ALKALINE PHOSPHATASE, MINERALS AND BONE MINERAL DENSITY IN CHRONIC KIDNEY DISEASE PATIENTS A COMPARITIVE STUDY A. LALITHAMMA 1 & S.

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1 TJPRC: International Journal of Pharmacology And Physiology (TJPRC: IJPP) ISSN (P): Applied; ISSN (E): Vol. 3, Issue 1, Jun 2017, 1-8 TJPRC Pvt. Ltd. ALKALINE PHOSPHATASE, MINERALS AND BONE MINERAL DENSITY IN CHRONIC KIDNEY DISEASE PATIENTS A COMPARITIVE STUDY A. LALITHAMMA 1 & S. VADIVEL 2 1 Assistant professor, Department of Physiology, Karpaga Vinayaga Institute of Medical Sciences, Dr. M.G.R. University, Tamil Nadu, India 2 Professor & HOD, Department of Physiology, Karpaga Vinayaga Institute of Medical Sciences, Dr. M.G.R. University, Tamil Nadu, India ABSTRACT Background Chronic Kidney Disease is considered as one of the public health problems, which is due to loss of kidney function and structure to decrease in GFR for three months or more. Aim & Objective Of this study is to compare the serum calcium, serum phosphorus and alkaline phosphate and T and Z scores of CKD pre dialysis with post dialysis patients. Materials & Methods 20 patients of both sexes, with chronic kidney disease formed the subjects of the present study. Bone mineral density is measured by dual energy X-ray absorptiometry and biochemical parameters are estimated by using standard lab techniques. The data obtained were analyzed with SPSS software. Results Original Article The study showed significantly lower egfr, hemoglobin, serum calcium and T and Z scores of the Lumbar spine and Neck of the femur in CKD pre and post dialysis patients. The serum phosphorus, serum alkaline phosphatase, serum creatinine and blood urea levels are significantly increased in CKD pre and post dialysis patients. The forearm T-Score (P-0.97), Z Score (P-0.12) indicates small variation and statistically not significant. Conclusion Estimation of Serum Creatinine and urea provides an important means for assessing the degree of renal failure. In haemodialysis patients with elevated levels of serum AP are associated with secondary hyperparathyroidism. The prolonged treatment with maintenance of hemodialysis is associated with worsening of radiographic evidence of bone disease in most patients, irrespective of calcium concentration in dial sate. KEYWORDS: Chronic Kidney Disease, egfr, Alkaline Phosphate & Bone Mineral Density Received: Aug 22, 2017; Accepted: Sep14, 2017; Published: Sep 23, 2017; Paper Id.: TJPRC:IJPPJUN20171 INTRODUCTION Chronic kidney disease is also known as chronic renal failure. Chronic kidney disease is defined as an irreversible deterioration of renal function over 3 months or more, in the CKD the glomerular filtration rate

2 2 A. Lalithamma & S. Vadivel decreased, leading to the increase in the creatinine concentration and other organic substance in the blood 1. Higher levels of S.cr indicate renal failure. If the S.cr levels increases, the egfr value decreases and the urinary output is less than 0.5ml/min. In early stages, the creatinine levels are normal. In end stages, the nephrones lose its function and gradually there is decrease in kidney function. So, the creatinine levels are very high and decreased egfr values indicates end stage renal failure. This is also called established chronic kidney disease or CKF or CRF. Decrease in kidney function causes hypertension, uremia, hyperkalemia, Anemia and metabolic acidosis 2. CKD in the End Stage require renal replacement therapy 1. METHODS AND MATERIALS Patients A comparison was done in the Nephrology Department of Sri Venkateshwara Institute of Medical Sciences after obtaining permission from a medical ethics committee of the institute. A Study were carried out in stages 3, 4 and 5 of 20 CKD patients before and after dialysis aged between years of both male and female attending Nephrology o.p for the past 6 months. The patients are categorized into 2 groups. Group I: 20 CKD patients (Before dialysis) aged between yrs, 10 males and 10 females attending Nephrology O.P for 6 months taken as controls. Group II: 20 CKD patients (After dialysis) aged between yrs, 10 males and 10 females, attending Nephrology O.P for 6 months. All the patients are undergoing haemodialysis treatment twice a week in Nephrology as out patients. Exclusion Criteria Past history of alcohol Smoking Acute renal failure cases Pediatrics patients Patients with primary endocrine abnormalities Diabetes mellitus Pulmonary tuberculosis and Hypertension Sample Collection For estimation of serum creatinine, blood urea, hemoglobin, calcium, phosphorus and alkaline phosphate the fasting blood sample was collected into a clean tube allowed the blood to clot for at least 30 min at room temperature. Separated the serum by centrifugation and stored in a refrigerator and assessed by using standard laboratory methods with commercially available kits.

3 Alkaline Phosphatase, Minerals and Bone Mineral Density in 3 Chronic Kidney Disease Patients A Comparitive Study Bone Mineral Density (BMD) Bone mineral density (BMD) of the lumbar spine, Forearm and neck of the femur were measured by using Dual energy X-ray absorptiometry (Discovery A, Hologic Inc. version USA). All Bone Mineral Density measurements were performed by the same experienced operator. Bone Mineral Density results were obtained with absolute values (g/cm2), in T-score and in Z- score. T-Score is the number of standard deviations from the mean of a healthy adult population and is used to determine osteoporosis or osteopenia. The Z - score is the number of standard deviations from the mean of a healthy age and gender-matched normal population, which allows the comparison of Bone Mineral Density between patients of different age and gender. Osteoporosis were defined as a Bone Mineral Density T- score at any site less than -2.5 and Osteopenia as a Bone Mineral Density T-Score between -1 and 2.5 The reference values were obtained from an Italian normal population. STATISTICAL ANALYSIS The mean values of all parameters of chronic kidney disease patients and controls were statistically analyzed by applying student t test and calculated 'p' values Results Table 1: Comparison of Basic Parameters in Group-I and Group II Group-I Group-II T P Mean SD Mean SD Age (yrs) ; NS BMI (kg/m 2 ) ; NS S.cr (mgldl) ; NS egfr (mgldl) ; NS Blood Urea (mg/dl) ; NS Hb (g/dl) ; NS Figure 1: Comparison of Basic Parameters in Group-I and Group II

4 4 A. Lalithamma & S. Vadivel Table 2: Comparison of S.Ca 2+, SPO 4 and Alkaline Phosphate in Group I and Group II Group-I Group-II t P Mean SD Mean SD SCa2+(mg/dl) ; NS Spo4 (mg/dl) ; NS SAP ( IU/dl ; S Figure 2: Comparison of S.Ca 2+, SPO 4 and Alkaline Phosphate in Group I and Group II Table 3: Comparison of BMD T and Z Scores of LS, Fore Arm and Hip in Group I and Group II Group-I Group-II t P Mean SD Mean SD LST Score ; S LSZ- Score ; S Hip T-Score < 0.001; S Hip Z-scores ; S Fore arm T-score ; NS Fore arm Z-score ; NS Figure 3

5 Alkaline Phosphatase, Minerals and Bone Mineral Density in 5 Chronic Kidney Disease Patients A Comparitive Study RESULTS The results of this study indicate no gross variation in both genders of all parameters. There is no statistical significance of all parameters between post and pre dialysis patients except serum alkaline phosphate, which is increasing and statistically significance between post and pre dialysis patients. The T and Z Scores of LS &Hip are decreased in group I&II statistically significantly. T&Z Scores of fore arm show small variation and statistically not significant. DISCUSSIONS Metabolic bone disease is common in the course of renal failure. It is observed in a number of studies that renal osteodystrophy is common in End Stage Renal Disease (ESRD) patients, under dialysis treatment. It is the most common cause of mortality in ESRD. Secondary hyperparathyroidism is the main cause for renal osteodystrophy. To prevent this complications screening for bone changes, including scans is used to diagnose and to start treatment for bone disease. In the present study, bone mineral density is studied by Dual Energy X-ray Absorptiometry (DEXA) in renal failure patients undergoing Dialysis alternate Days for the past 6 years and also before dialysis patients. Changes are compared to both men and women. In the present study 19 patients are on stage -5, 1 patient in stage -4 in post dialysis patients. 8 patients in stage 5, 9 patients with stage -4, 3 patients in stage 3 in pre dialysis patients. Staging of CKD is identified by egfr levels. There is no gross variation in men and women in this study in all parameters, and also no gross variation of all parameters in post dialysis and pre dialysis patients except alkaline phosphatase. In this study, the mean values of BMI are much less in Renal Failure Patients. This may be due to the effects of the Renal Disease with Anemia and infections. The egfr values are low in after dialysis and before dialysis. These results are also supported by the studies of Sanjay K. Agarwal, et al (2007) 3. The stages of CKD from Stage 1 to Stage 5 on the basis of egfr were 1.6%, 4.8%, 16.9%, 30.1% and 46.6% respectively. The reduced egfr, decreases in renal excretion of water and solutes, and many of the waste products of metabolism such as urea and creatinine. Blood Urea, S.Cr Levels are high in ckd patients compared with controls. This result agreed with the other studies 4, 5. An increase in the urea and creatinine level occurs in CKD patients because the kidney loses ability to eliminate nitrogenous wastes from the blood results in accumulation of these substances in the blood. Other reasons of increase urea and creatinine in the blood from the excessive protein intake, shock, gastrointestinal hemorrhage etc. could also contribute to this 6. Hemoglobin levels are low in before and after dialysis, because patients with severe chronic renal failure always develop anemia. Many of the studies showed that anemia was the most common complication of advanced chronic renal disease this result was agreed with previous studies 7, 8, 9. The most important cause of this is decreased erythropoietin secretion from the kidney due to damage of renal parenchyma. This causes decreased red blood cell production from bone marrow 10 leads to anemia. Uremia toxic accumulation in the blood is considered another cause of anemia in the CKD. 11 Iron deficiency also one of the reasons for anemia in chronic kidney disease. 12 Hyperparathyroidism, folic acid and B12 vitamin deficiency also develop anemia anemia. 13 It is observed that Sca 2+ is decreased in CKD patients and the values are not much altered in before and after dialysis. In contract Serum PO 4 levels are raised in CKD patients not much change observed in before and after dialysis.

6 6 A. Lalithamma & S. Vadivel Mineral metabolism is Sca 2+, PO 4 are regulated by renal mechanisms. So, damage to kidneys disturbs the Sca 2+, PO 4 levels. Abnormalities observed in patients with filtration rate <60 ml/min. In Last stages of CKD Sca 2+ level decreases and serum PO 4 levels increases. These changes are mainly due to secondary hyperparathyroidism. These results are also supported by the studies of Hou SH, et al (1991) 14, the acute effects of varying dialysate calcium concentration, on plasma concentrations and dialyzer fluxes of calcium and phosphorus in adult hemodialysis patients. Seven individuals with stable end-stage renal failure were dialyzed 4 hours, three times weekly. The effects of dialysates containing 1.75, 1.25 or 0.75 mmol/l (70.1, 50.1 or 30.1 mg/l) of calcium were compared. Compared with the predialysis mean value of 2.27 mmol/l (9.1 mg/dl), the plasma total calcium concentration increased, remained constant, or decreased with the 1.75, 1.25 or 0.75 mmol/l calcium dialysates, respectively. The 0.75 mmol/l calcium dialysate did not cause signs or symptoms of hypocalcemia, and the plasma calcium concentration did not fall below 1.8 mmol/l (7.2 mg/dl). Plasma phosphorous concentrations decreased equally from a predialysis mean value of 2.16 mmol/l (6.7mg/dl), regardless of the dialysate calcium concentration. After 4 hours of treatment with the three different dialysates, the cumulative calcium fluxes were significantly different, with 1.75mmol/L calcium; mean bodily calcium accumulation was 21.9 mmol (879 mg). With 1.25 mmol/l, there was no net calcium flux with 0.75 mmol/l, mean patient calcium loss was 5.8mmol (231mg) The serum phosphorus levels are increased in this study because the concentrations of serum PO 4 during the fasting state are usually normal or lower than normal in the early stages of renal failure. Hyperphosphatemia becomes apparent, when GFR falls below 20ml/min. Many factors affect the serum concentration of phosphorus in patients with advanced renal failure and are responsible for the wide variations. The serum phosphorous levels decrease during dialysis secondary to its removal by dialytic procedure. Serum phosphorus concentration increases during the interdialytic period, the rapidity of the rise depending on the dietary intake of phosphorus, the adherence to therapy with phosphate binding antacids, and the severity of secondary hyperparathyroidism. In this study the serum alkaline phosphatase levels are higher in CKD patients after dialysis than before dialysis. Because the patient with advanced renal failure and those treated with hemodialysis may have normal. Moderately elevated, or markedly increased serum levels of alkaline phosphatase. This enzyme is increased in skeletal conditions associated with the enhanced osteoblastic activity. Patients with renal failure have osteomalacia and / or secondary hyperparathyroidism, both of which are associated with increased bone turnover rate; it is not surprising that the serum levels of alkaline phosphatase are elevated in these patients. The serum levels of alkaline phosphatase in a large number of dialysis patients correlate with osteoid surface covered with osteoblasts, osteoclastic resorption surface, number of osteoclasts, and percentage of osteoid seams labeled with tetracycline. Measurements of the serum level of alkaline phosphatase every 1 or 2 months can provide a useful guide to the progression of base disease or to its healing during therapy with Vitamin D. 15 In the present study the BMD T and Z scores are lower in post dialysis CKD patients. This result is supported with Ha SK (1996). 16 Decreased BMD Z Scores on weight bearing bone were pronounced at L 1 lumbar vertebra, femur trochanter, femur neck and ward s triangle. Positive linear correlations were found between creatine clearance and trunk, ribs, pelvis and spine BMDs. There were inverse linear correlations between total BMD and total BMD Z Score and alkaline phosphate in the patient group.

7 Alkaline Phosphatase, Minerals and Bone Mineral Density in 7 Chronic Kidney Disease Patients A Comparitive Study CONCLUSIONS The prolonged treatment with maintenance of hemodialysis is associated with worsening of radiographic evidence of bone disease in most patients, irrespective of calcium concentration in dialysate. Adequate control of the serum levels of phosphorus within the normal range may possibly ameliorate. The BMD T and Z Scores are lower in post dialysis CKD patients. This indicates that the dialysis has no effect on skeletal changes. REFERENCES 1. Dor, A., Pauly, M., Eichleay, M.A. and Held, P.J End-stage renal disease and economic incentives: the international study of health care organization and financing. National Bureau of Economic Research Cambridge, Mass., USA. 2. Wikipedia: The free encyclopedia: chronic kidney disease Agarwal S.K.: Assessment of Renal Bone mineral Disorder in naïve CKD patients : A single centre prospective study: Indian Journal of Nephrology. 2007: Murray R. L. Non protein Nitrogen compounds, in clinical chemistry; Theory, Analysis and co-relation Kaplan L. A. and pesce A. J., Eds. C. V. Mosby, Toronto, 1984, National Institute for Health and clinical excellence clinical guideline 73 : chronic kidney disease ( nice. org. uk/cg73) London: Sharon M. Moe, Stuart M. Sprague. Mineral bone disorder in chronic kidney disease. The kidney: Brenner: 2006:2:52: Ahmed Methab Athab et al., C-Reactive Protein and Renal Function Tests in Chronic Renal Failure Patients on Hemodialysis and Kidney Transplantation, International Journal of Medicine and Pharmaceutical Sciences (IJMPS), Volume 6, Issue 3, May - June 2016, pp Meyer, Timothy, W., Hostetter and Thomas, H "Uremia". New England Journal of Medicine. 357 (13): Souza, C., Oliveira, S. and Guedes, A.M. et al Avaliação das dosagens de ureia pré e póshemodiálise em uma unidade de saúde. Cadernos de Graduação Ciências Biológicas e da Saúde. Jan/Jun. 13(13): Anderson, W.A.D Kidneys in Anderson s Pathology, 5th edition (CV Mosby Company), St LouiseBatlomore Philadelphia Toronto, pp: Patel, T.V. and Singh, A.K Anemia in chronic kidney disease: new advances. Heart Fail Clin. 6(3): Astor, B. C., Muntner, P., Levin, A., Eustace, J.A. and Coresh, J Association of kidney function with anemia: the Third National Health and Nutrition Examination Survey ( ). Archives Internal Medicine. 162: Stevens, P.E Anemias, diabetes and chronic kidney disease: where are we now? Journal of Renal Care. 38(Suppl. 1): Drüeke, T.B., Locatelli, F., Clyne, N., Eckardt, K.U., Macdougall, I.C., Tsakiris, D., Burger, H.U. and Scherhag, A.2006.CREATE Investigators: Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med.355: George, S.V., Pullockara, J.K., Sailesh, K.S., Mukkadan, J.K mA study to assess changes in the hematological profile in chronic kidney disease. The Pharma Innovation Journal. 4(6): Fishbane, S Iron supplementation in renal anemia. Semin Nephrol; 26(4):

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