Effectiveness of a Disease Management Program (DMP) in controlling the progression of Chronic Kidney Disease among hypertensives and diabetics.

Background The occurrence rate of stage 5 chronic kidney disease (CKD) will be 151 per million population in India in the coming years. Comorbidities like diabetes mellitus and hypertension are the usual triggers of CKD. Hence this study aimed to control the progression of CKD and to note the effectiveness of a structured education program that would help in the prevention of complications related to diabetes and hypertension. Methods This quasi-experimental study was conducted among 88 participants who had hypertension, diabetes mellitus, or both for five or more years. The study objective was to find the effect of a Disease Management Program on delaying progression of CKD in patients with hypertension or diabetes mellitus. The baseline data were obtained from demographic proforma, and the clinical data collected were the blood pressure, serum creatinine, and random blood sugar (RBS) of the participants. The management of hypertension and diabetes mellitus was taught to them. In the fourth and the eighth month, blood pressure and blood sugar were reassessed. At one-year blood pressure, blood sugar, and serum creatinine were tested. Baseline and one-year follow-up blood pressure, blood sugar, and estimated Glomerular Filtration Rate were compared. Descriptive statistics and "Wilcoxon signed-rank test" were used to analyze the data. Results In one year, the mean systolic blood pressure reduced by six mm of Hg and mean blood sugar by 24 mg/dl. The prevalence of CKD stage three and above (< 60 ml/min/m2) was nine (10.22%). The median decline in eGFR was 5 ml/min/m2 (Z= 5.925, P< 0.001). Conclusion The Disease Management Program led to improvements in blood pressure and diabetes control and median progression of CKD was estimated at five ml/min/m2/year.

with hypertension or diabetes mellitus.
The baseline data were obtained from demographic proforma, and the clinical data collected were the blood pressure, serum creatinine, and random blood sugar (RBS) of the participants.The management of hypertension and diabetes mellitus was taught to them.In the fourth and the eighth month, blood pressure and blood sugar were reassessed.At one-year blood pressure, blood sugar, and serum creatinine were tested.Baseline and one-year follow-up blood pressure, blood sugar, and estimated Glomerular Filtration Rate were compared.Descriptive statistics and "Wilcoxon signed-rank test" were used to analyze the data.

Results
In one year, the mean systolic blood pressure reduced by six mm of Hg and mean blood sugar by 24 mg/dl.The prevalence of CKD stage three and above (< 60 ml/min/m2) was nine (10.22%).The median decline in eGFR was 5 ml/min/m2 (Z= 5.925, P< 0.001).

Conclusion
The Disease Management Program led to improvements in blood pressure and diabetes control and median progression of CKD was estimated at five ml/min/m2/year.

Introduction
Chronic Kidney Disease (CKD), which is defined as a glomerular filtration rate (GFR) less than 60 ml/min/1.73m 2 or the existence of any renal decline indicators in the urine such as albumin (Liyanage et al., 2022) is a major public health issue worldwide (Hasan et al., 2018).The global predicted prevalence of diabetes among adults is 439 million by 2030 (Shaw, Sicree, & Zimmet, 2010).Hypertension and diabetes are associated with CKD (Zhang et al., 2012).The estimated global prevalence of diabetes in 2019 is 9.3% expected to rise to 10.2% by 2030(Saeedi et al., 2019)).Stage 3 Chronic Kidney Disease (CKD) in people with diabetes is reported to be high (56%) in Cambodia (Thomas, van, Mehrotra, Robinson-Cohen, & LoGerfo, 2014) .CKD was 10Á8% in rural areas of China.In the United States, 23.5% of individuals aged above 18 years, had CKD (McFarlane et al., 2011).
In India, the occurrence of diabetes in adults has increased (Tandon et al., 2018).The prevalence of diabetes mellitus was 8.3%, with only 18% receiving treatment (Tripathy et al., 2017).Type 2 DM and hypertension were the usual triggers of CKD (Rajapurkar et al., 2012).Hyperglycemia is causing an increase of CKD cases in India.Awareness Programs are needed to reduce the risk factors of diabetes mellitus (Tripathy, 2018).CKD was found in 34.91% of the general population, aged above 18 years, from Varanasi, India (Rai, Jindal, Rai, Rai, & Rai, 2014).Screening programs are needed to identify CKD in a risk group (Ene-Iordache et al., 2016).The occurrence rate of stage 5 CKD was 151 per million population (Modi & Jha, 2006).Lack of knowledge about CKD was observed in people with diabetes (Fiseha & Tamir, 2020).Diabetes and hypertension were associated with low eGFR and proteinuria (Singh et al., 2009).
Screening of high-risk populations for CKD helps in the initial detection of CKD (Bradshaw et al., 2019).It is observed that people are unaware of the complications of diabetes and hypertension.Educating the people is essential before they can land up with CKD (Hussain, Habib, & Najmi, 2019).The CKD was found to be 24.2%among people aged above 50 years in rural Pondicherry, India.The study suggests targeted screening of adults to prevent further progression of CKD (Kumar, Dongre, Muruganandham, Deshmukh, & Rajagovindan, 2019).A structured education program helps in the prevention of diabetes-related complications (Iqbal & Heller, 2018).
The National kidney foundation has defined five stages in CKD, and in the fifth stage, a patient needs dialysis or kidney replacement to live.GFR can be estimated by using the Chronic Kidney Disease -Epidemiology Collaboration (CKD -EPI) formula (Michels et al., 2010).Serum creatinine is widely used to measure the eGFR (Coresh et al., 2002).Detection of CKD at the beginning stages helps to slow down progress, which in turn reduces the financial load on individuals, families, and communities.
Studies suggest that the prevalence of hypertension and diabetes is increasing in India and it is the main cause of CKD.By this it is clear that there is a lack of knowledge about the risks associated with uncontrolled diabetes and hypertension.Most of the population are diagnosed with type 2 DM but are not aware of the complications associated with it.So, this lack of knowledge has been identified as one of the major reasons for the progress of CKD.Hence the present study intends to look at this aspect and educate the population about the same and monitor their progress across one year period.

Study design and participants
A quantitative approach with quasi-experimental, one group pretest-posttest design was used in this study.The aim of this study was to find the effect of a Disease Management Program (DMP) on delaying progression of CKD in patients with hypertension or type 2 diabetes mellitus.

REVISED Amendments from Version 2
The manuscript was modified as per the reviewer's suggestions.The version 1 manuscript needed a lot of improvement in the flow and readability and language.The references were not relevant to the explanation.The sample size description was not adequate and also the objective of the study was found to be missing.The results of the study were clear and needed more clarification.The version 1 had also repeated information in the discussion as well as in the introduction which was not noticed.The modifications were noted from version 1 and the changes were made accordingly version 2 and version 3.There were few errors found in language and grammar throughout the manuscript which was reassessed and corrected in version 3. The present manuscript is modified and is written in a simple, scientific language for easy understanding of the readers.Few of the abbreviations were not expanded at the beginning of the manuscript, which was looked upon in version 2 and 3. Also the references were added accordingly based on the articles which had similar inferences.The limitations of the study are elaborated and mentioned in version 3. All the necessary changes are made in the manuscript and the language looks appropriate after the modifications.
Any further responses from the reviewers can be found at the end of the article The people diagnosed with hypertension and/or diabetes for five or more year's duration and treatment were the participants of the study.People visiting rural health centers of Udupi District, Karnataka State, India, aged 30 years and above were the sampled population.Enumerative sampling technique was used.Sample size calculated to reach statistical significance with a power of 0.8, a standard deviation of eight, decline in eGFR in one year of five, and significance level 0.05, the total sample required was 22 each in stages one, two, and three of CKD.Keeping a 5% nonresponse rate total sample estimated was 70.The Chronic Kidney Disease stage was known after the serum creatinine test and formula application; hence the total sample taken was 103.Out of 103, for one year, 15 participants failed to follow up and hence 88 samples were analyzed.

Study instruments
The data were collected using demographic proforma which includes, age, gender, height, weight, serum creatinine, blood pressure, RBS, hypertension, and diabetes mellitus status, and duration of illness.A calibrated weighing scale was used to measure the weight.New measuring tape, sphygmomanometer, and glucometer were used to assess the height, blood pressure, and blood sugar, respectively.For checking blood pressure calibrated sphygmomanometer with appropriate cuff size of 13.1 Â 23.5 cm was used.It was made sure that the sample has not consumed tea or coffee, smoked or exercised vigorously in the last 30 minutes before the blood pressure measurement.Blood pressure was measured in the sitting position on the upper arm with the arm supported, and sphygmomanometer at the level of the heart.The investigator checked blood pressure twice in one sitting and average of the two readings recorded.The intervention, DMP, refers to educating the participants about the management of hypertension or diabetes mellitus on a one-to-one basis (explaining and giving leaflets) and follows up on every fourth month, till one year, with teaching reinforcement along with random blood sugar and blood pressure assessment, as well.
Development of the education module and leaflet about hypertension and diabetes mellitus was prepared by the researcher by reviewing the published and unpublished literature and validated by experts.The education module contains the meaning, causes and risk factors, signs and symptoms, diagnosis, and management.Management included nutrition, exercise, monitoring of blood sugar and blood pressure, pharmacologic therapy.Participants' questions were answered, and the education module was explained in an easy-to-understand manner.Complications were explained to improve the compliance level.The importance of exercise, nutrition, and compliance with medication in controlling blood sugar and blood pressure were also explained.
The researcher filled in the demographic proforma by collecting information from the participants and assessed height, weight, blood pressure, and Random Blood Sugar (RBS).Blood for serum creatinine was collected using serum vacutainer and assessed using the standard Jaffe method calibrated to Isotope Dilution Mass Spectrometry (IDMS).CKD-EPI formula was used to estimate GFR.Teaching was given about managing hypertension and diabetes mellitus, and a leaflet about the same was distributed during the baseline data collection.In the fourth and eighth-month blood pressure and RBS were reassessed, and teaching was reinforced.At one-year blood pressure, RBS, and serum creatinine were tested.

Study variables
Demographic variables were age, gender, serum creatinine height, and weight.Teaching regarding management of Hypertension and Diabetes Mellitus is the independent variable.Blood pressure and RBS were the dependent variables that affect kidney function and eGFR is the key variable.Other variables are disease conditions (Diabetes Mellitus or Hypertension or both) and duration of illness.

Data analysis
Data were analyzed using SPSS.Continuous variables are summarized using mean or median whichever is applicable and categorical variables using proportions.Frequency and percentage were used to describe the participant characteristics.Blood pressure and RBS were the dependent variables that affect kidney function.Mean, standard deviation, and range were used to summarize blood pressure, RBS, and paired't' test to compare baseline and at one year follow up systolic blood pressure (SBP), diastolic blood pressure (DBP), and RBS.As per, kidney disease: Improving Global Outcomes (KDIGO) Guidelines CKD is classified into five stages.Stage 1 (GFR ≥ 90 ml/min), stage 2 (GFR = 60-89 ml/min), Stage 3 (GFR = 30-59 ml/min), Stage 4 (GFR = 15-29 ml/min), stage 5 (GFR < 15 ml/min).Cross table was used to explain the number of participants who improved, remained in the same stage of CKD, and progressed to a higher stage of CKD."Wilcoxon signed-rank test" was used to find the effectiveness of DMP as data (eGFR) were not following normality.The difference between baseline and one-year follow-up GFR is done and categorized into ≤1 ml, 1-10 ml, and more than 10 ml.

Ethical considerations
The study protocol was approved by the Kasturba Medical College and Kasturba Hospital Institutional Ethics Committee.(IEC184/2011).The participant information sheet was given to the participants, and the study process was explained and informed written consent was obtained from the participants before data collection.

Demographic characteristics of participants
Demographic characteristics of baseline and one-year follow-up are summarized in Table 1.About 87.5 % of them belong to the age group of 51 years, and above, 46.6% of them were hypertensive, and 35.2% of them had both hypertension and type 2 DM.  2 shows mean, standard deviation, range of blood pressure, and RBS at the four-month interval and results of paired t' test applied to compare baseline and at one year follow up systolic blood pressure (SBP), diastolic blood pressure (DBP) and RBS.At baseline, most (69.44%) of them had SBP of 141-220 mm of Hg, 29.78% of them had an RBS level of 201-400 mg/dl.Mean SBP reduced by 6 mm of Hg and mean RBS by 24 mg/dl at one year, follow-up.There was a significant reduction in blood pressure and RBS (p < 0.001) for one-year follow-up.
Baseline and one-year follow-up stages of CKD Table 3 shows the baseline and one-year follow-up stages of CKD.At baseline, 47 participants had stage 2 CKD.Among them, four of them improved to stage 1, and 13 of them progressed to stage 3 CKD.At baseline, eight participants had CKD stage 3. Out of eight, two of them improved to stage 2, and one progressed to stage 4 CKD, and five remained in the same stage.

Effectiveness of the DMP
Table 4 shows the effectiveness of the DMP.The pre and post-intervention eGFR data of participants was not following normality, hence median, median difference, and 'Z' value of pre and post-intervention eGFR were assessed.The median fall in GFR is 5 ml/min/m 2 /year and there is a significant difference in GFR change in one year follow up, which says the intervention is not effective.The intervention helped to delay renal function deterioration.Table 5 shows the progression of CKD for a one-year follow-up.About 36.4% of participants lost only less than 1ml of GFR for one year.

Discussion
The result of the present study shows that CKD stage 3 and higher amounts to 10.22% of the participants.There have been few large community-based studies looking at the prevalence of CKD among hypertensive and diabetic populations in India and other countries.A study done in India reported that among 6129 participants, 2578 are having hypertension and CKD is present in 23.5% of hypertensive patients (Farag et al., 2014).Another study done in China among 1039 patients diagnosed with type 2 DM aged over 30 years shows 32.8% of CKD stage 3-5 (Lu et al., 2008).Collectively the reflection indicates that Type 2 DM and hypertension are the important public health issues, and it is associated with kidney disease.
The present study shows, in a year, mean systolic blood pressure decreased by 6 mm of Hg.A few participants confided that they were skipping the medication as signs and symptoms of the disease were not evident, but due to DMP, they returned to regular medication.Studies done in other countries suggested that DMP and assessing blood pressure, blood sugar, and GFR helps to sensitize the patients about their disease condition and to seek nephrology references if needed.DMP leads to improved hypertension control and eGFR among participants with CKD stage four or five (Richards et al., 2008).A study done in India by kidney help to screen the entire population of one village and provide medication for hypertension and diabetes showed a decrease in the prevalence of CKD (Prabahar, Chandrasekaran, & Soundararajan, 2008).Another study done in Australia among patients with diabetes, CKD, and hypertension showed no significant improvement in the intervention group (n = 36) in terms of medication adherence and blood pressure control.However, there was a 6 mm Hg reduction in SBP (Williams, Manias, Walker, & Gorelik, 2012b).Another study showed no significant differences in drug adherence between the intervention and control groups (Williams, Manias, Liew, Gock, & Gorelik, 2012a).The study on the impact of eGFR reporting on referral rates shows that eGFR reporting was useful in reducing the late referral to nephrology services (Foote et al., 2014).Hence it is necessary to identify the early stages of CKD, educate them about the importance of disease management.
The present study reports that the rate of drop in eGFR in one year was 5 ml/minute/1.73m 2 .At one year follow-up, 36.4% lost less than 1 ml, and 21.6% lost 1-10 ml of eGFR.However, there are no research studies done in India to compare the change in eGFR in one year.The fall in eGFR ranges from 2-20 ml/minute/1.73m 2 /year (Snyder & Pendergraph, 2005).In a study done in the US among people with diabetes, the eGFR dropped at 2.8 ml/min/1.73m 2 per year (Hanratty et al., 2010).A study done among the Rural Diabetic Cambodian population shows, at a median of 433 days follow up, 32% of patients lost more than or equal to 5 ml/min/m 2 of eGFR (Thomas, Pelt, Mehrotra, Robinson-Cohen, & LoGerfo, 2014).Further studies are required to find the rate of decline in GFR in normal individuals and individuals with comorbidities.

Study limitation
Glomerular Filtration Rate was estimated and not measured.The control group was not used due to ethical reasons.Only patients with diabetes and hypertension aged 30 years and above were studied.The participants with other health conditions were not included in the study which may also contribute as risk factors for CKD.

Conclusion
The Disease Management Program led to improvements in blood pressure and diabetes control and median progression of CKD was estimated at 5 ml/min/m 2 /year.Regular assessment of eGFR of the risk group, sensitizes the patient about their renal function.Teaching about the management of hypertension and diabetes mellitus and checking blood pressure and RBS helps to know about their disease control and to take action to control blood pressure and blood sugar.
Implications to nursing practice, management, policy education and future research People in the community are unaware of the seriousness of CKD.In the prevention and control of CKD, nurses can play an important role.In the outpatient department, nurses can educate the patients with hypertension and diabetes mellitus, and thus implement an effective DMP at the early stages of CKD.The nurse can work in the field with peripheral clinic workers for monitoring and evaluating each person by checking blood pressure and blood sugar and screening for CKD.

Data availability
Figshare: Progression of chronic kidney disease in patients with hypertension or type 2 diabetes mellitus, can it be delayed?DOI: https://doi.org/10.6084/m9.figshare.20278266-Authors should provide supporting data on Disease Management Plan (DMP) to improve clinical outcomes in order to strengthen the study rationale.Methods: -Sample size calculation is not clearly articulated.
-Authors should provide supporting references used to develop DMP.
-Authors should add details about how follow up was done.
-Specify who delivered the DMP in the study and if they were trained to do so.
-The SPSS version needs to be specified. Results: -Tables headings should be relevant to the presented -Provide relevant percentages with the numbers.
The abstract says that 100000 patients enter ESRD per year.Does this refer to the Indian population or the global population?In the second paragraph of the introduction, 'the occurrence rate of stage 5 CKD' is mentioned to be 151 per million population in India which amounts to around 200000 entering CKD5.Perhaps these statements could be coalesced and mentioned in the introduction for clarity.

2.
The criteria used to diagnose CKD stages 2 and 1 could be clarified as nearly 90% of the participants were in this category.How were they diagnosed to have CKD as eGFR was above 60 -did they have evidence of structural damage (proteinuria, abnormal urine sediment, radiological abnormalities, hereditary diseases.)?As an example, an individual aged 40 with an eGFR of 100 does not have CKD stage 1 unless there is evidence of structural damage.Likewise, an individual with eGFR 78, aged 70 does not have CKD stage 2 unless there is evidence of structural damage.The eGFR is to be used merely for the staging of diagnosed CKD except when the eGFR is <60 when it is used for diagnosing CKD.

3.
A discussion of how using RBS by glucometer would compare with using HBA1C or FBS/PPBS as a measure of DM control would be relevant while discussing the strengths and limitations of the study as the RBS is the main dependent variable.Likewise, the method of BP measurement -number of attempts, device used, measured by whom, average of readings in a single sitting -is also worth discussing as the effect size was small (5mm hg of SBP, nil In DBP) and BP was the main dependent variable.

4.
I note that the eGFR was merely a key variable rather than the dependent variable.That diminishes the stated intent of the study.

Are the conclusions drawn adequately supported by the results? No
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: eGFR, CKD, Dialysis I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.Uncontrolled hypertension and diabetes were the main causes of CKD.Hence the researcher studied the people with hypertension and diabetes. 1.
The abstract was modified adding this sentence -The occurrence rate of stage 5 CKD was 151 per million population in India.

2.
Classification of CKD is done based on eGFR.Other diagnostic measures were not done.
That is one of the limitations.

3.
For checking blood pressure calibrated sphygmomanometer with appropriate cuff size of 13.1 × 23.5 cm was used.Before blood pressure measurement was taken it was made sure that the samples has not consumed tea or coffee, smoked or exercised vigorously in the last 30 minutes.Blood pressure was measured in the sitting position on the upper arm with the arm supported, and sphygmomanometer at the level of the heart.The investigator checked blood pressure twice in one sitting and average of the two readings recorded.The researcher mainly focused on eGFR.Kidney function depends on Control of blood sugar and blood pressure also.

4.
eGFR is a dependent variable and Disease management program was the independent variable.

5.
Included in the data sheet.6.
Statistically significant change in eGFR was observed.People with hypertension and diabetes, there will be more chances of decrease in eGFR.But intervention helped to delay the progression of GFR.The research design was not strong to prove this.Control group was not included, based on the experts suggestion.

7.
In the studies selected for the discussion , the study population was representative of the population.

8.
Blood pressure was checked for all patients and entered in data sheet only for patients with history of hypertension.

9.
Fall in BP could be due to the education and sensitization of the people about the complications of uncontrolled hypertension.

10.
Correction is done in the data sheet.11.
Base line and at one year GFR included in the data sheet.12.

Competing Interests:
No competing of interest.
The benefits of publishing with F1000Research: Your article is published within days, with no editorial bias • You can publish traditional articles, null/negative results, case reports, data notes and more • The peer review process is transparent and collaborative • Your article is indexed in PubMed after passing peer review • Dedicated customer support at every stage • For pre-submission enquiries, contact research@f1000.com No Z value and p value is shown Discussion: -The first paragraph repeats the information in the Introduction section.Here, authors should summarise the key results.-Limitations should be more detailed and add strengths, if any.Conclusion: Implications should be moved to the Discussion section.Is the work clearly and accurately presented and does it cite the current literature?YesIs the study design appropriate and is the work technically sound?YesAre sufficient details of methods and analysis provided to allow replication by others?PartlyIf applicable, is the statistical analysis and its interpretation appropriate?PartlyAre all the source data underlying the results available to ensure full reproducibility?YesAre the conclusions drawn adequately supported by the results?PartlyCompeting Interests: No competing interests were disclosed.Reviewer Expertise: Diabetes, critical care, sepsis I have the following comments to make:Can the research question be more clearly elucidated?More specifically, was the study looking at whether the DMP impacted the eGFR change or whether the DMP impacted the BP and RBS?The assignment of BP and RBS as dependent variables suggests the latter was the study research hypothesis but the title suggests otherwise.

Table 1 .
Demographic characteristics of participants at baseline and one-year follow-up.

Table 2 .
Mean, standard deviation and range of BP and RBS and comparison of SBP, DBP & RBS using paired't' test.Mean, standard deviation and range of BP and RBS and comparison of SBP, DBP & RBS using paired t' test Table

Table 3 .
CKD stages at baseline and one year follow up using CKD -EPI formula.
Values in the parenthesis are row percentages.This is cross table; row total represents the baseline and column total represents the one year follow up stages of CKD.

Table 4 .
Median, median difference, and 'Z' value of pre and post intervention eGFR.

Table 5 .
Progression of CKD for one year follow up.
Tripathy JP, Thakur JS, Jeet G, et al.: Prevalence and risk factors of diabetes in a large community-based study in North India: results from a STEPS survey in Punjab, India.Diabetol.Metab.Syndr.2017; 9(1): 8. PubMed Abstract|Publisher Full Text Tripathy JP: Burden and risk factors of diabetes and hyperglycemia in India: findings from the Global Burden of Disease Study 2016.Diabetes Metab.Syndr.Obes.: Targets Therapy.2018; 11: 381-387.PubMed Abstract|Publisher Full Text Williams A, Manias E, Liew D, et al.: Working with CALD groups: testing the feasibility of an intervention to improve medication self-management in people with kidney disease, diabetes, and cardiovascular disease.Ren.Soc.Australas.J. 2012a; 8(2): 62-69.Williams A, Manias E, Walker R, et al.: A multifactorial intervention to improve blood pressure control in co-existing diabetes and kidney disease: a feasibility randomized controlled trial.J. Adv.Nurs.2012b; 68(11): 2515-2525.
Thank you for the detailed review.Please find the response for the comments.Title is modified -Effectiveness of a Disease Management Program (DMP) in controlling the progression of Chronic Kidney Disease among hypertensives and diabetics.