Approach to a patient with Acute

Kidney Injury

Dr. Sayan ChakrabortyJR-3, Dept. of Tropical Medicine,School of Tropical Medicine, KolkataEmail: dr.sayan@gmail.com

Epidemiology• 5-7% of acute care hospital admissions• 30% of ICU admissions with mortality rates –

50%• AKI worsens CKD• Severe AKI requiring dialysis increases risk of

developing dialysis-requiring-ESRD.• Community-acquired AKI: Volume depletion,

ADRs & obstruction of the urinary tract. • Hospital-acquired AKI: Sepsis, major surgical

procedures, heart or liver failure, IV iodinated contrast and nephrotoxic drugs

AKI in Tropics

• Diarrhoeal diseases• Envenomations from snakes, spiders,

caterpillars, and bees• Malaria• Leptospirosis• Crush injuries from earthquakes and

resultant rhabdomyolysis

Definition of AKI

KDIGO criteria (ungraded)

• Increase in SCr by ≥0.3 mg/dl (≥26.5 umol/l) within 48 hours;

or• Increase in SCr to ≥1.5 times baseline,

which is known or presumed to have occurred within the prior 7 days;

or• Urine volume <0.5 ml/kg/h for 6 hours.

KDIGO- Staging of AKI

RIFLE Criteria

R iskI njuryF ailureL oss of functionE nd-Stage Renal

disease

RIFLE Criteria

R isk

Increase in Cr of 1.5-2.0 X baseline or urine output < 0.5 mL/kg/hr for more than 6 hours.

I njury

F ailure

L oss of function

E nd-Stage Renal disease

RIFLE Criteria

R isk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for more than 6 hrs

I njury• increase in Cr 2-3 X baseline (loss of 50% of GFR) or • urine output < 0.5 mL/kg/hr for more than 12 hours.

F ailure

L oss of function

E nd-Stage Renal disease

RIFLE Criteria

R isk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for > 6 hrs

I njury: Inc Cr 100-200% or U.O. < 0.5 mL/kg/hr > 12 hrs

F ailure increase in Cr rises > 3X baseline Cr (loss of 75% of GFR)

or an increase in serum creatinine greater than 4 mg/dL, or urine output < 0.3 mL/kg/hr for more than 24 hours or

anuria for more than 12 hours.

L oss of function

E nd-Stage Renal disease

RIFLE Criteria

R isk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for > 6 hrs

I njury: Inc Cr 100-200% or U.O. < 0.5 mL/kg/hr > 12 hrs

F ailure: Inc Cr > 200% or > 4 mg/dL or U.O. < 0.3 mL/kg/hr > 24 hrs or anuria for more than 12 hours

L oss of function persistent renal failure (i.e. need for dialysis) for

more than 4 weeks.

E nd-Stage Renal disease

RIFLE Criteria

R isk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for > 6 hrs

I njury: Inc Cr 100-200% or U.O. < 0.5 mL/kg/hr > 12 hrs

F ailure: Inc Cr > 200% or > 4 mg/dL or U.O. < 0.3 mL/kg/hr > 24 hrs or anuria for more than 12 hours

L oss of function: Need for dialysis for more than 4 weeks

E nd-Stage Renal disease persistent renal failure (i.e. need for dialysis) for more

than 3 months.

Etiopathogenesis of

AKI

Classification of AKIAcute Kidney Injury

Pre-renal Intrinsic Post-renal

Glomerular Interstitial VascularTubular

55% 40% 5%

85%10%<5% <5%

Pre-renal AKI

Non- oliguric AKI• Non- Oliguric: In hospital set-up, secondary

Nephrotoxic agents like:Aminoglycosides (10-30%), even in therapeutic

ranges, manifestation after 5-7 days of therapyAmphotericin B: Dose & duration dependent;

polyuria, hypomagnesemia, hypocalcemia, &nongap metabolic acidosis

• Non-oliguric has better prognosis than oliguric

one.

ICU vs Non-ICU AKI

• Non-ICU AKI, kidney usually being the only failed organ, mortality rates of up to 10%.

• ICU AKI often associated with sepsis and

with non-renal multi-organ system failure, mortality rates of over 50%

Diagnostic Evaluation History and Physical examination:• Pre-renal: History: vomiting, diarrhoea, glycosuria

causing polyuria, and several medications including diuretics, NSAIDs, ACE inhibitors, and ARBs.

Examination: Physical signs of orthostatic hypotension, tachycardia, reduced jugular venous pressure, decreased skin turgor, and dry mucous membranes are often present in prerenal azotemia

Diagnostic EvaluationINTRINSIC RENAL:Review all medications • Cause of AKI .• Dose Adjustment.

Systemic vasculitis with Glomerulonephritis: • Palpable purpura• Pulmonary hemorrhage,• Sinusitis.

Atheroembolic • Livedo reticularis and other signs of emboli to the legs.• Rhabdomyolysis.• Signs of limb ischemia

Diagnostic Evaluation• Post- Renal:Colicky flank pain radiating to the groin suggests

acute ureteric obstruction.

Nocturia and urinary frequency or hesitancy can be seen in prostatic disease.

Abdominal fullness and suprapubic pain can accompany massive bladder enlargement. Definitive diagnosis of obstruction requires radiologic investigations.

Blood Tests

• CBC• BUN/creatinine • Electrolytes• Uric acid• PT/aPTT

Urine Analysis

•Volume•Osmolality•Proteinuria•Urinary Indices: FeNa& Urinary Sodium •Sediments

Imaging

• Renal ultrasound (useful for obstructive forms)

• Doppler (to assess renal blood flow)• CT Scan • Pyelography• Nuclear Medicine Scans :

DMSA: anatomy. DTPA and MAG3: renal function,

urinary excretion and upper tract outflow.

Important biomarkers

•Cystatin C

•Neutrophil gelatinase-associated lipocalin (NGAL)

•Interleukin-18 •Kidney injury molecule-1

•N-acetyl-D-glucosaminidase

Cystatin-C

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

• Identifies kidney injury while creatinine levels remain normal

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

Kidney Injury Molecule-1 (KIM-1)

• 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)

• Highly upregulated after inflammation and kidney injury

• Can be detected in the plasma & urine within 2 hours of cardiopulmonary bypass–associated AKI.

• Considered equivalent to troponin in acute coronary syndrome.

Complications of AKI

Major causes of AKI in Specific

Clinical settings

Treatment of AKI

General Issues

1. Optimization of systemic and renal hemodynamics 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

Pre-Renal AKI

• Prevention and treatment of prerenal azotemia requires optimization of renal perfusion.

• Severe acute blood loss should be treated with PRBC transfusion.

FLUIDS• KDIGO advocates use of isotonic crystalloids

rather than colloids (albumin or starches) .

• Colloids may be chosen to avoid excessive fluid administration 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

• Appropriate use of vasoactive agents improve kidney perfusion in volume-resuscitated patients with vasomotor shock.

• Dopamine 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 SBP

• Bridge therapies [in combination with IV Inf albumin (25–50 mg/d)] include: terlipressin (a vasopressin analog), combination therapy with octreotide (a

somatostatin analog) and midodrine (an α 1-adrenergic agonist), and norepinephrine

Cardio-Renal Syndrome

• Optimization of cardiac function .

• May require use of inotropic agentspreload- and afterload-reducing agents,antiarrhythmic drugs,mechanical aids such as an intra-aortic

balloon pump.

Treatment of Intrinsic AKI

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

• KDIGO suggest not using diuretics to treat AKI, except in the management of volume overload

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

FENOLDOPAM

• Fenoldopam mesylate: pure dopamine type-1 receptor agonist

• Without systemic adrenergic stimulation.• No conclusive studies available.• 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.

Erythropoietin • Potential clinical benefit of erythropoietin in AKI in animal studies.

• Renoprotective action of erythropoietin related to pleomorphic properties including anti-apoptotic & anti-oxidative 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/day)

• Alkaline fluids beneficial

• Diuretics may be used if fluid repletion is adequate & no urine output

• Dialysis

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

Glomerulonephritisor 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 t/t of infections unless no suitable, less nephrotoxic, therapeutic alternatives are available

• Avoid in high risk patients of age > 65 years, DM, septic shock

• Single dose daily rather than multiple-dose daily t/t regimens

• 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

• Use 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 lipid complex or colloidal dispersion forms

Post-renal

• Prompt relief of urinary tract obstruction.

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

Indications for Dialysis

A – Acidosis E – Electrolyte disturb, usually

hyperkalemia I – Intoxications (lithium, ethylene glycol,

etc) O – Overload (volume overload) U – Uremia (symptoms, signs )

Modes Of Dialysis

• Hemodynamically stable- IHD

• Hemodynamically unstable1. CRRT2. PD3. SLED

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.

Recent Publications

Recent Publications

• Diagnose early – Biomarkers have great potential

• Look for etiology• Prevent rather than treat• No role of low dose dopamine, diuretics in

prevention and treatment• Initiate RRT when indicated

References• Brenner and Rector's The Kidney 9th ed. - M. Taal (Saunders,

2012) • Harrison's Principles of Internal Medicine, 19th edition (2015)• Paul Marino The ICU Book(3rd Ed)• The Washington manual of Critical care 2nd edition• Kidney Disease: Improving Global Outcomes (KDIGO) Acute

Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1–138

• Rahman et al Acute kidney injury: A guide to diagnosis and management; American Family Physician, Volume 86, Number 7 October 1, 2012

• Ronco C Acute Kidney Injury: from clinical to molecular diagnosis; Ronco Critical Care (2016) 20:201