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Clin J Am Soc Nephrol. 2010 Aug; 5(8): 1401–1409.
PMCID: PMC2924407
Original Articles

Obesity-Related Glomerulopathy: Body Mass Index and Proteinuria


Background and objectives: Obesity-related glomerulopathy (ORG) is an increasing cause of end-stage renal disease, but evidence concerning the effects of treatments is rather limited. This study was aimed at exploring the renoprotective effects of weight loss on patients with ORG.

Design, setting, participants, & measurements: A total of 63 patients with renal biopsy–proven ORG had food and exercise intervention in the physician-supervised weight loss program and were divided into three groups on the basis of the percentage of weight change from baseline to follow-up: significant weight loss (>3% reduction in body mass index [BMI]), stable weight, or significant weight gain (>3% increase). Metabolic parameters and renal lesions were evaluated regularly for 2 years.

Results: After 6 months, 27 patients lost weight by 8.29 ± 4.00%, with a mean decrease in proteinuria of 35.3%, whereas 24 months later, 27 patients achieved a 9.20 ± 3.78% reduction in BMI and a 51.33% reduction in urine protein secretion. The levels of serum triglyceride, serum uric acid, and BP were also decreased. Contrarily, in patients with increased BMI, urine protein was increased by 28.78%. Correlation analysis showed proteinuria was associated with BMI, serum triglyceride, and uric acid, and multivariate regression analysis indicated the changes in BMI were the only predictor of proteinuria (P < 0.01).

Conclusions: Weight loss intervention benefited remission of proteinuria in patients with ORG, whose function could not be replaced by conventional pharmacotherapy.

Profound lifestyle changes in modern China have resulted in a remarkable increase in the population of obesity (1). Sequelae of obesity include type 2 diabetes, hypertension, cardiovascular diseases, and the progression of renal diseases (2,3). Weight loss, either after bariatric surgery or after lifestyle modification, normalizes blood glucose (4) and decreases BP and plasma lipids (5,6) in obese patients. Similarly, a significant reduction in urinary albumin excretion and glomerular hyperfiltration has been reported in morbidly obese patients with a dramatic decrease of body mass index (BMI) (7,8). Moreover, even a small decrease in BMI is related to the reduction of proteinuria in patients with diabetic nephropathy and other chronic kidney diseases (911).

Obesity-related glomerulopathy (ORG) has been reported in more and more obese patients without overt diabetes and pre-existing renal diseases (12,13). It is a secondary form of focal and segmental glomerulosclerosis (FSGS) manifested as proteinuria and progressive renal dysfunction (14). The prognosis for patients with ORG were significantly different from those with diabetic nephropathy or with the primary form of FSGS (15). However, the relationship between weight loss and the outcome of ORG has not been clarified until now. Conclusions from the studies of diabetic nephropathy (9) and unidentified chronic kidney diseases (10,11,16) could be different from those of histologic-proven ORG. And evidence from case reports (17,18) concerning the aggressive treatment of ORG with bariatric surgery is unpersuasive because only a small population was involved. In addition, the long-term effects of weight loss in patients with ORG are not studied. So far, no well-designed clinical research studies for histologic-proven ORG are available, especially those concerning the long-term effects of weight loss and lifestyle modification.

In this regard, this study was designed to observe the relationship between body weight reduction and the changes in proteinuria in patients with ORG. Patients who were diagnosed with ORG by renal biopsy were included in the physician-supervised weight loss program in our institute and followed up for 2 years. It was the first study demonstrating that the remission of ORG could be achieved in patients with weight loss, but not in patients with increasing body weight.

Materials and Methods

Patient Selection

Patients with biopsy-proven ORG diagnosed in our institute from February 2002 to August 2007 were recruited into this study. The inclusion criteria included the following: (1) The presence of obesity [BMI no less than 28 kg/m2 according to the Working Group on Obesity in China (19)]; (2) fasting blood glucose level <7.0 mmol/L and postprandial glucose <11.1 mmol/L; (3) 24-hour urinary protein excretion >0.4 g, without gross hematuria or evident microscopic hematuria; (4) pathologic features included glomerulomegaly with or without focal segmental glomerular sclerosis, and pauci-immune complex deposition with or without nonspecific or segmental C3 and IgM deposition; (5) other underlying renal diseases such as IgA nephropathy, membranous nephropathy, and diabetic nephropathy were excluded carefully. Informed signed consents were obtained for 63 patients, and this study was approved by the Human Investigation Committee at Jinling Hospital, Nanjing, China.

Study Design

Upon baseline investigation, patients were assigned to the physician-supervised weight loss program in the Outpatient Center in our institute. A diet with an energy reduction of 500 kcal with respect to their total caloric requirements was assigned to all of the patients, which were calculated according to sex, height, and weight by the Harris-Benedict formula as 135% of the basal metabolic rate. The diet contained 55 to 65% carbohydrates, 20 to 30% fat, and 15% protein (20). Patients were encouraged to do aerobic exercise for at least 60 minutes at a frequency of at least 3 d/wk. The types of exercise were chosen by patients according to their preference, mainly including walking, jogging, and swimming. Anerobic exercise and anti-obesity medication was avoided. The implementation of diet and exercise was carried out at home. Patients were regularly interviewed every 3 months about the implementation of the dietary and exercise intervention. Angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) and rhein were given to the patients and lipid-lowering drugs were used in patients with refractory dyslipidaemia. The patients were assessed 6 and 24 months later at the same outpatient center. Evaluation included the BMI, BP, 24-hour urine protein, estimated GFR (eGFR), fasting blood glucose level, serum triglyceride (TG), serum total cholesterol, HDL cholesterol (HDL), LDL cholesterol (LDL), and serum uric acid (UA). BP was measured in the morning in duplicate at each visit after 30 minutes of rest. On the basis of the changes in BMI, patients were divided into three groups: increased BMI group (an increase in BMI >3%), stable BMI group (the changes in BMI no greater than 3%), and decreased BMI group (a decrease in BMI >3%).

Pathologic Features

Selected renal biopsy specimens were examined by two experienced nephrologists blind to the study. Glomerular lesions, proximal tubular atrophy, interstitial fibrosis, interstitial inflammatory cell infiltration, and hyaline degeneration of small arteries were recorded. On the basis of the percentage of area with proximal tubular atrophy, interstitial fibrosis, and interstitial inflammatory cell infiltration in the renal cortex, the severity was classified into mild (≤25%), intermediate (26% to approximately 50%), and severe (>50%). On the basis of the percentage of small arteries with hyaline degeneration in all interstitial small arteries, the severity was divided into mild (≤25%), intermediate (26% to approximately 50%), and severe (>50%).

Other Definitions

On the basis of the outcome of proteinuria changes, the patients were divided into four groups: complete remission group (proteinuria <0.4 g/24 h with stable renal function), partial remission group (a decrease in proteinuria >50% of baseline value yet proteinuria >0.4 g/24 h), stability group (a change in proteinuria <50% of baseline value), and deterioration group (an increase in proteinuria >50% of the baseline value). Smoking was defined as currently smoking or smoking within 1 year. Hypertension was defined as systolic pressure of 140 mmHg or greater or diastolic pressure of 90 mmHg or greater or ongoing use of anti-hypertensive medications. eGFR was calculated according to the Modification of Diet in Renal Disease (MDRD) formula. New use of drugs was defined as beginning to use the drug after or within 2 weeks before enrollment.

Statistical Analyses

The quantitative data with normal distribution were expressed as mean ± SD and those with abnormal distribution as median (minimum, maximum). The qualitative data were presented as percentages. ANOVA, U test, or χ2 test was performed for comparisons among groups. Paired t test was used for comparisons between data before and after follow-up. Pearson, Spearman, or Kendall correlation analyses were used to analyze the relationship among different parameters. A value of P < 0.05 was considered statistically significant. Univariate linear regression was performed to screen the factors related to the changes in proteinuria in which the factor with a value of P < 0.05 was further applied into stepwise multivariate regression analysis. The statistical analysis was done with SPSS version 11.0.


As shown in Table 1, 63 patients with pathologically confirmed ORG were recruited. The mean BMI was 30.83 ± 2.86 kg/m2. Proteinuria was noted in all of the patients with a mean 24-hour urine protein excretion of 1.48 ± 0.87 g. Among these patients, three had heavy proteinuria (>3.5 g/24 h) but without hypoalbuminemia. The mean eGFR was 103.8 ml/min and eight patients had an eGFR <60 ml/min. Significant glomerulomegaly was present in all of the patients, whereas FSGS lesions were found in 35 of them. Correlation analysis indicated diastolic pressure was the only factor related to BMI.

Table 1.
General information for 63 patients with ORG and the correlation with BMI

Short-Term Effects of BMI Changes on Renal Injury and Metabolic Disturbance

A total of 56 patients returned for the first assessment at the sixth month. We divided them into increased BMI (n = 8), stable BMI (n = 21), and decreased BMI (n = 27) groups. No significant difference in the parameters at baseline was observed among these groups (Table 2). As shown in Table 3, in the decreased BMI group, the mean proteinuria was decreased from 1.57 ± 0.99 to 1.10 ± 0.92 g/24 h (P < 0.05) with a mean reduction of 35%. No profound changes in urine protein excretion were found in the stable and the increased BMI group. Figure 1a shows the distribution of the proteinuric outcome at the sixth month. Remission was observed in 48.1% of the patients with decreased BMI, and nearly half of them were completely remitted. However, in the increased BMI group, only one (12.5%) patient obtained remission and four patients (50%) obtained deteriorated proteinuria (P = 0.087). The TG/HDL ratio in the decreased BMI group was markedly reduced, but no difference of TG/HDL ratio changes was observed among groups.

Table 2.
General information for the patients at baseline
Table 3.
Changes in renal lesions and metabolic parameters after the diet and exercise intervention
Figure 1.
Relationship between changes in body weight and outcome of proteinuria at the (a) 6th month (short term) and (b) 24th month (long term).

Long-Term Effects of BMI Changes on Renal Injury and Metabolic Disturbance

Forty-eight patients completed the second assessment at the 24th month. On the basis of the changes in BMI, the patients were re-divided into increased BMI (n = 9), stable BMI (n = 12), and decreased BMI (n = 27) groups (Table 3). The proteinuria was reduced from 1.71 ± 1.24 to 0.88 ± 1.00 g/24 h with a mean reduction of 51.3% in the decreased BMI group (P < 0.01) and increased by 28.78% in the increased BMI group (P < 0.05). As shown in Figure 1b, in the decreased BMI group, 25.8% of patients obtained complete remission from proteinuria, and partial remission was observed in 29.6%, which made an overall remission rate of 55.6%. Nevertheless, in the increased BMI group, no patient was found to have complete remission in proteiuria and even four (44.4%) of the patients had deteriorated proteinuria. A significant difference in the remission rate of proteinuria was observed among these groups. But no difference was noted in renal function among these groups.

Profound changes in metabolic parameters were also observed (Table 3). In the decreased BMI group, the TG/HDL ratio and TG was decreased by 17.3 and 17.1%, respectively (P < 0.05), and UA was decreased from 421 ± 127 to 388 ± 74 μmol/L (P < 0.01). In addition, in the patients with decreased BMI, the systolic pressure and diastolic pressure were significantly decreased, with a mean reduction of 7.44 and 9.50%, respectively.

Factors Related to the Outcome of Proteinuria Changes

As described above, weight control could confer short-term and long-term protective effects against proteinuria in patients with ORG. To explore the factors related to the outcome of proteinuria changes, we ran univariate and stepwise multivariate regression modeling analyses, using the changes in proteinuria as a dependent variate. Besides weight changes, the following covariates were examined in the analyses: gender, age, baseline weight, both baseline and percentage change of BP, serum glucose, cholesterols, triglycerides, uric acid, new use of ACEI/ARB, rhein, and lipid-lowering drugs after 24 months. Results showed a strong relationship between decreased proteinuria and weight loss, decreased serum triglyceride level, and reduced serum uric acid level (Figure 2). However, multivariate stepwise regression analysis indicated the changes in body weight, but not the serum triglyceride level and uric acid level, were the only factor related to the changes in proteinuria (R2 = 0.278; P = 0.001).

Figure 2.
Results from univariate regression analysis, relating change in proteinuria (dependent variable) at the 24th month. Ch, serum cholesterol; Glu, fasting blood glucose; SBP, systolic BP; DBP, diastolic BP; ΔACEI/ARB, new use of angiotensin-converting ...

Factors Related to the Outcome of Proteinuria and Renal Function in Patients with Decreased BMI

Although patients with decreased BMI tended to have a better outcome of proteinuria, there were still 12 (44.4%) patients who obtained no apparent remission. To explore the factors causing the difference in the outcome of proteinuria changes, these patients were subdivided into two groups: remission group (complete and partial remission) and nonremission group (stable and deteriorated proteinuria). The laboratory findings and pathologic features were compared between the groups. Greater reduction in BMI in the remission group than that in the nonremission group was found (10.76 ± 3.72% versus 7.28 ± 2.97%; P < 0.05). Meanwhile, the reduction in TG (−35.68 ± 16.96 versus 4.91 ± 40.95%; P < 0.01) and UA (−11.51 ± 11.23 versus −2.08 ± 8.60%; P < 0.05) in the remission group was also greater. Figure 3 showed the patients could be easily divided into two categories by the combination of reduction in BMI, TG, and UA level. Although both groups had similar reduction in BP, the BP level at the follow-up was not consistent. The diastolic pressure level in the remission group was lower than that in the nonremission group (73.8 ± 5.7 versus 81.5 ± 9.0 mmHg; P < 0.05) and systolic pressure had the same tendency (122.6 ± 8.4 versus 129.1 ± 7.7 mmHg; P = 0.07). Furthermore, no significant difference was noted between these two groups in the drug use and pathologic features are noted in Table 4.

Figure 3.
Relationships between the extent of reduction in BMI, TG, UA, and outcome of proteinuria in 27 patients with decreased BMI after a 2-year follow-up. Solid spots represent remission in proteinuria (complete remission and improvement in proteinuria; n ...
Table 4.
Relationship of pathologic features and medications with the outcome of renal lesions in 27 patients with decreased BMI

Reduction of BMI and proteinuria did not benefit renal function in this study. During the 2 years of follow-up, only one patient, who had sustained moderate proteinuria, developed a doubled serum creatinine level. A reduction in eGFR >20% was noted in 13 patients, among whom two (22.2%) had increased BMI, four (33.3%) stable BMI, and seven (25.9%) decreased BMI. To further explore the factors related to renal function, the medication, laboratory findings, and pathologic features (Table 4) of the 27 patients with reduced BMI were analyzed. However, no significant factors were found to be correlated with renal function decline, and the percentage of tubular atrophy and renal interstitial fibrosis >25% would be suggested as a best candidate for predicting the deterioration of renal function with a P value at 0.084.


Our study, for the first time, demonstrated that weight loss reduced proteinuria in ORG patients. The renoprotective effect of weight loss was independent of conventional medication. With the decrease of BMI, diet and exercise intervention also benefitted patients with ameliorated plasma lipids, uric acid, and BP.

Weight loss by lifestyle modification decreased urinary protein by 35% after 6 months and by 51% after 24 months, respectively. Previous reports about diabetic patients had suggested an average of 30 to 50% reduction of proteinuria after significant weight loss by hypocaloric diet in 1 or 5 months (9,10) and a >50% reduction after a 12-month follow-up (21). It seemed that the short-term effects of weight loss on patients with ORG were comparable to those with diabetic nephropathy. Although a longer term effect had not been observed previously, our results showed that persistent weight loss helped to reduce proteinuria in 2 years and weight gain increased the risk of disease progression.

Weight loss alleviates glomerular hyperfiltration in obese patients (7,8). If it saved renal function in patients with chronic kidney diseases is still under debate. Reduced urinary protein excretion by weight loss intervention is expected to stabilize renal function (22). But unintentional weight loss is also reported as being associated with the progression of renal diseases (23), which might reflect nutritional deficit being related to disease progression (24). In our study, we aimed to observe the effect of weight loss intervention in the renal function of patients with overt ORG, but failed to find a correlation between weight changes and changes in eGFR. It might be due to the relatively short duration of follow-up (15,25). In fact, most of our patients had stable renal function, and only one patient doubled serum creatinine at the end of the follow-up. Longer term follow-up would be needed to further clarify this question. Nevertheless, we found that tubular atrophy and interstitial fibrosis might be the best candidate predictors of renal function (P = 0.084), raising the importance of the pathologic examination upon diagnosis. It should also be acknowledged that eGFR calculated by the MDRD equation is not reliable in obese patients, especially those with an eGFR >60 ml/min. Therefore, further studies using iothalamate studies are warranted.

Our observations suggested that metabolic factors other than BMI had an effect on proteinuria, including plasma lipids, uric acid, and BP. The decrease of TG/HDL ratio was an early manifestation after weight loss. The TG/HDL ratio was not only strongly related to BMI but also a sensitive indicator reflecting the insulin resistance in nondiabetic patients with obesity (26). Thus, the reduced TG/HDL ratio might imply the improvement of insulin resistance in patients with decreased BMI. Both the regression analyses and the factor analyses in patients with weight loss showed that reduction of plasma TG and UA is partly associated with the uric protein–lowering effect of weight loss, which was consistent with previous reports (5,6,27). Interestingly, although patients with weight loss had significant decreased BP, the influence of BP on proteinuria seemed to be more related to the absolute pressure, implicating that there might be a threshold value of BP related to the outcome of proteinuria.

ACEI/ARB was widely used in patients with renal diseases because of its effect of reducing proteinuria (28). And all of our patients were given the medication except for those having contraindications. Meanwhile, rhein was used in most of the Chinese patients with diabetic nephropathy. It was demonstrated to reverse the cellular hypertrophy, fibronectin synthesis, and excessive glucose uptake of the diabetic mesangial cells, by inhibiting the hexosamine pathway (29). Therefore, the use of two drugs may have additional benefits for patients with ORG. No profound correlation was found between new use of ACEI/ARB and proteinuria, possibly implicating the occurrence of aldosterone escape. However, it is difficult to assess the effects of these drugs because they were widely used in our patients. A multicentered, randomized, double-blind, placebo-controlled phase III clinical trial of rhein is now being undertaken in China in patients with diabetic nephropathy, which will help us to further investigate its effect.

Compliance with the diet and exercise treatment is a crucial issue in assessment of therapeutic effectiveness. According to our observation, there were 15 out of 63 patients that were poorly adherent and lost in the 2-year follow-up, which might suggest poor compliance in a small group of patients. However, most patients had good compliance with the therapy. In 27 patients who lost weight at the 6th month, 23 of them showed a continuous decreased BMI at the 24th month. Although lifestyle adjustment is difficult for obese patients to stick to, the report of favorable outcome of weight control in a relatively short period (6 months) may be very encouraging and enhance their adherence with the therapy. A frequent follow-up and education may also help physicians to discover existing problems and improve the effects of lifestyle modification in ORG.




This work was supported by the National Natural Science Foundation of China (Grant 30800546) and the Doctoral Foundation of Education, Ministry of China (Grant 200802841008).


Published online ahead of print. Publication date available at www.cjasn.org.

Access to UpToDate on-line is available for additional clinical information at http://www.cjasn.org/


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