DRUG UTILIZATION OF ANTI HYPERTENSIVES IN CKD PATIENTS: A RANDOMIZED PROSPECTIVE STUDY AT A TERTIARY CARE TEACHING HOSPITAL

 

 

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ABOUT AUTHORS
ASHIKA RANJANI. M*, SAHITHI GOUD. B, AMATUL WADOOD SUMAYYA, SYEDA NABILA FIRDOUS, AMATUL ALI SAMEERA
Dept. of Pharmacy Practice
Sree Dattha Institute of Pharmacy, Jawaharlal Nehru Technological University (Hyderabad)
Sheriguda (V), Ibrahimpatnam (M), Ranga Reddy (Dist), Telangana, India

ABSTRACT
AIMS AND OBJECTIVES: Our aim was to evaluate the clinical use of Antihypertensive drugs in patients with chronic Kidney disease at a tertiary care teaching hospital.

METHOD: An observational, prospective cohort study was conducted at a tertiary care teaching hospital in Hyderabad, T.S, India. A total of 184 patients from the inpatient department of nephrology Department at  Gleneagles Global Hospitals, Bairamalguda, LB Nagar, Hyderabad. All information significant to the study was collected from the case records and discussions conducted with the in-patients and bystanders during ward rounds, with the support of a physician, which were analyzed by SPSS software. Moreover, daily follow-ups were conducted to assemble data on amendment in therapy, add-on therapy, and clinical improvement.

RESULTS: The Mean Age was 59.29 years and the standard deviation was 1.116 of the population, 60% were smokers and 40% were alcoholics. The most commonly used Class of anti-hypertensive drugs are Calcium channel blockers with percentage of 64.13%, Diuretics with percentage of 57.60%, β blockers with percentage of 43.47%. Whereas most commonly used Calcium channel blockers are Amlodipine with percentage of 52%, and Cilindipine with percentage of 9.10%.Diuretics are are Furosemide with percentage of 36.90% and Toresemide 11.40%. Most commonly used Adenergic Antagonist are in β Blockers are Metoprolol with percentage of 31.50%, In α blockers are prazosin with percentage of 26%, In α+β blocker are Carvedilol with percentage of 8.60%. Most commonly used ARB’s are Telmisartan with percentage of 6.50%, and ACE’s are Ramipril with percentage of 1%. Most commonly used central sympatholytics are Clonidine with percentage of 18.40%, Vasodilators are Minoxidil with percentage of 1%. Medication adherence have been done, In which patients with High Adherence are with percentage of 16.21%, Medium Adherence are with percentage of 45.94%, Low Adherence are with percentage of 37%. This is done by Morisky medication adherence scale 8.

CONCLUSION: We have concluded that the CCB’s, diuretics and β-blockers are the most commonly used anti-hypertensive classes in hypertensive patients with CKD. Use of anti-hypertensives in CKD patients does not deviate from the guidelines laid down by NKF KDOQI guidelines. The patients should be educated about the rational use of drugs to decrease medication adherence.

Reference Id: PHARMATUTOR-ART-2652

PharmaTutor (Print-ISSN: 2394 - 6679; e-ISSN: 2347 - 7881)

Volume 7, Issue 03

Received On: 03/01/2019; Accepted On: 18/02/2019; Published On: 01/03/2019

How to cite this article: Ranjani, A.M., Goud, S., Sumayya, A., Firdous, S. and Sameera, A. 2019. Drug Utilization of Anti Hypertensives in CKD Patients: A Randomized Prospective Study at a Tertiary Care Teaching Hospital. PharmaTutor. 7, 3 (Mar. 2019), 41-72. DOI:https://doi.org/10.29161/PT.v7.i3.2019.41

INTRODUCTION
Chronic kidney disease most often results from a progressive loss of functioning nephrons caused by a primary kidney disease or as a secondary complication of certain systemic diseases, but it can also result from an acute event causing irreversible damage to the kidneys. (Mary Anne Koda-Kimble et al., 2008)

Both Hypertension (HTN) and CKD are serious interrelated global public health problems. Nearly 30% and 15% of US adults have HTN and CKD, respectively. Because HTN may cause or result from CKD, HTN prevalence is higher and control more difficult with worse kidney function. (Horowitz B et al., 2015)
There is a high prevalence of HTN in renal patients, which depends on the type of nephropathy and the degree of renal failure. Other independent risk factors for HTN in patients with renal disease are: advanced age, the presence of diabetes, hyper triglyceridaemia and the severity of proteinuria. BP control in renal patients is quite poor and should be improved to reduce progression of the renal disease. (Ridao N etal., 2001)

The Third National Health and Nutrition Examination Survey (NHANES III), a national study of more than 18,000 persons 20 years of age or older conducted from 1988 through 1994, provides information on the stages of CKD in the U.S. population. From these data, it is estimated that 8. 3million Americans have CKD stages 3 to 5. They also reported that 11.3 million Americans are at risk for developing or have mild decrease in kidney function (CKD stage 1 and 2).Data describing the ESRD population are made available annually by the U.S. Renal Data System (USRDS). The reports characterize the development, treatment, morbidity, and mortality associated with ESRD in the United States and include data from patients with kidney transplants. Based on the most recent data from the USRDS, more than 472,000 patients were receiving renal replacement therapy for ESRD at the end of 2004, with approximately 104,000 new patients starting treatment during that year. A continued increase in incidence rates of ESRD has been observed over the past decade, although this rate has decreased to approximately 1.5% to 5% per year over the past 5 years. The continued increase in incidence rates of ESRD, in conjunction with a relatively stable death rate for this population, accounts for the overall increase in the prevalence of ESRD. CKD has been identified as one of the focus areas for the Healthy People 2010 national health initiative; one of the specific objectives is to reduce the number of new cases of ESRD.4 Populations at increased risk for developing ESRD include males and the older population, particularly patients 65 years of age and older. More than 49% of incident hemodialysis patients in 2004 were age 65 or older, a much larger percentage than for the peritoneal dialysis and transplant populations.3 Racial distribution of the dialysis population shows that the prevalence is greatest in whites (61%) and blacks (32%), followed by Hispanics (14%) and Asians (4%). Blacks and Native Americans have a three to four times greater incident rate of kidney failure than white individuals.

A variety of causes are responsible for the remaining cases of ESRD, among which are cystic kidney disease, other urologic causes, and acquired immunodeficiency syndrome (AIDS) nephropathy. Mortality Advances in dialysis and transplantation have improved patient care; however, mortality rates during the first year of ESRD have not improved over the past decade (first-year adjusted death rate is 234/1,000 patient-years in the year 2003 for prevalent ESRD patients).Patients with cardiovascular disease on dialysis have a fivefold greater risk of all-cause mortality when compared with the general Medicare population and with patients with CKD not yet requiring renal replacement therapy. (Mary Anne Koda-Kimble et al., 2008) Comorbid conditions, low albumin, malnutrition, and anemia at initiation of dialysis are strong predictors of mortality. Life expectancy is 20% to 25% of that of the general population. Cardiovascular-related events, particularly cardiac arrest and myocardial infarction, are the leading causes of death in the ESRD population. This is not surprising given the high prevalence of coexisting cardiac disorders in patients with ESRD and the elevated risk for mortality associated with these conditions. The Healthy People 2010 initiative for CKD will also focus on decreasing deaths from cardiovascular disease.4 Infection (predominantly septicemia) and cerebrovascular disease are also substantial contributors to overall mortality in patients with ESRD. (Mary Anne Koda-Kimble et al., 2008)

It has been estimated that at least 6% of the adult U.S. population have chronic renal damage with a GFR 60 mL/min per 1.73 m2 (stages 1 and 2 CRD) and hence are at imminent risk of a progressive further decline in GFR. An additional 4.5% of the U.S. population are in stages 3 and 4 CRD. Diabetic and hypertensive nephropathy are the leading underlying etiologies of both CRD and ESRD. Hypertension is a particularly common cause and consequence of CRD in the elderly, in whom chronic renal ischemia due to renovascular disease may be an under recognized additional contribution to the pathophysiologic process. It should be noted that cardiovascular mortality precludes most patients with CRD from reaching the stage of ESRD. Identification of CRD as a major risk factor for cardiovascular morbidity and mortality, and the expectation of effective interventions to diminish premature cardiovascular mortality, and increasing longevity overall, will increase the cohort of patients reaching ESRD. Although the clinical manifestations of the declining GFR per se dominate the clinical presentation in all forms of CRD, in many cases the underlying etiology can be presumed from associated additional clinical information. (Kasper et al., 2008)

Hypertension is present in more than 80% of patients with CKD and contributes to progression of kidney disease toward end stage (ESRD) as well as to cardiovascular events such as heart attack and stroke. In fact the risk for cardiovascular death in this patient population is greater than the risk for progression to ESRD. Proteinuria is an important co-morbidity in hypertensives with CKD and increase risk of disease progression and cardiovascular events. Treatment of hypertension is therefore imperative. The National Kidney Foundation clinical practice guidelines recommend a blood pressure goal of <130 mmHg systolic and <80 mmHg diastolic for all CKD patients. Recent post-hoc analyses of the Modification of Diet in Renal Disease study indicate that lower blood pressure may provide long-term kidney protection in patients with non-diabetic kidney disease. Specifically a mean arterial pressure <92 mmHg (e.g. 120/80 mmHg) as compared to 102-107 mmHg (e.g. 140/90 mmHg) is associated with reduced risk for ESRD. In most cases achieving this goal requires both non-pharmacologic and pharmacologic intervention. Dietary sodium restriction to no more than 2 grams daily is important. In addition, moderate alcohol intake, regular exercise, weight loss in those with a body mass index greater than 25 kg/M(2) and reduced amount of saturated fat help to reduce blood pressure.

The first line pharmacologic intervention should be an angiotensin converting enzyme inhibitor or angiotensin II type 1 receptor blocker in those with diabetes or non-diabetics with more than 200 mg protein/gram creatinine on a random urine sample. For non-diabetics with less than 200 mg protein/gram creatinine on a random urine sample, no specific first-line drug class is recommended. After initial dosing with an ACEi, ARB or other drug, a diuretic should be added to the regimen. Thereafter, beta-blockers, calcium channel blockers, apha blockers and alpha 2 agonists (e.g. clonidine) and finally vasodilators (e.g. minoxidil) should be added to achieve blood pressure goal. Combinations of ACEi and ARB are helpful in reducing proteinuria and may also lower blood pressure further in some some cases. Blood pressure should be monitored closely in hypertensive patients with CKD and both clinic and home blood pressure measurements may help the clinician adjust treatment. (Toto RD, 2005)

Adjustments in dietary intake and use of loop diuretics, occasionally in combination with metalozone, may be needed to maintain salt and hence extracellular fluid volume balance. In contrast, overzealous salt restriction and diuretic use may cause hypovolemia and precipitate a further decline in GFR. Occasional patients with salt-wasting states need to be given sodium-rich diets or sodium supplements. Water restriction is indicated only if there is a demonstrated propensity to hyponatremia. Intractable ECFV expansion, despite dietary restriction and diuretic use, indicates the need to initiate renal replacement therapy. Hyperkalemia often responds to dietary restriction of potassium, avoidance of potassium-containing or -retaining medications, and to) the use of diuretics if they are also indicated for management of sodium balance. Many salt substitutes contain potassium instead of sodium, and patients with CRD seeking to avoid sodium should be cautioned accordingly as part of their dietary counseling. Potassium-binding resins taken with cathartics can promote gastrointestinal potassium losses and thus are useful as temporizing measures in the treatment or avoidance of hyperkalemia in CRD patients. However, the need for such treatment over a prolonged period, in the absence of other reversible causes of hyperkalemia, usually signifies the need to initiate renal replacement therapy. (Kasper, 2008)

In a small proportion of people with kidney disease, the condition will eventually get to a point where their kidneys stop working. This rarely happens suddenly, so there should be time to plan the next stage of your treatment. One of the options when CKD reaches this stage is to have dialysis. This is a procedure to remove waste products and excess fluid from the blood.

There are two main types of dialysis:

Haemodialysis: This involves diverting blood into an external machine, where it's filtered before being returned to the body.

Peritoneal dialysis: This involves pumping dialysis fluid into the space inside your tummy to draw out waste products from the blood passing through vessels lining the inside of your tummy.
Haemodialysis is usually done about three times a week, either at hospital or at home. Peritoneal dialysis is normally done at home several times a day, or overnight. If there is no use of kidney transplant, treatment with dialysis usually need to be done lifelong. (British Kidney Patient Association 2006) 

LITERATURE REVIEW

DEFINITION
Chronic kidney disease is characterized by a progressive deterioration in kidney function ultimately leading to irreversible structural damage to existing nephrons (Mary Anne Koda-Kimble et al., 2008). Kidney damage is indicated by pathologic abnormalities or markers of injury, including abnormalities in blood or urine tests and imaging studies. The presence of protein in the urine (defined as proteinuria, albuminuria, or micro albuminuria based on protein type and amount) is an early and sensitive marker of kidney damage.

STAGES
Based on the progressive nature of this condition, a staging system has been established to classify kidney disease according to the eGFR, which is estimated clinically using creatinine clearance (ClCr). Specifically, CKD is defined as kidney damage with a normal or a mildly decreased eGFR (stages 1 and 2) or a eGFR (Mary Anne Koda-Kimble et al., 2008).

TABLE-1: Stages according to National Kidney Foundation. NKF-K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification (Mary Anne Koda-Kimble et al., 2008).

Stages according to National Kidney Foundation

CKD is classified by cause of kidney disease, glomerular filtration rate (GFR) category, and albuminuria level based on new recommendations from the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, referred to as CGA staging (cause, GFR, albuminuria) (Barbara G. Wells et al., 2015).

EPIDEMOLOGY
Both hypertension (HTN) and CKD are serious interrelated global public health problems. Nearly 30% and 15% of US adults have HTN and CKD, respectively. Because HTN may cause or result from CKD, HTN prevalence is higher and control more difficult with worse kidney function. Etiology of CKD, presence and degree of albuminuria, and genetic factors all influence HTN severity and prevalence. In addition, socioeconomic and lifestyle factors influence HTN prevalence and control. There are racial and ethnic disparities in the prevalence, treatment, risks, and outcomes of HTN in patients with CKD. Control of blood pressure (BP) in Hispanic and African Americans with CKD is worse than it is whites. There are disparities in the patterns of treatment and rates of progression of CKD in patients with HTN. The presence and severity of CKD increase treatment resistance. HTN is also extremely prevalent in patients receiving hemodialysis, and optimal targets for BP control are being elucidated. Although the awareness, treatment, and control of HTN in CKD patients is improving, control of BP in patients at all stages of CKD remains suboptimal (Horowitz B et al., 2015).

RISK FACTORS
Age: Renal function decreases with age in both men and women (Iseki K, 2005) Thus, the elderly population is more prone to develop CKD after various renal insults (Falodia J. Singla MK 2012). At any age and various conditions can lead to CKD. After the age of 40, kidney filtration begins to fall by approximately 1% per year. In addition to the natural aging of the kidneys, many conditions that damage the kidneys are more common in older people including diabetes, high blood pressure, and heart disease (Centers for Disease Control and Prevention 2018).

Gender: These include gender differences in kidney anatomy, kidney hemodynamic stress response, effect of sex hormones, diet, lipid metabolism, and blood pressure (Neugarten J. Golestaneh L 2013; Silbiger S. Neugarten J 2013).
Anatomically, the kidney is usually larger in men, due to a larger body surface area. The hemodynamic stress response of the kidney differs between men and women; men may develop higher filtration fraction in response to angiotensin II infusion (Miller JA. 1999).
Low birth weight: The intrauterine growth restriction might cause a low nephron number, which could predispose to hypertension and renal disease (Mackenzie HS. 1999). Low nephron number leads to intraglomerular hypertension and hyper filtration in the available nephrons and lower over-all GFR and higher urine albumin-to-creatinine ratio (Vikse BE et al., 2008).

Smoking: Smoking can increase the CKD risk through proinflammatory state, oxidative stress, prothrombotic shift, endothelial dysfunction, glomerulosclerosis and tubular atrophy (Mirrakhimov AE. 2012)

Nephrotoxins: Medications can cause or worsen kidney dysfunction and these effects are exacerbated in patients with underlying CKD. Many commonly used drugs, including over-the-counter medications, can cause nephrotoxicity (The UMHS Clinical Guideline on Chronic Kidney Disease. 2013)

Alcohol and recreational drugs have been linked to CKD progression as well as excessive use of analgesic drugs and exposure to heavy metals (Falodia J. Singla MK, 2012).
Diabetes Mellitus: Diabetes mellitus (DM) is the leading cause of CKD and ESRD .Mechanisms that lead to kidney disease in diabetes include hyper filtration injury, advanced glycosylation end products, and reactive oxygen species.

Hypertension: High blood pressure can damage blood vessels throughout your body. This can reduce the blood supply to important organs like the kidneys. High blood pressure also damages the tiny filtering units in your kidneys. As a result, the kidneys may stop removing wastes and extra fluid from your blood. The extra fluid in your blood vessels may build up and raise blood pressure even more (McClellan WM. Flanders WD, 2003).

Obesity: Obesity may contribute to the pathogenesis of kidney damage through inflammation, oxidative stress, endothelial dysfunction, prothrombotic state, hypervolemia, and adipokine derangements.
Glomerular hypertrophy and hyper filtration may accelerate kidney injury by increasing capillary wall tension of the glomeruli and decreasing podocyte density (Lea JP. Nicholas SB, 2002). Obesity may contribute to the pathogenesis of kidney damage through inflammation, oxidative stress, endothelial dysfunction, prothrombotic state, hypervolemia, and adipokine derangements (National Kidney Foundation-Hypertension). Besides high BMI, carrying excess weight around the abdomen is linked to an increased risk of CKD (Chang A. Kramer H, 2012).

Family history: Family members of CKD patients have a high prevalence of CKD and its risk factors due to hereditary disorders and urologic causes (Kwakernaak AJ et al., 2013).

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