Weight gain after renal transplant: Incidence, risk factors, and outcomes.

BACKGROUND: Renal transplantation is the definitive treatment for patients with end-stage renal disease (ESRD). It is associated with better quality of life and patient survival. Nevertheless, these benefits come with rising concerns about weight gain and metabolic abnormalities, which adversely impact transplant outcomes.
OBJECTIVE: The objective of this study is to estimate the incidence of weight gain in the first year post-renal transplant in addition to the assessment of potential risk factors and the resulting outcome of the graft.
METHODS: We conducted a single-center retrospective cohort study of all 295 patients who underwent kidney transplantation at King Abdulaziz Medical City (KAMC) between January 2016 and December 2019. Clinical and laboratory variables were collected from electronic records. Continuous variables were reported as mean ± standard deviation. Comparison between groups was assessed by unpaired t-test or Mann-Whitney U test while follow-up data were compared using paired t-test and repeated measures ANOVA. Association between the potential risk factors and the weight gain was assessed by means of binary logistic regression analysis.
RESULTS: Significant weight gain was observed in 161 (54.6%) patients. Females were 119 (40.30%) of the cohort. The mean age was 45.3±15.1 years. The prevalence of diabetes was 234 (79.6%), while hypertensives constituted 77 (26.3%). The comparison between patients who gained weight significantly and patients with stable weight showed a numerical higher prevalence of female gender in patients who had more weight gain (44.1% vs. 35.8%), higher diabetes, higher rate of a living donor, and statistically significant lower dialysis duration before transplant. Other clinical and laboratory variables were comparable between the two groups.
CONCLUSION: Our study showed a high incidence of clinically significant weight gain among patients post-renal transplantation. Patients with lower dialysis duration, a living kidney donor and those who are obese at baseline were at higher risk of gaining weight. Patients who underwent kidney transplantation should be monitored closely for weight gain and further studies are needed to determine the risk factors and appropriate interventions.

Introduction

Renal transplantation is the definitive treatment for patients with end-stage renal disease (ESRD). It is associated with better quality of life and patient survival when compared to other renal replacement modalities, such as hemodialysis and peritoneal dialysis [1-3]. Nevertheless, these benefits come with rising concerns about the increased risk of cardiovascular disease in renal transplant recipients due to the development or worsening of hypertension, dyslipidemia, post-transplant new-onset diabetes mellitus, and obesity [4-6].

Obesity is a frequent post-renal transplant complication. Approximately 50% of patients gain weight after renal transplantation, more prominently within the first year, regardless of their pre-transplant nutritional status [7, 8]. In the USA, the prevalence of obesity among kidney transplant recipients had increased to over 30% whereas almost 10% of them had morbid obesity in 2011 as compared to less than 20% in the 1990s [9, 10]. In one study, weight gain in the first year post renal transplantation varied between 6 and 10 kg, reciprocating a mean change in BMI of 2 and 3.8 kg/m2 respectively [11]. Another study, that reviewed the characterization of body composition and fat mass distribution one year after renal transplantation, revealed an increased body mass index, total body fat, and visceral fat [12].

Various studies have been done to investigate the risk factors that may contribute to an increase in weight post-renal transplantation. Female gender, lower pre-transplant weight, younger age, living donor transplant, use of corticosteroids, and poor physical activity have been identified as potential risk factors [13-17]. By the same token, increasing body weight post kidney transplant is associated with undesirable metabolic consequences such as post-transplant diabetes mellitus, and may lead to a higher graft-failure rate and higher mortality [18-20]. An analysis of the United States Renal Data System database showed a U-shaped relationship between patient/graft survival and both extreme weight loss or weight gain post kidney transplantation [21].

Due to the lack of studies evaluating the incidence, risk factors, and outcome of increased BMI post-renal transplantation in Saudi Arabia and the Gulf population, we aimed to study the incidence of weight gain in the first-year post-renal transplant in addition to the assessment of potential risk factors and the resulting outcome of the graft.

Patients and methods

We conducted a single-center retrospective cohort study of all 295 patients who underwent kidney transplantation at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia between January 2016 and December 2019. We exclude all patients who missed follow up during this period and patients who experienced a loss of graft function in the first year. BMI was calculated as weight in kilograms divided by the square of the height in meters (kg/m2). The study was reviewed and approved by the Institutional Ethics Review Board of King Abdullah International Medical Research Center (KAIMRC) with Memo Ref. No. IRB/1146/20.

Data were collected from the electronic recording system (BESTcare) used in KAMC. All recipients had a measurement of body weight and height during routine follow up at 1 month, 6 months, and one-year post-transplant in addition to their last BMI before renal transplant. Baseline characteristics including age, gender, comorbidities, past medical history, immunosuppressant medications, graft function and routine laboratory-based results were documented as well. Type of graft and whether the recipient had rejection or not were also collected from the electronic medical chart.

Patients were divided into two groups; patients who gained more weight defined by an increase BMI > = 2 kg/m2 in the first-year post-transplant, and patients with stable weight who did not meet the definition for the first group.

Data were analyzed using IBM SPSS statistics software (version 24.0) (SPSS Inc., Chicago, IL, USA). Continuous variables were reported as mean ± standard deviation. Comparison between groups was assessed by unpaired t-test or Mann-Whitney test while follow-up data were compared using paired t-test. We performed general linear model repeated measures ANOVA to check for within-group effects of the longitudinal change in creatinine, eGFR, BMI, FBS, HbA1c, systolic and diastolic blood pressure throughout study time points. Categorical variables were presented as numbers and percentages and analyzed using the Chi-square or Fisher’s exact tests as appropriate. All clinically relevant variables were tested to confirm a lack of multicollinearity among them, then we conducted backward elimination multivariable logistic regression to assess the potential risk factors and the weight gain after controlling for age and gender. All reported P values are two-sided, and P value less than 0.05 was considered statistically significant.

Result

Out of the 311 patients who underwent kidney transplantation between January 2016 and December 2019, 295 patients were evaluated and 16 patients were excluded due to age less than <18 years old (n = 9), or lost follow up post-transplant in our transplant center (n = 7). Weight gain was observed in 161 (54.6%) patients and weight remained stable in 134 (45.4%) patients during one year of follow up. The baseline characteristics of the patients are shown in (Table 1). Females were 119, constituting 40.30% of the cohort. The mean age was 45.3±15.1 years. The prevalence of diabetics was 234 (79.6%), hypertensive people constituted 77 (26.3%), and smokers were 24 (8.1%). Only 12 (4.1%) patients had undergone gastric sleeve surgery before kidney transplantation. The majority of renal transplant operations utilized grafts from living donors constituting 227 (76.9%). As for induction therapy, 185 (62.7%) of patients received anti-thymocyte globulin (ATG). All patients had the same immunosuppressive maintenance regimen including prednisolone 5 mg daily, tacrolimus and mycophenolate mofetil. The assessment of the functional status of our cohort using the Eastern Cooperative Oncology Group (ECOG) performance status score showed that 86.30% were fully active and able to carry on all pre-disease performance without restriction (ECOG 0) (Table 1).

Table 1

Baseline characteristics.

Characteristic	Total (n = 295) n (%)	Gained Weight (n = 161) n (%)	Stable Weight (n = 134) n (%)	P value
Age a	45.3±15.1	45.0±14.6	45.7±15.7	0.751
Gender b
Female	119 (40.30)	71 (44.10)	48 (35.80)	0.155
Male	176 (59.70)	90 (55.90)	86 (64.20)
Non-Smoker b	258 (87.50)	139 (86.30)	119 (88.80)
Ex-smoker	13 (4.40)	10 (6.20)	3 (2.20)	0.262
Smoker	24 (8.10)	12 (7.50)	12 (9.00)
DM b	77 (26.30)	44 (27.50)	33 (24.80)	0.689
HTN b	234 (79.60)	129 (80.10)	105 (78.90)	0.885
CAD b	39 (13.40)	19 (11.90)	20 (15.20)	0.490
Gastric sleeve surgery b	12 (4.10)	8 (5.00)	4 (3.00)	0.557
Duration of dialysis in years a	2.3±2.4	2.0±2.2	2.6±2.6	0.032
ECOG b
0	251 (86.30)	143 (89.90)	108 (81.80)
1	32 (11.00)	14 (8.80)	18 (13.60)	0.083
2	8 (2.70)	2 (1.30)	6 (4.50)
Donor b
Living	227 (76.90)	131 (81.40)	96 (71.60)	0.053
Deceased	68 (23.10)	30 (18.60)	38 (28.40)
Induction b
ATG	185 (62.70)	98 (60.90)	87 (64.90)	0.546
Basiliximab	110 (37.30)	63 (39.10)	47 (35.10)

a The P value was calculated by the unpaired t-test.

b The P value was calculated by the Fisher’s exact test.

The comparison between patients who gained weight significantly (i.e., BMI increased more than 2 kg/m2) and patients with stable weight showed that most variables were comparable except for the numerical higher prevalence of female gender in patients who had more than 2 kg/m2 BMI increment (44.1% vs. 35.8%), higher living donor, higher diabetes mellitus, and statistically significant lower dialysis duration before transplantation.

The longitudinal follow-up data of BMI and laboratory variables for one year are presented in (Table 2). The bassline BMI for the first group was lower than the second group, (25.5±5.1 vs. 26.7±5.2, respectively; p = 0.051). The weight gain difference started to become evident from the second half of the first year onward.

Table 2

Metabolic & laboratory variables.

Characteristic	Total	Gained Weight	Stable Weight	P value
BMI a
Pre	26.0±5.2	25.5±5.1	26.7±5.2	0.051
Post 1 month	26.0±5.2	26.0±5.3	26.0±5.2	0.989
Post 6 months	27.5±5.3	28.4±5.2	26.3±5.1	0.001
Post 12 months	28.6±5.6	30.7±5.5	26.7±5.2	<0.001
Creatinine umol/L a
1 week	111.5±65.1	105.3±55.3	118.8±74.7	0.077
1 month	102.3±36.8	98.0±34.2	107.3±39.2	0.031
6 months	97.9±33.1	92.8±29.0	103.9±36.6	0.004
12 months	93.5±29.7	90.7±26.5	96.9±33.0	0.073
eGFR ml/min a
1 week	73.6±27.9	76.1±28.6	70.6±26.9	0.089
1 month	73.9±22.5	76.5±22.8	70.8±21.73	0.031
6 months	75.8±21.1	78.4±20.7	72.7±21.2	0.020
12 months	79.5±20.6	80.4±20.2	78.4±21.1	0.402
Proteinuria * b N (%)
1 month	88 (29.80)	46 (28.60)	42 (31.30)	0.612
6 months	80 (27.10)	36 (22.40)	44 (32.80)	0.049
12 months	72 (24.40)	37 (23.00)	35 (26.10)	0.587
HbA1c b N (%)
<5.7%	189 (93.60)	100 (93.50)	89 (93.70%)	1
5.7%-6.9%	32 (71.10)	17 (70.80)	15 (71.40)	1
>6.9%	59 (81.90)	35 (83.30)	24 (80.00)	0.763
HbA1c (%) a
3 months	6.4±1.6	6.4±1.6	6.4±1.6	0.909
6 months	6.7±1.7	6.6±1.6	6.7±1.8	0.656
12 months	6.8±1.8	6.8±1.8	6.8±1.7	0.825
FBS (mmol/L) b N (%)
<5.5	165 (92.20)	85 (88.50)	80 (96.40)	0.091
5.5–7	48 (77.40)	25 (69.40)	23 (88.50)	0.123
>7	67 (82.70)	39 (78.00)	28 (90.30)
FBS (mmol/L)a
1 month	7.0±3.6	7.3±4.1	6.7±2.8	0.188
6 months	7.0±3.4	7.1±3.4	6.9±3.4	0.498
12 months	6.8±3.3	7.0±3.6	6.6±2.9	0.369
LDL (mmol/L) a
Pre	2.6±0.8	2.6±0.8	2.5±0.8	0.294
3 months	2.5±0.9	2.5±0.8	2.6±1.0	0.602
12 months	2.5±0.9	2.5±0.7	2.5±1.0	0.869

*Proteinuria = Urine albumin creatinine ratio (ACR) of 3 mg/mmol or more.

a The P value was calculated by the unpaired t-test.

b The P value was calculated by the Fisher’s exact test.

Creatinine, and similarly eGFR, was better in the first group after one week and significantly better after 1 and 6 months. When tested for the change across the four time points of the study using general linear model repeated measures ANOVA, no significant within group effects were detected in both groups, and no interaction between group and time as well. Other parameters such as FBS, HbA1c and LDL were comparable. Regarding blood pressure, analysis with repeated measures ANOVA for the readings at one, six, and twelve months showed no significant within group effects in both groups for systolic and diastolic BP over the study period (Figs 1 and 2).

Fig 1

Mean and 95% confidence interval of the systolic BP (mmHg) in the first year of the study in both groups (BMI < 2 vs. BMI > = 2).

Fig 2

Mean and 95% confidence interval of the diastolic BP (mmHg) in the first year of the study in both groups (BMI < 2 vs. BMI > = 2).

The list of complications that occurred in both groups is shown in (Table 3). There was no significant difference in the incidence of biopsy-proven allograft rejection or delayed graft function (DGF) which was defined as the requirement of dialysis in the first week post-transplant. Urological complications such as urine leak and wound infection were comparable as well, nevertheless, cytomegalovirus (CMV) viremia, as detected by screening PCR, was significantly lower in patients with higher weight gain, p = 0.007. Moreover, no significant differences were detected in new-onset diabetes after transplant (NODAT) and mortality rates.

Table 3

Complications.

Characteristic	Total n (%)	Gained Weight n (%)	Stable Weight n (%)	P value
Rejection a	29 (9.80)	18 (11.20)	11 (8.20)	0.437
DGF a	18 (6.10)	9 (5.60)	9 (6.80)	0.808
Wound infection a	6 (2.00)	4 (2.50)	2 (1.50)	0.693
Urine leak a	3 (1.00)	2 (1.20)	1 (0.80)	1
UTI a	79 (26.80)	41 (25.50)	38 (28.40)	0.599
NODAT a	14 (4.80)	7 (4.30)	7 (5.30)	0.787
CMV viremia a	158 (53.70)	75 (46.60)	83 (62.40)	0.007
BK viremia a	52 (17.70)	29 (18.00)	23 (17.30)	0.880
Arrhythmia a	7 (2.40)	2 (1.20)	5 (3.70)	0.251
ACS a	3 (1.00)	0 (0.00)	3 (2.20)	0.093
Mortality a	14 (4.70)	6 (3.70)	8 (6.00)	0.418
Started insulin a	8 (2.70)	5 (3.10)	3 (2.20)	0.732

a The P value was calculated by Fisher’s exact test.

We conducted multivariate backward selection logistic regression analysis to identify potential risk factors associated with weight gaining. The best-fit model is presented in Table 4. Only living donor [OR = 1.80; 95%CI (1.02 to 3.18); p = 0.043] and baseline BMI > = 30 [OR = 0.572; 95%CI (0.32 to 0.99); p = 0.048] were found significant predictors in our model.

Table 4

Multivariate analysis for risk factors.

Predictor	P value	Odds ratio	95% CI lower	95% CI upper
Age > 40	0.714	1.104	0.651	1.872
Female sex	0.080	1.559	0.948	2.563
Pre Transplant BMI > = 30	0.048	0.572	0.328	0.996
DM	0.432	1.266	0.703	2.281
Living donor	0.043	1.802	1.02	3.184

Discussion

This retrospective cohort study aimed to assess the incidence, risk factors, and outcomes of weight gain among patients who underwent renal transplantation in King Abdulaziz Medical City (KAMC) from January 2016 to December 2019 during the first year of follow up. The incidence of significant weight gain in the first year after renal transplantation was estimated as (54.6%) in our cohort. This is similar to other studies which showed a high incidence of weight gain post-renal transplantation.

In our study, we found a numerical higher prevalence of female gender (44.1% vs. 35.8%), higher living donor, and higher diabetic patients in kidney transplant recipients who had more than 2 kg/m2 BMI increment, but it was not statistically significant. On the other hand, statistically significant weight gain was only observed in patients with lower dialysis duration before transplant. This can be explained by the poor nutritional status of patients on prolonged dialysis periods as they need longer recovery time post-transplantation. A study in Poland reported that BMI was increased in almost 65% of kidney recipients, and the weight gain was higher in patients with normal BMI pre-transplantation compared to those classified as overweight or obese [22]. Additionally, our findings did not show that females were at higher risk to gain weight, unlike other reported studies that have estimated their risk to be up to two times higher than males [16, 23].

We examined related laboratory parameters at specific intervals from kidney transplant throughout the first year then compared the findings between the group who gained more weight and those with stable weight. Acknowledging the limitation of the small number of patients and length of the follow-up, we did not notice significant differences in those parameters. In contrast, Aminu et al. have reported that obese patients post-renal transplantation were more prone to graft dysfunction and progression of atherosclerosis, including higher mean arterial blood pressure, total cholesterol, triglycerides, left ventricular mass index, and higher carotid intima-media thickness [24]. This could be explained by the fact that the mean duration of follow-up in the Aminu et al. study was 60 ± 18.8 (range 36–89) months while it was 12 months in our study.

Our study has not shown any statistically significant differences in biopsy-proven allograft rejection, wound infection, UTI or urine leak between the two groups. Although prior study done in our center have shown that higher baseline BMI was associated with a higher risk of delayed graft function (DGF) [25], our results failed to show deterioration of graft function during the first year of follow up despite weight gain. However, another study showed a statistically significant increase in graft loss in patients with a 5% increase in BMI in the first-year post-transplantation [23]. Interestingly, we found that the frequency of CMV viremia was lower in patients who had more weight gain (p = 0.007), despite the fact that all our recipients were seropositive for CMV IgG, and they have been maintained on valganciclovir 450 mg daily dose for 3 months post-transplantation as per the standard protocol in our center. We could not find an explanation for this finding yet this is consistent with Cristina et al. findings, where patients who gained more than 5% of weight had a lower rate of CMV infection [23].

The data on the association between new-onset diabetes post kidney transplantation (NODAT) and weight gain are controversial. A meta-analysis study, done in 2018 to check the correlation between NODAT and increasing BMI post-transplant, showed that increased BMI is an independent risk of having NODAT [26]. Furthermore, a recent study, done in 2020, showed that post-transplant obesity was associated with a higher rate of type 2 DM and NODAT [27]. Nevertheless, another study showed that higher BMI patients are more likely to develop NODAT, yet patients with NODAT had lower weight gain post-transplant [28].

In contrast, our study has not shown any significant relationship between increasing BMI and developing NODAT (P = 0.787).

In our study, we did not include the effect of exercise, nutritional status and types of various diets. A previous randomized controlled trial implemented an intensive diet versus a standard diet in patients with renal transplantation to examine the impact on weight gain post-transplant. The study demonstrated no significant difference between the two groups. instead, the increase of the BMI in both groups was <5%, which was lower than other studies where the increase was equal to or more than10% [29]. This suggests that dietary and exercise measures are beneficial in avoiding excessive weight gain among kidney transplant patients.

Our study has several limitations; it is a retrospective study with a relatively short follow-up period for the detection of complications that may take years to develop. Additionally, we did not investigate all variables related to weight and metabolic outcomes such as body composition, exercise role, dietary habits, and family history of obesity. However, we have been able to show the high incidence of weight gain post kidney transplantation and identify some risk factors. A prospective study would be able to illustrate the risk factors of weight gain post-transplantation and guide the interventions to prevent it.

Conclusion

Our study showed a high incidence of weight gain among patients post-renal transplantation in the first year of follow-up. Patients with lower dialysis duration before transplant, receiving living donor graft and those who are obese at baseline were at higher risk of gaining weight. We have not been able to present evidence of the association between graft dysfunction during the period of follow up and weight gain. Overall, post kidney transplantation patients should be monitored closely for weight gain, and further studies are needed to determine the risk factors and appropriate interventions.

8 Nov 2021

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: https://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,

John Richard Lee, M.D.

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For more information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

3. Please include your full ethics statement in the ‘Methods’ section of your manuscript file. In your statement, please include the full name of the IRB or ethics committee who approved or waived your study, as well as whether or not you obtained informed written or verbal consent. If consent was waived for your study, please include this information in your statement as well.

4. Please include a separate caption for each figure in your manuscript.

Additional Editor Comments;

In addition to the reviewers’ comments, please consider the following:

1) It’s unclear to me that weight gain was observed in 235 patients and weight decreased in 57 patients but Table 1 shows gained weight (n=161) and stable weight (n=134).

2). How did the authors choose a BMI >2 as a cutoff? Do the authors have literature support this cutoff?

3) Table 1 should have legend explaining the test comparing the two groups (i.e. Fisher’s exact test and/or unpaired t-test). Also Table 2 and Table 3.

4) What were the maintenance immunosuppression in each group? This data should be included. Was the weight gain driven by prednisone? Are differences in other regimens?

5) Is the repeated measured analysis with contrasts? Can you please explain more detail in the methods how this was done since you are comparing groups at different time points?

6) How did you define proteinuria? Did you quantify the proteinuria with a Urine P/C ratio?

7) More detail is needed in Table 3: how did you define rejection, DGF, CMV, and BK? How long was the follow up for patients, was this all at 1 year?

8) In the multivariable logistic regression, how did you choose the variables that went into the multivariable analysis? Did you do a univariate analysis and those significant went into the multivariable analysis? How did you come to choose age > 40 rather than continuous variable?

9). The authors note mortalities? Did this occur in the first year? If so, how was the weight account for if the patient died before 1 year?

10) Figure 1 and Figure 2 need legends and should be separated

11) The manuscript would benefit from grammatically editing

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

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. 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: No

**********

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

Reviewer #1: I Don't Know

Reviewer #2: No

**********

3. 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

**********

4. 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

**********

5. 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: This is a single center retrospective cohort study of 295 kidney transplant recipients in Saudi Arabia whose objective is to estimate the prevalence of weight gain in the first-year post kidney transplantation, identify potential risk factors, and assess allograft outcomes. The authors observe weight gain in nearly 80% of patients, with patients with lower dialysis duration having significantly higher risk of weight gain. Graft outcomes were comparable in both the “stable weight” and “gained weight” groups. As noted by the authors, a limitation is the short follow up period for potential complications.

Overall, the authors’ findings will be beneficial to the field, adding to data regarding the prevalence and significance of weight gain post renal transplantation, particularly in a population from Saudi Arabia that has not been well studied. The manuscript is organized and written reasonably well. However, it requires careful review and proofreading of grammatical and typographical errors. My recommendations include the following:

1. The authors report that patients “had the same tacrolimus-based maintenance immunosuppression regimen”. It would be useful to clarify if patients are on steroid-free or steroid maintenance immunosuppression and report if there are differences in steroid use between the groups.

2. Abbreviations and acronyms such as CMV, BK, DM, FBS should be spelled out in full the first time they are used, and the standard abbreviation provided in parentheses.

3. In the Results section there is mention of 57 patients having decreased weight. Were these patients categorized under the “stable weight” group?

4. In Table 1, please report units of measurement for “Duration of dialysis” (e.g. months or years).

5. In Figures 1 and 2, please report units of measurement for blood pressure. In Figure 2, please label the two groups appropriately by adding “BMI” to “<2” and “>=2”.

6. In Table 2, please clarify criteria for “proteinuria”.

7. In Table 2, “FBS” is reported as mg/dL, however the values provided appear to be consistent with mmol/L.

8. In Table 3, please define “BK”. For instance, is this referring to BKV nephropathy, BKV viremia or BKV viruria?

9. The authors report CMV infection was significantly less common in the group that gained more weight, and they could not find an explanation for this finding. However, they do not discuss any further analysis that may have been done. It may be useful to explore variables such as CMV serostatus of the donor/recipient pair, CMV prophylaxis regimen, and donor type (there was a trend toward more deceased donors in the "stable weight" group).

10. There are numerous typographical and grammatical errors throughout the manuscript. Recommend a meticulous review and proofreading of the manuscript.

Thank you for the opportunity to review this manuscript.

Reviewer #2: 1. In methods, clarify "Comparison between groups was assessed by unpaired t-test or Mann-Whitney test while

follow-up data were compared using paired t-test and repeated measures ANOVA". what does groups and follow up data refer to? Also, express age as median and interquartile range since it is a skewed distribution.

2. The induction therapy in about 60% was ATG, what was the regimen in the remaining? What is the tacrolimus based regimen- does it include steroids? Need to clarify the immunosuppresive regimen

3. Many descriptions used in the table is ambiguous- what does "bariatric" refer to? What is the unit used to express duration of dialysis. What does DM, HTN and CAD stand for. Similarly table 2 also needed to be revised to correct for incomplete descriptions and units. What was the definition of CMV infection used for the manuscript?

4. Many abbreviations are used throughout the manuscript without mentioning their expansion in the manuscript.

5. Since the authors have not rigorously studied if the outcomes were directly related only to the weight gained post transplant and it is a retrospective study, it is not appropriate to use the term "outcomes" in the title and conclusion

6. Since the authors looked at weight gain post transplantation, it is looking at incidence rather than prevalence of weight gain

7. The manuscript needs to rigorously reviewed again for several grammatical errors and poor sentence construction

**********

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: No

[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.

6 Jan 2022

1. All patients had the same tacrolimus-based maintenance immunosuppression regimen which include Prednisolone 5 mg daily, Tacrolimus and mycophenolate.

2. Abbreviations added to revised manuscript.

3. corrected in revised manuscript.

4. Duration of dialysis counted by years. clarified in revised manuscript.

5. units of measurement for blood pressure. done

6. definition of proteinuria added to revised manuscript.

7. FBS” is reported as mg/dL, corrected with mmol/L.

8. define “BK”= means BK viremia .

9. CMV infection : CMV serostatus and prophylaxis regimen has been added to revised manuscript.

detail answer added to respond to reviewer.

Submitted filename: Response to Reviewers..docx

Click here for additional data file.

17 Feb 2022

7 Apr 2022

Hi

thank you for reviewing my manuscript.

correction has been made .

thank you

Submitted filename: Responses to reviewers.docx

Click here for additional data file.

21 Apr 2022

Weight Gain After Renal Transplant: incidence, Risk Factors, and Outcomes

PONE-D-21-31746R2

Dear Dr. Altheaby,

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,

John Richard Lee, M.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

23 May 2022

PONE-D-21-31746R2

Weight Gain After Renal Transplant: Incidence, Risk Factors, and Outcomes

Dear Dr. Altheaby:

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. John Richard Lee

Academic Editor

PLOS ONE