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Diurnal urine volume estimates in schizophrenic patients with polydipsia during water-loaded versus nonloaded states
Diurnal Urine Volume Estimates in Schizophrenic Patients with Polydipsia during Water-Loaded versus Nonloaded States Michael S. Shutty, Jr, Robert A. Leadbetter, and Kevin McCulley K e y W o r d s : Polyuria, polydipsia, urine creatinine, urine volume, schizophrenia, water regulation BIOL PSYCHIATRY 1997;41:374--376
Introduction Estimates of diurnal urine volume (DUV) based upon urine creatinine concentrations are frequently used to help diagnose polydipsia and polyuria in schizophrenic patients. Two methods of estimating DUV are available (Koczapski et al 1989; Vieweg et al 1992) with reported associations between methods ranging from kappa coefficients of .70 to correlations of .98, respectively (Verghese et al 1994; Vieweg et al 1992). Goldman et al (1992) reported the overlap of Koczapski's formula with actual 24-hour DUV to be 85% of the variance. It is unclear how sensitive estimated DUV values are to conditions of water loading observed in polydipsic patients. Furthermore, the impact of the frequency and timing of urine creatinine sampling used to estimate DUV remains unassessed. Koczapski's method allows for two urine creatinine samples (taken at 6:00 AM-8:00 AM and 4:00 PM-6:00 PM), whereas Vieweg's formula utilizes two or more urine creatinine samples, prompting the question of whether Q.I.D. versus B.I.D. sampling produces more accurate estimates. Given the frequent impracticality of collecting actual 24-hour DUV, a reliable estimation method is desirable for clinical and research use. We compare these two methods of estimating DUV under
water-loading and nonloading conditions where actual 24-hour fluid intake and DUV are monitored; the use of B.I.D. and Q.I.D. urine creatinine sampling is also compared using Vieweg's method.
Subjects We studied 4 male patients with a DSM-IV diagnosis of schizophrenia who met the following 6-month inclusion criteria: a) two episodes of hyponatremia secondary to polydipsia; b) two episodes of diurnal weight gain greater than 5% of baseline body weight; and c) urine specific gravity less than 1.008. Comprehensive physical and neurological exams were given to exclude patients with endocrine disturbances that alter water regulation (e.g., adrenal insufficiency, hypothyroidism); patients receiving medications known to cause hyponatremia, such as thiazide diuretics and carbamazapines, were excluded. Average age was 35.0 years (SD = 2.8), with a mean illness duration of 17.8 years (SD = 2.6). All patients were stabilized on standard neuroleptic and side-effect medication regimens; the average chlorpromazine (CPZ) equivalence was 1568.75 mg/day (SD = 1306.29).
Procedure From Western State Hospital, Statmton, Virginia; and University of Virginia Medical Center, Charlottesville, Virginia. Address reprint requests to Michael S. Shutty, Jr, PhD, Western State Hospital, Box 2500, Staunton, VA 24402-2500. Received April 8, 1996; revised August 26, 1996.
© 1997 Society of Biological Psychiatry
Patients were placed on water restriction at midnight until 6:00 AM, when they were randomly assigned to either of two counterbalanced conditions both involving water loading and nonloading across two consecutive days. All patients were studied under both conditions. In the loading condition, patients 0006-3223/97/$17.00 PII S0006-3223(96)00433-7
Brief Reports
BIOL PSYCHIATRY 1997;41:374-376
Table 1. Amount of Shared Variance (r 2) between Methods of Estimating Diurnal Urine Volume and Actual Urine Volume Condition Water-loaded
Non-waterloaded
Method/sampling schedulea
r2
Vieweg/6:00 PM, 6:00 AM Vieweg/12:00 PM, 6:00 PM, 12:00 AM, 6:00 AM Koczapski/6:00 PM, 6:00 AM Koczapski/6:00 AM, 6:00 PM Actual fluid intake Urine creatinine concentration (6:00 PM) Vieweg/6:00 PM, 6:00 AM Vieweg/12:00 PM, 6:00 PM, 12:00 AM, 6:00 AM Koczapski/6:00 t'M, 6:00 AM Koczapski/6:00 AM, 6:00 PM Actual fluid intake Urine creatinine concentration (6:00 eta)
5.8 4.0 8.4 10.2 9.6 16.8 3.6 32.5 34.8 60.8 72.2 16.0
h, hours. aThe24-h studyperiodbeganat 6:00AM (day 1) andendedat 6:00AM(day2).
were allowed to increase their water intake until one of the following conditions were met: a) serum sodium less than 130 mmol; b) serum osmolality less than 280; or c) body weight gain of greater than 7% from 6:00 AM weight. In the nonloading condition, water input was limited to 120 mL/hour. Water intake and urine volume were measured using calibrated cups and urinals. Patients were attended by staff in a hospital room throughout the study and were asked to provide a urine sample during each sampling period. Other instances of urination were measured using the urinals; no problems in patient compliance were encountered. Urine creatinine concentrations (UCR) were assessed at 6:00 AM (day 1), 12:00 PM, 6:00 PM, 12:00 AM, and 6:00 AM (day 2). Smoking was limited to one cigarette per hour, and a standard dally diet of 2900 cal (including 7 oz of meat) without caffeine-containing beverages was provided. Using Vieweg's formula, the 6:00 AM weight was multiplied by 20 mg/kg to estimate daily urine creatinine excretion (DUCE). Mean urine creatinine concentration (MUCR) was calculated from at least two samples (mg/dL) spread out during the day. DUV in milliliters = (DUCE/MUCR) × 100. Koczapski's method involved obtaining a 6:00 AM (day l) weight in kilograms (WT) and urine creatinine concentrations (mg/dL) at 6:00 AM (UCR1) and 1800 hours (UCR2). DUV in liters = 0.875 × [(WT/UCR1) + (WT/UCR2)]. For B.I.D. measurement of UCR, we used 6:00 aM and 6:00 AM (day 2) samples. This sampling regimen insures coverage of the entire day's drinking by sampling the midpoint and end point of the 24-hour study period. Our timing capitalizes upon the delay between drinking and both urine creatinine dilution and subsequent voiding, while minimizing carryover effects from the previous day's drinking. We also used 6:00 AM and samples for Koczapski's method, since these specific times were recommended in the literature. Using Vieweg's formula only, Q.I.D. measurement of UCR added 12:00 PM and 12:00 AM samples. All sampling schedules examined are summarized in Table 1.
375
Results On average, patients drank 12.92 L (SD = 2.00) of water and excreted 11.31 L (SD = 1.80) of urine during the water-loading condition, as contrasted with 2.36 L (SD = 0.56) drunk and 5.12 L (SD = 2 . 2 7 ) eliminated during nonloading. The mean 6:00 AM weight change of 1.9% (SD = 0.8) across conditions indicated little carryover effect of fluid retention during the 2-day period, however, patients eliminated more fluid than they drank during nonloading. Data were aggregated and analyzed separately for each condition. Due to the small sample size, we report hivariate regression coefficients (r 2) to indicate the amount of variance shared between the estimated and actual DUV. As seen in Table 1, no estimates of DUV shared more than 17% of the variance with actual DUV in the water-loaded condition. Actual fluid intake did not afford any better prediction than the formulae, whereas the 6:00 PM UCR provided the best prediction of actual DUV with 16.8% shared variance. In contrast, estimates of DUV during the nonloading condition varied widely, sharing as much as 60.8% of the variance with actual DUV (for Koczapski's method using 6:00 AM and 6:00 PM same-day sampling). Actual fluid intake predicted actual DUV slightly better than all other methods with 72% of shared variance, whereas the 6:00 PM UCR shared only 16.0% of the variance.
Discussion Our results demonstrate the impact that fluctuations in drinking (and voiding) behavior can have upon the estimation of DUV. The only adequate prediction coefficient was obtained for Koczapski's method using 6:00 AM and 6:00 PM same-day UCR samples. Goldman et al (1992) reported similar findings, indicating that Koczapski's method with a 60% confidence interval was able to accurately classify their patients as having polyuria (greater than 3 L DUV) without error. Use of actual fluid intake, although impractical, performed better than other prediction methods only in the nonloading condition, whereas 6:00 PM UCR values did not improve prediction in either condition. Further studies employing larger sample sizes need to evaluate UCR sampling protocols with respect to capturing delays in free water clearance, particularly during fluctuating drinking patterns. The potential effects of medication status remain uninvestigated and should be addressed in large-scale studies, as the research literature examining the effects of standard neuroleptic medication upon water homeostasis is equivocal (Leadbetter and Shutty 1994). For research and clinical applications, we advocate using actual DUV whenever possible, as estimated DUV may over- or underestimate actual DUV by nearly 25% on average in the best of conditions. Spot UCR determinations, although frequently used in clinical situations, performed poorly during the n o n water-loading condition, but accounted for 16% of the variance during water loading. Consequently, spot UCR determinations may have limited utility with patients who have been observed drinking heavily, exhibit large diurnal weight gains, and meet the inclusion criteria described earlier.
376
8IOLPSYCHIATRY 1997;41:374-376
Brief Reports
References Goldman MB, Marks RC, Blake L, Petkovic M, Hedeker D, Luchins DJ (1992): Estimating daily urine volume in psychiatric patients: Empiric confirmation. Biol Psychiatry 31: 1228-1231. Koczapski AB, Millson RC, MacEwan GW, Bhopal JS, Ancill RJ (1989): Estimation of fluid intake in polydipsic schizophrenics. Presented at the Second Biannual International Congress on Schizophrenia Research, San Diego, California. Leadbetter RA, Shutty MS (1994): Differential effects of neuro-
leptics and clozapine on polydipsia and intermittent hyponatremia. J Clin Psychiatry 55:110-113. Verghese C, McGrory A, Nair C, McCann E, Martin N, De Leon J (1994): Urine concentration of creatinine: Comparison of methods to detect polyuria. Presented at the 49th Annual Society of Biological Psychiatry Convention, Philadelphia, Pennsylvania. Vieweg WVR, Pandurangi AK, Pelonero AL (1992): Estimating daily urine volume in chronic psychosis. Schizophr Res 8:89-91.
Introduction Estimates of diurnal urine volume (DUV) based upon urine creatinine concentrations are frequently used to help diagnose polydipsia and polyuria in schizophrenic patients. Two methods of estimating DUV are available (Koczapski et al 1989; Vieweg et al 1992) with reported associations between methods ranging from kappa coefficients of .70 to correlations of .98, respectively (Verghese et al 1994; Vieweg et al 1992). Goldman et al (1992) reported the overlap of Koczapski's formula with actual 24-hour DUV to be 85% of the variance. It is unclear how sensitive estimated DUV values are to conditions of water loading observed in polydipsic patients. Furthermore, the impact of the frequency and timing of urine creatinine sampling used to estimate DUV remains unassessed. Koczapski's method allows for two urine creatinine samples (taken at 6:00 AM-8:00 AM and 4:00 PM-6:00 PM), whereas Vieweg's formula utilizes two or more urine creatinine samples, prompting the question of whether Q.I.D. versus B.I.D. sampling produces more accurate estimates. Given the frequent impracticality of collecting actual 24-hour DUV, a reliable estimation method is desirable for clinical and research use. We compare these two methods of estimating DUV under
water-loading and nonloading conditions where actual 24-hour fluid intake and DUV are monitored; the use of B.I.D. and Q.I.D. urine creatinine sampling is also compared using Vieweg's method.
Subjects We studied 4 male patients with a DSM-IV diagnosis of schizophrenia who met the following 6-month inclusion criteria: a) two episodes of hyponatremia secondary to polydipsia; b) two episodes of diurnal weight gain greater than 5% of baseline body weight; and c) urine specific gravity less than 1.008. Comprehensive physical and neurological exams were given to exclude patients with endocrine disturbances that alter water regulation (e.g., adrenal insufficiency, hypothyroidism); patients receiving medications known to cause hyponatremia, such as thiazide diuretics and carbamazapines, were excluded. Average age was 35.0 years (SD = 2.8), with a mean illness duration of 17.8 years (SD = 2.6). All patients were stabilized on standard neuroleptic and side-effect medication regimens; the average chlorpromazine (CPZ) equivalence was 1568.75 mg/day (SD = 1306.29).
Procedure From Western State Hospital, Statmton, Virginia; and University of Virginia Medical Center, Charlottesville, Virginia. Address reprint requests to Michael S. Shutty, Jr, PhD, Western State Hospital, Box 2500, Staunton, VA 24402-2500. Received April 8, 1996; revised August 26, 1996.
© 1997 Society of Biological Psychiatry
Patients were placed on water restriction at midnight until 6:00 AM, when they were randomly assigned to either of two counterbalanced conditions both involving water loading and nonloading across two consecutive days. All patients were studied under both conditions. In the loading condition, patients 0006-3223/97/$17.00 PII S0006-3223(96)00433-7
Brief Reports
BIOL PSYCHIATRY 1997;41:374-376
Table 1. Amount of Shared Variance (r 2) between Methods of Estimating Diurnal Urine Volume and Actual Urine Volume Condition Water-loaded
Non-waterloaded
Method/sampling schedulea
r2
Vieweg/6:00 PM, 6:00 AM Vieweg/12:00 PM, 6:00 PM, 12:00 AM, 6:00 AM Koczapski/6:00 PM, 6:00 AM Koczapski/6:00 AM, 6:00 PM Actual fluid intake Urine creatinine concentration (6:00 PM) Vieweg/6:00 PM, 6:00 AM Vieweg/12:00 PM, 6:00 PM, 12:00 AM, 6:00 AM Koczapski/6:00 t'M, 6:00 AM Koczapski/6:00 AM, 6:00 PM Actual fluid intake Urine creatinine concentration (6:00 eta)
5.8 4.0 8.4 10.2 9.6 16.8 3.6 32.5 34.8 60.8 72.2 16.0
h, hours. aThe24-h studyperiodbeganat 6:00AM (day 1) andendedat 6:00AM(day2).
were allowed to increase their water intake until one of the following conditions were met: a) serum sodium less than 130 mmol; b) serum osmolality less than 280; or c) body weight gain of greater than 7% from 6:00 AM weight. In the nonloading condition, water input was limited to 120 mL/hour. Water intake and urine volume were measured using calibrated cups and urinals. Patients were attended by staff in a hospital room throughout the study and were asked to provide a urine sample during each sampling period. Other instances of urination were measured using the urinals; no problems in patient compliance were encountered. Urine creatinine concentrations (UCR) were assessed at 6:00 AM (day 1), 12:00 PM, 6:00 PM, 12:00 AM, and 6:00 AM (day 2). Smoking was limited to one cigarette per hour, and a standard dally diet of 2900 cal (including 7 oz of meat) without caffeine-containing beverages was provided. Using Vieweg's formula, the 6:00 AM weight was multiplied by 20 mg/kg to estimate daily urine creatinine excretion (DUCE). Mean urine creatinine concentration (MUCR) was calculated from at least two samples (mg/dL) spread out during the day. DUV in milliliters = (DUCE/MUCR) × 100. Koczapski's method involved obtaining a 6:00 AM (day l) weight in kilograms (WT) and urine creatinine concentrations (mg/dL) at 6:00 AM (UCR1) and 1800 hours (UCR2). DUV in liters = 0.875 × [(WT/UCR1) + (WT/UCR2)]. For B.I.D. measurement of UCR, we used 6:00 aM and 6:00 AM (day 2) samples. This sampling regimen insures coverage of the entire day's drinking by sampling the midpoint and end point of the 24-hour study period. Our timing capitalizes upon the delay between drinking and both urine creatinine dilution and subsequent voiding, while minimizing carryover effects from the previous day's drinking. We also used 6:00 AM and samples for Koczapski's method, since these specific times were recommended in the literature. Using Vieweg's formula only, Q.I.D. measurement of UCR added 12:00 PM and 12:00 AM samples. All sampling schedules examined are summarized in Table 1.
375
Results On average, patients drank 12.92 L (SD = 2.00) of water and excreted 11.31 L (SD = 1.80) of urine during the water-loading condition, as contrasted with 2.36 L (SD = 0.56) drunk and 5.12 L (SD = 2 . 2 7 ) eliminated during nonloading. The mean 6:00 AM weight change of 1.9% (SD = 0.8) across conditions indicated little carryover effect of fluid retention during the 2-day period, however, patients eliminated more fluid than they drank during nonloading. Data were aggregated and analyzed separately for each condition. Due to the small sample size, we report hivariate regression coefficients (r 2) to indicate the amount of variance shared between the estimated and actual DUV. As seen in Table 1, no estimates of DUV shared more than 17% of the variance with actual DUV in the water-loaded condition. Actual fluid intake did not afford any better prediction than the formulae, whereas the 6:00 PM UCR provided the best prediction of actual DUV with 16.8% shared variance. In contrast, estimates of DUV during the nonloading condition varied widely, sharing as much as 60.8% of the variance with actual DUV (for Koczapski's method using 6:00 AM and 6:00 PM same-day sampling). Actual fluid intake predicted actual DUV slightly better than all other methods with 72% of shared variance, whereas the 6:00 PM UCR shared only 16.0% of the variance.
Discussion Our results demonstrate the impact that fluctuations in drinking (and voiding) behavior can have upon the estimation of DUV. The only adequate prediction coefficient was obtained for Koczapski's method using 6:00 AM and 6:00 PM same-day UCR samples. Goldman et al (1992) reported similar findings, indicating that Koczapski's method with a 60% confidence interval was able to accurately classify their patients as having polyuria (greater than 3 L DUV) without error. Use of actual fluid intake, although impractical, performed better than other prediction methods only in the nonloading condition, whereas 6:00 PM UCR values did not improve prediction in either condition. Further studies employing larger sample sizes need to evaluate UCR sampling protocols with respect to capturing delays in free water clearance, particularly during fluctuating drinking patterns. The potential effects of medication status remain uninvestigated and should be addressed in large-scale studies, as the research literature examining the effects of standard neuroleptic medication upon water homeostasis is equivocal (Leadbetter and Shutty 1994). For research and clinical applications, we advocate using actual DUV whenever possible, as estimated DUV may over- or underestimate actual DUV by nearly 25% on average in the best of conditions. Spot UCR determinations, although frequently used in clinical situations, performed poorly during the n o n water-loading condition, but accounted for 16% of the variance during water loading. Consequently, spot UCR determinations may have limited utility with patients who have been observed drinking heavily, exhibit large diurnal weight gains, and meet the inclusion criteria described earlier.
376
8IOLPSYCHIATRY 1997;41:374-376
Brief Reports
References Goldman MB, Marks RC, Blake L, Petkovic M, Hedeker D, Luchins DJ (1992): Estimating daily urine volume in psychiatric patients: Empiric confirmation. Biol Psychiatry 31: 1228-1231. Koczapski AB, Millson RC, MacEwan GW, Bhopal JS, Ancill RJ (1989): Estimation of fluid intake in polydipsic schizophrenics. Presented at the Second Biannual International Congress on Schizophrenia Research, San Diego, California. Leadbetter RA, Shutty MS (1994): Differential effects of neuro-
leptics and clozapine on polydipsia and intermittent hyponatremia. J Clin Psychiatry 55:110-113. Verghese C, McGrory A, Nair C, McCann E, Martin N, De Leon J (1994): Urine concentration of creatinine: Comparison of methods to detect polyuria. Presented at the 49th Annual Society of Biological Psychiatry Convention, Philadelphia, Pennsylvania. Vieweg WVR, Pandurangi AK, Pelonero AL (1992): Estimating daily urine volume in chronic psychosis. Schizophr Res 8:89-91.