Journal of Obesity and Metabolism
Open Access

Chronic kidney condition; Veverimer; Bicarbonate sodium; Hyperkalemia; Carbamylation; Urea; Plan for research

Introduction

Patients suffer metabolic consequences and lose the ability to excrete the daily dietary acid load as kidney function deteriorates [1]. In advanced CKD, metabolic acidosis is a common complication that has been linked to impaired immune response, early mortality, cardiovascular events, adverse bone and muscle outcomes, and worsening kidney function.

In CKD, decreased net acid excretion by the kidneys causes metabolic acidosis. Endothelin-1, renin-angiotensin-aldosterone system activation, and complement activation all appear to be involved in the detrimental effects of metabolic acidosis on kidney function.

Lower serum bicarbonate has previously been linked to the progression of CKD in a number of observational studies. Some of these studies showed an increased risk of CKD progression (kidney failure or a 40% reduction in eGFR), while others showed no association after adjusting for baseline eGFR.12 Many of these studies were small or from a single center [2]. A recent large cohort study of over 51,000 CKD patients found that kidney failure or a decline in eGFR of 40% or more were associated with a lower serum bicarbonate value at baseline.

Notably, these studies only looked at the relationship between serum bicarbonate at a single point in time and repeated bicarbonate measurements over time. This study tracked down a 7% decrease in renal occasions (commencement of renal substitution treatment (RRT), splitting of eGFR, or a 25 ml/min per 1.73 m2 decline of eGFR from pattern), and was finished in patients circled back to as a component of the Constant Renal Deficiency Partner, which followed patients selected at 7 clinical focuses across the US.14 We conjectured that the span of time a patient is presented to held corrosive (metabolic acidosis) and a vertical or descending direction of held corrosive is probably going to influence the degree of the unfriendly impact of metabolic acidosis on the kidney. Laboratory measurements, variability, volume status, kidney function, concurrent medications, and dietary intake are all potential causes of serum bicarbonate fluctuation. As a result, comparing a single value to multiple bicarbonate measurements over time may provide a more accurate risk indicator.

To find out if there was a link between changes in serum bicarbonate from baseline and the progression of kidney disease, we conducted a retrospective cohort study of over 24,000 patients with CKD and metabolic acidosis (serum bicarbonate 12 to 22 mmol/l) and longitudinal serum bicarbonate data [3].

Methods and Materials

Metabolic acidosis in CKD

In patients with chronic kidney disease (CKD), metabolic acidosis occurs when H+ retention occurs and net acid (H+) excretion falls below net endogenous H+ production [4]. Metabolic acidosis is diagnosed when the primary decrease in serum bicarbonate (HCO3) falls below 22 mmol/L. As glomerular filtration rate (GFR) decreases, the prevalence of metabolic acidosis rises: 19–37 percent in CKD G4 and 2–13 percent in CKD category G3. Extra gamble factors for metabolic acidosis incorporate albuminuria, weakness, smoking, and utilization of renin-angiotensin framework (RAS) blockers and mineralocorticoid receptor bad guys. Because potassium-rich foods like fruits and vegetables are also high in alkalis, a diet low in potassium may worsen metabolic acidosis.

Patient-reported outcomes (such as fatigue and shortness of breath) to accelerated CKD progression, increased catabolism and mortality, more severe chronic kidney disease–mineral and bone disorder (CKDMBD), increased risk of urolithiasis due to increased urinary calcium excretion and decreased citraturia, and hyperkalemia are among the reported effects of metabolic acidosis in CKD.

Loss of renal function is linked to metabolic acidosis in people with and without CKD. It also contributes to CKD-MBD by increasing PTH secretion and osteoclastic activity, suppressing osteoblast-induced collagen synthesis. Besides, metabolic acidosis advances skeletal muscle proteolysis by enacting ubiquitin-protein ligases because of intracellular fermentation [5]. Sarcopenia and malnutrition will be favored, and serum urea levels may rise as a result.

Excess extracellular H+ prevents H+ from leaving cells in exchange for sodium entry during metabolic acidosis. As less sodium needs to be extruded, this results in an increase in intracellular H+ and a decrease in intracellular sodium. As a result, the cell membrane Na+/K+ ATPase activity decreases. As a result, plasma potassium concentration will rise and potassium entry into cells will decrease [6]. Because organic anions also enter cells without causing an electrical imbalance, normochromic metabolic acidoses like lactic acidosis or ketoacidosis are less likely to cause this effect.

In observational studies, metabolic acidosis is associated with increased mortality in CKD patients [5]. Endothelial dysfunction is facilitated by metabolic acidosis, which is linked to malnutrition, inflammation, and oxidative stress, all of which may increase mortality.

A recent meta-analysis of 14 clinical trials with 1394 participants found that a low-acid diet or the administration of sodium bicarbonate slowed the progression of chronic kidney disease (CKD) with evidence of moderate to low certainty. Serum potassium, calcium, phosphate, albumin, parathyroid hormone levels, and midarm muscle circumference were not significantly different between the groups. Base administration, on the other hand, increased CKD-MBD and muscle wasting in some studies. The impact on specific parameters may be affected by factors like the efficacy of therapy and the design of the trials as well as the presence of abnormalities in these parameters at baseline. Another meta-analysis found that oral sodium bicarbonate protected kidney function in CKD patients with chronic metabolic acidosis or low normal serum bicarbonate (22–24 mmol/L). We presently give a concise outline of treatment for metabolic acidosis in CKD and afterward center around the effect of sodium zirconium cyclosilicate (SZC) on serum bicarbonate and urea, the likely systems of activity, and the possible clinical outcomes to at last propose an examination guide to explain sub-atomic pathways and clinical effect.

Treatment of metabolic

Treatment of metabolic acidosis in CKD Diet and sodium bicarbonate are common treatments for metabolic acidosis in CKD. SZC and verier have also recently been shown to raise serum bicarbonate [7]. In spite of the fact that there has been worry about expected difficulties of revising metabolic acidosis, going from advancing endovascular and tissue calcification to sodium maintenance while recommending sodium bicarbonate. However, when sodium is given as a salt that does not contain chloride, it is thought to cause less sodium retention. However, neither short-term nor long-term studies have shown that sodium has a significant effect on tissue calcification, systolic or diastolic blood pressure, weight gain, or the onset of congestive heart failure.

Diet

Following an assessment of one’s dietary intake, nutritional approaches include increasing alkali-rich foods like fruits and vegetables and reducing acid-rich foods specifically [8]. Hyperkalemia is common in CKD, and alkali-rich foods may also contain a lot of potassium.

Sodium bicarbonate

NKF-KDOQI and KDIGO rules suggest endorsing base when serum bicarbonate fixation is < 22 mmol/L to keep up with serum bicarbonate focus ≥ 22 mmol/L. Sodium bicarbonate is presently the most utilized antacid treatment.

Over the course of 28 weeks, the pilot study Bicarbonate Administration to Stabilize eGFR (BASE) demonstrated that a higher sodium bicarbonate prescription dose (0.8 mg/kg of lean body weight versus 0.5 mg/kg of lean body weight) was effective, safe, and adhered. Oral bicarbonate increased urinary sodium and albumin, decreased urinary ammonium excretion, and increased serum bicarbonate by less than 2 mmol/L (baseline serum bicarbonate was above 24 mol/L). Urea levels in the blood were not reported. Despite being inexpensive, bicarbonate causes stomach acid and water to produce gas (carbon dioxide), which can be unpleasant. There are also soft capsules containing sodium bicarbonate and enteric-coated tablets [9]. The enclosed base is shielded from stomach acid by these formulations, limiting carbon dioxide production and increasing bicarbonate availability. In patients with CKD, alkali that contain potassium, such as potassium bicarbonate and others, may encourage hyperkalemia.

Protein carbonylation and urea

The decreased levels of urea seen in patients receiving SZC treatment may have a negative impact on protein carbonylation. Urea is in equilibrium with electrophilic species like cyanate and isocyanate, which can react with free amino acid amino groups and protein lysine residues to form homo-citrulline, also known as -amino-carbamoyllysine, or protein carbonylation. Carbamylation is a non-enzymatic post-translational modification that cannot be reversed. It can occur at multiple lysine sites within a protein and builds up over time, resulting in protein dysfunction. In such manner, protein carbonylation is viewed as a sign of maturing and is related with unfriendly cardiovascular results and mortality in patients with CKD, and explicit carbamylated proteins, for example, carbamylated sortilin are unthinkingly connected to cardiovascular calcification in patients with CKD [10]. Carbamylation preferentially targets proteins with long half-lives, such as extracellular matrix proteins like type I collagen and elastin, which favors fibrosis development.

Conclusion

In conclusion, SZC doses that are clinically relevant to treat hyperkalemia, its primary indication, increased serum bicarbonate and decreased serum urea in placebo-controlled clinical trials. The limiting of stomach NH4+ is the most probable component of activity. Since the serum bicarbonate level increased by more than 22 mmol/L; this effect of SZC may have a clinical impact on outcomes, as suggested by clinical guidelines—a hypothesis that should be evaluated in specifically designed studies. The benefit may theoretically be contingent on both acidosis correction and lower urea levels, as lower urea levels may reduce protein carbamylation.

Acknowledgement

None

Conflict of Interest

None

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