How To Prevent AKI From Progressing To CKD
Feb 10, 2023
Acute kidney injury (AKI) is a huge health burden worldwide, associated with chronic kidney disease (CKD), end-stage renal disease (ESRD), cardiovascular disease (CVD), and death.
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AKI can lead to a wide range of outcomes from complete recovery to end-stage kidney disease.
Previously improvements in serum creatinine (SCr) and blood urea nitrogen (BUN) were considered to indicate complete recovery from AKI, but many AKIs are now recognized to lead to the development of chronic kidney disease (CKD).
Even in hospitalized patients with small increases in serum creatinine (1.2 to <1.5-fold), the risk of developing CKD and long-term mortality was significantly increased.
According to the KDIGO 2012 guidelines, one of the following conditions can be defined as AKI:
An increase in SCr of more than 0.3 mg/dl (≥ 26.5 μmol/L) within 2 days;
An increase in SCr of more than 50% within a week;
Urine output <0.5 ml/(kg h) for 6 hours.
CKD is defined as abnormal kidney structure or function for more than 90 days, and acute kidney disease (AKD) is defined as neither.
A meta-analysis including more than 2 million patients showed that patients hospitalized with AKI were at increased risk of new or progressive CKD (HR 2.67), ESRD (HR 4.81), and death (HR 1.8). The more severe the acute kidney injury, the higher the risk of CKD progression.
In addition, risk factors for the transition from AKI to CKD include the patient's age, gender, proteinuria, hypoalbuminemia, and previous chronic diseases such as hypertension, heart failure, and diabetes.
Factors leading to acute kidney injury
Acute kidney injury has many different etiologies and generally falls into three categories.
Prerenal factors, insufficient blood flow to the kidneys due to severe blood loss, diarrhea, dehydration, etc.;
Renal factors, such as vasculitis, drugs, infection, etc. cause kidney disease;
Post-renal factors, urinary tract obstruction due to stones, tumors, etc.
A study published in CAJSN in 2015 showed that more than 40% of AKI cases are drug-induced. Mainly include nephrotoxic drugs, non-steroidal anti-inflammatory drugs, antibiotics, and anticancer drugs. In high-income countries, AKI mainly occurs in hospitalized patients, whereas in low-income countries, AKI is mainly community-acquired due to gastroenteritis, acute infection, and toxin-induced dehydration.
Like other organs, the kidney has its repair and compensation functions. When injury disrupts the compensatory response, the kidney cannot perform tissue repair. Impaired angiogenesis, dysfunctional cell cycle, loss of intracellular structure, differentiation of the tubular epithelium toward a myofibroblast phenotype, increased extracellular matrix, and persistent immune infiltration after injury all contribute to the progression of CKD.
Preventive action and early detection
For AKI, preventive action and early detection are of the utmost importance. This may provide the possibility to control disease progression and predict outcome actively. The current gold standard for diagnosing AKI is still represented by serum creatinine, but this method has significant limitations because it can only detect advanced AKI.
To assess the risk of AKI transition to CKD, it is necessary to find new biomarkers to detect the early stages of AKI and suggest an impaired repair process, not only to detect early AKI but also to help distinguish adaptive renal repair from fibrosis later prognostic markers. Urinary neutrophil gelatinase-associated lipocalin (NGAL) has been used as a marker of early renal tubular injury in some clinical trials in Europe and Asia.
In addition, kidney injury molecule-1 (KIM-1) has been studied as a biomarker of renal tubular injury and can predict CKD development. Tissue inhibitors of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) are commercially available urine biomarkers for AKI risk assessment in critically ill patients and have the potential for further clinical application.
Urinary procollagen type III N-telopeptide (PIIINP), a product of collagen synthesis, maybe a proxy for renal fibrosis. Urinary epidermal growth factor (EGF) was inversely correlated with interstitial fibrosis and had the potential to represent renal repair processes.
In addition, follow-up of AKI is warranted as a secondary or tertiary prevention measure. Studies have shown that most AKI patients lack awareness of their condition and risk factors after discharge from the hospital. The current KDIGO guidelines recommend the evaluation of patients 3 months after AKI. Follow-up management recommendations include patient education, medication adjustments, nephrotoxin avoidance, and renal function monitoring.
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