A Few Questions about Acute Renal Failure

Acute Renal Failure (ARF) is not a topic that creates serious problems for medical students, but a novice while working with this subject will definitely face a few pitfalls. Below you can find some questions (with answers, of course, :-) which can confuse beginners in nephrology.

Q: Is oliguria an immanent sign of ARF?

A: No, it is not.

Comment: ARF is referred to a rapid decline in renal filtration, but a decline in filtration does not automatically imply a reduction in urinary output. Urinary output depends on two processes: filtration and reabsorption, therefore if both processes are affected, a patient may develop non-oliguric ARF.

Q: Is serum creatinine level always elevated in patients with ARF?

A: No, it is not.

Comment: A well know fact is that creatinine is filtered through the glomerulus, partially secreted by renal tubules, and almost non-reabsorbed. These features of creatinine metabolism are used in determination of a major parameter of renal function: glomerular filtration rate. Because serum creatinine level is inversely proportional to glomerular filtration rate (GFR), we can expect all ARF patients to have an increased concentration of serum creatinine. But during the first few hours of acute renal failure, when glomerular filtration was shut down recently, there would be a gradual increment in serum creatinine and a single measurement might produce normal figures. Moreover, certain pathologic conditions, like acute glomerulonephritis, are associated with activation of tubular secretion of creatinine; therefore even in the situation when GFR significantly falls down, serum creatinine level will only slightly raise.

Because ARF is a dynamic pathologic process, which can require different approaches in management at different stages of pathogenesis, the specialists in renal diseases prefer the term “acute kidney injury” (AKI) instead of “acute renal failure”. In widely accepted RIFLE (2004) classification of AKI, the whole process of kidney damage is divided in five stages: Risk of renal dysfunction, Injury to the kidney, Failure or Loss of kidney function, and End-stage kidney disease. Each stage of AKI is characterized by a certain set of urinary output, glomerular filtration rate, and creatinine concentration (1).

Q: If urinary output and serum creatinine remain WNL how are we able to diagnose AKI?

A & Comment: It is unusual that both indexes stay unaffected in the patient with AKI. Besides we can also use some more parameters like

1) Pace of serum creatinine elevation, e.g. from 0.7 to 1.2 mg/dL during a day

2) An increase in BUN concentration

3) Casts in urinary sediment (dirty-brown granular casts in ATN)

Q: Do elevated levels of serum creatinine and BUN always indicate AKI?

A: No, they do not

Comment: We always have to keep in mind other reasons for elevation of these nitrogen compounds. E.g., some drugs like trimethoprim and cimetidine may decrease creatinine secretion with subsequent rise in serum creatinine in patients with normal renal function. An increment in BUN can be associated with severe burns, GI bleeding, steroid use, tetracycline administration, or dietary protein overload, not only with GFR decline.

Why we use BUN/creatinine ratio?

A & Comment: Both creatinine and urea are products of protein metabolism and are excreted with urine. Definitely, blood levels of both substances will be higher in patients with renal failure. But from the course of physiology we remember two characteristic features of urea behavior within the kidneys: 1) a significant proportion of filtered urea is reabsorbed in the proximal tubules; 2) process of urea reabsorption is influenced by two factors: velocity of urinary flow through the tubular system and a tone of the renal microvasculature. In early stages of pre-renal AKI, when filtration is inhibited and urinary flow is diminished, there is a burst in vasodilatory mediators with subsequent rise in tubular reabsorption of BUN and elevation of its plasma level. BUN/creatinine ratio, which in normal individual fluctuates from 10:1 to 15:1 (2), in patients with pre-renal AKI is usually higher than 20:1. If severe pre-renal AKI stays untreated, it will eventually progress to renal AKI when tubular epithelium gets badly damaged and vasodilation turns to vasoconstriction. In such conditions urea reabsorption slows down and ratio may turn to ordinary figures.

For differential diagnosis of pre-renal and renal AKI, besides BUN/creatinine ratio we can use the following indices: urine specific gravity, urine osmolarity, urine sodium, urine-plasma creatinine ratio and, of course, fractional excretion of sodium, but that will be another story.

References

1. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. Aug 2004;8(4):R204-12.

2. Balogun RD, Ocusa MA. Diagnosis of acute tubular necrosis and prerenal disease.

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