Microvascular inflammation in the absence of human leukocyte antigen-donor-specific antibody and C4d: An orphan category in Banff classification with cytotoxic T and natural killer cell infiltration.

Isolated microvascular inflammation (iMVI) without HLA donor-specific antibodies or C4d deposition in peritubular capillaries remains an enigmatic phenotype that cannot be categorized as antibody-mediated rejection (ABMR) in recent Banff classifications. We included 221 kidney transplant recipients with biopsies with ABMR (n = 73), iMVI (n = 32), and normal (n = 116) diagnoses. We compared peripheral blood leukocyte distribution by flow cytometry and inflammatory infiltrates in kidney transplant biopsies among groups. Flow cytometry showed fewer lymphocytes and total, CD4+, and CD8+ peripheral T cells in iMVI compared with ABMR and normal cases. ABMR and iMVI had fewer total natural Killer (NK) cells but more NKG2A+ NK cells. Immunohistochemistry indicated that ABMR and iMVI had greater CD3+ and CD68+ glomerular infiltration than normal biopsies, whereas CD8+ and TIA1+ cells showed only increased iMVI, suggesting they are cytotoxic T cells. Peritubular capillaries displayed more CD3+, CD56+, TIA1+, and CD68+ cells in both ABMR and iMVI. In contrast, iMVI had less plasma cell infiltration in peritubular capillaries and interstitial aggregates than ABMR. iMVI displayed decreased circulating T and NK cells mirrored by T cell and NK cell infiltration in the renal allograft, similar to ABMR. However, the lesser plasma cell infiltration in iMVI may suggest an antibody-independent underlying stimulus.

Podocytopathy in patients with monoclonal gammopathy: three patients and literature review.

BACKGROUND: Renal manifestations of monoclonal gammopathies are of increasing interest among nephrologists. Typical manifestations include light chain cast nephropathy, amyloidosis or renal damage mediated by monoclonal immunoglobulin deposition. Podocytopathies in the setting of an underlying monoclonal gammopathy constitute a rare manifestation of these diseases and, although being described in the literature, remain a challenge since most data derive from case reports. METHODS: A retrospective review of the clinical data of Hospital del Mar and Hospital Vall d'Hebron was performed to identify patients with minimal change disease (MCD) or focal and segmental glomerulosclerosis (FSGS) in the setting of neoplasms that produce monoclonal (M) protein. Additionally, a literature review on this topic was performed. This study aims to describe the clinical characteristics and outcomes of these patients. RESULTS: Three patients were identified to have podocytopathy and monoclonal gammopathy between the years 2013 and 2020. All three were males and  >65 years of age. Two patients were diagnosed with MCD and one patient was diagnosed with FSGS. All patients underwent a kidney biopsy and light and electron microscopic studies were performed. The underlying causes of monoclonal gammopathy were multiple myeloma in two cases and Waldeström macroglobulinemia in one case. Two patients developed nephrotic syndrome during the follow-up. All patients were under active hematological treatment. One patient presented a complete remission of proteinuria whereas the other two presented a partial remission. CONCLUSIONS: Podocytopathies may infrequently be found in patients with monoclonal gammopathies. Patients with overt glomerular proteinuria and hematological disorders with M protein should undergo a kidney biopsy for prompt diagnosis and to specify a prognosis. In addition, further study on this matter must be done to understand the pathophysiology and treat these patients appropriately.