Renal Failure

Definition

  • Acute kidney injury (AKI) used to describe acute renal failure
  • No consensus definition for AKI but pRIFLE often used as one way of defining kidney injury in the PICU. 

                        
  • Other used definitions include 50% increase in Cr and/or 50% decrease in GFR
  • BIomarkers [i.e. neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, kidney injury molecule-1 (KIM1)] may provide further insight and earlier detection of kidney injury
  • Schwartz formula
     


Pathophysiology

  • Kidneys regulate plasma water and electrolyte concentrations by filtering through the glomerular membrane into the renal tubules, where the filtrate is then selectively reabsorbed by the renal tubular epithelium
  • Injury can thus occur as a result of damage to the glomeruli or the renal tubules
  • Renal perfusion is key for glomerular filtration
    • Kidneys receive ~25% of cardiac output
    • The kidneys are able to autoregulate to maintain a constant renal perfusion pressure by altering the renal vascular resistance depending on blood volume and systemic blood pressure
      • For example, if cardiac output decreases, the afferant arteriole dilates, reducing renal vascular resistance, and thereby improving renal blood flow
      • When cardiac output decreases, the body also compensates by activating the renin-angiotensin-aldosterone system, which functions to provide systemic vasoconstriction to support systemic perfusion. The kidney is able to produce local prostaglandin (ie prostaglandin I2) which serve as local vasodilators to protect renal perfusion. Hence, NSAIDS can exacerbate renal injury by blocking local prostaglandin production that would normally protect the kidneys in the context of reduced systemic perfusion
      • Angiotensin II and epinephrine serve to vasoconstrict the efferent arteriole, improving filtration fraction and GFR. Hence, an ACE inhibitor would counteract this efferent vasoconstriction and thus produce reduced renal filtration in a kidney that relies upon efferent vasoconstriction 
      • Renal autoregulatory ability is limited (much like cerebral autoregulation) and extremes of blood pressure as well as preexisting injury can limit this autoregulatory capacity even further
  • 4 Major Mechanisms leading to reduced GFR
    • 1: Reduced renal blood flow (i.e. due to increased afferent vasoconstriction, endothelial cell swelling, capillary congestion)
    • 2: Reduced Kf (capillary ultrafiltration coefficient) due to decreased surface area for filtration, altered permeability
    • 3: Renal tubular injury and subsequent tubular obstruction
    • 4: Backleakage of tubular ultrafiltrate into the renal interstitium
  • Phases of renal injury: 
    • Initiation Phase
      • Ischemia, toxins, etc. damage renal cells, leading to renal shutdown 
      • Intervention at this phase may reverse renal failure or prevent progression
    • Maintenance Phase 
      • Further damage to renal cells occurs, leading to irreversible loss of renal function 
      • Dialysis may be needed at this point 
    • Recovery Phase 
      • Return of renal function to normal, frequently accompanied by a brisk diuresis and hypertension
  • When renal autoregulation is compromised or its ability is exceeded, renal injury occurs as a result of relative hypoperfusion and hypoxemia. Most notably, this leads to tubular injury, commonly referred to as acute tubular necrosis. Classically oliguric in nature but can also be nonoliguric

Figure 1: The Glomerulus and Nephron


Diagnosis

  • Generally categorized into prerenal, intrinsic renal, and postrenal (obstructive) processes 
    • Fractional excretion of sodiumFENa = (UNa/SNa)/(UCr/SCr) × 100: FeNA <1% in prerenal azotemia when not on diuretics (although if <1% in a patient taking diuretics, would also suggest prerenal azotemia). Only should be used in oliguric patients as otherwise, sodium excretion more dependent on sodium intake
    • Fractional excretion of urea: FeUrea= (SerumCr * UUrea ) / (SerumUrea x UCr): FeUrea <35% suggests prerenal azotemia (can be used with patient on diuretics)
    • Urine sodium generally  <20 mEq/L when prerenal injury
    • Urine osmolarity and urine specific gravity have a linear relationship. Urine that is isoosmotic to serum has a specific gravity of approximately 1.010
    • Serum BUN/Cr ratio >20 generally indicative of prerenal azotemia whereas a ratio <20 is more consistent with ATN
    • Urine protein excretion with urine protein/creatinine ratio (nl is <0.2 for children >3 yrs of age) can suggest glomerulopathies
    • Urine pH: should be <5.3 in the context of a non-gap metabolic acidosis (where you might be concerned for renal tubular acidosis)
  • ICU relevant signs and laboratory derangements 
    • hyperkalemia
    • severe hypertension (both due to hypervolemia and hyperreninemia)
    • volume overload leading to pulmonary edema and potentially congestive heart failure (less common in pediatric population)
    • metabolic acidosis
    • hypocalcemia/hyperphosphatemia
    • Uremia

Treatment

  • NO evidence that dopamine improves renal outcomes ("renal dose dopamine"). While it does increase renal blood flow and GFR via stimulation of dopamine receptors (producing vasodilation), it does not appear to improve outcomes related to renal injury. In addition, there are concerns dopamine may have immunomodulatory effects, inhibit proloactin, and inhibit TRH from the hypothalamus
  • Loop diuretics have been shown to increase renal blood flow, decrease renal vascular resistance, and decrease renal oxygen consumption (via inhibition of the NKCC2 channel, thus requiring less cellular work). Nonetheless, while they may aid in attenuating volume overload, they also have the potential to exacerbate renal injury via intravascular hypovolemia and reduced renal perfusion (See FeNa and FeUrea calculations above)
  • Bumetanide (Bumex) conversion to Lasix: 1 mg Bumetanide: 40 mg Lasix
  • N-acetylcysteine has been studied for the prevention of contrast induced nephropathy (CIN) but meta-analyses have failed to show consistent benefit while demonstrating significant heterogeneity between studies. It seems N-acetylcysteine may falsely lower serum creatinine by impairing its production rather than by promoting renal filtration. 
  • Volume loading prior to contrast or amphotericin has demonstrated some benefit
  • Limit substances typically cleared by the kidneys (ie potassium, phosphorous, protein)
  • Renal replacement therapies remain the mainstay of treatment for renal failure given the relative paucity of effective treatments for renal injury aside from careful supportive therapy
Figure 2: Diuretics and sites of action in the Nephron

References

1) F.B. Plotz, A.B. Bouma, J.A. van Wijk, et al.: Pedatirc acute kidney injury in the ICU: an independent evaluation of pRIFLE criteria. Intersive Care Med. 34 (9):1713-17172008 Sep
2) B.D. Myers, S.M. Moran: Hemodynamically mediated acute kidney failure. N Engl J Med. 314:97 1986 3510383
3) G.J. Schwartz, G.B. Haycock, C.M. Edelmann, et al.: A simple estimate of glomerular filtration rate in childrens derived from body length and plasma creatnine.Pediatrics. 58 (2):259-263 1976