Importance of serum phosphate in elderly patients with diabetes mellitus.

BACKGROUND: Metabolic disturbances including changes in serum calcium, magnesium or phosphate (P) influence the prevalence of type 2 diabetes mellitus (DM). We assessed the importance of serum P in elderly patients with type 2 DM vs non-diabetes mellitus (non-DM) in relation to renal function. AIM: To determine the association between serum P and serum glucose or insulin resistance in diabetic and non-diabetic patients. METHODS: One hundred-ten subjects with a mean age of 69.02 ± 14.3 years were enrolled. Twenty-nine of the participants had type 2 DM (26.4%). The incidence of hypertension, smoking and receiving vitamin D (vitD) derivates were recorded. The participants were classified by both estimated glomerular filtration rate (eGFR) and albuminuria categories according to the Kidney Disease Improving Global Outcomes 2012 criteria. RESULTS: We divided the patients in two groups according to the P cut-off point related to DM value. A comparison between high and low P showed that body mass index 30.2 ± 6.3 vs 28.1 ± 4.6 (P = 0.04), mean glucose 63.6 vs 50.2 (P = 0.03), uric acid 6.7 ± 1.6 vs 6.09 ± 1.7 (P = 0.05), mean intact-parathyroid hormone 68.06 vs 47.4 (P = 0.001), systolic blood pressure 147.4 ± 16.7 vs 140.2 ± 16.1 (P = 0.02), mean albuminuria 63.2 vs 50.6 (P = 0.04) and eGFR 45.6 ± 22.1 vs 55.4 ± 21.5 (P = 0.02) were significantly different. χ 2 tests showed a significant association between high P and DM, hypertension, receiving vitD, smoking and eGFR stage (χ 2 = 6.3, P = 0.01, χ 2 = 3.9, P = 0.03, χ 2 = 6.9, P = 0.009, χ 2 = 7.04, P = 0.01 and χ 2 = 7.36, P = 0.04, respectively). The adjusted model showed that older age, female gender and increased body mass index were significant predictors of type 2 DM when entering the covariates. CONCLUSION: High serum P contributes to vascular and metabolic disturbances in elderly patients with type 2 DM and renal impairment.

Triglycerides to High-Density Lipoprotein Cholesterol Ratio Predicts Chronic Renal Disease in Patients without Diabetes Mellitus (STELLA Study).

BACKGROUND: The triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been included in the potential indices for atherosclerosis in chronic kidney disease (CKD). In this study, we addressed the role of the TG/HDL-C ratio on CKD prediction defined by both classified estimated glomerular filtration rate (eGFR) and classified urinary albumin-to-creatinine ratio (UACR) in non-diabetic participants. METHODS: One hundred and eighty-three subjects with a mean age 67.3 ± 15.6 years old were included. Our participants were classified in both eGFR and UACR categories according to the Kidney Disease Improving Global Outcomes 2012 criteria. Estimated pulse wave velocity (ePWV) was calculated using an equation from age and mean blood pressure. The TG/HDL-C ratio was calculated. X2 tests and adjusted models were applied using confounders. RESULTS: The TG/HDL-C ratio was inversely associated with eGFR and positively with both UACR and ePWV. We divided our patients in two groups according to the found ROC curve of the TG/HDL-C ratio cut-off point, either with an eGFR of less or more than 60 mL/min/1.73 m2. X2 tests showed significant association between the high TG/HDL-C ratio and classified eGFR, and classified UACR and hypertension (x2 = 24.5, p = 0.001, x2 = 12.5, p = 0.002 and x2 = 12.6, p = 0.001, respectively). The adjusted model showed the high TG/HDL-C ratio to be an independent predictor for both a low eGFR and UACR (OR = 1.5, 1.2-1.9 and OR = 1.22, 1.02-1.47, respectively) in combination with old age and hypertension. CONCLUSION: The TG/HDL-C ratio was revealed to be a potential predictor for both a low eGFR and micro/macroalbuminuria in non-diabetic patients. The arterial stiffening was included in the main underlying pathophysiological mechanisms.

Factors related to peripheral arterial disease in patients undergoing hemodialysis: the potential role of monocyte chemoattractant protein-1.

Peripheral arterial disease (PAD) is substantially prevalent among patients in the end stage of renal disease (ESRD). We considered factors related to peripheral arterial disease in patients undergoing hemodialysis including the important role of monocyte chemoattractant protein-1 (MCP-1) serum concentrations. We studied 150 patients in on-line-predilution hemodiafiltration. Dialysis sufficiency was defined by Kt/V for urea. PAD was defined using clinical criteria, ankle-brachial index and Doppler ultrasound in the lower limbs. MCP-1 serum concentrations were measured using enzyme-linked immunoabsorbed assay (ΕLISA). We performed chi-square tests and logistic regression analysis to investigate risk factors for the prevalence of PAD in these patients including MCP-1 serum concentrations. The patients with manifested PAD had elevated MCP-1, higher BP, higher arterial stiffness markers, higher markers of malnutrition, uncontrolled metabolic acidosis, bone disease and lower obtained dialysis adequacy than the patients without PAD. The association between PAD manifestation and high MCP-1 was found significant (x2 = 9.6, p = 0.001). The built logistic regression analysis showed that the high MCP-1 increased the risk for PAD 3.2 (95% C.I 1.3-8.2) folds after adjustment for confounders. PAD was also significantly associated with non-administration of vitamin D agents during dialysis (x2 = 3.5, p = 0.04).Malnutrition, low-grade inflammation mainly defined by high MCP-1 serum concentrations, metabolic acidosis and bone disease were included in significant predictors for peripheral arterial disease in patients undergoing hemodiafiltration. The obtained dialysis sufficiency and the therapy during dialysis sessions seem to play an additional role in the demonstration of peripheral vascular disease in these patients.

Oxidized Low-Density Lipoprotein Serum Concentrations and Cardiovascular Morbidity in End Stage of Renal Disease.

INTRODUCTION: Oxidized low-density lipoprotein (ox-LDL) is considered a main biomarker of oxidative stress, a common characteristic in end stage renal disease. We examined the relationship between ox-LDL serum concentrations and cardiovascular disease in permanent hemodiafiltration therapy patients. METHODS: Ox-LDL values were measured by ELISA and were corrected for LDL-cholesterol (LDL-C) in 96 participants and in 45 healthy control subjects. We performed chi-square tests and adjusted models for the role of ox-LDL on cardiovascular morbidity including coronary artery disease, left ventricular hypertrophy, systolic, diastolic dysfunction and peripheral arterial disease. RESULTS: ox-LDL/LDL-C values were significantly higher in patients than in control group (p = 0.02), due to increased ox-LDL serum levels rather than to low LDL-C. The unadjusted relationship between high ox-LDL/LDL-C and low ejection fraction was found significant (x² = 9.04, p = 0.003), although the association with the other cardiovascular manifestations was found non-significant. In the adjusted model for the prediction of systolic cardiac dysfunction, high ox-LDL/LDL-C, old age and non-administration of vitamin D supplementation during dialysis session were found to be significant predictors after adjustment to the confounder. Moreover, the association between systolic cardiac dysfunction and non-administration of vitamin D derivatives during dialysis sessions was found significant (x² = 6.9, p = 0.008). CONCLUSIONS: This study showed a significant association between high ox-LDL and systolic cardiac dysfunction in permanent hemodiafiltration therapy patients. This relationship seems to be influenced by aging and pharmaceutical therapy during dialysis sessions, including vitamin D derivatives.

The Association between Intradialytic Hypertension and Metabolic Disorders in End Stage Renal Disease.

BACKGROUND: Intradialytic hypertension was associated with a high mortality risk. We examined the relationship between intradialytic hypertension and metabolic disorders in hemodialysis treatment patients. METHODS: We studied 76 patients in online hemodiafiltration. Dialysis adequacy was defined by Kt/V for urea. Normalized protein catabolic rate (nPCR), as a marker of protein intake, was calculated. Sodium removal was determined as percent sodium removal. Metabolic acidosis was determined by serum bicarbonate less than 22 mmol/L. Interdialytic urine volume more than 100 ml was recorded. Intradialytic hypertension was defined by an increase in systolic blood pressure equal to 10 mmHg from pre- to posthemodialysis. Arterial stiffness was assessed as carotid-femoral pulse wave velocity (c-fPWV) and carotid augmentation index (AIx). Chi-square tests and logistic regression analysis were applied for intradialytic hypertension prediction. RESULTS: Patients with intradialytic hypertension were older and had significantly lower hemoglobin, nPCR, urine output, and serum bicarbonate and significantly higher c-fPWV, though similar Kt/V for urea, than patients without intradialytic hypertension. They also had increased sodium removal and pulse pressure related to less urine output. Serum bicarbonate was inversely associated with c-fPWV (r = -0.377, p = 0.001). Chi-square test showed significant association between intradialytic hypertension and serum bicarbonate < 22 mmol/L (x2 = 5.6, p = 0.01), which was supported by an adjusted model. CONCLUSION: The intradialytic hypertension was significantly associated with metabolic disorders including malnutrition/inflammation and uncontrolled metabolic acidosis in hemodialysis treatment patients. Severe metabolic acidosis may reflect sodium imbalance and hemodynamic instability of these patients resulting in volume overload and increased vascular resistance.

The Relationship of Residual Renal Function with Cardiovascular Morbidity in Hemodialysis Patients and the Potential Role of Monocyte Chemoattractant Protein-1.

BACKGROUND: Residual renal function (RRF) provides several benefits to patients on dialysis. Monocyte chemoattractant protein-1 (MCP-1) plays an important role in atherosclerotic lesions. We considered the relationship between RRF and cardiovascular morbidity and the significant role of MCP-1 serum concentrations in hemodiafiltration (HDF) patients. METHODS: We enrolled 76 patients on on-line HDF. RRF was defined by interdialytic urine output, and we studied the patients in two groups according to the preservation or not of urine output. MCP-1 levels were measured using enzyme-linked immunosorbent assay. χ2 tests were applied for the association between RRF and left ventricular hypertrophy (LVH), coronary artery disease (CAD), peripheral artery disease (PAD), and systolic and diastolic cardiac dysfunction. We built an adjusted model using logistic regression analysis for the factors which might impact on the loss of urine output. RESULTS: χ2 tests showed a significant association between the loss of urine output and LVH, diastolic dysfunction, and PAD (χ2 = 7.4, p = 0.007; χ2 = 14.3, p = 0.001; χ2 = 4.2, p = 0.03, respectively), although the association with CAD and systolic dysfunction was found to be nonsignificant. The patients without RRF had significantly higher MCP-1, and the urine volume was inversely associated with MCP-1 (r = -465, p = 0.03). In the built adjusted model, the elevated MCP-1 was found to be a significant predictor for the loss of RRF. CONCLUSION: The loss of RRF was significantly associated with LVH, diastolic dysfunction, and PAD in HDF patients. The increased MCP-1, affected by the lack of urine, may act as an additional underlying factor on this relationship, reflecting a progressive inflammation/oxidative stress condition.

The relationship between concentrations of magnesium and oxidized low-density lipoprotein and Beta2-microglobulin in the serum of patients on the end-stage of renal disease.

The end-stage of renal disease is associated with increased oxidative stress and oxidative modification of low-density lipoproteins (LDLs). Beta2 microglobulin (beta2M) is accumulated in the serum of dialysis patients. Magnesium (Mg) plays a protective role in the development of oxidative stress in healthy subjects. We studied the relationship between concentrations of magnesium and oxidized LDL (ox-LDL) and beta2M in the serum of patients on the end stage of renal disease. In 96 patients on on-line- predilution hemodiafiltration, beta2M and intact parathormone were measured by radioimmunoassays. High-sensitivity C-reactive protein (hsCRP) and ox-LDL were measured using ΕLISA. Serum bicarbonate levels were measured in the blood gas analyser gas machine. We performed logistic regression analysis models to investigate Mg as an important independent predictor of elevated ox-LDL and high beta2M serum concentrations, after adjustment to traditional and specific for dialysis patients' factors. We observed a positive correlation of Mg with ox-LDL (r = 0.383, P = 0.001), but the association of Mg with beta2M, hsCRP, and serum bicarbonate levels was significantly inverse (r = -0.252, P = 0.01, r = -0.292, P = 0.004, and r = -0.282, P = 0.04 respectively). The built logistic-regression analysis showed that Mg act as a significant independent factor for the elevated ox-LDL and beta2M serum concentrations adjusting to traditional and specific factors for these patients. We observed a positive relationship between magnesium and acidosis status- related ox-LDL concentrations, but the inverse association between magnesium and beta2M serum concentrations in hemodialysis patients.

Association between Low Serum Bicarbonate Concentrations and Cardiovascular Disease in Patients in the End-Stage of Renal Disease.

BACKGROUND: Metabolic acidosis, a common condition particularly in the end-stage of renal disease patients, results in malnutrition, inflammation and oxidative stress. In this study, we focused on the association between low serum bicarbonate and cardiovascular disease in patients on intermittent dialysis. METHODS: We studied 52 on-line-pre-dilution hemodiafiltration (on-l HDF) patients, 32 males and 20 females, with a mean age of 58.01 ± 15.4 years old. Metabolic acidosis was determined by serum bicarbonate concentrations less than 22 mmol/L. Residual renal function (RRF) was defined by interdialytic urine volume. Kaplan-Meier curves and Cox regression models were performed to predict coronary artery disease (CAD), defined by ejection fraction <50%, or diastolic dysfunction congestive heart failure (CHF) and peripheral vascular disease (PVD). RESULTS: Kaplan-Meier analyses showed that a lower or higher than 22 mmol/L serum bicarbonate metabolic acidosis status was significantly associated with both PVD and diastolic dysfunction (log-rank = 5.07, p = 0.02 and log-rank = 5.84, p = 0.01, respectively). A similar prevalence of serum bicarbonate on CAD or CHF by low ejection fraction was not shown. The RRF was associated with PVD event and serum bicarbonate less than 22 mmol/L (log-rank = 5.49, p = 0.01 and log-rank = 3.9, p = 0.04, respectively). Cox regression analysis revealed that serum bicarbonate and RRF were significant risk factors for PVD after adjustment for confounders. Furthermore, RRF adjusted for covariates was shown to be a significant risk factor for diastolic dysfunction. CONCLUSION: Low serum bicarbonate was associated with peripheral vascular disease and diastolic dysfunction in intermittent dialysis. The residual renal function may impact patients' outcomes through its relationship with metabolic acidosis status, particularly for peripheral vascular disease manifestation.

The relationship between glycemic control, beta2-microglobulin and inflammation in patients on maintenance dialysis treatment.

BACKGROUND: Hyperglycemia appears to play a significant role on the inflammatory cytokines production. Beta2-microglobulin (beta2M) is accumulated in the circulation of dialysis patients. We studied the relationship between glycemic control defined by glucose serum concentrations and insulin resistance, beta2M and markers of inflammation in patients on renal replacement therapies with or/and without diabetes mellitus. METHODS: We enrolled 96 dialyzed patients, 62 males and 34 females. The treatment modalities which were applied were : regular hemodialysis (HD, n = 34), predilution hemodiafiltration (HDF, n = 42) and peritoneal dialysis (PD, n = 20). Dialysis adequacy was defined by Kt/V for urea.Beta2M and insulin serum concentrations were measured by radioimmunoassays. hsCRP and TNF-α serum concentrations were measured by ELISA. Insulin resistance was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR).We examined the association of elevated serum glucose with inflammatory factors and we built a multivariable model to investigate if glucose could be a potential determinant of beta2M serum levels. RESULTS: Serum glucose was positively correlated with beta2M and TNF-α (r = 0.320, p = 0.002 and r = 0.215, p = 0.03 respectively).We observed significant association between the patients with higher serum glucose concentrations and the patients with greater beta2Μ concentrations (x(2) = 4.44, p = 0.03). Multivariable model showed that glucose acts as a significant independent determinant of beta2M adjusting for age, gender, dialysis modality and metabolic acidosis status. CONCLUSIONS: The elevated glucose concentrations were positively associated with both, greater beta2M serum concentrations and up-regulated inflammatory procedure in dialysis patients with or/and without diabetes mellitus.

Glucose Serum Concentrations and Cardiovascular Disease in Patients on the End Stage of Renal Disease without Diabetes Mellitus.

Background/Aim: It is still controversial whether tighter glycemic control is associated with better clinical outcomes in patients with kidney failure. We examined the association between glucose serum concentrations and cardiovascular disease in patients on the end stage of renal disease without diabetes mellitus. Methods: We studied 76 patients on on-line hemodiafiltration. Cardiovascular disease was defined by the existence of coronary disease (CD). Arterial stiffness was measured as carotid-femoral pulse wave velocity (c-fPWV) and carotid augmentation index (AIx). The concentrations of beta2-microglobulin (ß2M) and insulin were measured by radioimmunoassays and insulin resistance by HOMA-IR. We built a logistic-regression analysis to examine the role of glucose on cardiovascular disease after adjustment for the traditional and specific risk factors for dialysis patients. Results: Serum glucose was positively correlated with beta2M, insulin and HOMA-IR (r = 0.361, p = 0.002, r = 0.581, p = 0.001 and r = 0.753, p = 0.001 respectively). Logistic-regression analysis did not show significant impact of glucose concentrations on cardiovascular disease after adjustment for traditional and specific risk factors. Conclusions: The association between elevated glucose serum concentrations and represented by coronary syndrome cardiovascular disease in patients on the end stage of renal disease without diabetes mellitus was not found significant.

ß2-Microglobulin, pulse pressure and metabolic alterations in hemodialysis patients.

BACKGROUND/AIM: Pulse pressure (PP) is a result of arterial stiffness seen in dialysis patients, but may be a consequence of fluid overload. We examined the role of ß(2)-microglobulin (ß(2)M) in PP in relation to metabolic alterations in patients on different hemodialysis (HD) modalities. METHODS: We studied 76 hemodialyzed patients on regular HD (n = 34), predilution bagged hemodiafiltration (n = 19) and online predilution hemodiafiltration (n = 23). ß(2)M levels were measured by radioimmunoassay, and the clearance of ß(2)M was assessed by Kt/V for ß(2)M. Arterial stiffness was measured as carotid-femoral pulse wave velocity, and PP was derived. Insulin levels were measured using immunoradioassay, and insulin resistance was calculated using homeostasis model assessment insulin resistance (HOMA-IR). Serum bicarbonate levels were measured using a blood gas analyzer, and percent sodium removal was calculated. RESULTS: ß(2)M levels predict increased PP (p = 0.02) adjusting for age, HD modalities, HD duration, HOMA-IR and percent sodium removal. ß(2)M was positively associated with HOMA-IR (r = 0.306, p = 0.007). Serum bicarbonate levels and carotid-femoral pulse wave velocity were inversely associated (r = -0.719, p = 0.001). CONCLUSIONS: ß(2)M levels were positively associated with PP, which was influenced mainly by dialysis modality fluid and sodium balance and less by arterial stiffness. ß(2)M levels were positively associated with insulin resistance. Uremic acidosis may contribute to arterial stiffness.

Circulating antibodies to endogenous erythropoietin and risk for HIV-1-related anemia.

OBJECTIVES: In a previous retrospective study we have shown that circulating antibodies to endogenous erythropoietin (anti-EPO) are associated with HIV-1-related anemia. The present longitudinal cohort study was conducted to examine the effect of anti-EPO on the risk of developing anemia over time. METHODS: The study population consisted of 113 HIV-1 seropositive patients, who were screened for the presence of anti-EPO, with a mean+/-SD follow up of 105+/-40 months, for a total of 2190 visits. Anti-EPO were detected with an ELISA assay. RESULTS: Anti-EPO were detected in 41% (46/113) at enrollment and 29% (320/1094) for all visits, and were associated with higher EPO levels for all visits (45.7+/-60.4 vs. 31.8+/-31.7 IU/ml, p<0.001). After adjusting for other significant confounders, anti-EPO has been associated with increased risk of anemia both at enrollment (odds ratio [OR], 5.07; 95% confidence interval [CI], 1.25-20.49) as well as for all visits ([OR], 2.15; 95% [CI]: 1.29-3.56). During follow up, a decline in prevalence of both anti-EPO and anemia was observed as the percentage of patients receiving HAART was increasing. CONCLUSIONS: Anti-EPO are an independent risk factor for anemia in HIV-1-infected patients. HAART seems to reduce both anti-EPO and anemia prevalence.

Changes of plasma levels of gastrointestinal peptides over the course of acute pancreatitis. Any significance for the pathophysiology and treatment of acute pancreatitis?

BACKGROUND/AIMS: Acute pancreatitis may be accompanied by alterations of the secretion of pancreatic and gastrointestinal peptides as a result of pancreatic inflammation. These changes, that may constitute targets of therapeutic manipulation, led to the study of the serum levels of various pancreatic and gastrointestinal peptides over the course of acute pancreatitis before and after the administration of octreotide and ranitidine. METHODOLOGY: Concentrations of gastrin, glucagon, vasoactive intestinal peptide, neurotensin and pancreatic polypeptide were determined by radioimmunoassay in the plasma of 22 patients with acute pancreatitis on the first, sixth and 11th day of the disease. All patients were treated with octreotide s.c. while 14 of them were also administered ranitidine i.v. Treatment was initiated after taking the first blood sample. RESULTS: Mean gastrin levels in patients receiving ranitidine was 56.76 ng/L and in patients not receiving ranitidine 47.16 ng/L on the first day (pNS) remaining stable throughout the course of acute pancreatitis. Mean glucagon, vasoactive intestinal peptide, neurotensin and pancreatic polypeptide levels on the first day were 52.05 pmol/L, 8.90 pmol/L, 9.80 pmol/L and 22.06 pmol/L, respectively, and no changes were found through the course of acute pancreatitis. CONCLUSIONS: Plasma levels of gastrointestinal peptides remain constant over time and they are not significantly affected by the administration of octreotide or ranitidine. However more studies are necessary to document the significance of these findings.