Multiple myeloma-associated microscopic nephrocalcinosis without cast nephropathy
Shih-Che Hua1, Chih-Yen Hsiao1, Peir-Haur Hung1,2
1Department of Internal Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan; 2Department of Nursing, Chia-Yi School, Chang Gung Institute of Technology, Chiayi, Taiwan-
Running title: Multiple myeloma’s microscopic nephrocalcinosis without cast nephropathy
Correspondence to: Dr. Shih-Che Hua
Department of Internal Medicine,
Chia-Yi Christian Hospital, Chiayi, Taiwan
No. 539, Jhongsiao Road, Chiayi City 600, Taiwan
Tel: 886-5-2765041 ext. 7635
E-mail:
Abstract
Significant renal dysfunction frequently develops in patients with multiple myeloma (MM) and is the second leading cause of death in addition to infection. Cast nephropathy is the most common cause of renal failure in MM patients. We present a 39-year-old man with MM who had hypercalcemia-related acute kidney injury (AKI). The renal pathology revealed nephrocalcinosis without myeloma casts nephropathy. The hypercalcemia was controlled and the renal dysfunction was reversed after medical treatment. This is the first biopsy-proven case report of MM-associated microscopic nephrocalcinosis without myeloma casts in MM-related AKI patients.
Key words: acute kidney injury, hypercalcemia, multiple myeloma, nephrocalcinosis, Bence-Jones protein
Introduction
Multiple myeloma (MM), a neoplastic monoclonal disorder of plasma cells [1], could lead to several renal pathologic manifestations. The most frequent and typical manifestation is cast nephropathy[2] . The manifestation of microscopic nephrocalcinosis without co-existing myeloma casts has never been reported. We presented here a patient with MM who initially presented in acute kidney injury (AKI). The renal pathology revealed microscopic nephrocalcinosis without myeloma casts. Possible mechanisms will also be discussed.
Case report
A 39-year-old man had been in good health until 2 weeks prior to admission for the complaint of progressive polydipsia, polyuria, nocturia, general malaise, and anorexia. There was no history of of vitamin D ingestion, excessive use of milk, or absorbable alkali. His renal function was within normal limits three months prior to admission. On admission, the patient was drowsy with disturbed mentation. The temperature was 37°C, pulse rate 120/min, respiratory rate 22/min, and the blood pressure was 190/85 mmHg. The skin turgor was dry. A urinalysis showed trace proteinuria; the sediment revealed 2-5 red cells, and without casts identified under microscopic high power field. The hemoglobin was 12.8 g/dL and the white cell count was 8850 x 109/L, with 3% band forms and 78% neutrophils. The biochemical profile were: blood urea nitrogen, 19.99 mmol/L; creatinine, 388.96 µmol/L; albumin, 35 g/L; and calcium, 3.83 mmol/L; arterial pH and HCO3, 25 mmol/L. Renal sonography showed bilateral enlarged kidneys (right, 12.7 cm; left, 11.3 cm) without obstructive signs of urinary tract. The serum immunoelectrophoresis showed a dense band of IgG-λ monoclonal globulin. The urine immunoelectrophoresis showed a dense band of Bence-Jones protein. The 24-hour urinaryλchain was 2.23 gm. A bone marrow biopsy showed hypercellularity with 50% neoplastic plasma cells. All neoplastic plasma cells were positive forλchain. The renal histology showed several calcium crystals deposition in the tubular lumen, epithelium, and occasionally in the peritubular tissues, with acute tubular necrosis (ATN). Regenerative tubules in the resolving phase were also prominent, but without myeloma casts identified (Figure 1). An immunofluorescent study demonstrated no granular deposition for IgA , IgG, IgM, C3, C1q, or properdin. A diagnosis of MM stage IIIB and AKI due to microscopic nephrocalcinosis was made. X-ray films of the skull revealed multiple punched-out lesions (Figure 2). Under the impression of hypercalcemia and AKI, 0.9% saline (3000 ml daily) was administered in addition to calcitonin and bisphosphonates. The azotemia and hypercalcemia improved gradually after chemotherapy with vincristine, adriamycin, and dexamethasone. He was discharged after 24 days of hospitalization with a blood urea nitrogen of 9.42 mmol/L, a creatinine of 88.4 µmol/L , and a serum calcium level of 1.73 mmol/L.
Discussion
Renal involvement is common in MM[3] . The most common pattern of renal parenchymal disease associated with MM is myeloma cast nephropathy. Less frequent renal lesions include amyloidosis, monoclonal immunoglobulin deposition disease, light-chain Fanconi syndrome, and cryoglobulinemic glomerulonephritis[4,5] . Other potential renal complications in this patient population include nephrocalcinosis, urate nephropathy, and pyelonephritis[6,7] . As microscopic nephrocalcinosis has rarely been postulated, nephrocalcinosis without co-existing myeloma casts has never been reported yet[4] .
Nephrocalcinosis reflects an increment in the calcium content of the kidneys[8] . Nephrocalcinosis takes three forms: an increased intracellular calcium concentration; crystalline calcium precipitate forming microscopic nephrocalcinosis, and macroscopic nephrocalcinosis visible with naked eye or imaging techniques[8] . Primary hyperparathyroidism (41.7%), hyperchloremic acidosis (18.8%), and chronic pyelonephritis (15.4%) are three major causes leading to nephrocalcinosis[8] . Other risk factors responsible for calcium deposition in renal tissue include elevation of the calcium times phosphate content in the blood, and urine alkalization[8] . In this patient, hyperparathyroidism, vitamin D intoxication, and milk-alkali syndrome were excluded by a negative history and laboratory parameters. The improvement in renal function following saline hydration supported the diagnosis of dehydration-related ATN, and the renal parameters continued to improve following chemotherapy. One possible mechanism explaining the lack of cast formation in the kidney of our patient may have been due to the low urinaryλchain excretion (2.23 g /day).
In summary, we described an unique patient with IgG-λMM who presented with hypercalcemia and AKI. The renal biopsy revealed two related, but distinct processes (hypercalcemia-associated microscopic nephrocalcinosis and ATN). Microscopic nephrocalcinosis should be considered in the differential diagnosis of hypercalcemia and AKI in patients with MM.
Fig. 1.
Fig. 2.
Legends for figures
Figure 1.
Pathologic findings. The renal tissue showed a moderate degree of calcium crystals in the tubular lumen, epithelium, and peritubular intersitium with tubular necrosis. There were no casts in the lumen. (Hematoxylin and eosin, original magnification 200)
Figure 2.
X-ray films of the skull showed multiple punched-out lesions.
References
1. Bataille R, Harousseau JR: Multiple myeloma. New Engl J Med 1997; 336:1657-64.
2. Montseny JJ, Kleinknecht D, Meyrier A, Vanhille P, Simon P, Pruna A, Eladari D:
Long-term outcome according to renal histological lesions in 118 patients with monoclonal gammopathies. Nephrol Dial Transplant 1998; 13:1438-45.
3. Bladé J, Fernández-Llama P, Bosch F, Montolíu J, Lens XM, Montoto S, Cases A, Darnell A, Rozman C, Montserrat E: Renal failure in multiple myeloma: presenting features and predictors of outcome in 94 patients from a single institution. Arch Intern Med 1998; 158:1889-93.
4. Korbet SM, Schwartz MM: Multiple myeloma. J Am Soc Nephro 2006; 17: 2533- 45
5. Déret S, Denoroy L, Lamarine M, Vidal R, Mougenot B, Frangione B, Stevens FJ, Ronco PM, Aucouturier P: Kappa light chain-associated Fanconi’s syndrome: Molecular analysis of monoclonal immunoglobulin light chains from patients with and without intracellular crystals. Protein Eng 1999; 12:363–9.
6. Henrich D, Hoffmann M, Uppenkamp M, Bergner R: Ibandronate for the treatment of hypercalcemia or nephrocalcinosis in patients with multiple myeloma and acute renal failure: Case reports. Acta Haematol 2006; 116:165-72.
7. Pillon L, Sweeting RS, Arora A, Notkin A, Ballard HS, Wieczorek RL, Leung N: Approach to acute renal failure in biopsy proven myeloma cast nephropathy: is there still a role for plasmapheresis? Kidney Int 2008; 74:956-61.
8. Wrong O: The patient with renal stone disease. 8.4: Nephrocalcinosis. In: Davison AM, ed. Oxford texbook of clinical nephrology. New York City, NY, USA: Oxford University Press, 2005:1257-79.
腎鈣質沉積症與多發性骨髓瘤腎病變相關，卻非骨髓瘤管型腎病
花士哲1，蕭志彥1，洪培豪1,2
1嘉義基督教醫院內科部
2長庚技術學院嘉義分部
中文摘要
嚴重腎功能異常發生於多發性骨髓瘤病人，為僅次於感染性疾病的第二大死因。骨髓瘤管型腎病是多發性骨髓瘤病人發生腎衰竭最常見之原因。吾人報告一位三十九歲的多發性骨髓瘤病人併發高血鈣引發之急性腎損傷。腎臟病理切片結果顯示有腎鈣質沉積症，但無發現骨髓瘤管型腎病。此病患之高血鈣控制後，腎功能隨之改善。本病案為多發性骨髓瘤併發急性腎損傷病人，首例腎臟病理切片證實與腎鈣質沉積症相關，卻無骨髓瘤管型腎病。
關鍵詞: 急性腎損傷、高血鈣、多發性骨髓瘤、腎鈣質沉積症、貝司瓊斯氏(Bence-Jones)蛋白
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