RETARDATION OF PROGRESSION OF CHRONIC KIDNEY DISEASE THROUGH PHARMACOLOGICAL INTERVENTIONS

Abstract: 
Objective: Chronic Kidney Disease (CKD) patients have multiple co-morbidities and complications, and are prescribed with large number of medications. Studies on therapeutic strategies to slow the chronic kidney disease progression in India are limited. Aim of the study: The present study was undertaken to evaluate retardation of progression of Chronic Kidney Disease through pharmacological interventions. Materials and Methods: This was a retrospective study conducted during 6 months period from August 2017 to January 2018 on 180 patients diagnosed with CKD  Results: The present study found the mitigating effect of the pharmacotherapy on indicator parameters in reducing the progression of CKD for the DM-CKD and Non DM-CKD groups  Conclusion: The findings of present study conclude that pharmacological interventions of Seven indicator parameters in the management Diabetes mellitus , Anaemia, Hypertension, Hyperphosphatemia, Hyperuricemia, proteinuria and Metabolic acidosis was beneficial to slow the progression of renal disease in DM-CKD and Non DM-CKD patients. 
  
Key words: Chronic kidney disease, pharmacological, intervention, Diabetes mellitus, progression. 
 


INTRODUCTION
Chronic kidney disease (CKD) is a worldwide public health problem with increasing incidence and prevalence, poor outcomes and high cost for treatment due to co-morbidities and poly pharmacy 1 . CKD is widely prevalent non-communicable disease that progress toward end stage renal failure and is responsible for increasing morbidity in India 2 .
There is clear evidence from clinical studies that hypertension and proteinuria are the key players in the pathophysiology of CKD progression in humans. Other potential contributors include diabetes mellitus (DM), smoking, obesity, genetic background, anaemia, altered mineral homeostasis, dyslipidemia, oxidative stress and chronic inflammation 3,4 . Efficient control of blood pressure and minimization of proteinuria are the two most important measures to preserve residual kidney function. Other factors, such as good glycemic control, prevention and treatment of anaemia, dyslipidaemia, and disorders of mineral metabolism, have an experimental basis, although their clinical importance is less clear to date. CKD patients due to associated co-morbidities and complications are prescribed, with more number of medications, that might alter the rate of progression of decline in kidney function 5 . Because of the multiple medications, CKD patients are at higher risk of developing drug related problems. Due to the complex therapeutic regimen there might be a need of requiring frequent monitoring and follow up. Drug utilization changes by the physician, time period, disease conditions and population makes it important to study the intervention of the drug continuously over a period of time 6 . Drug utilization studies in CKD patients helps to understand and build evidence for the medication use. CKD patients need to take medicines lifelong which makes it is very important to study the prescribing trends on a regular basis. There is very limited evidence from India that studied the effect of pharmacological interventions that slows the progression of chronic kidney disease. Hence the present study was taken up for evaluating the retardation of progression of Chronic Kidney Disease through pharmacological interventions.

Materials and Methods:
This was a retrospective study conducted during 6 months period from August 2017 to January 2018 in the Department of Nephrology at Sri Venkateswara institute of medical Sciences, Tirupati, Andhra Pradesh, India. The study included 180 patients diagnosed with CKD as per KDIGO guidelines 7 . Among them 90 were CKD patients with DM of either gender of age group above 18 years as first group and remaining 90 were CKD patients without DM of either gender of age group above 18 years as second group. In both the groups patients below age group of 18 years, pregnant and lactating women and CKD patients on dialysis were excluded. The study was conducted after obtaining approval from the institutional ethics committee (IEC number: 674) and written informed consent from the participants in the study was taken before sample collection. The suitable designed data collection form was used to collect all the necessary information to evaluate the progression with respect to the pharmacological interventions. Data was collected from patient medical record for the demographic details such as age, gender, diagnosis, co-morbid conditions, and number of medications per prescription, laboratory parameters and other relevant information . Past medical condition and medication history was obtained from patients or attenders. Statistical analysis: Data was recorded on a predesigned proforma and entered using Microsoft excel worksheet (Microsoft Corp, Redmond, WA). Numerical data was expressed as mean ± Standard deviation (SD). Categorical values were presented as counts and percentage. Mean values between two groups were compared by using unpaired t-test . Comparison across the groups for the three consecutive years was done by using the repeated measures of ANOVA (Analysis of Variance). A p value of < 0.05 was considered statistically significant. The statistical software IBM SPSS Statistics Version 20.0 (IBM Corp Somers NY, USA) was used for data analysis.

Results:
The present study evaluated medical records of 180 CKD patients for the last 3 consecutive years retrospectively for a period of 6 months. The 180 patients with CKD were further sub divided into two groups based on diabetes status. First group was 90 patients as DM-CKD Group and second group was 90 patients as Non DM-CKD Group.   DM-CKD group:  In the present study for the Non DM-CKD Hyperphosphatemia Management Calcium acetate (51.1%) and Sevelamer (8.88%) were used. By using above pharmacological interventions the phosphate levels were 3.9 ± 0.94 mg/dl, 3.86 ± 0.74 mg/dl, & 3.94 ± 0.99 mg/dl in the years 2015, 2016 and 2017 respectively, but was found to be not significant [p= 0.881]. In this group for Hyperphosphatemia management 44 patients [48.8%] were using single drug and 5 patients [5.55%] were using two drug combination.
In the present study for the Non DM-CKD Hyperuricemia Management Febuxostat (41.1%) and Allopurinol (3.33%) were used. By using above pharmacological interventions the uric acid levels were 6.33 ± 1.85mg/dl, 6.26 ± 2.02mg/dl and 5.7 ± 1.38mg/dl in the years 2015, 2016 and 2017 respectively, well maintained in 3 years duration but was found to be not significant (p = 0.140).
In the present study for the Non DM-CKD Protineuria Management with Telmisartan and Ramipril mean value of 24hrs urinary protein levels was maintained in range of 243±150mg/24hrs. In the present study annual GFR decline in DM-CKD group according to MDRD equation was 6.00 ±1.10 ml/min/1.73m 2 and CKD-EPI equation was 5.90 ±1.20 ml/min/1.73m 2 . In the present study annual GFR decline in Non DM-CKD group according to MDRD   The anti-hypertensive treatment in CKD was shown to slow the progression of diabetic and non-diabetic renal disease in comparison to placebo group 13,14 . These findings are supported by the present study results which observed a well maintained BP status on antihypertensive treatment during the three years follow up and reduction in proteinuria.
In the present study all the phosphate binders have been found to be equally effective in terms of phosphate control if given in equivalent doses for the management of hyperphosphatemia in patients with CKD of both the groups 15 .
In the present study SUA was well maintained in three years period. Kanji et al suggested that allopurinol significantly reduces SUA levels, blood pressure, and statistically significant improvement in e GFR 16 . These findings are comparable to the present study findings.
In the present study, erythropoiesisstimulating agents for the treatment of anemia in patients with chronic kidney disease resulted in hemoglobin level of approximately 11. 0 g/dL in both DM-CKD group and Non DM-CKD group. This finding was in agreement to the recommended acceptable range of hemoglobin levels of 11.0-12.0 g/dL for patients with chronic kidney disease as reported by Singh AK et al 17 .
In Chronic kidney disease, the progression is inexorable resulting in progressive decline in renal function which might be life threating to the patients. In such a situation optimistic control on the factors causing deterioration of renal function by enthusiastic and collaborative participation of the medical team brings out appreciable and beneficial outcomes to the patients. The present study high-lighted the mitigating effect of the pharmacotherapy on indicator parameters in reducing the progression of CKD in DM and Non-DM groups effectively. Hence shared decision-making is an integral component of this process and revisions to the care plan based on the changing needs and preferences of the patient and family must be considered 18 .

Conclusion:
The incidence and prevalence of CKD is increasing at an alarming rate, and it is unlikely that the economic resources and infrastructures might be able to meet this demand. At present, the best available evidence suggests that blood pressure and glycemic control will have the greatest impact on delaying the progression of both chronic kidney disease and cardiovascular disease. The present study evaluated pharmacological interventions of Seven indicator parameters in the management of Diabetes mellitus , Anaemia, Hypertension, Hyperphosphatemia, Hyperuricemia, proteinuria and Metabolic acidosis to slow the progression of renal disease in two groups of patients [DM-CKD & Non DM-CKD] and found the beneficial role of pharmacotherapy to slow the future growth of ESRD. These findings also might conclude that pharmacotherapy must be instituted early in order to improve cardiovascular outcomes and potentially stabilise and retard the disease progression.