Updated CKD Guidelines Promote Cystatin C, Risk Equations, and SGLT2 Inhibitors

Use of cystatin C and SGLT2 inhibitors were highlighted in the Kidney Disease: Improving Global Outcomes (KDIGO) organization’s updated clinical practice guideline.

In a synopsis of the recently published guideline — serving as an update to 2012 guidelines — the KDIGO Work Group discussed new recommendations (level 1) and suggestions (level 2) along with practice points for the evaluation, risk assessment, and management of patients with chronic kidney disease (CKD) not receiving kidney replacement therapy (KRT).

“Practice points represent consensus-based expert judgment of the Work Group and are intended to aid implementation of a recommendation or guide practice where evidence generation is considered impossible or absurd. Together the recommendations and practice points provide guidance for how to evaluate and manage persons with CKD,” Magdalena Madero, MD, of the Instituto Nacional de Cardiología Ignacio Chávez in Mexico, and colleagues wrote in Annals of Internal Medicine.

CKD Evaluation

If cystatin C is not available, a creatinine-based estimated glomerular filtration rate (eGFR) should be used to assess patients at risk for CKD. But if it is available, GFR should be estimated using a combination of creatinine and cystatin C (eGFRcr-cys) because it allows for a “truer” GFR estimate, Madero and co-authors said.

“The evidence for this recommendation is that compared with equations based on creatinine and cystatin C alone, equations using both creatinine and cystatin C come closest to the gold standard (measured GFR) most consistently demonstrating higher accuracy, and data demonstrate that the combined eGFRcr-cys equation is superior for distinguishing GFR risk stages,” they pointed out.

However, some patient characteristics can influence creatinine or cystatin C eGFR, and therefore “clinicians may choose the most appropriate biomarker for an individual, which upholds our goal toward more personalized approaches,” they said.

Creatinine is influenced by extremes of muscle mass, malnutrition, dietary intake, and drugs that impair tubular secretion of creatinine; cystatin C is potentially influenced by smoking, chronic inflammation, adiposity, cancer, chemotherapy, thyroid function, and glucocorticoid excess. Some conditions can impact both.

When computing eGFR, don’t include race as a factor, the work group advised. Different equations may need to be used for adults and children.

In cases where more accurate ascertainment of GFR might impact treatment decisions, the authors encouraged GFR not be estimated and instead be measured using plasma or urinary clearance of an exogenous filtration marker, “which are insensitive to such biological factors.”

In cases where there is limited access to a laboratory, they suggested using point-of-care testing for creatinine and urine albumin measurement.

Risk Assessment for CKD

When estimating the absolute risk of kidney failure, Madero’s group recommend using an externally validated risk equation for patients with CKD GFR categories 3 (30-59 mL/min/1.73 m²) to 5 (<15 mL/min/1.73 m²), one of the most validated being the Kidney Failure Risk Equation.

“Using patient’s sex, age, uACR [urine albumin-to-creatinine ratio], and eGFR, the Kidney Failure Risk Equation provides 2- and 5-year estimates of the probability of kidney failure requiring KRT in those with eGFR less than 60 mL/min/1.73 m²,” they wrote, adding that using a validated risk equation such as this allows for personalization and tailoring of treatment and care plans.

Two-year kidney failure risk over 10% can be used to determine timing of multidisciplinary care, while a 2-year risk over 40% can be used to determine the modality education and timing of KRT preparation, such as vascular access planning or transplant referral.

Meanwhile, a 5-year kidney failure risk of 3-5% can be used to determine need for nephrology referral in addition to criteria based on eGFR or uACR, they said.

When predicting cardiovascular risk to add preventive therapies, Madero’s group said clinicians should use externally validated models that are either developed within CKD populations or that incorporate eGFR and albuminuria. Also, only externally validated models specifically developed in the CKD population should be used to predict mortality risk.

Managing, Delaying CKD Progression

Graded as a level 1 recommendation, SGLT2 inhibitors should be given to CKD patients with an eGFR of at least 20 mL/min/1.73 m² and uACR of 200 mg/g or greater, those with heart failure regardless of level of albuminuria, and those with comorbid type 2 diabetes. SGLT2 inhibitors — which include canagliflozin (Invokana), dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and the dual SGLT1/2 inhibitor sotaglifozin (Inpefa) — should be continued until no longer tolerated, eGFR falls below 20 mL/min/1.73 m², or KRT is started, the authors advised.

Adding on an SGLT2 inhibitor to the patient’s treatment regimen shouldn’t change frequency of CKD monitoring, Madero’s group added. Also, the reversible decrease in eGFR on initiation is “generally” not a reason to stop SGLT2 therapy.

Graded as a level 2 suggestion, SGLT2 inhibitors should also be considered in those with an eGFR 20 to 45 mL/min/1.73 m² with uACR below 200 mg/g.

Uric acid-lowering intervention is recommended in patients with symptomatic hyperuricemia, but such agents shouldn’t be used in asymptomatic hyperuricemia to delay CKD progression.

For patients age 50 and older, a statin or statin/ezetimibe combination is recommended for those an eGFR <60 mL/min/1.73 m² not treated with chronic dialysis or kidney transplantation, while a statin is recommended for those with eGFRs above that threshold. As for patients under 50 not treated with chronic dialysis or kidney transplantation, a statin should only be used if the patient also has known coronary disease, diabetes, prior ischemic, stroke, or an estimated 10-year incidence of coronary death or nonfatal myocardial infarction over 10%.

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