What is the initial workup and management for a patient with chronic kidney disease (CKD)?

Chronic Kidney Disease Workup

Begin CKD workup by simultaneously testing both eGFR (using serum creatinine) and urine albumin-to-creatinine ratio (ACR), as these two markers together define CKD diagnosis, guide staging, and determine treatment intensity. 1

Initial Diagnostic Testing

Primary Laboratory Tests

• Measure serum creatinine and calculate eGFR using a validated equation (eGFRcr) as the initial assessment of kidney function 1
• Obtain urine albumin-to-creatinine ratio (ACR) from a random spot urine sample, which is more sensitive than protein-to-creatinine ratio for detecting early kidney damage 1, 2
• If eGFR or ACR is abnormal, repeat testing within 3 months to confirm chronicity and exclude acute kidney injury 1
• Consider adding cystatin C to improve GFR estimation accuracy (eGFRcr-cys), particularly when clinical decisions are significantly impacted or when creatinine-based estimates may be unreliable (extremes of muscle mass, dietary factors) 1

Comprehensive Metabolic Panel

• Check complete metabolic panel including electrolytes (sodium, potassium, chloride), bicarbonate, calcium, phosphorus, blood urea nitrogen, and glucose 1
• Measure serum albumin to assess nutritional status and interpret proteinuria 1
• Obtain complete blood count to screen for anemia, which becomes increasingly common as CKD progresses 1

Additional Laboratory Studies

• Perform urinalysis with microscopy examining for red blood cell casts (suggesting glomerulonephritis), white blood cells (infection), and cellular elements 1
• Measure parathyroid hormone (PTH) in patients with eGFR <45 mL/min/1.73m² (CKD G3b-G5) to screen for mineral-bone disease 1
• Check 25-hydroxyvitamin D levels as deficiency is common in CKD and contributes to secondary hyperparathyroidism 1
• Obtain lipid panel (total cholesterol, LDL, HDL, triglycerides) for cardiovascular risk assessment 3
• Measure hemoglobin A1c in all patients to screen for diabetes, a leading cause of CKD 4

Establishing Chronicity

CKD requires evidence of kidney damage or dysfunction persisting for at least 3 months. 3, 1

Methods to Confirm Chronicity

• Review prior laboratory records for previous eGFR measurements or creatinine values to document duration of kidney dysfunction 1
• Examine historical urinalysis results for prior albuminuria, proteinuria, or hematuria 1
• Use renal ultrasound findings showing reduced kidney size (<9 cm in adults) or cortical thinning as evidence of chronic disease 1
• Consider kidney biopsy findings demonstrating fibrosis, tubular atrophy, or glomerulosclerosis when available 1

Common pitfall: Do not diagnose CKD based on a single abnormal test—acute kidney injury can present identically and requires different management. 1

Determining the Cause of CKD

Clinical Assessment

• Obtain detailed history focusing on diabetes duration and control, hypertension, cardiovascular disease, recurrent urinary tract infections, kidney stones, and autoimmune conditions 1
• Review medication history for nephrotoxic agents including NSAIDs, lithium, calcineurin inhibitors, aminoglycosides, and proton pump inhibitors 1
• Document family history of kidney disease, polycystic kidney disease, Alport syndrome, or hereditary nephritis 1
• Assess social and environmental exposures including occupational toxins, herbal supplements, and heavy metals 1

Pattern Recognition by Laboratory Findings

• Albuminuria with preserved kidney size suggests diabetic nephropathy, hypertensive nephrosclerosis, or early glomerular disease 1
• Hematuria with dysmorphic red blood cells or red cell casts indicates glomerulonephritis requiring further serologic workup 3
• Rapid eGFR decline (>5 mL/min/1.73m² per year) warrants investigation for acute-on-chronic processes or rapidly progressive glomerulonephritis 4

Imaging Studies

• Perform renal ultrasound to assess kidney size, echogenicity, cortical thickness, and identify structural abnormalities such as cysts, stones, or hydronephrosis 1
• Avoid iodinated contrast when possible in patients with eGFR <30 mL/min/1.73m² due to contrast-induced nephropathy risk 3
• If gadolinium-based MRI contrast is required in patients with eGFR <30 mL/min/1.73m², use Group II or III agents at the lowest diagnostic dose to minimize nephrogenic systemic fibrosis risk 3, 1

When to Consider Kidney Biopsy

• Refer for biopsy consideration when the cause remains unclear after initial workup, when glomerulonephritis is suspected, or when biopsy results would change management 1
• Specific indications include: unexplained nephrotic-range proteinuria (>3.5 g/day), rapidly progressive kidney function decline, active urinary sediment with cellular casts, or suspected systemic disease affecting kidneys 1

Risk Stratification

Kidney Failure Risk Assessment

• Calculate 5-year kidney failure risk using validated equations (such as the Kidney Failure Risk Equation) that incorporate age, sex, eGFR, and ACR in patients with CKD G3-G5 1, 5
• Use 5-year risk of 3-5% as a threshold to consider nephrology referral 1, 5
• Calculate 2-year kidney failure risk with >10% triggering multidisciplinary care planning and >40% initiating kidney replacement therapy preparation 5

Cardiovascular Risk Assessment

• Apply CKD-specific cardiovascular risk models that incorporate both eGFR and albuminuria, as traditional risk calculators underestimate risk in CKD populations 1, 5
• Recognize that CKD itself is an independent cardiovascular risk factor, with risk increasing as eGFR declines and albuminuria worsens 4

Monitoring for CKD Complications

Metabolic Complications

• Screen for metabolic acidosis by checking serum bicarbonate, particularly when eGFR <45 mL/min/1.73m² 5
• Monitor for hyperkalemia especially in patients on RAS inhibitors or with eGFR <30 mL/min/1.73m² 3
• Assess for hyperphosphatemia when eGFR <45 mL/min/1.73m², as this contributes to mineral-bone disease 6

Anemia Screening

• Check hemoglobin at least annually in CKD G3, every 6 months in CKD G4-G5, as anemia prevalence increases with declining kidney function 6

Blood Pressure Monitoring

• Measure blood pressure at every clinical encounter using standardized technique 3
• Consider 24-hour ambulatory blood pressure monitoring for more accurate assessment, particularly when office readings are borderline or white-coat hypertension is suspected 3

Initial Management Considerations During Workup

While completing the diagnostic workup, immediately initiate evidence-based therapies that reduce mortality and slow CKD progression. 5

Immediate Interventions

• Start ACE inhibitor or ARB in patients with albuminuria ≥30 mg/g (A2-A3), regardless of blood pressure, titrating to maximum tolerated dose 3
• Initiate SGLT2 inhibitor in patients with eGFR ≥20 mL/min/1.73m² who have diabetes, ACR ≥200 mg/g, or heart failure 3
• Prescribe statin therapy for all patients ≥50 years with CKD, or younger patients with diabetes, prior cardiovascular events, or 10-year cardiovascular risk >10% 3, 5
• Target blood pressure <130/80 mmHg in patients with albuminuria and <140/90 mmHg in those without albuminuria 5

Lifestyle Modifications

• Advise sodium restriction to <2 g/day (equivalent to <5 g salt/day) 3, 5
• Recommend protein intake of 0.8 g/kg/day in CKD G3-G5, avoiding high protein intake >1.3 g/kg/day 3, 5
• Encourage 150 minutes weekly of moderate-intensity physical activity adjusted to cardiovascular tolerance 3, 5
• Promote plant-based dietary pattern with reduced ultraprocessed foods 3, 5

Medication Safety

• Review and discontinue nephrotoxic medications including NSAIDs, unless absolutely necessary 4
• Adjust all medication doses based on eGFR, particularly antibiotics, oral hypoglycemics, and anticoagulants 3

Referral Criteria to Nephrology

Refer to nephrology when 5-year kidney failure risk is 3-5%, eGFR <30 mL/min/1.73m² (CKD G4-G5), ACR ≥300 mg/g (A3), or rapid eGFR decline >5 mL/min/1.73m² per year. 5, 4

Additional Referral Indications

• Uncertain CKD etiology requiring specialized diagnostic evaluation or kidney biopsy 1
• Hereditary kidney disease suspected based on family history or clinical presentation 3
• Resistant hypertension (uncontrolled on 3 agents including a diuretic) 4
• Recurrent or persistent hematuria with negative urologic workup 3
• CKD complications including refractory anemia, mineral-bone disease, or metabolic acidosis 6

Critical pitfall: Delayed nephrology referral is associated with worse outcomes, including higher mortality and inadequate preparation for kidney replacement therapy. Refer early rather than late. 4