Establishment and validation of a predictive nomogram for polyuria during general anesthesia in thoracic surgery.

BACKGROUND: To develop and evaluate a predictive nomogram for polyuria during general anesthesia in thoracic surgery. METHODS: A retrospective study was designed and performed. The whole dataset was used to develop the predictive nomogram and used a stepwise algorithm to screen variables. The stepwise algorithm was based on Akaike's information criterion (AIC). Multivariable logistic regression analysis was used to develop the nomogram. The receiver operating characteristic (ROC) curve was used to evaluate the model's discrimination ability. The Hosmer-Lemeshow (HL) test was performed to check if the model was well calibrated. Decision curve analysis (DCA) was performed to measure the nomogram's clinical usefulness and net benefits. P < 0.05 was considered to indicate statistical significance. RESULTS: The sample included 529 subjects who had undergone thoracic surgery. Fentanyl use, gender, the difference between mean arterial pressure at admission and before the operation, operation type, total amount of fluids and blood products transfused, blood loss, vasopressor, and cisatracurium use were identified as predictors and incorporated into the nomogram. The nomogram showed good discrimination ability on the receiver operating characteristic curve (0.6937) and is well calibrated using the Hosmer-Lemeshow test. Decision curve analysis demonstrated that the nomogram was clinically useful. CONCLUSIONS: Individualized and precise prediction of intraoperative polyuria allows for better anesthesia management and early prevention optimization.

Arginine vasopressin deficiency: diagnosis, management and the relevance of oxytocin deficiency.

Polyuria-polydipsia syndrome can be caused by central diabetes insipidus, nephrogenic diabetes insipidus or primary polydipsia. To avoid confusion with diabetes mellitus, the name 'central diabetes insipidus' was changed in 2022 to arginine vasopressin (AVP) deficiency and 'nephrogenic diabetes insipidus' was renamed as AVP resistance. To differentiate the three entities, various osmotic and non-osmotic copeptin-based stimulation tests have been introduced in the past decade. The hypertonic saline test plus plasma copeptin measurement emerged as the test with highest diagnostic accuracy, replacing the water deprivation test as the gold standard in differential diagnosis of the polyuria-polydipsia syndrome. The mainstay of treatment for AVP deficiency is AVP replacement with desmopressin, a synthetic analogue of AVP specific for AVP receptor 2 (AVPR2), which usually leads to rapid improvements in polyuria and polydipsia. The main adverse effect of desmopressin is dilutional hyponatraemia, which can be reduced by regularly performing the so-called desmopressin escape method. Evidence from the past few years suggests an additional oxytocin deficiency in patients with AVP deficiency. This potential deficiency should be further evaluated in future studies, including feasible provocation tests for clinical practice and interventional trials with oxytocin substitution.

Biological Variation Estimates for Plasma Copeptin and Clinical Implications.

BACKGROUND: Plasma copeptin measurement is useful for the differential diagnoses of polyuria-polydipsia syndrome. It has also been proposed as a prognostic marker for cardiovascular diseases. However, limited information is available about the within- (CVI) and between-subject (CVG) biological variation (BV). This study presents BV estimates for copeptin in healthy individuals. METHODS: Samples were collected weekly from 41 healthy subjects over 5 weeks and analyzed using the BRAHMS Copeptin proAVP KRYPTOR assay after at least 8 h of food and fluid abstinence. Outlier detection, variance homogeneity, and trend analysis were performed followed by CV-ANOVA for BV and analytical variation (CVA) estimation with 95% confidence intervals. Reference change values (RCVs), index of individuality (II), and analytical performance specification (APS) were also calculated. RESULTS: The analysis included 178 results from 20 males and 202 values from 21 females. Copeptin concentrations were significantly higher in males than in females (mean 8.5 vs 5.2 pmol/L, P < 0.0001). CVI estimates were 18.0% (95% CI, 15.4%-21.6%) and 19.0% (95% CI, 16.4%-22.6%), for males and females, respectively; RCVs were -35% (decreasing value) and 54% (increasing value). There was marked individuality for copeptin. No result exceeded the diagnostic threshold (>21.4 pmol/L) for arginine vasopressin resistance. CONCLUSIONS: The availability of BV data allows for refined APS and associated II, and RCVs applicable as aids in the serial monitoring of patients with specific diseases such as heart failure. The BV estimates are only applicable in subjects who abstained from oral intake due to the rapid and marked effects of fluids on copeptin physiology.

Antidiuretic hormone deficiency secondary to inactive hydrocephalus: a case report.

BACKGROUND: Diabetes insipidus is a syndrome characterized by polyuria, which is almost always associated with polydipsia. The most frequent cause is central diabetes insipidus, which is the result of an inadequate secretion of the antidiuretic hormone, and diagnosis involves differentiating it from other causes of polyuria and polydipsia. CASE PRESENTATION: Here, we present a clinical case of a previously healthy 13-year-old Nepali boy, who, in December 2022, was found to have intense polydipsia accompanied by polyuria. He had bilateral lower limb weakness at the time of presentation. Biochemical evaluation demonstrated raised serum sodium (181 mEq/L), serum creatinine (78 µmol/L), and serum uric acid (560 µmol/L) with suppressed serum potassium (2.7 mEq/L), which was the major concern to the clinicians. Further laboratory workup revealed an increased serum osmolarity (393.6 mOsm/kg) with reduced urine osmolarity (222.7 mOsm/kg). On contrast magnetic resonance imaging of the brain, a thick-walled third ventricular cyst with bilateral foramen obstruction, thin membrane-like structure at top of aqueduct of Sylvius with gross obstructive hydrocephalus (inactive), and compressed and thinned pituitary gland with no bright spot was observed. The laboratory findings, radiological findings, and case presentation provided the provisional diagnosis of diabetes insipidus due to hydrocephalus and third ventricular cyst. CONCLUSIONS: Central diabetes insipidus due to hydrocephalus, though rare, can have serious complications including the predilection to develop a deficit of other pituitary hormones. Thus, even if hydrocephalus is dormant with normal intracranial pressure, it must be addressed during investigations of central diabetes insipidus.

The diagnostic performance of copeptin in clinical practice: A prospective study.

OBJECTIVE: Plasma copeptin is a relatively new biomarker for evaluation of arginine vasopressin (AVP) secretion. The aim of this study was to test the diagnostic performance of copeptin in patients with polyuria-polydipsia syndrome. DESIGN, PATIENTS AND MEASUREMENTS: This was a prospective study where 88 patients with polyuria-polydipsia syndrome were evaluated with a water deprivation test (WDT). Weight, urine osmolality, urine specific gravity, and plasma copeptin were collected at baseline, after 8 h, and at termination of the WDT when one of the following had been reached: (i) >3% weight reduction, (ii) urine specific gravity >1.017 or urine osmolality >600 mOsm/kg, or (iii) intolerable adverse symptoms. RESULTS: Of 88 patients (57 women), 21 (24%) were diagnosed with central diabetes insipidus (cDI), 5 (6%) with nephrogenic DI (nDI), and 62 (71%) with primary polydipsia (PP). Median (interquartile range) copeptin at baseline was 1.7 (1.4-2.5) pmol/L in cDI, 22 (18-65) pmol/L in nDI, and 2.7 (2-4) pmol/L in PP. After 8 h of WDT, the highest copeptin in patients with cDI was 4.0 pmol/L. In patients with PP: (i) 41 had urine osmolality <600 mOsm/kg, 7 (17%) of these had copeptin >4.0 pmol/L, (ii) 21 had urine osmolality ≥600 mOsm/kg, 14 (67%) of these had copeptin >4.0 pmol/L. CONCLUSIONS: Copeptin >4.0 pmol/L after an overnight WDT can be used to rule out cDI and copeptin ≥21 pmol/L at baseline to diagnose nDI. The diagnostic performance of copeptin in the context of the WDT is otherwise limited in the diagnostic work-up of patients with polyuria-polydipsia syndrome.

The laboratory investigation of diabetes insipidus: A review.

Diabetes insipidus (DI) is a group of disorders that lead to inappropriate production of large volumes of dilute urine. The three main forms are central DI (CDI), nephrogenic DI (NDI) and primary polydipsia (PP). Differentiating CDI/NDI from PP is important as patients with true DI are at risk of severe dehydration without treatment. Biochemical testing is key in the diagnosis of DI. The indirect water deprivation test (WDT) is commonly used in the investigation of DI but has drawbacks including being cumbersome and sometimes producing equivocal results. Direct measurement of AVP has theoretical advantages but has generally only been used in specialist centres. Disadvantages include the requirement to measure AVP under hypertonic stimulation and pre-analytical/analytical challenges. Copeptin (CT-proAVP) is a proxy marker for AVP that is more stable, easier to measure and has been studied more widely in recent years. Historically, the evidence supporting the diagnostic performance of these tests has been relatively poor, being based on a few small, usually single-centre studies. However more recent, well-designed prospective studies are improving the evidence base for investigation of DI. These studies have focused on the utility of copeptin measurements during stimulation tests. There is evidence that measurement of copeptin under stimulation offers improved diagnostic performance compared to the WDT. There is currently a lack of systematic, evidence-based guidelines on the diagnosis of DI, but as the quality of the evidence defining the diagnostic performance of tests for DI continues to improve, a clearer consensus on the optimal approach should become achievable.

An exceptional cause of polyuria-polydipsia syndrome in a 10-year-old boy.

Polyuria-polydipsia syndrome is a frequent symptom in pediatrics, primarily attributed to diabetes mellitus. In the context of diabetes insipidus, this syndrome can stem from central or nephrogenic factors. Sjögren's syndrome, an uncommon autoimmune disease in children, can affect multiple organs. Kidney involvement as described in adults is usually related to glomerular or tubular impairment, often linked to distal tubular acidosis. As a kidney involvement during childhood, Sjögren's syndrome has rarely been reported. Hereby, we present the case of Sjögren's syndrome revealed by polyuria-polydipsia syndrome in a 10-year-old boy.

The diagnostic role of arginine-stimulated copeptin in the differential diagnosis of polyuria-polydipsia syndrome (PPS) in pediatric age.

PURPOSE: In recent years, copeptin stimulation through arginine administration has been evaluated as a new potential tool in the differential diagnosis of polyuria-polydipsia syndrome (PPS) in adults; to date very few data, all retrospective, exist in pediatric age. The aim of this prospective study is to evaluate the diagnostic performance of the arginine-stimulation test for copeptin in a cohort of pediatric patients affected by PPS. METHODS: All children (<18 years) referred to the Department of Pediatric Endocrinology of the Regina Margherita Children Hospital for polyuria-polydipsia in the period January 2021-June 2023 were enrolled. The Arginine-stimulation test for copeptin was performed in all patients presenting PPS after water deprivation test (WDT). Patients with polyuria-polydipsia were then classified as having primary polyuria (PP), complete and partial central diabetes insipidus (CDI), according to the standardized interpretation. Arginine-stimulation test for copeptin was also performed in a control cohort. RESULTS: A significant difference in arginine-stimulated copeptin values was observed at baseline (p = 0.005), at 60 min (p = 0.01), and at 90 min (p = 0.005) in 7 subjects presenting PP, 6 patients affected by CDI and 50 subjects of the control cohort. Plasma osmolality values remained stable at all measurements. The arginine-stimulated copeptin test demonstrated sensitivity and specificity of 100%, whereas the sensitivity of the WDT test was 83.3% and the specificity was 85.7%. CONCLUSION: Given the reliability and the minor adverse effects and costs, the copeptin level after arginine administration could replace the WDT in the diagnostic workup of these in pediatric age.

The prevalence and predictive factors of nocturnal polyuria in Japanese patients with nocturia: a multicentral retrospective cohort study.

The aims of this study were to determine the prevalence and predictors of nocturnal polyuria (NP) in Japanese patients. This multicentral, observational study enrolled patients with the chief complaint of nocturia at 17 Japanese institutions between January 2018 and December 2022. The frequency of daily voiding and volume of urination were evaluated using bladder diaries. NP was diagnosed in patients with an NP index of > 33%. The primary endpoint was NP prevalence in patients with nocturia. The secondary endpoints were the prevalence of NP according to sex and age and the identification of factors predicting NP. This study analyzed 875 eligible patients. NP was present in 590 (67.4%) patients, with prevalence rates of 66.6% and 70.0% in men and women, respectively. Age ≥ 78 years, body mass index (BMI) < 23.0 kg/m2, and patients with ischemic heart or cerebrovascular disease were significant predictors of NP (P < 0.001, P < 0.001, P = 0.014, P = 0.016, respectively). This is the first large multicenter study to investigate the prevalence of NP in Japanese patients with nocturia. NP has a prevalence of 67.4%. Significant predictors of NP include age, BMI, and cardiovascular disease.

Use of copeptin in interpretation of the water deprivation test.

INTRODUCTION: Currently, the water deprivation test remains the standard method for distinguishing primary polydipsia (PP) from cranial diabetes insipidus (cDI) and nephrogenic diabetes insipidus (nDI). There is increasing interest in a direct estimate of antidiuretic hormone using plasma copeptin as a stable and reliable surrogate marker. We present our experience of measuring copeptin during the water deprivation test. METHODS: Forty-seven people (17 men) underwent a standard water deprivation test between 2013 and 2021. Plasma copeptin was measured at the start of the test and at the end of the period of water deprivation (maximum osmotic stimulation). Results were classified using prespecified diagnostic criteria. As it is known that a significant proportion of tests will reveal indeterminate results, a final diagnosis was obtained by including relevant pre- and post-test clinical criteria. This diagnosis was then used to plan individual treatment. RESULTS: Basal and stimulated copeptin were significantly higher in the nephrogenic DI group than other categories (p < .001). There was no significant difference in basal or stimulated copeptin between PP, cDI or partial DI. Nine results were indeterminate where the serum and urine osmolality did not give a unified diagnosis. Stimulated copeptin was helpful in reclassifying these patients into the final diagnostic groups. CONCLUSION: Plasma copeptin has additional clinical utility in interpretation of the water deprivation test and may continue to have a place alongside newer stimulation tests.

Impact of Nocturnal Polyuria and Sleep Quality in Kidney Transplant Recipients With Nocturia.

BACKGROUND: To investigate the quality of life (QOL) of patients with nocturia after kidney transplantation (KT) and the association between nocturnal polyuria and sleep quality. METHODS: In a cross-sectional study, a patient who consented was evaluated using the following items: international prostate symptom QOL score, nocturia-quality of life score, overactive bladder symptom score, Pittsburgh sleep quality index, bladder diary, uroflowmetry, and bioimpedance analysis. Clinical and laboratory data were obtained from medical charts. RESULTS: Forty-three patients were included in the analysis. Approximately 25% of patients urinated once at night, and 58.1% had nocturia twice. Nocturnal polyuria was observed in 86.0% of patients, and overactive bladder was observed in 23.3% of patients. According to the Pittsburgh sleep quality Index, 34.9% of patients had poor sleep quality. Multivariate analysis revealed that patients with nocturnal polyuria tended to have a high estimated glomerular filtration rate (P = .058). On the other hand, multivariate analysis for poor sleep quality revealed that high body fat percentage and low nocturia-quality of life total score were independently correlated factors (P = .008 and P = .012, respectively). Furthermore, the patients with nocturia ≥3/night were significantly older than those with nocturia ≤2/night (P = .022). CONCLUSION: Nocturnal polyuria, poor sleep quality, and aging may decrease the QOL of patients with nocturia after KT. Further investigations, including optimal water intake and interventions, can lead to better management after KT.

[Post-obstructive diuresis, by the internal physician]. / Le syndrome de levée d'obstacle, vu par l'interniste.

Post-Obstructive Diuresis (POD) is a polyuria that occurs following the release of an obstruction from the urinary tract that prevents the flow of urine. POD requires prompt diagnosis to avoid complications. Although its pathophysiology is better understood, there is little scientific evidence for its treatment. Restoration of renal homeostasis requires correction of blood volume and electrolyte disturbances to prevent complications, which can be serious. In this article, we propose a synthesis of knowledge on the subject, as well as a management strategy.

Transient diabetes insipidus in critically ill COVID19 patients.

PURPOSE: Vasopressin has become an important vasopressor drug while treating a critically ill patient to maintain adequate mean arterial pressure. Diabetes insipidus (DI) is a rare syndrome characterized by the excretion of a large volume of diluted urine, inappropriate for water homeostasis. We noticed that several COVID19 patients developed excessive polyuria suggestive of DI, with a concomitant plasma sodium-level increase and/or low urine osmolality. We noticed a temporal relationship between vasopressin treatment cessation and polyuria periods. We reviewed those cases to better describe this phenomenon. METHODS: We retrospectively collected COVID19 ECMO patients' (from July 6, 2020, to November 30, 2021) data from the electronic medical records. By examining urine output, urine osmolality (if applicable), plasma sodium level, and plasma osmolality, we set DI diagnosis. We described the clinical course of DI episodes and compared baseline characteristics between patients who developed DI and those who did not. RESULTS: Out of 37 patients, 12 had 18 episodes of DI. These patients were 7 years younger and had lower severity scores (APACHE-II and SOFA). Mortality difference was not seen between groups. 17 episodes occurred after vasopressin discontinuation; 14 episodes were treated with vasopressin reinstitution. DI lasted for a median of 21 h, with a median increase of 14 mEq/L of sodium. CONCLUSIONS: Temporary DI prevalence after vasopressin discontinuation in COVID19 ECMO patients might be higher than previously described for vasopressin-treated patients.

Nocturnal polyuria in women: results from the EpiNP study.

INTRODUCTION AND HYPOTHESIS: Data from a large US population-based, cross-sectional, epidemiological study (the EpiNP Study) were used to assess the symptoms and bother experienced by women with nocturnal polyuria (NP). METHODS: Consenting participants recruited from an online panel completed the baseline EpiNP survey online (Lower Urinary Tract Symptoms Tool and urological comorbidities). All reporting ≥2 voids/night and a random sample of 100 respondents, each reporting 0 or 1 void/night were asked to complete a 3-day web-based bladder diary recording time, volume, and urgency rating of each void. NP was calculated by the proportion of urine production that occurred during nocturnal hours using a Nocturnal Polyuria Index (NPI33) threshold of >0.33 or nocturnal urine production of >90 ml/h (NUP90). The frequency of participants reporting LUTS and bother was determined by age and NP: idiopathic NP, NP associated with overactive bladder (NPOAB), NP associated with comorbidities (NPCom), and no NP (did not meet NP criteria). RESULTS: A total of 5,290 women completed the baseline survey. Mean age (range) was 54.9 (30-95) years; 1,841 (34.8%) reported ≥2 nocturnal voids. The prevalence of LUTS increased across the lifespan; however, bother associated with each LUTS decreased with increasing age. The percentage of women rating bother by nocturia episodes ≥2 "> somewhat" ranged from 40.3% to 68.3%, with bother ratings highest in the NPOAB and No NP groups. CONCLUSIONS: NP is prevalent in women with considerable bother and is often associated with other urinary symptoms. Multifactorial causes and potential treatments of NP should be considered, particularly at a later age.

A case of nephrogenic diabetes insipidus likely caused by anti-neutrophil cytoplastic antibody-associated vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a relatively rare form of autoimmune disease. Diabetes insipidus (DI) is characterized by diluted polyuria and thirstiness, and is clinically categorized into central and nephrogenic DI depending on damaged organs. In most previously reported cases, ANCA-related disorders have been implicated in central DI, which is attributed to impaired secretion of arginine vasopressin (AVP) from the posterior pituitary. However, no previous case of AAV-related nephrogenic DI has been reported in the English literature. Herein, we report a case of nephrogenic DI likely caused by AAV. A 76-year-old man was admitted to our hospital for acute kidney injury. He showed dehydration, polyuria, and polydipsia. Laboratory tests demonstrated elevated levels of serum urea and creatinine and a high myeloperoxidase ANCA titer. In the present case, both plasma AVP concentration and response of AVP secretion to 5% saline load test were normal. In addition, 1-desmino-8-arginine vasopressin administration could not increase urinary osmolarity. Kidney biopsy specimen revealed tubulointerstitial nephritis with findings that appeared to indicate peritubular capillaritis. Therefore, the patient was diagnosed with nephrogenic DI likely owing to ANCA-associated tubulointerstitial nephritis. Immediately after prednisolone administration, urinary volume decreased, urinary osmolarity increased, and kidney function was improved. This case demonstrates that AAV that extensively affects the tubulointerstitial area can result in nephrogenic DI.

A 75-Year-Old Woman with a 5-Year History of Controlled Type 2 Diabetes Mellitus Presenting with Polydipsia and Polyuria and a Diagnosis of Central Diabetes Insipidus.

BACKGROUND Central diabetes insipidus (CDI) is a rare disorder characterized by large volumes of dilute urine because of a lack of antidiuretic hormone. Co-existing CDI and diabetes mellitus without inherited disorders such as Wolfram syndrome are rare. It is both important and challenging to diagnose this combination because the 2 conditions present with thirst, polydipsia, and polyuria. A few cases of CDI developing in patients with type 2 diabetes mellitus (T2D) have been reported. We report an unusual case of CDI that developed in an older patient with T2D. The aims of this report are to share the clinical course and discuss clues to the early diagnosis of CDI in T2D. CASE REPORT A 70-year-old Japanese woman developed T2D with hyperglycemia symptoms, including thirst, polydipsia, and polyuria. After starting medical treatment, the hyperglycemia and its symptoms improved. The glycated hemoglobin level decreased from 9% to 6%. However, 5 years later (at 75 years of age), she re-exhibited thirst, polydipsia, and polyuria despite stable glycemic control. Her urine volume was large (6.3 L/day). A urine glucose test was negative. The plasma osmolality was high (321 mOsm/kg), while the urinary osmolality was low (125 mOsm/kg). A significant increase in urinary osmolality following vasopressin administration indicated a diagnosis of CDI. Desmopressin therapy effectively relieved the symptoms. CONCLUSIONS This case highlights the need to consider CDI as a rare but important comorbid disorder in patients with diabetes mellitus, including T2D, particularly those presenting with thirst, polydipsia, and polyuria despite well-controlled glycemia.