Chronic Kidney Disease Management to Include SGLT2 Inhibitors

Teresa Chen, MD

New risk assessment tools incorporating glomerular filtration rate (GFR) and albuminuria can help manage treatment for chronic kidney disease (CKD).

A team, led by Teresa K. Chen, MD, Johns Hopkins University School of Medicine, conducted a literature search involving 998 clinical trials, meta-analyses, practice guidelines and systematic reviews, as well as review articles and observational studies, such as cross-sectional studies.

Currently, optimal management of chronic kidney disease includes cardiovascular risk reductions, such as statins and blood pressure management, treatment of albuminuria using angiotensin-convertin enzyme inhibitors or angiotensin II receptor blockers, avoidance of potential nephrotoxins, including nonsteroidal anti-inflammatory drugs, and adjustments to drug dosing.

One of the suggestions for the CKD patient populations is managing diabetes.

Glycemic control may delay progression of CKD, with most guidelines recommending a goal hemoglobin A1c of ~ 7.0% and dose adjustments in oral hypoglycemic agents may be necessary.

Generally, drugs that are largely cleared by the kidneys should be avoided because drugs metabolized by the liver and/or partially excreted by kidneys may require dose reduction or discontinuation, particularly when eGFR falls below 30 mL/min/1.73 m².

SGLT-2 inhibitors should also be used in patients with severely increased albuminuria.

In the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, investigators found among 4401 patients with type 2 diabetes and CKD stage G2-G3/A3 (baseline eGFR 30 to <90 mL/min/1.73 m² and urine ACR>300 to 5000 mg/24 hours) taking ACE-I or ARB therapy, those randomized to canagliflozin had a 30% lower risk (43.2 vs 61.2 events per 1000 patient-years) of developing the primary composite renal outcome.

Treating patients with both hypertension and CKD has also been presented in guidelines recently.

“Blockade of the renin-angiotensin-aldosterone system with either an angiotensin-converting enzyme inhibitor (ACE-I) or an angiotensin II receptor blocker (ARB) is recommended for adults with diabetes and a urine ACR of at least 30 mg per 24 hours or any adult with a urine ACR of at least 300 mg per 24 hours,” the authors wrote. “Dual therapy with an ACE-I and an ARB is generally avoided, given associated risks of hyperkalemia and acute kidney injury.”

In past trials, these medications have shown cardiovascular benefits that could extend to patients with CKD who have lower levels of albuminuria.

Chronic kidney disease, defined as a persistent abnormality in kidney structure of function for more than 3 months, affects 8-16% of the population globally. The prevalence of this condition is generally attributed to diabetes and hypertension in developed countries.

This condition is commonly identified through routine screening with serum chemistry profile and urine studies. CKD is also frequently found incidentally.

However, less than 5% of patients with early chronic kidney disease report awareness of the disease. Because CKD is asymptomatic, screening is an essential tool for the early detection of the disease.

A new kidney profile test, developed by the National Kidney Foundation, includes measuring both serum creatinine for estimating GFR and urine ACR. Many clinical practice guidelines also call for a risk-based approach to screening for those older than 60 or with a history of diabetes or hypertension.

Screening is also recommended for those with clinical risk factors, including autoimmune disease, obesity, kidney stones, recurrent urinary tract infections, reduced kidney mass, exposure to certain medications such as NSAIDs or lithium, and prior episodes of acute kidney injury.

As a result of the CREDENCE study, the US Food and Drug Administration (FDA) recently expanded the approval of the SGLT-2 inhibitor canagliflozin (INVOKANA) to include end-stage kidney disease and cardiovascular event risk reduction in patients with type 2 diabetes, representing the first approved drug for diabetic kidney disease in nearly 20 years.

In an interview with MD Magazine®, Lucia Novak, MSN, NP, a specialist in the fields of Advanced Diabetes Management and Adult Health, detailed what the new canagliflozin indication means for patients and physicians, how it may influence renal screening, and what to expect with SGLT2 inhibitors.

The double-blind CREDENCE study showed the drug when coupled with standard care was associated with a 32% reduction in end-stage kidney disease alone (HR, 0.68; (95% CI, .54 — .86; P = .0015).

Canagliflozin also reduced risk of cardiovascular death and hospitalization for heart failure by 31% (HR, .69; 95% CI, .57—.83; P = .0001) and major cardiovascular events (MACE) by 20% (HR, .80; 95% CI, .67 — .95; P = .0121).

Additionally, there were fewer reported adverse events and serious adverse events among the treatment arm, with no statistically significant difference in incidence of amputations or adjudicated fractures.

The study, “Chronic Kidney Disease Diagnosis and Management,” was published online in JAMA.