Poliuria en el adulto. Una aproximación diagnóstica basada en la fisiopatología / Polyuria in adults. A diagnostic approach based on pathophysiology

La poliuria es una condición clínica frecuente caracterizada por un volumen de orina inapropiadamente alto para los niveles de presión arterial y sodio plasmático del paciente (volumen de orina >3L/24h). Desde el punto de vista fisiopatológico se clasifica en 2 tipos: debido a una mayor excreción de solutos (osmolaridad urinaria >300mOsm/L) o debido a una incapacidad de aumentar la concentración de solutos (osmolaridad urinaria <150mOsm/L). En ocasiones pueden coexistir ambos mecanismos (osmolaridad urinaria 150-300mOsm/L). La poliuria supone un reto diagnóstico y su tratamiento correcto exige una evaluación de la historia clínica, la determinación de la osmolaridad urinaria, la estimación del aclaramiento de agua libre, el uso de pruebas de deprivación hídrica en la poliuria acuosa y la medición de electrólitos en sangre y orina en el caso de la poliuria osmótica (AU)

Polyuria is a common clinical condition characterized by a urine output that is inappropriately high (more than 3 liters in 24 hours) for the patient's blood pressure and plasma sodium levels. From a pathophysiological point of view, it is classified into two types: polyuria due to a greater excretion of solutes (urine osmolality >300 mOsm/L) or due to an inability to increase solute concentration (urine osmolality <150 mOsm/L). Sometimes both mechanisms can coexist (urine osmolality 150-300 mOsm/L). Polyuria is a diagnostic challenge and its proper treatment requires an evaluation of the medical record, determination of urine osmolality, estimation of free water clearance, use of water deprivation tests in aqueous polyuria, and measurement of electrolytes in blood and urine in the case of osmotic polyuria (AU)

Management of severe polyuria in idiopathic Fanconi syndrome.

BACKGROUND: Polyuria is a common problem in patients with tubular diseases, especially for those with CKD and high-output Fanconi syndrome. There are currently no guidelines on how to treat debilitating polyuria, in children or adults, and vasopressin is usually not effective. CASE-DIAGNOSIS/TREATMENT: A 13-year-old female with idiopathic Fanconi syndrome and an eGFR of 69 mL/min/1.73 m2 was severely affected by polyuria of 5 L per day (voiding at least 11 times during the day and up to 8 times at night), impacting her mood (measured by the RCADS-child) and academic performance at school. In the absence of guidelines and with literature discouraging the use of indomethacin in this condition, we attempted indomethacin treatment at a dose of 2 mg/kg divided in two doses with substantial success. Urine output dropped to 2.5L and this was accompanied by a substantial decrease of her sodium wasting from 24.6 to 7.7 mmol/kg/day. Over the course of 18 months, the patient's eGFR dropped temporarily to 60 mL/min/1.73 m2 and was 68 mL/min/1.73 m2 at last follow-up. However, a sodium-23 (23Na) MRI of her thigh revealed ongoing moderate sodium decrease in her skin and substantial Na+ decrease in her muscle when compared to age-matched peers with normal kidney function. CONCLUSIONS: Indomethacin may be a safe and effective treatment option for polyuria in idiopathic Fanconi syndrome.

First voided volume: A novel approach to characterize nocturia.

AIMS: Nocturnal polyuria syndrome (NPS) denotes nocturnal polyuria (NP) in the absence of identifiable contributory factors. The trajectory of nocturnal urine production (NUP; typically expressed as ml/hour) may be useful in delineating between NP patients with versus without NPS, but changes in absolute urine volume, the directly measured substrate for behavioral and pharmacologic interventions targeting nocturnal urine production, have not been well characterized. This study compares the ratio of the first nocturnal voided volume (FNVV) to the nocturnal average voided volume (NAVV) in patients with versus without NPS. METHODS: Secondary analysis of 24-h voiding diaries from male patients greater than or equal to 18 years of age with two or more nocturnal voids and NP using two different criteria for NP: NUP greater than or equal to 90 ml/h and nocturnal polyuria index (NPi) greater than or equal to 0.33. Patients with diabetes insipidus and CPAP-adherent obstructive sleep apnea (OSA) were excluded. Patients were divided into 2 groups: secondary NP (OSA, congestive heart failure, and chronic kidney disease) and NPS (absence of edema, diuretic use, and the aforementioned comorbidities). FNVV was defined as the volume of urine accompanying the first nocturic episode. NAVV was defined as nocturnal urine volume/(number of nocturnal voids + 1). The nocturnal urine trajectory ratio (NUTR) was defined as FNVV/NAVV. RESULTS: At NUP greater than or equal to 90 ml/h, NUTR was significantly greater in patients with (n = 73) versus without (n = 28) NPS (1.10 [0.89-1.33] vs. 0.91 [0.55-1.15], p = .012). At NPi greater than or equal to 0.33, NUTR was likewise significantly greater in patients with (n = 92) versus without (n = 32) NPS (1.09 [0.90-1.33] vs. 0.91 [0.57-1.17], p = .010). CONCLUSIONS: The volume of urine produced in the early hours of sleep is central to identification of NPS in patients with nocturia.

Defining nocturnal polyuria in women.

AIMS: Nocturnal polyuria (NP) is defined by the International Continence Society (ICS) as "excessive production of urine during the main sleep period" and is one of the main causes of nocturia. The ICS recognized that "excessive" is not clearly defined and that this needs to be highlighted in both clinical and research settings. The aim of this study was to identify different definitions of NP and apply them to a population of women attending the Urogynaecology clinic. METHODS: This was a retrospective study of complete bladder diaries collected from women attending a tertiary Urogynaecology Unit. Six different definitions were identified and were divided into "absolute," "relative," and "functional definitions." Prevalence data were calculated and values generated for sensitivity, specificity, positive and negative predictive values when related to women voiding ≥ 2 times per night. RESULTS: Complete bladder diaries were obtained from 1398 women, over 6 years, with a mean age of 57 years. Prevalence varied across the definitions from 21.5% (absolute definition) to 77% (relative definition). Sensitivity ranged from 43% (absolute) to 87% (relative). The definitions that showed the highest combined sensitivity and specificity were the functional definitions. CONCLUSION: From this study it is clear that more work needs to be done to arrive at a consensus for defining NP to enable accurate diagnosis and development of treatment pathways. We propose that a relative definition may provide a more clinically relevant method of defining NP.

Associations between nighttime and daytime maximum voided volumes: Relevance for nocturia?

AIM: The relationship between maximum voided volumes (MVV) during the night and day is poorly understood. Such measurements are important because they are often used to indicate functional bladder capacity (FBC), a relevant parameter for nocturia. This study examined the association of such nighttime and daytime measurements in men with nocturia. METHODS: We retrospectively analyzed 356 24-hour voiding diaries showing ≥2 nocturnal voids from 220 men at an outpatient urology clinic. We defined small FBC as MVV ≤ 200 mL. RESULTS: A total of 131 entries demonstrated a nocturnal MVV ≤ 200 mL, of which a majority (98 [74.8%]) also showed a 24-hour MVV ≤ 200 mL (ie, global small FBC), and 33 (25.2%) exceeded the 200 mL threshold during the day (ie, nocturnal-specific small FBC). Correspondingly, among voiding diaries without global small FBC (n = 258), most (225/258 [87.2%]) showed a nocturnal MVV > 200 mL. Data were similar when analyzing only the first complete voiding diary per case, when limiting analyses to those without benign prostatic obstruction, and when limiting analyses to cases with nocturnal polyuria. CONCLUSION: Nocturia may be attributable to nocturnal-specific small FBC or global small FBC. Although the etiology of nocturnal-specific small FBC remains unclear, it was present in a significant minority of patients with small FBC, thus necessitating more directed research. Conversely, diminished nocturnal MVV was nevertheless relatively uncommon in the absence of global small FBC, such that nocturnal-only voiding diaries may provide a rational alternative for follow-up evaluation in patients with nocturia due to global small bladder capacity.

Rationale, design, and methods of electroencephalography-based investigation of the effects of oral desmopressin on improving slow-wave sleep time in nocturnal polyuria patients (the DISTINCT study): protocol for a single-arm, open-label, single-assignment trial.

BACKGROUND: Nocturia is one of the most bothersome lower urinary tract symptoms and often impairs sleep quality in the elderly. Although previous studies on nocturia have indicated that the successful treatment of nocturia improves sleep quality, most used questionnaires and activity devices to analyze sleep/wake patterns. Therefore, there is little information about the treatment effects of desmopressin on objective sleep quality. The aim of the DISTINCT study is to investigate the change in subjective and objective sleep quality using electroencephalography (EEG) and the Pittsburgh Sleep Quality Index (PSQI) after the administration of desmopressin in patients with nocturia due to nocturnal polyuria. METHODS: A total of 20 male patients, ≥65 years old, with nocturnal polyuria, defined as a nocturnal polyuria index (NPi) (nocturnal urine volume / 24 h urine volume) value ≥0.33, will participate in this study. The participants must have a nocturnal frequency of ≥2 and the first uninterrupted sleep period (FUSP) must occur within < 2.5 h. Desmopressin 50 µg per day will be orally administered before going to bed for 4 weeks. Urinary frequency volume charts (FVC) and EEG will be recorded prior to treatment and at 1 week and 4 weeks after the initiation of treatment. The PSQI will be completed before and 4 weeks after treatment. The primary endpoint is the change from baseline in the mean time of slow-wave sleep (sleep stages N3 and N4) at 4 weeks. The secondary endpoints include the change in the mean value of each sleep variable, the mean delta power during the FUSP, the correlation between nocturnal urinary frequency and slow-wave sleep time, and the change in PSQI score before and after treatment. DISCUSSION: The DISTINCT study will provide valuable evidence to indicate that oral desmopressin treatment for nocturnal polyuria prolongs the FUSP, resulting in the extension of slow-wave sleep time associated with sleep quality. TRIAL REGISTRATION: The Japan Registry of Clinical Trials ( jRCTs051190080 ). Registered 9 December, 2019.

Lessons learnt from an old foe.

Neurotuberculosis usually responds well to standard antitubercular therapy. Some; patients have prolonged course A 11 year old boy diagnosed TBM, an immunocompetent patient, had an unusual course of illness in the form of prolonged fever, persistent hyponatremia and CSF; pleocytosis despite adequate treatment. Clinical course in the management of TBM can be; protracted with complications despite adequate therapy.

Prevalence, subtypes, and correlates of nocturia in the symptoms of Lower Urinary Tract Dysfunction Research Network cohort.

AIMS: We determined the prevalence, severity, and correlates of nocturia in a large clinical cohort of patients. METHODS: Patients presenting with lower urinary tract symptoms (LUTS) completed 3-day bladder diaries. Nocturia was quantified based on the mean number of nighttime voids documented over the 3 days. Nocturia subtypes (global polyuria, nocturnal polyuria [NP], reduced global bladder capacity, and reduced nocturnal bladder capacity) were assessed. Bother due to nocturia was measured by the LUTS Tool. Sleep quality was assessed with the Patient-Reported Outcomes Measurement Information System Sleep Scale. Multivariable multinomial regression was used to explore patient characteristics associated with nocturia. RESULTS: In 502 participants with analyzable diaries (285 men and 217 women), the mean number of nocturia episodes over 3 days was 0 in 103 (20.5%), >0 to <1 in 151 (20.1%), 1 to <2 in 165 (32.9%), and ≥2 in 83 (16.5%). Sixty-seven percent of the participants with nocturia ≥1 reported significant bother from their nocturia. NP was the most common nocturia subtype and was present in 17% of those with nocturia = 0, 40% of those with nocturia >0 to <1, 65% of those with nocturia 1 to <2%, and 77% with nocturia 2+. Higher degrees of nocturia were associated with male sex, greater sleep disturbance, and a higher likelihood of exhibiting multiple nocturia subtypes. CONCLUSIONS: Nocturia ≥1 occurred in 49% of LUTS patients and caused significant bother in the majority of them. The most common subtype was NP, but a substantial proportion of patients exhibited additional characteristics.

Time of peak nocturnal diuresis rate between men with secondary nocturnal polyuria versus nocturnal polyuria syndrome.

AIM: Compare the circadian trajectory of diuresis between nocturnal polyuria (NP) patients with versus without identifiable contributory comorbidities. METHODS: Retrospective analysis of frequency-volume charts from male patients with clinically-significant nocturia (≥2 nocturnal voids) and NP (defined by nocturnal urine production [NUP] ≥90 mL/hour or nocturnal polyuria index [NPi] ≥0.33). Patients with NP and chronic kidney disease, congestive heart failure, and/or undertreated obstructive sleep apnea (OSA) were deemed to have secondary NP. Nocturnal polyuria syndrome (NPS) was defined as NP without edema, loop diuretic use, or the aforementioned conditions. Patients with diabetes insipidus or OSA with appropriate continuous positive airway pressure utilization were excluded. The timing and volumes of nocturnal voids were used to derive "early" and "late" nocturnal diuresis rates (mL/hour of urine produced before and after the first nocturnal awakening, respectively). The likelihood of an early peak nocturnal diuresis rate (ie, early >late nocturnal diuresis rate) was compared between patients with NPS versus secondary NP using both a crude and adjusted odds ratio. RESULTS: The likelihood of an early peak nocturnal diuresis rate in patients with NPS compared with secondary NP was 2.58 (1.05-6.31) at NUP ≥ 90 mL/hour and 1.96 (0.87-4.42) at NPi ≥ 0.33 on crude analysis, and 2.44 (0.96-6.24) and 1.93 (0.83-4.48) after adjustment, respectively. CONCLUSIONS: A peak early nocturnal diuresis rate was significantly more likely in patients with NPS at NUP ≥ 90 mL/hour, with similar odds ratios at NPi ≥ 0.33 and following adjustment. Delineating nocturic patients by NP subgroup may facilitate more individualized management. PATIENT SUMMARY: Many people have to wake up to urinate because they produce too much urine at night-a condition known as "nocturnal polyuria." Nocturnal polyuria might be caused by drinking too much fluid, other behavioral factors, or conditions that make your body hold on to too much fluid, like heart disease, kidney disease, and sleep apnea. In cases of nocturnal polyuria where no clear cause can be identified, it is thought that patients may suffer from a deficiency in nighttime vasopressin, a hormone that plays a key role in how much urine you produce. In this study, we compared the pattern of nighttime urine production in patients with different causes of nocturnal polyuria, which may lead to more personalized treatment options for patients with this condition.

ICI-RS 2019 nocturia think tank: How can experimental science guide us in understanding the pathophysiology of nocturia?

INTRODUCTION: The following is a report on the proceedings of the 2019 International Consultation on Incontinence-Research Society nocturia think tank (NTT). OBJECTIVES: The objectives of the 2019 NTT were as follows: (a) to evaluate the role of urothelium in the pathophysiology of nocturia; (b) to determine whether nocturia is a circadian disorder; (c) to discuss the role of melatonin in nocturia; (d) to consider ambulatory urodynamic monitoring in evaluating patients with nocturia; (e) to explore studies of water handling in human compartments utilizing heavy water; and (f) to explore whether basic science is the key to understanding the treatment options for diminished bladder capacity in patients with nocturia. METHODS: A compendium of discussions of the role of experimental science in understanding the pathophysiology of nocturia is described herein. RESULTS AND CONCLUSIONS: Translational science will play an increasing role in understanding the pathophysiology of nocturia, which may result in improved treatment strategies.

Identifying men with global polyuria on a nocturnal-only voiding diary.

AIMS: Nocturnal polyuria (NP) and global polyuria (GP) are not mutually exclusive. However, by rate, the common criteria for GP (40 mL/kg/24 hours [117 mL/kg/hour in a 70-kg individual] or 3000 mL/24 hours [125 mL/h]) are more stringent than those for NP (90 mL/hour during the sleep period or NP index [NPi; nocturnal volume/24-hour volume] > 0.33 [no minimum rate]). It remains unclear whether total nocturnal urine volume (NUV) may reliably delineate between NP patients with and without comorbid GP. METHODS: A clinical database of men with lower urinary tract symptoms was searched for voiding diaries completed by patients reporting greater than or equal to 1 nocturnal void(s). Four separate analyses were performed using all combinations of the two NP and two GP criteria listed above. For each analysis, patients were included if they met the criteria for NP, and then stratified by presence or absence of GP (ie, NP + GP vs isolated NP). RESULTS: Median NUV was greater among patients with NP + GP for all criteria combinations. Sensitivities greater than or equal to 80%/90%/100% for NP + GP were observed at 1275/1230/1085 mL for {NPi > 0.33 + 24-hour volume > 3000 mL}; 1075/1035/1035 mL for {NPi > 0.33 + 24-hour volume > 40 mL/kg}; 900/745/630 mL for {NUP > 90 mL/hour + 24-hour volume > 3000 mL}; and 1074/1035/990 mL for {NUP > 90 mL/hour + 24-hour volume > 40 mL/kg}. CONCLUSIONS: An inordinate NUV among men with NP is fairly sensitive for comorbid GP. In the appropriate clinical setting, nocturnal-only diaries may suffice in the evaluation and follow-up of patients with NP, so long as outlying nocturnal volumes prompt a 24-hour diary/urine collection.

Management of Nocturia and Nocturnal Polyuria.

Nocturnal polyuria (NP), characterized by overproduction of urine at night (greater than 20%-33% of total 24-hour urine volume depending on age), is a major contributing factor in most nocturia cases. Nocturia can be caused by intake, urological, nephrological, hormonal, sleep, and cardiovascular factors. It is therefore important to accurately diagnose both the type of nocturia and the potentially associated medical conditions to determine appropriate treatment. Diagnostic tools, in addition to a thorough history and physical examination, include voiding/bladder diary analyses and questionnaires to diagnose nocturia type (NP, diminished nocturnal/global bladder capacity, global polyuria) and causative factors. Lifestyle modifications are the first intervention implemented for the management of nocturia and NP but, as symptoms progress, such measures may be insufficient, and pharmacotherapy may be initiated. While drugs for benign prostatic hyperplasia and overactive bladder have demonstrated statistically significant reductions in nocturnal voids, patients often fail to achieve a clinically meaningful response. Antidiuretic treatment is warranted for patients with nocturia due to NP because, in many patients, it treats the underlying cause (ie, insufficient secretion of antidiuretic hormone arginine vasopressin) that leads to overproduction of urine at night and has been shown to provide statistically significant reductions in nocturnal voids. Desmopressin, a synthetic analog of arginine vasopressin, is the only antidiuretic treatment indicated specifically for nocturia due to NP. Overall, the pathophysiology of NP is complex and differs from that of other types of nocturia. A multidisciplinary approach is necessary to effectively diagnose and manage this bothersome condition.

Pathophysiological Mechanisms of Nocturia and Nocturnal Polyuria: The Contribution of Cellular Function, the Urinary Bladder Urothelium, and Circadian Rhythm.

Alterations to arginine vasopressin (AVP) secretion, the urinary bladder urothelium (UT) and other components of the bladder, and the water homeostasis biosystem may be relevant to the pathophysiology of nocturia and nocturnal polyuria (NP). AVP is the primary hormone involved in water homeostasis. Disruption to the physiological release of AVP or its target effects may relate to several urinary disturbances. Circadian dysregulation and the effects of aging, for example, the development of oxidative stress and mitochondrial dysfunction, may play a role in nocturia voiding symptoms. The urinary bladder UT not only acts as a highly efficient barrier that is maintained during the filling and voiding of the urinary bladder, but is also capable of sensory and transducer function through a network of functional receptors and ion channels that enable reciprocal communication between UT cells and neighboring elements of the bladder mucosa and wall. Functional components of the UT (eg, claudins and receptors or ion channels) play important roles in AVP-mediated water homeostasis. These components and functions involved in water homeostasis, as well as kidney function, may be affected by the aging process, including age-related mitochondrial dysfunction. The characteristics of NP are discussed and the association between NP and circadian rhythm is examined in light of reports that suggest that nocturia should be considered as a type of circadian dysfunction. Many possible pathologic mechanisms that underlie nocturia and NP have been identified. Future studies may provide further insight into pathophysiology with the hope of identifying new treatment modalities.

Diuretic Effects of Sodium Glucose Cotransporter 2 Inhibitors and Their Influence on the Renin-Angiotensin System.

The renin-angiotensin system (RAS) plays an important role in regulating body fluids and blood pressure. However, inappropriate activation of the RAS contributes to the pathogenesis of cardiovascular and renal diseases. Recently, sodium glucose cotransporter 2 (SGLT2) inhibitors have been used as anti-diabetic agents. SGLT2 inhibitors induce glycosuria and improve hyperglycemia by inhibiting urinary reabsorption of glucose. However, in the early stages of treatment, these inhibitors frequently cause polyuria and natriuresis, which potentially activate the RAS. Nevertheless, the effects of SGLT2 inhibitors on RAS activity are not straightforward. Available data indicate that treatment with SGLT2 inhibitors transiently activates the systemic RAS in type 2 diabetic patients, but not the intrarenal RAS. In this review article, we summarize current evidence of the diuretic effects of SGLT2 inhibitors and their influence on RAS activity.

Usefulness of the frequency-volume chart over the International Prostate Symptom Score in patients with benign prostatic hyperplasia in view of global polyuria.

PURPOSE: We aimed to determine the usefulness of the frequency-volume chart over the International Prostate Symptom Score in patients with benign prostatic hyperplasia. Furthermore, we investigated the clinical characteristics suggesting that patients could benefit from frequency-volume chart assessment in addition to International Prostate Symptom Score assessment. METHODS: A total of 193 patients with benign prostatic hyperplasia were analyzed. The relationship between the information obtained from the frequency-volume chart and the International Prostate Symptom Score was assessed. Because the urine output per kilogram per hour was not associated with any question in the International Prostate Symptom Score questionnaire, patients were divided into 2 groups according to the presence of global polyuria, defined as urine output >40 mL·kg-1·h-1. Multivariable analysis was performed to determine the predictors of global polyuria, and the results were externally validated using 397 patients with benign prostatic hyperplasia. RESULTS: Although the other information obtained from the frequency-volume chart correlated with the International Prostate Symptom Score, the urine output was not associated with the International Prostate Symptom Score. Based on these results, patients were dichotomized into the global polyuria group (n = 19, 9.8%) and the non-global polyuria group. Although the patient characteristics did not differ between the 2 groups, the number of voids was higher in patients with global polyuria. Multivariable analysis showed that diabetes mellitus (odds ratio: 3.497, p = 0.039) and increased number of voids (odds ratio: 1.320, p < 0.001) were significant predictors of global polyuria. On external validation, the area under curve for the model was 0.723. CONCLUSIONS: Global polyuria cannot be suspected using the International Prostate Symptom Score, although it worsens the lower urinary tract symptoms of patients with benign prostatic hyperplasia. Assessment with the frequency-volume chart needs to be considered in diabetic patients with increased number of voids.

Bladder overdistension with polyuria in a hypertensive rat model.

AIMS: Polyuria can lead to progressive chronic bladder overdistension. The impact of polyuria on the bladder has been extensively studied in settings of either diabetes or sucrose diuresis in animals. The goal of this study was to investigate the outcomes of polyuria in a hypertension setting. MATERIALS AND METHODS: Male Dahl/SS rats, a hypertension model, received a high-salt or normal diet for 6 weeks. Twenty-four-hour water intake, micturition patterns, and blood pressures were recorded biweekly. Conscious cystometry was carried out at the end of this period. Bladders were collected to measure contractile force and for histological analysis. Paired t-tests were used to compare changes between Week 0 and Week 6 within each group. Unpaired t-tests were used for comparisons between groups for all parameters at Week 6. RESULTS: Six weeks of high-salt diet significantly increased water intake and total urine. Blood pressures and volume of urine per micturition was higher in rats on high-salt diet. Bladder overdistension in the high-salt diet group was confirmed by cystometry, shown by a significantly higher bladder capacity, and compliance. No difference in detrusor contractility was observed between both groups. Collagen content was significantly higher in the lamina propria of the high-salt group compared to the normal group, while the opposite was observed in the muscularis. CONCLUSIONS: Polyuria, in a hypertension context, leads to changes in bladder morphology and function. These findings help clarify the deleterious clinical impact of polyuria on voiding function, highlighting the variable consequences of bladder overdistension according to the underlying pathology.

Combination exposure of melamine and cyanuric acid is associated with polyuria and activation of NLRP3 inflammasome in rats.

The molecular mechanisms of melamine-induced renal toxicity have not been fully understood. The purpose of the study aimed to investigate whether melamine and cyanuric acid induced NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation in the kidney, which may contribute to abnormal water and sodium handling in a rat model. Wistar rats received melamine (Mel; 200 mg·kg body wt-1·day-1), cyanuric acid (CA; 200 mg·kg body wt-1·day-1), or Mel plus CA (Mel + CA; 100 mg·kg body wt-1·day-1, each) for 2 wk. Mel + CA caused damaged tubular epithelial structure and organelles, dilated tubular lumen, and inflammatory responses. Crystals were observed in urine and serum specimen, also in the lumen of dilated distal renal tubules. The combined ingestion of Mel and CA in rats caused a markedly impaired urinary concentration, which was associated with reduced protein expression of aquaporin (AQP)1, 2, and 3 in inner medulla and α-Na-K-ATPase and Na-K-2Cl transporters in cortex and outer medulla. Mel + CA treatment was associated with increased protein expression of CD3 and mRNA levels of CD68 and F4/80 as well as phosphorylation of NF-κB in the kidney. Mel + CA treatment increased protein and mRNA expression of NLRP3 inflammasome components apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, and IL-1ß in the inner medulla of rats. NF-κB inhibitor Bay 11-7082 reduced IL-1ß expression induced by Mel + CA and prevented downregulation of AQP2 in inner medullary collecting duct cell suspensions. In conclusion, Mel + CA treatment caused urinary-concentrating defects and reduced expression of renal AQPs and key sodium transporters, which is likely due to the inflammatory responses and activation of NLRP3 inflammasome induced by crystals formed in the kidney.