What is the difference between osmotic and water diuresis

Results are presented as counts and percentages and as median, first and third quartile. Patient characteristics are given in Table 1.

All patients received enteral nutrition during time of rise in serum sodium and were intubated and sedated. All patients were normonatraemic on admission except for one patient who was hyponatraemic.

During ICU stay, serum sodium began to rise to finally reach hypernatraemia. During rise of serum sodium, none of the patients received either furosemide or mannitol. Five patients received hydrocortisone treatment during the rise in serum sodium and six patients received catecholamines. Figure 1 shows the course of serum sodium starting with the day of rise until the maximum sodium concentration. Characteristics of patients with ICU-acquired hypernatraemia due to osmotic urea diuresis.

The fractional excretion of sodium was 0. Table 2 gives an overview of fluid and electrolyte balances of days of rising serum sodium compared to days with stable serum sodium. Fluid and electrolyte balances of patients during development of hypernatraemia and during time of stable serum sodium a. Values are presented as median and first and third quartiles. In order to illustrate the pathophysiologic mechanisms leading to hypernatraemia due to osmotic diuresis, we also describe 10 patients with episodes of ICU-acquired hypernatraemia due to sodium gain.

In this study, we characterized a series of patients with ICU-acquired hypernatraemia caused by osmotic urea diuresis. We showed that calculation of FWC as a measure of renal water handling, as often postulated in textbooks and publications [ 15—17 ], is misleading in the setting of osmotic urea diuresis.

On the contrary, calculation of EFWC explicitly indicated renal loss of free water as the cause of rising serum sodium levels. The association of tube feeding with hypernatraemia and azotaemia was made early in the literature [ 18 , 19 ]. However, current studies focusing on the etiology of hypernatraemia in critically ill patients often do not take this important constellation into account [ 4 ].

Previous studies could show the association between the occurrence of hypernatraemia in the ICU and an increase in mortality [ 1 , 20—24 ]. This together with known effects of hypernatraemia on metabolism and cardiac as well as neurologic function should create awareness for rising serum sodium levels [ 2 , 7 , 25—27 ].

When serum sodium begins to rise, a thorough analysis of fluid and electrolyte balance on basis of total infused fluids and nutrition solutions as well as fluid and electrolyte output as measured by urinalysis is indicated. Thus, it seems logical that the osmolality-based FWC has no role in the differential diagnosis of sodium disorders.

On the contrary, EFWC, based on the relation of urinary sodium and potassium to serum sodium clearly showed ongoing renal loss of free water in our patients, making it a valuable tool in the differential diagnosis of polyuria and consequently hypernatraemia.

Especially in the intensive care setting, where urinalysis and 24 h urine measurement are often performed routinely, the calculation of EFWC under circumstances of rising serum sodium values can be of help in the differential diagnosis of polyuria and hypernatraemia.

Additionally, EFWC might help guiding therapy for the correction of hypernatramia. It allows an estimation of how much free water is lost at the moment, which is equal to the minimum amount of free water that has to be given to the patient in order to at least keep the momentary serum sodium.

In daily clinical practice, when serum sodium starts to rise in a patient who is receiving enteral nutrition or is in a catabolic state , polyuria combined with a high urea in urine which is exceeding the amount of sodium and potassium in urine should be considered a hint for the presence of osmotic urea diuresis without use of formulas.

Under these circumstances, steps should be undertaken to reduce the urea load for the patient or if this is not possible to provide enough free water e. Nevertheless, calculation of EFWC will rapidly answer the question of whether renal loss of free water is present or not. In any case of rising serum sodium, urine chemistry is necessary to determine the cause.

In our patients, we tried to differentiate whether urea stemmed from enteral nutrition or catabolism, which was difficult since five of the patients experienced acute kidney injury during their ICU stay, making the comparison of actual protein intake by enteral nutrition and the calculated protein equivalent output difficult.

Moreover, administration of steroids as often performed in critically ill patients led to an increase in protein catabolism. However, the absolute rise in creatinine in these patients makes a significant concentration defect unlikely so this should not be influencing our results. Our study is limited by its retrospective design and the small patient number.

The potentially helpful role of calculation of EFWC in the differential diagnosis of hypernatraemia in critically ill patients should be examined in a prospective study. Fractional excretion of sodium was quite low in our patients potentially indicating volume contraction.

On the other hand, central venous pressure was 16 mmH 2 O, which at least should rule out more severe hypovolaemia. In conclusion, we present a series of seven critically ill patients with ICU-acquired hypernatraemia with the often neglected diagnosis of osmotic urea diuresis. We could show that calculation of EFWC identifies ongoing renal loss of free water, while the classic FWC indicates water retention by the kidney.

Physicians should be aware of osmotic diuresis due to urea as the cause of polyuria and rising serum sodium values. Google Scholar. Google Preview. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign In. Advanced Search.

Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Materials and methods. Osmotic diuresis due to urea as the cause of hypernatraemia in critically ill patients.

Effect of Low Potassium Diet The kidney and muscle have a role in compensation for acute effects of low potassium diet on urine volume and AQP2 levels. Amlal et al. Interestingly, whereas an early urinary concentrating defect was induced from the down-regulation of cortical AQP2, later onset of the same defect resulted from decreased medullary AQP2 [ 26 ]. Effect of High Protein Diet High protein diets are included in this review because protein intake is a factor in osmotic diuresis.

In addition to electrolytes, such as sodium and potassium, urea from a high protein diet and glucose are the main solutes responsible for osmotic diuresis [ 28 , 29 ]. Total solute loss is higher than the loss of water in osmotic diuresis, and serum osmolality decreases [ 29 ]. Previous studies have shown the effects of high and low-protein diets on the expression of AQP2 [ 30 - 32 ]. Urine concentration decreased after a low-protein diet in both humans and rats.

A decrease in AQP2 protein expression was also accompanied by reduced urine concentrating ability [ 30 , 31 ]. In contrast, a high-protein diet led to increased absorption of water and increased urine AQP2 Effect of Hypercalciuria Hypercalciuria is one of the causes of voiding dysfunction in children, including nocturnal enuresis and daytime frequency syndrome.

The effect of hypercalciuria on AQP2 was investigated in 80 children with NE and 9 controls, 24 hour urine day and night was collected in control and NE groups [ 33 ]. The NE subjects were divided into three groups G1: low vasopressin levels and nighttime diuresis, G2: low vasopressin levels and balanced diuresis, G3: normal vasopressin and daytime diuresis. A study was recently published on how NE can be improved through a low calcium diet using vasopressin in children with NE and hypercalciuria [ 34 ].

The same research group recently reported that there is a relationship between urinary calcium excretion and AQP2 [ 35 ]. Hypercalciuria was induced by bone demineralization for 7 days of adaptation and 24 days of bed rest in 10 healthy men [ 35 ].

Urinary calcium excretion increased in the first 7 days, and then gradually decreased over 35 days. AQP2 excretion increased in the first 7 days, decreased through day 14, and then increased again until day 35 [ 35 ].

One possible explanation for this result is that the increased urinary calcium excretion may temporarily down-regulate AQP2, and since plasma volume is reduced by increased water excretion, AQP2 levels recover after calcium excretion is normalized [ 35 ]. Conclusion The expression of renal AQP2 is mainly regulated by the absorption and excretion of sodium and water. Plasma concentration of other electrolytes, such as potassium and calcium, and nutrients, including protein, ingested through the diet can also regulate AQP2 concentration.

It is relatively clear that AQP2 is upregulated by water loading and high protein diet intake and down regulated by water restriction, low protein diet, low K diet and fasting. AQP2 is also down regulated by hypercalciuria Fig. However, the regulation of AQP2 by Na intake is contradictory as shown in table 1.

The contradictory results may be caused by many factors, such as different experimental conditions, and compensatory mechanisms that regulate AQP2.

Urine sampling of AQP2 in spot urine samples has also limited ability to reflect renal AQP2 concentration, and results differ significantly depending on the time to evaluation and duration of specific diets. Because drinking a significant amount of water can induce maximum diuresis after 2 hours, reduced water intake could greatly help to reduce nighttime diuresis.

The effect of a high salt diet on AQP2 expression was shown to be inconsistent in previous studies, and therefore requires further investigation. Hypercalciuria can reduce AQP2 and increase urine volume, so reducing intake of calcium rich foods may also help reduce nighttime diuresis. References 1. Renal aquaporins and water balance disorders. Biochim Biophys Acta. Aquaporins in the kidney: from molecules to medicine.

Physiol Rev. The distribution and function of aquaporins in the kidney: resolved and unresolved questions. Anat Sci Int. Solute and water transport along the nephron: tubular function. Elsevier Mosby, St. Louis: Aquaporins, vasopressin, and aging: current perspectives. Urinary concentration does not exclusively rely on plasma vasopressin.

A study between genders. Gender and diurnal urine regulation. Acta Physiol Oxf. Gender difference in antidiuretic response to desmopressin. Am J Physiol Renal Physiol. Downregulation of aquaporin-2 and -3 in aging kidney is independent of V 2 vasopressin receptor. American journal of physiology Renal physiology. Alterations in circadian rhythmicity of the vasopressin-producing neurons of the human suprachiasmatic nucleus SCN with aging. Brain research. Sex differences in osmotic regulation of AVP and renal sodium handling.

Journal of applied physiology. Comparison of three methods to quantify urinary aquaporin-2 protein. Kidney International. Dissociation between urine osmolality and urinary excretion of aquaporin-2 in healthy volunteers.

J Intensive Care Med ; In critically ill patients, high protein supply, hypercatabolism, gastrointestinal bleeding, and high doses of corticosteroids may promote excessive urea generation, osmotic diuresis, and consequently hypernatremia.

Osmotic diuresis due to urea as the cause of hypernatraemia in critically ill patients. Nephrol Dial Transplant ; The following case report illustrates the diagnostic approach of hypernatremia associated with osmotic diuresis secondary to the excessive urea generation, focusing on the importance of the calculation of electrolyte-free water clearance in this context.

Electrocardiogram showed left bundle branch block, but markers for myocardial necrosis were negative and cardiac catheterization did not show significant obstructions.

Laboratory tests at admission did not demonstrate noteworthy alterations. On the fourth day of hospitalization, she was extubated, but presented severe laryngospasm refractory to clinical measures, as corticoid therapy, needing reintubation. Treatment with 0. Then, during the ventilator weaning process, physical examination evidenced right hemiparesis. Cranial computed tomography revealed a hemorrhagic stroke in the left middle cerebral artery region.

After extubation, the patient remained with aphasia and dysphagia, persisting with the need of enteral diet. Table 1 summarizes the evolution of laboratorial parameters and relevant clinical data. On the 14th day of hospitalization, the nephrology team was assessed for additional investigation of hypernatremia. The patient was clinically hypervolemic, tending to hypertension, with an accumulated positive fluid balance despite diarrhea and febrile condition, and urine volume UV around two liters per day.

Furosemide had been discontinued on the 12th day of hospitalization due to worsening renal function and hypernatremia. According to the estimated weight of 60 kg, she was receiving 1. Based on these results, the diagnosis of hypernatremia was established. Box 1 describes the formulas and calculations used in this case. After diagnosis, the initial approach was the reduction of the protein supply of the enteral diet to 1.

Five days from the establishment of these measures, urinary urea decreased to Likewise, progressive decrease on plasma urea and sodium levels were observed Table 1. This report illustrates a case of hypernatremia of multifactorial etiology in the intensive care unit ICU.

Although furosemide has an initial role in elevating serum sodium levels, we will highlight the role of osmotic diuresis by excessive generation of urea, an underdiagnosed and a not well-known cause of hypernatremia. Although prevalence data in the literature are scarce, the study by Lindner G et al. Below, we discuss a clinical approach to the diagnosis of urea-induced osmotic diuresis and hypernatremia, emphasizing the utility of physiological concepts on the understanding of the development of hypernatremia.

As shown in Figure 1 A, when the UV collected in 24 hours is dismembered, part of the volume is designated to the solute clearance osmolar and part to the water clearance. Osmolar clearance COsm is defined as the part of UV necessary to excrete all solutes, electrolytes sodium, potassium, etc and non-electrolytes urea, creatinine, glucose, etc , in a supposedly isotonic urine compared to plasma.

On the other hand, the portion of UV free from all solutes represents the free water clearance CH 2 O , which can also be defined as the amount of water that needs to be added or removed from COsm in order to complete the total UV measured in 24 hours. In addition, the part of UV that is free only from the solutes composed by electrolytes is called electrolyte-free water clearance C e H 2 O. Electrolyte-free water clearance: a key to the diagnosis of hypernatremia in resolving acute renal failure.

Clin Exp Nephrol ; Figure 1 A. Urinary volume U VOL composition and its relation with osmolar clearance COsm , free-water clearance CH 2 O , and electrolyte-free water clearance C e H 2 O in situations with different urinary tonicity: isosmolar, hypertonic, and hypotonic. Usual situation during a hypertonic urine production: CH 2 O is negative, indicating that the body is saving water. It occurs because of the increase of solute-free water reabsorption in the collecting duct by antidiuretic hormone, referred to as T C H 2 O.

In this scenario, the CH 2 O modulation is specially determined by the antidiuretic hormone ADH , which in turn varies according to the natremia. Usually, in the presence of increased serum osmolarity, the CH 2 O becomes negative due to ADH increase, making the urine hyperosmolar compared to the plasma and indicating that the body is saving water. Conversely, the reduction of serum osmolarity makes CH 2 O positive, and urine osmolarity UOsm turns lower than the plasmatic.

This indicates that the body is losing water.