Nephrogenic Diabetes Insipidus--Prodromal Phase of Multiple Myeloma
| Title: | Nephrogenic Diabetes Insipidus--Prodromal Phase of Multiple Myeloma |
|---|---|
| Authors: | Goranov, S.; Hristova, I.; Pencheva, K. |
| Publisher: | Folia Medica |
| Date Published: | 1994 |
| Reference Number: | 115 |
We report on a 65-year-old female patient with an A-kappa multiple myeloma diagnosed on the grounds of bone pain, anemia and extremely elevated erythrocyte sedimentation rate (ESR). Eight years prior to admission to the Clinic of Haematology the patient started to excrete a considerable amount of urine (4-6 liters per 24 hrs) with low specific gravity and to experience hardly controllable thirst. The disorder was specified in a specialised endocrinologic clinic as diabetes insipidus with ambiguous aetiology. The administered treatment with adiuretin had a small effect. A course of cyclophosphamide and glucocorticosteroids was started after myeloma was diagnosed--this had a considerable effect on the polyuria and polydipsia; the specific gravity of the urine increased. This effect, as well as the proven light chain proteinuria in the patient, leads to the interpretation of the early complaints of the patient as onset of the underlying disease in the form of nephrogenic diabetes insipidus--a rare light chain tubular syndrome.
INTRODUCTION
Light chain nephropathy in plasma cell dyscrasias is basically associated with various tubule dysfunctions. They are classified into well-differentiated proximal, distal and mixed tubule syndromes and are practically not found in the absence of Ben Jones (BJ) proteinuria1-4. The most common tubular syndromes are the occasional functional disorders such as tendency toward polyuria, impaired concentration capacity, calciuria and/or phosphaturia. The adult Fanconi syndrome is the most complex proximal tubular syndrome. It is characterised by polyuria, calciuria, phosphaturia, aminoaciduria, glucosuria, and proximal renal tubular acidosis. Although rare, it is known in clinical practice as an early onset of multiple myeloma (MM)5-8. The other tubular dysfunctions, such as distal tubular acidosis, nephrogenic vasopressin-resistant diabetes, and light chain osteomalacia are considered only as theoretical or casuistic possibility2,9,10.
We had the rare opportunity to diagnose and observe a distal tubular syndrome nephrogenic diabetes insipidus as an onset of multiple myeloma.
CASE REPORT
B. M. M., 65 years old (Reg. No 19009/728, 1983), was admitted to the Clinic of Haematology with an unclear anemic syndrome, extremely elevated ESR, diffuse ostealgia, and a history of subtrochanteric fracture of the left femoral bone. Simultaneously, she had cardiac complaints, dyspnea, fatigability, and extra-systoles due to combined rheumatic mitral valvular disease. In 1975, the patient started to excrete a substantial amount of urine (4-6 litres per 24 hrs) with low specific gravity and to suffer from excessive unquenchable thirst. The disorder was identified in a specialised endocrinologic clinic as diabetes insipidus with obscure aetiology. An osteoalgic syndrome developed in 1980 and the patient underwent treatment in sanatoria with a diagnosis of arthrosoarthritis. The polyuria and polydipsia continued unabated, little affected by the treatment with adiuiretin [sic].
The physical examination showed the patient to have anemic appearance of the sclera. The ausculatory [sic] finding in the lungs was a light hypostatic rales, in the heart - absolute arrythmia [sic] with a syndrome of combined mitral valvular disease. The liver was palpated 2 cm below the costal arch. The spleen and peripheral lymph nodes could not be palpated.
The laboratory investigation yielded the following results: ESR, 114/124; Hb, 105 g/i; erythrocytes, 3.06 x 1012/i; leucocytes [sic], 5.1 x 109/i; thrombocytes, 128 x 109/i. Total protein, 87 g/i; albumin, 36 g/i; gamma globulins, 38 g/i. Immuno-electrophoresis: M - gradient - IgA, 16 g/i. Urine immuno-diffusion: monoclonal kappa light chains. Sternal myelogram: ripe plasmocytic hyperplasia - in more than 20% of the cellular substance. Serum calcium, 2.28 mmol/i. Calciuria, 4.75 - 5.02 mmol/24 hrs. Serum phosphorus, 1,28mmol/i. Phosphaturia, 21.60 mmol/24 hrs. Blood sugar, 4.8 mmol/i; serum creatinine, 112 mm/i. Diuresis, from 3 to 4.5 i/24 hrs with low specific gravity (1003 - 1005). Slight proteinuria, 0.5 - 1.2 g/i, selective, tubular immunoelectrophoretic variant. No sugar was detected in the urine. Roentgenography of flat bones: multiple osteolitic lesions on the cranial bones, the pelvis, and the ribs. The diagnose [sic] made was multiple myeloma in III A clinical stage, IgA-kappa type. Myelomanephropathy. Vasopressin-resistant diabetes. Treatment with cytostatics was initiated. A progressive decrease of diuresis with increase of the specific gravity which reached 1012 - 1014 at diuresis of 1.8 - 2.2 i/24 hrs was registered as early as in the middle of the course with cyclophosphamid [sic]. The sharp drop of polydipsouria after treatment with cyclophosphamide and glucocorticosteroids at the proven light chain proteinuria was interpreted as a correction of the distal tubular syndrome in the form of vasopressin-resistant diabetes, a prodromal phase of the multiple myeloma diagnosed.
DISCUSSION
Pathogenetically, tubule dysfunctions are an expression of morphologic and functional impairment of the tubule epithelium in excessive BJ proteinuria3,4,11. The reason why some of the tubular syndromes, such as Fanconi syndrome, light chain osteomalacia, and nephrogenic diabetes insipidus, dominate the clinical picture before the major manifestations of myeloma is still unclear. It is likely that there is slow plasmocytic proliferation with a single manifestation - the metabolic tubular syndrome. It is noteworthy that in all similar onsets it is the kappa type of BJ proteinuria that is dominant2,5-8.
Poliuria [sic] to the degree of nephrogenic diabetes insipidus was described for the first time by McKenzie in the disease of Waldenstrom12. N. Smithline, et al discribed [sic] a patient with an IgG-kappa multiple myeloma showing evidence of renal diabetes, aminoaciduria, phosphaturia, uricosuria, distal tubular acidosis, that is, a combined tubular syndrome in the background of a considerable light chain proteinuria of 40 to 140 i per 24 hrs4.
We present herein a new case of nephrogenic diabetes insipidus diagnosed on the basis of preceding extensive polyuria with low specific gravity, polydipsia, confirmed BJ proteinuria of the kappa type, absence of satisfactory effect from treatment with adiuretin and very effective specific cytostatic treatment. In making the differential diagnosis we took into account the specific effect of hypercalcaemia: decrease of the osmotic gradient in the medulla with dicreased [sic] permeability of the tubular epithelium to water by inhibition of adenylcyclase. If there had been calcium abnormalities they would have progressed but such were absent at the time of making the diagnosis. Yet, calciuria cannot be excluded being at the upper limit of the normal, but it was hardly the cause of the polydipsouric syndrome eight years prior to the diagnosis of the main process.
The presented new case of nephrogenic diabetes insipidus enriches our ideas for the variety of the onset of multiple myeloma. Besides, this case also poses diagnostic problems as well: in all adult patients in whom late and sudden tubular dysfunctions are found a diagnosis of light chain nephropathy in plasmocellular dyscrasia should be sought.
REFERENCES
- De Fonzo RA, Cooke JR, Humphrey RL. Renal functoin [sic] in patients with multiple myeloma. Medicine 1978;57:151-166.
- Fang LST. Light chain nephropathy. Kidney Int 1985;27:582-592.
- Ganeval D, cathomen N, Noel LH, et al. Kidney involvement in multiple myeloma and related disorders. Contr Nephrol 1982;33:210-222.
- Smithline N, Kassirer JI, Cohen JJ. Light chain nephropathy. Renal tubular dysfunction associated with light chain proteinuria. N Engl J Med 1976;294:71-74.
- Finkel PN, Kroneberg K, Pesce JA, et al. Adult Fanconi syndrome, amyloidosis and marked kappa light chain proteinuria. Nephron 1973; 10:1-24.
- Kamm DE, Fischer MS. Proximal renal tubular acidosis and the Fanconi syndrome in a patient with hypergammaglobuliemia. Contr Nephrol 1972;9:208-210.
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- Rochmann J, Lichtig C, Osterweil D, et al. Adult Fanconi syndrome with renal tubular acidosis in association with amyloidosis. Arch Int Med 1980;140:1361-1363.
- Lasar GS, Feistein FJ. Distal renal tubular acidosis in multiple myeloma. Arch Int Med 1981;141:655-656.
- Rao DS, Parfitt WM, Villanueva AR, et al. Hypophospahtemic [sic] osteomalacia and adult Fanconi syndrome due to light chain nephropathy. Am J Med 1987;82:333-338.
- Clyne DN, Pollak VE. Ranal handling and pathophysiology of Bence Jones proteins. Contr Nephrol 1981;24:78-87.
- MacKenzie MR, Fudenberg HH. Macroglobulinemia. An analysis of 40 patients. Blood 1972;39:874-889.
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University of Medicine, Clinic of Haematology, 15A Vassil Aprilov St., 4000 Plovdiv, Plovdiv, Bulgaria (S. Goranov, I. Hristova, K. Pencheva)
Received 12 April 1993; Accepted for publication 30 June 1993 Address correspondence and reprint requests to S. Goranov, University of Medicine, Clinic of Haematology, 15A Vassil Aprilov St., 4000 Plovdiv, Bulgaria |
This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
On rare occasions, one of these disorders will precede the onset of myeloma, which is a disease giving rise to one or more tumors in bone marrow. Goranov, et al., report on a case where NDI preceded multiple myeloma (tumors found in more than one site in the bone marrow). The patient was a 65-year-old woman who, eight years previously, started to display the classic symptoms of NDI: excessive thirst and urination. She was treated with adiuretin, a synthesized antidiuretic hormone, to no avail. When the authors examined her, they found she still had excessive thirst and excessive dilute urine as well as an excess of serum proteins in her urine.
The authors, on the basis of the patient's excessive, dilute urine, chronic, extreme thirst, and excessive protein in her urine, diagnosed her for NDI. Her other symptoms led to the diagnosis of multiple myeloma. The authors treated her for multiple myeloma and began administering cytostatics (agents that suppress cell growth and multiplication) to her. These cytostatics (cyclophosphamide and glucocorticosteroids) progressively reduced the patient's excessive urination and made her urine more concentrated.
Science cannot at present explain why kidney tubule dysfunction sometimes precedes the onset of myeloma, but the authors recommend diagnosing for light chain kidney disease in all adult patients who manifest late and sudden tubular dysfunctions.