Causes and Risk Factors
The diffuse cutaneous form of systemic sclerosis (dcSSc) is a risk factor, with more cases (10% to 25%) occurring in patients with this subtype compared to those with limited disease (1% to 2%). A rapid progression of skin thickening, particularly early in the disease course, also indicates an increased likelihood of SRC. About 75% of SRC cases emerge within the first four years of a scleroderma diagnosis, with a median onset around eight months.
The presence of specific autoantibodies serves as a predictor for SRC. Individuals positive for anti-RNA polymerase III antibodies are at a higher risk of developing this complication. These antibodies are found in many SRC patients and are strongly associated with the diffuse cutaneous subtype.
High-dose corticosteroid therapy, particularly doses exceeding 15 mg of prednisolone per day, is a contributing factor. While corticosteroids are sometimes used to manage other aspects of scleroderma, their use at higher dosages has been linked to an increased risk of SRC.
Warning Signs and Symptoms
Recognizing the warning signs of scleroderma renal crisis (SRC) is important. The primary sign is a new onset or sudden worsening of high blood pressure, often reaching high levels. This malignant hypertension is a hallmark of SRC.
Despite the silent nature of high blood pressure, other symptoms can emerge as SRC progresses. Severe headaches are common, often accompanied by vision disturbances like blurry vision from high blood pressure. Individuals may also experience shortness of breath, indicating fluid buildup in the lungs or heart strain. In more severe instances, brain effects can lead to confusion, altered mental status, or even seizures.
The Diagnostic Process
Confirming a diagnosis of scleroderma renal crisis (SRC) involves several evaluations. The primary diagnostic step is consistent blood pressure monitoring. A new onset of elevated blood pressure, often exceeding 150/85 mmHg, in a patient with scleroderma is a strong indicator.
Beyond blood pressure, laboratory tests provide evidence of kidney involvement. Blood tests measure serum creatinine levels; a rapid increase indicates declining kidney function. Urine tests detect abnormalities like proteinuria (protein leakage) or hematuria (blood in the urine). These findings indicate kidney damage.
Checking for specific autoantibodies, like anti-RNA polymerase III antibodies, can further support an SRC diagnosis. In some cases, a kidney biopsy might be considered to observe changes like “onion skin” proliferation within renal arteries, but this is less common and usually not required for treatment initiation.
Primary Treatment Strategies
Immediate, aggressive administration of ACE (angiotensin-converting enzyme) inhibitors is the cornerstone of treatment for scleroderma renal crisis (SRC). This drug class has transformed the prognosis of SRC, improving survival rates since their introduction. Before ACE inhibitors, the one-year mortality rate for SRC was as high as 85%, but with their use, this figure has dropped, often to around 24%.
ACE inhibitors work by blocking the body’s production of angiotensin II, a chemical that narrows blood vessels and raises blood pressure. By inhibiting this process, these medications lower blood pressure and reduce kidney damage. Treatment is initiated promptly, often with a short-acting ACE inhibitor like captopril, allowing rapid dose adjustments for quick blood pressure control.
The goal is to gradually reduce systolic blood pressure by about 20 mmHg within 24 hours, aiming for a target of around 120/70 mmHg within 72 hours, while avoiding excessively low pressure. Even if initial creatinine levels appear to rise slightly after starting ACE inhibitors, therapy is continued for its long-term benefits in preserving kidney function. This initial rise may reflect the kidneys adjusting to improved blood flow.
Supportive care becomes necessary if kidney failure is severe, including dialysis. However, the primary aim of aggressive ACE inhibitor therapy is often to prevent the need for long-term dialysis or to facilitate kidney function recovery enough to discontinue dialysis. While ACE inhibitors are effective, some patients (19-78%) may still require permanent dialysis despite treatment.
Recovery and Long-Term Outlook
Recovery following a scleroderma renal crisis (SRC) can vary, but treatment advancements have improved outcomes. While some patients may initially require temporary or permanent dialysis from severe kidney damage, many can recover enough kidney function to discontinue dialysis. This recovery is seen in those who receive early and aggressive ACE inhibitor treatment.
Kidney function recovery can be a gradual process, often taking about one year, and may continue to improve for up to three years after the crisis. About 50% of patients who initially require dialysis may regain enough kidney function to discontinue it. However, mortality rates remain higher in patients who continue to require dialysis compared to those who achieve kidney function recovery.
Lifelong blood pressure monitoring is a key aspect of long-term management after SRC, even if kidney function has recovered. Ongoing oversight by specialists (rheumatologists and nephrologists) is also important to manage ongoing scleroderma manifestations and monitor kidney health. For individuals with irreversible kidney failure, renal transplantation is a consideration, though outcomes can differ, and SRC recurrence in the transplanted kidney is rare.