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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2018  |  Volume : 29  |  Issue : 2  |  Page : 318-325
Impact of body mass index on progression of primary immunoglobulin a nephropathy


1 Department of Nephrology, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
2 Department of Nephrology, Guntur City Hospital, Guntur, Andhra Pradesh, India
3 Department of Nephrology, Madras Mission Hospital, Chennai, Tamil Nadu, India
4 Department of Nephrology, Mahatma Gandhi Hospital, Narasaraopet, Andhra Pradesh, India
5 Department of Pharmacy Practice, NGSM Institute of Pharmaceutical Sciences, Nitte University, Mangalore, Karnataka, India
6 Department of Statistics, Prasanna School of Public Health, Manipal University, Manipal, Karnataka, India
7 Department of Pathology, Kasturba Medical College, Manipal University, Manipal, Karnataka, India

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Date of Web Publication10-Apr-2018
 

   Abstract 

The role of obesity in the progression of primary glomerular diseases is controversial. A few studies report overweight/obesity as a risk factor for disease progression in immunoglobulin A nephropathy (IgAN), and the real impact of it still remains unclear. The aim of this study was to elucidate the effect of body mass index (BMI) on disease progression and proteinuria in patients with IgAN in Indian population. A cohort of biopsy-proven primary IgAN patients diagnosed between March 2010 and February 2015 who had a follow-up for a minimum of 12 months were included in the study. We defined two groups of patients according to the BMI value at diagnosis: non-obese group (Group N) with BMI <23 Kg/m2 and the overweight/obese group (Group O) with BMI >23 Kg/m2 as per Asia-Pacific task force criteria. Baseline characteristics were compared between the groups. The estimated glomerular filtration rate (eGFR) and urine protein-creatinine ratio (UPCR) were followed up at entry time, 6 months, 12 months, and at the end of follow-up. Outcomes studied were change in eGFR, proteinuria, and progression to end-stage renal disease. Statistical analysis was done using the Statistical Package for the Social Sciences version 15.0. Of 51 patients, 25 (49%) had BMI <23 kg/m2 (Group N) and 26 (51%) had BMI >23 kg/m2 (Group O) (P = 0.01). The baseline clinical, histopathological, and treatment characteristics of both the groups were comparable. The BMI at the time of diagnosis did not have any significant effect on eGFR (P = 0.41) or proteinuria (P = 0.99) at presentation. At the end of follow-up, both the groups had a similar reduction of proteinuria (UPCR) (P = 0.46) and eGFR (P = 0.20). Two patients in each group have reached chronic kidney disease Stage 5. In the present study, BMI at presentation did not have any impact on eGFR or proteinuria, either at diagnosis or at follow-up. It needs further large multicenter randomized control studies to see the effect of BMI on progression of IgAN.

How to cite this article:
Nagaraju SP, Rangaswamy D, Mareddy AS, Prasad S, Kaza S, Shenoy S, Saraf K, Attur RP, Parthasarathy R, Kosuru S, Mateti UV, Guddattu V, Koulmane Laxminarayana SL. Impact of body mass index on progression of primary immunoglobulin a nephropathy. Saudi J Kidney Dis Transpl 2018;29:318-25

How to cite this URL:
Nagaraju SP, Rangaswamy D, Mareddy AS, Prasad S, Kaza S, Shenoy S, Saraf K, Attur RP, Parthasarathy R, Kosuru S, Mateti UV, Guddattu V, Koulmane Laxminarayana SL. Impact of body mass index on progression of primary immunoglobulin a nephropathy. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2020 Jun 6];29:318-25. Available from: http://www.sjkdt.org/text.asp?2018/29/2/318/229261

   Introduction Top


Obesity has been implicated as an etiology for secondary focal segmental glomerulosclerosis. The impact of obesity on primary glomerular disease is unclear. Immunoglobulin A nephropathy (IgAN) (Berger's disease) is the most common form of glomerulonephritis worldwide.[1] It is characterized by dominant or codominant deposition of the IgA antibody on immunofluorescence. It has variable course and progression depends on multiple factors such as degree of proteinuria, hypertension control, and episodes of macroscopic hematuria.[1],[2] Emerging epidemiologic evidence indicates that overweight and obesity are risk factors for progression of chronic kidney disease (CKD) and end-stage renal disease (ESRD)[3],[4],[5] The impact of obesity on IgAN is unclear. In few studies, obesity has been studied as one of the risk factors for progression in IgAN.[6],[7],[8],[9],[10] Since there is a lack of evidence on the impact of obesity on IgAN progression, we conducted the present study to see the effect of body mass index (BMI) on disease progression and proteinuria in our patients with IgAN.


   Methodology Top


A cohort of biopsy-proven adult (>18 years) primary IgAN patients diagnosed between March 2010 and February 2015 who had a follow-up for a minimum of 12 months were included in this retrospective study.

Inclusion criteria

All the biopsy-proven primary IgA patients with estimated glomerular filtration rate (eGFR) >15 mL/min/1.73 m2 at presentation were included in the study.

Exclusion criteria

Patients with eGFR <15 mL/min/1.73 m2 at presentation, coexisting with other proteinuric diseases such as lupus, autoimmune diseases, or diabetes mellitus were excluded from the study.

After getting clearance from the ethical committee, the case records of all patients were reviewed in detail and data pertaining to clinical, biochemical, serological, and histopathological parameters were recorded.

The clinical and biochemical details included were age, gender, smoking, presence of hypertension, micro- or macroscopic hematuria, edema, mean arterial pressure (MAP), body weight, height, BMI, treatment history, serum albumin, urine protein-creatinine ratio, 24 h proteinuria, serum uric acid, and serum creatinine at admission and on follow-up. The histopathological data were collected as per Oxford classification and looked for the presence of four variables (MEST score) such as mesangial proliferation (M), endocapillary proliferation (E), glomerular sclerosis (S), and interstitial fibrosis and tubular atrophy (T) for all the patients. MEST score criteria is as follows:

M0:Mesangial hypercellularity present in ≤50% of the glomeruli.
M1: Mesangial hypercellularity present in >50% of the glomeruli.
S0: Segmental glomerulosclerosis absent.
S1: Segmental glomerulosclerosis present.
E0: Endocapillary hypercellularity Absent.
E1: Endocapillary hypercellularity Present.
T0: Tubular atrophy/ interstitial fibrosis 0%–25% of cortical area.
T1: Tubular atrophy/interstitial fibrosis 26–50% of cortical area.
T2: Tubular atrophy/interstitial fibrosis >50% of cortical area.

The severity of the renal lesions in histology was also appreciated using the global optical score (GOS). The GOS (range 0–20) was the sum of glomerular (0–6), vascular (0–5), tubular (0–4), and interstitial (0–5) indices with an additional glomerular score (0–2) when the percentage of affected glomeruli by crescents and/or hyalinosis and/or obsolescence was over 25%. The GOS of >8 was considered severe. Absolute renal risk (ARR) score was calculated by counting the number of risk factors present at diagnosis: hypertension, proteinuria >1 g/day, and severe pathologic lesions (GOS >8).

The eGFR was calculated by abbreviated Modified Diet in Renal Disease (MDRD) formula for all the patients adjusted to body surface area. The following is the isotope dilution mass spectrometry (IDMS)-traceable MDRD study equation (for creatinine methods calibrated to an IDMS reference method) used to estimate GFR.

GFR (mL/min/1.73 m2) = 175 χ (Scr)–1.154 × (Age)–0.203 × (0.742 if female) × (1.212 if African American)[11]

Baseline BMI was defined as weight in kilograms divided by the square of the height in meters. Due to the ethnic specificity of BMI, obesity/overweight is defined as per Asia-Pacific task force criteria.[12],[13],[14],[15] BMI categories were as follows: underweight (<18.5 kg/m2), normal or lean BMI (18.5–22.9 kg/m2), overweight (23.0–24.9 kg/m2), and obese (≥25 kg/m2). The patients were divided into two groups according to the BMI value at diagnosis: nonobese group (Group N) with BMI <23 Kg/m2 and the overweight/obese group (Group O) with BMI >23 Kg/m2. Baseline characteristics were compared between the groups. The eGFR and UPCR were followed up at entry, six months, 12 months, and at the end of follow-up. Outcomes studied were impact of BMI on change in eGFR, proteinuria, and progression to ESRD.


   Statistical Analysis Top


The results were expressed as the mean ± standard deviation for normally distributed data and median with interquartile range for skewed data. The nominal and ordinal data were analyzed by Chi-square or Fisher's exact test between the two groups and continuous variables were analyzed by independent sample t-test for normally distributed data and Mann–Whitney U-test for skewed data with P <0.05 being considered as statistically significant. The statistical analysis of data was done using the Statistical Package for the Social Sciences (SPSS) version 15.0 for Windows (SPSS Inc., Chicago, IL, USA).


   Results Top


A total number of 51 patients were included in the study. The mean age of the study population was 31.69 ± 10.51 years. The distribution of patients as per BMI is as shown in [Figure 1]. Out of 51 patients, 25 (49%) had BMI <23 kg/m2 (Group N) and 26 (51%) had BMI >23 kg/m2 (Group O) (P = 0.01). The baseline clinical, biochemical, histopathological, and treatment characteristics of both the groups are shown in [Table 1]. The mean BMI for the Group N was 19.63 ± 2.24 Kg/m2 compared to Group O which had the mean BMI 26.04 ± 2.7 Kg/m2. The median serum creatinine at presentation was 1.3 mg/dL in Group N with an eGFR of 47.36 mL/min/1.73 m2. The median serum creatinine at presentation was 1.7 mg/dL in Group O with an eGFR of 41.5 mL/min/ 1.73 m2 and it was comparable between the groups (P = 0.95 and 0.41, respectively). The proteinuria was similar at presentation in both the groups with Group N having an UPCR of 2.6 g/g whereas Group O had 2 g/g (P = 0.99).
Figure 1: The distribution of patients as per BMI at admission.
BMI: Body mass index.


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Table 1: Comparison of baseline characteristics of patients between both groups.

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Nine patients in Group N and seven patients in Group O had nephrotic syndrome at presentation. Both the groups were treated with supportive care and immunosuppression therapy as per standard recommendations by the treating nephrologists. The treatment regimens were comparable between the groups. The histological features of IgAN as per Oxford classification, i.e. MEST score (the M1, E1, S1, and T1 lesions) in the biopsy specimens were similar between the groups [Table 1]. Seven patients in each group had crescents at presentation. S1 (segmental sclerosis) was the most common lesion in both groups. None of the patients had T2 lesion at presentation in our study population. Five patients in the each group had the GOS >8. The predominant ARR score was 2 in both the groups accounting for 64% in Group N and 69.23% in Group O, respectively. The ARR score categories were also equally distributed between the groups as shown in [Table 1]. The median follow-up was 12 months in Group N and 16 months in Group O.

At the end of follow-up, there was a decline in eGFR in both the groups. Among patients in Group N, the median fall in eGFR was 4.18 mg/mL/1.73 m2 and in Group O was 2.65 mL/ min/1.73 m2 (P = 0.76) at the end of follow-up. The Group N had a median fall of eGFR of 0.35 mL/min/1.73 m2/month and Group O had 0.11 mL/min/1.73 m2/month (P = 0.93). Both the groups had reduction in proteinuria. The median change in proteinuria was 1.4 g/g in Group N and 1.3 g/g in Group O (P = 0.76).

Hence, in our study, BMI at the time of diagnosis did not have any significant effect on either eGFR (P-value 0.41) [Figure 2] or proteinuria (P-value 0.99) [Figure 3] at presentation or at the end of follow-up [Table 2]. At the end of follow-up, two patients in each group have reached CKD Stage 5. There was no mortality in our cohort during the study period.
Figure 2: Change in median eGFR between the groups (mL/min/1.73 m2).
eGFR: estimated glomerular filtration rate, BMI: Body mass index.


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Figure 3: Change in UPCR (mg/mg) between the groups.
UPCR: Urine protein-creatinine ratio.


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Table 2: Outcomes at the end of follow-up between groups.

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   Discussion Top


Epidemiological studies have shown that IgAN is the most frequent type of primary glomerulonephritis worldwide and represents one of the leading causes of ESRD in the Asian population. The three major independent risk factors for progression to dialysis/death in IgAN are hypertension, proteinuria ≥1 g/day, and severe pathological score at diagnosis.[2],[16],[17] The identification of patients with IgAN, who are at a higher risk of progression, would be important for clinical practice. Therefore, there is a compelling need for determining more indicators to predict prognosis, in order to effectively facilitate planning of treatment. The prevalence of obesity continues to increase worldwide.[18] Obesity is a significant predictor for ESRD in CKD patients. More attention has been given to the the influence of obesity on CKD. Several mechanisms involved in the association between obesity and CKD have been proposed, and weight loss has been recommended.[3],[4],[5] In Asia, IgAN is the predominant component of CKD among glomerular diseases. A few studies from China and Japan have focused on the relationship between BMI and renal outcome in IgAN. Most of them revealed that excessive BMI was a risk factor for progressive renal disease in IgAN.[6],[7],[8],[9],[10]

Kataoka et al showed that a BMI >25 kg/m2 was a highly sensitive predictor of disease progression in IgAN patients.[8] Similarly, in the study by Bonnet et al from France, IgAN patients with high BMI >25 kg/m2 had a faster progression.[6] In a study by Shimamoto et al from Japan, IgAN patients with BMI >23 Kg/m2 had a rapid progression. Contrary to the above studies, Ouyang et al in their large cohort study of 930 primary IgAN patients with a mean follow-up period of 47.1 months showed that underweight was associated with increased risk of renal function decline in IgAN.[19]

In contrast to the above studies, we did not find any significant effect of BMI on progression of disease or proteinuria (P = 0.76). Ours is the first study to look into the effect of BMI on IgAN in Indian population. The previous studies were all done in other parts of Asia, i.e., China and Japan and in France. The variation in results may probably be due to ethnic and regional variation of the study population and the degrees of urbanization, socioeconomic conditions, food habits, and culture. The associations between BMI, percentage of body fat, and health risks may be different for different populations. The cut off value of BMI for defining obesity was also different among the studies. Kataoka et al[8] and Bonnet et al[6] took BMI >25 Kg/m2 as obese group, whereas in our study and Shimamoto et al[9] from Japan, BMI >23 kg/m2 was considered as overweight/obesity. The limitations of our study were that it was retrospective in nature and had a small cohort and short duration of follow-up. Furthermore, we did not look into the waist-hip ratio and abdominal circumference which would have given a better input on visceral fat distribution and the risk of progression.

The progression of IgAN depends on multiple factors, and there is no effect of BMI in our study and underweight contributing to the progression in Ouyang et al,[19] and it is difficult to conclude the overall effect of BMI on progression of IgAN with present existing evidence. These current findings emphasize the need for further research and evidence for confirming obesity as a risk factor for progression of IgAN.


   Conclusion Top


In the present study, BMI at presentation did not have any impact on progression of disease or proteinuria in patients with IgAN. It needs further large multicenter prospective randomized control studies to define the effect of BMI on IgAN.


   Acknowledgement Top


We would like to thank all patients with IgA nephropathy admitted in our hospital.

Conflict of interest: None declared.

 
   References Top

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Iseki K, Ikemiya Y, Kinjo K, et al. Body mass index and the risk of development of end-stage renal disease in a screened cohort. Kidney Int 2004;65:1870-6.  Back to cited text no. 3
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Wang L, Zhang Y, Chen S, et al. Association of metabolic syndrome and igA nephropathy. J Clin Pathol 2010;63:697-701.  Back to cited text no. 7
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Kataoka H, Ohara M, Shibui K, et al. Overweight and obesity accelerate the progression of IgA nephropathy: Prognostic utility of a combination of BMI and histopathological parameters. Clin Exp Nephrol 2012;16:706-12.  Back to cited text no. 8
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Shimamoto M, Ohsawa I, Suzuki H, et al. Impact of body mass index on progression of IgA nephropathy among Japanese patients. J Clin Lab Anal 2015;29:353-60.  Back to cited text no. 9
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World Health Organization. The Asia-Pacific Perspective: Redefining Obesity and Its Treatment; 2000. Available from: http://www.apps. who.int/iris/bitstream/10665/206936/1/095770 8211_eng.pdf. Last accessed18 February 2015.  Back to cited text no. 13
    
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WHO Expert Consultation. Appropriate bodymass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004;363:157-63.  Back to cited text no. 15
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Donadio JV, Grande JP. IgA nephropathy. N Engl J Med 2002;347:738-48.  Back to cited text no. 16
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McCarthy M. The economics of obesity. Lancet 2004;364:2169-70.  Back to cited text no. 18
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Ouyang Y, Xie J, Yang M, et al. Underweight is an independent risk factor for renal function deterioration in patients with igA nephropathy. PLoS One 2016;11:e0162044.  Back to cited text no. 19
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Correspondence Address:
Dr. Shankar Prasad Nagaraju
Department of Nephrology, Kasturba Medical College, Manipal University, Manipal, Karnataka
India
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DOI: 10.4103/1319-2442.229261

PMID: 29657199

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    Figures

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    Abstract
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