1 Departments of Internal Medicine and 2 Pathology, University of Tartu, 3 Dialysis Unit, Pelgulinna Hospital, 4 Pathology Division, Mustamäe Hospital, Tallinn, Estonia, and 5 Nephrology Division, University of Heidelberg, Germany light-chain deposition disease; nodular glomerulosclerosis; proteinuria; renal biopsy
Keywords: light-chain deposition disease; nodular glomerulosclerosis; proteinuria; renal biopsy
Introduction
Nodular glomerulosclerosis is usually considered the hallmark of diabetic nephropathy. Similar morphology may also be seen, however, in some relatively rare non-diabetic conditions. The following case gives unique information on the natural history of one of these conditions, i.e. light-chain deposition disease.
Case
A 38-year-old female patient was admitted for further evaluation. She had a 6 months' history proteinuria, pretibial oedema, and normochromic anaemia. There was no history of renal disease and serum creatinine concentration was in the normal range. She complained of chronic fatigue and decreased appetite. She was noted to have moderated hypertension (160170/90100 mmHg), but physical examination was otherwise unremarkable.
Initial laboratory findings included of urinary abnormalities, i.e. proteinuria in the non-nephrotic range (3.1 g/24 h), microhaematuria, no casts or lipids. A test for Bence Jones protein in the urine was negative. Bone marrow biopsy failed to show atypical cells. Total IgG was in the normal range. Endogenous creatinine clearance was 93 ml/min. Hb was 101 g/l. Renal biopsy showed nodular glomerulopathy with moderate mesangial proliferation with a deposition of PAS-positive and Congo-red negative deposits in the mesangium (Figure 1a).
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Comment
This patient was treated at a time when in Estonia facilities for advanced immunohistological diagnosis were scarce. In view of the scarcity of dialysis facilities, renal transplantation was performed and this treatment strategy provided the unique observation concerning the evolution of this condition after transplantation. This finding, so to speak, fulfils one of the postulates concerning the pathogenetic relevance of the light chains. In a retrospective analysis in collaboration with Professor Weening (Amsterdam), appropriate immunohistological studies clearly documented that this was a case of nodular glomerulosclerotic light-chain deposition disease. The immunohistological examination revealed linear tubular basement membrane staining for kappa light chains and negative staining for lambda light chains (Figure 2).
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Discussion
Light-chain deposition disease (LCDD) is seen mostly in patients with myeloma. However, it also occurs in other plasma cell dyscrasias. Light-chain deposition disease (LCDD) was first reported by Antonovych et al. 1973 [1]. Later, systemic nature of light-chain deposition without overt myeloma was described. Monoclonal immunoglobulins and free immunoglobulin light chains are produced by plasma cells as a result of their clonal expansion in plasma cell dyscrasia. These proteins are pivotal in the development of pathological and clinical symptoms of plasma cell dyscrasia and renal manifestations are frequently the presenting and leading features of this process [2]. The frequency of the disease is impossible to evaluate because light-chain-specific antibodies are still not being used in systematic fashion. Therefore the disease can be missed without immunohistochemical examination.
Differential diagnosis
Nodular glomerulosclerosis, the characteristic lesion of LCDD, is demonstrated in light microscopy by amorphous PAS-positive, Congo-red negative material and argyrophilic widened mesangium. The diagnosis of light-chain deposition nephropathy is based on the immunohistochemical demonstration of monoclonal light-chain deposits within connective tissue matrix, and on the presence at the ultrastructural level of electron-dense granular deposits along glomerular and tubular basement membranes. Nodular glomerulosclerosis is the characteristic lesion of LCDD but not universal to this condition, since it is present in less than 5060% of patients [3]. Light microscopy features of LCDD resemble those seen in cases of the following types.
Serodiagnostics
Detection of serum monoclonal immunoglobulins helps to diagnose a disease. However, immunoelectropheresis of both serum and urine did not demonstrate a monotypical light chain or immunoglobulin in almost 35% of the population with LCDD.
Teaching Point
In the non-diabetic proteinuric patient with nodular glomerulosclerosis, consider light-chain deposition disease.
It is important to establish the diagnosis because it will recur in the renal graft after transplantation.
Acknowledgments
The authors thank Professor Jan Weening (Amsterdam) for consultations concerning the renal biopsy data.
Notes
Supported by an educational grant from
Correspondence and offprint requests to: Dr Mai Ots, Tartu University Clinics, Department of Internal Medicine, 6 Puusepa Str., 51014 Tartu, Estonia.
References