Mediators of
the process include abnormal glomerular hemodynamics, hypoxia, proteinuria,
hypertension, and several vasoactive substances (i.e, cytokines and growth
factors). However,
hypertension is recognized as one of the main contributing factors and
complication of CKD.3, 4 Hypertension
in CKD increases the risk of important adverse outcomes, including loss of
kidney function and kidney failure, early development and accelerated
progression of cardiovascular disease (CVD), and premature death.5 It has been convincingly
demonstrated that lowering of blood pressure below what is recommended for
patients with essential hypertension slows the progression.6 There is
growing evidence that some of the adverse outcomes of CKD can be prevented or
delayed by preventive measures, early detection, and treatment. In theory, all antihypertensive
drugs should slow the progression of CKD. However, different antihypertensives
alter glomerular haemodynamics to different extents. Treatments to delay
progression are aimed at treating the primary disease and at strictly
controlling the systemic blood pressure and proteinuria. Accumulating data suggest that
for any given level of systemic BP reduction, angiotensin converting enzyme
inhibitors (ACE-I) produce superior antiproteinuric and renoprotective effects,
especially in diabetics and in patients with established proteinuria.7 JNC
VI (published in 1997) recommend that hypertensive patients with CRF should
receive, unless contraindicated, an ACE-I inhibitor as first line agent.8 Recent JNC- VII report published in
2003 describes that multidrug regimens will often be necessary, and diuretics
are suggested as the second AHT drug. Angiotensin receptor blockers (ARBs) are
increasingly seen as alternative AHTs in renal failure.9 Optimal outcome
of medical treatment in routine care depends not only on patient compliance
with drug regimens, but also on prescriptioner adherence to evidence-base or
therapeutic guidelines. In JNC VII the recommended target BP was
<130/80 mmHg for all patients with chronic kidney disease.9 Management
of Hypertension is more difficult in renal patients and requires multi drug
therapy, which is further influenced adversely by diabetic condition. In a
small number of studies, reduction in blood pressure with antihypertensive
medication has been shown to improve measures of renal disease progression and
cardiac hypertrophy in patients with advanced CKD. Reduction in blood pressure
with antihypertensive medication clearly improves measures of kidney function,
slows the progression to end-stage renal disease (ESRD), and improves clinical
outcomes such as clinical cardiovascular events and mortality in this
individual10. The present study was done to find prescription trend
in Indian nephrology practice and its adherence to therapeutic guidelines.
Another objective was to compare no. of anti-hypertensive drugs required for
control of blood pressure in diabetic and non-diabetic patients with chronic
kidney disease.
MATERIALS AND METHODS:
Study
Methodology: Based on the physicians’ diagnosis, 120
patients out of all patients with CKD from various hospitals in western area
were analyzed according to structured data evaluation sheet. In the clinic, all
patients were seen by one of three senior nephrologists and only on occasion by
junior nephrologists. Patient having blood pressure greater or equal to 140/90
mm Hg and fulfilling inclusion-exclusion criteria were enrolled for present
study. Initially, age, gender and medical history of each patient were recorded.
At week 0, Patients were tested for random blood sugar level to confirm whether
diabetic or not. Level of Serum Creatinine and Blood Pressure were recorded at
0 week, 4 week, 8 week and 12 week. In treatment, Goal of blood pressure is to
achieve BP up to <130/80 mmHg for all patients. In treatment strategy,
same antihypertensive drugs along with other concomitant medications were
continued to each patient for 3 months. Antihypertensive drugs were
administered according to physician’s judgment, not necessarily following any
specific guidelines. Prescribed antihypertensive drugs, doses and frequency
were recorded from patient case file. Patients who failed to follow up
regularly were drop out from this study. Patient data requiring additional
drugs and/or omission of one or more antihypertensive drugs during study period
were not used for statistical consideration. Collected data will be analyzed
using Ms Excel. Laboratory Examination: All blood and urine sample collection will be analysed at local
laboratory facility of site and as per laboratory standards.
Method of blood Pressure measurement:
Measurement of BP of each patient were done by using mercury
sphygmomanometer with an appropriate-sized cuff (cuff bladder encircling at
least 80 percent of the arm) on right arm in sitting position. To ensure accuracy, at least three
readings obtained two minutes apart for each patient.
Inclusion
criteria:
1. Patient should be having chronic
kidney disease of any stage having Serum creatinine value ≥ 1.4 mg/dl.
2. Age should be greater than 18
years.
3. Measured blood pressure should
be greater or equal to 140/90 mm Hg as the mean of three readings obtained two
minutes apart.
Exclusion
criteria:
1. Renal transplant recipient
patients.
2. Patients who are on dialysis.
3. Patient with serious cardio vascular-illness,
malignancy and/or other serious illness.
4. Pregnancy or lactation.
5. Patients with known
hypersensitivity to any of components of study medication.
Withdrawal
Criteria:
1.
If patient develop serious side effects due
to study drug.
2. Patient undergoing meantime
dialysis and/or renal transplant.
All
study medications prescribed in present study were approved and marketed
products in India. Medications were prescribed by qualified nephrologists of
hospital. Protocol of present study designed to eliminate any risk. This is to
justify that there was no need of patient informed consent. Although materials
and methods were not risky or injurious, patient falling under discontinuation
criteria were immediately dropped out and prescribed additional drugs and/or
omission of one or more drugs.
Statistical
Consideration:
MS
Excel was used to check co-relation between variables. From collected data of
Age, gender and Serum creatinine, e-GFR will be calculated as per MDRD formula.Data
collected at 0, 4, 8 and 12 weeks after treatment was compared to those
obtained before treatment. A paired Student's t-test will used to
compare quantitative variables. A value of P < 0.05 will be
considered significant; quantitative results were expressed as mean 
SD.
RESULTS AND DISCUSSION:
Patients'
characteristics: A total of 277 hypertensive patients with CKD were identified in
outpatient department. Of these, 90 received renal replacement therapy, and 67 patients
were excluded due to lack of contact with nephrologists. Thus, a total of 120
patients were included in the study. Patient characteristics are shown in Table
1-Table 2.
Table 1: Patient
Characteristics
|
Parameters |
Total |
|
Total (N) |
120 |
|
Sex
(Male/Female) |
66/54 |
|
Age (years)
(Mean ± S.D.) |
50.63±14.02 |
|
Diabetes (N) |
42 |
Table 2: No. of Patient with diabetic
condition
|
|
Male |
Female |
Total |
|
Diabetes |
23 |
9 |
32 |
|
Non diabetic |
43 |
45 |
88 |
|
Total |
66 |
54 |
120 |
Aetiology:
The underlying
cause of the CKD is given in Table 3.
Table 3: Aetiology of Chronic
Kidney Disease
|
Aetiology |
N |
% |
|
Chronic Glomerulonephritis |
28 |
23% |
|
Obstructive Nephropathy |
12 |
10% |
|
Diabetic Nephropathy |
17 |
14% |
|
Polycystic kidney disease |
5 |
4% |
|
Renovascular disease |
6 |
5% |
|
Nephrosclerosis |
5 |
4% |
|
Heart failure |
4 |
3% |
|
Chronic tubulointestinal disease |
2 |
2% |
|
Amylodiasis |
3 |
3% |
|
Other Systematic disease |
9 |
8% |
|
Unknown |
29 |
24% |
|
Total |
120 |
100% |
Prescription frequency of antihypertensive Medication: The most frequently prescribed
drug substance with antihypertensive effect was frusemide (n=82 or 68%).
Diuretics (frusemide, thiazides, spironolactone) were prescribed in Majority of
cases (n=104 or 87%) as one drug along with other antihypertensive drugs. Prescription frequencies of
different anti-hypertensive drugs have shown in Table No.4
Table 4: Prescription frequency
of AHTs in CKD patients
|
Class of AHT |
N |
% |
|
Diuretics |
104 |
87% |
|
ACE inhibitors |
33 |
28% |
|
β- Adrenergic blockers |
42 |
35% |
|
Calcium channel blockers |
88 |
73% |
|
α-Adrenergic blockers |
35 |
29% |
|
ARBs |
27 |
23% |
Calcium channel blockers were prescribed
as a total of 88 patients (73%) had an second largest prescription use. ACE
inhibitors were prescribed for 33 patients and ARBs were prescribed for 27
patients. Thus, total of 60 (50%) patients receive drugs which act on renin
angiotensin system. JNC VI recommended that a combination of ACE-I and loop
diuretic was a part of the drug regimen for 24 (20%) of the patients. ACE-I (n=9)
or ARB (n=4) was a part of the antihypertensive regimen for 13 of the 32
patients with diabetes.
BP and achievement of
BP goals: Failure to achieve
target BP was observed among patients prescribed a varying number of AHTs
ranging from 1 to 5. (Table 5).
|
Number of AHTs |
Patients |
SBP and DBP goal
achieved |
||
|
|
N |
% |
N |
% |
|
1 |
11 |
9% |
3 |
3% |
|
2 |
40 |
33% |
11 |
9% |
|
3 |
46 |
38% |
19 |
16% |
|
4 |
19 |
16% |
9 |
8% |
|
5 |
4 |
3% |
2 |
2% |
|
Total |
120 |
100 |
44 |
37% |
It was not possible
to find causal relation between BP and number of AHTs. The mean number of AHTs prescribed
per patient was 3.Present study find that mean number of AHTs prescribed for
diabetic patients (n=3.3) is more than non diabetic patient. (n=2.7)
Table 6: Blood Pressure and Goal achievement
|
Parameters |
Total (n=120) |
|
SBP |
|
|
Mean(mmHg) (95% CI ) |
143 |
|
Goal Achievement (%) (95% CI) |
40 |
|
DBP |
|
|
Mean(mmHg) (95% CI ) |
84 |
|
Goal Achievement (%) (95% CI) |
67 |
Univariate linear regression analyses were performed
with SBP and DBP as the dependent and one of the following as the independent
variable: age, gender, S-Cr, GFR and diabetes mellitus (yes/no). The only
statistically significant association found was a higher SBP with increasing
age (P=0.005).
Present
study found that failure to control SBP was more common than failure to control
DBP. Out of all patients, 37% of the patients achieved both the SBP and the DBP
goal. Further data on the extent of BP goal achievement are given in Table 6.