Can amyloidosis affect the kidneys?

Can Amyloidosis Affect the Kidneys?

Yes, amyloidosis significantly affects the kidneys, particularly in AL amyloidosis where the kidney is one of the most common sites of amyloid deposition, with involvement in approximately 70% of patients. 1

Type-Specific Kidney Involvement

AL Amyloidosis: High Frequency and Severe Impact

Kidney involvement in AL amyloidosis is both common and clinically significant, typically presenting as nephrotic syndrome with progressive renal dysfunction. 1

• The kidneys are affected in approximately 70% of AL amyloidosis patients, making it one of the most frequently involved organs 1
• The hallmark presentation is nephrotic syndrome characterized by high-grade proteinuria, marked hypoalbuminemia, and anasarca 1, 2
• Progressive loss of kidney function accompanies the proteinuria in most cases 1
• A small proportion of patients have amyloid deposition limited to the kidney interstitial compartment and/or vasculature, presenting with reduced kidney function but minimal proteinuria 1

ATTR Amyloidosis: Usually Subclinical

Direct kidney involvement in ATTR amyloidosis is typically subclinical, with most kidney dysfunction resulting from cardiorenal syndrome rather than direct amyloid deposition. 1

• Although direct kidney involvement has been demonstrated with several TTR mutations (Val30Met, Val30Ala, Phe33Cys, Gly47Glu, Val142Ile) and wild-type ATTR, the involvement is usually subclinical 1
• The vast majority of kidney disease in ATTR patients is due to cardiorenal syndrome, which also frequently occurs in AL cardiac amyloidosis 1
• Autonomic nervous system involvement in both AL and ATTR disease can contribute to hemodynamically-mediated kidney impairment 1

Clinical Manifestations and Progression

Nephrotic Syndrome Features

• Nephrotic syndrome can be severe with high-grade proteinuria, marked hypoalbuminemia, and anasarca 1, 2
• The combination of unexplained proteinuria, impaired renal function, and anasarca represents a classic triad for AL amyloidosis with renal involvement 3
• Progression to end-stage renal disease occurs eventually in 50% of patients with proteinuria 2

Impact of Treatment on Kidney Outcomes

In AL amyloidosis, eradication of the amyloidogenic light chain with anti-plasma cell therapy often leads to improvement in kidney manifestations, though the response pattern differs from cardiac involvement. 1

• Proteinuria typically decreases progressively over many months to several years after achieving a hematologic complete response or very good partial response, and can resolve fully if the hematologic response is sustained 1, 2
• Although GFR usually does not improve, kidney function often stabilizes after amyloidogenic light chain production is halted 1, 2
• This contrasts with cardiac manifestations of AL amyloidosis where abnormalities frequently persist despite treatment 1

Critical Assessment Pitfalls

Accurate Kidney Function Evaluation

Standard serum creatinine-based estimates of kidney function are unreliable in amyloidosis patients due to muscle wasting, leading to overestimation of GFR. 1

• Serum concentrations of cystatin C, a marker independent of muscle mass, provide better indications of kidney function 1, 2
• Cystatin C-based GFR estimating equations and determination of creatinine clearance with 24-hour urine collection should be used when muscle mass is reduced 1

Limitations of Kidney Biopsy After Treatment

• If kidney function declines despite documented eradication of the amyloidogenic light chain, a kidney biopsy is usually not helpful 1
• Amyloid persists in tissue, making it impossible to distinguish new amyloid deposits from pre-existing ones 1, 4

Treatment Considerations Based on Kidney Involvement

Disease-Directed Therapy

• For patients with AL amyloidosis and renal impairment, aggressive anti-plasma cell therapy to halt light chain production is essential 4
• Daratumumab-CyBorD is the preferred first-line treatment for most patients, achieving very good partial response or better in 78.5% of patients 4

Drug Dosing Adjustments

• Diflunisal (an NSAID and TTR stabilizer) is not generally recommended for patients with significant kidney impairment (typically eGFR <45 mL/min/1.73 m²) or volume overload due to potential deleterious effects on kidney hemodynamics, potassium excretion, and sodium excretion 1

Supportive Management

• Dietary sodium restriction combined with loop diuretics forms the cornerstone of nephrotic syndrome management 1, 4
• Torsemide or bumetanide, or intravenously administered loop diuretics, may be more effective than oral furosemide for patients with significant intestinal wall edema 1
• ACE inhibitors or angiotensin receptor blockers can be used for anti-proteinuric effects if blood pressure tolerates 1