CKD: Sodium Requirements (2010)
To discuss the treatment of hypertension in four target patient groups with chronic renal disease: patients with chronic renal insufficiency (CRI) with and without proteinuria, patients with end-stage renal disease (ESRD) treated by HD; patients with ESRD treated by peritoneal dialysis (PD); and renal transplant patients (RTR).
Article inclusion criteria not specified.
Recruitment: Article selection methods not specified.
Design: Narrative Review.
Blinding Used (if applicable): not specified.
Intervention (if applicable): not specified.
Statistical Analysis: not specified.
Timing of Measurements: not specified.
Dependent Variables: not specified.
Independent Variables: not specified.
Control Variables: not specified.
Initial N: 229 references used.
Attrition (Final N): 229
Age: not specified.
Ethnicity: not specified.
Other Relevant Demographics: not specified.
Anthropometrics: not specified.
Location: worldwide studies
Clinical recommendations
1. The prevalence of hypertension in chronic renal disease (CRD) is ~60% to 100%, depending on the target population, cause of kidney disease, and level of kidney function.
2. Hypertension is associated with CVD outcomes in all CRD target populations. In patients with chronic renal insufficiency (non dialysis) and renal transplant recipients (RTR), hypertension is associated with CRD outcomes.
3. The preferred therapy is control of extracellular fluid (ECF) volume and maintenance of dry weight through dietary salt reduction in all target populations, diuretics in patients with CRI and RTR.
4. In CRI and probably in RTR, target blood pressure for antihypertensive therapy should be <125/75 mm Hg in patients with proteinuria (urine protein excretion >1 g/d) and < 130/85 mm Hg in patients without proteinuria, to improve CRD outcomes, as well as CVD outcomes. Given equivalent levels of blood pressure control, regimens containing angiotensin-converting enzyme (ACE) inhibitors are suggested to improve CRD outcomes.
Background
1. The Sixth Joint National Committee for Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) for target blood pressure for antihypertensive therapy to improve CVD outcomes:
a. defines optimal systolic and diastolic blood pressure as <120 and <80 mm Hg, respectively.
b. defines hypertension as systolic or diastolic blood pressure >140 or >90 mm Hg, respectively.
c. defines a blood pressure goal <140 and <90 mm Hg, for systolic and diastolic, respectively, with antihypertensive therapy in patients with essential hypertension.
2. Hypertension can be either a cause or a consequence of CRD.
a. based on epidemiological data from the National High Blood Pressure Education Program and National Health and Nutrition Examination Surveys (NHANES), stroke, MI, and CHF have decreased by ~15% to 40% whereas hypertensive nephropathy as a cause of ESRD is increasing at an annualized rate of 10% for the least several years.
b. the prevalence of hypertension in CRD is far higher than in the general population, ranging from 60% to 100%, depending on the target population.
c. when patients with CRD are treated with antihypertensive medications, patients’ compliance must be closely monitored because of multiple medications and also must be monitored for therapeutic effectiveness while monitoring renal function.
Target population: chronic renal insufficiency
1. The prevalence of hypertension in patients with CRI varies according to the cause of renal disease, level of renal function, and other patient characteristics; MDRD Study baseline cohort statistics on hypertension:
a. blacks: 93%
b. whites: 81%
c. glomerular disease: 85%
d. tubulointerstitial disease: 63%
e. GFR of 50-80 mL/min/1.73 m2: 65%
f. GFR of 10-20 mL/min/1.73 M2 :90%
2. As in the general population, hypertension is not adequately treated in CRI.
a. MDRD Study, although 91% of patients were treated with antihypertensive agents, only 54% had blood pressures <140/90 mm Hg.
b. epidemiological studies report even lower percentages of patients with CRI adequately treated, especially African-Americans.
CVD outcomes
1. The prevalence of CVD and related outcomes in CRI has not been evaluated in large-scale epidemiological studies, and little is known about CVD mortality and morbidity in CRI.
a. many authors report a high prevalence of left ventricular hypertrophy (LVH) in patients with CRI and those initiating RTR; multivariate analysis has shown an association between higher systolic blood pressure, lower renal function, more severe anemia, and older age, with higher left ventricular mass index.
b. Jungers showed a higher incidence of clinical CVD events in patients with CRI than expected in the general population; multivariate analysis found higher systolic blood pressure, lower HDLcholesterol, cigarette smoking and higher fibrinogen levels to be independent predictors of CVD.
CRD outcomes
1. The strongest argument supporting the role of hypertension in the progression of CRI are clinical trials showing a beneficial effect of antihypertensive therapy in slowing the rate of progression and in delaying the onset of ESRD.
a. in renal disease due to type I diabetes, decreasing blood pressure <140/90 mm Hg slows the worsening of albuminuria and decline in GFR.
b. in both the MDRD Study and the African- American Study of Hypertension and Kidney Disease Pilot Study, there were lower blood pressure goals for those with proteinuria.
2. The role of specific classes of antihypertensive agents, rather than target blood pressure levels, also has been investigated.
a. ACE inhibitors in combination with other drugs appear to be more effective in improving CRD outcomes than antihypertensive regimens not including ACE inhibitors; in most of the studies, the renal protective effect of ACE inhibition appeared to be independent of the level of blood pressure, suggesting a beneficial effect of the ACE inhibitor.
Therapy
1. Nonpharmacological therapy is not as effective in treating hypertension as in the general population and antihypertensive medications are usually required; salt restriction must be emphasized either as primary or adjunct therapy to antihypertensive therapy in CRI however:
a. as renal function declines, expansion of ECF volume frequently contributes to the elevation in blood pressure, especially in patients with significant proteinuria and/or the nephrotic syndrome.
b. a high salt intake sustains ECF volume expansion and limits the effect of antihypertensive medications.
b. a high salt intake also limits the beneficial effect of ACE inhibitors and nondihydropyridine calcium channel blockers on proteinuria.
c. restriction of dietary sodium to 2-3 g/d may be necessary to achieve the target blood pressure.
Target population: renal transplant recipients
Prevalence
1. The prevalence of hypertension in RTRs is 70% to 85%, which is higher than in the general population and higher than in patients with CRI with comparable levels of renal function.
a. the pretransplantation level of blood pressure seems to have little relationship with the posttransplantation blood pressure level.
b. the pathophysiology of hypertension is thought to be a combination of fluid overload due to reduced renal function of renal allograft and systemic vasoconstriction due to antirejection therapy with more than one cause operating simultaneously.
c. cyclosporine and other immunosuppressive agents may enhance vasoconstriction of systemic arteries; vasoconstriction is also due, in part, to activation of the rennin-angiotensin system in the allograft or the remaining native kidneys.
CVD outcomes
1. Hypertension is associated with an increased risk of CVD outcomes including CAD, LVH, and death in RTR.
a. some studies suggest that the incidence of CAD events in RTRs is higher than can be accounted for by the level of blood pressure and other known risk factors.
b. no controlled studies have been performed in RTRs to assess the effect of blood pressure control on CVD outcomes.
CRD outcomes
1. A large prospective observational study from the Collaborative Transplant Group documents that higher blood pressure is associated with more rapid progression of renal disease and graft failure in RTR.
a. there have been no controlled trials to assess the effect of blood pressure control on CRD outcomes.
Therapy
1. As in CRI, nonpharmacological therapy alone is not effective in lowering elevated blood pressure and antihypertensive medications are usually required.
a. dietary salt restriction is helpful as an adjunct.
b. almost all drug classes have been studied and shown to lower blood pressure effectively.
c. ACE inhibitors have not been rigorously compared to other antihypertensive agents in randomized controlled trials, but as in CRI, they may slow the progression of allograft dysfunction, especially in patients with proteinuria.
Pathogenetic mechanisms for hypertension in CRD
Based on these studies, JNC-FI recommended a target blood pressure <125/75 mm Hg in patients with CRI and proteinuria >1 g/d, and <130/85 mm Hg in patients without proteinuria.
1. Studies provide strong support for the clinical recommendation that ACE inhibitors provide a beneficial effect on CRD outcomes in CRI due to type 1 diabetes mellitus.
2. It also appears that ACE inhibition provides a beneficial effect on CRD outcomes and possibly CVD outcomes in patients with type 2 diabetes as well.
3. Most studies show that ACE inhibitors are beneficial in nondiabetic renal disease in slowing the decline in renal function.
Careful monitoring of weight, blood pressure, renal function, and serum electrolytes is necessary to judge the efficacy of therapy and to avoid ECF volume depletion in patients following a salt-restricted diet.
It is likely that lowering blood pressure to <140/90 mm Hg improves CVD outcomes in RTRs but the target blood pressure and preferred antihypertensive agents have not been adequately defined.
It is likely that the adverse effects of hypertension on the renal allograft are similar to those observed in other renal diseases: <130/85 mm Hg in TRT without proteinuria and <125/75 mm Hg in patients with proteinuria.
ACE inhibitors are widely used in RTR and may have side effects similar to those observed in CRI and may aggravate cyclosporine-induced hyperkalemia.
| University/Hospital: | Northshore University Hospital, NYU School of Medicine, New England Medical Center, Tuffs University |
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Quality Criteria Checklist: Review Articles
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| Relevance Questions | |||
| 1. | Will the answer if true, have a direct bearing on the health of patients? | Yes | |
| 2. | Is the outcome or topic something that patients/clients/population groups would care about? | Yes | |
| 3. | Is the problem addressed in the review one that is relevant to dietetics practice? | Yes | |
| 4. | Will the information, if true, require a change in practice? | Yes | |
| Validity Questions | |||
| 1. | Was the question for the review clearly focused and appropriate? | Yes | |
| 2. | Was the search strategy used to locate relevant studies comprehensive? Were the databases searched and the search termsused described? | No | |
| 3. | Were explicit methods used to select studies to include in the review? Were inclusion/exclusion criteria specified andappropriate? Wereselectionmethods unbiased? | No | |
| 4. | Was there an appraisal of the quality and validity of studies included in the review? Were appraisal methodsspecified,appropriate, andreproducible? | No | |
| 5. | Were specific treatments/interventions/exposures described? Were treatments similar enough to be combined? | Yes | |
| 6. | Was the outcome of interest clearly indicated? Were other potential harms and benefits considered? | Yes | |
| 7. | Were processes for data abstraction, synthesis, and analysis described? Were they applied consistently acrossstudies and groups? Was thereappropriate use of qualitative and/or quantitative synthesis? Was variation in findings among studies analyzed? Were heterogeneity issued considered? If data from studies were aggregated for meta-analysis, was the procedure described? | No | |
| 8. | Are the results clearly presented in narrative and/or quantitative terms? If summary statistics are used, are levels ofsignificance and/or confidence intervals included? | Yes | |
| 9. | Are conclusions supported by results with biases and limitations taken into consideration? Are limitations ofthe review identified anddiscussed? | Yes | |
| 10. | Was bias due to the review's funding or sponsorship unlikely? | Yes | |