Joint Program in Nuclear Medicine

The Role of Gallium-67 Imaging in Acute Renal Failure

Alexander Matthies, MD 
Donald E. Tow, MD

November 5, 1996

Presentation

A 62 year old male suffered an acute spinal cord injury at level of C5/6 following an accidental fall. Recurrent temperature spikes were noted and blood cultures were positive for Staphylococcus aureus. Because of Penicillin allergy the patient was started on Gentamicin and Vancomycin. About 10 days later elevation of the previously normal BUN and Creatinine values were noted. This was attributed to Gentamicin induced acute tubular necrosis. Over a period of 3 weeks serum creatinine rose and reached a peak at 4.6 mg/dl before declining to the current value of 1.8 . Two weeks later, an abdominal CT showed a subcapsular hematoma of the left kidney, which had not been noted on a renal ultrasound one month before.

Imaging Findings

A renal scan with Tc-99m-DTPA was performed 4 days after the CT scan in order to assess the impact of the hematoma on the renal function. The calculated GFR was 40 ml/min with a 37 % contribution from the left kidney.

A follow-up CT of the abdomen one week after the initial CT showed no significant change compared to the prior study nor any evidence of abscess formation in the abdomen. A follow-up renal scan one week after the initial scan revealed an unchanged total GFR, but a further reduction of the left kidney’s contribution to 22 %.

Because of recurrent episodes of unexplained fever a Ga-67 scan was performed to rule out abscess formation in the left perinephric hematoma. There was no uptake in the left kidney region. The right kidney, however, showed intense homogeneous Gallium uptake. Four months after the initial rise in creatinine a follow-up Gallium scan showed no abnormal tracer uptake in either kidney.

Discussion

In acute renal failure the history, clinical picture, urine analysis, blood and urine chemistry are often suggestive of one of the possible etiologies. In reality however it can sometimes be difficult to establish the exact cause. One problem is the differentiation between acute tubular necrosis and acute interstitial nephritis.

Acute Tubular Necrosis

Acute tubular necrosis (ATN) occurs usually due to renal ischemia in the setting of major surgery, trauma, hypovolemia, sepsis, burns or due to direct nephrotoxicity. The latter is caused by exogenous nephrotoxins like: antibiotics (especially aminoglycosides), organic solvents, chemotherapeutic, immunsuppressive and antiinflammatory drugs as well as contrast media. Acute tubular necrosis due to nephrotoxicity also occurs in the setting of rhabdomyolysis, hemolysis, hyperuricemia and myeloma (1).

The following features support the diagnosis of acute tubular necrosis :

Acute tubular necrosis secondary to Aminoglycosides occurs in 10-30 % of courses of aminoglycoside administration (1). The precise cellular mechanism of toxicity is unknown. However it is presumed, that interference with normal processing of membrane phospholipids plays an important role in the pathophysiology. Risk factors for aminoglycoside nephrotoxicity include:

Noninfectious Acute Interstitial Nephritis

Noninfectious acute interstitial nephritis (AIN) is characterized by an acute inflammatory process, that involves the renal interstitium and is associated with variable degree of tubular damage. The etiology is not completely understood; however it is believed that a hypersensitivity reaction to offending drugs plays an important role in the pathophysiology. Renal biopsies show infiltration of the interstitial compartment by inflammatory cells, especially T-cells, monocytes, plasma cells, and eosinophils. Occasionally the separation of tubules is seen and in severe cases tubular basement membrane disruption can be found (1).

Acute interstitial nephritis is usually caused by pharmaceuticals, especially:

Clinical features include acute deterioration in renal function combined with fever, arthralgia, maculopapular skin rash and eosinophilia. However the frequency of these signs is variable. Patients with acute interstitial nephritis due to Penicillin derivatives show a rash in less than 50 %, fever in 75 %, eosinophilia in 80 % of the time. The combination of all 3 signs occurs in less than 33 % of cases (1).

The differentiation between these two syndromes is of major importance. In addition to withdrawal of the offending agent in either syndrome, most clinicians favor high dose steroid therapy in acute interstitial nephritis . Furthermore plasmapheresis should be considered in patients with anti-TBM antibodies or lupus induced interstitial nephritis. None of these therapeutic approaches is indicated for acute tubular necrosis.

Gallium Scintigraphy in the Differential Diagnosis of Acute Renal Failure

It has been postulated, that intense renal Ga-67 uptake is a consistent finding in acute interstitial nephritis, but not in acute tubular necrosis (2) with the exception of renal transplant recipients (3). Linton et. al. conducted two studies, that included Ga-67 scanning in patients with acute renal failure. In the first study with a total of 27 patients he found intense Gallium uptake in all 9 patients with interstitial nephritis, but none in the 6 patients with acute tubular necrosis (4). He suggested Ga-67 scanning as a possible way to differentiate between both syndromes. This was disputed by other authors, who claim that the Gallium uptake in acute interstitial nephritis is unpredictable.

Graham et. al. (5) studied 12 patients with biopsy proven noninfectious interstitial nephritis. Only 7 (= 58 %) of these showed intense Gallium uptake. 5 scans (= 42 %) were false negative. However all patients in this study had chronic renal insufficiency, which changes the histological pattern. A second study by Linton et.al. (6) with a total of 108 patients revealed intense Gallium uptake in all 11 patients with biopsy proven acute interstitial nephritis . There was no or only minimal Gallium uptake in 12 patients with acute tubular necrosis, of which only 2 were proven by biopsy . One of the largest studies on renal Gallium uptake reviewed 500 Ga-67 images with 996 kidneys (7). None or minimal uptake was seen in 94.4 % of kidneys. 5.6 % of kidneys showed increased uptake at 48 hours (equal to spine intensity or higher). Of these 56 kidneys with abnormal Ga-67 uptake 18 % (=10) were due to drug induced renal damage (acute interstitial nephritis ), while only 2 % (=1) was due to acute tubular necrosis.

Conclusions

The described case is therefore a rare presentation of abnormal renal Gallium uptake at 48 hours due to acute tubular necrosis. It suggests, that the proposed differentiation between acute tubular necrosis and acute interstitial nephritis with the help of Gallium scans may not be possible.

References

1. Brenner B : The Kidney WB Saunders, 5th edition, 1996

2. Wagner H et. al. : Principles of Nuclear Medicine WB Saunders, 2nd edition, 1995

3. Sherman R, Byun K : Nuclear Medicine in acute and chronic renal failure. Seminars in Nuclear Medicine 1982; 12: No.3

4. Linton A, Clark W, Driedger A, Turnbull D, Lindsay R : Acute interstitial nephritis due to drugs. Annals of Internal Medicine 1980; 93: 735-741.

5. Graham G, Lundy M , Moreno A : Failure of Gallium 67 scintigraphy to identify reliably noninfectious interstitial nephritis. J Nucl Med 1983; 24; 568-570.

6. Linton A, Richmond J, Clark W, Lindsay R, Driedger A, Lamki L : Gallium 67 scintigraphy in the diagnosis of acute renal disease. Clinical Nephrology 1985; 24: 84-87.

7. Lin D , Sanders J, Patel B: Delayed renal localization of Ga 67. J Nucl Med 1983; 24: 894-897.

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J. Anthony Parker, MD PhD, Tony_Parker@bidmc.harvard.edu