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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT  
Year : 2016  |  Volume : 27  |  Issue : 4  |  Page : 805-807
Fanconi syndrome due to light chain proximal tubulopathy in a patient with multiple myeloma


1 Department of Nephrology, Sawai Man Singh Hospital, Jaipur, India
2 Department of Nephrology, John Hunter Hospital, NSW, Australia
3 Department of Pathology, Manipal Hospital, Bengaluru, Karnataka, India
4 Department of Oncology, Apollo Hospital, Bengaluru, Karnataka, India

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Date of Web Publication5-Jul-2016
 

   Abstract 

Fanconi syndrome (FS) in an adult patient is an unusual finding and it merits thorough evaluation. Paraproteinemias are one of the common etiologies in adult FS and need to be ruled out. Among the various forms of renal involvement in multiple myeloma, light chain proximal tubulopathy (LCPT) is the rarest. Usually, it causes proximal tubular dysfunction which is characterized by intracytoplasmic deposition of crystallized, mostly kappa monoclonal light chains in proximal tubules; however, glomerular crystal deposition is unusual. Herein, we are presenting a patient with renal dysfunction and FS. On evaluation, she was found to have multiple myeloma and renal biopsy showed LCPT with extensive crystal deposition in the proximal tubular epithelium along with crystal deposition in the glomerular capillary endothelium. The treatment of the underlying multiple myeloma caused remission of the FS.

How to cite this article:
Mathur M, Chacko B, Vankalakunti M, Patil C. Fanconi syndrome due to light chain proximal tubulopathy in a patient with multiple myeloma. Saudi J Kidney Dis Transpl 2016;27:805-7

How to cite this URL:
Mathur M, Chacko B, Vankalakunti M, Patil C. Fanconi syndrome due to light chain proximal tubulopathy in a patient with multiple myeloma. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2020 Dec 3];27:805-7. Available from: https://www.sjkdt.org/text.asp?2016/27/4/805/185268

   Introduction Top


Fanconi syndrome (FS) in an adult patient along with renal dysfunction generally implies a serious underlying disorder. [1] Meticulous evaluation is necessary to ascertain the etiology of the FS since often, the only manifestation of the underlying disorder may be FS. Among various causes, paraproteinemias should be considered in adults as a cause of FS. [1] Renal involvement in multiple myeloma is very common; [2] however, light chain proximal tubulopathy (LCPT) causing FS is a rare manifestation. [3],[4],[5] Although FS due to LCPT in multiple myeloma has been a well-established entity, only few case series and case reports have been published. [6],[7],[8] LCPT has a distinct light microscopy and ultrastructural appearance and occurs due to intracytoplasmic deposition of monoclonal kappa light chains. [3],[5],[9] It is generally reversible upon adequate treatment of multiple myeloma. [4],[9],[10]


   Case Report Top


A 45-year-old woman was admitted with complaints of malaise, fatigue, and anorexia of six weeks duration. She was found to have elevated serum creatinine (2.6 mg/dL) and was referred for further evaluation. From her investigations, she was found to be anemic and her biochemical evaluation showed that she had glycosuria, 1.6 g/24 h of proteinuria along with low-normal phosphate and uric acid levels in serum. These features were suggestive of incomplete FS along with renal dysfunction. There was no history of any drug intake or exposure to heavy metals. Further workup was initiated and she underwent renal biopsy, which showed widespread changes of proximal tubulopathy and diffuse interstitial monoclonal plasma cell infiltrates. Proximal tubules and glomerular endothelium showed numerous intracytoplasmic variably shaped fuchsinophilic crystals [Figure 1]a. Immunofluorescence studies showed kappa restriction. Ultrastructural study of the proximal tubule confirmed intracytoplasmic crystalline material of variable shapes [Figure 1]b.
Figure 1:

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Suspecting an underlying paraproteinemia, serum protein electrophoresis (SPEP) with immune fixation was performed; these were noncontributory, with only mild elevation of kappa band. However, the suspicion of an underlying paraproteinemic disorder persisted due to the typical renal biopsy findings. To this end, bone marrow aspiration and biopsy were done. In the meantime, serum free light chain levels were obtained, which showed elevated kappa levels (39.5 mg/L; normal: 3.3-19.4 mg/L). The subsequent bone marrow report confirmed the diagnosis of multiple myeloma; there were 52% plasma cells (CD138 + ) with kappa restriction.

She was treated with four cycles of bortezomib/thalidomide/dexamethasone regimen, resulting in complete remission of multiple myeloma and with near normalization of her renal functions.


   Discussion Top


FS in an adult is usually associated with a serious underlying disorder and most often some form of paraproteinemia is detected. [1] Its association with multiple myeloma was established more than a half century ago. [6] FS in a patient with multiple myeloma occurs due to intracytoplasmic deposition of monoclonal light chains in proximal tubular epithelial cells. This entity is called as LCPT or light chain FS. [3],[4],[5] LCPT is a relatively rare form of renal disease and fewer than 100 cases have appeared in the medical literature, predominantly as isolated cases and small series. [6],[7],[8] Almost all cases of LCPT have been associated with kappa (κ) light chains, in particular, the Vκ1 subgroup.[5],[9],[11] The excess free light chains pass through the glomerular basement membranes and undergo endocytosis by the proximal tubular epithelial cells. Following endocytosis, the variable region of the light chain resists degradation and accumulates within the lysosome, where it undergoes spontaneous crystallization causing proximal tubular injury, resulting in FS. [3],[4],[9] Typical features include normoglycemic glycosuria, aminoaciduria, uricosuria, hyperphosphaturia (with hypophosphatemia), and type II renal tubular acidosis. [1] The crystal deposition is most often seen in the proximal tubules; glomerular involvement is unusual. However, in our case, there was extensive crystal deposition in both the tubules and the glomerular endothelium.

It is a relatively difficult diagnosis to make as most often; the FS is incomplete with only subtle biochemical abnormalities. Even the renal biopsy on light microscopy only shows nonspecific acute or chronic tubulointerstitial changes. [3],[4],[9] The visualization of the crystals in the tubules and the glomerular endothelium (as in our case) on light microscopy is an extremely rare phenomenon. [2],[4],[5] Most often, the diagnosis is established on electron microscopy, which shows the intralysosomal rhomboid crystals. [2],[4],[5] To add to this situation, most often the multiple myeloma in this set of patients is indolent with only subtle clinical and laboratory features. [2],[4],[9] In our case, an underlying paraproteinemic disorder was suspected but the SPEP was noncontributory, immune fixation studies showed only a mild spike in the kappa region.

This is because the amount of light chains (kappa or lambda) needed to produce a significant spike is usually more than 100-fold of normal, lower levels may not show a significant spike. [2],[3],[4],[5] In mild or indolent myeloma patients, such high amount of light chains may not be produced, leading to a "normal" SPEP. Hence, it is important to obtain serum free light chain levels as they may show elevated monoclonal light chain levels. [2],[3],[4],[5],[9],[10],[11]

If LCPT is diagnosed early, it can be reversed upon treating the underlying multiple myeloma. Hence, it is imperative to meticulously search for an underlying cause in an adult patient with FS as often the underlying cause is plasma cell dyscrasia.

Conflict of interest: None declared.

 
   References Top

1.
Roth KS, Foreman JW, Segal S. The Fanconi syndrome and mechanisms of tubular transport dysfunction. Kidney Int 1981;20:705-16.  Back to cited text no. 1
[PUBMED]    
2.
Hutchison CA, Batuman V, Behrens J, et al. The pathogenesis and diagnosis of acute kidney injury in multiple myeloma. Nat Rev Nephrol 2011;8:43-51.  Back to cited text no. 2
[PUBMED]    
3.
Batuman V. Proximal tubular injury in myeloma. Contrib Nephrol 2007;153:87-104.  Back to cited text no. 3
[PUBMED]    
4.
Herlitz LC, Roglieri J, Resta R, Bhagat G, Markowitz GS. Light chain proximal tubulopathy. Kidney Int 2009;76:792-7.  Back to cited text no. 4
[PUBMED]    
5.
Kapur U, Barton K, Fresco R, Leehey DJ, Picken MM. Expanding the pathologic spectrum of immunoglobulin light chain proximal tubulopathy. Arch Pathol Lab Med 2007;131:1368-72.  Back to cited text no. 5
[PUBMED]    
6.
Engle RL, Wallis LA. Multiple myeloma and the adult Fanconi syndrome. Am J Med 1957;1:5-23.  Back to cited text no. 6
    
7.
Maldonado JE, Velosa JA, Kyle RA, Wagoner RD, Holley KE, Salassa RM. Fanconi syndrome in adults. A manifestation of a latent form of myeloma. Am J Med 1975;58:354-64.  Back to cited text no. 7
[PUBMED]    
8.
Messiaen T, Deret S, Mougenot B, et al. Adult Fanconi syndrome secondary to light chain gammopathy. Clinicopathologic heterogeneity and unusual features in 11 patients. Medicine (Baltimore) 2000;79:135-54.  Back to cited text no. 8
[PUBMED]    
9.
Sanders PW. Mechanisms of light chain injury along the tubular nephron. J Am Soc Nephrol 2012;23:1777-81.  Back to cited text no. 9
[PUBMED]    
10.
Rajkumar SV. Treatment of multiple myeloma. Nat Rev Clin Oncol 2011;8:479-91.  Back to cited text no. 10
[PUBMED]    
11.
Decourt C, Bridoux F, Touchard G, Cogné M. A monoclonal V kappa l light chain responsible for incomplete proximal tubulopathy. Am J Kidney Dis 2003;41:497-504.  Back to cited text no. 11
    

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Correspondence Address:
Mohit Mathur
Department of Nephrology, Sawai Man Singh Hospital, Jaipur, Rajasthan
India
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DOI: 10.4103/1319-2442.185268

PMID: 27424703

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