Glomerular Neovascularization in Nondiabetic Renal Allograft Is Associated with Calcineurin Inhibitor Toxicity

Abstract

<b><i>Introduction:</i></b> Extra efferent arterioles, also known as polar vasculosis (PV), are often observed in the glomerular vascular pole and are associated with glomerular hypertrophy, indicating early recurrent diabetic kidney disease (DKD) in renal allografts. However, its significance in patients without diabetes remains uncertain. <b><i>Methods:</i></b> A total of 9,004 renal allograft biopsy specimens obtained between January 2007 and December 2017 at Tokyo Women’s Medical University were retrospectively analyzed to examine the clinical and pathological significance of PV in renal allografts. PV was identified in 186 biopsy specimens obtained from 165 patients. The PV group comprised 46 patients; 35 patients without DKD and 11 patients with DKD as the initial cause of ESRD, whose clinical information was available and treated with the calcineurin inhibitor (CNI) tacrolimus. The non-PV group comprising patients with renal allografts matched for age and postoperative day included 93 patients without DKD and 16 patients with DKD as the initial cause of ESRD. <b><i>Results:</i></b> In patients with nondiabetic renal allografts, systolic blood pressure was significantly higher in the PV group than in the non-PV group. The trough tacrolimus levels during the overall study period and at 2 weeks, 1 month, and 2 years after transplantation were significantly higher in the PV group compared with the non-PV group. Glomerulomegaly was significantly more common. Moreover, ah and aah scores in Banff score were significantly higher in the PV group than in the non-PV group. In those with diabetic renal allografts, although the clinical parameters and tacrolimus trough levels in all time periods were not significantly different between the PV and non-PV groups, the ah score was significantly higher in the PV group. <b><i>Conclusion:</i></b> PV was associated with CNI toxicity in nondiabetic but not in diabetic renal allografts. The pathogenesis of PV in renal allografts is considered to be multifactorial.

Polar vasculosis is associated with better kidney outcome in type 2 diabetes with biopsy‐proven diabetic kidney disease: A multicenter cohort study

“…In the multivariate logistic regression analysis, IFTA was negatively associated with polar vasculosis, whereas subendothelial widening of GBM, glomerulomegaly, glomerular class by the RPS classification ≥IIb, vascular lesions, age, eGFR, and hemoglobin A1c were positively associated with polar vasculosis. Previous several studies have shown the relationships between polar vasculosis and more advanced mesangial expansion, glomerulomegaly, and arteriolar hyalinosis in human DKD, consistent with this study 5 , 6 , 7 , 11 . Notably, this study also found a negative correlation between polar vasculosis and IFTA in addition to previous findings.…”

“…Abnormal angiogenesis is involved in the pathogenesis of DKD, and the development of extra vessels, termed polar vasculosis (perihilar neovascularization), is noted as an early kidney lesion in DKD 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 . Although the exact structure of polar vasculosis is currently unknown, a study using reconstruction of three‐dimensional images suggests that these vessels are angiogenesis connecting afferent arterioles, anastomosed glomerular capillaries, efferent arterioles, and peritubular capillaries 4 .…”

Development of angiogenic periglomerular microvessels after acute glomerular lesions in IgA nephropathy

“…It is well known that the polar type of PGMVs is observed in hypertensive nephropathy, thrombotic microangiopathy, and calcineurin inhibitor nephrotoxicity in transplanted kidney. 23,24 On the other hand, it is possible that PGMVs may not be present in renal diseases with severe vascular damage, such as antineutrophil cytoplasmic antibody-associated vasculitis presenting with rapidly progressive glomerulonephritis, where good angiogenesis and capillary regeneration cannot be induced and renal biopsy is usually performed in the acute phase of diseases. Glomeruli are constructed by a highly developed and differentiated vascular network.…”