Acute Renal Failure

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Acute Renal Failure

• Anthony R Mato, MD

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Basic Facts

• Renal failure over the course of hours to days.
• The result will be failure to excrete nitrogenous
  waste and electrolyte imbalance.
• Hard to define in 26 studies, no two used the
  same definition!!!

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Classic laboratory definition

• Cr increase of .5 mg / dl.
• Increase in more than 50 over baseline Cr.
• Decreased in calculated Cr Clearance by more than
  50.
• Any decrease in renal function that requires
  dialysis.

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Basic Differential Diagnosis

• Pre-Renal Decreased renal perfusion without
  cellular injury.
• 70 of community acquired cases.
• 40 of hospital acquired cases.
• 1 cause of Intra-Renal failure.

• Intra-Renal
• ATN Ischemic, toxic insult to the renal tubule.
  Tubular
• AIN Inflammation and edema.
• GNInjury to the filtering mechanism.
• Post-Renal obstruction the urinary outflow
  tract.  

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Prerenal Failure

• Often rapidly reversible if we can identify this
  early.
• The elderly at high risk because of their
  predisposition to hypovolemia and renal
  atherosclerotic disease.
• This is by definition rapidly reversible upon the
  restoration of renal blood flow and glomerular
  perfusion pressure.
• THE KIDNEYS ARE NORMAL.
• This will accompany any disease that involves
  hypovolemia, low cardiac output, systemic
  dilation, or selective intrarenal
  vasoconstriction.

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Differential Diagnosis

• Hypovolemia
• GI loss Nausea, vomiting, diarrhea
• Renal loss diuresis, hypo adrenalism, osmotic
  diuresis (DM)
• Sequestration pancreatitis, peritonitis,trauma,
  low albumin.
• Hemorrhage, burns, dehydration.

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Differential Diagnosis

• Renal vasoconstriction hyper Ca, norepi, epi,
  cyclosporine, tacrolimus, ampho B.
• Systemic vasodilation sepsis, medications,
  anesthesia, anaphylaxis.
• Cirrhosis with ascites
• Hepato-renal syndrome
• Impairment of autoregulation NSAIDs, ACE, ARBs.
• Hyperviscosity syndromes MM, WM, PCV

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Differential Diagnosis

• Low CO
• Myocardial diseases
• Valvular heart disease
• Pericardial disease
• Tamponande
• Pulmonart HTNPE
• Pos pressure mechanical ventillation

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• Reduced arterial stretch and activated
  baro-receptors ?
• Neuro-humoral responses activated to maintain
  blood volume and pressure ?
• Sympathetic nervous system
• AT II system
• AVP system
• They will act together to maintain flow to the
  heart and the brain at the expense of other
  non-essential vascular beds.
• Renal afferent vaso-dilation is triggered via
  PGE2 (afferent), Local myogenic reflex,
  ATII(efferent)
• We have maximum dilation at SBP of 80 mm Hg.

PHYSIOLOGY OF HYPOVOLEMIA
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Intrinsic Renal Disease

• Anatomic organization seems to work best. ARF
  DOES NOT EQUAL ATN.
• 30 of cases of intrinsic renal failure will not
  show any evidence of ATN on UA.
• Glomerulus
• Vessels
• Interstitum
• Tubules

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THE DIFFERENTIAL DIAGNOSIS
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Differential Diagnosis
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Tubules ATN

• Ischemic Injuries to the renal tubule
• Takes 1-2 weeks to recover from after perfusion
  has been normalized.
• In the extreme form this can lead to bilateral
  renal cortical necrosis
• Three phases
• Initiation phase
• Tubuloglomerular feedback afferent arteriole
  constriction triggered by an increase in the salt
  delivery sensed by the macula densa.
• Recovery phase tubular epithelial cell repair
  and regeneration. This may be associated with a
  marked diuretic phase.

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ATN Ischemic

• Hypovolemia
• Low cardiac output
• Renal vasoconstriction
• Systemic dilation
• Hemorrhage

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ATN Toxic

• Exogenous
• Radiocontrast
• CSP
• TAC
• Amino glycosides
• Chemotherapy
• Ethylene glycol
• Tylenol

• Endogenous
• Myoglobin
• Hemoglobin
• Uric acid
• Oxylate
• Light chains

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ATN Toxic facts

• ATN Exacerbated in the elderly, CRI,
  hypovolemia, and exposure to multiple toxins.
• Intrarenal vaso-constriction radiocontrast,
  cyclosporin, tacrolimus. Initially they will look
  prerenal.
• Contrast toxicity is worst in patients with
  CRI, DM, MM, CHF, hypovolemia. This is dose
  related.
• Direct toxicity to epithelial cells frequent
  offenders are acyclovir, foscarnet,
  aminoglycosides (30 of patients with therapeutic
  levels will have ARF), Ampho B (causes
  vasoconstriction as well as direct toxicity).
• Cisplatin (mitochondrial injury).
• Myoglobin and hemoglobin will both increase
  epithelial cell oxidative stress. They also
  inhibit NO ? vasoconstriciton.
• Light chains can form intratubular casts and
  are directly toxic. UA crystal deposition.

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Allergic AIN
Allergic reaction in the tubules. IT IS PARAMOUNT
TO IDENTIFY THE OFFENDING AGENT AND REMOVE IT.
There may be some role for steroids in the case
of AIN.
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AIN Allergic

• Beta lactams / Cephalosporins
• Sulfinamides
• TMP
• NSAIDs
• Diuretics
• Captopril
• Autoimmune diseases
• Infiltrative diseases
• Infections Legionella / Hanta virus

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Others

• Infection Pyelonephritis, CMV, Candida
• Infiltration lymphoma, leukemia, sarcoid
• Intratubular deposition and obstruction

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Post Renal Causes
If we can identify this early, this can be
readily reversible. This accounts for fewer than
5 of cases of ARF.
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Differential Diagnosis

• BPH 1
• Prostatitis
• Prostate / Cervical cancer
• Retroperitoneal fibrosis / disorders
• Extraluminal malignancy
• Neurogenic bladder / anticholinergic drug use
  functional obstruction
• Bilateral renal calculi
• Myeloma light chains

• Papillary necrosis
• Urethritis with spasm
• Inadvertent surgical ligature
• Intraluminal Thrombosis
• Intraluminal (collecting system) crystal disease
• Uric acid
• Calcium oxylate
• Acyclovir
• Sulfonamide
• MTX

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Rickys Story

• 50 year old man presents to the ED with a 1
  day history of RUQ pain, N/V. He also reports
  fever and chills and decreased urine output. PMH
  is a sore throat a week ago, tx w/ an antibiotic.
  He is on ibuprofen only. T 102, HR 123, BP
  80/60. In general, he is an ill-appearing. Abd
  tenderness RUQ no peritoneal signs remainder
  of exam is WNL.

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Rickys Story

• Labs
• WBC 20 w/
• 16 bands
• Hgb 14
• Plts 300
• Na 140
• K 4.1
• Cl 111
• HCO3 22
• BUN 35
• Cr 1.6 (baseline is 0.7) 

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H and P Prerenal

• Thirst, orthostatic dizziness, hypovolemia on
  exam, tachycarida, decreased JVP, poor skin
  turgor, dry mucous membranes, reduced axillary
  sweating.
• Start of new medications NSAIDs, ACE, ARBs.
  Stigmata of chronic liver disease. Advanced CHF.
  Signs of sepsis.

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H and P Intrinsic Renal

• Recent history or hypovolemia / septic shock.
  Careful review of clinical data, pharmacy,
  nursing, and radiology records for evidence of
  toxin exposure. History of myeloma. Recent
  rhabdo.
• Flank pain (worry for arterial occlusion) SC
  nodules, livedo reticularia, hollenhorst plaques,
  digital ischemia with palpable pulses. Fevers,
  arthralgias, pruritis erythemetous rash AIN.

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H and P Post renal

• Presence of suprapubic and flank pain. Pain
  radiating to the groin. History of nocturia,
  frequency, hesitancy.
• History of anticholinergic medication use.  

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What is your differential?
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What additional workup do you want to diagnose
the etiology of his ARF / abdominal pain?
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Urinalysis

• Dip pH, SG, glucose, protein, nitrite, leuk
  esterase, bili, heme.
• Micro RBCs, WBCs, casts, crystals, bacteria.
• Normal 0-2 RBCs, 0-4 WBC, occasional hyaline
  cast.

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Urinalysis Prerenal / Post-renal

• Sediment is acellular and may contain hyaline
  casts
• This is protein that is normally part of the
  urine (Tamm-Horsfall Protein).
• Post renal Sediment is classically acellular
  and bland.
• May also see pyuria and hematuria. No casts.

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Renal ATN

• Muddy brown casts
• (contain tubular-epithelial cells).
• They are usually associated with microscopic
  hematuria and mild tubular proteinuria (lt 1 g /
  d) from impaired re-absorption.
• CASTS ARE ABSENT IN 30 OF THE CASES OF ATN.

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Renal GN

• Red blood cell casts are the classic finding.
• Dysmorphic RBCs.
• These indicate glomerular injury.
• These are rarely seen in acute ATN.
• May also see proteinuria gt 1 g / day.

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Renal AIN

• White cell / granular casts.
• KEEP IN MIND THAT BROAD GRANULAR CASTS REFELCT
  CHRONIC RENAL DISEASE (fibrosis).
• Eosinophiluria (gt 5) is a classic finding
  (Hansels Stain) especially in antibiotic
  associated AIN.

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Common UA Patterns

• Rhabdo dip is pos for heme, neg for RBCs
• MM dip is neg for protein, for light chains on
  UPEP
• EG look for calcium oxylate crystals, elevated
  AG, elevated osm gap.
• TLS uric acid crystals (can also be a normal
  variant of concentrated urine)

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URINE BLING
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Results

• Tbili 2.0
• Alk 269
• ALT 44
• AST 44
• UA SG 1.02, trace ketones
• Micro No cells, No casts, No crystals
• Urine Na 10
• Urine Cr 80

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Renal Failure Indices

• Fractional excretion of Na this will relate the
  clearance of Na to that of Cr.
• In the case of prerenal disease Na is actively
  reabsorbed to restore intravascular volume.
• This is not the case in renal injury (absorptive
  mechanisms are broken). In either case Cr is NOT
  reabsorbed. So we have the makings of a
  comparative ratio. The cut off is 1.
• U Na / P Na
• __________ x 100 .14 (Prerenal)
• U Cr / P Cr

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Keep in mind

• Keep in mind that when pre renal patients are
  receiving diuretics or have bicarbonaturia all
  bets are off.
• Also salt wasting states such as CRI and adrenal
  insufficiency will also alter results.
• In 15 if patients with ATN FeNa can be lt 1
  reflecting patchy injury with partially preserved
  function.
• In GN, acute urinary post renal obstruction, and
  vascular diseases the FeNa will often be lt 1.
• Urine sodium, specific gravity, urine osm, BUN
  Cr ratio are less sensitive and of limited value
  in differentiating this differential.

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Additional Labs

• Peak Cr
• In prerenal disease may fluctuate with
  hemodynamics. Rise will be rapid. This is true
  for contrast (5 days to peak and 7 to normal)
• Atheroembolization (later peak and return to
  baseline), and ischemia (later peak and return to
  baseline).
• Rise will be delayed in toxin exposure.
• Rhabdo elevated K, Phos, hypocalcemia with
  elevations in CK and UA.
• TLS elevated UA, K, Phos, low Ca, elevated Cr
  and elevated LDH (intracellular enzyme).
• Elevated anion gap elevated osm gap suggests
  ethylene glycol / methanol exposure.
• Anemia may suggest hemolysis, MM, or TTP.
• Eosinophillia may suggest AIN, atheroembolic
  disease, PAN.

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Back to Ricky

• An abdominal CT with contrast shows acute
  cholecystitis. He is given an intravenous dose of
  ampicillin and gentamycin, along with normal
  saline.
• The next morning you note LE edema and bibasilar
  crackles. His blood pressure has improved to
  110/70 and fever has resolved. His overnight
  urine output was 150cc.
• Na 137, K 6.7, Cl 100, H2CO3 15, BUN 37, Cr 2.7

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Why is he hyperkalemic?What is the
management?Does need dialysis?
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Hyperkalemia

• Plasma Potassium gt 5.0
• Pseudohyperkalemia
• Prolonged tourniquet use
• Hemolysis
• Leukostasis / Thrombocytosis

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Physiology

• A large meal has enough potassium to kill us. How
  will the body handle this load initially.
• Buffering system will stimulate liver / muscle
  N-K ATPase
• Insulin
• Epinephrine
• Aldosterone

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The Kidney to the Rescue

• Kidney handles it in a unique way.
• It virtually reabsorbs 100 of the K in the
  proximal tubule (70) and the loop of henle
  (30).
• Solvent Drag
• Single Effect / Paracellular pathway
• We reabsorb almost all of the K before we reach
  the distal segments.

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The Principal Cell

• BL membrane we have a Na/ K ATPase
• On the apical side we have amilloride Na channels
  and other channels that allow the movement for K.
  
• Tight junctions - the potential across the apical
  membrane is 30. The BM is at - 70mv.
• The common denominator intracellular K will
  raise electrochemical gradient for K inside of
  the cell will cause an increase in K secretion
  into the urine.

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The Key Players

• 1. K concentration
• 2. Aldosterone
• 3. Flow
• 4. Distal Na
• 5. ADH
• 6. Acid base status of the blood

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Differential Diagnosis

• Increased intake rare except in iatrogenesis
• Cellular release
• TLS, Rhabdomyolysis, exercise, trauma
• Metabolic acidosis
• Insulin deficiency
• Hyperkalemic periodic paralysis
• Digoxin toxicity, beta blockers
• Adrenal insufficiency
• Succinylcholine

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Differential Diagnosis

• Impaired excretion
• Renal failure
• Primary hypoaldosteronism
• Secondary hypoakdosteronism
• ACE, NSAIDs, Heparin, Type 4 RTA
• Aldo resistance
• K sparing diuretics, bactrim, pentamidine, sickle
  cell disease, multiple myeloma.
• Gordons syndrome (enhanced Cl reabsorption, less
  K secretion, HTN)
• Ureter Diversion to Jejunum.

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Symptoms / Signs

• Flaccid paralysis
• Arrhythmia
• Peaked T waves
• PR / QRS prolongation
• AV conduction delay
• Loss of P waves
• Sine wave
• V fib

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Treatment Keep the Physiology in mind.

• EKG changes necessitate treatment
• Calcium gluconate stabilized myocardium
• Insulin / Glucose intracellular shift
• Bicarbonate intracellular shift
• Beta 2 agonists intracellular shift
• Diuretics IV Lasix
• Kayexylate exchanges K for Na
• Dialysis

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Dialysis Needs

• A acidosis
• E electrolytes
• I intoxication (methanol, ethylene glycol,
  isopropanol, theophylline, lithium, salicylates)
• O volume overload
• U uremia (pericarditis, seizures,
  encephalopathy)

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Why did his renal failure worsen?
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Additional Labs

• U OSM 300
• Muddy brown casts
• U Na 80
• U Cr 40

Calculate FeNa? What is highest on your
differential? How does this alter your treatment
plan?
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Treatment

• Prevention is the key.
• Appropriate volume resuscitation.
• Renal dosing of potentially toxic meds
• To estimate GFR Cockcroft-Gault Formula takes
  weight and age into account. (ONLY IN STABLE
  CREATININE) MULTIPLY BY .85 IN WOMEN.
• When appropriate follow serum drug levels for
  dosage adjustment.
• Use of NSAIDS, ACR, ARBs, diuretics should be
  used sparingly in patients who are hypovolemic or
  have renovascular disease.
• Allopurinol / IVFs use in patients high risk for
  TLS.
• Ethanol for EG toxicity / NAC for tylenol
  toxicity.
• Alkalinization of urine to prevent MTX
  toxicity.

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Prerenal disease

• IVFs keep in mind where the loss is coming from
  and administer fluids accordingly.
• Inotropes, preload / after-load reduction,
  anti-arrythmics, mechanical aids in CHF.
• Large volume paracentesis to decrease
  intra-abdominal pressure and increase venous
  return from the kidneys.

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Post Renal Treatment

• Foley catheter
• Nephrostomy tube
• Stenting
• 5 will develop a salt wasting diuresis.

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Intrinsic Renal Disease

• Intrinsic renal disease NO SPECFIC REVERSING
  THERAPIES FOR ISCHEMIC AND NEPHROTOXIC DISEASE.
  SUPPORTIVE CARE.
• Follow electrolytes. Avoid further insult.
• GN may respond to steroids, alkylating agents,
  plasmapheresis.
• AIN glucocorticoids may be of use.
• Malignant HTN control of blood pressure.
• Scleroderma HTN and ARF may responsive to ACE.

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Case 2 Fred

• 85 year old man with a PMHx significant for
  osteoarthritis is admitted to the hospital for
  confusion. Physical exam reveals a thin,
  disoriented man T 98, HR 80, BP 120/80, wt
  75 kg, and a suprapubic mass. He takes no
  medication except for naproxen.
• Labs Na 131, K 4.8, Cl 98, HCO3 15
• BUN 65, Cr 7.3 (baseline on computer 1.3)

What is the FeNa? What is the baseline Cr
clearance?
Cockcroft-Gault (140-age) x wt/(Cr x 72)
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What is your differential?
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The Intervention

• The next morning the creatinine is 2.5 and his
  mental status has cleared.

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Geraldine

• 45 yr old female with a PMH for HTN presents
  with HEADACHE, low back pain, and left should
  pain. You decide to order labs and discover
  discover a Cr 2.0 (baseline 1.0), Calcium 10.0,
  and mild pan-cytopenia (Hb 10.0, Pts 144). FeNa
  is 2.0. UA dip is bland (no protein, no leuks,
  no nitrites)

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What additional tests would you like?
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Multiple Myeloma

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Multiple Myeloma

• The minimal criteria for the diagnosis of
  multiple myeloma include a bone marrow usually
  containing more than 10 percent plasma cells (or
  presence of a plasmacytoma) plus at least one of
  the following
• A monoclonal protein (M-protein) in the serum
  (usually gt3 g/dL)
• An M-protein in the urine
• Lytic bone lesions.
• Additionally, at least some of the following
  Anemia, hypercalcemia, azotemia, hypoalbuminemia,
  bone demineralization (THE MINOR CRITERIA)

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Sams Case
30 year old man with diabetes, hypertension and
chronic renal insufficiency (baseline creatinine
of 2.5) presents to VA clinic for routine
follow-up. His medications are captopril, HCTZ
and insulin. Physical exam is unremarkable. Na
138, K5.8, Cl110, HCO320, BUN30,
Cr2.4,Glu129  
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What is your differential for elevated Potassium?
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What is your plan management plan?
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Acid / Base Basics

• The normal renal response to acidemia is to
  reabsorb all of the filtered bicarbonate and to
  increase hydrogen excretion primarily by
  enhancing the excretion of ammonium ions in the
  urine. Each hydrogen that is secreted results in
  the regeneration of a bicarbonate ion in the
  plasma.

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Proximal Tubule

• Reabsorption of filtered bicarbonate
  predominantly occurs in the proximal tubules
  primarily by Na-H exchange.
• Approximately 85 to 90 percent of the filtered
  load is reabsorbed proximally.
• By comparison, 10 percent is reabsorbed in the
  distal nephron primarily via hydrogen secretion
  by a proton pump (H-ATPase).
• Under normal conditions, virtually no bicarbonate
  is present in the final urine.

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Distal Tubule

• We need to deal with acid load from protein
  catabolism.
• There must be sufficient buffering compounds
  available to bind hydrogen ions.
• The principal buffers in the urine are ammonia
  (excreted and measured as ammonium) and phosphate
  (referred to and measured as titratable acidity).
  
• Failure to excrete sufficient ammonium ? net
  retention of H and metabolic acidosis.
• Impaired hydrogen ion secretion is the primary
  defect in distal RTA while impaired
  ammoniagenesis is the primary defect in type 4
  RTA and renal failure.

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Renal Tubular Acidosis

• Renal tubular acidosis (RTA) is a disorder of
  renal acidification out of proportion to the
  reduction in GFR.
• RTA is characterized by hyperchloremic metabolic
  acidosis with a normal serum anion gap Na
  (Cl HCO3).
• There are multiple forms of RTA, depending on
  which aspects of renal acid handling have been
  affected.

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Type I (DISTAL)

• Distal nephron does not lower urine pH normally
• The collecting ducts permit back-diffusion of H
  from lumen to blood with inadequate transport of
  H.
• Causes a reduction in ammonium excretion.
• Urinary and K conservation can be impaired.
• Chronic acidosis lowers tubule reabsorption of
  calcium ? hypercalciuria and mild 2nd
  hyperparathyroidism.
• Hypercalciuria, alkaline urine, and urine citrate
  cause calcium phosphate stones.
• Growth retardation is common and improves with
  correction of the acidosis by alkali.
• Since the kidney does not conserve potassium or
  concentrate the urine normally, polyuria and
  hypokalemia occur. Sometimes fatal.

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Diagnosis and Treatment

• Normal AG acidosis
• Urine pH gt 5.5
• Nephrocalcinosis
• Oral ammonium load will worsen acidosis.
• Urine anion gap is positive (vs. GI)
• Na K Cl

• Treat with bicarbonate.

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Type II RTA (Proximal)

• Bicarb resorption in prox tubule is impaired.
• Distal tubule resorption is overwhelmed at first.
• Equilibrium is established at bicarb of 16.
• Urine pH is normal / high.
• Ammonium challenge does not affect urine
  acidification.
• Expect bicarbonaturia. FE Bicarb.
• Bicarbonate must be given in LARGE doses. Alkali
  therapy can worsen hypokalemia.

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Type IV RTA

• Distal secretion of K and H is abnormal
  producing a non AG acidosis with hyperchloremia.
• Hypo aldosteronism DM, ACE, NSAIDs, TMP, adrenal
  disease (high Renin level).
• Tubular inflammation (low Renin state) with
  interstitial inflammation (SSD), K sparing
  diuretics (aldactone, amilloride).
• HYPERKALEMIA IS THE PRIMARY PROBLEM. K MAY INHIB
  IT AMMONIA EXCRETION.
• Do not have bicarbonaturia (vs. Type II).
• Urine is APPROPRIATELY acidic (pH lt 5.5)

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Treatment

• Lower potassium
• Remove drugs that lower aldosterone production.
• High dose mineralocorticoids (beware of CHF).
• Liberal Na intake.
• Exchange resins.

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