Medicine_acute Renal Failure

7/31/2019 Medicine_acute Renal Failure

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OUTLINE

I. Definition: ARFII. Pre-Renal Failurea. Etiologyb. Pathophysiology

III. Intrinsic Renal Failurea. Classificationb. Etiologyc. Pathology

IV. Post-RenalV. Approach to Renal Failure

Acute Renal Failure

Definition:

characterized by a rapid decline in glomerular filtrationrate (GFR) over hours to days

complicates approximately 57% of hospitaladmissions and up to 30% of admissions to intensive

care units

usually asymptomatic and diagnosed when biochemicalmonitoring of hospitalized patients reveals a new

increase in blood urea and serum creatinineconcentrations.

ARF is often considered to be reversible but may alsocontribute to progression to chronic kidney disease

Clinical Features:

Retention of nitrogenous waste products (BUN) oliguria (urine output


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Angiotensin II : increases filtration fraction andpreserves GFR, maintains glomerular pressure

Increases biosynthesis of vasodilator prostaglandins(e.g., prostaglandin E2 and prostacyclin), also resultingin afferent arteriolar vasodilation.

induces preferential constriction of efferent arterioles. With more severe hypoperfusion, these

compensatory responses are overwhelmed and GFR

falls, leading to prerenal ARF.

Who are at risk?

the elderly patients with diseases that affect the integrity of

afferent arterioles hypertensive nephrosclerosis, diabetic vasculopathy occlusive (including atherosclerotic)/ renovascular

disease)

Drugs that inhibit renal prostaglandin biosynthesis:NSAIDs, ACE inhibitors, ARBs

NSAIDS do not complicate GFR of healthy individuals,only those patients with volume depletion and chronic

kideney disease (in whom GFR is maintained, in part,

through prostaglandin hyperfiltration by the remaining

functional nephrons)

Hepatorenal Syndrome

unique form of prerenal ARF that frequentlycomplicates advanced cirrhosis as well as acute liver

failure

is a life-threatening medical condition that consists ofrapid deterioration in kidney function in individuals with

cirrhosis or fulminant liver failure

kidneys are structurally normal but fail due tosplanchnic vasodilation and arteriovenous shunting,

resulting in profound renal vasoconstriction.

Coreection of underlying liver disease (e.g. Livertransplantation) results in resolution of the acute renal

failure

2 forms:

1. Type 1- more aggressive form, ARF progresses even afteroptimization of systemic hemodynamics and carries

mortality rate of >90%

2. Type II- associated with ascites that does not improvewith standard diuretic medications.

Intrinsic Renal Failure

PreRenal ARF prolonged hypoperfusion IntrinsicRenal Failure

Other Names: Ischemic or Nephrotoxic ARF/ Acute Tubular

Necrosis/ Acute Kidney Injury)

renal tubular epithelial/endothelial cells are injured 40% of acute renal failure cases More severe or prolonged hypoperfusion may lead to

ischemic injury, often termed acute tubular necrosis, or

ATN. of renal hypoperfusion.

Although many patients with ischemic or nephrotoxicARF do not have morphologic evidence of cellular

necrosis, this disease is often referred to as acute

tubular necrosis, or ATN.

More recently,because of the important role of sublethalinjury to tubular epithelial and other renal cells (e.g.,

endothelial cells) in the pathogenesis of this syndrome,

the term acute kidney injury (AKI) has been proposed.Classsification of Intrinsic Renal Failure

(1) ischemic or nephrotoxic tubular injury termed acutetubular necrosis eventhough there is no morphologic evidence of

cellular necrosis


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(2) tubulointerstitial diseases

(3) diseases of the renal microcirculation and glomeruli, and

(4) diseases oflarger renal vessels

Etiology of Intrinsic Renal Failure

I. Renovascular obstruction (bilateral, or unilateral in the

setting of one kidney)A. Renal artery obstruction: atherosclerotic plaque,

thrombosis, embolism, dissection aneurysm, large vessel

vasculitis

B. Renal vein obstruction: thrombosis or compressionII. Diseases of the glomeruli or vasculature

A. Glomerulonephritis or vasculitis

B. Other: thrombotic microangiopathy, malignant

hypertension, collagen vascular diseases (systemic lupus

erythematosus, scleroderma), disseminated intravascular

coagulation, preeclampsiaIII. Acute tubular necrosis

A. Ischemia: causes are the same as for prerenal ARF,

but generally the insult is more severe and/or more prolonged

B. Infection, with or without sepsis syndromeC. Toxins: intrarenal vasoconstriction/ generate

reactive oxygen species/direct toxicity/ obstruction

1. Exogenous: radiocontrast, calcineurininhibitors, antibiotics ( aminoglycosides),

chemotherapy (cisplatin), antifungals(amphotericin B), ethylene glycol

2. Endogenous: rhabdomyolysis, hemolysis

IV. Interstitial nephritisA.Allergic: antibiotics (-lactams, sulfonamides,

quinolones, rifampin), nsaids, diuretics)B. Infection: pyelonephritis (if bilateral)

C. Infiltration: lymphoma, leukemia, sarcoidosis

D. Inflammatory, nonvascular: Sjgrens syndrome,

tubulointerstitial nephritis with uveitisV. Intratubular obstruction

A. Endogenous: myeloma proteins, uric acid (tumor

lysis syndrome), systemic oxalalosis

B. Exogenous: acyclovir, gancyclovir, methotrexate,

indinavir

Etiology and Pathophysiology of Ischemic ATN

part of manifestation of renal hypoperfusion in most severe form, ischemia leads to bilateral renal

cortical necrosis and irreversible renal failure

differs from prerenal ARF in that the renal tubularepithelial cells are injured in ischemic ATN

recovery typically takes 12 weeks after normalization ofrenal perfusion, as it requires repair/regeneration of

renal cells

4 phases:o Initiation- lasting hours to days.

- GFR declines because of 1) reducedglomerular ultrafiltration pressure as

blood flows falls, 2)flow of filtrate withintubules is obstructed by casts, epithelial

cells and necrotic debris, 3)backleak of

glomerular filtrate though injured tubular

epithelium.

- Ischemic injury most prominent in the S3segment of proximal tubule and medullary

portion of thick ascending loop of Henle.

These segments are sensitive to ischemia

because of high rates of active(ATP-

dependent) solute transport and location

in outer medulla where partial pressure of

oxygen is low

o Extension- continued ischemic injury andinflammation secondary to endothelial damage.

o Maintenance- typically 1-2 weeks. GFR stabilizes at its

nadir (typically 5-10 ml/min), urine

output at its lowest, and uremic

complications.

- Persistent intrarenal vasoconstrictionand medullary ischemia triggered by

dysregulated release of vasoactive

mediators

o Recovery- repair and regeneration as well as agradual return of GFR toward premorbid levels

Etiology and Pathophysiology of Nephrotoxic ARF

Nephrotoxic ATN may complicate exposure to manystructurally diverse pharmacologic agents. With mostnephrotoxins, the incidence of ARF is increased in the

elderly and in patients with preexisting chronic kidneydisease, true or effective hypovolemia, or concomitant

exposure to other toxins.

Radiocontrast agents, cyclosporine, and tacrolimus(FK506) cause kidney injury through intrarenal

vasoconstriction acute fall in renal blood flow andGFR, relatively benign urine sediment, and a low

fractional excretion of sodium.

Contrast nephropathy is also thought to result from thegeneration of reactive oxygen species that are directly

toxic to renal tubular epithelial cells. (preexisting

chronic kidney disease, diabetes mellitus, congestive

heart failure, hypovolemia, or multiple myeloma.)

Antibiotics and anticancer drugs typically cause ATNthrough direct toxicity to the tubular epithelial cells

and/or intratubular obstruction.

- Aminoglycoside- cause oxidative stress and cellinjury. Damage occurs in proximal and distal

- Amphotericin B-dose related through intrarenalvasoconstriction and direct toxicity to proximal

tubules

- Foscarnet and pentamidine- Cisplatin and carboplatin- similar to

aminoglycoside

- Ifosphamide- leads to hemorrhagic cystitis Endogenous nephrotoxins include calcium, myoglobin,

hemoglobin, urate, oxalate, and myeloma light chains.Hypercalcemia can compromise GFR, predominantly byinducing intrarenal vasoconstriction as well as volume

depletion from obligate water loss.

Pathology of Intrinsic Renal Failure (ATN)

patchy and focal necrosis of the tubular epithelium, withdetachment of cells from the basement membrane,

Occlusion of tubule lumens with casts composed of intactor degenerating epithelial cells, Tamm-Horsfall protein,

and pigments.

Leukocyte accumulation is frequently observed in vasarecta

glomeruli and renal vasculature is characteristicallynormal.

Postrenal Failure

Urinary tract obstruction accounts for fewer than 5% ofcases of hospital-acquired ARF

Bladder neck obstruction is the most common cause ofpostrenal ARF and is usually due to Prostatic disease,

neurogenic bladder, or therapy with anticholinergicdrugs

Ureteric obstruction may result from intraluminalobstruction (e.g., calculi, blood clots, sloughed renal

papillae), infiltration of the ureteric wall (e.g.,

neoplasia), or External compression (e.g.,

retroperitoneal fibrosis, neoplasia or abscess,inadvertent surgical ligature)

Approach to Renal Failure

1. Acute or Chronic ARF?- Acute-If review of lab records demonstrates recent rise

in BUN and crea

- Chronic- anemia, evidence of renal osteodystrophy(radiologic or laboratory) and small scarred kidney

2. Etilogy and specific treatment?

3. Prevention and management?

Diagnostics:

Urinalysis BUN, Creatinine Na, K, Cl KUB ultrasound


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CBCApproach to Renal Failure: Acute or Chronic?

Approach to ARF: Clinical Assessment

Prerenal ARF- thirst and orthostatic dizziness.- orthostatic hypotension, tachycardia,- jugular venous pressure- decreased skin turgor- dry mucous membranes

Intrinsic/ Ischemic ARF- Hypovolemia, septic shock, and major surgery- Persistence of ARF despite restoration of

hemodynamics

- Fever, arthralgias, and a pruritic erythematousrash following exposure to a new drug suggest

allergic interstitial nephritis

- Flank pain may be a prominent symptom followingocclusion of a renal artery or vein

- Oliguria, edema, and hypertension, with an activeurine sediment (nephritic syndrome), suggestsacute gomerulonephritis or vasculitis

- Malignant hypertension may result in ARF, oftenin association with hypertensive injury to otherorgans (e.g., papilledema, neurologic dysfunction,

left ventricular hypertrophy)

PostRenal ARF- Suprapubic and flank pain due to distention of

the bladder and of the renal collecting system and

capsule

- Colicky flank pain radiating to the groin suggestsacute ureteric obstruction

- Prostatic disease - nocturia, frequency, andhesitancy and BPH on rectal examination

- Neurogenic bladder - anticholinergicmedications or with physical evidence of

autonomic dysfunction.

Urinalysis

PreRenal ARF:- acellular & contains transparent hyaline casts

(bland, benign, inactive urine sediment)- Hyaline casts are formed in concentrated urine

from normal constituents of urineprincipallyTamm-Horsfall protein, which is secreted by

epithelial cells of the loop of Henle

Intrinsic ARF:

- Pigmented muddy brown granular casts andcasts containing tubule epithelial cells are

characteristic of ATN ( ischemic/ nephrotoxic)

- mild tubular proteinuria (5% of urine leukocytes) is a

common finding (~90%) in antibiotic-inducedallergic interstitial nephritis

- Lymphocytes may predominate in allergicinterstitial nephritis induced by NSAIDs,and some

other drugs (i.e., ampicillin, rifampicin, and

interferon )

- uric acid crystals prerenal or uratenephropathy

- Proteinuria of >1 g/d suggests glomerularproteinuria or excretion ofmyeloma light

chains.- Hemoglobinuria or myoglobinuria should be

suspected if urine is strongly positive for heme by

dipstick but contains few red cells

- Bilirubinuria may provide a clue to the presenceofHepatorenal Syndrome

Postrenal ARF- Anuria/ wide fluctuations in urine output- inactive sediment, although hematuria and pyuria

are common in patients with intraluminal

obstruction or prostatic disease.

Etiology


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Prerenal vs Renal

- The fractional excretion of sodium (FENa) is mostuseful in this regard. The FENa relates sodium clearance

to creatinine clearance.

- Sodium is reabsorbed avidly from glomerular filtrate inpatients with prerenal ARF, in an attempt to restore

intravascular volume.

- creatinine is not reabsorbed in either prerenal orintrinsic renal failure.

- The FENa tends to be high in ischemic ATN but is oftenlow in patients with sepsis-induced, contrast-associated).

- Patients with prerenal ARF typically have a FENa of


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- Nephrotoxic ATN - Eliminate nephrotoxicagents, Consider toxin-specific measures: (e.g.,

forced alkaline diuresis for rhabdomyolysis,

allopurinol/rasburicase for tumor lysissyndrome

- Other Diseases ( Glomerulonephritis/vasculitis) - Immunosuppresion(Glucocorticoids, alkylating agents, and/or

plasmapheresis)

Supportive Measures:1. Salt & Water restriction2. Diuretics/ Ultrafiltration

3. Low K diet/ K-binding resins/ Insulin+glucose

4. Sodium bicarbonate

5. Protein and calorie intake to avoid net

negative nitrogen balance

6. Avoid other nephrotoxins7. Drug dosing

8. Dialysis

Dialysis: Indications:

uremic syndrome refractory hypervolemia,

hyperkalemia, or acidosis empirically, blood urea levels of

>100 mg/dL 2 types: Hemodialysis and peritoneal dialysis

According to harrisons, hemodialysis appears to

be somewhat more effective than peritoneal

dialysis for management of ARF, but Dr.

Alcantara said their just the same.

Hemodialysis

Hemodialysis

- Internal Jugular Catheter- Arterio-venous Fistula/ Graft- Subclavian vein is avoided because of risk of

subclavian stenosis

Peritoneal Dialysis

- Preferred if there is diificulty obtaining vascularaccess

- Associated with more protein loss- Contraindicated in those who have undergone

recent surgery or those with ongoing infection

ARF Acute Kidney Injury

new terminology considers the disease as a spectrumof injury.

Acute Dialysis Quality Initiative (ADQI) and devisedthe RIFLE definition and staging system

Acute Kidney Injury Network (AKIN) group modifiedthe RIFLE staging system

Kidney Disease: Improving Global Outcomes(KDIGO) harmonises the previous definitions and

staging systems proposed by both ADQI and AKIN 5

KDIGO staging system for acute kidney injury

Biomarkers of AKI

serum creatinine and urine outputremain the bestbiomarkers for AKI.

despite the fact that serum creatinine represents a poorbiomarker


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