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.