A 67-year-old male patient was
admitted to the hospital because of dizziness for 2 days. He
had been a vegetarian and had diabetes mellitus for 13 years.
He took nateglinide daily and his average fasting plasma
glucose was around 120 mg/dL. He had been taking some Chinese
herbs to improve liver function for 3 years, despite normal
liver function profiles previously. He had been otherwise well
until half a year earlier prior to this entry when he began to
experience flatulence sensation and poor appetite. There was
no weight loss over the 6 months. Two days before this
admission, a sudden onset of dizziness developed. The
dizziness sensation worsened when he changed position from
supine to upright position. The symptom was persistent and
could not be relieved by lying down or taking a rest. One day
later, he presented to the Emergent Department of this
hospital where macrocytic anemia (Hb 8.6 g/dL; mean
corpuscular volume [MCV] 106fL) was found. He was ill-looking
and leaned on the pillow in the bed. The conjunctivae was pale
and leg was mildly edematous. He showed dyspnea with uremic
odor. The blood pressure measured at the Emergent Department
was 106/56 mmHg which was lower than what he usually recorded.
Under the initially diagnosis of macrocytic anemia deficiency
which may resulted to long time vegetarian, he was admitted
for further management.
The patient did not have tarry or
bloody stools, bowel habit change or small-caliber stools over
the 6 months. He smoked every day and had a little social
drinking. His family history is non-contributory.
At admission, the patient's
consciousness was clear and alert. The blood pressure was
130/70 mmHg after he received fluid infusion and blood
transfusion at ER. The blood pressure was 110/ 60 mmHg and the
heart rate was 85 beats per minute. His conjunctivae were
pale. The eye-ground examination showed no prominent of
diabetes retinopathy. His breath sound was clear and the heart
beats were regular without murmur. The abdomen was soft and
flat. There was no abdominal tenderness. His liver and spleen
was impalpable. His skin turgor was fair. There was no pitting
edema or skin rash. The muscle power and deep tendon reflex
were intact. The remainders of physical or neurological
examination were unremarkable.
< Laboratory data
>
1. Hemogram at hospital
admission
WBC /μl |
RBC M/μl |
Hb g/dl |
Hct % |
MCV fL |
MCHC g/dl |
PLT K/μl |
4610 |
2.51 |
7.6 |
26.6 |
106 |
32.3 |
189 |
Meta % |
Band % |
Seg % |
Eos % |
Baso % |
Mono % |
Lym % |
0 |
0 |
68.6 |
2.2 |
0.2 |
4.1 |
24.9 |
2. Biochemistries and electrolytes at hospital
admission
BUN mg/dl |
Cre mg/dl |
Uric acid mg/dl |
Na mmole/L |
K mmole/L |
Ca mmole/L |
P mg/dl |
24.1 |
2.4 |
4.7 |
137 |
4.6 |
2.09 |
2.5 |
T-Bil mg/dl |
D-Bil mg/dl |
Alb g/dl |
ALT U/L |
LDH U/L |
Glucose mg/dL |
|
0.33 |
3.09 |
4.1 |
17 |
369 |
98 |
|
Variables |
Folic acid ng/ml |
Vit B12 pg/ml |
Fe μg/dl |
TIBC μg/dl |
Ferritin ng/ml |
Result |
4.92 |
295 |
76 |
334 |
513 |
Normal Value |
3.1~12.4 |
239~931 |
75~178 |
275~332 |
17.9~464 |
Variables |
Stool OB |
Ret.
% |
Ret. index |
HbA1c % |
|
Result |
(-) |
2.07 |
0.61 |
5.6 |
|
Variables |
U/O |
Ccr ml/min
|
Protein loss g/day |
FEuric acid % |
FENa % |
Tubular reabsorption of phosphorus % |
Result |
2400ml |
40 |
2.2 |
23.72 |
2.86 |
56.4 |
Normal value |
|
|
<150 mg/day
|
5.5~11.1% |
<1% |
83~93% | Calculate fractional
excretion (FE) of Substance S; FES=
urine S * serum creatinine / urine
creatinine * serum S
3. Urine Urinalysis at hospital admission
Variables |
Sp Gr. |
PH |
Protein mg/dl |
Glucose g/dl |
Ketone |
OB |
Urobil EU/dl |
Result |
1.015 |
6.5 |
100 |
0.1 |
- |
2+ |
0.1 |
Variables |
Bil |
RBC /HPF |
WBC /HPF |
Epi /HPF |
Cast /LPF |
Crystal |
Bacteria |
Result |
- |
- |
0-2 |
- |
Gr(5-10) |
- |
- |
4. Coagulation profiles at hospital admission
BT (surgicut) min |
PT sec |
PT INR |
PTT sec |
6 mins |
12.7 |
1.14 |
26.8 |
5. Urine electrophoresis
Variables |
Albumin % |
Alpha-1 % |
Alpha-2 % |
Beta % |
Gama % |
Result |
16.4 |
15.5 |
35.3 |
27.6 |
5.2 |
< Course
and treatment >
After admission, he
received folic acid and cobolamin supplement. The serum level
of folic acid and Vitamin B12 were within lower limits. The
reticulocyte production index and liver function were also
within the normal ranges. Urine electrophoresis showed a high
proportion of low molecular weight protein. The high FEuric
acid, high FENa, and low tubular reabsorption of phosphorus
were compatible with Fanconi's syndrome. The serum creatinine
was mildly elevated; however, the anemia was severe. His past
medical history was notable for taking Chinese herb. Taken
together, all the clinical manifestations and laboratory data
raised the suspicion of Chinese herbs nephropathy (CHN).
Finally, he underwent renal biopsy. The renal specimen
revealed marked tubular atrophy with significant interstitial
fibrosis. The glomeruli were relatively spared. The pathology
showed the classical findings of Chinese herb
nephropathy.
< Discussion
>
A new renal disease called 'Chinese-herb nephropathy' (CHN)
has been reported to occur in women who have ingested slimming
pills containing powdered extracts of the Chinese herb
Stephania tetrandra (漢防己). Moderate to end-stage renal disease
developed, requiring renal replacement therapy by dialysis or
transplantation. Phytochemical analyses of the pills revealed
the presence of aristolochic acids (AA) (馬兜鈴酸) instead of
tetrandrine, suggesting the substitution of ST (漢防己) by
Aristolochia fangchi containing nephrotoxic and carcinogenic
AA. A typical histological feature of CHN is a progressive
interstitial fibrosis leading to a severe atrophy of the
proximal tubules, as documented by the urinary excretion rates
of markers of tubular integrity (reduction of neutral
endopeptidase enzymuria and high levels of microproteinurias).
Removal of the native kidneys and ureters in patients with
end-stage CHN revealed a high prevalence of urothelial
carcinoma (46%). Tissue samples contained AA-related DNA
adducts, which are not only specific markers of prior exposure
to AA but are also directly involved in tumorigenesis.
Exposure to Aristolochia species (馬兜鈴科) is associated with the
development of renal interstitial fibrosis and urothelial
cancer in humans. Health professionals should be aware that in
traditional Chinese medicine, Aristolochia spp. are considered
interchangeable with certain other herbal ingredients and are
also sometimes mistaken for ST (漢防己), Akebia (木通莖精華), Asarum
(細辛), Clematis spp. (鐵線蓮屬) and Cocculus spp. (木防己屬) in herbal
remedies.
< References
>
- Nortier JL, Vanherweghem JL. Renal
interstitial fibrosis and urothelial carcinoma associated
with the use of a Chinese herb (Aristolochia fangchi).
Toxicology 2002;181-182:577-80.
- Guh JY, Chen HC, Tsai JF, Chuang
LY. Herbal therapy is associated with the risk of CKD in
adults not using analgesics in Taiwan. Am J Kidney Dis
2007;49:626-33.
- Hong YT, Fu LS, Chung LH, Hung SC, Huang YT, Chi CS.
Fanconi's syndrome, interstitial fibrosis and renal failure
by aristolochic acid in Chinese herbs. Pediatr Nephrol
2006;21:577-9.
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