Clinical features of CKD-MBD in Japan: cohort studies and registry

Abstract

Randomized controlled trials (RCTs) are essential for evidence-based medicine; however, cohort studies and registries provide an important information about risk factors and, hence, shed light on the target of laboratory parameters. The uniqueness of the current Japanese CKD-MBD guidelines lies in the lower target range of intact parathyroid hormone levels than those used in other countries, which is based on analyses of the nationwide Japan Renal Data Registry. Cohort studies were also useful in exploring risk factors of renal outcome in predialysis patients. It was revealed that low vitamin D status (very prevalent in Japan) and high fibroblast growth factor 23 (FGF23) levels predict poor renal outcome. The reported association of FGF23 levels with left ventricular hypertrophy (LVH) and heart failure observed in cohort studies may support the idea of adding the 4th component of CKD-MBD, namely, "LVH" to the three original components. When it is not feasible to conduct RCTs regarding intervention, we have no choice but to rely on observational studies with sophisticated analysis methods, such as facility-level analysis and marginal structural model minimizing indication bias. Observational studies conducted in Japan revealed that the side effects of medications for CKD-MBD, resultant compliance, and effective doses in terms of hard outcome in Japanese patients were found to be different from those in other countries. For example, the MBD-5D study confirmed the benefit of cinacalcet in terms of mortality despite its median dose of only 25 mg/day. These data are very helpful for future guidelines specific to Japanese patients with CKD.

Parathyroid hormone and premature thymus ageing in patients with chronic kidney disease

“…Since atherosclerosis comprises vascular wall inflammation that is affected by the immune system, thymic atrophy in association with immune ageing might cause CVD. Serum PTH level is associated with the onset of CVD, infectious disease, and mortality in an epidemiological study 7,10,12,14 . For these reasons, PTH may be involved in the pathogenesis of these complications by inducing immune abnormality through thymic atrophy in addition to regulating bone metabolism.…”

Chronic Kidney Disease-Mineral and Bone Disorder in Asia

“…Ongoing economic development in these countries and areas will certainly contribute to the improvement of management in the near future. Policies for publishing and sharing of data regarding Asian CKD patients is most urgently required [48] , which should include data on pre-dialysis CKD patients and kidney transplant recipients [49] . Such data should also include costeffectiveness analyses [50,51] that take the local medical costs and system into consideration.…”

Cardiac hypertrophy in chronic kidney disease—role of Aldosterone and FGF23

“…Although this mechanism teleologically serves to act as an adaptive regulatory factor to maintain serum phosphate levels constant, further deterioration of CKD causes the elevation in serum phosphate concentrations, which hence would stimulate FGF23 production. Furthermore, of importance is the finding that elevated serum FGF23 concentrations are associated with the development of cardiac disorders [20][21][22][23]. Thus, apparently homeostatic mechanism for phosphate metabolism may act to aggravate cardiac disease, leading to cardiac hypertrophy and heart failure.…”