Correlation between Calcium Phosphorus Product and Mean Arterial Pressure among Hemodialysis Patients with End Stage Renal Disease

Background: The mean arterial pressure serves as an expression of blood pressure in patients on chronic hemodialysis. Serum calcium phosphorus product is considered as a risk factor of vascular calcification that is associated with hypertension in the patients of end stage renal disease. The literature regarding this relationship is inconsistent therefore this study is designed to determine the correlation between calcium phosphorus product and mean arterial pressure among hemodialysis patients with end stage renal disease. Methods: A total of 110 patients of end stage renal disease on hemodialysis for at least one year, 20 to 60 years of age were included. Patients with primary or tertiary hyperparathyroidism, peripheral vascular disease, malignancy, hypertension secondary to any cause other than kidney disease were excluded. Mean arterial pressure was calculated according to the standard protocol in lying position. Blood samples for estimation of serum calcium and phosphorous were taken and was sent immediately to the laboratory for serum analysis. Results: Mean age was 44.17 ± 10.94 years. Mean calcium phosphorous product was 46.71 ± 7.36 mg/dl and mean arterial pressure was 103.61 ± 12.77 mmHg. The values of Pearson correlation co-efficient (r) were 0.863 for age group 20 to 40 years and 0.589 for age group 41 to 60 years. This strong positive correlation means that high calcium phosphorous product goes with high mean arterial pressure (and vice versa) for both the age groups. Conclusion: A strong positive relationship exists between the mean arterial pressure and calcium phosphorous product and is independent of patients’ age.


Introduction
Chronic kidney disease (CKD) is a worldwide public health problem. In the United States, chronic kidney disease is the ninth leading cause of death and recently there has been upsurge both in the incidence and prevalence of kidney failure (1). About 90% patients of CKD suffer from hypertension that is a major risk factor for progression towards end stage renal disease (ESRD) (2, 3). Oppositely the progressive renal disease may also exacerbate uncontrolled hypertension due to volume expansion and increased systemic vascular resistance (4). The leading cause of mortality in patients with ESRD is cardiovascular disease (5). Compared with the general population, dialysis patients have a 3 to 30 folds increase in mortality, depending on the age group examined (6). Thus, it is of utmost importance to explore the causative agents of hypertension and exterminate them to halt the progression of both renal and cardiovascular ailments. Blood pressure is multi-factorial, and its management is quite a challenge in patients with ESRD. In patients on chronic hemodialysis, hypertension is monitored in terms of Mean Arterial Pressure (MAP) instead of measuring systolic and diastolic blood pressure (7). Serum calcium phosphorus product is considered as an indicator of vascular calcification that aggravates hypertension in the patients of ESRD (8). These calcifications are equal to bone formation resulting from vascular smooth muscle differentiation as evident in patients of CKD and lead to higher mortality attributed to increased left ventricular after-load and disturbed coronary perfusion (9). Jean et al. concluded that vascular calcifications are highly prevalent in hemodialysis patients and not linked to blood pressure (10). However, Adragao et al. conducted a prospective study and concluded that higher vascular calcification scores in dialysis patients were significantly associated with MAP and coronary artery disease (11). In another cross-sectional study conducted by Ashkar, it was cited that calcium phosphorous product (CPP) is positively associated with MAP and unrelated to pulse pressure (12). The inconsistency of the results regarding relationship between CPP and MAP is apparent in the existing literature thus this study is

Significance:
The mean arterial pressure serves as an expression of blood pressure in patients on chronic hemodialysis1. Serum calcium phosphorus product is considered as a risk factor of vascular calcification that is associated with hypertension in the patients of end stage renal disease. The literature regarding this relationship is inconsistent therefore this study is designed to determine the correlation between calcium phosphorus product and mean arterial pressure among hemodialysis patients with end stage renal disease.

Correlation between CPP and MAP
designed to explore further evidence regarding the relationship between CPP and MAP and its dependency upon age.

Materials and Methods
Study was approved by Ethical Review committee of King Fahad Central Hospital, Gizan, Kingdom of Saudi Arabia. Total of 110 volunteer male and female patients with permitted range for age, 20 to 60 years with ESRD were selected by non-probability consecutive sampling at nephrology department of hospital. A detailed informed written consent was obtained from all the patients. Patients either having pre-dialysis glomerular filtration rate less than 15ml per minute or the patients requiring at least two session a week for last one year were declared cases of ESRD. Patients were excluded after being scrutinized for primary or tertiary hyperparathyroidism, diabetic mellitus, peripheral vascular disease, malignancy, calciphylax is and secondary hypertension unrelated to kidney disease. MAP was determined by taking the resting systolic and diastolic blood pressure of the patients in lying position before and after dialysis. Averages of the pre-dialysis and post-dialysis systolic and diastolic blood pressures were taken as final reading. Mean arterial pressure was calculated using the formula: MAP = 2/3 (diastolic pressure) + 1/3 (systolic pressure) Corrected serum calcium levels were used according to serum albumin. Serum Calcium corrected= serum calcium + 0.8(4serum albumin mg/dl). Serum calcium phosphorous product was calculated by multiplying the corrected serum calcium level in mg/dl with serum level of phosphorous in mg/dl.Blood samples for estimation of serum calcium and phosphorous were taken by using aseptic measures and was sent immediately to the laboratory for serum analysis. Data was entered and analyzed using SPSS version 25. Numerical variable i.e. age, MAP and CPP were summarized as mean and standard deviation. Pearson correlation coefficient (r) was calculated to measure the correlation between CPP and MAP.

Results:
Age range in this study was from 20 to 60 years with mean age of 44.17 ± 10.94 years. 66 patients (60%) were between 41 to 60 years of age and 44 patients (40%) were between 20 to 40 years of age. Mean calcium phosphorous product was 46.71 ± 7.36 mmHg and mean arterial pressure was 103.61 ± 12.77 mmHg. The values of Pearson correlation coefficient (r) were 0.863 for age group 20 to 40 years ( Figure 1) and 0.589 for age group 41 to 60 years (Figure 2). Correlation between calcium phosphorous product and mean arterial pressure for both the age groups showed strong positive correlation. This correlation was stronger in age group 20 to 40 years than age group 41 to 60.

Discussion
In our study the value of Pearson correlation coefficient (r) is > 1declaring a strong positive correlation between CPP and MAP thus higher the calcium phosphorous product higher will be the mean arterial pressure (and vice versa). Our investigation was in agreement with Block et al., who analyzed a random sample of 2669 patients haemodialysed for more than 1 year (mean 4.5 years) and reported that higher the CPP higher is the mortality risk (13). In a cross-sectional study on fifty four hemodialysis patients during a 6-month period, linear Correlation between CPP and MAP regression analysis as applied on the averages of CPP and blood pressures concluded that CPP was significantly associated with pre-dialysis systolic BP and diastolic BP, pre-dialysis MAP, and post-dialysis diastolic BP (12). Strozecki et al., investigated the predisposing factors for cardiac valve calcifications and revealed that no significant correlations were found with respect to calcium, phosphorus, and calcium-phosphorus product (14). Similarly, Menon et al., concluded in a randomized cohort study of renal disease that serum phosphate levels and CPP were statistically unrelated to cardiovascular disease linked mortality (15 (11). The total serum calcium x phosphate product is an indicator of the risk of mineral crystallization in soft tissues, (17) which can lead to cutaneous and systemic calciphylaxis, conjunctival precipitation, visceral and in particular, cardiovascular calcification (18). Lundin et al first identified an elevated CPP as a predictor of cardiac mortality along with age at onset of dialysis and sustained hypertension (19). In hemodialysis patients, the pathogenesis of vascular calcification is multifaceted and the process includes certain factors that may promote or inhibit calcification (16). An elevated Ca _ P combination is likely to be a predominant risk factor and Ca alone may also be problematic because, in general, a positive Ca balance may blood pressure and calcium phosphorous product, so maintaining a tight control of calcium phosphorous product will help to manage hypertension by administration of drugs, leading to improved management and decreased the mortality and morbidity associated with hypertension. Promote or accelerate soft-tissue and vascular calcification even in the absence of hypercalcemia (20). On the whole, it is concluded that there is a strong positive relationship between

Conclusion
The study concludes that in patients of ESRD there is a strong positive correlation between the serum calcium phosphorous product and mean arterial pressure in both age groups (20-40years and 41-60 years).