How to properly interpret the creatinine (Cr)

The house officer wades through a swamp of daily creatinines. Unfortunately there is poor example setting on what to do with these. The classic example is the 90 year old with a “normal” creatinine of 90.

Nobody likes formulae, but it is important to refer to a couple here in order to understand what is to come.

Cr Clearance = (Urine volume x urine concentration of Cr) / Plasma Cr

The exact formula is irrelevant for your purposes but it is important to take home the concept that from this formula we can say that Cr clearance is inversely proportional to serum Cr.

Of course we don’t calculate Cr clearance by taking samples of everybody’s piss. That would be far too unwieldy. Instead we estimate Cr clearance using formulae, such as Cockgrauft- Gault, which takes sex, age and weight and spits out a result.

Of course it would be foolish to think we can accurately determine someone’s muscle mass and rate of Cr production even with fancy maths, so these formulae are estimates only, especially at the extremes of age and weight.

What this really boils down to is that I’m more likely to win the lottery than a 90 year old is to have “normal” renal function with a Cr of 90. This, at least, is commonly accepted, although commonly ignored, probably because we all have a habit of only looking at the exact number if it appears in red.

The nephron deepens

There are more interesting conclusions we can come to just from looking at the Cr clearance formula. Consider the graph that plots the function y = 1/x (CrCl being proportional to 1 / Cr)

inverse

If the y axis is Cr clearance and the x axis is Cr, what you can see is that

  • On the first part of the graph a fairly significant fall in Cr clearance is accompanied by only a small increase in Cr
  • Towards the end of the graph a fairly small drop off in Cr clearance is accompanied by a large increase in Cr

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Plasmalyte is safe (and actually better) in hyperkalemia

In some indistinct corner of a ward somewhere where I spent the majority of my first house officer year, a laminated sign is blu-tacked to the wall which reads as follows:

“Normal Saline is the only fluid that should be used for patients with end stage renal failure”.

While on the face of it this serves to prevent some poor house officer charting fluid with 20mmol KCL in it to a patient on dialysis, normal saline is actually a poor choice for someone with renal failure or hyperkalemia.

While surgeons are known to sometimes insist on some bizarre things, their insistence on using plasmalyte as a resus fluid is well founded. This elegantly balanced crystalloid contains not only physiological amounts of Na and Cl (unlike NaCl which delivers an unphysiologic 150mmol/L of Cl) but also magnesium, acetate and gluconate. The latter two are converted into bicarbonate, and their metabolism provides 66kJ of energy per litre of fluid (1).

Plasmalyte also contains 5mmol per litre of potassium, hence the twitchiness of people to use it in hyperkalemia or renal failure. This worry, however, appears to be a misapplication of physiology.

If you take a second to think about it, there is no reason why addition of normokalemic fluid to plasma should make someone hyperkalemic (for a potassium of 5 is still a normal potassium). In fact, if you replaced all of someone’s plasma with plasmalyte, you could not get a potassium above 5. This is explained much more elegantly in this post on the veritable emcrit blog (2).

The second important point also explained in this post is that most potassium is intracellular and potassium levels are really largely dependent on cellular shifts more than anything else. Normal saline tends to cause a hyperchloremic metabolic acidosis because of the unphysiological quantities of chloride, which impair H+ excretion. Potassium will shift out of cells in response to buffer this. The end result is that potassium levels rise more with the administration of normal saline, even though  it contains no potassium in the bag, than with plasmalyte, which has a significant alkalinising effect (2).

Of course theory is no good without the studies to back it up, and the studies all strongly point in one direction. Three studies (3-5) looked at the perioperative administration of Ringers Lactate (LR) (a fluid similar to plasmalyte which contains 4 mmol/L of potassium) compared to Normal Saline in patients with end stage renal disease undergoing transplantation. Average potassium levels rose in the Normal Saline group in all three studies and fell or stayed the same in the LR groups. In fact, the first study had to be terminated early because 19% of the NS group developed hyperkalemia while none in the LR group did.

To satisfy you fully, let us turn to the evidence for plasmalyte directly. Adwaney and colleagues (6) demonstrated that, in the same setting of renal transplantation, recipients of plasmalyte had a significantly lower need for renal replacement therapy in days 1-3 post-op (OR of 0.15) and had a 2% incidence of hyperkalemia versus 17% in the NS group (despite pre-op potassium being the same).

Also recently Weinberg et al. (7) confirmed that NS caused significantly more hyperkalemia and acidosis in renal transplant recipients than plasmalyte.

Conclusion

The evidence is quite uniform and strong in a way that is uncommon for this type of topic. Not only does plasmalyte appear to be safe in renal failure/hyperkalemia, it is actually safer than normal saline. Understanding why this is the case delivers an important lesson in fluid physiology.

 

References

  1. http://www.medsafe.govt.nz/profs/Datasheet/p/plasmalytesol.pdf
  2. https://emcrit.org/pulmcrit/myth-busting-lactated-ringers-is-safe-in-hyperkalemia-and-is-superior-to-ns/
  3. Anesth Analg. 2005 May;100(5):1518-24, table of contents. A randomized, double-blind comparison of lactated Ringer’s solution and 0.9% NaCl during renal transplantation. O’Malley CM1, Frumento RJ, Hardy MA, Benvenisty AI, Brentjens TE, Mercer JS, Bennett-Guerrero E.
  4. Ren Fail. 2008;30(5):535-9. doi: 10.1080/08860220802064770. Effects of normal saline vs. lactated ringer’s during renal transplantation. Khajavi MR1, Etezadi F, Moharari RS, Imani F, Meysamie AP, Khashayar P, Najafi A.
  5. Saudi J Kidney Dis Transpl. 2012 Jan;23(1):135-7. A comparative study of impact of infusion of Ringer’s Lactate solution versus normal saline on acid-base balance and serum electrolytes during live related renal transplantation. Modi MP, Vora KS, Parikh GP, Shah VR.
  6. Perioperative Plasma-Lyte use reduces the incidence of renal replacement therapy and hyperkalaemia following renal transplantation when compared with 0.9% saline: a retrospective cohort study . Anamika Adwaney David W Randall  Mark J Blunden  John R Prowle Christopher J Kirwan. Clinical Kidney Journal, Volume 10, Issue 6, 1 December 2017, Pages 838–844, https://doi.org/10.1093/ckj/sfx040
  7. Effects of intraoperative and early postoperative normal saline or Plasma-Lyte 148® on hyperkalaemia in deceased donor renal transplantation: a double-blind randomized trial. BJA October 2017Volume 119, Issue 4, Pages 606–615. L. Weinberg, L. Harris, R. Bellomo, F.L. Ierino, D. Story, G. Eastwood, M. Collins, L. Churilov, P.F. Mount