Targeting the Trafficking of Kidney Water Channels for Therapeutic Benefit.

The ability to regulate water movement is vital for the survival of cells and organisms. In addition to passively crossing lipid bilayers by diffusion, water transport is also driven across cell membranes by osmotic gradients through aquaporin water channels. There are 13 aquaporins in human tissues, and of these, aquaporin-2 (AQP2) is the most highly regulated water channel in the kidney: The expression and trafficking of AQP2 respond to body volume status and plasma osmolality via the antidiuretic hormone, vasopressin (VP). Dysfunctional VP signaling in renal epithelial cells contributes to disorders of water balance, and research initially focused on regulating the major cAMP/PKA pathway to normalize urine concentrating ability. With the discovery of novel and more complex signaling networks that regulate AQP2 trafficking, promising therapeutic targets have since been identified. Several strategies based on data from preclinical studies may ultimately translate to the care of patients with defective water homeostasis.

Perioperative fluid balance and major postoperative complications in surgery for advanced epithelial ovarian cancer.

OBJECTIVE: Appropriate fluid balance in the perioperative period is important as both hypo- and hypervolemia are associated with increased risk of complications. Women undergoing cytoreductive surgery (CRS) for advanced epithelial ovarian cancer (EOC) may have major fluid shifts. The optimal perioperative fluid balance in these women is yet to be determined. Our objective was to investigate the association between perioperative fluid balance and major postoperative complications. METHODS: Women with advanced stage EOC who underwent surgery at Karolinska University Hospital, Stockholm, Sweden were identified from the institutional database. Women subjected to surgery with curative intent were included in the analysis. Additional data were retrieved from medical records. The association between perioperative fluid balance and major postoperative complications was investigated by multivariable regression and adjusted for predefined confounders. RESULTS: Of the 270 women identified in the institutional database during 2014-2017, 184 women were included in the analyses. Of these women, 22% (n = 40) experienced a major postoperative complication. The fully adjusted odds of major postoperative complications increased when perioperative fluid balance exceeded >3000 mL, (Odds Ratio (OR) 4.85, 95% Confidence Interval (CI) 1.23-19.2, p = 0.02) and > 5000 mL (OR 33.7, 95% CI 4.13-275, p < 0.01). There was no association between negative fluid balance and major postoperative complications (OR 3.33, 95% CI 0.25-44.1, p = 0.36). CONCLUSIONS: Fluid balance >3000 mL perioperatively during surgery for advanced EOC increased the odds of major postoperative complications. Management of perioperative fluid balance in advanced EOC surgery remains a challenge.

Fluid status in the first 10 days of life and death/bronchopulmonary dysplasia among preterm infants.

OBJECTIVE: To investigate the association between fluid and sodium status in the first 10 postnatal days and death/bronchopulmonary dysplasia (BPD) among infants born <29 weeks' gestation. STUDY DESIGN: Single center retrospective cohort study (2015-2018) of infants born 23-28 weeks'. Three exposure variables were evaluated over the first 10 postnatal days: cumulative fluid balance (CFB), median serum sodium concentration, and maximum percentage weight loss. Primary outcome was death and/or BPD. Multivariable logistic regression adjusting for patient covariates was used to assess the association between exposure variables and outcomes. RESULTS: Of 191 infants included, 98 (51%) had death/BPD. Only CFB differed significantly between BPD-free survivors and infants with death/BPD: 4.71 dL/kg (IQR 4.10-5.12) vs 5.11 dL/kg (IQR 4.47-6.07; p < 0.001). In adjusted analyses, we found an association between higher CFB and higher odds of death/BPD (AOR 1.56, 95% CI 1.11-2.25). This was mainly due to the association of CFB with BPD (AOR 1.60, 95% CI 1.12-2.35), rather than with death (AOR 1.08, 95% CI 0.54-2.30). CONCLUSION: Among preterm infants, a higher CFB in the first 10 days after delivery is associated with higher odds of death/BPD. IMPACT: Previous studies suggest that postnatal fluid status influences survival and respiratory function in neonates. Fluid balance, serum sodium concentration, and daily weight changes are commonly used as fluid status indicators in neonates. We found that higher cumulative fluid balance in the first 10 days of life was associated with higher odds of death/bronchopulmonary dysplasia in neonates born <29 weeks. Monitoring of postnatal fluid balance may be an appropriate non-invasive strategy to favor survival without bronchopulmonary dysplasia. We developed a cumulative fluid balance chart with corresponding thresholds on each day to help design future trials and guide clinicians in fluid management.

Extracellular water/total body water ratio as predictor of mortality in hemodialysis patients.

BACKGROUND: Overhydration is a predictor of mortality in hemodialysis (HD) patients. Bioimpedance spectroscopy (BIS) is used to determine the body composition. Extracellular Water/Total Body Water (ECW/TBW) ratio has been proposed to predict mortality. METHODS: Multicenter, prospective, observational, proof-of-concept study to estimate the impact of ECW/TBW in global and cardiovascular mortality and the relationship with cardiovascular biomarkers. The study included 60 patients (mean age, 71.8 ± 11.4 years; mean time on HD, 52.3 ± 30.8 months) with a median follow-up of 30.5 months (IQ range, 17.2-34 months). RESULTS: Post-dialysis ECW/TBW was directly associated with NT-proBNP and cTnT. During the study 28 patients died, most of them (43%) due to cardiovascular events. Compared to the survivors, these subjects had a higher post-dialysis ECW/TBW ratio (p = 0.006), while for cardiovascular mortality the only significant difference was a higher pre-dialysis ECW/TBW. The ability of post-dialysis ECW/TBW ratio to predict all-cause mortality had an area under the ROC curve (AUC) of 0.71 (CI 95%, 0.57-0.81; p = 0.002), with a cutoff point of 0.5023. For cardiovascular mortality the AUC was 0.66 (CI 95%, 0.52-0.77; p = 0.045), with a cutoff point of 0.4713. CONCLUSIONS: The post-dialysis ECW/TBW ratio measured by BIS can be a predictor of all-cause and cardiovascular mortality.

Prevalence and control of hypertension among patients on haemodialysis.

BACKGROUND: Earlier studies provided considerably variable estimates on the prevalence and control rates of hypertension in haemodialysis because of their heterogeneity in definitions and blood pressure (BP) measurement techniques applied to detect hypertension. MATERIALS AND METHODS: In this cross-sectional study, 116 clinically stable haemodialysis patients from 3 dialysis centres of Northern Greece underwent home BP monitoring for 1 week with the validated automatic device HEM-705 (Omron, Healthcare). Routine BP recordings taken before and after dialysis over 6 consecutive sessions were also prospectively collected and averaged. Hypertension was defined as: (a) 1-week averaged home BP ≥ 135/85 mm Hg; (b) 2-week averaged predialysis BP ≥ 140/90 mm Hg; and (c) 2-week averaged postdialysis BP ≥ 130/80 mm Hg. Participants on treatment with ≥1 antihypertensives were also classified as hypertensives. RESULTS: The prevalence of hypertension was 88.8% by home, 86.2% by predialysis and 91.4% by postdialysis BP recordings. In all, 96 participants (82.7%) were being treated with an average of 2.0 ± 1.1 antihypertensive medications. Among drug-treated participants, 32.6% were controlled by home, 50.5% by predialysis and 45.3% by postdialysis BP recordings. In multivariate logistic regression analysis, greater use of antihypertensive medications and postdialysis overhydration, assessed with bioimpedance spectroscopy, were both independently associated with higher odds of inadequate home BP control. CONCLUSIONS: This study shows that the prevalence, but mainly the control rates of hypertension in patients on haemodialysis, differs between peridialytic and interdialytic BP recordings. Therefore, the wider use of home BP monitoring may improve the determination of BP control status in this high-risk population.

The dynamic relationship between serum chloride and cardiorenal syndrome.

Low serum sodium concentration has long been recognized as an established marker of short- and long-term morbidity and mortality in patients with heart failure (HF), and is commonly included in various risk prediction models. Mechanisms leading to hyponatremia (e.g. maladaptive neurohormonal activation) could also lead to concurrent decline in serum chloride levels. Besides, chloride has distinct biological roles (e.g. modulation of renal tubular sodium transporters) that are relevant to the pathophysiology and therapy of HF, making it a potent cardiorenal connector. Several clinical studies have recently reported on a potentially overlooked link between low serum chloride levels and adverse outcomes in patients with a wide variety of HF syndromes, which could indeed be stronger than that of sodium. While evidence on predictive value of chloride is accumulating in various patient populations and settings, the limited available interventional studies have so far yielded conflicting results. It remains to be elucidated whether hypochloremia represents a marker of disease severity and prognosis, or it is an actual pathogenetic mechanism, hence being a potential novel target of therapy. Current ongoing studies are designed to better understand the mechanistic aspects of the role of hypochloremia in HF and shed light on its clinical applicability.

The impact of fluid balance on outcomes in premature neonates: a report from the AWAKEN study group.

BACKGROUND: We evaluated the epidemiology of fluid balance (FB) over the first postnatal week and its impact on outcomes in a multi-center cohort of premature neonates from the AWAKEN study. METHODS: Retrospective analysis of infants <36 weeks' gestational age from the AWAKEN study (N = 1007). FB was defined by percentage of change from birth weight. OUTCOME: Mechanical ventilation (MV) at postnatal day 7. RESULTS: One hundred and forty-nine (14.8%) were on MV at postnatal day 7. The median peak FB was 0% (IQR: -2.9, 2) and occurred on postnatal day 2 (IQR: 1,5). Multivariable models showed that the peak FB (aOR 1.14, 95% CI 1.10-1.19), lowest FB in first postnatal week (aOR 1.12, 95% CI 1.07-1.16), and FB on postnatal day 7 (aOR 1.10, 95% CI 1.06-1.13) were independently associated with MV on postnatal day 7. In a similar analysis, a negative FB at postnatal day 7 protected against the need for MV at postnatal day 7 (aOR 0.21, 95% CI 0.12-0.35). CONCLUSIONS: Positive peak FB during the first postnatal week and more positive FB on postnatal day 7 were independently associated with MV at postnatal day 7. Those with a negative FB at postnatal day 7 were less likely to require MV.

Predialysis fluid overload and gait speed: a repeated measures analysis among patients on chronic dialysis.

BACKGROUND: Slow gait speed is associated with hospitalization and death. We examined whether predialysis fluid overload contributes to gait speed impairment. METHODS: We measured predialysis gait speed at baseline and 12 and 24 months among 298 patients recruited in the A Cohort Study to Investigate the Value of Exercise in ESRD/Analyses Designed to Investigate the Paradox of Obesity and Survival in ESRD. We used multivariable linear mixed modeling to examine associations between patient data and gait speed. We then added either bioimpedance-estimated volume of predialysis fluid overload or volume of delivered ultrafiltration to ascertain whether fluid excess was associated with gait speed and its trajectory. We also tested whether fluid overload change with time was predictive of gait speeds. RESULTS: The mean baseline gait speed was 1.01 m/s and it declined by an average of 0.08 m/s/year. Older age, nonwhite race, Hispanic ethnicity, diabetes, recent fall, recent hospitalization, tobacco use and lower serum albumin were associated with slower gait speed. Each liter of predialysis fluid overload was associated with a 0.02 m/s slower gait speed [95% confidence interval (CI) 0.01-0.04, P = 0.008] and 0.05 m/s additional slowing per year (95% CI 0.03-0.06, P < 0.0001). Higher ultrafiltration volumes were associated with 0.07 m/s slower gait speed per 3% body weight removed (0.002-0.14, P = 0.045) but not with gait speed trajectory (P = 0.08). Patients who increased fluid overload walked 0.08 m/s slower compared with those who decreased fluid overload (95% CI 0.003-0.15, P = 0.04). CONCLUSIONS: Predialysis fluid overload was associated with slower gait speed and gait speed decline over time. Interventions that limit fluid overload may lead to improvements in physical performance.

Impact of protocolized diuresis for de-resuscitation in the intensive care unit.

OBJECTIVE: Administration of diuretics has been shown to assist fluid management and improve clinical outcomes in the critically ill post-shock resolution. Current guidelines have not yet included standardization or guidance for diuretic-based de-resuscitation in critically ill patients. This study aimed to evaluate the impact of a multi-disciplinary protocol for diuresis-guided de-resuscitation in the critically ill. METHODS: This was a pre-post single-center pilot study within the medical intensive care unit (ICU) of a large academic medical center. Adult patients admitted to the Medical ICU receiving mechanical ventilation with either (1) clinical signs of volume overload via chest radiography or physical exam or (2) any cumulative fluid balance ≥ 0 mL since hospital admission were eligible for inclusion. Patients received diuresis per clinician discretion for a 2-year period (historical control) followed by a diuresis protocol for 1 year (intervention). Patients within the intervention group were matched in a 1:3 ratio with those from the historical cohort who met the study inclusion and exclusion criteria. RESULTS: A total of 364 patients were included, 91 in the protocol group and 273 receiving standard care. Protocolized diuresis was associated with a significant decrease in 72-h post-shock cumulative fluid balance [median, IQR - 2257 (- 5676-920) mL vs 265 (- 2283-3025) mL; p < 0.0001]. In-hospital mortality in the intervention group was lower compared to the historical group (5.5% vs 16.1%; p = 0.008) and higher ICU-free days (p = 0.03). However, no statistically significant difference was found in ventilator-free days, and increased rates of hypernatremia and hypokalemia were demonstrated. CONCLUSIONS: This study showed that a protocol for diuresis for de-resuscitation can significantly improve 72-h post-shock fluid balance with potential benefit on clinical outcomes.

Fluid overload is an independent predictor of atrial fibrillation in end-stage renal disease: A prospective study using insertable cardiac and body composition monitors
.

BACKGROUND: Fluid overload and atrial fibrillation (AF) are frequently encountered in patients with end-stage renal disease (ESRD). We used subcutaneously insertable cardiac monitors (ICM) to detect AF and associated it with the hydration status, determined with a body composition monitor (BCM) in dialysis patients. MATERIALS AND METHODS: 69 patients were recruited. Fluid overload was defined based on BCM measurements as a ratio of overhydration (OH) and extracellular water (OH/ECW) of > 15% at baseline. AF episodes lasting ≥ 2 minutes were collected. RESULTS: 45 in-center hemodialysis patients, 11 on peritoneal dialysis, 12 on home hemodialysis, and 1 predialysis-stage patient were followed up for a median of 2.9 years (25th - 75th percentile 1.9 - 3.1). 29% were overhydrated at baseline, and the percentage remained similar throughout the study. Overhydrated patients had a lower body mass index, a higher prevalence of type 1 diabetes mellitus (DM) and diabetic nephropathy, higher systolic blood pressure, greater ultrafiltration (UF) during dialysis, and a smaller lean tissue index than normohydrated patients. Chronic or paroxysmal AF was known to occur in 20.3% at entry, and a further 33.3% developed AF during the study, with an overall prevalence 53.6%. In univariable logistic regression, OH/ECW > 15% was strongly associated with AF prevalence (OR 6.8, 95% CI 1.7 - 26.5, p = 0.006), as were UF, age, coronary heart disease (CHD), DM, and the echocardiogram-derived ejection fraction and left atrial diameter. In multivariable analyses, OH/ECW > 15% remained an independent predictor of AF alongside age and CHD. CONCLUSION: The occurrence of AF is independently associated with BCM-measured fluid overload, which is common among ESRD patients.

Urine Electrolytes in the Intensive Care Unit: From Pathophysiology to Clinical Practice.

Assessment of urine concentrations of sodium, chloride, and potassium is a widely available, rapid, and low-cost diagnostic option for the management of critically ill patients. Urine electrolytes have long been suggested in the diagnostic workup of hypovolemia, kidney injury, and acid-base and electrolyte disturbances. However, due to the wide range of normal reference values and challenges in interpretation, their use is controversial. To clarify their potential role in managing critical patients, we reviewed existing evidence on the use of urine electrolytes for diagnostic and therapeutic evaluation and assessment in critical illness. This review will describe the normal physiology of water and electrolyte excretion, summarize the use of urine electrolytes in hypovolemia, acute kidney injury, acid-base, and electrolyte disorders, and suggest some practical flowcharts for the potential use of urine electrolytes in daily critical care practice.

Using Bioimpedance Spectroscopy to Assess Volume Status in Dialysis Patients.

The aim of the paper is to reflect on the current status of bioimpedance spectroscopy (BIS) in fluid management in dialysis patients. BIS identifies fluid overload (FO) as a virtual (overhydration) compartment, which is calculated from the difference between the measured extracellular volume and the predicted values based on a fixed hydration of lean and adipose tissue mass. FO is highly prevalent in both hemodialysis (HD) and peritoneal dialysis (PD) patients, while levels of FO are at a population level comparable between PD patients and HD patients when measured before the dialysis treatment. Even mild levels of FO are independently related to outcome in patients on HD, PD as well as in nondialysis patients with advanced chronic kidney disease. FO is not only related to left ventricular hypertrophy (LVH) but also forms part of a multidimensional spectrum with noncardiovascular risk factors such as malnutrition and inflammation. Even after multiple adjustments, FO remains an independent predictor of mortality. BIS-assisted adjustment of dry weight in HD patients has been shown to improve hypertension control and LVH and has resulted in a decline in intradialytic symptomatology. On the other hand, with increased fluid removal, target weight may not always be reached due to an increase in intradialytic symptomatology, and care should be applied in target weight adjustment in fluid overloaded patients with severe malnutrition and/or inflammation. Although a reduction in hospitalization rate was suggested, the effect of BIS-guided dry weight adjustment on mortality has not yet been shown, however, although available studies are underpowered. In PD patients, results have been more equivocal, which may be partly related to differences in treatment protocols or study populations. Future large-scale studies are needed to assess the full potential of BIS.

Benefits of peritoneal ultrafiltration in HFpEF and HFrEF patients.

BACKGROUND: Peritoneal ultrafiltration (pUF) in refractory heart failure (HF) reduces the incidence of decompensation episodes, which is of particular significance as each episode incrementally adds to mortality. Nevertheless, there are insufficient data about which patient cohort benefits the most. The objective of this study was to compare pUF in HFrEF and HFpEF, focusing on functional status, hospitalizations, surrogate endpoints and mortality. METHODS: This study involves 143 patients, who could be classified as either HFpEF (n = 37, 25.9%) or HFrEF (n = 106, 74.1%) and who received pUF due to refractory HF. RESULTS: Baseline eGFR was similar in HFrEF (23.1 ± 10.6 mg/dl) and HFpEF (27.8 ± 13.2 mg/dl). Significant improvements in NYHA class were found in HFpEF (3.19 ± 0.61 to 2.72 ± 0.58, P <  0.001) and HFrEF (3.45 ± 0.52 to 2.71 ± 0.72, P <  0.001). CRP decreased in HFrEF (19.4 ± 17.6 mg/l to 13.7 ± 21.4 mg/l, P = 0.018) and HFpEF (33.7 ± 52.6 mg/l to 17.1 ± 26.3 mg/l, P = 0.004). Body weight was significantly reduced in HFrEF (81.1 ± 14.6 kg to 77.2 ± 15.6 kg, P = 0.003) and HFpEF (86.9 ± 15.8 kg to 83.1 ± 15.9 kg, P = 0.005). LVEF improved only in HFrEF (25.9 ± 6.82% to 30.4 ± 12.2%, P = 0.046). BCR decreased significantly in HFrEF and HFpEF (55.7 ± 21.9 to 34.3 ± 17.9 P > 0.001 and 50.5 ± 68.9 to 37.6 ± 21.9, P = 0.006). Number of hospitalization episodes as well as number of hospitalization days decreased significantly only in HFpEF (total number 2.88 ± 1.62 to 1.25 ± 1.45, P <  0.001, days 40.4 ± 31.7 to 18.3 ± 22.5 days, P = 0.005). CONCLUSIONS: pUF offers various benefits in HFpEF and HFrEF, but there are also substantial differences. In particular, hospitalization rates were found to be significantly reduced in HFpEF patients, indicating a greater medical and economical advantage. However, LVEF was only found to be improved in HFrEF patients. While pUF can now be regarded as an option to supplement classical HF therapy, further studies are desirable to obtain specifications about pUF in HFpEF, HFmEF and HFrEF patients.

Pulmonary artery pressure as a method for assessing hydration status in an anuric hemodialysis patient - a case report.

BACKGROUND: Setting the dry weight and maintaining fluid balance is still a difficult challenge in dialysis patients. Overhydration is common and associated with increased cardiac morbidity and mortality. Pulmonary hypertension is associated with volume overload in end-stage renal dysfunction patients. Thus, monitoring pulmonary pressure by a CardioMEMS device could potentially be of guidance to physicians in the difficult task of assessing fluid overload in hemodialysis patients. CASE PRESENTATION: 61-year old male with known congestive heart failure deteriorated over 3 months' time from a state with congestive heart failure and diuresis to a state of chronic kidney disease and anuria. He began a thrice/week in-hospital hemodialysis regime. As he already had implanted a CardioMEMS device due to his heart condition, we were able to monitor invasive pulmonary artery pressure during the course of dialysis sessions. To compare, we estimated overhydration by both bioimpedance and clinical assessment. Pulmonary artery pressure correlated closely with fluid drainage during dialysis and inter-dialytic weight gain. The patient reached prescribed dry weight but remained pulmonary hypertensive by definition. During two episodes of intradialytic systemic hypotension, the patient still had pulmonary hypertension by current definition. CONCLUSION: This case report observes a close correlation between pulmonary artery pressure and fluid overload in a limited amount of observations. In this case we found pulmonary artery pressure to be more sensitive towards fluid overload than bioimpedance. The patient remained pulmonary hypertensive both as he reached prescribed dry weight and experienced intradialytic hypotensive symptoms. Monitoring pulmonary artery pressure via CardioMEMS could hold great potential as a real-time guidance for fluid balance during hemodialysis, though adjusted cut-off values for pulmonary pressure for anuric patients may be needed. Further studies are needed to confirm the findings of this case report and the applicability of pulmonary pressure in assessing optimal fluid balance.

Markers of potassium homeostasis in salt losing tubulopathies- associations with hyperaldosteronism and hypomagnesemia.

BACKGROUND: Renal loss of potassium (K+) and magnesium (Mg2+) in salt losing tubulopathies (SLT) leads to significantly reduced Quality of Life (QoL) and higher risks of cardiac arrhythmia. The normalization of K+ is currently the most widely accepted treatment target, however in even excellently designed RCTs the increase of K+ was only mild and rarely normalized. These findings question the role of K+ as the ideal marker of potassium homeostasis in SLT. Aim of this hypothesis-generating study was to define surrogate endpoints for future treatment trials in SLT in terms of their usefulness to determine QoL and important clinical outcomes. METHODS: Within this prospective cross-sectional study including 11 patients with SLTs we assessed the biochemical, clinical and cardiological parameters and their relationship with QoL (RAND SF-36). The primary hypothesis was that QoL would be more dependent of higher aldosterone concentration, assessed by the transtubular-potassium-gradient (TTKG). Correlations were evaluated using Pearson's correlation coefficient. RESULTS: Included patients were mainly female (82%, mean age 34 ± 12 years). Serum K+ and Mg2+ was 3.3 ± 0.6 mmol/l and 0.7 ± 0.1 mmol/l (mean ± SD). TTKG was 9.5/3.4-20.2 (median/range). While dimensions of mental health mostly correlated with serum Mg2+ (r = 0.68, p = 0.04) and K+ (r = 0.55, p = 0.08), better physical health was associated with lower aldosterone levels (r = -0.61, p = 0.06). TTKG was neither associated with aldosterone levels nor with QoL parameters. No relevant abnormalities were observed in neither 24 h-ECG nor echocardiography. CONCLUSIONS: Hyperaldosteronism, K+ and Mg2+ were the most important parameters of QoL. TTKG was no suitable marker for hyperaldosteronism or QoL. Future confirmatory studies in SLT should assess QoL as well as aldosterone, K+ and Mg2+.

Clinical effect and safety of continuous renal replacement therapy in the treatment of neonatal sepsis-related acute kidney injury.

BACKGROUND: Sepsis is the leading cause of acute kidney injury (AKI) in the neonatal intensive care unit (NICU). The aim of the study is to explore the efficacy and security of continuous renal replacement therapy (CRRT) in the treatment of neonatal sepsis-related AKI. METHOD: Totally12 sepsis-related AKI neonates treated with CRRT were hospitalized in the NICU of Shanghai Children's Hospital between November 2012 and November 2019, and the clinical data of these 12 cases were retrospectively analyzed. Renal function, acid-base balance, electrolytes, blood pressure and hemodynamics indexes were recorded before CRRT initiation, 12/24/48 h after CRRT initiation and at the end of CRRT respectively. The efficacy of CRRT was evaluated and the clinical outcome was observed in these 12 sepsis-related AKI neonates. Repeated measurement analysis of variance was used for statistical analysis of the data. RESULT: (1) Continuous veno-venous hemodialysis filtration (CVVHDF) was used in 12 cases of sepsis-related AKI neonates. There were 6 cases with oliguria, 3 cases with fluid overload (FO), 3 cases with septic shock. The duration of CRRT was 49 ~ 110 h, average (76.2 ± 23.5) h. (2) The blood pressure (BP) of 12 sepsis -related AKI neonates could reach the normal level (40-60 mmHg) 12 h after CRRT initiation, and the normal BP level could be maintained during the CRRT treatment. After 12 h CRRT, the blood pH value increased to the normal range (7.35 ~ 7.45). After 12 h CRRT treatment, the oxygenation index of 12sepsis-related AKI neonates could reach 200 mmHg. After 24 h CRRT treatment, it could rise to more than 300 mmHg. Serum potassium, serum urea nitrogen and serum creatinine levels decreased significantly 12 h after CRRT initiation, and reached the normal range 24 h after CRRT initiation. The urine volume significantly increased 24 h after CRRT initiation. (3) Venous catheterization was performed successfully in all sepsis-related AKI neonates. We observed 2 cases of thrombocytopenia, 1 case of obstruction and 1 case of hypotension in the course of CRRT. There were no complications such as hypothermia, hemorrhage, thrombosis and infection.11 neonates were cured and discharged. One neonate was treated with CRRT and passed through the oliguria stage of AKI, but died after the parents gave up the treatment. CONCLUSIONS: It is safe and effective to treat neonatal sepsis-related AKI with CRRT, which should be an effective measure for the treatment of sepsis-related AKI neonates.

Bio-electrical impedance analysis for perioperative fluid evaluation in open major abdominal surgery.

Water retention and intercompartmental redistribution occur frequently in association with adverse postoperative outcomes, yet the available strategies for non-invasive assessment are limited. One such approach for evaluating body water composition in various circumstances is bio-electrical impedance analysis (BIA). This study aims to appraise the usefulness of the Body Composition Monitor (BCM, Fresenius Medical Care, Germany) in assessing body fluid composition and intercompartmental shifts before and after open major abdominal surgery. This prospective, clinician blinded observational study enrolled all the patients scheduled consecutively for elective major open abdominal surgery during a 1-year period starting from January 1st, 2016. BIA parameters-total body water (TBW), extracellular water (ECW), intracellular water (ICW), absolute fluid overload (AFO), and relative fluid overload (RFO) were measured before and after surgery. The results were compared with fluid balance and outcome parameters such as organ dysfunction, ICU-and hospital length of stay (-LOS). The study population included 71 patients aged 60.2 ± 12 of whom 60.6% men and with a BMI of 26.3 ± 5.1 kg/m2. Postoperative acute kidney injury, respiratory dysfunction, and infections occurred in 14.0%, 19.7% and 28.1% of cases, respectively. The median LOS in ICU was 20 h and the hospital-LOS was 10 days. Positive intraoperative fluid balance (2.4 ± 1.0 L) resulted in a significant increase of TBW (1.4 ± 2.4 L) and of ECW (1.4 ± 1.2 L). Intraoperative fluid balance significantly correlated with TBW change (r = 0.23, p = 0.04) and with AFO change (r = 0.31, p < 0.01). A significant correlation was found between pre- and postoperative AFO and RFO on one hand, and ICU-LOS on the other. BIA may be a useful tool for the perioperative assessment of volume status.

Sodium Intake and Chronic Kidney Disease.

In Chronic Kidney Disease (CKD) patients, elevated blood pressure (BP) is a frequent finding and is traditionally considered a direct consequence of their sodium sensitivity. Indeed, sodium and fluid retention, causing hypervolemia, leads to the development of hypertension in CKD. On the other hand, in non-dialysis CKD patients, salt restriction reduces BP levels and enhances anti-proteinuric effect of renin-angiotensin-aldosterone system inhibitors in non-dialysis CKD patients. However, studies on the long-term effect of low salt diet (LSD) on cardio-renal prognosis showed controversial findings. The negative results might be the consequence of measurement bias (spot urine and/or single measurement), reverse epidemiology, as well as poor adherence to diet. In end-stage kidney disease (ESKD), dialysis remains the only effective means to remove dietary sodium intake. The mismatch between intake and removal of sodium leads to fluid overload, hypertension and left ventricular hypertrophy, therefore worsening the prognosis of ESKD patients. This imposes the implementation of a LSD in these patients, irrespective of the lack of trials proving the efficacy of this measure in these patients. LSD is, therefore, a rational and basic tool to correct fluid overload and hypertension in all CKD stages. The implementation of LSD should be personalized, similarly to diuretic treatment, keeping into account the volume status and true burden of hypertension evaluated by ambulatory BP monitoring.

Angiotensin II and salt-induced decompensation in Balb/CJ mice is aggravated by fluid retention related to low oxidative stress.

Balb/CJ mice are more sensitive to treatment with angiotensin II (ANG II) and high-salt diet compared with C57BL/6J mice. Together with higher mortality, they develop edema, signs of heart failure, and acute kidney injury. The aim of the present study was to identify differences in renal gene regulation that may affect kidney function and fluid balance, which could contribute to decompensation in Balb/CJ mice after ANG II + salt treatment. Male Balb/CJ and C57BL/6J mice were divided into the following five different treatment groups: control, ANG II, salt, ANG II + salt, and ANG II + salt + N-acetylcysteine. Gene expression microarrays were used to explore differential gene expression after treatment and between the strains. Published data from the Mouse Genome Database were used to identify the associated genomic differences. The glomerular filtration rate (GFR) was measured using inulin clearance, and fluid balance was measured using metabolic cages. Gene ontology enrichment analysis of gene expression microarrays identified glutathione transferase (antioxidant system) as highly enriched among differentially expressed genes. Balb/CJ mice had similar GFR compared with C57BL/6J mice but excreted less Na+ and water, although net fluid and electrolyte balance did not differ, suggesting that Balb/CJ mice may be inherently more prone to decompensation. Interestingly, C57BL/6J mice had higher urinary oxidative stress despite their relative protection from decompensation. In addition, treatment with the antioxidant N-acetylcysteine decreased oxidative stress in C57BL/6J mice, reduced urine excretion, and increased mortality. Balb/CJ mice are more sensitive than C57BL/6J to ANG II + salt, in part mediated by lower oxidative stress, which favors fluid and Na+ retention.

Tubule-vascular feedback in renal autoregulation.

Afferent arteriole (Af-Art) diameter regulates pressure and flow into the glomerulus, which are the main determinants of the glomerular filtration rate. Thus, Af-Art resistance is crucial for Na+ filtration. Af-Arts play a role as integrative centers, where systemic and local systems interact to determine the final degree of resistance. The tubule of a single nephron contacts an Af-Art of the same nephron at two locations: in the transition of the thick ascending limb to the distal tubule (macula densa) and again in the connecting tubule. These two sites are the anatomic basis of two intrinsic feedback mechanisms: tubule-glomerular feedback and connecting tubule-glomerular feedback. The cross communications between the tubules and Af-Arts integrate tubular Na+ and water processing with the hemodynamic conditions of the kidneys. Tubule-glomerular feedback provides negative feedback that tends to avoid salt loss, and connecting tubule-glomerular feedback provides positive feedback that favors salt excretion by modulating tubule-glomerular feedback (resetting it) and increasing glomerular filtration rate. These feedback mechanisms are also exposed to systemic modulators (hormones and the nervous system); however, they can work in isolated kidneys or nephrons. The exaggerated activation or absence of any of these mechanisms may lead to disequilibrium in salt and water homeostasis, especially in extreme conditions (e.g., high-salt diet/low-salt diet) and may be part of the pathogenesis of some diseases. In this review, we focus on molecular signaling, feedback interactions, and the physiological roles of these two feedback mechanisms.