In an ongoing effort to study the effects of bariatric surgery on chronic kidney disease (CKD), a team of Cleveland Clinic researchers in Florida have identified reduced renal blood flow (RBF) as a potentially reversible mechanism of kidney injury among patients with severe obesity.
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According to lead author David Romero Funes, MD, “Most of the literature suggests that diabetes and hypertension are the driving factors in the development of kidney disease, but we hypothesize that there is another potential leading mechanism at work.”
Through previous studies involving institutional data, investigators at Cleveland Clinic Weston Hospital observed that patients with CKD undergoing bariatric surgery benefited from improved kidney function.
In a study using a small sample population from institutional data published in the Annals of Surgery, the patients most at risk of kidney failure (CKD stages ≥3) experienced a reduction in proteinuria (urinary albumin to creatinine ratio) at 12-month follow-up, leading to 70% and 60% relative reductions in estimated risk of kidney failure at 2 and 5 years, respectively.
In another study published last year in Surgery for Obesity and Related Disease, the team conducted a retrospective chart review of patients from 2010 to 2019 who underwent sleeve gastrectomy, the most common bariatric procedure now performed. Here, too, they noted significant improvement in kidney function, as measured by estimated glomerular filtration rate (eGFR), among patients in CKD stages ≥2 at 12-month follow-up that appeared to be independent of weight loss.
“We’ve demonstrated the beneficial effects of bariatric surgery on baseline CKD among our patients as well as within a large national sample of patients with severe obesity,” says Dr. Funes. He points to the team’s retrospective analysis of the U.S. National Inpatient Sample database for the years 2010–2015 that found a significantly lower rate of CKD in patients with obesity who underwent bariatric surgery (5.3%) compared to patients who did not (12%).
Now the team has turned its efforts to identifying the underlying mechanisms responsible for the post-operative change in kidney function. In its latest observational study, accepted for presentation at this year’s Annual Meeting of the American Society for Metabolic and Bariatric Surgery (ASMBS), Dr. Funes and his colleagues propose that a chronic increase in intra-abdominal pressure (IAP) may induce a reversible chronic kidney injury driven by a reduction in renal blood flow.
“We know from the literature that increased IAP is present in patients with severe obesity and that its detrimental effect on the kidney is attributed to decreased renal blood flow,” explains Dr. Funes. “In our own institutional research published in the journal Surgery, we demonstrated that an increased IAP triggers the Cushing’s reflex resulting in an increased release of vasopressin. We believe that the mechanical effect of increased IAP on the renal vasculature, in synchrony with the effects of a chronically increased vasopressin release, results in a decreased renal blood flow.”
To lay the groundwork for this next stage of query, the team conducted a retrospective chart review of all patients who underwent bariatric surgery at Cleveland Clinic Weston Hospital from 2003 to 2021 to:
To satisfy the primary objective of their study, the team’s initial analysis included all patients with a pre-operative BMI of 35-50 (class II and III obesity), an eGFR <90, and at least two different pre-operative measurements of BUN/Cr ratio used to establish a reduction in RBF. Patients with a hypertension or diabetes mellitus (DM) diagnosis were excluded in order to satisfy the definition of metabolically healthy.
“We used the BUN to creatinine ratio as an indirect measurement of renal blood flow to differentiate between pre-renal and intrinsic kidney injury,” says Dr. Funes. Following the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines, patients with a BUN/Cr ratio that exceeds 20 are categorized as pre-renal.
The Chronic Kidney Disease Epidemiology Collaboration Study (CKD-EPI) classification system, which relies on eGFR, was used to stratify patients by CKD stage. Patients with data to calculate a 3-month average pre-operative eGFR and BUN/Cr ratio, as well as a single 15-month post-operative eGFR and BUN/Cr ratio were included in order to determine the primary objective of the study.
Of the 2,924 patients included in the initial analysis, 11% (N=325) presented with decreased RBF at baseline with no history of hypertension or DM. For the secondary analysis, 714 patients had the recorded pre- and post-operative data necessary for inclusion. Of this group, 228 were classified as CKD stage ≥ 2.
“We observed both significantly improved renal blood flow and kidney function in patients with baseline stage 2 and 3 CKD, though not in patients with higher stage kidney disease, stage 4 and 5 CKD,” notes Dr. Funes.
Patients with baseline stage 2 CKD demonstrated a pre-operative BUN/Cr 20.85±10.23 decreasing to 14.99±9.10 at 12-month follow-up (p=0.0001). Likewise, patients with baseline stage 3 CKD presented with a pre-operative BUN/Cr 23.88±8.75 decreasing to 16.38±9.27 (p=0.0001). Patients with stage 2 and 3 CDK also saw post-operative eGFR improvement, increasing by 10.22 mL/min/1.73m2 and 22.72 mL/min/1.73m2, respectively.
According to Dr. Funes, the team’s findings suggest that improved kidney function in an otherwise healthy patient with severe obesity and baseline CKD could be attributed to changes in RBF following bariatric surgery. He notes this is an unstudied and potentially reversible mechanism of obesity-related kidney injury.
“Larger retrospective and prospective trials will be needed to confirm both the positive effect of bariatric surgery on renal blood flow and the mechanism at work,” says Dr. Funes. “Our next step will be to explore the role of IAP on renal blood flow by means of direct measurement.”
According to the National Kidney Foundation, 37 million U.S. adults have CKD, and about two-thirds of cases are a result of diabetes and high blood pressure. “Among the other 30%, there are metabolically healthy individuals with obesity-related CKD. These individuals could benefit if bariatric surgery is proven to halt and potentially reverse CKD progression.”