mL/min/1.73 m, and 46.0±20.4 mL/min/1.73 m in the CNI elimination, CNI minimization, and control groups, respectively. Differences between CNI elimination (1.12 mL/min/1.73 m, 95% confidence interval [CI] -3.51 to 5.76, P=0.63) and CNI minimization (0.59 mL/min/1.73 m, 95% CI -3.88 to 5.07, P=0.79) versus controls at month 24 were nonsignificant that is, the primary endpoint was not met. No efficacy endpoint differed significantly between groups. Post hoc analyses showed that patients with baseline creatinine clearance (CrCl) more than 50 mL/min had a significantly greater increase in measured GFR after CNI elimination versus controls (difference 11.4 mL/min/1.73 m, 95% CI 2.1 to 20.8 mL/min/1.73 m, P=0.017). Adverse events resulted in discontinuation in 36 (28.3%) CNI elimination patients, 24 (16.7%) CNI minimization patients, and 5 (4.1%) controls (P<0.001 vs. CNI elimination; P=0.020 vs. CNI minimization).
Conversion to everolimus with CNI elimination or minimization a mean of 5.6 years after kidney transplantation had no overall renal benefit and was associated with more frequent adverse events and discontinuations. Patients with CrCl more than 50 mL/min may benefit from a change in therapy more than 6 months after renal transplantation.
[Show abstract][Hide abstract] ABSTRACT: Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is a rare metabolic disease with lipid deposition in several organs. The authors report a man with hypertension and proteinuria. Renal biopsy revealed glomerular changes, including peculiar thrombus-like deposits, consistent with LCAT deficiency. He was found to be compound heterozygous for two mutations of the LCAT gene. He received a kidney graft from his father. The authors also describe LCAT deficiency-related lesions in the explanted native kidneys and in biopsies at 2 days, 6 weeks, and 1 year after transplantation. The morphology of this disease is characteristic, and the diagnosis should be suspected from the ultrastructural findings.
No preview · Article · Feb 2011 · Ultrastructural Pathology