Acute Kidney Injury

Acute Renal Failure
Acute renal failure (ARF) is a syndrome characterized by rapid decline GFR with retention of nitrogenous waste products and perturbation of extracellular fluid volume and electrolyte and acid–base homeostasis. It is defined as a measurable increase in serum creatinine concentration, usually a relative increase of 50% or absolute increase by 0.5–1.0 mg/dL.
 
RIFLE CRITERIA:
1. Risk — Increase in the serum creatinine by 50%, or glomerular filtration rate (GFR) decrease by 25 percent, or urine output <0.5 mL/kg/hr for 6 hours
2. Injury — Increase in the serum creatinine by 100%, or GFR decrease by 50 percent, or urine output <0.5 mL/kg/hr for 12 hours
3. Failure — Increase in the serum creatinine by 200%, or GFR decrease by 75 percent, or urine output of <0.3 mL/kg/ hr for 24 hours, or anuria for 12 hours
4. Loss — Complete loss of kidney function (eg, need for renal replacement therapy) for more than four weeks
5. ESRD — Complete loss of kidney function (eg, need for renal replacement therapy) for more than three months
 
AKIN CRITERIA:
1. Stage 1: Increase in the serum creatinine by 0.3mg/dl or by 50% or urine output < 0.5 mL/kg per hour for 6 hours
2. Stage 2: Increase in the serum creatinine by 100% or urine output <0.5 mL/kg per hour for 12 hours
3. Stage 3: Increase in the serum creatinine by 200% or urine output of <0.3 mL/kg per hour for 24 hours, or anuria for 12 hours
 
KDIGO CRITERIA:
1. Increase in serum creatinine by ≥0.3 mg/dL within 48 hours; or
2. Increase in serum creatinine by ≥1.5 times baseline, within the prior seven days; or
3. Urine volume < 0.5 mL/kg/h for six hours. 
The KDIGO staging system is similar to AKIN staging. 
All diagnostic criteria should be used only after optimal state of hydration has been achieved.
 
Etiology:
 
1. Prerenal ARF
a) Hypovolemia due to GI losses, diuretics, burns, pancreatitis and dehydration
b) Altered renal hemodynamics resulting in hypoperfusion/shock
  • Systemic vasodilation: sepsis, anaphylaxis, antihypertensives, vasodilators
  • Renal vasoconstriction: hypercalcemia, catecholamines, calcineurin inhibitors, amphotericin B
  • Impairment of renal autoregulatory responses: cyclooxygenase inhibitors (e.g., NSAIDs), angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers
  • Hepatorenal syndrome
  • Cradiorenal syndrome: low cardiac output states like CHF, right heart failure, Pulmonary hypertension, massive PE. There might be decreased venous return in conditions like abdominal compartment syndrome or positive pressure ventilation. In Cardio renal syndrome, increased CVP will result in increased renal vein pressures, thereby causing renal edema and raised renal interstitial pressure. This leads is reduced ultrafiltration gradient and thereby decreased GFR.
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2. Intrinsic renal ARF
a) Renovascular obstruction ( Renal artery or vein obstruction due to atherosclerotic plaque, thrombosis, embolism, aortic dissection
b) Disease of glomeruli or vasculature
  • Glomerulonephritis and vasculitis
  • Other: TTP, malignant hypertension, collagen vascular diseases (SLE,scleroderma), DIC, preeclampsia
c) Acute tubular necrosis
  • Ischemia: Causes are the same as for prerenal ARF, but generally the insult is more severe and/or more prolonged.
  • Infection, with or without sepsis syndrome
  • Exogenous toxins: Radio contrast, calcineurin inhibitors, antibiotics (aminoglycosides), chemotherapy (e.g., cisplatin), antifungals (e.g.amphotericin B), ethylene glycol
  • Endogenous toxins: rhabdomyolysis, hemolysis
d) Interstitial nephritis
  • Allergic: antibiotics (e.g., β-lactams, sulfonamides, quinolones, rifampicin), NSAIDs, diuretics
  • Infection: pyelonephritis (if bilateral)
  • Infiltration: lymphoma, leukemia, sarcoidosis
  • Inflammatory, nonvascular: Sjögren’s syndrome, tubulointerstitial nephritis with uveitis
e) Intratubular obstruction
  • Endogenous: myeloma proteins, uric acid (tumor lysis syndrome), systemic oxalalosis
  • Exogenous: acyclovir, ganciclovir, methotrexate, indinavir
3. Postrenal ARF (obstruction)
a) Ureteric (bilateral, or unilateral in the case of 1 kidney): calculi, blood clots, sloughed papillae, cancer, external compression (e.g., retroperitoneal fibrosis)
b) Bladder neck: neurogenic bladder, prostatic hypertrophy, calculi, blood clots, cancer
c) Urethra: stricture or congenital valves
 
 
Diagnostic Approach
An acute process is easily established if a review of laboratory records reveals a recent increase in BUN and creatinine concentrations. Findings that suggest chronic renal failure include anemia, neuropathy, and radiologic evidence of renal osteodystrophy or small, scarred kidneys.
 
Renal failure indices
  1. Fractional excretion of sodium :  (FENa): (UNa × PCr / PNa × UCr) × 100.
  • Prerenal ARF: < 1 but can be >1, if receiving diuretics or have bicarbonaturia, preexisting chronic renal failure complicated by salt wasting, or adrenal insufficiency. This is based on the idea that in prerenal azotemia, tubular function is intact and sodium avidity is an appropriate response to decreased renal perfusion.
  •  Intrinsic renal ARF: usually >1. The relatively high FENa in ATN can be due to one or both of the following factors: inappropriate sodium wasting due to tubular damage; and/or an appropriate response of the remaining well- preserved nephrons to volume expansion. The FENa may remain below 1 percent when ATN is superimposed upon a chronic prerenal disease such as cirrhosis or heart failure, or in a minority of patients with nonoliguric post ischemic (ischemic) ATN who may have persistent renal ischemia and less severe ATN.
  1. Renal failure index :  UNa / (UCr/PCr)
  • Prerenal ARF: <1
  • Intrinsic renal ARF: usually >1
  • Post renal ARF: often <1
  1. Urine sodium concentration
  • Prerenal ARF: <10 mmol/L. However, A patient with prerenal disease who is highly water-avid due to increased secretion of antidiuretic hormone may have a higher than expected urine sodium concentration, despite a low rate of sodium excretion.
  • Intrinsic renal ARF: &gt;20 mmol/L. Decreased water reabsorption in ATN due to impaired concentrating ability can lower the urine sodium concentration by dilution.
  1. Urine specific gravity
  • Prerenal ARF: >1.020
  • Intrinsic renal ARF: ~1.010
  1. Urine osmolality
  • Prerenal ARF: >500 mosmol/kg H2O. A urine osmolality above 500 mosmol/kg is highly suggestive of prerenal disease, since it reflects both the hypovolemic stimulus to the secretion of antidiuretic hormone and the maintenance of normal tubular function
  • Intrinsic renal ARF: ~350 mosmol/kg H2O.  Loss of concentrating ability is an early and almost universal finding in ATN with the urine osmolality being below 450 mosmol/kg in almost all cases and usually below 350 mosmol/kg .
  1. Blood urea-to- creatinine ratio
  • Prerenal ARF: >20. This is due to the increase in the passive reabsorption of urea that follows the enhanced proximal reabsorption of sodium and water
  • Intrinsic renal ARF: <10–15
  1. Fractional excretion of urea : used if patient is on loop diuretics
  • Prerenal ARF: <35%
  • Intrinsic renal ARF > 50%
  1. Urinalysis
  • Prerenal ARF: Acellular with transparent hyaline casts. Occasional uric acid crystals (pleomorphic in shape) are common in concentrated urine. Consider acute urate nephropathy if these are abundant.
  • Intrinsic renal ARF: Pigmented &quot;muddy brown&quot; granular casts and casts containing tubule epithelial cells are usually found in association with microscopic hematuria and mild &quot;tubular&quot; proteinuria. Casts are absent in 20–30% of patients with ischemic or nephrotoxic ARF and are not a requisite for diagnosis. 
  1. RBC casts are highly specific for glomerular injury
  2. WBC casts and nonpigmented granular casts suggest interstitial nephritis.
  3. Broad waxy granular casts are characteristic of chronic renal disease.
  4. Eosinophiluria (&gt;5% of urine leukocytes) is a common finding (~90%) in antibiotic-induced allergic interstitial nephritis (with Hansel’s stain). 
  5. Lymphocytes may predominate in allergic interstitial nephritis induced by NSAIDs and in atheroembolic ARF.
  6. Oxalate (envelope-shaped) and hippurate (needle-shaped) crystals suggest ethylene glycol ingestion and toxicity.
  7. Proteinuria &gt;1 g/d suggests injury to glomerular ultra filtration barrier (&quot;glomerular proteinuria&quot;) or excretion of myeloma light chain
  8. Heavy proteinuria is a frequent finding (~80%) in combined allergic interstitial nephritis and minimal change glomerulopathy when treated with NSAIDs, ampicillin, rifampicin, or interferon α.
  9. Suspect hemoglobinuria or myoglobinuria if urine is strongly positive for heme by dipstick, but contains few erythrocytes
  • Postrenal ARF: Hematuria and pyuria are common with intraluminal obstruction or prostatic disease. Urinary sediment is usually bland.
 
Diagnostic Procedures
 
Renal biopsy: Reserved for patients in whom prerenal and postrenal ARF have been excluded and the cause of intrinsic renal ARF is unclear
Particularly useful in diagnoses other than ischemic or nephrotoxic injury that may respond to disease-specific therapy
  • Glomerulonephritis
  • Vasculitis
  • Hemolytic–uremic syndrome
  • Thrombotic thrombocytopenic purpura
  • Allergic interstitial nephritis
 
Treatment Approach
  • Rapidly reverse the contributing factors 
  • Tailor replacement fluids for hypovolemia according to the composition of lost fluid.
  • ARF due to other intrinsic renal diseases (e.g., acute glomerulonephritis or Vasculitis) may respond to glucocorticoids, alkylating agents, and/or plasmapheresis, depending on primary abnormality
  • Aggressive control of systemic arterial pressure to limit renal injury in malignant hypertensive nephrosclerosis
  • Nutritional management during maintenance phase of ARF involves providing sufficient calories to avoid catabolism and starvation ketoacidosis while minimizing production of nitrogenous waste. Also, restrict dietary protein to ~ 0.6 g/kg per day of protein of high biologic value (i.e., rich in essential amino acids).
  • Uremic bleeding usually responds to correction of anemia, administration of desmopressin or estrogens, or dialysis.
  •  Daily rather than alternate-day schedule is clinically superior and confers improved survival. However, new trials contradicted this. 
 
Contrast nephropathy
 
The onset of kidney injury is probably within minutes of exposure to contrast agents. However clinical manifestations such as oliguria or an increase in the serum creatinine are generally observed within 24 to 48 hours after contrast exposure. Most patients are nonoliguric.
 
The urinary sediment may show classic findings of acute tubular necrosis (ATN), including muddy brown granular and epithelial cell casts and free renal tubular epithelial cells. 
 
The optimal intravenous solution (isotonic saline, one-half isotonic saline, or isotonic sodium bicarbonate) and its volume and duration of administration pre- and post-contrast for prevention of contrast nephropathy is unclear.
 
Prevention is by administering NS@1ml/kg/hr for 12 hrs before procedure and 12 hours after procedure. Other alternative is Bicarb drip@3ml/kg/hr for 1 hour before procedure and for 6 hours after procedure.
 
 
PEARLS:
  • Serum creatinine does not accurately reflect the GFR in a patient in whom it is not in steady state. In the early stages of AKI, the serum creatinine may be low, even though the actual (not estimated) GFR is markedly reduced, since there may not have been sufficient time for the creatinine to accumulate. When the serum creatinine is rising, estimates of GFR based on creatinine values will overestimate the true GFR; conversely, estimates of GFR will underestimate the true GFR during recovery of kidney function, when the serum creatinine concentration is declining.
  • Creatinine is removed by dialysis. As a result, it is usually not possible to assess kidney function by measuring the serum creatinine once dialysis is initiated.
  • Composition of crystalloids:
http://image.slidesharecdn.com/intravenousfluids-crystalloidsandcolloids-130402081937-phpapp01/95/slide-14-638.jpg?cb=1364908879
  • NSAIDS block the prostaglandin mediated dilation of afferent renal arterioles
  • ACEI/ARB’s block the efferent arteriole constriction, resulting in decrease in GFR
  • Trimethoprim blocks tubular secretion of creatinine and may falsely elevate creatinine values.
  • Disproportionate elevation in BUN relative to creatinine may suggest GI bleed.  It is due to increased urea production from the heme protein breakdown due to gastrointestinal bleeding.
  • Among patients with CKD, the urine sodium concentration and the FENa are difficult to interpret. Ability to concentrate urine is often impaired in CKD.
  • Hyperkalemia in AKI should strongly be suspicious of post-renal cause. Potassium values should not rise in pre renal and intrinsic renal failure unless GFR< 15. 
  • Oliguria is 100-400ml and anuria is less than 100ml
  • Following hemodialysis, potassium levels may rebound as much as 30% up to 5 hours post-treatment. Therefore, if a patient is being treated for hyperkalemia, a post-treatment potassium level should not be drawn until 2-3 hours after the completion of dialysis
  • Bacteria can be recovered from the ultrafiltrate in CRRT
  • High chloride in NS compared with plasmalyte caused more kidney damage in a study. Also, in another study on post op renal transplant patients, NS resulted in more vasopressor requirements.
  • In a study by raghunathan, patients receiving balanced fluids have significantly lesser mortality regardless of amount of fluid given.
  • Hyperchloremia causes renal vasoconstriction and fall in GFR.
  • Chloride rich crystalloids may also damage glycocalyx and increase interstitial fluid volume resulting in interstitial edema.
  • In IHD, drug dosing is for GFR <10. In CRRT, dose meds for GFR< 30
  • IHD vs. CRRT both have equal outcomes.
  • Alternative to CVVHD is SLED( sustained low efficiency dialysis)
  • Early RRT didn’t improve outcomes compared with conservative strategy.
  • Most intensivists would start RRT at AKI stage 3. In CONVINT study, at the time of dialysis initiation, the average BUN was 150 and creatinine was 3.6.
  • CRRT can increase systemic bleeding and hence, in bleeding patients, IHD is preferable.
  • Patients with brain edema can have massive fluid shifts with IHD and hence, CRRT is preferable in these patients.
  • CRRT is better than IHD in tumor lysis syndrome because of greater solute removal and avoidance of solute rebound
  • 25% albumin has more volume expansion effect than 5% albumin.
  • RENAL study showed that high dose CRRT vs. standard dose CRRT (25ml/kg/hr) has equal outcomes.
  • CRRT intensity as determined by effluent rate increases the elimination of antibiotics like meropenem, zosyn and vancomycin. Hence, their doses need to be adjusted. Also, in another study, CRRT clearance of antibiotics doesn’t correlate that well. Hence, they recommend giving normal antibiotic doses in CRRT. 
  • Diuretics in AKI are associated with increased mortality. Hence, if need be, use RRT instead of diuretics. Don’t burden the kidneys with more lasix. It is almost like resting lungs in ARDS.
  • Early RRT is associated with improved mortality compared with traditional indications for RRT. However, too early or too late RRT has worst outcomes. The best outcomes are when RRT is started between 24-48 hrs after AKI stage 3. Also, in patients who are expected to recover soon, early RRT is associated with increased mortality. In practice, it’s better to wait for 24 hrs to see if pt improves and if not, start RRT immediately.
  • Lasix challenge in AKI: In pts with good renal reserve, lasix will show some response and they are found to have good recovery without RRT. In pts who do not respond to lasix, they have poor renal reserve and they should be dialyzed sooner. 
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