What is chronic kidney disease (CKD)?

Chronic Kidney Disease: Definition, Diagnosis, and Clinical Significance

Definition and Core Diagnostic Criteria

Chronic kidney disease (CKD) is defined as either kidney damage or decreased kidney function (GFR <60 mL/min/1.73 m²) persisting for 3 or more months. 1

CKD is diagnosed through two primary markers:

• Persistent albuminuria (urinary albumin-to-creatinine ratio ≥30 mg/g) measured on a random spot urine collection 1
• Reduced estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m²) representing loss of half or more of normal kidney function 1
• Other manifestations including abnormalities in urine sediment, blood/urine chemistry, or imaging studies 1

Epidemiology and Population Impact

• CKD affects 8-16% of the global population, with approximately 17% of persons older than 60 years having eGFR <60 mL/min/1.73 m² 1, 2
• In diabetic populations, CKD occurs in 20-40% of patients, making diabetes the leading cause of end-stage kidney disease in the United States 1
• Less than 5% of patients with early CKD are aware of their disease, highlighting the critical need for screening 2

Staging and Classification

Normal kidney function: GFR in young adults is approximately 120-130 mL/min per 1.73 m² and declines with age 1

CKD stages are defined by eGFR thresholds:

• Stage G1-G2: eGFR ≥60 mL/min/1.73 m² with evidence of kidney damage (albuminuria) 1
• Stage G3: eGFR 30-59 mL/min/1.73 m² 1
• Stage G4: eGFR 15-29 mL/min/1.73 m² 1
• Kidney failure: GFR <15 mL/min/1.73 m² or need for dialysis/transplantation 1

Albuminuria classification:

• Normal: <30 mg/g creatinine 1
• Moderately elevated: 30-299 mg/g creatinine 1
• Severely elevated: ≥300 mg/g creatinine 1

Clinical Significance and Complications

The most critical outcome of CKD is cardiovascular disease, not kidney failure—CVD events are more common than progression to end-stage kidney disease. 1

Patients with CKD should be considered in the highest risk group for subsequent cardiovascular events. 1

CKD-associated complications include:

• Cardiovascular disease (the leading cause of death in CKD patients) 1
• Hypertension requiring aggressive blood pressure management 1
• Anemia from decreased erythropoietin production 1
• Mineral and bone disorders including hyperphosphatemia, vitamin D deficiency, and secondary hyperparathyroidism 1, 2
• Metabolic acidosis 2, 3
• Neuropathy from uremia and electrolyte imbalances 1, 4
• Malnutrition and decreased quality of life 1

Diagnostic Approach

For screening, obtain a spot urine albumin-to-creatinine ratio (UACR) and serum creatinine for eGFR calculation. 1

Important diagnostic considerations:

• Two of three UACR specimens collected within 3-6 months should be abnormal before confirming persistent albuminuria, due to >20% biological variability 1
• Avoid testing during acute illness, exercise within 24 hours, infection, fever, heart failure, or marked hyperglycemia, as these cause false elevations 1
• eGFR declines with age but remains an independent predictor of adverse outcomes regardless of age, requiring the same diagnostic criteria in elderly patients 1

When to Suspect Alternative Diagnoses

Refer to nephrology promptly for:

• Active urinary sediment (red/white blood cells or cellular casts) 1
• Rapidly increasing albuminuria or rapidly decreasing eGFR 1
• Nephrotic syndrome 1
• Absence of retinopathy in type 1 diabetes (rare for diabetic kidney disease to occur without retinopathy) 1
• Gross hematuria 1

Referral Criteria

Mandatory nephrology referral when:

• eGFR <30 mL/min/1.73 m² 1
• Continuously increasing urinary albumin levels and/or continuously decreasing eGFR 1
• Uncertainty about etiology of kidney disease 1
• Rapidly progressing kidney disease 1
• Albuminuria ≥300 mg per 24 hours indicating high risk of progression 2

Prevention and Early Detection

Early detection through routine laboratory measurements can prevent or delay adverse outcomes. 1

The age-related decline in GFR, while common, is not benign—decreased GFR in elderly patients independently predicts death and cardiovascular disease. 1

Drug dosing adjustments are required when eGFR is reduced, particularly for antibiotics, oral hypoglycemic agents, and other renally cleared medications 1, 2