DISEASES OF SALT AND WATER: QUESTIONS A NEPHROLOGIST IS OFTEN ASKED - PowerPoint PPT Presentation

DISEASES OF SALT AND WATER: QUESTIONS A NEPHROLOGIST IS OFTEN ASKED Stu Linas U. Colorado SOM

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

1) Is my patient (IP or OP) on the correct dose of diuretics?

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)  Lab: 140/3.8/102/23  BUN 26-30 Creat 1.8-1.9

In the ‘real’ world in a tough to diurese patient, what is the best way to determine the correct dose of diuretics? 1) I/O 2) Daily weights 3) BUN/Creatinine ratio 4) ‘Spot’ Urine Na

Answer: ‘Spot’ Urine Na

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)

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

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

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

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

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????

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

Schematic of transporters ENaC NHE3 NaCl CoTx NaK2Cl CoTx NN

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

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

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

3) When I get the urine Na ‘right’ the creatinine goes up. What should I do?

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

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

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

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.

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

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

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

5) Why did my salt retaining patient become hyponatremic after diuretics?

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

‘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

6) How much water can my CHF (CKD, Liver d.) patient drink without becoming hyponatremic?

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

How much water can my patient drink without becoming more hyponatremic?  Approximately: 1) nothing! 2) 1000 cc/d 3) 2000 cc/d 4) 3000 cc/d

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)

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

Bottom line: To maintain Serum Na at 128 Meq/l  Patient can drink insensible losses only: 1000 cc/d  If he drinks more than 100cc/d, what will happen to his serum Na?  More hyponatremic

7) In my hyponatremic patient, what can I do if water restriction alone doesn’t work?

Increase free water excretion  Medications :  Furosemide  Urea  Demethylchlortetracycline (Declomycin)  Vaptans

Mechanisms of action  Furosemide  IV: rapid flow in CT impairs water reabsorption  PO: water and salt losses—only salt replaced  Urea  Osmotic effect limits water reabsorption in CT  Declomycin  Tetracycline antibiotic  Decreases ADH signaling in CT

Mechanisms (2)  Vaptans: selective V2 receptor antagonists  V1 receptor: Blood vessels and platelets (VWF)  Vasoconstriction  ‘sticky’ platelets  V2 receptor: Kidney CT  Water reabsorption

CJASN 7 742 2012 300

Background  Vaptans are a new therapeutic approach to treating hyponatremia in SIADH  Efficacy, safety and cost compared to usual therapies is not known

Methods  Patients with well described chronic SIADH  Vaptans for a year  8-day holiday  Oral urea (15-30 gms/d)

Serum Na

Conclusions  Urea is at least as effective as vaptans in maintaining serum Na in SIADH  Equal tolerability  hypernatremia, thirst

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?

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

Question: To maintain the serum sodium at 120 Meq/l how much D5W (or orals) should I recommend?  Approximately: 1) No additional fluid 2) 100 cc/hr 3) 200 cc/hr 4) 400 cc/hr

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

9) My patient with BPH had a catheter placed for acute urinary retention. What fluid should I use for replacement?