Sulfate and acid-base balance.

It has been acknowledged for years that compounds containing sulfur (S) are an important source of endogenous acid production. In the metabolism, S is oxidized to sulfate, and therefore the mEq sulfate excreted in the urine is counted as acid retained in the body. In this study we show that pH in fluids with constant [Na] and [HEPES] declines as sulfate ions are added, and we show that titratable acidity increases exactly with the equivalents of sulfate.

Strong ions and charge-balance.

It has been shown that the ability to predict the pH in any chemically characterized fluid, together with its buffer-capacity and acid content can be based on the requirement of electroneutrality, conservation of mass, and rules of dissociation as provided by physical chemistry. More is not required, and less is not enough. The charge in most biological fluids is dominated by the constant charge on the completely dissociated strong ions but, nonetheless, a persistent narrative in physiology has problematized the notion that these have any role at all in acid-base homeostasis.

Acid content and buffer-capacity: a charge-balance perspective.

Rational treatment and thorough diagnostic classification of acid-base disorders requires quantitative understanding of the mechanisms that generate and dissipate loads of acid and base. A natural precondition for this tallying is the ability to quantify the acid content in any specified fluid. Physical chemistry defines the pH-dependent charge on any buffer species, and also on strong ions on which, by definition, the charge is pH-invariant.

Tissue, urine and serum NMR metabolomics dataset from a 5/6 nephrectomy rat model of chronic kidney disease.

Serum, urine and tissue from a rat model of chronic kidney disease (CKD) were analysed using nuclear magnetic resonance (NMR) spectroscopy-based metabolomics methods, and compared with samples from sham operated rats. Both urine and serum were sampled at multiple timepoints, and the results have been reported elsewhere (https://doi.org/10.

Respiratory Dialysis-A Novel Low Bicarbonate Dialysate to Provide Extracorporeal CO2 Removal.

Objectives: We designed a novel respiratory dialysis system to remove CO2 from blood in the form of bicarbonate. We aimed to determine if our respiratory dialysis system removes CO2 at rates comparable to low-flow extracorporeal CO2 removal devices (blood flow < 500 mL/min) in a large animal model.

Design: Experimental study.

Citrate NMR peak irreproducibility in blood samples after reacquisition of spectra.

Background: In our metabolomics studies we have noticed that repeated NMR acquisition on the same sample can result in altered metabolite signal intensities.

Aims: To investigate the reproducibility of repeated NMR acquisition on selected metabolites in serum and plasma from two large human metabolomics studies.

Methods: Two peak regions for each metabolite were integrated and changes occurring after reacquisition were correlated.

Modeling Acid-Base by Minimizing Charge-Balance.

In this study, we show that equilibrium pH can be obtained for any specified fluid with any number of buffers and dissociations. This is done by root finding in the equation for charge balance. We demonstrate that this equation is monotonic in proton concentration for conceivable buffers.

Tissue, urine and blood metabolite signatures of chronic kidney disease in the 5/6 nephrectomy rat model.

Introduction: Progressive chronic kidney disease (CKD) is an important cause of morbidity and mortality. It has a long asymptomatic phase, where routine blood tests cannot identify early functional losses, and therefore identifying common mechanisms across the many etiologies is an important goal.

Objectives: Our aim was to characterize serum, urine and tissue (kidney, lung, heart, spleen and liver) metabolomics changes in a rat model of CKD.

A Proof of Concept Study, Demonstrating Extracorporeal Carbon Dioxide Removal Using Hemodialysis with a Low Bicarbonate Dialysate.

Extracorporeal carbon dioxide removal (ECCO2R) devices remove CO2 directly from blood, facilitating ultraprotective ventilation or even providing an alternative to mechanical ventilation. However, ECCO2R is not widely available, whereas dialysis is available in most intensive care units (ICUs). Prior attempts to provide ECCO2R with dialysis, by removing CO2 in the form of bicarbonate, have been plagued by metabolic acidosis.

Whole body acid-base modeling revisited.

The textbook account of whole body acid-base balance in terms of endogenous acid production, renal net acid excretion, and gastrointestinal alkali absorption, which is the only comprehensive model around, has never been applied in clinical practice or been formally validated. To improve understanding of acid-base modeling, we managed to write up this conventional model as an expression solely on urine chemistry. Renal net acid excretion and endogenous acid production were already formulated in terms of urine chemistry, and we could from the literature also see gastrointestinal alkali absorption in terms of urine excretions.

Preadmission Diuretic Use and Mortality in Patients Hospitalized With Hyponatremia: A Propensity Score-Matched Cohort Study.

Background: Hyponatremia is associated with increased mortality and is frequently induced by diuretic use. It is uncertain whether diuretic use is linked to mortality risk in patients with hyponatremia.

Study Question: To measure the prognostic impact of diuretic use on 30-day mortality among patients hospitalized with hyponatremia.

Thrombotic Microangiopathy in Inverted Formin 2Mediated Renal Disease.

The demonstration of impaired C regulation in the thrombotic microangiopathy (TMA) atypical hemolytic uremic syndrome (aHUS) resulted in the successful introduction of the C inhibitor eculizumab into clinical practice. C abnormalities account for approximately 50% of aHUS cases; however, mutations in the non-C gene diacylglycerol kinase- have been described recently in individuals not responsive to eculizumab. We report here a family in which the proposita presented with aHUS but did not respond to eculizumab.

Strong Relationships in Acid-Base Chemistry - Modeling Protons Based on Predictable Concentrations of Strong Ions, Total Weak Acid Concentrations, and pCO2.

Understanding acid-base regulation is often reduced to pigeonholing clinical states into categories of disorders based on arterial blood sampling. An earlier ambition to quantitatively explain disorders by measuring production and elimination of acid has not become standard clinical practice. Seeking back to classical physical chemistry we propose that in any compartment, the requirement of electroneutrality leads to a strong relationship between charged moieties.

The frequently used intraperitoneal hyponatraemia model induces hypovolaemic hyponatraemia with possible model-dependent brain sodium loss.

What is the central question of this study? The brain response to acute hyponatraemia is usually studied in rodents by intraperitoneal instillation of hypotonic fluids (i.p. model).

Use of eculizumab in crescentic IgA nephropathy: proof of principle and conundrum?

IgA nephropathy (IgAN) is characterized by a variable clinical course and multifaceted pathophysiology. There is substantial evidence to suggest that complement activation plays a pivotal role in the pathogenesis of the disease. Therefore, complement inhibition using the humanized anti-C5 monoclonal antibody eculizumab could be a rational treatment.

Hyponatremia and mortality risk: a Danish cohort study of 279 508 acutely hospitalized patients.

Objective: We aimed to investigate the impact of hyponatremia severity on mortality risk and assess any evidence of a dose-response relation, utilizing prospectively collected data from population-based registries.

Design: Cohort study of 279 ,508 first-time acute admissions to Departments of Internal Medicine in the North and Central Denmark Regions from 2006 to 2011.

Methods: We used the Kaplan-Meier method (1 - survival function) to compute 30-day and 1-year mortality in patients with normonatremia and categories of increasing hyponatremia severity.

Validity of the International Classification of Diseases, 10th revision discharge diagnosis codes for hyponatraemia in the Danish National Registry of Patients.

Objective: To examine the validity of the International Classification of Diseases, 10th revision (ICD-10) codes for hyponatraemia in the nationwide population-based Danish National Registry of Patients (DNRP) among inpatients of all ages.

Design: Population-based validation study.

Setting: All somatic hospitals in the North and Central Denmark Regions from 2006 through 2011.

ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3.

Nephronophthisis is an autosomal recessive cystic kidney disease that leads to renal failure in childhood or adolescence. Most NPHP gene products form molecular networks. Here we identify ANKS6 as a new NPHP family member that connects NEK8 (NPHP9) to INVS (NPHP2) and NPHP3.

Clinical review: practical approach to hyponatraemia and hypernatraemia in critically ill patients.

Disturbances in sodium concentration are common in the critically ill patient and associated with increased mortality. The key principle in treatment and prevention is that plasma [Na+] (P-[Na+]) is determined by external water and cation balances. P-[Na+] determines plasma tonicity.