29 Sep 2020

9/16/20: Fanconi Syndrome 2/2 Tenofovir

PGY2 Michael Dittmar presented a case of a 80 y/o Chinese female with history of CKD Stage 4, HBV and HTN presents with progressive SOB x10 days.  The SOB is associated with chest pain, which radiates from her epigastrum to her neck.  She describes the SOB and chest pain as constant but unable to describe the quality of the chest pain.  The pain is non-exertional.  She is still able to ambulate without difficulty with the help of her walker.  No orthopnea or PND.  She uses 1 pillow to sleep at night.  Reports nonproductive cough for the past 10 days that is associated with dry mouth and rhinorrhea.  No reported fevers, chills, nausea/vomiting/diarrhea, abdominal pain or dysuria.  Home medications include Tenofovir 300mg qday and Amlodipine 5mg qday.  She lives in an apartment complex for the elderly and denies any tobacco/ethanol/drug use.

Vitals: T 37, HR 140, RR 26, BP 115/94, O2 sat 100% RA

Physical Exam significant for irregular irregular rhythm, tachypenic with accessory muscle use and trace bilateral wheezing.  No JVD or b/l LE edema noted.

CBC: WBC 15.3> Hb 12.9/Hct 37.7 <Plt 383(MCV 97.6, RDW 15.7%)

Diff: 89.9% PMN, 2.7% lymph, 7% monocytes, 0% eosinophils, and 0.4% basophils

CMP:

Na 141/K 2.3/Cl 114/HCO3 <5/BUN 69/Cr 6 <Glucose 180 (AG: 22, delta delta 0.5)

ALP 135>T.protein 7.3/Albumin 4.8/AST 56/ALT 38/Tbili 0.4/Dbili 0.2

TSH 0.82

Coags:PT 15.2, INR 1.22

Cardiac workup:

  • Trop 0.14 > 0.12
  • BNP 24928 pg/mL (normal <125)
  • EKG: wide complex tachycardia, RBBB and LPFB, atrial fibrillation

CXR with no evidence of acute pathology.

Infectious workup:

  • BCx negative x2
  • Procal 0.45 ng/mL
  • Lactate 1.2
  • Acute hepatitis panel
    • Hep A IgM non-reactive
    • Hep B core Ab Reactive
    • Hep B core IgM nonreactive
    • Hep B surface Ag Positive
    • Hep C Ab: non-reactive
  • HIV non-reactive
  • RPR non-reactive

Renal workup:

  • UA with 100 protein, 500 glucose, trace ketones, moderate blood (RBC 0-2) and neg leuk/nitrite
  • pH: 7.17/19/40/7
  • PTH 454 (normal 15-65)
  • Urine Lytes
    • UNa: 51
    • UUrea: 105
    • UCr: 15
    • UGluocse: 1026
    • UPotassium: 11
    • UProtein/Cr: 5.2
    • Uosm: 274
  • Serum Osm: 308
  • APAP negative, ASA negative
  • Utox negative
  • ETOH negative
  • ANA negative
  • ANCA negative
  • SSA, SSB negative

Treatment: Given the Afib with RVR and RBBB, patient given diltiazem 10mg in ED with conversion to sinus rhythm.  She was continued on diltiazem 30mg qday.  Reanl was consulted emergently and patient received 1 session of HD and aggressive potassium repletion.  Her acidosis improved with bicarb PO replacement and maintained good UOP and HD was not continued.  Patient was thought to have Fanconi Syndrome 2/2 tenofovir not properly renally dosed.  Her Cr improved from initial 6 to 2.35 and she was discharged with PMD follow-up.

Take home points:

  1. This patient’s acid-base calculations:
    1. Anion gap 22
    1. Delta delta 0.5 indicating a combination of NAGMA + AGMA
    1. VBG with acidosis and low pCO2, indicating a compensatory respiratory alkalosis (why the patient was tachypneic)
      1. Winter’s formula: pCO2 = 1.5 * HCO3 + 8 +/-2
    1. AGMA likely from uremia since no other indications found
    1. NAGMA differential diagnosis: HARDNUP
      1. Hyperaugmentation – too much Cl in fluids, TPN
      1. Acetazolamide
      1. RTA
      1. Diarrhea
      1. Ureteral diversion
      1. Pancreatoduodenal fistula
      1. To differentiate GI vs Renal cause of NAGMA, will need urine anion gap (UNa +UK – UCl).  Positive indicate renal etiology and neGUTive indicates GI etiology.  For this patient, her urine anion gap is 12 (positive).
      1. To identify if RTA, can also calculate a urine osmolality gap: urine osm – calculate urine osm.  If greater than 150, can also indicate RTA
RTA Type 1RTA Type 2RTA Type 4
PathDistal problem, can’t secrete H+Proximal, can’t reabsorb HCO3Distal problem, problem of the principal cells
HCO3LowLowLow
KLowLowHigh
UpHHighLowLow
DiagnosisAssociated with autoimmune disease (SLE, Sjogrens), Calcium phosphate stone; treat with K-citrateFanconi Syndrome – see glucosuria, hypokalemia, phosphaturia; seen also in autoimmune, MM and glue sniffingDM, hypoaldosteronism, Tacrolimus, heparin/Bactrim, spironolactone

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