Acute Kidney Injury; Approach

Wisit Cheungpasitporn, M.D.Chulalongkorn University

Acute Renal Failure :Basic Facts

• Characterized by a rapid decline(hours to days) in renal function accompanied by retention of nitrogenous waste products and electrolyte disorders.

• Hard to define: in 26 studies, no two used the same definition!!!

Medical progress:The New England journal of Medicine:May 30,1996

Definition - ARF

• Cr increase of >.5 mg / dl.

• Increase in more than 50% over baseline Cr.

• Decreased in calculated Cr Clearance by more than 50%.

• Any decrease in renal function that requires dialysis.


Epidemiology

• 1% of patients on admission to hospital

• 2-5% of hospitalized patients

• 7-23% of ICU patients

• 20-60% require dialysis; of those who survive initial dialysis, <25% require long-term dialysis

Epidemiology

• Mortality:– 7% among patients admitted with pre-renal

ARF– 50-80% among patients with multiorgan

failure– Rates not significantly decreased over past 50

years despite advances in dialysis and critical care (increased patient age and co morbid illnesses)

Epidemiology

• Most common causes of death in patients with ARF– Before dialysis: hyperkalemia, uremic

complications, volume overload– Now: sepsis, cardiovascular and pulmonary

complications

Classification of ARFAcute Renal Failure

Pre-renal Intrinsic Post-renal

Glomerular Interstitial VascularTubular

55% 40% 5%

85%10%<5% <5%

Harrison’s principles of Internal Medicine 16th Edition

Prerenal Failure

•Decrease in blood flow that leads to a decrease in GFR

•Often rapidly reversible if we can identify this early. •Sustained prerenal azotemia is the main factor that predisposes patients to ischemia- induced acute tubular necrosis (ATN)

Prerenal Causes

I. Hypovolemia (Intravascular volume depletion)

II. Low cardiac output

III.Altered renal systemic vascular resistance ratio

IV.Impaired renal autoregulatory responses

V. Hyperviscosity syndrome(rare)

Prerenal Causes

• Intravascular volume depletion– GI: vomiting, diarrhea, NG losses– Renal: diuresis– Blood loss– Insensible losses (ex. fever, burns)– Sequestration in extravascular space (ex.

pancreatitis, peritonitis, severe hypoalbuminemia)

Prerenal Causes

• Low cardiac output– MI– Cardiomyopathy– Valvular heart disease– Constrictive pericarditis– Tamponade– Arrhythmias– Pulmonary hypertension (ex. massive PE)

Prerenal Causes

• Altered renal systemic vascular resistance ratio– Systemic vasodilation: sepsis, anaphylaxis,

antihypertensives, general anesthetics– Renal vasoconstriction: epi, norepi,

cyclosporine, ampho B, hypercalcemia

Prerenal Causes• Impaired renal autoregulatory responses

– NSAIDs: inhibit production of prostaglandins which are needed to dilate afferent arterioles to maintain GFR in conditions of decreased renal perfusion (ex. CHF, cirrhosis)

– ACEIs: inhibit production of ATII which is needed to constrict efferent arterioles to maintain GFR in conditions of decreased renal perfusion

• Most important in bilateral renal artery stenosis (or unilateral in a solitary functioning kidney)

Prerenal Causes

• Hyperviscosity syndrome– Multiple myeloma– Macroglobulinemia– Polycytemia

Prerenal ARF

Suggestive Clinical Features

- Evidence of true volume depletion (thirst, postural or absolute hypotention and tachycardia, low JVP, dry mucous membranes,weight loss, fluid output> input) or decreased “effective” circulatory volume (e.g. Heart failure, Liver failure), Rx with NSAIDs or ACEIs.

Intrinsic Renal Causes

• Accounts for 40% of cases of ARF

• Types:– Acute glomerulonephritis <5%– Interstitial nephritis 10%– Intrarenal vascular disease <5%– Tubular: ATN 85%

Tubular: ATN

Three phases: •Initiation phase : face with initiation insults eg. Ischemia and nephrotoxic substances

•Maintenance phase : ↑Cr , ↓GFR

•Recovery phase: tubular epithelial cell repair and regeneration. This may be associated with a marked diuretic phase.

Tubular: ATN


• Ischemic Injuries to the renal tubule:– Takes 1-2 weeks to recover from after perfusion

has been normalized.

– In the extreme form this can lead to bilateral renal cortical necrosis ,especially if the disease process includes microvascular coagulation such as may occur with obstetrical complications, snake bites, or the hemolytic uremic syndrome.

ATN: Ischemic

ATN : Toxic

• Exogenous – radiocontrast, cyclosporin, ATB (e.g. aminoglycosides), Chemotherapy (cisplatin) ,organic solvents(e.g.ethylene glycol), acetaminophen, illegal abotifacients

• Endogenous – rhabdomyolysis, hemolysis, uric acid, oxalate, plasma cell dyscrasia (e.g. myeloma)

ATN

Suggestive Clinical Features• Ischemia – Recent hemorrhage, hypotention,

Surgery• Exogenous toxins – Recent radiocontrast

study, nephrotoxic ATB or anticancer agents.• Endogenous toxins – Hx suggestive of

rhabdomyolysis (seizures,coma,ethanol abuse, trauma), Hx suggestive of massive hemolysis (Blood transfusion)

Interstitial Nephritis

• Inflammation localized to the renal interstitium +/- tubulesI. Allergic: ATB (e.g. B-lactams, sulfonamides, trimethoprim,rifampicin), diuretics,NSAIDs, captoprilII. Infection: bacterial (Acute pyelonephritis,leptospirosis), viral (e.g.CMV), fungal(e.g.candidiasis)III. Infiltration : lymphoma, leukemia, sarcoidosisIV. Idiopathic

• Suggestive Clinical FeaturesAllergic lnterstitial Nephritis : Recent ingestion of drug and fever, rash ,or arthalgias

Acute bilateral pyelonephritis : Frank pain and tenderness, toxic , febrile

Interstitial Nephritis

I. Glomerulonephritis and vasculitis

II. HUS,TTP,DIC,toxemia of pregnancy, accelerated hypertension,radiation nephritis, SLE, Scleroderma

Diseases of glomeruli and small vessels

• Inflammation within the glomerular capillaries which results in impairment of glomerular filtration

• Primary renal disease : PSGN, Other post-infectious GN, RPGN

• Systemic diseases : SLE,HSP,Vasculitis (ex. PN, Wegener’s),Goodpasture’s, Infective endocarditis

AGN

Small vessel

• Small vessel disease: interferes with glomerular filtration – glomerular capillary thrombosis or occlusion

• HUS• TTP

– disruption of afferent and efferent arteriolar function• Malignant hypertension• Scleroderma

Diseases of glomeruli and small vessels

• Suggestive Clinical Features– Glomerulonephritis/vasculitis : Compatible clinical

history (e.g.,recent infection) , sinusitis, lung hemorrhage , skin rash or ulcers, arthralgias, new cardiac murmur, Hx of HBV or HCV infection

– HUS/TTP : Compatible clinical history (recent GI infection,cyclosporin,anovulants),fever,pallor, ecchymosis,neurologic abnormalities

– Malignant HT : Severe HT with Headaches, cardiac failure,retinopathy,neulologic dysfuction, papilledema

Large renal vessels

• Large vessel disease interferes with glomerular perfusion

• Must be bilateral to cause ARF (or unilateral with solitary functioning kidney)I. Renal artery obstruction :thrombosis,

embolism,dissecting aneurysm, vasculitis

II. Renal vein obstruction : thrombosis , compression

• Suggestive Clinical Features– Renal a. thrombosis : Hx of AF or recent MI;

flank or abdominal pain– Atheroembolism : Age usually > 50 yrs, recent

manipulation of aorta, retinal plaques, subcutaneous nodules, palpable purpura, livedo reticularis, vasculopathy, HT, antigoagulant

– Renal v. thrombosis : Evidence of nephrotic syndrome or pulmonary embolism, frank pain

Large renal vessels

Post-renal Causes of ARF

• Account for 5% of cases of ARF

• ARF occurs when both urinary outflow tracts are obstructed or when one tract is obstructed in a patient with a single functional kidney

Post-renal Causes of ARF

• Ureter – Calculi, Blood clot, Sloughed papilla, cancer, external compression(e.g. retroperitoneal fibrosis)

• Bladder neck – Neurogenic bladder ,BPH, Calculus,Blood clot,Carcinoma

• Urethra – Stricture,Congenital valve, phimosis• Suggestive Clinical Features

– Abdominal or flank pain, palpable bladder

Acute renal failure: diagnosis

• Suggestive Clinical Features

• Urine analysis

• Renal Indices

• Confirmatory tests

Pre-renal hyaline cast

Renal : ATN Muddy brown casts

Renal : ATN Renal tubular epithelial cell

casts

Renal : GN Red blood cell casts

Renal : AIN White cell / granular casts

• White cell / granular casts.

• KEEP IN MIND THAT BROAD GRANULAR CASTS REFELCT CHRONIC RENAL DISEASE (fibrosis).

• Eosinophiluria (> 5%) is a classic finding (Hansel’s Stain) – especially in antibiotic associated AIN.

Reabsorption of water and sodium:

- intact in pre-renal failure

- impaired in tubulo-interstitial disease and ATN

Since urinary indices depend on urine sodium concentration, they should be interpreted

cautiously if the patient has received diuretic therapy

Renal indices

Renal Failure Index (RFI)

RFI: urine [Na]

urine creatinine / serum creatinine

Renal indices

Fractional Excretion of Na (FENa)

FENa: [ urine Na/serum Na] x 100 %

[urine creatinine/serum creatinine]

urine and serum laboratory values

Prerenal Renal

BUN/ Cr >20 <10-15

FeNa <1% >1%

RFI <1% >1%

UNa (mEq/ L) <10 > 20

Specific gravity >1.020 ~1.010


Management of ARF

– Prevention– Specific Rx– Supportive Measures– Indications and modalities of dialysis

Prevention

• recognize patients at risk (postoperative states, cardiac surgery, septic shock)

• prevent progression from prerenal to renal• preserve renal perfusion

– isovolemia, cardiac output, normal blood pressure

– avoid nephrotoxins (aminoglycosides, NSAIDS, amphotericin)

Specific Rx

Prerenal ARF

• Volume restoration

• Treat underlying cardiac disease (arrhythmia, MI, tamponade)

• Inotropes as necessary to increase cardiac output or support systemic BP in distributive shock

• Stop NSAIDs and ACEIs

AIN

• Remove offending agent

• Most patients recover full kidney function in 1 year

• Poor prognostic factors– ARF > 3 weeks– Advanced age at onset

Specific Rx

Specific Rx

ATN

• Volume restoration

• Remove any offending agent

• Most pts return to baseline Cr in 7-21 days

AGN / vasculitis

• May respond to glucocorticoids, alkylating agents, and/or plasmapheresis, depending on primary pathology

Specific Rx

Post-renal

• Foley catheter

• May need to consult urology for placement of percutaneous nephrostomy tubes for upper tract obstruction

Supportive Measuresand Treatment of

complication• Intravascular volume overload :

– Salt(1-2 g/d) and water(usually<1L/d) restriction

– Diuretics (usually loop blockers +/- thiazide)– Ultrafiltration or dialysis

• Hyponatremia : – Restriction of enteral free water intake(<1 L/d)– Avoid hypotonic IV solutions


complication• Hyperkalemia :

– Restriction of dietary K intake(usually <40 mmol/d)

– Eliminate K supplements and K sparing diuretics– K-binding ion-exchange resins– Glucose(50 ml of 50% dextrose)+insulin(RI10 u)– Sodium bicarbonate(usually 50-100 mmol)– 10% Calcium gluconate 10 ml over 5 min– Dialysis (with low K dialysate)


complication• Metabolic acidosis :

– Restriction of dietary protien(usually 0.6 g/kg/d)– NaHCO3 (maintain serum bicarbonate>15

mmol/L, or arterial pH>7.2)

• Hyperphosphatemia- Restriction of dietary phosphate intake

(usually<800mg/d)- Phosephate binding agents(calcium carbonate,

aluminium hydroxide)


complication• Hypocalcemia :

– Calcium carbonate(if symptomatic or if sodium bicarbonate to be administered)

– Calcium gluconate (10-20 ml of 10% solution)

• Hypermagnesemia- Discontinue Mg containing antacids

• Hyperuricemia- Rx usually not necessary(if <890 μmol/L)

(<15mg/dL)


complication• Nutrition :

– Restriction of dietary protein(~0.6g/kg/d)– Carbohydrate (~100 g/d)– Enteral or parenteral nutrition (if recovery

prolonged or patient very catabolic)

Indications for Dialysis in ARF

• Clinical evidence of uremia

• Intractable intravascular volume overload

• Hyperkalemia or severe acidosis resistance to conservative measures

• Prophylaxis dialysis when – Urea > 100-150 mg/dL – Creatinine > 8-10 mg/dL


• Prophylaxis dialysis when – Urea > 70 mg/dL – Creatinine > 7 mg/dL– Hypercatabolic ARF ↑BUN>20, ↑Cr>1.5 /day

Indications for Dialysis in ARF

Evidence-Base Clinical Practice Guideline 2548

Modalities of Dialysis

• Dialysis replaces renal function until regeneration and repair restore renal function

• Hemodialysis and Peritoneal dialysis appear equally effective for Mx of ARF

• Peritoneal dialysis may be preferable if the patient is hemodynamically unstable

• Hemodialysis after abdominal Sx involving the peritoneum

• Recent evidence suggests that more intensive hemodialysis is clinically superior and confers improved survival.

• The bulk of evidence to date suggests that intermittent and continuous dialytic Rx are equally effective in the context of ARF.

• Continuous renal replacement therapies(CRRTs) : CAVHD,CVVHD, CAVH,CVVH

Modalities of Dialysis

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Acute Kidney Injury; Approach

Health & Medicine

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