GLOMERULAR DISEASE DIAGNOSIS
In this session of Nephropathology Essentials, Dr. Bijol utilized a case-based approach to review a variety of important nephropathology topics. Our Moderator’s Notes are derived from her live presentation.
By Dr. Pravir Baxi
Rarely, patients can have chronic, indolent glomerulonephritis that may be undiagnosed due to the absence of overt nephrotic/nephritic findings (e.g., asymptomatic, non-nephrotic proteinuria). These patients can potentially progress to have clinically significant renal disease.
Histologically active lesions on a renal biopsy can be missed or appear absent due to the focal nature of the disease and/or a result of a sampling error (e.g., medulla versus cortex). This can lead to delay in diagnosis or inadequate treatment, leading to an increased risk of CKD/ESKD.
In patients with pauci-immune (+ANCA) crescentic glomerulonephritis (GN), a complete search for secondary causes, including medications and infections, is recommended.
Common medications: hydralazine, allopurinol, anti-thyroid drugs (propylthiouracil>>methimazole), minocycline, penicillamine, levamisole
Typically, these patients will have very high MPO or PR3 levels, elevated ANA, low C3/C4, or atypical features on histopathology, such as low-level Ig deposition.
Vascular endothelial grow factor (VEGF) inhibition
VEGF inhibitors act through various mechanisms (via numerous downstream signaling pathways) and can lead to nephrotoxicity.
Most common renal presentations related to these agents are hypertension, proteinuria (which can progress to full nephrotic syndrome), and thrombotic microangiopathy (TMA). ATN has also been described.
On renal biopsy, common histologic findings include endotheliosis, podocytopathy, TMA, and MPGN-pattern of injury.
Estrada CC, Maldonado A, Mallipattu S. Therapeutic Inhibition of VEGF Signaling and Associated Nephrotoxicities. J Am Soc Nephrol. 2019. https://www.ncbi.nlm.nih.gov/pubmed/?term=30642877
Hacking S, Uppal NN, Khan N, Ionescu M, and Bijol V. Systemic p-ANCA vasculitis with fatal outcome, arising in the setting of methimazole use. Clin Nephrol Case Stud. 2019. https://www.ncbi.nlm.nih.gov/pubmed/31008018
Radhakrishnan J, Perazella MA. Drug-induced glomerular disease: attention required! Clin J Am Soc Nephrol. 2015. https://www.ncbi.nlm.nih.gov/pubmed/25876771