Castleman Disease and Kidney Thrombotic Microangiopathy

Introduction: Idiopathic Multicentric Castleman Disease (iMCD) is a rare, life-threatening disorder that causes multiorgan dysfunction, generalized lymphadenopathy and systemic hyperinflammation that rarely affects the kidney. Thrombotic microangiopathy (TMA) is characterized by microvascular thrombosis due to vessel wall abnormalities in arterioles and capillaries. Kidney TMA is a rare manifestation of iMCD. We report a rare case of iMCD with kidney TMA in a young patient. Case Description: 19 year-old male presented with diarrhea, night sweats, leg swelling and dark urine. Initial workup included creatinine 1.5 mg/dL, albumin 1.9 g/dL, C-reactive protein 310 mg/L, LDH 317 U/L, and platelet 90 K/µL. Urinalysis showed 2+ protein and small blood, urine protein-creatinine ratio 0.3 mg/mg. Kidney biopsy showed glomerular mesangiolysis with fragmented red blood cells and platelets, subendothelial widening and focal areas of glomerular basement membrane duplication consistent with membranoproliferative pattern of TMA. He was started on eculizumab. Further studies revealed normal complements, negative ANA, anti-ds DNA, anti-cardiolipin antibodies, HHV-8, and HIV. CT scan showed multiple retroperitoneal lymph nodes and adrenalitis, concerning for Castleman Disease with supportive excision lymph node biopsy results. His kidney function continued to decline, and hemodialysis was started after three weeks. Siltuximab and high-dose steroids were started after iMCD diagnosis. Discussion: iMCD has an estimated yearly incidence of 3-4 cases nationwide. Kidney complications are very rare, though kidney TMA and AA amyloidosis have been reported. The pathogenesis of kidney TMA in iMCD is unclear; may involve increased production of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) by proliferating plasma cells within lymph nodes. Elevated serum levels of VEGF and IL-6 are reported to decrease VEGF expression within glomerular podocytes, which may have a role in thrombotic glomerular injury. There is no standard treatment for iMCD; IL-6 inhibitors, tocilizumab and siltuximab have demonstrated kidney recovery. In our patient, kidney function rapidly declined requiring dialysis. This highlights the importance of having iMCD as a differential diagnosis for kidney TMA with an atypical presentation and promptly starting treatment.