SLIDE 1 DISEASES OF SALT AND WATER: QUESTIONS A NEPHROLOGIST IS OFTEN ASKED
Stu Linas
SLIDE 2 Take Home Messages:
- Renal 101 Prevails
- Beaker Principle of Nephrology to understand
diseases of water (and salt)
- Separate Diseases of Salt from Diseases of
Water
SLIDE 3 1) Is my patient (IP or OP)
diuretics?
SLIDE 4 Case 1
- 66 year old woman with CKD secondary to
DM and hypertension. Admitted to the hospital with increasing edema felt to be related to CKD and high dietary salt. On Furosemide 40 mg bid she is loosing weight nicely (86 to 83 kg)
BUN 26-30 Creat 1.8-1.9
SLIDE 5 In the ‘real’ world in a tough to diurese patient, what is the best way to determine the correct dose
1) I/O 2) Daily weights 3) BUN/Creatinine ratio 4) ‘Spot’ Urine Na
SLIDE 6
Answer: ‘Spot’ Urine Na
SLIDE 7 Renal 101: Balance
- What you eat—or the intern gives you—must
be ‘peed’ or something bad is going to happen:
you die (K) or you blow up/prune down (Na)
SLIDE 8 Na balance-practical application: 24 hr urinary (or ‘spot’) Na reflects dietary intake
- 24 hr urine sodium excretion(Meq/Gms)
Normal diet 150-250/ 8-12 No added salt diet 60-80/2.5-3.5
SLIDE 9
How to use the ‘spot’ Na in edematous patients on (or not yet on) furosemide
Spot Na Interpretation Plan
(Meq/l)
< 40 I>O Increase Fur 60-80 I=O Increase Fur 80-100 I<O Right dose Fur 120-150 I<<O Decrease Fur
SLIDE 10
What would you recommend if Urine Na was 250 Meq/l in an edematous patient on furosemide who is gaining weight?
1) Increase furosemide 2) Add spironolactone 3) Add thiazide
4) Have a heart to heart talk to the patient
SLIDE 11 Answer: Have a heart to heart talk to the patient about dietary sodium
- Urine Na of 250 Meq/l implies patient must be
eating more than 250 Meq/d if gaining weight
SLIDE 12 2) My patient is on a large dose of
Fur (240 mg/bid) and will not
- diurese. What should I do next?
1) Increase Furosemide 2) Switch to Bumetamide 3) Add thiazide 4) Another test. What????
SLIDE 13 Answer: Another Test!! Measure Spot Urine Na and K
- If Urine Na very high---importance of dietary
Na
- If Urine Na low—use spot Urine K to guide
SLIDE 14 Schematic of transporters
ENaC NaCl CoTx NHE3 NN NaK2Cl CoTx
SLIDE 15
Practical approach to Renal Na transport: urine K can give a hint as to which Tx is active Tubule Site/Transporter Urine K
Proximal Tubule-NHE3 low
Ascending Limb-Na/K/2Cl low Distal tubule-NaCl low Cortical collecting tubule-ENaC high
SLIDE 16 Urine K in diuretic (furosemide) resistance
- Na transporters up regulated by furosemide
Low urine K
Proximal tubule (NHE3)--Acetazolamide Distal tubule (NaCl cotransporter)--
Thiazide/Metolazone
High urine K
Cortical collecting tubule (ENaC)--Aldosterone
antagonist
SLIDE 17 Urine K in diuretic (furosemide) resistance
- Low Urine K ( < 20 -30 Meq) implies intense
proximal or DCT Na reabsorption
add Thiazide
- High urine K (>60 Meq) implies CCT Na
reabsorption
add Spironolactone
SLIDE 18 3) When I get the urine Na ‘right’ the creatinine goes
SLIDE 19 Case 2
- 65 yr old man with CHF, CKD (DM), CAD and
marked pulmonary and peripheral edema. On Furosemide 80 mg bid, Spironolactone 25 mg/d as well as a BB. ARB discontinued.
- Wt 72-69 kg over 4 days
- Creat 1.4-1.9 mg/dl
- UNa <10-65 Meq/l U K 35 Meq/l
- Urine output 1liter/d
SLIDE 20
What would you do next?
1) ‘bite the bullet’ and not change anything 2) add albumin 3) substitute bumetamide for furosemide 4) reduce the dose of furosemide
SLIDE 21 Answer: ’Bite the bullet’ hard! Renal 101 Prevails
- Cardiorenal syndrome-effect of diuretics
Decreased LV filling--decreased CI--’Unhappy ‘
baroreceptor--CA, angiotensin--decreased RBF and GFR
- Renal 101: gotta ‘pee’ what you eat or you’ll
be back with pulmonary edema
SLIDE 22
4) I can tolerate a small increase in creatinine but the creatinine increased from 1.4 to 3.2 and didn’t improve when I stopped the diuretics.
SLIDE 23 Diuretic-induced major increase in creatinine
- Consider atherosclerotic RAS
- Must give back some salt even in edematous
patient
- But………..Renal 101 trumps (again):
Na Output must equal or exceed Intake
SLIDE 24 Alternative option: Ultrafiltration
- How does UF improve Cardiac Index when
decreases in LV filling should result in decreases in CI by a the same Starling mechanism as diureses ?
‘Geometry’ Hemodynamics : subendocardial perfusion
SLIDE 25 Subendocardial perfusion:
- Outside/In—Pericardium to subendocardium
- Systemic pressure minus LV pressure
BP EDP(mmHg) LVEDP Perfusion Pressure
Normal 80 5 75 ‘Bad’ CHF 70 25 45 CHF + UF 65 5 60
SLIDE 26
5) Why did my salt retaining patient become hyponatremic after diuretics?
SLIDE 27 Water metabolism
- Factors which cause Na retention result in
water retention as well
- CHF ( CI) or Liver disease ( ) SVR)
‘Unhappy’ baroreceptor Ang, Catechols, ADH Na and H2O retention
SLIDE 28 ‘Beaker’Principle of Nephrology
- Serum Na depends on TB Na and TB H2O
- Decreases in serum Na indicated water is
increased relative to TB Na
TB Na depletion—GI, Renal, Skin
Water replaced in excess of Na
TB Na normal—SIADH TB Na excess—CHF, Liver d, Nephrotic Syndrome
SLIDE 29
6) How much water can my CHF (CKD, Liver d.) patient drink without becoming hyponatremic?
SLIDE 30 Case 2
- 65 yr old man with CHF, CKD (DM), CAD and
marked pulmonary and peripheral edema. On Furosemide, Spironolactone and BB. ARB has been discontinued.
- Wt 72-69 kg over 4 days
- Creat 1.4-1.9
- UNa 83 Meq/l U K 45 Meq/l
- SNa 128 Meq/l
- Urine output 1liter/d
SLIDE 31 How much water can my patient drink without becoming more hyponatremic?
1) nothing! 2) 1000 cc/d 3) 2000 cc/d 4) 3000 cc/d
SLIDE 32 Answer: 1000 cc/d
- He can drink amount of free water lost each
day:
- Water losses: Insensible plus renal
Insensible losses: around 1000 cc/d Renal losses: Electrolyte Free Water (CH2O)
SLIDE 33 Electrolyte free water calculation in clinical practice
- Urine Output (Vol) = Electrolyte clearance (Ce)
plus Free water clearance (C H2O)
Vol = Ce + CH2O CH2O = Vol - Ce
Ce = [(U Na + U K) / S Na] x Vol C e = [83 + 45] / 128] x 1l/d = 1000 cc/d C H2O = V – Ce = 1l/d-1l /d = 0 cc/d
SLIDE 34 Bottom line: To maintain Serum Na at 128 Meq/l
- Patient can drink insensible losses
- nly: 1000 cc/d
- If he drinks more than 100cc/d, what
will happen to his serum Na?
More hyponatremic
SLIDE 35
7) In my hyponatremic patient, what can I do if water restriction alone doesn’t work?
SLIDE 36 Increase free water excretion
Furosemide Urea Demethylchlortetracycline (Declomycin) Vaptans
SLIDE 37 Mechanisms of action
IV: rapid flow in CT impairs water reabsorption PO: water and salt losses—only salt replaced
Osmotic effect limits water reabsorption in CT
Tetracycline antibiotic Decreases ADH signaling in CT
SLIDE 38 Mechanisms (2)
- Vaptans: selective V2 receptor
antagonists
V1 receptor: Blood vessels and platelets (VWF)
Vasoconstriction ‘sticky’ platelets
V2 receptor: Kidney CT
Water reabsorption
SLIDE 39 CJASN 7 742 2012
300
SLIDE 40 Background
- Vaptans are a new therapeutic approach to
treating hyponatremia in SIADH
- Efficacy, safety and cost compared to usual
therapies is not known
SLIDE 41 Methods
- Patients with well described chronic SIADH
- Vaptans for a year
- 8-day holiday
- Oral urea (15-30 gms/d)
SLIDE 42
Serum Na
SLIDE 43 Conclusions
- Urea is at least as effective as vaptans in
maintaining serum Na in SIADH
hypernatremia, thirst
SLIDE 44 8) I have a volume depleted, hyponatremic patient who I resuscitated with NaCl. The patient suddenly became polyuric. I am afraid the serum sodium will correct too
- quickly. What should I do?
SLIDE 45 Case 4
- 26 year old woman with several days of
diarrhea and vomiting who replaced herself with tea, toast and soda. In ER received several liters of NaCl plus K. (48Kg)
- Vol 10 cc/hr—150 cc/hr
- Na 110—120 Meq/l
- UNa <10--20
- UK <10--20
SLIDE 46 Question: To maintain the serum sodium at 120 Meq/l how much D5W (or orals) should I recommend?
1) No additional fluid 2) 100 cc/hr 3) 200 cc/hr 4) 400 cc/hr
SLIDE 47 Answer: 100 cc/hr
- CH2O = Vol-Ce
- C H2O = 150 cc/hr – [(20 + 20)/120] x 150 cc/hr
= 100 cc/hr
If give less than 100 cc/hr---serum sodium will increase If give more than 100 cc/hr---serum sodium will decrease
SLIDE 48
9) My patient with BPH had a catheter placed for acute urinary retention. What fluid should I use for replacement?
SLIDE 49 Case 5
- 85 yr old man with acute obstrutive uropathy
from BPH. After bladder decompressed, he made 100 cc/hr urine
- PE: BP 170/95 mmHg and marked edema
- Lab: Na 128 K 5.8 BUN 87 Creat 5.6
CH2O 60 cc/hr
SLIDE 50
Question: what fluid should be utilized?
1) None 2) D5 3) 0.45% nl NaCl 4) 0.9% nl NaCl
SLIDE 51 Answer: No fluids at this time
- Separate salt from water requirements
- TB Na markedly increased---edema
No need for NaCl replacement
- TB H2O increased more than TB Na—
hyponatremia
No need for H2O replacement
SLIDE 52
Suppose the Serum Na was 145 Meq/l. Would you ‘hang’:
1) No fluid 2) D5 3) 0.45% NaCl 4) 0.9% NaCl
SLIDE 53 Answer: D5
No need for NaCl
CH2O 60 cc/hr Serum Na will increase unless you administer
60 cc/hr D5
SLIDE 54 Take Home Messages:
- Renal 101
- Beaker Principle of Nephrology
- Separate Diseases of Salt from Water