Urine-concentrating Ability Research Articles

Air pollution aggravates renal ischaemia-reperfusion-induced acute kidney injury.

Chronic kidney disease (CKD) has emerged as a significant global public health concern. Recent epidemiological studies have highlighted the link between exposure to fine particulate matter (PM2.5) and a decline in renal function. PM2.5 exerts harmful effects on various organs through oxidative stress and inflammation. Acute kidney injury (AKI) resulting from ischaemia-reperfusion injury (IRI) involves biological processes similar to those involved in PM2.5 toxicity and is a known risk factor for CKD. The objective of this study was to investigate the impact of PM2.5 exposure on IRI-induced AKI. Through a unique environmentally controlled setup, mice were exposed to urban PM2.5 or filtered air for 12 weeks before IRI followed by euthanasia 48 h after surgery. Animals exposed to PM2.5 and IRI exhibited reduced glomerular filtration, impaired urine concentration ability, and significant tubular damage. Further, PM2.5 aggravated local innate immune responses and mitochondrial dysfunction, as well as enhancing cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway activation. This increased renal senescence and suppressed the anti-ageing protein klotho, leading to early fibrotic changes. In vitro studies using proximal tubular epithelial cells exposed to PM2.5 and hypoxia/reoxygenation revealed heightened activation of the STING pathway triggered by cytoplasmic mitochondrial DNA, resulting in increased tubular damage and a pro-inflammatory phenotype. In summary, our findings imply a role for PM2.5 in sensitising proximal tubular epithelial cells to IRI-induced damage, suggesting a plausible association between PM2.5 exposure and heightened susceptibility to CKD in individuals experiencing AKI. Strategies aimed at reducing PM2.5 concentrations and implementing preventive measures may improve outcomes for AKI patients and mitigate the progression from AKI to CKD. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Physiological Functions of Aquaporin-3 in Mediating Water and Solutes

Aquaporins (AQP), are a family of membrane channel proteins that facilitate the transmembrane diffusion of water and some small non-charged solutes such as glycerol and urea by osmosis or solute gradient. AQP3, an aquaglyceroporin, is expressed in the kidney, skin, and testes, etc. Mice lacking AQP3 have symptoms of diabetes insipidus. In addition, the absence of AQP3 leads to dry skin in mice. AQP4 is permeable to water only. To understand the specific function of the water permeability and small solute transport mediated by AQP3, we generated AQP3 knock-out (AQP3 KO) mice and AQP4 knock-in mice (AQP4 KI) with AQP4 replacing AQP3 in situ. In the basal condition, knock-out of AQP3 in mice led to increased urine volume, decreased urine osmolality and tubule dilation. Interestingly, in AQP4 KI mice, these phenomena were reversed, showing improved urine concentration and tubular morphology. However, there was no significant difference in non-urea solute concentrations between both genotypes. Subsequently, we conducted acute urea loading tests and high-protein diet experiments to further increase the production and excretion of urea in mice. The experimental results showed that both urea loading and high-protein diet had little impact on urine osmolality and urinary urea concentration in AQP3 KO mice. But the urine osmolality and urinary urea concentration in AQP4 KI mice were altered by exogenous administration of urea. Our data indicates that the absence of AQP3 prevents urea accumulation in the kidney, disrupting urine concentration mechanism. The knock-in of AQP4 can restore AQP3 mediated water channel function and help to regulate the urine concentration ability. The water permeability, other than solute transport, of AQP3 plays important role in urine concentrating mechanism. AQP3 KO mice exhibited significant epidermal thickening, excessive keratinization, decreased skin hydration and elasticity. The replacement of AQP4 in situ did not improve these phenomena, indicating that solute transport mediated by AQP3 may play a role in maintaining normal skin function. Therefore, we constructed a mouse model of psoriasis induced by imiquimod (IMQ). It was found that AQP3 expression was reduced in the lesional skin of wildtype (WT) mice, while AQP3 KO mice and AQP4 KI mice exhibited dry skin, excessive epidermal proliferation, and increased inflammatory response. Local treatment with urea (10%) could alleviate these symptoms. These experimental results confirmed the important role of AQP3 in the pathogenesis of psoriasis and the potential role of urea in the treatment of psoriasis. Our study suggests the diverse physiological functions of AQP3 in different tissues. This research was supported by Beijing Natural Science Foundation (7232249). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Differential Regulation of Autophagy on Urine-Concentrating Capability through Modulating the Renal AQP2 Expression and Renin-Angiotensin System in Mice.

Autophagy, a cellular process of "self-eating", plays an essential role in renal pathophysiology. However, the effect of autophagy on urine-concentrating ability in physiological conditions is still unknown. This study aimed to determine the relevance and mechanisms of autophagy for maintaining urine-concentrating capability during antidiuresis. The extent of the autophagic response to water deprivation (WD) was different between the renal cortex and medulla in mice. Autophagy activity levels in the renal cortex were initially suppressed and then stimulated by WD in a time‑dependent manner. During 48h WD, the urine-concentrating capability of mice was impaired by rapamycin but not 3-Methyladenine, accompanied by the suppressed renal aquaporin 2 (AQP2), V2 receptor (V2R), renin, and angiotensin-converting enzyme (ACE) expression, and the levels of prorenin/renin, angiotensin II (AngII), and aldosterone in the plasma and urine. In contrast, 3-Methyladenine and chloroquine suppressed the urine-concentrating capability in WD72 mice, accompanied by downregulation of AQP2 and V2R expression in the renal cortex. 3-Methyladenine and chloroquine further increased AQP2 and V2R expression in the renal medulla of WD72 mice. Compared to 3-MA and CQ, Rapa administration yielded completely opposite results on the above parameters in WD72 mice. In addition, 3-Methyladenine and chloroquine abolished the upregulation of prorenin/renin, AngII, and aldosterone levels in the plasma and urine in WD72mice. Taken together, our study demonstrated that autophagy regulated urine-concentrating capability through differential regulation of the renal AQP2/V2R and ACE/AngII signaling during WD.

Abstract 2131: The higher integrin α5β1 levels in the male kidney cortex indicate a potential reason for the better urine concentration ability in men than women

Abstract 2131: The higher integrin α5β1 levels in the male kidney cortex indicate a potential reason for the better urine concentration ability in men than women

PS-BPB05-6: TOLVAPTAN INDUCES BODY FLUID LOSS AND ACTIVATION OF RENAL UREA-DRIVEN WATER CONSERVATION IN NORMAL RATS

Objective: We recently reported that body fluid loss models such as high salt-induced natriuresis, impaired urine concentration ability via kidney injury, and enhanced transepidermal water loss due to skin barrier dysfunction exhibit initial water loss and subsequent activation of the water conservation system in multiple organs. This activation of the water conservation system restores or even increases water content at the tissue level, which may be involved in abnormal body fluid distribution in various disease models. The water conservation system consists of renal urea recycling, the energy-intensive nature of hepato-muscular ureagenesis, and suppression of cardiovascular energy expenditure to save energy for ureagenesis. However, it is not clarified whether pharmacological fluid loss by diuretics activates the water conservation system. In this study, we examined the effects of water diuresis by tolvaptan, a selective vasopressin V2 receptor antagonist, on the water conservation system in normal rats. Design and method: 10-week-old male Sprague Dawley rats were fed with a control diet or a diet containing 0.1% tolvaptan. We measured water intake and urine volume for two weeks and also evaluated time-dependent changes in renal urea recycling and hepato-muscular ureagenesis in these rats. In addition, we also evaluated the effects of tolvaptan on blood pressure, heart rate, and renal sympathetic nerve activity by a radiotelemetry system in separate animals. Results: Tolvaptan markedly increased urine volume up to 126.7 ± 25.9 ml on day-1, which gradually decreased as much as one-third (48.1 ± 18.0 ml) on day-7. Tolvaptan significantly decreased body water content and increased plasma albumin concentration, an indicator of oncotic pressure, on day-1, suggesting that tolvaptan decreased body fluid and plasma volume on day-1. These changes in total body water content and plasma albumin concentration were restored on day-7. The restoration of body fluid on day-7 was associated with an increase in urea transporter A1-associated renal urea recycling. On the other hand, tolvaptan did not alter hepato-muscular ureagenesis or cardiovascular energy expenditure throughout the treatment. Conclusions: Tolvaptan induces initial body fluid loss by water diuresis and subsequent activation of renal urea recycling to restore the water loss. Activation of the water conservation system in addition to a rise in urine volume may be involved in the unknown distinct effect of the diuretics.

Rac1 deficiency impairs postnatal development of the renal papilla

Development of the renal medulla continues after birth to form mature renal papilla and obtain urine-concentrating ability. Here, we found that a small GTPase, Rac1, plays a critical role in the postnatal development of renal papilla. Mice with distal tubule-specific deletion of Rac1 reached adulthood but showed polydipsia and polyuria with an impaired ability to concentrate urine. The elongation of renal papilla that occurs in the first weeks after birth was impaired in the Rac1-deficient infants, resulting in shortening and damage of the renal papilla. Moreover, the osmoprotective signaling mediated by nuclear factor of activated T cells 5, which is a key molecule of osmotic response to osmotic stress in renal medulla, was significantly impaired in the kidneys of the Rac1-deficient infants. These results demonstrate that Rac1 plays an important role in the development of renal papilla in the postnatal period, and suggested a potential link between Rac1 and osmotic response.

Contributions of renal water loss and skin water conservation to blood pressure elevation in spontaneously hypertensive rats.

We recently reported that skin vasoconstriction to suppress transepidermal water loss (TEWL) leads to hypertension in renal injury model rats with impaired urine concentration ability. In this study, we investigated the pathogenesis of hypertension in spontaneously hypertensive rats (SHRs) from the perspective of renal water loss and skin water conservation. We compared the urinary concentration ability, body sodium and water balance, blood pressure, and TEWL in SHRs and control normotensive Wistar-Kyoto rats (WKYs). SHRs showed significantly higher urine volume and lower urinary osmolality than those of WKYs, while there were no significant differences in water intake, urinary osmolyte excretion, and plasma osmolarity between the groups. SHRs exhibited significantly higher blood pressure, skin sodium content, and lower TEWL compared with those is WKYs. Skin vasodilation, induced by elevating body temperature, increased TEWL in both SHRs and WKYs, and significantly reduced blood pressure in SHRs but not WKYs. These findings suggest that physiological adaptation can reduce dermal water loss in SHRs to compensate for renal water loss. Vasoconstriction required for successful cutaneous water conservation explains SHR hypertension. Renal concentration ability and skin barrier function for water conservation may become a novel therapeutic target for essential hypertension.

Kruppel-like factor 1–GATA1 fusion protein improves the sickle cell disease phenotype in mice both in vitro and in vivo

AbstractSickle cell disease (SCD) and β-thalassemia are among the most common genetic disorders worldwide, affecting global health and mortality. Hemoglobin A2 (HbA2, α2δ2) is expressed at a low level in adult blood due to the lack of the Kruppel-like factor 1 (KLF1) binding motif in the δ-globin promoter region. However, HbA2 is fully functional as an oxygen transporter, and could be a valid antisickling agent in SCD, as well as a substitute for hemoglobin A in β-thalassemia. We have previously demonstrated that KLF1-GATA1 fusion protein could interact with the δ-globin promoter and increase δ-globin expression in human primary CD34+ cells. We report the effects of 2 KLF1-GATA1 fusion proteins on hemoglobin expression, as well as SCD phenotypic correction in vitro and in vivo. Forced expression of KLF1-GATA1 fusion protein enhanced δ-globin gene and HbA2 expression, as well as reduced hypoxia-related sickling, in erythroid cells cultured from both human sickle CD34+ cells and SCD mouse hematopoietic stem cells (HSCs). The fusion proteins had no impact on erythroid cell differentiation, proliferation, and enucleation. Transplantation of highly purified SCD mouse HSCs expressing KLF1-GATA1 fusion protein into SCD mice lessened the severity of the anemia, reduced the sickling of red blood cells, improved SCD-related pathological alterations in spleen, kidney, and liver, and restored urine-concentrating ability in recipient mice. Taken together, these results indicate that the use of KLF1-GATA1 fusion constructs may represent a new gene therapy approach for hemoglobinopathies.

Synergistic Contribution of Epac1‐/‐ and Epac2‐/‐ for Urinary Concentrating Ability

Epac is a relatively new direct downstream effector of cAMP. Two known Epac isoforms, Epac1 and Epac2 are abundantly expressed in the renal epithelial cells of the proximal tubule and the collecting duct. We recently demonstrated that Epac1‐/‐ and Epac2‐/‐ mice develop polyuria largely due to decreased NHE‐3 expression in the proximal tubule. In contrast, AQP2‐dependent water reabsorption in the collecting duct was unaffected. In this study, we utilized double Epac knockout mice to determine whether both isoforms contribute complementarily to the urinary production and concentrating ability. We found that Epac1&2‐/‐ produced significantly higher 24h urinary volume and lower osmolarities compared to the values in single Epac knockouts. These differences were further exacerbated in response to water deprivation test suggesting a defect in the collecting duct. Consistently, Epac1&2 blockade with ESI‐09 inhibited AQP2 translocation to the apical plasma membrane in CD cells in response to AVP. At the same time, inhibition of a single Epac isoform fails to do so. Overall, our results demonstrate that concomitant Epac1‐/‐ and Epac2‐/‐deletion compromises reabsorption in both PT and CD, thus leading to a much greater in urine volume and decrease urinary concentrating ability than the single isoform Epac knockout.

Chronic Lithium Therapy and Urine-Concentrating Ability in Individuals With Bipolar Disorder: Association Between Daily Dose and Resistance to Vasopressin and Polyuria

IntroductionLithium treatment can induce nephrogenic diabetes insipidus (NDI), but no consensus intervention is offered to date. We evaluated in these patients patterns of urine concentration and the correlates of 24-hour urine output.MethodsProspective, single-center, observational study of 217 consecutive lithium-treated individuals, with 24-hour urine collection, desmopressin (1-deamino-arginine vasopressin [DDAVP]) concentrating test, fasting plasma vasopressin measurement (copeptin measurement in n = 119), and measured glomerular filtration rate (mGFR). Maximal urine osmolality (MaxUosm) was the highest level during the DDAVP test.ResultsOf the individuals, 21% displayed polyuria (>3 l/d), but 55% displayed elevated fasting vasopressin level (>5 pg/ml). Uosm was significantly lower and urinary output and free water clearance were significantly higher in individuals treated for >10 years. MaxUosm was >600 mOsm/KgH2O in 128 patients (59%), among which vasopressin was increased in 51%, associated with higher lithium dose (950 [750–1200] vs. 800 [500–1000] mg/d, P < 0.001). All patients with lithium daily dose ≥1400 mg/d had high vasopressin levels. In multivariable analysis, 24-hour urine output was associated with higher lithium daily dose (β 0.49 ± 0.17, P = 0.005), female sex (β −359 ± 123, P = 0.004), daily osmolar intake (β 2.21 ± 0.24, P < 0.001), MaxUosm (β −2.89 ± 0.35, P < 0.001), and plasma vasopressin level (β 10.17 ± 4.76, P = 0.03).ConclusionHigher lithium daily dose was associated with higher vasopressin levels and higher urine output, independently of other factors. Daily osmolar intake was also associated with higher 24-hour urine output. These results suggest that controlled salt and protein intake and lithium dose might reduce polyuria in these patients.

The long-term effects of rapamycin-based immunosuppressive protocols on the expression of renal aquaporins 1, 2, 3 and 4 water channels in rats.

To this day, the effect of multi-drug immunosuppressive protocols on renal expression of AQPs is unknown. This study aimed to determine the influence of rapamycin-based multi-drug immunosuppressive regimens on the expression of aquaporins (AQPs) 1, 2, 3, and 4 in the rat kidney. For 6 months, 24 male Wistar rats were administered immunosuppressants, according to the three-drug protocols used in patients after organ transplantation. The rats were divided into four groups: the control group, the TRP group (tacrolimus, rapamycin, prednisone), the CRP group (cyclosporine A, rapamycin, prednisone), and the MRP group (mycophenolate mofetil, rapamycin, prednisone). Selected red cell indices and total calcium were measured in the blood of rats and quantitative analysis of AQP1, AQP2, AQP3 and AQP4 immunoexpression in the kidneys were performed. In the TRP and CRP groups, a mild increase of mean corpuscular hemoglobin concentration, hematocrit and total calcium were observed. Moreover, decreased expression of AQP1-4 was found in all experimental groups, with the highest decrease in the CRP group. The long-term immunosuppressive treatment using multi-drug protocols decreased AQP1-4 expressions in renal tubules, possibly leading to impaired urine-concentrating ability in rat.

Water intake and progression of chronic kidney disease: the CKD-REIN cohort study.

Optimal daily water intake to prevent chronic kidney disease (CKD) progression is unknown. Taking the kidney's urine-concentrating ability into account, we studied the relation of kidney outcomes in patients with CKD to total and plain water intake and urine volume. Including 1265 CKD patients [median age 69 years; mean estimated glomerular filtration rate (eGFR) 32 mL/min/1.73 m2] from the Chronic Kidney Disease-Renal Epidemiology and Information Network cohort (2013-19), we assessed fluid intake at baseline interviews, collected 24-h urine volumes and estimated urine osmolarity (eUosm). Using Cox and then linear mixed models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for kidney failure and eGFR decline associated with hydration markers, adjusting for CKD progression risk factors and eUosm. Patients' median daily intake was 2.0 L [interquartile range (IQR) 1.6-2.6] for total water and 1.5 L (1-1.7) for plain water, median urine volume was 1.9 L/24 h (IQR 1.6-2.4) and mean eUosm was 374 ± 104 mosm/L. Neither total water intake nor urine volume was associated with either kidney outcome. Kidney failure risk increased significantly with decreasing eUosm ˂292 mosm/L. Adjusted HRs (95% CIs) for kidney failure associated with plain water intake were 1.88 (1.02-3.47), 1.59 (1.06-2.38), 1.76 (0.95-3.24) and 1.55 (1.03-2.32) in patients drinking <0.5, 0.5-1.0, 1.5-2.0 and >2.0 L/day compared with those drinking 1.0-1.5 L/day. High plain water intake was also significantly associated with faster eGFR decline. In patients with CKD, the relation between plain water intake and progression to kidney failure appears to be U-shaped. Both low and high intake may not be beneficial in CKD.

Inhibition of α2-adrenoceptor is renoprotective in 5/6 nephrectomy-induced chronic kidney injury rats

In the present study, we investigated the renoprotective effects of long-term treatment with yohimbine, an α2-adrenoceptor inhibitor, in a 5/6 nephrectomy-induced chronic kidney disease (CKD) rat model. Male Sprague–Dawley rats were randomly allocated into the following groups: sham-operated, 5/6-nephrectomized (5/6 Nx), 5/6 Nx + low or high dose of yohimbine (0.3 or 3.0 mg/L in drinking water, respectively), and 5/6 Nx + hydralazine (250 mg/L in drinking water). The 5/6 Nx group presented with renal dysfunction, hypertension, noradrenaline overproduction, and histopathological injuries. Blood pressure decreased in both the yohimbine- and hydralazine-treated groups. Treatment with high dose of yohimbine, but not hydralazine, apparently attenuated urinary protein excretion and noradrenaline concentration of renal venous plasma. Renal fibrosis and upregulated fibrosis-related gene expression were suppressed by high dose of yohimbine. Furthermore, yohimbine, but not hydralazine, treatment ameliorated the urinary concentration ability. These findings suggest that long-term yohimbine treatment can be a useful therapeutic option to prevent the progression of CKD.

Urine concentration ability is reduced to the same degree in adult dominant polycystic kidney disease compared with other chronic kidney diseases in the same CKD-stage and lower THAN in healthy control subjects - a CASE control study

BackgroundConcentration of the urine is primarily regulated via vasopressin dependent aquaporin-2 water channels in the apical membrane of kidney principal cells. It is unclear whether urine concentration ability in ADPKD differs from other patients with similar degree of impaired renal function (non-ADPKD patients). The purpose of this case control study was to measure urine concentration ability in ADPKD patients compared to non-ADPKD patients and healthy controls.MethodsA seventeen hour long water deprivation test was carried out in 17 ADPKD patients (CKD I-IV), 16 non-ADPKD patients (CKD I-IV), and 18 healthy controls. Urine was collected in 4 consecutive periods during water deprivation (12 h, 1 h, 2 h and 2 h, respectively) and analyzed for osmolality (u-Osm), output (UO), fractional excretion of sodium (FENa), aquaporin2 (u-AQP2) and ENaC (u-ENaC). Blood samples were drawn trice (after 13-, 15-, and 17 h after water deprivation) for analyses of osmolality (p-Osm), vasopressin (p-AVP), and aldosterone (p-Aldo).ResultsU-Osm was significantly lower and FENa significantly higher in both ADPKD patients and non-ADPKD patients compared to healthy controls during the last three periods of water deprivation. During the same periods, UO was higher and secretion rates of u-AQP2 and u-ENaC were lower and at the same level in the two groups of patients compared to controls. P-AVP and p-Osm did not differ significantly between the three groups. P-Aldo was higher in both groups of patients than in controls.ConclusionsUrine concentration ability was reduced to the same extent in patients with ADPKD and other chronic kidney diseases with the same level of renal function compared to healthy controls. The lower urine excretion of AQP2 and ENaC suggests that the underlying mechanism may be a reduced tubular response to vasopressin and aldosterone.Trial registrationCurrent Controlled Trial NCT04363554, date of registration: 20.08.2017.

The urea transporter UT-A1 plays a predominant role in a urea-dependent urine-concentrating mechanism

Urea transporters are a family of urea-selective channel proteins expressed in multiple tissues that play an important role in the urine-concentrating mechanism of the mammalian kidney. Previous studies have shown that knockout of urea transporter (UT)-B, UT-A1/A3, or all UTs leads to urea-selective diuresis, indicating that urea transporters have important roles in urine concentration. Here, we sought to determine the role of UT-A1 in the urine-concentrating mechanism in a newly developed UT-A1-knockout mouse model. Phenotypically, daily urine output in UT-A1-knockout mice was nearly 3-fold that of WT mice and 82% of all-UT-knockout mice, and the UT-A1-knockout mice had significantly lower urine osmolality than WT mice. After 24-h water restriction, acute urea loading, or high-protein (40%) intake, UT-A1-knockout mice were unable to increase urine-concentrating ability. Compared with all-UT-knockout mice, the UT-A1-knockout mice exhibited similarly elevated daily urine output and decreased urine osmolality, indicating impaired urea-selective urine concentration. Our experimental findings reveal that UT-A1 has a predominant role in urea-dependent urine-concentrating mechanisms, suggesting that UT-A1 represents a promising diuretic target.

Impact of passive heat acclimation on markers of kidney function during heat stress.

What is the central question of this study? Does passive heat acclimation alter glomerular filtration rate and urine-concentrating ability in response to passive heat stress? What is the main finding and its importance? Glomerular filtration rate remained unchanged after passive heat stress, and heat acclimation did not alter this response. However, heat acclimation mitigated the reduction in urine-concentrating ability and reduced the incidence of albuminuria in young healthy adults after passive heat stress. Collectively, these results suggest that passive heat acclimation might improve structural integrity and reduce glomerular permeability during passive heat stress. Little is known about the effect of heat acclimation on kidney function during heat stress. The purpose of this study was to determine the impact of passive heat stress and subsequent passive heat acclimation on markers of kidney function. Twelve healthy adults (seven men and five women; 26±5 years of age; 72.7±8.6kg; 172.4±7.5cm) underwent passive heat stress before and after a 7day controlled hyperthermia heat acclimation protocol. The impact of passive heat exposure on urine and serum markers of kidney function was evaluated before and after heat acclimation. Glomerular filtration rate, determined from creatinine clearance, was unchanged with passive heat stress before (pre, 133±41mlmin-1 ; post, 127±51mlmin-1 ; P=0.99) and after (pre, 129±46mlmin-1 ; post, 130±36mlmin-1 ; P=0.99) heat acclimation. The urine-to-serum osmolality ratio was reduced after passive heating (P<0.01), but heat acclimation did not alter this response. In comparison to baseline, free water clearance was greater after passive heating before (pre, -0.86±0.67mlmin-1 ; post, 0.40±1.01mlmin-1 ; P<0.01) but not after (pre, -0.16±0.57mlmin-1 ; post, 0.76±1.2mlmin-1 ; P=0.11) heat acclimation. Furthermore, passive heating increased the fractional excretion rate of potassium (P<0.03) but not sodium (P=0.13) or chloride (P=0.20). Lastly, heat acclimation reduced the fractional incidence of albuminuria after passive heating (before, 58±51%; after, 8±29%; P=0.03). Collectively, these results demonstrate that passive heat stress does not alter the glomerular filtration rate. However, heat acclimation might improve urine-concentrating ability and filtration within the glomerulus.

P0618PREOPERATIVE LOW URINE SPECIFIC GRAVITY PREDICTS ACUTE KIDNEY INJURY AFTER CARDIAC SURGERY

Abstract Background and Aims Acute kidney injury (AKI) is a common and serious complication following cardiac surgery. However, strategies that effectively predict AKI risk before cardiac surgery are scarce. Recent investigations identified urinary osmolality to be associated with non-glomerular kidney damage in normal kidney function individuals, suggesting urine concentration ability to be a surrogate of early kidney damage. Therefore, hypothesizing that urine specific gravity (SG) could reflect asymptomatic kidney damage, the clinical implication of preoperative urine specific gravity on AKI occurrence after cardiac surgery was investigated in subjects with normal kidney function. Method A total of 4135 patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from were enrolled. Patients whose eGFR was lower than 60mL/min/1.73m2 were excluded. Fasting urinary SG was measured from the morning first void a day before the surgery. The patients were divided into tertiles based on urine SG. The primary outcome was occurrence of AKI within 48hours of cardiac surgery. AKI was defined according to Acute Kidney Injury Network criteria. Results The mean age of the patients was 60 years and 60% were male. Diabetes consisted of 25.6% of the patients and 54.5% were hypertensive. The mean eGFR and urine SG was 98.8mL/min/1.73m2 and 1.020, respectively. AKI developed in 1,089 (26.3%) patients. The incidence of AKI was highest in the lowest urine SG tertile group (410, 29.0%) and lowest in the highest tertile group (304, 23.5%) (P &amp;lt; 0.001). Multivariable logistic regression analysis revealed that being included in the lowest preoperative urine SG tertile group was significantly related with higher post cardiac surgery AKI incidence risk (odd ratio (OR), 1.33; CI, 1.12-1.57; P =0.001). This association was significant even after adjustments were made for confounding factors. Conclusion Low urine SG was associated with increased risk of cardiac surgery associated AKI in patient with normal renal function. Evaluating preoperative urine SG may be useful in stratifying post cardiac surgery AKI risk.

Treatment of Nephrogenic Diabetes Insipidus Patients With cGMP-Stimulating Drugs Does Not Mitigate Polyuria or Increase Urinary Concentrating Ability

Treatment of Nephrogenic Diabetes Insipidus Patients With cGMP-Stimulating Drugs Does Not Mitigate Polyuria or Increase Urinary Concentrating Ability

Urinary Metabolic Profile of Patients with Transfusion-Dependent β-Thalassemia Major Undergoing Deferasirox Therapy

Introduction: Renal dysfunction is a frequent complication in patients suffering from β-thalassemia major (β-TM). The aim of this study was to analyze the renal function and urine metabolomic profile of β-TM patients undergoing transfusions and deferasirox (DFX) therapy, in order to better characterize and shed light on the pathogenesis of renal disease in this setting. Methods and Subjects: 40 patients affected by β-TM treated with DFX and 35 age- and gender-matched healthy controls were enrolled in the study. Renal function was assessed. Glomerular filtration rate (GFR) was estimated with CKD-EPI and Schwartz formula for adults and children, respectively. Renal tubular function and maximal urine concentration ability were tested. Urine specimens were analyzed by nuclear magnetic resonance spectroscopy to identify the urinary metabolite profiles. Results: The study of renal function in β-TM patients revealed normal estimated (e)GFR mean values and the albumin-to-creatinine ratio was <30 mg/g. The analysis of tubular function showed normal basal plasma electrolyte levels; 60% of patients presented hypercalciuria and many subjects showed defective urine concentration. Several amino acids, N-methyl compounds, and organic acids were overexcreted in the urine of thalassemic patients compared with controls. Discussion: The major finding of this work is that β-TM patients and controls exhibit different concentrations of some metabolites in the urine. Early recognition of urinary abnormalities may be useful to detect and prevent kidney damage.

Bile acid signaling in renal water regulation.

Emerging evidence has shown that bile acids play important roles in renal physiology and diseases by activating two major receptors, the nuclear farnesoid X receptor (FXR) and the membrane G protein-coupled bile acid receptor-1 (Gpbar1; also known as TGR5). Both FXR and TGR5 have been identified in human and rodent kidneys, where they are deeply involved in renal water handling. In mice, FXR- or TGR5-related gene deficiency has been associated with reduced aquaporin-2 expression accompanied with impaired urinary concentration ability. In this mini-review, we briefly discuss the current understanding of FXR/TGR5 signaling in the kidneys, with a special focus on the regulation of aquaporin-2 expression by bile acids in the collecting ducts and its potential significance in disease conditions.