Nephrology

Chronic Kidney Disease Diagnosis and Evaluation

SUMMARY:

Chronic kidney disease affects roughly 15% of adults in the United States, often silently, with an estimated 40% of patients with CKD unaware of their decreased renal function. Even in the absence of symptoms, CKD increases a patient’s risk of cardiovascular disease, hospitalization and death. Early detection of CKD and management of the contributing underlying causes (e.g., diabetes and hypertension) are critical in slowing progression of the disease, decreasing healthcare spending, and improving morbidity and mortality.

Definitions and Staging

Chronic kidney disease is defined as
- Abnormalities of kidney structure or function
- Lasting > 3 months
- Associated with health implications (e.g., markers of kidney damage)
Markers of kidney damage include: Albuminuria | Abnormal urine sediment | Abnormal renal imaging | Electrolyte derangements | Acid-base derangements | Abnormalities detected by histology | History of kidney transplant | GFR < 60 mL/min/1.73m²
The normal GFR in young adults is approximately 125 mL/min/1.73m²
Stages of CKD are defined by estimated GFR (mL/min/1.73m²)
- Stage 1: ≥ 90 AND ≥ 1 marker of kidney damage
- Stage 2: 60 to 89 AND ≥ 1 marker of kidney damage
- Stage 3a: 45 to 59
- Stage 3b: 30 to 44
- Stage 4: 15 to 29
- Stage 5: <15, or dialysis dependent
Staging is further broken down by cause and location of renal disease
- Glomerular diseases | Tubulointerstitial diseases | Vascular diseases | Cystic and congenital diseases
AND degree of albuminuria defined by the albumin excretion rate (AER)
- A1 − Normal or mildly increased albuminuria | AER < 30 mg/day
- A2 − Moderately increased albuminuria | AER 30 to 299 mg/day
- A3 − Severely increased albuminuria | AER ≥ 300 mg/day
The terms microalbuminuria and macroalbuminuria have been replaced by the A1, A2 and A3 language above

Screening and Detection

Screening

Annual screening for CKD with a creatinine and spot urine albumin/creatinine ratio is recommended for all patients with:
- Diabetes
- Hypertension
Patients with additional risk factors for CKD should be considered for annual screening
Additional risk factors include:
- Cardiovascular disease
- Older age
- History of low birth weight
- Obesity
- Family history of CKD
The ACP and AAFP recommend against screening for CKD in asymptomatic adults in the absence of risk factors

Detection Tests

Serum creatinine | Serum cystatin C
- Serum Cystatin C is a filtration marker that can more accurately estimate GFR in cases where false-positive CKD results are suspected (e.g., patients with eGFR < 60 L/min/1.73m² yet no evidence of albuminuria or structural kidney disease)
- Serum cystatin C is NOT reliable in patients with: Acute kidney injury | Inflammatory states | Thyroid dysfunction
Estimated GFR (eGFR)
- Calculated via serum creatinine and/or serum cystatin C based equation

eGFR Calculator

Urine albumin/creatinine ratio
- Is a measurement of albumin excretion rate (AER)
- Should be obtained via spot early morning, first void urine collection
- Is more sensitive that total protein/creatinine ratio
- Can be falsely elevated by certain clinical scenarios (e.g. Heavy exercise | High protein meals | Menstruation | UTI treatment)
- Should be obtained twice within 3 to 6 months to confirm albuminuria
Urinalysis
- Sensitive for high levels of proteinuria (>300mg/day), but may not identify A1 or A2 levels of proteinuria (< 300mg/day)
24-hour urine collections are no longer recommended for initial diagnosis of CKD

Evaluation

Etiology

Once CKD has been confirmed, patients should undergo a thorough diagnostic evaluation to determine the etiology
Initial diagnostic evaluation should include
- Review of systems: Pay special attention to signs or symptoms that may indicate systemic disease (e.g., Rash | Joint pain/swelling) and exposures that may contribute to renal disease (e.g., Recent infections | High risk drug use)
- Medical history: Diabetes | Hypertension
- Family history: Paying attention to gender and generation of family members affected can be helpful in discerning an autosomal dominant disease (e.g., autosomal dominant polycystic kidney disease) vs. a sex-linked recessive disease (e.g., Alport syndrome)
- Physical Exam: Look for evidence of PAD | CAD | Heart failure | Connnective tissue diseases
- Laboratory tests: Serum electrolytes | Fasting lipids | A1C | Spot urine albumin/creatinine ratio | Urinalysis + Microscopic urine sediment | HIV | HCV | HBV
- Imaging: Renal ultrasonography

Complications

All patients with CKD should be evaluated for complications of their disease
Anemia
- Annual CBC in patients with CKD 3, more frequent checks may be indicated especially as renal function declines
- If anemia is present, additional lab work includes: Absolute reticulocyte count | Ferritin | Transferrin saturation | B12 | Folate
- AAFP recommends against checking serum erythropoietin levels in an ambulatory setting
Bone and mineral disorders
- Osteoporosis screening for CKD stages 1 to 3a is the same as the general population
- For CKD Stage 3a and more advanced stages, bone mineral density scan is recommended if it will alter treatment plans
- CKD stage 3a to 5 CKD should have the following serum tests checked regularly: Calcium | Phosphorus | 25-hydroxyvitamin D | Parathyroid hormone | Alkaline phosphatase

When to Refer to Nephrology

In patients with severely elevated albuminuria (e.g., A3 disease, > 300mg/day), spot urine protein/creatinine ratio should be obtained
- If < 500mg/g, start ACE-I or ARB and repeat test in 6 months; if albuminuria has not resolved refer to nephrology
- If > 500mg/g, start ACE-I or ARB and refer to nephrology
All patients with CKD stage 4 or 5 disease (e.g., eGFR < 30 mL/min/1.73m²)
CKD patients with a calculated risk of renal failure of > 10% within one year
- Risk can be calculated via this calculator

The Kidney Risk Failure Equation

Patients with an unclear etiology of their CKD (e.g., not clearly due to hypertension or diabetes) should be referred to nephrology for further work up and consideration of renal biopsy
Any patients with uncontrolled complications of kidney disease
- Anemia with Hgb <10 g/dL
- Bone and mineral disease
- Refractory HTN
- Persistent potassium abnormalities
- Recurrent nephrolithiasis | Concern for nephrocalcinosis

KEY POINTS:

Chronic kidney disease is defined as abnormalities in kidney structure or function lasting at least three months and associated with health implications
The most common etiologies of CKD are diabetes and hypertension
Select patients should undergo annual screening with a creatinine and spot urine albumin/creatinine ratio to monitor for development of CKD
Management of CKD focuses on treating the underlying etiology to prevent progression, as well as management of complications such as anemia, edema, bone disease, and electrolyte abnormalities