Management of the Hospitalized Patient Nephrology Cases€¦ · [ADD PRESENTATION TITLE: INSERT TAB...

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10/26/20151

Management of the Hospitalized PatientNephrology CasesKerry C. Cho, MDAssociate Professor of Clinical MedicineFellowship Program DirectorDivision of Nephrology

October 16, 2015

Case 1: Hyponatremia

HPI: 49 yo M without significant medical hx had minor MVA 2 weeks prior to admission. He was the restrained passenger of a car when his car was rear-ended by another car. He had mild occipital trauma and brief LOC for an unclear duration, possibly minutes. At an OSH, he was evaluated, head CT was negative, and he discharged home with Norco, Flexeril, and Naproxen.

Over the next two weeks, he had progressive nausea, vomiting, headaches, confusion, and difficulty concentrating.

He came to ED at UCSF for evaluation.

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10/26/20152

Case 1, continued

Temp 36.9°, Pulse 71, Resp 16, 135/93, O2 sat 98% RA, Wt 80 kg

Nystagmus with bilateral lateral gaze

Lateral chest wall contusions from seat belt

Labs

118 86 13 glucose 94 serum osms 259

4.5 22 0.72 AG 10 LFT, TSH, cortisol negative

Urine Na 99, Urine K 53 UA trace ketones

Physical examination

3

Case 1, continued

Given 1 L normal saline in ED, Na decreased from 118 to 117

Repeat Head CT negative

Admitted to medicine service

Initiated on 3% hypertonic saline at 40 mL/hour, free water restricted

Na corrected to 125 mEq/L, HTS d/c, Na dropped to 120.

I/O not adequately recorded

Nephrology consulted for persistent hyponatremia

Neurology consulted for nystagmus

ED Course

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10/26/20153

What is 0.9% and 3% Saline?

154 mEq/L of NaCl

0.9% = 0.9 g/dL = 0.9 g per 100 mL = 9 g/L

2 gram per day Na diet = 5 grams NaCl

Hypertonic Saline

513 mEq/L of NaCl

3% = 3 g/dL = 3 g per 100 mL = 30 g/L

Normal Saline

5

Basic Nephrology for Hospitalists

EFWC = Urine Flow x [1 – (UNa + UK/PNa)]

where UNa + UK are urine concentrations, and PNa is plasma [Na]

Implications of (UNa + UK) > PNa

Free water restriction will not work

Hypertonic saline will likely be necessary to prevent desalination with retention of free water

Consider nephrology consultation

Electrolyte Free Water Clearance (EFWC)

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10/26/20154

“Safe” Serum Sodium Correction

Symptomatic/severe hyponatremia FAST correction

Raise serum Na 4-6 mEq/L within 6 hours

Consider 3% HTS bolus 50-100 mL IV

Goal correction rate: 4-6 mEq/L and ≤ 8 mEq/L over any 24 hour period

Chronic severe hyponatremia with mild/moderate symptoms: SLOW

HTS AND desmopressin 1-2 mcg IV/SQ q 8 hrs for 24 to 48 hours*

Desmopressin prevents unanticipated water diuresis from reversible cause of ADH release. Contraindicated in patients who cannot adhere to water restriction

Fast and Slow correction

7

General Advice for Hypertonic Saline in Hyponatremia Mgmt

Rule of thumb: HTS infusion rate is typically <0.5 mL/kg/hour

If > 0.5 mL/kg/hour, then you either made a mathematical error or you’re correcting the serum Na too quickly.


Severe Symptomatic Hyponatremia

Na < 120 mEq/L typically acute (< 48 hours) OR hyponatremicpatients who cannot tolerate increased ICP

3% HTS 100 mL IV q 10 mins prn, up to 2-3 total doses

Goal: rapid correction of hyponatremia by 4-6 mEq/L

Hypertonic Saline

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10/26/20155

Treatment of Osmotic Demyelination or Na Correction Rate > 8 mEq/L per 24 hr

D5W at 6 mL/kg lean body weight IV over two hours, repeat prn

Desmopressin 2 mcg IV/SQ q 6 hours

Goal: drop serum Na by 1 mEq/L per hour to original target Na

• Example: Initial Na 110 mEq/L, original goal Na 116 mEq/L, actual Na 125 mEq/L.

• Treatment with D5W and desmopressin should return Na to 116 mEq/L over about 8-10 hours

Limitations: rat model, case reports in humans; ideal goal Na and rate of correction undefined.

9

Hospital Course, continued

3% Hypertonic restarted at 40 mL/hour, Na checks q 2-3 hours

Na reached 125 mEq/L, 3% HTS d/c, Na returned to 120 with next lab draw

Urine output never adequately recorded

Pt insistent that free water restriction followed

Nystagmus

Labyrinthine dysfunction given +head thrust to R and gaze evoked nystagmus to L, probable labyrinthine concussion

Hyponatremia likely related to TBI, recommended MRI

Hyponatremia

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10/26/20156


Multiple areas susceptibility in the left occipital lobe, likely due to age indeterminate microhemorrhages, possibly traumatic.

With recurrent hyponatremia off HTS, tolvaptan 15 mg PO given once

Na corrected 6-8 mEq/L over first 24 hours

Second dose of tolvaptan 15 mg the following day, observed overnight then discharged.

Required 2-3 additional doses of tolvaptan over next two weeks at outpatient

Na normalized on labs 2, 3, and 6 weeks post-discharge

Brain MR

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ADH receptor antagonists: Vaptans

V1a - vasoconstriction

V1b - ACTH release

V2 - antidiuretic response

Vaptans – ADH receptor antagonists

V2R specific: tolvaptan, mozavaptan, satavaptan, and lixivaptan(only tolvaptan available in the US)

Conivaptan: V2 and V1a antagonist, IV formulation, available in US

True aquaretics/diuretics, not natriuretics: free water loss with neutral effect on Na balance

Three receptors for vasopressin/ADH

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10/26/20157

Tolvaptan Information

15 and 30 mg tablets available in US

Tablets > 30 mg available outside US; 45, 60, and 90 mg tablets

Not approved for usage in symptomatic/severe hyponatremia

Poorly tolerated chronically due to aquaresis, nocturia, thirst, dry mouth

Limited data on clinical outcomes and long term outcomes

May result in overrapid correction of serum Na, especially if used inappropriately.

Dosages, Indications and Adverse Effects

13

Tolvaptan Information

Should not be used for longer than 30 days

Contraindicated in patients with liver disease (including cirrhosis)

Higher incidence of increased AST and ALT (0.9% in tolvaptangroup vs. 0.4% in placebo group) in Tempo 3:4 ADPKD trial, NEJM 2012;367(25):2407.

FDA Warning

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10/26/20158

Practical Advice on Vaptans

Start with tolvaptan 15 mg PO x 1, first dose during daytime

D/C exogenous sources of Na (NaCl tablets, normal saline, hypertonic saline)

D/C free water restriction: thirst and access to free water protect against overly rapid correction of serum [Na]

Repeat serum [Na] within 4-6 hours of first dose

• Onset of action 2-4 hours, peak action 4-8 hours

Expensive (list price $400 per tablet)


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Teaching Points

MVA and traumatic brain injury hyponatremia

(UNa + UK) > PNa Free water restriction will not be effective, consider hypertonic saline

Consider nephrology consultation if you are considering hypertonic saline, ddAVP, or tolvaptan use

Tolvaptan: Stop exogenous Na intake and free water restriction, monitor serum Na closely

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10/26/20159

Case 2

Reason for Consultation: increased osmolar gap

62 yo WM hx morbid obesity, OSA, CHF presents with several year hx of malaise, weakness, dizziness, and head/hand tremor over the last several years, worsening over the last few weeks. He is a difficult historian with inappropriate affect, delusions, grandiosity, and confabulation.

Case 2

Medical History

Morbid obesity

Obstructive sleep apnea

Congestive heart failure

Atrial fibrillation

Parathyroid carcinoma s/p PTX

Kidney stones

CKD, creatinine 2.0-2.6

Hypothyroidism


10/26/201510

Case 2, continued

Medications Allergies:

KCl 8 mEq day Cefazolin

HCTZ 25 mg daily Dilantin

Amiodarone 200 mg daily PCN

Synthroid 125 mcg daily

Metoprolol 100 mg daily

Furosemide 20 mg daily

Atorvastatin 10 mg daily

Coumadin

Vitamin C

Case 2, continued

Family Hx: Non-contributory

Social Hx

Lives at home with a friend, formerly homeless.

Worked for the British Royal Family

Doctorates in criminology and business, master degree in business administration and social psychology

Former UC Berkeley professor


10/26/201511

Case 2,

Health-related behaviors

Former smoker with 7 pack-years

No EtOH or drugs.

Review of Systems

Dizziness, weakness, feeling of impending doom, uneasiness, insomnia, anhedonia, depression

Case Presentation

Physical Exam

36.5 158/92 65 18 99% RA

HEENT normal

Cardiac normal

Chest normal

Abdomen obese, otherwise normal

Ext trace pitting edema

Skin abrasion over RLE, no rash

Psych grandiosity


10/26/201512

Case Presentation

CBC Hb 12.8 otherwise normal

LFT Normal INR 2.7 Albumin 3.5

Glucose 114 Ca/Mg/PO4 normal

142 100 17

3.3 31 2.4

Anion gap 11

Serum Osms 354 344 (normal 285-293)

Osmolar Gap

Osm Gap = Measured Osms – Estimated Osms

Estimated Osms =

2Na + BUN/2.8 + Glucose/18 + Ethanol/4.6

Normal Osm Gap < 10

In this case,

Estimated Osms = 2 x 142 + 17/2.8 + 114/18 = 297

Osm Gap = 354 – 297 = 57


10/26/201513

Quick note about units

Glucose

Molecular weight: 180 daltons

Measured in mg/dL

Conversion mg/dL to mmol/L: 10 dL/L x 1 mmol/180 mg

Urea

Molecular weight: 60 daltons

BUN = blood urea nitrogen, concentration measured mg/dL

Nitrogen component of urea: 2 nitrogens = 28 daltons

Conversion mg/dL to mmol/L: 10 dL/L x 1 mmol/28 mg

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Differential Diagnosis?


10/26/201514

DDx: Increased Osmolar Gap

Increased Osmolar Gap AND Increased Anion Gap

Ethylene glycol, methanol

Formaldehyde, paraldehyde

Diabetic and Alcoholic ketoacidosis

ESRD without dialysis

Lactic Acidosis

Increased Osmolar Gap with Normal Anion Gap

Isopropanol, diethyl ether, mannitol

Hypertriglyceridemia*, hyperparaproteinemias*

Case 2: Additional History

He reports bathing with isopropanol (isopropyl alcohol) when he was morbidly obese because it was difficult for him to get into a shower or bathtub.

After losing a significant amount of weight, he continued to wash with isopropanol up to 15 times/day using 3-4 quarts/day.


10/26/201515

Additional Information

Urine toxin screen – negative

Serum ethanol – negative

Serum isopropanol – none detected

Serum acetones – 166 mg/dL, roughly 28 mmol/L

Common Uses of Isopropanol

Antifreeze

De-icers

Liquid detergent

Disinfectant

Glass cleaner

Jewelry cleaner

Rubbing alcohol

Spot stain remover


10/26/201516

Isopropanol Ingestion

Pediatrics – accidental ingestion

Adults – substitute for ethanol, “blue heaven”

Toxicity

20 mL signs/symptoms intoxication

150-200 mL lethal dose

Isopropanol Pharmacology

Orally absorbed within 2 hours

Metabolized by liver alcohol dehydrogenase into acetone

Kidneys - 80% excreted as acetone, 20% excreted unchanged

Half-life 3 to 7.3 hours


10/26/201517

Alcohol Intoxications

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Methanol Ethanol Isopropyl Alcohol

Ethylene Glycol

Fruity odor Y Y Y N

Met. Acid Severe Mild N Severe

Anion gap Large Moderate Slight Large

Osm gap Y Y Y Y

Low glucose N Y Y N

Metabolites Formic acid Hydroxy-butyric

Acetone Glycolic and oxalic acids

Other Blindness Acetoacetic acids

Gastritis

UGIB

Crystalluria

Management: Supportive

No role for activated charcoal or gastric lavage

Isopropanol decreases gluconeogenesis

Concurrent rhabdomyolysis/AKI from depressed CNS

Fluids

Indications for Hemodialysis

Isopropanol level > 400 mg/dL

Respiratory failure, mechanical ventilation

Hypotension requiring pressors


10/26/201518

Transdermal Absorption of Isopropanol?

Rat model of topical isopropanol absorption

Boatman RJ et al. Drub Metab Dispos 1998;26:197-202.

Alcohol hand-rubs in hospitals

q 10 mins x 4 hours

Measurable serum isopropanol levels, 0.5-1.8 mg/L

Turner P et al. J Hospital Infection 2004;56:287-90.

Hemorrhagic gastritis from alcohol rubdown for fever reduction

Dyer S et al. Ann Pharmacother 2002;36:1733-5.

Teaching Points of Case 2

Remember to check serum osmolarity when considering ingestions and altered mental status

Estimated Osmolalty: Remember conversions and BUN

DDx of Osmolar Gap with Normal Anion Gap

• Isopropanol, diethyl ether, mannitol

• Hypertriglyceridemia*, hyperparaproteinemias*

Methanol, ethanol, and ethylene glycol increase serum osmolality, osmolar gap, and anion gap (with metabolic acidosis)

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10/26/201519

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Case 3

CC: acute kidney injury (case seen in 2008)

28 yo WM hx nephrolithiasis and bilateral ureteral stents.

First episode of nephrolithiasis in 2002 as 22 year old. Bilateral ureteral stents were placed. Patient lost to follow-up.

Returns for follow-up and found by urology to have a complete R ureteral stent and a fragmented L ureteral stent.

Underwent bilateral nephrolithotomy with calcified ureteral stent removal and partial stone removal.

Bilateral upper pole nephrostomy tubes inserted.

Case 3: History

Post-operative course

Ciprofloxacin IV

Hypoxia and respiratory failure, transferred to ICU, started on BiPAP then intubated

Vanco and Zosyn

Heparin gtt for possible PE until Chest CTA negative

LE Doppler US negative for DVT


10/26/201520

History

Baseline creatinine 1.2 mg/dL on admission in April and previously in February 2008

Following AM, creatinine 2.34 mg/dL with excellent urine output from nephrostomy tubes, ~ 60 mL/hour mostly from R nephrostomy tube.

Medical History

CKD, baseline creatinine 1.2 mg/dL

HTN

Nephrolithiasis

History

Allergies: NKDA

Medications

Dilaudid, heparin gtt, atenolol, Zosyn, vancomycin, albuterol/atrovent

Social Hx: No tobacco/EtOH/drugs

Family Hx: Dad with 2 kidney stones


10/26/201521

History

Physical Exam T 37.3 RR 10-38

HR 70-100 BP 130-190/50-80 130.8 kg

Obese

Intubated

RRR normal JVP, no m/r/g

Decreased breath sounds L>R

Bilateral nephrostomy tubes and Foley

Soft nt nd +BS

1+ edema

Labs

138 104 20 WBC 14.4, Hb 11.5, Plts 312

4.4 26 2.34

Calcium 1.79 (11.2 mg/dL on admission)

Mg 1.9 PO4 2.9

UA: 100 protein, large Hb, +LE

Sediment: many non-dysmorphic rbcs, few granular casts


10/26/201522

Radiology

CXR: decreased lung volumes, moderate L pleural effusion

Renal US:

R kidney 12.6 cm, no hydro/stones, previous hydro resolved.

L kidney 13.1 cm, grade 3 hydro, dilated calyces, mx stones

DDx

ATN

Obstructive nephropathy

Hypercalcemic ARF


10/26/201523

Recommendations

No acute need for IHD or CRRT

IR to fix non-functioning L nephrostomy tube

Aggressive hydration

IV furosemide

Zometa IV

PTH, vitamin D

Endocrinology consult

Nephrostogram

L nephrostomy tube malpositioned

Injection of contrast into L nephrostomy tube flowed into pleural space with respiratory variation of urine in Foley tubing

R nephrostomy tube: properly positioned, but no flow of injected contrast into ureter.

Next day in IR

Bilateral ureteral stents and nephrostomy tubes

L chest tube for pleural effusion


10/26/201524

Evaluation of Hypercalcemia

25-hydroxyvitamin D: 19 (low)

1,25-dihydroxyvitamin D: 47 (normal)

PTH: 181, 989, 630

TSH, free TF: negative

Cortisol: normal

Stone analysis: calcium oxalate monohydrate

Endocrinology Consult for MEN syndrome

Quick Comments about Calcium

Total Calcium

Measured in mg/dL, normal range 8.8 to 10.3 mg/dL

Ionized Calcium

Measured in mmol/L, normal range 1.16 to 1.36 mmol/L

Molecular weight calcium = 40 daltons

Total calcium normal range is 2.3 to 2.575 mmol/L

Ionized calcium is 40-50% of total calcium

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10/26/201525

CreatinineArrow = bilateral nephrostomy tubes

Ionized CalciumArrow = Zometa IV


10/26/201526

History

Physical Exam T 37.3 RR 10-38

HR 70-100 BP 130-190/50-80 130.8 kg

Obese

Intubated

RRR normal JVP, no m/r/g

Decreased breath sounds L>R

Bilateral nephrostomy tubes and Foley

Soft nt nd +BS

1+ edema

Labs

138 104 20 WBC 14.4

4.4 26 2.34 Hb/Hct 11.5 34.5

Plt 312

Calcium 1.79 (11.2 mg/dL on admission)

Mg 1.9 Phosphate 2.9

UA: 100 protein, large Hb, +LE

Sediment: many non-dysmorphic rbcs, few granular casts


10/26/201527

Radiology

CXR: decreased lung volumes, small-moderate L pleural effusion

Renal US:

R kidney 12.6 cm, no hydro/stones, previous hydro resolved.

L kidney 13.1 cm, grade 3 hydro, dilated calyces, mx stones

Anatomy for Nephrostomy Tubes

Campbell-Walsh Urology, 9th Ed. 2007

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10/26/201528

Teaching Points for Case 3

Nephrostomy tubes

• Can be inserted above or below 12th rib

• Tubes over the 12th rib may enter the pleural space

• Displaced nephrostomy tubes can cause pleural effusions from urine leaks

• Urine leak confirmed with Fluid Creatinine > Serum Creatinine

Severe nephrolithiasis consider primary etiology

55

Drug Toxicity Case

65 yo M hx schizophrenia, gastritis, HTN, resident of board/care facility. Brought in by ambulance after being found down at home with altered mental status. Noted to have slurred speech and tremulousness.

Initial Evaluation: CXR normal. Brain CT negative.

Medication reconciliation between caretaker and primary MD revealed that he had been taking lithium 600 mg BID instead of the prescribed 300 mg BID for unclear duration.

Other medications include mirtazapine 15 mg and olanzapine 5 mg at night.

Baseline creatinine 1.2 in April 2015.

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10/26/201529


Physical Exam: normal vitals, afebrile, normal O2 saturation

Cachectic, incoherent, slurred speech

Dry MM

Neuro: somnolent, not following commands, tremulousness, normal reflexes.

Labs:

144 120 32 glucose 109, Ca 9.3, Mg 3.1, PO4 3.4

5.0 19 1.86 Li 4.3

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Lithium level 4.3, measured 12 hours after presentation to ED

Nephrology and psychiatry consultation

R femoral temporary dialysis catheter placed for urgent dialysis

Li level prior to 1st HD 3.6, decreased to 2.0 mEq/L 8 hours after HD

2nd HD treatment reduced Li level to 1.5

3rd HD treatment today October 16, 2015

Urine output 3+ L/day despite minimal PO intake and hypovolemia

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10/26/201530

Treatment of Lithium Toxicity

Airway/Breathing/Circulation: Monitor mental status, seizures

Hydration

• Lithium induced nephrogenic diabetes insipidus due to chronic exposure May require NS for hypovolemia and D5W for prevention/treatment of hypernatremia

GI decontamination

• Activated charcoal No role

• Whole bowel irrigation/polyethylene glycol: Large acute ingestions or sustained release Li formulations

• Sodium polystyrene theoretical benefit, impractical

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Lithium Toxicity: Hemodialysis

Lithium easily dialyzed: Small, not protein bound

Indications for hemodialysis: Unclear/controversial

• Serum [Li] > 4 mEq/L regardless of symptoms

• Serum [Li] > 2.5 mEq/L with symptoms (seizures, altered mental status), reduced GFR from AKI or CKD that limits Li excretion

• Consider consultation with medical toxicology or poison control center

Nephrology consultation for hemodialysis

• Continuous renal replacement therapy (CRRT) for unstable patients

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10/26/201531

SILENT: Syndrome of Irreversible Lithium Effectuated Neurotoxicity

Prolonged neurological and neuropsychological symptoms following lithium toxicity

Symptoms

• Cerebellar dysfunction (most common)

• Extrapyramidal symptoms, brainstem dysfunction, dementia

• Blindness, nystagmus, choreoathetoid movements, myopathy

Symptoms can persist for months to years

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Teaching Points for Case 4

Medication reconciliation was key to patient care

Lithium toxicity may require consultation with medical toxicology (or poison control), psychiatry and nephrology

Consider hemodialysis

• Lithium level > 4 mEq/L, regardless of symptoms

• Lithium level > 2.5 mEq/L with symptoms

Multiple HD treatments may be needed to remove lithium

Nephrogenic diabetes inspidus from chronic lithium use may be present and may cause polyuria, hypernatremia, hypovolemia

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10/26/201532

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