Aute renal failure part one

ARF –DEFINITION,CAUSES, DIAGNOSIS AND MANAGEMENT 2014 BY DR. MAGDI AWAD SASI

ACUTE RENAL FAILURE

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ACUTE RENAL FAILURE

Acute kidney failure — also called acute renal failure or acute kidney injury — develops rapidly over a few hours or a few days. Acute kidney failure is most common in people who are already hospitalized, particularly in critically ill people who need intensive care.

Acute kidney failure can be fatal and requires intensive treatment. However, ARF may be reversible. If you're otherwise in good health, you may recover normal kidney function.

DEFINITION------An abrupt increase in the BUN and Creatinine with corresponding problems in handling of fluids, Potassium, Phosphorus, and acid-base balance. This is usually a greater than 50% decline in the GFR.

It is a sudden fall in renal function characteristic by azotemia.

FOR DIAGNOSIS; raising blood urea nitrogen

Raising creatinine concentration.

Problems with the Definition :

• Serum Creatinine does NOT reflect the degree of renal dysfunction or improvement

• Urine output or lack of may also not reflect the degree of dysfunction

• A better definition may be Acute Kidney Injury (AKI).

Types of Acute Kidney Injury:

Acute Renal Failure can be:

1. Oliguric <400 ml/day or

2. Non-Oliguric >400 ml/day

Non-Oliguric has a much better prognosis.

-In the Pre-Dialysis Era, ARF had a 50------70% Mortality Rate.

--Today with Dialysis, ARF still has a 50----70% Mortality Rate .

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Types of Acute Renal Failure:

ARF

Pre- Renal PostRenal

Intrinsic Renal

Vascular Glomerular Interstitial Tubular

Phases of Acute Renal Failure:

Initiation Phase-drop in BP, nephrotoxins, early sepsis—rise in BUN/Cr, decreasing urine output

• Oliguric Phase-usually less than 400 ml/da, may require dialysis

• Recovery/Diuretic Phase-increasing urine output, decreasing BUN/Cr, Potassium, Phosphorus, and Magnesium .

PRE –RENAL ARF:A decreasein either total circulatory volume or effective circulatory volume (I.e. CHF or Sepsis). This leads to activation of the Renin-Angiotensin--Aldosterone System and ADH. Thus enhanced Na and H2O reabsorbtion.

1. CAUSES:40—60% of cases Caused by diminution in the renal blood flow

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Major causes include:1. GIT loss: DEHYDRATION

Diarrhea, vomiting( what ever the cause--- infection like cholera or organic obstruction) intraluminal fluid in bowel obstruction ,intraluminal gut fluid , bowel wall oedema((IBD)),Fistula, Excessive sweating .

2. Sequestration of intravascular volume--- burns ,pancreatitis , sepsis3. Hepatic: liver cirrhosis , chronic hepatitis4. Cardiac : CCF , cardiogenic shock , pericardial temponade5. Hemorrhage: active bleeding with large amount6. Diuretic phase of ARF or Post-Obstructive Diuresis 7. Medications:

Loop diuretics----frosemide , Bumetanide ,Thiazide diureticACE-I or ARBs---- commonly seen in CCU after few days of treatment.The prolonged use of diuretic result in loss of concentrating function.Non oliguric prerenal ARF may also caused by inhibition of the effect of antidiuretic hormone(ADH/Vasopresin)on the collecting D. BY LITHIUM

CLINICAL FEATURES:

1.History:

Sometimes acute kidney failure causes no signs or symptoms and is detected through lab tests done for another reason. It is mandatory to look for unexplained symptoms in a patient who had a risk factor for acute renal injury like organ failure , drug intake , systemic medical illness , HTN or DM.

Symptoms are not specific :

1. CNS symptoms---- syncopy, dizziness , fatigue, confusion, seizures , coma

2. UROLOGICAL symptoms--- change of urine frequency and amount ,thirsty

3. H/O fluid loss--- diarrhea , vomiting persistent , bleeding from orifices

4. H/O Fluid retention, swelling in your legs, ankles --CCF , liver cirrhosis with ascitis

5. CARDIAC symtoms--- dyspnea , chest pain

H/O use of diuretics

2.Physical examination:

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Postural change in pulse and blood pressure A large weight loss may indicate volume depletion Weght gain may accompany intravascular volume loss with total body volume

overload-:--

1. SIGNS OF CCF2. ASCITIS AND OEDEMA3. CHRONIC STASIS DERMATITIS4. ULCERS IN THE LOWER LIMBS

Hemodynamic – persistent low pulmonary capillary wedge pressure suggests hypovolemia where as raising or high PCWP suugests CCF and under perfusion.

In a pt with cardiac or pulmonary disease , hemodynamic monitoring plays a rule in diagnosis.

WHAT ARE THE DIAGNOSTIC CRETERIA?

I. Signs of volume depletion or third space fluid lossII. Volume depletion by hemdynamic criteria such as pulmonary capillary wedge pressure.

III. Urinalysis and laboratory findings IV. Response to volume repletion with reversal of azotemia PLUS if oliguric ; increase in urine out

put with normalization of urinary indices V. No evidence of obstruction on ultrasound abdomen if oliguric stage persists.

POST-RENAL ARF

Cause :

2---25% ARF cases . Generally , the patient is oliguric or anuric. Due to changes in the obstructing lesions with the patients position, there may be

wide variety in urine out put.

1 .Intrauretric obstruction:

Stones , blood clots ,pus ,tissue papillary necrosis—DM ,Analgesic drug excess

2.Extraureteric obstruction:

A- Most commonly – tumors involving the retroperitoneal lymph nodes

Lymphoma , testicular carcinoma , cervical cancer –70% OF female ARF caused by pelvic tumors, colon cancer

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B- 5% -- Retroperitoneal fibrosis from radiation therapy and ergot alkaloids.

3.Lower urinary tract obstruction----neurogenic bladder, prostate hypertrophy 80% of cases, cancer, bilateral renal caliculi ,bladder cancer

CLINICAL FEATURES:

1.History: historical features include---

A .NephrolithiasisB .Repeated pyelonephritis ,immune deficiency with fungal diseaseC . Hematuria , gross hematuriaD .Previous pelvic tumour or lymphomaE. Previous abdominal radiation treatment --- fibrosisF. Drug ingestion---- ergot alkaloidsG. Dribbling, frequency ,incontinance ,dysuria

2. H/O nausea ,vomiting ,irritability, headache , dyspnea

2.Physical examination:

I. Bilateral flank pain & tenderness---70---80%Costo vertebral angle tenderness-----ascending infection

II. Signs of inferior vena cava or lymphatic obstruction (( lymphedema)).

DIAGNOSTIC FEATURES:

History is mandatory for exploration of urological symptoms or significant past medical os surgical history that signifies renal complication, H/O hematouria ,H/O difficulty of urination

Laboratory indices similar to prerenal azotemia.

Ultrsonography evidence of bilateral hydronephrosis , unilateral hydronephrosis if a single kidney is present , evidence of intraabdominal ,retroperitoneal , pelvic obstructive masses.

Evidence of obstructed flow on retrograde pyelography

Evidence of bilateral obstructed flow on radiohippurate scans

Urinary catheter which once done the patient passed large amount of urine with gradual reduction of renal parameters and improvement of pt day by day.

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INTRA-RENAL FAILURE

30---50% of ARF. Direct insult to the kidney .

May be a result of vascular, Glomerular, interstitial, or tubular causes. Final common pathway of untreated prerenal or postrenal failure .

TWO TYPES:

1.Primary parenchymal disease 10 ----20% ARF2.Acute tubular necrosis ((ATN))

Vasomotor changes produce tubular ischemia -----------------tubular dysfunction---tubuloglomular feed back------------- decrease GFR

CAUSES:

1.Primary renal disease:

i. Vascular :Post stertococcalGlomerulonephriris SLEPolyarteritis nodosa wegners granulomatosisScleroderma Good pastures syndromMalignant HTN IgA BURGERSHEMOLYTIC UREMIC SYNDROME renal artery stenosisRENAL EMBOLIZATIONTHROMBOTIC THROMBOCYTOPENIC PURPURA

ii. Tubulo-interstitial diseases:Myeloma proteinsHypercalcemiaHypokalemiaAllergic interstitial nephritis---nonsteroidal –antiinflammatory, b-lactamase-penicillins

iii. Crystallization within the tubular lumen:Oxylate crystalsUrate crystals ( hyperuricemia 18—20mg/dl )Methtrexate derivativesTumor lysis syndrome---- urate , calcium phosphate

iv. Post –angiogram ,CABG , sustained hypotensionv. Rhabdomyolysis

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ACUTE TUBULAR NECROSISPathophysiology----

Hypoxia of the tubular microvasculature leads to tubular necrosis and loss of reabsorbtion and secretory abilities of the tubules .

Afferent and Efferent Arteriolar Vasoconstriction

• Mesangial Contraction WITH Release of Reactive Oxygen species, NO, ATII, PG’s, Catecholamines

• Tubular Necrosis due to tubular obstruction and back-leak With Cellular Edema

• Increased free Ca++ WITH Release of compartmentalized enzymes

• Destruction in Cytoskeleton

• Reperfusion injury from reactive Oxygen species, WBC’s, Complements, and

cellular debris

TYPES OF ATN:

A. ISCHEMIC TUBULAR NECROSIS :1. Hypotention 2. Surgery ---cardiovascular or abdominal surgery.3. Sever burns4. Sever muscle injury or extreme physical exertion.5. Sepsis , aortic cross –clamping 6. Prerenal azotemia .

B.TOXIC TUBULAR NECROSIS:

Substances, such as medicines that are toxic to the kidneys. Many substances that are not toxic to the kidneys in a healthy person may become toxic in a person who has existing kidney problems or another condition that increases his or her risk of acute renal failure, such as heart failure, diabetes, or multiple myeloma.

1. Heavy metals 2. Myoglobin (rabdomylosis) 3. Hemoglobin(extensive hemolysis)4. Medications (aminglycoside) 5. Halogenated alkanes .

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DIAGNOSTIC FEATURES:

1RY Parenchymal disease----.Urinanalysis.Severe hypertension is common.No evidence of obstruction on USS abdomen

No signs ,symptoms, hemodynamic indications of ongoing hypovolemia or persistent ARF following correction of hypovolemia.

Urinalysis and laboratory finding No evidence of obstruction No response to volume repletion

CLINICAL FEATURES:

History----

1. H/O URTI suggests post infectious glomerulonephritisFever , rash or pleuritic pain may point to vasculitis

2. H/O drug intakeNSAID ,ANTICOAGULANTS ,ANTIBIOTIC ,CIMETIDINE ,DIURETIC, CYCLOPHOSPHAMIDE, METHOTREXATE, AMINOGLYCOSIDE, RADIOLOGIC CONTRAST MATERIAL.

3. H/O sepsis --- once there is no cause4. H/O blood transfusion--- hemolysis ,transfusion reaction ,microangiopathic hemolysis5. Rhabdomylosis---unconscious or seizures. Hypokalemia/hypophosphatemia cause it.6. Examination may find evidence of vasculitis.

Rashes are often present. Sclerodectaly---scleroderma HTN---85%7. H/O preexsisting prerenal azotemia may point to progression to ATN.8. Hypotension does not need to be documented in postsurgical patient ,60 year in

order for the physign to suspect ATN

RECOMMENDED DIAGNOSTIC APPROACH:

i. Urinalysis:

Red blood cell casts -----evaluate autoimmune disease

ii. Urine osmolality –(Uosm)Specific gravity of limited value in ATN (affected by glucose or protein).1. Pre-renal--- 90% have Uosm more than500mosm/l2 .Post renal ARF --- INITIAL like prerenal azotemiaPersistent obstruction ---- tubular damage---low Uosm

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3. ATN—90% have Uosm less than 350 mosm/lLoss of the concentrating ability with tubular dysfunction4.Uosm/Posm:The overlap range (Uosm 350 to 500 mosm/l) is not diagnostically useful.90% of patients with ATN have Uosm/Posm less than 1.0790% of patients with prerenal azotemia have Uosm/Posm more than 1.25

iii. BUN and creatinine:1. Creatinine---with complete cessation of glomerular filtrate , serum creatinine

increase by a bout 1mg/dl/dayDaily increase is less in patients with decreased muscle mass( older)More 2.5mg/dl/day in young muscular males.

2. Urea:Urea is freely filtred and variably absorbed.

Reabsorption is proportional to water flow in tubules ,the presence of ADH , local tubular damage, peritubular blood flow.

Production of urea is affected by hepatic disease

Decrease BUN---

LOW PROTEIN DIET STARRVATION HEPATIC FAILURE

Increase BUN ( hypercatabolism)---

BURNS SEPSIS INFECTION GLUCOCORTICOID USE TRAUMA POSTSURGICAL

The rate of BUN rises with complete recession of glomerular filtration --- 24-60mg/ml/d

IV -- plasma BUN/creatinine ratio:

Routine urea is increased greatly in prerenal and post renal uremia. BUN/Creatinine ratio more than 20/1 is present in 80% of renal and postrenal

azotemia. Intrarenal ARF &ATN are characterized by proportionate BUN/ CRET 10/1

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V-- URINE CREATININE:

1. Urine creatinine :

Is a marker of ability to concentrate urine as creatinine is filtred without reabsorption

2. Ucreatinine /P creatinine

˂ 10----------85% of pt with ATN

˃20------85% OF PT with prerenal ARF

VI --Urine sodium (U Na):

1. The ability to conserve Na in proportional to the amount filtered is a marker of intact tubular function .

2. UNa ˂20meq /l occurs in 90% of prerenal azotemia

˃40 meq/l is found in 90% of pt with ATN

VII—Fractional exertion of sodium( EF Na)

1.A more sensitive test is the calculated EF Na

U Na /P Na x P creat /U creat

2. 90% of prerenal azotemia ˂1%

90% of ATN ˃2%

3. EF Na less than 1%Common in renal parenchymal disease ,particularly glomerulonephritis as tubules retain function and attempt to compensate in response to diseased glomeruli.

VIII Other laboratory tests:

1. A clue to presence of tubuloischemic necrosis ----------- hyperchloremic acidosis of rapid onset

2. Myoglobin levels in urine may confirm rabdomyolysis3. A SEVER ANION GAP METABOLIC ACIDOSIS WITH OXALATE CRYSTALS IN URINE

MAY INDICATE ETHYLENE GLYCEROL TOXICITY.4. Hyperchloremic acidosis with hyperkalemia--- 80% of pt w post obstructive

dieresis

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IX ULTRSOUND:

1. 85% of case , the cause of obstruction can be detected by USS (ureter,kidney,pelvis)2. If the index of suspicion of obstruction is high (single kidney , kidney

transplant ,abdominal mass), retrograde pyelogram may be indicated.

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X Nuclear studies:

1. Flow studies (glucoheptonadte) Measure renal perfusion and exclude vascular problems

2. Hippurate functional studies Measure renal functionSuggest or confirm the presence of ATNDiagnose obstruction Suggest renal transplant rejection

XI IV urpgraphy:

Limited by fear of exacerbating ARF & difficulty of giving dye to patient with marginal Marginal fluid status.

XI Renal biobsy:

Indication---- oliguria that persists for longer than 3 weeks OR when treatable disease is strongly suspected

TEST PRERENAL AZOTEMIA ATN POSTRENAL

OSMOLALITY ˃500mosm/l ˂350mosm/l ˃500mosm then derease

Uosm/Posm ˃ 1.25 ˂ 1.07 variable

BUN/CREAT (PLASMA) ˃ 20/1 10/1 ˃ 20/1

Ucreat / P creat ≥ 20 ≤ 10 variable

UNa ≤ 20 ≥ 40 ≥100 post obs

FE Na ˂ 1% ˃ 2% variable

1. Duration <3 months

2. Oliguria <400 ml urine/24 hours

3. Absolute increase Scr by 0.5 or 1.0 mg/dl or relative increase 25%

4. Cockcroft – Gault Equation

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(140-age) x wt(kg)

------------------------

Serum Cr x 72

SUMMARY OF INITIAL EVALUATION:

a. Consider possible etiologies and direct evaluation b. Medications should always be suspected c. Standard Blood Testing :

a. Electrolyte/renal panel, Ca2+, Phosphate, Mg2+, Albumin

b. Complete Blood Count

c. Foley catheter to rule out bladder obstruction AND take sample of urine.

1. Urine for electrolytes, dipstick and microscopic analysis

a. Osmolality, creatinine, Na+, K+, Cl-

b. Urine spot protein to creatinine ratio (normal is <0.2)

c. Pigment: Hemoglobin (myoglobin)

d. Cells, Casts, Crystals, Organisms

e. Consider Urine culture

2. More informative for the cause :i. Renal/Pelvic Sono - stones, hydronephrosis, mass ii. Consider Abdominal radiograph if ultrasound is not done to rule out stones iii. ESR, ASO titer, ANA, C3/C4 Anti-GBM Abs iv. Renal Biopsy in rapidly progressing disease v. ANCA and Anti-GBM diseases - consider cyclophosphamide + glucocorticoids vi. Idiopathic rapidly progressive glomerulonephritis often ANCA positive (other

inflammatory diseases such as bacterial endocarditis can given ANCA+)

WHAT OTHER THE DIFFERENT TYPES OF GN?(( pathological))

1. Glomerular Involvement :

a. Diffuse: all glomeruli in a section are diseased

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b. Focal: some glomeruli in a section are diseased

c. Segmental: parts of individual glomerulus affected

2. Focal Glomerulonephritis:

a. Some glomeruli are dead( necrosis, collapse, sclerosis ). B .Acute or chronic inflamation is often seen.

3. Crescent Glomerulonephritis (very poor prognosis)

Crescent (moon shaped) formation in glomerulus Affected glomeruli are non-functional Focal and Segmental Glomerulosclerosis: portions of many glomeruli are destroyed

5. Minimal Change Glomerulonephritis : Glomeruli appear okay, but function is poor Electron microscopic evidence of basement membrane disease Response to glucocorticoids is usually very good

6. IgA Deposition:

IgA nephropathy Deposition of IgA immune complexes Differential includes Systemic Lupus (SLE) and Henoch-Schonlein Purpura (HSP)

7. Proliferative Glomerulonephritis

Increase in mesangeal cell number Usually follows insults (eg. Post-Streptococcal) May be seen in collagen vascular disease, SLE.

8. Collapsing Glomerulonephritis

Major form seen in HIV nephropathy Usually late stage Rapid progression to renal failure (weeks-months) No effective therapy to date

9. Tubular Necrosis

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Tubular cells die and slough off basement membrane The dead tubular cells form casts which can occlude lumen Glomular basement membrane may also be damaged

MANAGEMENT OF ARF:

A. Renal Diet :

Low phosphate, potassium, sodium, and protein High calcium and vitamin D dietVarious multivitamin formulas available for renal patients, eg. Nephrovit®. Low protein diet may slow progression slightly in chronic renal disease Phosphate and Calcium Dangerous if product of Calcium and Phosphage > ~70 (mg/dl) (will lead to precipitation) If product is close to 70, then phosphate should be lowered with aluminum compounds These compounds should be given with meals to bind the phosphate directly If product is <60, then calcium should be given 500-1000mg po tid with meals If calcium is low but phosphate normal, then calcium should be given before meals Consider using 1,25 dihyroxyvitamin D supplements

B. AVOIDABLE COMPLICATIONS SHOULD BE FOLLOWER.1.Acidosis Renal tublar acidosis (RTA) is common in early renal failure

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Make/think about the diagnosisTreat life threatening conditionsIdentify the cause if possibleHypovolemiaToxic agents (drugs, myoglobin)ObstructionTreat reversible elementsHydrateRemove drugRelieve obstruction


Oral bicitra (citrate replaces bicarbonate) may be used Bicitra is contraindicated in edematous states due to high sodium content 2.Hyperuricemia Check uric acid levels Uric acid deposition in renal tubules may worsen progression of renal failure Allopurinol may be given (100-200mg po qd) to attempt normalization of uric acid

3.Hypertension ACE inhibitors generally contraindicated in moderate to severe renal failure Calcium blockers such as nifedipine can be used. Labetolol is also very effective but patient should have LV EF>50% and no

bronchospasm Consider Hydralazine for afterload reduction Pure alpha-adrenergic blocking agents may be effective, but tachyphylaxis may occur Diuretic improve hypertension/ volume overload

4. Volume overload

Attempt to maximize cardiac output and improve intravascular volume Diuretics often worsen renal failure but may be necessary to prevent pulmonary edema In general, potassium sparing diuretics should be avoided (high risk hyperkalemia) Dopamine or mannitol can be tried, but are usually not effective Albumin infusions are probably not helpful, but may help diuresis in low albumin states Dialysis may be required particularly in severe volume overload situations

5. Protein Load

Reducing protein load is thought to reduce azotemia . Appears to slow progression of CRF. Patients with moderate renal disease - some decrease in progression on low protein

diet . Patients with severe renal disease show no benefit on low protein diet .

Hospital inpatients with ARF ~50% mortality rate.

6.Newer Agents Atrial natriuretic factor (ANF)= dilators + diuretic ANF (Auriculin®) ? efficacy in oliguric ARF ANF may increase renal dysfunction in diabetics receiving radiocontrast

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Brain derived natriuretic factor (BDNF) may be effective some patients Other vasodilators (eg. calcium channel blockers) are not effective Investigation renal growth/regeneration factors

8. Dialysis Indications:1. Severe fluid overload2. Refractory hypertension3. Uncontrollable hyperkalemia4. Nausea, vomiting, poor appetite, gastritis with hemorrhage5. Lethargy, malaise, somnolence, stupor, coma, delirium, asterixis, tremor,

seizures,6. Pericarditis (risk of hemorrhage or tamponade)7. bleeding diathesis (epistaxis, gastrointestinal (GI) bleeding and etc.)8. Severe metabolic acidosis9. Blood urea nitrogen (BUN) > 70 – 100 mg/dl

C. Volume Overload

o Hemofiltration or hemodialysis can be used to allow recovery of kidney after ARF o Average duration of need for these therapies was 9 days in ARF o After this time, kidneys regain function and increase urine output o Native kidneys may continue with minimal function for 6-12 months of hemodialysis o After that, native kidneys usually shut down permanently

D. Kidney Transplantation

Excellent (and improving) results with cadaveric grafts. Living Related Donor kidneys superior to CRT New kidney usually placed in extraperitoneally in the pelvis Cyclosporin ,Prednisone, OKT3, mycophenolic acid, FK506 immunosuppression Combined Kidney Pancreas transplant in Diabetic ESRD patients

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Aute renal failure part one

Health & Medicine

Transcript of Aute renal failure part one