The impact of GLP-1 receptor agonist liraglutide on blood pressure profile, hydration, natriuresis in diabetic patients with severely impaired kidney function.

Chronic treatment with GLP-1R agonists may moderately lower blood pressure due to increased natriuresis and RAAS inhibition. Short-term effect of these drugs on blood pressure may be opposite and its mechanism remains unclear. We investigated the effect of a single dose of liraglutide on diurnal blood pressure profile, natriuresis, hydration and serum concentration of renin, aldosterone and atrial natriuretic peptide (ANP) in diabetic kidney disease (DKD). 17 patients with eGFR < 30 ml/min/1.73 m2 and 17 with > 60 ml/min/1.73 m2 received in a random order a single subcutaneous dose 1.2 mg liraglutide and placebo with subsequent 24 h blood pressure and natriuresis monitoring. Before and after each medication thoracic fluid index and plasma renin, aldosterone and ANP were also assessed. The blood pressure load in the daytime and nighttime were significantly increased after liraglutide compared to placebo in patients with eGFR < 30 ml/min/1.73 m2. In patients with eGFR > 60 ml/min/1.73 m2 the changes of arterial pressure were comparable, while the morning surge was significantly reduced after liraglutide compared to placebo. After liraglutide 24 h urine sodium excretion increased in both groups vs. placebo (p < 0.001), the effect was greatest in subjects with eGFR > 60 ml/min/1.73 m2. Plasma ANP increased after liraglutide in both groups, most in patients with eGFR < 30 ml/min/1.73 m2 group. Plasma aldosterone (p = 0.013) and thoracic fluid index (p = 0.01) decreased after liraglutide compared to placebo (p = 0.013 and p + 0.01, respectively. Plasma renin concentration remained unchanged. In severe chronic kidney disease liraglutide induces a transient increase of blood pressure due to reduced natriuresis. The natriuretic effect of liraglutide in DKD may be related to increased ANP and decreased aldosterone secretion.

Effects of Oral Bicarbonate Supplementation on the Cardiovascular Risk Factors and Serum Nutritional Markers in Non-Dialysed Chronic Kidney Disease Patients.

Background and Objectives: Kidneys play a key role in maintaining the acid−base balance. The aim of this study was to evaluate the effect of a 3-month oral sodium bicarbonate administration on arterial wall stiffness, arterial pressure and serum nutritional markers in non-dialysed patients with chronic kidney disease (CKD) stages 3−5 and metabolic acidosis. Methods: Eighteen CKD patients with eGFR < 45 mL/min/1.73 m2 and capillary blood bicarbonate (HCO3) < 22 mmol/L were enrolled in this single-centre, prospective study. Anthropometric parameters, pulse wave velocity, 24-h ambulatory blood pressure measurements, blood and urine parameters were assessed at the beginning and at the end of the study. The patients received supplementation with 2 g of sodium bicarbonate daily for three months. Results: A significant increase of pH: 7.32 ± 0.06 to 7.36 ± 0.06; p = 0.025, HCO3 from 18.7 mmol/L (17.7−21.3) to 22.2 mmol/L (20.2−23.9); p < 0.001 and a decrease in base excess from −6.0 ± 2.4 to −1.9 ± 3.1 mmol/L; p < 0.001 were found. An increase in serum total protein from 62.7 ± 6.9 to 65.8 ± 6.2; p < 0.013 and albumin from 37.3 ± 5.4 to 39.4 ± 4.8; p < 0.037 but, also, NT-pro-BNP (N-Terminal Pro-B-Type Natriuretic Peptide) from 794.7 (291.2−1819.0) to 1247.10 (384.7−4545.0); p < 0.006, CRP(C Reactive Protein) from 1.3 (0.7−2.9) to 2.8 (1.1−3.1); p < 0.025 and PTH (parathyroid hormone) from 21.5 ± 13.7 to 27.01 ± 16.3; p < 0.006 were observed, as well as an increase in erythrocyte count from 3.4 ± 0.6 to 3.6 ± 0.6; p < 0.004, haemoglobin from 10.2 ± 2.0 to 11.00 ± 1.7; p < 0.006 and haematocrit from 31.6 ± 6.00 to 33.6 ± 4.8; p < 0.009. The mean eGFR during sodium bicarbonate administration did not change significantly: There were no significant differences in pulse wave velocity or in the systolic and diastolic BP values. Conclusion: The administration of sodium bicarbonate in non-dialysed CKD patients in stages 3−5 improves the parameters of metabolic acidosis and serum nutritional markers; however, it does not affect the blood pressure and vascular stiffness.

Utility of copeptin and standard inflammatory markers in the diagnostics of upper and lower urinary tract infections.

BACKGROUND: A new serum marker of inflammation copeptin (CPP) a stable C-terminal pro-vasopressin was assessed along with conventional markers such as C-reactive protein (CRP), procalcitonin (PCT) and IL-6 to discriminate between lower and upper bacterial urinary tract infections (UTI). METHODS: Study population comprised 45 patients including 13 with lower UTI (L-UTI) and 32 with upper UTI (U-UTI) and 24 healthy controls. Serum markers, blood cultures and urine cultures were assessed before commencing antibiotic treatment and repeated 24, 48 h and 7 days thereafter. Receiver operating curves (ROC) were plotted to assess a diagnostic utility of different inflammatory markers. RESULTS: Before antibiotic therapy all inflammatory markers including serum CPP (2821.1 ± 1072.4 pg/ml vs. 223.8 ± 109.3 pg/ml; p < 0.05) were higher in UTI than in controls. CPP was not different between L- and U-UTI (2253 ± 1323 pg/ml vs 3051 ± 1178 pg/ml; p = 0.70) despite significant differences in hsCRP (2.09 ± 1.7 mg/dl vs 127.3 ± 62.4 mg/dl; p < 0.001), PCT (0.05 ± 0 vs 5.02 ± 0.03 ng/ml p < 0.001) and IL-6 (22.5 ± 1.6 vs 84.8 ± 67 pg/ml p < 0.001). For U-UTI the areas under the ROC curves were 1.0 for both hsCRP and CPP, 0.94 for PCT and 0.7 for IL-6 and for L-UTI 0.571, 1, 0.505 and 0.73, respectively. After 7 days of treatment all markers decreased in parallel to clinical response. CONCLUSION: Although elevated serum copeptin may become a marker of UTI it seems to be inferior compared to traditional serum inflammation markers for differentiation of bacterial infections involving upper and lower urinary tract.

Influence of hemodialysis on incretin hormones and insulin secretion in diabetic and non-diabetic patients.

BACKGROUND: Incretin hormones are secreted in the gut after a meal and stimulate insulin production. Both major incretins, that is, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are eliminated by the kidneys. Little is known about the influence of end-stage renal disease (ESRD) on the incretin axis. The aim of the study was to assess the effect of the commencement of chronic hemodialysis (HD) therapy on serum GLP-1 and GIP, and insulin sensitivity in diabetic and non-diabetic patients. SUBJECTS AND METHODS: The study comprised 56 patients (23 F, 33 M; mean age 57 ± 14 years) with ESRD in the course of diabetic nephropathy (n = 23) and non-diabetic renal diseases (n = 34) who started chronic HD. Glucose metabolism, including incretin hormones concentration, was assessed before the first HD session and repeated after the first 6 months of the therapy. RESULTS: After 6 months of HD, a significant increase in fasting GLP-1 concentration was observed in both diabetic and non-diabetic patients [by 2.27 pmol/l (45 %) and 1.28 pmol/l (22 %), respectively, p = 0.0003]. Serum GIP increased significantly only in diabetic patients [by 30.9 pg/ml (55 %); p = 0.008]. No significant change of fasting glucose was found but HOMA-IR and serum insulin decreased significantly in diabetic patients (p = 0.01 and p = 0.008, respectively). In contrast, HOMA-B was unchanged in both groups. Changes of HOMA-IR did not significantly correlate with serum GLP-1 or GIP concentrations. CONCLUSION: Our results indicate that starting the hemodialysis therapy helps to restore the incretin axis in particular in patients with the diabetic kidney disease.