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© JAPI • june 2012 • VOL. 60

Case Report

Hypercalcemia with Renal Failure

Nisha Bhavani1, Valiyaparambil Pavithran Praveen1, Rohinivilasam Vasukutty Jayakumar2,
Vasantha Nair2, Mangath Muraleedharan2, Harish Kumar2, Ambika Gopalakrishnan Unnikrishnan2,
Vadayath Usha Menon2

Abstract
We report a case of nephrocalcinosis with renal failure which on evaluation was found to have hypercalcemia.
Further investigations showed an inappropriately normal intact parathormone (iPTH) and 1,25 dihydroxy
-vitamin D level in the setting of renal failure. Probing for a cause of non- PTH mediated hypercalcemia led to the
diagnosis of sarcoidosis. Treatment with glucocorticoids could partially reverse the renal failure and control the
hypercalcemia. This case illustrates the importance of careful interpretation of laboratory parameters especially
levels of iPTH and Vitamin D metabolites in renal failure.

Introduction serum creatinine was 7.4 mg/dl with an estimated GFR of 14.3 ml/
minute. His corrected calcium was 12.3 mg /dl and phosphorus
T here are several causes of hypercalcemia in patients with
chronic renal failure. We report a very rare case of a patient
presenting with renal failure and hypercalcemia which was
was 5.5 mg/dl. He had a iPTH of 30(15-68) pg/ml, 25 OH Vitamin
D of 24.77 (30-50) ng/ml, 1, 25 di hydroxy-vitamin D of 49 (18-72)
pg/ml and a 24 hour urine calcium of 423.4 mg. Serum ACE
eventually diagnosed to be due to sarcoidosis. This case levels were 164 U/L (9-67 ). Work up for multiple myeloma and
highlights the importance of considering alternate explanation tuberculosis were negative. Skeletal survey and whole body
for hypercalcemia other than hyperparathyroidism in patients skeletal scintigraphy showed no evidence of any metabolic bone
with nephrocalcinosis and renal failure. In addition, we also disease. Chest X ray revealed left upper lobe lung fibrosis (Figure
point out the clinical clues which alerted us to the diagnosis of 1). Pulmonary function tests showed a restrictive lung disease
sarcoidosis in this case. pattern and non contrast HRCT lungs and abdomen confirmed
the presence of fibrosis in left upper lobe of lungs, spleenomegaly
Case Report with coarse parenchymal echotexture and bilateral medullary
A 47 year old male was referred to our tertiary care endocrine nephrocalcinosis with small shrunken kidneys (Figure 2).
center for evaluation of hypercalcemia associated with renal In the presence of hypercalcemia and hyperphosphatemia
failure. He was apparently well till 5 years ago, when he with renal failure, and an inappropriately low PTH for the renal
presented elsewhere with generalized tiredness, anorexia failure, a non- PTH mediated cause for the hypercalcemia was
and history of passing stones in the urine. At that time he was thought of. The additional findings of spleenomegaly and left
diagnosed to have bilateral nephrocalcinosis and renal failure upper lobe fibrosis made sarcoidosis the most probable diagnosis.
with a serum creatinine of 9 mg/dl for which he underwent
lithotripsy following which he improved symptomatically and
the serum creatinine came down to 2 mg/dl. No reports of his
calcium profile at that time were available. Two years later he
had a recurrence of his symptoms and he underwent lithotripsy
once more. Now he presented to the referring physician with
progressive itching throughout the body and pain both legs with
intermittent passage of stones in the urine. He also had history
of class 2 exertional dyspnoea and occasional dry cough for the
last 2 years. Investigations done at this time revealed a serum
creatinine of 6 mg/dl, serum calcium of 12.5 (8.6-10.2) mg/dl,
phosphorous of 5.7 (2.5-4.5) mg/dl, and an iPTH of 28 (15-68)
pg/ml. A Technetium Setamibi scan and a CT scan of neck were
negative for parathyroid adenoma. He was referred here for
further management.
At the time of presentation to this center, physical examination
showed mild dehydration, generalised scratch marks and a 5
cm firm spleenomegaly. His hemogram was normal except for
a low platelet count of 120 KU/l and an ESR of 40 mm/hr. Urine
showed hematuria and a proteinuria of 250 mg/ 24 hours. His

Clinical Associate Professor, 2Clinical Professor, Department of

1

Endocrinology and Diabetes, Amrita Institute of Medical Sciences,

Cochin 682041, Kerala, India.
Received: 08.02.2011; Accepted: 03.06.2011
Fig. 1 : Chest X Ray Showing Left Upper Lobe Fibrosis
© JAPI • june 2012 • VOL. 60 53
Fig. 2 : Computed Tomography of the Abdomen Showing
Spleenomegaly and Nephrocalcinosis
Serum ACE levels were elevated and 1, 25 di hydroxy-vitamin
D was inappropriately normal for the degree of renal failure. A
bone marrow biopsy was done which revealed normocellular
marrow with trilineage maturation and focal non-caseating
granulomas which were AFB(Acid Fast Bacilli) and PAS (Periodic
Acid Shiff ) negative suggestive of sarcoidosis (Figure 3).
To summarise, this gentleman had non-PTH mediated
hypercalcemia with hyperphosphatemia with renal failure along
with spleenomegaly, medullary nephrocalcinosis, an elevated
ACE level and inappropriately normal 1, 25 dihydroxy-vitamin
D levels with non-caseating granuloma in the bone marrow. So
a diagnosis of sarcoidosis was made and a decision was taken
to see the therapeutic response to glucocorticoids. Further
confirmatory tests including a transbronchial lung biopsy and a
renal biopsy were planned if there was no response to steroids.
Patient was started on 0.5 mg /kg of oral prednisolone and
gradually tapered over the next 6 months to 5 mg prednisolone
daily. The serum calcium improved within a week of starting
steroids and the renal failure too improved which has ever since
remained stable at a serum creatinine of 4 mg/dl. Initially there
was slight worsening of the hypercalciuria which later settled.
At the time of last follow up, patient has a normal serum calcium
level and a stable renal function with relief of his itching.
Discussion
Sarcoidosis presenting as renal failure with nephrocalcinosis
and hypercalcemia is rare.1 The immediate differential diagnosis
of hypercalcemia with nephrocalcinosis and renal failure is
hyperparathyroidism either primary or tertiary. The PTH levels
usually are elevated due to secondary hyperparathyroidism in
renal failure. An inappropriately normal PTH in renal failure
should point towards a non PTH mediated cause for the
hypercalcemia which can be either PTHrP mediated or vitamin
D mediated. The cause for hypercalcemia in sarcoidosis is the
expression of 1 alpha hydroxylase by the macrophages in the
granulomas which convert 25 hydroxy-vitamin D into 1, 25 di-
Fig. 3 : Histopathology of Bone marrow showing Non Caseating
Granuloma
hydroxy-vitamin D which is the active metabolite which helps
in the absorption of calcium and phosphorous from the intestine
and also renal reabsorption of calcium and phosphorous.2 The
proximal tubules are the main site of production of 1, 25 di
hydroxy- Vitamin D normally and in renal failure their levels
will be very low. Our patient had an inappropriately normal 1, 25
di-OH-Vitamin D for the degree of renal failure which indicates
an extrarenal source of 1 alpha hydroxylase. The presence of
hypercalcemia associated with renal failure is a good prognostic
indicator in sarcoidosis; patients with hypercalcemia will improve
their renal failure more often with steroids than those without
hypercalcemia.3 Raised serum ACE levels are very nonspecific
and can be seen in a variety of conditions apart from sarcoidosis.
The causes of renal failure in sarcoidosis are interstitial nephritis,
nephrocalcinosis and sarcoid glomerulopathy.4 Our patient
definitely had nephrocalcinosis and in the absence of renal
biopsy, the presence of other components cannot be confirmed.
Spleenomegaly in sarcoidosis is also variable and has been
reported in 2-40 % of cases. The presence of spleenomegaly
portends more extrathoracic involvement and splenectomy is
indicated only in severe hypersplenism, prophylaxis of splenic
rupture and neoplastic exclusion. A single case report of
coexisting primary hyperparathyroidism with sarcoidosis who
presented with severe hypercalcemia and renal failure has been
published in Endocrine Journal in 2008.5
To conclude, this case highlights the importance of
considering the diagnosis of rare diseases like sarcoidosis induced
hypercalcemia in patients presenting with nephrocalcinosis and
renal failure, the treatment of which can potentially prevent
progression to end stage renal failure. The importance of
interpreting serum levels of iPTH and vitamin D metabolites in
renal failure is also highlighted.
Acknowledgements
We acknowledge the contributions of Dr. Anish Ahamed
and Dr. Ajish TP (Endocrine trainees) who helped to manage
the patient in the ward.
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References 3. Mahavas M, Lescure FX et al. Renal Sarcoidosis-clinical, laboratory

and histological presentation and outcome in 47 patients. Medicine
1. Berliner AR, Haas M etal Sarcoidosis – the nephrologist’s (Baltimore) : 2009;88:98-106.
perspective. Am J kidney Dis : 2006;48:856-70.
4. Monge M, Micquel o. Sarcoidosis and the kidney- not only
2. Falk S, Kratschz J et al. Hypercalcemia as a result of sarcoidosis granulomatous interstitial nephritis. Clin Nephrol: 2009;71:192-5.
with normal serum concentrations of vitamin D. Med Sci Monit :
5. Yoshida T, Iwasaki Y; etal; Coexisting primary hyperparathyroidism
2007;13:CS133-136.
and sracoidosis in a patient with severe hypercalcemia. Endocr J
Epub 2008;55:391-5.