Introduction

Despite increasing knowledge of the uraemic syndrome, both morbidity and mortality remain unacceptably high in patients with chronic kidney disease (CKD) ¹.

Secondary hyperparathyroidism which characterized by increased secretion of parathermone (PTH), is one of the major serious complications in patients with CKD on long-term hemodialysis (HD). Strict control of serum calcium and phosphate concentrations is very important to prevent secondary hyperparathyroidism in those patients ².

Efficient removal of middle-molecular-weight (MMW) uremic toxins is expected to improve patient outcomes in dialysis ³.

Convective transport is the main driver for an enhanced clearance of such toxins. Consequently, hemodiafiltration (HDF), a dialysis procedure effectively combining diffusive and convective transport, has now become the standard dialysis technique in many countries ⁴.

MMW substances are not readily cleared by diffusion, which is the main elimination mechanism in low-flux HD ⁵.

            European Dialysis Working Group (EUDIAL) defined hemodiafiltration as a blood purification therapy combining diffusive and convective solute transport such that the latter is achieved by an effective convection volume of at least 20% of the total blood volume processed. Convection volume is the sum of the substitution fluid volume and the volume of fluid removed during a session (i.e., the difference between the postdialysis and predialysis weights) ¹.

In modern HDF, fluid balance is maintained by the infusion of ‘online’ prepared substitution fluid, which can be administered before the dialyser (pre-dilution), midway (mid-dilution) or after the dialyser (post-dilution) ⁶.

Since the vast majority of publications on HDF and clinical outcome concern online post-dilution HDF, this study will focus on this type of treatment.

This prospective switchover study investigated the differences between conventional hemodialysis and hemodiafiltration in the context of chronic kidney disease metabolic bone disease (CKDMBD) findings [serum calcium (sCa), serum phosphate (sPO4) and intact parathyroid hormone (PTHint) concentrations].

Patients and Methods

This cross over study investigated the differences between conventional hemodialysis and hemodiafiltration in the context of CKDMBD findings stems from the fact that the same patients were examined by two different therapeutic modalities.

This study was approved by Almaadi hospital committee and included 95 patients with CKD5 on regular hemodialysis (HD) in Almaadi Nephrology Unit for at least 6 months prior starting. They were selected after informing consent, full history, examination reviewing their medical records and fulfillment the study inclusion and exclusion criteria. They were divided into two groups: Group A included 60 patients scheduled 6 months conventional high flux hemodialysis (hf-HD) (Period 1)) immediately followed by 6 months of post-dilutional -HDF (Period 2). Group B (controls) included 35 patients. They were kept on conventional hf-HD for 12 months. (Period 3) for 1^st 6 months and (Period 4) for 2^nd 6 months. The main variables evaluated at the start as well as at the end of each period were sCa, sPO4 and PTHint.

Variables in this study were evaluated both at the start and at the end of each period of observation. They included serum calcium (sCa; mg/dL), serum phosphorus (sPO4; mg/dL), serum intact parathyroid hormone (PTHint; ng/mL), total serum protein (sProt; g/dL), serum albumin (sAlb; g/dL), plasma sodium (Na; mmol/L), plasma potassium (K; mmol/L), magnesium (Mg; mg/dL), CBC, high sensitive CRP, equilibrated Kt/V (eKt/V), body weight (BW; kg), liver function tests, ECG, pre-dialysis systolic blood pressure (SBP; mmHg) and diastolic blood pressure (DBP; mmHg). All biochemical parameters were drawn before midweek dialysis session to be assayed by their standard methods.

• Along the study, all patients (95 patients) used ultrapure dialysate as well as the same high flux dialyzer (High flux dialyzer, polysulfone F80 Fresenius Medical Care).
• Treatment of mineral bone derangement weas performed according to the American Kidney Disease Outcome Quality Initiative clinical practice guidelines for bone metabolism and disease in chronic renal failure recommendations.In group A, prescription and dosage changes of the phosphate binders done before the beginning of period 1 and were kept constant during Period 2. While in group B, changes in the dosage and prescription of phosphate binders supplementation were allowed according to guidelines.

The study included patients above 18 years old on regular HD for at least 6 months and with urinary output below150 mL/interdialytic. While Patient swith active malignancy, chronic infections, decompensated liver cirrhosis, unstable within 3 months before study (myocardial infarction, congestive heart failure, stroke, recent surgery, or severe sepsis), patients who developed hyperphosphatemia were excluded, Vascular access dysfunction (blood flow rate < 300 mL/min) and urinary output more than150 mL/ interdialytic were excluded from the study.

Dialysis prescription

Postdilution HDF was performed using the 5008 CorDiax HDF machine (Fresenius Medical Care, Bad Homburg, Germany).The dialysate solution is bicarbonate for all patients with sodium Na⁺ 140mEq/L, K⁺ 2mEq/L, Ca⁺⁺ 1.75mEq/L, Mg 0.5mEq/L, Cl⁻ 109.5mEq/L, HCO3 35mEq/L, CHcooH 3mEq/L & the blood pump was kept between 300-400mL/min with dialysate flow 500 mL/min, and heparin sodium as anticoagulant were given 2500 IU as a bolus on initiation of dialysis followed by 500-1000 IU/Hr.

All procedures follow Al-Azhar University Ethical committee regulations, and patient consent was taken from all patients.

Statistical Analysis:

Recorded data were analyzed using the statistical package for social sciences, version 20.0 (SPSS Inc., Chicago, Illinois, USA). Quantitative data were expressed as mean± standard deviation (SD). Qualitative data were expressed as frequency and percentage. The following tests were done: Independent-samples t-test of significance was used when comparing between two means. Chi-square (c²) test of significance was used in order to compare proportions between qualitative parameters. A one-way analysis of variance (ANOVA) when comparing between more than two means.  Post Hoc test: Least Significant Difference (LSD) was used for multiple comparisons between different variables. The confidence interval was set to 95% and the margin of error accepted was set to 5%. So, the p-value was considered significant as the following:  Probability (P-value)  P-value 0.05 was considered insignificant.

Results

The study shows no statistically significant differences between groups as regards demographic data.

Figure (1): Comparison between groups according to Hb.

This figure shows statistically significant difference between groups according to Hemoglobin (Hb). From after 1months to average of overall.

There is no significant statistical difference between the four groups as regard Hemoglobin level in the basal (p>0.05),While there is significant statistical increase in Hemoglobin level in period 2 compared to other groups after the 1^st, 2^nd, 3^rd, 4^th, 5^th month and average of overall (p<0.05) and highly significant statistical increase in Hemoglobin level in period 2 compared to other groups after the 6^th month (p<0.001).

Figure (2): Comparison between groups according to Ph.

This figure shows statistically significant difference between groups according to Phosphorus (Ph) from after 1months to Average of overall.

There is no significant statistical difference between the four groups as regard Phosphorus level in the basal (p>0.05), While there is significant statistical derease in Phosphorus level in period 2 compared to other groups after the 1^st month (p<0.05) and highly significant statistical decrease in Phosphorus level in period 2 compared to other groups after 2^nd, 3^rd, 4^th, 5^th,6^th month and average of overall (p<0.001).

Table (1): Comparison between groups according to Parathormone.

Figure (3): Comparison between groups according to PTH.

As shown in table (1) and figure (3), there was a statistically significant difference between groups according to Parathormone (PTH) from after 1months to Average of overall.

There is no significant statistical difference between the four groups as regard Parathormone level in the basal (p>0.05), While there is significant statistical derease in Parathormone level in period 2 compared to other groups after 1month to 6^th month and average of overall (p<0.05).

Figure (4): Comparison between groups according to Albumin.

This figure shows statistically significant difference between period 2 and overall of the periods according to albumin from after 2months to Average of overall.

There is no significant statistical difference between the four groups as regard Albumin level in the basal and after 1^st month (p>0.05), While there is significant statistical derease in Albumin level in period 2 compared to other groups after 2^nd to 6^th month and average of overall (p<0.05).

Table (2): Comparison between groups according to C reactive Protein.

Figure (5): Comparison between groups according to CRP.

This figure shows statistically significant difference between period 2 and overall of the periods according to CRP from after 1months to Average of overall.

There is no significant statistical difference between the four groups as regard CRP in the basal (p>0.05)), While there is significant statistical derease in CRP in period 2 compared to other groups after 1^st to 6^th month and average of overall (p<0.05).

Figure (6): Comparison between groups according to kt/v.

This figure shows statistically significant difference between groups according to kt/v from after 1months to Average of overall.

There is no significant statistical difference between the four groups as regard kt/v in the basal (p>0.05)), While there is significant statistical inrease in kt/v in period 2 compared to other groups after 1^st to 6^th month and average of overall (p<0.05).