Phenotyping nocturnal polyuria: circadian and age-related variations in diuresis rate, free water clearance and sodium clearance

Abstract Background this study compares diuresis rate, sodium clearance and free water clearance (FWC) by age and time of day (nighttime vs. daytime) in subjects with and without nocturnal polyuria (NP) to determine whether these variables affect the phenotype of NP. Methods post hoc analysis of two prospective observational studies. Eight urine samples collected at 3-h intervals and a single blood sample were used to calculate daytime (10a/1p/4p/7p/10p) and nighttime (1a/4a/7a) diuresis rates, sodium clearance and FWC. Three mixed linear models were constructed for diuresis rate, sodium clearance and FWC using four predictor variables: NP status (present [nocturnal urine production >90 ml/h] vs. absent [≤90 ml/h]), time of day, age and study identification. Results subjects with NP experienced higher nighttime versus daytime diuresis rates, sodium clearance and FWC. Regardless of NP status, increased age was accompanied by an increase in the ratio of nighttime/daytime diuresis rate, nighttime sodium clearance and daytime sodium clearance. FWC showed a complex age effect, which was independent of time of day or NP status. Conclusions age-related increases in nighttime/daytime diuresis rate, 24-h sodium clearance and 24-h FWC are not specific to subjects with NP. The age-related surge in either nocturnal sodium clearance or nocturnal FWC may represent the relevant substrate for behavioural or pharmacologic interventions targeting sodium diuresis or free water diuresis, respectively. Increases in FWC in older age groups may reflect impaired circadian rhythmicity of endogenous AVP or changes in responsiveness of the aged nephron to water clearance.

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0823 Age-Related Changes in Nocturnal Urine Composition

SLEEP ◽

10.1093/sleep/zsaa056.819 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A313-A314

Author(s):

D L Bliwise ◽

T F Monaghan ◽

J M Lazar ◽

M R Epstein ◽

C W Agudelo ◽

...

Keyword(s):

Linear Models ◽

Free Water ◽

Time Of Day ◽

High Rate ◽

Continuous Measure ◽

Elderly Persons ◽

Free Water Clearance ◽

Age Related ◽

Urine Production ◽

Sodium Clearance

Abstract Introduction In humans sleeping nocturnally, nocturnal polyuria (NP) refers to high rate of overnight urine production. NP is a heterogeneous condition that may reflect both free water and/or sodium diuresis, but the influence of age on differential fluid handling remains poorly understood. This study examined diuresis rate, sodium clearance, and free water clearance (FWC) by age, time of day (nighttime vs. daytime) and NP status (positive/negative) in subjects under entrained conditions sleeping nocturnally. Methods Convenience samples (age range 18-91; 82 men, 148 women) recruited from a urology ambulatory care unit (n=135) or continence clinic (n=95) collected 8 urine samples at 3-hour intervals over a single 24-hr period. Three separate mixed linear models were constructed for diuresis rate, sodium clearance, and FWC using four predictors: NP status (present [>90mL/h] vs. absent), time of day (night = 0100, 0400, 0700), age (as a continuous measure), and study source. Results Subjects with NP experienced both higher nighttime vs. daytime diuresis rate (1.89 vs. 1.44 mL/min, p<0.001), sodium clearance (0.91 vs. 0.74 mL/min, p<0.001), and FWC (-0.38 vs. -0.71 mL/min, p<0.001), whereas subjects without NP demonstrated lower nighttime vs. daytime diuresis rate (0.94 vs. 1.06, p=0.004) and no difference in sodium clearance (0.59 vs. 0.64, p=0.120) or FWC (-0.80 vs. -0.86, p=0.268). Regardless of NP status, FWC increased with age (p=0.039), and older age (>70) was accompanied by an increase in the ratio of nighttime/daytime diuresis rate and both nighttime and daytime sodium clearance. Conclusion Irrespective of NP, older adults experience proportionally greater nocturnal sodium clearance, as well as a complex surge in both daytime and nighttime FWC. The data imply that both nocturnal sodium clearance and FWC may reflect the relevant substrate underlying excess nocturnal urine production in elderly persons. Support N/A

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RENAL DIURESIS AFTER INJECTIONS OF THE FRESHWATER EEL AND ANTIDIURESIS ARGININE VASOTOCIN IN (ANGUILLA ANGUILLA L.)

Journal of Endocrinology ◽

10.1677/joe.0.0610487 ◽

1974 ◽

Vol 61 (3) ◽

pp. 487-500 ◽

Cited By ~ 50

Author(s):

I. W. HENDERSON ◽

N. A. M. WALES

Keyword(s):

Body Weight ◽

Glomerular Filtration ◽

Free Water ◽

Anguilla Anguilla ◽

Arginine Vasotocin ◽

Free Water Clearance ◽

Response Characteristics ◽

Arterial Blood ◽

Urine Production ◽

Water Clearance

SUMMARY The renal responses of the freshwater-adapted eel, Anguilla anguilla L. to arginine vasotocin ([8-arginine]-oxytocin) have been examined. The quality of the responses to the intravenously administered peptide was found to vary with the dose. Less than 0·1 ng/kg body weight reduced glomerular filtration rate, free water clearance and rate of urine production for up to 60 min. Doses greater than 1·0 ng/kg body weight induced a 'glomerular diuresis', i.e. increased rates of urine production, glomerular filtration and free water clearance for 40–60 min. Neither the diuretic nor the antidiuretic doses produce changes in urinary composition, and no obvious direct tubular actions of the peptide were found. Arterial blood pressure, measured in the dorsal aorta, increased with some of the diuretic doses, whilst the lower doses (less than 10 ng/kg body weight) had little or no cardiovascular actions. The mechanisms involved in these dose—response characteristics are discussed with particular regard to the renal function of lower vertebrates. It is suggested that arginine vasotocin plays a primary or secondary role in the modulation of 'glomerular intermittency'.

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Aldosterone increases urine production and decreases apical AQP2 expression in rats with diabetes insipidus

AJP Renal Physiology ◽

10.1152/ajprenal.00158.2005 ◽

2006 ◽

Vol 290 (2) ◽

pp. F438-F449 ◽

Cited By ~ 57

Author(s):

Jakob Nielsen ◽

Tae-Hwan Kwon ◽

Jeppe Praetorius ◽

Jørgen Frøkiær ◽

Mark A. Knepper ◽

...

Keyword(s):

Creatinine Clearance ◽

Diabetes Insipidus ◽

Free Water ◽

Sodium Balance ◽

Apical Plasma Membrane ◽

Sodium Reabsorption ◽

Outer Medulla ◽

Free Water Clearance ◽

Urine Production ◽

Water Clearance

Vasopressin and aldosterone are essential hormones in the regulation of water and sodium balance. Aldosterone regulates sodium reabsorption, although synergistic effects on collecting duct water permeability have been shown. We investigated the effects of 7-day aldosterone infusion or oral spironolactone treatment on water balance and aquaporin (AQP) 2 expression in rats with 21 days of lithium-induced nephrogenic diabetes insipidus (Li-NDI). In rats with Li-NDI, aldosterone markedly increased (271 ± 14 ml/24 h), whereas spironolactone decreased (74 ± 11 ml/24 h) urine production compared with rats treated with lithium only (120 ± 11 ml/24 h). Aldosterone increased free-water clearance and creatinine clearance, whereas spironolactone caused a decreased creatinine clearance but unchanged free-water clearance. Immunoblotting showed unchanged AQP2 expression in cortex/outer stripe of the outer medulla and inner medulla. In the inner stripe of the outer medulla aldosterone caused a decreased AQP2 expression, whereas spironolactone caused an increase compared with rats treated with lithium only. Semiquantitative confocal immunofluorescence microscopy of AQP2 immunolabeling showed reduced AQP2 expression in the apical plasma membrane domain in connecting tubule (CNT) and initial cortical collecting ducts (iCCD) in response to aldosterone-treated rats compared with rats treated with lithium only. Spironolactone significantly increased apical AQP2 expression in the iCCD compared with rats treated with lithium only. We also tested whether similar changes could be observed in vasopressin-deficient BB rats and found similar changes in urine production and subcellular AQP2 expression in the CNT and iCCD in response to aldosterone and spironolactone. This study shows that aldosterone treatment perturbs diabetes insipidus and is associated with AQP2 redistribution in CNT and iCCD likely mediated by the spironolactone-sensitive mineralocorticoid receptor.

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Primate kidney function in hemorrhagic shock as influenced by dibutyryl cyclic AMP

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1976.230.3.724 ◽

1976 ◽

Vol 230 (3) ◽

pp. 724-730 ◽

Cited By ~ 2

Author(s):

EE Selkurt

Keyword(s):

Cyclic Amp ◽

Hemorrhagic Shock ◽

Free Water ◽

Dibutyryl Cyclic Amp ◽

Water Reabsorption ◽

Free Water Clearance ◽

Water Handling ◽

Fractional Clearance ◽

Sodium Clearance ◽

Water Clearance

Standardized hemorrhagic shock was employed to study alterations in electrolyte and water handling in the owl monkey, either normally hydrated or moderately dehydrated. Increase in fractional clearance of osmolarity,sodium, and calcium occurred with retransfusion after the hypotensive phase. In the hydrated animals, free-water clearance became positive, and the urine-to-plasma osmolarity ratio [(U/P)osM] decreased below 1.0. In the dehydrated animals, free-water reabsorption (TCH2O) decreased but remained negative,while (U/P)osM remained above 1.0. Dibutyryl cyclic AMP (DBcAMP) was infused into the renal arterial supply in an attempt to correct a possible deficiency of cyclic AMP production. In the hydrated group, free-water clearance (CH2O) became more positive with infusion, and (U/P)osM decreased even further, with no effect on fractional sodium clearance. Effects were less or absent in the dehydrated group. Possible explanations for the observed effects of DBcAMP are considered. It was concluded that the loss of concentrating power seen in hemorrhagic shock occurs at a step beyond the production of cyclic AMP by adenylate cyclase.

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