In our cross-sectional survey involving various geographic regions in China, the treatment of MBD was found to be sub-optimal among patients receiving mountainous dialysis. Uncontrolled hyperphosphatemia is especially prominent.
Hyperphosphatemia is an independent risk factor for both mortality [1, 10, 11] and renal function decline in CKD patients [12, 13]. A recent analysis of DOPPS  indicated that the lowest mortality was seen among patients with serum phosphorus 3.6 to 5.0 mg/dL, and higher mortality was observed in facilities with a higher proportion of patients with serum phosphorus greater than 6.0 mg/dL. Similarly, a meta-analysis indicated that the risk of death increased by 18% for every 1.0 mg/dL increase in serum phosphorus (relative risk of 1.18, 95% CI 1.12-1.25) in individuals with CKD . Compared with results from DOPPS, control of hyperphosphatemia in our study is sub-optimal, which may be related to the following factors. Firstly, restriction of dietary phosphorus is the primary strategy for controlling hyperphosphatemia. Unfortunately, nutritionist was not available for most HD and PD centers in China. In our analysis, although we did not have information of dietary intake of phosphorus, residency in southern China was observed to be an independent risk factor for hyperphosphatemia. It is well known that in southern China, foods containing rich phosphorus (eg. seafood and meat soup) are more likely to be consumed than in Northern China. A study using 24-hour dietary recalls also indicated that phosphorus intake was higher among Southern Chinese compared with that of Northern Chinese, which was 562 ± 67 mg/1000 kcal and 378 ± 76 mg/1000 kcal, respectively . Secondly, insufficient use of phosphorus binder was observed in our analysis. On the other hand, 46.5% of patients with serum calcium level above 9.5 mg/dL still were using calcium-containing phosphorus binder. In China, non-containing calcium phosphorus binders were not available. Therefore, inappropriate application of phosphorus binder may be related to hyperphosphatemia. Finally, our analysis revealed that HD was independently associated with higher risk of hyperphosphatemia, compared with PD patients. It has been shown that certain hemodialysis prescription may increase phosphorus clearance. Nocturnal HD [15, 16] and short daily HD [17, 18] was shown to reduce serum phosphorus levels and requirement for phosphorus binders. Membrane surface area itself has a potentially important impact on phosphorus removal. In a recent study in 18 patients over a period of 6 weeks, doubling of membrane area by the use of 2 dialyzers in parallel (with blood flow equally split between the dialyzers) resulted in a 1.34 mg/dL decline in predialysis serum phosphorus levels compared with conventional HD . A recent randomized controlled trial evaluated the effect of different hemodialysis prescription on hyperphosphatemia among 493 patients . It was shown that phosphorus levels decreased from 5.18 ± 0.10 mg/dL at baseline to 4.87 ± 0.10 mg/dL at 6 months in hemodiafiltration patients (P < 0.001) and were stable in low-flux HD patients (5.10 ± 0.10 mg/dL at baseline and 5.03 ± 0.10 mg/dL after 6 months, P = 0.5). After adjustment for phosphorus binder use, hemodiafiltration still have an advantage of improving phosphorus control over low-flux HD. In our study, low-flux HD was applied in the majority of our dialysis centers, which may also be related to poor phosphorus control. In summary, reducing phosphorus intake under the instruction of nutritionist, proper use of phosphorus binder, and adopting dialysis prescription with better phosphorus clearance may improve the sub-optimal treatment of hyperphosphatemia in China.
In K/DOQI guidelines, the optimal PTH levels was recommended to be 150-300 pg/ml for dialysis patients, which was based on the predictive ability of PTH for low-and high-turnover bone disease . However, the early studies of MBD parameters evaluated survival as a function of a single time point baseline measurement of PTH, thereby ignoring important changes in the parameter . Conversely, time dependent approaches are influenced strongly by events immediately proximal to the outcome and therefore may reflect worsening parameters caused by rapidly declining health status [10, 21]. More recently, there have been attempts at using cumulative-effects models by the Hemodialysis (HEMO) Study investigators to better capture the relationship between bone mineral metabolism parameters and survival, and they also have found higher ceilings for PTH levels than previous work . Analysis from the DOPPS also revealed an increased risk for all-cause mortality (not cardiovascular mortality) only when PTH > 600 pg/mL . Therefore, in the recently released guidelines from the kidney Disease: Improving Global Outcomes (KDIGO), it is suggested that iPTH levels should be maintained in the range of approximately two to nine times the upper limit of normal for patients receiving dialysis . In our study, about 56.7% of participants met the KDIGO target for PTH. However, more studies (especially interventional studies) are needed to verify the range suitable for better clinical outcome. In our study, the proportion of PD patients with PTH less than 150 pg/mL is not higher than HD patients. This may be related to the relatively low proportion of diabetes in PD patients and with short time on dialysis.
To date, there is no DOPPS-equivalent study looked at the management of mineral metabolism in PD patients. Compared with the data from Canadian PD patients , the present study demonstrated that the percentage of patients reached the K/DOQI targets for Ca (44.0% vs 44.7%) and iPTH (27.3% vs 28.4%) were similar among PD patients. However, the percentage of patients with hyperphosphatemia (> 5.5 mg/dL) and hypercalcemia (> 9.5 mg/dL) were higher than Canadian PD patients, which were 47.4% vs 21.2% and 36.6% vs 16.7%, respectively. It indicates that based on K/DOQI guidelines, Chinese PD patients are not within optimal target ranges and there is room for improvement.
Our study has several limitations that deserve mention. Firstly, study sites were enrolled on a voluntary basis, which might introduce bias. However, most of participants came from tertiary hospitals. Therefore, the direction of bias would be to overestimate the control rate of MBD. Secondly, some information of factors related to the MBD were not available in our study, such as diet, residual renal function, dialysis prescription and dialysis adequacy. Thirdly, laboratory tests were not performed in one central laboratory, therefore variability of measurement may affect the interpretation of our results. The same limitation exists for the comparison between our study and DOPPS study. Fourthly, the demographic characteristics and medical conditions of patients in our study might be different from those of participants in DOPPS study, which might contribute to the difference in parameters of MBD. Finally, the cross-sectional design limited our ability to make causal inference.