azotemia

• Azotemia and Urinary Abnormalities


  Nephrologic syndromes that consist of several elements reflecting underlying pathologic processes
• Elements of nephrologic syndromes

  • Reduction in glomerular filtration rate (GFR)
  • Abnormalities of urine sediment
  • Abnormal urinary excretion of serum proteins
  • Disturbances in urine volume
  • Presence of hypertension and/or expanded total body fluid volume
  • Electrolyte abnormalities
  • Fever/pain (in some syndromes)
• GFR


  Primary metric for kidney "function", direct measurement involves administration of a radioactive isotope filtered at the glomerulus into the urinary space and calculated from the rate of appearance of the isotope in the urine over several hours
• In most clinical circumstances, direct GFR measurement is not feasible
• Plasma creatinine (PCr)


  Used as a surrogate to estimate GFR, related directly to urine creatinine (UCr) excretion and inversely to PCr
• In the outpatient setting, PCr serves as an estimate for GFR


  In patients with chronic progressive renal disease, there is an approximately linear relationship between 1/PCr (y axis) and time (x axis), and the slope of that line remains constant for an individual
• Signs and symptoms of uremia, the clinical symptom complex associated with renal failure, develop at significantly different levels of PCr depending on the patient, underlying renal disease, existence of concurrent diseases, and true GFR
• Azotemia


  Retention of nitrogenous waste products such as urea, resulting from reduced renal perfusion, intrinsic renal disease, or postrenal processes
• Precise determination of GFR is problematic as both commonly measured indices (urea clearance and creatinine) have characteristics that affect their accuracy as markers of clearance
• Creatinine clearance (CrCl)


  An approximation of GFR, measured from plasma and urinary creatinine excretion rates for a defined period and expressed in milliliters per minute
• Creatinine is produced from muscle and excreted at a relatively constant rate
• Cockcroft-Gault and four-variable MDRD (Modification of Diet in Renal Disease) formulas


  Used widely to estimate kidney function from PCr when a timed collection for CrCl is not available
• CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) estimated GFR (eGFR)


  A newer formula that appears to be more accurate than Cockcroft-Gault and MDRD
• The gradual loss of muscle from chronic illness, chronic use of glucocorticoids, and malnutrition can mask significant changes in GFR with small or imperceptible changes in PCr
• The use of the "race modifier" in calculating eGFR using CKD-EPI and other equations has come under scrutiny, and many medical centers have recently stopped reporting eGFRs that have been calculated using a race modifier
• The development of alternative methods for estimating GFR, such as using serum cystatin C, has been led by the limitations in creatinine-based eGFR
• Approach to the patient with azotemia

  Once GFR reduction has been established, the physician must decide if it represents acute or chronic renal injury
• Laboratory abnormalities characteristic of chronic renal failure, including anemia, hypocalcemia, and hyperphosphatemia, are often present in patients presenting with acute renal failure
• Radiographic evidence of renal osteodystrophy is seen only in chronic renal failure, typically in patients with end-stage renal disease maintained on dialysis
• Patients with advanced chronic renal insufficiency often have some proteinuria, nonconcentrated urine, and small kidneys on ultrasound, characterized by increased echogenicity and cortical thinning
• Treatment of azotemia


  Directed toward slowing the progression of renal disease and providing symptomatic relief for edema, acidosis, anemia, and hyperphosphatemia
• Causes of acute renal failure

  • Prerenal processes
  • Intrinsic renal diseases
  • Postrenal processes
• Prerenal failure


  Decreased renal perfusion, accounting for 40-80% of cases of acute renal failure, and readily reversible if appropriately treated
• Etiologies of prerenal azotemia

  • Any cause of decreased circulating blood volume
  • Volume sequestration
  • Decreased effective arterial volume
• Mechanisms of maintaining GFR in prerenal failure

  Prostaglandin-mediated dilatation of afferent arterioles and angiotensin II-mediated constriction of efferent arterioles
• Blockade of prostaglandin production by NSAIDs or blocking angiotensin action with ACE inhibitors or ARBs can result in severe vasoconstriction and acute renal failure
• Distinguishing prerenal azotemia from acute tubular necrosis (ATN)

  The urinalysis and urinary electrolyte measurements are useful, with prerenal azotemia characterized by a concentrated urine, avid Na retention, and a normal or hyaline/granular urine sediment
• The fractional excretion of sodium (FENa) is typically >1% in ATN, but may be <1% in patients with milder, nonoliguric ATN or underlying "prerenal" disorders such as congestive heart failure or cirrhosis
• Urinary biomarkers associated with tubular injury are a promising technique to detect subclinical ATN and help further diagnose the exact cause of acute renal failure
• Postrenal azotemia


  Urinary tract obstruction, accounting for <5% of cases of acute renal failure
• Prerenal Failure


  Tubules are intact, leading to concentrated urine and avid Na retention
• FENa


  Typically >1% in ATN, but may be <1% in patients with milder, nonoliguric ATN or underlying "prerenal" disorders like CHF, cirrhosis or hepatorenal syndrome
• Prerenal urine sediment


  Usually normal or has hyaline and granular casts
• Sediment of ATN


  Usually filled with cellular debris, tubular epithelial casts, and dark granular casts
• Urinary biomarkers associated with tubular injury

  Promising technique to detect subclinical ATN and help further diagnose the exact cause of acute renal failure
• Postrenal Azotemia


  Urinary tract obstruction accounts for <5% of cases of acute renal failure, usually reversible and must be ruled out early
• Complete obstructive acute renal failure


  Requires obstruction at the urethra or bladder outlet, or bilateral ureteral obstruction, or unilateral obstruction in a patient with a single functioning kidney
• Obstruction diagnosis


  Presence of ureteral and renal pelvic dilation on renal ultrasound. Early in the course or if ureters unable to dilate, ultrasound may be negative, requiring other imaging like furosemide renogram
• Intrinsic Renal Disease


  When prerenal and postrenal azotemia have been excluded, an intrinsic parenchymal renal disease is present
• Intrinsic renal disease


  Can arise from processes involving large renal vessels, intrarenal microvasculature and glomeruli, or the tubulointerstitium