What causes elevated serum creatinine levels, indicating Impaired renal function?

From the Guidelines

Elevated creatinine levels are primarily caused by impaired kidney function, which can result from various factors including acute kidney injury, chronic kidney disease, and other conditions that affect kidney function. According to the American College of Radiology 1, acute kidney injury (AKI) is a common cause of elevated creatinine, affecting up to 20% of hospital inpatients and between 30% to 60% of critically ill patients. AKI can be categorized as prerenal, renal, or postrenal, with prerenal factors including impaired blood flow from any cause, renal causes including diseases that damage renal parenchyma, and postrenal AKI resulting from ureteral, bladder, or urethral obstruction.

Some of the key causes of elevated creatinine include:

• Dehydration and hypovolemia, which can lead to prerenal AKI 1
• Certain medications, such as NSAIDs, aminoglycosides, and some antibiotics, which can cause renal damage 1
• Contrast dyes used in imaging studies, which can cause AKI 1
• Chronic conditions, such as diabetes, high blood pressure, and glomerulonephritis, which can lead to chronic kidney disease (CKD) 1
• Muscle breakdown conditions, such as rhabdomyolysis, which can release large amounts of creatinine into the bloodstream 1
• Certain medications, such as trimethoprim and cimetidine, which can block tubular secretion of creatinine and increase levels without actual kidney damage 1

It's essential to note that identification of the specific cause of AKI is critical, as there are different treatments for diseases such as glomerulonephritis, vasculitis, and ureteral obstruction 1. Evaluation of the patient with AKI or CKD includes a thorough history, physical examination, and laboratory analysis of blood and urine, as well as imaging studies and renal biopsy if necessary 1. If you have elevated creatinine, it's crucial to stay well-hydrated, review medications with your doctor, control underlying conditions like diabetes and hypertension, and follow up with appropriate kidney function testing as recommended by your healthcare provider.

From the FDA Drug Label

Nephrotoxicity Adverse renal effects, as demonstrated by the presence of casts, cells or protein in the urine or by rising BUN, NPN, serum creatinine or oliguria, have been reported. Hyperuricemia has been reported to occur at approximately the same frequency as the increases in BUN and serum creatinine

Elevated creatinine can be caused by:

• Nephrotoxicity, as demonstrated by the presence of casts, cells or protein in the urine or by rising BUN, NPN, serum creatinine or oliguria, which has been reported in patients treated with gentamicin 2
• Hyperuricemia, which has been reported to occur at approximately the same frequency as the increases in BUN and serum creatinine in patients treated with cisplatin 3

From the Research

Causes of Elevated Creatinine

Elevated creatinine levels can be caused by various factors, including:

• Medications such as gentamicin, which can cause nephrotoxicity, leading to increased creatinine levels 4
• Non-steroidal anti-inflammatory drugs (NSAIDs), which can cause kidney injury, especially in older adults 5
• Certain antibiotics and antimicrobials, which can trigger structural and functional renal impairment 6
• Cisplatin therapy, a chemotherapeutic agent known to cause nephrotoxicity 7
• Dehydration, which can occur due to various reasons such as vomiting, diarrhea, or fever, and can lead to acute kidney injury (AKI) 8

Medication-Induced Nephrotoxicity

Medication-induced nephrotoxicity is a common cause of acute kidney injury (AKI) among hospitalized patients. Certain medications, such as:

• Gentamicin, which requires dose adjustment in patients with impaired renal function to prevent nephrotoxicity 4
• NSAIDs, which can cause kidney injury, especially in older adults, although the association between NSAID use and kidney health outcomes is inconsistent 5
• Antibiotics and antimicrobials, which can trigger structural and functional renal impairment 6
• Cisplatin, which can cause nephrotoxicity, and hydration and diuresis can help decrease its incidence 7

Patient Risk Factors

Certain patient risk factors can increase the likelihood of developing elevated creatinine levels, including:

• Pre-existing chronic kidney disease (CKD) 8, 6
• Age ≥ 70 years 8, 5
• Heart failure 8
• Concomitant use of medication with nephrotoxic potential 6