Joint Program in Nuclear Medicine

Radionuclide Evaluation of Renal Function

Chandra Dass, MD
J. Anthony Parker, MD, PhD

January 28, 1997

Presentation

A 32 year old male status post multiple episodes of pyelonephritis with subsequent obstruction and right nephrostomy tube placement underwent an intravenous urogram (IVU) which revealed severe dilatation of the pelvicalyceal system on the right side and normal functioning left kidney. Subsequent nephrostogram revealed obstruction of the proximal right ureter near the UPJ, probably congenital. A renal scan was performed to help direct therapy.

Imaging Findings

The renal scan revealed reduced function on the right. The uptake in the kidneys from 1 to 3 minutes on the renogram curves was used to calculate the split renal function; the left-to-right ratio was 85% to 15%. Given that he remained symptomatic and that the right kidney had poor function, a nephrectomy rather than a pyeloplasty was performed.

Discussion

Several radionuclide techniques have been developed for the evaluation of renal pathology, e.g. flow/perfusion study, global/split renal clearance (Glomerular Filtration Rate, Effective Renal Plasma Flow, Tubular Extraction Rate) studies, renal transit times, and techniques for the evaluation of renovascular hypertension and obstructive uropathy. Renal clearance in the form of GFR or ERPF are the commonly used parameters in the initial and followup evaluation of several renal diseases. The various methods available for the estimation of renal clearance can be broadly classified in one of three categories: classic methods - those in which both urine collection and plasma sampling are required (either with non-radioactive or radioactive substances); those in which plasma sampling alone is required (plasma disappearance curve); gamma camera methods with or without blood sampling (from the amount of tracer extracted from the plasma by the kidneys). The classical methods are not used clinically because they are expensive, time consuming, requires steady state plasma concentration and extremely accurate urine collection.

Radionuclides

The methods of GFR and ERPF are identical except for the time scales and the radiopharmaceuticals used. Analogs of inulin yield GFR; analogs of PAH yield ERPF. Of the various radiopharmaceuticals available, Tc-99m DTPA & Cr-51 EDTA are used for the estimation of GFR; I-123 Hippuran for ERPF; Tc-99m MAG3 for TER (1). Because ERPF tracers are excreted much more rapidly than GFR agents, their plasma clearance can be measured accurately in less than an hour; comparable accuracy in GFR requires several hours.

Methods

The most accurate estimation of clearance using radiotracers involves determination of both the initial rapid and the late slow components of the plasma disappearance curve with multiple blood samples and analyzing the data either by the Stewart-Hamilton type formulation or by fitting the curve to two exponential terms (2). These techniques are used as a standard to which technically simple methods are compared. If one delays plasma sampling until redistribution of the tracer throughout the body compartments occurs, the plasma disappearance curve becomes a monoexponential function that can be defined by obtaining two plasma samples (3). To simplify the procedure further, single plasma sample methods that relate the activity of the tracer remaining in the plasma at a specified time after injection to either a reference curve derived from an index population (empirical methods) or to the slow monoexponential portion of the plasma disappearance curve (compartmental methods) have been developed (4,5).

In contrast to plasma sampling techniques, imaging methods determine the clearance from the amount of radiotracer extracted from the plasma by the kidneys during the uptake phase of the renogram. These techniques either require the knowledge of the plasma activity during this period obtained from a region-of-interest drawn over a vascular region and a single plasma sample, or determine clearance directly from the renal uptake alone. In the latter case, the renal uptake is then related to the clearance by a regression formula obtained from an index population. The accuracy of those methods that do not include a plasma sample has been a matter of recent controversy (2).

Relative Accuracy

The spectrum of accuracy varies widely based on the method chosen to calculate clearance. The complete plasma clearance curve is the most accurate but requires multiple blood samples. The two blood sample method is only slightly more accurate than the one sample method, while the gamma camera techniques are less accurate than all of the plasma methods. However, the gamma-camera techniques have been shown to be more accurate than creatine clearance and further more, do not require either plasma or urine samples. Methods using plasma sampling yield only global function estimates, while gamma camera methods measure both global and differential renal functions. The best results are obtained by combining both approaches; i.e., single blood sample for total clearance and camera acquisition for the relative contribution of each kidney to the total function. In patient management, the question of relative contribution of each kidney to the total renal function is often more important than the global function itself. For this reason the results are expressed in relative units (% of total function) rather than absolute units (ml/min). This information cannot be easily obtained from any non-radionuclide method. At very low levels of renal function urinary clearance is felt to be more accurate, and in patients with edema or ascites multiple sample approach is required.

Conclusions

The simplified radionuclide methods for quantifying renal function are estimates of function, with clinically acceptable levels of error. The error of the estimates typically increases in the setting of very poor renal function, but so does the error associated with the presently used biochemical tests, such as creatine clearance. To be used clinically, a method need not be highly accurate; it is more important it is reproducible. One problem limiting the more general acceptance of radionuclide method is cost, which is often greater than that of the biochemical tests used. Radionuclide methods are most useful in patients in whom urine collection is difficult, among them poorly cooperative patients, children, and in those with renal insufficiency. Camera based methods offer another advantage - quantitation of individual renal function (6).

References

1. Blaufox MD, Aurell M, Bubeck B, et al. Report of the Radionuclides in Nephrology Committee on Renal Clearance. J Nucl Med 1996; 37:1883-1890.

2. Summerville DA, Potter CS, Treves TS. The use of Radiopharmaceuticals in the measurement of Glomerular Filtration Rate: A Review. Nucl Med Annual 1990:191- 221.

3. Rootwelt K, Falch D, Sjokvist R. Eur J Nucl Med 1980;5:97-102.

4. Tauxe WH, Dubovsky EV (eds) in Nuclear Medicine in Clinical urology and Nephrology 1985, Appleton-Century- Crofts. Pp 61-106.

5. Russell CD, Dubovsky EV. Measurement of Renal function with Radionuclides. J Nucl Med 30:2053-2057, 1989.

6. Thrall JH, Ziessman HA.(eds) in Nuclear Medicine -The Requisites. 1995, Mosby-Year Book, Inc. Pp 293-297.

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