Karine Dahan

Outcome of Renal Transplantation in Eight Patients with Candida sp. Contamination of Preservation Fluid

The complications of kidney graft preservation fluid infected by Candida sp. may range in severity from trivial infections to life‐threatening complications, including graft arteritis and anastomotic rupture. Mandatory nephrectomy has recently been proposed as a means of preventing arterial wall rupture in such cases. We describe the clinical features and outcome of renal transplantation from a cadaveric donor in eight recipients with preservation fluid testing positive for Candida sp. Six patients were treated with antifungal drugs. After 1–2 years of follow‐up, including regular imaging, none of the patients had developed arterial aneurysm, and all had a functional allograft and were alive. The contamination of renal graft preservation fluid with Candida sp. may be uneventful and should not systematically lead to removal of the graft. Until other risk factors for vascular complications have been determined, early antifungal treatment and repeated radiological monitoring are advisable for the prevention and/or early detection of such complications.

Intragraft Levels of Foxp3 mRNA Predict Progression in Renal Transplants with Borderline Change

The optimal therapeutic management of borderline lymphocytic infiltrates in renal allografts, described by Banff criteria, is unknown, largely because of the inability to predict clinical outcome in these cases. For determination of molecular factors that may predict outcome in cases of borderline change histology, mRNA levels of Foxp3, Granzyme B, IFN-gamma, IL-23, and RORgammat were measured in renal tissue from 46 untreated patients. Twenty-five patients were considered nonprogressive, defined by a serum creatinine that remained <110% of baseline during the 40 d after biopsy. Twenty-one patients were considered progressive, defined by an increase in serum creatinine >110% from baseline and by repeat histologic examination within 40 d showing progression toward acute rejection. Only Foxp3 mRNA levels were significantly higher in nonprogressors than in progressors (P = 0.001). Analysis of receiver operating characteristic curves demonstrated that the outcome for patients with biopsies showing borderline change could be predicted with 90% sensitivity and 79.1% specificity using the optimal Foxp3 mRNA cutoff value. Our findings suggest that the measurement of Foxp3 mRNA offers a means of improving prediction of outcome of borderline change.

Renal Transplantation in Patients with Sarcoidosis: A French Multicenter Study

BACKGROUND AND OBJECTIVESnSarcoidosis is a multisystem disorder of unknown etiology. The outcome of renal transplantation on patients with sarcoidosis is not well known. A few case reports have described recurrence of sarcoidosis after transplant. Here, we report for the first time results and outcome of renal transplantation in a series of patients with sarcoidosis.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnEighteen patients with sarcoidosis who underwent renal transplantation were identified retrospectively in eight French renal transplantation departments. Patient medical charts, demographics, and the outcome of renal transplantation were reviewed.nnnRESULTSnInitial renal disease was related to sarcoidosis in 10 patients. At the end of the follow-up (median, 42 months), patient and death-censored graft survival were 94.4% and the mean GFR was 60 ml/min per 1.73 m(2). Five patients (27%) experienced recurrence of sarcoidosis including extra-renal involvement in two patients and renal involvement in three patients. Median GFR was lower in the group of patients with renal recurrence compared with that of the entire cohort: 31 ml/min per 1.73 m(2). Recurrence occurred shortly after transplantation (median period, 13 months). Risk factors for recurrence included primary renal disease related to sarcoidosis and a shorter delay between the last episode of sarcoidosis and renal transplantation.nnnCONCLUSIONSnOur results indicate that renal transplantation may be carried out safely in transplant candidates with sarcoidosis. Recurrence is not rare and is likely to affect graft outcome. These results fully justify a specific clinical and histologic monitoring mainly during the early posttransplant period.

Arteriolar Hyalinization Predicts Delayed Graft Function in Deceased Donor Renal Transplantation

Delayed renal graft function (DGF) remains a largely unpredictable and burdensome consequence of deceased donor renal transplantation. There is growing evidence that histologic and molecular analyses of baseline donor kidney biopsies can predict both short- and long-term graft outcome. We performed histologic analyses of 172 preimplantation kidney biopsies to determine reliable histologic risk factors for DGF. Fifty-six recipients presented a DGF (incidence 32%). Univariate analysis revealed that arteriolar hyalinization (P=0.019), arterial intima fibrosis (0.004), donor age (P=0.001), duration of cold ischemia time (P=0.001), and recipient age (P=0.001) were significantly associated with DGF. Multivariate analysis revealed that the only independent histologic factor was arteriolar hyalinization (P=0.036). This histologic predictive factor, together with previously identified clinical risk factors, could guide clinical decisions regarding use, allocation, or immunosuppression protocols for minimization of DGF.

Renal Allograft Biopsies with Borderline Changes: Predictive Factors of Clinical Outcome

The clinical outcome and appropriate management for patients showing ‘borderline changes’ on allograft biopsy after renal transplantation is still controversial. In an attempt to identify predictive factors of clinical outcome of patients with such lesions, we reviewed the clinical course of 91 patients with borderline changes. Multivariate analysis revealed significant and independent effects of histological stage (i + t ≤ or > 2) and time to borderline changes (≤ or >3 months after transplant) on serum creatinine levels at 1 year from borderline changes episodes (respectively, p = 0.04 and p = 0.02) and only a significant effect of time to borderline changes on serum creatinine levels at 2 years (p = 0.005). Renal function at 1 year and 2 years as 5‐ and 8‐year graft survival were not significantly different in the group of patients treated with antirejection therapy (T group, n = 49) compared with the untreated group (UT group, n = 42). This study strongly suggests that borderline changes with histological score (i + t) > 2 and late episodes of borderline changes should be considered to be of poor prognosis.

Paradoxical embolism following thromboaspiration of an arteriovenous fistula thrombosis: a case report

IntroductionParadoxical embolism is an increasingly reported cause of arterial embolism. Several embolic sources have been described, but thrombosis of an arteriovenous fistula as a paradoxical emboligenic source has not, to the best of our knowledge, been reported.Case presentationA 50-year-old Caucasian woman received a renal graft for primary hyperoxaluria. After transplantation, she was maintained on daily hemodialysis. Thrombosis of her arteriovenous fistula occurred two weeks post-transplantation and was treated by thromboaspiration, which was partially successful. During a hemodialysis session immediately following thromboaspiration, she developed a coma with tetraplegia requiring intensive cardiorespiratory resuscitation. Brain magnetic resonance imaging revealed various hyperdense areas in the vertebrobasilar territory resulting from bilateral occlusion of posterior cerebral arteries. Transesophageal echocardiographic examination showed a patent foramen ovale, while pulse echography of the arteriovenous fistula revealed the persistence of extensive clots that were probably the embolic source. A paradoxical embolus through a patent foramen ovale was suggested because of the proximity of the neurological event to the thrombectomy procedure.ConclusionsThe risk of paradoxical embolism in a hemodialyzed patient with a patent foramen ovale deserves consideration and requires careful evaluation in situations of arteriovenous fistula thrombosis.

Urinary mRNA for the Diagnosis of Renal Allograft Rejection: The Issue of Normalization

Urinary messenger RNA (mRNA) quantification is a promising method for noninvasive diagnosis of renal allograft rejection (AR), but the quantification of mRNAs in urine remains challenging due to degradation. RNA normalization may be warranted to overcome these issues, but the strategies of gene normalization have been poorly evaluated. Herein, we address this issue in a case‐control study of 108 urine samples collected at time of allograft biopsy in kidney recipients with (n = 52) or without (n = 56) AR by comparing the diagnostic value of IP‐10 and CD3ε mRNAs—two biomarkers of AR—after normalization by the total amount of RNA, normalization by one of the three widely used reference RNAs—18S, glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) and Hypoxanthine‐guanine phosphoribosyltransferase (HPRT)—or normalization using uroplakin 1A (UPK) mRNA as a possible urine‐specific reference mRNA. Our results show that normalization based on the total quantity of RNA is not substantially improved by additional normalization and may even be worsened with some classical reference genes that are overexpressed during rejection. However, considering that normalization by a reference gene is necessary to ensure polymerase chain reaction (PCR) quality and reproducibility and to suppress the effect of RNA degradation, we suggest that GAPDH and UPK1A are preferable to 18S or HPRT RNA.

Factors Associated With Pathogenicity of Anti-Glomerular Basal Membrane Antibodies : A Case Report

AbstractAntiglomerular basement membrane (GBM) disease is known as a super-acute proliferative glomerulonephritis caused by auto-antibodies targeting the NC1 domain of the &agr;3 chain of type IV collagen.Here, we describe a case of atypical anti-GBM disease presenting as a dialysis-dependent acute renal failure with unusual mild glomerular involvement. We found that immunoglobulin G (IgG) deposits were restricted to the uncommon IgG2 and IgG4 subclasses, and that blood was positive for anti-GBM antibodies by immunofluorescence, but not by Enzyme Linked Immunosorbent Assay (ELISA). The patient was treated with plasma exchanges, corticosteroids, and cyclosphosphamide. He eventually regained a normal renal function.This case demonstrates that biopsy-proven anti-GBM disease can have reduced pathogenicity. Referring to previous studies of anti-GBM detection in the blood from healthy or minimally ill individuals, we discuss the antigenic specificities, the IgG subclasses, and the involvement of complement in this observation.We suggest that anti-GBM disease is a heterogeneous entity and that the study of IgG subclasses by immunofluorescence may help to distinguish categories with different severities.

Urinary mRNA analysis of biomarkers to epithelial mesenchymal transition of renal allograft

Renal allograft loss is most often a chronic process, irrespective of the mechanism at stake. In this prospective study, we studied the expression of epithelial to mesenchymal transition (EMT) markers vimentin and β-catenin by immunohistochemistry in the surveillance biopsy and measured the mRNA encoding vimentin (VIM), CD45, GAPDH and uroplakin 1a (UPK) by quantitative PCR in urinary cells in 75 renal transplant patients. The aim is to establish a simple screening test for chronic renal allograft dysfunction. We found that the value of the mRNA of vimentin and CD45 relative to the uroplakin 1a (UPK) mRNA is correlated with the score in vimentin immunostaining in routine biopsies. These biomarkers could be used as a noninvasive tool to monitor the renal graft fibrogenesis. This test could be used for early detection of fibrotic diseases of the kidney transplant.

Urinary transcriptomics reveals patterns associated with subclinical injury of the renal allograft

AIMnSubclinical pathological features in renal allograft biopsies predict poor outcomes, and noninvasive biomarkers are wanted. RNA quantification in urine predicts overt rejection. We hypothesized that a whole transcriptome analysis would be informative, even for discrete injury.nnnPATIENTS & METHODSnWe performed an mRNA microarray with an optimized normalization method on 26 urinary cell pellets to study renal partial epithelial to mesenchymal transition (pEMT) in stable kidney allografts.nnnRESULTS & CONCLUSIONnUnbiased pathway analysis revealed immune response as the main underlying biological process. In a subgroup of pristine biopsies, isolated pEMT was associated with reduced metabolic functions. Thus, pEMT translates into specific urinary mRNA patterns, in other words, increased inflammation and decreased metabolic functions. Deposited in Gene Expression Omnibus (GSE89652).