Elevated serum bicarbonate concentration in chronic kidney disease: a call to find the cause

In this issue, Dobre et al1 reported an observational study looking at results of annually measured serum bicarbonate concentration in participants with chronic kidney disease (CKD) enrolled in the Chronic Renal Insufficiency Cohort (CRIC) using the marginal structural model, a validated statistical method,2 to estimate the cumulative effect over the period of the study and their effects on adjudicated heart failure events, atherosclerotic events, renal disease progression, and mortality. In their analysis, they included patients aged 21 to 74 years with estimated glomerular filtration rate of 20 to 70 mL/min per 1.73 m2 and excluded patients with NYHA Class III/IV heart failure. The final study population of this analysis included 3586 participants. They adjusted all models for age, gender, race/ethnicity, clinical center, estimated glomerular filtration rate, proteinuria, diabetes, systolic blood pressure, cardiovascular disease at baseline, chronic obstructive pulmonary disease, tobacco use, diuretic and alkali medication used, low-density lipoprotein, Fibroblast growth factor-23 (FGF-23), and high-sensitivity C-reactive protein. In their analysis, over an average of 6 years of followup, they found a statistically significant higher rate of heart failure events and mortality in participants who maintained serum bicarbonate \u3e26 mmol/L, while participants who maintained serum bicarbonate \u3c22 mmol/L had increased risk of renal disease progression defined as halving of estimated glomerular filtration rate or end-stage renal disease. On the other hand, there was no association between serum bicarbonate levels and atherosclerotic cardiovascular events. In subgroup analysis, the relationship between serum bicarbonate concentration and heart failure and renal events was consistent across categories of race/ ethnicity, diabetes, or baseline kidney function. The strength of association between serum bicarbonate \u3e26 and \u3c22 and heart failure and renal events, respectively, persisted after excluding participants taking alkali therapy, or who had chronic obstructive pulmonary disease (COPD) or cardiovascular disease at baseline. On the other hand, the study was not powered to exclude participants on diuretic therapy (60% of the study cohort were taking diuretics), which is a major cause of metabolic alkalosis

Pregnancy Induced Microangiopathy, HELLP OR TTP!

Introduction: Thrombotic thrombocytopenic purpura (TTP) in pregnancy is rare and can be fatal if misdiagnosed.Typically patients present with microangiopathic hemolytic anemia, thrombocytopenia, Altered mental status, fever, and renal abnormalities Case Description: We are presenting a case of 26 year old pregnant female presented with elevated BP. She had scattered Bruises in her legs, thighs and arms along with +2 bilateral pitting leg edema. Initial and subsequent laboratory studies showed features of microangiopathic hemolytic anemia (MAHA), which brought up the suspicion of HELLP (hemolysis, elevated liver enzymes, low platelets )syndrome initially. Labor was induced after transfusion of 2 units of PRBCs and 2 units of Platelets. The patient platelets and hemoglobin showed no improvement after delivery and she continued to have hemolysis despite delivery and steroids administration. So daily therapeutic plasma exchange was initiated as the index of suspicion for TTP increased. After two sessions, there was a significant improvement in the platelet count and hemolysis profile which were normalized by the 4th session. Conclusion: Congenital TTP is a rare syndrome that clinicians should be aware of. Early initiation of plasma exchange dramatically improves survival from less than 10% to approximately 80%. This can only be achieved by having high level of suspicion and awareness to this possibility

Alkali Therapy in Lactic Acidosis

This report attempts to frame the debate about clinical administration of sodium bicarbonate in the setting of lactic acidosis in terms of simple questions. Specifically, we address why we develop lactic acidosis in some circumstances, how acute lactic acidosis impairs cardiovascular function and why sodium bicarbonate may have deleterious effects which limit its utility. We also attempt to explore treatment alternatives to sodium bicarbonate

Can charcoal improve outcomes in COVID-19 infections?

COVID-19 infection causes considerable morbidity and mortality, especially to those who are aged, have impaired renal function and are obese. We propose to examine the potential utility of oral activated charcoal with the hypothesis that such treatment would lower absorption of microbiome derived toxins and ameliorate systemic oxidant stress and inflammation

Fluid balance concepts in medicine: Principles and practice.

The regulation of body fluid balance is a key concern in health and disease and comprises three concepts. The first concept pertains to the relationship between total body water (TBW) and total effective solute and is expressed in terms of the tonicity of the body fluids. Disturbances in tonicity are the main factor responsible for changes in cell volume, which can critically affect brain cell function and survival. Solutes distributed almost exclusively in the extracellular compartment (mainly sodium salts) and in the intracellular compartment (mainly potassium salts) contribute to tonicity, while solutes distributed in TBW have no effect on tonicity. The second body fluid balance concept relates to the regulation and measurement of abnormalities of sodium salt balance and extracellular volume. Estimation of extracellular volume is more complex and error prone than measurement of TBW. A key function of extracellular volume, which is defined as the effective arterial blood volume (EABV), is to ensure adequate perfusion of cells and organs. Other factors, including cardiac output, total and regional capacity of both arteries and veins, Starling forces in the capillaries, and gravity also affect the EABV. Collectively, these factors interact closely with extracellular volume and some of them undergo substantial changes in certain acute and chronic severe illnesses. Their changes result not only in extracellular volume expansion, but in the need for a larger extracellular volume compared with that of healthy individuals. Assessing extracellular volume in severe illness is challenging because the estimates of this volume by commonly used methods are prone to large errors in many illnesses. In addition, the optimal extracellular volume may vary from illness to illness, is only partially based on volume measurements by traditional methods, and has not been determined for each illness. Further research is needed to determine optimal extracellular volume levels in several illnesses. For these reasons, extracellular volume in severe illness merits a separate third concept of body fluid balance

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Hypertonic saline infusion for hyponatremia: Limitations of the Adrogué-Madias and other formulas

Hypertonic saline infusion is used to correct hyponatremia with severe symptoms. The selection of the volume of infused hypertonic saline (VInf) should address prevention of overcorrection or under correction. Several formulas computing this VInf have been proposed. The limitations common to these formulas consist of: (a) failure to include potential determinants of change in serum sodium concentration ([Na]) including exchanges between osmotically active and inactive sodium compartments, changes in hydrogen binding of body water to hydrophilic compounds, and genetic influences, and (b) inaccurate estimates of baseline body water entered in any formula and of gains or losses of water, sodium and potassium during treatment entered in formulas that account for such gains or losses. In addition, computing VInf from the Adrogué-Madias formula by a calculation assuming a linear relation between VInf and increase in [Na] is a source of errors because the relation between these two variables was proven to be curvilinear. However, these errors were shown to be negligible by a comparison of estimates of VInf by the Adrogué-Madias formula and by a formula using the same determinants of the change in [Na] and the curvilinear relation between this change and VInf. Regardless of the method used to correct hyponatremia, monitoring [Na] and changes in external balances of water, sodium, and potassium during treatment remains imperative

Can Charcoal Improve Outcomes in COVID-19 Infections?

COVID-19 infection causes considerable morbidity and mortality, especially to those who are aged, have impaired renal function and are obese. We propose to examine the potential utility of oral activated charcoal with the hypothesis that such treatment would lower absorption of microbiome derived toxins and ameliorate systemic oxidant stress and inflammation