2

Rapid loss of renal function leading to abnormal water, electrolyte and solute balance.

Occurs over a period of hours to days. Usually associated with oliguria. Some

patients develop non oliguric ARF eg. After radiocontrast media.

It can be reversed with treatment of the cause.

Acute-on top of chronic renal failure may occur.

3

RIFLE classification of acute kidney injury

GradeGFR criteriaUO criteria

RiskSCr 1.5UO < 0.5 mL/kg/hour

6 hours

InjurySCr 2UO < 0.5 mL/kg/hour

12 hours

FailureSCr 3 or SCr > 350

mol/L with an acute rise > 40 mol/L

UO < 0.3 mL/kg/hour 24 hours

LossPersistent AKI > 4 weeks

ESKDPersistent renal failure >

3 months

AKI, acute kidney injury; ESKD, end-stage kidney disease, GFR, glomerular filtration rate; SCr, serum creatinine; UO, urine output.

4

Acute Renal Failure

Pre-renal causes

Intrinsic renal causes

Post-renal causes

Glomerular disease

Tubular injury

Vascular disease

Interstitial nephritis

Ischaemic

Toxic

5

Causes of Acute Renal Failure

Renal loss – diuretics, osmotic diuresis (DKA). Addisonian crisis.

Extrarenal loss – vomiting, diarrhea, skin losses (burns, excessive sweating).

Hemorrhage. Pancreatitis.

Prerenal (Reduced renal perfusion)1) Volume depletion:

Congestive heart failure, reduced myocardial function, arrhythmias.

Severe valvular heart disease.

2) Hypotension (regardless of cause):3) Cardiovascular:

6

Radiographic contrast. Prostaglandin inhibition (NSAIDs). Cyclosporine and tacrolimus. ACE inhibitors. Amphotericin. Hypercalcemia.

4) Hemodynamic (intense intrarenal vasoconstriction):

5) Hepatorenal syndrome (bland urinary sediment, oliguria, low urine sodium, not reversed with volume repletion, reversible with successful liver transplant).

7

Renal infarction, renal artery stenosis, renal vein thrombosis.

Malignant hypertension, scleroderma renal crisis, atheroemboli.

1) Vascular:

Ischemic-prolonged prerenal state, sepsis syndrome, systemic hypotension.

Nephrotoxic-aminoglycosides, methotrexate, cisplatin, myoglobin (rhabdomyolysis), hemoglobin

(intravascular hemolysis).

2) Tubular:

Intrinsic or intrarenal

8

Acute glomerulonephritis. Good pasture syndrome. Vasculitis (Wegener’s granulomatosis, polyarteritis). Thrombotic microangiopathy (hemolytic uremic

syndrome, TTP).

3) Glomerular:

Medications–penicillins, cephalosporins, ciprofloxacin, NSAIDs, phenytoin.

Tumor infiltration (lymphoma, leukemia). Sarcoidosis, sjogren syndrome.

4) Interstitium:

9

Prostate hypertrophy, neurogenic bladder Intraureteral obstruction-crystals stones, clots,

tumor. Extraureteral obstruction-tumor (cervical,

prostate), retroperitoneal fibrosis. Ureteric ligation during pelvic surgery.

Postrenal (obstruction)

10

* Pre-renal failure :- There is hypotension with signs of poor preripheral

perfusion.- Postural hypotension.- Signs of hypovolemia.- Manifestations of the cause.- Metabolic acidosis and K may be present.

* Established renal ARF :- Oliguria (urine volume < 400ml/d) or anuria (< 100ml/d).- Disturbances of water, electrolyte and acid base

balance ( K, pH, Dilutional Na).- Uremic features include anorexia, nausea, vomiting,

hiccough, acidotic breathing ….

11

* Post-renal (ARF) :

- Loin pain (which may be constant or intermittent)

- Complete anuria with bilateral obstruction or

complete obstruction of single kidney.

- Infection may fever, septicaemia.

- Bladder outflow obstruction Hesitancy, weak

urine stream, terminal drippling, re-tension with

overflow may occur

- Screening of urinary tract by sonar is essential.

12

Probable Causes of Acute Renal Failure Based on the Findings of The History

HistoryProbable causes of acute renal failure

Review of systemsPulmonary system

Sinus, upper respiratory or pulmonary symptoms

Pulmonary-renal syndrome or vasculitis

Cardiac system

Symptoms of heart failureDecreased renal perfusion

Intravenous drug abuse, prosthetic valve or valvular disease

Endocarditis

Gastrointestinal System

Diarrhea, vomiting or poor intake.Hypovolemia

Colicky abdominal pain radiating from flank to groin

Urolithiasis

Genitourinary System

Symptoms of benign prostatic hypertrophy.

Obstruction

Bone pain in the elderlyMultiple myeloma or prostate cancer

Trauma or prolonged immobolizationRhabdomyolysis (pigment nepbropathy)

13

(Cont.)

HistoryProbable causes of acute renal failure

Skin

RashAllergic interstitial nephritis, vasculitis, systemic lupus erythematosus, atheroemboli or thrombotic thrombocytopenic purpura.

Constitutional symptoms

Fever, weight loss, fatigue or anorexiaMalignancy or vasculitis

Past medical history

Multiple sclerosis, diabetes mellitus or stroke

Neurogenic bladder

Past surgical history

Recent surgery or procedureIschemia, atheroemboli, endocarditis or exposure to contrast agent

Medication history

Angiotensin-converting enzyme inhobitors, nonsteroidal anti-inflammatory drugs, antibiotics or acyclovir (Zovirax)

Decreased renal perfusion, acute tubular necrosis or allergic interstitial nephritis

14

Probable Causes of Acute Renal Failure Based on the Physical Findings

Physical Examination

Probable causes of acute renal failure

Vital signs

TemperaturePossible infection.Blood pressure

Hypertension: G.N or malignant hypertension.Hypotension: volume depletion or sepsis.

Weight loss or gain

Hypovolemia or hypervolemia.

MouthDehydrationJugular veins and axillae (perspiration)

Hypovolemia or hypervolemia

Pulmonary system

Signs of pneumonia, cavitations, pleurisy.

HeartNew murmur of endocarditis or signs of congestive heart failure

15

(Cont.)

Physical Examination

Probable causes of acute renal failure

Abdomen Bladder distention suggesting uretheral obstruction

PelvisPelvic massRectumProstate enlargementSkinRash of interstitial nephritis, purpura of

microvascular disease, livedo reticularis suggestive of atheroembolic disease, or splinter hemorrhages or Osler’s nodes of endocarditis.

16

* Blood urea nitrogen and serum creatinine are elevated.

* ABG, electrolytes, CBC, and serology.* U/S kidneys (The size of the kidneys is usually

normal.* Serology: ANA, ANCA, Anti DNA, HBV, HCV, Anti

GBM. Cryoglobulin, CK, urinary myoglobin.

17

* Urine analysis :- Unremarkable in pre and post renal causes.- Differentiates ATN vs. AIN. vs. AGN

* Hansel stain for Eosinophiluria.

Granular casts in ATN. WBC casts in AIN. RBC casts in AGN.

- Urine electrolytes (Na) and osmolality.

18

LAB Findings of Specific Types of Acute Renal Failure

Findings on blood testsDiagnosis to considerVery high uric acid levelSuggestive of malignancy or tumor lysis

syndrome leading to uric acid crystals; also seen in prerenal acute renal failure.

Elevated creatinine kinase or myoglobin levels

Rhabdomyolysis.

Elevated prostate-specific antigenProstate cancer.

Abnormal serum protein electrophoresis

Multiple myeloma.

Low complement levelsSystemic lupus erythematosus, postinfectious glomerulophritis, subacute bacterial endocarditis

Positive antineurtrophic cytoplasmic antibody (ANCA)

Small-vessel vasculitis (Wegener’s granulomatosis or polyartheritis nodosa)

19

LAB Findings of Specific Types of Acute Renal Failure (Cont.)

Findings on blood testsDiagnosis to consider

Positive antinuclear antibody to double-stranded DNA

Systemic lupus erythematosus

Positive antibody to glomerular basement membrane

Goodpasture’s syndrome

Positive antibodies to streptolysin O, streptokinase or hyaluronidase

Poststreptocaccal glomerulonephritis.

Schistocytes on peripheral smear, decreased hepatoglobin level, elevated lactate dehydrogenase level or elevated serum bilirubin level

Hemolytic uremic syndrome or thrombotic thrombocytopenic purpura

Low albumin levelsLiver disease or nephrotic syndrome

20

Laboratory Findings in Acute Renal Failure To Differentiate Pre-Renal from Renal Failure

IndexPrerenal AzotemiaOliguric Acute Renal Failure (ATN)

BUN/PCR Ratio> 20 : 110-15 : 1

Urine sodium (UNa)

meg/L

< 20> 40

Urine osmolality, mosmol/L H2O

> 500< 350

Fractional excretion of sodium

< 1 %> 2 %

Response to volume

ImprovementNo improvement

Urinary SedimentBlandATN: muddy brown granular casts, cellular debris, tubular

epithelial cells

21

ARF is common in the ICU.

ARF is an independent factor for prognosis

in the ICU.

The incidence of ARF in the ICU 40-60%

compared to 1-3% in the ward.

ARF still has a mortality of 50% since it

occurs in very sick patients with multiorgan

failure.

22

Predisposing factors to ARF include old age

sepsis pre existing renal disease heart

disease and chronic liver disease.

Mechanical ventilation has an adverse effect

on renal blood flow and GFR and subsequent

renal function.

23

• Patients with ICU acquired ARF were classified into the following :

- Oliguric (urine volume of < 400 ml/day).- Nonoliguric (urine volume of > 400 ml/day).- Anuric (urine volume of < 100 ml/day).

A) According to the urine output:

1) Prerenal ARF.2) Ischemic acute Tubular necrosis.3) Nephrotoxic ARF (ATN or AIN).4) Sepsis induced ARF.5) Hepato-renal syndrome.6) Other causes (e.g. obstructive uropathy,

pigment nephropathy, microangiopathies).

B) According to the cause:

24

1) Prerenal ARF was defined as ARF to renal hypoperfusion with recovery after correction of hemodynamic disturbances.

2) Ischemic Acute tubular necrosis (IATN) was diagnosed when renal function did not improve after correction of possible prerenal causes, and when hepatorenal syndrome, vascular, interstitial, glomerular and obstructive aetiologies were excluded.

25

Any documented decline in blood pressure to less than 90/60 mmHg.

Overt volume contraction on physical examination (postural hypotension, decreased skin turgor, …), and central venous pressure (CVP) less than 5 cm H2O.

Clinically evident congestive heart failure with improvement in renal function following appropriate treatment of heart failure.

• Decreased renal perfusion was identified by the following observations :

26

3) Nephrotoxic ARF (either AIN or ATN)

Nephrotoxic Acute Interstitial Nephritis

(AIN): history of drug ingestion, fever, rash, or

arthralgias. Urinary increase in WBCs (frequently

eosirophiluria), WBC casts RBCs, and

proteinuria, with systemic eosinophilia, if

histologically demonstrated by renal biopsy or

when there was a high grade of clinical

suspicion.

27

Nephrotoxic Acute Tubular Necrosis (ATN): was defined as ARF occurring after administration of drugs known to cause ATN (e.g. aminoglycosides, amphotericin, contrast media etc …).

Concurrent administration of vancomycin & aminoglycosides to critically ill septic patients with normal renal function of baseline induces mainly slight and transient toxic tubular effects.

28

Radiographic contrast media, were determined to

be the cause of renal insufficiency when the

serum creatinine concentration increased – as

defined – within 72 hours following a radiologic

procedure employing these agents (e.g.

intravenous pyelogram – angiography – computed

tomography scan).

29

4) Sepsis induced ARF was diagnosed if ARF is associated with at least one of the following three conditions:

Documented bacteremia. A known focus of infection Immunosuppression with neutropenia,

and at least two additional findings: rigors – unexplained hyperventilation unexplained sudden fall in blood pressure – abrupt rise in temperature to more than 38C not due to transfusion reaction – unexplained leukocytosis of more than 15.000 mm3.

30

5) Hepatorenal syndrome was assigned as the

cause of renal failure if the patient had severe liver

failure (e.g. ascites – jaundice, hepatic

encephalopathy) – and a urine sodium concentration

less than 10 mEq/Liter, and the renal function did not

respond to a volume expansion.

31

6) Other causes:

Obstruction was determined to be the cause of

renal failure if obstruction was present by

physical examination (as enlarged bladder) or by

radiological evaluation and if improvement in

renal function followed relief of obstruction.

32

Pigment induced-ARF, history suggestive of

rhabdomyolysis, urine dispstick positive for blood

(heme) without microscopic haematuria

hyperkalemia, hyperphosphatemia, hypocalcemia,

increased creatine kinase-MM fraction and serum

uric acid.

33

Associated with emboli of fragments of atherosclerotic plaque from aorta and other large arteries.

Diagnose by history, physical findings (evidence of other embolic phenomena, ischemic digits, “blue toe” syndrome, etc), low serum C3 and C4, peripheral eosinophiluria, rarely WBC casts.

Commonly occur after intravasculer procedures or cannulation (cardiac catheter, CABG).

Atheroembolic ARF:

34

Number of patients admitted in different

ICUs with acquired ARF in each ICU

ICUNo. of admitted patients

No. & % of patients with ICU acquired ARF in each ICU

Medical ICU1123402 (35.7 %)

Gynecology ICU43198 (22.7 %)

Surgical ICU33653 (15.7 %)

Neurology ICU11617 (14.6 %)

Chest ICU40957 (13.9 %)

Coronary Care Unit72278 (10.1 %)

Cardiosurgery ICU42543 (10.1 %)

Total3562748 (21 %)

35

Causes of ICU acquired-ARF in 748 patients

CausesNo. & % of patients

iATN283 (37.8 %)

Prerenal198 (26.5 %)

Toxic ARF80 (10.6 %)

Sepsis induced ARF89 (11.9 %)

HRS73 (9.8 %)

Others25 (3.4 %)

iATN = ischemic acute tubuler necrosis. Toxic ARF = toxic acute renal failure. HRS – hepatorenal syndrome.

36

Number & Percentage of patient mortality

in each ICU

ICUNo. of patients with ICU acquired

ARF

Mortality No. & % in each ICU

Medical ICU402261 (64.9 %)

Coronary Care Unit7820 (25.6 %)

Chest ICU5728 (49.1 %)

Neurology ICU179 (52.9 %)

Surgical ICU5310 (18.8 %)

Cardiosurgery ICU4319 (44.1 %)

Gyne & obst. ICU9842 (42.8 %)

Total748389

37

* The initiation of RRT in patients with AKI prevents uremia and immediate death from the adverse complications of renal failure.

* It is possible that variations in the timing of initiation, modalities, and/or dosing may affect clinical outcomes.

* Multiple modalities of RRT are currently available. These include intermittent hemodialysis (IHD), continuous renal replacement therapies (CRRTs), and hybrid therapies, such as sustained low-efficiency dialysis (SLED). Despite these varied techniques mortality in patients with ARF remains high greater than 50% in severely ill patients.

38

1. Indications for dialysis.

2. Timing of initiation of dialysis.

3. Optimal modality.

4. Optimal Dosing.

5. Discontinuation of therapy.

39

1) Refractory fluid overload.2) Hyperkalemia (plasma potassium concentration >

6.5 meq/L) or rapidly rising potassium levels.3) Metabolic acidosis (pH less than 7.1).4) Signs of uremia e.g. pericarditis and decline in

mental state.5) Certain alcohol and drug intoxications.

* The likelihood of requiring RRT is increased in

patients with underlying CKD (Acute on top of

chronic).

40

Studies published during the 1960s and 1970s

suggested that improved outcomes were associated

with the initiation of hemodialysis when BUN reached

exceeded 150 to 200 mg/dL.

41

More recent studies have evaluated the relationship

between the timing of RRT initiation and clinical

outcomes. Several non-randomized studies have

reported that improved outcomes, including survival,

are associated with early versus late initiation of RRT.

It has been suggested that initiation of RRT dialysis

prior to the development of overt symptoms and

signs of renal failure due to AKI improves the

outcome.

42

There is at least theoretical concern that dialysis might have detrimental effects on renal function.

Three factors may be important in this regard:

Can dialysis delay recovery of renal function ?

1) A reduction in urine output; Both removal of excess volume and of urea contribute to a reduction in or even cessation of the urine output. The fall in urine output should not delay the regeneration of tubules.

2) Induction of hypotension; Autoregulation is impaired in ATN, because vascular endothelial injury reduces the release of vasodilating substances so recurrent ischemic tubular injury is more likely to occur, thereby delaying the restoration of function.

43

3) Complement activation resulting from a blood-dialysis membrane interaction, can lead to neutrophilic infiltration into the kidney (and other tissues) and prolonged acute kidney injury.

4) High flux membranes can enhance removal of putative toxins and improve outcome, but may also allow the back transport (from dialysate to blood).

44

1) Intermittent hemodialysis (IHD).

2) Continuous renal replacement therapy (CRRT).

3) Peritoneal dialysis.

45

Dialysis = diffusion = passive movement of solutes across a semi-permeable membrane down concentration gradient.

Principles of dialysis

Figure (1): Principles of dialysis (top panel) and filtration

(lower panel).

* Good for small molecules.

(Ultra) filtration = convection = solute + fluid removal across semi permeable membrane down a pressure gradient (solvent drag).* Better for removal of fluid

and medium-size molecules.

46

Hemodialysis = solute passively diffuses down concentration gradient.

Principles of dialysis

Dialysate flows countercurrent to blood flow. Urea, creatinine, K move from blood to dialysate. Ca and bicarb move from dialysate to blood.

Ultrafiltration = This is the convective flow of water and dissolved solutes down a pressure gradient caused by hydrostatic or osmotic forces.

Hemodiafiltration = combination of dialysis and ultrafiltration

47

Oldest and most common technique. Primarily diffusive treatment: blood and

dialysate are circulated in countercurrent manner.

Intermittent hemodialysis (IHD)

Also some fluid removal by ultrafiltration due to pressure driving through circuit.

Best for removal of small molecules.

Typically performed 4 hours 3x / wk or daily.

48

CRRT strategies are particularly useful in haemo-dynamically compromised patients with ARF.

They allow slow and gentle removal of solutes and fluid, avoiding major intravascular fluid shifts and minimizing electrolyte disturbances, hypotension and arrhythmias.

Inflammatory mediators may also be continuously removed by CRRT, so it may be useful in sepsis syndrome.

Continuous Renal Replacement Therapy (CRRT)

49

Types of Continuous Renal Replacement Therapies (CRRT)

Blood accessContinuous arteriovenous hemofiltration (CAVH).Continuous arteriovenous hemodialysis (CAVHD).Continuous arteriovenous hemodiafiltration (CAVHDF).Continuous venovenous hemofiltration (CVVH).Continuous venovenous hemodialysis (CVVHD).Continuous venovenous hemodiafiltration (CVVHDF).Slow low efficiency dialysis (SLED).Slow continuous ultrafiltration (SCUF).Extended daily dialysis (EDD).

Peritoneal accessContinuous equilibrium peritoneal dialysis.Blood acce

50

Provides solute clearance by convection as solutes are dragged down pressure gradient with water.

It provides better removal of large MW solutes e.g. B2-microglobulin, improved clearance of low MW uraemic toxins and better cardiovascular stability and Bp control than HD.

Inflammatory markers are improved.

Haemofiltration

51

Uses conventional dialysis machines but blood flow of 100-200 ml/M and dialysate flow of only 100 ml/M for 8-24 hr/D.

Major advantages: Flexibility of duration and intensity, reduced costs.

Excellent tolerability, cardiovascular stability and solute removal.

Sustained low-efficiency daily dialysis(SLED):

52

Used for fluid removal in overloaded CHF patients with refractory edema without severe renal failure.

Blood is driven through a highly permeable filter in a venovenous mode to primarily remove water, not solute.

The ultrafiltrate produced during membrane transit is not replaced.

Slow continuous ultrafiltration ((SCUF):

Simultaneous use of HD and UF. It is good with CVS instability. It can remove the inflammatory mediators.

Haemodiafiltration (HDF):

53

* Current data suggest that survival and recovery of renal function are similar with both CRRT and IHD.

* Advocates for CRRT have claimed that CRRT is associated with the following advantages compared with IHD:

1) Enhanced hemodynamic stability, in hemodynamically

unstable patients.

2) Increased net salt and water removal, thereby

permitting superior management of volume overload

and nutritional requirements.

54

3) Enhanced clearance of inflammatory mediators, which

may provide benefit in septic patients, particularly

using convective modes of continuous therapy.

4) Among patients with acute brain injury or fulminant

hepatic failure, continuous therapy may be associated

with better preservation of cerebral perfusion.

55

Least useful form of CRRT in the ICU.

Diffusive treatment: Blood in capillaries of peritoneal membrane exposed to dialysate in abdomen.

Continuous or intermittent.

Inefficient solute/ volume clearance if unstable or poor intestinal blood flow.

Can’t use if intra-abdominal pathology – risk of peritonitis.

Respiratory burden.

Peritoneal dialysis:

56

* Intermittent hemodialysis – Dosing in IHD is based upon the dose delivered per session plus the frequency of sessions.

* Improved survival was observed with a higher Kt/V (greater than 1), which was particlarly evident among patients with intermediate levels of illness severity.

* Compared with every other day dialysis, daily therapy was associated with a significant reduction in mortality, fewer hypotensive episodes during hemodialysis, and more rapid resolution of acute renal failure.

57

* In contrast, the Acute Renal Failure Trial Network (ATN) Study did NOT find a difference in mortality associated with a more intensive dosing strategy for renal replacement therapy.

* The Hanover Dialysis Outcome study compared extended duration dialysis, provided for approximately 8 hours per day, to a more intensive regimen where additional 8-hour treatment sessions were provided to maintain the BUN < 42 mg/dL. No difference in survival or recovery of kidney function was observed with more intensive treatment.

58

• The Randomized Evaluation of Normal versus Augmented Legal of RRT study and two meta-analyses were performed. All studies found that, compared with standard intensity dialysis, higher intensity dialysis did not result in improved survival or clinical benefits.

• It is recommended that IHD be provided 3 times/week with monitoring of the delivered dose of therapy to ensure a minimum delivered Kt/V of 1.2 per treatment.

59

RRT is usually continued until the patient manifests evidence of recovery of kidney function.

1. Increase in urine output.2. A progressive decline in serum creatinine

concentration after initial attainment of stable values (assessed daily during CRRT or predialysis in patients managed with IHD) despite a constant dose of renal support.

3. Measurement of creatinine clearance e.g. on six- hour timed urine collections obtained when the urine output exceeded 30 mL/hour based on an average serum creatinine at the beginning and end of the timed collection.

60

A precise level of kidney function needed to

allow discontinuation of renal support has not

been established; however,

Creatinine clearance < 12 mL/min no discontinuation.

Creatinine clearance > 20 mL/min discontinue.

Creatinine clearance 12 to 20 mL/min optional.

61

1) No drugs are currently available to enhance or hasten renal recovery once ARF occurs.

2) There is now clear evidence that ARF is associated with excess mortality, irrespective of whether the patient requires renal replacement therapy.

3) Hense prevention is the only powerful tool to improve outcome of AKI.

62

Identification of patients at high risk to develop AKI-Elderly, DM, HT. Sepsis etc ....

Non PharmacologicalPharmacological Ensuring adequate

hydration (reversing dehydration,

Maintenance of adequate mean arterial pressure,

Minimizing exposure to nephrotoxins.

Loop diuretics, Mannitol, Dopamine &

Fenoldopam. Natriuretic Peptides.

63

NS, albumin, plasma …. CVP = 8-12 cm H2O, MAP > 65 mmHg. Optimal rate of infusion remain unclear and

should be individualized.

Target MAP 65 mmHg. Which vasopressors to be used. Role of low dose dopamine..

64

Noradrenaline is the drug of choice in AKI in

sepsis. Norepinephrine has been demonstrated to

preserve splanchnic blood flow better than

dopamine. Optimise fluid before starting vasopressors. Low dose dopamine should not be used for

renal protection in severe sepsis.

65

Meta-analysis: Low-Dose Dopamine Increases Urine Output but Does Not Prevent Renal Dysfunction or Death

Low-dose dopamine offers transient improvements in renal physiology, but no good evidence shows that it offers important clinical benefits to patients with or at risk for acute renal failure.

66

In animal studies the use of mannitol and loop

diuretic minimize the degree of renal injury if

given at the time of ischemic injury.

Loop diuretics decrease the active Na

transport in the thick ascending loop

decreasing the energy requirement.

67

Increasing the urine output by loop diuretic

make the management easier but does not

affect cell injury or the severity of the renal

damage.

Loop diuretic increase the urine output in the

remaining nephrons and therefore huge

doses are required that may cause deafness.

68

ANP had been tried in experimental models without any benefit despite their ability to increase renal blood flow and Na excretion.

Calcium channel blockers decrease Ca influx to the cells that lead to cell injury.

Most human studies were done on established ATN.

69

Uncontrolled studies showed that those

patients who respond to diuretics or mannitol

may have better outcome but these patients

has less severe disease.

Controlled studies failed to show any

evidence that low dose dopamine have any

protection of cell injury in ischemic renal

damage.

70