The Kidney Disease: Improving Global Outcomes (KDIGO) organization has released a new 2024 clinical practice guideline document on evaluating and managing nondialysis-dependent chronic kidney disease (CKD).

The guideline – a much anticipated update from 2012 – contains mostly new recommendations based on a systematic review of moderate- to high-quality studies conducted up to July 2023. It is designed to assist health care providers with decision-making with respect to the evaluation and management of CKD, defined as abnormalities of kidney structure or function persisting for more than 3 months (excluding dialysis and kidney transplantation).

Key highlights include guidance updates on the measurements of estimated glomerular filtration rate (eGFR) and albuminuria, use of CKD risk prediction equations, and personalized treatment recommendations for kidney and cardiovascular risk reductions tailored to individual patient needs and preferences. Managing blood pressure, diabetes, lipids, CKD-MBD, and anemia (to be updated in 2024) has been addressed in detail in other KDIGO guidelines.

It remains important to determine the cause of each patient’s CKD, whether congenital or genetic, a consequence of systemic diseases, or primary using serum and urine tests, imaging, biopsy, and/or genetic testing.

“Recent advancements in GFR evaluation, risk prediction, and the arrival of novel treatments are poised to enhance CKD prognosis and management,” work group co-chair Adeera Levin, MD, stated in a KDIGO news release. “We also hope the guideline’s emphasis on multidisciplinary teamwork, patient engagement, and a holistic, evidence-based approach to care will help catalyze positive change, resulting in more coordinated CKD care management worldwide.”

Gauging Glomerular Filtration Rate

The guideline provides actionable recommendations based on graded evidence as well as consensus-based practice points on established CKD, staged preferably using the race-free eGFRcr-cys equation and albumin-to-creatinine ratio. If a more accurate assessment of GFR is needed for clinical decision-making, clinicians may measure GFR using plasma or urinary clearance of exogenous filtration markers.

In patients with CKD G3-G5, the guideline recommends using an externally validated risk equation to estimate the absolute risk of kidney failure. Patients believed to have immunoglobulin A nephropathy (IgAN) or autosomal dominant polycystic kidney disease (ADPKD) may want to use disease-specific, externally validated prediction equations, according to a practice point. Risk prediction tools for cardiovascular disease or mortality need to include eGFR and albuminuria or be specific to the CKD population.

Delaying CKD Progression

A practice point encourages clinicians to form a comprehensive and tailored treatment strategy to reduce patients’ risks of progression of CKD and its associated complications. Clinicians should prevent and treat clinical symptoms and signs, such as blood pressure; maintain physical function; and monitor and treat laboratory abnormalities such as anemia, CKD-MBD, potassium disorders, and acidosis, as appropriate.

Activity: According to the guideline, adults with CKD should undertake moderate-intensity physical activity for at least 150 minutes per week, if tolerable.

Diet: The guideline suggests maintaining a dietary protein intake of 0.8 g/kg body weight/d in adults with CKD G3-G5 (evidence level 2C). A practice point suggests avoiding high protein intake exceeding 1.3 g/kg body weight/d. Plant-based, Mediterranean style diets appear prudent, and working with a renal dietitian and receiving appropriate medical nutrition therapy can be beneficial. The guideline also suggests limiting sodium intake to less than 2 g of sodium per day. Special considerations are given for children and older adults.

Blood pressure: With respect to blood pressure control in adults, the guideline recommends that high blood pressure and CKD be treated to a target systolic blood pressure (SBP) of less than 120 mm Hg, when tolerated, using standardized office BP measurement. In children, 24-hour mean arterial pressure by ambulatory blood pressure monitoring should be lowered to the 50th percentile or less for age, sex, and height.

The guideline recommends starting renin-angiotensin-system inhibitors (RASi) (eg, angiotensin-converting enzyme inhibitor [ACEi] or angiotensin II receptor blocker [ARB]) for patients with severely increased albuminuria (G1-G4, A3) without diabetes and suggests this step for patients with moderately increased albuminuria (G1-G4, A2) without diabetes. It also recommends RASi for patients with moderately-to-severely increased albuminuria (G1-G4, A2, and A3) who have diabetes. Avoid any combination of ACEi, ARB, and direct renin inhibitor therapy in the CKD population.

At RASi initiation or dose change, practice points suggest checking within 2-4 weeks for changes in blood pressure, serum creatinine, and serum potassium. Clinicians should continue ACEi or ARB therapy unless serum creatinine rises by more than 30% within 4 weeks. Consider reducing the dose or discontinuing ACEi or ARB if there is symptomatic hypotension or uncontrolled hyperkalemia despite medical treatment, or to reduce uremic symptoms while treating kidney failure.

The guideline suggests a nonsteroidal mineralocorticoid receptor antagonist with proven kidney or cardiovascular benefit for adults with type 2 diabetes, an eGFR exceeding 25 mL/min/1.73m², normal serum potassium concentration, and albuminuria exceeding 30 mg/g despite maximum tolerated dose of RASi.

Glycemic control: The guideline recommends treating patients with type 2 diabetes, CKD, and an eGFR of at least 20 mL/min/1.73m² with a sodium-glucose cotransporter-2 inhibitors (SGLT2i). This advice also applies to patients with CKD alone (without diabetes) who have heart failure or a urine ACR of 200 mg/g or more. SGLT2i is also suggested for adults with an eGFR of 20 to 45 mL/min/1.73m² with urine ACR less than 200 mg/g.

In adults with type 2 diabetes and CKD who have not achieved individualized glycemic targets despite use of metformin and SGLT2i, or who are unable to use those medications, the guideline recommends a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA).

Hyperuricemia: The guideline recommends patients with CKD and symptomatic hyperuricemia should be offered uric acid-lowering intervention. Practice points suggest xanthine oxidase inhibitors rather than uricosuric agents. For acute gout, low-dose colchicine or intra-articular/oral glucocorticoids are preferable to nonsteroidal anti-inflammatory drugs (NSAIDs). Patients without symptoms should not receive uric acid-lowering drugs.

Preventing and Managing Cardiovascular Disease

Lipid management: Statins are recommended for adults aged 50 years and older with stage 1-5 CKD (not on dialysis or receiving a transplant). A statin/ezetimibe combination should only be considered for patients with stage 3-5 CKD. Younger adults with coronary disease (myocardial infarction or coronary revascularization), diabetes mellitus, prior ischemic stroke, or an estimated 10-year incidence of coronary death or nonfatal myocardial infarction exceeding 10% should also consider a statin.

Antiplatelet therapy: The guideline recommends oral low-dose aspirin for secondary prevention of recurrent ischemic cardiovascular disease events.

Coronary artery disease: In stable, stress-test confirmed ischemic heart disease, clinicians may first attempt intensive medical therapy. Unstable or acute conditions may warrant an invasive strategy.

Atrial fibrillation: The guideline recommends non-vitamin K antagonist oral anticoagulants rather than vitamin K antagonists such as warfarin for thromboprophylaxis in atrial fibrillation in people with CKD G1-G4.

Imaging: The guideline suggests following advice from radiology societies. Patients with CKD, acute kidney injury (AKI), diabetes, reduced intravascular volume, or concomitant nephrotoxic drugs have increased risk for contrast-associated AKI.

Medication Management and Drug Stewardship

The guideline offers myriad practice points for safe medication use including limiting over-the-counter medicines and herbal and dietary supplements, considering the nephrotoxic effects of medications, reviewing teratogenicity in case of pregnancy, and monitoring eGFR to balance effectiveness and potential adverse effects.

Dose adjustments by eGFR are frequently required for medications cleared by the kidneys. While creatinine-based eGFR is appropriate for drug dosing in most cases, using equations that combine both creatinine and cystatin C, or measured GFR may be indicated when drugs have a narrow therapeutic or toxic range. Use eGFR nonindexed for body surface area in people with extremes of body weight. Adapt drug dosing when the volume of distribution is not in steady state.

Medications discontinued due to illness or prior to elective surgery or acute management of adverse effects should have a plan for restart.

Periodic medication review and pharmacist involvement is necessary.

Optimal Models of Care

The guideline offers a series of practice points to optimize care. Referral to specialist kidney care services is warranted when the cause of CKD is uncertain and in cases of  hereditary kidney disease or recurrent extensive nephrolithiasis. It is also warranted when the 5-year risk for kidney replacement therapy exceeds 5%, eGFR drops by 20%-30%, or eGFR falls below 30 mL/min/1.73m². Significant albuminuria and microscopic hematuria also require further evaluation and management.

Referral of children and adolescents to specialist kidney care services is indicated when urine ACR is 30 mg/g or PCR is 200 mg/g or more or there is persistent hematuria, a sustained decrease in eGFR, hypertension, kidney outflow obstruction, kidney and urinary tract anomalies, suspected CKD, or recurrent urinary tract infection. Transition from pediatric to adult care should begin at age 11 to 14 years using checklists to assess readiness and guide preparation. Kidney transplantation is recommended, either preemptively or when kidney failure occurs.

Timely referral to specialist kidney care is paramount to avoid poor outcomes, such as hospitalization.

Symptoms: A practice point suggests screening people with CKD G4-G5, age older than 65 years, poor growth, or symptoms such as involuntary weight loss, frailty, or poor appetite twice annually for malnutrition using a validated assessment tool. The guideline also offers lifestyle and pharmacologic options for managing other symptoms such as pain, poor sleep, and uremic pruritus.

Multidisciplinary care: Clinicians should ensure access to dietary counseling, medication management, education, and counseling about kidney replacement modalities, transplant options, dialysis access surgery, and ethical, psychological, and social care for people with CKD.

Dialysis Initiation

According to practice points, dialysis is indicated when symptoms or signs attributable to kidney failure are present, such as neurologic signs of uremia, pericarditis, anorexia, medically resistant acid-based or electrolyte abnormalities, intractable pruritus, serositis, and acid-base or electrolyte abnormalities or the patient has inability to control volume status or blood pressure. This often occurs when GFR is 5 to 10 mL/min/1.73 m².

Consider planning for preemptive kidney transplantation and/or dialysis access in adults when the GFR is less than 15 to 20 mL/min/1.73m² or risk of KRT exceeds 40% over 2 years. Pediatric patients have special considerations and should ideally seek transplantation.