Nephrology Case Challenge: Man on Keto Diet Has Severe Diarrhea and Neurogenic Bladder

C. Elena Cervantes, MD


February 06, 2023


In the context of significant weight loss, serum creatinine levels may overestimate eGFR, leading to a delayed diagnosis of chronic kidney disease (CKD) and late referral to a specialist. This patient has a decline in kidney function, low-level low molecular weight proteinuria, and bland urinalysis findings. Even though chronic urinary retention due to the neurogenic bladder and incomplete recovery from recurrent episodes of prerenal azotemia may explain his CKD, the patient's autonomic dysfunction symptoms, such as orthostatic hypotension and bowel and bladder dysfunction in an individual with a prior monoclonal gammopathy, raise concerns about an evolving systemic process. Of note, the absence of a chronic or recurrent inflammatory condition makes amyloid A (AA) amyloidosis unlikely in this case.

Subsequent tests revealed a cystatin C level of 2.9 mg/L (reference range, 0.7-1.1 mg/L), which resulted in an eGFR of 28 mL/min based on the combined CKD-EPI creatinine–cystatin C equation. Paraproteinemia testing demonstrated a normal kappa/lambda ratio of 0.37, with elevated lambda light chains of 50 mg/L, and a high beta M-spike (0.39 g/dL [reference range, 0 g/dL]). Serum immunofixation revealed an IgA lambda monoclonal band despite normal findings on serum and urine protein electrophoresis. A transthoracic echocardiogram showed moderate concentric hypertrophy of the left ventricle with a preserved ejection fraction and a reduction in global longitudinal strain with a relative sparing of the apex.

The patient was referred to hematology-oncology and cardiology for evaluation of possible systemic amyloidosis. The bone marrow biopsy revealed no abnormality. Two endomyocardial biopsies suggested cardiac amyloidosis; however, there was insufficient tissue to determine the type of amyloid protein. A renal biopsy confirmed amyloidosis, with amyloid protein deposits in the tubules and blood vessels. Mass spectrometry identified the lambda subtype.

Amyloidosis is caused by the deposition and aggregation of insoluble, misfolded B-pleated protein fibrils in tissue, causing progressive organ dysfunction. At least 36 proteins have been identified in humans, with 17 showing systemic involvement and the rest presenting as localized diseases. The two most common types of systemic acquired disease are wild-type transthyretin (ATTR) amyloidosis and monoclonal Ig light chain (AL) amyloidosis. AA amyloidosis is another form of acquired systemic disease that results from high levels of serum AA protein, an acute phase reactant associated with chronic inflammation.[1,2,3]

Amyloidosis may be suspected on the basis of the clinical history, presentation, and organ involvement; however, the diagnosis can be confirmed only by the identification of the parent protein on biopsy. ATTR amyloidosis is characterized by aggregation of transthyretin predominantly in the heart and peripheral nervous system. AA amyloidosis affects persons with chronic infections or autoinflammatory diseases and primarily involves the kidneys. AL amyloidosis often occurs in persons with monoclonal gammopathy and typically affects the heart and kidneys, although the peripheral and autonomic nervous systems, gastrointestinal tract, and other organs may be involved.[1]


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