Mesangial proliferative glomerulonephritis in murine malaria parasite, Plasmodium chabaudi AS, infected NC mice.

BACKGROUND: Malaria is an important tropical disease and has remained a serious health problem in many countries. One of the critical complications of malarial infection is renal injury, such as acute renal failure and chronic glomerulopathy. Few animal models of nephropathy related to malarial infection have been reported. Therefore, we developed and investigated a novel malarial nephropathy model in mice infected by murine malaria parasites. METHODS: NC mice and C57BL/6J mice were infected with Ttwo different murine malaria parasites, Plasmodium (P.) chabaudi AS and P. yoelii 17X. After the infection, renal pathology and blood and urinary biochemistry were analyzed. RESULTS: NC mice infected by the murine malaria parasite P. chabaudi AS, but not P. yoelii 17X, developed mesangial proliferative glomerulonephritis with endothelial damage, and decreased serum albumin concentration and increased proteinuria. These pathological changes were accompanied by deposition of immunoglobulin G and complement component 3, mainly in the mesangium until day 4 and in the mesangium and glomerular capillaries from day 8. On day 21, renal pathology developed to focal segmental sclerosis according to light microscopy. In C57BL/6J mice, renal injuries were not observed from either parasite infection. CONCLUSION: The clinical and pathological features of P. chabaudi AS infection in NC mice might be similar to quartan malarial nephropathy resulting from human malaria parasite P. malariae infection. The NC mouse model might therefore be useful in analyzing the underlying mechanisms and developing therapeutic approaches to malaria-related nephropathy.

Blood color is influenced by inflammation and independently predicts survival in hemodialysis patients: quantitative evaluation of blood color.

Blood color of dialysis patients can be seen routinely. Darkened blood color is often observed in critically ill patients generally because of decreased oxygen saturation, but little is known about the other factors responsible for the color intensity. In addition, quantitative blood color examination has not been performed yet. Therefore, no one has evaluated the predictive power of blood color. The aim of this study was to evaluate if blood color darkness reflects some medical problems and is associated with survival disadvantage. Study design is a prospective cohort study. One hundred sixty-seven patients were enrolled in this study. Quantification of blood color was done using a reflected light colorimeter. Demographic and clinical data were collected to find out the factors that can be related to blood color. Follow-ups were performed for 2 years to analyze the risk factors for their survival. Regression analysis showed that C-reactive protein and white blood cell count were negatively correlated with blood color. In addition, blood color was positively correlated with mean corpuscular hemoglobin concentration and serum sodium concentration as well as blood oxygen saturation. During a follow-up, 34 (20.4%) patients died. Cox regression analysis revealed that darkened blood color was an independent significant risk factor of mortality in hemodialysis patients as well as low albumin and low Kt/V. These results suggest that inflammation independently affects blood color and quantification of blood color is useful to estimate prognosis in patients undergoing hemodialysis. It is possible that early detection of blood color worsening can improve patients' survival.

Growth factor Midkine is involved in the pathogenesis of renal injury induced by protein overload containing endotoxin.

BACKGROUND: Growth factor Midkine (MK), which expresses on endothelial cells and renal proximal tubules, has been implicated in inflammation-related kidney diseases such as ischemic reperfusion-induced tubulointerstitial injury and diabetic nephropathy. The biological actions of MK are elicited through its chemotactic activity and chemokine-driven inflammatory pathway. Post-infectious glomerulonephritis is caused by the deposition of immune complexes into glomeruli by infiltrating a number of inflammatory cells. Therefore, we investigated whether MK might be involved in the pathogenesis of acute glomerulonephritis. METHODS: We induced endocapillary proliferative glomerulonephritis in 129/SV mice using intraperitoneal injections of a large amount of protein. RESULTS: In contrast to mice deficient in MK (Mdk (-/-)), Mdk (+/+) mice induced by protein overload demonstrated more diffuse cellular proliferation in the mesangial areas and capillary lumens, eventually leading to glomerular damage and tubulointerstitial injury. This pathological observation could be attributable to neutrophil infiltration through the chemotaxis and stimulation of the MK-macrophage inflammatory protein (MIP)-2 pathway, but appeared to be due to the MK-related immunoglobulin (Ig)G deposition and C3 activation. These findings are often seen in infectious-related glomerular injury. Furthermore, the profile of MK expression was strongly consistent with that of glomerular damage and tubulointersititial injury. CONCLUSION: This study might provide a new insight into understanding the deleterious role of MK in endocapillary proliferative glomerulonephritis induced by protein overload.

The quantitative evaluation of online haemodiafiltration effect on skin hyperpigmentation.

BACKGROUND: Skin pigmentation is a common problem for dialysis patients, but little is known about the factor responsible for the colour intensity. Middle-molecular-weight (MMW) substances have been suggested to be responsible for the skin colour. Several papers have reported that ß(2)-microglobulin (ß(2)-MG) correlates with the skin colour, and haemodiafiltration (HDF) is effective to reduce the skin hyperpigmentation. However, a quantitative skin colour follow-up on patients treated with online haemodiafiltration (online HDF) has not been performed. METHODS: Sixty-one patients were enrolled in this study. Quantification of skin colour was done using a reflected light colorimeter. Among them, 51 patients were under haemodialysis (HD), and the other 10 patients were under online HDF. Follow-ups to estimate the skin colour change were performed for 6 months. Among 10 patients under online HDF, four patients were also investigated by crossover way between HD and online HDF. RESULTS: Compared with controls, patients treated with HD had darker skin. The colour value was well correlated with age, haematocrit, sex, diabetes and ß(2)-MG but not with Kt/V. The skin colour got worse under HD treatment as well as the values of ß(2)-MG, but online HDF improved the hyperpigmentation and the ß(2)-MG values. CONCLUSIONS: Our data show the effectiveness of online HDF on skin colour and suggest that HD patients' skin colour can be improved by modality change.

Identification of hemodialysis patients' common problems using the International Classification of Functioning, Disability and Health.

The aim of this study was to identify the common health problems of Japanese patients on hemodialysis (HD) using the International Classification of Functioning, Disability and Health (ICF). The participants of this study had been on HD for at least five years when they were interviewed. The ICF checklist was used to initially interview 32 HD patients. Fifty-seven categories of the ICF Checklist were identified as impaired; another 35 ICF categories, chosen based on interviews and expert discussion, as well as 8 categories relevant to HD, were included in the final checklist. This final checklist was then used to interview 104 patients. Overall, 10 categories in "Body functions" and 3 categories in "Body structures" were reported as problems by more than 50% of patients. Two categories in "Activities and participation" and 4 categories in "Environmental factors" were reported as restricted or a barrier for more than 30% of patients. A higher percentage of patients who started HD before 50 years of age and had a longer duration of HD reported problems in "Body functions" and "Body structures", while more patients with a shorter duration of HD reported problems in relationships with their family. Japanese patients on maintenance HD have various physical and psychosocial problems. In addition, HD duration and the age when HD was started affect patients' reports of physical and psychosocial problems.