Improvement of End-stage Renal Disease in an Obese Diabetic Patient After Gastric Bypass

| October 21, 2013 | 0 Comments

by Ji Yeon Park, MD, and Yong Jin Kim, MD, PhD

Drs. Park and Kim are from the Department of Surgery, Soonchunhyang University Hospital, Daesagwan-ro, Yongsan-gu, Seoul, 140-887, Republic of Korea.

Funding: No funding was provided.
Disclosures: The authors report no conflicts of interest relevant to the content of this article.

Bariatric Times. 2013;10(10):22–24.

Background: Obesity is a growing health problem worldwide. Obesity is not only closely associated with increased incidence of various comorbidties, such as diabetes and hypertension, but also serves as an independent risk factor for progression of renal insufficiency. Significant weight reduction appears to be the most important therapeutic approach to the management of obesity-related renal dysfunction. Methods: We report a case of a female patient with morbid obesity with stage V chronic kidney disease whose renal function was improved and stabilized following substantial weight loss after Roux-en-Y gastric bypass. Results: The present case showed that surgical treatment of morbid obesity could improve or stabilize creatinine in patients with chronic renal failure. The reduction of glomerular hyperfiltration and blood pressure as well as improved insulin resistance might have contributed to the decrease in serum creatinine level in the patient. Conclusion: Bariatric surgery can be performed safely on patients with chronic renal disease and might have a role in retarding the progression of renal dysfunction in carefully selected patients with morbid obesity.

Obesity is a growing health problem worldwide. Obesity is not only associated with increased incidence of various morbidities, such as diabetes, hypertension, dyslipidemia, and coronary artery disease, but also with increased mortality and reduction in life expectancy.[1] It is also implicated as a major risk factor for the initiation and development of chronic kidney disease (CKD), because of its association with diabetes and hypertension, which are the two most common causes of CKD. Furthermore, accumulating evidence suggests it is likely that obesity has independent effects on renal dysfunction.[2,3]

At present, bariatric surgery is proven to be the most effective method to achieve sustained weight loss in the long term. Post-surgical weight loss in patients with morbid obesity improves all obesity-related comorbidities in consequence.[4] Individuals with morbid obesity and type 2 diabetes benefit from weight loss, as this allows better glycemic control and modifies the co-existing risk factors for heart disease and other comorbidities that constitute the metabolic syndrome.[5] Several studies have shown that obesity-related renal alterations in patients with morbid obesity were considerably ameliorated with extensive weight loss after bariatric surgery.[6–8]

Here, we report a case that illustrates the improvement of renal function after Roux-en-Y gastric bypass (RYGB) in a patient with morbid obesity with type 2 diabetes.

Case Report
A 54-year-old woman with obesity (body mass index [BMI] 41.4kg/m2) was referred to the endocrinology and nephrology department for preoperative medical evaluation and management before RYGB surgery for morbid obesity. She had type 2 diabetes for about 15 years and being treated with insulin therapy. She had associated diabetic nephropathy and retinopathy for 10 years. She had long-standing hypertension treated with combination of angiotensin receptor blocker (ARB), calcium channel blocker, and diuretics for 10 years. She also had coronary artery disease, which required coronary stent insertion in 2009. Since then, she has been on antiplatelet medications (aspirin and clopidogrel). She was diagnosed with stage V CKD, but had not yet undergone dialysis, and was considering undergoing renal replacement therapy in the near future.

Her pre-surgical evaluation showed excess body weight of 43.7 percent, fasting plasma glucose (FPG) of 187mg/dL, fasting plasma insulin of 18.7μU/mL, glycosylated hemoglobin A1c (HbA1c) of 9.3 percent. She was admitted for strict preoperative glycemic control two weeks before surgery, which was barely achieved with daily administration of high dose insulin. Serum blood urea nitrogen (BUN), creatinine, and cystatin-C level was 61.0mg/dL, 3.1mg/dL, and 3.9mg/L, respectively. The estimated glomerular filtration rate (GFR) was 13.6mL/min. A 24-hour urine collection demonstrated proteinuria of 2147.6mg/24hr and microalbuminuria of 1027.7mg/24hr. She did not show detectable peripheral edema.

In September 2012, she underwent RYGB, creating a small gastric pouch and a Roux loop with a 75cm alimentary limb. There were no complications observed during the postoperative period.

The patient’s characteristics and laboratory results of renal parameters are summarized in Table 1. On her 30-day postoperative visit, she showed a weight loss of 17.64 pounds (8kg) with good tolerance for food. Her serum BUN, creatinine, and cystatin-C level decreased to 29mg/dL, 2.04mg/dL and 2.6mg/L, respectively, with estimated GFR of 27.0mL/min. As she experienced hypoglycemic symptoms with the same insulin dosage prescribed before surgery, the dose was reduced accordingly by her endocrinologist. The dose of her hypertension medications was also reduced. At six months after surgery, she showed weight loss of 37.48 pounds (17kg) with a BMI of 34.2kg/m2. Serum BUN and creatinine level reached 27mg/dL and 1.92mg/dL, respectively, showing improved GFR of 28.9mL/min. With reduced dosage of insulin, she showed FPG of 126mg/dL and HbA1c of 6.6 %; therapy with insulin administration was discontinued and replaced by oral antihyperglycemic medication instead. All antihypertensive drugs were also discontinued except for the ARB for diabetic nephropathy.

Several recent epidemiologic studies have shown that obesity and the metabolic syndrome are independent predictors of CKD.[2,9,10] The pathophysiology of obesity-related CKD is complex and multifactorial. Obesity may promote kidney damage indirectly by developing diabetes and hypertension, as these two conditions are closely associated with morbid obesity and are known to account for approximately 70 percent of end-stage renal disease (ESRD), requiring dialysis and/or renal transplantation in patients with obesity.[10,11] In diabetic nephropathy, hyperglycemia triggers a cascade of events that are injurious to the kidney, including the production of vasodilatory prostaglandins, inflammatory cytokines, advanced glycosylation products, and reactive oxygen species.

Obesity may also result in renal injury. The exact mechanism of obesity-related nephropathy is still unclear, but may include hemodynamic and various hormonal factors induced by obesity itself. Obesity raises blood pressure by increasing renal tubular sodium reabsorption, impairing pressure natriuresis. This causes volume expansion because of activation of the sympathetic nervous system and renin-angiotensin system and by physical compression of the kidneys, especially when visceral obesity is present.[12,13]

Obesity also causes renal vasodilation and glomerular hyperfiltration that initially serve as compensatory mechanisms to maintain sodium balance in the face of increased tubular reabsorption. In the long-term, however, these changes, along with the increased systemic arterial pressure, create a hemodynamic burden on the kidneys that causes glomerular injury. Glomerular hyperfiltraton favors the occurrence of microalbuminuria and proteinurian in patients with obesity with unknown renal disease and, in addition, can lead to progression of pre-existing renal disease to ESRD.[14–16]

There is also growing evidence that obesity itself is a pro-inflammatory state. Several studies have shown that adipose tissue, especially visceral adipose tissue, is a major source of cytokine secretion, which in turn mediates insulin resistance.[17–19] Furthermore, insulin resistance potentiates further chronic inflammation, as insulin is an anti-inflammatory hormone.[20] Increased level of acute phase reactants and cytokines, as well as reactive oxygen species in patients with obesity have potentially nephrotoxic effects, which promotes glomerular inflammatory responses leading to progression of CKD.[3,21,22] Leptin secreted from excess adipose tissue might directly lead to renal fibrosis.[23] In addition, Chalmers et al suggested that the various mediators associated with oxidative stress results in progressive renal fibrosis.[24]

Kambham et al reported distinct histopathological changes in the glomeruli of patients with obesity, referred to as obesity-related glomerulopathy, that are characterized by glomerulomegaly and focal segmental glomerulosclerosis (FSGS).[25] This entity defers from idiopathic FSGS with more indolent course and less presentation of classic symptoms and signs of nephrotic syndrome, which is regarded as a distinct disease process related specifically to the degree of obesity. With prolonged obesity, there is increasing urinary protein excretion and gradual loss of nephron function that worsens with time and exacerbates hypertension. With the worsening of metabolic disturbances and the development of type 2 diabetes in some patients with obesity, kidney disease progresses much more rapidly.[26]

Weight loss should be encouraged for patients with CKD and obesity as weight loss reduces proteinuria and glomerular hyperfiltration, which is frequent in this patient population. Although some studies have shown that treatment with renoprotective drugs, such as angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers, are useful in reducing obesity-related proteinuria, these treatments seem to have temporary effects with a late proteinuria rebound.[27]
Significant weight reduction would appear to be the most important therapeutic approach to the management of obesity-related renal dysfunction. Bariatric surgery might provide an approach that limits the progression of nephropathy to ESRD in these patients. For patients with obesity on dialysis treatment who are eligible for kidney transplantation, weight loss is recommended to prevent obesity-related surgical complications and improve patient and graft survival after transplantation.[28,29] It is controversial to exclude this patient population from transplant candidacy based on their obesity because there are insufficient data to support this and patients with obesity selected for transplant may gain clinical benefits compared with long-term dialysis. However, most of the transplant centers use BMI as a selection criterion, with a range of 35 to 45kg/m2 as the upper limit to initiate an evaluation for transplantation in practice.[30] If all other conservative or pharmacological measures fail, bariatric surgery may be the only option for patients with severe obesity.

The renal function of the patient in this case report had improved after losing weight, as presented by the reduction in serum creatinine, BUN, and cystatin C. The beneficial effect of bariatric surgery in this case may include various factors including the following: 1) improved glomerular hymodynamic, 2) decrease in hyperfiltration, 3) reduced production of inflammatory cytokines, and 4) improved insulin resistance and blood pressure. Although she still has an elevated creatinine, her planned dialysis was postponed. Whether serum creatinine level will continue to decrease if she loses more weight remains to be seen.

It is conceivable that weight loss would delay the progression of renal dysfunction. The present case showed that surgical treatment of morbid obesity could improve or stabilize creatinine in patients with chronic renal failure. Since this is an observation of one patient during a relatively short period of time, it is still early to conclude that bariatric surgery is a benefit in prolonging renal disease. Further studies with longer outcomes need to be performed to determine whether bariatric surgery can assist to improve renal function in the long term. These studies should also focus on identifying those patients with obesity and renal insufficiency who may benefit from bariatric surgery. This might require intervention early in the disease process. Bariatric surgery might be considered as another potential therapeutic option in carefully selected patients with morbid obesity and CKD.

1.    Peeters A, Barendregt JJ, Willekens F, et al. Obesity in adulthood and its consequences for life expectancy: a life-table analysis. Ann Intern Med. 2003; 138:24–32.
2.    Wang Y, Chen X, Song Y, et al. Association between obesity and kidney disease: a systematic review and meta-analysis. Kidney Int. 2008;73:19–33.
3.    Wahba IM, Mak RH. Obesity and obesity-initiated metabolic syndrome: mechanistic links to chronic kidney disease. Clin J Am Soc Nephrol. 2007;2:550–562.
4.    Bouldin MJ, Ross LA, Sumrall CD, et al. The effect of obesity surgery on obesity comorbidity. Am J Med Sci. 2006;331:183–193.
5.    Group DR. Diabetes Control and Complications Trial (DCCT): the effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin dependent diabetes mellitus. N Engl J Med. 1993; 329:977–986.
6.    Chagnac A, Weinstein T, Herman M, et al. The effects of weight loss on renal function in patients with severe obesity. J Am Soc Nephrol. 2003;14:1480–1486.
7.    Navarro-Diaz M, Serra A, Romero R, et al. Effect of drastic weight loss after bariatric surgery on renal parameters in extremely obese patients: long-term follow-up. J Am Soc Nephrol. 2006; 17:S213–S217
8.    Izzedine H, Coupaye M, Reach I, Deray G. Gastric bypass and resolution of proteinuria in an obese diabetic patient. Diabet Med. 2005; 22:1761–1762.
9.    Iseki K, Ikemiya Y, Kinjo K, et al. Body Cystatin C (mg/L)mass index and the risk of development of end-stage renal disease in a screened cohort. Kidney Int. 2004; 65:187–1876.
10.    Hsu CY, McCulloch CE, Iribarren C, et al. Body mass index and risk for end-stage renal disease. Ann Intern Med. 2006; 144:21–28.
11.    Kincaid-Smith P. Hypothesis: obesity and the insulin resistance syndrome play a major role in end-stage renal failure attributed to hypertension and labelled “hypertensive nephrosclerosis.” J Hypertens. 2004;22:1051–1055.
12.    Sugerman HJ. Increased intra-abdominal pressure in obesity. Int J Obes Relat Metab Disord. 1998;22:1138.
13.    Bloomfield GL, Blocher CR, Fakhry IF, et al. Elevated intra-abdominal pressure increases plasma renin activity and aldosterone levels. J Trauma. 1997;42:997–1004; discussion 1004–1005.
14.    Chagnac A, Weinstein T, Korzets A, et al. Glomerular hemodynamics in severe obesity. Am J Physiol Renal Physiol. 2000; 278:F817–F822.
15.    de Jong PE, Verhave JC, Pinto-Sietsma SJ, Hillege HL. Obesity and target organ damage: the kidney. Int J Obes Relat Metab Disord. 2002; 26 Suppl 4:S21–S24.
16.    Praga M, Hernandez E, Herrero JC, et al. Influence of obesity on the appearance of proteinuria and renal insufficiency after unilateral nephrectomy. Kidney Int. 2000;58:2111–2118.
17.    Xu H, Barnes GT, Yang Q, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112:1821–1830.
18.    Weisberg SP, McCann D, Desai M, et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112:1796–1808.
19.    Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993; 259:87–91.
20.    Wisse BE. The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol. 2004; 15:2792–2800.
21.    Griffin KA, Kramer H, Bidani AK. Adverse renal consequences of obesity. Am J Physiol Renal Physiol. 2008; 294:F685–696.
22.    Bullo M, Garcia-Lorda P, Megias I, Salas-Salvado J. Systemic inflammation, adipose tissue tumor necrosis factor, and leptin expression. Obes Res. 2003;11:525–531.
23.    Wolf G, Hamann A, Han DC, et al. Leptin stimulates proliferation and TGF-beta expression in renal glomerular endothelial cells: potential role in glomerulosclerosis [seecomments]. Kidney Int. 1999;56:860–872.
24.    Chalmers L, Kaskel FJ, Bamgbola O. The role of obesity and its bioclinical correlates in the progression of chronic kidney disease. Adv Chronic Kidney Dis. 2006;13:352–364.
25.    Kambham N, Markowitz GS, Valeri AM, et al. Obesity-related glomerulopathy: an emerging epidemic. Kidney Int. 2001;59:1498–1509.
26.    Hall JE, Henegar JR, Dwyer TM, et al. Is obesity a major cause of chronic kidney disease? Adv Ren Replace Ther. 2004;11:41–54.
27.    Praga M, Hernandez E, Morales E, et al. Clinical features and long-term outcome of obesity-associated focal segmental glomerulosclerosis. Nephrol Dial Transplant. 2001;16:1790–1798.
28.    Meier-Kriesche HU, Arndorfer JA, Kaplan B. The impact of body mass index on renal transplant outcomes: a significant independent risk factor for graft failure and patient death. Transplantation. 2002; 73:70–74.
29.    Gore JL, Pham PT, Danovitch GM, et al. Obesity and outcome following renal transplantation. Am J Transplant. 2006;6:357–363.
30.    Lentine KL, Delos Santos R, Axelrod D, et al. Obesity and kidney transplant candidates: how big is too big for transplantation? Am J Nephrol. 2012; 36:575–586.

Category: Case Report, Past Articles

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