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 ultrasonography (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 intake (HS), and again after 5 days of low salt diet (LS). Sonovue® (0.015 ml/kg/min) was perfused as contrast agent and four consecutive destruction-reperfusion sequences were analyzed per visit. Primary outcome measure was the (change in) mean perfusion index (PI) of the renal cortex. Results Forty healthy volunteers (mean age±SD 50±8 years) and 18 CKD stage 2-4 patients (aged 55±11 years, eGFR 54±28 ml/min/1.73m²) were included and underwent CEUS without side effects. Under HS conditions, cortical PI was significantly lower in CKD patients (1618±1352 vs 3176 ±2278 arbitrary units 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 continuous analysis, PI correlated with eGFR (spearman's r = 0.54, p = 0.005) but not with age, sex, blood pressure or aldosterone levels. Conclusion 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 a low salt diet in CKD patients. Whether a low perfusion index is an early sign of kidney damage and predicts renal function decline needs further 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.

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 hours after different protein loads (L-arginine, protein shake or meat). 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, p<0.05 and from 1.130±0.087 to 1.318±0.163, 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 no 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.

Background and Aims Vascular factors such as capillary rarefaction, increased vascular stiffness and reduced vasodilatation due to endothelial dysfunction probably play an important role in the pathophysiology of chronic kidney disease (CKD). However, our understanding of the underlying mechanisms is hampered by the lack of non-invasive techniques to quantify renal microvasculature in humans. The aim of this study was to assess whether contrast-enhanced ultrasonography (CEUS) can identify (1) differences in renal microcirculation and (2) the degree of nitroglycerin-induced vasodilatation (NIV) as a measure of renal flow reserve between CKD-patients and age-matched healthy volunteers. Method All participants underwent CEUS under standardized conditions. Sonovue© (0.015 ml/kg/min) was perfused as contrast agent until a steady state was obtained, followed by four destruction-refilling sequences. Outcome measure of CEUS was the mean (change in) perfusion index (PI) of the outer renal cortex (see figure for an example). In a subgroup of participants, CEUS was repeated before and five minutes after the sublingual administration of nitroglycerin (0.2mg). Renal resistive index (RRI) as a measure of vascular stiffness was also measured at each time point with Doppler ultrasound. Results A total of 38 healthy volunteers (aged 50±8 years, eGFR 95±13 ml/min/1.73 m, 69% women) and 18 CKD stage 2-3 patients (aged 55±15 years, eGFR 64±32 ml/min/1.73m, 56% women) were included. Renal PI was significantly lower in CKD patients (1304±762 vs 2989 ±2503 arbitrary units, p=0.034), whereas RRI did not differ (0.66± 0.07 vs 0.63± 0.04), p=0.10). PI was lower in CKD due to vascular nephropathy (n=3) or interstitial nephritis (n=4) than CKD due to diabetes (n=4) or other causes (7). In continuous analysis, PI correlated with eGFR (spearman’s r=0.54, p=0.005) but not with blood pressure. Renal PI did not change after nitroglycerin in both groups; RRI decreased in healthy (from 0.64±0.03 to 0.61±0.02, p=0.01) but not in CKD patients. Conclusion In this study, contrast-enhanced ultrasound identified important alterations in renal microperfusion in patients with moderate CKD. Whether a low perfusion index predicts renal function decline needs further study. Sublingual nitroglycerin seems to have limited potential as a new test of renal flow reserve.