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Annals of Biomedical Engineering, Vol. 33, No. 5, May 2005 (© 2005) pp.

DOI: 10.1007/s10439-005-1438-2

Smelling Renal Dysfunction via Electronic Nose

Department of Medical Engineering, University of Applied Sciences Jena, Germany; 2 Jenasensoric e.V., Am Planetarium 5, Germany;
Department of Internal Medicine III, Division of Nephrology, Friedrich-Schiller-University of Jena, Germany; and 4 Department
of Dermatology and Allergology, Friedrich-Schiller-University of Jena, Germany

(Received 14 May 2004; accepted 19 November 2004)

Abstract—The human body odor plays an important role in social to be low, whereas urea concentration in the sweat fluid
communication in various situations, like the olfactory identifica- was found to be present at a much higher concentration
tion of partners and relatives as well as in parents–child interac-
than the serum level.2 Patients do not smell their uremic
tions. In patients with renal dysfunction the compound of sweat
and volatile gases is changed because of the limited ability for odor themselves because their ability to smell is severely
removing metabolic products from the blood. The regulation of impaired and related to the degree of renal impairment and
electrolyte composition and acid–base balance are also altered so the degree of accumulation of uremic toxins.4 Olfactory
that the body odor of these patients may be significantly influenced evaluation can provide diagnostic clues, guide the labora-
by these disorders. We show the ability of an electronic nose to
tory evaluation, and help in the choice of immediate and
detect changes in the human body odor in consequence of renal
dysfunction by reducing multivariate sensor signals with principal appropriate therapy.10
component analysis to its first and second principal odor compo- In recent years the progress in sensor systems (electronic
nent (POC). All healthy subjects could clearly be distinguished noses) performance opened the way to the possibility of fast
from patients with renal failure using quadratic discriminant anal- and simple analysis of odors in many fields, and, recently
ysis, whereas a correct classification of 95.2% (98.4% using 1st–
in medicine for analyzing volatiles secreted outside the
3rd POC) of patients between end stage renal failure and chronic
renal failure was found. This methodology of analyzing human human body to get information about the health status.9,13
body odor may also provide new approaches for investigating Our present study shows the application of an electronic
symptoms of renal failure and for diagnosing other diseases of nose system based on doped semiconductor metal oxide
internal or cutaneous origin. gas sensors for investigating human body odor in patients
with different stages of renal insufficiency and the relation
between body odor and medical standard parameters.
Keywords—Body odor, Electronic nose, Principal component
analysis, Discriminant analysis.
More than a hundred years ago “malodorous perspi- The body odor was examined in 42 patients with
ration” in humans with malfunctioning general condition end stage renal failure (dialysis patients—DP, mean age
was first reported.7 Also human kidney diseases which are 59 ± 15 years) who underwent regular hemodialysis three
accompanied by a significantly reduced glomerular filtra- times a week, 20 patients with chronic renal failure (CRF,
tion rate influence breath as well as body odor. Simenhoff stages 3–5 in accordance with the practice guidelines of
et al.11 also showed that uremic breath reflects the sys- the Kidney Disease Outcomes Quality Initiative—K/DOQI,
temic accumulation of potentially toxic volatile metabo- mean age 63 ± 15 years) and 11 healthy controls (CON,
lites. These metabolites change the composition of se- mean age 47 ± 14 years). Blood samples were collected
cretion products from exocrine glands and therefore the for determination of biochemical parameters immediately
compounds of volatile gases released by the skin, which before investigating the body odor. Table 1 shows the mean
characterizes the individual body odor. The concentration values and standard deviation of the biochemical param-
of creatinine and uric acid in the sweat fluid was shown eters. Measurements were performed between 7am and
10am in CRF and CON, in DP in the first 30 min of dialysis
Address correspondence to Prof. Dr. A. Voss, University of Applied
session. The sensor head (volume 5 ml) of the electronic
Sciences Jena, Carl-Zeiss-Promenade 2, 07745 Jena, Germany. Electronic- nose8 was placed on patients leg as shown in Fig. 1. Three
mail: sensor signals were recorded and corrected/calibrated to
C 2005 Biomedical Engineering Society
Smelling Renal Dysfunction via Electronic Nose 657

TABLE 1. Biochemical parameters.


Mean SD Mean SD Mean SD p

Creatinine (µmol/l) 887 258 403 123 80 15 ∗ † ‡

Potassium (mmol/l) 5.17 0.77 4.72 0.49 4.03 0.20 † ‡

Phosphorus (mmol/l) 2.06 0.49 1.59 0.37 1.18 0.20 ∗ † ‡

pH 7.40 0.04 7.31 0.06 7.30 0.05 ∗ †

Albumin (g/l) 59.5 6.0 35.7 4.9 41.4 4.9 ∗ † ‡

Haemoglobin (mmol/l) 6.79 0.82 7.01 0.90 8.97 0.97 † ‡

Haematocrit 0.32 0.04 0.35 0.04 0.43 0.05 † ‡

Serum iron (µmol/l) 12.1 3.6 12.9 3.1 23.8 8.8 † ‡

iPTH (ng/l) 251.3 238.0 225.9 136.7 26.1 12.7 † ‡

25-OHD (ng/ml) 16.7 8.1 24.7 13.0 29.6 14.0 †

1,25-(OH)2-D3 (pg/ml) 8.2 8.2 20.9 9.5 64.1 16.9 ∗ † ‡

Blood sugar (mmol/l) 5.80 2.09 8.15 3.30 5.72 2.02

Calcium∗ phosphate product (mmol/l2 ) 4.53 1.16 3.71 1.03 2.81 0.52 ∗ †

Creatinine clearance (ml/min∗ 1.73 m2 ) 0.33 0.18

Note. Mann–Whitney Test, significant parameters (p < 0.01) are indicated as follows: between DP and CRF (∗ ),
DP and CON († ), CRF and CON (‡ ).

compensate for the reading from ambient air before princi- 385◦ C to adapt the sensor’s sensitivity. The sensor layers
pal component analysis has been carried out. are sensitive to oxidizing and reducing volatile gases such
as methane, butane, alcohols, ketones, carbon monoxide,
Electronic Nose nitrogen oxide, ammonia and humidity, which cause the
sensor resistance to change.
The measuring system8 consists of an array of three The sensor resistance was measured in the range from
thick-film metal oxide based gas sensors with heater ele- 200◦ C to 385◦ C, which lasted approximately 2 min. Ten
ments. Each of the sensors has a slightly different sensitivity measuring cycles were recorded per patient to yield an
to various odorant molecular types. Molecular components overall measurement time of 20 min. For the assessment of
in the gas phase are allowed to pass by the sensors and the body odor only the last measuring cycle was used, since
the interactions between molecules and the sensors involve after 18–20 min the gas milieu in the sensor was the best
reactions with oxygen on the sensor surface, which lead representation of the substances released by the skin. Each
to a change of the free charge carrier concentrations in the measurement was accompanied by a calibration procedure
conducting metal oxide. Advantages of these sensors are in which a calibration factor cf from the ambient air was
high sensitivities and long duration. The integrated plat- determined. Therefore, the three corrected sensor signals
inum heater allows the sensor to operate from 200◦ C up to (CSS) were calculated from the sensor resistance (R1−3 )
and gain control resistance (Rk ) in the following:
R1 R3 R2 R1
CSS1 = − cf 1 , CSS2 = − cf 2 ,
Rk Rk Rk Rk
R3 R2
CSS3 = − cf 3
Rk Rk

Multivariate Analysis
To discriminate between complex body odors in the dif-
ferent groups the corrected sensor signals were analyzed
using Principal Component Analysis6 (PCA). This is an ef-
fective method to reduce our multidimensional data space
(3 sensors, each operating at 185 different temperatures)
to its main components and therefore improves the human
perception ability of the data.
PCA determines the linear combinations of the sensor
values such that the maximum variance between all
FIGURE 1. Measurement setup of the electronic nose system. data points can be obtained in mutually orthogonal
658 VOSS et al.

FIGURE 2. First and second principal odor components.

dimensions. This results in the largest variance between variance—but show a small overlapping area. Quadratic
sensor values from the first principal odor component discriminant analysis of the 1st and 2nd POC from the two
and produces decreasing magnitudes of variance from groups of renal patients reveals a correct classification of
the second to the third odor components and so on. To 95.2% (three patients are misclassified), whereas correct
associate these odor components with clinical parameters classification increases to 98.4% (only one patient is mis-
Pearson’s correlation coefficients were calculated. To classified) using 1st–3rd POC.
assess dissimilarities in the body odor we reduced the Table 2 shows all significant correlation coefficients
complete sensor signals to its first and second principal odor between biochemical parameters and 1st and 2nd POCs.
component. The left column of this table represents the correlations
Quadratic discriminant analysis3 was then applied as including all three groups and the right column the results
statistical analytical technique to test the ability of the elec- where only the two groups of renal patients are considered.
tronic nose for separating the odor of healthy subjects from The reason for this is to account for (1) the different odor
those of patients with renal dysfunction. The variables used compounds between healthy subjects and all renal patients,
for this purpose are the first and second principal odor which mainly caused the variance in the 1st POC, and (2)
components. the different odor compounds in CRF and DP that mainly
cause the variance in the 2nd POC.
RESULTS As can be seen from the left column in Table 2 (consider-
ing CRF, DP and CON) the 1st POC correlates significantly
The 1st and 2nd principal odor components (POC) for with 1,25-(OH)2-D3 (r = 0.58), serum iron (0.57), creati-
each subject are drawn in Fig. 2. They account for 91% of nine (r = −0.52) and other clinical parameters. This can
the variance in the data and 1st–3rd POC even for 97% vari- easily be attributed to the significant differences between
ance because of the expected high correlation between sen- renal patients and CON as shown in Table 1 and the already
sor values at different temperatures. The cluster of healthy mentioned variance in the 1st POC caused by the different
controls (oval) can be separated from all renal patients by odor compounds in renal patients and CON. Therefore,
quadratic discriminant analysis to 100%. It is obvious that the correlations with the 1st POC disappear (right part of
POCs also differ between CRF (square points) and DP Table 2) if only the two groups of renal patients are consid-
(triangle points)—the group with the highest intra-group ered for correlation analysis.
Smelling Renal Dysfunction via Electronic Nose 659

TABLE 2. Significant correlation coefficients (p < 0.01) between the first two principal odor
components and clinical parameters.

Correlations, including Correlations, only renal

all three groups patients considered

1st POC 2nd POC 1st POC 2nd POC

Creatinine (µmol/l) −0.52 −0.42 −0.52

Potassium (mmol/l) −0.48
Phosphorus (mmol/l) −0.43
pH −0.30 −0.51 −0.55
Albumin (g/l) −0.41 −0.65 −0.69
Haemoglobin (mmol/l) 0.35
Haematocrit 0.38 0.33
Serum iron (µmol/l) 0.57
iPTH (ng/l)
25-OHD (ng/ml)
1,25-(OH)2-D3 (pg/ml) 0.58 0.40
Blood sugar (mmol/l) 0.51
Calcium∗ phosphate product (mmol/l2 ) −0.38

Note. No entry means not significantly correlated.

The 2nd POC, whose variance is mainly caused by rather showed the applicability for investigating renal fail-
varying odor compounds of DP and CRF shows the high- ure patients’ odor with an electronic nose. This methodol-
est significant correlation with albumin (r = −0.69), pH ogy may also provide an approach for identifying symptoms
(r = −0.55) and creatinine (r = −0.52). Table 1 shows of chronic renal failure. Pruritus is one such symptom that is
that these parameters differ significantly between the two characterized by an intense itching sensation that produces
groups. the urge to rub or scratch the skin to obtain relief and cannot
be characterized in the laboratory so far.14 We speculate that
DISCUSSION the composition of perspiration should be changed in these
patients. If principal odor components measured with an
The present results show the ability of an electronic electronic nose could help in the classification of renal fail-
nose system to classify human body odor of patients with ure patients with and without pruritus, it should be possible
different stages of renal insufficiency (Fig. 3). All healthy to link this odor components with clinical correlates that
subjects could be discriminated from renal patients using may improve the understanding of the pathogenesis of this
the first two principal odor components and quadratic dis- symptom. Besides the identification of renal dysfunction it
criminant analysis. Furthermore, a correct classification of may be possible to apply our methodology to the diagnosis
95.2% (1st and 2nd POC) and 98.4% (1st–3rd POC) was of other diseases of internal or cutaneous origin.
achieved in discriminating different stages of chronic renal In our analysis we did not investigate the influence of the
failure, especially DP and CRF. measuring site, which was shown to affect the composition
Nevertheless, the aim of this study was not to find a new of sweat and therefore body odor.12 This, however, might
method for the identification of renal failure patients, we yield further improvements in the discrimination between
different stages of renal insufficiency. Concentrations of
electrolytes, glucose and urea in sweat were reported to
increase with age, whereas concentrations of lactate, total
protein and total lipids, however, were not age-dependent.1
Furthermore, Haze et al.5 reported an age-related change
of body odor. Even though in our investigation age differed
significantly between renal patients and healthy subjects,
the 1st and 2nd principal odor components were not cor-
related with age and therefore age differences did not con-
tribute to the high discrimination rate between the groups.
In conclusion, we showed that the application of an elec-
tronic nose system for analyzing human body odor allowed
the distinction between different stages of renal dysfunc-
FIGURE 3. Correct classification rate in each two groups com-
parison with quadratic discriminant analysis using the 1st and tion. Now it has to be investigated if this methodology may
2nd POC (or 1st–3rd POC, respectively). also be used to identify symptoms of chronic renal failure,
660 VOSS et al.

which could improve the understanding of its underlying tends to increase with aging. J. Invest. Dermatol. 116(4):520–
pathological processes. 524, 2001.
Jackson, J. E. A User’s Guide to Principal Components, pp.
1–25, Wiley, 1991.
ACKNOWLEDGEMENT Jaeger, G. Stoffwirkung in Lebewesen. Grundgesetzliches für
Lebenslehre und Lebenspraxis. Leipzig. Ernst Günther’s Verlag,
This work was partly supported by grants from the Fed- 1892.
Löber, G., and H. Ahlers. Patent DE 101 09 148 A 1. Anordnung
eral Ministry of Education, Science, Research and Tech- zur Detektion von Körperflüssigkeiten und—bestandteilen.
nology BMBF 0312704C. 9
Mantini, A., C. Di Natale, A. Magagnano, R. Paolesse, A.
Finazzi-Agro, and A. D’Amico. Biomedical application of
an electronic nose. Crit. Rev. Biomed. Eng. 28(3–4):481–485,
Senol, M., and P. Fireman. Body odor in dermatologic diagnosis.
1 Cutis 63(2):107–111, 1999.
al-Tamer, Y. Y., and E. A. Hadi. Age dependent reference in-
tervals of glucose, urea, protein, lactate and electrolytes in Simenhoff, M. L., J. F. Burke, J. J. Saukkonen, A. T. Ordinario,
thermally induced sweat. Eur. J. Clin. Chem. Clin. Biochem. and R. Doty. Biochemical profile or uremic breath. N. Engl. J.
32(2):71–77, 1994. Med. 297(3):132–135, 1977.
2 12
al-Tamer, Y. Y., E. A. Hadi, and I. I. al-Badrani. Sweat urea, uric Taylor, R. P., A. A. Polliack, and D. L. Bader. The analysis of
acid and creatinine concentrations in uraemic patients. Urol. metabolites in human sweat: analytical methods and potential
Res. 25(5):337–340, 1997. application to investigation of pressure ischaemia of soft tissues.
3 Ann. Clin. Biochem. 31(Pt 1):18–24, 1994.
Croux, C., and C. Dehon. Robust linear discriminant analysis
using S-estimators. Can. J. Statist. 29:473–492, 2001. Thaler, E. R., D. W. Kennedy, and C. W. Hanson. Medical appli-
4 cations of electronic nose technology: review of current status.
Griep, M. I., P. Van der Niepen, J. J. Sennesael, T. F. Mets, D.
L. Massart, and D. L. Verbeelen. Odor perception in chronic Am. J. Rhinol. 15(5):291–295, 2001.
renal disease. Nephrol. Dial Transplant. 12(10):2093–2098, Virga, G., S. Mastrosimone, G. Amici, G. Munaretto, F.
1997. Gastaldon, and A. Bonadonna. Symptoms in hemodialysis pa-
5 tients and their relationship with biochemical and demographic
Haze, S., Y. Gozu, S. Nakamura, Y. Kohno, K. Sawano, H. Ohta,
and K. Yamazaki. 2-Nonenal newly found in human body odor parameters. Int. J. Artif. Organs 21(12):788–793, 1998.