Proteomics for Biomarker Discovery for Diagnosis and Prognosis of Kidney Transplantation Rejection

Renal transplantation is currently the treatment of choice for end-stage kidney disease, enabling a quality of life superior to dialysis. Despite this, all transplanted patients are at risk of allograft rejection processes. The gold-standard diagnosis of graft rejection, based on histological analysis of kidney biopsy, is prone to sampling errors and carries high costs and risks associated with such invasive procedures. Furthermore, the routine clinical monitoring, based on urine volume, proteinuria, and serum creatinine, usually only detects alterations after graft histologic damage and does not differentiate between the diverse etiologies. Therefore, there is an urgent need for new biomarkers enabling to predict, with high sensitivity and specificity, the rejection processes and the underlying mechanisms obtained from minimally invasive procedures to be implemented in routine clinical surveillance. These new biomarkers should also detect the rejection processes as early as possible, ideally before the 78 clinical outputs, while enabling balanced immunotherapy in order to minimize rejections and reducing the high toxicities associated with these drugs. Proteomics of biofluids, collected through non-invasive or minimally invasive analysis, e.g., blood or urine, present inherent characteristics that may provide biomarker candidates. The current manuscript reviews biofluids proteomics toward biomarkers discovery that specifically identify subclinical, acute, and chronic immune rejection processes while allowing for the discrimination between cell-mediated or antibody-mediated processes. In time, these biomarkers will lead to patient risk stratification, monitoring, and personalized and more efficient immunotherapies toward higher graft survival and patient quality of life.info:eu-repo/semantics/publishedVersio

A proteomic evaluation of urinary changes associated with cardiopulmonary bypass

Additional file 4: Table S4. Correlation filtered 2D DDA/IDA and SWATH protein difference values

Serum Biomarkers of Renal Fibrosis: A Systematic Review

Chronic kidney disease (CKD) is a widely diffuse pathological condition which deeply impacts upon an affected patient’s quality of life and its worldwide rate is predicted to further rise. The main biological mechanism underlying CKD is renal fibrosis, a non-reversible process representing, for the affected system, a point of no return of tissue damage and dysfunction, deeply reducing the possible therapeutic strategies at the disposal of physicians. The best tool clinicians can use to address the extent of renal fibrosis at any level (glomeruli, tubule-interstitium, vasculature) is kidney biopsy that, despite its overall safety, remains an invasive procedure showing some shortcomings. Thus, the identification of novel non-invasive renal fibrosis biomarkers would be of fundamental importance. Here, when systematically reviewing the available evidence on serological biomarkers associated with renal fibrosis evaluated in patients suffering from CKD in the last five years, we found that despite the presence of several promising biomarkers, the level of observed evidence is still very scattered. Probably, the use of multiple measures capable of addressing different aspects involved in this condition would be the most suitable way to capture the high complexity characterizing the renal fibrotic process, having consequently a great impact on clinical practice by maximizing prevention, diagnosis, and management

Mass spectrometry-based proteomics for advancing solid organ transplantation research

Scarcity of high-quality organs, suboptimal organ quality assessment, unsatisfactory pre-implantation procedures, and poor long-term organ and patient survival are the main challenges currently faced by the solid organ transplant (SOT) field. New biomarkers for assessing graft quality pre-implantation, detecting, and predicting graft injury, rejection, dysfunction, and survival are critical to provide clinicians with invaluable prediction tools and guidance for personalized patients' treatment. Additionally, new therapeutic targets are also needed to reduce injury and rejection and improve transplant outcomes. Proteins, which underlie phenotypes, are ideal candidate biomarkers of health and disease statuses and therapeutic targets. A protein can exist in different molecular forms, called proteoforms. As the function of a protein depends on its exact composition, proteoforms can offer a more accurate basis for connection to complex phenotypes than protein from which they derive. Mass spectrometry-based proteomics has been largely used in SOT research for identification of candidate biomarkers and therapeutic intervention targets by so-called “bottom-up” proteomics (BUP). However, such BUP approaches analyze small peptides in lieu of intact proteins and provide incomplete information on the exact molecular composition of the proteins of interest. In contrast, “Top-down” proteomics (TDP), which analyze intact proteins retaining proteoform-level information, have been only recently adopted in transplantation studies and already led to the identification of promising proteoforms as biomarkers for organ rejection and dysfunction. We anticipate that the use of top-down strategies in combination with new technological advancements in single-cell and spatial proteomics could drive future breakthroughs in biomarker and therapeutic target discovery in SOT

Renal Failure

The book "Renal Failure - The Facts" consists of some facts about diagnosis, etiopathogenis and treatment of acute and chronic renal failure. Acute, as well as chronic renal failure is great medical problems and their treatment is a burden for the budget of each government. The purpose of the chapters is to present some important issues of diagnosis and causes of AKI, as well as caused by snakes and arthropods, after cardiac surgery, as well as some therapeutic achievements in AKI. Well presented are the psychological condition in patients on haemodialysis, as well as the treatment of diabetic uremics. The book is aimed at clinicians with a special interest in nephrology, but it should also prove to be a valuable resource for any generalists who encounter a nephrological problems in their day-to-day practice

Biomarkers of chronic allograft injury in children after renal transplantation

Renal transplantation (RTx) is a treatment of choice for children with end-stage renal disease. Excellent short-term survival is followed by moderate long-term results, and a considerable number of kidney grafts fail over the decades. Chronic allograft injury (CAI) is a multifactorial entity that manifests as a progressive deterioration of glomerular filtration rate (GFR), and histopathologically as interstitial fibrosis and tubular atrophy (IF/TA). CAI leads slowly to graft dysfunction and graft loss. This thesis aimed to investigate potential biomarkers of CAI. Selected biomarkers reflect the consequences of post-transplant immune response or complications of immunosuppression. Post-transplant human leukocyte antigen (HLA) antibodies, immunohistochemical biomarkers, presence of anemia, low-grade inflammation and BK polyomavirus were analyzed to identify pediatric RTx recipients at risk for CAI. Understanding the effect of these post-transplant risk factors on allograft function is important for the adequate monitoring and early identification of graft failure. The study cohort included 240 pediatric kidney transplant recipients who underwent RTx in Finland between 1988 and 2014. Data were retrospectively collected from patient records, and biomarker analyses were performed on stored serum samples or allograft biopsies. Luminex assay was used to detect donor-specific HLA antibodies (DSA) and immunoperoxidase staining to detect biomarker expression in biopsies. Finally, immunoassay method was used to detect inflammation and anemia related biomarkers and polyomavirus in blood samples. HLA antibodies were detected in half of the routine follow-up samples of 123 pediatric RTx recipients. One-third of the patients had DSA, mostly against class II antigens. Donor-specificity, as such, was not predictive of subsequent deterioration of allograft function, questioning the need for modifications of immunosuppression in otherwise stable patients. Immunohistochemical staining of 165 biopsies from 56 patients revealed progressive IF/TA changes during the first 3 years post-RTx. Intense staining of collagen IV and vimentin associated with decreased GFR later on, although there was no additional prognostic value on graft function compared to routine IF/TA score. Post-transplant anemia and low-grade inflammation were common complications even years after RTx in 128 patients followed for a median of 10 years. Low Hb levels preceded IF/TA findings in protocol biopsies and associated with poor subsequent graft function. BK viremia was detectable in nine patients with a tendency for decreased long-term graft function. Polyomavirus-associated nephropathy was detected in three patients. The studied risk factors of post-transplant allograft nephropathy were rather common in this pediatric study population, but the clinical impact of a single biomarker on the long-term graft function was relatively minor. These findings support the follow-up of different pathophysiologic pathways in order to identify the high-risk recipients of CAI before the loss of graft function.Munuaisensiirto on käypä hoito munuaisten vajaatoiminnan loppuvaiheessa. Siirron jälkeinen ennuste on erinomainen, mutta pitkänajan ennustetta heikentää osalle potilaista kehittyvä munuaissiirteen krooninen vaurio ja siirteen vajaatoiminta, joka johtaa lopulta siirteen menetykseen vuosikymmenten kuluessa. Munuaissiirteen krooninen vaurio on monitekijäinen kokonaisuus, joka ilmenee munuaissiirteen toiminnan heikkenemisenä ja solutason muutoksina, kuten munuaiskudoksen arpeutumisena ja munuaistiehyiden surkastumisena. Väitöskirjassa tutkittiin munuaissiirteen kroonista vauriota kuvaavia merkkiaineita, jotka kuvastavat siirron jälkeisen immuunivasteen aktivoitumista ja seurauksia, sekä hyljinnänestolääkitykseen liittyviä komplikaatioita. Tutkimme siirron jälkeisiä HLA (human leukocyte antigen) vasta-aineita ja immunohistokemiallisia kudosmerkkiaineita sekä matala-asteisen tulehduksen, anemian ja BK polyoomaviruksen (BKPyV) vaikutuksia munuaissiirteen toimintaan lapsipotilailla. Siirron jälkeen havaitut HLA-vasta-aineet olivat yleisiä ja kolmasosalla potilaista HLA-vasta-aineet kohdistuivat siirteen luovuttajan HLA antigeenejä vastaan. Kudoskoepalojen merkkiaineista kollageeni ja vimentiini olivat yhteydessä myöhempään munuaistoiminnan heikkenemiseen, mutta nämä merkkiaineet eivät tuoneet merkittävää lisää perinteisen Banff-luokituksen ennustearvoon. Myös anemia oli yleistä vielä vuosia siirron jälkeen ja matalat hemoglobiini-arvot edelsivät munuaissiirteen heikkenevää toimintaa. Munuaissiirron jälkeisen BK polyoomaviruksen havaitseminen verenkierrossa ennakoi munuaistoiminnan hiipumista jo ennen munuaiskoepaloissa havaittavaa virusinfektioon liittyvää munuaistautia. Tutkimusaineistossa oli mukana 240 lapsipotilasta, joille on tehty munuaisensiirto Suomessa vuosina 1988 2014. Seeruminäytteistä ja munuaissiirteen kudoskoepaloista analysoitiin siirteen vauriota osoittavia merkkiaineita retrospektiivisesti. Munuaistoiminnan mittarina ja pitkäaikaisseurannan vastemuuttujana käytettiin mitattua 51Cr-EDTA-puhdistumaa. Väitöskirjatutkimuksen tulokset lisäävät tietämystä kroonisen munuaisvaurion riskitekijöistä munuaisensiirtolapsilla. Yksittäisten merkkiaineiden kliininen hyöty munuaistoiminnan ennustajana on rajallinen, mutta löydökset tukevat eri patofysiologisten tekijöiden pitkäaikaisseurantaa munuaissiirteen krooniselle vauriolle alttiiden riskipotilaiden varhaiseksi tunnistamiseksi

Clinical Studies, Big Data, and Artificial Intelligence in Nephrology and Transplantation

In recent years, artificial intelligence has increasingly been playing an essential role in diverse areas in medicine, assisting clinicians in patient management. In nephrology and transplantation, artificial intelligence can be utilized to enhance clinical care, such as through hemodialysis prescriptions and the follow-up of kidney transplant patients. Furthermore, there are rapidly expanding applications and validations of comprehensive, computerized medical records and related databases, including national registries, health insurance, and drug prescriptions. For this Special Issue, we made a call to action to stimulate researchers and clinicians to submit their invaluable works and present, here, a collection of articles covering original clinical research (single- or multi-center), database studies from registries, meta-analyses, and artificial intelligence research in nephrology including acute kidney injury, electrolytes and acid–base, chronic kidney disease, glomerular disease, dialysis, and transplantation that will provide additional knowledge and skills in the field of nephrology and transplantation toward improving patient outcomes