Nephrology Week 1 Summary

Question 1

Describe the acid-base diagnosis in the following case (for example, metabolic acidosis with compensatory respiratory alkalosis):

A 41 year old male presents to the ER with the following lab results (hint: look for multiple simultaneous problems):

Na: 140 mmol/L
K: 4.0 mmol/L
Cl: 110 mmol/L
pH: 7.0
pCO₂: 35 mmHg
pO₂: 75 mmHg
HCO₃: 8 mmol/L

The primary disturbance in this patient is an acidosis, as indicated by the acidemic pH in the blood (pH 7.0). The normal bicarbonate concentration is 24 mmol/L but this patient’s bicarbonate concentration is 8 mmol/L. This indicates a fall in bicarbonate of 16 mmol/L.

Thus, there is a primary metabolic acidosis.

The anion gap is 22.
Recall, anion gap is calculated by the formula:

AG = Na – HCO₃ – Cl
AG = 140 – 8 – 110
AG = 22

The normal anion gap is about 12, so the anion gap is increased.

Thus, there is an anion gap metabolic acidosis.

The anion gap is increased by 10 but the bicarbonate has fallen by 16 mmol/L. Therefore, there is also a fall in bicarbonate that is not accounted for by the H+ ions that accompanied the unmeasured anions in this case – this means there is also a non-anion gap metabolic acidosis.

The bicarbonate has decreased by 16.

We would expect that in a metabolic acidosis, there would be a 1 mmHg fall in pCO₂ for every 1 mmol/L of bicarbonate.

Therefore, we would expect that the pCO₂ would be 24 mmHg. Since it is 35 mmHg, it is too high and this represents a respiratory acidosis.

Therefore, this is a case of a

1. Anion gap metabolic acidosis
2. Non-anion gap metabolic acidosis
3. Respiratory acidosis

Question 2

Name 5 causes of an increased osmolar gap with an elevated anion gap metabolic acidosis.

The concentration of solutes in the plasma determines the plasma osmolality. It is primarily determined by the concentration ofNaCl, NaHCO₃, glucose and urea.

The formula to calculate plasma osmolality (Posm) is:

Calculated Posm = 2 * [plasma Na] + [glucose] / 18 + [BUN] / 2.8

When glucose and BUN are measured in mg/dL

And

Calculated Posm = 2 * [plasma Na] + [glucose] + [BUN]

When glucose and BUN are measured in mmol/L

The osmolal gap is the difference between the measured osmolality and the calculated osmolality.

Therefore,

Osmolal gap = measured osmolality – calculated osmolality

Any difference is accounted for by unmeasured osmoles. Causes of an osmolal gap include such molecules as:

• ethanol,
• methanol,
• ethylene glycol,
• isopropyl alcohol,
• glycerol,
• mannitol,
• sorbitol,
• and acetone.

A metabolic acidosis can be seen along with an osmolal gap in the following situations:

• Methanol intoxication – the methanol accounts for the osmolal gap, and an anion-gap metabolic acidosis develops due to the production of formic acid.
• Ethylene glycol intoxication – the ethylene glycol accounts for the osmolal gap, and an anion-gap metabolic acidosis develops due to the production of glycolic acid and oxalic acid.
• Lactic acidosis – the osmolal gap is thought to be due to the accumulation of glycogen breakdown products, the acidosis is due to the lactic acidosis
• Diabetic/Alcoholic ketoacidosis – the osmolal gap is due to acetone and the acidosis is due to ketoacid production

Question 3

Name 5 causes of severe anion gap metabolic acidosis that could reasonably explain a HCO₃ below 8 mmol/L.

This could be explained by:

• methanol intoxication,
• ethylene glycol intoxication,
• salicylate intoxication,
• lactic acidosis,
• and diabetic ketoacidosis.

Question 4

A multipart question:

1. What is the normal urinary albumin to creatinine ratio?
2. What is the normal urinary protein to creatinine ratio?
3. Why are these different?
4. What are the units?
5. What is the definition of microalbuminuria?

Normally, small amounts of albumin and other proteins are filtered at the glomerulus. These proteins are almost completely reabsorbed at the proximal tubule. Since not all protein is completely reabsorbed, it is normal to have a small amount of urinary protein.

In a 24 hour urine collection, it would be considered normal to have up to 150 mg per day of protein, of which approximately 10 mg is albumin. 24 hour urine collections are often impractical and it is difficult to ensure a complete collection. Therefore, spot urine samples can be assessed for the ratio of protein to creatinine and albumin to creatinine. One can then estimate by extrapolation what the 24 hour excretion rate would be.

1. Normal urine albumin to creatinine ratio is <17 mg albumin/g creatinine for men, <25 mg albumin/g creatinine for women.
2. Normal urine protein to creatinine ratio is <200 mg protein/gram creatinine.
3. Urinary protein can be comprised of both albumin and other proteins. Therefore, the urine albumin would not account for all protein excretion.
4. See above. Note that the values are different depending on whether youmeasure urine creatinine in mmol/L or mg/dL.
5. Microalbuminuria refers to albumin excretion of 30-300 mg/day, which correlates to a urine albumin:creatinine ratio of 17-250 mg/g for men and 25-355 mg/g for women.

K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification PART 5. EVALUATION OF LABORATORY MEASUREMENTS FOR CLINICAL ASSESSMENT OF KIDNEY DISEASE

Levey AS et al. Ann Intern Med. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. 2003 Oct 7. 139(7):605.

Question 5

Using the Cockcroft-Gault and MDRD formulas, calculate the estimated glomerular filtration rate (eGFR) in the following patient:

A 70 year old Caucasian male with serum creatinine 250 micromol/L and weight of 70kg. BUN and albumin are unavailable.

In which populations and at what GFRs do these estimation formula perform poorly?

Cockcroft Gault creatinine clearance is 24.1 ml/min. MDRD estimated GFR is 23.7 ml/min.

The Cochcroft-Gault formula is:

Creatinine clearance
= (140-age[years]) * weight [kg]
—————————-
(72 X serum creatinine)

For women, multiply by 0.85.

The abbreviated MRDRD formula:

GFR = 186.3 * (SCR)^-1.154 * (age in years)^-0.203 * 1.212 (if patient is black) * 0.742 (if female)

The CKD-EPI has been developed to be a more accurate tool to estimate GFR. It performs particularly well when GFR is relatively preserved.

MDRD and CKD-EPI eGFR can be calculated at:

https://qxmd.com/calculate/mdrd-egfr
https://qxmd.com/calculate/egfr-using-ckd-epi

iPhone, iPad, Windows 10 and Android users can get an eGFR calculator at
http://qxmd.com/calculate

These formula may not be reliable in pregnant women, children, or patients with normal renal function, obesity,or prior amputations.

References:

Cockcroft DW and Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16(1): 31-41.

Levey et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med. 1999; 130(6):461-70.

Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A New Equation to Estimate Glomerular Filtration Rate. Ann Intern Med 150(9):604-12. (2009)