Study Population and Data Source
All stable adult MHD patients in our center during the period January 1, 2007 through December 31, 2011, were included in this retrospective study. Inclusion criteria were age > 18 years and underwent MHD for at least 3 months, exclusion criteria were hospitalization within 3 months before the study, combined with uncured malignant tumor or active liver disease. The study was approved by the Ethics Committee of Qianfoshan Hospital, and all subjects gave their informed consent.
Demographic and biochemical data
Base-line and follow-up datas were collected from medical records. The following data were collected at base-line: demographic factors (age, sex, and vintage); whether comorbid diabetes; physical constitution (systolic blood pressure(SBP) and diastolic blood pressure(DBP) before single dialysis); hemoglobin(Hb) and serum biochemical data (albumin(Alb), creatinine(Cr), blood urea nitrogen(BUN), calcium(Ca), phosphorus(P), magnesium(Mg), intact parathyroid hormone(iPTH), triglyceride(TG), cholesterol(CH), low density lipoprotein(LDL).
Blood samples were drawn from dialysis pipeline immediately after initiation of single hemodialysis treatment and shipped to our central laboratory, where measurements were made using automated and standardized methods. The S-Alb level was determined with the BCG method; the normal reference range in this study was 4.0-5.5g/dl. The corrected total serum calcium (S-Ca) and serum magnesium (S-Mg) was calculated according to the following formula: corrected S-Ca (mmol/L) = measured S-Ca (mmol/L) + (40 – S-Alb [g/L]) × 0.02, S-Mg (mmol/L) = measured S-Mg (mmol/L) + (40 – S-Alb[g/L]) × 0.005.
Follow-up and study endpoints
All patients were followed up to the study endpoint, administrative censoring (including renal transplantation, switch to peritoneal dialysis, transfer to another HD center, loss to follow-up or withdrawal from treatment) or the end of the study follow-up period (31 July 2018). The primary study endpoint was mortality, the secondary endpoint was hospitalization. Causes of death and hospitalization were collected, for subgroup analysis. If a death or hospitalization had two or more potential causes, we generally ascribed to the initial presenting condition.
Categorical data are presented as frequencies and percentages. Continuous variables are expressed as mean ± standard deviation (SD) for normally distributed variables and as median and interquartile range (IQR, 25th–75th percentile) for variables with skewed distribution.
All these above demographic and biochemical data were assessed as potential predictors of hospitalization and mortality outcomes by univariable and multivariable Cox regression. If there were 2 or more hospitalizations, the first hospitalization was taken into Cox regression analyses. The adjustments were as follows: Model 1 (case mix): sex, age and all parameters that were significant in univariable analysis comorbidities; Model 2 (bone mineral metabolism factors): sex, age, comorbid diabetes, S-Alb, corrected S-Ca, S-P, corrected S-Mg, iPTH; Model 3(classic cardiovascular and cerebrovascular risk factors) : sex, age, comorbid diabetes, SBP, DBP, S-Alb, TG, CH, LDL.
The non-liner relationships of base-line S-Alb levels and outcomes were evaluated by restricted cubic spline(RCS) fitting univariable or multivariable Cox model; 6 knots were set and percentiles were P5, P23, P41, P59, P77, P95, respectively. For RCS fitting multivariable Cox model, only model 1 was used respectively.
All statistical analyses were two-tailed and P value <0.05 was considered significant. RCS were conducted in Stata/IC 14 (StataCorp, College Station, TX), other analyses were performed using the SPSS version 13.0 (SPSS, Chicago, IL).