Can Chronic Kidney Disease (CKD) stage V have multiple causes, such as diabetes and hypertension, or is it typically caused by a single factor?

Can CKD Stage V Have Multiple Causes?

Yes, CKD stage V is frequently multifactorial, with diabetes and hypertension often coexisting as combined causes, though a single dominant etiology may be identifiable in many cases. 1, 2

Understanding the Multifactorial Nature of Advanced CKD

The progression to CKD stage V (kidney failure with GFR <15 mL/min/1.73 m²) typically involves multiple contributing factors rather than a single isolated cause:

Primary Etiologies Often Coexist

• Diabetes and hypertension together account for the majority of kidney failure cases in developed countries, with diabetic kidney disease alone representing 30-40% of end-stage renal disease. 2, 3
• Hypertension creates a bidirectional relationship with kidney disease—it both causes kidney damage AND results from kidney dysfunction, creating a dangerous cycle that accelerates progression. 2, 3
• In China, chronic glomerulonephritis and diabetes together account for more than 50% of CKD cases, illustrating how multiple disease processes frequently overlap. 1, 2

Why Multiple Factors Accumulate

CKD itself generates additional risk factors as it progresses, making the disease inherently multifactorial by the time patients reach stage V:

• Approximately 85% of persons with CKD have hypertension, and those with proteinuria have even higher blood pressure levels than those with non-proteinuric CKD. 1
• CKD is associated with high prevalence of diabetes, dyslipidemia (especially hypertriglyceridemia), and hypertension—all diet-related cardiovascular risk factors that further damage the kidneys. 1
• Diabetic patients have approximately 50% higher risk of progressing to end-stage renal disease compared to patients with similar GFR from other causes, suggesting that diabetes adds independent risk beyond just the baseline kidney function. 3

Clinical Implications for Identifying Causes

When evaluating a patient with CKD stage V, you should systematically identify all contributing factors:

Look for Multiple Concurrent Etiologies

• Evaluate for diabetes (fasting glucose, HbA1c, history of diabetic retinopathy or neuropathy). 1
• Assess hypertension control (blood pressure history, evidence of end-organ damage such as cerebrovascular accident or left ventricular hypertrophy). 1, 2
• Screen for glomerulonephritis (urinalysis for hematuria, pyuria, or casts; consider kidney biopsy if atypical features present). 1, 4
• Identify nephrotoxic exposures (NSAIDs, lithium, calcineurin inhibitors, aminoglycosides, heavy metals, agrochemicals). 2
• Review family history (polycystic kidney disease, hereditary nephritis, family members with kidney failure). 2, 3

Recognize That Acute Kidney Injury Can Be Multifactorial Too

AKI is often multifactorial but generally categorized as prerenal, renal, or postrenal, with prerenal and intrinsic renal causes accounting for more than 97% of cases. 1

• Prerenal factors include hypotension, hypovolemia, decreased cardiac output, or renal artery occlusion. 1, 3
• Intrinsic renal causes include vasculitis, acute tubular necrosis, glomerulonephritis, interstitial nephritis, and drug/toxin injury. 1, 3
• Repeated episodes of AKI accelerate progression to CKD, adding another layer of multifactorial causation. 1

Common Pitfalls to Avoid

• Never assume a single cause explains all kidney damage—even when diabetes or hypertension is present, up to 30% of patients with presumed diabetic kidney disease have other causes on kidney biopsy. 2
• Don't overlook environmental and genetic factors—obesity, family history, older age, racial/ethnic minority status, and nephrotoxin exposure all independently contribute to CKD risk. 2, 5, 6
• Avoid missing treatable secondary causes—obstruction, vasculitis, and rapidly progressive glomerulonephritis require specific interventions beyond standard CKD management. 1, 4

The Bottom Line

While you may identify one dominant cause (such as diabetic nephropathy or hypertensive nephrosclerosis), CKD stage V almost always involves multiple contributing factors that have accumulated over years of disease progression. 1, 2, 5 The key is to identify ALL modifiable risk factors—not just the primary etiology—because addressing hypertension, proteinuria, metabolic abnormalities, and nephrotoxic exposures can still impact outcomes even at advanced stages. 1, 7