The pathogenesis of LCDD is similar to that of primary amyloidosis. Both are monoclonal plasma cell proliferative disorders characterized by tissue deposition of light chain fragments, leading to organ impairment. Myeloma is diagnosed in about 40% of patients with LCDD . In LCDD light chain fragments do not form amyloid fibrils; they are defined as non-amyloid immunoglobulin light chains, and are mostly kappa chains. They cause renal failure and extra-renal manifestations usually secondary to heart, liver and peripheral nerve involvement . Survival is quite variable, ranging from 1 month to 10 years from the onset of symptoms, and mortality is mainly due to heart or liver failure, or progression to multiple myeloma . Serum creatinine at the time of diagnostic renal biopsy seems to be the only predictive factor of renal function and patient survival [1, 3].
In plasma cell disorders with dysproteinemia, the aggregation of non-amyloid immunoglobulin light chains forms granular deposits, diffusely distributed in systemic basement membranes, which suggest a mechanism of aggregation and deposition different from primary amyloidosis . Several cofactors have been suggested to play a role in promoting fibrilogenesis, such as the binding to subunit proteins, the stabilization of fibrils, and their protection from degradation . In the kidneys, LCDD is often associated with deposits in the tubular basement membranes and Bowman's capsule, which may be more prominent than those deposits seen in the glomeruli. Clinical presentation depends in part on the site of deposition: it follows that patients with predominant glomerular deposition develop nephrotic syndrome, while those with predominant tubular deposition develop renal failure and mild proteinuria . In most cases, renal function declines rapidly, with the clinical features of subacute tubulointerstitial nephritis or rapidly progressive glomerulonephritis . In our patient, the clinical presentation showed similar characteristics, but it was initially misunderstood. An ACE-inhibitor was prescribed without paying sufficient attention to the slight increase in creatinine levels, and the subsequent worsening of renal function was ascribed to that medication. Such a misunderstanding delayed the correct diagnosis, and the clinical management was erroneously focussed on the cardiac manifestations. Indeed, atrial fibrillation associated with restrictive cardiomyopathy is a quite uncommon presentation of LCDD, and the patient was referred to the nephrology unit only when the renal disease impairment became severe.
Endomyocardial biopsy is the gold standard to demonstrate heart involvement in LCDD. Histologic examination of deep-frozen specimens shows amorphous Congo red-negative deposits that are positive for light chains on immunofluorescence [6, 7]. Clinical manifestations of heart involvement are variable and similar to those observed in restrictive cardiomyopathy induced by amyloidosis. They can range from congestive heart failure to arrhythmias and conduction disorders; myocardial infarction has also been reported [8, 9]. Recently Toor et al.  described cardiac nonamyloidotic immunoglobulin deposition disease in 8 patients who underwent endomyocardial biopsy. The median age was 49.5 years, none of them were symptomatic and on echocardiography six patients had concentric left ventricular hypertrophy with diastolic dysfunction. One of them developed atrial fibrillation during chemotherapy and responded to therapy with digoxin.
In our patient left ventricular morphology and the transmitral inflow pattern demonstrated by doppler echocardiography were consistent with diastolic ventricular dysfunction due to restrictive cardiomyopathy . Response to treatment may differ between amyloidosis-induced and LCDD-induced cardiomyopathy, and the latter could resolve after successful treatment of the underlying plasma cell disorder . However, whatever signs and symptoms may reveal heart impairment in LCDD, they usually occur in the advanced stages of the disease.
To our knowledge, atrial fibrillation associated with restrictive cardiomyopathy has never been previously reported in the medical literature as a first clinical manifestation of restrictive cardiomyopathy due to LCDD. Although Palladini et al.  demonstrated that NT-proBNP assay can be useful in detecting cardiac involvement in amyloidosis, we observed that natriuretic peptide levels were no more effective than echocardiography in evaluating heart disease in a patient with primary amyloidosis and uraemia . However, the very high levels of NT-proBNP observed in the patient in this present case report could have been the result of the combination of heart involvement and impaired renal function, as renal failure can influence NT-proBNP assay performed by Roche method .
In conclusion, this unusual case suggests that the onset of acute arrhythmias associated with restrictive cardiomyopathy and impaired renal function might be related to LCDD.