Cortical perfusion as assessed with contrast-enhanced ultrasound is lower in patients with chronic kidney disease than in healthy subjects but increases under low salt conditions.

BACKGROUND: Disturbances in renal microcirculation play an important role in the pathophysiology of chronic kidney disease (CKD), but the lack of easy accessible techniques hampers our understanding of the regulation of the renal microcirculation in humans. We assessed whether contrast-enhanced ultrasound (CEUS) can identify differences in cortical perfusion and alterations induced by different dietary salt intakes in CKD patients and controls. METHODS: Participants underwent CEUS twice: once after 5 days of high-salt (HS) intake, and again after 5 days of low salt (LS) diet. Sonovue® (0.015 mL/kg/min) was perfused as contrast agent and four consecutive destruction-reperfusion sequences were analysed per visit. The primary outcome measure was the (change in) mean perfusion index (PI) of the renal cortex. RESULTS: Forty healthy volunteers (mean age ± standard deviation 50 ± 8 years) and 18 CKD Stages 2-4 patients [aged 55 ± 11 years, estimated glomerular filtration rate (eGFR) 54 ± 28 mL/min/1.73 m2] were included and underwent CEUS without side effects. Under HS conditions, cortical PI was significantly lower in CKD patients [1618 ± 1352 versus 3176 ± 2278 arbitrary units (a.u) in controls, P = 0.034]. Under LS, renal PI increased in CKD patients (with +1098 to 2716 ± 1540 a.u., P = 0.048), whereas PI remained stable in controls. In the continuous analysis, PI correlated with eGFR (Spearman's r = 0.54, P = 0.005) but not with age, sex, blood pressure or aldosterone levels. CONCLUSIONS: CEUS identified important reductions in cortical micro-perfusion in patients with moderate CKD. Lowering salt intake increased perfusion in CKD patients, but not in controls, underlining the benefits of an LS diet in CKD patients. Whether a low PI is an early sign of kidney damage and predicts renal function decline needs further study.

Contrast-Enhanced Ultrasound and Protein Shakes Are No Alternatives for Inulin Clearance and Meat to Assess Renal Functional Reserve in Humans.

INTRODUCTION: The measurement of renal functional reserve (RFR) can unmask glomerular hyperfiltration in residual nephrons, but its determination is time-consuming. In this study, we assessed whether contrast-enhanced ultrasound (CEUS) is a valuable alternative to the gold standard inulin clearance and whether L-arginine or protein shakes lead to similar changes in glomerular filtration rate (GFR) as animal proteins in men and women. METHODS: Changes in GFR and renal microperfusion were studied in 25 healthy subjects (8 men, 17 women) by simultaneously performing inulin clearance and CEUS (perfusion index, PI) before and 1 and 2 h after different protein loads (L-arginine, protein shake or meat). The Doppler parameters - renal resistive index (RRI) and pulsatility index (PuI) - were also measured. RESULTS: None of the oral protein loads induced significant changes in CEUS-assessed PI. Only meat increased inulin clearance (from 111.2 ± 16.0 to 149.8 ± 27.2 mL/min, p < 0.05) and mobilized RFR, while L-arginine decreased GFR (106.7 ± 45.3 to 86.3 ± 42.6 mL/min, p < 0.05). Protein shakes had a neutral effect. There were no correlations between changes in inulin clearance and PI. At Doppler, RRI and PuI increased after meat intake (from 0.647 ± 0.029 to 0.694 ± 0.050 a.u., p < 0.05 and from 1.130 ± 0.087 to 1.318 ± 0.163 a.u., p < 0.05, respectively), but their changes also did not correlate with changes in inulin clearance. Results were similar in both sexes. CONCLUSIONS: CEUS is not a valuable alternative for inulin clearance to measure RFR. Meat ingestion leads to modest changes in renal Doppler parameters and to glomerular hyperfiltration in both women and men, while protein shakes and L-arginine do not.

Reference values and sex differences in absolute and relative kidney size. A Swiss autopsy study.

BACKGROUND: Men have larger kidneys than women, but it is unclear whether gender remains an independent predictor of kidney size (expressed as weight or length) after correction for body size. We analysed autopsy data to assess whether relative renal length and weight (e.g. corrected for body weight, height or body surface area (BSA)) are also larger in men. Assuming that kidney size is associated with nephron number, opposite findings could partly explain why women are less prone to the development and progression of chronic kidney disease than men. METHODS: All forensic autopsies performed between 2009 and 2015 at the local university hospital of Geneva in individuals of European descent aged ≥18 years without a known history of diabetes and/or kidney disease were examined. Individuals with putrefied or severely injured bodies were excluded. Relative renal weight and length were respectively defined as renal weight divided by body weight or BSA and renal length divided by body height or BSA. RESULTS: A total of 635 autopsies (68.7% men) were included in the analysis. Left kidneys were on average 8 g heavier and 2 mm longer than right kidneys (both: p < 0.05). Absolute renal weight (165 ± 40 vs 122 ± 29 g) and length (12.0 ± 1.3 vs 11.4 ± 1.1 cm) were higher in men. Relative renal weight was also higher in men, but relative renal length was larger in women. In multivariable regression analysis, body height, body weight, the degree of blood congestion or depletion at autopsy and age were determinants of renal weight, whereas arterial hypertension and smoking were not. Percentile curves of renal weight and length according to sex and body height were constructed. CONCLUSION: Absolute and relative renal weights were both smaller in women. This is in line with recent studies stating that nephron numbers are also lower in women. Relative renal length was longer in women, suggesting that female kidneys have a more elongated shape. In comparison with older autopsy studies, renal weight appears to be stable over time.

Determinants of Renal Micro-Perfusion as Assessed with Contrast-Enhanced Ultrasound in Healthy Males and Females.

(1) Background: The renal microcirculation is essential to maintain the renal function, but its determinants in humans have been poorly studied. Contrast-enhanced ultrasound (CEUS) allows the non-invasive quantification of the cortical micro-perfusion at the bedside using the perfusion index (PI). The aims of this study were to assess whether differences exist in PI between healthy males and females and to identify clinical determinants associated with cortical micro-perfusion. (2) Methods: Healthy, normotensive volunteers (eGFR > 60 mL/min/1.73 m2, no albuminuria) underwent CEUS under standardized conditions with the destruction-reperfusion (DR) technique. The mean PI of four DR sequences was reported as the primary outcome measure (3) Results: A total of 115 subjects (77 females and 38 males) completed the study; the mean ± SD age was, respectively, 37.1 ± 12.2 and 37.1 ± 12.7 years in females and males, and the mean eGFR was 105.9 ± 15.1 and 91.0 ± 17.4 mL/min/1.73 m2. The PI (median) was higher in females than in males, i.e., 2705 (IQR 1641-3777) vs. 1965 (IQR 1294-3346) arbitrary units (a.u), p = 0.02). A correlation analysis showed positive associations between PI and eGFR, female sex, heart rate, plasma renin activity (PRA) and plasma aldosterone concentrations (PAC), negative associations with potassium, bicarbonate and systolic blood pressure, and no associations with age, body mass index and renal resistive index (RRI). In a multivariate linear regression analysis, only PRA remained significantly associated with PI. (4) Conclusions: Although the PI was higher among females, this association was no longer significant after adjustment for covariates. There was no difference in females tested during the follicular or the luteal phases. In conclusion, the PI was only weakly influenced by classic clinical variables, but was positively associated with PRA, suggesting that the renin-angiotensin system plays a role in the regulation of the cortical micro-perfusion in humans. Identifying which other factors contribute to the large variations in micro-perfusion across individuals needs further study.