Whta is the new insight on Acute Kidney Injury?
Mar 17, 2022
Contact: Audrey Hu Whatsapp/hp: 0086 13880143964 Email: audrey.hu@wecistanche.com
Acute kidney injury: current concepts and new insights
Keywords: Acute kidney injury, kidney, renal.
Abstract:
Background: Acute kidney injury, which was previously named acute renal failure, is a complex clinical disorder and continues to be associated with poor outcomes. It is frequently seen in hospitalized patients, especially in critically ill patients. The primary causes of acute kidney injury are divided into three categories: prerenal, intrinsic renal, and postrenal. The definition and staging of acute kidney injury are mainly based on the risk, injury, failure, loss, end-stage kidney disease (RIFLE) criteria, and the acute kidney injury network criteria, which have previously been defined. However, the clinical utility of these criteria is still uncertain. Several biomarkers such as Cystatin C and neutrophil gelatinase-associated lipocalin have been suggested for the diagnosis, severity classification, and most importantly, the modification of outcome in acute kidney injury.
Methods: Current literature on the definition, biomarkers, management, and epidemiology of acute kidney injury was reviewed by searching keywords in Medline and PubMed databases.
Results: The epidemiology, pathophysiology, and diagnosis of acute kidney injury were discussed. The clinical implications of novel biomarkers and management of acute kidney injury were also discussed.
Conclusions: The current definitions of acute kidney injury are based on the RIFLE, acute kidney injury network, and KDIGO criteria. Although these criteria have been widely validated, some limitations remain. Since acute kidney injury is common and harmful, all preventive measures should be taken to avoid its occurrence. Currently, there is no definitive role for novel biomarkers.
Cistanche can avoid acute kidney injury.
Introduction
Acute kidney injury is a complex clinical disorder that is associated with severe morbidity and mortality. Despite technological advances in renal replacement therapy, acute kidney injury continues to be associated with poor outcomes. acute kidney injury is a syndrome of a sudden loss of the kidney's excretory function, often with oliguria, which usually occurs over hours to days. acute kidney injury is common in hospitalized patients, especially in critically ill patients. 1 In the majority of patients, recovery of the kidney function is usually seen; however, many patients remain dialysis-dependent or are left with severe renal impairment. 1,2 Since severe acute kidney injury is associated with a high mortality rate, all preventive measures should be taken to avoid the heavy burden of this common, but usually overlooked, clinical entity.
Epidemiology
In the Kidney Disease Improving Global Outcome (KDIGO) clinical practice guidelines, acute kidney injury is defined as any of the following: increase in serum creatinine (sCr) by≥0.3 mg/dl (≥26.5 µmol/l) within 48 hours; or an increase in serum creatinine to ≥1.5 times baseline, which is known or presumed to have occurred within the preceding 7 days; or a urine volume <0.5 ml/kg/h for 6 hours. 3 The definition and staging of acute kidney injury are based on the risk, injury, failure, loss, end-stage kidney disease (RIFLE) criteria 4 and the acute kidney injury network criteria, 5 which have previously been defined.
The incidence of acute kidney injury varies according to the different patient populations, differences in parameters used for the criteria, and timing of endpoints. In a population-based study of acute kidney injury using the RIFLE criteria, the annual incidence of acute kidney injury was 2147 per million population. 6 This study examined hospitalized patients in whom only sCr had been measured. In another community study, the annual incidence of non-dialysis-requiring and dialysis-requiring acute kidney injury were respectively 3841 and 244 per million population. 7 However, the criteria used for the diagnosis of acute kidney injury were different from the RIFLE criteria, and the baseline creatinine was derived from the lowest creatinine during admission.
Recent hospital studies have reported that 3.2-21 % of all hospitalized patients and up to 50% of patients admitted to the intensive care unit develop acute kidney injury. 8-10
Pathophysiology
Acute kidney injury is now considered to be a broad clinical syndrome encompassing various etiologies, including acute tubular necrosis, pre-renal azotemia, acute interstitial nephritis, acute glomerular and vasculitic renal diseases, and acute postrenal obstructive nephropathy. Some of these conditions may coexist in the same patient. 4,5 Impaired renal blood flow can lead to hypoxic injury to the renal tubular cells by depleting intracellular ATP, disrupting the intracellular calcium homeostasis, infiltration of leukocytes, injuring the endothelium, releasing cytokines and adhesion molecules, and causing apoptosis. 11 However, this ischemic cascade has little clinical relevance to illnesses such as sepsis. 12 Another important characteristic of this ischemic model is the little relevance to periods of decreased perfusion, as can be seen during major surgery, since 80% renal-artery occlusion for 2 h does not lead to sustained renal dysfunction. 13
In acute kidney injury, the renin-angiotensin-aldosterone system, the renal sympathetic system, and the tubuloglomerular feedback system are activated. These circulatory changes induce renal vasoconstriction and lead to increased release of arginine vasopressin, which contributes to water retention. 14
Diagnosis
The clinical evaluation of acute kidney injury includes a careful history and thorough physical examination. Since there is no specific symptom or a sign for acute kidney injury, it is usually diagnosed in the context of another acute illness. The most common sign is oliguria, but it is neither specific nor sensitive. 15 sCr and urea concentrations are the most widely used parameters. In patients with increased sCr concentrations, it is important to distinguish whether the patient has acute kidney injury, chronic kidney disease, or acute illness superimposed on chronic disease. In this context, some diagnostic clues that suggest the presence of chronic kidney disease may be helpful, namely, abnormal sCr before presentation, associated risk factors (eg, hypertension or diabetes), a slow clinical course for presenting illness, and normocytic anemia. Renal ultrasonography may provide evidence of chronic disease with small kidneys. 16
In some cases, acute kidney injury occurs secondary to inflammatory parenchymal diseases such as vasculitis, glomerulonephritis, and interstitial nephritis. In such patients, the clinical features of these diagnoses include systemic manifestations in vasculitis, the presence of macroscopic haematuria in glomerulonephritis, and/or the recent initiation of treatment with a drug known to cause interstitial nephritis should be considered. Malignant hypertension, bilateral cortical necrosis, pyelonephritis, amyloidosis, and nephrotoxins are well-known other causes of parenchymal acute kidney injury. 16
In the absence of obstruction or a clear prerenal cause, urinary microscopy with haematuria, proteinuria or fragmented red cells, red-cell casts, white cell casts, or granular casts and any combination of these factors considerably suggests glomerular pathological changes. Although the sensitivity of the test is poor, urine samples should be tested for eosinophils in the suspicion of interstitial nephropathy. 16
sCr concentrations and plasma urea concentrations are insensitive markers of glomerular filtration rate, as they are modified by nutrition, gastrointestinal bleeding, corticosteroid therapy, high protein diet, muscle mass, age, sex, and aggressive fluid resuscitation. 16,17 Indeed, increased levels of these waste products are observed only when the glomerular filtration rate decreases by more than 50% and does not show dynamic changes in infiltration rates. Due to the limitations of sCr mentioned above, it is not an ideal marker for renal function. However, the sCr level is highly associated with the outcome in patients with acute kidney injury. 18
Drugs and acute kidney injury
In drug-induced acute kidney injury, many patients present with a polyuric state, and thus, a high index of suspicion is needed for the diagnosis. 16,17 Some frequently pre-scribed drugs such as aminoglycosides, amphotericin, non–steroidal anti-inflammatory drugs, methotrexate, cisplatin, ciclosporin, angiotensin-converting-enzyme inhibitors, and angiotensin-receptor blockers seem to be responsible for acute kidney injury in roughly 20% of patients, especially in critically ill patients. 19
An important cause of acute kidney injury is the use of iodinated contrast agents in diagnostic procedures such as angiography. 20 Contrast-induced nephropathy can be prevented by the use of iso-osmolar agents and isotonic saline infusion. 20,21
Novel Biomarkers
As mentioned above, the creatinine level does not detect acute kidney injury promptly. Over the past decade, the discovery and validation of unique biomarkers of kidney injury have gained significant interest. Among these biomarkers, neutrophil gelatinase-associated lipocalin (NGAL) and Cystatin C are the most frequently studied. These promising markers seem to change earlier than sCr concentrations do, by showing different aspects of renal injury. For example, Cystatin C concentrations are related to changes in glomerular filtration rate, 22 whereas concentrations of NGAL are related to tubular stress or injury. 23 Changes in these biomarkers with treatment or recovery suggest that they can also be used to monitor interventions. 24 Furthermore, they can distinguish a majority of patients who do not have acute kidney injury according to creatinine-based criteria but have a degree of kidney stress or injury that is associated with worse outcomes. 25
Cystatin C is now considered a superior marker when compared with sCr in both animal models and clinical settings of chronic kidney disease. 26,27 However, it is unclear whether the value of cystatin C is generalizable to all forms of acute kidney injury or not. Moreover, the analysis of cystatin C is affected by diabetes, hyperthyroidism, inflammation, large doses of corticosteroids, hyperbilirubinemia, rheumatoid factor, and hypertriglyceridemia. 28
NGAL is the most extensively studied renal biomarker and it has been demonstrated in a recent meta-analysis that serum and urine NGAL levels are
not only diagnostic of acute kidney injury, but that they have also predicted the clinical outcomes, such as the need for initiation of dialysis, and mortality. 25
To date, several other biomarkers such as microalbumin, N-acetyl-ß-D-glucosaminidase, kidney injury molecule-1, interleukin-18, liver fatty acid-binding protein, netrins, and nestin have been studied for the diagnosis, severity classification, and most importantly, the modification of the outcome in acute kidney injury. 29,30 However, more clinical studies will be required to prove the true superiority and cost effectivity of novel biomarkers over creatinine.
General Management
Since there is no established pharmacotherapy for acute kidney injury, all preventive measures should be taken to prevent its occurrence. For example, if pre-renal factors contribute, they should be identified and rapid administration of intravenous fluids should be quickly undertaken. In this regard, the association between a positive fluid balance and increased 60-day mortality should be kept in mind. 31 In fluid-resuscitated critically ill patients with pronounced oliguria or anuria, the avoidance of fluid overload can be provided by the initiation of renal replacement therapy at an early stage. 16
Central volume status can be monitored by physical examination, central venous pressure, and measurement of blood pressure and heart rate. Nutritional support should be started as early with adequate calories, protein, trace elements, and vitamins. 17
Hyperkalemia should be treated with insulin, dextrose, a bicarbonate infusion, and/or nebulized salbutamol. If the serum potassium concentration is higher than 7 mmol/L or if electrocardiographic signs of hyperkalemia are present, 10 ml of 10% calcium gluconate should also be given intravenously. 16,17
As the nephroprotective effect of renal-dose or low-dose dopamine has been refuted by findings from several systematic reviews, the use of this strategy is not recommended. 17,32,33
Although loop diuretics such as furosemide and bumetanide are commonly used in the management of acute kidney injury, their use is not recommended for the prevention or treatment of acute kidney injury, except in the management of volume overload. 17
Renal replacement therapy
When deciding for renal replacement therapy (RRT), the clinicians must consider some factors such as potassium, creatinine, and urea concentrations; fluid status; urine output; the overall course of the patient’s illness; and the presence of other complications.
Absolute indications for initiation of RRT: 16
1. Anuria (negligible urine output for 6h)
2. Severe oliguria (urine output <200 ml over 12h)
3. Hyperkalemia (potassium concentration >6.5mmol/L)
4. Severe metabolic acidosis (pH<7.2 despite normal or low partial pressure of carbon dioxide in arterial blood)
5. Volume overload (especially pulmonary edema unresponsive to diuretics)
6. Pronounced azotemia (urea concentrations >30 mmol/L or creatinine concentrations >300 µmol/L)
7. Clinical complications of uremia (eg, encephalopathy, pericarditis, neuropathy)
Since the only studies linking timing with the outcome are observational, the optimal time to start RRT is still debatable. 34,35 The available forms of RRT include: continuous, intermittent, and peritoneal dialyzes. Continuous RRT includes filtration alone (ie, continuous venous-venous haemofiltration) or diffusion alone (eg, continuous venovenous hemodialysis), or both (eg, continuous venovenous haemodiafiltration). 16 Since no randomized controlled trials are comparing intermittent or continuous RRT intermittent hemodialysis, slow low-efficiency dialysis, with continuous RRT, all seem to be acceptable options. 36
As it is unclear, the Acute Renal Trial Network (ATN) 37 and Randomised Evaluation of Normal versus Augmented Level of Renal Replacement Trial (RENAL) 38 studies
have been designed to investigate the appropriate intensity of RRT. Both have shown no difference in survival rates with increasing intensity of RRT. The current evidence suggests that the prescribed dose of RRT should be equivalent to 20-30 ml/kg/h of continuous RRT or intermittent RRT three times weekly. This requires careful monitoring as there is often a significant reduction in the dose delivered versus prescribed. Hemodynamically unstable patients should preferably receive continuous RRT. 37,38,39
Conclusion
Since acute kidney injury is common, harmful, and treatable, all efforts should be focused on minimizing the causes of acute kidney injury, on increasing awareness of the importance of serial measurements of sCr in high-risk patients, and on documenting the urine volume in acutely ill patients to achieve early diagnosis; there is as yet no definitive role for alternative biomarkers.
References
The source is by Yavuzer Koza, Department of Cardiology, Ataturk University Faculty of Medicine, Erzurum, Turkey
