APS Program Community Q&A Series

The APS Program Community Q&A Series, written by Yu (Ray) Zuo, MD, MSCS, was created to answer questions we receive from the APS Program community and covers a variety of topics. In this month’s edition, Dr. Zuo discusses how APS can impact your kidneys and the steps that you can take to keep your kidneys healthy.

How does APS impact my kidneys?

Our kidneys represent a special filtering system that balances fluid levels, maintains blood pressure, and removes waste products from the blood.

Antiphospholipid syndrome (APS) can impact kidney health in various ways. It can cause blockages in the relatively large arteries and veins that supply the kidneys (though blood thinners typically do a good job of preventing such blockages). 

APS can also affect the smaller blood vessels of the kidneys, which leads to a unique condition known as APS nephropathy. This entity was first identified in the 1990s when research studies observed microscopic blood clots in the kidney biopsies of some patients with positive testing for antiphospholipid antibodies (1). By 1999, preliminary criteria were established to distinguish APS nephropathy from other types of kidney disease based on unique findings under the microscope after a kidney biopsy (2).

Over the years, research has linked APS nephropathy to other aspects of APS, including previous strokes, livedoid skin rashes (red-purple blotchy skin), positive lupus anticoagulant testing, and catastrophic APS (1). A systematic review of the literature by an international task force led to the inclusion of APS nephropathy in the 2023 APS Classification Criteria, where the definitions of APS nephropathy were updated and refined (3, 4). 

To make a diagnosis of APS nephropathy, either fresh or chronic changes should be present when the pathologist reviews the biopsy specimen under the microscope:

1. Fresh (Acute) Changes: These appear as sudden damage to the kidney’s microscopic blood vessels and filters (glomeruli). Small clots made up of a protein called fibrin are often appreciated. There should not be significant antibody or complement (a type of blood protein) deposits as one would expect in patients with lupus.
2. Chronic Lesions: These are longer-term changes in the kidneys that develop over months or years. Examples include old/healed clots, narrowing of blood vessels due to a build-up of scar tissue-like thickening in the vessel walls, shrinkage of kidney tissue, and changes in the kidney tubules that carry urine out of the kidneys.

Patients with APS nephropathy may present with new or worsening high blood pressure, microscopic blood in the urine, protein in the urine, and loss of the kidney’s filtering efficiency as determined by blood tests. However, a kidney biopsy is the only way to make a sure diagnosis.

APS nephropathy is thought to be relatively rare, with an estimated prevalence amongst patients with APS of 10-20%. On average, such patients do seem to have worse outcomes compared to other APS, including the risk of progressing to end-stage renal disease requiring dialysis (5).

Though APS nephropathy does not have a standardized treatment protocol proved by clinical trials, some combination of anticoagulants and immunosuppressants is typically recommended. Recent research has also revealed promising new targets for treatment. Notably, our research group has identified a critical role for neutrophil extracellular traps (NETs) in causing vessel damage in APS patients, which appears to be a key factor in developing APS nephropathy (6). Whether new or repurposed treatments that disrupt NETs should be part of future treatment regimens is something we are actively studying (7).

What can I do to keep my kidneys healthy?

It is crucial to maintain control of other major risk factors for kidney problems, especially diabetes and high blood pressure. Both of these issues are well known to damage the kidney’s filtering system, which can eventually lead to the kidneys having trouble removing wastes and extra fluid from your body. High blood pressure is an especially tricky situation since kidney problems lead to fluid and salt buildup that further raises blood pressure, creating a dangerous cycle. Fortunately, some simple lifestyle factors can decrease the risk of kidney disease.

Here are some simple steps you can do to prevent kidney disease in APS:

• Manage blood sugar and blood pressure effectively and proactively whenever possible.
• Take APS medications as prescribed.
• Choose a healthy diet low in processed foods, salt, and added sugar.
• Get regular physical activity.
• Maintain a healthy weight.
• If you smoke, quit.
• Ensure you get adequate sleep.

Although APS nephropathy is relatively rare, its onset can significantly worsen health outcomes, underscoring the importance of actively monitoring and maintaining kidney health. Since kidney disease is almost always silent in its early stages, we monitor kidney function with blood and urine testing at most APS clinic visits. We encourage you to discuss your kidney health during your next medical visit. Early detection of kidney disease allows for earlier treatment, which is vital in protecting your kidneys.

References:

1. Xourgia E, Tektonidou MG. Antiphospholipid syndrome nephropathy: Current knowledge and unanswered questions. Clin Immunol. 2023;255:109735.

2. Nochy D, Daugas E, Droz D, Beaufils H, Grunfeld JP, Piette JC, et al. The intrarenal vascular lesions associated with primary antiphospholipid syndrome. J Am Soc Nephrol. 1999;10(3):507-18.

3. Barbhaiya M, Taghavi M, Zuily S, Domingues V, Chock EY, Tektonidou MG, et al. Efforts to Better Characterize "Antiphospholipid Antibody Nephropathy" for the 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria: Renal Pathology Subcommittee Report. J Rheumatol. 2024;51(2):150-9.

4. Barbhaiya M, Zuily S, Naden R, Hendry A, Manneville F, Amigo MC, et al. The 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria. Arthritis Rheumatol. 2023;75(10):1687-702.

5. Gaspar P, Sciascia S, Tektonidou MG. Epidemiology of antiphospholipid syndrome: macro- and microvascular manifestations. Rheumatology (Oxford). 2024;63(SI):SI24-SI36.

6. Ambati A, Zuo Y, Knight JS. An update on inflammation in antiphospholipid syndrome. Curr Opin Rheumatol. 2023;35(2):89-97.

7. Ambati A, Knight JS, Zuo Y. Antiphospholipid syndrome management: a 2023 update and practical algorithm-based approach. Curr Opin Rheumatol. 2023;35(3):149-60.

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