In the following case report we present a particular pattern of acute renal failure documented in a patient treated with the aminoglycoside amikacin.

CASE REPORT
A 23 year-old woman was referred to our Nephrology Department presenting elevated serum creatinine levels in the context of normal serum urea.

Three month before admission she had suffered a fracture of her first and fourth lumbar vertebrae as a consequence of a car crash. In order to stabilize her spinal column, she had had to undergo an operation. Unfortunately she had developed a wound abscess. It was then when she was referred to our hospital where she had to be operated again. Bone samples were obtained and they confirmed the presence of an acute osteomyelitis secondary to Pseudomona Aeruginosa and metil-resistance Staphylococcus Aureus. Intravenous vancomicin 2 g/day, amikacin 1 g/day, piperacilin 16 g/day were prescribed.

After a month of treatment with this antimicrobial schedule an increase in her plasma creatinine level was detected: 1.2 mg/dl (initial value: 0.9 mg/dl). This acute renal failure was a non-oligoanuric one: diuresis: 4000 cc/day, and with low osmolality urine: 210 mosm/l. The antibiotic schedule was changed to a non nephrotoxic one and daily blood samples were taken to check urea and creatinine plasma levels. The patient had neither liver disease nor a low-protein diet. Her nutritional parameters were within the normal range, with a height and weight of 1.64 m and 61 kg respectively.

We appreciated a progressive increase in plasma creatinine levels without a significant alteration in plasma urea ones. Even more, the lowest plasma urea level (22 mg/dl) was detected when the highest plasma creatinine level (2.6 mg/dl) was documented (Table I).

TABLE 1: Substance Levels During Hospital Admission

Aiming at explaining this phenomenon we measured urea and creatinine in blood and urine samples in order to calculate the fractional excretion of urea (FEU). As we can appreciate in Table I, fractional excretion of urea was excessively high (FEU: 103%), meaning that this substance was markely excreted, phenomenon that could explain the paradoxical normal plasma urea level in the context of an acute renal failure.

Since nephrotoxic drugs were removed, the acute renal failure progressively healed normalizing plasma creatinine values.

DISCUSSION
The acute renal failure previously described could be caused by two potential mechanisms: bone infection and nephrotoxic antibiotics. However, since renal deterioration begun after these drugs were iniciated and their remotion led to a clear renal function recovery we considered antibiotics as the main cause of this disturbance. Even though the three antibiotics prescribed in this case are potentially nephrotoxic². Amikacin, an aminoglycoside, is the most nephrotoxic of them³.

Aminoglycosides undergoes renal excretion by glomerular filtration, although a small percentage of filtered drug is reabsorbed proximally. This reabsorbtion is done by pinocytosis through apical surface of tubular epithelial cells causing later perturbation of mitochondrial integrity and disruption of lysosomes into the proximal tubular cells^{4, 5}. Aminoglycosides toxicity is mediated by necrotic and non-necrotic (apoptotic) mechanisms⁵. Parenchimal accumulation within the renal cortex occurs with these agents with tissue concentrations exceeding serum levels several fold, and on this tissue accumulation is based aminoglycoside proximal tubule toxicity³. However, dissociation between tissue accumulation and preservation of renal function has been reported⁴.

Aminoglycosides may alter urinary concentratation mechanisms and also reduce collecting tubule response to antidiuretic hormone³. The previous described statements could explain the low-osmolality polyuria documented in our patient.

The striking point of this case is the presence of normal plasma urea level in a context of renal insufficiency. In this case it could not be explained by the existence of a low muscle mass as she was neither malnourished nor small built or old.

In normal physiologic conditions, about 50% of the filtered urea is invariably reabsorbed in the proximal convoluted tubule. Some urea must also be reabsorbe in part of the distal nephron located in the cortex. Given the high cortical blood flow and the vascular-tubular organization in this area of the kidney, it seems highly unlike that any of this urea could be reintroduced in the nephron lumen. Thus, at least 50% of the filtered urea cannot be excreted. Because of that fractional excretion of urea higher than 50% could means urea reabsortion alteration or urea secretion. Since most of urea reabsortion is done in proximal tubules, area damaged by amikacin, a reduced proximal urea reabsorbtion could explain part of the high FEU found in this case^{6, 7, 8}. The concomitantely elevated fractional excretion of sodium and potassium reinforce the hypothesis of an alteration of tubular reabsorbtion mechanisms.

Besides, since high urinary rate is another cause of increased urea excretion, the documented water diuresis in our patient, secondary to nephrogenic diabetes insipidus, could be another reason of her high FEU⁶.

Regarding creatinine, its high plasma levels could be not only explained by its reduced filtration (acute renal failure), but also by an alteration in its secretion due to amikacin-induced proximal toxicity.

CONCLUSION
Acute renal failure with normal urea plasma levels, in case of a young properly nourished patient, could be a marker of proximal tubular disfunction with diabetes insipidus.

REFERENCES:

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8.- Kaplan A, Kohn O. Fractional excretion of urea as a guide to renal dysfunction. Am J Nephrol 1992; 12: 49-54