Acute kidney injury (aki)

Acute kidney Injury(AKI)

Dr Iqbal MahmudMD (Phase-A) student

Renal function

• Kidney has many roles:

Renal function

• Kidney has many roles:

- Excretory function

Renal function

• Kidney has many roles:

- Excretory function - Osmolality regulation

Renal function

• Kidney has many roles:

- Excretory function - Osmolality regulation - Acid base balance

Renal function

• BP regulation through salt and water balance

Renal function

• Kidney has many roles:

- Excretory function - Osmolality regulation - Acid base balance - BP regulation through Salt and water balance - Hormone secretion ( Erythropoietin, Vit D3)

Definition of Acute Kidney Injury

AKI has variably been defined as an abrupt deterioration in parenchymal renal function, which is usually but not invariably, reversible over a period of days or weeks.

Oliguria is usually but not invariably, a feature of AKI. Urine volume can be variable :

Anuria < 50 ml/dayOliguria 100 – 400 ml/dayNon-oliguria > 400 ml/day

Definition of Acute Kidney Injury Acute usually reversible decline in renal function*• Rapid time course( < 48 hrs)• Reduction of kidney function: A) Rise in serum creatinine, defined by either: 1. absolute increase in serum creatinine of >0.3mg/dl ( >26µmol/l) 2. % increase in serum creatinine of > 50% B) Reduction in urine output, defined as < 0.5ml/kg/hr for

more than 6 hrs• The diagnostic criteria should only be applied after volume status has been optimized. • Urinary tract obstruction needs to be excluded if oliguria is used as the sole criterion.• Only one criterion (creatinine or urine output) has to be fulfilled to qualify for a stage.

RIFLE classification scheme for ARF

AKI is staged for severity according to the following criteria

Comparison of RIFLE and AKIN criteria for diagnosis and classification of AKI

Acute kidney disease(AKD)

• Strict adherence to definitions of both AKI and CKD may miss individuals with functional or structural abnormalities present for < 3 months but may benefit from active intervention to restore kidney function.

• For this reason KDIGO have proposed the term AKD to include not only those with AKI ,but also those with GFR<60ml/min/1.73m2 for < 3 months or a decrease by ≥ 35% or an increase in s.cr by>50% for <3 months.

Incidence of AKI

• Approximately 7% of all hospitalized patient ( 65% of intensive care admission)

• 20% of acutely ill patient developed AKI• Incidence of AKI needing dialysis 200/pm/year• Pre renal and acute tubular necrosis (ATN) accounts for

75% of the cases of AKIMortality: • 5-10% in uncomplicated AKI• 50-70% in AKI secondary to other organ failure,infections• > 50% in dialysis requiring AKI

Acute kidney injury

Pre renal

- ↓ Effective renal blood flow:1- Haemorrhage 2- Volume depletion 3- Low cardiac output4- Sepsis5- CCF6- Cirrhosis

- Arterial stenosis/Occlusion

- Vasomotor:1- NSAID2- ACEI/ ARBs

Intrinsic

Post renal

Acute kidney injury

Pre renal Intrinsic

Vascular1- Vasculitis2- Thrombotic microangiopathy3- Scleroderma renal crisis4- Renal vein thrombosis5- Cholesterol emboli

Acute GN Glomerluo-

nephritis

Acute TIN tubulointestitia

l nephritis

ATN acute tubular

necrosis

Post renal

Acute kidney injury

Pre renal Intrinsic

Vascular1- Vasculitis2- Thrombotic microangiopathy3- Scleroderma renal crisis4- Renal vein thrombosis5- Cholesterol emboli

Acute GN (Glomerluo-

nephritis)

Acute TIN (tubulointestitial nephritis)

ATN acute tubular

necrosis

Ischaemic Nephrotoxic

Post renal

Acute kidney injury

Pre renal Intrinsic

Vascular1- Vasculitis2- Thrombotic microangiopathy3- Scleroderma renal crisis4- Renal vein thrombosis5- Cholesterol emboli

Acute GN (Glomerluo-

nephritis)

Acute TIN (tubulointestitial nephritis)

ATN acute tubular

necrosis

Ischaemic Nephrotoxic

Endogenous 1- Haemoglobinuria2- Myoglobinuria 3- Casts and Crystals

Exogenous 1- Nephrotoxic drugs2- Radiocontrast

Post renal

Acute kidney injury

Pre renal

- ↓ Effective circulatory volume:1- Haemorrhage 2- Volume depletion 3- Low cardiac output4- Sepsis5- CCF6- Cirrhosis

- Arterial stenosis/Occlusion

- Vasomotor:1- NSAID2- ACEI/ ARBs

Intrinsic

Vascular:1- vasculitis2- Thrombotic microangiopathies3- hypertensive emergencies

Acute GN ( Glomerluo-

nephritis)

Acute TIN (tubulo-intestitial nephritis)

ATN (acute tubular necrosis)

Ischaemic Nephrotoxic

Endogenous 1- Haemoglobinuria2- Myoglobinuria 3- Myoglobin casts4- Intratubular crystals

Exogenous 1- Nephrotoxic drugs2- Radiocontrast

Post renal

Obstruction 1- Bladder out-let obstruction2- Bilateral ureteral obstruction

Pre-renal AKI

Etiology and Pathophysiology

• Hypovolemia leads to glomerular hypoperfusion, but filtration rate are preserved during mild hypoperfusion through several compensatory mechanisms.

• During states of more severe hypoperfusion, these compensatory responses are overwhelmed and GFR falls, leading to prerenal AKI.

Etiology and Pathophysiology

1.Hypovolemia • Hemorrhage, burns, dehydration • Gastrointestinal fluid loss: vomiting, surgical drainage, diarrhea• Renal fluid loss: diuretics, osmotic diuresis (e.g., diabetes

mellitus), hypoadrenalism• Sequestration in extravascular space: pancreatitis, peritonitis, trauma, burns,• Severe hypoalbuminemia

Etiology and Pathophysiology

II. Low cardiac output• Diseases of - myocardium, valves, and pericardium; arrhythmias; tamponade• Other: pulmonary hypertension, massive pulmonary embolusIII. Altered renal systemic vascular resistance ratio • Systemic vasodilatation: sepsis, anaphylaxis IV. Renal hypoperfusion with impairment of renal autoregulatory responses

Etiology and Pathophysiology

IV. NSAIDS- they reduce affarent renal vasodilationV. ACEIs and ARBs- limit renal efferent vasoconstriction

Prerenal AKI can complicate any disease that induces : hypovolemia, low cardiac output,systemic vasodilatation, or selective renal vasoconstriction.

Diagnosing pre-renal AKI

• Is the patient volume depleted?

Diagnosing pre-renal AKI

• Is the patient volume depleted?• Is cardiac function good?

Diagnosing pre-renal AKI

• Is the patient volume depleted?• Is cardiac function good?• Is the patient septic?

Diagnosing pre-renal AKI

• Is the patient volume depleted?• Is cardiac function good?• Is the patient septic?

History ExaminationInvestigation

Diagnosing pre renal AKI

• History

• Examination : 1. Signs of Hypovolaemia:

a) Low BP( and reduced pulse pressure) b) Postural BP drop ( a fall in systolic BP > 10mmHg) c) Sinus tachycardia and postural increase in heart rate ( increase in HR > 15 beat/min). d) Low JVP even when the patient is supine e) Cool peripheries and vasoconstriction f) Poor urine output

Diagnosing pre-renal AKI 2. Sings of hypervolaemia( high extracellular fluid):

a) Increased circulating volume:

- High BP

- Elevation of the JVP

b) Increased interstitial fluid:

- Peripheral or generalized oedema

- Pulmonary oedema (tachypnoea, tachycardia,

third heart sound)

- Pleural effusion

- Ascites

Diagnosing Intrinsic Renal AKI

• Has pre-renal and post renal been excluded?

• History - Drug, Rash, joints, nose bleed, haemoptysis, hearing loss, claudication, IHD,

diabetes, fever or night sweat, Recent infection

• Examination - Oedema, rash, mouth ulcer, hearing loss, uveitis, ischaemic toe, bruits, evidence of

scleroderma, prosthetic valve or stigmata of Endocarditis• Laboratory investigations - Urine including microscopy for dysmorphic RBC, Protein, Bence Jones protein,

protein/creatinine ratio or 24hr protein excretion - Blood – nephritic screen – ANA, dsDNA, ANCA, antiGBM, Immunoglobulines protein electrophoresis, Rh-factor, HBV, HCV, HIV, cryoglobulins, blood film, CK, C3,C4, ASO-titre , ESR and CRP• US kidneys

. Renal biopsy

Diagnosing post renal AKI• History - pain, anuria, haematuria, prostatism

• Examination - palpable bladder, central abdo mass, PR, PV

• Observation

• Laboratory investigations - Urine - Blood - Imaging – US, CT

Pathophysiology of postrenal AKI

• It involves hemodynamic alterations triggered by an abrupt increase in intratubular pressures

• An initial period of hyperemia from afferent arteriolar dilation is followed by intrarenal vasoconstriction from the generation of angiotensin II, thromboxane A2, and vasopressin, and a reduction in NO production.

Nature of Obstruction

• Outside - Tumours, prostate, retroperitoneal fibrosis, cervical Ca

• Within wall - Tumours, strictures

• Within lumen - Stones, tumours

Investigations:

FBC : Hb% ↓- Haemolysis, GI bleeding ↑/ ↓ WCC: infection ↓platelets and altered coagulation : DIC, thrombotic

microangiopathy Pancytopenia : marrow infiltration, others malignancyPBF : fragmented RBC : send LDH,haptoglobulin,reticulocyte

countBiochemistry :U & E: raised s.ur,Cr ratio indicate pre-renal AKI↑ K: needed urgent managementNa :usually normal, ↓ in case of volume overload and diuretics↓HCO3 : metabolic acidosis

Investigations :• LFT : ↓ albumin- imply proteinuria and GN ↑ billirubin : hepatorenal syndrome,• Calcium and phosphates : ↑ Ca ++: myeloma, sarcoidosis, malignancy• CRP : for infection/ inflammation, (procalcitonin if available)• Ck: rhabdomyolysis, • Urate : tumour lysis/ pre-eclampsia• Lactate : to asses underperfusion and tissue ischemiaMinimum AKI panel: Urine dipstick, FBC, U&E, Ca, PO4, Albumin, LFT, CK, CRP, ABG/

venous HCO3

Urinalysis in AKI

Urinalysis in AKIUrinalysis in AKI

• Dipstick test: trace or no proteinuria with pre-renal and post-renal AKI;

• mild to moderate proteinuria with ATN and moderate to severe proteinuria with glomerular diseases.

• RBCs and RBC casts in glomerular diseases• Crystals, RBCs and WBCs in post-renal ARF.

3. Radiography/imaging

• Ultrasonography: helps to see the presence of two kidneys, for evaluating kidney size and shape, and for detecting hydronephrosis or hydroureter.

• It also helps to see renal calculi, and renal vein thrombosis.

• Retrograde pyelography: is done when obstructive uropathy is suspected

•Cystatin C

•Neutrophil gelatinase-associated lipocalin(NGAL)

•Interleukin-18 •Kidney injury molecule-1

•N-acetyl-D-glucosaminidase.

Important Biomarkers:

Cystatin-C

• Superior to serum creatinine, as a surrogate marker of early and subtle changes of kidney function.

• It identifies kidney injury while creatinine levels remain in the normal range.

• Allows detection of AKI, 24-48 hours earlier than serum creatinine

Kidney Injury Molecule-1 (KIM-1)

• KIM-1 is a type 1 trans-membrane glycoprotein

• Served as a marker of severity of AKI

• Can be used to predict adverse outcomes in hospitalized patients better than conventionally used severity markers.

Neutrophil gelatinase-associated lipocalin(NGAL)

• NGAL is highly upregulated after inflammation and kidney injury and can be detected in the plasma and urine within 2 hours of cardiopulmonary bypass–associated AKI.

• Considered equivalent to troponin in acute coronary syndrome.

Diuretic• Renoprotective : Potentially lessening ischemic injury.

• Can also be harmful, by worsening established AKI.

• No evidence of incidence reduction.

• KDIGO recommend not using diuretics to prevent AKI. (1B)

• KDIGO suggest not using diuretics to treat AKI, except in the management of volume overload. (2C)

• Indicated only for management of fluid balance, hyperkalemia, and hypercalcemia.

Clinical Approach to patient with AKI

Step Item Evaluation process & Response

1 Evaluate volume status

Physical Exam, weight, CVP, PCWP.Fluid challenge.

Clinical Approach to patient with AKI

Step Item Evaluation process & Response

1 Evaluate volume status

Physical Exam, weight, CVP, PCWP.Fluid challenge.

2 Rule out Obstruction Physical Exam, patency of catheters, Renal ultrasound.Foley catheterization.

Clinical Approach to patient with AKI

Step Item Evaluation process & Response

1 Evaluate volume status

Physical Exam, weight, CVP, PCWP.Fluid challenge.

2 Rule out Obstruction Physical Exam, patency of catheters, Renal ultrasound.Foley catheterization.

3 Renal function tests BUN, creatinine & electrolytes. Hemoglobin, calcium & phosphorus.

Clinical Approach to patient with AKI

Step Item Evaluation process & Response

1 Evaluate volume status

Physical Exam, weight, CVP, PCWP.Fluid challenge.

2 Rule out Obstruction Physical Exam, patency of catheters, Renal ultrasound.Foley catheterization.

3 Renal function tests BUN, creatinine & electrolytes. Hemoglobin, calcium & phosphorus.

4 Probable cause for renal dysfunction

Evaluate nephrotoxic (drug) exposure – NSAIDs, aminoglycosides, hypotension, etc.

Clinical Approach to patient with AKI

Step Item Evaluation process & Response

1 Evaluate volume status

Physical Exam, weight, CVP, PCWP.Fluid challenge.

2 Rule out Obstruction Physical Exam, patency of catheters, Renal ultrasound.Foley catheterization.

3 Renal function tests BUN, creatinine & electrolytes. Hemoglobin, calcium & phosphorus.

4 Probable cause for renal dysfunction

Evaluate nephrotoxic (drug) exposure – NSAIDs, aminoglycosides, hypotension, etc.

5 Urine Routine & Microscopy

Specific gravity, protein, glucose, blood, casts – granular &/or cellular, cells & crystals.

Clinical Approach to patient with AKI

Step Item Evaluation process & Response

1 Evaluate volume status

Physical Exam, weight, CVP, PCWP.Fluid challenge.

2 Rule out Obstruction Physical Exam, patency of catheters, Renal ultrasound.Foley catheterization.

3 Renal function tests BUN, creatinine & electrolytes. Hemoglobin, calcium & phosphorus.

4 Probable cause for renal dysfunction

Evaluate nephrotoxic (drug) exposure – NSAIDs, aminoglycosides, hypotension, etc.

5 Urine Routine & Microscopy

Specific gravity, protein, glucose, blood, casts – granular &/or cellular, cells & crystals.

6 Urinary Indices Fractional Excreation of sodium (FeNa)

Obtain spot urine sodium & creatinine.

Acute Chronic

Treatment

General Issues

  1. Optimization of systemic and renal hemodynamic through volume resuscitation and judicious use of vasopressors

2. Elimination of nephrotoxic agents (e.g., ACE inhibitors, ARBs, NSAIDs, aminoglycosides) if possible

3. Initiation of renal replacement therapy when indicated

Dietary measure

• Adequate nutritional support should be ensured

• High protein intake should be avoided

• Enteral/ parenteral nutrition may be required.

• providing nutrition preferentially via

the enteral route in patients with AKI

Nutritional and glycaemic control

• Insulin therapy targeting plasma glucose 110–149 mg/dl

• Total energy intake of 20–30 kcal/kg/d in patients with any stage of AKI. We suggest administering

• 0.8–1.0 g/kg/d of protein in noncatabolic AKI patients without need fordialysis (2D),

• 1.0–1.5 g/kg/d in patients with AKI on RRT (2D), and up to a maximum of 1.7 g/kg/d In patients on CRRT and in hypercatabolic patients. (2D)

FLUIDS

• KDIGO suggest using isotonic crystalloids in absence of haemorrhagic shock rather than colloids (albumin or starches) .

• Colloids may be chosen in some patients to avoid excessive fluid administration in patients requiring large volume resuscitation, or in specific patient subsets (e.g., a cirrhotic patient with spontaneous peritonitis, or in burns).

• Colloids- Albumin is renoprotective and Hyperoncotic starch shows nephro- toxicity.

Vasopressors

• The Work Group emphasized that vasoactive agents should not be withheld from patients with vasomotor shock over concern for kidney perfusion.

• Indeed, appropriate use of vasoactive agents can improve kidney perfusion in volume-resuscitated patients with vasomotor shock.

• The use of dopamine was associated with a greater number of adverse events than Nor-epinephrine.

Low Dose Dopamine

• Its use has been abandoned by most subsequent to negative results of various studies .

• KDIGO recommends not using low-dose dopamine to prevent or treat AKI. (1A)

Cirrhosis and Hepatorenal Syndrome

• Albumin may prevent AKI in those treated with antibiotics for spontaneous bacterial peritonitis.

• Bridge therapies that have shown promise include terlipressin (a vasopressin analog), combination therapy with octreotide (a somatostatin analog) and midodrine (an α 1-adrenergic agonist), and norepinephrine, all in combination with intravenous albumin (25–50 mg per day, maximum 100 g/d).

Intrinsic Acute Kidney Injury

Diuretic

• Reno protective : Potentially lessening ischemic injury.

• Can also be harmful, by worsening established AKI.

• No evidence of incidence reduction.

• KDIGO recommend not using diuretics to prevent AKI. (1B)

• KDIGO suggest not using diuretics to treat AKI, except in the management of volume overload. (2C)

• Indicated only for management of fluid balance, hyperkalemia, and hypercalcemia.

FENOLDOPAM

• Fenoldopam mesylate is a pure dopamine type-1 receptor agonist Without systemic adrenergic stimulation.

• For critically ill patients with impaired renal function, a continuous infusion of fenoldopam 0.1mg/kg/min improves renal function when compared to low dose dopamine.

• KDIGO suggest not using it to treat AKI

Erythropoietin

• Recent animal studies suggest a potential clinical benefit of erythropoietin in AKI.

• The renoprotective action of erythropoietin may be related to pleomorphic properties including antiapoptotic and antioxidative effects, stimulation of cell proliferation, and stem-cell mobilization.

• Although one recent RCT in the prevention of human AKI was negative, the usefulness of erythropoietin in human AKI should be further tested in RCTs.

Growth factor intervention

• IGF-1 is a peptide with renal vasodilatory, mitogenic and anabolic properties.

• KDIGO Work Group recommends against its use in patients with AKI.

Rhabdomyolysis

• Aggressive volume repletion (may require 10 L of fluid per day).

• Alkaline fluids are beneficial.

• Diuretics may be used if fluid repletion is adequate and there is no urinary output.

• Dialysis.

• Focus on calcium and phosphate status because of precipitation in damaged tissue.

Glomerulonephritis or Vasculitis

• May respond to immunosuppressive agents and/or plasmapheresis .

• Allergic interstitial nephritis due to medications requires discontinuation of the offending agent.

• Glucocorticoids have been used, but not tested in randomized trials. • AKI due to scleroderma (scleroderma renal crisis) should be treated with ACE inhibitors.

Aminoglycoside Induced AKI

• KDIGO suggest not using aminoglycosides for the treatment of infections unless no suitable, less nephro - toxic, therapeutic alternatives are available.

• Avoid in high risk patients age more than 65 years, DM, cases of septic shock.

• KDIGO suggests using single dose daily rather than multiple-dose daily treatment regimens.

• It also suggest using topical or local applications of aminoglycosides (e.g., respiratory aerosols, instilled antibiotic beads), rather than i.v. application, when feasible .

AMPHOTERICIN B NEPHROTOXICITY

• KDIGO suggest using lipid formulations of amphotericin B rather than conventional formulations of amphotericin B.

• KDIGO recommend using azole antifungal agents and/or the echinocandins rather than conventional amphotericin B, if equal therapeutic efficacy can be assumed.

• Some studies indicate that the liposomal form of amphotericin B is less nephrotoxic than amphotericin B lipid complex or amphotericin B colloidal dispersion.

Treatment of intrinsic renal AKI

• ATN -aim of treatment is to keep the patient alive until spontaneous

recovery - In-hospital mortality 19-37%* - Recovery could take up to 6 weeks** - Self correcting (full 60%, some 30%, dialysis 5-10%) - Very severe – permanent cortical necrosis

* Oxford handbook of Nephrology and Hypertension 2009** Kumar and Clark/ Clinical Medicine July 2012

Post-renal

• Prompt relief of urinary tract obstruction by catheterization in urethral obstruction, correction of ureteric obstruction by ureteric stent or percutaneous nephrostomy

• Relief of obstruction is usually followed by an appropriate diuresis and may require continued administration of intravenous fluids and electrolytes for a period of time.

Indications for Dialysis

A – Acidosis(pH<7.25) E – Electrolyte disturb., usually hyperkalemia ( k>6 mmol/lt despite medical treatment I – Intoxications (lithium, ethylene glycol, etc) O – Overload (volume overload-pulmonary oedema) U – Uremia (urea> 180-210 mg/dl,cr> 6.78 mg/dl) & complications(pericarditis) S- sepsis

Modes Of Dialysis

• Hemodynamically stable- IHD

• Hemodynamically unstable1. CRRT2. PD3. SLED (Slow Low-efficiency dialysis).

Prognosis

• Pre-renal and Post- renal better prognosis.• Kidneys may recover even after dialysis requiring

AKI.• 10% of cases requiring dialysis develop CKD.• Die early even after kidney function recovers

completely.

Complications of AKI

• Hyperkalaemia • Pulmonary oedema• Acidosis • Uremia• Other electrolyte disturbance such as

hyperphosphataemia and hypocalcaemia

Who is a risk?

Many cases of AKI should never occur in the first place

1- Elderly2- Pre-existing renal disease3- Surgery, trauma, sepsis or myoglobinuria4- Diabetes5- Volume depletion( Nil By Mouth, bowel obstruction, burn)6- LV dysfunction 7- Nephrotoxic drugs8- Cirrhosis (reduce arterial volume)

Reducing risk perioperatively

• Three principles: 1- Avoid dehydration 2- Avoid nephrotoxins 3- Review clinical status and renal function those at risk

• Optimize volume status 1- No patient should go to theatre dehydrated 2- Review daily weight, input and output chart 3- Calculate losses especially those NBM ( use 0.9% N saline and NOT 5% Dextrose)

Reducing risk perioperatively

• Optimize blood sugar control in DM ( use sliding scale

• Catheterize those with prostate disease • Avoid surgery if possible immediately after a

contrast procedure • Stop nephrotoxic drugs 24-48hrs

preoperatively • Review the patient EARLY postoperatively

Summary

• 3 categories of AKI• Simple clinical assessment will define which• Be aware of life threatening complications and

emergency treatment • Recognise those at risk

Resource materials

• Davidson’s Principles & Practice of Medicine• Kumar & Clark Clinical Medicine• Oxford textbook of Clinical Nephrology • Oxford handbook of Nephrology and

hypertension • Renal Association website( www.renal.org) • KDIGO guideline (www.kidney.org)• AKI network ( www.akinet.org)