When should I consider bicarbonate (BC) replacement in my patient with renal insufficiency?

Metabolic acidosis is one of the earliest complications of chronic kidney disease (CKD), with a direct correlation between the decline in glomerular filtration rate (GFR) and reduction in serum BC1.

Epidemiologic studies in patients with CKD have reported an independent association between serum BC (<22 meq/L considered low) and adverse renal outcomes and mortality1. Limited data from small interventional trials of alkali therapy supplementation and dietary interventions (eg, increased fruit and vegetable intake) have shown the benefits of raising serum BC. Specifically, 1 study involving patients with CKD stages 4 and 5 and another involving CKD stage 2 hypertensive nephropathy reported slower decline in creatinine clearance/eGFR in patients receiving BC replacement2,3.  

Less is known on the potential benefit of BC replacement in patients with acute kidney injury (AKI) with a recent Cochrane review finding no randomized controlled trials4 and national guidelines not recommending either in favor or against its use AKI5. Of note, BC therapy has also been associated with sodium and fluid overload, an increase in lactate and PCO2, and a decrease in serum ionized calcium6.

References

  1. Dobre M, Rahman M, Hostetter TH. Current status of bicarbonate in CKD. J Am Soc Nephrol 2015;26:515-523.
  2. de Brito-Ashurst I, Varagunam M, Raftery MJ, et al. Bicarbonate supplementation slows progression of CKD and improves nutritional status. J Am Soc Nephrol 2009; 20: 2075–2084.
  3. Mahajan A, Simoni J, Sheather SJ, et al. Daily oral sodium bicarbonate preserves glomerular filtration rate by slowing its decline in early hypertensive nephropathy. Kidney Int 2010;78: 303–309.
  4. Hewitt J, Uniacke M, Hansi NK, et al. Sodium bicarbonate supplements for treating acute kidney injury. Cochrane Database of Systematic Reviews 2012; Jun 13; (6):CD009204. doi: 10.1002/14651858.
  5. Palevsky PM, Liu KD, Brophy PD, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. Am J Kidney Dis 2013;61:649-72.
  6. Sabatini S, Kurtzman NA. Bicarbonate therapy in severe metabolic acidosis. J Am Soc Nephrol 2009;20:692-695.

 

Contributed in part by Cynthia Cooper, MD, Mass General Hospital, Boston, MA.

When should I consider bicarbonate (BC) replacement in my patient with renal insufficiency?

What are the potential pitfalls in reliance on serum creatinine levels or urine output in sepsis-associated acute kidney injury (SA-AKI)?

Although serum creatinine and urine output are usually easily measured, several limitations in their interpretation in patients suspected of having sepsis and AKI are worth emphasizing1.

First, there is an inherent lag of hours between a drop in glomerular filtration rate (GFR) and a rise in serum creatinine concentration. Second, in critically ill hypotensive patients with sepsis receiving aggressive fluid resuscitation, hemodilution may mask serum creatinine rise and delay the diagnosis of AKI by a day. Third, sepsis itself may reduce muscular production of creatinine, even in the absence of weight loss, as demonstrated in animal studies2.  Fourth, patients receiving diuretics may fail to meet criteria for AKI diagnosis based on reduced urine output alone because of increased urine output.  

Lastly, as renal function deteriorates, the half-life of serum creatinine increases from several hours to several days3, prolonging the time needed to achieve a new steady-state that may be more reflective of the concurrent GFR.

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 References

  1. Godlin M, Murray P, Mehta. Clinical approach to the patient with AKI and sepsis. Semin Nephrol 2015;35:12-22.
  2. Doi K, Yuen PST, Eisner C, et al. Reduced production of creatinine limits its use as marker of kidney injury in sepsis. J Am Soc Nephrol 2009;20:1217-21.
  3. Chiou WL, Hsu FH. Pharmacokinetics of creatinine in man and its implications in the monitoring of renal function and in dosage regimen modifications in patients with renal insufficiency. J Clin Pharmacol. 1975; 15(5-6):427-34.
What are the potential pitfalls in reliance on serum creatinine levels or urine output in sepsis-associated acute kidney injury (SA-AKI)?

How is the pathophysiology of sepsis-associated acute kidney injury (SA-AKI) different than AKI due to non-septic conditions?

Sepsis accounts for up to one-half of AKI cases in developed countries1.  Although sepsis-mediated hypoperfusion causing tubular necrosis has traditionally been implicated as the primary basis for SA-AKI,  an increasing number of studies have suggested that SA-AKI is a distinct subset of AKI differentiated from other causes by unique hemodynamic and inflammatory/immune-related mechanisms.  

Many animal and limited human studies have found that renal blood flow is an inconsistent predictor of SA-AKI, possibly related to the redistribution of blood in the renal microvasculature to the detriment of the renal medulla in sepsis2.

Cytokine-mediated response in sepsis can also lead to tubular cellular injury without necessarily causing necrosis. Of interest, an autopsy study found histological features of acute tubular necrosis in only 22% of patients with clinical diagnosis of SA-AKI 3.  

Differences in its pathophysiology may at least in part explain why oliguria, renal function recovery, hemodialysis and death are more common among SA-AKI patients4.

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References

  1. Alobaidi R, Basu RK, Goldstein SL, Bagshaw SM. Sepsis-associated acute kidney failure. Semin Nephrol 2015;35:2-11.  https://www.ncbi.nlm.nih.gov/pubmed/25795495
  2. Maiden MJ, Otto S, Brealey JK, et al. Structure and function of the kidney in septic shock. Am J Resp Crit Care Med 2016;194:692-700. https://www.atsjournals.org/doi/abs/10.1164/rccm.201511-2285OC
  3. Langenberg C, Bagshaw SM, May CN, Bellomo R. The histopathology of septic acute kidney injury: a systemic review. Crit Care 2008;12:R38.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2447560/
  4. Cruz MG, de Oliveira Dantas JGA, Levi TM, et al. Septic versus non-septic acute kidney injury in critically ill patients: characteristics and clinical outcome. Rev Bras Ter Intensiva 2014;26:384-391. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4304467/
How is the pathophysiology of sepsis-associated acute kidney injury (SA-AKI) different than AKI due to non-septic conditions?