Hemolytic Uremic Syndrome

Today, we talked about the case of a middle aged woman with recent diagnosis of metastatic breast cancer on palliative Paclitaxel who was admitted with acute onset of bloody diarrhea found to have Shiga toxin and progression to HUS!  She developed neurologic manifestations for which she underwent PLEX and is now recovering in rehab.


Clinical Pearls

  • TTP and HUS present very similarly and are difficult to distinguish clinically.  HUS typically has worse renal failure than TTP and rarely has neurologic manifestations.
  • Because they are tough to tease apart, start PLEX early if TTP is on your differential for HUS because TTP has a high mortality rate.
  • Acute diarrhea requires work up in those with severe illness, inflammatory features, risk factors, persistent symptoms, or work in fields that are of public health related concern (food handlers, daycare workers, etc.)
  • The most common cause of acute bloody diarrhea worldwide is shigella.
  • Bloody diarrhea with a normal fecal leukocyte/lactoferrin count is highly suggestive of E. histolytica.
  • Majority of shiga toxin produced in adults is by E coli.
  • Avoid antibiotics if possible in a patient with bloody diarrhea due to shiga toxin as it can precipitate HUS.

Indications for work up of acute diarrhea:

  • Age >65
  • Immunocompromised
  • Significant volume depletion
  • Blood in stool
  • Fever
  • Severe abdominal pain
  • Recent antibiotics
  • Known or suspected IBD
  • Food handler, daycare worker, healthcare worker
  • Recent travel

DDx for acute bloody diarrhea:

  • IBD
  • Ischemic colitis
  • Invasive infections
    • Shigella (most common)
    • EHEC and EIEC (most commonly associated with shiga toxin)
    • Campylobacter
    • Nontyphoidal salmonella
    • Entamoeba histolytica
    • Schistosoma (more common in resource limited settings)

Work up for acute bloody diarrhea:

  • Enteric pathogen panel (NAAT):
    • Campylobacter, salmonella, shigella species, vibrio, yersinia, shiga toxins, norovirus, and rotavirus
  • Stool culture
    • Grows campylobacter, Shigella, Salmonella, and E coli strains. If suspecting other organism, must specifically request that culture from lab
  • Stool leukocytes or lactoferrin
    • More helpful if negative to rule in amebiasis.

Shiga toxin mediated hemolytic uremic syndrome

  • Characterized by the triad of MAHA, thrombocytopenia, and acute renal failure. Rare neurologic manifestations can occur as in our patient.
    • Other clinical symptoms ⇒ bloody stools, absence of fever, WBC>10k, and abdominal pain.
    • 23-47% require hospitalization
  • 6-9% of people infected with EHEC (O157:H7 and O104:H4) can go on to developing HUS and it is much more common in children.
  • Pathophys
    • Ingestion of undercooked beef and E coli
    • Shiga toxin produced by E coli binds to vascular endothelial cell surface, thereby inhibiting protein synthesis, generating lots of cytokines and chemokines, and causing end organ damage and thrombosis.
  • Clinical course
    • HUS develops 5-10 days after onset of diarrhea
    • Up to 50% of patients require dialysis and 39% have long term renal injury.
    • Mortality is 3-5%
  • Treatment:
    • Supportive care is the mainstay
    • Some data from an outbreak in Germany suggests there may be benefit to plasma exchange (PLEX) via removal of shiga toxin and prothrombotic factors from the body
    • Eculizumab ⇒ beneficial in patients with complement-mediated HUS (not shiga-toxin mediated)

TTP: 

  • Main distinguishing features from HUS
    • Renal failure can often be mild
    • Neurologic impairment is more common
    • Mortality rates are much higher
    • Confirmatory test is ADAMTS13
    • Mainstay of treatment is PLEX!

Moral of this story: start PLEX while you’re waiting to decide if it’s HUS or TTP!

Hydralazine-induced ANCA associated vasculitis!

Thanks to Jen for presenting the case of a middle-aged lady with h/o HTN on hydralazine and PE noted to have progressively worsening glomerulonephritis and a discoid skin rash, with anti-MPO and anti-histone antibody positive serologies concerning for drug-induced ANCA associated vasculitis!


Clinical Pearls

  • Many cases of drug-induced lupus are actually drug-induced ANCA vasculitis!
  • Medications associated with drug induced ANCA-vasculitis include hydralazine (most common and most severe presentation), followed by methimazole/PTU, and minocycline.
  • Drug-induced vasculitis tends to present with anti-histone antibody positivity (sensitive but less specific).  Drug-induced ANCA vasculitis can be anti-MPO positive especially in the case of hydralazine.
  • Treatment involves witholding the offending agent.  In the case of hydralazine induced ANCA-vasculitis, steroids and additional immunosuppressive therapy (cytoxan or rituxan) are also indicated to reduce progression to ESRD.

Eosinophilia

  • Severity:
    • >500 eos ⇒ eosinophilia
    • > 1500 eos ⇒ severe eosinophilia
    • > 5000 eos ⇒ severe eosinophilia at risk of end organ damage
  • Etiology (NAACP-P)
    • Neoplasms
      • Monoclonal leukemias (eosinophil proliferation)
      • Polyclonal: T cell lymphomas, Hodgkin lymphoma, some solid organ tumors (cervical, ovarian, gastric, colon, urotherlial, and squamous cell carcinomas)
    • Allergies
    • Adrenal insufficiency (super rare)
    • CTD
      • EGPA, RA
    • Parasites/bugs
      • Parasites: remember that only multicellular parasites can cause eosiniphilia
      • Other bugs: ABPA, cocci, HIV
    • Primary eosinophilic syndromes

Drug-induced lupus:

  • M:F is 1:1 but hydralazine induced lupus is more common in women
  • Mechanism is poorly understood and genetic predisposition may play a role. More likely to happen in patients who are slow acetylators
  • Autoantibodies:
    • Anti-histone antibodies: 95% sensitive
    • Other antibodies are uncommon
  • Drugs: long list!
    • Procainamide, hydralazine, chlorpromazine, quinidine, minocycline, PTU, statins, anti-TNF agents, IFN, methyldopa
    • Weaker associations: AEDs, antimicrobials, beta blockers, lithium, HCTZ, amiodarone, cipro etc.
  • Treatment:
    • Stop offending agent
    • Joint symptoms: NSAIDs
    • Skin symptoms: topical steroids
    • Hydral-induced vasculitis: need cytotoxic or other immunosuppressive therapy. Treatment similar to ANCA positive vasculitis
  • Prognosis:
    • Resolution of symptoms weeks to months

Drug induced ANCA positive vasculitis:

  • Patients typically present with constitutional symptoms, arthralgias/arthritis, and cutaneous vasculitis
  • Strongest association with hyperthyroidism meds, hydralazine, and minocycline (hydral is the most common)
  • Rare, but should be aware of this association because it impacts management and because it is often not diagnosed until too late in the disease course.  In fact, many cases of drug induced lupus are actually drug induced ANCA-associated vasculitis
  • In a small case series of hydral-induced ANCA-associated vasculitis of 10 patients, 90% had renal involvement of whom 7 recovered at 6 month follow up (though one required HD).
    • Hydralazine-induced ANCA vasculitis is generally p-ANCA pattern with anti-MPO positivity (might also have anti-lactoferrin or anti-elastase)
    • Treatment involves immunosuppression with steroids and cytoxan or rituxan.
  • Non-hydralazine drug-induced ANCA vasculitis is typically treated with stopping the offending agent and has a better prognosis than its hydralazine-induced counterpart. In fact, ANCA positivity without clinical vasculitis is common especially in cases involving PTU.

Severe Metabolic Acidosis Secondary to… Methanol Poisoning 4/3/2019

Credit goes to Eric for informing us about this case!

A 48yo M presents with acute onset encephalopathy. He has a distant history of alcohol abuse, and during the day of presentation he had complained about not being able to see. On presentation, his labs were notable for an anion gap of 35 with bicarb of 4, lactic acid of 11.9,  ABG of 6.56/52/336, and osm gap of 65. Volatile screen ultimately came back positive for methanol level of 145.56 mg/dL (yes this is very high). He was given bicarb pushes, fomepizole, and urgent dialyzed.

It turns out that he might have ingested Klean Strip denatured alcohol, which is 40-60% methanol!


Methanol Toxicity

Pathophysiology

  • Toxic metabolite of methanol poisoning is formic acid, which is formed from formic acid after methanol is metabolized in the liver by alcohol dehydrogenase and aldehyde dehydrogenase
  • Leads to retinal injury and eventual blindness (permanent)
  • Formic acid can also cause ischemic or hemorrhagic injury to the basal ganglia, hence in methanol poisoning you might see changes around the area (putamen is part of the basal ganglia).
  • Ingestion of 1g/kg is fatal, and toxicity has been reported in as little as one teaspoon
  • Ethylene glycol, on the other hand, mainly causes renal damage. (Flank pain, hematuria, oliguria). Buzz words = calcium oxalate crystals in urine.

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Presentation

  • Visual blurring, central scotomata (black spot in center of vision), and blindness are suggestive of methanol poisoning.
  • Eye exam might reveal: mydriasis, retinal edema, hyperemia of the optic disk
  • Co-ingestion of ethanol can delay presentation of toxicity.
  • Labs:
    • Profound AGMA, bicarb often < 8 mEqL
    • High serum lactate
    • Elevated plasma osmo gap
      • Calculated osmolality = 2 x [Na mmol/L] + [glucose mg/dL] / 18 + [BUN mg/dL] / 2.8 + [Ethanol/3.7]
      • OG = Measured osmo – calculated osmo
      • Nrl < 10
    • Typical agents that inc the osmolar gap:
      • Methanol
      • Ethylene Glycol
      • Diuretics (osmotic diuretics i.e. mannitol)
      • Isopropyl alcohol
      • Ethanol
    • Osmo gap takes Into account the quantity of uncharged molecules, hence it will only be elevated in presence of the parent alcohols.
    • In late presentation: most alcohols have been metabolized already into charged active metabolic, hence osmo gap is not very sensitive in late presentation.

Management

  • ABC comes first.
  • Sodium bicarb administration
    • Corrects systemic acidosis, which limits penetration of formic acid by converting it into negatively charged formate, which cannot cross cell membrane to cause damage.
      • Formic Acid <- -> H+  & Formate-, adding bicarb dec H+, hence driving the equilibrium equation to the right. See? College O-chem is still helpful.
    • HCO3 (mEq) required = 0.5 x weight (kg) x [24 – serum HCO3 (mEq/L)], and in general up front give 1-2 mEq/kg via IV bolus for any patients with pH < 7.3 followed by a sodium bicarb D5 gtt, at least 150-250cc/hr to correct acidosis
      • Goal of infusion is to keep pH above 7.35
    • Bicarb can be found in:
      • Most common: 8.4%, 1mEq/mL, 1Amp = 50mEq, you will see these in the crash cart, very helpful to familiarize yourself with setting the syringe up for injection in a code blue situation!
      • Gtt: 100-150 mEq/1000 mL in D5
      • Concentrated gtt: 1mEq/mL, might need pharmacy’s help in formulating this. You can only use this in the ICU!
      • PO tabs: Useful for CKD patients
  • Inhibition of alcohol dehydrogenase in the liver
    • Fomepizole
      • 1st line
      • Loading: 15mg/kg, followed by 10mg/kg Q12hr, continue until blood pH is normalized and serum methanol is less than 20mg/dL
    • Ethanol: ADH has better affinity for ethanol, leading to competitive inhibition.
      • Difficult to dose, sedating effect, cannot be used in cirrhosis patients, pregnant patients.
  • HD indicated if:
    • Severe acid-base derangements, or even high AGMA regardless of drug level
    • Severe levels of methanol
    • End organ damage
    • Interacts with fomepizole, hence if concurrent therapy, fomepizole should be dosed Q4H
  • Co-factor therapy
    • All methanol patients treated with ADH inhibition should also receive:
      • Leucovorin 50mg IV (folinic acid) or folic acid Q6H
      • Thiamine also commonly administered due to unclear nutritional status.
  • GI decontamination: Has no role whatsoever.

Aspirin toxicity

We discussed the case of a middle aged woman admitted with AMS, found to have AGMA and respiratory alkalosis with work up revealing ASA toxicity, managed with HD!


Clinical Pearls

  • In suspected ASA toxicity, check serum levels every 2 hours until two consecutive levels decrease from peak value
  • The goal in treatment of ASA overdose is to keep ASA in its charged and deprotonated state which has less end organ toxicity.
    • Give bicarb with the goal of maintaining urine pH of 7.5-8 and serum pH <7.60.
    • Treat hypokalemia aggressively (see below).
  • Patients with ASA overdose have a high minute ventilation so avoid intubation if possible to allow them to maintain their minute ventilation.
  • Call renal early for HD if indicated ⇒ AMS, cerebral/pulmonary edema, fluid overload, kidney injury, severe acidemia, ASA level >100 mg/dL, or clinical deterioration in spite of aggressive management

Management of ANY patient with suspected toxic ingestion:

  • ABCs (Airway, Breathing, Circulation)
  • Call Poison Control! (1800 222-1222)
  • Can patient get Activated Charcoal? (usually only within 1 hour of ingestion)
  • Check Utox, Salicylate screen, acetaminophen screen, +- alcohol and volatile screen if suspected. You don’t want to miss a potential co-ingestion! 

ASA overdose

  • Remember that ASA can be found in other compounds like topical salicyclic acid, herbal medications, bismuth subsalicyclate (part of Pepto-Bismol), and Oil of Wintergreen so don’t forget about those topical medications!
  • Most sensitive vital sign abnormality in early ASA overdose is tachypnea with hyperventilation. 
  • Classic acid/base abnormality is anion gap metabolic acidosis with respiratory alkalosis (see below)

How does ASA work?

  • Inhibition of cyclooxygenase results in decreased synthesis of prostaglandins, prostacyclin, and thromboxanes. This contributes to platelet dysfunction and gastric mucosal injury
  • Stimulates the chemoreceptor trigger zone to cause Nausea and Vomiting
  • Activates the respiratory center in the medulla leading to hyperventilation and respiratory alkalosis
  • Interferes with cell metabolism (Krebs cycle and decouples oxidative phosphorylation) leading to metabolic acidosis

Metabolism

  • Reaches peak concentration within 1 hour of ingestion. Takes longer with the enteric coated formulations
  • Detox occurs normally by the liver and then metabolites are excreted by the kidney. In OD, liver is overwhelmed so more of the drug becomes dependent on renal excretion (slow and can take up to 30 hours).

Clinical features

  • Tinnitus
  • Vertigo
  • Nausea and vomiting
  • Diarrhea
  • Hyperpnea (tachypnea and hyperventilation)
  • Hyperthermia (due to disturbances with oxidative phosphorylation)
  • Lethargy and confusion

Making the diagnosis

  • Check salicylate level and if elevated, check levels every two hours until two consecutive levels decrease from peak , value is less <40, and patient is asymptomatic.
    • <30 = therapeutic, >40 = toxic, >100 = absolute indication for HD regardless of symptoms
  • Check serum creatinine– ASA is renally excreted so significant renal failure will change management.
  • Check potassium level-need to treat hypokalemia aggressively (see below)

Other labs that can support diagnosis but not required

  • Coagulation studies (large overdose can cause hepatotoxicity and interfere with Vit K metabolism)
  • Lactate (can be elevated due to uncoupling of oxidative phosphorylation)
  • CXR if concern for pulmonary edema (potential complication of ASA overdose)

Treatment ASA overdose

  • Goal: keep salicylate (weak acid) in its charged and deprotonated form to prevent it from crossing into the blood brain barrier by maintaining alkalemia
  • ABCs
  • Fluids
  • Activated Charcoal if <1 hour from ingestion
  • AVOID intubation if possible (remember that these patients have high minute ventilation (RR x TV) due to ASA effect on the medulla and this can be hard to reproduce on the ventilator without causing significant auto-peep)
  • Volume resuscitation (be careful of pulmonary edema/cerebral edema)
  • Alkalinize urine with sodium bicarbonate
    • Sodium Bicarbonate 1-2 meQ/kg IV bolus followed by 100-150 meQ/D5W and titrated to maintain urine pH of 7.5 to 8.0 and continued until salicyclate level <30. It is OK to continue sodium bicarbonate even with alkalemia as long as pH<7.60Alkalinizing the urine keeps ASA in the non-acidic form (Sal-), thus avoiding a lot of the complications of ASA overdose.
  • Treat hypokalemia aggressively to maintain alkalinization. If hypokalemia is not corrected, the body will reabsorb potassium and acidify the urine, which is the opposite of what we want.
  • Consider giving glucose for neuro-glycopenic symptoms (controversial but patient can have neuro-glycopenic symptoms due to low CNS glucose even with a normal serum glucose)
  • Call renal early if patient may need hemodialysis 
    • Indications
      • AMS
      • Cerebral edema/pulmonary edema
      • Fluid overload
      • Acute or chronic kidney injury
      • Severe acidemia
      • ASA level >100 mg/dL
      • Clinical deterioration despite aggressive care

RCA infarct, bradycardia, & hyperkalemia!

Today, we discussed the case of an elderly woman with significant history of vasculopathy and ESRD who presented with weakness, found to be bradycardic to 30s, hypotensive, and hyperkalemic to 7.2.  Her hyperkalemia was treated with dialysis but she underwent cardiac cath due to up trending troponins, found to have a 100% occlusion of the RCA!


Clinical Pearls

  • First step in managing a patient with bradycardia is ABCs!
  • First medication for symptomatic bradycardia is atropine.  Remember that atropine works at the level of the AV node and higher so if the block is occurring somewhere below the AV node, then atropine will not be effective.
  • Other pharmaceutical agents are dopamine, epi, or isoproterenol
  • Anyone with bradycardia and unstable hemodynamics in spite of above treatments should receive transcutaneous pacing.  This buys you time until you can place a transvenous pacemaker (less painful, more effective)
  • ECG has a low sensitivity but high specificity for hyperkalemia-induced cardiomyocyte instability.
  • ECG changes associated with hyperkalemia in progressive severity:
    • Peaked T waves
    • P wave widening, PR prolongation, P wave disappearance
    • QRS widening, AV block, bradycardia
    • Sine wave
    • VF/asystole/PEA

Bradycardia approach

1. ABCs!

  • Pharmaceutical agents
  • Atropine (0.5 mg – 1 mg q3-5 mins for a total of 0.03 mg/kg)
  • If no improvement, consider dopamine or epi
  • If still symptomatic, then start transcutaneous pacing

2. Find underlying cause and treat it 

  • Meds: BB, CCB, amio, digoxin, clonidine, lithium, acetylcholinesterase inhibitors
  • Ischemia (up to 25% of patient with acute MI present with bradycardia)
  • ↑ vagal tone: if young, athlete
  • Metabolic: hypoxia, sepsis, ↓T4, hypothermia, hypoglycemia, hyperkalemia
  • OSA
  • Elevated ICP
  • Infections: legionella, lyme, Q fever, typhoid, malaria, RMSF, yellow fever, leptospirosis, dengue, Chagas disease
  • Infiltrative processes: sarcoid, amyloid, hemochromatosis

In our patient, the cause was severe hyperkalemia as well as an RCA infarct.  Given her clinical instability, and the potential for worsening hyperkalemia from cardiac catheterization alone, the team normalized her serum potassium before performing cardiac cath which led to the RCA MI diagnosis.

Hyperkalemia

  • ECG changes are not sensitive for hyperkalemia and can miss up to 39% of patients even with a K of 7-9.
  • Sweet spot for potassium appears to be a mean K of 3.5 to 4.5 mEq/L. There is not a well-defined treatment threshold.
  • Bottom line for management: if you have the kidneys available, use the kidneys to excrete as much potassium as possible.
  • Newer agents like sodium zirconium and patiromer. Mix with water. Well tolerated and highly effective.

Agents that reduce serum potassium via transient intracellular shift:

  • Insulin: give with D50 if normoglycemic to avoid hypoglycemia and be sure to check FSG hourly for 4 hours after to ensure no hypoglycemia develops
  • Albuterol (10-20 mg) nebs: this is significantly higher than the dose we give in COPD (2.5 mg) and is equal to ~8 treatments! So make sure to continue the nebs when the patient arrives on the floor from the ER if they are still hyperkalemic.
  • NaHCO3: best for management of chronic hyperkalemia in the outpatient setting.  In the acute management of hyperkalemia, alkalinization of serum with a large bicarb load can lead to a reduction in serum calcium levels.  Lower serum calcium can lead to more cardiac membrane instability and fatal arrhythmias!

Agents that eliminate potassium from the body:

  • Loop diuretics: first choice if a functioning kidney is available!
  • Cation exchange binders: preferred when kidneys are not available
    • Patiramer (available at VMC), much more tolerable than kayexalate and highly effective at lowering serum potassium.  Like kayexalate, it works over hours to days.
    • Sodium zirconium: similar to patiramer but not currently available
    • Kayexalate: not pleasant to take orally. Also carries with it the slight risk of colonic ischemia especially in post renal transplant patients and those with baseline colonic dysfunction (due to infection or inflammation).
  • Dialysis

Indication for using calcium gluconate: when EKG changes are noted.  Repeat doses (maximum 3) until EKG changes have resolved.

EKG Changes in Hyperkalemia:

  • K > 5.5 ⇒ repolarization abnormalities:
    • Peaked T waves are the earliest sign
  • K > 6.5 ⇒ progressive paralysis of the atria:
    • P wave widens and flattens
    • PR segment lengthens
    • P wave eventually disappears
  • K > 7.0 ⇒ conduction abnormalities and bradycardia:
    • QRS widens
    • High-grade AV block, slow junctional and ventricular escape rhythms
    • Any kind of conduction block (bundle branch blocks, fascicular blocks)
    • Sinus bradycardia or slow AF
    • Sine waves
  • K > 9.0 ⇒ cardiac arrest:
    • Asystole
    • Ventricular fibrillation
    • PEA with bizarre, wide complex rhythm

ANCA-mediated glomerulonephritis! 03/14/2019

Happy Pi Day!

Thanks to Brayden for presenting a case of a 48yo M with no significant medical or family history presenting with 2-3 months of LE edema, generalized weakness, malaise, myalgias, and arthralgias (general, no particular pattern). He was found to be anemic, and urine studies were notable for nephritic range proteinuria and microscopic hematuria. His complements levels were normal. Ultimately renal biopsy revealed the presence of crescents in the glomeruli, and MPO positivity indicating a P-ANCA related vasculitides. Based on his history, his final diagnosis is RPGN Type 3 secondary to most likely MPA.


Hematuria: First step is to see if there is actually RBC in the urine! 

  • With RBC
    • RBC Casts, proteinuria, AKI
      • Glomerular pathology
    • No casts, no AKI
      • Non-glomerular bleed
        • UTI
        • BPH
        • Renal cysts
        • Sickle Cell
        • Interstitial disease
        • Nephrolithiasis
        • Post exercise
        • Tumors
    • Without RBC
      • Porphyria, Beeturia, Rhabdomyolysis

All About Casts! Presence of certain casts in the urine can provide useful information.

  • Hyaline casts: Nephrotic syndrome, pre-renal azotemia, normal
  • Fatty oval bodies: Nephrotic syndrome
  • RBC casts: GN
  • Granular cast: ATN, interstitial nephritis, note that you can see ATN even without casts!
  • WBC cast: Interstitial nephritis, acute pyelonephritis, acute GN

Glomerulonephritis

  • Presentation
    • Glomerular inflammatory leading to hematuria, variable range proteinuria, HTN, edema, RBC casts or dysmorphic RBC
  • Etiology
    • Immune Complex Deposition GN
      • Typically LOW complement levels
      • Differential
        • SLE GN: ANA, DS-DNA
          • C3 way lower than C4
        • PIGN (post-infectious or strep GN, infection related GN): Streptococcal antibodies i.e. ASO, recent infection
          • Low C3, Low CH50, normal C4
          • Supportive care + antibiotics
          • Typically weeks after an infection but can occur during infection
        • IgA nephropathy: MOST COMMON, recent respiratory or GI infection, kidney biopsy with IgA deposits, normal complements
        • Cryglobulinemic GN: Cryoglobulin, HCV association
          • C4 way lower than C3
        • Membranoproliferative GN (MPGN): Complement activation, immune-staining positivity on biopsy
        • HSP (nrl complements), palpable purpura, abd pain. IgA, IgG, C3 deposition. Closely related to IgA Nephropathy but with systemic/extra-renal involvement.
        • Subacute bacterial endocarditis (Low C3, fever, + cultures)
        • Atheroembolism: + eosinophilia + eosinouria
    • Anti-GBM (Good Pastures) GN
      • NORMAL complement levels
      • Positive anti-GBM
      • Lung and renal involvement, young patients <30 are more likely to have involvement of both and older patients > 50 are more likely to present with isolated GN. Male predominance in younger patients and female predominance in older patients.
    • ANCA related GN aka Pauci-immune GN (PIGN)
      • NORMAL complement levels
      • Absent extra-renal disease: ANCA-associated crescentric GN
      • Systemic necrotizing vasculitis, P-ANCA/MPO: Microscopic polyangiitis (MPA)
      • Respiratory sx, sinusitis, granulomas, C-ANCA/PR3: Granulomatosis with polyangiitis (GPA)
      • Asthma and eosinophilia, P-ANCA/MPO: EGPA
      • Biopsy: None to few immune deposits in the glomeruli in IF and EM. 96% will be positive for ANCA, the other 4% are ANCA-negative pauci-immune GN
        • Focal necrotizing, crescentic glomeruli
    • RPGN: Rapid renal failure with extensive crescent formation that can lead to ESRD within weeks to months. Can present in any age group.
      • Association: Goodpasture, SLE, GPA, idiopathic
      • Complements: Nrl
      • Bx: Crescent formation in > 50-75% of glomeruli
      • IM: Linear IgG
      • Types: 3 types depending on immunofluorescence pattern.
        • Type 1: 20%, anti-GBM
        • Type 2: 25%, immune complex deposition, SLE, GSP, IgA nephropathy, acute proliferative GN
        • Type 3: Aka Pauci-immune GN, 55%, glomeruli damaged in unclear mechanism. Can be idiopathic or related to ANCA associated vasculitis like GPA, MPA, EPGA. Most common.
  • Diagnosis
    • Kidney biopsy for definitive diagnosis but it can be deferred if a diagnosis can be determined via serologies or if pts have fibrotic kidneys, which makes the risks for that diagnostic piece of information outweigh the benefits.
  • Management of GN:
    •  Treat underlying cause if any.
    • Immunosuppression: Usually high dose steroids + cyclophosphamide, rituximab may also be used. Plasmapheresis is also an option.
    • Initial therapy: Methyprednisolone 500-1000mg daily for 3 days
    • No different between use of rituxuimab vs cyclophosphamide (RAVE, RITUXVAS)
    • Cyclophosphamide: Available in PO formulation in a daily dosing, favored by some Nephrologist.
    • Prognosis
      • If left untreated, RPGN progresses to ESRD over weeks to months. Fewer crescents (<50%) is associated with slower progression.

Summary (souce: Grepmed)

GN

Cardiorenal Syndrome 3/5/2019

Thanks Elan for presenting a case of a 63yo M with HIV HFrEF (25%), EtOH cirrhosis (CP Class A, MELD 8), HTN, HLD, and ongoing alcohol use with dietary nonadherence presenting with shortness of breath and anasarca. His JVD was elevated on presentation, and CT PE/AP in the ED revealed dilated IVC and e/o pulmonary edema.

He underwent diuresis and initially improved, but 48 hours into his hospitalization, he developed oliguric AKI, hepatic encephalopathy, and relative hypotension.

Urine studies were consistent with activation of RAAS and ADH (kidneys seeing low perfusion, and echo was concerning for biventricular failure with EF < 20%. A trial of Lasix managed to produce a UOP of 800cc in 24 hours, so a decision was made to transfer pt to the Stepdown for dobutamine assisted diuresis for suspected Cardiorenal Syndrome. Pt ultimately diuresed 18L of fluid (his weight also went down 10+kg, that’s around 22lbs!) and his renal function quickly returned to baseline after aggressive diuresis.


Cardiorenal Syndrome

The diagnosis dilemma for this case was the etiology of pt’s AKI. He was exposed to contrast, hence 48 hours later contract-induced nephropathy can be expected. He also has liver cirrhosis with acute decompensation, hence hepatorenal syndrome (HRS) is something that we cannot miss. Given his poor cardiac function, cardiorenal syndrome (CRS) is also high on the differential!

Keep in mind that there are 5 types of Cardiorenal Syndrome:

  • Type 1: Acute heart failure -> AKI, decreased renal arterial flow due to acutely decompensated HF
  • Type 2: Chronic HF leading to chronic renal hypoperfusion leading to CKD
  • Type 3: AKI leading to adverse cardiac events
  • Type 4: CKD leading to adverse cardiac events
  • Type 5: Multifactorial, systemic insult leads to both cardiac and renal failure

Regardless, the general principle is to restore renal perfusion. Given his biventricular failure, volume status, and initial presentation, Cardiorenal is suspected as more likely, hence pt received inotropic support (improves forward flow) and diuresis (Get pt back on the right side of the Frank Starling curve, also improves forward flow). Overall management of CRS is not much different compared to acute decompensated heart failure.

There is some evidence that more aggressive diuresis is associated with better outcomes (ESCAPE trial).