The Kidney Disease: Improving Global Outcomes (KDIGO) Work Group has issued a 2022 update to its 2020 guideline for the management of diabetes in chronic kidney disease (CKD). KDIGO, which develops and publishes guidelines, said the update was an endorsement of “a layered approach to care” integrating lifestyle changes and clinically-proven “first-line pharmacotherapy” as the starting point for treatment.
A synopsis of the update, led by Sankar D Navaneethan (Baylor College of Medicine, Houston, USA), Sophia Zoungas (Monash University, Melbourne, Australia) and Kamlesh Khunti (University of Leicester, Leicester, UK) has been published in the Annals of Internal Medicine. Basing the changes on a review of new evidence up to February 2022, the Work Group, co-chaired by Ian de Boer (Kidney Research Institue, Seattle, USA) and Peter Rossing (Steno Diabetes Center, Copenhagen, Denmark) encompassed “nephrologists, endocrinologists, cardiologists, primary care physicians, registered dietitians, and patients”. They employed the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system to assess the quality of the evidence and conclusions of a variety of studies, before using them to formulate graded recommendations and “consensus practice points”.
The evidence for the update was taken exclusively from randomised controlled trials. The “overall scope and systematic literature search for the update” have remained unchanged from the 2020 guideline, and it continues to address treatment of type 1 and type 2 diabetes, as well as CKD, kidney transplant, and both peritoneal and haemodialysis patients.
Primary among the change in recommendations is a renewed focus on employing a “holistic approach to patient care,” which includes “control of multiple risk factors” as well as a more “collaborative partnership among patients with CKD” from clinicians. There have been changes to the stage at which KDIGO recommends use of certain pharmacologic therapies, with SGLT2 inhibitors, in combination with metformin, now “the preferred first-line pharmacologic therapy for patients with type 2 diabetes and CKD”.
In the 2020 guideline, SGLT2 inhibitors were recommended for CKD patients with an estimated glomerular filtration rate (eGFR) of at least 30 mL/min/1.73 m2, while the update recommends them for those with and eGFR of 20 mL/min/1.73 m2. This change is based on the findings of seven large trials “examining the cardiovascular and kidney effects of various SGLT2 inhibitors”, four of which “demonstrated benefits for cardiovascular events and kidney disease progression as a pre-specified secondary end point”.
The second-line class of drug the guideline recommends for lowering glucose in type 2 diabetes and CKD patients who have not achieved individualized glycemic targets despite the use of metformin and SGLT2i or who are unable to use those medications, meanwhile, is GLP-1 RAs, which was justified with reference to the AMPLITUDE-O trial. Nonsteroidal MRAs are also recommended for patients with type 2 diabetes, eGFR ≥25 mL/min/1.73 m2, normal serum potassium, and albuminuria ≥30 mg/g [≥3 mg/mmol].
The KDIGO Work Group supports starting each new treatment one at a time, adjusting for any resulting changes in a patient’s condition. They strongly advocate “ongoing monitoring” as “critical” to tracking these changes. Given the new therapies for CKD and limitation of cardiovascular disease burden, healthcare providers should, the guideline suggests, “focus on preserving kidney function and maintaining well-being rather than replacing kidney function”. Wide implementation of the new therapies for CKD and diabetes demands engagement from “health systems, payers, regulators, and life science industries” as well as patients, the Work Group states. Similar widespread action is also required for earlier detection of CKD.
Obstacles to such implementation are acknowledged by the guideline, which points to the high initial cost of the new treatments it includes. That cost is offset, the Work Group says, by the eventual savings provided by earlier and more effective treatment of CKD, limiting its later demands on healthcare providers. It may be more cost-effective “to implement new therapies while we await more data to support broader access” to them, while “team-based, integrated care focused on risk evaluation and patient empowerment” can help to improve quality of life for patients.
In its conclusion, the report directly tackles the issue of confusion caused by multiple sets of guidelines from various professional societies. The “appearance of inconsistency” it projects, say Navaneethan, Zoungas et al, is a “concern”, but one that KDIGO has addressed by partnering with the American Diabetes Association to issue “a consensus report on the diagnosis and management of diabetes and CKD”. In this report, the two societies together offer “aligned, evidence-based recommendations” while also alerting clinicians to the most “high-priority interventions” for each condition and addressing “CKD prevention, screening, and diagnosis”, which the KDIGO report does not.