Hepatocyte Growth Factor in Predialysis and Hemodialysis Chronic Kidney Disease Patients.

Chronic kidney disease (CKD) which is characterized by progressive loss of renal function and renal fibrosis is a worldwide public health problem. Hepatocyte growth factor (HGF) is a polypeptide that exhibits multiple functions including antifibrotic effects on kidneys. The present study was aimed at evaluating HGF levels and studying its association with markers of inflammation and oxidative stress in patients of predialysis and dialysis CKD. A total of 80 subjects including 20 healthy controls, 40 patients of CKD stage 1 to stage 5 (predialysis), and 20 CKD patients with end-stage renal disease on hemodialysis were recruited. HGF, high-sensitivity C-reactive protein (hsCRP), malondialdehyde (MDA), and ferric reducing ability of plasma (FRAP) were measured in all the subjects. HGF levels were significantly higher in all patients with CKD compared to controls. The levels were found to be lower in patients on dialysis than in the predialysis group; however, the difference was not statistically significant. hsCRP, MDA, and FRAP were significantly higher in all patients with CKD than in controls. HGF levels did not show a significant correlation with the markers studied. HGF levels were increased in response to renal injury in CKD patients. The levels were higher in predialysis patients of CKD than in CKD patients on dialysis. HGF levels may be used as an indicator of renal fibrosis in patients with CKD.

Efficacy of oral rosuvastatin intervention on HDL and its associated proteins in men with type 2 diabetes mellitus.

PURPOSE: High-density lipoprotein (HDL) undergoes structural and functional modification in patients with type 2 diabetes mellitus (T2DM). There are limited data on effect of rosuvastatin on HDL-associated proteins and the antiatherogenic effects of rosuvastatin. The present study intended to study the efficacy of rosuvastatin intervention on HDL-associated proteins and its other antiatherogenic effects in men with T2DM. METHODS: Men with T2DM on oral antidiabetic treatment, with LDL-C levels > 75 mg/dL and willing for rosuvastatin intervention (20 mg/day orally for a period of 12 weeks), were included. Fasting glucose, lipid profile were measured using standard methods. Oxidized low-density lipoprotein (oxLDL), oxidized HDL (oxHDL), paraoxonase-1 (PON-1), tumour necrosis factor-α (TNF-α) and lecithin:cholesterol acyltransferase (LCAT) in serum were measured by ELISA; serum myeloperoxidase (MPO) by spectrophotometric method and cholesterol efflux by fluorometric assay. Carotid intima-media thickness (cIMT) measurement to assess vascular health status was done using doppler. RESULTS: Rosuvastatin produced a significant decrease (p < 0.05) in lipids (total cholesterol, triglycerides, LDL-C); oxidative stress (oxLDL, oxHDL, MPO); inflammation (TNF-α); LCAT concentration; cIMT; significant increase in antiatherogenic HDL and cholesterol efflux (p < 0.05) and no change in apoA-I levels from baseline to 12 weeks of follow-up. A decrease in MPO activity was found to be independently associated with an increase in cholesterol efflux. CONCLUSIONS: Post intervention there is a quantitative and qualitative improvement in HDL, which helps in its reverse cholesterol transport (RCT) and antioxidant functions. Improvement in HDL functions and suppression of inflammation by rosuvastatin lead to regression in cIMT, which is beneficial in decreasing the progression of cardiovascular disease (CVD) in men with diabetes.

Correction to: Efficacy of oral rosuvastatin intervention on HDL and its associated proteins in men with type 2 diabetes mellitus.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Osteopontin, Cardiovascular Risk Factors and Carotid Intima-Media Thickness in Chronic Kidney Disease.

The pleiotropic cytokine osteopontin (OPN) is found to be involved in the pathogenesis of both kidney and cardiovascular disease (CVD). We evaluated the relationship between OPN, other cardiovascular risk factors and carotid intima-media thickness (CIMT) in chronic kidney disease (CKD) (predialysis) patients. This is a 2-year cross-sectional prospective study involving 75 patients with CKD from stage 1 to stage 5 attending the nephrology outpatient department and 25 healthy controls. Routine biochemical parameters were analyzed on clinical chemistry Autoanalyzer Beckman Coulter DXC 600 Synchron, USA. OPN was estimated by ELISA method. Carotid intima-media wall thickness was estimated by Doppler of carotid vessels. Serum OPN and other nontraditional cardiovascular risk factors such as CIMT, lipoprotein (a) Lp(a), fibrinogen, and homocysteine were significantly increased in patients of CKD compared to controls. OPN, Lp(a), fibrinogen, CIMT, parathyroid hormone, and homocysteine progressively increased from early stages of CKD and increased further with progression of the disease, but nitric oxide (NO) level progressively decreased with progression of CKD. OPN showed a positive correlation with CIMT, Lp(a), fibrinogen, and homocysteine and negative correlation with estimated glomerular filtration rate and NO. There was a close direct association between circulating levels of OPN and the presence of atherosclerotic plaques in carotid arteries of patients with CKD. Osteopontin and nontraditional CVD risk factors are altered in early stages of CKD and might predict adverse outcomes in these patients.

Carbamylated Hemoglobin can Differentiate Acute Kidney Injury from Chronic Kidney Disease.

Carbamylated hemoglobin (CarHb) was found to have a potential role in the differentiation of patients with acute kidney injury (AKI) from chronic kidney disease (CKD). This study was aimed at the evaluation of the diagnostic performance and usefulness of CarHb in the differentiation of AKI from CKD. Forty patients with renal disease and twenty age- and sex-matched healthy controls were included in the study. Urea, creatinine, Hb, and CarHb were measured in all the subjects. Patients with AKI and CKD were found to have significantly increased levels of CarHb when compared to controls (P < 0.05 for both groups). Patients with CKD had significantly increased levels of CarHb when compared to patients with AKI (P < 0.05). CarHb showed significant positive correlation with urea in patients with renal disease (r = 0.776, P < 0.0001). Significant area under curve (AUC = 0.840, P < 0.0001) was obtained for CarHb and a cut-off value of 98.33 µg VH/g Hb resulted with the best combination of 85% sensitivity and 75% specificity. CarHb may provide clinical utility since patients with AKI and CKD have similar clinical presentation usually. A cut-off value of 98.33 µg VH/g Hb has been found to be useful to differentiate AKI from CKDs.

Simultaneous determination of arginine, citrulline, and asymmetric dimethylarginine in plasma by reverse-phase high-performance liquid chromatography.

BACKGROUND: Arginine, citrulline and asymmetric dimethylarginine (ADMA) are three molecules in the nitric oxide (NO) pathway which provide useful information about vascular endothelial function. ADMA accumulates with patients with chronic kidney disease (CKD) and inhibits NO synthesis. We describe the modification of a previously established method for the measurement of amino acids analysis for simultaneous detection of arginine, citrulline, and ADMA in plasma and to validate its performance in patients with CKD. MATERIALS AND METHODS: Arginine, citrulline, and ADMA were simultaneously separated by reverse-phase high-performance liquid chromatography by precolumn derivatization with O-phthalaldehyde using the modified method. It was then applied for analysis in thirty patients with CKD and thirty healthy controls so as to cover the entire measuring range, i.e., normal and uremic range. RESULTS: The method showed a good performance in terms of linearity, precision, and recovery. The detection limit of the assay for ADMA was found to be 0.05 µmol/L at a signal-to-noise ratio of 3:1. The average within run coefficient of variation for ADMA using this method was 4.7% in the normal range and 1.9% in the uremic range, while the average between-day precision in the normal and uremic range was 6.5% and 5.2%, respectively. Patients with CKD were found to have higher concentration of ADMA compared to controls. CONCLUSION: This method can be useful in assessing the baseline cardiovascular risk in an individual as well as in the follow-up of the patients who are receiving L-arginine, and thus, assess the response to treatment by simultaneous measurement of arginine and ADMA.

Role of Gut-derived Uremic Toxins on Oxidative Stress and Inflammation in Patients with Chronic Kidney Disease.

Several cardiovascular disease (CVD) risk factors have been identified among patients with chronic kidney disease (CKD). Gut-derived uremic toxins (GDUT) are important modifiable contributors in this respect. There are very few Indian studies on GDUT changes in CKD. One hundred and twenty patients older than 18 years diagnosed with CKD were enrolled along with forty healthy subjects. The patients were classified into three groups of forty patients based on stage of CKD. Indoxyl sulfate (IS), para cresyl sulfate (p-CS), indole acetic acid (IAA), and phenol were estimated along with the assessment of oxidative stress (OS), inflammatory state, and bone mineral disturbance. All the GDUT increased across the three groups of CKD. All patients had higher levels of malondialdehyde (MDA), ferric reducing ability of plasma (FRAP), high-sensitivity C-reactive protein (hsCRP), and interleukin-6 (IL-6) as compared to controls. IS and IAA showed positive association with MDA/FRAP corrected for uric acid, whereas IS and p-CS showed positive association with IL-6. IS, IAA, and phenol showed a positive association with calcium × phosphorus product. GDUT increase OS and inflammatory state in CKD and may contribute to CVD risk.

Utility of saliva as a sample to assess renal function and estimated glomerular filtration rate.

Diagnosis of renal diseases by assessing renal parameters in saliva. Biochemical investigations using serum form important component of monitoring patients with renal disease. Utility of saliva, in diagnosis and monitoring of patients with renal disease and for calculation of estimated glomerular filtration rate (eGFR), was studied. Sixty patients with renal disease and sixty ageand sex-matched healthy controls were studied. Urea, creatinine, sodium, potassium, uric acid, calcium, and phosphorus were measured in both serum and saliva. eGFR was calculated using salivary creatinine. Data were expressed as mean ± standard deviation. Comparison and correlation between groups were assessed by Student's t-test and Pearson correlation, respectively. Bland-Altman plot, mountain plot, and intra-class correlation coefficient were used to test agreement. A P <0.05 was considered statistically significant. Statistical analysis was done using Microsoft excel spreadsheets, Medcalc Version 10.0, and SPSS version 11.5. Salivary levels of urea, creatinine, uric acid, sodium, potassium, and phosphorus were higher in patients compared to controls. Potassium and phosphorus levels were higher (P = 0.001) and creatinine, sodium, calcium, and uric acid levels were lower (P = 0.001) in saliva compared to serum in both patients and controls. Positive correlation was observed between serum and salivary urea and creatinine (P < 0.0001). eGFR values calculated from salivary creatinine showed good agreement with those calculated form serum creatinine. Salivary urea (>6 mmol/L) and creatinine (>14.6 µmol/L) and eGFR calculated from salivary creatinine can be used to identify patients with renal disease.

Nitric oxide status in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) are at an increased risk of cardiovascular (CVD) morbidity and mortality, mainly due to atherosclerosis. Decreased production or reduced bioavailability of nitric oxide (NO) can result in endothelial dysfunction (ED). Multiple mechanisms are known to cause a state of NO deficiency in patients with CKD. Patients in various stages of CKD grouped as group-1 (CKD stage 1 and 2), group-2 (CKD stage 3 and 4), group-3 (CKD stage 5) and healthy controls were included in the study. Each group of patients and controls comprised 25 subjects. Plasma nitrites, L-arginine, asymmetric dimethyl arginine (ADMA) and citrulline were measured in all the subjects. Patients in all stages of CKD had lower NO and higher ADMA levels compared to controls. Further, group-2 and group-3 patients had lower levels of NO and higher levels of ADMA than group-1 patients. L-arginine levels showed no difference between patients and controls. However, group-3 patients had lower L-arginine levels compared to group-1 patients. Citrulline levels were decreased in group-3 patients. NO production was decreased in patients in all stages of CKD. The decrease could be due to decreased availability of the substrate, L-arginine or due to an increased ADMA, a potent inhibitor of endothelial NO synthase. Therapeutic interventions directed towards improvement of NO production in addition to management of other CVD risk factors may prevent development of ED and facilitate proper management of CKD patients who are at increased risk for CVD.