Effect of Dietary Phosphorous Restriction on Fibroblast Growth 2 Factor-23 and sKlotho Levels in Patients with Stages 1–2 Chronic Kidney Disease

Round 1

Reviewer 1 Report

1. Why authors did not use a standardized CKD-EPI equation according to KDIGO recommendations? - please add explanation in the paper. Nevertheless, in line 82, please add which MDRD formula was used (short, long)? 

2. Please provide what method to creatinine measurements was used?

3. Was the sample size calculated, as there is a great concern abot the power of the tests used in the paper. If no, please provide post-hoc power analysis.

4. What was the rationale to divide groups according to phosphorus intake < and >=1000 mg/day?

5. Why authors did not check the distributions of data?. There is a great concenr about missleading statistical analysis due to skeweness of data (such as f.e.: iPTH, urinary phosphorus, sKlotho). Values with skewed distribution should be presented with median and lower/upper quartiles.

6. Line 145 - p should be lowercase.

7. Please round age without decimals.

8. Significant p-values should be presented as p < 0.05, < 0.01 and < 0.001 in the whole paper.

9. In my opinion all analysis should be done taking sex into account.

10. Table 4 should be replaced by the multivariable linear or non-parametric regression.

11. Regarding the data decimals should be set appropriate to the measurement significance as f.e. Table 6 is hard to see.

 

Author Response

Reviewer 1  Queries 1- 11    Thank you for your queries  and suggestions. Reply to the queries is given below: 

1. Why authors did not use a standardized CKD-EPI equation according to KDIGO recommendations? - please add explanation in the paper. Nevertheless, in line 82, please add which MDRD formula was used (short, long)? 

Reply: Thank you for your comment. Short MDRD formula was used in place of CKD-EPI equation as the MDRD formula was recommended by experts in the research/doctoral committee hence we had to comply by the recommendations. Every project goes through scrutiny before it is submitted to the ethics committee and reviewed annually. The internal and external experts were nephrologists, immunologists.

2. Please provide what method to creatinine measurements was used?

Reply: Jafee’s method was used for creatinine measurements.

 

3. Was the sample size calculated, as there is a great concern about the power of the tests used in the paper. If no, please provide post-hoc power analysis.

Reply: Sample size was calculated for the project. However, because of word limit, the details on sample size calculation etc were withheld.

To find the association of FGF-23, Klotho, PTH levels with dietary phosphorus in CKD Stages 1 and 2 sample sizes was calculated in consultation with a bio-statistician. According to the null hypothesis, when r =0, there is no correlation. A negative correlation will be at r= 0.5 and positive >0.5 at a power of 90%.  Accordingly, for this study, a minimum sample of 37 was sufficient to ascertain the association.

Hence, a total of 187 study subjects were enrolled from May 2016-December 2018 for the study out of which 81 were taken as controls and 83 as CKD patients who gave their consent for participating in the study. Out of 81 healthy controls. After drop outs a total of 79 CKD

Note: This project was reviewed by research/doctoral committee which ensures all the salient features like sample size, methodology etc which determine the quality of the work are fulfilled before submitting the project to the Ethics committee

4. What was the rationale to divide groups according to phosphorus intake < and >=1000 mg/day?

Reply: The rationale to divide groups according to phosphorus intake <1000 and >=1000 mg/day was based on  an average healthy Indian’s protein intake which is 0.6-0.7g/kg/d (equal to approximately 700-800 mg/d of phosphorus intake daily). Hence, the groups were divided based on KDOQI guidelines for  phosphorus intake  in CKD, which is 800-1000 mg/d (although in CKD stages 1 or 2, neither phosphorus restriction nor use of phosphate binders is recommended). (Reference: Salomo L, Kamper AL, Poulsen GM, Poulsen SK, Astrup A, Rix M. Habitual dietary phosphorus intake and urinary excretion in chronic kidney disease patients: a 3-day observational study. Eur J Clin Nutr. 2017;71(6):798-800.)

5. Why authors did not check the distributions of data?. There is a great concenr about missleading statistical analysis due to skeweness of data (such as f.e.: iPTH, urinary phosphorus, sKlotho). Values with skewed distribution should be presented with median and lower/upper quartiles.

Reply : Thank you for your suggestion.

 Normality of data was examined by Shapiro Wilk test. Results were presented as Mean ± SD for normally distributed while Median (IQR) for skewed data and Categorical as n (%). This project was reviewed by research/doctoral committee which ensures all the salient features like sample size, methodology etc which determine the quality of the work are fulfilled before submitting the project to the Ethics committee

6. Line 145 - p should be lowercase.

Reply: Thank you for your suggestion.  “P” changed to  lowercase “p”

7. Please round age without decimals.

    Reply: Thank you for your suggestion.  Rounded up age without decimals.  Mean 38.00±12.06      Male  41.00±9.22      Female  35.00±13.91

9. In my opinion all analysis should be done taking sex into account.

Reply: Analyzed data sex wise. Tables are given below:

Table 1b. Clinical characteristics of CKD patients (n=79).

			Male(n=42)		Female(n=37)
Diet type- Veg	46		23 (29.11%)		23 (29.11%)
non-veg	33		19 (24.05%)		14 (17.72%)
Diabetes, number (%)	26 (32.9%)		13 (16.4%)		13 (16.4%)
Dyslipidemia	15 (18.9%)		6 (7.59%)		9 (11.39%)
Hypertensive		23 (29.1%)		12 (15.18%)		11 (13.92%)
Family history with CKD	37 (46.8%)		18 (22.78 %)		19 (24.05%)
Mean age, years	38.27±12.06		41.42±9.22		34.70±13.91
Glomerular filtration rate, ml/min/1.73m2	83.69±17.37		85.10±17.95		82.08±16.78
Renal diagnosis
Diabetic kidney disease	18 (22.7%)		10 (12.65%)		8 (10.12%)
Polycystic kidney disease	14 (17.7%)		6 (7.59%)		8 (10.12%)
Other renal diseases	16 (20.2 %)		9 (11.39%)		7 (8.86%)
Unknown	31 (39.2 %)		17 (21.51%)		14 (17.72%)
Medications
Anti-hypertensive drug(s)	23 (29.1%)		12 (15.18%)		11 (13.92%)
Statins	16 (20.2 %)		7 (8.86%)		9 (11.39%)
Insulin or oral hypoglycaemic agent	26 (32.9%)		13 (16.4%)		13 (16.4%)

Values are presented in Mean±SD/n (%).CKD: Chronic Kidney Disease.

 

 

Table 3b. Demographic and baseline biochemical data of the CKD patients based on gender.

 

	Male(n=42)	Female(n=42)	p value
GFR	85.8(67.6-99.7)	90.1(64-93.7)	0.415
Serum creatinine (mg/dL)	1(0.9-1.2)	0.8(0.7-1.1)	<0.001
Serum phosphorous(mg/dL)	3.7(3.2-4.1)	3.5(2.8-3.8)	0.374
iPTH (pg/mL)	51.5(43.3-60.1)	51.8(44.7-60.2)	0.655
FGF-23 (pg/mL)	57.3(53.6-61.6)	55.2(52.2-59.1)	0.196
sKlotho(pg/mL)	702.8(648.7-811.7)	703.6(673.9-840.7)	0.482
Urinary phosphorous(mg/day)*	661(476.6-798.6)	638.9(403.4-804.3)	0.448
Urinary protein (mg/mL)#	20.5(18.3-22.5)	19.4(15.8-22.5)	0.124
Serum calcium(mg/dL)	8.9(8.6-9.1)	9(8.3-9.3)	0.555
Vitamin D (ng/mL)	28.1(19.8-32.4)	27.4(18.7-30.8)	0.613
Energy intake (kcal /kg/day)	10.2(7.8-14.6)	11(7.4-14.5)	0.804
Dietary Protein intake (gm/ day)	43.7(38.7-52.1)	40.3(36.6-47.9)	0.054
Dietary phosphorous (mg/day)	1161.7(883.5-1376.1)	1140.9(867.6-1238.9)	0.455
Phosphorous to protein ratio	24.6(22.8-26.2)	25.1(22.8-27.2)	0.356

p value was calculated by Mann Whiney U test

 

Table 3b indicates that the Serum Creatinine was statistically higher among male as compared to female (p<0.001).

 

Table 4b. Correlation of biochemical parameters with dietary phosphorous and phosphorous protein ratio in CKD patients among Male and Female.

Parameters(unit)	‘r’ value, p-value
	Male (n=42)		Female (n=37)
	Dietary Phosphorous	P-P Ratio	Dietary Phosphorous	P-P Ratio
GFR (ml/min/1.73m2)	-0.239,0.128	0.886,<0.001	0.006,0.971	0.653,<0.001
Serum phosphorous(mg/dL)	0.704,<0.001	-0.099,0.534	0.425,0.009	0.19,0.259
iPTH (pg/mL)	0.353,0.022	0.577,<0.001	0.283,0.09	0.204,0.227
FGF-23 (pg/mL)	0.6,<0.001	0.246,0.117	0.388,0.018	0.114,0.503
sKlotho(pg/mL)	-0.639,<0.001	0.537,<0.001	-0.623,<0.001	0.092,0.589
Urinary phosphorous(mg/day)*	0.168,0.342	-0.515,<0.001	-0.159,0.409	-0.287,0.085
Urinary protein (mg/mL)#	0.602,<0.001	0.162,0.359	0.439,0.022	-0.12,0.536
Serum calcium(mg/dL)	-0.023,0.884	0.574,0.001	-0.131,0.438	0.119,0.554
Vitamin D (ng/mL)	0.226,0.15	0.077,0.63	0.159,0.348	-0.057,0.737
Dietary Protein intake (gm/ day)	0.901,<0.001	0.164,0.3	0.616,<0.001	0.044,0.794
Phosphorous to protein ratio	0.886,<0.001	-	0.653,<0.001	-

 

Table 5b. Multivariate logistic regression to identify the risk factors for CKD progression

Parameters	Adj. Odds Ratio (AOR)	95% Confidence Interval(CI)	p-value
Diet type (veg/non-veg)	2.146	1.04-4.43	0.039
Hypertension	0.137	0.038-0.493	0.002

 

Table 6b. Comparison of biochemical parameters before and after dietary counselling and dietary intervention based on  gender

Parameters(unit)	Groups	Baseline	At 6 months	At 12 months	p-value
GFR (ml/min/1.73m2)	Male	85.8(67.6-99.7)	94.47(69.9-100.2)	91.04(74.24-106.67)	0.004
	Female	90.1(64-93.7)	83.28(69.67-94.46)	80.99(68.8-95.75)	0.342
Serum creatinine (mg/dL)	Male	1(0.9-1.2)	0.98(0.87-1.25)	0.96(0.84-1.2)	0.004
	Female	0.8(0.7-1.1)	0.85(0.73-1.02)	0.85(0.71-1)	0.15
Serum phosphorous(mg/dL)	Male	3.7(3.2-4.1)	3.32(2.78-3.97)	3.31(2.87-4)	0.171
	Female	3.5(2.8-3.8)	3.26(2.62-3.7)	3.14(2.72-3.72)	0.089
iPTH (pg/mL)	Male	51.5(43.3-60.1)	55.03(48.31-61)	51.02(43.76-62.32)	0.003
	Female	51.8(44.7-60.2)	55.05(48.21-63.9)	52.42(47.03-61.87)	0.005
FGF-23 (pg/mL)	Male	57.3(53.6-61.6)	56.22(51.81-58.84)	52.49(46.98-60.43)	0.072
	Female	55.2(52.2-59.1)	56.15(51.44-61.62)	55.53(49.33-59.1)	0.009
sKlotho(pg/mL)	Male	702.8(648.7-811.7)	802.4(734.73-914.98)	819.22(682.73-1024.1)	<0.001
	Female	703.6(673.9-840.7)	893(751.91-983.19)	853.85(762.54-1020.45)	<0.001
Urinary phosphorous(mg/day)	Male	661(476.6-798.6)	597.1(464.73-714.24)	692.37(534.29-791.48)	0.136
	Female	638.9(403.4-804.3)	585.5(357.39-725.81)	699.7(568.21-789.45)	0.071
Urinary protein (mg/mL)	Male	20.5(18.3-22.5)	21.06(18.42-25.56)	18.95(16.91-22.19)	0.003
	Female	19.4(15.8-22.5)	19.63(16.45-22)	18.58(15.82-22.18)	0.835
Serum calcium (mg/dL)	Male	8.9(8.6-9.1)	9.09(7.02-10.18)	8.5(7.95-10.3)	0.645
	Female	9(8.3-9.3)	8.95(8.04-9.44)	8.8(7.3-9.76)	0.795
Vitamin D (ng/mL)	Male	28.1(19.8-32.4)	26.3(19.43-30.98)	26.32(21.88-30.12)	0.518
	Female	27.4(18.7-30.8)	26.6(23.7-32.4)	27.4(24.38-33.09)	0.819
Dietary Protein intake	Male	43.7(38.7-52.1)	40.89(38.43-46.1)	41.21(38.44-45.32)	0.001
	Female	40.3(36.6-47.9)	39.31(34.75-43.41)	38.4(35.08-43.1)	0.002
Dietary phosphorous intake (mg/day)	Male	1161.7(883.5-1376.1)	1027.56(905.01-1194.04)	957(887.69-1095)	0.03
	Female	1140.9(867.6-1238.9)	967.35(824.56-1148.85)	871.73(842-1003)	<0.001

p value was calculated by Friedman test

 

 

10. Table 4 should be replaced by the multivariable linear or non-parametric regression.

Reply: Since reviewer 2 has not made any suggestions to this effect, the authors have added Multivariate logistic regression to identify the risk factors for CKD progression as Table 5b

Table 5b. Multivariate logistic regression to identify the risk factors for CKD progression

Parameters	Adj. Odds Ratio (AOR)	95% Confidence Interval(CI)	p-value
Diet type (veg/non-veg)	2.146	1.04-4.43	0.039
Hypertension	0.137	0.038-0.493	0.002

 

11. 11. Regarding the data decimals should be set appropriate to the measurement significance as f.e. Table 6 is hard to see.

Reply: Apoplogies for the inconvenience caused as the formatting of the table is totally lost. I am attaching Table 6 as a separate file as the formatting is getting lost in the manuscript.

Parameters(unit)

Groups

n

Baseline

At 6 months

At 12 months

p-value

GFR (ml/min/1.73m2)

HPhI

39

80.93±15.34

84.11±15.38

87.43±18.27

0.012

RPhI

34

85.19±17.98

86.76±18.96

87.45±21.01

0.304

Serum phosphorous(mg/dL)

HPhI

39

3.95±0.50

3.36±0.78

3.36±0.78

0.000

RPhI

34

3.15±0.57

3.25±0.61

3.32±0.64

0.177

iPTH (pg/mL)

HPhI

39

54.74±10.41

57.54±10.35

54.97±11.42

0.097

RPhI

34

48.68±8.71

52.09±7.67

50.69±10.23

0.055

Serum creatinine (mg/dL)

HPhI

39

1.00±0.21

0.96±0.18

0.94±0.22

0.102

RPhI

34

0.96±0.21

0.95±0.22

0.95±0.24

0.307

FGF-23 (pg/mL) Normal range: 8.2 to 54.3 pg/mL

HPhI

31

60.67±6.26

58.00±7.07

53.29±9.48

0.000

RPhI

30

53.70±3.98

54.54±6.84

53.07±8.59

0.428

sKlotho(pg/mL) Normal range: 239 to 1266 pg/mL

HPhI

30

656.54±51.26

815.35±109.96

855.42±163.29

0.000

RPhI

26

800.58±75.21

881.43±169.18

891.37±233.58

0.022

Urinary phosphorous(mg/day)

HPhI

24

574.37±214.22

541.32±218.35

624.64±137.67

0.052

RPhI

20

649.02±185.07

638.16±153.54

724.37±128.15

0.071

Urinary protein (mg/mL)

HPhI

25

22.57±3.09

23.61±3.98

22.01±3.39

0.071

RPhI

20

16.79±2.95

17.76±2.91

16.42±2.56

0.202

Serum calcium (mg/dL)

HPhI

37

8.69±0.93

8.49±1.46

8.68±1.75

0.663

RPhI

33

8.93±0.53

9.17±1.06

9.07±1.47

0.518

Vitamin D (ng/mL)

HPhI

39

27.02±8.55

24.75±8.23

26.24±7.74

0.394

RPhI

28

26.91±8.04

28.65±8.07

28.05±6.17

0.295

RPHI

878.86±54.18

888.55±89.58

914.60±127.06

0.177

Dietary Protein intake  (gm/ day)

HPhI

39

49.26±5.45

43.55±5.89

42.47±6.65

0.000

RPHI

878.86±54.18

888.55±89.58

914.60±127.06

0.177

RPhI

34

37.87±2.76

37.54±4.25

38.54±4.89

0.319

RPHI

878.86±54.18

888.55±89.58

914.60±127.06

0.177

Dietary phosphorous intake (mg/day)

HPhI

39

1322.09±132.66

1157.00±156.25

1040.86±191.36

0.000

RPHI

878.86±54.18

888.55±89.58

914.60±127.06

0.177

RPhI

34

871.88±59.98

879.32±82.76

905.23±116.62

0.156

RPHI

878.86±54.18

888.55±89.58

914.60±127.06

0.177

Phosphorous to protein ratio

HPhI

39

27.16±4.35

26.94±4.86

24.75±4.34

0.000

1317.51±137.20

1229.29±151.87

1137.48±172.15

0.00

RPhI

34

23.11±2.11

23.74±3.61

23.84±4.18

0.379

RPHI

 

 

 

 

 

 

 

Author Response File: Author Response.docx

Reviewer 2 Report

Hyperphosphatemia has emerged as an independent risk factor for cardiovascular disease (CVD) and excess mortality in chronic kidney disease (CKD). Using a one-year interventional study conducted on a 79 stage 1 and 2 CKD patients, Anita et. al found that dietary phosphorous restriction (<1g/d)  improves renal function and attenuates hyperphosphatemia. 

Major concerns

1.  Dietary protein is known to affect CKD. However, patients in DPHI 

 and RPI groups have varied protein intake (Table 3). As such, how they can state that the improvement of renal function and hyperphosphatemia is due to phosphorous restriction.

2. It would be nice showing the reason for the sample size and also showing the data with Mean±SEM.

3. Dietary Protein intake (gm/ day) is assumed to be Dietary Protein intake (g/ day)?

4. In addition to high phosphorous load, are these any other dietary components (either nutrients or non-nutrients like phytochemicals) that can affect FGF-23 levels? This is important because  patients  between DPHI  and RPI groups have many differences in respects of dietary foods.

5. Table 6 should be shown in one page.

6. How about the title "Effect of dietary phosphorous restriction on fibroblast growth 2 factor-23 and sKlotho levels in patients with stage 1-2 chronic kidney disease.

 

 

Author Response

Reviewer 2  Thank you for your queries and comments and suggestions.

Reply to Queries 1-6 is given below:

Major concerns

1. Dietary protein is known to affect CKD. However, patients in DPHI and RPI groups have varied protein intake (Table 3). As such, how they can state that the improvement of renal function and hyperphosphatemia is due to phosphorous restriction.

Reply Table 3a.is h=showing the  baseline biochemical data of the CKD patients based on their dietary phosphorous intake (mg/day). The infererence is based on table

Tab Table 6a.Comparison of biochemical parameters before and after dietary counselling and dietary intervention.

Parameters(unit)	Groups	n	Baseline	At 6 months	At 12 months	p-value
Serum phosphorous(mg/dL)	HPHI	39	3.95±0.50	3.36±0.78	3.36±0.78	0.001
	RPI	34	3.15±0.57	3.25±0.61	3.32±0.64	0.177
GFR (ml/min/1.73m2)	HPHI	39	80.93±15.34	84.11±15.38	87.43±18.27	0.012
	RPI	34	85.19±17.98	86.76±18.96	87.45±21.01	0.304

 

2. It would be nice showing the reason for the sample size and also showing the data with Mean±SEM.

 Reply: Sample size was calculated for the project. However, because of word limit, the details on sample size calculation etc were withheld.

To find the association of FGF-23, Klotho, PTH levels with dietary phosphorus in CKD Stages 1 and 2 sample sizes was calculated in consultation with a bio-statistician. According to the null hypothesis, when r =0, there is no correlation. A negative correlation will be at r= 0.5 and positive >0.5 at a power of 90%.  Accordingly, for this study, a minimum sample of 37 was sufficient to ascertain the association.

Hence, a total of 187 study subjects were enrolled from May 2016-December 2018 for the study out of which 81 were taken as controls and 83 as CKD patients who gave their consent for participating in the study. Out of 81 healthy controls. After drop outs a total of 79 CKD

We have represented data as Mean+/- SD as it describes the dispersion of data points about mean which helps in under standing the distribution of data whereas Mean+/- SEM describes the sampling distribution of sample mean. 

Note: This project was reviewed by research/doctoral committee which ensures all the salient features like sample size, methodology etc which determine the quality of the work are fulfilled before submitting the project to the Ethics committee

 

2. Dietary Protein intake (gm/ day) is assumed to be Dietary Protein intake (g/ day)?

Reply: Thank you for your suggestion Protein intake is g/ day and it has been corrected in the manuscript.

3. In addition to high phosphorous load, are these any other dietary components (either nutrients or non-nutrients like phytochemicals) that can affect FGF-23 levels? This is important because  patients  between DPHI  and RPI groups have many differences in respects of dietary foods.

Reply: Thank you for your suggestion.  Yes, phyotochemicals and antioxidants do have a bearing on phosphate metabolism, but this aspect was not examined. This statement has been included in methodology.

4. Table 6 should be shown in one page.

Reply: Thank you for your comment. Table 6 is losing formatting therefore table 6 is attched as a separate file.

6. How about the title "Effect of dietary phosphorous restriction on fibroblast growth 2 factor-23 and sKlotho levels in patients with stage 1-2 chronic kidney disease.

Reply: I respect the experience of the reviewer and his/her suggestion to improve the title.. If the   reviewer has suggested the title” "Effect of dietary phosphorous restriction on fibroblast growth 2 factor-23 and sKlotho levels in patients with stage 1-2 chronic kidney disease.” I would not mind improvising the title to "Effect of dietary phosphorous restriction on fibroblast growth 2 factor-23 and sKlotho levels in patients with stage 1-2 chronic kidney disease. as suggested by the reviewer 2.

 

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

1. Please provide the sample size calculation, otherwise the power of the significant results.

2. Tables - please change the number of decimal places accordingly to its measurements (it is wrong to show age 38.00 with sd = 12.06, should be rounded to whole numbers, GFR rounded to 1 decimal place, and so on).

3. Table 1 - please provide % of male/female and diet type. For DM male lack of %).

4. Tables - there should be spaces between +- sign and numbers as well as between numbers and parenthesis.

5. Table 1, lack of info below table about mean/sd/median/quartiles.

6. Table 2, lack of info below table about median/quartiles. It should be started with upper case S.

7. Table 4a/4b should be removed and proper multivariable analyses should be done. Based on this conclusions should be made.

8. Instead multivariate use multivariable.

9. Table 6a - change significant p-values accordingly to its presentation in the text.

 

Author Response

All the queries raised have been answered and incorporated in the manuscript.

1. Please provide the sample size calculation, otherwise the power of the significant results.

Sample size: To find association  of FGF-23, Klotho, PTH levels with dietary Phosphorus  in Chronic Kidney Disease Stages 1 and 2 sample size was calculated in consultation with Head department of Biostatistics SGPGIMS. . According to null hypothesis, when r =0, there is no correlation. Negative Correlation will be at r= 0.5 and positive >0.5 at power of 90% .  Accordingly a minimum sample of  73 and not 37 (apologies for typing error which was overlooked over and over again despite being reminded) would suffice to ascertain  the association.

z tests - Correlations: Two independent Pearson r's Analysis:

A priori: Compute required sample size Input: Tail(s) = Two

Effect size q = -0.5493061

α err prob = 0.05

Power (1-β err prob) = 0.90

Allocation ratio N2/N1 = 1

Output: Critical z = -1.9599640

 Sample size group 1 = 73

Sample size group 2 = 73

Total sample size = 146

 Actual power = 0.9014357

 

Please Note :total sample size both intervention and control were 73 each. However  in this manuscript  only CKD   patients  (n 79 ) have been included. The calculations are given here but not included in the manuscript. The sample size has been corrected.                                                                          

 

 

2. Tables - please change the number of decimal places accordingly to its measurements (it is wrong to show age 38.00 with sd = 12.06, should be rounded to whole numbers, GFR rounded to 1 decimal place, and so on).

Reply Thankyou for  your comment. WE have done the  needful

Diet type- Veg Male Female non-veg Male Female	46 23 (50%)*23 (50%)* 33 19(57.6%)* 14(42.4%)*
Mean age, years Male Female	38.±12.† 41.±9.† 35.±13†

 

 

3. Table 1 - please provide % of male/female and diet type. For DM male lack of %).

Diabetes, number (%) Male

26 (32.9%)* 13 (16.4%)*

Please Note: a lot of information was lost in the Tables because of changes in the formatting

4. Tables - there should be spaces between +- sign and numbers as well as between numbers and parenthesis.

Reply Thankyou for  your comment. WE have done the  needful

5. Table 1, lack of info below table about mean/sd/median/quartiles.

Reply Thankyou for  your comment. WE have done the  needful for all the Tables

Table 2 *n=63#n=59FGF-23: Fibroblast Growth Factor-23; iPTH: Intact Parathyroid Hormone Values are presented in ^$Mean ±  SD and  ^†Median (Q1 – Q3)

Table 3 a *n=29 (RPI) and n=34 (HPhI)# n=28 (RPI) and n=31 (HPhI)FGF-23: Fibroblast Growth Factor-23; iPTH: Intact Parathyroid Hormone; GFR: Glomerular Filtration RateValues are presented in Mean .± SD and Median (Q1 – Q3).

^@ p value was calculated using independent sample t-test; ^$ p value was calculated by Mann Whiney U test;†p-value calculated by chi-square test

Table 3 b Data is represented as Median (Q1 – Q3)

p value was calculated by Mann Whiney U test

Table 3b indicates that the serum creatinine was statistically higher among male as compared to female (p<0.001).

 

Table 4a Univariable logistic regression analysis showed diet type, family history and hypertension as risk factors for CKD progression in  CKD (Table 4a).

Multivariable logistic regression analysis was performed to find out the risk factors for CKD progression based on phosphorus intake of CKD patients. Risk factors which had a statistical bearing on the progression of CKD were, hypertension (AOR= 0.082, p value=0.002) and family history of CKD (AOR = 2.895, p value = 0.047).

 

Table 5 Comparison of biochemical parameters before and after dietary counselling and dietary intervention.  (On deleting previous Table 4 Table 5 is now table 4 and Table 6 is now Table 5)

Table 1 b Values are presented in Mean±SD/n (%).CKD: Chronic Kidney Disease

Table 1 a Values are presented in Mean ± SD/n (%).CKD: Chronic Kidney Disease

6. Table 2, lack of info below table about median/quartiles. It should be started with upper case S.

Reply Thankyou for  your comment. We have done the  needful

 *n=63#n=59FGF-23: Fibroblast Growth Factor-23; iPTH: Intact Parathyroid Hormone Values are presented in ^$Mean ±  SD and  ^†Median (Q1 – Q3)

 

7. Table 4a/4b should be removed and proper multivariable analyses should be done. Based on this conclusions should be made.

Reply  Thankyou for  your comment.  Table 4a nd 4b have been deleted

The findings of the study emphasize that in CKD patients, on  predominantly animal-based diets, there is a  need for cautious dietary phosphorus intake  from early stages of CKD as the univariable analysis  has shown dietary phosphorus as  a risk factor for CKD progression. However in multivariable analysis the  dietary phosphoorus consumption did not appear as a risk factor for CKD progression , rather only family history of CKD and hyperrension were  risk factor for CKD

Tables 5 a and b are Tables 4 a and b

Table 4a Univariable logistic regression analysis showed diet type, family history and hypertension as risk factors for CKD progression in  CKD (Table 4a).

Multivariable logistic regression analysis was performed to find out the risk factors for CKD progression based on phosphorus intake of CKD patients. Risk factors which had a statistical bearing on the progression of CKD were,hypertension (AOR= 0.082, p value=0.002) and family history of CKD (AOR = 2.895, p value = 0.047).

 

Discussion:  Most of our CKD patients who were non-vegetarian; were in the higherHPhI group, this being responsible for their high phosphorus intake. The findings of the study emphasize that in CKD patients, on  predominantly animal-based diets, there is a  need for cautious dietary phosphorus intake  from early stages of CKD as the univariable analysis  has shown dietary phosphorus as  a risk factor for CKD progression. However in multivariable analysis the  dietary phosphoorus consumption did not appear as a risk factor for CKD progression , rather only family history of CKD and hyperrension were  risk factor for CKD progression.While taking the dietary recall, the renal dietician should educate  and counsel CKD patient on the sources of phosphorus, and type of diet the patient should prefer. Also, the importance of low phosphorus–to-protein-ratio diet should be emphasized in dietary counselling and educating patients with CKD.²⁷

 

 

8. Instead multivariate use multivariable.

Reply  Thankyou for  your comment. We have used the term  “multivariable.”

 

9. Table 6a - change significant p-values accordingly to its presentation in the text.

Reply  Thankyou for  your comment.. Previous Table 6ais table 5a now. We have done the needful. Please Note: Table 5a is being sent to as a separate file as the in the manuscript the formatting is getting lost (is not maintained)

 

 

 

 

 

 

 

 

 

 

 

 

 

Author Response File: Author Response.pdf