Why isn’t my patient with congestive heart failure or end-stage liver disease losing weight despite being on diuretic therapy? Is the diuretic dose too low, or is the salt intake too high?

When a patient with congestive heart failure (CHF) or end-stage liver disease (ESLD) doesn’t respond as expected to diuretic therapy, measurement of urinary sodium (Na) can be helpful.

In low effective arterial blood volume states (eg, CHF and ESLD) aldosterone secretion is high, resulting in high urine potassium (K) and low urine Na concentrations. However, in the presence of diuretics, urinary Na excretion should rise.

Patients undergoing active diuresis are often restricted to a 2 g (88 mEq) Na intake/day, with ~10 mEq excreted via non-urinary sources (primarily stool), and ~ 78 mEq excreted in the urine to “break even” — that is, to maintain the same weight.

Although historically measured 1, a 24-hour urine Na and K collection is tedious, making spot urine Na/K ratio more attractive as a potential proxy.  Approximately 90% of patients who achieve a urinary Na/K ratio ≥1 will have a urinary Na excretion ≥78 mEq/day — that is to say, they are sensitive to the diuretic and will have a stable or decreasing weight at the current dose. 2,3

Urine Na/K may be interpreted as follows:

  • ≥1 and losing weight suggests effective diuretic dose, adherent to low Na diet
  • ≥1 and rising weight suggests effective diuretic dose, non-adherent to low Na diet
  • <1 and rising weight suggests ineffective diuretic dose

The “ideal” Na/K ratio as relates to responsiveness to diuretics has ranged from 1.0 to 2.5.4 In acutely decompensated heart failure patients on spironolactone, a K-sparing diuretic, Na/K ratio >2 at day 3 of hospitalization may be associated with improved outcome at 180 days. 5

Remember also that if the patient’s clinical syndrome is not correlating well with the ratio, it’s always a good idea to proceed to a 24-hour urine collection.



  1. Runyon B. Refractory Ascites. Semin Liver Dis. Semin Liver Dis. 1993 Nov;13(4):343-51. https://www.ncbi.nlm.nih.gov/pubmed/8303315
  2. Stiehm AJ, Mendler MH, Runyon BA. Detection of diuretic-resistance or diuretic-sensitivity by spot urine Na/K ratios in 729 specimens from cirrhotics with ascites: approximately 90 percent accuracy as compared to 24-hr urine Na excretion (abstract). Hepatology 2002; 36: 222A.
  3. da Silva OM, Thiele GB, Fayad L. et al. Comparative study of spot urine Na/K ratio and 24-hour urine sodium in natriuresis evaluation of cirrhotic patients with ascites. GE J Port Gastroenterol 2014;21:15-20 https://pdfs.semanticscholar.org/4dc3/4d18d202c6fa2b30a1f6563baab80d877921.pdf
  4. El-Bokl M, Senousy, B, El-Karmouty K, Mohammed I, Mohammed S, Shabana S, Shelby H. Spot urinary sodium for assessing dietary sodium restriction in cirrhotic ascites. World J Gastroenterol 2009; 15:3631. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721236/
  5. Ferreira JP, Girerd N, Medeiros PB, et al. Spot urine sodium excretion as prognostic marker in acutely decompensated heart failure: the spironolactone effect. Clin Res Cardiol 2016;105:489-507. https://www.ncbi.nlm.nih.gov/pubmed/26615605


Contributed by Alyssa Castillo, MD, with valuable input from Sawalla Guseh, MD, both from Mass General Hospital, Boston, MA.

Why isn’t my patient with congestive heart failure or end-stage liver disease losing weight despite being on diuretic therapy? Is the diuretic dose too low, or is the salt intake too high?

Should my patient with compensated heart failure be placed on a sodium-restricted diet?

Although sodium restriction is routinely recommended for patients with heart failure (HF), the data is often conflicting with a number of studies suggesting that it may be harmful in some HF patient. 

Two randomized trials (by the same group) involving patients with compensated HF recently discharged from the hospital reported that “less restricted” sodium diet (2.8 gm/d) along with fluid restriction (1 liter/d) and high-dose furosemide (at least 125-250 mg furosemide bid) was associated with less rates of readmissions and improved levels of brain natriuretic peptide, aldosterone and plasma renin activity when compared to patients on more restricted sodium diet (1.8 gm/d).1,2

Analysis of data from the multihospital HF Adherence and Retention Trial enrolling New York Heart Association functional class II/III HF patients found that sodium restriction (<2.5 gm/d) was associated with significantly higher risk of death or HF hospitalization but only in patients not on an angiotension converting enzyme inhibitor or angiotensin receptor blocker.3

In normal subjects who are not sodium deprived, excess sodium intake has been shown to cause expansion of intravascular volume without increasing total body water.4 Thus, sodium restriction combined with diuretics may reduce intravascular volume and renal perfusion, further stimulating the renin-angiotensin-aldosterone system and fluid retention.5

Now that’s interesting! Did you know that the 2013 American College of Cardiology Foundation/American Heart Association guidelines downgraded the recommendation for sodium restriction to Class IIa (reasonable) with Level of Evidence:C? 6



  1. Paterna S, Gaspare P, Fasullo S, et al. Normal-sodium diet compared with low-sodium diet in compensated congestive heart failure: is sodium an old enemy or a new friend? Clin Sci 2008;114:221-230. https://www.ncbi.nlm.nih.gov/pubmed/17688420
  2. Paterna S, Parrinello G, Cannizzaro S, et al. Medium term effects of different dosage of diuretic, sodium, and fluid administration on neurohormonal and clinical outcome in patients with recently compensated heart failure. Am J Cardiol 2009;103:93-102. https://www.ncbi.nlm.nih.gov/pubmed/19101237
  3. Doukky R, Avery E, Mangla A, et al.Impact of dietary sodium restriction on heart failure outcomes. J Am Coll Cariol HF 2016;4:24-35. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705447/
  4. Heer M, Baisch F, Kropp J et al. High dietary sodium chloride consumption may not induce body fluid retention in humans. Am J Physiol Renal Physiol 2000;278:F585-F595. https://www.ncbi.nlm.nih.gov/pubmed/10751219
  5. Rothberg MB, Sivalingam SK. The new heart failure diet: less salt restriction, more micronutrients. J Gen Intern Med 25;1136-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955483/
  6. Yancy CW, Jessup M, Bozkurt B, et al. 2013 CCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;62:e147-239. https://www.ncbi.nlm.nih.gov/pubmed/23741058
Should my patient with compensated heart failure be placed on a sodium-restricted diet?

My patient with hypercalcemia complains of polyuria. What is the mechanism of hypercalcemia-associated polyuria?

Polyuria is considered a classic symptom of hypercalcemia and was one of the symptoms described in the first published case of hyperparathyroidism (1). Several potential mechanisms may explain this phenomenon.

The calcium sensing receptors (CaSRs) found in the kidney play a major role in volume status due to their expression in the thick ascending loop (TAL) of Henle and the collecting duct. Interestingly, hypercalcemia activates the CaSR in the medullary portion of TAL, causing inhibition of the same cotransporter (Na-K-2Cl) inhibited by furosemide and other loop diuretics (2-4)! Hypercalcemia also inhibits vasopressin action ( therefore urine concentration) by activating CaSR in the collecting duct (5).  Lastly, inhibition of Na+-K+ ATPase in the proximal convoluted tubule may further contribute to natriuresis and subsequent polyuria.

Thus, hypercalcemia may lead to polyuria by interfering with the absorption of sodium as well as inhibiting the action of vasopressin.  One can’t help but compare its effect to that of a patient with diabetes insipidus taking a loop diuretic!  No wonder these patient may suffer from polyuria!



  1. Goldfarb S, Agus ZS. Mechanism of the polyuria of hypercalcemia. Am J Nephrol. 1984;4:69-76.
  2. Quamme GA. Effect of hypercalcemia on renal tubular handling of calcium and magnesium. Can J Physiol Pharmacol. 1982;60:1275-80.
  3. Peterson LN. Vitamin D-induced chronic hypercalcemia inhibits thick ascending limb NaCl reabsorption in vivo. Am J Physiol. 1990;259:122-9.
  4. Riccardi D, Brown EM. Physiology and pathophysiology of the calcium-sensing receptor in the kidney. Am J Physiol Renal Physiol. 2010;298:485-99.
  5. Toka HR, Pollak MR, Houillier P. Calcium sensing in the renal tubule. Physiology (Bethesda). 2015;30:317-26.


Contributed by Michael Hughes, Medical Student, Harvard Medical School


My patient with hypercalcemia complains of polyuria. What is the mechanism of hypercalcemia-associated polyuria?