Chronic Kidney Disease (CKD): Comprehensive Overview
Definition and Diagnostic Criteria
CKD is diagnosed when kidney abnormalities persist for more than 3 months, defined by either an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² or evidence of kidney damage (such as albuminuria ≥30 mg/g, abnormal imaging, or biopsy findings) at any eGFR level. 1, 2
The 3-month persistence requirement is critical—it distinguishes chronic from acute kidney injury and requires documentation on at least two separate occasions. 1, 2
Key Diagnostic Tests
- Serum creatinine to calculate eGFR using the CKD-EPI equation (preferred over MDRD due to less bias, especially at eGFR ≥60 mL/min/1.73 m²) 1, 3, 2
- Urine albumin-to-creatinine ratio (UACR) on a random spot urine sample 1
- Urinalysis with microscopy to detect hematuria, cellular casts, or other abnormalities 1
When creatinine-based eGFR is uncertain (e.g., extremes of muscle mass), confirm with cystatin C-based or combined creatinine-cystatin C equations. 1, 3
Staging System: The CGA Classification
CKD must be classified using the complete CGA system: Cause, GFR category, and Albuminuria category—never stage by GFR alone. 3, 2
GFR Categories (G Stages)
| Stage | eGFR (mL/min/1.73 m²) | Description |
|---|---|---|
| G1 | ≥90 | Normal/high function (requires evidence of kidney damage for CKD diagnosis) |
| G2 | 60-89 | Mildly decreased (requires evidence of kidney damage for CKD diagnosis) |
| G3a | 45-59 | Mild-to-moderate decrease |
| G3b | 30-44 | Moderate-to-severe decrease |
| G4 | 15-29 | Severe decrease |
| G5 | <15 | Kidney failure |
Critical point: For G1 and G2, you cannot diagnose CKD based on eGFR alone—you must document kidney damage (albuminuria, imaging abnormality, biopsy findings, or abnormal sediment). 3, 2
The subdivision of Stage 3 into 3a and 3b is mandatory because these ranges have markedly different mortality, cardiovascular risk, and progression profiles. 3, 2
Albuminuria Categories (A Stages)
| Category | UACR (mg/g) | Description |
|---|---|---|
| A1 | <30 | Normal to mildly increased |
| A2 | 30-300 | Moderately increased |
| A3 | >300 | Severely increased (includes nephrotic range) |
The 30 mg/g threshold represents approximately 3 times the normal value and independently predicts CKD complications, cardiovascular mortality, and progression to kidney failure. 3, 2
Combined Risk Stratification (KDIGO Heat Map)
The combination of GFR and albuminuria categories determines overall risk:
- Low risk (green): G1-G2 with A1 3
- Moderately increased risk (yellow): G1-G2 with A2, or G3a with A1 3
- High risk (orange): G1-G2 with A3, or G3a with A2, or G3b with A1 3
- Very high risk (red): G3a with A3, or G3b with A2-A3, or any G4-G5 (regardless of albuminuria) 3
This risk stratification directly guides monitoring frequency, blood pressure targets, nephrology referral timing, and cardiovascular risk-reduction strategies. 3
Causes and Risk Factors
Primary Causes
In developed countries, the two dominant causes are:
- Diabetes mellitus (diabetic kidney disease develops in 20-40% of diabetic patients) 4, 5, 6
- Hypertension (hypertensive nephrosclerosis) 5, 6
Other important causes include glomerulonephritis, polycystic kidney disease, and chronic interstitial nephritis. 3
Risk Factors for Development
- Age >60 years 7, 8
- Diabetes mellitus 5, 8
- Hypertension 5, 8
- Cardiovascular disease 7, 8
- Family history of kidney disease 1, 8
- Exposure to nephrotoxic medications (NSAIDs, certain antibiotics, contrast agents) 5, 8
Risk Factors for Progression
- Elevated blood pressure 1
- Hyperglycemia 4
- Higher degrees of albuminuria 4, 5
- Rapid eGFR decline (≥5 mL/min/1.73 m²/year or ≥30% decrease over 2 years) 2, 5
Clinical Evaluation
Initial Assessment
When CKD is suspected or detected, perform:
- Focused history: duration of diabetes or hypertension, family history of kidney disease, medication review (especially NSAIDs, ACE inhibitors, ARBs), symptoms of uremia (nausea, pruritus, altered mental status), volume status 1, 5
- Physical examination: blood pressure measurement, volume assessment (edema, jugular venous pressure), signs of uremia 1
- Laboratory tests:
- Imaging: Renal ultrasound to assess kidney size, echogenicity, and rule out obstruction 1
Monitoring Frequency by Stage
- G1-G2 (with kidney damage): Annual monitoring 3
- G3a: Every 6-12 months depending on albuminuria level 1, 3
- G3b: Every 3-6 months 3
- G4-G5: Every 1-3 months 3
Management by Stage
Stage 1-2 (eGFR ≥60 with kidney damage)
Primary goals: Slow progression, reduce cardiovascular risk, treat underlying cause
- Blood pressure control: Target <130/80 mmHg, especially with albuminuria ≥300 mg/g 1, 5
- ACE inhibitors or ARBs: First-line for patients with UACR ≥30 mg/g 1
- Glycemic control: HbA1c target individualized but generally <7% in diabetics 4
- Cardiovascular risk reduction: Statin therapy for lipid management 4, 5
- Lifestyle modifications: Sodium restriction, smoking cessation, weight management 5
- Avoid nephrotoxins: NSAIDs, aminoglycosides, contrast agents when possible 5, 8
Stage 3a (eGFR 45-59)
Continue all Stage 1-2 measures, plus:
- Intensify blood pressure and proteinuria control 1
- Begin monitoring for complications: Anemia, mineral bone disease 4, 1
- Adjust medication doses according to eGFR 5, 8
- Consider nephrology referral if UACR ≥300 mg/g or rapid progression 1, 5
Stage 3b (eGFR 30-44)
Continue all previous measures, plus:
- Systematic evaluation for CKD complications:
- Strict medication dose adjustments 5, 8
- Nephrology referral strongly recommended 1, 5
Stage 4 (eGFR 15-29)
All Stage 4 patients require nephrology referral. 1, 7, 5
- Intensive management of complications 4, 1
- Preparation for renal replacement therapy:
- Dietary modifications: Protein restriction (0.6-0.8 g/kg/day), potassium and phosphate restriction 7
Stage 5 (eGFR <15)
Kidney failure requiring renal replacement therapy when uremic symptoms develop or metabolic complications become unmanageable. 4, 3
- Initiate dialysis when indicated (uremic symptoms, refractory hyperkalemia, metabolic acidosis, volume overload, pericarditis) 4, 3
- Continue transplant evaluation if candidate 7
Specific Therapies to Slow Progression
Renin-Angiotensin System Blockade
ACE inhibitors or ARBs are first-line for patients with UACR ≥300 mg/g and/or eGFR <60 mL/min/1.73 m². 1
These agents reduce proteinuria and slow CKD progression independent of blood pressure effects. 5 Do not combine ACE inhibitors with ARBs—this increases adverse events without additional benefit. 5
SGLT2 Inhibitors
SGLT2 inhibitors reduce CKD progression and cardiovascular events in patients with diabetes and CKD. 1
These agents provide kidney protection beyond glycemic control and should be considered in diabetic CKD patients with eGFR ≥20 mL/min/1.73 m². 4, 1
Blood Pressure Management
Target blood pressure <130/80 mmHg, particularly in patients with albuminuria ≥300 mg/g. 1, 5
Lower targets may be appropriate for patients with higher degrees of proteinuria, but monitor for acute eGFR decline when initiating or intensifying therapy. 4
Nephrology Referral Criteria
Refer to nephrology when:
- eGFR <30 mL/min/1.73 m² (all Stage 4-5 patients) 1, 7, 5
- UACR ≥300 mg/g 1, 5
- Rapid eGFR decline (≥30% decrease over 2 years or ≥5 mL/min/1.73 m²/year) 2, 5
- Difficulty managing CKD complications (anemia, mineral bone disease, metabolic acidosis) 1, 5
- Uncertain etiology requiring kidney biopsy 5
- Active urinary sediment (dysmorphic RBCs, RBC casts) suggesting glomerulonephritis 5
Early referral (at Stage 3b-4) improves long-term outcomes and reduces costs by allowing adequate preparation for renal replacement therapy. 7
Common Pitfalls and Caveats
Diagnostic Errors
- Never diagnose CKD on a single abnormal test—the abnormality must be documented on at least two occasions ≥3 months apart. 3, 2
- Do not rely on serum creatinine alone—a "normal" creatinine (e.g., 1.2 mg/dL) in an elderly patient with low muscle mass may represent significant kidney dysfunction (eGFR 40-50 mL/min/1.73 m²). 2
- Always classify using the complete CGA system—stating "Stage 3 CKD" without specifying 3a vs 3b and albuminuria category provides incomplete risk stratification. 3, 2
Management Errors
- Avoid therapeutic nihilism—patients with CKD derive equal or greater benefit from evidence-based cardiovascular therapies (statins, blood pressure control) compared to the general population. 9
- Do not withhold ACE inhibitors/ARBs due to mild creatinine elevation—a 20-30% increase in creatinine after initiation is acceptable and does not indicate harm. 5 However, increases >30% warrant investigation for renal artery stenosis or volume depletion. 5
- Adjust medication doses according to eGFR—many antibiotics, oral hypoglycemics, and other drugs require dose reduction to prevent toxicity. 5, 8
- Screen for and avoid nephrotoxins—NSAIDs are particularly harmful in CKD and should be avoided. 5, 8
Acute Kidney Injury Superimposed on CKD
Patients with CKD are at higher risk for acute kidney injury from volume depletion, contrast agents, or medications. 4 When eGFR drops acutely, repeat measurement within days (not months) to distinguish acute from chronic decline. 4
Epidemiology and Public Health Impact
CKD affects 8-16% of the global population and is the 16th leading cause of years of life lost worldwide. 5, 6 However, less than 5% of patients with early CKD are aware of their disease. 5
Patients with CKD are 5-10 times more likely to die (primarily from cardiovascular disease) than to progress to end-stage kidney disease. 6, 9 This cardiovascular risk increases exponentially as kidney function declines and persists even after adjustment for traditional risk factors. 9
CKD should be considered a coronary heart disease risk equivalent, warranting aggressive cardiovascular risk factor management. 4, 9