Download Anorexia nervosa: an important cause of chronic tubulointerstitial

Nephrol Dial Transplant (1999) 14: 957–959
Nephrology
Dialysis
Transplantation
Case Report
Anorexia nervosa: an important cause of chronic tubulointerstitial
nephropathy
Yoshihide Arimura, Hiroshi Tanaka, Tetsuhiko Yoshida, Michiya Shinozaki, Taihei Yanagida,
Takashi Ando, Hideki Hirakata and Masatoshi Fujishima
The Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan
Key words: anorexia nervosa; chronic renal failure;
eating disorder; hypokalaemia; interstitial nephritis;
osteoporosis; renal cysts
Introduction
Brotman et al. [1] reported that in as many as 70% of
patients, anorexia nervosa is associated with various
renal manifestations, which include decreased glomerular filtration rate, decreased concentrating ability,
high blood urea nitrogen, electrolyte abnormalities,
urolithiasis, and pitting oedema. A rise in blood urea
nitrogen is often disproportionate to that of serum
creatinine because of fluid depletion with adequate
dietary protein intake.
More than 60 cases with chronic hypokalaemia and
clinical nephropathy have undergone renal biopsy
[2,3]. The kidney showed chronic tubulointerstitial
nephritis, glomerulosclerosis, and juxtaglomerular
apparatus hyperplasia [2–6 ]. Most of these reports
have included hypokalaemia of various aetiologies,
such as diuretic or laxative abuse. The renal changes
in anorexia nervosa have been reported in less than 20
cases [3,4]. In this report, a case with anorexia nervosa,
osteoporosis, and chronic interstitial nephritis is
presented.
Case
A 33-year-old female was admitted to our hospital for
evaluation of hypokalaemia and renal failure. Her
family reported that she had had a history of binge
eating and vomiting as well as alcohol drinking since
the age of 26 years. At age 29 she noted amenorrhoea.
She experienced urolithiasis at age 30 years, then a
fracture of the right femoral neck at age 31. At age 32
she was found at a regular health checkup to have
Correspondence and offprint requests to: Hideki Hirakata MD, The
Second Department of Internal Medicine, Faculty of Medicine, Kyushu
University, Maidashi 3–1-1, Hidashi-ku, Fukuoka, 812–8582, Japan.
proteinuria. At age 33 she visited a physician for a
gouty attack involving the right first toe. On this
occasion renal impairment with a serum creatinine
3.1 mg/dl, hyperuricaemia (17.6 mg/dl ) and hypokalaemia (2.0 mmol/l ) were noted. She was referred to our
hospital. The patient denied taking any medications or
health products.
On admission the patient had a height of 163 cm
and a weight of 35 kg (body mass index 13.1 kg/m2).
Skin turgor was decreased. Blood pressure was
106/60 mmHg without postural changes. Twelve of the
teeth had been treated for dental caries. Other physical
examinations including neurology were unremarkable.
Urinalysis was positive for blood and protein. The
24-h urinary protein excretion was 0.1–0.3 g.
Haematocrit was 30%. Serum total protein was
8.5 g/dl, blood urea nitrogen 34 mg/dl, creatinine
2.6 mg/dl, uric acid 11.2 mg/dl, sodium 136 mmol/l,
potassium 2.3 mmol/l, chloride 80 mmol/l, calcium
9.9 mg/dl and phosphate 4.1 mg/dl. Arterial blood
showed pH 7.531, pO 77.9 mmHg, pCO 57.4 mmHg,
2
2
and HCO− 48 mmol/l. Endocrinological examination
3
demonstrated intact parathyroid hormone 340 pg/ml
(15–50), 1,25-dihydroxy vitamin D 13.6 pg/ml
(20–60), plasma renin activity 16 ng/ml/h (2.5–21.4),
plasma aldosterone 170 pg/ml (30–159), and angiotensin II 48 pg/ml (10–30). Creatinine clearance was
19 ml/min and urinary chloride was less than
15 mmol/l. Repeated urinary test for furosemide was
negative.
Ultrasonography showed a small cyst in the left
kidney.
The patient was considered to have anorexia nervosa, hypovolaemia, and chloride-sensitive metabolic
alkalosis. After administration of normal saline and
acetazolamide, blood urea nitrogen, serum creatinine,
and bicarbonate improved to 19 mg/dl, 1.4 mg/dl, and
24 mmol/l respectively. Percutaneous renal biopsy was
performed on the 16th hospital day ( Figure 1). Three
of 15 glomeruli were sclerotic, while eight showed
wrinkling of the capillary wall. There were extensive
tubular atrophy and interstitial mononuclear cell infiltration. The juxtaglomerular apparatus was hyper-
© 1999 European Renal Association–European Dialysis and Transplant Association
958
Fig. 1. ( Upper) Light microscopy of the kidney biopsy specimen.
Note diffuse mononuclear cell infiltration and glomerular wrinkling.
PAS stain×180. (Lower) Hypertrophy of the juxtaglomerular apparatus. PAS stain×270.
plastic. Immunofluorescence was negative for immunoglobulins, complements, or fibrin. Histologically the
patient was diagnosed to have chronic tubulointerstitial
nephritis. She was transferred to the Department of
Psychosomatic Medicine for further treatment.
Discussion
Prolonged hypokalaemia is known to cause chronic
tubulointerstitial nephritis. In 1956 Relman and
Schwartz [7] summarized 13 hypokalaemic cases with
renal abnormalities including tubular vacuolation, and
suggested that hypokalaemic nephropathy is a distinct
entity. Bock et al. [2,5] reported 23 cases of hypokalaemic nephropathy, which included nine of anorexia
nervosa. In their report, renal histological findings in
nine of 23 patients with hypokalaemia of various
causes showed hydropic degeneration, atrophy,
destruction and regeneration of the tubular cells,
damage of the brush border and the basal labyrinth,
thickening of the tubular basement membrane, interstitial lymphocytic infiltration, interstitial fibrosis,
Y. Arimura et al.
glomerular and vascular changes, and juxtaglomerular
apparatus hyperplasia.
Riemenschneider and Bohle [3], who evaluated 40
patients with hypokalaemic nephropathy including 12
cases of anorexia nervosa, confirmed the equivalent
histological findings and found that impairment in
renal function was more pronounced when advanced
interstitial fibrosis was seen. The role of angiotensin II
in the genesis of such interstitial fibrosis remains to be
clarified [8]. Mechanism of hypokalaemic nephropathy
is speculated to be an ammonia-mediated activation
of the alternative complement pathway [9]. Although
it is reasonable to assume that those renal morphological changes are due to hypokalaemia per se, it is not
clear whether anorexia nervosa itself has different
histological characteristics from hypokalaemic nephropathies of other causes.
The number of cases with anorexia nervosa who
underwent renal histological evaluation is limited.
Apart from the above two reports [2,3], only one case
was reported which showed chronic tubulointerstitial
changes and non-specific glomerulosclerosis [4]. Many
patients have been reported to have hyperplasia of the
juxtaglomerular apparatus, which is seen most often
in Bartter’s syndrome but also can be observed in
patients with other hyperreninaemic status [10].
Although it was not evident in the present case, diuretic
and/or laxative abuse often coexist in patients with
eating disorders [3]. Also, abuse of other undocumented drugs or health products has to be considered.
Whether anorexia nervosa can cause a distinct variant of chronic tubulointerstitial nephritis remains to
be clarified. Clinically, such patients are characterized
by low body mass index, dental caries and hypokalaemia. Some other features may support the diagnosis
of anorexia nervosa: i.e. osteoporosis, urolithiasis, and
renal cysts. Biller et al. [11] indicated that severe spinal
osteopenia was present in 50% of patients with anorexia nervosa. Bachrach et al. [10] reported that significant osteoporosis was noted within 2 years of the
onset of anorexia nervosa. Urolithiasis is common in
patients with anorexia nervosa because of high dietary
oxalate intake and chronic dehydration [1,6 ]. Renal
cysts are occasionally seen in cases with prolonged
hypokalaemia. Torres et al. [12] reported that 44% of
patients with chronic hypokalaemia had renal cysts,
which were usually medullary, multiple, and bilateral.
In patients with anorexia nervosa who progressed to
end-stage renal disease, multiple renal cysts were
observed in three of four cases [4].
Bock et al. [2] reported that progressive decline in
glomerular filtration rate was associated with duration
of hypokalaemia. In a prospective study, Herzog et al.
[13] showed that elevated serum creatinine indicated a
chronic, prolonged course, i.e. resistance to various
therapeutic attempts, as Abdel-Rahman and Moorthy
[4] reported four cases that had reached end-stage
renal disease.
Halmi et al. [14] found that 19% of female college
students had experienced all of the major symptoms
of bulimia. In view of this potentially high incidence,
Anorexia nervosa and chronic tubulointerstitial nephropathy
anorexia nervosa should always be considered in the
differential diagnosis of chronic tubulointerstitial
nephropathy, especially when it is accompanied by
osteoporosis, urolithiasis, and/or multiple renal cysts.
959
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9.
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Received for publication: 15.10.98
Accepted in revised form: 25.11.98