SGLT2 Inhibitors Correct Fluid Overload in Adult Kidney Transplant Recipients-A Prospective Observational Study.

In this longitudinal observational study, we measured urinary glucose concentration, body composition and volume status (bioimpedance spectroscopy) and plasma renin and aldosterone concentrations in n = 22 kidney transplant recipients (KTRs) initiating on SGLT2I at baseline (BL), and after 1 week and 1, 3, and 6 months. Estimated glomerular filtration rate (eGFR) decreased by -2 mL/min/1.73 m2 (IQR -10-0) after 1 week and remained stable thereafter. Urinary glucose concentration was 10 (3-24) g/g creatinine after 1 week and correlated with eGFR (r2 = 0.273; p = 0.057). SGLT2I did not affect HbA1c, fasting blood glucose, body weight, fat or lean mass. SGLT2I decreased fluid overload dependent on baseline overhydration (OH, r2 = 0.54, p = 0.0003) without occurrence of dehydration. Plasma aldosterone increased at day 7, while plasma renin did not change significantly. In conclusion, SGLT2I corrected fluid overload in patients with elevated overhydration at baseline, while in euvolemic KTRs fluid status remained stable without reduction of body water below the reference range, thus promoting the safety of SGLT2I therapy in patients following kidney transplantation. Glucosuria, together with effects of SGLT2I on blood glucose control and body weight, is attenuated in KTRs dependent on eGFR.

Diabetes Mellitus and Fluid Imbalance: The Need for Adequate Hydration.

The effect of hydration in modulating metabolic disease risk is a comparatively recent concept. Diabetic patients are at increased risk of dehydration due to osmotic diuresis. Undiagnosed or undertreated hyperglycemia may lead to electrolyte imbalance and elevated renal burden of glucose excretion, which may alter fluid reabsorption in the kidney. Also, the presence of one or more contributory factors, such as inadequate fluid intake, strenuous exercise, high temperatures, alcohol consumption, diarrhea, acute illnesses, fever, nausea, and vomiting, may put diabetic patients at increased risk of dehydration and electrolyte imbalance. Certain antidiabetic agents used by diabetic patients may cause fluid retention/deficits and/or electrolyte abnormalities in a few patients. Thus, drinking ample amounts of water and fluids with appropriate electrolyte composition is important to prevent dehydration. Successful management of dehydration in patients with diabetes is an unmet need and can best be accomplished by maintaining adequate hydration status.

Cardiorenal Syndromes and Their Role in Water and Sodium Homeostasis.

Sodium is the main osmotically active ion in the extracellular fluid and its concentration goes hand in hand with fluid volume. Under physiological conditions, homeostasis of sodium and thus amount of fluid is regulated by neural and humoral interconnection of body tissues and organs. Both heart and kidneys are crucial in maintaining volume status. Proper kidney function is necessary to excrete regulated amount of water and solutes and adequate heart function is inevitable to sustain renal perfusion pressure, oxygen supply etc. As these organs are bidirectionally interconnected, injury of one leads to dysfunction of another. This condition is known as cardiorenal syndrome. It is divided into five subtypes regarding timeframe and pathophysiology of the onset. Hemodynamic effects include congestion, decreased cardiac output, but also production of natriuretic peptides. Renal congestion and hypoperfusion leads to kidney injury and maladaptive activation of renin-angiotensin-aldosterone system and sympathetic nervous system. In cardiorenal syndromes sodium and water excretion is impaired leading to volume overload and far-reaching negative consequences, including higher morbidity and mortality of these patients. Keywords: Cardiorenal syndrome, Renocardiac syndrome, Volume overload, Sodium retention.

Prognostic value of hypochloremia on mortality in patients with heart failure: a systematic review and meta-analysis.

AIMS: Electrolyte imbalances are common in patients with heart failure. Several studies have shown that a low serum chloride level is associated with adverse outcomes in hospitalized patients with acute heart failure and in outpatients with chronic heart failure. We performed a systematic review and meta-analysis to assess the association of hypochloremia with all-cause mortality in patients with heart failure. METHODS: Data search was conducted from inception through 1 February 2023, using the following MeSH terms: ('chloride' OR 'hypochloremia') AND 'heart failure'. Studies evaluating the association between serum chloride and all-cause mortality in patients with heart failure were included. The predefined primary outcome was all-cause mortality. Pooled hazard ratios and 95% confidence intervals (CIs) were used as effect estimates and calculated with a random-effects model; fixed-effects model and leave-one-out sensitivity analyses were also performed. RESULTS: A total of 15 studies, involving 25 848 patients, were included. The prevalence of hypochloremia ranged from 8.6 to 31.5%. Follow-up time ranged from 6 to 67 months. Hypochloremia as a categorical variable was associated with an increased risk of all-cause mortality [hazard ratio 1.56; 95% confidence interval (CI) 1.38-1.75; P  < 0.001]. As a continuous variable, serum chloride was associated with all-cause mortality (hazard ratio per mmol/l decrease in serum chloride: 1.06; 95% CI 1.05-1.07; P  < 0.001). Results were confirmed by using several sensitivity analyses. CONCLUSION: Hypochloremia exhibits a significant prognostic value in patients with heart failure. Serum chloride can be used as an effective tool for risk stratifying in patients with heart failure.

Electrolyte disturbances in patients hospitalized for COVID-19 infection: An observational study.

There are multiple mechanisms by which The Coronavirus-19 (COVID-19) infection can cause electrolyte abnormalities, which may not be the case for bacterial causes of pneumonia. This study aimed to assess the differences in electrolyte levels between patients suffering from COVID-19 and bacterial pneumonia. This is an original, retrospective study. Two cohorts of hospitalized patients were included, 1 suffering from COVID-19 and the other from bacterial pneumonia. Their day 1 and day 3 levels of sodium, potassium, magnesium, and phosphorus, as well as their outcomes, were extracted from the charts. Statistical analysis was subsequently performed. Mean admission levels of sodium, potassium, phosphorus, and magnesium were 135.64 ±â€…6.13, 4.38 ±â€…0.69, 3.53 ±â€…0.69, and 2.03 ±â€…0.51, respectively. The mean day 3 levels of these electrolytes were 138.3 ±â€…5.06, 4.18 ±â€…0.59, 3.578 ±â€…0.59, and 2.11 ±â€…0.64, respectively. Patients suffering from bacterial pneumonia were significantly older (N = 219, mean = 64.88 ±â€…15.99) than patients with COVID-19 pneumonia (N = 240, mean = 57.63 ±â€…17.87). Bacterial pneumonia group had significantly higher serum potassium (N = 211, mean = 4.51 ±â€…0.76), and magnesium (N = 115, mean = 2.12 ±â€…0.60) levels compared to COVID-19 group (N = 227, mean = 4.254 ±â€…0.60 for potassium and N = 118, mean = 1.933 ±â€…0.38 for magnesium). Only magnesium was significantly higher among day 3 electrolytes in the bacterial pneumonia group. No significant association between electrolyte levels and outcomes was seen. We found that COVID-19 patients had lower potassium and magnesium levels on admission, possibly due to the effect of COVID-19 on the renin-angiotensin-aldosterone system as well as patient characteristics and management. We did not find enough evidence to recommend using electrolyte levels as a determinator of prognosis, but more research is needed.

Evaluating fluid overload in critically ill children.

PURPOSE OF REVIEW: To review the evaluation and management of fluid overload in critically ill children. RECENT FINDINGS: Emerging evidence associates fluid overload, i.e. having a positive cumulative fluid balance, with adverse outcome in critically ill children. This is most likely the result of impaired organ function due to increased extravascular water content. The combination of a number of parameters, including physical, laboratory and radiographic markers, may aid the clinician in monitoring and quantifying fluid status, but all have important limitations, in particular to discriminate between intra- and extravascular water volume. Current guidelines advocate a restrictive fluid management, initiated early during the disease course, but are hampered by the lack of high quality evidence. SUMMARY: Recent advances in early evaluation of fluid status and (tailored) restrictive fluid management in critically ill children may decrease complications of fluid overload, potentially improving outcome. Further clinical trials are necessary to provide the clinician with solid recommendations.

[Morphological predictors of water-electrolyte disorders in patients with preventive ileostomy after rectal resection for cancer]. / Issledovanie morfologicheskikh prediktorov vodno-elektrolitnykh narushenii u patsientov so sformirovannoi preventivnoi ileostomoi pri rezektsii pryamoi kishki po povodu raka.

OBJECTIVE: To analyze morphological changes in wall of functioning and non-functioning small intestine in patients with preventive ileostomy and to determine histological predictors of water-electrolyte disorders. MATERIAL AND METHODS: We prospectively analyzed 57 patients >18 years old who underwent rectal resection with preventive ileostomy between January 2022 and November 2023. Anthropometric data included gender, age, body mass index, ECOG and ASA classes. Complications associated with large losses through ileostomy were water-electrolyte disorders, dehydration and acute renal failure with repeated hospitalization. Morphological analysis implied intraoperative full-layer biopsy of small intestine on anterior abdominal wall (ileostomy). Intraoperative biopsy of efferent and afferent loops was also carried out. Tissue samples were examined by light microscopy. We analyzed mean height of mucous membrane villi and depth of crypts, as well as their ratio. Fibrosis and swelling of submucosa were evaluated too. The results were analyzed in the SPSS Statistics 20 software. RESULTS: Mean height of intestinal villi <465 microns (p=0.028), ratio of their height to crypt depth <4.38 (p=0.034) and submucosal fibrosis (p=0.031) significantly affected malabsorption and readmission of patients. The risk of readmission was 11.5 and 5.5 times higher in univariate analysis. Multivariate analysis revealed in-hospital dehydration with resumption of infusion therapy as a predictor of readmission (p=0.046). CONCLUSION: Ileostomy is a certain stress for the patient's body. Not every patient is able for adaptation. One of the adaptation mechanisms is hypertrophy of mucous membrane villi involved in digestion. This mechanism is less pronounced in patients with repeated hospitalizations. Preoperative morphological examination of ileum mucosa may be an additional objective predictor of possible complications of preventive ileostomy.

Effects of overhydration, Kt/Vurea, ß2-microglobulin on coronary artery calcification and mortality in haemodialysis patients.

AIM: We studied the effects of overhydration (OH), Kt/Vurea and ß2-microglobulin (ß2-MG) on coronary artery calcification and mortality in patients undergoing haemodialysis (HD). METHODS: The Agatston coronary artery calcium score (CACS), postdialysis body composition using bioimpedance analysis, single-pool Kt/Vurea and predialysis ß2-MG at baseline were assessed and followed up for 3 years in patients undergoing HD. We performed logistic regression analyses for a CACS ≥400 and Cox proportional hazard analyses for all-cause and cardiovascular mortality. RESULTS: The study involved 338 patients with a median age of 67 (56-74) years, dialysis duration of 70 (33-141) months and diabetes prevalence of 39.1% (132/338). Patients with a CACS ≥400 (n = 222) had significantly higher age, dialysis duration, male prevalence, diabetes prevalence, C-reactive protein, predialysis ß2-MG, OH, extracellular water/total body water and overhydration/extracellular water (OH/ECW) but significantly lower Kt/Vurea than patients with a CACS <400 (n = 116) (p < .05). OH/ECW, Kt/Vurea and predialysis ß2-MG were significant predictors of a CACS ≥400 (p < .05) after adjusting for age, dialysis duration, serum phosphate and magnesium. In all patients, cut-off values of OH/ECW, Kt/Vurea and predialysis ß2-MG for a CACS ≥400 were 16%, 1.74 and 28 mg/L, respectively. After adjusting for dialysis duration, OH/ECW ≥16%, Kt/Vurea ≥1.74 and ß2-MG ≥28 mg/L were significant predictors of 3-year all-cause mortality but not 3-year cardiovascular mortality. CONCLUSION: Higher OH/ECW, higher predialysis ß2-MG and lower Kt/Vurea values are significant risk factors for a CACS ≥400 and 3-year all-cause mortality in patients undergoing maintenance HD.

[Mckittrick-Wheelock syndrome as a rare manifestation of villous adenoma of the rectum]. / Sindrom Makkittrika­Uiloka kak redkoe proyavlenie vorsinchatoi adenomy pryamoi kishki.

McKittrick-Wheelock syndrome is a rare disease when villous adenoma of the distal colon predisposes to profuse watery diarrhea with subsequent severe electrolyte disturbances and acute renal damage. A differentiated approach to correct diagnosis requires in-depth pathophysiological knowledge of regulation of water-electrolyte metabolism, functional and organic disorders of gastrointestinal tract and clinical manifestations of hypoosmolar dehydration. The peculiarity of the McKittrick-Wheelock syndrome is a 100% probability of death without treatment and complete regression of symptoms under complex correction of homeostasis and total resection of tumor. We demonstrate the main clinical trends of the McKittrick-Wheelock syndrome. This report may be useful for general practitioners, gastroenterologists, oncologists, nephrologists and anesthesiologists.

Development and validation of potential phenotypes of serum electrolyte disturbances in critically ill patients and a Web-based application.

BACKGROUND: Electrolyte disturbances are highly heterogeneous and severely affect the prognosis of critically ill patients. Our study was to determine whether data-driven phenotypes of seven electrolytes have prognostic relevance in critically ill patients. METHODS: We extracted patient information from three large independent public databases, and clustered the electrolyte distribution of ICU patients based on the extreme value, median value and coefficient of variation of electrolytes. Three plausible clinical phenotypes were calculated using K-means clustering algorithm as the basic clustering method. MIMIC-IV was considered a training set, and two others have been designated as verification set. The robustness of the model was then validated from different angles, providing dynamic and interactive visual charts for more detailed characterization of phenotypes. RESULTS: 15,340, 12,445 and 2147 ICU patients with electrolyte records during early ICU stay in MIMIC-IV, eICU-CRD and AmsterdamUMCdb were enrolled. After clustering, three reasonable and interpretable phenotypes are defined as α, ß and γ according to the order of clusters. The α and γ phenotype, with significant differences in electrolyte distribution and clinical variables, higher 28-day mortality and longer length of ICU stay (p < 0.001), was further demonstrated by robustness analysis. The α phenotype has significant kidney injury, while the ß phenotype has the best prognosis. In addition, the assignment methods of the three phenotypes were developed into a web-based tool for further verification and application. CONCLUSIONS: Three different clinical phenotypes were identified that correlated with electrolyte distribution and clinical outcomes. Further validation and characterization of these phenotypes is warranted.

Spontaneous tumor lysis syndrome (STLS) during biopsy for burkitt lymphoma: a case report.

BACKGROUND: Tumor lysis syndrome (TLS) is a hematologic oncological emergency characterized by metabolic and electrolyte imbalances. On breakdown of tumor cells, enormous amounts of potassium, phosphate, and nucleic acids are released into systemic circulation. TLS mainly occurs during chemotherapy. However, there are rare incidences of spontaneous tumor lysis syndrome (STLS) prior to commencement of therapy. CASE PRESENTATION: In the case being reported, the child had just undergone a biopsy. As the incision was being closed, there was a sudden onset of high fever, arrhythmia, severe hyperkalemia, hypocalcemia, and acidosis. Following timely symptomatic treatment and continuous renal replacement therapy(CRRT), the child's laboratory results improved, and organ function was restored to normal. The final pathological diagnosis confirmed Burkitt lymphoma. The boy is currently on maintenance chemotherapy. CONCLUSIONS: TLS is a potentially life-threatening complication in hematologic oncology. Several important conclusions can be drawn from this case, reminding clinicians to: (1) be fully aware of the risk factors of TLS and evaluate the level of risk; (2) pay attention to the possibility of STLS during operation, if surgical procedures are necessary and operate with minimal trauma and in the shortest time possibly; (3) take preoperative prophylaxis actively for high-risk TLS patients, including aggressive fluid management and rational use of diuretics and uric-acid-lowering drugs. In addition, this case confirms the effectiveness of CRRT for severe STLS.

[Features of water-electrolyte balance in persons of the older age group].

Age-related changes have a great influence on the regulation of water and electrolyte homeostasis in the body, which is regulated by a complex interaction of environmental factors, drinking behavior, the secretion of a number of hormones and hormone-like substances, as well as the innervation and functional state of the kidneys. It is well known that the changes that are part of physiological aging underlie fluid and electrolyte imbalances, exacerbated by the presence of age-related diseases, medications, or a number of external factors such as malnutrition, fluid intake, and the presence of dementia. This review considers literature data on the effect of normal aging on the development of pathology of the water-sodium balance, including dehydration of senile patients, hyponatremia, hypernatremia, changes in the secretion of antidiuretic hormone and the activity of elements of the renin-angiotensin-aldosterone system.

[Application and control of intravenous fluids in German intensive care units : A national survey among critical care physicians]. / Die Applikation und Steuerung von intravenösen Flüssigkeiten auf deutschen Intensivstationen : Eine nationale Umfrage unter Intensivmediziner:innen.

BACKGROUND: The administration of intravenous fluids includes various indications, e.g., fluid replacement, nutritional therapy or as a solvent for drugs and is a common routine in the intensive care unit (ICU); however, overuse of intravenous fluids can lead to fluid overload, which can be associated with a poorer outcome in critically ill patients. OBJECTIVE: The aim of this survey was to find out the current status of the use and management of intravenous fluids as well as the interprofessional cooperation involving clinical pharmacists on German ICUs. METHODS: An online survey with 33 questions was developed. The answers of 62 participants from the Scientific Working Group on Intensive Care Medicine of the German Society for Anesthesiology and Intensive Care Medicine were evaluated. RESULTS: Fluid overload occurs "frequently" in 62.9% (39/62) and "very frequently" in 9.7% (6/62) of the ICUs of respondents. An established standard for an infusion management system is unknown to 71.0% (44/62) of participants and 45.2% of the respondents stated that they did not have a patient data management system. In addition, the participants indicated how they define fluid overload. This was defined by the presence of edema by 50.9% (28/55) and by positive fluid balance by 30.9% (17/55). According to the participants septic patients (38/60; 63.3%) and cardiological/cardiac surgical patients (26/60; 43.3%) are most susceptible to the occurrence of fluid overload. Interprofessional collaboration among intensive care physicians, critical care nurses, and clinical pharmacists to optimize fluid therapy was described as "relevant" by 38.7% (24/62) and "very relevant" by 45.2% (28/62). Participants with clinical pharmacists on the wards (24/62; 38.7%) answered this question more often as "very relevant" with 62.5% (15/24). CONCLUSION: Fluid overload is a frequent and relevant problem in German intensive care units. Yet there are few established standards in this area. There is also a lack of validated diagnostic parameters and a clear definition of fluid overload. These are required to ensure appropriate and effective treatment that is tailored to the patient and adapted to the respective situation. Intravenous fluids should be considered as drugs that may exert side effects or can be overdosed with severe adverse consequences for the patients. One approach to optimize fluid therapy could be achieved by a fluid stewardship corresponding to comparable established procedures of the antibiotic stewardship. In particular, fluid stewardship will contribute to drug safety of intravenous fluids profiting from joined expertise in a setting of interprofessional collaboration. An important principle of fluid stewardship is to consider intravenous fluids in the same way as medication in terms of their importance. Furthermore, more in-depth studies are needed to investigate the effects of interprofessional fluid stewardship in a prospective and controlled manner.

Interpreting epigenetic causes of recurrent hypokalemia and seizures: Gitelman syndrome co-exist with pseudohypoparathyroidism type 1B.

We describe a unique case of 27-year-old male with Gitelman syndrome (GS) co-exist with pseudohypoparathyroidism type 1B (PHP1B). The patient presented with a 5-year history of seizures, tetany, and numbness of the extremities. Further examinations showed recurrent hypokalemia, inappropriate kaliuresis, hypocalcemia, hyperphosphatemia, and elevated PTH levels. A novel variant of autosomal recessive GS (p.Val287Met SLC12A3) and a novel 492.3Kb deletion containing the whole of STX16, were discovered by a whole-exome sequencing. Following the diagnosis, calcitriol, calcium, and potassium supplements were started. Hematuria calcium and phosphorus levels, as well as blood potassium levels, have recovered and remained within normal ranges after 3 years of follow-up. Our findings have important consequences for supporting the idea that heterozygosity for variants have effects on the patients' clinical performance with autosomal recessive inheritance disorders. Further study is need for the putative effects of the variant. Likewise, further investigation with regards to the gene-gene interaction relations between GS and other electrolyte imbalance disorders is warranted.