Manabe, S. (Tsukuba/Tokyo); Nitta, K. (Tokyo); Nagata, M. (Tsukuba)
Chronic kidney disease (CKD) is a global health burden with a high economic cost to the health system that results from the increasing number of patients with diabetes and hypertension, and from the aging of the population. CKD has been associated with increased risks of cardiovascular morbidity, premature mortality, and/or decreased quality of life (QOL). The current volume entitled Recent Advances in the Pathogenesis and Treatment of Kidney Diseases incorporates many papers reviewed by faculty members of the Department of Medicine, Kidney Center, Tokyo Women’s Medical University, Tokyo, Japan.
The first paper in this volume of the book series Contributions to Nephrology discusses the role of caveolae in albumin passage through glomerular endothelial and epithelial cells, as shown by Moriyama et al. The authors suggest that albumin enters into glomerular endothelial and epithelial cells through caveolae; subsequent transcytosis of albumin is not actin- or microtubule-dependent in glomerular endothelial cells, but is actin-dependent in glomerular epithelial cells.
Iwabuchi et al. describe that rituximab has a beneficial effect, with the sustained remission or reduction of proteinuria in patients with steroid-dependent minimal change nephrotic syndrome. Rituximab is a chimeric murine/human monoclonal immunoglobulin G1 antibody that targets CD20, a B-cell differentiation marker. B-cell recovery begins at approximately 6 months following the completion of treatment.
Kataoka et al. show that the renal corpuscle size (glomerular size) is an easily measurable parameter and potentially acts as a predictor of long-term renal function. Large renal corpuscles could be used to guide therapy. In this review, after identifying the pitfalls regarding the assessment of mean values in medical research, we propose that the measurement of the maximum glomerular profile in renal biopsies would provide valuable insights into the diagnosis, prognosis, and management of kidney diseases.
According to Mochizuki et al., hereditary cystic kidney diseases are considered as “ciliopathies” caused by abnormalities of the “primary cilia” situated on the tubules. As a result of dysplasia and dysfunction of cilia, formation of cysts occurs at various stages of life. Although occurring at a low incidence, hereditary cystic kidney diseases that develop from the fetal stage to childhood are diverse and are often associated with systemic disorders.
Karasawa et al. demonstrate the concept of therapeutic approach for lupus nephritis (LN). In LN induction therapy until recently, cyclophosphamide in combination with prednisone (PSL) has been the standard method of treatment of proliferative forms of LN. Recently, the combination of mycophenolate mofetil has become a standard treatment option. Furthermore, multi-target therapy with tacrolimus added to PSL and mycophenolate mofetil, with reference to regimen after organ transplantation, has also been reported.
Hanafusa et al. report that older dialysis population is growing, and malnutrition and wasting syndrome is a great concern in this population. However, whether management in the forms of an increase in protein intake has a beneficial effect on muscle mass has not been demonstrated. In this volume, Hanafusa et al. evaluated an association between changes in normalized protein catabolic rate and percent creatinine generation rate (%CGR) in patients receiving hemodialysis (HD). The results showed that increase in normalized protein catabolic rate was associated with increase in %CGR. The association was stronger in patients with baseline %CGR levels below 100%.
Ogawa et al. describe that there was no consideration in terms of iron metabolism or the long-term safety of intravenous iron supplementation. This study presents information regarding iron metabolism in patients on HD, factors that influence iron metabolism in such patients, and the problems with existing treatment guidelines in Japan, apart from discussing the optimal iron levels and optimal Hb production indices.
Oka et al. introduce the therapeutic efficacy of cell sheet transplantation in the treatment of kidney disease. The 2-dimensional cell sheet can produce proteins such as erythropoietin, and is thus suitable for transplantation into the living body. It would be desirable to develop cell sheet therapy for the suppression of kidney damage in future, taking advantage of the beneficial characteristics of cell sheets.
Ogawa et al. show the pathogenesis and treatment of left ventricular diastolic dysfunction (LVDD) in CKD patients. The pathogenesis of LVDD includes abnormal ventricular filling in diastole and a higher LV filling pressure because of LV hypertrophy in addition to myocardial interstitial fibrosis. Therefore, LVDD tends to cause pulmonary congestion. The main strategy for treating LVDD is to minimize the large volume shift to control blood pressure and prevent myocardial interstitial fibrosis.
Unagami et al. describe post-transplantation anemia (PTA), which could be related to a variety of factors, including the renal function status, graft rejection episodes, and infectious causes. Early PTA is associated with a risk of death and cardiovascular disorders; however during this phase, priority is given to appropriate maintenance of immunosuppression rather than to the treatment of anemia. Maintenance-phase PTA exerts a strong influence on the survival, prognosis of the transplanted kidney, QOL, etc. Proper management of PTA could be expected to be associated with an improvement prognosis of the transplanted kidney and improved patient survival in kidney transplant recipients.
Nitta et al. show the role of frailty on outcomes of dialysis patients. Frailty has recently come to be considered one of the risk factors for mortality in the older dialysis population. Interventions to improve frailty have the potential to contribute to better QOL and lower mortality among dialysis patients. In addition, greater attention should be focused on the possibility that early rehabilitation of dialysis patients might improve poor outcomes.
Takura et al. describe the cost effectiveness of rituximab for treating nephrotic syndrome. The research team compared the number of relapses and total medical costs in the 24-month period before and the same period after patients took rituximab. We found that relapse decreased, and the total medical costs shrunk. The study also identified a correlation between lower urinary protein levels and a reduction in total medical costs. Rituximab therefore proved to be clinically beneficial and was also cost-effective.
Omae et al. demonstrate the results of the study by showing the relationship between the use of beta-blocker and ischemic cerebral and cardiovascular deaths in HD patients. A total of 108 matched pairs were extracted from a whole cohort. Through the use of beta-blockers, a significant increase in ischemic cerebral and cardiovascular deaths was observed. Beta-blocker administration to dialysis patients may worsen the cardiovascular prognosis, so sufficient examination will be needed in the future.
Manabe et al. show the direct effects of immunomodulatory agents on podocytes in immune-mediated glomerular diseases. In immune-mediated glomerular diseases, a variety of immunomodulatory agents are used to maintain podocytes by systemic immunosuppression. However, in contrast to the indirect therapeutic strategy mediated by immunosuppression, recent data suggest that immunomodulatory agents directly act on podocytes in an agent-dependent manner. In this review, they discuss the molecular targets and mechanisms by which immunomodulatory agents alleviate podocyte injury and examine their clinical significance.
We hope that you will enjoy the diverse range of papers published in this volume of Contributions to Nephrology and that you will plan a future clinical research to find new diagnostic markers and to establish useful therapeutic approach for various kidney diseases.
Kosaku Nitta, Tokyo
Nitta K (ed): Recent Advances in the Pathogenesis and Treatment of Kidney Diseases. Contrib Nephrol. Basel, Karger, 2018, vol 195, pp 1–11 (DOI: 10.1159/000486929)
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