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Acute Tubular Necrosis
Acute Tubular Necrosis
Acute Tubular Necrosis
Acute Tubular Necrosis
Acute Tubular Necrosis
Acute Tubular Necrosis
Acute Tubular Necrosis
Acute Tubular Necrosis
Acute Tubular Necrosis
Acute Tubular Necrosis
Acute Tubular Necrosis
Acute Tubular Necrosis
Acute Tubular Necrosis
Acute Tubular Necrosis
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Acute Tubular Necrosis

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  • 1. Introduction ΣΚΟΠΟΣ ΤΟΥ ΠΑΡΟΝΤΟΣ ΑΡΘΡΟΥ = Η ΕΠΙΚΕΝΤΡΩΣΗ ΣΤΗΝ ΠΑΘΟΦΥΣΙΟΛΟΓΙΑ, ΔΙΑΓΝΩΣΗ ΚΑΙ ΔΙΑΧΕΙΡΗΣΗ ΤΗΣ ΟΞΕΙΑΣ Background ΣΩΛΗΝΑΡΙΑΚΗΣ ΝΕΚΡΩΣΗΣ ΤΑ ΑΙΤΙΑ ΟΞΕΙΑΣ ΝΕΦΡΙΚΗΣ ΑΝΕΠΑΡΚΕΙΑΣ (ARF) ΣΥΜΒΑΤΙΚΑ Biomarkers ΤΑΞΙΝΟΜΟΥΝΤΑΙ ΣΕ : ARF = ΟΡΙΖΕΤΑΙ ΩΣ ΑΠΟΤΟΜΗ ΕΛΑΤΤΩΣΗ ΤΗΣ ΝΕΦΡΙΚΗΣ o ΠΡΟΝΕΦΡΙΚΑ ΛΕΙΤΟΥΡΓΙΚΟΤΗΤΑΣ ΠΟΥ ΤΕΚΜΗΡΙΩΝΕΤΑΙ ΜΕ ΑΥΞΗΣΗ ΣΤΙΣ o ΝΕΦΡΙΚΑ ΣΥΓΚΕΝΤΡΩΣΕΙΣ ΤΩΝ : BUN (blood urea nitrogen) ΚΑΙ serum o ΜΕΤΑΝΕΦΡΙΚΑ creatinine, ΣΕ ΔΙΑΣΤΗΜΑ ΩΡΩΝ ΕΩΣ ΗΜΕΡΩΝ ΕΩΣ ΕΒΔΟΜΑΔΩΝ ΚΑΙ ΣΥΝΗΘΩΣ ΕΙΝΑΙ ΠΡΟΝΕΦΡΙΚΗ ARF = ΦΥΣΙΟΛΟΓΙΚΟΣ, ΛΕΙΤΟΥΡΓΙΚΟΣ ΝΕΦΡΟΣ Ο ΟΠΟΙΟΣ ΑΝΤΑΠΟΚΡΙΝΕΤΑΙ ΣΕ ΧΑΜΗΛΗ ΠΑΡΟΧΗ ΚΑΙ ΔΕΝ ΥΠΑΡΧΕΙ ΟΜΟΦΩΝΙΑ ΣΤΗΝ ΑΠΟΛΥΤΗ ΑΥΞΗΣΗ ΤΩΝ ΜΕΙΩΝΕΙ ΤΟ ΡΥΘΜΟ ΣΠΕΙΡΑΜΑΤΙΚΗΣ ΔΙΗΘΗΣΗΣ (GFR). ΣΥΓΚΕΝΤΡΩΣΕΩΝ ΚΡΕΑΤΙΝΙΝΗΣ ΚΑΙ BUN ΠΟΥ ΝΑ ΟΡΙΖΟΥΝ ΤΟΗ ΕΓΚΑΤΕΣΤΗΜΕΝΗ ΣΩΛΗΝΑΡΙΑΚΗ ΝΕΚΡΩΣΗ AND THIS has ΝΕΦΡΙΚΗ or intrinsic ARF = ΕΝΔΟΝΕΦΡΙΚΟ ΑΙΤΙΟ posed a major limitation to epidemiologic studies. ΜΕΤΑΝΕΦΡΙΚΗ = ΑΠΟΦΡΑΞΗ ΚΑΠΟΥ ΣΤΗΝ ΟΥΡΟΦΟΡΟ In 2002, the Acute Dialysis Quality Initiative (ADQI) was ΟΔΟ created with the primary goal of developing consensus- and evidence-based guidelines for the treatment and ΟΞΕΙΑ ΣΩΛΗΝΑΡΙΑΚΗ ΝΕΚΡΩΣΗ [ Acute tubular necrosis] prevention of ARF. (ATN) = ΤΟ ΠΛΕΟΝ ΚΟΙΝΟ ΑΙΤΙΟ ΕΝΔΟΝΕΦΡΙΚΗΣ ΟΞΕΙΑΣ ΑΝΕΠΑΡΚΕΙΑΣ 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 AKI In 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 = ΤΟ 2Ο ΠΛΕΟΝ ΚΟΙΝΟ ΑΙΤΙΟ ΟΝΑ ΣΕ each representing a major clinical nephrology or critical care society. ΕΝΔΟΝΟΣΟΚΟΜΕΙΑΚΟΥΣ ΑΣΘΕΝΗΣ, ΜΕΤΑ ΤΗΝ ΠΡΟΝΕΦΡΙΚΗ Among its proposals, AKIN has advised that the term acute kidney ΑΖΩΘΑΙΜΙΑ – ΣΕ ΕΞΩΤΕΡΙΚΟΥΣ ΑΣΘΕΝΗΣ ΤΟ 2Ο ΠΛΕΟΝ injury (AKI) be used to represent the full spectrum of renal injury, ΚΟΙΝΟ ΑΙΤΙΟ ΜΕΤΑ ΤΗΝ ΑΖΩΘΑΙΜΙΑ ΕΙΝΑΙ Η ΑΠΟΦΡΑΞΗ from mild to severe, with the latter having increased likelihood for 2 unfavorable outcomes (eg, loss of function and ESRD). ΣΠΕΙΡΑΜΑΤΟΝΕΦΡΙΤΙΔΑ ΔΙΑΜΕΣΗ ΝΕΦΡΙΤΙΔΑ : ΔΥΝΑΤΟ ΕΚΔΗΛΩΝΟΝΤΑΙ ΔΙΚΗΝ ΟΞΕΙΑΣ ΝΕΦΡΙΚΗΣ ΑΝΕΠΑΡΚΕΙΑΣ ΠΡΟΣ ΤΕΚΜΗΡΙΩΣΗΣ ΤΟΥ ΥΠΟΚΕΙΜΕΝΟΥ ΑΙΤΟΥ ΤΗΣ ΟΝΑ, ΑΞΙΟΛΟΓΟΥΝΤΑΙ ΤΑ ΚΑΤΩΘΙ : [ ΙΣΤΟΡΙΚΟ – ΣΗΜΕΙΑ – ΕΡΓΑΣΤΗΡΙΑΚΑ – ΥΠΕΡΗΧΟΣ ΝΕΦΡΟΥ – ΟΥΡΟΛΟΓΙΚΗ ΕΞΕΤΑΣΗ ]
  • 2. This has led to research to find more accurate kidney function Definition and diagnostic criteria for acute kidney biomarkers (serum and/or urine). 4 injury Most 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, once identified, will permit early diagnoses, as well as aid in rendering acute kidney injury: appropriate treatment strategies long before permanent damage has set in. ΑΠΟΤΟΜΗ ΛΕΙΤΟΥΡΓΙΚΗ ΕΛΑΤΤΩΣΗ ΕΝΤΟΣ 48ΩΡΟΥ o to 0.3 mg/dL (≥ 26.4 μmol/L) o ΑΥΞΗΣΗ ΚΡΕΑΤΙΝΙΝΗΣ =>50% (1.5-fold from baseline) o ΟΛΙΓΟΥΡΙΑ <= than 0.5 mL/kg per hour for more than six hours Several previously identified molecules—including : ΚΡΙΤΗΡΙΑ RIFLE : o N-acetyl-β-glucosaminidase, o β2 -microglobulin, 3 ΣΤΑΔΙΑ ΟΞΕΙΑΣ ΒΛΑΒΗΣ o α1 -microglobulin, and o retinol binding protein o ΠΡΟΔΙΑΘΕΣΗ o ΒΛΑΒΗ have led to the discovery of potential biomarkers, such as : o ΑΝΕΠΑΡΚΕΙΑ o kidney injury molecule 1 (KIM-1), 2 ΕΚΒΑΣΕΙΣ : o human neutrophil gelatinase-associated lipocalin (NGAL), o interleukin-18 (IL-18), o ESRD = END STAGE RENAL DISEASE o cystatin C, o ΑΠΩΛΕΙΑ ΝΕΦΡΙΚΗΣ ΛΕΙΤΟΥΡΓΙΑΣ o clusterin, fatty acid binding protein, and o osteopontin. ΤΟ ΜΕΓΕΘΟΣ ΤΗΣ ΒΛΑΒΗΣ ΒΑΣΙΖΕΤΑΙ Although the discovery of new biomarkers could revolutionize our understanding of AKI, prospective clinical trials will be needed to ΣΤΗ ΣΥΓΚΕΝΤΡΩΣΗ ΤΗΣ ΚΡΕΑΤΙΝΙΝΗΣ compare them to each other over a period of many months and to ‘Η / ΚΑΙ ΣΤΟΝ (GFR) investigate such factors as their natural tendencies to occur in ‘Η / ΚΑΙ ΣΤΟΝ ΟΓΚΟ ΟΥΡΩΝ certain disease states or in periods of high stress and their occurrence in specific demographics. these are the most commonly used markers of renal function. It must be recognized, however, that such markers are imperfect. ΔΕΝ ΕΙΝΑΙ ΕΥΙΚΤΟΣ Ο ΠΡΟΣΔΙΟΡΙΣΜΟΣ ΤΗΣ ΥΠΟΚΕΙΜΕΝΗΣ ΒΛΑΒΗΣ ΜΕ ΤΙΣ ΩΣ ΑΝΩ ΠΑΡΑΠΜΕΤΡΟΥΣ NGAL ΠΑΡΟΜΟΙΩΣ Η ΔΙΑΧΕΙΡΗΣΗ / ΧΟΡΗΓΗΣΗ ΥΓΡΩΝ ΘΑ ΜΕΤΑΒΑΛΛΕΙ ΤΟΝ ΚΥΚΛΟΦΟΡΟΥΝΤΑ ΟΓΚΟ ΥΓΡΩΝ, The exact physiologic role played in the kidney by NGAL (also ΕΠΗΡΕΑΖΟΝΤΑΣ ΤΙΣ ΜΕΤΡΟΥΜΕΝΕΣ ΣΥΓΚΕΝΤΡΩΣΕΙΣ ΚΡΕΑΤΙΝΙΝΗΣ, ΑΛΛΟΙΟΝΟΝΤΑΣ ΤΗΝ ΣΥΣΧΕΤΙΣΗ ΜΕ ΤΗΝ called lipocalin - 2 or siderocalin), a 25-kD protein, remains a ΠΡΑΓΜΑΤΙΚΗ ΝΕΦΡΙΚΗ ΛΕΙΤΟΥΡΓΙΑ ΣΕ ΑΛΗΘΙΝΟ ΧΡΟΝΟ mystery. One possibility, however, is that it is involved in renal morphogenesis, eg, induction of repair and reepithelialization. It has been shown to be elevated in the plasma and urine of ΕΠΙΣΗΣ ΔΥΝΑΤΟ ΝΑ ΥΦΙΣΤΑΤΑΙ ΣΗΜΑΝΤΙΚΟ ΧΡΟΝΙΚΟ animal models of ischemic and nephrotoxic acute kidney injury, ΔΙΑΣΤΗΜΑ ΩΡΩΝ ΕΩΣ ΗΜΕΡΩΝ ΑΠΟ ΤΗΝ ΑΛΛΑΓΗ ΣΤΙΣ ΩΣ and hence is considered by some to be a novel urinary ΑΝΩ ΜΕΤΑΒΛΗΤΕΣ ΚΑΙ ΤΗΝ ΕΓΚΑΤΑΣΤΑΣΗ ΑΝΑΤΟΜΙΚΗΣ / biomarker for ischemic injury.5 ΔΟΜΙΚΗΣ ΒΛΑΒΗΣ The expression of the NGAL mRNA (messenger ribonucleic Knowing the above limitations of currently used kidney acid) and protein in the kidney has been shown to be function markers, it is accepted that they may be unable to significantly increased in the kidney tubules of patients with detect any acute injury or process; in fact, their levels may rise ischemic, septic, or post-transplantation AKI,6 as well as within coincident with a late period in the injury process. 2-6 hours post–cardiopulmonary bypass surgery,7 at frequent intervals for 24 hours post–cardiopulmonary bypass surgery in children,8 and even following contrast administration.9
  • 3. Urinary NGAL expression has been suggested as an early and tested (the current NHE3 assay being particularly marker of AKI in children, although the results in adults have cumbersome, requiring ultracentrifugation and Western blot been less convincing.10 analysis.15 ) IL-18 Conclusion A candidate biomarker for renal parenchymal injury, the Further research (phase 4 clinical trials) will be needed for cytokine interleukin-18 (IL-18), is formed in the proximal the development and clinical validation of new biomarkers for tubules and detected in the urine.11 It has been shown in animal the eventual definition of kidney injury. Such trials will require models to exacerbate tubular necrosis; neutralizing antibodies large cohorts of subjects; some trials are already underway in formed against IL-18 were found to reduce renal injury in government- and industry- sponsored studies. mice. As these new biomarkers evolve, so will our understanding of Parikh et al12 determined that patients with ATN had AKI. The work of Parikh et al has shown that some of these significantly higher levels of IL-18 in their urine than did biomarkers might enable the distinction between prerenal control subjects or persons with other forms of kidney azotemia, ATN, and other glomerular disorders.12 disease. On the other hand, patients with delayed graft function during the immediate post-transplantation period had Ultimately, the goal of biomarker research is the early higher urinary levels of IL-18 than did patients who had diagnosis of AKI (within hours, rather than within days or immediate graft function. weeks). In that way, appropriate preventative and preemptive strategies, as well as treatment regimens, can be rendered at After evaluating the potential use of such biomarkers in a phase whereby permanent loss of function can be avoided, patients with AKI (post-cardiopulmonary bypass), there has making AKI truly reversible. been some suggestion that urinary levels of NGAL and IL-18 may be sequential markers; NGAL levels peak within the first 2-4 hours following AKI, while IL-18 peaks at the 12th hour. KIM-1 Another molecule that is upregulated in post–ischemic injury in Pathophysiology the proximal tubule is KIM-1. Urinary KIM-1 has been suggested as another biomarker for the diagnosis of ischemic Acute tubular necrosis ATN.13 ATN usually occurs after an acute ischemic or toxic It has been suggested that high urinary KIM-1 may be an independent predictor (versus creatinine clearance, event, and it has a well-defined sequence of events. proteinuria, or donor age) for graft loss in post–renal transplantation patients.14 The initiation phase is characterized by an acute decrease in GFR to very low levels, with a sudden Cystatin C increase in serum creatinine and blood urea nitrogen (BUN) concentrations. Cystatin C is a 13-kD cysteine protease inhibitor that has gained popularity as an alternative to serum creatinine in the The maintenance phase is characterized by a sustained measurement of renal function of GFR. In contrast to the 3 severe reduction in GFR, and this phase continues for previously discussed biomarkers, however, serum cystatin C a variable length of time, most commonly 1-2 weeks. levels are usually noted when the tissue injury has led to significant changes in the kidneys’ filtration function or capability. This is the same drawback that is encountered with Because the filtration rate is so low during the serum creatinine. maintenance phase, the creatinine and BUN continue to rise. Sodium/hydrogen exchanger isoform 3 (NHE3) The recovery phase, in which tubular function is NHE3 is the most abundant apical membrane sodium restored, is characterized by an increase in urine transporter in the proximal tubules. Believed to be shed into volume (if oliguria was present during the the urine after tubular injury, it is analogous to serum maintenance phase) and by a gradual decrease in BUN troponins after cardiac muscle injury. and serum creatinine to their preinjury levels. In one study, it was shown that urinary NHE3 proved to be a better gauge than did the time-honored fractional excretion Ischemic acute tubular necrosis of sodium (FENa) in distinguishing prerenal versus intrinsic kidney failure. A clinical assay is yet waiting to be developed
  • 4. Ischemic ATN is often described as a continuum of This loss of epithelial cell barrier can result in the prerenal azotemia. above-mentioned back leak of filtrate. Indeed, the causes of the 2 conditions are the same Another change is relocation of Na+/K+ -ATPase (see Causes). pumps and integrins to the apical membrane. Ischemic ATN results when hypoperfusion Cell death occurs by both necrosis and apoptosis. overwhelms the kidney's autoregulatory defenses. Sloughing of live and dead cells occurs, leading to cast Under these conditions, hypoperfusion initiates cell formation and obstruction of the tubular lumen. See injury that often, but not always, leads to cell death. the images below. Injury of tubular cells is most prominent in the straight portion of the proximal tubules and in the thick ascending limb of the loop of Henle, especially as it dips into the relatively hypoxic medulla. The reduction in GFR that occurs from ischemic injury is a result not only of reduced filtration due to hypoperfusion but also of casts and debris obstructing the tubule lumen, causing back leak of filtrate through the damaged epithelium (ie, ineffective filtration). Acute tubular necrosis. Intratubular cast formation. In addition, ischemia leads to decreased production of vasodilators (ie, nitric oxide, prostacyclin [PGI2]) by the tubular epithelial cells, leading to further vasoconstriction and hypoperfusion. On a cellular level, ischemia causes depletion of adenosine triphosphate (ATP), an increase in cytosolic calcium, free radical formation, metabolism of membrane phospholipids, and abnormalities in cell volume regulation. The decrease or depletion of ATP leads to many problems with cellular function, not the least of which is active membrane transport. Acute tubular necrosis. Intratubular cast formation. With ineffective membrane transport, cell volume and electrolyte regulation are disrupted, leading to cell swelling and intracellular accumulation of sodium and calcium. Typically, phospholipid metabolism is altered, and membrane lipids undergo peroxidation. In addition, free radical formation is increased, producing toxic effects. Damage inflicted by free radicals apparently is most severe during reperfusion. The earliest changes in the proximal tubular cells are apical blebs and loss of the brush border membrane followed by a loss of polarity and integrity of the tight Sloughing of cells, which is responsible for the formation of granular casts, a feature of junctions. acute tubular necrosis (ATN).
  • 5. of patients admitted. Prerenal causes are responsible The maintenance phase of ATN is characterized by a for approximately half of all cases. The frequency of stabilization of GFR at a very low level, and it each type of intrinsic renal disease varies depending on typically lasts 1-2 weeks. the population studied, but ATN (other than prerenal azotemia) is the most common cause of ARF in Complications (eg, uremic and others, see hospitalized patients. Complications) typically develop during this phase. Mortality/Morbidity The mechanisms of injury described above may contribute to continued nephron dysfunction, but As with other causes of ARF, complications associated tubuloglomerular feedback also plays a role. with ATN are often life threatening. The in-hospital survival rate of patients with ATN is approximately Tubuloglomerular feedback in this setting leads to 50%, with about 30% of patients surviving for 1 year. constriction of afferent arterioles by the macula densa Factors that are associated with an increased mortality cells, which detect an increased salt load in the distal rate include poor nutritional status, male sex, the tubules. presence of oliguria, the need for mechanical ventilation, acute myocardial infarction, stroke, or The recovery phase of ATN is characterized by seizures. regeneration of tubular epithelial cells.16 Disturbances in fluid and electrolyte balance During recovery, an abnormal diuresis sometimes occurs, causing salt and water loss and volume o Hyperkalemia can be associated with life- depletion. The mechanism of the diuresis is not threatening cardiac arrhythmias (see completely understood, but it may in part be due to the Complications). delayed recovery of tubular cell function in the setting o Salt and water retention often leads to of increased glomerular filtration. hypertension, edema, and congestive heart failure (CHF). In addition, continued use of diuretics (often o Hyponatremia causes concern because of its effects administered during initiation and maintenance on the central nervous system. phases) may also add to the problem. o Other electrolyte disturbances include hyperphosphatemia, hypocalcemia, and Nephrotoxic acute tubular necrosis hypermagnesemia. o Metabolic acidosis Most of the pathophysiologic features of ischemic ATN are shared by the nephrotoxic forms. Uremia results from the accumulation of nitrogenous waste. It is a potentially life- Thus, the cellular events described above apply to threatening complication associated with ARF. nephrotoxic ATN as well. o Neurologic impairment and pericarditis can occur. Nephrotoxic ATN has induction, maintenance, and o Platelet dysfunction is common and can lead to recovery phases, and recovery can be associated with life-threatening hemorrhage. an abnormal diuresis as is described above in ischemic ATN. Infections Nephrotoxic injury to tubular cells occurs by multiple o For ARF, the mortality rate is 20-50% in patients mechanisms. These include direct drug toxicity, with underlying medical illnesses, but the mortality intrarenal vasoconstriction, and intratubular rate is as high as 60-70% with patients in a surgical obstruction. setting. If multiorgan failure is present, especially severe hypotension or acute respiratory distress Frequency syndrome, the mortality rate ranges from 50-80%. o With dialysis intervention, the frequency of United States uremia, hyperkalemia, and volume overload as causes of death have decreased. The most common The syndrome of ARF is observed in about 5% of all causes of death now are sepsis, cardiovascular and hospital admissions. In the ICU, it occurs in up to 30%
  • 6. pulmonary dysfunction, and withdrawal of life support. o Angiotensin II and prostaglandins play central roles in the maintenance of GFR in the face of volume depletion. ACE Clinical inhibitors and angiotensin receptor blockers have gained popularity not only as antihypertensive agents but also as renoprotective agents that either slow or halt the progression of History diabetic and nondiabetic kidney disease. They have also been shown in several studies to have a role in CHF as well as The patient's history is very important in the diagnosis of ATN. It ventricular remodeling. The use of these agents is limited by the frequently reveals recent hypotension, sepsis, muscle necrosis, or tendency to cause prerenal failure, especially in patients who are volume depletion, as well as exposure to nephrotoxic agents. ATN is considered to be at high risk; risk factors include advanced age, more likely to occur in patients with a history of recent surgery, underlying renovascular disease, concomitant use of diuretics or sepsis, or hypovolemia. The history is also important in establishing vasoconstrictors, such as nonsteroidal anti-inflammatory drugs risk factors for the development of ATN. (NSAIDs), COX-2 inhibitors, and calcineurin inhibitors, and elevated baseline serum creatinine. Physical o Serum creatinine and electrolytes, especially potassium, should be measured before and at least Physical examination findings may be unremarkable because 1 week after starting or changing the dose of the medication. An increase in serum creatinine of greater than 0.5 ARF is often found incidentally during routine laboratory mg/dL if the initial serum creatinine is less than 2.0 mg/dL, or an studies (ie, elevated BUN and creatinine levels). However, if increase in serum creatinine of greater than 1.0 mg/dL if the symptoms are present, they may include a pericardial friction baseline serum creatinine is greater than 2.0 mg/dL, has been rub, asterixis, and/or excoriation marks related to uremic suggested as a threshold for discontinuation of therapy. An pruritus. Hypertension or edema may be noted. Otherwise, the increase in serum creatinine of up to 30% is acceptable, but a physical examination findings are more likely to reflect the continued rise of over 30% should prompt immediate underlying disease process. discontinuation of the medication. Alternatively, discontinuation of ACE inhibitor or angiotensin receptor blocker therapy is not necessary if smaller increases in serum creatinine occur. If and Causes when prerenal ARF does develop, one should commence looking for underlying heart disease, volume depletion, hypotension, ATN is generally caused by an acute event, either concomitant use of vasoconstrictors, or renovascular disease. ischemic or toxic. Nephrotoxic acute tubular necrosis Ischemic acute tubular necrosis The kidney is a particularly good target for toxins. Not only does it have a rich blood supply, receiving 25% Ischemic ATN may be considered part of of cardiac output, but it also helps in the excretion of the spectrum of prerenal azotemia, and, these toxins by glomerular filtration and tubular indeed, ischemic ATN and prerenal secretion. azotemia have the same causes and risk factors. Specifically, these include the Exogenous nephrotoxins following: Aminoglycosides o Hypovolemic states - Hemorrhage, volume depletion from GI or renal losses, burns, fluid sequestration o ATN occurs in 10-30% of patients receiving o Low cardiac output states - CHF and other diseases of aminoglycosides, even when blood levels are in myocardium, valvulopathy, arrhythmia, pericardial diseases, apparently therapeutic ranges. Risk factors for the tamponade o Systemic vasodilation - Sepsis, anaphylaxis development of aminoglycoside-induced ATN include o Disseminated intravascular coagulation preexisting liver disease, preexisting renal disease, o Renal vasoconstriction - Cyclosporine, amphotericin B, concomitant use of other nephrotoxins (eg, amphotericin norepinephrine, epinephrine, hypercalcemia B, radiocontrast media, cisplatin), advanced age, shock, o Impaired renal autoregulatory responses - Cyclooxygenase (COX) female sex, and a higher aminoglycoside level 1 hour after inhibitors, ACE inhibitors, angiotensin receptor blockers dose. A high trough level has not been shown to be an independent risk factor. Patients usually present with nonoliguric renal failure, with onset of nephrotoxicity (manifested by an elevation in serum creatinine), that occurs after 7-10 days of therapy. Characteristically, an elevated FENa is usually accompanied by wasting of potassium, calcium, and magnesium. o Aminoglycosides preferentially affect the proximal tubular cells. These agents are freely filtered and quickly taken up by the proximal tubular
  • 7. epithelial cells, where they are incorporated into Radiographic contrast media lysosomes after first interacting with phospholipids on the brush border membranes. They exert their main toxic effect within the tubular cell by altering phospholipid o ARF occurring secondary to exposure to metabolism. In addition to their direct effect on cells, contrast media used in radiologic or aminoglycosides cause renal vasoconstriction. angiographic procedures is referred to as o The 2 critical factors in the development contrast-induced nephropathy (CIN) or of ARF secondary to aminoglycoside radiocontrast nephropathy (RCN). This type of nephropathy commonly occurs in patients with several nephrotoxicity are namely dosing and risk factors, such as elevated baseline serum creatinine, duration of therapy. preexisting renal insufficiency, underlying diabetic o Aminoglycoside uptake by the tubules is a nephropathy, CHF, or high or repetitive doses of contrast media. Other risk factors include volume depletion and saturable phenomenon, so uptake is limited after a concomitant use of diuretics, ACE inhibitors, or single dose. Not surprisingly, a single daily large dose is angiotensin receptor blockers. preferable to 3 doses per day. One dose per day presumably causes less accumulation in the tubular cells o Although the pathogenesis of CIN once the saturation point is reached. In fact, clinical remains incompletely understood, it is nephrotoxicity develops much more commonly with 3 doses per day than with 1 dose per day; in one study, most likely the result of renal 24% of patients receiving 3 daily doses developed vasoconstriction and direct renal tubular clinical nephrotoxicity, compared to only 5% of patients receiving 1 daily dose. However, other studies epithelial cell toxicity. comparing a single daily dose to multiple daily doses o Whereas FENa below 1% usually indicates have failed to find a difference in the incidence of prerenal failure, although CIN is a common cause nephrotoxicity. of exogenous nephrotoxic ATN, FENa tends to o Therapeutic efficacy is not diminished by single be less than 1%, characteristically. (This is an daily dosing. exception to the rule. See myoglobinuric renal failure, below.) Amphotericin B o Patients usually present with nonoliguric renal failure, with an acute elevation in serum o Amphotericin B tends to bind to sterols in cell creatinine that is noted 24-48 hours after the membranes, thereby creating pores that compromise contrast-requiring procedure; it may peak 3-5 membrane integrity and increase membrane days after the onset of renal failure and then may return permeability. It binds not only to ergosterol in fungal cell to baseline within 7-10 days. More importantly, the walls but also to cholesterol in human cell membranes; temporal relationship between the time of this is what accounts for its nephrotoxicity. Multiple administration of contrast media and the onset of segments of the renal tubule are involved, namely, the elevation in serum creatinine is particularly suggestive of proximal tubule, the medullary ascending limb of the the diagnosis. One must differentiate CIN from loop of Henle, and the collecting duct. Characteristic atheroembolic renal disease, which occurs in the same electrolyte abnormalities include wasting of potassium scenario, but atheroembolic renal disease is and magnesium. The back-leak of hydrogen ions in the characterized by embolic lesions (mottling of the skin collecting duct leads to distal renal tubular acidosis over the lower extremities), peripheral eosinophilia, and (dRTA). serum hypocomplementemia, all of which are notably o Several risk factors for the development of absent in CIN. amphotericin B nephrotoxicity include male sex, o Most patients with CIN will have subsequent renal maximum daily dose (nephrotoxicity is more likely to recovery; however, those patients with preexisting occur if > 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 B o 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 cell o Other risk factors should be corrected, including membranes, such lipid formulations do not contain saline infusion to correct volume depletion and deoxycholate. The lipid formulations also bind more avidly to fungal cell wall ergosterol as opposed to the discontinuation 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 the with 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 of o 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 renal antagonists at least 24 hours before and after the tubular epithelial cell toxicity as a result of procedure. 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 that been 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 the lead 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 of microangiopathy 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 theophylline o 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 proven urinary 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 has chloride 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 reduces with saline. Some investigators advocate the use of the likelihood of clinical nephrotoxicity. Isotonic amifostine, 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 body chloroacetaldehyde, 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, thereby secondary 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 are deposit 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 phase, thereby accounting for agents, such as aminoglycosides, which is common transient hypercalcemia. For this reason, calcium practice in the immunosuppressed. It is noted for administration is generally not recommended hypomagnesemia and hyperkalemia. during the acute phase of rhabdomyolysis, unless the patient is symptomatic. o Sulfa drugs, acyclovir, and indinavir cause o Preventive strategies include aggressive volume ARF by tubular obstruction due to crystal resuscitation with normal saline at 1000-1500 formation in the tubular urine. Acyclovir mL/h with a goal urine output of 300 mL/h. may lead to the formation of intratubular Caution should be exercised to avoid producing a crystals, which appear as birefringent compartment syndrome, especially in those needle shaped crystals when viewed on patients who remain oligoanuric despite infusions microscopy. Occasionally, such crystals of large volumes of fluid. In the presence of can also elicit an acute interstitial nephritis. sufficient urine output, urine alkalinization to  Endogenous nephrotoxins achieve a urine pH of greater than 6.5 is recommended to increase the solubility of the Myoglobinuria heme-proteins within the tubules. This has also been shown to reduce the generation of ROS. o Rhabdomyolysis refers to the breakdown of Mannitol has not been shown to be more skeletal muscle fibers, which leads to the release of efficacious as compared to volume expansion with potentially nephrotoxic intracellular contents into normal saline alone. the circulation. Rhabdomyolysis is the most common cause of heme-pigment associated ARF. Three mechanisms cause the development of ARF in this setting, as follows: renal vasoconstriction, heme-mediated proximal tubular epithelial cell toxicity, and intratubular cast formation. Heme- o Hemoglobinuria: ARF is a rare complication of proteins are believed to be involved in the hemolysis and hemoglobinuria. Most often, it is generation of ROS, which are known to cause associated with transfusion reactions. In contrast to tubular injury through peroxidation of membrane myoglobin, hemoglobin has no apparent direct lipids and intracellular enzymes. tubular toxicity, and the ARF in this setting is o Rhabdomyolysis can be caused by traumatic or probably related to hypotension and decreased nontraumatic injuries. Most cases of renal perfusion. rhabdomyolysis are nontraumatic (eg, alcohol o Crystals: Acute crystal-induced nephropathy is abuse, drug-induced muscle toxicity [statins alone encountered in conditions where the crystals are or in combination with fibrates]). generated endogenously due to high cellular o Clinically, patients present with severe muscle turnover (ie, uric acid, calcium phosphate), as pains and generalized soreness. Physical observed in certain malignancies or the treatment examination may disclose tender "dough" muscles, of malignancies. However, this condition is also with significant edema of the involved extremities. associated with ingestion of certain toxic In severe cases, compartmental compression substances, such as ethylene glycol, or nontoxic syndromes, particularly characterized by substances, such as vitamin C. neurovascular compromise, may occur. o Multiple myeloma: Multiple myeloma causes renal o Whereas FENa under 1% usually indicates failure by several mechanisms, such as prerenal prerenal failure, although rhabdomyolysis is a azotemia due to volume contraction, cast common cause of endogenous nephrotoxic ATN, nephropathy due to increased light chain proteins FENa tends to be less than 1%, characteristically. precipitated into the tubular lumen, hypercalcemia, (This is another exception to the rule. See CIN, uric acid nephropathy, and drug-induced interstitial above) nephritis. o An important finding on urinalysis is that of a positive dipstick test for blood, with typical absence of RBCs on microscopy. Furthermore, hyperkalemia, hyperphosphatemia, and
  • 10. Differential Diagnoses CBC count: ΑΝΑΜΕΝΕΤΑΙ ΑΝΑΙΜΙΑ, ΑΦΟΥ ΥΠΟΛΕΙΠΕΤΑΙ Η ΣΥΝΘΕΣΗ Acute Renal Failure ΕΡΥΘΡΟΠΟΙΗΤΙΝΗΣ ΑΛΛΑ ΚΑΙ Azotemia ΑΙΜΟΠΕΤΑΛΙΑΚΗ ΔΙΑΤΑΡΑΧΗ ΑΠΟ ΤΗΝ Chronic Renal Failure Glomerulonephritis, Acute Nephritis, Interstitial Other Problems to Be Considered Urinalysis: ΤΑ ΦΥΓΟΚΕΝΤΡΗΘΕΝΤΑ ΟΥΡΑ ΕΙΝΑΙ ΠΟΛΤΥΜΙΑ [ΧΡΩΣΤΙΚΕΣ – ΛΑΣΠΩΔΕΙΣ ΚΑΦΕ ΚΥΛΙΝΔΡΟΙ – ΚΟΚΚΩΔΕΙΣ Prerenal azotemia ΚΥΛΙΝΔΡΟ ] = Ο.ΣΛ.Ν Acute interstitial nephritis Renal vasculitis 20 – 30 % = ΔΕΝ ΑΝΕΥΡΙΣΚΟΝΤΑΙ ΤΑ ΩΣ ΑΝΩ Obstructive uropathy ΗΛΕΚΤΡΟΛΥΤΕΣ ΟΥΡΩΝ = ΧΡΗΣΙΜΟΤΗΤΑ ΣΤΗ Workup ΔΔ Ο.ΣΛ.Ν ΑΠΟ ΠΡΟΝΕΦΡΙΚΗ ΑΖΩΘΑΙΜΙΑ Laboratory Studies Fractional excretion of a Serum chemistries: By definition, BUN substance is calculated and serum creatinine concentrations are increased in ARF. by the formula (U/P)z/(U/P)Cr X 100, In addition : o hyponatremia, ??????? o hyperkalemia, where z is the substance, o hypermagnesemia, o o hypocalcemia, and hyperphosphatemia U and P represent urine may be present. and plasma A metabolic acidosis is also found. concentrations, and Cr stands for creatinine. Remember that Imaging Studies hypercalcemia and  An abdominal radiograph is of limited benefit in ARF, with the exception of diagnosing (or helping hyperuricemia may  to exclude) nephrolithiasis. Ultrasonography, computed tomography (CT) suggest a malignant scanning, and MRI are extremely useful to exclude obstructive uropathy and to measure renal size and condition as a cause. cortical thickness. Renal ultrasonography is a simple procedure that should be undertaken in all patients who present with ARF. Procedures  Biopsy is rarely necessary. It should be performed only when the exact renal cause of ARF is unclear
  • 11. Acute tubular necrosis (ATN). Flattening of the renal tubule cells due to tubular dilation. and the course is protracted. Prerenal and postrenal causes must be ruled out first. The diagnosis of ATN is made on a clinical basis, that is, with the help of a detailed and accurate history, a thorough physical examination, and pertinent laboratory examinations and imaging studies. A more urgent indication for renal biopsy is in the setting of clinical and urinary findings that suggest renal vasculitis rather than ATN; the diagnosis needs to be established quickly so that appropriate immunomodulatory therapy can be initiated. The biopsy is performed under ultrasound or CT scan guidance after ascertaining the safety of the procedure. A biopsy may also be more critically important in the setting of a renal transplant patient to rule out rejection.17,18 Acute tubular necrosis. Intratubular cast formation. Histologic Findings In most circumstances, the histology demonstrates the loss of tubular cells or the denuded tubules. As illustrated in the image below, the tubular cells reveal swelling, formation of blebs over the cellular surface, and exfoliation of the tubular cells into the lumina. The earliest finding could be loss of the cellular brush border. (See also images below.) Acute tubular necrosis. Intratubular obstruction due to the denuded epithelium and cellular debris. Note that the denuded tubular epithelial cells clump together due to rearrangement of intercellular adhesion molecules (ICAM). 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). Sloughing of cells, which is responsible for the formation of granular casts, a feature of acute tubular necrosis (ATN).
  • 12. Η ΣΗΨΗ ΑΠΟΤΕΛΕΙ ΚΟΙΝΟ ΑΙΤΙΟ ΚΑΤΑΛΗΞΗΣ, ΟΠΟΤΕ Treatment o ΑΜΕΣΗ ΑΝΤΙΜΕΤΩΠΙΣΗ ΛΟΙΜΩΞΕΩΝ o ΤΡΟΠΟΠΟΙΗΣΗ ΔΟΣΕΩΝ ΤΩΝ ΦΑΡΜΑΚΩΝ ΑΝΑΛΟΓΑ ΜΕ ΤΗ ΝΕΦΡΙΚΗ ΛΕΙΤΟΥΡΓΙΑ Medical Care Dialysis treatment Prevention Ischemic ATN: Be attentive to optimizing cardiovascular o In general, no clear consensus is established on when function as well as maintaining intravascular volume, or how often to perform hemodialysis in the setting of especially in patients with preexisting risk factors or those ARF. Some studies have suggested that early initiation taking nephrotoxic medications. Medicines that reduce may be beneficial, but, in one prospective trial, systemic resistance (eg, afterload reducers) may cause aggressive dialysis did not improve recovery or survival renal vasoconstriction or affect the kidney's autoregulatory response (eg, ACE inhibitors, COX inhibitors) and also should rates. However, hemodialysis is still considered be used with caution. standard therapy in severe ARF. In addition, continuous hemodialysis (continuous venovenous Nephrotoxic ATN hemodiafiltration [CVVHD] and continuous arteriovenous hemofiltration with dialysis [CAVHD])  Aminoglycosides: ΕΧΕΙ ΑΠΟΔΕΙΧΘΕΙ Η ΕΛΑΧΙΣΤΟΠΟΙΗΣΗ and peritoneal dialysis are also available. No ΚΙΝΔΥΝΟΥ ΤΟΞΙΚΟΤΗΤΑΣ ΜΕ ΧΟΡΗΓΗΣΗ ΣΕ ΜΙΑ ΗΜΕΡΗΣΙΑ compelling studies suggest that one mode is better ΔΟΣΗ than another. In general, patients with multiorgan  Amphotericin B: ΑΠΑΙΤΕΙΤΑΙ ΕΛΑΧΙΣΤΟΠΟΙΗΣΗ ‘Η ΚΑΙ failure and hemodynamic instability may benefit from ΔΙΑΚΟΠΗ ΚΑΙ ΔΙΑΣΦΑΛΗΣΗ ΕΠΑΡΚΟΥΣ ΕΞΩΚΥΤΤΑΡΙΟΥ ΟΓΚΟΥ ΥΓΡΩΝ a continuous mode because it is typically less taxing on  Cyclosporin and tacrolimus: ΑΠΑΙΤΕΙΤΑΙ ΤΑΚΤΙΚΟΣ the hemodynamics. ΑΙΜΑΤΟΛΟΓΙΚΟΣ ΕΛΕΓΧΟΣ o Some studies suggest that the use of biocompatible  Radiocontrast dye: Isotonic sodium chloride solution membranes instead of cuprophane membranes may infusion has proven benefits in the prevention of CIN. improve the recovery rate and decrease the mortality Typically, isotonic sodium chloride solution (0.9%) administered at a rate of 1 mL/kg/h 12 hours before and rate in ARF. 12 hours after the administration of the dye load is most effective, especially in the setting of prior renal Treatment of nephrotoxic ATN: Generally, the insufficiency and diabetes mellitus. Nonionic contrast treatment of choice is to stop all nephrotoxic agents to media is also protective in patients with diabetic nephropathy and renal insufficiency. NAC has been prevent further damage to the kidney. Of note, calcium tried with success in high-risk patients to prevent channel blockers may have some use in cyclosporine contrast-induced nephrotoxicity. toxicity, where they may reduce the vasoconstrictive action of the drug. However, their use is typically Treatment avoided because of possible hypotension. General treatment Diet o The main goal of treatment is to prevent further injury to ΕΙΝΑΙ ΞΕΚΑΘΑΡΗ Η ΣΗΑΣΙΑ ΤΗΣ ΔΙΑΧΕΙΡΗΣΗΣ ΥΓΡΩΝ ΚΑΙ the kidney. ECF volume should be assessed promptly, ΗΛΕΚΤΡΟΛΥΤΩΝ either on clinical grounds or by invasive means (Swan- Ganz catheter), and repletion of any deficit should be Η ΕΓΚΑΙΡΗ ΚΑΙ ΔΥΝΑΜΙΚΗ ΘΡΕΠΤΙΚΗ ΥΠΟΣΤΗΡΙΞΗ ΣΥΜΒΑΛΛΕΙ initiated promptly. A renal ultrasound should be ΣΕ ΒΛΕΤΙΩΣΗ ΣΤΑ ΠΟΣΟΣΤΑ ΕΠΙΒΙΩΣΗΣ performed to exclude obstruction. All possible nephrotoxic drugs should be stopped. Despite some controversy in the literature, in general, if oliguria is ΑΠΑΙΤΕΙΤΑΙ ΙΚΑΝΟΠΟΙΗΤΙΚΗ ΠΡΟΣΛΗΨΗ ΠΡΩΤΕΙΝΗΣ ΚΑΙ present, make an attempt to increase urine output using ΘΕΡΜΙΔΩΝ : intravenous loop diuretics. Only use diuretics if ECF volume and cardiac function are first carefully assessed o ΥΦΙΣΤΑΤΑΙ ΕΚΣΕΣΗΜΑΣΜΕΝΟΣ ΚΑΤΑΒΟΛΙΣΜΟΣ ΕΙΔΙΚΑ ΣΕ and found adequate. ΣΟΚ, ΣΗΨΗ, ΡΑΒΔΟΜΥΟΛΥΣΗ o IV furosemide or bumetanide in a single high dose (ie, 100-200 mg of furosemide) = ΚΟΙΝΗ ΚΑΘΗΜΕΡΙΝΗ ΚΑΤΑΣΤΑΣΕΙΣ ΑΝ ΟΧΙ ΣΥΝΟΝΥΜΕΣ, ΣΥΧΝΑ ΣΥΝΥΠΑΡΧΟΥΣΕΣ ΠΡΑΚΤΙΚΗ ΑΛΛΑ ΔΕΝ ΕΧΕΙ ΑΠΟΔΕΙΧΘΕΙ ΟΤΙ ΒΕΛΤΙΩΝΕΙ ΤΗΝ ΜΕ : ΕΞΕΛΙΞΗ ΤΗΣ ΝΟΣΟΥ. ΠΡΕΠΕΙ ΝΑ ΧΟΡΗΓΕΙΤΑΙ ΒΡΑΔΕΩΣ = ΚΙΝΔΥΝΟΣ ΚΟΦΩΣΗΣ ΚΑΙ ΕΠΙ ΜΗ ΒΕΛΤΙΩΣΗΣ ΠΡΕΠΕΙ ΝΑ ΔΙΑΚΟΠΤΕΤΑΙ. Η ΧΡΗΣΗ ΝΤΟΠΑΜΙΝΗΣ ΔΕΝ ΣΥΝΙΣΤΑΤΑΙ o ΚΑΚΗ ΘΡΕΨΗ ΠΛΕΟΝ o ΥΠΟΛΕΙΠΟΜΕΝΗ ΑΝΟΣΟΛΟΓΙΚΗ ΙΚΑΝΟΤΗΤΑ o Aggressively treat any complications that develop. ΓΛΥΚΟΖΗ + ΙΝΣΟΥΛΙΝΗ binding resins, ‘Η ΔΙΑΛΥΣΗ ΕΠΙ ΥΠΕΡΚΑΛΙΑΙΜΙΑΣ ΔΙΚΑΡΒΟΝΙΚΑ ‘Η ΔΙΑΛΥΣΗ ΕΠΙ Medication ΜΕΤΑΒΟΛΙΚΗΣ ΟΞΕΩΣΗΣ. ΧΟΡΗΓΗΣΗ ΑΙΜΑΤΟΣ ΕΠΙ ΑΝΑΙΜΙΑΣ. ΔΕΝ ΥΦΙΣΤΑΤΑΙ ΙΚΑΝΟΠΟΙΗΤΙΚΗ ΦΑΡΜΑΚΕΥΤΙΚΗ ΘΕΡΑΠΕΙΑ
  • 13. ΣΤΟΧΟΙ = [ ΠΡΟΛΗΨΗ – ΑΠΟΦΥΓΗ / ΕΠΙΒΡΑΔΥΝΣΗ ΠΕΡΑΙΤΕΡΩ ΒΛΑΒΗΣ – ΑΝΤΙΜΕΤΩΠΙΣΗ ΥΠΟΚΕΙΜΕΝΩΝ ΑΙΤΙΩΝ – ΕΠΙΘΕΤΙΚΗ ΑΝΤΙΜΕΤΩΠΙΣΗ ΤΩΝ ΕΠΙΠΛΟΚΩΝ ] Follow-up Antioxidants Complications May prevent reperfusion damage as well as improve renal hemodynamics. ATN and ARF have several complications. Electrolyte abnormalities o Hyperkalemia: Arrhythmias have been reported in up to 30% of patients. In addition to these worrisome cardiac effects, hyperkalemia can also lead to neuromuscular dysfunction and, N-acetylcysteine (Mucomyst, Mucosil) potentially, respiratory failure. o Hyponatremia ΕΝΔΕΙΞΗ = ΤΟΞΙΚΟΤΗΤΑ acetaminophen ΚΑΙ o Hyperphosphatemia ΗΠΑΤ5ΟΝΕΦΡΙΚΟ ΣΥΝΔΡΟΜΟ o Hypermagnesemia o Hypocalcemia: Hypocalcemia may be secondary to both deposition of calcium phosphate and reduced levels of 1,25 ΠΙΘΑΝΗ ΔΡΑΣΗ = ΒΕΛΤΙΩΣΗ ΝΕΦΡΙΚΗΣ ΑΙΜΟΔΥΝΑΜΙΚΗΣ ‘Η / dihydroxyvitamin D. It is usually asymptomatic, but ΚΑΙ ΠΕΡΙΟΡΙΣΜΟΣ ΑΜΕΣΗΣ ΟΞΕΙΔΩΤΙΚΗΣ ΒΛΑΒΗΣ hypocalcemia may result in nonspecific ECG changes, muscle cramps, or seizures. Adult 600 mg PO bid for 2 d (administer 1 day before and on the day of exposure to radiocontrast dye) o Metabolic acidosis o Intravascular volume overload: In its most severe Pregnancy manifestation, this may lead to respiratory failure from pulmonary edema. o Hypertension: Hypertension is suspected to mainly be B - Fetal risk not confirmed in studies in humans but has been due to salt and water retention. About 25% of patients shown in some studies in animals with ARF develop some hypertension. o Uremic syndrome: This may manifest as pericardial Precautions disease, GI symptoms (ie, nausea, vomiting, cramping), and/or neurologic symptoms (ie, lethargy, confusion, GI distress may occur asterixis, seizures). o Anemia: Anemia may develop from many possible causes. Indeed, erythropoiesis is reduced in ARF, but platelet dysfunction is also observed in the setting of uremia, which may predispose to hemorrhage. In addition, volume overload may lead to hemodilution, Diuretics and red cell survival time may be decreased. o Polyuric phase of ATN: This complication can lead to ΠΑΙΖΕΙ ΡΟΛΟ ΣΤΟ ΝΑ ΜΗΝ ΕΓΚΑΤΑΣΤΑΘΕΙ ΟΛΙΓΟΥΡΙΑ hypovolemia and create a setting for prerenal azotemia and perpetuation of ATN. One must be wary of the Furosemide (Lasix) potential for multiple electrolyte deficiencies (eg, hypokalemia, hypocalcemia) during this period as a result of increased urinary excretion. ΑΝΑΛΟΓΩΣ ΤΗΝ ΑΝΤΑΠΟΚΡΙΣΗ : 20-40 mg, ΟΧΙ ΤΑΧΥΤΕΡΑ ΑΠΟ 6-8 h ΑΠΟ ΤΗΝ ΠΡΟΗΓΟΥΜΕΝΗ ΔΟΣΗ, until desired diuresis occurs. o Infections: Infections remain the leading cause of morbidity and mortality and can occur in 30-70% of patients with ARF. Infections are more likely in these When treating infants, titrate with 1-mg/kg per dose patients because of an impaired immune system (eg, increments until a satisfactory effect is achieved. uremia, inappropriate use of antibiotics) and because of increased use of indwelling catheters and intravenous Adult needles. 20-80 mg/d PO/IV/IM; titrate up to 600 mg/d for severe Prognosis edematous states ΘΝΗΤΟΤΗΤΑ = 50% ΠΙΘΑΝΟΛΟΓΕΙΤΑΙ ΜΕΓΑΛΥΤΕΡΗ ΣΥΣΧΕΤΙΣΗ ΜΕ ΤΗΝ ΥΠΟΚΕΙΜΕΝΗ ΝΟΣΟΛΟΓΙΑ ΠΑΡΑ ΜΕ ΤΗΝ ΣΩΛΗΝΑΡΙΑΚΗ ΝΕΚΡΩΣΗ
  • 14. Ο.ΣΛ.Ν + ΣΗΨΗ = 60% ΦΥΣΙΚΗ ΚΑΤΑΛΗΞΗ Ο.ΣΛ.Ν + ΝΕΦΡΟΤΟΞΙΝΗ = 30% ΦΥΣΙΚΗ ΚΑΤΑΛΗΞΗ However, remember the following points: o ΕΑΝ ΥΠΑΡΧΕΙ ΟΛΙΓΟΥΡΙΑ ΕΙΝΑΙ ΧΕΙΡΟΤΕΡΗ Η ΠΡΟΓΝΩΣΗ : ΕΝΔΕΧΟΜΕΝΩΣ ΕΙΝΑΙ ΕΚΤΕΝΕΣΤΕΡΗ Η ΝΕΚΡΩΣΗ, ΠΛΕΟΝ ΣΗΜΑΝΤΙΚΕΣ ΟΙ ΔΙΑΤΑΡΑΧΕΣ ΣΤΗΝ ΗΛΕΚΤΡΟΛΥΤΙΚΗ ΙΣΟΡΡΟΠΙΑ o ΜΙΑ ΣΗΜΑΝΤΙΚΗ ΜΕΤΑΒΟΛΗ ΤΗΣ ΚΡΕΑΤΙΝΙΝΗΣ (ie, > 3 mg/dL) ΘΕΤΕΙ ΕΞ ΟΡΙΣΜΟΥ ΧΕΙΡΟΤΕΡΗ ΠΡΟΓΝΩΣΗ, ΑΝΤΑΝΑΚΛΩΝΤΑΣ ΕΝΔΕΧΟΜΕΝΩΣ ΜΙΑ ΒΑΡΕΙΑ ΥΠΟΚΕΙΜΕΝΗ ΝΟΣΟ. ΑΠΟ ΤΟΥΣ ΕΠΙΖΗΣΑΝΤΕΣ : 50% ΜΟΝΙΜΗ ΝΕΦΡΙΚΗ ΒΛΑΒΗ – 5% ΣΥΝΕΧΙΖΕΤΑΙ Η ΕΠΙΔΕΙΝΩΣΗ – 5% ΑΠΑΙΤΕΙΤΑΙ ΔΙΑΛΥΣΗ. Patient Education  eMedicine's Diabetes Center.  eMedicine's article = Acute Kidney Failure.

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