Innovations in 2023 in Nephrology

Elliott Van Regemorter1, Nada Kanaan1, Michel Jadoul1, Arnaud Devresse1, Laura Labriola1, Thibaut Gervais2, Antoine Buémi3, Tom Darius3, Yannick France3, Michel Mourad3, Véronique Deneys2, Corentin Streel1, Eric Goffin1 Published in the journal : February 2024 Category : Nephrology

The year 2023 witnessed a number of significant advances in understanding and managing kidney disease. Among these figure the discoveries concerning the genetic variants in the gene encoding apolipoproteine L1 (APO-L1), shown to be closely associated with an increased risk of developing chronic kidney disease, particularly among populations of African or African-American descent. The precise mechanisms by which these APO-L1 variants contribute to the development of kidney disease have not been fully elucidated. Nevertheless, several studies have suggested that these variants may lead to an impaired podocyte function at the glomerular level. The discovery of the links between APO-L1 abnormalities and kidney disease has actually opened new perspectives for research pertaining to the development of targeted therapies. Understanding how these genetic variants influence the progression of kidney disease could similarly allow for the development of more effective prevention and treatment strategies, in addition to the identification of high-risk patient subgroups.

A new therapeutic approach to anemia in chronic kidney disease was made available last year. Roxadustat (EvrenzoR) belongs to a class of drugs known as hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors. These drugs act on the HIF-dependent erythropoiesis. Unlike the traditional treatment of kidney-disease-associated anemia consisting of subcutaneous or intravenous injections of recombinant erythropoietin (EPO), Evrenzo is administered orally. Consequently, this more convenient administration route could improve patient compliance and simplify the therapeutic process. In addition, in most patients, roxadustat was demonstrated to exhibit a safety and tolerability profile similar to that of recombinant EPO.

Another 2023 breakthrough was the approval of imlifidase in kidney transplantation. Imlifidase is a proteolytic enzyme that acts by selectively cleaving IgG antibodies. This agent can be employed to desensitize patients with high levels of pre-existing antibodies against human leukocyte antigen (HLA) antigens, meaning that transplantation could be considered even in the presence of immunological incompatibility with the donor. This approach may help improve access to transplantation for hyper-immunized patients.

These novelties developed in 2023 will gradually be implemented in clinical practice in 2024.

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Innovations 2022 in Nephrology

Guillaume Fernandes, Yassin Akachar, Laura Labriola, Michel Jadoul, Nathalie Demoulin, Johann Morelle Published in the journal : February 2023 Category : Nephrology

We discuss the negative results of a randomized controlled trial of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers cessation in G4 or G5 stage chronic kidney disease. We next review the initiation modalities of dapagliflozine and finerenone in chronic kidney disease patients. Lastly, we review the recent therapeutic advances in IgA nephropathy treatment.

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2021 innovations in nephrology

Valentine Gillion, Johann Morelle, Michel Jadoul, Nathalie Demoulin Published in the journal : February 2022 Category : Nephrology

In 2021, Kidney Disease: Improving Global Outcomes (KDIGO) published the updated guidelines concerning the management of glomerular diseases. Herein, we have briefly discussed several key points in regard to the management of the three most common glomerular diseases in adults. Next, we have reviewed the clinical benefits, considering both renal and cardiovascular perspectives, which were observed in Type 2 diabetics with chronic kidney disease (CKD), randomized to either finerenone or placebo. Based on these encouraging data, we can assume that this molecule will soon belong to the armamentarium deemed able to delay CKD progression in Type 2 diabetics. Lastly, we have discussed the results of a recent trial showing that chlorthalidone, a thiazide diuretic, proves to be still effective in Stage 4 CKD and this, in contrast to the prevalent dogma.

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SARS-CoV-2 vaccination of kidney transplant recipients

Hélène Georgery (1*), Arnaud Devresse (1*), Jean Cyr Yombi (2), Eric Goffin (1), Nada Kanaan (1) Published in the journal : September 2021 Category : Nephrology

Kidney transplant recipients (KTRs) are at increased risk of developing severe and lethal COVID-19 compared to the general population. Current therapies against severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infections are still limited. Nevertheless, growing evidence has revealed that KTRs exhibit a poor response to standard vaccine regimens, with humoral immune responses of roughly 50% at one month following two mRNA anti-SARS-CoV-2 vaccine doses. Moreover, most responders were shown to exhibit low antibody titers. Our experience at Cliniques universitaires Saint-Luc is perfectly in line with such data.

Considering these disappointing results, it is apparent that other strategies are required for KTRs and immunosuppressed patients, including a third vaccine dose along with monoclonal antibody therapy. This work’s aim is to provide a review on this topic and report on our experience at Cliniques universitaires Saint-Luc.

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Ongoing therapeutic revolution in primary Type 1 hyperoxaluria

Arnaud Devresse, Nathalie Godefroid, Nada Kanaan Published in the journal : March 2021 Category : Nephrology

Primary hyperoxaluria Type I (PH1) is an autosomal recessive disease caused by the functional defect of hepatic alanine-glyoxylate aminotransferase, which results in overproduction of oxalate. The condition can be especially devastating for the kidneys, leading to end-stage renal disease (ESRD) during the first two to three decades of life in most patients. Currently, while the conservative treatment options are limited, they often prove inefficient in preventing ESRD. Consequently, many PH1 patients require kidney transplantation, and liver transplantation as well, which is currently the only definitive treatment option for counteracting the hepatic metabolic defect. Nevertheless, a therapeutic revolution is underway. Indeed, innovative drugs are currently being tested in clinical trials, and some preliminary data reveal their impressive efficacy in reduce hepatic oxalate overproduction. This paper reviews the current knowledge on this subject.

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2020 innovations in Nephrology

Hélène Georgery, Fabienne Oguz, Nathalie Demoulin, Michel Jadoul, Arnaud Devresse, Johann Morelle Published in the journal : February 2021 Category : Nephrology

In 2020, a large-sized randomized study provided reassuring results about the cardiovascular safety of febuxostat, a xanthine oxidase inhibitor used for the treatment of symptomatic hyperuricemia.

The cardiovascular and renal benefits of sodium-glucose co-transporter 2 (SGLT-2) inhibitors were confirmed in 2020, and their indications even extended. Notably, the DAPA-CKD trial demonstrated that dapagliflozin is strongly nephroprotective in both proteinuric diabetics and non-diabetics. Thus, the standard of care for managing these patients is likely to soon include an SGLT2- inhibitor in addition to an angiotensin converting enzyme inhibitor or angiotensin II receptor blocker.

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COVID-19, kidney, and renal diseases

Johann Morelle, Arnaud Devresse, Nathalie Demoulin, Valentine Gillion, Eric Goffin, Nada Kanaan, Laura Labriola, Michel Jadoul Published in the journal : May 2020 Category : Nephrology

This short contribution first focuses on the growing evidence showing that the kidney is a target for the coronavirus, with signs of kidney disease being a marker of COVID-19 severity. It next discusses the reasons not to withdraw angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in high-risk groups, as well as the potential risk of virus transmission inside the hemodialysis unit or via peritoneal dialysis. Finally, the article summarizes the data available regarding COVID-19 in kidney transplant recipients and concludes with some considerations concerning the major challenges faced when it comes to ensuring high-quality medical care during this pandemic.

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2019 innovations in Nephrology

Eric Goffin, Sophie Coche, Laura Labriola, Corine Hubinont, Valentine Gillion, Nathalie Demoulin, Anne-Catherine Pouleur, Michel Jadoul Published in the journal : February 2020 Category : Nephrology

In 2019, we welcomed several major advances made in the management of kidney disease. We have decided to highlight herein two major developments. Firstly, pregnancy can now be considered in a patient upon chronic dialysis. Secondly, two new potassium binders are on the horizon, which is great news for patients with chronic kidney disease requiring renin angiotensin system (RAS) blockade.

Pregnancy, which is in fact rare in women with end-stage kidney failure, is associated with increased feto-maternal morbidity. Recent data, along with our own experience, highlight that pregnancy can now be considered in women on maintenance hemodialysis, who are ready to perform intensive home hemodialysis, along with a strict and regular obstetrical follow-up.

Hyperkalemia is common in chronic kidney disease patients, especially in those under RAS blockade, and can be life-threatening. Since the old K-binders have limited efficacy and are poorly tolerated, RAS blockade is frequently discontinued in such patients. Nevertheless, two new K-binders are on the horizon. The first one, patiromer, has been reimbursed since 2019 for the treatment of chronic hyperkalemia. The other one, sodium cyclosilicate of zirconium (SZC), has been approved for use in Europe, though this drug is not yet reimbursed in Belgium. We briefly review these molecules’ efficacy and safety and discuss their role in maintaining RAS blockade, especially in CKD patients with proteinuria or heart failure.

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Innovations in Nephrolgy in 2018

Eric Goffin (1), Arnaud Devresse (1), Jean-François Baurain (2), Isabelle Tromme (3), Michel Mourad (4), Nada Kanaan (1) Published in the journal : February 2019 Category : Nephrology

This article reviews innovations in kidney transplantation, particularly in terms of cutaneous carcinomas and ABO incompatibility. Kidney transplant recipients are at risk of developing basal cell or squamous cell carcinomas due to immunosuppression induced by anti-rejection therapy. A multidisciplinary approach to these skin lesions is required to optimize the therapeutic management, thereby improving patient prognosis. Kidney transplantation from ABO-incompatible living donor patients was introduced in 1982 and successfully taken up in our institution last year. It is rendered possible due to a strategy combining desensitization of the recipient and reinforced immunosuppression. Survival of patients and grafts appears to be equivalent to that observed in ABO compatible transplant patients.

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Innovations in nephrology: what to remember from 2017?

Johann Morelle, Nathalie Demoulin, Michel Jadoul, Hubert Piessevaux Published in the journal : February 2018 Category : Nephrology

In 2017, the treatment of severe forms (proteinuric and/or with impaired kidney function) of IgA nephropathy, the most common primary chronic glomerulonephritis, proved to be of particular interest. Several studies highlighted that the risks associated with conventional immunosuppressive therapy, still mainly based on corticosteroids outweighs the potential benefits. A Targeted (enteric)-release corticosteroids constitutes a new therapeutic agent will soon be tested in a Phase 3 study, following encouraging results from Phase 2. Furthermore, several observational studies, conducted in 2017, suggested that the nephrotoxicity due to proton pump inhibitors be more common than hitherto appreciated, though the causal relationship between both must still be firmly demonstrated. In this paper, we discuss the implications from these studies concerning the use of this widely prescribed family drug.

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