The magnitude of undernutrition and associated factors among adult chronic kidney disease patients in selected hospitals of Addis Ababa, Ethiopia.

BACKGROUND: Undernutrition is a common comorbidity in chronic kidney disease patients which augments the progression of the disease to an end-stage renal disease, renal dysfunction and related morbidity and mortality. However, in Ethiopia, there is a dearth of research evidence in this regard. Therefore, this study aimed to assess the magnitude of undernutrition and its associated factors among adult chronic kidney disease patients.
METHODS: An institution-based cross-sectional study was conducted in selected hospitals of Addis Ababa from May to August 2018. Data were collected by structured and pretested questionnaires. Patients' charts were reviewed from their medical profiles. Body mass index was calculated from anthropometric measurements using calibrated instruments. Serum albumin level was determined by reference laboratory standard procedure. Data were entered into Epi- data version 3.1 and exported to SPSS version 21 for analysis. Descriptive statistics were calculated and presented by tables, graphs and texts. Binary and multivariable logistic regression analyses were computed and the level of statistical significance was declared at p-value <0.05.
RESULTS: From the total sample size of 403 participants, 371 were involved in the study. The prevalence of undernutrition (BMI<18.5) among adult chronic kidney disease patients was 43.1% (95% CI: 38%-48%). Undernutrition (BMI<18.5) was significantly higher among patients with diabetic nephropathy [AOR = 2.00, 95% CI, 1.09-2.66], serum albumin value less than 3.8g/dl [AOR = 4.21: CI, 2.07-5.07], recently diagnosed with diabetes mellitus [AOR = 2.36, 95% CI, 1.03-3.14] and stage V chronic kidney disease [AOR = 3.25:95% CI, 1.00-3.87].
CONCLUSION: Undernutrition in chronic kidney disease patients was significantly higher among patients with diabetic nephropathy, patients on stage V chronic kidney disease, recently diagnosed with diabetes mellitus and serum albumin value less than 3.8g/dl.

Background

Chronic kidney disease is defined as abnormalities of kidney structure or function present for more than three consecutive months [1]. Although the incidence and prevalence of chronic kidney disease (CKD) have upsurge globally, the trend is not similar between developed and developing countries. Evidence from sub-Saharan Africa suggests 12–23% of adults have Chronic Kidney Disease (CKD) and are therefore at risk of developing (End Stage Renal Diseases) ESRD [2-4].

Undernutrition among CKD patients is found to be 29% using body mass index (BMI) as a diagnostic tool. It is a major comorbidity in CKD and ESRD patients as equal to others like hypertension, Diabetes Mellitus (DM) and cardiovascular diseases [5]. Undernutrition in CKD patients is one of the early complications which indicate the poor prognosis of the disease. Moreover, it speed up prognosis of the disease to ESRD which does not have options of treatment other than lifelong dialysis or renal replacement therapy [6].

Undernutrition is common in CKD patients but it is an enormously dominant comorbidity in ESRD patients. ESRD can be attributable to multiple factors including lower intakes of protein and calorie, diabetes mellitus, hypertension, lack of exercise, age, losses of nutrients, family history of the same disease, frequent hospitalization, gastrointestinal diseases, frequent dialysis, stage of GFR and multiple medications [7-9].

Limited evidence suggests undernutrition is a rapidly growing predisposing factor for several underlying diseases which complicates the care and treatment of CKD patients. However, nutritional status of CKD patients is left unknown fully [7-10]. Therefore, this study aimed to assess the undernutrition and associated factors among adult CKD patients in selected hospitals of Addis Ababa, Ethiopia.

Methods and materials

Study design, period and setting

An institution-based cross-sectional study was conducted from May to August 2018. The study was carried out at Saint Paul’s and Zewditu Memorial Hospitals in Addis Ababa, Ethiopia. The two hospitals have been selected because of their well-established renal outpatient departments and mostly referred by other health institutions from all over the country. Saint Paul`s hospital is in Addis Ketema Kifle Ketema and was reformed as a medical college in 2007. It has more than 13 departments; of which internal medicine is one where renal care is practiced and has a capacity of around 1440 patients in a year. It has three outpatient departments (OPD) working twice per week. Zewditu Memorial Hospital is one of the most popular hospitals in Addis Ababa which is in Arada-Kifleketema, Addis Ababa, Ethiopia. Currently, the hospital provides many services including dialysis. The hospital has one renal OPD working twice per week.

Population

All adult chronic kidney disease patients who are on follow-up care in the selected two hospitals during the study period were the source population of the study. CKD patients on follow-up care for at least three months were included in the study. Patients diagnosed with liver disease and who are on dialysis were excluded from the study.

Sample size determination and sampling procedure

By using single population proportion formula and considering confidence level /Z/ of 95%, marginal of error 5%, a reasonable estimate for the proportion of undernutrition in CKD patients (P = 0.5) and adding a none response rate of 5%, a total sample size of 403 CKD patients was obtained. The total sample size was allocated using average number of CKD patients visiting renal OPDs in the two selected hospitals. The average number of patients visiting OPD at Saint Paul`s hospital in one month was 100 and Zewditu Memorial Hospital was 50. The total numbers of patients being treated in the two hospitals in one month was estimated to be 150. Accordingly, from Saint Paul`s hospital = 403*100/150 = 268 patients and from Zewditu Memorial Hospital = 403*50/150 = 135 patients were included in the study. Every 3rd and 5th patient has been included in the study using a systematic sampling technique after determining the sampling interval of 403/268 = 3 in Saint Paul’s and 403/135 = 5 in Zewditu Memorial Hospital. The first participant was recruited by using the lottery method in each hospital.

Variables of the study

Dependent variable

Undernutrition in CKD patients (Yes/No).

Independent variables

Socio-demographic factors

Age, sex, place of residence, occupation, marital status, income, educational level, dietary intake.

Clinical factors

Stage of CKD, duration of illness, cause of disease, comorbidity, family history of the disease, type of disease, serum albumin level.

Lifestyle factors

Exercise, smoking, alcoholism, sleep patterns.

Nutritional factors

Frequency of meal, dietary diversity, nutrition counseling, place of meal preparation, patient appetite.

Operational definitions

Undernutrition

Chronic kidney disease patients whose measured BMI level of less than 18.5 [11].

Chronic kidney disease

Confirmed chronic abnormalities of kidney structure or function, present for >3 months with implications for health [12].

Glomerulonephritis

CKD patients with persistent proteinuria and occasional hematuria [13].

Stages of CKD

Stage 1CKD (GFR ≥ 90 mls/min), stage 2 CKD (GFR 60-89mls/min), stage 3 CKD (GFR = 59–30 mls/min), stage 4 CKD (GFR = 15–29 mls/ min) and stage 5 CKD (GFR < 15mls/min) [14].

Hypoalbuminemia

Serum albumin level less than 3.8 g/dl.

Data collection procedures

Socio-demographic and dietary data were collected by professional nurses and phlebotomists using interviewer-administered, pre-tested and structured questionnaires. Clinical data on the cause of the disease, stage of GFR and comorbidities were retrieved from patients’ medical charts.

Measurement of weight was recorded using a standard digital scale. The digital scale readout was checked reading of zero before measuring weight. Measurements were done after participants standing on the center of the weight scale platform dressing light clothes. Weight measurement results were recorded to the nearest of 0.1 kg.

Height was measured using a standard stadiometer. The study participants were asked to remove their shoes and stand erect. The heels of the feet were placed together with both heels touching the base of the vertical board. The head is maintained in the Frankfort Horizontal Plane position while the examiner lowers the horizontal bar snugly to the crown of the head with sufficient pressure to compress the hair. Results were recorded to the nearest 0.1cm. Participants’ BMI was calculated using their weight and height measurements; weight/ (height) 2(Kg/m2).

Serum albumin was determined by the Ethiopian Public Health Institute national HIV reference laboratory standard procedure. Appropriate precautions were undertaken to ensure the safe collection of blood samples. Ten milliliters of venous blood was collected following standard aseptic techniques and then centrifuged for five minutes at 3000 revolutions per minute. The separated serum was restored in a separate tube (Nunk tube) and was stored in a deep freezer and the serum albumin level was determined.

Dietary intake data were gathered using 24 hours dietary recall technique. Patients were asked to list out all the foods and drinks they had in the last 24 hours and the information has been recorded.

Data collection tools and data quality assurance

The data were collected by using pre-tested questionnaire. The questionnaire was pre-tested at Minilik Hospital on 5% of CKD patients before actual data collection. The questionnaire was translated from English to the Amharic language by a person who is fluent in both languages. Three days of training was given for data collectors. Calibration of weight and height measuring instruments was done after each measurement then the data were entered in ENA SMART software to see relative Technical Error of Measurements (TEM). The TEM output was compared with the acceptable range for relative TEM using beginner anthropometric levels for inter-examiners and was found to be in the acceptable range, < 2.0%.

Multicollinearity test was done and reported by Variance Inflation Factor (VIF) and found in the acceptable range <5. Specimen collection and preparation were done by experienced clinical laboratory professionals using standard equipment and following standard procedures. The overall clinical data collection was supervised by a Nephrologist.

Data analysis and management

The collected data were entered into Epi- data Version 3.1 and exported to SPSS version 21 for analysis. Frequencies, proportion, summary statistics and cross-tabulation of study variables was done and presented in simple frequency tables, graphs and texts. The assumptions for binary logistic regressions were first checked and then bivariable analysis was carried out to identify candidate variables at p-value <0.25 for multivariable analysis. Multivariable logistic regression analysis was done using those candidate variables to identify the statistically significant and independent associations between dependent and independent variables. The strength of associations was presented using an adjusted odds ratio with its 95% CI. Finally, variables whose p-value < 0.05 in multivariable logistic regression model were declared as statistically significantly associated.

Ethics approval and consent to participate

The study was approved by the Research Ethics Review Committee, College of Health Science and Medicine, Wolaita Sodo University. Participants were informed clearly about the purpose, risks and benefits of the study. Informed written consent was obtained from each participant. Confidentiality of participants’ information was kept throughout the research process. Personal privacy and cultural norms were respected. All biomedical waste products were discarded maintaining standard safety protocols.

Results

Socio demographic characters

From the total sample size of 403 study participants, 371 were actually involved in the study making the response rate of 92%. Out of the total study partakers, 231 (62.3%) were males the rest were females. The mean age of the participants was 43 years with a standard deviation of ±14 years. A high proportion 276 (74.4%) of the participants were urban dwellers and 110 (29.7%) of them were a government employees. Twenty-four (6.5%) of the respondents reported they had lost their jobs because of the disease. Regarding educational status, the majority 307 (82.8%) attended above primary education and more than half 237 (63.9%) were married “Table 1”.

Table 1

Socio demographic characteristics of chronic kidney disease patients in Saint Paulo’s and Zewditu Memorial Hospitals in Addis Ababa, Ethiopia, 2018.

Variable	Frequency	Percent (%)
Sex (n = 371)
Male	231	62.3
Female	140	37.7
Age in years (n = 371)
18–24	32	8.6
25–54	257	69.3
55–64	52	14.0
≥65	30	8.1
Place of Residence (n = 371)
Urban	276	74.4
Rural	95	25.6
Occupation (n = 371)
Farmer	28	7.5
Merchant	40	10.8
Daily laborer	28	7.5
Government employee	110	29.7
Non-government employee	76	20.5
Retired	39	10.5
Lost job	24	6.5
Others *	26	7.0
Marital status(n = 371)
Married	237	63.9
Single	103	27.8
Widowed	8	2.2
Divorce	23	6.2
Educational level (n = 371)
No formal education	64	17.3
Primary	129	34.8
Secondary	132	35.6
Higher education	46	12.4
Monthly income in ETB (n = 371)
<700	94	25.3
701–2000	104	28
2001–5000	136	36.7
>5001	37	10

* = Self-employed, house wives, religious workers

ETB = Ethiopian Birr

Life style patterns of CKD patients in Saint Paulo’s and Zewditu Memorial Hospitals

In this study, the majority 286 (77.1%) never drank alcohol, while 27 (7.3%) of them quit smoking. A high proportion of 341 (92%) of the participants did not have regular physical activity “Table 2”.

Table 2

Life style patterns of CKD patients in Saint Paulo’s and Zewditu Memorial Hospitals in Addis Ababa, Ethiopia, 2018.

Variable	Frequency	Percentage
Drinking alcohol(n = 371)
Never drink	286	77.1
Quit drinking	84	22.6
I drink now	1	.3
Smoking (n = 371)
Never smoked	343	92.5
Quit Smoking	27	7.3
Currently smoking	1	.3
Physical activities(n = 371)
Yes	30	8.1
No	341	91.9
Sleep pattern(n = 371)
Difficulty in falling asleep	80	21.6
Do not get enough sleep	72	19.4
No change	219	59.0

Prevalence of undernutrition and nutritional habits of chronic kidney disease patients in Saint Paul’s and Zewditu Memorial Hospitals

The overall prevalence of undernutrition among the study participants was found to be 160 (43.1%) having a measured BMI level of less than 18.5. The mean BMI value was 22.8 with the standard deviation of ±3.5 “Fig 1”. From the total study respondents, only 235 (63.3%) afforded eating meals three times a day. One hundred fourteen (30%) of the participants had provided nutritional counseling and 299 (80.6%) reported they prepare meals at their homes. Two hundred seventy one (73%) and 251 (67.7%) respondents had decreased appetite and weight respectively in the past 3 months before the study. Regarding food diversity, the majority 300 (80.9%) of the participants reported they eat less than or four food groups in the last 24 hours “Table 3”.

Fig 1

BMI measures of chronic kidney disease patients in Saint Paulo’s and Zewditu Memorial Hospitals in Addis Ababa, Ethiopia, 2018.

Table 3

Nutritional habits of chronic kidney disease patients in Saint Paulo’s and Zewditu Memorial Hospitals in Addis Ababa, Ethiopia, 2018.

Variables	Frequency	Percentage
Frequency of meal in a day (n = 371)
2meals a day	66	17.8
3 meals a day	235	63.3
4 meals a day	70	18.9
Dietary diversity (n = 371)
≤4	300	80.9
>4	71	19.1
Nutrition counseling (n = 371)
Yes	114	30.7
No	257	69.3
Where your meals prepared (n = 371)
Home	299	80.6
Out of home	72	19.4
Appetite (n = 371)
Decreased	271	73.0
Increased	13	3.5
No change	85	22.9
Unnoticed	2	0.5
Weight (n = 371)
Decreased	251	67.7
Increased	13	3.5
No change	107	28.9

Clinical conditions of the study participants in Saint Paulo’s and Zewditu Memorial Hospital, Addis Ababa, Ethiopia

From the total of 371 participants involved in the study, 195(52.5%) of them were diagnosed with CKD for less than 4 years. Diabetic nephropathy was found to be the predominant cause of CKD accounting for 166 (44.7%) and about 147 (39.6%) diagnosed with DM in the last three months before the study. Hypoalbuminemia (serum albumin level less than 3.8g/dl) was seen in 161 (43.4%) of the study participants “Table 4”.

Table 4

Clinical conditions of chronic kidney disease patients in Saint Paulo’s and Zewditu Memorial Hospitals, Addis Ababa, Ethiopia, 2018.

Variable	Frequency	Percentage
Duration of disease (n = 371)
1–3 years	195	52.5
≥4 Years	176	47.5
Diagnosed with DM (n = 371)
Yes	147	39.6
No	224	60.4
Cause of Disease (n = 371)
Diabetic nephropathy	166	44.7
Hypertensive nephropathy	92	24.8
Glomerulonephritis	113	30.5
Family History (n = 371)
Yes	58	15.6
No	313	84.4
Diagnosed with HTN (n = 371)
Yes	190	51.2
No	181	48.8
Albumin level (n = 371)
<3.8 g/dl	161	43.4
≥3.8 g/dl	210	56.6

The stages of CKD among study participants in Saint Paulo’s and Zewditu Memorial Hospitals

Stages of chronic kidney disease were determined by glomerular filtration rate. The stage IV CKD was found in 138 (37%) and stage III in 133 (36%). The magnitude of stage I and stage II CKD was 59 (16%). Stage V was found in 41 (11%) of study participants “Fig 2”.

Fig 2

Stages of CKD among study participants in Saint Paulo’s and Zewditu Memorial Hospitals, 2018.

Factors associated with undernutrition among chronic kidney disease patients of Saint Paulo’s and Zewditu Memorial Hospitals

In the binary logistic regression analysis: stage of the disease, cause of the disease, duration of the disease, meal pattern, serum albumin values and recent diagnosis with DM were significantly associated at the p-value of <0.25 and were candidate variables for multivariable logistic regression analysis. In the multivariable logistic regression analysis: cause of the disease, stage of the disease, recent diagnosis with DM status and serum albumin value remain independently and significantly associated with undernutrition among CKD patients. Undernutrition was significantly higher in patients with diabetic nephropathy and hypertensive than those with glomerulonephritis [AOR = 2.00: 95% CI, 1.09–2.66] and [AOR = 2.13: 95% CI, 1.01–3.87] respectively. Stage V CKD patients were three times more likely to develop undernutrition than stage I and II patients [AOR = 3.25: 95% CI, 1.00–3.87]. Those patients in stage III [AOR = 2.01: 95% CI, 98–4.76] and stage IV [AOR = 2.03: 95% CI, 1.85–4.01] had more than two times higher chance of developing undernutrition than those in stage I & II.

Undernutrition was significantly higher among CKD patients whose serum albumin value less than 3.8 g/dl than those patients whose serum albumin value of greater than 3.8g/dl [AOR = 4.21: CI, 2.07–5.07] “Table 5”.

Table 5

Factors associated with undernutrition among CKD patients in Saint Paulo’s and Zewditu Memorial Hospitals in Addis Ababa, Ethiopia, 2018.

Variables	BMI		COR (95%CI)	AOR (95%CI)
	Greater than 18.5 (%)	Less than 18.5 (%)
Cause of CKD (n = 371)
Diabetic nephropathy	98(59%)	68(41%)	2.19(1.28–3.56)	2.00(1.09–2.66)*
Hypertension	61(66.3%)	31(33.7%)	1.62(1.33–3.63)	2.13(1.01–3.87)*
Glomerulonephritis	52(46%)	61(54%)	1	1
Stage of CKD (n = 371)
Stage 3	36(64.2%)	20(35.8%)	2.12(0.87–5.14)	2.01(0.98–4.76)
Stage 4	80(59.7%)	54(40.3%)	2.95(1.34–6.53)	2.03(1.85–4.01)*
Stage 5	23(56%)	18(44%)	2.18(1.23–4.82)	3.25(1.00–3.87)*
Stage 1 and 2	72(51.4%)	68(48.6%)	1	1
Serum albumin value (n = 371)
<3.8 g/dl	72(44.7%)	89(55.3%)	2.13(1.78–3.25)	4.21(2.07–5.07)*
≥3.8 g/dl	139(66.5%)	71(33.5%)	1	1
Recently diagnosed with DM (n = 371)
Yes	104(70.7%)	43(29.3%)	1.52(1.06–3.47)	2.36(1.03–3.14)*
No	107(47.7%)	117(52.3%)	1	1

* = variables significantly associated at p-value <0.05

Discussion

This particular study has described the prevalence of undernutrition and associated factors among CKD Patients in Saint Paul’s and Zewuditu Memorial Hospitals in Addis Ababa, Ethiopia. The prevalence of undernutrition among chronic kidney disease patients based on BMI level was found to be 160 (43.1%) out of the total sample size of 371 (100%). This finding is consistent with the studies done in teaching hospitals of Southern Nigeria, Nigeria and India, where the studies reported that the prevalence of undernutrition was 43.2%, 46.7%, and 42.7% [15-17]. The prevalence of undernutrition in the present study is not consistent with the study done in Jordan where the prevalence was 65% among chronic kidney disease patients [18]. However, it is much higher when compared to the study result of Bordeaux University Hospital, Bordeaux, France 24.2% [19]. The possible reasons for variation in the prevalence of undernutrition can be attributed to differences in socio-demographic, economic, case mix, comorbidity and the differences in the diagnostic criteria used.

In the current study, diabetic nephropathy accounts for 166 (44.7%) of all CKD. This finding is inconsistent with the study result in Sub-Saharan Africa region where it was estimated to be the cause of CKD in 6–16% [3, 16]. In the present study, of those patients who have been diagnosed with DM 166(45%), 68(41%) of them were undernourished (BMI <18.5). This finding is much higher than the study result of Bordeaux University Hospital, Bordeaux, France, where the study shows the minimum BMI among all the CKD study participants greater than 22.5 [19].

In the recent study, an increasing trend of undernutrition had been reported from stage I CKD to stage V and the highest prevalence 18 (44%) was seen in of stage V CKD patients. This finding is lower than the study result of Nigeria where the magnitude of 69% was reported in stage V CKD patients [16]. The disparity might be explained in terms of differences in socio-demographic and economic, socio-cultural and nutritional habits.

The risk of undernutrition was significantly higher in hypertensive and diabetic patients than those with glomerulonephritis [AOR = 2.00: 95% CI, 1.09–2.66] and [AOR = 2.13: 95% CI, 1.01–3.87] respectively. This result is not corroborated with the study result of the teaching hospital of Southern, Nigeria where the study reported no significant association between being hypertensive or diabetic and undernutrition in CKD patients [20]. The possible explanation for the difference might be due to the differences in sample size, study design, food taboos and cross-cultural variability in food selection.

The current study identified that being in stage V CKD was a risk for undernutrition than being in stage I and II [AOR = 3.25: 95% CI, 1.00–3.87] and the risk of undernutrition increases as the patients CKD stage progresses from stage I to stage V. This result is similar with the study results of Southern Nigeria and the Catholic University of Korea, South Korea [20-22].

In this study, patients recently diagnosed with DM were more than 2 times more likely to be undernourished than those who know their DM status three months before the study [AOR = 2.36: 95% CI, 1.03–3.14]. The possible explanation for this might be food restriction, being on anti- DM medications, stress due to recent diagnosis and complicated DM.

In this study, serum albumin value was also identified as a significant predictor of undernutrition among CKD patients. Undernutrition was significantly higher among CKD patients whose serum albumin value is less than 3.8g/dl when compared with their counterparts [AOR = 4.21: CI, 2.07–5.07]. This result is parallel to the study reports of teaching hospital of Southern Nigeria, USA, Stockholm, Sweden [21, 23, 24].

Study strengths

This study has covered the prevalence of undernutrition among chronic kidney disease patients which was not well addressed previously. Moreover, in this study, the extent of anemia among CKD patients which is an important nutritional status indicator was determined by using the serum value of albumin. The generalizability of the study findings was high because the hospitals included in the study serve much population which comes from throughout Addis Ababa city and its surroundings.

Study limitations

This study has limitations. First, as the study sample consisted of adult CKD patients who come to selected health facilities and therefore we cannot generalize our findings to other districts elsewhere in Ethiopia or other sub-Saharan developing countries. Second, this study has assessed undernutrition using only BMI measures which may miss the comprehensive nutritional status. Information was collected on exposures and outcomes simultaneously, thus causal relationships are difficult to establish.

Conclusions

This study concludes that the prevalence of undernutrition among adult chronic kidney patients was found to be high. Stage of disease, cause of disease, recent diagnosis of diabetes mellitus and serum albumin value were found to be significant predictors of undernutrition among the CKD patients.

Analytical procedures done for albumin determination.

(DOCX)

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Questionnaire English version.

(DOCX)

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Amharic version of questionnaire.

(DOCX)

Click here for additional data file.

15 Jan 2021

PONE-D-20-35996

The magnitude of under nutrition and associated factors among adult chronic kidney disease patients in selected hospitals of Addis Ababa, Ethiopia

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Dear Authors, your manuscript has been reviewed by relevant experts. They found manuscript interesting but raised several concerns on its presentation, result interpretation, study limitations and interpretations. Referees are unable to fully assess the manuscript due to syntax and grammar errors throughout the manuscript. I will suggest to please consider the proofread service or Native speaker so this draft could be better assessed by the reviewers.

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Reviewer #1: Asefa et al have reported the prevalance of protein-energy wasting (PEW) in chronic kidney disease (CKD) patients in 2 local tertiary institutions in Ethiopia. They found that cause, duration, and stage of CKD and serum albumin levels are significant predictors of PEW.

Although the findings are not new, this interesting topic deserves to be published. The paper is unnecessary long, language is poor, methods and discussion sections and tables require significant revision.

I consider there is a lot of re-writing by a native speaker. In discussion section there is insufficient circumspection in both interpretations of the findings reported and their relationship to the literature.

I will be honored to review the renovated form of the paper

Reviewer #2: I read carefully the paper entitled " The magnitude of under nutrition and associated factors among adult chronic kidney disease patients in selected hospitals of Addis Ababa, Ethiopia".

This cross-sectional study aimed to assess the magnitude of under nutrition in chronic kidney disease patients in Addis Ababa.

The research question is clear and important, the methodology used is sound but the manuscript needs major revision for structure, language and presentation of results.

I have some comments that could help the authors improve their manuscript.

Major comments:

1- General: The manuscript should be revised for English and authors need to format their references list.

2-The introduction has so many paragraphs, it should be structured using three paragraphs: what we know, what we still are lacking and the hypothesis of the study.

3-Methodology: authors need to explicitly define "under nutrition" in the methods paragraph.

4-Results: in the tables and in text, authors should specify the unit of each variables: age in years, the income's currency. Table 3 was mentioned before table 2 in the text.

5-Authors need to use their references appropriately and specify in their statement the exact characteristics of patients in the cited reference (for instance reference 7 was mentioned after mentioning hemodialysis patients; however, this reference addresses pre-dialysis patients).

6-The limitations of this study should be thoroughly addressed and cited: the reader will not be satisfied by the statement " These study shares the limitations of facility based cross-sectional study".

Minor comments:

1. Abstract:

-Readers would like to see the number of participants in the paragraph "results" of the abstract.

-What do authors mean by "diabetic patients with glomerulonephritis"?

-In the conclusion: "The prevalence of under nutrition in this study was higher"....higher than?

2. Introduction

-Authors should consider using other terms than "frightening", and "worst stage" and "victims".

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Mabel Aoun

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

4 Mar 2021

Response to reviewers

General note for academic editor regarding the overall progress

First of all, we would like to acknowledge the academic editor for giving us adequate time to revise and address all the concerns of the reviewers and journal requirements. Following, we the authors of this manuscript have been working extensively since we have been notified with the academic editor and expert reviewer’s reports of the manuscript giving a due attention for all the concerns raised by the academic editor and expert reviewers to be well addressed.

The presentations of the results of the study have been critically worked and made to be in a logical and coherent sequence, study limitations and interpretations are re-written and sufficiently and clearly elaborated. The whole manuscript file has almost been re-written correcting all the syntax and grammatical errors. We hope the academic editor and the expert reviewers get it as much improved manuscript. Thank you so much!

A. Point by point response letter to academic editor

1. We have checked again our manuscript for fulfillment of PLOS ONEs style requirements including the naming of files and it has been written accordingly. Thank you!!

2. We have amended the abstract and placed the abstract after the title page as per the recommendation. Thank you!!

3. We placed the ethics approval statement at the end of methods section only and removed it from the prior section of the manuscript. Thank you in advance!!!

4. As per your recommendation, we inserted caption for figure 2 .Thank you in advance!!!

B. Point by point response letter to reviewer one

First of all we would like to express our gratefulness for the reviewer for appropriately recognizing the topic as one of the important area of research and for being interested on the topic. Following our acknowledgement, the reviewers concerns are point by point addressed in the following bullets

� The reviewer’s comment regarding the papers being unnecessarily long is well accepted. We make the current revised version clear and focused only to the study objectives. All the other out of the scope of the study which made the paper unnecessarily long have been removed and the study objectives related contents are further and adequately elaborated. We hope the reviewer will get the revised version clear and to the point of the study objectives. Thank you so much!

� The reviewer’s comment regarding the language errors are also the right concerns and we have re-written each and every statement throughout the manuscript correcting all the grammatical and punctuation errors consulting English language experts in Wolaita Sodo University. We hope the reviewer will get the revised version is clear and improved. Thank you!

� The reviewer’s comments regarding methods, discussion and tables of the previous manuscript require significant revision is well accepted. In the current revised version, we made all the methods followed during the study are well and clearly explained, in the discussion section the important finding are clearly discussed, tables and figures are well revised. Thank you!

� The reviewer’s comments about the discussion sections lack of sufficient circumspection both in the interpretation and relationship with the extant literature are right. In the recent revised version we have appropriately re-written the whole discussion section and we made the interpretations clear and discussed the findings with relevant and up to date results in the extant literature. Thank you!

� As overall, the recent revised manuscript file is adequately renovated version and we hope the reviewer will get the manuscript as much improved. Thank you so much in advance!

C. Point by point response letter to reviewer two

� Before all, we would also like to express our thankfulness of reviewer two for carefully and critically reviewing this manuscript sacrificing crucial time and effort for maintaining scientific integrity of the manuscript and to be considered for publication meeting the scientific and journal requirements. Following our gratefulness of the reviewer, we have addressed all the reviewers concerns point by point as follows:

Point by point response to major comments of reviewer two

1. The reviewers concerns about revision of the language and formatting reference list is well accepted. Accordingly, we have thoroughly read the whole manuscript file’s each and every statement for any grammatical errors and corrected throughout the document and we have formatted the reference list as it appears in the manuscript document sequentially. Thank you!

2. The reviewers comments regarding the structure of the introduction section of the previous version has been accepted and we re-structured the introduction section of this revised manuscript as per the reviewers recommendation in to three parts “what have been known in the existing body of knowledge”, “what is lacking in the current literature” and “the hypothesis of the this particular study”. Thank you so much!

3. The reviewer’s comment to explicitly define “undernutrition” in methods section is accepted and as per the reviewers recommendation we have explicitly defined undernutrition and other relevant concepts in the methods section of the manuscript. Thank you!

4. The reviewer’s comments regarding the some important variables lack of unit of measurement (age in years and currency) and mentioning Table 3 before Table 2 have been accepted. We have included the units of measurements for age and currency and all the tables are sequentially placed in the manuscript file. Thank you!

5. The authors would like to thank the reviewer for the best insight regarding incomparable referencing of the characteristics of CKD patients. Reference number 6 has been removed from the text and reference list, because the study was on CKD patients who were on hemodialysis which is not in the scope of this study and the concept held in reference number 7 has been elaborated further because it is a matched reference with the current study. Thank you!

6. The reviewer’s comments about unsatisfactorily addressing of the limitations of the study in the previous version are right and well accepted. In the current revised version, we have appropriately and satisfactorily addressed the limitations of the study including all the possible limitations of this particular study. We hope the reviewer will get the concerns are well addressed. Thank you in advance!

Point by point response to minor comments of reviewer two

1. The reviewer’s comment regarding the number of participants to be included in the abstract results part is right and it has been included. Thank you!

2. According to the reviewers comment, we noticed the phrase “diabetic glomerulonephritis” was unnecessary and irrelevant to this particular study and it has been removed from the manuscript file. Instead, we have operationalized the term “glomerulonephritis” which is an important variable for the study and included in operational definition section of the main manuscript file. Thank you!

3. The reviewers comments regarding the comparison of the “prevalence of undernutrition among chronic kidney disease patients” in the abstract conclusion section is accepted. As per the suggestion of the reviewer in the current revised version the “prevalence of undernutrition among chronic kidney disease patients” has been described relative to its public health significance when compared to its prevalence in the Sub-Saharan Africa region. Thank you!

4. The reviewer’s comment regarding the words which are unnecessarily terrifying has been accepted and replaced with appropriate ones. Thank you!

Thank you!

Submitted filename: Response to reviewers.docx

Click here for additional data file.

6 Apr 2021

PONE-D-20-35996R1

The magnitude of undernutrition and associated factors among adult chronic kidney disease patients in selected hospitals of Addis Ababa, Ethiopia

PLOS ONE

Dear Dr. Baza,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by May 21 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Tauqeer Hussain Mallhi, Ph.D

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

Thank for submitting the revised version. However, manuscript requires further improvement as suggested by the reviewer such as methodology, English/grammatical corrections, and statistical analysis. Please incorporate the comments of the reviewer so we could reach an appropriate decision.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: I Don't Know

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: As I mentioned in my first review, although the findings are not new, this topic deserves to be published. After major revisions, the paper looks well. I consider that it can be accepted in its current form.

Reviewer #2: Dear editor,

Thank you for the opportunity to read the revised version of the manuscript " The magnitude of undernutrition and associated factors among adult chronic kidney disease patients in selected hospitals of Addis Ababa, Ethiopia".

The authors put some efforts in order to improve their paper, however it still needs further work.

1-Vocabulary and grammar.

-In the abstract: comorbid is an adjective and not a noun; you can say "comorbid condition" or "comorbidity". "This study aimed " and not "was aimed".

-In the introduction: evidence not evidences. "Fasten" does not mean makes it faster in English! What do you mean by "primary complication"? An important complication?

Authors used ESRD and ESKD: one nomenclature is less confusing to the reader.

-In the methodology: patients were actually "included" not "participated".

-In the discussion: "has described" not "had". 160 has no meaning without the total: 160 out of...and it is not a magnitude, it is a prevalence.

Third sentence of the discussion lacks a verb.

Etc, etc.

2-Minor comments:

-In the abstract, results' section: Better to remove 160 and leave 43.1% for the prevalence.

-The definition of glomerulonephritis is usually not biological.

3-Major comments:

-Why did the author define hypoalbuminemia as less than 3.8 and not 3.5 g/dL? If you take the threshold of 3.5 as hypoalbuminemia, would hypoalbuminemia be associated with the low BMI?

-The interpretation of the results of the regression analysis should be different. The conclusion should state that a factor is associated to the outcome (dependent variable) and it is not a comparison of groups.

-In the whole manuscript including abstract, it is not explicitly said in the methodology that undernutrition is defined as a low BMI. What is your definition of undernutrition? BMI<18.5? This should be clearly stated in the methods.

-In the strengths of the study: what do authors mean by "considering the serum albumin to see the anemia clinically".

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Mabel Aoun

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

23 Apr 2021

General note to academic editor

First of all, we would like to express gratitude for the academic editor for giving us sufficient time to address all concerns of the reviewer. Following, our acknowledgment we have been working extensively since we have been notified to address the concerns of the expert reviewer and explained point by point in the following bullets.

Point by point response for reviewer 2

• Before all, we would like to express our thankfulness of reviewer two for carefully and critically reviewing revised manuscript. We found the comments and recommendations of the reviewer are very important inputs to maintain standards of the journal requirements for publication.

1. Point by point response to vocabulary and grammar errors for reviewer

• The reviewer comment regarding vocabulary and grammar errors are the right concerns. We have incorporated the recommendations of the reviewer and also checked the whole manuscript for similar errors and corrected accordingly. We hope the reviewer can access all the revisions in the clean copy of the manuscript and also from the revised manuscript with track changes. Thank you in so much!

2. Point by point response to minor comments of reviewer 2

• The reviewer comment regarding to remove 160 and leave 43.1% for the prevalence is acceptable and we have corrected accordingly. Thank you!

• The concern of the reviewer about the definition of glomerulonephritis is right. However, we defined it as it appears in the studied hospitals diagnostic criteria. Thank you!

3. Point by point response to major comments of reviewer 2

• The reviewer concern regarding the cut-point off hypoalbuminemia is appropriate and right. However, when we collect the information for the study, we have raised the concern with the clinicians on follow up care for the CKD patients. The normal serum albumin for general population ranges from 3.5g/dl- 5.2g/dl. The minimum cut- off value of 3.8g/dl was being used as a lower limit to consider hypoalbuminemia in the studied hospitals because CKD patients are vulnerable group for nutritional anemia. To avoid any delays in nutritional interventions for the CKD patients, the lower cut-off limit has been raised from 3.5g/dl to 3.8g/dl. This is why the studied hospitals are using 3.8g/dl as lower limit to consider hypoalbuminemia and we have used the same lower limit for the study. Thank you so much!

• According to the reviewer suggestion we have removed the comparison of the findings from the conclusion section and associated factors with the dependent variable has been stated in the current revised version of the manuscript. Thank you!

• The reviewer comment regarding explicit definition of the undernutrition in the abstract and the method sections is appropriate and acceptable. We have explicitly defined undernutrition as BMI<18.5 in both sections. Thank you!

• The reviewer comment regarding the strength of the study section is right. We have revised the section in the recent revised version and made clear. Thank you!

Submitted filename: Response to reviewer.docx

Click here for additional data file.

3 May 2021

The magnitude of undernutrition and associated factors among adult chronic kidney disease patients in selected hospitals of Addis Ababa, Ethiopia

PONE-D-20-35996R2

Dear Dr. Baza,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Tauqeer Hussain Mallhi, Ph.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: No

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The main subject of the manuscript deserves to be published. After language revision, the paper looks better. It can be accepted.

Reviewer #2: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

29 Jun 2021

PONE-D-20-35996R2

The magnitude of undernutrition and associated factors among adult chronic kidney disease patients in selected hospitals of Addis Ababa, Ethiopia

Dear Dr. Baza:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Tauqeer Hussain Mallhi

Academic Editor

PLOS ONE