Acute Tubular Necrosis

Click here to load reader

Embed Size (px)

Transcript of Acute Tubular Necrosis

  • 1. Introduction = , Background (ARF) Biomarkers :ARF = o o : BUN (blood urea nitrogen) serum o creatinine, ARF = , (GFR). BUN AND THIS has or intrinsic ARF = posed a major limitation to epidemiologic studies. = In 2002, the Acute Dialysis Quality Initiative (ADQI) was created with the primary goal of developing consensus- and evidence-based guidelines for the treatment and [ Acute tubular necrosis] prevention of ARF. (ATN) = The first order of business was to create a uniform, accepted definition of ARF; hence the RIFLE (Risk of renal dysfunction, Renal biopsy findings are shown below.Injury to the kidney, Failure or Loss of kidney function, and End-stage renal disease [ESRD]) criteria were born.RIFLE = RISK OF FAILURE LOSS END STAGE A photomicrograph of renal biopsy shows renal medulla, which is composed mainly of renal tubules. Patchy or diffuse denudation of the renal tubular cells is observed, suggesting acute tubular necrosis (ATN) as the cause of acute renal failure (ARF).When the failure classification is achieved by UO criteria, the designation of RIFLE-FO is used to denote oliguria. The initial stage, risk, has high sensitivity; more patients will be classified in this mild category, including some who do not actually have renal failure. Progression through the increasingly severe stages of RIFLE is marked by decreasing sensitivity and increasing specificity.Classification of AKIIn September 2004, the Acute Kidney Injury Network (AKIN) was formed. The group consists of well-renowned nephrologists and intensivists (including members of ADQI and representatives from the American Society of Nephrology, the International Society of Nephrology, the National Kidney Foundation, the European Society of Intensive Care Medicine, and the Society of Critical Care Medicine), ATN = 2 each representing a major clinical nephrology or critical care society. , Among its proposals, AKIN has advised that the term acute kidney 2 injury (AKI) be used to represent the full spectrum of renal injury, from mild to severe, with the latter having increased likelihood for2 unfavorable outcomes (eg, loss of function and ESRD). : , :[ ]

2. This has led to research to find more accurate kidney function Definition and diagnostic criteria for acute kidneybiomarkers (serum and/or urine).4injuryMost likely a handful of kidney function biomarkers exist, rather A report by the AKIN proposed the following criteria for than a single one. It is hoped that such biomarkers, onceidentified, will permit early diagnoses, as well as aid in rendering acute kidney injury:appropriate treatment strategies long before permanent damagehas set in. 48o to 0.3 mg/dL ( 26.4 mol/L) o =>50% (1.5-fold from baseline) o 3 g is administered) and duration of therapy, hospitalization in the critical care unit at the initiation of renal insufficiency may show a further decline in therapy, and concomitant use of cyclosporine.renal function. o Prevention is key in amphotericin Bo Prevention is important in the management of CIN. nephrotoxicity. By saline loading, maintenance Some investigators recommend the avoidance of of a high urine flow rate has been shown to be contrast-requiring procedures, if at all possible. helpful. Likewise, various lipid formulations of Magnetic resonance imaging (MRI) studies usually amphotericin B have been developed, namely,necessitate the use of gadolinium as a contrast amphotericin B colloid dispersion (ABCD), amphotericin agent, which, in several studies, has been shown to B complex (ABLC), and liposomal amphotericin B; these lipid formulations are believed to be less nephrotoxic be less nephrotoxic than conventional contrast intrinsically. Whereas amphotericin B is suspended in bile media. salt deoxycholate, which has a detergent effect on cello Other risk factors should be corrected, including membranes, such lipid formulations do not containsaline infusion to correct volume depletion and deoxycholate. The lipid formulations also bind more avidly to fungal cell wall ergosterol as opposed to thediscontinuation of potential nephrotoxic agents, cholesterol in human cell membranes. Liposomal such as NSAIDs and COX-2 inhibitors. In those amphotericin B is preferred in patients with renal patients with underlying volume depletion, insufficiency or evidence of renal tubular dysfunction.withholding ACE inhibitors and/or angiotensin 8. receptor blockers may even be necessary. Using o Similarly, theophylline, an adenosine antagonist, the lowest possible amount of contrast media in thewith a similar mechanism of action as NAC, is procedure is also recommended. viewed as another potential agent to prevent CIN; o To date, several interventions have been suggested the main difference being the lower risk profile to decrease the risk of CIN, such as furosemide, associated with the latter. mannitol, dopamine, and fenoldopam, but none ofo Aside from the recommended prophylactic these agents have been shown to be significantly medications discussed above, other guidelines effective. The use of N -acetylcysteine (NAC) as a recommend withholding NSAIDs, COX inhibitors, prophylactic agent has gained popularity; based on diuretics, ACE inhibitors, and angiotensin receptor the theory that contrast media cause direct renalantagonists at least 24 hours before and after the tubular epithelial cell toxicity as a result ofprocedure. Metformin should be withheld at least exposure to reactive oxygen species (ROS), NAC 48 hours before the procedure and until CIN has is believed to have antioxidant properties thatbeen ruled out. potentially counteract the effects of ROS. o Cyclosporine and tacrolimus (calcineurin o Based on what is known now, making a strong, inhibitors): These drugs cause ARF by inducing evidence-based recommendation for the use of afferent arteriolar vasoconstriction. Usually, renal NAC in the prevention of CIN is not possible.insufficiency is easily reversed by a reduction of Recognizing that NAC is inexpensive and is not the dosage. On the other hand, persistent injury can associated with significant complications, in thelead to interstitial fibrosis. absence of other effective pharmacologic therapy,o Clinically, patients may present with hypertension. its use in clinical practice is not entirely They may also be hyperkalemic and have tubular inappropriate. Additional large randomized injury induced urinary wasting of phosphate and controlled trials of NAC are needed to better define magnesium. its proper role in preventing CIN. o Tacrolimus has been shown to cause thrombotic o Several studies have looked at the possibility ofmicroangiopathy as a result of endothelial injury. using theophylline as a prophylactic agent. Based on the idea that contrast media causes local release Others: Cisplatin, ifosfamide, foscarnet, and of adenosine, a known vasoconstrictor, and pentamidine are other causes of drug-induced considered by some to have a potential role in the tubular toxicity. pathogenesis of CIN, theophylline is a known adenosine antagonist. Although theophyllineo Cisplatin usually affects the proximal and distal appears to be promising, just as with NAC, further tubules. Characteristically, it is associated with randomized trials are required to show any provenurinary wasting of magnesium. Cisplatin causes benefit of theophylline in the prevention of CIN.the release of toxic hydroxyl radicals when o The prevention of contrast nephrotoxicity haschloride ions in the cis position are replaced by received attention. In susceptible patients, the use water. The key is prevention by volume loading of nonionic, low-osmolar contrast media reduceswith saline. Some investigators advocate the use of the likelihood of clinical nephrotoxicity. Isotonicamifostine, a thiol donor that serves as an saline, given at 1 mL/kg of body weight/h for 24 antioxidant. Others prefer using carboplatin, a less hours, starting on the morning of the contrast-nephrotoxic alternative. requiring procedure, has been shown to be superior o Ifosfamide usually causes a Fanconi syndrome to half normal saline infusions. A single center,(proximal tubule dysfunction) presentation with randomized, controlled trial demonstrated that significant hypokalemia. It is a known analog of isotonic sodium bicarbonate (3 mL/kg of body cyclophosphamide. While the latter is not weight/h given 1 h prior to the contrast-requiring nephrotoxic, ifosfamide, by virtue of its metabolite procedure and then continued at 1 mL/kg of bodychloroacetaldehyde, is, with preferential weight/h for 6 h postprocedure) may offer even involvement of the proximal tubule. greater protection than isotonic sodium chloride.o Foscarnet is used to treat resistant cytomegalovirus The postulated mechanism is being attributed to(CMV) infections. It causes acute interstitial the inhibition of oxidant injury by the administered nephritis and intratubular crystal obstruction. It is alkali.notable for inhibiting proximal tubular o Studies have also suggested that pretreatment with reabsorption of phosphate (leading to oral NAC (600 mg or 1200 mg bid on the day prior hypophosphatemia) by virtue of it being a and on the day of the contrast-requiring procedure)phosphate analog. Hypocalcemia is also noted, acts as an antioxidant, scavenging ROS, therebysecondary to chelation of calcium. reducing the nephrotoxicity of contrast media. 9. o Pentamidine is used to treat Pneumocystis carinii hyperuricemia are characteristic. Calcium tends to infection in individuals who aredeposit in the injured muscle, thereby leading to immunocompromised. Risk factors for hypocalcemia. Such deposited calcium is nephrotoxicity include volume depletion and eventually released back into the circulation during concomitant use of other nephrotoxic antibiotic the recovery ph