Acute Renal Failure (ARF)

Acute renal failure due to intratubular crystal precipitation can be seen in a variety of clinical settings, the most common being acute uric acid nephropathy Acute renal failure (ARF) is defined as a sudden decrease of normal kidney function that compromises the normal renal regulation of fluid, electrolyte, and acid–base homeostasis.

ARF (Acute renal failure) is characterized by :

• · Decrease in GFR (reversible).
• · Retention of nitrogenous wastes.
• · Disturbance of balance of fluid volume, electrolytes and acid-base.
• Oliguria: Urine output <0.5 mL/kg/h in infants or <500 mL/1.73 m²/d in older children
• Anuria: Total cessation of urinary output
• Polyuria: Urine output >2 L/m²/d in infants and children or 3 L/d in adults
• ·Oliguria – i.e. urine output <400 ml/day.
• Pre-renal and post-renal failure may be reversible by prompt and appropriate treatment.
• ARF is usually asymptomatic. It is diagnosed by a recent increase in blood urea and creatinine.

ARF may be of 3 types:

• 1. Prerenal
• 2. Renal
• 3. Post renal.
• Pre-renal –
  • There is renal hypoperfusion. Renal pa­renchyma is normal.
• Renal –
  • Renal parenchymal disease is present.
• Post renal –
  • There is urinary tract obstruction lead­ing to renal failure.
• ARF is mostly reversible.

PRERENAL ARF

• It is reversible by proper perfusion of kidneys so that glomerular ultrafiltration pressure becomes normal. Renal parenchymal tissue is normal.
• If tissue hypoperfusion persists there is damage of renal parenchyma.
• Due to hypoperfusion there is :
• Activation of sympathetic nervous system.
• Activation of renin angiotensin – aldosterone sys­tem .
• Release of AVP / ADH (arginine vasopressin / antidiuretic hormone).
• Norepinephrine, angiotensin II and AVP cause vasoconstriction in non-essential areas, inhibit salt loss through sweat glands, stimulate thirst, promote salt and water retention.
• Prostaglandin E₂and prostacyclin cause dilata­tion of afferent arterioles.
• Angiotensin II causes preferential constriction of efferent arterioles.
• Thus glomerular filtration pressure is increased and glomerular filtration rate is increased.
• All these processes help to counter the renal hypoperfusion.
• GFR (Glomerular filtration rate) is maintained only if systemic pressure is above 80 mmHg.

Hepatorenal syndrome

• In advanced cirrhosis and other liver diseases there is severe form of ARF, called hepatorenal syndrome.
• Mortality is very high.

INTRINSIC RENAL ARF

• This may be due to :
• 1. Disease of larger renal vessels
• 2. Disease of glomeruli
• 3. Ischemic and nephrotoxic ARF
• 4. Tubulointerstitial disease.

Common causes of intrinsic ARF

• · Ischemia (Acute tubular necrosis)
• · Nephrotoxins.

Acute tubular necrosis

• Acute tubular necrosis or Ischemic ARF occurs in trauma, haemorrhage, sepsis, volume depletion. It can occur on preexisting renal disease.

POST RENAL ARF

• Post renal ARF is usually due to obstructive causes and are fully reversible with surgical treatment .

MAJOR CAUSES OF ARF PRERENAL

• Haemorrhage
• Burns
• Dehydration
• Vomiting and diarrhea
• Diabetes mellitus (osmotic diuresis)
•  Pancreatitis Peritonitis
•  Hypoalbuminemia
• Low cardiac output Pulmonary hypertension Sepsis
• Anti hypertensives
• Norepinephrine Epinephrine
• Cirrhosis and ascites (Hepatorenal)
•  ACE inhibitors
• Multiple meyloma.

Renal Causes of ARF

• Renal artery obstruction by thrombus, embolism Renal vein thrombosis
• Glomerulonephritis
• Vasculitis
• Thrombotic thrombocytopeniac purpura Toxaemia of pregnancy
• DIC (Disseminated intravascular coagulation) SLE (Systemic lupus erythematosus) Scleroderma
• Acute tubular necrosis (Ischemia or hypoperfusi6n)
• Toxins
• PPH (Post Partum Haemorrhage) Abruptio placentae
• Drugs  Cyclosporin
•  Antibiotics
• NSAIDs
• Radiocontrast dye
• Interstitial nephritis Infections.
• Calculi Cancer
• Clot
•  Stricture Bladder neck obstruction
• Urethral obstruction.

Pathophysiology

• ARF is commonly precipitated by an ischemic or nephrotoxic event.
• Initial vasodilatation is followed by intense vasoconstriction, with blood redistributed from the cortex to the juxtamedullary nephrons
• Intratubular debris and cast formation develop.
• Tubular fluid leaks backward across the injured tubular membrane, which, in addition to tubular obstruction, causes further hemodynamic changes.

FEATURES TO DIFFERENTIATE ACUTE AND CHRONIC RENAL FAILURE ARF

• Recent increase in urea and creatinine.
• There is history suggestive of the cause of ARF like diarrhoea, vomiting, burns etc.
• CRF
• Anaemia Neuropathy
• Rena I osteodystrophy Small, scarred kidneys
• Kidney size may be increased or normal in CRF due to :
• Diabetic nephropathy Amyloidosis
• Polycystic kidney disease
• Usually the kidney size is reduced in CRF .

Clinical features of ARF

• Thirst
• Orthostatic hypotension
• Systemic hypotension (BP <90 mmHg) –v Tachycardia (Pulse rate >100 Imin)
• Tachypnoea
• Raised JVP
• Dry skin and mucous membrane
• Reduced sweating
• History of NSAIDs, ACE-I (ACE inhibitors), ARBs
• (Angiotensin receptor blockers) v Decreased urine output
• Decreased body weig ht
• Hypovolemia
•  Sepsis
•  Hlo Radiocontrast dye
• Flank pain
• Atheroembolization suggested by Sic nodules, ischemia of fingers, toes
• Glomerulonephritis suggested by oliguria, edema, hypertension, active urine sediment.

 Interstitial nephritis suggested by

• Fever,
• arthralgias,
• pruritic (that itch) red rash.

Urinary obstruction suggested by –

• Colicky pain
• Suprapubic and flank pain
• oFlank pain – loin tropain.

Prostate enlargement suggested by

• Nocturia
• Frequency
• Hesitancy.

URINE

• Oliguria or Anuria.

Prerenal ARF

• · Urine is acellular
• · Inactive sediments or hyaline casts present.

Post renal ARF

• · Inactive sediment
• · Hematuria
• · Pyuria.

Acute tubular necrosis (ATN) i.e. Ischemic ARF, Nephrotoxic ARF

• · Pigmented, muddy brown granular casts with tubule epithelial cells in urine.
• · Mild proteinuria « 19/day

Glomerular involvement

• Tubulointerstitial disease – RBC casts in urine.

Interstitial nephritis

• · WBC casts in urine.
• · Nonpigmented granular casts in urine.

Chronic renal disease

• Broad granufar casts in urine.
• Eosinophils -in urine – allergic interstitial nephritis. Uric a~id crystal~ in – acute urate nephropathy.

Proteinuria >1g/day suggests gIomerular disease. Heavy proteinuria> 1 g/day also seen in patients on NSAIDs, ampicillin, rifampicin, interferon alpha. Bilirubin in urine in hepatorenal syndrome. Fractional excretion of sodium

• FE Na < 1 % in prerenal ARF
• FE Na > 1 % in ischemic, nephrotoxic (tubular disease).

BLOOD

• Serum creatinine: increases progressively in renal failure and is a very good indicator of renal failure.
• Hyperkalemia
• Hyperphosphatemia
• Hypocalcemia
• Hyperuricemia
• Anaemia

ULTRASOUND

• Ultrasonography is useful for post renal ARF to diag­nose causes like – urinary tract obstruction, pelvicalyceal dilatation, retroperitoneal fibrosis, neo­plasia.

CT, MRI PLAIN X-RAY ABDOMEN

• For nephrolithiasis.

PYELOGRAPHY –

retrograde, antegrade –

• for lo­calization of site of obstruction.
• For patency of renal arteries and veins.

MR ANGIOGRAPHY

• Non-invasive renal vascular study. CONTRAST ANGIOGRAPHY

RENAL BIOPSY –

• For definitive diagnosis.
• For intrinsic renal ARF e.g. glomerulonephritis, vas­culitis, thrombocytopenic purpura, interstitial nephri­tis.

COMPLICATIONS

• There is impairment of renal excretion of sodiurtl, potassium and water.
• · Volume overload
• · Raised JVP
• · Hyponatrem ia
• · Hyperkalemia
• · Hyperphosphatemia
• · Hypocakemia
• · Hypermagnesemia
• · Metabolic acidosis
• · Uremia
• · Weight gain
• · Basal lung rales
• · Dependent edema
• · Pulmonary edema
• · Cerebral edema
• · Seizures
• · Arrhythmias
• · Metabolic acidosis
• · Lactic acidosis
• · Hemolysis
• · Leucocytosis
• · GI bleeding and bleeding from other sites
• · Infections
• MI
• Pericarditis Pericat”dial effusion Pulmonary embolism Uremic syndrome.

Causes of Hypocalcemia in ARF

• Metastatic deposition of calcium phosphate when the serum calcium X phosphate in mgjdl is > 70.
• Tissue resistance to parathyroid hormone. Decreased 1,25 dihydroxyvitamin D.

Effects of hypocalcemia

• Muscle cramps Seizures Hallucinations Confusion
• Prolonged QT.

TREATMENT OF ARF

• Prevention of pre-renal and post-renal causes Avoid drugs causing ARF
• Low drug dosage of nephrotoxic drugs Maintain fluid balance
• Maintain sodium, potassium, phosphate, calcium levels
• Invasive and noninvasive hemodynamic moni­toring
• Low dose dopamine
• Loop diuretics (frusemide, torsemide) Antihyperte~sives like CCB (Calcium channel blockers) and Alpha-blockers
• Atrial natriuretic peptide
• Prostaglandins
• Antioxidants Glucocorticoids Alkylating agents Plasmapharesis
• Relief of obstruction of urinary tract
• Oral or IV sodium bicarbonate if arterial pH <7.2 or serum bicarbonate < 15 meq/L
• Restriction of dietary phosphate
• Oral aluminum hydroxide
• Calcium carbonate
• Vitamin D
• Restriction of dietary protein 0.6 g/kg/day Carbohydrate 100 g/day
• Blood transfusion if required
• Rarely erythropoietin for anemia
• Antacids
• PPI (proton pump inhibitor) and H₂blockers Anti biotics
• Dialysis – if hemodynamically unstable peritoneal dialysis is done
• Hemodialysis – in uremic syndrome, refractory hyperkalemia, acidosis
• Continuous renal replacement therapy (CRRT) Continuous arteriovenous hemodiafiltration (CAVHD)
• Continuous venovenous hemodiafiltration (CVVHD).