Prevalent in millions of people across the globe, kidney diseases manifest through various symptoms like blood and excess protein in urine, fluid retention causing swollen ankles, poor appetite and even the inability of the body to filter waste, resulting in acute kidney failure.
To boost the research and development of treatments for kidney diseases, Kidney Research UK offered more than £2.5 million ($2.97 million) in grants for projects and startups in November 2022, with the hopes of accomplishing medical milestones in the field.
As we observe World Kidney Day on March 9, here are five advancements in kidney disease research in the past year.
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New discovery in minimal change disease: A potential drug target?
A recent study has detected antibodies that target nephrin, which is a protein expressed in the kidney’s specialized cells called podocytes that maintains the glomerular filtration barriers. This discovery has been regarded as a step forward in kidney research, particularly in minimal change disease studies.
Minimal change disease, which underlies nephrotic syndrome, a condition that causes the loss of proteins via the kidneys, affects 10 to 15 in 100,000 children, and is less frequent in adults. Some symptoms of the disease include high triglyceride and cholesterol levels in blood along with excess protein in the urine.
“What causes MCD is not totally understood and there have been different hypotheses that have been investigated over the years,” said Fady Riad, CEO at life sciences consulting firm Centurion Life Sciences.
However, the study sheds light on the disorder as researchers led by Astrid Weins, a pathologist at Brigham and Women’s Hospital in Boston, evaluated the sera of patients with minimal change disease. Using methods like genome sequencing, renal biopsy and enzyme-linked immunosorbent assay (ELISA) tests, the researchers found circulating nephrin autoantibodies which have a pathogenic effect in the kidneys.
Riad said: “This discovery is groundbreaking because not only does it give us a better understanding of the disease, but also because these antibodies have the potential to be very pertinent drug targets.”
FDA approves diabetes drug for chronic kidney disease
The landmark EMPA-kidney trial which ended in November 2022 after obtaining positive results for the efficacy of the drug empagliflozin, received approval from the U.S. Food and Drug Administration (FDA) for adults with chronic kidney disease (CKD) in January 2023.
The drug, sold under the brand name Jardiance, developed by German-based biopharma Boehringer Ingelheim in collaboration with U.S.-based pharma Eli Lilly, is an oral SGLT-2 inhibitor, which reduces the amount of glucose being absorbed in the kidneys so that it is passed out in the urine. Proven for its effectiveness for type 2 diabetes, empagliflozin has demonstrated a reduced risk of cardiovascular death in patients with CKD.
“SGLT-2 inhibitors have long been studied in CKD patients, but the EMPA-KIDNEY trial is the largest trial to date to investigate the potential of SGLT-2 inhibitors in reducing the risk of cardiovascular death as well as the progression of kidney disease in CKD patients who are at risk of disease progression,” said Riad.
Having been granted Fast Track designation by the FDA in 2020 in order to expedite treatments for serious conditions, empagliflozin’s FDA approval was led by a 28% reduction in the possibility of kidney disease progression against a placebo.
“This marks another exciting milestone for Jardiance, potentially extending its ability to positively impact the approximately one billion people diagnosed with a cardio, renal or metabolic condition,” said Jeff Emmick, vice president of Product Development at Lilly.
New study determines drug efficacy in mice in the field of acute kidney injury
A study conducted by researchers at the University of Edinburgh has gained promising results in the field of acute kidney injury (AKI), a condition where the kidneys suddenly stop functioning properly due to the reduction of blood flow to the kidneys.
The disease, which can be fatal if not treated in time, can potentially lead to CKD and other cardiovascular issues, according to Fady Riad.
The research which tested certain endothelin-A antagonists, which has been used to treat people with pulmonary hypertension, a condition caused by high blood pressure in the lungs’ blood vessels, was observed in mice.
These drugs, which inhibit endothelin from binding to its receptor, helped mice stabilize their blood pressure and even improved vascular functions, possibly preventing long-term complications caused by AKI.
“More studies are needed to fully understand the potential of this drug class but this could certainly pave the way for already marketed drugs being approved in this indication or even having novel compounds developed for this condition,” said Riad.
Biopharma Calliditas launches drug for immunoglobulin A (IgA) nephropathy
An advancement in both kidney disease and rare disease research, a new drug was launched by Swedish biopharma Calliditas Therapeutics in January 2022 after receiving FDA approval in 2021 for the treatment of IgA nephropathy. This was followed by the European Commission granting conditional marketing authorisation in July 2022.
With an incidence of 2.5 per 100,000 people worldwide, although IgA nephropathy manifests in the kidneys, research has shown that it originates in the gut. The Peyer’s patches which consist of lymphoid follicles to keep pathogens at bay, situated in the ileum, the end region of the small intestine, have mucosal-type IgA1 antibodies. When these antibodies are in excess, an autoimmune response is generated resulting in the deposition of immune complexes in the glomeruli of the kidneys, leading to the destruction of the glomeruli. The condition exhibits itself through symptoms such as blood in urine and proteinuria, excess protein in urine.
Calliditas’ drug, Tarpeyo, is the only therapy that targets the origins of the disease with a view to being disease modifying, according to Renee Aguiar-Lucander, CEO of Calliditas.
Tarpeyo, which targets the Peyer’s patches to downregulate IgA1, successfully completed clinical trials that confirmed a significant reduction in proteinuria in IgA nephropathy patients.
“Calliditas helped pioneer the use of proteinuria as a surrogate endpoint in kidney disease clinical research, and was the first drug approved under this accelerated pathway by the FDA,” said Aguiar-Lucander.
Aguiar-Lucander expressed that the approval of Tarpeyo “marked the first time that IgAN patients in the U.S. and Europe had access to a medication specifically designed for and approved for their disease, providing access to a targeted treatment approach which may have disease modifying potential for patients suffering with this chronic autoimmune disease.”
The company is also currently focused on an upcoming clinical trial for the treatment of Alport Syndrome, another rare kidney disease.
Steroids could treat IgA nephropathy, according to new study
A study that investigated the effect of oral steroids on patients with IgA nephropathy in 2022, has garnered attention as it could prove to be a potential treatment for the disease.
The research showed that the six to nine-month course of methylprednisolone, a corticosteroid which acts as an immunosuppressant, reduced the risk of kidney function decline.
However, findings detailed limitations such as the drug having increased the risk of adverse events, which led to modifying the original protocol to a lower dose regimen. Although improvements in kidney performance were noted, it was derived that other therapies in parallel with corticosteroids may need to be administered in order to optimize kidney function.
According to Riad: “While more safety data is still needed, the results of this trial are likely to impact clinical practice and set the tone for future IgA nephropathy trials design.”