“Renal perfusion plays an essential role in kidney health, as the kidneys receive up to 25% of cardiac output,” explains Menno Pruijm, PhD. “Although autoregulation mechanisms keep the perfusion of each kidney as constant as possible, acute reductions in global renal blood flow and disturbances in renal microcirculation (arterioles, capillaries, glomeruli)—such as that encountered during hypovolemic shock or sepsis—can lead to ischemia and acute kidney injury.”

In chronic conditions, Dr. Pruijm adds, stable hemodynamics are also important for kidney homeostasis. “Arterial hypertension (AHT) and diabetes, two main causes of CKD, are both characterized by a damaged renal vasculature,” he says. “Biopsy studies suggest that capillary rarefaction is commonly found in both AHT and diabetes, as well as most forms of CKD, which may lead to alterations in the renal micro-circulation, independently of the macro-circulation. However, due to the limited size of renal biopsies and the lack of simple, non-invasive techniques to quantify the renal microcirculation of each kidney, proof of this hypothesis is inconclusive, as is our understanding of the factors that regulate renal microcirculation. Identification of disturbances in renal microcirculation, therefore, may help identify kidney damage at an earlier stage.”

Examining Low- & High-Salt Diets

For a paper published in Nephrology Dialysis Transplantation, Dr. Pruijm and colleagues assessed whether contrast-enhanced ultrasonography (CEUS) can identify differences in cortical micro-perfusion and alterations induced by dietary salt intake in patients with and without CKD. They used CEUS to measure cortical micro-perfusion, expressed as Perfusion Index (PI). Participants underwent CEUS twice: once after 5 days of high-salt intake and again after 5 days of low-salt intake. Four consecutive destruction-reperfusion sequences were analyzed per visit.

“We included patients with CKD and age- and sex-matched healthy volunteers to assess whether patients with CKD do indeed have a lower PI due to capillary rarefaction, as suggested by biopsy studies,” says Dr. Pruijm. “We also sought to determine if dietary salt intake changes renal microcirculation. Since too much salt is bad for kidneys, especially in patients with CKD, we hypothesized that a high-salt intake would induce disturbances in renal microcirculation.”

Kidney Damage Identified Earlier With CEUS

Dr. Pruijm and colleagues found that under low-salt conditions, the renal resistive index was slightly lower, and the cortical perfusion index significantly higher than under high-salt conditions among patients with CKD (Table). “We found that dietary sodium intake influences renal hemodynamics in patients with CKD, but not, or hardly, in patients with normal kidneys,” Dr. Pruijm says. “High-salt intake reduces cortical perfusion, possibly due to stiffening of the renal arteries.”

The researchers also confirmed that patients with CKD have a much lower cortical perfusion than those without kidney disease. “Cortical perfusion already diminished sharply when the estimated creatinine-based glomerular filtration rate was well above 60 ml/min/1.73m², the threshold used to diagnose CKD,” notes Dr. Pruijm. “This suggests that kidney damage is identified earlier with CEUS than with traditional biomarkers.”

Dr. Pruijm and colleagues hope their findings will encourage nephrologists and others who care for patients with CKD to utilize CEUS more often. “Non-radiologists are often unaware of this relatively new, safe technique that can be used in place of CT or MRI exams to characterize anatomical lesions,” he says, adding that CEUS could be used to assess the influence of different antihypertensive drugs—or inversely, vasopressors—on renal microperfusion. It could also be used to assess the influence of dietary factors other than salt on renal perfusion, he says.

While the study findings indicate that patients with CKD have a lower cortical perfusion than those without the disease, it is not known whether a low cortical microperfusion predicts faster decline in renal function, notes Dr. Pruijm. “If so, CEUS could become an integral part of the workup of any patient with CKD,” he says. “The next step, therefore, is to conduct a large prospective trial that assesses whether a low cortical perfusion index is associated with a faster decline in kidney function.”