The Tangential Extraperitoneal Retrorenal Approach in Kidney Transplant Biopsy: An Observational Study to Assess Complication and Adequacy Rates

Introduction: Ultrasound-guided percutaneous kidney allograft biopsy is the gold-standard for pathology work-up. Recent studies postulate better safety and efficacy for tangential approaches, however, there is no recommendation regarding biopsy needle path. In this context, we previously described the unified tangential extraperitoneal retrorenal (TER) approach for standard allograft biopsy.Methods: A single-center retrospective observational study evaluated safety and efficacy of the TER biopsy approach among 250 patients that underwent 330 ultrasound-guided kidney transplant biopsies between January 2011 and May 2020.Results: The overall major complication rate was 0.56% per biopsy attempt (1.21% per biopsy) including blood transfusion, arterial embolization and bladder catheterization for gross hematuria in 0.28, 0.14 and 0.14% of biopsy attempts, respectively (0.61, 0.30 and 0.30% of biopsies, respectively). Minor complications included subcapsular and/or perinephric hematoma, superficial bleeding, arteriovenous fistula and gross hematuria in 12.6, 3.0, 2.5 and 1.4% of biopsy attempts, respectively (27.0, 6.4, 5.5 and 3.0% of biopsies, respectively). Sample adequacy rate was 86.7%, ranging from 82.2 to 94.1% if one or ≥two cores were analyzed, respectively. Residents and consultants yielded similar complication and adequacy rates.Conclusion: According to current literature, ultrasound-guided TER kidney transplant biopsy is a safe and efficient approach eligible for nephrology training.

The Summarized Assessment of Endothelin A Receptor Expression in Renal Transplant Compartments Associated with Antibody-Mediated Rejection

The occurrence of anti-endothelin A receptor antibodies may be useful in diagnosis of transplant damage. We noticed that the presence of the endothelin A receptor (ETA receptor) in biopsy compartments is yet to be defined. We decided therefore to analysed the presence and relevance of the ETA receptor in biopsy to define the cause. Our study aims to evaluate the expression of ETA receptors in renal recipients after a biopsy due to the worsening of transplant function. Methods: The expression of ETA receptors was analyzed in renal transplant biopsies using the immunohistochemical method. The evaluation of ETA receptors was performed on paraffin sections. ETA receptor expression was analyzed in four compartments of renal transplant biopsies: glomeruli; vessels; tubular epithelium; and interstitium. The assessment was presented using a three-step scale (0: lack of expression; 1: mild to moderate immunoreactivity; 2: high expression). The results of each compartment from a single biopsy were summarized and assessed in the context of antibody-mediated rejection (AMR). Results: We analyzed 156 patients who had a renal allograft biopsy after renal transplantation. For each patient, we created a summarized ETA receptor expression score. The summarized ETA receptor expression score analysis showed statistically significant differences in patients with and without AMR. In addition, we noticed that patients with AMR had a significantly higher mean summarized expression of ETA receptor score of 3.28 ± 1.56 compared to patients who had a biopsy for other reasons with a mean summarized ETA receptor expression score of 1.47 ± 1.35 (p < 0.000001). ROC analysis of the ETA receptor expression score for detecting AMR status showed that the most appropriate cut-off for the test of the chosen binary classifier is between 2 and 3 of the summarized ETA receptor expression score. Conclusions: The expression of endothelin A receptors in renal transplant compartments may be associated with antibody-mediated rejection. The positive ETA receptor staining might be a vital feature in the diagnosis of damage in AMR. The summarized ETA receptor expression score seems to be an exciting diagnostic tool in transplant injury assessment.

Beyond the Biopsy: Monitoring Immune Status in Kidney Recipients

Improved long-term kidney allograft survival is largely related to better outcomes at 12 months, in association with declining acute rejection rates and more efficacious immunosuppression. Finding the right balance between under- and overimmunosuppression or rejection versus immunosuppression toxicity remains one of transplant’s holy grails. In the absence of precise measures of immunosuppression burden, transplant clinicians rely on nonspecific, noninvasive tests and kidney allograft biopsy generally performed for cause. This review appraises recent advances of conventional monitoring strategies and critically examines the plethora of emerging tests utilizing tissue, urine, and blood samples to improve upon the diagnostic precision of allograft surveillance.

De novo Glomerular Disease and the Significance of Electron Microscopy in Renal Transplantation

<b><i>Background:</i></b> De novo glomerular diseases comprising those both common and unique to transplant may develop in the renal allograft leading to posttransplant proteinuria, hematuria, or allograft failure. Electron microscopy (EM) is a useful adjunct to the standard light and immunofluorescence microscopy for accurately diagnosing these diseases and subsequently aiding the clinician in initiating appropriate treatments. <b><i>Summary:</i></b> De novo diseases are those new-onset diseases in renal transplantation that are unrelated to the original kidney disease in the recipient. They include virtually any primary or secondary glomerular, tubulointerstitial, or vascular diseases, ranging from subclinical to clinically overt, having acute, subacute, or chronic clinical presentations. This review focuses on common or significant, mainly glomerular, entities, with particular attention to the EM findings. The time of onset, stage, and severity of these diseases may often be modified by the current immunosuppressive protocols and other donor and recipient predisposing characteristics. <b><i>Key Messages:</i></b> A renal allograft biopsy not only improves our understanding of the pathophysiology but also provides diagnostic accuracy prognostic information, and potential for reversibility. In some cases, the biopsy leads to detection of unsuspected or clinically asymptomatic de novo diseases in the setting of other concomitant rejection processes, infection, or toxicity, which can dictate appropriate therapy. Routine EM in transplant kidney biopsies is a valuable modality in recognizing fully developed or early/subtle features of evolving de novo diseases, often during the subclinical phases, in “for cause” or surveillance/protocol allograft biopsies.

MicroRNA Expression Changes in Kidney Transplant: Diagnostic Efficacy of miR-150-5p as Potential Rejection Biomarker, Pilot Study

Background: The kidney allograft biopsy is considered the gold standard for rejection diagnosis but is invasive and could be indeterminate. Several publications point to the role of miRNA expression in suggesting its involvement in the acceptance or rejection of organ transplantation. This study aimed to analyze microRNAs involved in the differentiation and activation of B and T lymphocytes from kidney transplant (KT) patients’ peripheral blood leukocytes to be used as biomarkers of acute renal rejection (AR). Methods: A total of 15 KT patients with and without acute rejection (AR/NAR) were analyzed and quantified by miRNA PCR array. A total of 84 miRNAs related to lymphocyte differentiation and activation B and T were studied. The functions and biological pathways were analyzed to predict the potential targets of differential expressed miRNAs. Results: Six miRNA were increased in the AR group (miR-191-5p, miR-223-3p, miR-346, miR-423-5p, miR-574-3p, and miR-181d) and miR-150-5p was increased in the NAR group. In silico studies showed a total of 2603 target genes for the increased miRNAs in AR, while for the decrease miRNA, a total of 1107 target-potential genes were found. Conclusions: Our results show that KT with AR shows a decrease in miR-150-5p expression compared to NAR, suggesting that the decrease in miR-150-5p could be related to an increased MBD6 whose deregulation could have clinical consequences.