Utilizing Diet to Prevent Obesity, Preserve Kidney Function, With Holly Kramer, MD

Intervening clinically to prevent obesity and the risk the comorbidity poses to renal function may alleviate the development of chronic kidney disease (CKD) before end-stage kidney disease (ESKD), according to an expert.1

New insights from Holly Kramer, MD, a nephrologist at Loyola University Medical Center and editor in chief of Advances in Kidney Disease and Health, suggest clinical management, especially referring patients to dieticians early, can temper the pathophysiological mechanisms of obesity, which independently contribute to renal injury.1

While obesity has been independently associated with CKD progression, certain individuals may be predisposed to the glomerular effects based on their nephron number from birth. Their nephron endowment can range from 200,000 to 2 million per kidney, and is determined by genetic and environmental factors during gestation. 2,3

A reduced nephron endowment increases the risk for hypertension and CKD due to reduced renal functional capacity and compensatory glomerular hypertrophy. Other causes of reduced nephron count include premature birth, genetics, or conditions like diabetes or chemotherapy.2

When an individual has obesity, the kidney’s response is to increase glomerular capillary pressure, intraglomerular flow, and filtration at the level of each nephron. When intraglomerular hypertension is sustained, it can lead to mechanical stress on the glomerular basement membrane, podocyte injury and loss, glomerulosclerosis, progressive nephron dropout, and proteinuria.

Once nephron depletion transpires, an individual's remaining nephrons become exposed to increased levels of hyperfiltration, reinforcing a feedback loop. This fuels the hyperfiltration hypothesis of CKD progression, with obesity revealing itself as a strong physiologic driver.2,3

“So it's kind of like if you had a shoe factory and you fire, you know, three fourths of your employees, and then all of a sudden you say, Oh, by the way, we have to make three times as many shoes as what we normally do, you know,” explained Kramer, in an interview with HCPLive. “And so people get tired in that shoe factory. Same thing with those nephrons. In the setting of obesity and reduced nephron number, they just kind of wear out.”

At increased levels of body mass index (BMI), especially those > 40, systemic inflammation increases, adipokine signaling alters renal hemodynamics, and insulin resistance worsens glomerular stress. Additionally, patients often experience comorbidities of hypertension and diabetes, which can cause more damage to the kidneys.4

Often, clinical management of these symptoms can be delayed until patients reach ESKD and are on maintenance dialysis. Once patients reach this stage, obesity can pose barriers to receiving a transplant because of increased risk for complications during and after surgery.5

“Only about 10% of patients ever meet with a registered dietitian. But when they get on dialysis, everybody talks with the dietitian,” said Kramer. “It really makes sense that we should try to get our patients to be talking with a registered dietitian to slow kidney disease progression and get them to eat healthier.”

Kramer emphasizes the importance of medical nutrition therapy, which is covered by Medicare and most private insurances, and is crucial for managing kidney disease. She encourages patients to consult registered dietitians, either through telehealth or via the National Kidney Foundation's directory, to take disease management into their own hands, slow kidney disease and adopt healthier eating habits.5

References

1. Kovesdy CP, Furth SL, Zoccali C. Obesity and Kidney Disease. Canadian Journal of Kidney Health and Disease. 2017;4(1):205435811769866. doi:https://doi.org/10.1177/2054358117698669

2. Villani G, Zaza P, Lamparelli R, Maffei G. Kidney volume-to-birth weight ratio as an estimate of nephron endowment in extremely low birth weight preterm infants. Scientific Reports. 2024;14(1). doi:https://doi.org/10.1038/s41598-024-64897-6

3. Good PI, Li L, Hurst HA, et al. Low nephron endowment increases susceptibility to renal stress and chronic kidney disease. JCI insight. 2023;8(3):e161316. doi:https://doi.org/10.1172/jci.insight.161316

4. Garske KM, Kar A, Comenho C, et al. Increased body mass index is linked to systemic inflammation through altered chromatin co-accessibility in human preadipocytes. Nature Communications. 2023;14(1):4214. doi:https://doi.org/10.1038/s41467-023-39919-y

5. National Kidney Foundation. Nutrition and Kidney Disease, Stages 1-5 (Not on Dialysis). National Kidney Foundation. Published 2024. https://www.kidney.org/kidney-topics/nutrition-and-kidney-disease-stages-1-5-not-dialysis

‌