The complex pathology of diabetic nephropathy in humans

Abstract

This review summarizes the pathomorphological sequences of nephron loss in human diabetic nephropathy (DN). The relevant changes may be derived from two major derangements. First, a failure in the turnover of the glomerular basement membrane (GBM) based on an increased production of GBM components by podocytes and endothelial cells leading to the thickening of the GBM and accumulation of worn-out GBM in the mesangium. This failure may account for the direct pathway to glomerular compaction and sclerosis based on the continuous deposition of undegraded GBM-material in the mesangium. Second, an increased leakiness together with an increased propensity of glomerular capillaries to proliferate leads to widespread plasma exudations. Detrimental are those that produce giant insudative spaces within Bowman's capsule (BC) spreading around the entire glomerular circumference and along the glomerulo-tubular junction onto the tubule resulting in tubular obstruction and retroactively to glomerulosclerosis. Tubular atrophy and interstitial fibrosis develop secondarily by transfer of the glomerular damage onto the tubule. Interstitial fibrosis is locally initiated and apparently stimulated by degenerating tubular epithelia. This leads to a focal distribution of interstitial fibrosis and tubular atrophy (IFTA) accompanied by a varying interstitial mononuclear cell infiltration. Spreading of fibrotic areas between intact nephrons, much less to the glomerulus, has not been encountered.

Glomerular crescents are associated with the risk of type 2 diabetic kidney disease progression: a retrospective cohort study

“…Because this study was retrospective and depended solely on pathology texts, obtaining tissue slides poses a challenge. This limitation hampers further investigation in areas such as examining the presence of urinary space collagen with fibrotic crescents to gauge diabetesrelated injury or determining the location of fibrinogen deposition in immunofluorescence and other changes (e.g., misdirected filtration and fibrinoid exudation) to speculate on the causes of crescent formation [43][44][45]. It is pertinent to note that all biopsies underwent review by pathologists at each center, indicating the reliability of histological reports.…”

The role of long non‐coding RNAs in the development of diabetic kidney disease and the involved clinical application

“…30 During the progression of diabetes, mesangial matrix components such as laminin (LN), fibronectin (FN), and collagen-IV (col-IV) accumulate, leading to mesangial expansion, which is pathologically crucial in DKD glomerulosclerosis. 31 Mesangial expansion during DKD formation is mediated using an intricate process. Numerous in vivo and in vitro modelling investigations have demonstrated that HG causes MCs to proliferate abnormally for a brief period followed by an inhibitory phase, reducing the rate of cell proliferation and causing cell hypertrophy.…”

“…MCs have the function of maintaining glomerular structure 30 . During the progression of diabetes, mesangial matrix components such as laminin (LN), fibronectin (FN), and collagen‐IV (col‐IV) accumulate, leading to mesangial expansion, which is pathologically crucial in DKD glomerulosclerosis 31 . Mesangial expansion during DKD formation is mediated using an intricate process.…”

Nephrotic syndrome: ethiological factors and differential diagnosis

“…Важное значение в патогенезе диабетической нефропатии придают подоцитопатии с формированием вторичного ФСГС, развивающегося под действием клубочковой гиперфильтрации, характерной для этого заболевания, а также других ассоциированных с сахарным диабетом факторов (активация ренин-ангиотензин-альдостероновой системы, конечные продукты гликирования, гиперли пидемия, инсулинорезистентность и др.) [37,38]. Поражение почек при сахарном диабете проявляется альбуминурией с последующей нарастающей протеинурией, формированием НС и постепенным ухудшением функции почек, хотя возможен "нормоальбуминурический" вариант течения диабетической болезни почек (чаще при сахарном диабете 2 типа), при котором наблюдается постепенное снижение скорости клу бочковой фильтрации при отсутствии значимой альбуминурии (морфологически характеризуется преимущественно сосудистым и тубулоинтерстициальным повреждением).…”