Hypercalcemia after transplant nephrectomy in a hemodialysis patient: a case report
© Quack et al; licensee BioMed Central Ltd. 2007
Received: 02 August 2007
Accepted: 03 December 2007
Published: 03 December 2007
Hypercalcemia is a complication often seen in chronic hemodialysis patients. A rare cause of this condition is sarcoidosis. Its highly variable clinical presentation is challenging. Especially in patients suffering chronic kidney graft failure the nonspecific constitutional symptoms of sarcoidosis like fever, weight loss, arthralgia and fatigue may be easily misleading.
A 51 year old male developed hypercalcemia, arthralgia and B-symptoms after explantation of his kidney graft because of suspected acute rejection. The removed kidney showed vasculopathy and tubulointerstitial nephritis, which had not been overt in the biopsy taken half a year earlier. Despite explantation and withdrawal of the immunosuppression the patient's general condition deteriorated progressively. A rapid rise in serum calcium finally provoked us to check for sarcoidosis. CT scans of the lungs, broncho-alveolar-lavage and further lab tests confirmed the diagnosis.
This case demonstrates that withdrawal of immunosuppressive drugs sometimes unmasks sarcoidosis. It should be considered as differential diagnosis even in hemodialysis patients, in whom other reasons for hypercalcemia are much more common.
Hypercalcemia is a complication often seen in chronic hemodialysis patients. In these patients various circumstances can cause a high serum calcium level. Most of them can be detected easily like a tertiary hyperparathyreoidism, the use of 1α-hydroxylated vitamin D metabolites, the inappropriate medication with calcium phosphate binders or the use of a high dialysate calcium .
The challenge for the physician is to recognize the rare causes of hypercalcemia in hemodialysis patients such as non-hodgkin lymphoma, multiple myeloma or sarcoidosis as an example of granulomatous diseases.
Knowing that symptomatic sarcoidosis is usually treated with immunosuppressive drugs , it is easy to understand that the withdrawal of immunosuppression in transplanted patients no longer prevents the "de novo" development or the recurrence of sarcoidosis. Up to date literature counts only very few cases of sarcoidosis appearing shortly after withdrawal of immunosuppressive regimen, all of them recurrent forms of sarcoidosis [3–8]. In contrast to these reports, our case describes most likely a "de novo" sarcoidosis already appearing after reduction of the immunosuppressive regimen.
A transbronchial biopsy rendered only chronic-atrophic bronchitis. But broncho-alveolar lavage (BAL) revealed a CD4/CD8 ratio above the normal value. The diagnosis sarcoidosis was strengthened by further lab tests: Angiotensin-converting enzyme level: 158 U/l (normal value: 20–60 U/l). Soluble Interleukin2 receptor: 4133 U/ml (normal value: 220–710 U/ml) were elevated. We also found high levels for lysozyme, but no sign of a serum hypergammaglobulinaemia.
With the suspected diagnosis of sarcoidosis we decided to administer prednisone at a dose of 50 mg/day for 3 weeks. In the following time the dose was tapered 2.5 mg every week up to a permanent dose of 5 mg/day. In a short time the patient's general condition improved tremendously. Within a few days the body temperature returned to normal values and pain, anorexia and pruritus disappeared. Serum calcium values returned to normal levels (Fig. 1).
The suppressed PTH intact level found back to normal values within 8 weeks. Serum alkaline phosphatase and angiotensin converting enzyme returned to normal under steroid therapy: AP: 79 U/l, normal: 35–104 U/l, ACE: 54 U/L, normal: 20–60 U/l. In a CT scan in April 2006 the micronodulary alterations of both lungs were no longer seen. Number and size of the affected mediastinal lymphnodes were markedly reduced.
Bodyplethysmography still showed a restrictive alteration. We administered an inhalative salmeterol-fluticason combination. In April 2006 the pulmonary function was completely intact. No signs of restriction or obstruction were found in the tests.
For more than one year the patient is now without clinical and biological symptoms taking 5 mg alternating 2.5 mg prednisone per day.
Sarcoidosis is a multisystem disorder of unknown etiology characterized by the accumulation of lymphocytes, mononuclear phagocytes and non-caseating granuloma in involved tissues . Due to the frequency of pulmonary involvement bronchoscopy is an important diagnostic tool. Bronchoscopy enables the investigator to identify endobronchial lesions, which can be found in almost half of the cases . In our patient tissue biopsy did not show signs of sarcoidosis, but broncho-alveolar lavage rendered a lymphocytic alveolitis with a CD4/CD8-ratio (>3.5) which is highly consistent with sarcoidosis. The sensitivity of CD4/CD8-ratio ranges from 42 to 59% and specificity from 76–96% . Furthermore, it can be speculated if the tubulointerstitial nephritis was a sign of renal involvement and therefore responsible for graft failure. The true incidence of sarcoidosis kidney disease is hard to define. Notably granulomatous interstitial nephritis accounts only for 10–15% of renal involvement. Interstitial nephritis without granuloma has been described but seems much less common . In our case histology showed significant interstitial infiltration, moderate tubulitis and intimal arteriitis. Glomeruli had a normal morphology and no granulomata were found. Altogether, sarcoidosis cannot be ruled out, but sarcoid interstitial nephritis without granulomata is reported to be very rare, so that rejection seems to be more likely in our patient. However, the assumed epididymitis was probably a sarcoid lesion. In an autopsy series, 5% of cases had genital involvement (most frequently of the epididymis), with bilateral disease present in approximately one-third of them. It is often asymptomatic, but patients may also present with a scrotal mass or pain. Testicular granulomata are much less common . Finally it was only the synopsis of the clinical manifestations, the pathologic lab tests (hypercalcemia, ACE, IL-2-Receptor, lysozyme) and finally the response to treatment with steroids which allowed to confirm the diagnosis.
Cases reporting sarcoidosis after reduction of immunosuppression
Shen et al. Am J Med. 1986 Apr;80(4):699–702.
Reactivation of sarcoidosis in kidney graft
Brown et al. Nephrol Dial Transplant. 1992;7(2):173.
Reactivation after transplantation (steroid-free immunosuppressive regimen)
Herrero et al. Nephrol Dial Transplant. 1998 Dec;13(12):3280–1.
Reactivation in kidney graft after steroid withdrawal, Hypercalcemia
Schmidt et al. Transplantation. 1999 Nov 15;68(9):1420–3
Reactivation after steroid withdrawal (lung, pleura), Hypercalcemia
Kukura et al. Nephrol Dial Transplant (2004) 19: 1640–1642
Reactivation in graft after steroid withdrawal (during pregnancy)
Written informed consent has been obtained for publication.
The Authors are grateful to the patient for permitting the publication of the data regarding his case.
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