科研之友
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摘要
The changes in phosphate (PO4) metabolism across the spectrum of chronic kidney disease (CKD) and specific strategies to address these abnormalities by reducing PO4 loads are discussed in this review. This review also addresses briefly the evidence for specific PO4 serum targets in CKD and endstage renal disease (ESRD) and the potential for other biomarkers such as fibroblast growth factor-23 (FGF-23) to define disease and monitor the effectiveness of therapy. As renal function declines, single nephron excretion of PO4 must increase to maintain PO4 balance. Abnormalities in PO4 metabolism occur early in CKD. Compensatory changes in renal PO4 handling are sufficient to maintain a normal serum PO4 level in early stages of CKD, but in more advanced CKD, these processes no longer suffice and overt hyperphosphatemia develops. The resulting increased PO4 burden contributes directly to development of secondary hyperparathyroidism. The FGF-23 increases early in CKD, likely in response to abnormal PO4 metabolism, and mediates processes that help restore serum PO4 levels to normal in CKD stage 3 and in early stage 4. The increased PO4 burden and subsequent overt hyperphosphatemia are associated with increased mortality and morbidity. Dietary PO4 restriction, modification of dialysis prescriptions, and administration of oral PO4 binders can restore PO4 balance. As CKD progresses, population-based studies demonstrate that diet alone is typically not able to prevent or treat hyperphosphatemia. Dialysis modalities that are currently used often fail to remove sufficient PO4 to prevent hyperphosphatemia in patients with an inadequately controlled dietary PO4 load. This is particularly likely among patients without significant residual renal function. Thus, in the majority of ESRD patients, PO4 binders remain the mainstay of therapy for hyperphosphatemia. All currently available PO4 binders can restore serum PO4 to the required level when administered appropriately and in conjunction with dietary PO4 restrictions. PO4 binders differ regarding their potential side-effects and impact on long-term patient-centered outcomes. Which of the PO4 binders might result in the most favorable survival and cardiovascular morbidity profiles and which remain uncertain, remains a subject of considerable clinical investigation. Compelling observational and more limited randomized controlled trial (RCT) evidence support the view that PO4 binders might differ in their effects on mortality and/or morbidity. The limited evidence from RCTs is mostly congruent with the findings from large observational studies. In particular, evidences from both epidemiologic and RCT support the view that excess calcium administration may independently increase the risk of cardiovascular disease in individuals with normal renal function and in patients with CKD and ESRD. Additional RCT evidence might help determine the degree at which any increased risk from oral calcium exposure can be mitigated with the use of noncalcium-based PO4 binders.
Judicious control of PO4 early in CKD, possibly monitored by measures of FGF-23, could potentially reduce the risk of development of renal secondary hyperparathyroidism and all of the adverse clinical consequences of poorly controlled CKD-mineral and bone disorder. The mainstays of therapy are likely to include a balance of dietary restriction and PO4 binders to reduce PO4 input, and in ESRD patients, dialysis modalities to augment PO4 output.
- 出版日期2011-3
