(CKD) across both pediatric and adult patient populations and up to 11% of patients under 40 years reach end-stage kidney failure. Diagnostic genomics in the field of nephrology is ever-evolving and now plays an important role in the assessment and management of kidney transplant recipients and their related donor pairs. Genomic testing can help identify the cause of KF in. If a gene variant has been identified in the recipient, at-risk related donors can be assessed for the same and excluded if affected. This paper aims to address the indications for genomic testing in the context for kidney transplantation, the technologies are available for testing, the conditions and groups in which testing should be most often considered, and the role for the renal genetics multidisciplinary team in this process.

CLICK HERE TO GET 25% ECHINACOSIDE CISTANCHE FOR IMPROVING KIDNEY

;

The role that diagnostic genomics plays within the practice of nephrology is evolving. End-stage KF or KF of undetermined etiology continues to comprise a significant minority of patients being assessed for , with 5% of Australian patients with KF having an unknown primary kidney diagnosis.1 Kidney biopsy has been the gold standard in diagnosing many kidney diseases, but it is often avoided in patients with advanced CKD due to increased complication rates or risk of misclassification of disease when performed at such a late stage. As a result, many ascribed kidney diagnoses are incorrect or presumed.

Knowledge of the underlying cause of KF is important in the context of kidney transplantation. It can provide some understanding of graft survival and recurrence rates of primary kidney disease and help identify and exclude at-risk related donors in the context of heritable disease. Known monogenic forms of kidney disease account for approximately 70% of pediatric and 10% of adult cases of CKD.2-7 In the last decade, the number of genes associated with (GKD) has grown significantly,5,8,9 as has access to diagnostic genomic testing. Depending on the suspected monogenic kidney disease, the diagnostic yield from genetic testing varies from 10% to 73%.10-20 In a group of patients who reached KF of unknown cause before 40 years of age and were awaiting kidney transplantation, the diagnostic rate of pathogenic or likely pathogenic variants was 11%21 (Supplementary Table S1). With a lack of local guidelines and great interest in the role of genomic testing around kidney transplantation, this paper aims to discuss the indications and limitations associated with testing and to make suggestions for testing in the context of GKD and kidney transplantation.

Clinical practice in the realm of kidney genetics, similar to kidney transplantation, can be hard to navigate without a multidisciplinary team. There are practical challenges, including appropriate test selection, pretest counseling, interpretation and delivery of results, and counseling and management of concerned family members. Multidisciplinary renal genetics clinics are currently becoming more readily available in Australia, the United Kingdom, Canada, and the United States of America22-26 and are important in streamlining a number of these processes and using the knowledge and experience of nephrologists, clinical geneticists, and genetic counselors to manage these complex patients. Each individual has a specific role to play within this collaborative team, with the typical role in Australian multidisciplinary teams as follows: The nephrologists primarily review the phenotype of the patient, trying to identify the condition or group of conditions in which they fall. This is very important to select the genes or gene panels most likely to apply to the patient. The clinical geneticist provides appropriate pretest counseling and discussion around patterns of inheritance, the testing process, and diagnostic technologies. Once a genetic test result has been issued for a patient, a discussion between the nephrologist and clinical geneticist is important in reaching a consensus on whether the finding is diagnostic or not. In the situation where a result is negative, discussions will be about additional testing if the chance that there is an underlying genetic condition is high. The genetic counselors assist in obtaining further information about family members and their results, often having completed a full genogram before review in the clinic. They educate on the role of the clinic and set expectations for the patients, rediscuss genetic principles discussed in the clinic, and provide easily accessible support throughout the process. The general workflow of testing in a renal genetics multidisciplinary team has been outlined in Figure 1.

The first Australian multidisciplinary renal genetics clinic using this model was established in Brisbane in 2013, with initial outcomes reported previously.27 Using this model, the national KidGen Collaborative was formed in 2016, with the goal being to provide definitive diagnoses to patients with GKDs in renal genetics clinics across Australia (http://www.kidgen.org.au). Similar initiatives are underway internationally. It is recommended that, when available, families who require genetic testing in the context of renal transplantation are referred to or involved in discussion with such appropriate kidney genetics centers for counseling and management.

There are a number of clinical factors that should prompt consideration of genetic testing to determine the cause of primary kidney disease. Examples of these include a strong family history, early onset of disease, syndromic presentation, or extrarenal manifestations of a known genetic renal disease. In such situations where testing is offered and a positive result occurs, one is able to provide a diagnostic label to the patient's kidney disease, which will benefit planning before kidney transplant, cascade testing in their relatives (including live related donors), and reproductive planning for the proband and their relatives. In addition, in the future, there may be a role for pharmacogenetics in mainstream practice around transplantation.28-30

A situation in which genetic testing should be considered in a potential kidney transplant recipient is when the etiology of the recipient's kidney disease is unclear. In this situation, the recipient should be phenotyped, with the genomic test using either exome sequencing (ES) or genome sequencing (GS). Using these testing platforms, analysis of panel disease-specific genes or all monogenic kidney disease genes as is described in PanelApp Australia should be undertaken.31 Knowledge of the underlying cause of KF is important in the management of a patient peritransplant as the primary kidney disease may affect graft survival by the risk of recurrence or rejection. For example, genetic testing for steroid-resistant nephrotic syndrome (SRNS) assists in prognosticating around the risk of relapse after transplant and providing meaningful information regarding other manifestations such as malignancy, already an important post-transplant issue, which may be heightened in the case of potential WT1 mutations.

may guide potential live-related donors due to their chance of being affected by the same condition. In some instances, there is a clear family history of kidney disease but no known pathogenic variant, and so the potential recipient is the first in the family to be tested based on phenotype, with a positive result allowing cascade testing within the family. Although kidney donors generally have good outcomes, they are at increased risk of developing CKD, KF, and hypertension.5-7 This risk may be further increased if the donor and recipient are genetically related,32-34 and in this situation, the cause of the recipient's primary kidney disease should be identified wherever possible. Kidney Disease: Improving Global Outcomes guidelines suggest that for recipient kidney diseases with a high rate of identifying pathogenic variants, such as atypical hemolytic uremic syndrome, Alport syndrome, and focal segmental glomerular sclerosis, genetic testing of related recipient and donor pairs is undertaken.35 In the situation of a condition such as Fabry disease, it would be important to test potential related female donors, as alpha-galactosidase A levels may not sufficiently exclude a diagnosis of Fabry disease in these at-risk individuals. There have been cases of females donating a kidney to relatives but who subsequently find out that they also have Fabry disease.36 Fabry disease is 1 of the 6 described renal phenotypes on the American College of Medical Genetics secondary findings list which requires reporting if a pathogenic variant is incidentally detected.37

There are benefits in testing potential live-related donors, regardless of positive or negative outcomes. In the event of a positive gene test result, the affected relative has been diagnosed at an earlier stage in their disease which may result in earlier multidisciplinary care and potential access to and greater benefit from therapies. This is particularly important in conditions such as Fabry disease where there is specific enzyme replacement therapy or chaperone therapy. In the event of a negative gene test result, there would be an expected slight increase in the number of transplants from living-related donors, with confidence in accepting younger donors. This is particularly important in families with autosomal dominant polycystic kidney disease (ADPKD), as diagnosis of the condition cannot be ruled out based on imaging alone in young potential live-related donors.

or a mild phenotype that otherwise does not exclude them from the donation (e.g., microscopic hematuria without proteinuria).38

Supportive Service Of Wecistanche-The largest cistanche exporter in the China:

Email:wallence.suen@wecistanche.com 

Whatsapp/Tel:+86 15292862950

https://www.xjcistanche.com/cistanche-shop