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Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, SCSection of Nephrology, Medical Service, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC
Polyuria, defined as daily urine output in excess of 3.0 to 3.5 L/d, can occur due to solute or water diuresis. Solute-induced polyuria can be seen in hospitalized patients after a high solute load from exogenous protein administration or following relief of urinary obstruction. Similar clinical scenarios are rarely encountered in the outpatient setting. We describe a case of polyuria due to high solute ingestion and excessive water intake leading to a mixed picture of solute and water diuresis. Restriction of the daily solute load and water intake resulted in complete resolution of polyuria. Determination of the daily excreted urinary osmoles may yield important clues to the cause of polyuria and should be included in the routine workup of polyuria.
Polyuria can be incapacitating for patients by disrupting their daily activities and sleep cycle. Polyuria can result in volume depletion, rapid fluctuations in serum sodium levels, and distension of the renal outflow tract due to high urinary output volume.
The differential diagnosis of polyuria includes central diabetes insipidus, congenital or acquired nephrogenic diabetes insipidus, psychogenic polydipsia, high protein or hyperglycemic osmotic diuresis, salt-wasting nephropathies, mixed polyuria due to excess solute and water intake, and postobstructive diuresis following recovery from urinary obstruction.
However, this phenomenon is not commonly observed outside the hospital setting. We describe a case of a woman who presented with concerns regarding polyuria and polydipsia of more than one year duration. The diagnostic principles used in this teaching case illustrate the approach to the evaluation of polyuria in an outpatient setting.
Clinical History and Initial Laboratory Data
A 40-year-old woman with a history of migraines, depression, and anxiety disorder presented for evaluation of polyuria of 1.5 years’ duration. She had maintained a voiding diary that showed a daily urine output of 6.5 to 9.6 L/d. She also reported nocturia, with a night-time voiding frequency of 2 to 3 times per night and nocturnal urine volume of 2.0 L. Her average daily fluid intake was >7.5 L. There was no history of hematuria or symptoms suggestive of urinary tract infection. One week prior to evaluation, she was referred to an endocrinology clinic to undergo a water deprivation test (Fig 1). Based on the interpretation of the test results, treatment with oral desmopressin was prescribed. This was complicated by the onset of headache and nausea within 48 hours of starting treatment. Serum sodium levels were obtained and found to be low at 128 mEq/L, and desmopressin therapy was immediately stopped.
Results of a prior urologic assessment had been unremarkable. The patient had no significant surgical, social, or family history. Home medications included a stable dose of extended-release bupropion, 150 mg, daily; buspirone, 15 mg, 3 times a day; and clonazepam, 1 mg, 3 times a day as needed.
On physical examination, the patient was noted to be slightly anxious, well nourished, and in no acute distress. Vital signs showed blood pressure of 124/74 mm Hg and pulse rate of 63 beats/min. She was afebrile, weight was 65 kg, and body mass index was 19.95 kg/m2. Skin turgor was normal, oral mucosa was moist, and no edema was noted. Findings from the rest of the examination were unremarkable.
At the time of the evaluation, the patient had been restricting her fluid intake to 5.7 L/d and reported feeling “dehydrated.” Laboratory data showed serum sodium level of 143 mEq/L, serum osmolality of 295 mOsm/kg, and daily urine output of 7.8 L (Table 1). At this time, a 24-hour urine specimen was obtained to measure daily sodium, potassium, urea nitrogen, and creatinine excretion (Table 2). Results revealed remarkably high daily urinary excretion of 1,630 osmoles, suggesting high dietary solute intake.
On obtaining additional dietary history, the patient reported consuming a high-protein diet that included 4 oz of meat at each meal and a protein shake (Premier Protein, Premier Nutrition Corporation, St. Louis, MO) with 30 g of protein and a protein bar (Pure Protein, United States Nutrition, Inc., Bohemia, NY) with 20 g of protein. Her daily protein intake amounted to 133 g (2.0 g/kg/d). She also reported eating spinach (two 5-oz servings per day), broccoli, and cantaloupe daily, explaining her high potassium intake of 179 mEq/d. At the same time, she was not restricting sodium intake in her diet.
Therefore, the patient was advised to make dietary changes in order to restrict daily intake of sodium to <120 mEq/d, potassium to <100 mEq/d, and protein to 1.0 g/kg.
Polyuria due to solute and water diuresis.
The patient successfully followed these recommendations. Three weeks later, a new 24-hour urine specimen was collected to re-examine her daily solute excretion and urine volume. Results showed a significant reduction in daily solute excretion (Table 2). She reported feeling less thirsty as these dietary changes took effect. Concomitantly, her nocturia and polyuria improved and urine volume returned closer to a normal range of 3.5 L/d. She did not require additional therapy and continues to do well at the present time.
We present an interesting case of polyuria secondary to mixed water and solute diuresis with near-normal serum sodium levels. Polyuria may be seen in the inpatient setting due to administration of high protein feeds, uncontrolled hyperglycemia, and renal salt wasting due to cisplatin or cerebral salt wasting,
among other causes. However, solute diuresis leading to polyuria is rarely seen in the outpatient setting and may be easily confused with psychogenic polydipsia or diabetes insipidus. This interesting case highlights the importance of estimating daily solute excretion in the routine workup of polyuria. This essential step may often be overlooked but could be the answer to a perplexing clinical presentation, as seen in this patient (Fig 2).
Polyuria can be secondary to water or solute diuresis. Urine volume is in direct relation to the total number of osmoles excreted per day. Solutes responsible for driving water excretion could be electrolytes, such as sodium and potassium, or urea, glucose, and mannitol.
The daily osmole excretion is estimated to be ∼10 mOsm/kg, or 500 to 750 mOsm/d, leading to obligate water losses with the solutes. When solute intake is >900 mOsm/d, a noticeable increase in urinary volume is seen.
which was done one week prior to the patient’s evaluation. The patient was able to achieve high urine osmolality of 650 mOsm/kg after 12 hours of water deprivation. Despite achieving high urine osmolality, the patient inappropriately received desmopressin at that point, which did not result in a further increase in urine osmolality (Fig 1). Subsequently, results of the test were mistakenly interpreted as partial central diabetes insipidus, which led the treating physician to prescribe oral desmopressin. As a result, the patient developed iatrogenic hyponatremia, reflecting her habitual excessive water intake. Psychogenic polydipsia remained in the differential diagnosis. However, this clinical entity often results in suppression of vasopressin and urine osmolality < 100 mOsm/kg at presentation,
which was not the case in this patient. In search for other causes to explain the polyuria, we obtained a 24-hour urine collection for electrolytes, glucose, creatinine, and urea nitrogen. Her daily osmole excretion was calculated at 1,630 osmoles (Table 2), which is considerably higher than the expected average solute excretion based on a standard Western diet. We also performed a calculation for electrolyte free water excretion using the formula:
where UNa is urine sodium, UK is urine potassium, and SNa is serum sodium. The calculation was noted to be high at 5.5 L.
This can be attributed to osmotic diuresis from the high daily solute intake. Another important diagnostic indicator was the measured urine osmolality of 214 mOsm/kg, which is suggestive of a mixed polyuria rather than a pure solute or water diuresis
Consequently, institution of dietary changes to decrease total protein and electrolyte intake was recommended to the patient, and she was able to successfully reduce her daily solute intake. With this intervention, urine volume decreased significantly from 7.8 to 3.5 L/d, thus confirming the role of solute loading and excessive water intake in causing her polyuria.
The key difference in this case compared to intubated mechanically ventilated patients receiving total parenteral nutrition is that this patient drank water to match the urine losses and avoided significant hypernatremia. In contrast, intubated critically sick patients receiving total parenteral nutrition develop hypernatremia because they are unable to drink a copious amount of water to match the water losses. Polyuria persists as long as high solute intake does. If solute excretion diminishes, water loss diminishes and a decrease in thirst and water intake ensues.
Serum sodium level was 143 mEq/L on initial evaluation. Although this value is close to normal, it is reflective of a mild degree of hypernatremia. The patient had attempted to restrict her water intake for 3 days preceding the evaluation. However, despite this restriction, she was still drinking a large amount of water and arrived mildly hypernatremic. Thus, this finding highlights the pivotal role of solute loading in inducing polyuria in this patient despite excessive water intake. If present alone, this would have otherwise led to hyponatremia. Subsequently, serum sodium levels normalized after the dietary modifications took place.
In this age of health awareness, nutritional and protein supplements are abundantly available over the counter and heavily advertised to the general public or at athletic clubs and gymnasiums. Inadvertent increased solute intake through various dietary sources, including high-protein shakes, powders, and bars, can often be overlooked, leading to high solute excretion and polyuria. In parallel, the desire to stay well hydrated may result in excessive fluid intake and the ensuing phenomenon of habitual polydipsia.
As a result, an additive scenario of increased solute load and water diuresis can occur and mimic the clinical presentation of other more traditional forms of polyuria, such as diabetes insipidus or psychogenic polydipsia.
In conclusion, accurate estimation of daily urinary osmole excretion, as well as the nature of the osmoles, are of paramount importance and should be included in the routine evaluation of polyuria (Box 1; Fig 2).