4. Counterregulatory Responses to Decrease in Effective Circulating Blood Volume Increased Sympathetic Tone Increase in renin-angiotensin system characterized by a increase in angiotensin II and aldosterone Increase in ADH
5. Net Effects: Increased efferent arteriolar tone due to AII to maintain SNGFR Decreased afferent arteriolar tone due to increased nitric oxide and prostaglandin synthesis stimulated by AII to maintain SNGFR Increased tubular sodium reabsorption proximally due to AII and distally due to aldosterone Increase in water reabsorption and urinary concentration due to ADH Increase in urea reabsorption due to increased sodium and water reabsorption
6. Urinary indices will therefore display low urinary sodium (<20 Meq/l) Low fractional excretion of sodium (< 1%) Low fractional excretion of urea (< 35%) High urine osmolarity (> 600 mOsm) Urinalysis will show high urine SG and low urine pH BUN/Cr ratio will be > 20:1
7. Renal autoregulation will help maintain GFR and creatinine clearance Pre-renal azotemia simply means diminished renal blood flow and is reversible Low cardiac output due to low preload due to volume depletion, third-spacing or pulmonary hypertension (e.g. acute PE) Low cardiac output due to pump failure, valvular heart disease or tamponade Systemic vasodilation with shunting of blood away from renal vasculature such as in septic shock or liver failure Defects in autoregulation or medications that interfere with autoregulation
8. Treatments include: Restoring intravascular volume Stopping certain medications such as NSAIDs, ARBs or ACE Is Allowing BP to drift up with defective autoregulation Inotropic support with pump failure Norepinephrine, volume and perhaps vasopressin with vasodilatory shock
9. Post-renal Azotemia Due to obstruction to urinary outflow Diagnosed usually by ultrasound Urinalysis is bland Hyperkalemic metabolic acidosis common Treatment is to relieve the obstruction
11. Acute Tubular Necrosis Most common inpatient etiology Can be ischemic or due to nephrotoxins Urinalysis shows isosthenuric urine with granular casts, usually seen with ischemic oliguric ATN Urinary sodium >40 mEq/l, fractional excretion of sodium > 3% and fractional excretion of urea >35% with oliguria Urine osmolarity < 400 mOsm BUN/Cr ratio < 10:1
12. Nephrotoxic ATN can be due to endogenous toxins such as hemoglobin and myoglobin, or exogenous toxins such as aminoglycosides or dye Hemoglobin or myoglobin gives a positive dipstick for blood in the absence of RBCs Rhabdomyalysis can give rise in serum creatinine > 2 mg/dl/day Treatment of ischemic ATN is to restore renal perfusion Treatment of nephrotoxic ATN is usually fluids and to stop offending nephrotoxins
13. Vascular etiologies: Acute injury to renal vessels Characterized by elevations in BP, nonspecific urinalysis but often proteinuria and hematuria Urinary indices can look like pre-renal azotemia Examples include malignant hypertension, TTP and HUS which are all characterized by schistocytes Atheroemboli for which eosinophilia and eosinophiluria common Renal infarction-elevated LDH, ALT
14. Acute Glomerulonephritis Usually develops in outpatient setting Urinalysis is key to diagnosis and show proteinuria, hematuria and RBC casts Can see low urine sodium and isosthenuric urine Relatively rare cause compared to others Biopsy required for definitive diagnosis Treatment usually entails immunosuppression
15. Acute Interstitial Nephritis Usually allergic in origin from medications such as antibiotics Can see rash, fever, eosinophilia Urinalysis shows hematuria, pyuria, WBC casts and eosinophils NSAIDs do not give eosinophilia, eosinophiluria or rash but does give proteinuria due to MCD Treatment is to remove offending drug and perhaps steroids
16. Tubular obstruction Can be due to endogenous proteins such as Bence-Jones proteins (SSA positive) Can be due to endogenous crystals such as uric acid (acid urine, pleomorphic crystals and urine uric acid to creatinine ratio > 1) Exogenous crystals due to medications such as acyclovir, sulfa drugs and indinivir Treatment is intravenous fluids, forced diuresis and urinary alkalinization with uric acid
17. Trial of intravenous fluids often helpful General Diagnostic Approach Careful assessment of volume status Careful look at medications Careful look at recent radiologic studies Urinalysis Urinary Indices especially if oliguric Differential for eosinophilia and smear for schistocytes CPK, LDH and uric acid levels Renal ultrasound
18. If renal ultrasound does not show obstruction, azotemic medication avoidance and trial of intravenous fluids does not improve BUN and creatinine, then most likely etiology is intrarenal Renal biopsy usually indicated for suspicion of acute GN, unclear diagnosis, if immunosuppression being considered or if certain medication that cannot be withdrawn potentially implicated
19. Overview of Treatment Avoid nephrotoxins and renal dose medications that are renally excreted Low protein, low sodium and low potassium diet Phosphate binders Daily assessment of volume status and symptoms Daily weight, I/Os and screen 8
20. Indications for Dialysis Uremic symptoms Uremic Signs Congestive heart failure unresponsive to diuretics Severe hyperkalemia especially if associated with EKG changes Intractable acidosis
