Objective evidence of a high prevalence of renal damage in women with type 2 diabetes by technetium-99m DMSA renal cortex scan findings

Material and methods 

The study included three groups of patients: 28 control women without type 2 DM and a history of UTIs (age range 42 to 70 years), 25 male patients with type 2 DM but without a history of UTIs (age range 44 to 68 years), and 103 women with type 2 DM (age range 41 to 71 years; Table I). The exclusion criteria were pregnancy, known urinary tract abnormalities, and overt renal failure. No study subject had an acute UTI during 99mTc DMSA renal scanning. We defined DM as a fasting glucose concentration of at least 7.8 mmol/L (140 mg/dL) or a 2-hour glucose concentration of at least 11.1 mmol/L (200 mg/dL). Type 2 DM was the combination of a resistance to insulin action and an inadequate compensatory insulin secretory response. All study subjects were interviewed at baseline; their medical histories were obtained from the hospital records using a standardized questionnaire and included age, duration of DM, secondary complications of DM (retinopathy, neuropathy, or macrovascular diseases), and blood pressure. The following laboratory values were also obtained: glycosylated hemoglobin A1c, blood urea, serum creatinine, and 24-hour urinary protein values.

TABLE I. Detailed clinical data

	Characteristic	Female Controls	Type 2 DM Male Patients	Type 2 DM Female Patients
				Without UTI	Cystitis	Pyelonephritis
	Age (yr)	51 ± 5	50 ± 9	51 ± 7	52 ± 6	50 ± 8
	DM duration (yr)	—	10 ± 5	11 ± 2	10 ± 3	11 ± 3
	Secondary complications (%)	0	8.0	8.3	8.8	9.1
	Hypertension (>130/85 mm Hg) (%)	35.7	36.0	36.1	38.2	39.4
	HbA1c (%)	5.1 ± 0.7	11.5 ± 1.8	12.3 ± 1.9	11.6 ± 2.0	12.1 ± 2.1
	Blood urea (mg/dL)	20.1 ± 5.1	22.3 ± 7.5	22.1 ± 7.7	23.5 ± 9.0	23.3 ± 8.7
	Serum creatinine (mg/dL)	0.88 ± 0.21	0.89 ± 0.25	0.91 ± 0.34	0.90 ± 0.27	0.91 ± 0.29
	Urinary protein excretion (mg/24 hr)	90 ± 12	312 ± 125	310 ± 124	315 ± 129	320 ± 130

Key: DM = diabetes mellitus; UTI = urinary tract infection; HbA1c = glycosylated hemoglobin A1c.

All the women with type 2 DM were individually instructed to obtain a clean-catch midstream urine specimen aseptically. A diagnosis of UTI was made if two consecutive urine cultures grew the same organism of at least 105 colony-forming units/mL in asymptomatic subjects or at least 104 colony-forming units/mL in symptomatic subjects.10, 11 Cystitis was defined as the report of the presence of dysuria, frequency, urgency, stranguria, and/or abdominal discomfort. Pyelonephritis was defined as the findings for cystitis and/or the presence of flank and/or lower back pain and fever (temperature greater than 38.3°C).12 The history of UTI, including cystitis and pyelonephritis, was defined as at least three symptomatic UTIs in the past year before study enrollment. Therefore, the 103 women with type 2 DM were separated into three groups: 36 women without a history of UTI, 34 women with a history of cystitis only, and 33 women with a history of pyelonephritis.

In this study, the interval between 99mTc DMSA renal scanning and the last UTI episode was at least 1 month. 99mTc DMSA was prepared from a commercial kit (Amerscan DMSA Agent, Nycomed Amersham, Little Chalfont, Buckinghamshire, UK). Imaging was performed 3 hours after intravenous injection of 5 to 8 mCi of 99mTc DMSA. All studies were carried out with a rotating, large field-of-view, dual-head gamma camera fitted with a low-energy, high-resolution collimator. Planar images were acquired first in six projections (anterior, posterior, right anterior oblique, left anterior oblique, right posterior oblique, and left posterior oblique views of the kidneys), with a total of 600,000 counts per image in a 256 × 256 word mode matrix. Each scan was examined by three experienced nuclear medicine physicians who were unaware of clinical and laboratory data. The resulting diagnosis and degree of renal cortex defects were confirmed by at least two of the three interpreters. The 99mTc DMSA renal images were interpreted according to the following parameters.4, 13, 14 Normal 99mTc DMSA renal scan findings (Fig. 1) were as follows: (a) normal contour, defined as smooth and continuous without indentations, (b) homogeneous parenchymal uptake in all regions of both kidneys, and (c) normal size and reniform shape of both kidneys. Abnormal 99mTc DMSA renal scan findings were as follows:

1.Inflammation (Fig. 2): (a) bulging or normal contour; (b) single or multiple, focal or diffuse, areas of decreased activity in the parenchyma, with a diffuse or, rarely, spherical shape on at least two projections; (c) mild to severe degree of photopenia or, rarely, complete absence of activity; and (d) no volume loss

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FIGURE 2. 99mTc DMSA renal scan revealing normal contour, decreased activity in the lateral and medial aspects of upper pole in left kidney (arrow), and no volume loss. Post. = posterior; Ant. = anterior.

2.Scar (Fig. 3): (a) diffuse or sharp indentation in contour with thinning of cortex; (b) defects of any shape with loss of renal volume; and (c) severe degree of photopenia or absence of activity15

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FIGURE 3. 99mTc DMSA renal scan revealing multiple sharp indentations of completely absent activity in left kidney (arrows) with loss of renal contour and volume. Post. = posterior; Ant. = anterior.

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FIGURE 1. 99mTc DMSA renal scan revealing normal contour, normal size, normal shape, and homogeneous parenchymal uptake. Post. = posterior; Ant. = anterior; R.P.O. = right posterior oblique; L.A.O. = left anterior oblique; R.A.O. = right anterior oblique; L.P.O. = left posterior oblique.

Results 

The detailed data are listed in Table II. All 28 control women (100%) and 25 male patients with type 2 DM without a history of UTIs (100%) had normal 99mTc DMSA renal scan findings. However, 41 (39.8%) of the 103 women with type 2 DM had abnormal 99mTc DMSA renal scan findings. Women with type 2 DM without a history of UTI had a significantly lower prevalence of abnormal renal scan findings than did those with cystitis only and pyelonephritis (1 [2.8%] of 36 versus 40 [59%] of 67). In addition, the prevalence of abnormal renal scan findings was significantly higher in women with type 2 DM with pyelonephritis (27 [81.8%] of 33) than with cystitis only (13 [38.2%] of 34). Renal scarring on 99mTc DMSA renal scan findings was found in one third of women with type 2 DM with pyelonephritis (13 [39.4%] of 33). However, in the clinical data, no differences were found among women with type 2 DM without UTI, with cystitis, and with pyelonephritis (Table I). In addition, no differences were found among women with type 2 DM with normal findings, inflammation, and scar on 99mTc DMSA renal scanning (Table III).

TABLE II. Renal scan findings among female controls, male patients with DM, and female patients with DM

	Renal Scan Findings	Female Controls (n)	Type 2 DM Male Patients (n)	Type 2 DM Female Patients (n)
				Without UTI	Cystitis	Pyelonephritis
	Normal	28	25	35	21	6
	Inflammation	0	0	1	13	14
	Scar	0	0	0	0	13

Abbreviations as in Table I.

TABLE III. Comparison of detailed clinical data among women with DM and normal, inflammatory, and scarring renal scan findings

	Characteristic	Normal	Inflammation	Scarring
	Age (yr)	50 ± 5	51 ± 7	52 ± 6
	DM duration (yr)	10 ± 3	11 ± 3	11 ± 2
	Secondary complications (%)	8.1	10.7	7.7
	Hypertension (>130/85 mm Hg) (%)	35.5	39.3	38.5
	HbA1c (%)	11.3 ± 2.0	12.4 ± 1.8	12.2 ± 2.0
	Blood urea (mg/dL)	23.2 ± 6.7	23.1 ± 8.5	23.6 ± 8.0
	Serum creatinine (mg/dL)	0.90 ± 0.31	0.91 ± 0.25	0.91 ± 0.21
	Urinary protein excretion (mg/24 hr)	312 ± 121	317 ± 128	321 ± 132

Abbreviations as in Table 1.

Comment 

The postulated factors for the susceptibility of diabetic individuals to develop UTIs include functional defects of the phagocytes and bladder dysfunction, leading to poor emptying and impaired washout of bacteria.16 Because UTIs may lead to renal damage,1 awareness of renal damage among women with DM is important. However, the sensitivity of indirect tests such as antibody-coated bacteria in urine2, 17 or intravenous urography18 is limited. The 99mTc DMSA renal scan for detecting renal damage has been proved to be the most sensitive method in clinical practice.10, 19

Women with type 2 DM without a history of UTI had a significantly lower prevalence of abnormal renal scan findings than did those with UTI (cystitis and pyelonephritis). Our findings were compatible with a previous report.20 The inflammation noted on the 99mTc DMSA renal scan suggesting renal parenchymal abnormalities from pyelonephritis was found in 13 (38%) of 34 women with type 2 DM and a history of cystitis only. This result might mean that the diagnosis of pyelonephritis by traditional signs and symptoms is unreliable and potentially misleading. Perhaps these female patients with type 2 DM have a diminished systemic inflammatory response so that flank pain and/or fever is not always present, even when pyelonephritic inflammatory changes are present on 99mTc DMSA renal scanning. In the present study, irreversible renal damage (scar) was visualized in 13 (39.4%) of 33 women with type 2 DM and a history of pyelonephritis. These facts strongly support the possibility that pyelonephritis is an important cause of the renal scarring demonstrated on 99mTc DMSA renal scanning, although DM individuals are predisposed to other known causes of renal scarring,17, 21 such as large vessel disease-related renal artery stenosis and coronary and cerebrovascular disease. Related risk factors such as hyperlipidemia and hypertension can also cause ischemic renal scarring.17, 21 However, the analysis of the clinical data of the present three groups of patients showed that no statistically significant difference among the women with type 2 DM without UTI, with cystitis, and with pyelonephritis was found.

Previous studies have suggested that more false-positive defects are detected on single photon emission computed tomography (SPECT) than on planar DMSA images, although the overall accuracy of these two imaging techniques is essentially the same.22, 23, 24, 25 In addition, according to a recent review report,26 SPECT was performed often by only 22% of the experts. The role of SPECT in the evaluation of kidneys in adults suspected of having acute pyelonephritis remains controversial. Therefore, we assessed the prevalence and type of renal damage in women with type 2 DM and compared the findings with those of control women using planar images of the 99mTc DMSA renal scan.

We found that women with type 2 DM with a history of UTI, especially if they had had pyelonephritis, had a significantly higher prevalence of renal scarring than did those without UTI. The normal 99mTc DMSA renal scan findings suggested cystitis only, but abnormal findings, including inflammation and scar, indicated pyelonephritis.27 The optimal treatment for cystitis only and pyelonephritis is different. A 3-day regimen is effective for cystitis, but a 10 to 14-day regimen is recommended for pyelonephritis.28 99mTc DMSA renal scan findings may alter the therapy regimen or follow-up. Therefore, these observations warrant inclusion of 99mTc DMSA renal scanning as a routine examination to investigate renal damage, especially in women with type 2 DM and a history of UTIs.