Current Hypertension Reviews - Volume 10, Issue 2, 2014

The studies on the relation between Na intake and blood pressure were started at the Brookhaven National Laboratories in Upton (New York) by Lewis K Dahl in 1961, however the story goes back to our hunter-gatherer predecessors who, between 750,000 and 10,000 years ago, ate diets proving a Na intake of 690mg/day. The relevance of this finding became evident when the data of the studies on Yanomamo Indians of Brazil and Venezuela (living in the tropical forest) became available. They showed that in these populations sodium intake averages 1.34±2.01 mEq/24 hours, and that their blood pressure increases from the first to the second decade of life and then tapers down. Studies in chimpanzees, a species genetically similar to humans, the DASH Trial, the Intersalt Study, various meta-analyses, the data in persons with stroke, the blood pressure profile of newborns on low Na intake, and various studies in hypertensives with and without Chronic Kidney Disease, have demonstrated the beneficial effects of a restricted low salt intake alone or as an adjunct to drug therapy on blood pressure profiles.

In the last decade many guidelines and report have been published about the optimal restriction of sodium intake for blood pressure control which deserve to be discussed in the medical community at large. The list includes i. the 2005 Dietary Guidelines of the Department of Health and Human Services and US Department of Agriculture; ii. The 2010 Dietary Guidelines for Americans; iii. The 2011 Presidential Statement of American Heart Association; iiii. The 2012 WHO guidelines on sodium intake in adults and children, v. The 2013 Report of the Institute of Medicine of the National Academies of the United States. All of them support the efficacy and feasibility of sodium restriction for blood pressure control.

Hypertension is often difficult to control in patients with chronic kidney disease. Clinicians often view thiazide and thiazide-like diuretics as being ineffective in reducing blood pressure in patients with chronic kidney disease, and prefer to use loop diuretics, especially if the estimated glomerular filtration rate (eGFR) is below 50 ml/min/1.73m2. Recent clinical trial data indicate that thiazide and thiazide-like diuretics possess important and clinically significant antihypertension properties, that are likely independent of volume reduction, even in patients with eGFR in the 15-45 ml/min range. Thiazide and thiazide-like diuretics should be given consideration for use in the treatment of hypertension in patients with chronic kidney disease, especially if there is no clinical evidence of volume overload.

Hypertension (HT) is one of the major problems in chronic kidney disease (CKD), not only for adults, but also for children. It is one of the main factors in the progression of CKD, increased rate of cardiovascular disease, and impairment in quality of life. The most important devastating effect of HT is on the cardiovascular system. It may leave significant footprints in developing children that can be carried over to adulthood. Existing data clearly show that in CKD children with proteinuria the blood pressure goal should be 50th centile, while it is 75th centile in those without proteinuria. Renin-angiotensin system inhibitors are considered the first choice pharmacological option in hypertensive CKD stage 2 to 4 patients. However, in clinical practice, pediatric nephrologists may experience significant problems in treatment and follow-up of these patients, especially in compliance. Due to multiple drug use, physician-patient and family cooperation would be essential to improve the compliance. Remembering the fact that prevention is always cheaper than treatment, we need early detection of CKD and its devastating complications, like HT. Therefore, active screening programs should be encouraged in children, as well as trying to find new biomarkers, inspired from the footprints of HT. Although the researches on new urinary biomarkers for early detection of CKD and HT are promising, more studies are needed in this area. This review aims to give an overview of HT in CKD children, mainly focusing on importance of HT, basic principles of treatment, problems in follow up, and possible markers for early detection of CKD and HT.

Chronic kidney disease (CKD) has been consistently associated with cardiovascular disease; there is an inverse graded relationship between glomerular filtration rate and cardiovascular risk. Early-moderate CKD receives increasing recognition for its role as an independent risk factor as evidenced by its recent inclusion in the Joint British Societies' consensus recommendations for the prevention of cardiovascular disease. Data from both imaging and epidemiological studies suggest arterial stiffening and structural left ventricular disease (hypertrophy and fibrosis) are the key pathogenic mediators of cardiovascular disease in CKD. This review discusses the rationale for measuring central blood pressure in patients with CKD and whether it could provide incremental prognostic value beyond that of peripheral blood pressure.

The consensus conference on cardio-renal syndromes (2008) defined ‘cardio-renal syndromes’ as ‘disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other’ and identified five subtypes of the syndromes. Various pathophysiologic mechanisms underlie cardiorenal syndrome including hemodynamic derangements, reduced cardiac output leading to impaired renal perfusion, reduced stroke volume, raised atrial filling pressures, elevated atrial pressures, sodium and water retention, venous congestion, right ventricular dysfunction and venous hypertension causing increased renal venous pressure, intra-abdominal hypertension, various neurohormonal adaptations including activation of the renin-angiotensin-aldosterone system, adaptive activation of the sympathetic nervous system, cytokine release and oxidative stress. Although there are standardized clinical guidelines for the management of heart failure, and chronic kidney disease, respectively, there are no similar consensus clinical guidelines for the management of the cardiorenal syndromes. RAAS inhibition is advocated in treating systolic heart failure. There is evidence that RAAS inhibition is also useful in cardiorenal syndrome. However, RAAS inhibition, while potentially useful in the management of cardiorenal syndrome, is not the ‘magic bullet’, is sometimes limited by adverse renal events, is not applicable to all patients, and must be applied by physicians with due diligence and caution. Nevertheless, a more comprehensive multidisciplinary multipronged approach to managing patients with cardiorenal syndrome is even more pragmatic and commonsense given the multiple mechanisms and pathogenetic pathways implicated in the causation and perpetuation of cardiorenal syndrome.

Metabolic acidosis is a frequent but asymptomatic complication in chronic kidney disease (CKD). In early stages of CKD acidosis is limited to the renal tissue and progresses to reduced serum bicarbonate levels. Reduced renal tissue pH and increased ammoniagenesis are the key mechanisms of the kidney to enhance acid excretion to the urine. The expressed protein patterns in the proximal tubular epithelial cells change remarkably, the proximal convoluted tubule develops hypertrophy, and an intra-renal enhanced renin-angiotensin-system leads to interstitial fibrosis. Since nephrons are numerically reduced in CKD each remaining functional unit has to progressively increase these mechanisms to keep up the equilibrium. The adverse effects of chronic metabolic acidosis include aside from acceleration of progression of kidney disease, the development or exacerbation of bone disease, increased degradation of muscle with muscle wasting, enhanced protein degradation and inflammation. Genome wide association studies demonstrated that tubular acid-base transporters are involved in the development of arterial hypertension. Several retrospective analyses have indicated that low serum bicarbonate predicts death in cohorts with CKD and cardiovascular disease. All studies confirmed a U-shaped association of mortality and serum bicarbonate, indicating that both, acidosis and alkalosis are associated with increased mortality. Randomized controlled trials showed that base substitution, either by modification of the diet or by simply adding alkalizing agents, might halt the decline of kidney function in subjects with CKD. In 2012 a meta-analysis concluded that alkali therapy might provide a long-term favorable effect on renal function in patients with CKD.

Background: ESRD (end-stage renal disease) patients have a high cardiovascular mortality risk. A morphofunctional approach of vascular calcifications and myocardial perfusion is needed for the management of ESRD patients. We used SEVR (sub-endocardial viability ratio) and Kauppila score from the dialysis population of the Independent study to create a new morpho-functional score to assess cardiovascular risk in this population (the Solofra score). Materials and Methods: 184 patients were followed-up for 36 months. A side lumbar X-ray was performed to assess vascular calcifications of lumbar aorta using the Kauppila score. Central aortic pressure and pulse velocity wave (PWV) were assessed at the carotid artery site. Myocardial perfusion was estimated with SEVR. Independent risk mortality factors were identified with univariate regression analysis (p<0.01); significance was defined as p<0.05. Results: Kauppila score was 13±10(range 0-24); PWV was 9.5±4 m/sec; basal SEVR was 1.3±0.9. We observed an improvement of ROC curves for SEVR and Kauppila score together compared to the ones for SEVR or Kauppila score alone. Conclusion: A quantitative analysis of vascular calcifications should be associated to a qualitative evaluation of arterial damage to better estimate cardiovascular mortality risk of ESRD patients. Further studies are needed to verify our hypothesis.