AL amyloidosis secondary to a plasma cell dyscrasia is the most likely diagnosis. Amyloid consists of randomly oriented fibrils composed of various proteins that form organized β-pleated sheets within the tissues; amyloid resulting from monoclonal lambda or kappa light chains is termed AL amyloid. AL amyloid may present with nonspecific systemic symptoms such as fatigue or weight loss, but most commonly presents with symptoms associated with infiltration of different organ systems. These may include restrictive cardiomyopathy, peripheral neuropathy, hepatosplenomegaly, and, less commonly, cutaneous purpura and macroglossia. In amyloidosis involving the kidney, glomerular lesions tend to be prominent and present with proteinuria, often in the nephrotic range. However, amyloid deposits may also be found in tubular basement membranes, the interstitial space, and blood vessels. Findings on biopsy show deposits that stain apple green on Congo red staining under a polarizing microscope; these deposits are also visible on electron microscopy. In this patient, the presence of the nephrotic syndrome, autonomic symptoms (diarrhea and postural hypotension), and sensory neuropathy is highly suggestive of AL amyloidosis.

Although diabetes mellitus may present with similar systemic manifestations, such as autonomic and peripheral neuropathy and the nephrotic syndrome, these manifestations are typically seen after many years of diabetes, and this patient does not have evidence of diabetes on his current laboratory studies or on prior studies.

Myeloma nephropathy results from filtering of myeloma light chains with minimal albumin, with the light chains accumulating in the renal tubule causing tubular injury and typically forming casts (cast nephropathy). Filtered light chains are often not detected on routine dipstick testing and require identification with urine electrophoresis. The degree of albuminuria seen in this patient is less consistent with the findings typically seen in myeloma nephropathy.

Primary focal segmental glomerulosclerosis is a kidney-limited disease and is not associated with the systemic manifestations exhibited in this patient.