What are the risk factors for developing kidney disease in a healthy adult?

What Causes Kidney Disease in an Otherwise Healthy Adult

Diabetes and hypertension are the two dominant causes of chronic kidney disease in otherwise healthy adults, together accounting for the majority of CKD cases in developed countries, with diabetes alone responsible for 30-40% of end-stage kidney disease. 1, 2

Primary Disease Causes

Diabetes

• Diabetic kidney disease is the leading cause of CKD worldwide and the primary cause of end-stage kidney disease in the United States, accounting for more than 30-40% of cases in many countries. 1
• In type 1 diabetes, diabetic kidney disease typically develops after 10 years duration, but in type 2 diabetes it may already be present at diagnosis—studies show 6.5% of newly diagnosed type 2 diabetes patients already have urinary albumin concentration >50 mg/L. 1
• Approximately 20-40% of diabetic patients will eventually develop CKD, with 20-40% developing microalbuminuria within 10-15 years in uncontrolled type 2 diabetes, and 80-90% of those with microalbuminuria progressing to more advanced stages. 1, 2, 3

Hypertension

• Hypertension is one of the most frequent causes of CKD in developed countries and creates a dangerous bidirectional relationship: it both causes kidney damage AND results from kidney disease, creating a cycle that accelerates kidney function decline. 1, 2
• Approximately 70% of individuals with elevated serum creatinine have hypertension, making it the dominant risk factor in this population. 1
• Uncontrolled systolic blood pressure can accelerate the rate of GFR deterioration to 4-8 mL/min per year, particularly in patients with coexistent renal disease, and rates can exceed 10 mL/min/year in those with poorly controlled hypertension and macroalbuminuria. 1, 2

Glomerulonephritis

• Glomerulonephritis is another significant cause of CKD, particularly in certain regions, with chronic glomerulonephritis and diabetes together accounting for more than 50% of CKD cases in China. 1

Additional Risk Factors That Initiate CKD

Demographic and Genetic Factors

• Older age (>60 years) is a well-established risk factor, with CKD prevalence increasing substantially with advancing age. 4, 2, 5
• Family history of chronic kidney disease is highly significant—individuals who report a family member with kidney failure have increased prevalence of hypertension, diabetes, and earlier stages of CKD. 4, 2
• African Americans are 3 to 5 times more likely to develop end-stage renal disease than white Americans, despite similar overall CKD prevalence. 2

Metabolic and Cardiovascular Factors

• Obesity is an established risk factor for CKD development. 1, 2
• Cardiovascular disease is a well-established risk factor, with Medicare data showing 46% of CKD patients having atherosclerotic heart disease. 2
• Prediabetes significantly increases the risk of developing diabetic kidney disease, and the combination of prediabetes with hypertension and mixed hyperlipidemia creates a metabolic syndrome phenotype that dramatically accelerates CKD progression. 1

Nephrotoxic Exposures

• Nephrotoxin exposure can cause CKD, including nonsteroidal anti-inflammatory drugs (NSAIDs), heavy metals, agrochemicals, and contaminated drinking water. 1
• Other nephrotoxic medications include lithium, calcineurin inhibitors, and aminoglycosides. 1

Critical Screening Recommendations

Who Should Be Screened

All persons should be assessed during routine health encounters to determine if they are at increased risk for CKD based on clinical and sociodemographic factors. 4, 2

Target populations for screening include: 4, 2, 5

• Patients with diabetes (screen immediately at diagnosis for type 2, after 5 years for type 1)
• Patients with hypertension
• Age >60 years
• Family history of chronic kidney disease
• Racial/ethnic minorities (particularly African Americans)
• Patients with cardiovascular disease
• Patients with obesity

How to Screen

• Measure both estimated GFR (eGFR) and urinary albumin-to-creatinine ratio (UACR) immediately, as CKD can be diagnosed by either abnormality. 4, 1, 2
• Use UACR measurement instead of urine dipstick, which is a less sensitive test—screening with UACR on a random spot urine collection is recommended. 4, 1, 2
• CKD is defined as eGFR <60 mL/min/1.73 m² OR presence of albuminuria (UACR ≥30 mg/g) persisting for at least 3 months. 1, 2

Common Pitfalls to Avoid

• Do not rely on serum creatinine alone—always calculate eGFR using validated equations (CKD-EPI 2021), as serum creatinine can remain normal until significant kidney function is lost. 1
• Do not skip albuminuria testing—eGFR and UACR provide independent prognostic information for cardiovascular events, CKD progression, and mortality. 1
• Do not assume normal-sized kidneys on ultrasound exclude CKD—diabetic kidney disease and several other causes of CKD maintain normal kidney size despite progressive damage. 1
• In type 2 diabetes, do not wait to screen—CKD may already be present at diagnosis, with 28% of newly diagnosed patients already having hypertension. 1
• Do not overlook the absence of diabetic retinopathy as excluding diabetic kidney disease in type 2 diabetes—retinopathy is only moderately sensitive and specific for CKD in type 2 diabetes. 6