ARF and Glomerular Filtrationedited

Glomerular Filtration
and
Acute Renal Failure
Eva Sian Li
Glomerular Filtration
Regulation of GF
Under physiological conditions balance between the resistance in the afferent and
efferent arterioles
The Renal System. Basic Science and Clinical Conditions. Churcill Livingstone. 2001
Measuring the GFR
Inulin difiltrasi glomerulus, tidak mengalami reabsorpsi dan

sekresi
Kesulitan menentukan C in inulin harus diinfus, sulit diperiksa
Measuring the GFR

Kreatinin (Cr)
hasil metabolisme kreatin (komponen otot skelet)
Jumlah masa otot skelet
Difiltrasi
Tidak mengalami reabsorpsi
Disekresikan minimal
pada gangguan fungsi ginjal
Measuring the GFR

Creatinine (Cr)
Ucr x V : constant fo a
given individual under
steady state conditions
Fixed relationship
between GFR and
plasma creatinine, in
the form of rectangular
hyperbola
Measuring the GFR

Kreatinin (Cr)
Cr plasma bila LFG
50%
Cr : massa otot skelet
massa otot skelet
Cr plasma N walaupun
LFG )
Measuring the GFR

Rumus Cockroft dan Gault
Perkiraan LFG (mL/ min)
140 usia x BB (kg)
814 x plasma Cr (mmol/ L)
perempuan: x 0,85
Urea
Kurang bermakna dalam menentukan LFG
Produk utama hasil metabolisme protein
Disintesis di hati : ion amonium (katabolisme asam
amino)+CO2
Produksi urea
jumlah protein yang diabsorpsi dari usus
kecepatan katabolisme protein
Difiltrasi bebas di glomerulus

50% direabsorpsi
Fraksi urea filtrasi yang direabsorbsi tidak konstan
Status hidrasi
Laju aliran urin
klirens urea: + 50% LFG

Factors causing an increase in plasma

creatinine and urea concentration
Kreatinin
LFG
Massa otot skelet (jk panjang)
Urea
LFG
Laju aliran urin
Asupan protein
Diet
Perdarahan GI
Laju katabolik protein
Sepsis
Terapi steroid
Antibiotik tetrasiklin
Blood Urea Nitrogen and Serum Creatinine
www.kidneyatlas.org
Acute renal failure (ARF)

syndrome characterized
rapid (hours to weeks) decline in glomerular
filtration rate (GFR)
retention of nitrogenous waste products such
as blood urea nitrogen (BUN) and creatinine
independent risk factor for mortality

significant prolongation in length of
hospital stay
Brenner: Brenner & Rector's The Kidney, 7th ed. Saunders. Elsevier. 2004
Oxford Textbook of Clinical Nephrology, 3rd Edition. Oxford University Press 2005

(1) renal hypoperfusion in which the integrity of
renal parenchymal tissue is preserved
prerenal azotemia, prerenal ARF; 55% to 60%);
(2) involving renal parenchymal tissue

(intrarenal azotemia, intrinsic renal ARF; 35% to 40%)
(3) acute obstruction of the urinary tract

(postrenal azotemia, postrenal ARF; <5%)
Prerenal Azotemia
Major Causes of Prerenal Azotemia
Intravascular Volume Depletion
Hemorrhage: traumatic, surgical, gastrointestinal, postpartum
Gastrointestinal losses: vomiting, nasogastric suction, diarrhea
Renal losses: drug-induced or osmotic diuresis, diabetes insipidus, adrenal insufficiency
Skin and mucous membrane losses: burns, hyperthermia, other causes of increased insensible
losses
"Third-space" losses: pancreatitis, crush syndrome, hypoalbuminemia

Decreased Cardiac Output
Diseases of myocardium, valves, pericardium, or conducting system
Pulmonary hypertension, pulmonary embolism, positive-pressure mechanical ventilation
Systemic vasodilatation
Drugs: antihypertensives, afterload reduction, anesthetics, drug overdoses
Sepsis, liver failure, anaphylaxis

Renal Vasoconstriction
Norepinephrine, ergotamine, liver disease, sepsis, hypercalcemia

Pharmacologic Agents That Acutely Impair Autoregulation and Glomerular Filtration Rate in
Specific Settings
Angiotensin-converting enzyme inhibitors in renal artery stenosis or severe renal hypoperfusion
Inhibition of prostaglandin synthesis by nonsteroidal anti-inflammatory drugs during renal

hypoperfusion
Intrinsic Renal Azotemia

Major Causes of Acute Intrinsic Renal Azotemia
Diseases Involving Large Renal Vessels
Renal arteries: thrombosis, atheroembolism, thromboembolism, dissection, vasculitis (e.g.,

Takayasu)
Renal veins: thrombosis, compression

Diseases of Glomeruli and the Renal Microvasculature
Inflammatory: acute or rapidly progressive glomerulonephritis, vasculitis, allograft rejection,

radiation
Vasospastic: malignant hypertension, toxemia of pregnancy, scleroderma, hypercalcemia, drugs,

radiocontrast agents
Hematologic: hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura, disseminated

intravascular coagulation, hyperviscosity syndromes
Diseases Characterized by Prominent Injury to Renal Tubules Often with Acute Tubule Necrosis
Ischemia caused by renal hypoperfusion
Exogenous toxins (e.g., antibiotics, anticancer agents, radiocontrast agents, poisons;
Endogenous toxins (e.g., myoglobin, hemoglobin, myeloma light chains, uric acid, tumor lysis;
Acute Diseases of the Tubulointerstitium
Allergic interstitial nephritis (e.g., antibiotics, nonsteroidal anti-inflammatory drugs)
Infectious (viral, bacterial, fungal)
Acute cellular allograft rejection
Infiltration (e.g., lymphoma, leukemia, sarcoid)
Postrenal Azotemia
Causes of Acute Postrenal Azotemia
Ureteric Obstruction
Intraluminal: stones, blood clot, sloughed renal papillae, uric acid or
sulfonamide crystals, fungus balls
Intramural: postoperative edema after ureteric surgery, BK virusinduced ureteric fibrosis in renal allograft
Extraureteric: iatrogenic (ligation during pelvic surgery)
Periureteric: hemorrhage, tumor, or fibrosis
Bladder Neck Obstruction
Intraluminal: stones, blood clots, sloughed papillae
Intramural: bladder carcinoma, bladder infection with mural edema,
neurogenic, drugs (e.g., tricyclic antidepressants, ganglion blockers)
Extramural: prostatic hypertrophy, prostatic carcinoma
Urethral Obstruction
Phimosis, congenital valves, stricture, tumor
Phases of Acute Tubule Necrosis

initiation phase
hypothetical period of time during which renal
perfusion is compromised to the extent that it
precipitates a complex array of intrarenal events that
are responsible for persistence of renal dysfunction
long after the initiating cause has been resolved
maintenance phase
period of ongoing renal failure (lasting days to weeks)
that follows the initiation phase.
recovery phase
renal injury is repaired and relatively normal or
baseline renal function is reestablished
Pathophysiology of Acute Tubule

Necrosis (ATN)
Acute Tubule Necrosis in Sepsis
Consequences of Acute Tubule Injury:

Necrosis, Apoptosis, and Sublethal Injury
Common Complications of ARF
Clinical approach to the patient with

acute renal failure
Pengkajian
Acute Kidney Injury
An abrupt (within 48 h) reduction in kidney function defined as
an absolute increase in serum creatinine level of 26.4 mol/l
(0.3 mg/dl)
OR
a percentage increase in serum creatinine level of 50% (1.5fold from baseline)
OR
a reduction in urine output (documented oliguria of <0.5 ml/kg/h
for >6 h)
Nat Clin Pract Nephrol. 2007;3(8):439-442
Pengkajian
Nat Clin Pract Nephrol. 2007;3(8):439-442
Categories of renal failure
Urinary diagnostic indices in acute

renal failure (ARF)
Urinalysis in acute renal failure

(ARF)
MANAGEMENT OF ACUTE
RENAL FAILURE
Prerenal Azotemia
Rapidly reversible on restoration of renal
perfusion
The composition of replacement fluids for
treatment of hypovolemia varies depending on
the source of fluid loss.
Serum K+ concentration and acid-base status
should be monitored in all subjects
Prerenal Azotemia :
Cardiac Failure
Cardiac failure may require aggressive
management with loop diuretics, antiarrhythmic
drugs, positive inotropes, preload- and/or
afterload-reducing agents, and mechanical aids
such as an intra-aortic balloon pump.
Invasive hemodynamic monitoring is invaluable
for guiding therapy in complicated cases in
which clinical assessment of cardiovascular
function and intravascular volume may be
difficult and unreliable.
Intrinsic Renal Azotemia :

Prevention
Optimization of cardiovascular function and
intravascular volume is the single most
important maneuver in the management of acute
intrinsic azotemia.
Contrast nephropathy
Prophylactic infusion of half-normal saline
1 mL/kg for 12 hours before and after procedure
Prophylactic administration of oral acetylcysteine

600 mg twice daily, 24 hours before and 24 hours after the
procedure

Prevention
Diuretics, NSAIDs (including COX-2 inhibitors),
ACE inhibitors, and other vasodilators should be
used with caution in patients with suspected true
or effective hypovolemia or renovascular
disease, because they may convert prerenal
azotemia to ischemic ATN and sensitize the
patients to the actions of nephrotoxins
Careful monitoring of circulating drug levels
appears to reduce the incidence of ARF
associated with aminoglycoside antibiotics or
calcineurin inhibitors

Prevention
Allopurinol is useful for limiting uric acid
generation in patients at high risk for acute urate
nephropathy
Amifostine, an organic thiophosphate, has been
demonstrated to ameliorate cisplatin
nephrotoxicity in patients with solid organ or
hematologic malignancies
Forced diuresis and alkalinization of urine may
attenuate renal injury caused by uric acid or
methotrexate and after rhabdomyolysis

Prevention
N-Acetylcysteine limits acetaminophen-induced
renal injury if given within 24 hours of ingestion,
Dimercaprol, a chelating agent, may prevent
heavy metal nephrotoxicity
Ethanol inhibits ethylene glycol metabolism to
oxalic acid and other toxic metabolites and is an
important adjunct to hemodialysis in the
emergency management of this intoxication

"Renal dose dopamine" (1 to 3 mg/kg/min)
widely advocated for the management of oliguric ARF
has not been demonstrated to prevent or alter the
course of ischemic or nephrotoxic ATN
lack of efficacy
dopamine, even at low doses, is potentially toxic in
critically ill patients and can induce tachyarrhythmias
and myocardial ischemia among other complications.
routine administration of dopamine to patients

with oliguric ARF is not justified based on the
balance of experimental and clinical evidence

ANP (Atrial Natriuretic Peptide)
augments GFR by triggering afferent arteriolar
vasodilatation and increasing ultrafiltration coefficient
(Kf)
inhibits sodium transport and lowers oxygen
requirements in several nephron segments
Synthetic analogs of ANP have shown promise in the
management of ATN in the laboratory setting.
has failed to translate into clinically apparent benefit

The administration of high-dose
intravenous diuretics to individuals with
oliguric ARF
commonly practiced
may minimize fluid overload
no evidence that it alters the mortality rate or
the dialysis-free survival rate.
increased risk of death and nonrecovery of
renal function in patients treated in this
manner

ARF caused by other intrinsic renal
diseases, such as acute
glomerulonephritis or vasculitis, may
respond to corticosteroids, alkylating
agents, and/or plasmapheresis,
depending on the primary disease.
Corticosteroids appear to hasten
remission in some cases of allergic
interstitial nephritis

Plasma exchange and plasma infusion are
useful in the treatment of sporadic and
familial forms of HUS and TTP
Postdiarrheal HUS in children is usually
managed conservatively, and evidence
exists to suggest that early antibiotic
therapy may actually promote the
development of HUS

Plasmapheresis may also be of benefit in ARF
caused by myeloma cast nephropathy
Clearance of circulating light chains with
concomitant chemotherapy to decrease the rate
of production showed promise in reversing renal
injury in patients with circulating light chains,
heavy Bence Jones proteinuria, and ARF in a
single prospective study

Aggressive control of systemic arterial
pressure is of paramount importance for
limiting renal injury in malignant
hypertensive nephrosclerosis, and other
vascular diseases
Hypertension and ARF associated with
scleroderma may be exquisitely sensitive
to treatment with ACE inhibitors.

Management of Complications
Intravascular volume overload can usually be
managed by restriction of salt and water intake
and the use of diuretics
no proven rationale for routine administration of
diuretics to patients with ARF other than to treat
this complication
In the volume-overloaded patient
high doses of loop diuretics such as furosemide
(bolus doses of up to 200 mg or up to 20 mg/hour as
an intravenous infusion) or sequential thiazide and
loop diuretic administration may be required if there is
no response to conventional doses.

Diuretic therapy should be discontinued in resistant
patients to avoid complications such as ototoxicity.
Ultrafiltration or dialysis may be required for removal of
volume if conservative measures fail.
Hyponatremia associated with a fall in effective serum
osmolality can usually be corrected by restriction of
water intake.
Hypernatremia is treated by administration of water,
hypotonic saline solutions, or hypotonic dextrosecontaining solutions (the latter are effectively hypotonic
because dextrose is rapidly metabolized)

Mild hyperkalemia (<5.5 mEq/L)
initially by restriction of dietary potassium intake
elimination of K supplements and K-sparing diuretics.
Moderate hyperkalemia (5.5 to 6.5 mEq/L) in

patients without clinical or ECG evidence of
hyperkalemia
administration of K+-binding ion exchange resins
such as sodium polystyrene sulfonate (15 to 30 g
every 3 or 4 hours) with sorbitol (50 to 100 mL of 20%
solution) by mouth or as a retention enema.
Loop diuretics also increase K+ excretion in diureticresponsive patients.

serum K+ values greater than 6.5 mEq/L
ECG abnormalities or clinical features of
hyperkalemia
Emergency measures
Intravenous insulin
(10 U of regular insulin) and glucose (50 mL of 50%
dextrose)
promote K+ shift into cells within 30 to 60 minutes
lasts for several hours.
Sodium bicarbonate
(1 ampule, 44.6 mEq intravenously over 5 minutes)
promotes rapid shift of K+ into the intracellular space (onset
less than 15 minutes, duration 1 to 2 hours)

Intravenous albuterol (0.5 mg in 100 mL of 5%
dextrose over 5 minutes) or nebulized albuterol
(1020 mg).
Calcium solutions : calcium gluconate
(10 mL of 10% solution intravenously over 5 minutes)
antagonize the cardiac and neuromuscular effects of
hyperkalemia and provide a valuable emergency
temporizing measure while other agents reduce the
serum K+ concentration.
Dialysis is indicated if hyperkalemia is resistant

to these measures.

Metabolic acidosis does not require treatment
unless the serum HCO3- concentration falls
below 15 mEq/L.
More severe acidosis can be corrected by either
oral or intravenous bicarbonate administration.
should be monitored for complications of
bicarbonate administration, including metabolic
alkalosis, hypocalcemia, hypokalemia, volume
overload, and pulmonary edema.

Hyperphosphatemia
usually be controlled by restriction of dietary phosphate
intake and oral administration of agents (e.g., aluminum
hydroxide, calcium carbonate, sevelamer) that reduce
absorption of PO43- from the gastrointestinal tract.
Hypocalcemia
does not usually require treatment unless it is severe,
as may occur in patients with rhabdomyolysis or
pancreatitis or after administration of bicarbonate.
Hyperuricemia
usually mild in ARF (<15 mg/dL)
does not require specific intervention.

individualized nutritional management is
required, especially for critically ill patients
receiving renal replacement therapy, in whom
protein catabolic rates can exceed 1.5 g/kg body
weight per day
The objective of dietary modification in ARF is to
provide sufficient calories to preserve lean body
mass, avoid starvation ketoacidosis, and
promote healing and tissue repair, while
minimizing the production of nitrogenous waste.

If the duration of renal insufficiency is likely to be
short and the patient is not catabolic, then
dietary protein should be restricted to less than
0.8 g/kg body weight per day
Catabolic patients, including those receiving
continuous renal replacement therapy, may
receive up to 1.4 mg/kg body weight per day
Total caloric intake should not exceed 35 kcal/kg
body weight per day and will typically range from
25 to 30 kcal/kg body weight per day

The enteral route of nutrition is preferred,
because it avoids the morbidity associated with
parenteral nutrition while providing support to
intestinal function
Water-soluble vitamin supplementation is
advised, with the exception of vitamin C, which
can, in high doses (<200 mg/day), promote
urinary oxalate excretion and stone formation

Anemia may necessitate blood transfusion or the
administration of recombinant human erythropoietin if it is
severe or if recovery is delayed.
Uremic bleeding usually responds to desmopressin,
correction of anemia, estrogens, or dialysis.
Doses of drugs that are excreted by the kidney must be
adjusted for the degree of renal impairment.
Gastric stress ulcer prophylaxis is not indicated unless the
patient is intubated or has a concurrent coagulopathy
Febrile patients must be investigated aggressively for
infection and may require treatment with broad-spectrum
antibiotics while awaiting identification of specific
organisms.

Indications and Modalities of Dialysis
Dialysis does not hasten recovery from ARF.
Early and unnecessary hemodialysis may
potentially exacerbate renal hypoperfusion,
because transient hypotension is a common
complication of this treatment modality, and
leukocytes activated on exposure to dialysis
membranes may potentially aggravate ischemic
renal injury

Indications and Modalities of Dialysis
There is no firm consensus on the initiation of
dialysis in ARF.
Absolute indications for the commencement of
renal replacement therapy include
symptomatic uremia (asterixis, pericardial rub,
encephalopathy) and acidosis, hyperkalemia, or
volume overload that proves refractory to medical
management.
The choice of dialysis modality (peritoneal

dialysis, hemodialysis, or hemofiltration)
resources of the health care institution, the technical
expertise of the physician, and the clinical status of the
patient.
Postrenal Azotemia
Urethral or bladder neck obstruction is usually
relieved temporarily by transurethral or
suprapubic placement of a bladder catheter,
Ureteric obstruction may be treated initially by
percutaneous catheterization of the dilated
ureteric pelvis or ureter
Obstructing lesions can often be removed
percutaneously
Most patients experience an appropriate diuresis
for several days after relief of obstruction
Thank You

ARF and Glomerular Filtrationedited

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Glomerular Filtration

Measuring the GFR

Inulin difiltrasi glomerulus, tidak mengalami reabsorpsi dan

Measuring the GFR

Measuring the GFR

Measuring the GFR

Measuring the GFR

Difiltrasi bebas di glomerulus

klirens urea: + 50% LFG

Factors causing an increase in plasma

Blood Urea Nitrogen and Serum Creatinine

Acute renal failure (ARF)

Acute renal failure (ARF)

independent risk factor for mortality

Acute renal failure (ARF)

(2) involving renal parenchymal tissue

(3) acute obstruction of the urinary tract

Hemorrhage: traumatic, surgical, gastrointestinal, postpartum

Gastrointestinal losses: vomiting, nasogastric suction, diarrhea

Renal losses: drug-induced or osmotic diuresis, diabetes insipidus, adrenal insufficiency

"Third-space" losses: pancreatitis, crush syndrome, hypoalbuminemia

Diseases of myocardium, valves, pericardium, or conducting system

Pulmonary hypertension, pulmonary embolism, positive-pressure mechanical ventilation

Drugs: antihypertensives, afterload reduction, anesthetics, drug overdoses

Sepsis, liver failure, anaphylaxis

Norepinephrine, ergotamine, liver disease, sepsis, hypercalcemia

Angiotensin-converting enzyme inhibitors in renal artery stenosis or severe renal hypoperfusion

Inhibition of prostaglandin synthesis by nonsteroidal anti-inflammatory drugs during renal

Intrinsic Renal Azotemia

Renal arteries: thrombosis, atheroembolism, thromboembolism, dissection, vasculitis (e.g.,

Renal veins: thrombosis, compression

Inflammatory: acute or rapidly progressive glomerulonephritis, vasculitis, allograft rejection,

Vasospastic: malignant hypertension, toxemia of pregnancy, scleroderma, hypercalcemia, drugs,

Hematologic: hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura, disseminated

Ischemia caused by renal hypoperfusion

Exogenous toxins (e.g., antibiotics, anticancer agents, radiocontrast agents, poisons;

Allergic interstitial nephritis (e.g., antibiotics, nonsteroidal anti-inflammatory drugs)

Infectious (viral, bacterial, fungal)

Acute cellular allograft rejection

Infiltration (e.g., lymphoma, leukemia, sarcoid)

Phases of Acute Tubule Necrosis

Pathophysiology of Acute Tubule

Acute Tubule Necrosis in Sepsis

Consequences of Acute Tubule Injury:

Common Complications of ARF

Clinical approach to the patient with

Nat Clin Pract Nephrol. 2007;3(8):439-442

Nat Clin Pract Nephrol. 2007;3(8):439-442

Categories of renal failure

Urinary diagnostic indices in acute

Urinalysis in acute renal failure

Intrinsic Renal Azotemia :

Prophylactic administration of oral acetylcysteine

Intrinsic Renal Azotemia :

Intrinsic Renal Azotemia :

Intrinsic Renal Azotemia :

Intrinsic Renal Azotemia

routine administration of dopamine to patients

Intrinsic Renal Azotemia

Intrinsic Renal Azotemia

Intrinsic Renal Azotemia

Intrinsic Renal Azotemia

Intrinsic Renal Azotemia

Intrinsic Renal Azotemia