Relation of peritubular capillary features to class of lupus nephritis

Abstract

BackgroundExperimental studies have linked peritubular capillary (PTC) loss with progression of chronic kidney disease. Minimal information on PTC in lupus nephritis (LN) has been reported. We therefore evaluated the PTC area in different classes of LN and determined if specific clinical characteristics correlated with PTC changes.MethodsRenal biopsies of 253 subjects with LN (categorized using the ISN/RPS 2003 classification) and 13 normal renal donors (the controls) were retrospectively evaluated for PTC morphology by staining for CD31 with immunohistochemistry method. The percent positive area of PTC (% PTC) was correlated with serum and urinary measures of renal function and renal pathology.ResultsSignificant PTC loss was observed in all classes of LN compared to controls. The % PTC area was highest in controls (7.64±1.48 %) with levels of 1.95±1.50, 4.16±3.85, 4.19±4.45, 5.02±1.79, and 4.45±3.75 in classes II, III, IV, IV combined with V and V, respectively (all p values < 0.05). The lowest PTC density was observed in class II LN, but this may be because some cases with worse classes of LN showed increased PTC density due to abnormally dilated capillaries associated with acute inflammation and angiogenesis. %PTC was increased in those with hematuria (5.8±5.2 vs. 3.6±3.4 %, red blood cells 3-10 vs. < 3 cells/high power field, p < 0.05) and was reduced in those with a moderately declined renal function (3.29±3.40 vs. 4.42±4.12, eGFR 15-59 vs. ≥ 60 ml/min/1.73 m2, p < 0.05). Nephrotic-range proteinuria also trended to be associated with lower PTC density although it did not reach statistical significance (3.1±2.6 vs. 4.9±4.5, p= 0.067).ConclusionsLN is associated with PTC loss and the severity correlates with reduced renal function. Further studies are needed to investigate whether a loss of PTC can predict long term renal outcomes in LN.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-016-0388-2) contains supplementary material, which is available to authorized users.

Peritubular Capillary Rarefaction: An Underappreciated Regulator of CKD Progression

“…Regardless of initial insults, chronic injuries to the kidney frequently induce tubular atrophy, fibrosis, inflammation and peritubular capillary (PTC) rarefaction (Figure 1). PTC rarefaction is identified not only in diabetic nephropathy and hypertensive kidney diseases, two major causes of CKD [4][5][6], but also in advanced IgA nephropathy [7], congenital nephrotic syndrome [8], lupus nephritis [9], polycystic kidney disease [10,11], and allograft nephropathy [12,13], suggesting that PTC loss is a very common event in patients with CKD. Interestingly, the aging process itself accelerates PTC rarefaction [14].…”

Clinical Relevance of Computationally Derived Attributes of Peritubular Capillaries from Kidney Biopsies

“… 34 , 35 , 37 – 40 , 42 The observation that PTC rarefaction is associated with disease progression and age has also been validated in a variety of other human kidney diseases. 26 – 52 , 55 …”

“…Building on these observations 26 – 55 and leveraging the rich NEPTUNE dataset 13 and powerful image analysis tools, 11 , 12 , 21 we extracted selective PTC quantitative features, including density, size, and aspect ratio, from DL-derived PTC segmentations and assessed their associations with disease progression. We demonstrated that the shape of PTCs is a previously unrecognized biomarker of disease progression.…”

Treatment of renal interstitial fibrosis with an agonistic Tie2 monoclonal antibody via amelioration of peritubular capillary lesions in a mouse model of nephropathy

“…There is increasing evidence to show that peritubular capillaries play an important role in CKD and are a key regulator of CKD progression [39]. Peritubular capillary rarefaction is found not only in diabetic nephropathy [40] and hypertensive nephropathy [41], but also in IgA nephropathy [42], congenital nephrotic syndrome [43], lupus nephritis [44], and polycystic kidney disease [45]. Thus, protecting peritubular capillaries is a crucial approach to alleviating renal brosis [46][47][48][49].…”