Immune-complex glomerulonephritis in cats: a retrospective study based on clinico-pathological data, histopathology and ultrastructural features

Abstract

Background Chronic kidney disease (CKD) has typically a non-immune mediated origin in cats and immune-complex glomerulonephritis (ICGN) is scarcely described. Aims of this study were to characterize ICGN by light and electron microscopy and identify associations with clinico-pathological findings. In addition, comparisons between cats with ICGN and non immune-complex glomerulonephritis (non-ICGN) were performed. Renal samples examined between 2010 and 2019 were considered if both light and electron microscopy were performed. Signalment, feline immunodeficiency virus (FIV) and leukemia virus (FeLV) status, serum creatinine concentration, urine protein-to-creatinine (UPC) ratio, systolic blood pressure (SBP) and International Renal Interest Society (IRIS) stage were retrieved and used for comparisons. Results Sixty-eight client-owned cats were included. Thirty-seven cats (54.4%) had ICGN and 31 (45.6%) non-ICGN. Eighteen (48.6%) with ICGN had membranous glomerulonephropathy (MGN), 14 (37.8%) membranoproliferative glomerulonephritis (MPGN), and 5 (13.5%) mesangioproliferative glomerulonephritis (MeGN). Clinico-pathological data were not associated with any type of ICGN. Among cats with non-ICGN, 11 (35.5%) had end-stage CKD, 9 (29%) focal segmental glomerulosclerosis, 6 (19.4%) global and multifocal mesangiosclerosis, 2 (6.5%) glomerular atrophy, 2 (6.5%) renal dysplasia and 1 (3.1%) amyloidosis. Eight (25.8%) cats with non-ICGN had chronic interstitial nephritis (CIN) grade 1, 13 (41.9%) grade 2 and 10 (32.3%) grade 3; creatinine and UPC ratio increased with CIN grades ( p = 0.001, p < 0.001). Cats with ICGN were more frequently FIV or FeLV-infected (OR:11.4; 95%CI:1.4–94.4; p = 0.024), had higher UPC ratio (OR:6.8; 95%CI:2.5–18.2; p < 0.001) and were younger (OR:0.9; 95%CI:0.7–1.0; p = 0.042) than cats with non-ICGN. Conclusions MGN and MPGN were the most common morphological diagnoses of ICGN in cats. Unfortunately, none of the investigated findings differentiated ICGN morphological diagnoses. Serum creatinine concentration and UPC ratio were directly associated with grades of CIN (p = 0.001 and p < 0.001, respectively), confirming previous literature. More ICGN than non-ICGN was observed in cats with retroviral infections, younger cats and higher UPC ratio.

Clinicopathologic and pathologic characteristics of feline proteinuric kidney disease

“…13,14 An apparent male predilection exists for MGN; in the present study, 10/12 affected cats were males, similar to 8/11 and 11/18 affected cats described in previous studies. 10,14 MPGN was the second-most common cause of feline PLN in this study, similar to a previous report from Europe. 10 MPGN differs from MGN in that immune complexes are deposited beneath the endothelium, and in other species may be a primary or post-infectious, paraneoplastic or drugrelated autoimmune disease.…”

“…10,14 MPGN was the second-most common cause of feline PLN in this study, similar to a previous report from Europe. 10 MPGN differs from MGN in that immune complexes are deposited beneath the endothelium, and in other species may be a primary or post-infectious, paraneoplastic or drugrelated autoimmune disease. 5 In contrast to studies performed in dogs, focal segmental glomerulosclerosis was a relatively rare finding in our population of cats.…”

“…In a retrospective study evaluating European cats with ICGN, a much older population of cats was identified (median age 8.9 years). 10 This disagreement in signalment associated with ICGN underscores the need for further identification and study of this disease process in feline patients.…”

“…6 Additionally, in a study that compared cats with ICGN with cats without ICGN (including both cats with non-ICGN glomerular disease, as well as cats with TI nephritis), a UPC cut-off of >3.8 was necessary to distinguish ICGN from other causes of proteinuria. 10 Both studies suggest that higher UPCs are more likely to be glomerular in origin but that this is not an absolute rule. Similarly, in the present study, the median UPC for cats with PLN was 7.9 vs 1.1 in cats with TI disease.…”

“…6 In dogs, causes and outcomes of PLN have been previously described. 1,[8][9][10] PLN can be further subcategorized as immune-mediated vs non-immune, and appro ximately 50% of dogs biopsied for suspected glomerular disease have immune complex deposition within the glomerulus of the kidney (immune-complex glomerulonephritis; ICGN). 8,9 In these cases, treatment options are not limited to symptomatic therapies aimed at decreasing proteinuria (ie, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers).…”