Short Term Prognostic Utility of Tc-99m DMSA Renal Imaging in Sepsis Induced Acute Renal Failure; Provisional Data

doi:10.4236/ijcm.2013.412094

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International Journal of Clinical Medicine, 2013, 4, 543-547

Published Online December 2013 (http://www.scirp.org/journal/ijcm)

http://dx.doi.org/10.4236/ijcm.2013.412094

Open Access IJCM

543

Short Term Prognostic Utility of Tc-99m DMSA Renal

Imaging in Sepsis Induced Acute Renal Failure;

Provisional Data

Amr Amin1, Hatem Nasr1, Gehan Younis1, Hatem Gamal2

1Nuclear Medicine Unit, Faculty of Medicine, Cairo University , Cairo, Egypt; 2Intensive Care Unit, Faculty of Medicine, Cairo Uni-

versity, Cairo, Egypt.

Email: [email protected]

Received October 8th, 2013; revised November 3rd, 2013; accepted December 2nd, 2013

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Background: Sound prognostic data in sepsis induced acute renal failure (SARF) are lacking especially on the short

term outcome [STO] in the intensive care unit [ICU]. We addressed the use of Tc-99m DMSA [2,3-dimercaptosuc-

cinicacid] renal cortical imaging as a prognostic tool in SARF. Methods: Forty patients with acute renal failure due to

sepsis [age range 15 - 74 years; median 44.5] were subjected for full history taking complete physical examination, rou-

tine ICU monitoring, routine laboratory investigations, APACHE II [Acute Physiolog y and Chronic Health Evaluation]

and SOFA [Sequential Organ Failure Assessment] together with Tc-99m DMSA cortical renal scintigraphy. Patients’

death in the ICU or discharge was considered as the end point of the study representing the so-called short term out-

come [STO]. Results: 25% mortality rate [10/40] was found along the admission period in the ICU. All non-survivors

were abnormal with DMSA imaging [NPV & PPV 100% & 66.7% respectively]. Abnormal DMSA cases showed sig-

nificant positive associations with serum creatinine at admission [r = 0.5 ; P 0.02]; admission duration [r = 0.4; P 0.002];

APACHE II score [r = 0.5; P 0.004] and STO [r = 0.4; P 0.03]. Statistically significant difference was elicited between

subjects with normal and abnormal DMSA regarding the same parameters. Conclusion: This preliminary data could

raise Tc-99m DMSA renal imaging as a prognostic tool in SARF that could allow influential interference to prohibit

dramatic outcomes as mortality.

Keywords: Acute Renal Failure; Tc-99m DMSA; Sep sis Induced Acute R e n a l Failure

1. Introduction

Acute renal failure [ARF] is a sudden sustained decline

in glomerular filtration rate [GFR] usually associated

with uremia and a fall in urine output with a high

mortality rate [1]. Factors affecting its incidence and

outcomes are unclear therefore making optimal decision

for patients’ care is hindered [2]. Tc-99m labeled DMSA

(2,3-dimercaptosuccinicacid) is avidly taken up by cells

of the proximal tubule, with about 35% of the injected

activity being localized in the renal cortex by one hour

[3]. The renal uptake of Tc-99m DMSA parallels the

renal function as determined b y GFR and accordingly its

uptake is significantly decreased in nephropathy [4,5]

which is accepted as a poor prognostic sign [6]. Bern-

heim et al. in 1976 proposed renal scintigraphic scanning

as a tool to assess the prognosis of ARF using hippuran

and concluded that its uptake was a parameter which

authorized the prognosis of a favorable course whereas

its absence permitted one to envisage an unfavorable

course [7]. However, in a case report published in 1986;

a 35-year-old patient developed ARF on top of acute tu-

bular necrosis requiring hemodialysis and they stated that

failure to visualize acutely injured kidneys with Tc-99m

DMSA did not preclude recoverable function [4], while

the reverse was elicited in another two studies using hip-

puran [8,9]. Besides, much research is still needed be-

cause our understanding of what happens to the kidney in

ARF is still poor [10]. Hence, we aimed to evaluate the

predictive role of Tc-99m DMSA cortical scanning in

predicting the short term outcome [STO] of the ad-

mission period in the intensive care in sepsis-induced

ARF patie n ts [SARF] .

Short Term Prognostic Utility of Tc-99m DMSA Renal Imaging in Sepsis

Induced Acute Renal Failure; Provisional Data

544

2. Patients and Methods

Forty patients with SARF were enrolled in the study and

monitored for their ICU prognosis and outcome. ARF

patients with previous renal transplantation, known urin-

ary tract abnormalities or surgery or those with pre-exist-

ing CKD requiring regular haemodialysis and advanced

congestive heart failure were excluded. Patients were

subjected for routine ICU monitoring, routine lab s, Elec-

trocardiography, APACHE II [Acute Physiology and

Chronic Health Evaluation] and SOFA scores [Sequen-

tial Organ Failure Assessment]. APACHE II is used as

an indicator of severity of illness and likelihood of sur-

vival [10]. The patients were allocated to Tc-99m DMSA

cortical renal scintigraphy as performed in accordance

with a standard protocol. Imaging was done 3 hours after

injection of the trace 111 MBq [3 mCi] with obtained

anterior and poster ior views su ing “PHILIPS AX IS-2 VT;

the Netherlands” gamma camera. The scintigraph ic study

findings were blindly interpreted and defined as normal

or abnormal. We classified abnormal DMSA scans as

based on visual assessment of images into GRADE 1

[Gr1; mild to moderate reduction in overall uptake with

mild to moderate elevation of background] and GRADE

2 [Gr2; severe reduction in overall uptake with severe

elevation of background]. Patients’ death in the ICU or

discharge was considered as STO that was used in

calculating positive and negative predictive values [PPV

and NPV].

3. Statistical Analysis

Descriptive statistics included frequencies and percent-

ages for each variable while numerical measures were

represented as mean ± SD. Cross tabulation was utilized

to describe the relations between variables using the

contingency coefficient. T-test for testing the differences

between samples was used. Correlations were done using

Pearsons and Spearman correlation coefficients. Also;

NPV and PPV were calculated and P value <0.05 was

considered significant.

4. Results

40 patients [22 female & 18 males; mean age 47.2 ± 17

years] with ARF due to sepsis were enrolled in th is study.

Regarding their medical history; 32.5% were smokers

and hypertensive (using B-blockers and Angiotensin con-

verting enzyme inhibitors [ACE-I]), while diabetes was

found in 17.5% [using oral hypoglycemic drugs]. Sepsis

was the inducing factor for ARF with bronchopn eumonia

and pyelonephritis as the dominating clinical sources

[27.5% and 22.5% respectively]. Other less sources in-

cluded peritonitis and post-surgical sepsis [7 for each;

17.5%] and finally infected pace-maker [3 patients;

7.5%]. According to the STO in the ICU; patients were

classified into survivors and non-surv ivors [Figures 1(a)

and (b)] representing 30/40 [75%] and 10 [25%] respec-

tively. Their characteristics are detailed in Table 1.

According to the STO; patients were classified into

survivors and non-survivors representing 30/40 [75%]

and 10 [25%] respectively. DMSA cortical imaging

showed 25 and 15 cases as normal and abnormal [5 Gr1

and 10 Gr2 cases] respectively and all the non-survivors

were Gr2. Correlations between DMSA cortical imaging

and patients’ STO [survivors and non-survivors] with

various patients’ factors are shown in Table 2. There w a s

statistically significant difference between subjects with

normal and abnormal DMSA regarding need of mecha-

nical ventilation, serum creatinine on admission, admis-

sion duration, APACHE II Score and STO [P 0.02, P

0.03, P 0.01, P 0.01 and P 0.03 respectively]. Abnormal

DMSA showed significant positive associations only

with serum creatinine at admission time [r = 0.5; P 0.02],

admission duration [r = 0.4; P 0.002]; APACHE II score

[r = 0.5; P 0.004] and STO [r = 0.4; P 0.03]. Calculated

(a)

(b)

Figure 1. Tc-99m DMSA cortical renal scan [Left: anterior

and right: posterior]. (a) Non-survivor case where G2 was

elicited and the patient died a week after admission to ICU

nd (b) Survivor images with normal cortical uptake. a

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Short Term Prognostic Utility of Tc-99m DMSA Renal Imaging in Sepsis

Induced Acute Renal Failure; Provisional Data

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545

Table 1. Clinical and investigatory characteristics of the studied patients.

Survivors [n. 30] Non-survivors [n. 10]

Age [Mean ± SD] 47.4 ± 16.0 46.6 ± 20.3

Gender [n. %]

 Male [n. 18]

 Female [n. 22]

13 [72.2%]

17 [77.3%]

5 [27.8%]

5 [22.7%]

ICU admission duration [Days] 12.9 ± 7.7 19.1 ± 13.7

Creatinine [mg/dl]

 At admission

 At discharge

4.4 ± 1.6

2.2 ± 1.7

3.6 ± 0.9

2.9 ± 1.4

APACHE II score 19.6 ± 4.2 23.9 ± 3.2

SOFA score 7.1 ± 1.6 8.3 ± 1.7

Abnormal renal sonography 8/30 [26.5%] 3/10 [30%]

Echocardiographic findings

 Normal [n. 40]

 Abnormal [n. 0]

30 [75%]

10 [25%]

Need for mechanical ventilation 7/30 [23.3%] 9/10 [90%]

Need for dialysis 4/30 [13.3%] 1/10 [10%]

DMSA scan

 Normal [n. 15]

 Abnormal [n. 25]

15/15 [100%]

15/25 [60%]

0/15 [0%]

10/25 [40%]

Table 2. Correlations betw ee n DMSA c o r t ical imaging and patients’ short term final outcome with various patients’ factors.

DMSA scan Short term final outcome

Patients’ parameters Normal [n. 15] Abnormal

[n. 25] r-value

P value Survivors

[n. 30] Non-survivors

[n. 10] r value

P value

Age 43.3 ± 21 40.5 ± 19 r = 0.1

P 0.7 47.4 ± 16 46.6 ± 20.3 r = 0.1

P 0.8

Sex

Male

Females

6 [40% ]

9 [ 60%]

12 [48%]

9 [52%]

r = 0.2

P 0.5

13 [43.3%]

17 [56.7%]

5 [50%]

r = 0.1

P 0.7

Smoking 5 [33.3%] 8 [32%] r = 0.1

P 0.9 9 [ 30%] 4 [ 40%] r = 0.2

P 0.6

Source of sepsis

- r = 0.2

P 0.3

- r = 0.2

P 0.1

Need of hemodialysis 0 5 [20%]

r = 0.2

P 0.07 4 [13.3%] 1 [10%] r = 0.2

P 0.7

Need of mechanical

ventilation 5

[33.3%] 11

[44%] r = 0.5

P 0.02 7/30 [23.3%] 9/10 [90%] r = 0.5

P 0.0001*

Serum creatinine

On admission

On Discharge

3.8 ± 1

2.2 ± 1.7

5.5 ± 2

2.9 ± 1.5

r = 0.5

P 0.02*

r = 0.2

P 0.9

4.4 ± 1.6

2.2 ± 1.7

3.6 ± 0.9

2.9 ± 1.4

r = 0.2 P 0.1

r = 0.1 P 0.2

Abnormal renal

sonography [n. 11] 0 11 [44%]

r = 0.3

P 0.06 7/30 [23.3%] 2/10 [ 2 0%] r = 0.1 P 0.8

Admission duration 10.65 ± 7.8 18.1 ± 14.2 r = 0.4

P 0.002 12.9 ± 7.7 19.1 ± 13.7 r = 0.3

P 0.08

APACHE II score 16.2 ± 6 22.4 ± 8.1 r = 0.5

P 0.004* 17.6 ± 4.2 23.9 ± 3.2 r = 0.5

P 0.001*

SOFA score 5.5 ± 2 8. 5 ± 3 r = 0.3

P 0.051 7.1 ± 1.6 8.3 ± 1.7 r = 0. 3

P 0.052

Short term final outcome

survivors

Non-survivors

15/15 [100%]

0/15 [0%]

15/25 [60%]

10/25 [40%]

r = 0.4

P 0.03*

*P < 0.05 is considered si

gnificant.

Short Term Prognostic Utility of Tc-99m DMSA Renal Imaging in Sepsis

Induced Acute Renal Failure; Provisional Data

546

PPV and NPV for DMSA imaging were 66.7% and 100%

respectively.

5. Discussion

This study was carried out on 40 SARF patients and

showed a mortality rate of 25% along the ICU admission

period. Abnormal Tc-99m DMSA revealed a significant

positive asso ciation with STO [r = 0.4; P 0.03]. Although

different modalities for this clinically relevant task has

been proposed, to our knowledge no previous studies

have reported using Tc-99m DMSA cortical imaging as a

prognostic tool; hence, this prospective study was ad-

dressed.

Our patients were recruited from ICU unit, as in Egypt

ARF is usually treated in ICU and attributed mostly to

sepsis. The latter was reported as the commonest cau-

sative factor of ARF (up to 50%) [2,10,11]. In fact, ARF

is nowadays mostly observed as part of the multi-organ

dysfunction syndrome in severe sepsis and septic shock

[12]. 10/40 [25%] of our patients died in the ICU ad-

mission period and this agrees with Prescott et al. study

as many of his deaths [20% - 30%] were very early

where ARF was sepsis-induced. They concluded that the

presence of sepsis increased the risk of death; both as an

etiological factor and poor indicator of prognosis in a

startling manner [2].

Also, we have chosen the German Prevalence Study

[GPS] [13] for comparison with our elicited data as they

studied a cohort of ARF patients with and without sepsis

and compared both groups regarding patients’ various

factors and reported significant differences between

serum creatinine at admission, APACHE II and SOFA

scores. They reported a higher mortality rate [64.4% vs.

25%]. This disagreement could be explained by our small

patients’ number and the relatively younger age of our

cases that carries in general an expected better outcome.

Also, pulmonary infection was the most frequent source

for sepsis as in our study [59% vs. 40%]. In our study

significant statistical associations were found between

DMSA and STO, serum creatinine at admission, APACHE

II and need for mechanical ventilation in concordance

with the same significant parameters of GPS.

We tried to find an explanation for our findings; as

DMSA is avidly taken up by cells of the proximal tubule

and with sepsis damage of the proximal tubules might

occur and [3], so the higher the damage the lower is

DMSA uptake and the worst is outcome. Hence in Gr2

pattern extensive damage of the proximal tubules was

found in non-survivors.

Finally, since kidney injury in SARF plays an im-

portant role in prognosis; this preliminary data could

raise Tc-99m DMSA cortical imaging as a tool to predict

STO in such patients with 100% and 66.7% NPV and

PPV respectively. As said by Niccolo Machiavelli [The

Prince, 1513], “It ought to be remembered that there is

nothing more difficult to take in hand, more perilous to

conduct or more uncertain in its success than to take the

lead in the introduction of a new order of things” hence,

we tried to introduce DMSA renal imaging as a pro-

mising prognostic radiopharmaceutical with subsequent

interference to ban serious sequences as mortality. How-

ever, we recommend further larger studies to support

these provisional data.

6. Conclusion

Tc-99m DMSA cortical imaging could be raised as a

diagnostic tool to predict short term outcome in such

sepsis induced acute renal failure patients with 100%

NPV and 66.7% PPV respectively that could allow in-

fluential interference to prohibit dramatic outcomes as

mortality.

7. Acknowledgements

The authors thank Dr. Zeinab Nawito for contributions in

the finalization of this work regarding grammatical

aspects.

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