From the Guidelines
Yes, amyloid can cause nephrotic syndrome, particularly in AL amyloidosis, where kidney involvement is characterized by nephrotic syndrome and progressive loss of kidney function, as noted in approximately 70% of patients 1.
Key Points
- Amyloidosis is a condition characterized by the abnormal deposition of misfolded proteins called amyloid fibrils in various tissues and organs, including the kidneys.
- When amyloid deposits accumulate in the glomeruli (filtering units) of the kidneys, they damage the glomerular basement membrane and podocytes, disrupting the normal filtration barrier.
- The resulting nephrotic syndrome typically presents with heavy proteinuria (>3.5g/day), hypoalbuminemia, edema, and hyperlipidemia.
- Treatment focuses on addressing the underlying cause of amyloid production, such as chemotherapy for AL amyloidosis or controlling inflammation in AA amyloidosis, while managing the symptoms of nephrotic syndrome with diuretics, ACE inhibitors or ARBs, and sometimes statins for hyperlipidemia, as supported by the 2023 ACC expert consensus decision pathway on comprehensive multidisciplinary care for the patient with cardiac amyloidosis 1.
Management Considerations
- Supportive management for amyloidosis-associated nephrotic syndrome includes dietary sodium restriction, loop diuretic agents, and compression stockings to reduce peripheral edema.
- Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers can be used for their anti-proteinuric effects if the blood pressure is not prohibitively low.
- Nephrologists play a crucial role in the multidisciplinary care of patients with amyloidosis, particularly in managing nephrotic syndrome, cardiorenal syndrome, and metabolic complications of chronic kidney disease 1.
- The management of volume overload due to nephrotic syndrome or in the setting of cardiorenal syndrome requires a balance between efforts to remove excess fluid and resulting alterations in hemodynamic variables that reduce kidney perfusion and GFR.
From the Research
Amyloid and Nephrotic Syndrome
- Amyloid can cause nephrotic syndrome, as evidenced by several studies 2, 3, 4, 5, 6.
- Nephrotic syndrome is a common manifestation of renal involvement in primary systemic amyloidosis (AL) 5.
- The deposition of amyloid fibrils in the kidneys can lead to the development of nephrotic syndrome, characterized by massive proteinuria, hypoalbuminemia, and edema 2, 3, 4, 6.
Treatment and Outcomes
- Treatment of nephrotic syndrome due to amyloidosis can be effective with therapies such as melphalan and prednisone 2, autologous stem cell transplantation 3, 4, 6, and high-dose chemotherapy 4, 6.
- Renal response is an important therapeutic endpoint in the treatment of nephrotic syndrome due to amyloidosis 3.
- Long-term remission of renal amyloidosis with nephrotic syndrome can be achieved with autologous peripheral blood stem-cell transplantation 6.
Pathophysiology
- The monoclonal light chains form the fibrils that deposit and accumulate in tissues, leading to renal involvement and nephrotic syndrome in AL amyloidosis 5.
- The deposition of amyloid fibrils in the kidneys can disrupt normal renal function, leading to the development of nephrotic syndrome 2, 3, 4, 6.