SummaryHematuria is a common finding in various glomerular diseases. This article reviews the clinical data on glomerular hematuria and kidney injury, as well as the pathophysiology of hematuria-associated renal damage. Although glomerular hematuria has been considered a clinical manifestation of glomerular diseases without real consequences on renal function and long-term prognosis, many studies performed have shown a relationship between macroscopic glomerular hematuria and AKI and have suggested that macroscopic hematuria-associated AKI is related to adverse long-term outcomes. Thus, up to 25% of patients with macroscopic hematuriaassociated AKI do not recover baseline renal function. Oral anticoagulation has been associated with glomerular macrohematuria-related kidney injury. Several pathophysiologic mechanisms may account for the tubular injury found on renal biopsy specimens. Mechanical obstruction by red blood cell casts was thought to play a role. More recent evidence points to cytotoxic effects of oxidative stress induced by hemoglobin, heme, or iron released from red blood cells. These mechanisms of injury may be shared with hemoglobinuria or myoglobinuria-induced AKI. Heme oxygenase catalyzes the conversion of heme to biliverdin and is protective in animal models of heme toxicity. CD163, the recently identified scavenger receptor for extracellular hemoglobin, promotes the activation of anti-inflammatory pathways, opening the gates for novel therapeutic approaches.

IntroductionWhile some targeted agents should not be used in squamous cell carcinomas (SCCs), other agents might preferably target SCCs. In a previous microarray study, one of the top differentially expressed genes between adenocarcinomas (ACs) and SCCs is P63. It is a well-known marker of squamous differentiation, but surprisingly, its expression is not widely used for this purpose. Our goals in this study were (1) to further confirm our microarray data, (2) to analize the value of P63 immunohistochemistry (IHC) in reducing the number of large cell carcinoma (LCC) diagnoses in surgical specimens, and (3) to investigate the potential of P63 IHC to minimize the proportion of “carcinoma NOS (not otherwise specified)” in a prospective series of small tumor samples.MethodsWith these goals in mind, we studied (1) a tissue-microarray comprising 33 ACs and 99 SCCs on which we performed P63 IHC, (2) a series of 20 surgically resected LCCs studied for P63 and TTF-1 IHC, and (3) a prospective cohort of 66 small thoracic samples, including 32 carcinoma NOS, that were further classified by the result of P63 and TTF-1 IHC.ResultsThe results in the three independent cohorts were as follows: (1) P63 IHC was differentially expressed in SCCs when compared to ACs (p<0.0001); (2) half of the 20 (50%) LCCs were positive for P63 and were reclassified as SCCs; and (3) all P63 positive cases (34%) were diagnosed as SCCs.ConclusionsP63 IHC is useful for the identification of lung SCCs.

Background: Macroscopic hematuria (MH) may cause acute kidney injury (AKI) in IgA nephropathy. Up to 25% of patients with MH-associated AKI do not recover baseline renal function. Our objective was to identify subjects at high risk for an adverse renal function. Methods: We examined macrophages, oxidative stress markers (NADPH-p22 and HO-1) and the hemoglobin scavenger receptor (CD163) in renal biopsy specimens from 33 MH-AKI patients with complete recovery (CR, n = 17) or incomplete recovery (IR, n = 16) of renal function after 6.72 (range 0.5–21.5) years of follow-up. Results: CD163-expressing macrophages, HO-1 and NADPH-p22 expression were located in areas surrounding tubules with iron deposits and filled with erythrocyte casts. CD163-positive macrophages score and HO-1- and p22-positive staining correlated positively with percentage of tubules with erythrocyte casts and tubular necrosis. Macrophage infiltration, CD163-positive macrophage score, NADPH-p22- and HO-1-positive staining areas were significantly greater in IR patients when compared with CR patients. The CD163-positive macrophage score and oxidative stress markers (p22 and HO-1) were negatively correlated with renal function outcome, as determined by estimated glomerular filtration rate (eGFR) and proteinuria, at the end of the follow-up period. In multivariate analysis, the CD163-positive macrophage score remained significantly associated with final eGFR and proteinuria after adjustment by age, gender, duration of MH, initial eGFR and proteinuria. Conclusions: Increased macrophage infiltration, CD163 expression and oxidative stress are significant prognostic factors for an IR of renal function in patients with MH-associated AKI. These molecular pathways may be involved in the renal response to injury and could be useful to improve diagnosis and therapeutics.

IntroductionMicrothrombosis is often observed in lupus nephritis (LN) lesions, but its clinical significance is unknown. We evaluated the clinicopathologic correlations of renal microthrombosis and inflammatory markers in LN.MethodsKidney biopsies from 58 patients with systemic lupus erythematosus (SLE) proliferative nephritis were analyzed with immunohistochemistry (IHC) for intravascular platelet aggregates (CD61), macrophagic infiltration (CD68), and activated complement deposition (C4d). Clinical data at the time of kidney biopsy and follow-up were analyzed with regard to pathologic IHC data.ResultsMicrothrombosis was present in 52% of the tissues. It was significantly more prevalent in patients with antiphospholipid antibodies (aPLs) (62% versus 42%). The presence of microthrombosis significantly correlated with higher macrophagic infiltration. Macrophagic infiltration but not microthrombosis was significantly correlated with C4d deposition. Only macrophagic infiltration showed a correlation with SLE and renal activity (proteinuria and active sediment), whereas neither the presence of CD61+ microthrombi nor the extent of C4d deposition correlated with LN severity or outcome.ConclusionsMicrothrombosis is associated with higher macrophagic infiltration in LN but does not seem to increase independently the severity of renal damage. Macrophagic infiltration was the best marker of SLE and renal activity in this LN series.