CKD: Progression and Diabetes (2001)
The purpose of this review is to discuss strategies available to halt or delay the progression of renal disease and its comorbidities in patients with chronic renal insufficiency.
Recruitment: not specified. 26 articles included.
Design: Systematic 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: not specified
Attrition (Final N): not specified
Age: not specified
Ethnicity: not specified
Other Relevant Demographics: not specified
Anthropometrics: not specified
Location: not specified
Control of hypertension
Control of hypertension is of major importance in patients with chronic renal insufficiency (CRI) to minimize the progression of renal failure and to decrease the risk of cardiovascular complications associated with renal failure.
1. Multiple Risk Factor Intervention Trial (MRFIT):
a. 330,000 men were followed over a 16 yr period to assess the development of ESRD.
b. Higher blood pressure was a strong independent risk factor for ESRD.
2. The Hypertension Optimal Treatment (HOT) study:
a. assessed the association between 3 target diastolic blood pressures (<90, <85, and <80 mm Hg) during antihypertensive therapy and the incidence of major cardiovascular events.
b. Lowering blood pressure to < 85 mm Hg was associated with a reduction in the incidence of major cardiovascular events.
c. Lowering blood pressure was of particular benefit in the subgroup of patients with diabetes; there was a significant decrease (51%) in the incidence of major cardiovascular events in the decreased blood pressure target group compared with the increased blood pressure target group (P<0.005).
d. cardiovascular events were more frequent among patients with mild renal insufficiency (baseline creatinine clearance <60 ml/min) in all blood pressure target groups irrespective of the treatment offered.
3. Dasgupta et al, 1999
a. study evaluated the quality of blood pressure control in 145 patients admitted to a dialysis program over a 3-year period in England.
b. target diastolic pressure (British Hypertension Society, at time of study) <90 mm Hg was met by only 45% of the subjects.
c. poor blood pressure control probably contributed to the progression of renal failure in 32% of the subjects.
Use of ACE inhibitors and control of proteinuria
ACE inhibitors may have kidney-protecting properties independent of their antihypertensive effect. In addition, ACE inhibitors can reduce urinary protein excretion.
1. Collaborative Study Group, US
a. Randomized control trial to evaluate the effects of the ACE inhibitor (captopril), 25 mg TID on renal function; follow-up was 3 yr; subjects had a serum creatinine concentration <2.5 mg/dL and urinary protein excretion > 500 mg; target blood pressures were <140/<90 mm Hg.
b. the percentage of patients with a doubling of baseline creatinine to >2 mg/dL was significantly lower in the captopril group compared to the control group.
c. the percentage of patients requiring dialysis, transplantation or who died was significantly lower in the captopril group (11%) than the placebo group (21%)
2. Ramipril Efficacy in Nephropathy (REIN) study evaluated the benefits of an ACE inhibitor in non-diabetic patients with renal disease.
a. 352 patients were stratified at baseline into a lowurinary protein excretion group (1-3 g/24 hr) or a high urinary protein excretion group (>3 g/24 hr) and randomly assigned to ramipril or placebo + conventional antihypertensives to achieve a target diastolic blood pressure <90 mm Hg.
b. in the high urinary protein excretion group, there was a significant improvement in the rate of decline in GFR in patients with ramipril compared with patients on placebo.
c. urinary protein excretion significantly decreased from baseline in the ramipril group over the first month of treatment and remained below baseline throughout the study; urinary protein excretion did not change significantly in the placebo group.
d. only 23% of patients in the ramipril group compared with 45% of patients in the control group reached the combined endpoint of a doubling of the serum creatinine concentration or development of ESRD (P=0.02).
Control of diabetes
A prolonged period of intensive therapy to produce nearly normal blood glucose concentration is able to delay or prevent the earliest manifestation of diabetic nephropathy.
1. Diabetes Control and Complications Trial (DCCT) found that intensive treatment in type 1 diabetes to achieve near normal blood glucose and HbA1c resulted in a significant reduction in the incidence of microvascular complications when compared with conventional therapy.
a. during a 4-yr follow-up period of 1,441 patients originally enrolled in the DCCT, patients on conventional therapy were offered intensive therapy and progressive microalbuminuria (reduced 53%) and clinical proteinuria remained (86% reduction) in the former intensive treatment group in spite of worsening hyperglycemia after the DCCT was discontinued.
2. Steno Trial evaluated intensive vs. standard treatment in 150 patients with type 2 diabetes and microalbuminuria over 4 years in Denmark.
a. Ace inhibitors were prescribed irrespective of blood pressure and aspirin prescribed in the intensive group
b. progression to nephropathy, retinopathy and autonomic neuropathy were all significantly lower in the intensive group.
c. 10% of patients in the intensive group vs. 24% in the conventional group developed nephropathy during follow-up.
Dietary protein restriction
Dietary protein restriction in CRI patients has been the subject of clinical trials with restrictions of 0.4 to 0.6 g/kg associated with a modest decrease in the rate of CRI progression.
Restriction is difficult to achieve and maintain in most patients, therefore most nephrologists recommend 0.8 to 1.0 g/kg/d.
Control of hyperlipidemia
No studies of reasonable size have addressed specifically whether reversal of lipid abnormalities is of benefit in patients with renal disease. However, hyperlipidemia should be managed with the primary aim of improving cardiovascular outcomes.
Anemia management
Anemia is common in patients with CRI and treatment with epeotin (EPO) offers substantial clinical benefits in terms of improvements in quality of life and reductions in morbidity and mortality.
a. Jungers et al, 2001, in retrospective study of the rate of decline of creatinine clearance and the duration of the pre-dialysis period in 63 patients with CRI, 20 of whom had renal anemia (Hg 8.8 g/dL) and received EPO treatment; the remaining 43 had a similar degree of CRF but had asymptomatic anemia (mean Hg of 10.9 g/dL) and did not receive EPO.
1) the mean rate of decline in creatinine clearance was significantly lower (0.26 ml/min vs. 0.36 ml/min) in the EPO group with no significant change in the control group.
2) the mean time to start dialysis was 16.2 months in the EPO group vs. 10.6 months in the control group (P<0.01).
b. Fink et al, 2001, evaluated mortality for subjects receiving EPO during the pre-dialysis period on the subsequent incidence of mortality in patients who had progressed to ESRD.
1) of the 4,866 patients evaluated, 22.7% received EPO and the risk of death was significantly lower for those receiving EPO in the predialysis period with a relative risk of 0.8.
Hypertension is a strong independent risk factor for ESRD and there is a consensus that blood pressure management is an important aspect of care in patients with CRI.
Clinical studies have shown that ACE inhibitors have renoprotective properties independent of their antihypertensive benefits, which can delay the onset of ESRD.
Intensive treatment of type 1 and 2 diabetes to achieve near normal blood glucose, can reduce the incidence of progressive clinical proteinuria and may therefore, protect against ESRD.
Treatment of renal anemia with EPO can decrease mortality and delay the onset of dialysis in CRI patients, however more studies need to be done to confirm these findings.
| University/Hospital: | University of Western Ontario (Canada) |
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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? | ??? | |
| 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? | ??? | |
| 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 | |