Features of the course of hemorrhagic fever with renal syndrome in HIV-infected patients

Human immunodeficiency virus (HIV) is a significant medical and social problem for many developed countries. HIV infection is featured with developing chronic kidney pathology as well as acute renal damage. In some regions, hemorrhagic fever with renal syndrome (HFRS) can contribute somehow to developing renal pathology in HIVinfected subjects. The aim of the study was to identify clinical and laboratory features of HFRS course during HIV infection. A retrospective study was conducted by forming two groups: group 1 consisted of 9 patients suffered from HFRS together with verified HIV infection, group 2 — 53 patients with HFRS but lacking any clinical and epidemiological indications supporting HIV infection. Subjects in both groups were age- and sex-matched. The average age of the patients in group 1 and group 2 was 34 and 31 years, respectively. For statistical analysis, the licensed SPSS 22.0 software was used. A significance level p for statistical criteria was set equal to 0.05. In general, HFRS course in all patients was accompanied by characteristic signs: intoxication syndrome, impaired vision, hemorrhagic rash, pain in the lumbar region, decreased diuresis, thrombocytopenia, proteinuria, polymorphic urinary syndrome and azotemia. HFRS patients with concomitant HIV infection often complain of dry mouth, bloating, visible shortness of breath. Laboratory changes describe more severe kidney damage. A direct strong correlation was shown between leukocyte count and level of blood urea in patients with concomitant HIV infection (r = 0.798; p = 0.01). The combination of HFRS and HIV was accompanied by a milder HFRS course — rate of mild disease was almost 6-fold higher among patients of this group. In this case, no cases of severe hemorrhagic fever with renal syndrome combined with HIV were noted. Our study allowed to obtain unambiguous data. Predisposition of HIV-infected patients to renal pathology may be a determining factor in kidney damage upon emerging HFRS: more prominent rise in creatinine and urea level. Moreover, according to rating scale for assessing HFRS severity, it formally turned out that during concomitant HIV infection patients more often fit to a mild disease severity, even in the presence of more pronounced renal manifestations. The occurrence of acute renal pathology in HIV-infected patients is a life-threatening condition, a factor of deterioration of chronic renal pathology and a predictor of death. Consequently, this patient population requires thorough monitoring both at inpatient and outpatient stages.

Evaluation of ultrastructural alterations of glomerular basement membrane and podocytes in glomeruli by low-vacuum scanning electron microscopy

Background Low-vacuum scanning electron microscopy (LV-SEM) is applied to diagnostic renal pathology. Methods To demonstrate the usefulness of LV-SEM and to clarify the optimal conditions of pathology samples, we investigated the alterations of glomerular basement membrane (GBM) and podocytes in control and experimental active Heymann nephritis (AHN) rats by LV-SEM. Results On week 15 following induction of AHN, spike formation on GBM with diffuse deposition of IgG and C3 developed. Using LV-SEM, diffuse crater-like protrusions were clearly noted three-dimensionally (3D) on surface of GBM in the same specimens of light microscopy (LM) and immunofluorescence (IF) studies only after removal coverslips or further adding periodic acid-silver methenamine (PAM) staining. These 3D ultrastructural findings of GBM surface could be detected in PAM-stained specimens by LV-SEM, although true GBM surface findings could not be obtained in acellular glomeruli, because some subepithelial deposits remained on surface of GBM. Adequate thickness was 1.5–5 μm for 10% formalin-fixed paraffin-embedded (FFPE) and 5–10 μm for the unfixed frozen sections. The foot processes and their effacement of podocytes could be observed by LV-SEM using 10%FFPE specimens with platinum blue (Pt-blue) staining or double staining of PAM and Pt-blue. These findings were obtained more large areas in 2.5% glutaraldehyde-fixed paraffin-embedded (2.5%GFPE) specimens. Conclusion Our findings suggest that LV-SEM is a useful assessment tool for evaluating the alterations of GBM and podocytes in renal pathology using routine LM and IF specimens, as well as 2.5%GFPE specimens.

Change of Renal Gallium Uptake Correlated with Change of Inflammation Activity in Renal Pathology in Lupus Nephritis Patients

Background: Lupus nephritis (LN) often lead to end-stage renal disease in systemic lupus erythematosus patients. This study aimed to investigate the clinical application of renal gallium-67 scans for determining renal histological parameters in LN patients. Methods: Between 2006 and 2018, 237 biopsy-proven and 35 repeat biopsies LN patients who underwent renal gallium scans before or after biopsy were included for analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. A delayed 48-h gallium scan was performed and interpreted by semiquantitative methods using left kidney/spine (K/S) ratio. The renal histological results were compared with gallium uptake. Results: Out of 237 participants, 180 (76%) had proliferative LN. Baseline gallium left K/S ratio was significantly higher in class IV LN as compared to class III (median (interquartile range, IQR): 1.16 (1.0–1.3), 0.95 (0.9–1.1), respectively, p < 0.001). Furthermore, changes in gallium uptake between two biopsies were positively correlated with changes activity index (r = 0.357, p = 0.035), endocapillary hypercellularity (r = 0.385, p = 0.032), and neutrophils infiltration (r = 0.390, p = 0.030) in renal pathology. Conclusions: Renal gallium uptake is associated with active inflammation in LN. Changes in renal gallium uptake positively correlated with changes in activity index in renal pathology.

Coagulation Abnormalities in Renal Pathology of Chronic Kidney Disease: The Interplay between Blood Cells and Soluble Factors

Coagulation abnormalities in renal pathology are associated with a high thrombotic and hemorrhagic risk. This study aims to investigate the hemostatic abnormalities that are related to the interaction between soluble coagulation factors and blood cells, and the effects of hemodialysis (HD) on it, in end stage renal disease (ESRD) patients. Thirty-two ESRD patients under HD treatment and fifteen healthy controls were included in the study. Whole blood samples from the healthy and ESRD subjects were collected before and after the HD session. Evaluation of coagulation included primary and secondary hemostasis screening tests, proteins of coagulation, fibrinolytic and inhibitory system, and ADAMTS-13 activity. Phosphatidylserine (PS) exposure and intracellular reactive oxygen species (iROS) levels were also examined in red blood cells and platelets, in addition to the platelet activation marker CD62P. Platelet function analysis showed pathological values in ESRD patients despite the increased levels of activation markers (PS, CD62P, iROS). Activities of most coagulation, fibrinolytic, and inhibitory system proteins were within the normal range, but HD triggered an increase in half of them. Additionally, the increased baseline levels of ADAMTS-13 inhibitor were further augmented by the dialysis session. Finally, pathological levels of PS and iROS were measured in red blood cells in close correlation with variations in several coagulation factors and platelet characteristics. This study provides evidence for a complex coagulation phenotype in ESRD. Signs of increased bleeding risk coexisted with prothrombotic features of soluble factors and blood cells in a general hyperfibrinolytic state. Hemodialysis seems to augment the prothrombotic potential, while the persisted platelet dysfunction might counteract the increased predisposition to thrombotic events post-dialysis. The interaction of red blood cells with platelets, the thrombus, the endothelium, the soluble components of the coagulation pathways, and the contribution of extracellular vesicles on hemostasis as well as the identification of the unknown origin ADAMTS-13 inhibitor deserve further investigation in uremia.