Peritoneal equilibration test with conventional 'low pH/high glucose degradation product' or with biocompatible 'normal pH/low glucose degradation product' dialysates: does it matter?

BACKGROUND: The evaluation of the peritoneal transport characteristics is mandatory in peritoneal dialysis (PD) patients. This is usually performed in routine clinical practice with a peritoneal equilibration test (PET) using conventional dialysates, with low pH and high glucose degradation product (GDP) concentrations. An increasing proportion of patients are now treated with biocompatible dialysates, i.e. with physiological pH and lower GDP concentrations. This questions the appropriateness to perform a PET with conventional solutions in those patients. The aim of our study is to compare the results of the PET using biocompatible and conventional dialysates, respectively. METHODS: Nineteen stable PD patients (13 males, 6 females; mean age: 67.95±2.36 years, mean body surface area: 1.83±0.04 m2, dialysis vintage: 2.95±0.19 years) were included, among which 10 were usually treated with biocompatible and 9 with conventional solutions. Two PETs were performed, within a 2-week interval, in each patient. PET sequence (conventional solution first or biocompatible solution first) was randomized in order to avoid 'time bias'. Small (urea, creatinine and glucose), middle (beta-2-microglobulin) and large molecules' (albumin and alpha-2-macroglobulin) dialysate/plasma (D/P) concentration ratios and clearances were measured during each PET. Ultrafiltration (UF) and sodium filtration were also recorded. Results of both tests were compared by the Wilcoxon paired test. RESULTS: No statistical difference was found between both dialysates for small molecule transport rates or for sodium filtration and UF. However, a few patients were not similarly classified for small-solute transport characteristics within the PET categories. Beta-2-microglobulin and albumin D/P ratios at different time points of the PET were significantly higher with the biocompatible, when compared with the conventional, solutions: 0.10±0.03 versus 0.08±0.02 (P<0.01) and 0.008±0.003 versus 0.007±0.003 (P=0.01), respectively. A similar difference was also observed for beta-2-microglobulin that was higher with biocompatible dialysates (1.04±0.32 versus 0.93±0.32 mL/min, respectively). CONCLUSION: Peritoneal transport of water and small solutes is independent of the type of dialysate which is used. This is not the case for the transport of beta-2-microglobulin and albumin that is higher under biocompatible dialysates. Vascular tonus modification could potentially explain such differences. The PET should therefore always be carried out with the same dialysate to make longitudinal comparisons possible.

Urinary and dietary sodium and potassium associated with blood pressure control in treated hypertensive kidney transplant recipients: an observational study.

BACKGROUND: In kidney transplant (Kt) recipients , hypertension is a major risk for cardiovascular complications but also for graft failure. Blood pressure (BP) control is therefore mandatory. Office BP (OBP) remains frequently used for clinical decisions, however home BP (HBP) have brought a significant improvement in the BP control. Sodium is a modifiable risk factor, many studies accounted for a decrease of BP with a sodium restricted diet. Increased potassium intake has been also recommended in hypertension management. Using an agreement between office and home BP, the present study investigated the relations between the BP control in Kt recipients and their urinary excretion and dietary consumption of sodium and potassium. METHODS: The BP control defined by OBP <140/90 mmHg and HBP <135/85 mmHg was tested in 70 Kt recipients (mean age 56 ± 11.5 years; mean graft survival 7 ± 6.6 years) treated with antihypertensive medications. OBP and HBP were measured with a validated oscillometric device (Omron M6®). The 24-hour urinary sodium (Na+) and potassium (K+) excretions as well as dietary intakes were compared between controlled and uncontrolled (in office and at home) recipients. Non parametric Wilcoxon Mann-Whitney Test was used for between groups comparisons and Fisher's exact test for frequencies comparisons. Pearson correlation coefficients and paired t-test were used when sample size was >30. RESULTS: Using an agreement between OBP and HBP, we identified controlled (21%) and uncontrolled recipients (49%). Major confounding effects susceptible to interfere with the BP regulation did not differ between groups, the amounts of sodium excretion were similar (154 ± 93 vs 162 ± 88 mmol/24 h) but uncontrolled patients excreted less potassium (68 ± 14 vs 54 ± 20 mmol/24 h; P = 0.029) and had significantly lower potassium intakes (3279 ± 753 vs 2208 ± 720 mg/24 h; P = 0.009), associated with a higher urinary Na+/K + ratio. Systolic HBP was inversely and significantly correlated to urinary potassium (r = -0.48; P = 0.002), a positive but non significant relation was observed with urinary sodium (r = 0,30;P = 0.074). CONCLUSIONS: Half of the treated hypertensive Kt recipients remained uncontrolled in office and at home. Restoring a well-balanced sodium/potassium ratio intakes could be a non pharmacological opportunity to improve blood pressure control.

The faecal abundance of short chain fatty acids is increased in men with a non-dipping blood pressure profile.

BACKGROUND AND AIMS: Gut microbiota (GM) has been involved in the pathophysiology of hypertension (HT), notably via short chain fatty acids (SCFAs). Among the clinical manifestations of HT, the absence of a significant drop in night-time blood pressure (BP) (also known as the non-dipping BP profile) has been associated with poor renal and cardiovascular outcomes. The putative link between GM-derived metabolites and BP dipping status is still unknown. METHODS: Male volunteers (n = 44) were prospectively subjected to 24-hour ambulatory blood pressure monitoring, stool sample collection and a medical questionnaire. Metabolomics analyses of stool samples were conducted using Nuclear Magnetic Resonance (NMR). RESULTS: Higher amounts of acetate, butyrate and propionate were found in the stools of non-dippers (n = 12) versus dippers (n = 26) (p = 0.0252, p = 0.0468, and p = 0.0496, respectively; n = 38 in toto). NMR spectral data were not interpretable in 5 dippers and 1 non-dipper. A similar significant association was found when including only patients without anti-HT medications (p = 0.0414, p = 0.0108, and p = 0.0602, respectively; n = 21 in toto). A not significant trend was observed when focussing only on HT patients without anti-HT medications (p = 0.0556; n = 14 in toto). CONCLUSION: Our pilot study highlights a putative link between GM-derived SCFAs and the BP dipping status, independently of the BP status itself or the anti-hypertensive medications.

Human Stool Metabolome Differs upon 24 h Blood Pressure Levels and Blood Pressure Dipping Status: A Prospective Longitudinal Study.

Dysbiosis of gut microbiota (GM) has been involved in the pathophysiology of arterial hypertension (HT), via a putative role of short chain fatty acids (SCFAs). Its role in the circadian regulation of blood pressure (BP), also called "the dipping profile", has been poorly investigated. Sixteen male volunteers and 10 female partners were subjected to 24 h ambulatory BP monitoring and were categorized in normotensive (NT) versus HT, as well as in dippers versus non-dippers. Nuclear magnetic resonance (NMR)-based metabolomics was performed on stool samples. A 5-year comparative follow-up of BP profiles and stool metabolomes was done in men. Significant correlations between stool metabolome and 24 h mean BP levels were found in both male and female cohorts and in the entire cohort (R2 = 0.72, R2 = 0.79, and R2 = 0.45, respectively). Multivariate analysis discriminated dippers versus non-dippers in both male and female cohorts and in the entire cohort (Q2 = 0.87, Q2 = 0.98, and Q2 = 0.68, respectively). Fecal amounts of acetate, propionate, and butyrate were higher in HT versus NT patients (p = 0.027; p = 0.015 and p = 0.015, respectively), as well as in non-dippers versus dippers (p = 0.027, p = 0.038, and p = 0.036, respectively) in the entire cohort. SCFA levels were significantly different in patients changing of dipping status over the 5-year follow-up. In conclusion, stool metabolome changes upon global and circadian BP profiles in both genders.

[What is the ideal blood pressure goal for the hypertensive population in 2010? Review of the evidence in the literature]. / Quelle cible tensionnelle idéale pour nos patients hypertendus en 2010? Revue des preuves publiées.

The guidelines for treating high blood pressure, published in 2007, have been discussed in 2009. Currently, when hypertension is confirmed, it is proposed to treat the patients with a blood pressure goal of 130-139/80-85 mmHg whatever the diseases associated with hypertension. The authors recommended that if the patient tolerates lower blood pressures, the treatment could be continued. Many questions remained without any clear answer for the lowest protective target of blood pressure. The choice of antihypertensive agents appears to become more important in people with high cardiovascular risk. However, never forget to improve the cardiovascular risk by modifying the lifestyle and diet of the whole hypertensive population and by optimally acting on the associated risk factors identified.

Discrepancies between creatinine-based and cystatin C-based equations in estimating prevalence of stage 3 chronic kidney disease in an elderly population.

BACKGROUND: The prevalence of stage 3 chronic kidney disease (CKD) is increasing, calculated using the modification of diet in renal disease (MDRD) study equation for estimating glomerular filtration rate (GFR). Cystatin C-based equations are also being used to estimate GFR. Using creatinine-based and cystatin C-based equations, the aim of our study was to measure the difference in prevalence of stage 3 CKD in a population. METHODS: CKD screening is organized in the Province of Liege, Belgium. On a voluntary basis, people aged between 45 and 75 years are invited for screening. GFR is estimated using the MDRD study equation and by the three recent cystatin C-based equations proposed by Levey's group. The Levey 1 equation is based on cystatin C only and the Levey 2 equation on cystatin C corrected for age and sex. The Levey 3 equation combines cystatin C, creatinine, age and sex. RESULTS: The population screened comprised 754 people. Cystatin C is highly correlated with creatinine (r = 0.6196, p<0.0001). Prevalence of stage 3 CKD when GFR is estimated by the MDRD equation study is 17.2%, which is significantly and much higher than the prevalence obtained when cystatin C-based equations are used. Indeed, prevalence is 2%, 3.3% and 5.8% with the Levey 1, 2 and 3 equations, respectively. CONCLUSIONS: The prevalence of stage 3 CKD varies strongly following the method used for estimating GFR, creatinine-based or cystatin C-based equations. Such discrepancies must be confirmed and explained in additional studies using GFR measured with a reference method.

Gut Microbiota and Fecal Levels of Short-Chain Fatty Acids Differ Upon 24-Hour Blood Pressure Levels in Men.

Gut microbiota may influence blood pressure (BP), namely via end products of carbohydrate fermentation. After informed consent, male volunteers were prospectively categorized into 3 groups upon European Society of Hypertension criteria based on 24-hour ambulatory BP measurements: (1) hypertension, (2) borderline hypertension, and (3) normotension. Stool, urine and serum samples were collected in fasting conditions. Gut microbiota was characterized by 16S amplicon sequencing. Metabolomics, including quantification of short-chain fatty acids, was conducted using nuclear magnetic resonance. Two-way ANOVA combined with Tukey post hoc test, as well as multiple permutation test and Benjamini-Hochberg-Yekutieli false discovery rate procedure, was used. The cohort included 54 males: 38 hypertensive (including 21 under treatment), 7 borderline, and 9 normotensive. No significant difference was observed between groups concerning age, body mass index, smoking habits, and weekly alcohol consumption. The genus Clostridium sensu stricto 1 positively correlated with BP levels in nontreated patients (n=33). This correlation was significant after multiple permutation tests but was not substantiated following false discovery rate adjustment. Short-chain fatty acid levels were significantly different among groups, with higher stool levels of acetate, butyrate, and propionate in hypertensive versus normotensive individuals. No difference was observed in serum and urine metabolomes. Correlation between stool metabolome and 24-hour BP levels was evidenced, with R2 reaching 0.9. Our pilot study based on 24-hour ambulatory BP measurements, 16S amplicon sequencing, and metabolomics supports an association between gut microbiota and BP homeostasis, with changes in stool abundance of short-chain fatty acids.

Optimal blood pressure level and best measurement procedure in hemodialysis patients.

Hypertension occurs frequently among hemodialysis (HD) patients and can be due to many factors, such as salt intake, elevated sympathetic tone, and uremic toxins. It is responsible for the high cardiovascular risk associated with renal disease. Generally, in HD patients, while there is an elevation of systolic blood pressure (BP), diastolic BP seems to decrease, and the resultant effect is high pulse pressure, which can have a deleterious effect on the cardiovascular system. Although controversial, in the HD population the relationship between BP and risk of death seems to be U shaped, probably because of pre-existing cardiac disease in patients with the lowest BP. In chronic kidney disease, BP lower than 130/80 mmHg is recommended, but an appropriate target for BP in the HD population remains to be established. Moreover, there is no consensus regarding which routine peridialysis BP (pre- or post-dialysis BP, or both) can ensure the diagnosis of hypertension in this population. Ambulatory BP monitoring remains the gold standard to quantify the integrated BP load applied to the cardiovascular system. As well, home BP assessment could contribute to improve the definition of an optimal BP in the HD population. An ideal goal for post-dialysis systolic BP seems to be a value higher than 110 mmHg and lower than 150 mmHg. However, HD patients are generally old and often have cardiac complications, so a reasonable pre-dialysis target systolic BP could be 150 mmHg. It is prudent to suggest that an improvement in BP control is necessary in the HD population, first by slow and smooth removal of extracellular volume (dry weight) and thereafter by the use of appropriate antihypertensive medication.