UL, Ireland, research finds promising treatment to protect kidney function in diabetes

December 09, 2020

A clinical trial involving researchers at University of Limerick, Ireland has demonstrated the potential benefits of new drugs in protecting kidney function in diabetes.

The new study has found that combining two treatments that lower uric acid concentrations in the blood reduces the leakage of albumin in the urine, one of the earliest signs of kidney damage in diabetes.

The discovery could help to prevent kidney failure in diabetes patients, the UL researchers believe.

Researchers from the University of Limerick School of Medicine and University Hospital Limerick, working with investigators from the University of California San Diego, USA and AstraZeneca, found that the combination of Verinurad and Febuxostat reduced albuminuria in the urine by 39.4% in patients with Type 2 diabetes after 12 weeks of treatment compared to placebo.

The results of this AstraZeneca sponsored Phase 2a clinical trial were recently published in the American Journal of Kidney Disease.

Verinurad is a novel inhibitor of the uric acid transporter (URAT1) and is currently under investigation for the treatment of hyperuricaemia and kidney disease. Febuxostat is a potent, selective xanthine oxidase inhibitor used to lower urate levels in patients with gout and hyperuricaemia.

The CITRINE clinical trial results show that the combination of drugs reduces the leaking of protein through the kidney.

"This is exciting news as leaking of protein is the earliest clinical sign of kidney damage," said Professor Austin Stack, Foundation Chair of Medicine at UL's School of Medicine and Consultant Nephrologist at University Hospital Limerick, who was lead author of the study.

"The results are very promising as they demonstrate an important reduction in albuminuria and hyperuricaemia in patients with type 2 diabetes when treated with a combination of Verinurad and Febuxostat.

"If we can intervene early on then we are more likely to prevent patients from going into kidney failure. The findings raise hope for the 350 million people with type 2 diabetes globally who are at increased risk of kidney failure," added Professor Stack, director of the National Kidney Disease Surveillance System (NKDSS).

In the multicentre randomised clinical trial, 60 patients with type 2 diabetes with albuminuria and elevated uric acid levels were randomised to receive either Verinurad 9mg, and Febuxostat 80mg or placebo. The patients were followed up for 24 weeks.

The primary endpoint of the study was met and showed a 39% reduction in albuminuria, after 12 weeks with combined treatment of Verinurad and Febuxostat versus placebo. This effect persisted at 24 weeks with an overall 49% reduction in albuminuria. Treated patients also experienced a 57% reduction in uric acid levels at 12 weeks. Both Verinurad and Febuxostat were well tolerated by patients, according to the study.

"One of the earliest signals of kidney disease is development of albuminuria (leaking of albumin into the urine) and recent studies have shown that this can be associated with high levels of uric acid," said Professor Stack, a HRB-funded principal investigator whose work in this area has raised the profile of uric acid as a potential risk factor for kidney and heart disease.

"A key goal in protecting kidney function is the lowering of albuminuria in the urine, as patients with high levels are at risk of progressing to kidney failure. This clinical trial was designed to examine the effects of an intensive uric acid lowering strategy on albuminuria by combining Verinurad with Febuxostat in patients with type 2 diabetes mellitus with pre-existing albuminuria.

"Although these are early clinical findings, our results show that combined treatment with Verinurad and Febuxostat in patients with diabetes results in a rapid reduction in albuminuria that was sustained through week 24," Professor Stack added.

A larger clinical trial, the SAPPHIRE study, is currently underway to determine whether an intensive uric acid lowering strategy combining Verinurad with a xanthine oxidase inhibitor will slow the progression of chronic kidney disease.

"Diabetes is the greatest contributor to the 850 million globally with chronic kidney disease," explained Professor Stack.

"More than 40% of patients with diabetes are at risk for developing kidney disease and significant number of these will progress to kidney failure. Preventing kidney failure is a key goal in all healthcare systems to reduce morbidity of diabetes and improve patient outcomes," he added.
The study, Stack AG, Dronamraju N, Parkinson J, Johansson S, Johnsson E, Erlandsson F, Terkeltaub R, Effect of Intensive Urate Lowering With Combined Verinurad and Febuxostat on Albuminuria in Patients With Type 2 Diabetes: A Randomized Trial, has been published in the in American Journal of Kidney Disease. See more here: https://www.ajkd.org/article/S0272-6386(20)31072-6/fulltext.

For further information, please contact:

Alan Owens
Communications Officer
University of Limerick
+353 87 908 6633
+353 61 213000

About University of Limerick:

The University of Limerick is an independent, internationally focused university with 16,500 students and 1,700 staff. It is a young, energetic and enterprising university with a proud record of innovation in education and excellence in research and scholarship.

More information is available at http://www.ul.ie.

Tweet @UL
LinkedIn University of Limerick
Snapchat U of Limerick

UL Kidney Health Consortium

The UL Kidney Health Consortium at University Hospital Limerick and the UL School of Medicine is leading a number of national and international studies to improve the outcomes for patients with kidney disease.

About the National Kidney Disease Surveillance System (NKSS)

The major goal of the National Kidney Disease Surveillance System (NKSSS) and Quality Assurance (QA) Programme is to provide meaningful high-quality information on the frequency of kidney disease (acute and chronic) and its complications in the Irish health system. Based at University of Limerick, the programme will assess the quality of care provided to patients with kidney disease, and the effectiveness of different treatments for kidney disease.

University of Limerick

Related Diabetes Articles from Brightsurf:

New diabetes medication reduced heart event risk in those with diabetes and kidney disease
Sotagliflozin - a type of medication known as an SGLT2 inhibitor primarily prescribed for Type 2 diabetes - reduces the risk of adverse cardiovascular events for patients with diabetes and kidney disease.

Diabetes drug boosts survival in patients with type 2 diabetes and COVID-19 pneumonia
Sitagliptin, a drug to lower blood sugar in type 2 diabetes, also improves survival in diabetic patients hospitalized with COVID-19, suggests a multicenter observational study in Italy.

Making sense of diabetes
Throughout her 38-year nursing career, Laurel Despins has progressed from a bedside nurse to a clinical nurse specialist and has worked in medical, surgical and cardiac intensive care units.

Helping teens with type 1 diabetes improve diabetes control with MyDiaText
Adolescence is a difficult period of development, made more complex for those with Type 1 diabetes mellitus (T1DM).

Diabetes-in-a-dish model uncovers new insights into the cause of type 2 diabetes
Researchers have developed a novel 'disease-in-a-dish' model to study the basic molecular factors that lead to the development of type 2 diabetes, uncovering the potential existence of major signaling defects both inside and outside of the classical insulin signaling cascade, and providing new perspectives on the mechanisms behind insulin resistance in type 2 diabetes and possibly opportunities for the development of novel therapeutics for the disease.

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.

Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).

Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.

People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.

Read More: Diabetes News and Diabetes Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.