Relation between Calcium, Phosphorus, Calcium-Phosphorus Index and iPTH in Chronic Kidney Disease Patients.

BACKGROUND: The disturbance in homeostasis of calcium, phosphorus, vitamin D, and parathyroid hormone are frequently seen in chronic kidney disease patients. It is vital for physician to know the relation among them to treat chronic kidney disease patients. The main objective of the study is to 1) gather and analyze the data from chronic kidney disease patients undergoing dialysis to find out intact parathyroid hormone status 2) the relation between level of serum calcium, serum phosphorus, calcium-phosphorus index and serum intact parathyroid hormone in Nepalese population. METHODS: Verbal consent was taken from all the participants. Eighty participants between the age of 29 and 70 years with chronic kidney disease having indication of emergency hemodialysis were included in this study. Serum calcium, and phosphorus were measured by Fully Automatic Biochemistry Analyzer, and serum intact parathyroid hormone (iPTH) was measured using Chemi Luminescence Immuno Assay (CLIA) method. RESULTS: There is positive correlation between high calcium - phosphorus index and raised serum intact parathyroid hormone (r= 0.30).The relation is also true for serum calcium level and serum intact parathyroid hormone (r= 0.38). There is weak negative correlation between serum phosphorus and serum intact parathyroid hormone (r= -0.03). CONCLUSIONS: In Chronic kidney disease patients, high serum calcium or calcium - phosphorus index associated with raised level of serum intact parathyroid hormone and reverse is true for increased serum phosphate level. The relation may guide physician to suspect hyperparathyroidism in chronic kidney disease patients and manage the complications related to hyperparathyroidism like renal mineral bone disease, anemia resistant to erythropoietin.

Relation between Serum Intact Parathyroid Hormone Level and Hematocrit in Chronic Kidney Disease Patients.

Background Anemia is a common complication of chronic kidney disease. There are various causes of anemia in chronic kidney disease patients on hemodialysis. Secondary hyperparathyroidism is one of the less recognized causes of anemia in chronic kidney disease patients. Objectives The main objective of the study is to find the correlation between intact parathyroid hormone and hematocrit level in chronic kidney disease (CKD) patients undergoing hemodialysis. Method Verbal consent was taken from all the participants. Eighty participants between the age of 29 and 70 years with chronic kidney disease having indication of hemodialysis were included in this study. Hematocrit was measured by bioelectrical impedance method and serum intact parathyroid hormone was by using Chemi Luminescence Immuno Assay (CLIA) method. Result A weak reverse correlation was found between serum intact parathyroid level and hematocrit (r= -0.33). Conclusion In chronic kidney disease patient, there is reverse correlation between level of serum intact parathyroid and hematocrit level. This association may have clinical relevance in assessing the cause of unexplained low hemoglobin level in CKD patients.

Efficacy of IV iron compared to oral iron for increment of haemoglobin level in anemic chronic kidney disease patients on erythropoietin therapy.

INTRODUCTION: Anemia is the most common finding in chronic kidney disease patients. Iron supplements are commonly prescribed for these patients with or without erythropoietin therapy by means of oral and intravenous iron. Both oral and intravenous irons have their own advantage and disadvantage, and the efficacy is also different. The objective of the study is to analyze the efficacy of oral and intravenous iron in chronic kidney disease patients on erythropoietin therapy, an erythropoiesis stimulating agents for increment of haemoglobin. METHODS: This is a prospective study comparing intravenous iron to oral iron in chronic kidney disease patients who underwent maintenance hemodialysis at different centers and visited Kathmandu Medical College Teaching Hospital from April 2010 to April 2011. Patients having a haemoglobin level of < 11 g/dl, transferrin saturation (TSAT) < 25%, ferritin < 300ng/ml and who were on erythropoietin therapy were allocated alternately into two groups to receive oral iron (iron fumarate) or IV iron (iv sucrose). Haemoglobin was measured after 30 days of therapy. RESULTS: A significant increase in haemoglobin levels was observed in both groups. But the mean haemoglobin increment was more in the IV iron group than in the oral iron group. Sixty percent 60% of patients in the IV iron group had an increase in the haemoglobin level of more than 1gm/dl while only 20% of the oral iron group had this increase. CONCLUSIONS: Intravenous iron therapy is more effective in raising the hemoglobin level in hemodialysis dependent chronic kidney disease patients.

Role of CaCO3 alone and CaCO3 plus vitamin D3 in terms of calcium phosphorus product in chronic kidney diseases.

BACKGROUND: CaCO3 alone and CaCO3 plus vitamin D3 metabolites are commonly prescribed in CKD patients. The objective of this study is to analyze the changes in Ca x P product, calcium level and phosphorus level in CKD patients receiving calcium carbonate alone and calcium carbonate with vitamin D3 in combination. METHODS: A prospective, cross sectional study among CKD patients under maintenance hemodialysis two times a week were studied over a period of one year. The patients were divided into two groups receiving oral CaCO3 alone and CaCO3 plus vitamin D3 once a day. The patients were followed for 1 month and result of Ca x P product was analyzed accordingly. RESULTS: Mean decrease of Ca x P product in CaCO3 group is (50.42+/-8.85 to 47 +/-6.63) in one month, p value =0.001(0.6-5) and CI- 95%. There is also significant reduction of phosphorus level in CaCO3 group than CaCO3 plus vitamin D3 group. Mean decrease in phosphorus in CaCO3 group is (5.51+/-0.76 to 5.17+/- 0.05) in one month. P value =0.01(0.14-0.53) and CI 95%. CONCLUSIONS: There is a significant decrease in Ca x P product and phosphorus level was observed in CKD patients taking CaCO3 alone.

Effective control of hypertension in adults with chronic kidney disease.

INTRODUCTION: Adequate control of hypertension in Chronic Kidney Disease patients is difficult to achieve. This study was designed to analyze the adequacy of Hypertension control in adults with CKD using different classes of antihypertensive drugs. METHODS: A cross-sectional observational study was done that included 85 patients with CKD admitted to our Medicine Department over a period of two years (2006-2008 A.D.). Presence of CKD was defined as glomerular filtration rate <60 ml/min per 1.73 m2 for more than three months or presence of albuminuria (albumin:creatinine ratio >30ug/mg). Adequate blood pressure control was defined as systolic blood pressure less than or equals to 130 and diastolic blood pressure less than or equals to 80 mm Hg. Data and Statistical analysis was done using SPSS Version 12 for Windows. RESULTS: Of all the CKD patients, 51.4% required three Anti-Hypertensive drugs combination for the effective control of Hypertension, while only 21% of CKD patients with hypertension was controlled on two drugs. CONCLUSION: Adequate control of blood pressure in CKD patient was shown to be most effective on combination of three antihypertensive drugs. A poor control was seen on patients taking less than three antihypertensive drugs.

Successful management of idiopathic rapidly progressive glomerulonephritis with corticosteroids and cytotoxic agent.

A 19 years old, male patient presented with symptoms of smoky urine for 2 weeks, puffiness of face and diminished urine output for 3 weeks associated with occasional lower abdominal and flank pain. Patient's history, clinical findings and available investigations were strongly suggestive of Idiopathic Rapidly Progressive Glomerulonephritis. The patient showed excellent response to glucocorticoid and cytotoxic agent.

Detection and co-ordinated care management of chronic kidney disease at Kathmandu Medical College Teaching Hospital.

OBJECTIVE: The objective of our study was to analyze the detection parameters, categorization and co-ordinated management of Chronic Kidney Disease (CKD). The presenting clinical features, common lab investigations, applied treatment protocols and noticed complications were recorded. METHODOLOGY: A total of 40 patients of various stages of CKD on the basis of National Kidney Foundation (NKF), Kidney Disease Outcome Quality Initiative (K/DOQI) guideline were included in the study. RESULT: Out of them 24(60%) were males and 16(40%) were females. Constitutional symptoms like anorexia, nausea and generalized weakness were common presenting complaints present in 37(92.5%) patients and were associated with features of anaemia, metabolic acidosis and fluid overload in stage 5 CKD patients. The average age of presentation was 51.3 years. Among 40 patients 21(52.5%) were managed conservatively, 17((42.5%) were advised for Renal Replacement Therapy (RRT) through dialysis.2 (5%) patient expired during the treatment. The average duration of hospital stay was 5.6 days. Diabetes Mellitus was the most common cause 18 (45%), followed by Hypertension 14 (35%) and Chronic Glomerulonephritis (CGN) 5 (12.5%) leading to CKD. The patients were advised for regular follow up at Nephrology clinic.

Abnormal p38 mitogen-activated protein kinase signalling in human and experimental diabetic nephropathy.

AIMS/HYPOTHESIS: Inflammation and fibrosis are pathological mechanisms that are partially regulated by cell signalling through the p38 mitogen-activated protein kinase (MAPK) pathway. Elements of the diabetic milieu such as high glucose and advanced glycation end-products induce activation of this pathway in renal cells. Therefore, we examined whether p38 MAPK signalling is associated with the development of human and experimental diabetic nephropathy. METHODS: Immunostaining identified phosphorylated (active) p38 MAPK in human biopsies with no abnormality ( n=6) and with Type 2 diabetic nephropathy ( n=12). Changes in kidney levels of phosphorylated p38 were assessed by immunostaining and western blotting in mice with streptozotocin-induced Type 1 diabetes that had been killed after 0.5, 2, 3, 4 and 8 months, and in Type 2 diabetic db/db mice at 2, 4, 6 and 8 months of age. RESULTS: Phosphorylated p38 was detected in some intrinsic cells in normal human kidney, including podocytes, cortical tubules and occasional interstitial cells. Greater numbers of these phosphorylated p38+ cells were observed in diabetic patients, and phosphorylated p38 was identified in accumulating interstitial macrophages and myofibroblasts. A similar pattern of p38 activation was observed in both mouse models of diabetes. In mice, kidney levels of phosphorylated p38 increased (2-6 fold) following the onset of Type 1 and Type 2 diabetes. In both mouse models, interstitial phosphorylated p38+ cells were associated with hyperglycaemia, increased HbA(1)c levels and albuminuria. Further assessment of streptozotocin-induced diabetic nephropathy showed that interstitial phosphorylated p38+ cells correlated with interstitial fibrosis (myofibroblasts, collagen). CONCLUSIONS/INTERPRETATION: Increased p38 MAPK signalling is a feature of human and experimental diabetic nephropathy. Time course studies in mouse models suggest that phosphorylation of p38 plays a pathological role, particularly in the development of interstitial fibrosis.

Transport of viral proteins to the apical membranes and interaction of matrix protein with glycoproteins in the assembly of influenza viruses.

Influenza virus assembly and morphogenesis require transport of viral components to the assembly site at the apical plasma membrane of polarized epithelial cells and interaction among the viral components. In this report we have discussed the apical determinants present in the transmembrane domain (TMD) of influenza virus hemagglutinin (HA) and neuraminidase (NA), and the interaction of M1 with influenza virus HA and NA. Earlier studies have shown that the NA and HA TMDs possess determinant(s) for apical sorting and raft-association (Kundu et al., 1996. J. Virol 70, 6508-6515; Lin et al., 1998. J. Cell Biol. 142, 51-57). Analysis of chimeric constructs between NA and TR (human transferring receptor) TMDs and the mutations in the NA and HA TMD sequences showed that the COOH terminus of the NA TMD and NH(2) terminus of the HA TMD encompassing the exoplasmic leaflet of the lipid bilayers were significantly involved in lipid raft-association and that apical determinants were not discrete sequences but rather dispersed within the TMD of HA and NA. These analyses also showed that although both signals for apical sorting and raft-association resided in the NA TMD, they were not identical and varied independently. Interactions of M1 protein with HA or NA, the influenza virus envelope glycoproteins, were investigated by TX-100 detergent treatment of membrane fractions and floatation in sucrose gradients. Results from these analyses showed that the interaction of M1 with mature HA and NA, which associated with the detergent-resistant lipid rafts caused an increased detergent-resistance of the membrane-bound M1 and that M1 interacted with HA and NA both in influenza virus-infected cells as well as in recombinant vaccinia virus-infected cells coexpressing M1 with HA and/or NA. Furthermore, both the cytoplasmic tail and the TMD of HA caused an increased detergent-resistance of the membrane-bound M1 supporting their interaction with M1. Immunofluorescence analysis by confocal microscopy also showed colocalization supporting the interaction of M1 with HA and NA at the cell surface and during exocytic transport both in influenza virus-infected cells as well as in coexpressing cells.

Immunolocalization of aquaporin-9 in rat hepatocytes and Leydig cells.

The aquaporin (AQP)-9 gene was recently isolated from human and rat liver cDNA libraries as a member of the water channel family for water and neutral solutes. Although the expression of AQP9 mRNA has been demonstrated in several organs including the liver and testis by Northern blot analysis, the cellular and subcellular localization of the AQP9 protein remains unclear. In the present light and electron microscopic immunohistochemical study, the localization of the AQP9 immunoreactivity was examined in fifteen kinds of rat organs using an antibody against rat AQP9 synthetic peptide. The antibody immunostained a major band of approximately 33 kDa in the liver by Western blot analysis. Immunoreactivity for AQP9 was found exclusively in the liver and testis among the organs examined. In the liver, positive staining appeared selectively along the space of Disse. Immunoelectron microscopy confirmed the localization of AQP9 on the surface of hepatocyte microvilli facing the space of Disse. In the testis, the plasma membrane of Leydig cells located between seminiferous tubules was conspicuously immunoreactive to the antibody. Intense mRNA expression was detected in the liver and testis but not in other organs by ribonuclease protection assay. These findings suggest a specific role for AQP9 in the transport of water and non-charged solutes in hepatocytes and Leydig cells.

Expression profile of extracellular matrix and its regulatory proteins during the process of interstitial fibrosis after anti-glomerular basement membrane antibody-induced glomerular sclerosis in Sprague-Dawley rats.

Anti-glomerular basement membrane (GBM) nephritis in Sprague-Dawley (SD) rats was characterized by development of marked glomerular sclerosis and tubulointerstitial fibrosis. To elucidate sequential change of the glomerular sclerosis and tubulointerstitial fibrosis, accumulation and mRNA expression of extracellular matrix (ECM) components and transforming growth factor (TGF)-beta were examined in the glomerulus and cortex during the disease course by histology, immunostaining and ribonuclease protection assay. Mild proliferative and degenerative lesions appeared in the glomeruli by day 15 after anti-GBM antibody binding to GBM and progressed to glomerular sclerotic lesion thereafter. Conversely, interstitial change was first recognized by infiltration of mononuclear cells after day 20, followed by marked accumulation of ECM and tubular degeneration. The interstitial fibrosis was induced without apparent binding of anti-GBM antibody to tubular basement membrane. Accumulation of fibronectin, collagen type I and type IV was noted in the interstitium by immunofluorescence microscopy in association with enhanced expression of mRNA for these ECM components and their regulatory molecules such as matrix metalloproteinase (MMP2), tissue inhibitor of metalloproteinase (TIMP)-1 and TGF-beta1 both in glomeruli and cortex. The glomerular expression of these mRNA increased apparently by day 15 and reached a plateau or a peak at day 20. The expression of the same mRNA increased gradually from day 15 to day 29 in the cortex. These observations show that interstitial fibrosis follows glomerular sclerosis after anti-GBM antibody injection in SD rats, suggesting that at least a part of the mechanism for ECM accumulation in the glomerulus and interstitium is essentially the same in terms of composition of ECM and expression of its regulatory molecules.