Acute kidney injury: causes, clinical features and complications.

Causes for acute kidney injury ATIN:

Pre renal causes (most common):

Volume depletion (defective intravascular volume) :

• Diarrhoea or vomiting.
• Third space loss ( burn, pancreatitis, ascites).
• Decrease serum albumin.

Acute tubular necrosis it changed to ATIN ( acute tubule interstitial nephritis):

• Ischemia.
• Sepsis.
• Drugs.
• Contrast.
• Tumor lysis syndrome.
• Pigment nephropathy: hemolysis and rhabdomyolysis.
• Multiple (myeloma Myeloma cast nephropathy).
• Abruption-placenta 
• Acute pancreatitis 
• Snake bite

Criteria for defining ATIN:

• RIFLR criteria based on increase serum creatinine and decrease urine output.
• AKIN criteria.
• KDIGO criteria based on urine output and serum creatinine.

KDIGO stage 1:

• Creatinine 1.5 to 1.9 times the baseline.
• Absolute increase of more than 0.3 milligram per decilitre. 
• Urine output Less than 0.5 ml per kg per hour for 6 to 12 hours.

KDIGO stage 2:

• Creatinine 2-2.9 times the baseline.
• Urine output Less than 0.5 ml per kg per hour for more than 12 hours.

KDIGO stage 3:

• Creatinine in more than three times the baseline.
• Patient require in dialysis.
• Anurea more than 12 hours or less than 0.3 ml per kg per hour for more than 24 hour.

Site of tubular injury in ATIN:

S3 segment of proximal straight tubule > thick ascending loop of Henle.

New markers for ATIN:

Major drawback of serum creatinine: takes 24 to 48 hours for levels to rise

• NGAL – neutrophil gelatinates associated lepocalin.
• N-acetyl- D- glucosaminidase.
• IL- 18.
• Kidney injury molecules -1.
• Cystatin-C.

Phases of acute tubulo-interstitial nephritis:

Phase 1	Phase 2	Phase 3
Tubular injury	Tubuloglomerular feedback	Recovery (14days)
S.Na ↓	S.Na ↓	S.Na ↓
S.K ↓	S.K ↑	S.K ↓
S.Ca ↓	S.Ca ↓	S.Ca ↓
S.P ↓	S.P ↑	S.P ↓
S.Mg ↓	S.Mg ↑	S.Mg ↓
Urine output ↑	Urine output ↓↓ Acidosis	Urine output ↑

Site of tubular injury in ATIN:

 S3 segment of proximal straight tubule. Phase 2 can lead to volume overload, arrhythmia, metabolic acidosis, uremia, hyperkalemia.

Ischemia:

	Pre-renal AKI	Ischemic AKI
Urine	Normal (Non-specific hyalin cast)	Albumin-trace / + casts : RTEC (muddy brown epithelial cast)
BUN / S. creatinine	>20	<10
Urine specific gravity	1.020 to 1.040	= 1.010
Urine osmolality	800-900	289-290
Urine sodium	↓ <20 meq/L	>40 meq/L
Urine creatinine	>40 meq/L	<20meq/L
FeNa	<1%	>2%

FeNa : fractional excretion of sodium.

FeNa= urine sodium/ urine creative × plasma creatinine /plasma sodium.

Normal FeNa = 1:2%.

Best parameter for differentiating pre-renal vs Ischemic ATIN is FeNa.

Drugs causing ATIN:

Dose dependent tubular injury:

A – Aminoglycosides, Amphotericin B, Adefovir.

C – Cisplatin, Cyclophosphomide.

E – Ethylene glycol.

S – Salicylates.

Vancomycin.

Dose independent tubular injury with Type 4 hypersensitivity:

• B – Betalactem antibiotic.
• R – Rifampicin.
• A – Allopurinol, anti-convulsant.
• N- NSAIDs.
• D – Diuretics.
• PPI.

Drug dependent intratubular obstruction:

 M – Methotrexate.

I – Indinavir.

T – Triamterene.

A – Acyclovir.

S – Sulfonamide.

NSAID induce nephropathy and analgesic nephropathy:

 NSAID induced nephropathy:

• Blocking of prostaglandin induced a afferent arteriole vasodilation (pre-renal AKI) –  most common.
• ATIN – type 4 hypersensitivity second most common.
• Glomerular damage – minimal change disease.

Features:

• FeNa less than 1%.
• Oliguric AKI.
• Hyperkalemia.

Analgesic nephropathy:

• Phenacetin – aspirin – caffein combination.
• Renal papillary necrosis leading to CTID.

Infections / sepsis causing AKI – ATIN:

• Post operative sepsis.
• Complicated UTI.
• Pneumonia.
• Diabetic foot.
• Tropical infections ( leptospirosis and scrub typhus ).

Contrast induced nephropathy:

Low volume low osmolal contrast like Iohexal produce least injury. Caused by high volume high osmolar ionic contrast.

• Renal medullary hypoxia.
• Direct tubular injury.

Presentation: asymptomatic, non-oliguric renal failure with excellent prognosis.

Serum creatinine:

• Rise by 24 to 48 hours.
• Peaks by 3 to 5 days.
• Normalised by 7 to 10 days.

Prevention of contrast induce AKI:

• Use low volume low osmolar non-ionic contrast like Iohexal.
• Fluid and hydration.
• N-acetal Cystein.

Histopathology:

Vacuolar changes in PCT cells.

Contrast induced nephropathy can also cause FeNa less than 1%.

Nephrogenic systemic sclerosis and cholesterol embolism:

If eGFR less than 30 ml per minute avoid contrast MRI as Gadolinium use in these cases is associated with fibrosing lesions throughout the upper and lower limb causing nephrogenic systemic Fibrosis.

Cholesterol embolism (Atheroembolic renal disease):

Extensive atherosclerosis after:

• Endovascular intervention (30%).
• Heparin induce.
• Spontaneously.

Microvascular occlusion seen in:

• Kidney 75% – sub acute renal failure.
• Skin – livedo reticularis.
• Retina – Hollenhorst plaques.

Diagnosis : cholesterol cleft on skin biopsy.

Tumor lysis syndrome ( uric acid nephropathy ):

Seen with:

• ALL (highest risk).
• Burkitts lymphoma.
• DLBCL.
• AML high count.

Intratobular obstruction by uric acid crystals in DCT and collecting duct.

Diagnosis:

• Oliguric renal failure.
• Serum potassium increases, serum magnesium increases, serum phosphorus increases.
• Serum creative increases.
• Serum uric acid increase.
• Serum calcium decreases.

Treatment:

Hemodialysis or iv Rosburicase.

Prevention:

• Check LDH level before administration of chemotherapy.
• Aggressive hydration with 5 to 6 litter per day.
• Alkalization of urine.

Heme pigment nephropathy (Rhabdomyolysis):

Causes:

• Excessive strenous exercise.
• Electric shock.
• Snake bite.
• Inflammatory muscle disorder.
• genetic – mcArdles disease.
• Laptospirosis.
• Drug and toxins – statins,  deriphyllin, cocaine, amphetamine.

Presentation:

• Pain in the muscle.
• High colour urine.
• Non-oliguric renal failure.

Diagnosis:

Hyperkalemia, hypermagnenesemia, hyperphospatemia, hypocalcemia, increase CPK-mm.

Treatment:

• Vigorous and intense hydration.
• Urine alkalizasion.

Myeloma:

Manifestation of myeloma in the Kidney: tubulo-interstitial Light chain myeloma- Gamma light chain predominantly involved.

Light chain cast nephropathy – characterised by overflow proteinuria.

Dipstick negative for albumin with 24 hours urine protein high.

Cast seen here is fractured cast.

Renal cortical necrosis:

Seen with:

• Snake bite.
• Acute pancreatitis.
• Abruptio placenta.