Kidney function is important for many reasons. It is one of the main avenues to eliminate waste in our body, balance electrolytes as well as producing various hormones to regulate our bodily functions.  It is especially important to pharmacists because many medications are eliminated through our kidneys.  If there is any existing impairment, dosage adjustment or avoiding certain nephrotoxic medications are paramount.

But when it comes to how we assess kidney function, there are many theories and methods available. Some are highly research-focused and are not practical for every day use and others are practical to use daily but with limitations to bare in mind.

Chronic kidney disease can be categorized into 4 main stages which will help guide steps for further evaluation and management:

stages-of-chronic-kidney-disease
Adapted from N Eng J Med 2006; 354: 2473-83

In clinical practice, we estimate renal function with creatinine which is an endogenous marker.  There are primarily three formulas that have been studied.

1) The Cockcroft-Gault Equation

cockcroft-gault

The Cockcroft-Gault formula is the oldest formula developed in 1973 from a small sample size of 249 men, tend to underestimate renal function in the elderly population but has been the gold standard used for recommending dosage adjustment of medications.

2) The MDRD Equation

The MDRD formula was developed in 1999 based on data from 1628 patients with chronic kidney disease. This formula is more accurate in estimating renal function in non-hospitalized patients known to have chronic kidney disease.  In many routine lab reports, the eGFR is reported using this formula.

mdrd

3) The CKD-EPI Equation

The CKD-EPI equation was developed in 2009 based on data from over 5000 patients without chronic kidney disease. The development of this equation was aimed to improve the accuracy of estimating renal function in individuals without chronic kidney disease but has limited representation from the elderly population.

CKD EPI.png

All of these formulas have limitations. Cockcroft gault formula tends to underestimate renal function or loses accuracy in obese individuals (which can be accounted by using the adjusted body weight). MDRD may lose its accuracy at higher value of eGFR (e.g. above 60mL/min per 1.73²).  CKD-EPI has limited representation in the elderly population (~ 9%)

Further, there are limitations with using creatinine as a marker of renal function. It can be affected by conditions related to muscle wasting, amputation or tubular secretion and can change during the critically ill stage.

More recently, we are exploring the use of Cystatic C based formula to estimate renal function. It may be a better marker because it has characteristics of a good marker for glomerular filtration rate – it is endogenous, freely filtrated in the glomerulus with no tubular secretion or reabsorption.  It is also minimally affected by other factors such as age, body composition, gender and diet. It is thought to be strong risk predictor for adverse cardiovascular prognosis in different populations.  However, there are preliminary reports that Cystatin C is affected in individuals with thyroid disorders or concurrently taking glucocorticoids.

Nonetheless, I think we may be moving to a Cystatin C-based estimation of renal function in the near future.

While our current approach to estimating kidney functions have many limitations, below are some of my thoughts:

  • Clinical assessment is more important. We need to also assess the patient clinically.  Are there other signs of renal impairment or risk of drug toxicity (e.g. increased sedation possibly due to accumulation of renally cleared medications)?
  • Look for other markers of renal impairment.  Giving there are limitations with the current method of estimating kidney function, I look for other markers that may help to confirm renal impairment. For instance, digoxin which is also eliminated renally may be elevated in renal impairment. If I suspect the creatinine based estimation may be flawed (e.g. in multiple sclerosis, individuals with amputation), I trust the digoxin as a better marker of any renal impairment.
  • Decreased urine output is your earliest marker or warning for a decline in renal function. Although not all settings have the ability to measure urine output, it can be a very useful and earliest marker for renal impairment. If the urine output is significantly reduced but the reported serum creatinine value was normal from a recent lab report, I would pay close attention to the renal function. There is typically a lag time in when we see an increase in serum creatinine value.
  • Balance risks and benefits carefully. Sometimes as pharmacists, we are quick to adjust dosage of medications based on the calculated creatinine clearance. However if treating a serious infection, it may actually be a little beneficial to have higher level of antibiotic during the initial phase.  For instance, an individual being treated for diabetic foot infection with ciprofloxacin may benefit from an initial high dose of ciprofloxacin given it exhibits concentration dependent killing as well as allowing a better penetration of antibiotic to tissues with poor circulation.
  • Kidney function can fluctuate. In my experience, kidney function declines slowly with age in many cases but can also improve especially with the discontinuation of any nephrotoxic medications such as NSAIDs or ACE-inhibitors. It can fluctuate such as during an acute exacerbation of heart failure or COPD. Hence it is important to assess the renal function routinely. The consistent pattern and / or fluctuation over time along with clinical assessment gives a more accurate picture of the renal function than a single calculation or lab result that is done sporadically without any clinical considerations.

What are your thoughts and experiences? I am not an expert in nephrology and would also appreciate other experts to share their thoughts.

 

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