Chronic kidney disease is a progressive disorder characterized by abnormalities of kidney structure or function persisting for at least three months and having implications for health. The introduction of standardized staging systems by the National Kidney Foundation and subsequently by Kidney Disease: Improving Global Outcomes (KDIGO) has facilitated assessment of disease severity, prognosis, and appropriate management.[1,2]

CKD represents a major public-health problem worldwide. It is associated not only with progressive loss of renal function and eventual end-stage renal disease but also with cardiovascular morbidity, premature mortality, anemia, mineral and bone disorders, electrolyte abnormalities, and impaired quality of life.[3] The worldwide prevalence of CKD has been estimated at approximately 8-16%, with a particularly important burden in developing countries.[3]

Diabetes mellitus and hypertension are among the leading causes and comorbidities associated with CKD. In India, increasing prevalence of diabetes, hypertension, obesity, and cardiovascular disease is expected to contribute substantially to CKD burden.[4,5] Patients frequently present to tertiary-care centers at relatively advanced stages because early CKD may remain asymptomatic.

Pharmacotherapy in CKD is complex. Patients often require several medications concurrently for control of blood pressure, diabetes, anemia, volume overload, calcium-phosphate abnormalities, cardiovascular risk, gastrointestinal symptoms, and other complications. At the same time, impaired renal function affects the pharmacokinetics of numerous medicines and may increase the risk of drug accumulation, toxicity, drug interactions, and adverse reactions.[6]

Drug utilization research has been defined by the World Health Organization as the study of the marketing, distribution, prescription, and use of medicines in society, with special emphasis on the resulting medical, social, and economic consequences.[7] Such studies provide a means of evaluating the quality of prescribing and identifying opportunities for rationalization of drug therapy.

A drug-utilization assessment in CKD is therefore clinically valuable because the appropriateness of pharmacotherapy depends not merely on which medicines are prescribed but also on their indications, combinations, doses, renal adjustments, and resulting outcomes. The present study was undertaken to evaluate drug utilization patterns and selected clinical outcomes among patients with CKD treated at a tertiary-care teaching hospital in Central India.

Aim

To assess the drug utilization pattern and clinical outcomes in patients with chronic kidney disease.

Objectives

• To describe the demographic and clinical characteristics of patients with CKD.
• To determine the distribution of patients according to CKD stage.
• To analyze the major drug classes and individual medicines prescribed.
• To evaluate selected WHO prescribing indicators.
• To assess the prevalence of polypharmacy.
• To evaluate changes in blood pressure, hemoglobin, renal function, and dialysis requirement.
• To document adverse drug reactions and major clinical outcomes.
• To identify opportunities for improving rational prescribing in patients with renal impairment.

Study Design

A prospective, observational, hospital-based drug-utilization study was conducted.

Study Setting

The study was undertaken by the Department of Pharmacology, Chirayu Medical College&Hospital, Bhopal, Madhya Pradesh, in collaboration with the clinical departments managing patients with chronic kidney disease.

Study Period

The study was conducted over a period of 12 months, from February 2015 to January 2016.

Sample Size

A total of 100 patients fulfilling the eligibility criteria were included.

Study Population

Adult patients with an established diagnosis of chronic kidney disease who were attending the outpatient department or admitted to the hospital during the study period were evaluated.

Inclusion Criteria

• Patients aged ≥18 years.
• Patients diagnosed with CKD based on clinical, biochemical, or radiological criteria.
• CKD of at least three months' duration or documented evidence consistent with chronic renal impairment.
• Patients receiving pharmacological treatment for CKD or associated conditions.
• Patients willing to participate and with adequate clinical records for assessment.

Exclusion Criteria

• Isolated acute kidney injury without evidence of CKD.
• Patients with incomplete medication or follow-up records.
• Pregnant women.
• Patients transferred to another institution before adequate clinical assessment.
• Patients unable to complete the minimum required follow-up.

CKD Classification

Patients were categorized principally according to estimated glomerular filtration rate:

Data Collection

Clinical information was recorded using a structured case-record form. Variables included age and sex, duration and probable etiology of CKD, CKD stage, major comorbidities, blood pressure, hemoglobin, serum creatinine, eGFR, blood glucose where applicable, edema, dialysis status, details of prescribed medications, dosage form and route, generic or brand-name prescribing, number of drugs per prescription, adverse drug reactions, hospitalization, and clinical status at follow-up.

Drug Utilization Assessment

Prescriptions were analyzed for total number of drugs prescribed, mean number of drugs per patient, percentage of patients receiving individual drug classes, generic prescribing, injectable drug use, antimicrobial use, use of medicines appearing in an essential-medicine list, and frequency of potentially renal-dose-sensitive medications. Polypharmacy was defined operationally as the concurrent use of five or more medicines.

Assessment of Clinical Outcomes

1. Blood-pressure control among hypertensive patients.
2. Change in hemoglobin among patients with anemia.
3. Change in renal function based on serum creatinine and/or eGFR.
4. Requirement for initiation or continuation of dialysis.
5. Symptomatic improvement or stability.
6. Adverse drug reactions.
7. Hospitalization because of CKD-related complications.
8. Mortality during available follow-up.

Statistical Analysis

Data were entered into a computerized database and analyzed using descriptive and inferential statistical methods. Continuous data are expressed as mean ± standard deviation, while categorical variables are presented as frequencies and percentages. Paired continuous variables were compared using an appropriate paired statistical test. Categorical variables were analyzed using the chi-square test or Fisher's exact test where applicable. A two-sided p-value<0.05 was considered statistically significant.

Ethical Considerations

The study protocol was conducted in accordance with institutional ethical principles. Patient confidentiality was maintained throughout the study, and no personally identifying information was included in the analysis.

Demographic Characteristics

A total of 100 patients with chronic kidney disease were evaluated. The mean age was 55.8 ± 13.1 years, with the largest proportion belonging to the 51-60-year age group. Sixty-one patients were males and 39 were females.

Table 1. Age and sex distribution of study participants

Distribution According to CKD Stage

Stage 4 CKD was the most common category, accounting for 31% of the study population. Twenty-five patients had stage 5 disease.

Table 2. Distribution of patients according to CKD stage

Thus, 56% of patients had advanced CKD (stages 4-5).

Comorbidities and Complications

Hypertension was the most prevalent associated disorder and was observed in 78% of patients. Anemia was documented in 68%, while 46% had diabetes mellitus.

Table 3. Major comorbidities and CKD-related complications

Individual patients could have more than one condition.

Drug Utilization Pattern

A total of 612 medications were prescribed among 100 patients. The average number of medications was 6.12 ± 2.03 drugs per patient. Seventy-two patients were receiving five or more medicines and therefore fulfilled the study definition of polypharmacy.

Table 4. Major therapeutic drug classes prescribed

Antihypertensive Drug Utilization

Antihypertensive agents constituted the most commonly utilized cardiovascular medicines. Several patients were receiving more than one antihypertensive drug.

Table 5. Pattern of antihypertensive drug use

Among individual agents, amlodipine was the most frequently used antihypertensive, followed by furosemide, metoprolol, telmisartan/losartan, and ramipril. Use of renin-angiotensin-system blocking drugs was more frequent in patients with earlier stages of CKD and diabetic/proteinuric kidney disease, whereas their use was restricted in patients with severe hyperkalemia, symptomatic hypotension, or other clinical contraindications.

Pattern of Antidiabetic Therapy

Among 46 patients with diabetes mellitus, 42 were receiving active pharmacotherapy during the evaluation period.

Table 6. Antidiabetic treatment among diabetic CKD patients

Insulin was preferred particularly among patients with advanced renal impairment because of limitations associated with several oral hypoglycemic agents.

Treatment of Anemia

Among 68 patients with anemia, 44 (64.7%) received oral or intravenous iron, 36 (52.9%) received erythropoiesis-stimulating agents, 29 (42.6%) received folic acid supplementation, and 12 (17.6%) required packed-cell transfusion during the study period. Therapies were frequently used in combination according to clinical requirements.

Management of Mineral and Bone Abnormalities

Thirty-eight patients were receiving specific phosphate-lowering treatment.

Table 7. Drugs used for CKD-mineral and bone disorder

Some patients received more than one therapy.

WHO-Oriented Prescribing Indicators

Table 8. Prescribing indicators

The high mean number of medications reflected the multiple comorbidities and CKD-related complications prevalent in the study population.

Clinical Outcomes

Blood-Pressure Outcome

Among the 78 patients with hypertension, mean systolic and diastolic blood pressures showed improvement during follow-up.

Table 9. Change in blood pressure among hypertensive patients

Satisfactory individualized blood-pressure control was achieved in 50 of 78 hypertensive patients (64.1%).

Hemoglobin Outcome

Among the 68 patients with anemia, hemoglobin levels improved after treatment.

Table 10. Hemoglobin status among anemic CKD patients

Forty-four of the 68 anemic patients (64.7%) showed an increase in hemoglobin of at least 0.5 g/dL during follow-up.

Renal Function Outcomes

Table 11. Overall renal-function outcome

Improvement referred to a clinically meaningful reduction in serum creatinine and/or increase in eGFR in association with correction of reversible factors such as dehydration, uncontrolled hypertension, infection, or medication-related deterioration superimposed on CKD. As expected, patients with stage 4 or 5 disease were more likely to show progression than patients with stages 1-3.

Dialysis Requirement

Twenty-five patients had stage 5 CKD. Of these, 19 were receiving maintenance hemodialysis during most of the observation period and six initiated dialysis during follow-up. An additional small number of stage 4 patients required temporary dialysis for an acute deterioration but did not remain dialysis dependent.

Adverse Drug Reactions

Thirteen patients experienced at least one suspected adverse drug reaction.

Table 12. Adverse drug reactions observed

One patient could experience more than one adverse effect. No fatal adverse drug reaction was documented.

Overall Clinical Outcomes

Table 13. Final clinical outcome

Thus, 71% of patients demonstrated either improvement or clinical stability during the period of observation.

Relationship Between CKD Stage and Clinical Deterioration

Table 14. CKD stage and renal-function deterioration

Progressive deterioration was significantly more common among patients with advanced CKD (p<0.01).

The present study evaluated drug utilization and short-term clinical outcomes among 100 patients with chronic kidney disease treated at a tertiary-care hospital in Central India. The findings demonstrate the considerable pharmacotherapeutic complexity associated with CKD, with patients receiving an average of more than six medicines and nearly three-fourths fulfilling the

operational definition of polypharmacy.

The mean age of patients was 55.8 years, and approximately two-thirds were men. CKD is known to increase substantially with advancing age, while the distribution of patients attending tertiary-care facilities may also be influenced by patterns of referral, access to care, and underlying causes of renal disease. Jha et al. emphasized the substantial and increasing CKD burden in developing regions and the important contribution of diabetes and hypertension.[3]

More than half of the patients in the present study had stage 4 or stage 5 CKD. This predominance of advanced disease in a tertiary-care cohort is clinically plausible because many patients with early CKD remain asymptomatic and are managed at primary or secondary levels or remain undiagnosed. Late referral has historically represented an important challenge in CKD care in developing countries.

Hypertension was observed in 78% of the study population and represented the most frequent associated disorder. The relationship between hypertension and CKD is bidirectional: hypertension can initiate or accelerate renal injury, whereas declining renal function contributes to volume expansion, increased vascular resistance, and difficult-to-control blood pressure.[2,8] Appropriate blood-pressure management therefore constitutes a central component of CKD therapy.

Antihypertensive agents were the most frequently prescribed medications. Calcium-channel blockers, particularly amlodipine, were extensively utilized. This may reflect their effectiveness, convenient dosing, limited requirement for renal dose adjustment, and usefulness in patients with advanced kidney dysfunction. Diuretics were also used commonly, particularly among patients with edema and volume-dependent hypertension.

ACE inhibitors and angiotensin receptor blockers occupied an important role in selected patients, particularly those with diabetic or proteinuric kidney disease. Renin-angiotensin-system inhibition has established renoprotective and antiproteinuric benefits in appropriate CKD populations.[2,9,10] Nevertheless, these medicines require monitoring for hyperkalemia, hypotension, and changes in renal function. Their use in the present cohort was consequently less universal in advanced-stage CKD.

Blood-pressure control improved during follow-up, with mean systolic pressure decreasing from 154.6 to 139.2 mmHg and satisfactory individualized control documented in approximately 64% of hypertensive patients. Although multiple factors influence blood-pressure response, this finding supports the clinical importance of structured antihypertensive therapy in patients with CKD.

Diabetes mellitus was present in 46% of participants. Diabetes has emerged as one of the principal causes of CKD worldwide and represents an especially important problem in India.[3,4] Insulin was the most frequently used glucose-lowering treatment among diabetic patients in this study. Advanced renal dysfunction influences the metabolism and elimination of several antidiabetic medicines, and insulin often becomes a more practical means of glycemic management in patients with severe renal impairment, although its dose must be monitored carefully because declining renal clearance can increase the risk of hypoglycemia.[11]

Anemia was present in 68% of patients and was particularly prominent in advanced CKD. Renal anemia is mainly related to reduced erythropoietin production but can be aggravated by iron deficiency, inflammation, nutritional deficiencies, blood loss, and reduced red-cell survival.[12] Iron preparations and erythropoiesis-stimulating agents therefore constituted major components of therapy in the present study.

Mean hemoglobin improved from 8.9 to 9.8 g/dL following treatment, although complete normalization was neither expected nor necessarily desirable. KDOQI and KDIGO recommendations existing during the study period emphasized individualized management of anemia, correction of iron deficiency, and careful selection of patients for erythropoiesis-stimulating therapy.[12,13]

Mineral and bone abnormalities represented another important pharmacotherapeutic target. Calcium carbonate was the most commonly utilized phosphate binder, while calcium acetate and sevelamer were prescribed less frequently. Active vitamin D preparations were also frequently used. Disturbances in phosphate, calcium, parathyroid hormone, and vitamin D metabolism become increasingly important as CKD progresses and require individualized treatment.[14]

Gastroprotective drugs were prescribed to 55% of patients. Although gastrointestinal symptoms and use of multiple medications may partly account for this pattern, routine prolonged acid-suppressive therapy without a defined indication should be avoided. Drug-utilization review is helpful in recognizing medicines that may no longer be necessary.

The mean number of 6.12 drugs per patient reflects a high burden of polypharmacy. Polypharmacy cannot automatically be considered inappropriate in CKD because numerous medications may be required to treat distinct and legitimate conditions. Nevertheless, a larger number of concurrent medicines increases the possibility of drug interactions, duplication, non-adherence, prescribing cascades, and adverse reactions.[6,15]

Only 38.6% of drugs were prescribed by generic name. This indicates an opportunity for improvement. Greater generic prescribing can improve transparency and potentially reduce medication costs, provided medicines of assured quality are available. Approximately 70% of prescribed medicines were represented in essential-medicine lists, suggesting reasonable but incomplete alignment with essential-drug principles.

Injectable medicines were administered to 43% of patients. This apparently high proportion can be explained by the inclusion of insulin, injectable erythropoiesis-stimulating therapy, intravenous iron, antimicrobials in selected hospitalized patients, and other treatments frequently required in advanced CKD.

Antibiotics were prescribed to 17% of patients. Infectious complications remain important in CKD, particularly among hospitalized and dialysis-dependent patients. Antibiotic selection requires particular care because many antimicrobial agents depend substantially on renal elimination and require dose modification according to renal function.[6]

Adverse drug reactions were recognized in 13% of patients. Hypotension, hypoglycemia, hyperkalemia, gastrointestinal intolerance, edema, and excessive diuresis were among the observed events. CKD patients are inherently vulnerable to adverse medication effects because of altered pharmacokinetics, comorbidity, advanced age in many cases, and polypharmacy. Routine assessment of kidney function before prescribing and repeated review after changes in renal function are therefore essential.

Renal function remained stable in 58% of patients and improved in 15%, whereas 27% showed progression. These results should be interpreted in the context of CKD as a chronic progressive disease. Apparent improvement may occur when reversible contributors superimposed on CKD-such as volume depletion, infection, uncontrolled hypertension, or potentially nephrotoxic medication exposure-are corrected.

Progression was substantially more frequent in stages 4 and 5 than in stages 1-3. This observation is consistent with the expected natural history of advanced CKD and emphasizes the importance of earlier diagnosis and intervention.[1-3]

Twenty-five patients had stage 5 CKD and required or subsequently initiated maintenance renal replacement therapy. The necessity for dialysis among a substantial proportion of the cohort further demonstrates the advanced disease burden represented in tertiary-care hospital populations.

Overall, 71% of patients experienced improvement or clinical stability, whereas 20% showed significant progression requiring treatment intensification or hospitalization. Four deaths occurred during follow-up. Mortality in CKD is strongly influenced by cardiovascular disease, infection, advanced renal failure, diabetes, age, and other comorbidities.[3]

The findings underscore the role of pharmacologists, nephrologists, physicians, pharmacists, nurses, and other healthcare professionals in collaborative medication review. Identification of avoidable nephrotoxic agents, appropriate dosage modification, evaluation of drug interactions, encouragement of generic prescribing, monitoring for adverse reactions, and patient counseling may improve the quality of CKD pharmacotherapy.

Strengths of the Study

The study simultaneously evaluated prescribing patterns and relevant clinical outcomes rather than restricting analysis to prescription counts. It included patients across different stages of CKD and assessed drug utilization in relation to common complications including hypertension, diabetes, anemia, volume overload, and mineral-bone disturbances.

Limitations

The study was conducted at a single tertiary-care center with a sample size of 100 patients. Follow-up duration varied according to clinical attendance, and long-term renal and cardiovascular outcomes could not be assessed. Drug adherence outside the hospital was not measured objectively. Cost-effectiveness and detailed defined-daily-dose analysis were not undertaken. Furthermore, clinical outcomes may have been influenced by disease severity, dietary compliance, dialysis adequacy, and comorbid conditions in addition to pharmacotherapy.

Patients with chronic kidney disease require complex pharmacotherapy because of the presence of multiple comorbidities and complications. In the present cohort, patients received an average of 6.12 drugs, and 72% were exposed to polypharmacy. Antihypertensive drugs constituted the most frequently used therapeutic group, with calcium-channel blockers being particularly common. Treatments for anemia, fluid overload, diabetes, and CKD-related mineral and bone disorders also contributed substantially to medication use. Blood-pressure control and hemoglobin values improved significantly during follow-up, while renal function remained stable or improved in nearly three-fourths of patients. Nevertheless, progression remained common among patients with advanced CKD. The relatively low proportion of medicines prescribed by generic name and the substantial exposure to polypharmacy indicate areas where prescribing practices could be improved. Regular medication review, appropriate renal dose adjustment, avoidance of nephrotoxic drugs, monitoring for adverse reactions and drug interactions, and closer adherence to evidence-based and essential-medicine principles should form integral components of CKD management.

Recommendations

1. Renal function should be considered when initiating or adjusting every potentially renally eliminated medicine.
2. Polypharmacy should be reviewed periodically to discontinue unnecessary medications.
3. Generic prescribing should be encouraged wherever appropriate.
4. ACE inhibitors and ARBs should be used selectively according to indication, with monitoring of creatinine and serum potassium.
5. Blood pressure and glycemic status should be closely monitored to reduce CKD progression.
6. Hemoglobin and iron status should be assessed regularly in patients with moderate-to-advanced CKD.
7. Calcium, phosphate, and related mineral-bone parameters should be monitored in advanced CKD.
8. Potentially nephrotoxic drugs, particularly inappropriate NSAID use, should be avoided.
9. Pharmacovigilance should be strengthened because CKD patients are at increased risk of adverse drug reactions.
10. Larger prospective multicenter studies with longer follow-up should evaluate the relationship between prescribing quality and long-term renal and cardiovascular outcomes.

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