Glomerular Hematuria: Cause or Consequence of Renal Inflammation?

Abstract

Glomerular hematuria is a cardinal symptom of renal disease. Glomerular hematuria may be classified as microhematuria or macrohematuria according to the number of red blood cells in urine. Recent evidence suggests a pathological role of persistent glomerular microhematuria in the progression of renal disease. Moreover, gross hematuria, or macrohematuria, promotes acute kidney injury (AKI), with subsequent impairment of renal function in a high proportion of patients. In this pathological context, hemoglobin, heme, or iron released from red blood cells in the urinary space may cause direct tubular cell injury, oxidative stress, pro-inflammatory cytokine production, and further monocyte/macrophage recruitment. The aim of this manuscript is to review the role of glomerular hematuria in kidney injury, the role of inflammation as cause and consequence of glomerular hematuria, and to discuss novel therapies to combat hematuria.

Association of Proteinuria and Hematuria with Acute Kidney Injury and Mortality in Hospitalized Patients with COVID-19

“…For example, in-hospital AKI is associated with proteinuria, and this relationship increases with severity of AKI, possibly leading to CKD [23,24]. Hematuria was also reported to be associated with AKI, both as a possible cause through tubular obstruction and heme pigment-induced kidney injury as well as a consequence of AKI due to renal inflammation [25,26]. Data on the prevalence, risk, and associated outcomes related to proteinuria and hematuria in patients with COVID-19 are more limited.…”

Hematuria Is Associated with More Severe Acute Tubulointerstitial Nephritis

“…Along the same lines, we recently observed that up to 25% of IgA nephropathy patients with haematuria-associated AKI do not recover baseline renal function, suggesting long term negative effects [12]. The deleterious effects of haematuria include direct tubular damage by intratubular obstruction by red blood cell casts, toxic effects of haemoglobin (Hb) and haem on kidney epithelial cells, and erythrophagocytosis by renal tubular cells [13]. In tubular cells, Hb induces oxidative stress, cell death, and pro-inflammatory and pro-fibrotic responses [13].…”

“…The deleterious effects of haematuria include direct tubular damage by intratubular obstruction by red blood cell casts, toxic effects of haemoglobin (Hb) and haem on kidney epithelial cells, and erythrophagocytosis by renal tubular cells [13]. In tubular cells, Hb induces oxidative stress, cell death, and pro-inflammatory and pro-fibrotic responses [13].…”

Kidney Inflammation, Injury and Regeneration

“…This Special Issue covers research articles that investigated the molecular mechanisms of inflammation [1][2][3] and injury [4,5] during different renal pathologies and renal regeneration [6], diagnostics using new biomarkers [7][8][9], and the effects of different stimuli like medication or bacterial components on isolated renal cells or in vivo models [10][11][12], all of which were summarized in a very simplified manner. Furthermore, this Special Issue contains important reviews that dealt with the current knowledge of cell death and regeneration [13,14], inflammation [15][16][17][18], and the molecular mechanisms of kidney diseases [19][20][21][22]. In addition, the potential of cell-based therapy approaches that use mesenchymal stromal/stem cells (MSCs) or their derivates is summarized [23][24][25].…”

“…MSCs predominantly act through secreted factors, including microRNAs that are contained within extracellular vesicles, cytoprotective effects anti-inflammatory effects, anti-apoptotic effects, and the suppression of oxidative stress. In addition, further reviews summarized the inflammation-mediated mechanisms or the inflammasome in various renal diseases [15][16][17][18]26,27]. Very interesting and new approaches shed a light on the role of non-coding RNAs, either in the progression of glomerular or tubulointerstitial kidney diseases [20] or as new therapeutic targets or biomarkers for fibrotic changes [29].…”