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The systemic autoinflamatory diseases (SAIDs) are genetically based entities characterized by a wide range of systemic disorders, but there are very few reports with renal involvement.
Description of a clinical case
A 38-year-old male patient had a history of recurrent febrile episodes every 1 month, persisted 3 to 7 days, accompanied by asthenia, maculopapular rash, aphthous stomatitis, cervical lymphadenopathy, splenomegaly, episodic diarrhea, abdominal pain and arthralgias. He consulted in 2011 due to macroscopic hematuria with mild proteinuria during episodes of fever. In biochemical analyses, serum creatinine was 0.6 mg/dl, presence of hemoglobin ++ in urine and a urinary protein/creatinine ratio of 0.5 g/g. The immunological and serological profiles were normal, except for immunoglobulin A (397 mg/dl; normal reference <350). A renal biopsy (RBx) was performed that revealed IgA glomerulonephritis (GN), without inflammatory activity and no histological chronicity, thus he was treated with a low sodium diet and ramipril. Due to persistence of systemic symptoms, he received prednisone, azathioprine, and tocilizumab. During follow up, he presented persistence of hematuria, and three surveillance RBx was performed that confirmed IgA-GN, with inflammatory activity and a striking increase in chronicity. In this period, he received methylprednisolone (MP), cyclophosphamide, rituximab and mycophenolate. In 2018, canakinumab 150 mg monthly was begun with a complete disappearance of systemic symptoms.
In 2022, the patient was admitted due to abscesses in the paraspinal muscle. Concomitantly developed an AKI III (without sepsis or hypotension) that requires transiently renal replacement therapy. Immunological, serological and prothrombotic profiles were normal. Triphasic abdominal CT showed bilateral diffuse renal cortical hypoperfusion (Figure 1-A). A fifth RBx was performed, showing an infarction with ischemic necrosis and interstitial hemorrhage, IgA-GN with a fibrocellular crescent, with fibrosis and moderate chronic interstitial inflammation (Figure 1-B-F). Again, MP were administered and his renal function began to recover.
In 2023, a genetic study revealed two genetics variants (p.Val377IIe and p.Pro11Leu) associated with Mevalonate Kinase Deficiency (MKD), a kind of SAIDs. Due to the reappearance of his systemic symptoms, he restarted canakinumab, with an excellent clinical response. Currently, the patient is asymptomatic with creatinine of 1.46 mg/dl, persistence of microhematuria and proteinuria around 1 g per day.
In this patient two events converge: repeated infectious and inflammatory episodes added to an increase in the quantity and a defect in the quality of IgA, that could explain the pathogenic relationship between MDR and IgA-GN, and the marked progression of histological damage, with no response to the different immunosuppressive schemes.
On the other hand, patients with SAIDs had predisposition for thrombotic events. Schwartzman phenomenon could be acting in the development of renal cortical necrosis (RCN) in the context of a sustained inflammatory and infectious. A RCN under canakinumab´s treatment and with a pre-existing glomerular involvement has not been still reported in MKD. The pathogenic mechanisms described allow us to assume that MKD have been instrumental -causative- in the development of the renal manifestations.