Prognostic value of overhydration and bioelectrical impedance vector on short- and long-term outcomes in hospitalized patients with cancer.

BACKGROUND & AIMS: Water, an essential component of body composition, appears to be a significant predictor of adverse outcomes in clinical populations, despite being frequently underexplored. Bioelectrical impedance analysis (BIA) and vector analysis (BIVA) are easy and cost-effective bedside tools for estimating body composition, particularly water content. Therefore, our study aimed to assess the impact of hydration and fluid status using both BIA and BIVA on outcomes in hospitalized patients with cancer. METHODS: A prospective cohort study involving hospitalized individuals with cancer was conducted. Total body water (TBW) was estimated using BIA. Extracellular-water/TBW (ECW/TBW) and ECW/intracellular-water (ECW/ICW) ratios were calculated. BIVA ellipses vectors were constructed to enhance our analysis of hydration status. Participants were followed during their hospital stay and up to six months after discharge to assess outcomes, including in-hospital mortality, 6-month non-elective rehospitalization, and 6-month mortality. RESULTS: TBW, ECW/TBW, ECW/ICW ratios, and BIVA plots were not associated with non-elective rehospitalization during the follow-up period. However, TBW and an elevated ECW/ICW ratio were independent predictors of in-hospital mortality [hazard ratio (HR): 1.07 (1.01; 1.13) p = 0.020; HR: 4.23 (1.69; 10.58) p = 0.002]. Elevated ratios ECW/TBW and ECW/ICW were independent predictors of 6-month mortality [HR: 1.87 (1.10; 3.21) p = 0.022; HR: 2.49 (1.37; 4.51) p = 0.003]. BIVA vectors for in-hospital and 6-month mortality shifted significantly to the right, leading to cachexia and overhydration quadrants (p < 0.05). CONCLUSION: Abnormalities related to overhydration were important predictors of short- and long-term mortality in hospitalized patients with cancer.

On Whether Ca-125 Is the Answer for Diagnosing Overhydration, Particularly in End-Stage Kidney Disease Patients-A Systematic Review.

Overhydration (OH) is a prevalent medical problem that occurs in patients with kidney failure, but a specific marker has still not been found. Patients requiring kidney replacement therapy suffer from a water imbalance, which is correlated with mortality rates in this population. Currently, clinicians employ techniques such as bioimpedance spectroscopy (BIS) and ultrasound (USG) markers of overhydration or markers of heart and kidney function, namely NT-pro-BNP, GFR, or creatinine levels. New serum markers, including but not limited to Ca-125, galectin-3 (Gal-3), adrenomedullin (AMD), and urocortin-2 (UCN-2), are presently under research and have displayed promising results. Ca-125, which is a protein mainly used in ovarian cancer diagnoses, holds great potential to become an OH marker. It is currently being investigated by cardiologists as it corresponds to the volume status in heart failure (HF) and ventricular hypertrophy, which are also associated with OH. The need to ascertain a more precise marker of overhydration is urgent mainly because physical examinations are exceptionally inaccurate. The signs and symptoms of overhydration, such as edema or a gradual increase in body mass, are not always present, notably in patients with chronic kidney disease. Metabolic disruptions and cachexia can give a false picture of the hydration status. This review paper summarizes the existing knowledge on the assessment of a patient's hydration status, focusing specifically on kidney diseases and the role of Ca-125.

Eliminating the need for preoperative intravenous hyperhydration: Sodium thiosulfate as nephrotoxicity prevention in HIPEC-treated patients - A retrospective analysis.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment for peritoneal metastases. However, HIPEC with cisplatin is associated with renal toxicity. Sodium thiosulfate (ST) has been shown to prevent cisplatin-induced toxicity. METHODS: A retrospective, single-center analysis of patients treated curatively for peritoneal surface malignancy, who underwent cytoreductive surgery with cisplatin-based HIPEC between 2015 and 2020. Patients were categorized into three groups based on the management of cisplatin-induced renal toxicity: preoperative hyperhydration alone (PHH), preoperative hyperhydration with ST (PHH + ST), and ST alone. Renal function and complications, in terms of Acute (AKI) and chronic kidney injury (CKI), were monitored and analyzed during 3 postoperative months. RESULTS: This study included 220 consecutive patients. Mean serum creatinine levels were 95, 57 and 61 mmol/L, for PHH, PHH + ST and ST groups, respectively (p < 0.001). Glomerular Filtration Rate (GFR) were 96, 94 and 78 ml/min/1.73 m2, respectively (p < 0.001). AKI and CKI are respectively for PHH, PHH + ST and ST groups were 21 % (n = 46), 1 % (n = 2) and 0 % vs 19 % (n = 42), 0 % and 0 % (p < 0.001), for pairwise analysis did not show any difference between PHH + ST and ST alone combination, regarding nephrological outcomes. All patients were followed 3 months postoperatively. CONCLUSION: There is no need for preoperative hyperhydration when sodium-thiosulfate is used to prevent cisplatin-induced nephrotoxicity in patients undergoing cytoreductive surgery with HIPEC. These findings have implications for improving and simplifying the management of patients with peritoneal metastases undergoing HIPEC with cisplatin.

Why should we use a low sodium dialysis solution for peritoneal dialysis?

Overhydration is highly prevalent in patients on peritoneal dialysis (PD), with inappropriately high sodium load supposedly playing a central role in the pathophysiology of the conditions. Recent studies have revealed the novel role of the interstitium as a buffer system for sodium ions, and it has been reported that patients on dialysis, including PD, present increased levels of sodium in the interstitium, such as in subcutaneous tissue and muscle. Hence, therapy for correction of overhydration should target the excess extracellular volume and the excess sodium storage in the interstitium. The ultrafiltrate obtained using the currently available PD solutions is hypo- to isonatric as compared to serum, which is disadvantageous for prompt and efficient sodium removal from the body in patients with overhydration. In contrast, use of low sodium PD solutions is characterised by iso- to hypernatric ultrafiltrate, which may beneficial for reducing sodium storage in the interstitium. Trials of low sodium PD solutions have reported possible clinical merits, for example, decreased blood pressure, reduced dryness of mouth and decreased body water content as assessed using bioimpedance methods. Given these observations and the high prevalence of overhydration in current PD populations, it makes medical sense that low sodium solutions be positioned as the new standard solution in the future. However, for medical safety, that is, to avoid hyponatremia and excessive decreases in blood pressure, further studies are needed to establish the appropriate compositions and applications of low sodium solutions.

Impact of skin hydration on patterns of microthermal injury produced by fractional CO2 laser.

OBJECTIVES: The impact of skin hydration on patterns of thermal injury produced by ablative fractional lasers (AFLs) is insufficiently examined under standardized conditions. Using skin with three different hydration levels, this study assessed the effect of hydration status on microchannel dimensions generated by a fractional CO2 laser. METHODS: A hydration model (hyperhydrated-, dehydrated- and control) was established in ex vivo porcine skin, validated by changes in surface conductance and sample mass. After, samples underwent AFL exposure using a CO2 laser (10,600 nm) at two examined pulse energies (10 and 30 mJ/mb, fixed 10% density, six repetitions per group). Histological assessment of distinct microchannels (n = 60) determined three standardized endpoints in H&E sections: (1) depth of microthermal treatment zones (MTZs), (2) depth of microscopic ablation zones (MAZs), and (3) coagulation zone (CZ) thickness. As a supplemental in vivo assessment, the same laser settings were applied to hyperhydrated- (7-h occlusion) and normohydrated forearm skin (no pretreatment) of a human volunteer. Blinded measurement of MAZ depth (n = 30) was performed using noninvasive optical coherence tomography (OCT). RESULTS: Modest differences in microchannel dimensions were shown between hyperhydrated, dehydrated and control skin at both high and low pulse energy. Compared to controls, hyperhydration led to median reductions in MTZ and MAZ depth ranging from 5% to 8% (control vs. hyperhydrated at 30 mJ/mb; 848 vs. 797 µm (p < 0.003) (MAZ); 928 vs. 856 µm (p < 0.003) (MTZ)), while 14%-16% reductions were shown in dehydrated skin (control vs. dehydrated at 30 mJ/mb; MAZ: 848 vs. 727 µm (p < 0.003); MTZ: 928 vs. 782 µm (p < 0.003)). The impact of skin hydration on CZ thickness was in contrast limited. Corresponding with ex vivo findings, hyperhydration was similarly associated with lower ablative depth in vivo skin. Thus, median MAZ depth in hydrated skin was 10% and 14% lower than in control areas at 10 and 30 mJ/mb pulse energy, respectively (10 mJ: 210 vs. 180 µm (p < 0.001); 30 mJ: 335 vs. 300 µm (p < 0.001)). CONCLUSION: Skin hydration status can exert a minimal impact on patterns of microthermal injury produced by fractional CO2 lasers, although the clinical implication in the context of laser therapy requires further study.

Rhabdomyolysis Complicated with Hyponatremia Due to Water Intoxication and Severe Aspiration Pneumonia: Description of a Patient with Chronic Schizophrenia and Literature Review.

Hyponatremia due to water intoxication is frequently observed in patients with chronic schizophrenia. We herein present a 49-year-old man who developed schizophrenia at the age of 23 and had been admitted to the closed ward of our hospital for 7 years. He was found by a round nurse standing at the bedside, covering both ears with his hands and making groaning noises. He was disoriented and immediately after being returned to bed, a general tonic-clonic seizure occurred. Severe hyponatremia (Na 104 mEq/L) was noted and intravenous sodium correction was started. A few hours later, due to glossoptosis and massive vomiting, ventilation got worse to the point where he had to be put on a ventilator. On the following day, he developed aspiration pneumonia and antimicrobial treatment was started. In addition, a blood sample taken 36 hours later revealed an extensive elevation of creatine kinase (41,286 U/L), pointing to a possibility of rhabdomyolysis as a complication. Subsequently, the general condition gradually improved with antimicrobial therapy and sodium correction. He eventually recovered without any complications including central pontine myelinolysis. He had no history of polydipsia before this event but it was later found that esophageal stricture triggered complusive fluid intake, resulting in acute hyponatremia, seizure, aspiration pneumonia and rhabdomyolysis. A brief discussion will be provided on the issues surrounding hyponatremia, rhabdomyolysis and schizophrenia.

The Role of Pre- and Post-Transplant Hydration Status in Kidney Graft Recovery and One-Year Function.

Background and Objectives: Early improvements to graft function are crucial for good outcomes in kidney transplantation (kTx). Various factors can influence early graft function. This study aimed to evaluate the pre- and post-transplant hydration statuses of kTx recipients using bioimpedance analysis (BIA) and lung ultrasonography (LUS) and to investigate the hydration status' relationship with the function of the transplanted kidney during the first year after transplantation. Materials and Methods: This observational prospective cohort study included deceased kidney recipients transplanted in the Hospital of the Lithuanian University of Health Sciences between September 2016 and January 2023. BIA and LUS were performed before transplantation, on days 3 and 7, and at discharge. Data on recipient and donor clinical characteristics were collected. Graft function was evaluated according to the serum creatinine reduction ratio and the need for dialysis. Hydration status was evaluated by calculating B-lines (BL) on LUS and the ratio of extracellular/total body water on BIA. Results: Ninety-eight kTx recipients were included in the study. Patients with immediate graft function (IGF) were compared to those with slow or delayed graft function (SGF + DGF). Recipients in the SGF + DGF group had a higher sum of BL on LUS before transplantation. After transplantation in early postoperative follow-up, both groups showed hyperhydration as determined by BIA and LUS. After one year, recipients with no BL before transplantation had better graft function than those with BL. Logistic regression analysis showed that having more than one BL in LUS was associated with a 2.5 times higher risk of SGF or DGF after transplantation. Conclusions: This study found that lung congestion detected by LUS before kTx was associated with slower graft recovery and worse kidney function after 1 year. Meanwhile, the hyperhydration status detected by BIA analysis did not correlate with the function of the transplanted kidney.

Hyperhydration of Cancers: A Characteristic Biophysical Trait Strongly Increasing O2, CO2, Glucose and Lactate Diffusivities, and Improving Thermophysical Properties of Solid Malignancies.

Cancers are complex, heterogeneous, dynamic and aggressive diseases exhibiting a series of characteristic biophysical traits which complement the original biological hallmarks of cancers favouring progressive growth, metastasis, and contributing to immune evasion and treatment resistance. One of the prevalent differences between most solid tumors and their corresponding, healthy tissues is a significantly higher water content (hyperhydration) in cancers. As a consequence, cancers have distinctly higher (Fick's) diffusion coefficients D [cm2 s-1] for the respiratory gases O2 and CO2, the key substrate glucose, and for the oncometabolite lactate. In addition, cancers have (a) clearly increased specific heat capacities cp [J g-1 K-1], thus representing high-capacity-tissues upon therapeutic heating induced by electromagnetic irradiation, and (b) higher thermal conductivities k [W m-1 K-1], i.e., increased abilities to conduct heat. Therefore, in diffusion analyses (e.g., when describing critical O2 and glucose supplies or CO2 removal, and the development of hypoxic subvolumes) and for modeling temperature distributions in hyperthermia treatment planning, these specific cancer-related data must be considered in order to reliably reflect oncologic thermo-radiotherapy settings.

Hyperhydration to Improve Kidney Outcomes in Children with Shiga Toxin-Producing E. coli Infection: a multinational embedded cluster crossover randomized trial (the HIKO STEC trial).

BACKGROUND: Shiga toxin-producing E. coli (STEC) infections affect children and adults worldwide, and treatment remain solely supportive. Up to 15-20% of children infected by high-risk STEC (i.e., E. coli that produce Shiga toxin 2) develop hemolytic anemia, thrombocytopenia, and kidney failure (i.e., hemolytic uremic syndrome (HUS)), over half of whom require acute dialysis and 3% die. Although no therapy is widely accepted as being able to prevent the development of HUS and its complications, several observational studies suggest that intravascular volume expansion (hyperhydration) may prevent end organ damage. A randomized trial is needed to confirm or refute this hypothesis. METHODS: We will conduct a pragmatic, embedded, cluster-randomized, crossover trial in 26 pediatric institutions to determine if hyperhydration, compared to conservative fluid management, improves outcomes in 1040 children with high-risk STEC infections. The primary outcome is major adverse kidney events within 30 days (MAKE30), a composite measure that includes death, initiation of new renal replacement therapy, or persistent kidney dysfunction. Secondary outcomes include life-threatening, extrarenal complications, and development of HUS. Pathway eligible children will be treated per institutional allocation to each pathway. In the hyperhydration pathway, all eligible children are hospitalized and administered 200% maintenance balanced crystalloid fluids up to targets of 10% weight gain and 20% reduction in hematocrit. Sites in the conservative fluid management pathway manage children as in- or outpatients, based on clinician preference, with the pathway focused on close laboratory monitoring, and maintenance of euvolemia. Based on historical data, we estimate that 10% of children in our conservative fluid management pathway will experience the primary outcome. With 26 clusters enrolling a mean of 40 patients each with an intraclass correlation coefficient of 0.11, we will have 90% power to detect a 5% absolute risk reduction. DISCUSSION: HUS is a devastating illness with no treatment options. This pragmatic study will determine if hyperhydration can reduce morbidity associated with HUS in children with high-risk STEC infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT05219110 . Registered on February 1, 2022.

Is withdrawal of nocturnal hyperhydration possible in children with primary hyperoxaluria treated with RNAi?

Primary hyperoxaluria type 1 is a rare genetic disorder caused by bi-allelic pathogenic variants in the AGXT gene leading to an overproduction of oxalate which accumulates in the kidneys in the form of calcium oxalate crystals. Thus, patients may present with recurrent nephrocalcinosis and lithiasis, with progressive impairment of the  renal function and eventually kidney failure.  There is no specific treatment besides liver-kidney transplantation, and pre-transplantation management by 24 h-hyperhydration, crystallisation inhibitors and high-dose pyridoxine has a high negative impact on quality of life, especially because of the discomfort due to nocturnal hyperhydration. Since 2020, lumasiran, an RNA-interfering therapy, has been approved for the treatment of primary hyperoxaluria type 1 in adults and children. However, to date, there are no recommendations regarding the discontinuation of other supportive measures during RNAi therapy. In this report, we present two patients with primary hyperoxaluria type 1 who were treated with lumasiran and stopped nocturnal hyperhydration with positive outcomes, i.e. normal urinary oxalate, absence of crystalluria, stable kidney function and improved well-being. These data suggest that discontinuing nocturnal hydration may be safe in children responding to lumasiran, and may have a positive impact on their quality of life. Additional data are needed to update treatment recommendations.

Effect of Glycerol-Induced Hyperhydration on a 5-kilometer Running Time-Trial Performance in the Heat in Recreationally Active Individuals.

Maximal oxygen consumption (V˙O2max) is a major determinant of 5-km running time-trial (TT) performance. Glycerol-induced hyperhydration (GIH) could improve V˙O2max in recreationally active persons through an optimal increase in plasma volume. Moreover, ingestion of a large bolus of cold fluid before exercise could decrease thermal stress during exercise, potentially contributing to improved performance. We determined the effect of GIH on 5-km running TT performance in 10 recreationally active individuals (age: 24 ± 4 years; V˙O2max: 48 ± 3 mL/kg/min). Using a randomized and counterbalanced protocol, participants underwent two, 120-min hydration protocols where they ingested a 1) 30 mL/kg fat-free mass (FFM) of cold water (~4 °C) with an artificial sweetener + 1.4 g glycerol/kg FFM over the first 60 min (GIH) or 2) 7.5 mL/kg FFM of cold water with an artificial sweetener over the first 20 min (EUH). Following GIH and EUH, participants underwent a 5-km running TT at 30 °C and 50% relative humidity. After 120 min, GIH was associated with significantly greater fluid retention (846 ± 415 mL) and plasma volume changes (10.1 ± 8.4%) than EUH, but gastrointestinal (GI) temperature did not differ. During exercise, 5-km running TT performance (GIH: 22.95 ± 2.62; EUH: 22.52 ± 2.74 min), as well as heart rate, GI temperature and perceived exertion did not significantly differ between conditions. This study demonstrates that the additional body water and plasma volume gains provided by GIH do not improve 5-km running TT performance in the heat in recreationally active individuals.

Perioperative changes in fluid distribution and haemodynamics in acute high-risk abdominal surgery.

BACKGROUND: Understanding the pathophysiology of fluid distribution in acute high-risk abdominal (AHA) surgery is essential in optimizing fluid management. There is currently no data on the time course and haemodynamic implications of fluid distribution in the perioperative period and the differences between the surgical pathologies. METHODS: Seventy-three patients undergoing surgery for intestinal obstruction, perforated viscus, and anastomotic leakage within a well-defined perioperative regime, including intraoperative goal-directed therapy, were included in this prospective, observational study. From 0 to 120 h, we measured body fluid volumes and hydration status by bioimpedance spectroscopy (BIA), fluid balance (input vs. output), preload dependency defined as a > 10% increase in stroke volume after preoperative fluid challenge, and post-operatively evaluated by passive leg raise. RESULTS: We observed a progressive increase in fluid balance and extracellular volume throughout the study, irrespective of surgical diagnosis. BIA measured variables indicated post-operative overhydration in 36% of the patients, increasing to 50% on the 5th post-operative day, coinciding with a progressive increase of preload dependency, from 12% immediately post-operatively to 58% on the 5th post-operative day and irrespective of surgical diagnosis. Patients with overhydration were less haemodynamically stable than those with normo- or dehydration. CONCLUSION: Despite increased fluid balance and extracellular volumes, preload dependency increased progressively during the post-operative period. Our observations indicate a post-operative physiological incoherence between changes in the extracellular volume compartment and inadequate physiological preload control in patients undergoing AHA surgery. Considering the increasing overhydration during the observational period, our findings show that an indiscriminate correction of preload dependency with intravenous fluid bolus could lead to overhydration. Trial registration clinicaltrials.gov. (NCT03997721), Registered 23 May 2019, first participant enrolled 01 June 2019.

Case-based review of dietary management of cystinuria.

PURPOSE: The currently recommended treatment strategy for cystine stone formers is based on a progressive approach that starts with the most conservative measures. In patients with cystinuria, increased patient compliance with dietary management and medical treatment is associated with fewer stone interventions. In this case-based review, the dietary management of cystine stone former was reviewed under the guidance of evidence-based medicine. METHODS: The dietary management of the 13-year-old cystinuria patient, who underwent 18 endourological stone interventions, was reviewed in the light of evidence-based medicine. A literature search was performed in Pubmed, MEDLINE, Embase, and Cochrane Library databases according to PRISMA guidelines published from 1993 to September 2022. A total of 304 articles were included in this paper. RESULTS: In managing patients with cystinuria, hyperhydration, and alkalinization of the urine with medical treatment, the rational use of cystine-binding drugs by taking into account individual situations has come to the fore. A limited study has argued that a vegetarian diet is effective as the alkaline load from fruits and vegetables can reduce the amount of alkalizing substances required to achieve urinary alkalinization above pH 7.5, making it particularly suitable for the dietary treatment of cystine stone disease. CONCLUSION: Life-long follow-up with dietary modification, hyperhydration, and personalized medical therapy (alkalinization and cystine-binding drugs) are critical in preventing chronic kidney disease and kidney failure in cystinuria.

The uric acid-urea distribution volume ratio is a potential marker of hydration status in patients on hemodialysis.

The distribution volume of uric acid is affected by the amount of extracellular water (ECW), while urea distribution volume can be considered as total body water (TBW). Thus, the ratio of distribution volumes of uric acid and urea can be paralleled to and be considered as the proxy of ECW/TBW. A total of 108 patients at our facility was included. The uric acid and urea distribution volume ratio (UUVdR) calculated from the single-pool model, which was measured within 1 month of the time when the bioimpedance index was measured. ECW/TBW at the end of the HD session was measured by InBody S10. We investigated the association between the UUVdR and the ECW/TBW values and the factors affecting the residuals of the regression equation. We also evaluated the predictive ability of overhydration or dehydration in randomly selected two groups, i.e., the training group and the validation group. ECW/TBW correlated highly with UUVdR. Multivariate analysis demonstrated that only creatinine and ECW/TBW were significantly associated with regression residuals. The cutoff values of UUVdR for overhydration and dehydration were 0.666 and 0.579, respectively, in the training group. Their AUC were 0.872 and 0.898, respectively. The sensitivity and specificity values in the validation group were 0.571 and 0.868 for overhydration, and 0.444 and 0.953 for dehydration, respectively. UUVdR might be a proxy of hydration status in hemodialysis patients. It may be possible to predict hydration status without dedicated devices in the epidemiological study.

Bioimpedance spectroscopy fluid analysis in acute high-risk abdominal surgery, a prospective clinician-blinded observational feasibility study.

Objective assessment of fluid status in critical surgical care may help optimize perioperative fluid administration and prevent postoperative fluid retention. We evaluated the feasibility of hydration status and fluid distribution assessment by Bioimpedance spectroscopy Analysis (BIA) in patients undergoing acute high-risk abdominal (AHA) surgery. This observational study included 73 patients undergoing AHA surgery. During the observational period (0-120 h), we registered BIA calculated absolute fluid overload (AFO) and relative fluid overload (RFO), defined as AFO/extracellular water ratio, as well as cumulative fluid balance and weight. Based on RFO values, hydration status was classified into three categories: dehydrated (RFO < - 10%), normohydrated (- 10% ≤ RFO ≤ + 15%), overhydrated RFO > 15%. We performed a total of 365 BIA measurements. Preoperative overhydration was found in 16% of patients, increasing to 66% by postoperative day five. The changes in BIA measured AFO correlated with the cumulative fluid balance (r2 = 0.44, p < .001), and change in weight (r2 = 0.55, p < .0001). Perioperative overhydration measured with BIA was associated with worse outcome compared to patients with normo- or dehydration. We have demonstrated the feasibility of obtaining perioperative bedside BIA measurements in patients undergoing AHA surgery. BIA measurements correlated with fluid balance, weight changes, and postoperative clinical complications. BIA-assessed fluid status might add helpful information to guide fluid management in patients undergoing AHA surgery.

Benefits of BNP/NT-proBNP serum level evaluation for dry weight adjustment in pediatric hemodialysis patients.

BACKGROUND: Dry weight (DW) adjustment in children on hemodialysis (HD) can be challenging. It relies on clinical evaluation and additional supports. Our aim was to study the benefits of cardiac biomarker assessment, in addition to the more commonly used technique, bioimpedance spectroscopy (BIS), and clinical signs for DW prescription in pediatric HD patients. METHOD: Observational study including 41 children on HD in three pediatric HD centers in the Paris region. During one session, BIS was performed before the session and serum levels of BNP and NT-proBNP were analyzed before and after the session. RESULTS: Median pre-dialysis level of BNP was 87 ng/L [24-192] and NT-proBNP 968 ng/L [442-4828]. Cardiac biomarker levels showed positive correlation with the BIS hydration status evaluation (p = 0.004). The most appropriate cutoff for pre-dialysis BNP to detect significant overhydration (OH) was 165 ng/L (sensitivity 0.67, specificity 0.84). Based on the BIS evaluation, only 32% of patients with high blood pressure (BP) had OH, whereas in the normal BP group, 33% had significant OH. CONCLUSIONS: DW prescription for children on HD should not only rely on clinical evaluation, particularly BP, but should also include additional helpful parameters. BIS is well-validated in children, but it has limitations in non-cooperative patients, and its cost can limit its use in some settings. Cardiac biomarkers, especially BNP, were well-correlated to hydration status evaluated by BIS, and thus could add valuable information for individual patient management and DW assessment. A higher resolution version of the Graphical abstract is available as Supplementary information.

Severe hyponatremia due to surreptitious water intoxication in a hospitalized patient.

Hyponatremia is a common electrolyte abnormality among hospitalized patients and often present as first sign of other underlying medical conditions. Severe hyponatremia can be life threatening and requires prompt diagnosis and treatment. We present a case of refractory hyponatremia that was a diagnostic challenge requiring a prolonged hospitalization. Diagnosis of primary polydipsia was ultimately suspected due to improbable 24-h urine studies and confirmed through complete removal of free water access in the form of disconnecting the bathroom faucet in the patient's hospital room. Diagnosis and management of primary polydipsia is further discussed.

Seizure from water intoxication following bowel preparation: a case report.

BACKGROUND: Bowel preparation prior to colonoscopic examination is generally considered a safe process. Hyponatremia is a complication that has been reported in literature during bowel preparation. Individuals who develop severe symptomatic hyponatremia are often older and have comorbidities such as hypothyroidism, chronic kidney disease, or adrenal insufficiency. However, other mechanisms and circumstances can also lead to this potentially fatal complication. CASE PRESENTATION: We present a unique case of a patient who developed seizure prior to colonoscopy due to acute hyponatremia without any well-known risk factors. With the subsequent diagnosis of water intoxication, the use of desmopressin was believed to have contributed to this serious complication. CONCLUSION: In addition to the use of certain well-documented medications and the presence of comorbidities that can lead to hyponatremia, clinicians should also be aware of the use of desmopressin as an important risk factor. Thorough history taking can guide individualized bowel preparation regimens to minimize the risk of undesired complications.

Prevalence of cardiovascular diseases in kidney transplant recipients and its relationship with asymmetric dimethylarginine, fibroblast growth factor-23 and multiple inflammatory markers.

INTRODUCTION AND AIM: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase, a marker of endothelial damage and progression of atherosclerosis. Research confirms the association of ADMA with an increased risk of cardiac complications and an increased risk of death, graft loss among kidney transplant recipients (KTRs). The aim of our study was to establish the significance of ADMA and FGF-23 as biomarkers of cardiovascular risk as well as predictors of graft failure and progression of chronic transplant kidney disease in comparison to CKD subjects. In addition, an analysis of the relationship between ADMA, FGF23 and cardiovascular diseases in CKD subjects and KTRs was performed. MATERIAL AND METHODS: The study group included 132 KTRs. The control group consisted of age- and sex-adjusted 40 individuals with clinically stable CKD. ADMA, FGF-23, hs-CRP and IL-6 were measured by the enzyme-linked immunoassay method (ELISA). Parameters of body mass composition such as fat mass, FTI, lean tissue mass, LTI, body water and overhydration were assessed by multi-frequency bioimpedance analysis (BIA). RESULTS: Cardiovascular diseases (CVDs) were present in 31.8% of KTRs. Independent variables related to nutritional status (SGA, s-albumin), according to multivariate regression, may have an impact on the prevalence of CVD in the kidney transplant recipients' group. Our study findings suggested a correlation between ADMA and serum albumin (r=-0.41, p<0.05), oxLDL (r=-0.42, p<0.05) and overhydration (OH%, r=0.28, p<0.05). Moreover, administration of statins and/or angiotensin-converting-enzyme inhibitors was significantly related to a reduction of ADMA in KTRs. We have also identified a significant positive correlation between FGF-23 levels and inflammatory markers (hs-CRP, IL-6) and negative with overall index of renal function (eGFR-CKD EPI, eGFR-MDRD). CONCLUSION: Nutritional status, inflammation and endothelial dysfunction markers (ADMA, FGF-23) are considerably altered even in stable kidney transplant recipients.

AQP4-A25Q Point Mutation in Mice Depolymerizes Orthogonal Arrays of Particles and Decreases Polarized Expression of AQP4 Protein in Astrocytic Endfeet at the Blood-Brain Barrier.

Aquaporin-4 (AQP4) is characterized by the formation of orthogonal arrays of particles (OAPs) comprising its M1 and M23 isoforms in the plasma membrane. However, the biological importance of OAP formation is obscure. Here, we developed an OAP depolymerization male mouse model by transgenic knock-in of an AQP4-A25Q mutation. Analyses of the mutant brain tissue using blue native polyacrylamide gel electrophoresis, super-resolution imaging, and immunogold electron microscopy revealed remarkably reduced OAP structures and glial endfeet localization of the AQP4-A25Q mutant protein without effects on its overall mRNA and protein expression. AQP4A25Q/A25Q mice showed better survival and neurologic deficit scores when cerebral edema was induced by water intoxication or middle cerebral artery occlusion/reperfusion. The brain water content and swelling of pericapillary astrocytic endfeet processes in AQP4A25Q/A25Q mice were significantly reduced, functionally supporting decreased AQP4 protein expression at the blood-brain barrier. The infarct volume and neuronal damage were also reduced in AQP4A25Q/A25Q mice in the middle cerebral artery occlusion/reperfusion model. Astrocyte activation in the brain was alleviated in AQP4A25Q/A25Q mice, which may be associated with decreased cell swelling. We conclude that the OAP structure of AQP4 plays a key role in its polarized expression in astrocytic endfeet processes at the blood-brain barrier. Therefore, our study provided new insights into intervention of cerebral cellular edema caused by stroke and traumatic brain injury through regulating AQP4 OAP formation.SIGNIFICANCE STATEMENT Aquaporin-4 (AQP4) is characterized by orthogonal arrays of particles (OAPs) comprising the M1 and M23 isoforms in the membrane. Here, an OAP depolymerization male mouse model induced by AQP4-A25Q mutation was first established, and the functions of OAP depolymerization in cerebral edema have been studied. The results revealed that AQP4 lost its OAP structure without affecting AQP4 mRNA and protein levels in AQP4-A25Q mice. AQP4-A25Q mutation mice has neuroprotective effects on cerebral edema induced by water intoxication and middle cerebral artery occlusion/reperfusion through relieving the activation of astrocytes and suppressed microglia-mediated neuroinflammation. We concluded that the OAP structure of AQP4 plays a key role in its polarized expression in astrocytic endfeet processes at the blood-brain barrier. Therefore, our study provided new insights into intervention of cerebral cellular edema caused by stroke and traumatic brain injury through regulating AQP4 OAP formation.