Global Impact of Obesity and Diabetes on the Increase Incidence and Prevalence of Chronic Kidney disease (CKD) and End Stage Renal Disease (ESRD): A Systematic Review

doi:10.21203/rs.3.rs-199379/v1

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Global Impact of Obesity and Diabetes on the Increase Incidence and Prevalence of Chronic Kidney disease (CKD) and End Stage Renal Disease (ESRD): A Systematic Review

https://doi.org/10.21203/rs.3.rs-199379/v1

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Background: Obesity and diabetes are the main causes of chronic kidney disease (CKD) and end stage renal disease (ESRD). The objective of this study was to analyze the impact of obesity and diabetes on CKD and ESRD incidence and prevalence.

Methods: A comprehensive literature search was conducted from 2001 to 2018. 494 articles were retrieved via PubMed and 125 articles through Google scholar and reference list of the selected articles. Among which thirty (30) studies met our inclusion criteria consisting of 17 cohorts, 11 cross-sectional, and 2 case-control studies.

Results: Majority of the studies indicated direct relationship between body mass index (BMI) and ESRD risk. Notably, the association of obesity and diabetes potentially increases the incidence and prevalence of CKD and ESRD. Results from the cohort, case-control and cross-sectional studies pointed out a positive association between obesity, diabetes and risks for renal disease outcomes. Even though many complications may occur, renal transplantation (RT) is still the preferred renal replacement therapy (RRT) advised in multiple studies for diabetic ESRD patients. Renal transplantation was associated with better quality of life and survival advantage than dialysis. Interestingly, overweight and obese ESRD patients on dialysis had a significant survival advantage in comparison to lean body weight patients.

Conclusion: Taken together, obesity and diabetes are significantly associated with the increasing incidence and prevalence of CKD and ESRD. Regulation of Weight and diabetes are highly recommended in obese and diabetic patients to prevent the subsequent renal disease. Previous reviews have discussed the relationship between obesity and ESRD or diabetes and ESRD separately. However, importantly, this review gives an insight on the association between obesity, diabetes and CKD/ ESRD.

Urology & Nephrology

Chronic kidney disease (CKD)

End stage renal disease (ESRD)

Obesity

Diabetes

Incidence

Prevalence

Obesity has nearly tripled worldwide since 1975. More than 1.9 billion adults across the globe in 2016 were overweight, of these over 650 million were obese [1]. It is estimated that the obesity prevalence will reach up to 51% of the world population by the year 2030 [2, 3]. Obesity and diabetes are the major cause of chronic kidney disease (CKD) and end stage renal disease (ESRD). Therefore, considered as the leading public health problem worldwide [4, 5]. It was analyzed that weight loss in obese chronic kidney disease patients may improve renal function [6]. Interventions to prevent or minimize CKD and its progression to ESRD have the potential in saving large number of human lives and minimizing healthcare expenditures [7].

Obesity is a key determinant along with the two important causative agents for ESRD, namely type-2 diabetes (Non-Insulin Dependent Diabetes Mellitus or NIDDM) and hypertension [8–11]. Population based studies in USA [12] and Europe [13] have described an independent association between a higher body mass index (BMI) and risk for the incidence of CKD. Furthermore, the excessive adiposity advocates the risk of kidney disease in patients having CKD of various causes [14].

Obesity is well known for causing morbidity, mortality, disability and has been associated to an increasing number of cardiovascular and metabolic comorbidities, such as hypertension and diabetes mellitus (DM). However, the risk for CKD in obesity is mainly independent of these comorbidities [15].

Renal alterations due to obesity includes proteinuria and/or albuminuria, hyper filtration and low glomerular filtration rate (GFR), however, mechanism underlying these changes are still not completely understood [16]. The national kidney foundation has recommended weight loss for the diabetic patients of stage 1–4 CKD [17]. The available data has shown that the incidence of some kidney disease varies greatly across different regions worldwide that have different prevalence of obesity, indicating that obesity may be a principal risk factor for kidney disease [18–21].

The prevalence of diabetes is expected to increase globally and the patients requiring renal replacement therapy (RRT) may also increase [22]. If the prevalence of diabetes continues with the same rate, it is projected to reach 592 million cases by 2035 [23]. Kidney transplantation is the most preferred RRT for diabetic patients with ESRD [24]. Increase in the end stage renal failure (ESRF) population is immense and influenced by age, gender and diabetes [25]. The incidence of ESRD with type-2 diabetes is increasing markedly with improved survival on RRT [26]. However, due to better treatment and care, the diabetes related ESRD incidence continue to fall in US in the diabetic population of all age groups [27].

There is a strong association between ESRD and the notable risk factors namely diabetes, hypertension and glomerulonephritis [28]. Type-2 diabetes mellitus has a significant impact on the increase incidence of ESRD [29]. Overall, ESRD is a global public health problem with a massive financial burden on health care systems [30, 31].

The objective of our literature review was to analyze the impact of obesity and diabetes on the increase CKD and ESRD incidence and prevalence. Previous studies on this topic have discussed the relationship between obesity and CKD/ESRD [4, 32–34] or diabetes and ESRD [24] separately. Our review provides a comprehensive insight on the association between obesity, diabetes and CKD/ ESRD. We thoroughly assessed the epidemiologic evidence on the relationship between obesity, diabetes and kidney disease, and carried out a systemic review of the studies that have evaluated the association between obesity, diabetes and CKD/ ESRD.

Data sources and searches

To identify the studies related to our topic, a comprehensive literature search was conducted through PubMed and Google scholar. All those articles were included which were focusing mainly on the “impact of obesity and diabetes on the increasing incidence and prevalence of CKD and ESRD” from 2001 to 2018.

The search terms included BMI or obesity, diabetes or diabetes type-2 or diabetic nephropathy, end stage renal disease or ESRD, chronic kidney disease or CKD, renal replacement therapy or RRT, dialysis or peritoneal dialysis or hemodialysis or PD or HD and kidney transplantation or renal transplantation or RT.

Selection criteria

The manuscript published in English language as full text articles were included in the study. The searched articles by PubMed and Google scholar were analyzed initially by titles closely related to define the obesity, diabetes and their impact on renal disease specifically the ESRDs. Articles with not well-defined titles were reviewed only on the abstract level. Furthermore, we made an additional search to see potential eligible studies through reference list of review articles that might have been missed in the initial searching. All population-based studies addressing the impact of obesity and diabetes on CKD and ESRD incidence and prevalence were included in this review. We excluded the studies published in language other than English and those who addressed only type-1 diabetes (Insulin Dependent Diabetes). The risk of bias across the studies might exist, but to our best, we tried to include all those studies related to our topic, irrespective of their statistically significant data or journal of publication to avoid the selection bias and publication bias. All the authors were qualified and experienced enough to follow the protocol for the selection of the studies.

Data collection and extraction

In this study, (AK) independently screened all the retrieved titles and abstracts as part of the search strategies to identify potentially eligible articles and subsequently verified by (SG). The quality of methodology and the risk of biasness in the included studies were assessed by two authors and the disagreements were discussed and resolved in the weekly meetings. Data extraction was carried out for different variables, including information about the author, type of study, country, study period, sample size, mean age, study objectives, BMI, diabetes, type of renal disease, main findings, ORs (odd ratios) or RRs (relative risks), statistical analysis, registry/data source. Remarks in the tables corresponds to conclusion. ORs and RRs were used as measures of the association between obesity, diabetes and CKD or ESRD.

Literature search and inclusion

Figure 1 presents Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) flow diagram for the article selection [35]. We retrieved 494 articles concerning our topic through PubMed search, and 125 additional articles were identified through Google scholar and through the reference list of the selected articles. After the selection process, 30 eligible studies were included in this review.

Study design and quality assessment

All the selected studies were comprehensively analyzed, and an appropriate study design was applied for all the reviewed studies. Based on our search, four types of studies were identified 1- Retrospective, n = 13 (43.3%), 2- Prospective, n = 4 (13.3%), 3- Cross sectional, n = 11 (36.7%), 4- Case-control, n = 2 (6.7%).

General characteristics of the included studies

General characteristics of the chosen studies addressing obesity, diabetes and ESRD are shown in Table 1. Maximum number of the included studies were based on adult population consisting of 18 to 98 years, while, male ratio was higher than female. Importantly, by distributing the retrieved studies geographically according to the continents (Fig. 2), 13 (43.3%) studies were performed in North America, 9 (30%) in Europe, 7 (23.3%) in Asia and only one study was carried out in Australia.

Majority of the studies were carried out in North America (43.3%) followed by Europe (30%), Asia (23.3%) and the lowest studies were performed in Australia (3.3%).

Importantly, thirteen (13) studies identified that the increase in BMI (mainly the obesity) have an impact on the increase incidence of ESRD. In addition, 11 studies revealed that diabetes is the most prominent risk factor for the increase incidence of ESRD while in 06 studies the ESRD patients were both: obese and diabetic. Two studies identified that obesity, diabetes and additional risk factors such as hypertension, glumerulonephritis, smoking and proteinuria are the major causative agents of increasing ESRD incidence [28, 36]. A case control study [6] in two ethnic groups (black and white) revealed the differences between black and white population in the incidence of ESRD in relation to the association between obesity and ESRD. Importantly, significant differences were observed in the study between the two groups regarding the increase odds of ESRD.

Table 1

General characteristics of the included studies
Reference	Study design	Sample size (N)	Age (Years) (Mean/ Median)	Studies addressing
Reference	Study design	Sample size (N)	Age (Years) (Mean/ Median)	Obesity & diabetes & ESRD patients CKD/ESRD^* CKD/ESRD^* with obesity and diabetes^*
Akwo et al [37]	Case control	2528	53.7	√	x	x
Coresh et al [38]	Cross sectional	28721	44.8 and 46.2	√	x	x
Foster et al [39]	Prospective	2676	43	√	x	x
Evangelista et al [40]	Cross sectional	37002	45.1 ± 0.15	√	x	x
Fox et al [41]	Retrospective	2585	At baseline = 43 On follow up = 61	√	x	x
Gelber et al [12]	Prospective	11104	52.7 ± 7.7	√	x	x
Speckman et al [42]	Prospective	23822	1. Family history of ESRD = 57.7 ± 14.7 2. No family history of ESRD = 61.2 ± 15.0	√	x	x
Hallan et al [43]	Cross sectional	65193	50.2 ± 17.4	√	x	x
Iseki et al [44]	Retrospective	100753	≥20	√	x	x
Kramer et al [45]	Prospective	5897	Obese age = 50.2 ± 9.7	√	x	x
Othman et al [14]	Retrospective	125	Obese age = 60 ± 15.4	√	x	x
Tozawa et al [36]	Retrospective	5403	48 ± 9	√	x	x
Gomez et al [46]	Cross sectional	4585	61.9 ± 10.6	√	x	x
Assogba et al [29]	Retrospective	9494	67.0 ± 16.5	x	√	x
NG et al [47]	Retrospective	30	59	x	√	x
Icks et al [48]	Retrospective	544	70.3 ± 11.4	x	√	x
Khan et al [28]	Cross sectional	407	M = 43.38 F = 42.4	x	√	x
Iseki et al [49]	Retrospective	7125	> 40	x	√	x
Iseki et al [50]	Retrospective	106,177	20–98	x	√	x
HSU et al [51]	Retrospective	21655	20–74	x	√	x
Hochman et al [52]	Cross sectional	130907	≥18	x	√	x
Plantinga et al [53]	Retrospective	8188	57.7	x	√	x
Chadban et al [54]	Cross sectional	11247	≥ 25	x	√	x
Amato et al [55]	Cross sectional	3564	≥ 18	x	√	x
Ejerblad et al [56]	Case control	1924	18–74	x	x	√
Vinhas et al [57]	Cross sectional	5167	20–79	x	x	√
HSU et al [15]	Retrospective	320,252	40 ± 13 (For class III obese)	x	x	√
Kramer et al [58]	Prospective	615192	20 +	x	x	√
Otero et al [59]	Cross sectional	237	49.58	x	x	√
Otero et al [60]	Cross sectional	2746	49.5	x	x	√
*The sign √ in all the column indicates “yes” while × indicates “not concern”

Risk factors for CKD/ ESRD

Several risk factors were identified in the selected studies which had an impact on the increase incidence and prevalence of CKD and ESRD (Fig. 3). However, obesity and diabetes were the most prominent risk factors point out by majority of the authors.

Majority of the studies observed that obesity and DM are the major risk factors for CKD and ESRD. Abbreviations: DM, Diabetes Mellitus; HT, Hypertension; CVD, Cardiovascular disease; PU, Proteinuria; MS, Metabolic syndrome; GN, Glumerulonephritis; Fam hist of ESRD, Family history of ESRD

Obesity is associated with profound increased incidence and prevalence of CKD and ESRD

Previously, the association between obesity and kidney disease has been described in several studies. Table 2 briefly summarizes the main characteristics and findings of 13 eligible studies which describes the impact of obesity on end stage renal disease. Most of the studies (n = 7) were conducted in USA, 2 in Japan and one each in Korea, Norway, UK and Spain. The sample size included in the studies were varied significantly ranging from 125 to 100753 individuals [14, 44]. The analysis indicates that obesity is the prominent risk factor for kidney disease including CKD [38, 40, 43] and ESRD [37, 42, 44, 58] leading to the ultimate or instant need for renal replacement therapy such as HD and PD or renal transplantation (RT).

Table 2

Obesity and its effects on the increasing incidence and prevalence of CKD and ESRD
Reference, year of publication	Type of study, Country and study period	Study Objective	BMI (kg/m²) %	Type of Renal disease	OR/ RR and 95%CI	Registry/ Data source	Statistical analysis	Main findings	Remarks
Coresh et al [38] 2007	Cross sectional study USA 1988–1994 1999–2004	To update the estimated prevalence of CKD in the US	8079 (28%) Participants had BMI ≥ 30	CKD	Prevalence ratio for CKD Stage 4 (1999–2004) = 1.70 (1.11–2.51)	US-NHANES Survey	Logistic regression	Prevalence of CKD 1–4 increased from 10% in 1988–1994 to 13.1% in 1999–2000	Prevalence of CKD in the US in 1999–2004 is higher than it was in1988-1994
Evangelista et al [40] 2018	Cross sectional study Korea 2008–2014	Prevalence of obesity according to the stages of CKD	Prevalence rate of general obesity were 37.8% in stage 4/5 CKD patients	CKD	Obesity related CKD stage 3b, OR = 1.22 (0.43–2.30)	KNHANES Survey	Logistic regression	Obesity was more prevalent in CKD patients than those without CKD	Weight loss is good for the prevention of disease progression
Fox et al [41] 2004	Retrospective USA, 1978–1982, 1998–2001	Predictors identification of the development of new onset kidney disease	BMI at baseline with CKD = 26.8(± 4.2) BMI at follow up with CKD = 27.4(± 4.1)	KD	BMI as predictor of developing KD after mean of 18.5 y follow-up OR = 1.23 (1.08–1.41)	Framingham Offspring study	Logistic regression	Increase BMI, Diabetes and Smoking were related to development of KD.	BMI increased the odds of developing kidney disease by 23% per SD unit
Gelber et al [12] 2005	Prospective USA 14 Years follow-up	Association between BMI and risk for CKD	398 participants were obese (3.6%)	CKD	10% increase in BMI after 14y follow-up and risk for CKD OR = 1.27 (1.06–1.53)	PHS study	Logistic regression	Higher baseline BMI was associated with increased risk for CKD	BMI was associated significantly with increased risk for CKD after 14 years
Hallan et al [43] 2006	Cross sectional Norway 1995-97	Association between obesity smoking, physical inactivity and CKD	All categories of BMI were present	CKD	RR for BMI ≥ 30 kg/m² = 1.77 (1.47–2.14)	HUNT II study	Logistic regression	All classes of obesity (BMI ≥ 30 kg/m²) increased the risk of CKD	Obesity, smoking and physical inactivity were the significant risk factors for CKD
Iseki et al [44] 2004	Retrospective Japan (1983–2000)	Significance of BMI as a risk factor for the development of ESRD	25642 screeners were having a BMI of ≥ 25.5	ESRD	OR of BMI for developing ESRD= Men = 1.273 (1.121–1.446) Women = 0.950 (0.825–1.094)	OKIDS Registry (Okinawa)	Multi variate logistic analysis	404 screeners (232 men and 172 women) developed ESRD during the follow-up period	Higher BMI was responsible for the increased risk of ESRD in men but not in women
Kramer et al [58] 2005	Prospective USA, (1973–1979)	Association of overweight and obesity with incident CKD in hypertensive adults	3094(32%) Participants were obese	CKD	OR (Obesity and increase odds of incident CKD at year 5) 1.40 (1.201.63)	HDFP Data	Linear regression	The incidence of CKD at year 5 was 34% in obese group.	Obese adults with hypertension have an increased risk for CKD
Othman et al [14] 2009	Retrospective UK 10 y follow-up	Obesity impact on the rate of non-diabetic CKD progression	31% of the patients were obese	CKD	Higher baseline BMI (P = 0.018) and young age (P = 0.016) were significant predictors of eGFR fall / Y	Sheffield kidney institute UK record system	Uni and Multivariate regression analysis	The frequency of e GFR based CKD progression per year (> 1 ml /min/1.73 m²/y) was 62.5% in overweight and 79.5% in Obese compared to 44.7% in normal weight CKD patients (p = 0.007)	Baseline BMI is strongly and inde- pendently associa- ted with robust CKD progression based on the annual fall rate of eGFR
Tozawa et al [36] 2002	Retrospective Japan 1997-99	Analysis of the effects of obesity and smoking on the development of proteinuria	34% of the participants were obese	Proteinuria as a risk factor for ESRD	RR for developing proteinuria was 1.45 (1.13–1.86) for obesity	Okinawa general health Maintenance Association screening	Logistic regression analysis	5.8% of participants developed proteinuria. RR (95%CI) for developing proteinuria was 2.27(1.55–3.32) p < 0.0001 for DM	Obesity, DM, hypertension and smoking were the key risk factors for developing proteinuria
Gomez et al [46] 2006	Cross sectional Spain	Assessment of the prevalence RI in patients with essential hypertension and BMI ≥ 25 kg/ m²	2525 (55%) patients were obese and mean BMI was 35.1 ± 4.1	RI	High prevalence of RI was noted in the presence of Diabetes = 30.1% (24.4–32.9) vs 19.2% (17.6–20.8) in obese group	Spanish primary care centers data	Logistic regression analysis	Higher prevalence of Diabetes was observed in obese patients. Prevalence of RI was 22% (95%CI, 20.6–24.9) for overweight and 22.8% (95% CI, 21.0-24.7) for obesity	Overweight/Obese hypertensive patients seen in a primary care setting exhibit a high prevalence of MS and RI.
Akwo et al [37] 2015	Case control USA (2002–2009)	The relationship between BMI and ESRD in blacks and whites	Mean BMI at enrollment was (31.2 ± 7.7 kg/ m²)	ESRD	Whites with class III obesity had more than 3-fold increase odds OR = 3.31 (1.08, 10.12) of ESRD.	SCCS Participants	Conditional logistic regression	Overweight persons at age 21 had 44% increase odds (OR 1.44; 95%CI, 1.13, 1.85) and obese 3-fold increase odds (OR 2.88; 95%CI, 2.16, 3.83) for ESRD comparing normal weight persons.	BMI (overweight and obese) at age 21 was associated with increased ESRD incidents in whites than in blacks. Increase BMI at enrollment was associated with 2-fold increase odds of ESRD in obese whites
Foster et al [39] 2008	Prospective USA. Members who attended the (1978–1982) and (1998–2001) examination cycles were include in this study	Magnitude of association between BMI and CKD	36% of the sample was overweight and 12% was obese	CKD	One unit increase in BMI was associated with 5% increase in stage 3 CKD odds OR = 1.05 (1.02–1.09)	Framingham offspring participants	Logistic regression model	Obese individual had 68% increased odds of developing stage 3 CKD (OR 1.68 95% CI, 1.10–2.57)	Obesity is associated with significant increase risk of developing stage 3 CKD. .
Speckman et al [42] 2006	Retrospective USA 1995–2003	Relationship between obesity and family history of ESRD	Mean BMI for those with family history of ESRD Was 28.2 ± 8.0	ESRD	Reported family history of ESRD and association with being obese OR = 1.25 (1.14–1.37) and being Morbid obese OR = 1.40 (1.27–1.55)	Medicare supported RRT patient data	Logistic regression model	23% of patients reported family history of ESRD. Of these, 28.0% were overweight, 17.3% obese and 16.7% were morbidly obese	Obesity and the start of dialysis therapy were independently associated with reported family history of ESRD. Genetic factor may contribute to familial risk of ESRD.

In a community-based cohort of 2585 men and women, it was analyzed that each unit increase in BMI was associated with 23% (OR 1.23 95% CI, 1.08–1.41) increased risk of new onset renal disease [41]. The prevalence of CKD in the US in 1999–2004 was higher than 1988–1994. The cross-sectional analysis stated that prevalence of CKD increased from 10% in 1988–1994 to 13.1% in 1999–2004 with a prevalence ratio of 1.3 (95% CI, 1.2–1.4). This increase was due to the increase prevalence of diabetes and hypertension. This further raises concerns about future elevated incidence of kidney disease [38].

In a population-based study carried out by Evangelistq and colleague in South Korea determined that obesity was more prevalent in CKD patients than those without CKD. Importantly, prevalence rate of general obesity was 37.8% in stage 4 and 5 CKD patients. The study summarizes that weight loss is a good potential intervention to prevent the disease progression [40]. In a cohort of 11104 initially healthy men and 14 years of follow up, it was analyzed that higher baseline BMI was associated significantly with increased risk for CKD. The increase BMI (> 10%) was associated with significant increased risk for CKD (OR 1.27, 95%CI, 1.06–1.53) [12].

A case control study detected a significant difference between two ethnic groups: black and white in relation to the association between obesity and ESRD. BMI of overweight and obese persons at the age 21 was associated with increased ESRD incidence in both black and whites but more prominent in whites than in blacks, while BMI (overweight and obese) at enrollment was associated with non-significant odds of ESRD in blacks. However, significantly, obese whites had 2-fold increase odds of ESRD (OR 2.17, 95% CI, 0.94–4.98) [37].

Obesity is linked directly or indirectly in the development of chronic kidney disease. The results from the study with 18.5 years follow up, where 36% of the participants were overweight and 12% obese, revealed that 7.9% developed stage 3 CKD and 14.4% proteinuria. One unit increase in BMI was associated with 5% increase in the odds of stage 3 CKD (OR 1.05 (1.02–1.09) P = 0.005 [39].

Obesity, smoking and lack of physical activity are the significant risk factors for CKD [43], and the relative risk (RR) for BMI ≥ 30 kg/m² was 1.77 (95% CI,1.47–2.14). Using data from a community-based screening of 100735 participants in Okinawa, Japan, it was noted that a higher BMI is associated with the increased ESRD risk in men (OR 1.273, 95% CI, 1.121–1.446) P = 0.0002 but not in women in the general population [44].

Kramer et al in 2005, performed a prospective cohort study of 5897 incident dialysis patients with hypertension. Significant association of overweight and obesity was realized with the development of ESRD during a 5 year follow up. The incidence of CKD at year 5 was 34% in obese group and obese adults with hypertension had an increased risk for CKD, OR 1.40 (95% CI, 1.20–1.63) [58]. The cohort study with 23822 ESRD patients provides a detailed information about the association of obesity with the family history of ESRD in incident dialysis patients. Analysis showed that 23% of the patients reported family history of ESRD. Among which 28.0% were overweight, 17.3% obese and 16.7% were morbidly obese. Reported family history of ESRD was associated with being obese, OR 1.25 (95% CI, 1.14–1.37) and morbid obese, OR 1.40 (95% CI, 1.27–1.55) [42].

In summary, the obesity enhances the risk for developing the kidney disease particularly the ESRD in the general population. Furthermore, due to the large expenditures on the treatment of ESRD patients it is also an economic problem as well.

Diabetes is a prominent risk factor for the elevated burden of CKD and ESRD

A wide range of studies has been carried out to find the effect of diabetes on increasing kidney disease including ESRD. Table 3 explains the main characteristics and findings of 11 eligible studies defining the effect of diabetes on ESRD. Most of the studies were belonged to USA (n = 3), Japan (2), and one each from Pakistan, France, Malaysia, Germany, Australia and Mexico. High variations in the sample size of the included studies were identified ranging from 30 to 130907 individuals [47, 52]. By reviewing the summary of these studies, we concluded that diabetes is continue to be the prominent risk factor for kidney disease, including CKD [53, 55] and ESRD [49–52] leading to an urgent need for renal replacement therapy that is HD and PD or RT.

Table 3

Diabetes and its impacts on the rising incidence and prevalence of CKD and ESRD
Reference, year of publication	Type of study, Country and study period	Study Objective	Diabetes status	Type of Renal disease	OR/ RR and 95%CI	Registry/ Data source	Statistical analysis	Main findings	Remarks
NG et al [47] 2018	Retrospective Malaysia	Rate of progression of type-2 DM to ESRD in Malaysia	All the included patients were type-2 diabetic	ESRD	The difference b/w the two groups (RAAS blocker user VS non RAAS blocker user) Was P = 0.001 (-3.69 to -1.13)	ESRD patient’s data from Sultanah Bahiyah Hospital	SPSS, t-test and ANOVA	Short duration from DN to ESRD was noted, that is 5.63 ± 2.06 Y. Mean duration from DM to ESRD for pts receiving RAAS blocker Was 18.23 ± 2.38 as compared to 11.41 ± 2.94 who did not	The duration of DN to ESRD was shorter in Malaysian population compared to the other countries. RAAS blockers initiation is recommended in diabetic patients
Iseki et al [49] 2005	Observational (Retrospective) Japan 1997–2000	The effect of DM as a risk factor of developing ESRD	Incidence of DM was 2.3% (2.9% in men and 1.3% in women)	ESRD	OR of proteinuria as predictor for developing DM = 1.90 (1.14–3.17)	Dialysis unit (Okinawa)	Logistic regression analysis	Proteinuria was the strong predictor of the development of DM and higher the BMI, higher is the risk of ESRD	The prevalence of obesity and DM is increasing in Japan and many Asian countries and need sincere effort in lowering of BMI and DM related ESRD
Iseki et al [50] 2003	Retrospective Japan (1983–2000)	Clinical impact of proteinuria test on the development of ESRD	420 subjects developed ESRD, of which 100 (23.8%) had DM	ESRD	OR (ESRD and Protein urea) 2.71 (2.51–2.92)	OKIDS Registry (Okinawa)	Multi variate logistic analysis	Strong relationship was found b/w ESRD and proteinuria	Proteinuria is a strong and independent risk factor for ESRD
HSU et al [51] 2004	Retrospective USA, 1976–1980 1988–1994	To know whether the increasing incidence of ESRD in the US is preceded by increased prevalence of CRI	24 ESRD cases/1000 persons in NHANES II and 38 ESRD cases/1000 in NHANES III were diabetic	ESRD	RR for progression to ESRD 1.7 (1.1–2.7)	NHANES II NHANES III USRDS	Poisson regression model	From 1978–1991, the prevalence of CRI and the incidence of ESRD increased	Growth in incident ESRD outpaced the growth in prevalent CRI
Hochman et al [52] 2007	Cross sectional USA, USRDS Data of 2001	To estimate the prevalence and incidence of ESRD in the native American adults living on the Navajo nation	Majority of the ESRD Patients were diabetic	ESRD	ESRD prevalence was 0.63% and Incidence was 0.11%	USRDS	Two tailed Z-tests	Age adjusted prevalence and incidence of ESRD was 0.63% and 0.11% respectively	Higher prevalence and incidence were observed in native American adults living on the Navajo nation which requires further study
Plantinga et al [53] 2010	Retrospective USA 1999–2006	Estimation and comparison of CKD prevalence in people with diagnosed diabetes, undiagnosed diabetes, prediabetes, or no diabetes	826 were diabetics and 2272 prediabetes	CKD	CKD Prevalence by diabetes status for Diagnosed diabetes = 39.6 (35.1–44.3) and for undiagnosed diabetes = 41.7 (34.5–49.2)	US-NHANES Survey	Multi variate logistic regression analysis	39.6% of people with diagnosed and 41.7% with un-diagnosed diabetes had CKD	CKD was diagnosed in prediabetes and undiagnosed diabetes individuals, needs interventions to prevent CKD progression
Chadban et al [54] 2003	Cross sectional Australia	To determine the prevalence of indicators of kidney damage in Australian adult population	Participants were tested for blood plasma glucose on Fasting and 2 hours after giving standard 75 g oral glucose	ESRD	OR for Proteinuria of DM vs no DM was 2.5 (1.8–3.5)	Australian Diabetes study	Logistic regression analysis	The prevalence of Proteinuria was 4-fold higher in those with DM compared with those without (8.7%, 95%CI 6.6%, 10.7%) vs (1.9%; 95% CI: 1.2%, 2.5% P < 0.001)	Proteinuria, Hematuria and GFR examination in the early stage may provide a mean to reduce the ESRD burden
Amato et al [55] 2005	Cross sectional Mexico June 1999- Feb 2000	Assessment of the prevalence of CKD in a Mexican urban population	84 patients (siblings) had DM	CKD	DM as a risk factor for CKD in siblings OR = 1.9681 (1.34–2.90)	Questionnaire based data	Logistic regression analysis	The prevalence rate of Ccr < 15 ml/ min 1142 pmp and for Ccr < 60 ml/ min was 80.79 pmp.	Prevalence rate of CKD in Mexico is same as in developed countries. Increase prevalence may be due to DM but other factors such as genetic and socioeconomic may also play a role
Icks et al [48] 2010	Retrospective population-based study Germany 2002-08	Estimation of the incidences of RRT in diabetic and non-diabetic population in Germany	270 (49.6%) of the incident RRT patients had diabetes.	RRT	RR (standardize) for Men= 7.9(5.9–10.8) and Women = 8.0(4.7–13.5)	Data from regional dialysis center in North Rhine- Westphalia	Poisson regression model	DN was the most frequent reason for RRT (29.7%) followed by vascular nephropathy (25.6%) and Glumerulonephropathy (12.9%).	The relative risk of RRT in the estimated adult diabetic population has increased by 8-fold comparing the non-diabetic population.
Assogba et al [29] 2014	Retrospective France 2007–2011	Geographic variations and recent trends in the incidence of ESRD by diabetes status and type	The prevalence of diabetes type-2 increase from 2270 in 2007 to 2745 in 2011.	ESRD	Incidence rate of type2 diabetes related ESRD/Y increased till 2009 [6.9% (4.8–9.1)] Stabilized thereafter 0% (2.1–2.2)	REIN Data 2007-11	Logistic regression and Poisson regression model	ESRD incidence increased significantly for patients with type-2 diabetes (+ 7% annually till 2009) and stabilized then	Type-2 DM is the major cause of ESRD incidence. Preventive strategies are strongly recommended to reduce the ESRD incidences
Khan et al [28] 2016	Cross sectional Pakistan	To discover the association of ESRD with various risk factors	183 Patient (45%) had diabetes in which 128 patients had ESRD.	ESRD	OR for diabetes related ESRD was 11.04	Data taken from 3 Hosp.	Odd ratio analysis	ESRD in diabetic patients was 11.04 times more than non-diabetic pts. GN patients had 3.115 times more risk of ESRD than non-GN.	Strong relation was found between ESRD and three major risk factors namely diabetes, hypertension and Glumerulonephritis. The other risk factors found, were less significant.

The longitudinal study in France in the year 2007–2011 consisting of 9494 patients with 3410 type-2 diabetes and mean age 67.0 ± 16.5, found that ESRD incidence increased significantly for patients with type-2 diabetes (+ 7% annually) (95% CI, 4.8–9.1) P < 0.0001 till 2009 and seems to be stabilized after 2009 (0%) (95% CI, 2.1–2.2) however, type-2 diabetes is still a major cause of ESRD incidence [29].

Hochman and colleagues estimated the prevalence and incidence of ESRD in native American adults living on the Navajo nation using USRDS data. Higher prevalence and incidence were observed in native American adults living on the Navajo nation. Age adjusted prevalence and incidence of ESRD was 0.63% and 0.11% respectively. Majority of the ESRD patients were diabetic [52]. To assess the prevalence of CKD in a Mexican urban population, a population based cross sectional survey was conducted. Prevalence rate of CKD in Mexico was like those in the developed countries. Increase prevalence was partially due to DM, however other factors such as genetic and socioeconomic may also play a role. OR for DM as a risk factor for CKD in siblings was 1.9681 (95% CI, 1.34–2.90) [55]. Plantinga et al in 2010 determined the estimation and comparison of CKD prevalence. Interestingly, 39.6% people with diagnosed and 41.7% with un-diagnosed diabetes had CKD. Prevalence of CKD by diabetes status for diagnosed diabetes was 39.6 (35.1–44.3) and for undiagnosed diabetes 41.7 (34.5–49.2) [53].

In a study in Germany determined that incidences of ESRD in patients with and without diabetes were 157.9 and 25.6 per 100,000 person/year respectively (6.2-fold increased risk for those with diabetes).[61] Diabetic nephropathy was the most frequent reason for RRT (29.7%) and the relative risk of RRT in the estimated adult population was increased by 8-fold comparing the non-diabetic population [48]. Khan et al 2016, revealed a significant relation between ESRD and three major risk factors namely diabetes, hypertension and glumerulonephritis. Importantly, the ESRD in diabetic patients was 11.04 times more than non-diabetic patients [28].

The longitudinal study in Cyprus 2004–2011 found that 84.4 pmp (36.0%) with ESRD were due to diabetic nephropathy suggesting that diabetes is a major cause of ESRD and specially in population under 65 years of age [62]. Furthermore, in a retrospective study, it was analyzed that the use of RAAS blockers has a significant impact on the delay onset of ESRD in diabetic patients. In this study it was described that some DN patients not receiving RAAS blockers developed ESRD in two years, while those receiving RAAS blockers took an average of 7 ± 1.91Y to progress into ESRD. Mean duration for the onset of ESRD was 4.59 ± 1.50 Y for those who were not prescribed RAAS blockers. The statistically significant difference was observed between the two groups, P = 0.001 (95% CI -3.69 to-1.13) [47].

In a cross-sectional study, it was described that early examination of proteinuria, Hematuria and GFR can provide a mean to reduce the ESRD burden. Strikingly, the prevalence of proteinuria was 4-fold higher in DM patients compared with those without DM. 8.7% (95% CI, 6.6%-10.7%) vs 1.9% (95% CI, 1.2%- 2.5%) P < 0.001 [54].

The results of the different studies have confirmed that the ESRD incidence and prevalence is much higher in the diabetic than the non-diabetic population, demanding serious efforts to combat diabetes in order to stop or slow-down the ESRD progression.

The coupling of obesity and diabetes, and their ultimate impact in overwhelming growth of CKD and ESRD

The impact of obesity on the increase in the ESRD events have been carried out in several studies. However, obesity in combination with diabetes leads to ESRD risk much quickly than alone. Table 4 briefly describes the main characteristics and findings of 6 eligible studies in which the ESRD patients were obese and diabetic too. Four studies (2 each) were carried out in USA and Spain and one each in Sweden and Portugal. The sample size was varied among studies ranging from 237 to 615192 individuals [58, 59].

Table 4

Obesity, Diabetes and their effects on the increasing incidence and prevalence of CKD and ESRD
Reference, Year of publication	Type of study, Country and study period	Study Objective	BMI (kg/m²) %	Diabetes status	Type of renal disease	OR/ RR and 95%CI	Registry/ Data source	Statistical analysis	Main findings	Remarks
Ejerblad et al [56] 2006	Case control Sweden (May 1996-May1998)	Possible effects of Obesity on the incidence of moderately severe CRF	283 (14.7%) Patients had BMI ≥ 30 kg/m²	One third of the patients were diagnosed with diabetic nephropathy.	CRF	OR for CRF association with BMI = For (BMI ≥ 35 kg/m²) Men = 4.4 (2.4 to 8.2) Women = 3.1 (1.6 to 6.1)	Swedish National population register	Logistic regression model	Obesity (≥ 30 kg/m²) in men and (≥ 35 kg/m²) in women was associated with 3-4fold increased risk for CRF.	Obesity is linked, directly or indirectly, in the development of CKD and CRF. The risk of CRF is driven by type-2 diabetes and hypertension.
HSU et al [15] 2006	Retrospective USA 1964–1985	To determine the association between increase BMI and risk for ESRD	Of the total sample, there were n = 21856(6.8%) class I obese, n = 5540(1.7%) class II obese and n = 2417(0.8%) class III obese	6080 persons of class I, II and class III obesity were diagnosed with diabetes	ESRD	RR for ESRD was 3.57(3.05–4.18), 6.12(4.97–7.54) and 7.07(5.37–9.31) for class I, II and III obesity respectively	Member of Kaiser permanent of northern California	Multivariate analysis using cox model	Higher baseline BMI is an independent risk factor for ESRD even after adjustment for baseline BP and Diabetes mellitus.	Obesity is a strong and potentially modifiable risk factor for ESRD.
Kramer et al [58] 2006	Prospective USA (1995–2002)	Increase BMI and obesity in incident ESRD population and survival advantage	Mean BMI increased from 25.7 to 27.5 kg/m² among incident patients (1995–2002)	Increased From 44–51% (1995–2002)	ESRD	The forecast Prevalence of total obesity and obesity stage ≥ 2 among incident ESRD patients with diabetes in 2007 was 44.6% (43.0 to 46.2%) and 22.7% (21.7–23.6%) respectively	USRDS	Auto regression method	BMI slope was higher in ESRD population (8%) vs total US population (4%) (P < 0.0001)	In 2002 almost one third of all incident ESRD patients were obese. ESRD population on dialysis will be positively influenced due to the survival advantage with obesity.
Otero et al [59] 2005	Cross sectional Spain 2004	Epidemiology of CKD in the Spanish population and associated risk factors	Obesity prevalence was 8% at G3 stage of renal function	Diabetes prevalence was 16.7%	CKD	Risk of CKD and ARF. DM OR= 4.48 (1.54, 13.04) Obesity OR= 7.7 (2.65,22.3)	EPIRCE study	Logistic regression analysis	High prevalence of HT (31.5%) DM (8%) Obesity (13.1% Smoking (22.7%) Alcohol intake (24%) was found	Prevalence of CKD and cardiovascular risk factors was found high in the randomly selected sample of the GP
Otero et al [60] 2010	Cross sectional Spain Jan 2004- Jan2008	Prevalence of CKD in Spanish population	723(26.3%) participants were obese	420 were diabetic	CKD	Association b/w clinical characteristics and the presence of CKD. Obesity OR= 3.5 (2.0–6.0) HT OR= 6.2 (4.0-9.6) DM OR = 2.0 (1.4–2.8)	EPIRCE study	Logistic regression analysis	Obesity prevalence was (26.1%), Hypertension (24.1%) DM (9.2%) Dyslipidemia (29.3%)	Prevalence of CKD in Spain is high. Two modifiable risk factors namely diabetes and hypertension are responsible for the increased prevalence of CKD
Vinhas et al [57] 2011	Cross sectional Portugal, 2008-09	Prevalence of CKD, ESRD and associated risk factors in Portugal	The obesity prevalence was 33.7%	Diabetes prevalence was 11.7%, and Metabolic syndrome 41.5%	CKD	Adjusted OR for CKD: Diabetes = 1.20 (0.96–1.50) Obesity= 1.14 (0.94–1.39)	PREVADIAB Study	Logistic regression analysis	Prevalence of CKD stage 3–5 was 6% which is same as the other western countries but risk of ESRD was greater than the other European countries	Greater prevalence of CKD is not responsible for the high incidence of ESRD in Portuguese population, in fact the high prevalence of risk factors may account for the high incidence

Ejerblad and colleagues in the year 2006 described that obesity has direct or indirect impact in the development of chronic kidney disease and chronic renal failure. It was further analyzed that a strong association exist among obesity, diabetes and CRF risk, and the risk in the obese individual is mainly driven by type-2 diabetes and/or hypertension. OR for CRF association with BMI = For (BMI ≥ 35 kg/m²) Men = 4.4 (95% CI, 2.4–8.2) Women = 3.1 (95% CI, 1.6–6.1) [56].

The cohort study reported by Hsu et al elaborated the impact of increased BMI on the risk of ESRD based on historical cohort data gathered in a large, integrated health care system in California from 1964–1985 with a large sample size of 320252 and mean age of 41.7 ± 13.3 years. There were 2417 class 3 obese individuals with mean weight of 116.4 ± 17.5. It was noted that the rate of ESRD increases with the increase in BMI that is 10/100000 person/year among normal weight to 108/100000 persons/year among extreme obese (≥ 40 kg/m²). Remarkably, baseline BMI remained a strong risk factor for ESRD even after adjustment for diabetes and blood pressure [15].

Highest prevalence of obesity stage 2 (BMI ≥ 35 kg/ m²) was observed in ESRD population with DM at dialysis initiation between the age of 45–64 years. It positively influenced the ESRD population on dialysis due to the survival advantage with obesity [58].

Chen et al determined that obesity was associated with increased proteinuria in the early stage while it was beneficial in terms of improved renal survival in the later stages confirming the reverse epidemiology. 28.8% of the patients developed ESRD by the end of the study period [63].

A Cross sectional study observed that prevalence of CKD in Spain was high especially in the elderly population. Two modifiable risk factors namely diabetes and hypertension were responsible for the increased prevalence of CKD. Association between clinical characteristics and the presence of CKD for obesity verses normal was OR 3.5 (95% CI, 2.0–6.0), hypertension verses absence OR 6.2 (95% CI, 4.0-9.6) and DM verses absence OR 2.0 (95% CI, 1.4–2.8) [60].

In another study, it was found that prevalence of CKD and cardiovascular risk factors was high in the randomly selected sample of the general population. Prevalence of obesity and DM was 13.1% and 8% respectively. Risk factors significantly involved in kidney disease were obesity, OR 7.72 (95% CI, 2.65, 22.3), DM, 4.48 (95% CI, 1.54, 13.04) along with the other risk factors [59].

Interestingly, higher prevalence of CKD was not responsible for the high incidence of ESRD in Portuguese population. Infact the high prevalence of risk factors may account for the high incidence of CKD. The obesity prevalence was 33.7%, diabetes 11.7% and metabolic syndrome 41.5%. ESRD incidence was higher than other European countries but lower than the US. Adjusted OR (95% CI) for CKD: Diabetes = 1.20 (0.96–1.50) and Obesity = 1.14 (0.94–1.39) [57].

Even though some studies have shown that obesity is the major risk factor for developing ESRD, independent of diabetes. However, this review reveals that obesity enhances the risk for developing diabetes and they in combination give rise to the kidney disease particularly the ESRD in the general population.

ESRD in patients with obesity and diabetes is a life-threatening disease with a poor survival rate and is associated with high healthcare costs. In this review, we specified a clear eligibility-criteria and conducted a comprehensive research to achieve the objectives.

Obesity and its contribution in ESRD development

The obesity epidemics and diabetes are growing worldwide. It has a strong affect across the globe and have far reaching social and health consequences. Several studies carried out on this topic realized a strong co-relation between obesity, diabetes and kidney disease resulting that obesity and diabetes increases the risk of CKD and ESRD. Our systemic review based on retrospective, prospective, case control and cross-sectional studies, gives strong enough evidence regarding the unavoidable impact of obesity and diabetes on the increased growth of ESRD.

Fox et al evaluated that baseline BMI predicts subsequent kidney disease after a mean follow up of 18.5 years. In this cohort of 2285 men and women, increase of each unit in BMI was associated with 1.23-fold elevated risk for new onset kidney disease. Importantly in a cohort study (n = 100753), the relationship between obesity and the risk of kidney disease in men and women was analyzed. A strong dose-response relationship between BMI and risk of ESRD was found in men, but not in women [41].

In several other studies it was found that overweight and obesity is a common and strong risk factor for the development of ESRD in the general population. Furthermore, the increase in the BMI increased the rate of CKD, ESRD [15, 32, 39] and risk of chronic renal failure [56]. A case control study between two ethnic groups that is black and white showed a significant difference in the association between obesity and ESRD. Overweight and obesity at the age of 21 was associated with increased ESRD incidence in whites than in blacks. Strikingly, a 3-fold increase was observed in obese whites compared to normal weight person [37].

The risks for the adverse outcomes of obesity were progressive with increasing BMI. Furthermore, the obesity in the presence of DM increased the risk of graft failure. However, the study showed that obesity alone may also be a risk factor for a shorter time to graft failure [64]. Notably the prevalence of CKD in US in the year 1999–2004 was higher than 1988–1994 [38]. This increase in the prevalence was observed in the total sample regardless of their BMI state. As the data shows that 28% of the participants were obese, in our opinion, this would have been much better if the study had carried out on different BMI categories. On the other hand, the cross-sectional study by Evangelista et al provides enough information about obesity prevalence in CKD patients. Importantly, obesity was higher in prevalent CKD patients than non-CKD. This support the idea that weight loss might be a good potential intervention for the avoidance of disease progression [40].

Obese patients with family history of ESRD were at higher risk of developing ESRD than non-family history of ESRD. Obesity and the start of dialysis therapy were independently associated with patients having family history of ESRD and genetic factor may also contribute to the familial risk of ESRD [42]. It was concluded after 14 years of follow-up that higher baseline BMI was linked with enhanced risk for CKD [12]. Similar findings were carried out in another study where the baseline BMI was strongly and independently associated with rapid CKD progression [14].

The review study on “elevated BMI as a risk factor for CKD” summarized that the impact of obesity in the pathogenesis of CKD seemed to be independent of hypertension and DM [34]. Interestingly, the review study by Wang et al observed that obesity in women was associated with high risk than in man and a positive linkage was observed between BMI and risk for kidney disease [65].

Diabetes and its role in ESRD progression

Diabetes in ESRD patients is life threatening disease with low survival rate and high healthcare costs. The prevalence of diabetic ESRD is still on the rise while due to better management of healthcare system, the incidence rate has declined in the developed and some developing countries.

In the retrospective study, a high burden of CKD was observed among persons with undiagnosed diabetes and prediabetes. The prediabetes individuals need earlier detection and management strategies for the prevention of development, progression and complications of diabetes and CKD associated with DM [53]. Furthermore, early detection and treatment of DM can prevent the DM related ESRD, as DM has been the leading risk factor of incident dialysis in Japan since 1988 [49].

It was noted that diabetes related ESRD incidence was increased in the early 1990s in the US, however it decreased in the later years in all age groups due to reduction in prevalence of ESRD risk factors, better treatment and care. The ESRD patients with diabetes are better treated now than in the late 1990s. Similar findings were observed during the examined period (1978–1991), where the growth in ESRD incidence was higher than the growth in prevalent chronic renal insufficiency in the US [51].

In a cross-sectional study, it was analyzed that the prevalence of proteinuria was 4-fold higher in those with DM compared to those without DM, indicating that proteinuria is a good indicator of kidney damage. Furthermore, early investigation of proteinuria, hematuria and GFR in the initial stage of kidney disease may provide a mean to reduce the ESRD burden [54]. The findings of Iseki et al strengthens the results of Chadban et al where a strong relationship between ESRD and proteinuria was found. It was concluded that proteinuria is a strong and independent risk factor for ESRD [50, 54].

A cross sectional study was conducted by Hochman and colleagues to analyse the incidence and prevalence of ESRD in the native American adults living on the Navajo nation. Higher prevalence and incidence of ESRD were observed in native American adults living on the Navajo nation. Majority of the ESRD patients were diabetic and higher ESRD prevalence was noted than the incidence [52].

Moreover, to assess the prevalence of CKD in the Mexican urban population, a cross sectional study revealed that prevalence rate of CKD in Mexico was similar as in developed countries. The higher prevalence rate of kidney disease may be due to DM but other factors such as genetic and socioeconomic may also play a role. Diabetes was a prominent risk factor for CKD in the siblings [55].

A high proportion of RRT risk was due to diabetes [48]. Strong connection was found between ESRD and three major risk factors namely diabetes, hypertension and glomerulonephritis, and ESRF population was largely influenced by age, gender and diabetes [28]. Type-2 diabetes was found to be the major cause of ESRD incidence and preventive strategies were strongly recommended to reduce the burden of ESRD incidences [29]. The review study by Ghaderian and colleagues concluded that renal transplantation, particularly preemptive transplantation is the best renal replacement therapy in diabetic ESRD patients. Although many complications may be associated with renal transplantation, but several studies recommended that it is associated with survival benefit and better quality of life [24].

Our review has some limitations which needs to be mentioned. Firstly, our search strategy only included PubMed and Google scholar, which might have resulted in the loss of some important articles related to our topic. Secondly, we did not include the studies that have discussed only type 1 diabetes, and also those studies other than the English language, which also might have resulted in the loss of some important studies.

Our systematic literature review describes the significant effects of obesity and diabetes on the increasing incidence and prevalence of CKD and ESRD. It was analyzed that overweight and obesity in younger age is markedly and positively associated with future treated ESRD incidence. Obese individuals having family history of ESRD are at much higher risk than the general population. Furthermore, diabetes, particularly type-2 diabetes is the major cause of CKD and ESRD incidence leading to RRT. In conclusion, the incidence and prevalence of CKD and ESRD in diabetic and obese population is more than the non-diabetic and non-obese population. We strongly recommend regular provision of health education and awareness trainings by the healthcare professionals on the prevention of CKD and ESRD, to control the CKD and ESRD incidence and prevalence in the future.

BMI: Body mass index; OR: Odd ratio; RR: Relative risk; DN: Diabetic nephropathy; CKD: Chronic kidney disease; GFR: Glomerular filtration rate; ESRD: End stage renal disease; RAAS: Renal-angiotensin-angiotensinogen-system; US-NHANES: United States national health and nutrition examination survey; USRDS: United states renal data system; KNHANES: Korean national health and nutrition examination survey; SD: Standard deviation; PHS: Physicians health study; HUNT: Health survey of Nord-Trondelag County; OKIDS: Okinawa dialysis study; HDFP: Hypertension detection and follow-up program; eGFR: Estimated glomerular filtration rate; DM: Diabetes mellitus; RI: Renal insufficiency; CRI: Chronic renal insufficiency; MS: Metabolic syndrome; SCCS: Southern community cohort study; Ccr: Creatinine clearance; PMP: Per million population; RRT: Renal replacement therapy; REIN: Renal epidemiology and information network; CRF: Chronic renal failure; SRTR: Scientific registry of transplant recipients; ARF: Atherosclerotic risk factor; EPIRCE: Studio epidemiologico de la insuficiencia renal en Espana; HT: Hypertension; PREVADIAB: Prevalence diabetes.

Ethics approval and consent to participate

Not applicable

Consent for publication

Not applicable

Availability of data and materials

Not applicable

Competing interests

The authors declare that they have no competing interests.

Funding

Asmatullah Kakar was funded by Higher Education Commission (HEC) Pakistan. Furthermore, study design and manuscript writing were not associated with any funding.

Authors contributions

AK and SG have conceived and designed the study. AK screened and retrieved all the articles. NK, ACD and YM were involved in data analysis. AK and NK were involved in drafting the manuscript. Critical review was done by SG and AK. All authors have read and approved the final version.

Acknowledgments

The authors would like to thank Dr. Habib ur Rehman Kakar and Oumeima Senouci for their help and contribution to this study.

Organization WH. Obesity and overweight. Key Facts. World Health Organisation, 2020. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Accessed 3 July 2020.
Finkelstein EA, Khavjou OA, Thompson H, Trogdon JG, Pan L, Sherry B, et al. Obesity and severe obesity forecasts through 2030. Am J Prev Med. 2012;42:563–70.
Kelly T, Yang W, Chen C-S, Reynolds K, He J. Global burden of obesity in 2005 and projections to 2030. Int J Obes. 2008;32:1431.
Mallamaci F, Tripepi G. Obesity and CKD progression: hard facts on fat CKD patients. Nephrol Dial Transplant. 2013;28 suppl_4:iv105–8.
Maric-Bilkan C. Obesity and diabetic kidney disease. Med Clin North Am. 2013;97:59–74.
Bolignano D, Zoccali C. Effects of weight loss on renal function in obese CKD patients: a systematic review. Nephrology Dialysis Transplantation. 2013;28 suppl_4:iv82–98.
Zandi-Nejad K, Brenner BM. Strategies to retard the progression of chronic kidney disease. Med Clin North Am. 2005;89:489–509.
Srivastava T. Nondiabetic consequences of obesity on kidney. Pediatr Nephro. 2006;21:463–70.
Keller. From obesity to diabetes. Int J Vitam Nutr Res. 2006;76:172–7.
Ritz E. Diabetic nephropathy. Saudi J Kidney Dis Transpl. 2006;17:481–90.
Ram R, Goswami DN, Bhattacharya SK, Bhattacharya K, Saha BK, Saha J, et al. An epidemiological study on risk factors of diabetes mellitus among patients attending a medical college hospital in Kolkata, West Bengal. J Indian Med Assoc. 2006;104:428–30.
Gelber RP, Kurth T, Kausz AT, Manson JE, Buring JE, Levey AS, et al. Association between body mass index and CKD in apparently healthy men. Am J Kidney Dis. 2005;46:871–80.
Obermayr RP, Temml C, Knechtelsdorfer M, Gutjahr G, Kletzmayr J, Heiss S, et al. Predictors of new-onset decline in kidney function in a general middle-European population. Nephrol Dial Transplant. 2007;23:1265–73.
Othman M, Kawar B, El Nahas AM. Influence of obesity on progression of non-diabetic chronic kidney disease: a retrospective cohort study. Nephron Clin Pract. 2009;113:c16–23.
Hsu C, McCulloch CE, Iribarren C, Darbinian J, Go AS. Body mass index and risk for end-stage renal disease. Ann Intern Med. 2006;144:21–8.
Ix JH, Sharma K. Mechanisms linking obesity, chronic kidney disease, and fatty liver disease: the roles of fetuin-A, adiponectin, and AMPK. J Am Soc Nephrol. 2010;21:406–12.
KDOQI. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease. Am J Kidney Dis. 2007;49 2 Suppl 2:S12-154. https://www.ajkd.org/article/S0272-6386(06)01843-9/fulltext.
Serra A, Granada ML, Romero R, Bayés B, Cantón A, Bonet J, et al. The effect of bariatric surgery on adipocytokines, renal parameters and other cardiovascular risk factors in severe and very severe obesity: 1-year follow-up. Clin Nutr. 2006;25:400–8.
Agrawal V, Khan I, Rai B, Krause KR, Chengelis DL, Zalesin KC, et al. The effect of weight loss after bariatric surgery on albuminuria. Clin Nephrol. 2008;70:194–202.
Alexander JW, Goodman HR, Hawver LRM, Cardi MA. Improvement and stabilization of chronic kidney disease after gastric bypass. Surg Obes Relat Dis. 2009;5:237–41.
Navaneethan SD, Yehnert H. Bariatric surgery and progression of chronic kidney disease. Surg Obes Relat Dis. 2009;5:662–5.
Bell S, Fletcher EH, Brady I, Looker HC, Levin D, Joss N, et al. End-stage renal disease and survival in people with diabetes: a national database linkage study. QJM. 2014;108:127–34.
Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014;103:137–49.
Ghaderian SB, Hayati F, Shayanpour S, Mousavi SSB. Diabetes and end-stage renal disease; a review article on new concepts. J Renal Inj Prev. 2015;4:28.
Villar E, Remontet L, Labeeuw M, Ecochard R. Effect of age, gender, and diabetes on excess death in end-stage renal failure. J Am Soc Nephrol. 2007;18:2125–34.
Villar E, Chang SH, McDonald SP. Incidences, treatments, outcomes, and sex effect on survival in patients with end-stage renal disease by diabetes status in Australia and New Zealand (1991–2005). Diabetes Care. 2007;30:3070–6.
Burrows NR, Li Y, Geiss LS. Incidence of treatment for end-stage renal disease among individuals with diabetes in the US continues to decline. Diabetes Care. 2010;33:73–7.
Khan S, Hussain T, Salahuddin N, Mehreen S. Risk Factors of End Stage Renal Disease in Peshawar, Pakistan: Odds Ratio Analysis. Open Access Maced J Med Sci. 2016;4:381.
Assogba FG, Couchoud C, Hannedouche T, Villar E, Frimat L, Fagot-Campagna A, et al. Trends in the epidemiology and care of diabetes mellitus-related end-stage renal disease in France, 2007–2011. Diabetologia. 2014;57:718–28.
Arefzadeh A, Lessanpezeshki M, Seifi S. The cost of hemodialysis in Iran. Saudi J Kidney Dis Transpl. 2009;20:307.
Mousavi SSB, Sametzadeh M, Hayati F, Fatemi SM. Evaluation of acquired cystic kidney disease in patients on hemodialysis with ultrasonography. Iran J Kidney Dis. 2010;4:223.
Felizardo RJF, da Silva MB, Aguiar CF, Câmara NOS. Obesity in kidney disease: A heavyweight opponent. World J Nephrol. 2014;3:50–63.
Tran M-H, Foster CE, Kalantar-Zadeh K, Ichii H. Kidney transplantation in obese patients. World J Transplant. 2016;6:135–43.
Garland JS. Elevated body mass index as a risk factor for chronic kidney disease: current perspectives. Diabetes Metab Syndr Obes. 2014;7:347–55.
Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.
Tozawa M, Iseki K, Iseki C, Oshiro S, Ikemiya Y, Takishita S. Influence of smoking and obesity on the development of proteinuria. Kidney Int. 2002;62:956–62.
Akwo EA, Cavanaugh KL, Ikizler TA, Blot WJ, Lipworth L. Increased body mass index may be associated with greater risk of end-stage renal disease in whites compared to blacks: a nested case–control study. BMC nutrition. 2015;1:24.
Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, et al. Prevalence of chronic kidney disease in the United States. JAMA. 2007;298:2038–47.
Foster MC, Hwang S-J, Larson MG, Lichtman JH, Parikh NI, Vasan RS, et al. Overweight, obesity, and the development of stage 3 CKD: the Framingham Heart Study. Am J Kidney Dis. 2008;52:39–48.
Evangelista LS, Cho W-K, Kim Y. Obesity and chronic kidney disease: A population-based study among South Koreans. PloS one. 2018;13:e0193559.
Fox CS, Larson MG, Leip EP, Culleton B, Wilson PW, Levy D. Predictors of new-onset kidney disease in a community-based population. JAMA. 2004;291:844–50.
Speckman RA, McClellan WM, Volkova NV, Jurkovitz CT, Satko SG, Schoolwerth AC, et al. Obesity is associated with family history of ESRD in incident dialysis patients. American journal of kidney diseases. 2006;48:50–8.
Hallan S, de Mutsert R, Carlsen S, Dekker FW, Aasarød K, Holmen J. Obesity, smoking, and physical inactivity as risk factors for CKD: are men more vulnerable? Am J Kidney Dis. 2006;47:396–405.
Iseki K, Ikemiya Y, Kinjo K, Inoue T, Iseki C, Takishita S. Body mass index and the risk of development of end-stage renal disease in a screened cohort. Kidney Int. 2004;65:1870–6.
Kramer H, Luke A, Bidani A, Cao G, Cooper R, McGee D. Obesity and prevalent and incident CKD: the Hypertension Detection and Follow-Up Program. Am J Kidney Dis. 2005;46:587–94.
Gomez P, Ruilope LM, Barrios V, Navarro J, Prieto MA, Gonzalez O, et al. Prevalence of renal insufficiency in individuals with hypertension and obesity/overweight: the FATH study. J Am Soc Nephrol. 2006;17(12 Suppl 3):194–200.
Ng YP, Ahmed R, Ooi GS, Lau CY, Balasubramanian GP, Yap CH. The rate of progression of type 2 diabetes mellitus to end stage renal disease - A single centred retrospective study from Malaysia. Diabetes Metab Syndr. 2018;12:1025–30.
Icks A, Haastert B, Genz J, Giani G, Hoffmann F, Trapp R, et al. Incidence of renal replacement therapy (RRT) in the diabetic compared with the non-diabetic population in a German region, 2002–08. Nephrol Dial Transplant. 2010;26:264–9.
Iseki K. Predictors of diabetic end-stage renal disease in Japan. Nephrology. 2005;10:2–6.
Iseki K, Ikemiya Y, Iseki C, Takishita S. Proteinuria and the risk of developing end-stage renal disease. Kidney Int. 2003;63:1468–74.
Hsu C, Vittinghoff E, Lin F, Shlipak MG. The incidence of end-stage renal disease is increasing faster than the prevalence of chronic renal insufficiency. Ann Intern Med. 2004;141:95–101.
Hochman ME, Watt JP, Reid R, O’Brien KL. The prevalence and incidence of end-stage renal disease in Native American adults on the Navajo reservation. Kidney Int. 2007;71:931–7.
Plantinga LC, Crews DC, Coresh J, Miller ER, Saran R, Yee J, et al. Prevalence of chronic kidney disease in US adults with undiagnosed diabetes or prediabetes. Clin J Am Soc Nephrol. 2010;5:673–82.
Chadban SJ, Briganti EM, Kerr PG, Dunstan DW, Welborn TA, Zimmet PZ, et al. Prevalence of kidney damage in Australian adults: The AusDiab kidney study. J Am Soc Nephrol. 2003;14(7 Suppl 2):131–8.
Amato D, Alvarez-Aguilar C, Castañeda-Limones R, Rodriguez E, Avila-Diaz M, Arreola F, et al. Prevalence of chronic kidney disease in an urban Mexican population. Kidney Int Suppl. 2005;:S11-17.
Ejerblad E, Fored CM, Lindblad P, Fryzek J, McLaughlin JK, Nyrén O. Obesity and risk for chronic renal failure. J Am Soc Nephrol. 2006;17:1695–702.
Vinhas J, Gardete-Correia L, Boavida JM, Raposo JF, Mesquita A, Fona MC, et al. Prevalence of chronic kidney disease and associated risk factors, and risk of end-stage renal disease: data from the PREVADIAB study. Nephron Clin Pract. 2011;119:c35–40.
Kramer HJ, Saranathan A, Luke A, Durazo-Arvizu RA, Guichan C, Hou S, et al. Increasing body mass index and obesity in the incident ESRD population. J Am Soc Nephrol. 2006;17:1453–9.
Otero A, Gayoso P, Garcia F, de Francisco AL. EPIRCE study group. Epidemiology of chronic renal disease in the Galician population: results of the pilot Spanish EPIRCE study. Kidney Int Suppl. 2005;:S16-19.
Otero A, de Francisco A, Gayoso P, García F, EPIRCE Study Group. Prevalence of chronic renal disease in Spain: results of the EPIRCE study. Nefrologia. 2010;30:78–86.
Hoffmann F, Haastert B, Koch M, Giani G, Glaeske G, Icks A. The effect of diabetes on incidence and mortality in end-stage renal disease in Germany. Nephrol Dial Transplant. 2011;26:1634–40.
Connor TMF, Oygar DD, Gale DP, Steenkamp R, Nitsch D, Neild GH, et al. Incidence of end-stage renal disease in the Turkish-Cypriot population of Northern Cyprus: a population based study. PLoS ONE. 2013;8:e54394.
Chen H-M, Shen W-W, Ge Y-C, Zhang Y-D, Xie H-L, Liu Z-H. The relationship between obesity and diabetic nephropathy in China. BMC Nephrol. 2013;14:69.
Kwan JM, Hajjiri Z, Metwally A, Finn PW, Perkins DL. Effect of the obesity epidemic on kidney transplantation: obesity is independent of diabetes as a risk factor for adverse renal transplant outcomes. PloS one. 2016;11:e0165712.
Wang Y, Chen X, Song Y, Caballero B, Cheskin LJ. Association between obesity and kidney disease: a systematic review and meta-analysis. Kidney Int. 2008;73:19–33.

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Global Impact of Obesity and Diabetes on the Increase Incidence and Prevalence of Chronic Kidney disease (CKD) and End Stage Renal Disease (ESRD): A Systematic Review

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Abstract

Figures

Background

Methods

Data sources and searches

Selection criteria

Data collection and extraction

Results

Study design and quality assessment

General characteristics of the included studies

Risk factors for CKD/ ESRD

Obesity is associated with profound increased incidence and prevalence of CKD and ESRD

Diabetes is a prominent risk factor for the elevated burden of CKD and ESRD

Discussion

Obesity and its contribution in ESRD development

Diabetes and its role in ESRD progression

Conclusion

Abbreviations

Declarations

Ethics approval and consent to participate

Consent for publication

Availability of data and materials

Competing interests

Funding

Authors contributions

Acknowledgments

References

Supplementary Files

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