Monitoring Kidney Function in Diabetic Nephropathy

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S. GROTH, et al

Abstract:

Groth S. Petersen C. Dirksen A. Parving H.-H (Department of Clinical Physiology and Nuclear Medicine, Bispebjerg Hospital and Rigshospitalet. Hvidere Hospital, Copenhagen, Denmark). Monitoring kidney functions in diabetic nephropathy. journal of Internal Medicine 1989: 226: 341-43.

We investigated the validity of a one plasma sample method (I) compared with a multiple plasma sample method (11) for routine clinical determination of glomerular filtration rate (GFK) in 3 5 insulin-dependent diabetic patients suffering from nephropathy. GFK was measured after an intravenous bolus injection of 100 pCi S'Cr-EDTA by determination of plasma radioactivity in venous blood samples taken from the other arm 180. 200. 220 and 240 min after the injection (11). The plasma radioactivity in the sample drawn 240 min after injection was used in the method I. During the mean investigation period of 32 months (12-62 months), a total of 184 GFR determinations were performed. The average interval between the GFK measurements was 6 months (1-21 months). In 12 71 184 of the study intervals method, I indicated a decrease in GFR. The corresponding figure for method I1 was almost identical, 1301 184. The mean decline in GFR was 8.1. f 7.2 and 7.8 f 6.9 ml year-' 1.73 m-* using methods I and 11. respectively (NS). The methods essentially provided the same GFR values in absolute terms (r = 0.98. P < 0.001). We conclude that the one plasma sample method can be used as a valid routine technique in non-uraemic patients with nephropathy.

Keywords: diabetic nephropathy. glomerular filtration rate, insulin-dependent diabetes mellitus.

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Introduction

Diabetic nephropathy is characterized by persistent albuminuria, elevated arterial blood pressure, and a relentless decline in glomerular filtration rate [ 1, 21. To monitor the progression and effectiveness of various treatment modalities in this complication a valid method for GFR determination is required. Several studies have demonstrated that the plasma disappearance of "Cr-EDTA, followed for 4 h after intravenous bolus injection, is a very precise and rather accurate method for GFR determination as reviewed by Bochner-Mortensen [ 31. However, the capacity of the multiple plasma sample method is rather limited compared to the one plasma sample method [4].

Our study deals with a comparison between "Cr-EDTA clearance measured by a multiple plasma sample method and a single sample method in insulin-dependent diabetic (IDDM) patients suffering from nephropathy.

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Patients and methods

Twenty-four males and 11 females (mean age 37 years, range 2448 years) with IDDM and diabetic nephropathy were investigated prospectively by one of us (HHP). All patients were characterized by persistent proteinuria (> 0.5 g/24 h), serum creatinine less than 200 pmol I-', age less than 50 years, the onset of IDDM before the age of 31 years. All patients had diabetic retinopathy. The mean duration of diabetes was 22 years. All patients were insulin-dependent from the time of diagnosis and all received two daily injections of insulin (mean dose 0.61 IU kg-' d-'). Diabetic nephropathy was diagnosed clinically according to previously described criteria [ 51. Thirty-one patients initiated antihypertensive treatment (metoprolol, frusemide/thiazide, and hydralazine) during the investigation 'period.

The patients had their normal breakfast and morning insulin before the investigations, which were performed between 09.00 hours and 13.00 hours with the patients resting in the supine position. At each examination "Cr-EDTA clearance was determined by the standard multiple plasma sample (180,200,220, and 240 min after injection) method as suggested by Brechner-Mortensen [6]. and the single sample method described by us [4]. The single blood sample was drawn 240min after the tracer injection. On average "Cr-EDTA clearance was monitored for 32 (range 12-62) months. The mean interval between investigations was 6 months (1-2 1 months). The patients underwent a total of 184 GFR determinations.

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Results

The multiple plasma sample method yields a mean decline in "Cr-EDTA clearance of 7.8 f 6.9 ml year-' 1.73 m-2 as compared with the single sample method showing a decline of 8.1 & 7.2 ml year-' 1.73 m-'. In 130/184 and 127/84 of the study intervals, a decrease in "Cr-EDTA clearance as indicated by the multiple and the single sample method, respectively. The two methods provide virtually identical "Cr-EDTA clearance values (r = 0.98. P -= 0.001, Fig. 1). The individual time courses are shown in Figs. 1 and 2.

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Fig. 1. Individual time course of "Cr-EDTA clearance in 3 5 IDDM patients with nephropathy as measured by (A) a multiple plasma sample standard method (CIS,) and (B) by a single sample method (CI,*,).

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Fig. 2. Comparison of the individual time course of "Cr-EDTA clearance measured simultaneously by a multiple plasma sample standard methods (CIS, see Fig. 1A) and by a single sample method (CI-,, see Fig. 16) in 35 IDDM patients with nephropathy.

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Discussion

To obtain information on the prognosis and the effect of treatment in diabetic nephropathy, serial determination of GFR must be performed. Valid information on kidney function and/or changes in the function requires a sensitive, precise, and accurate method for GFR determination. The single short "Cr-EDTA plasma clearance technique based on samples taken 180. 200. 220 and 240 min after the tracer injection carried out in our study fulfills the above-mentioned requirements [ 1,2] as reviewed by Brechner-Mortensen [ 31. Our study suggests that the single sample method for determination of SICr-EDTA clearance provides precise information on GFR and changes in GFR in non-uraemic IDDM patients with nephropathy (GFR 2 25 ml min-' 1.73 m-2). This technique can be used for monitoring and diagnostic purposes instead of the more time and laboratory-space-consuming conventional methods. Since the GFR is about the same with and without strict bed rest during the 4-h clearance period [7]. we allow the patients to leave the department in order to sit in the waiting room or have an appointment in the out-patient clinic before returning for plasma sampling. The patient is in the supine position 15 min before blood sampling.

Determination of serum creatinine and creatinine clearance are still the most commonly used methods for estimation of GFR in kidney diseases. Unfortunately, creatinine must be regarded as an insensitive and unreliable filtration marker in glomerulopathic patients including diabetic nephropathy [2. 8, 9.1. This is mainly due to progressive hypersecretion of creatinine by remnant renal tubules as the kidney disease worsens, resulting in gross and unpredictable overestimations of the GFR [9]. Methods that require accurate urine collections, e.g. creatinine clearance, cannot be recommended in IDDM patients with nephropathy because a large fraction (3040%) of these patients suffer from incomplete emptying of the bladder due to diabetic cytopathic [ 101].