Causes of Stage 2 Chronic Kidney Disease
Stage 2 CKD is characterized by mild kidney damage with GFR 60-89 mL/min/1.73 m² plus evidence of kidney damage (such as albuminuria), and is most commonly caused by diabetes and hypertension, which together account for the majority of CKD cases in developed countries. 1, 2
Primary Etiologic Factors
Diabetes is the leading cause of CKD worldwide and accounts for 30-40% of cases, with diabetic kidney disease potentially present at the time of type 2 diabetes diagnosis rather than developing only after years of disease duration. 1, 2 In type 2 diabetes specifically, approximately 20-40% of patients will develop microalbuminuria within 10-15 years, and CKD can manifest even without the traditional albuminuria progression pathway. 1
Hypertension is one of the most frequent causes of CKD in developed countries, creating a bidirectional relationship where it both causes kidney damage and results from kidney disease, accelerating kidney function decline. 1, 2 Approximately 70% of individuals with elevated serum creatinine have hypertension, and uncontrolled systolic blood pressure can accelerate GFR deterioration to 4-8 mL/min per year. 1
Additional Contributing Causes
Glomerulonephritis represents another significant cause of CKD, particularly in certain geographic regions, with chronic glomerulonephritis and diabetes together accounting for more than 50% of CKD cases in some countries like China. 1
Autosomal dominant tubulointerstitial kidney diseases can lead to progressive tubulointerstitial fibrosis and eventual progression to end-stage renal disease. 3
Nephrotoxin exposure including nonsteroidal anti-inflammatory drugs, heavy metals, agrochemicals, and contaminated drinking water can cause CKD. 1
Important Risk Factors
- Age over 60 years substantially increases CKD prevalence and risk. 1
- Family history of kidney disease significantly elevates risk, with affected individuals showing increased prevalence of hypertension, diabetes, and earlier CKD stages. 1
- Obesity independently contributes to CKD development. 1
- Cardiovascular disease is present in approximately 34% of those at increased CKD risk. 3
Critical Diagnostic Requirements for Stage 2 CKD
Evidence of kidney damage must be present in addition to the GFR criteria for Stage 2 diagnosis. 3, 4, 5 This is a common pitfall—GFR 60-89 mL/min/1.73 m² alone is insufficient without demonstrable kidney damage. 4, 5
Kidney damage can be identified through:
- Albuminuria (UACR ≥30 mg/g) on random spot urine collection 1
- Proteinuria detected on urinalysis 5
- Hematuria or other urinary abnormalities 3, 5
- Pathological abnormalities on kidney biopsy 5
- Structural abnormalities on imaging studies 5
All abnormalities must persist for at least 3 months to distinguish chronic from acute kidney disease. 3, 4, 6
Clinical Context and Metabolic Syndrome
The combination of prediabetes with hypertension and mixed hyperlipidemia creates a metabolic syndrome phenotype that dramatically accelerates CKD progression. 1 This constellation of risk factors is particularly important to recognize, as approximately 20-40% of patients with diabetes eventually develop CKD. 1
Common Pitfalls to Avoid
Do not rely on serum creatinine alone without calculating eGFR using validated equations (CKD-EPI 2021), as serum creatinine varies with age, sex, muscle mass, and diet, with interlaboratory variation as high as 20%. 1, 7 The reference interval for serum creatinine includes up to 25% of people (particularly thin, elderly women) who have significantly reduced eGFR despite "normal" creatinine values. 7
Do not skip albuminuria testing, as eGFR and UACR provide independent prognostic information for cardiovascular events, CKD progression, and mortality. 1 Stage 2 CKD cannot be diagnosed without evidence of kidney damage alongside the mildly decreased GFR. 4, 5