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) Â Low fractional excretion of sodium (< 1%) Â Low fractional excretion of urea (< 35%) Â High urine osmolarity (> 600 mOsm) Â Urinalysis will show high urine SG and low urine pH Â 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
10. Intrarenal Etiologies include:  Vascular  Acute Tubular Necrosis  Acute Glomerulonephritis  Acute Interstitial Nephritis  Tubular 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. Â 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