From the Guidelines
Intrarenal acute kidney injury (AKI) is primarily caused by direct damage to the kidney structures themselves, with the main causes including nephrotoxic medications, rhabdomyolysis, glomerulonephritis, acute interstitial nephritis, and acute tubular necrosis, as well as systemic conditions like multiple myeloma, vasculitis, and thrombotic microangiopathies 1. The causes of intrarenal AKI can be multifactorial, but generally, they can be categorized into renal causes, which include any disease that damages renal parenchyma, such as vasculitis, acute tubular necrosis, glomerulonephritis, interstitial nephritis, renal infection or infiltration, drugs, and toxins 1. Some of the key causes of intrarenal AKI include:
- Nephrotoxic medications such as NSAIDs (ibuprofen, naproxen), aminoglycosides (gentamicin, tobramycin), contrast media used in imaging studies, and certain chemotherapeutic agents like cisplatin 1
- Rhabdomyolysis, where muscle breakdown releases myoglobin that damages kidney tubules
- Glomerulonephritis, an inflammatory condition affecting the glomeruli
- Acute interstitial nephritis, often triggered by drug hypersensitivity reactions
- Acute tubular necrosis resulting from prolonged ischemia or toxin exposure
- Systemic conditions like multiple myeloma, vasculitis, and thrombotic microangiopathies
- Severe infections leading to sepsis may damage kidneys through inflammatory mediators and microcirculatory dysfunction It is essential to recognize these causes early, as prompt intervention, including discontinuation of nephrotoxic agents and treatment of underlying conditions, can prevent progression to chronic kidney disease 1. The evaluation of the patient with AKI includes a thorough history, physical examination, and laboratory analysis of blood and urine, and renal biopsy may be indicated for differentiation of nephritic and nephrotic syndromes 1. In the management of medications for patients with AKI, evaluation of nephrotoxins as a plausible cause of AKI is the first consideration, and determining nephrotoxic causality involves assessment of the temporal sequence between administration and the onset of injury, other possible causes, response to the removal of a drug, and in some cases the effects of restarting the drug 1.
From the Research
Causes of Intrarenal Acute Kidney Injury (AKI)
The causes of intrarenal AKI can be attributed to various factors, including:
- Hemodynamic changes, such as renal ischemia caused by vasoconstriction with consecutive tubular necrosis 2
- Inflammatory reactions, which can lead to kidney damage and dysfunction 3
- Nephrotoxicity, caused by exposure to certain medications or substances 3, 4
- Acute tubular necrosis, caused by either ischemia or nephrotoxicity 4
- Microvascular changes, including various types of thrombotic microangiopathy 5
Pathophysiological Mechanisms
The pathophysiology of AKI is complex and involves multiple mechanisms, including:
- Intrarenal vasodilation together with microcirculatory changes and redistribution of blood flow, leading to a drop in glomerular filtration by functional changes 2
- Interactions and progression between hemodynamic changes, inflammatory reactions, and nephrotoxicity, which can determine the severity and duration of AKI 3
- Organ crosstalk and the interaction of concurrent therapies with these mechanisms, which can complicate the pathophysiology of AKI even further 3
Classification of AKI
AKI can be classified into three general categories: prerenal, intrarenal, and postrenal 4. However, AKI often has multifactorial causes and pathophysiologic features that can be divided into different categories.