Preimplantation Histological Score Associates with 6-Month GFR in Recipients of Perfused, Older Kidney Grafts: Results from a Pilot Study

<b><i>Background:</i></b> Biopsy-guided selection of older kidneys safely expands the organ pool, and pretransplant perfusion improves the preservation of these fragile organs. Herein, we studied morphofunctional variables associated with graft outcomes in perfused, histologically evaluated older kidneys. <b><i>Methods:</i></b> This single-center prospective cohort pilot study evaluated the relationships between preimplantation histologic scores and renal perfusion parameters during hypothermic, pulsatile, machine perfusion (MP) and assessed whether these morphofunctional parameters associated with GFR (iohexol plasma clearance) at 6 months after transplantation in 20 consecutive consenting recipients of a biopsy-guided single or dual kidney transplant from &#x3e;60-year-old deceased donors. <b><i>Results:</i></b> The donor and recipient age was 70.4 ± 6.5 and 63.6 ± 7.9 years (<i>p</i> = 0.005), respectively. The kidney donor profile index (KDPI) was 93.3 ± 8.4% (&#x3e;80% in 19 cases), histologic score 4.4 ± 1.4, and median (IQR) cold ischemia time 19.8 (17.8–22.8 h; &#x3e;24 h in 5 cases). The 6-month GFR was 41.2 (34.9–55.7) mL/min. Vascular resistances positively correlated with global histologic score (<i>p</i> = 0.018) at MP start and then decreased from 0.88 ± 0.43 to 0.36 ± 0.13 mm Hg/mL/min (<i>p</i> &#x3c; 0.001) in parallel with a three-fold renal flow increase from 24.0 ± 14.7 to 74.7 ± 31.8 mL/min (<i>p</i> &#x3c; 0.001). Consistently, vascular resistance reductions positively correlated with global histologic score (<i>p</i> = 0.009, <i>r</i> = −0.429). Unlike KDPI or vascular resistances, histologic score was independently associated with 6-month GFR (beta standardized coefficient: −0.894, <i>p</i> = 0.005). <b><i>Conclusions:</i></b> MP safely improves graft perfusion, particularly in kidneys with severe histologic changes that would not be considered for transplantation because of high KDPI. The preimplantation histologic score associates with the functional recovery of older kidneys even in the context of a standardized program of pulsatile perfusion.

P0677CONTRAST-ENHANCED ULTRASOUND TO ASSESS RENAL MICROCIRCULATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE

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.

Assessment of Perfusion and Oxygenation of the Human Renal Cortex and Medulla by Quantitative MRI during Handgrip Exercise

BackgroundRenal flow abnormalities are believed to play a central role in the pathogenesis of nephropathy and in primary and secondary hypertension, but are difficult to measure in humans. Handgrip exercise is known to reduce renal arterial flow (RAF) by means of increased renal sympathetic nerve activity.MethodsTo monitor medullary and cortical oxygenation under handgrip exercise–reduced perfusion, we used contrast- and radiation-free magnetic resonance imaging (MRI) to measure regional changes in renal perfusion and blood oxygenation in ten healthy normotensive individuals during handgrip exercise. We used phase-contrast MRI to measure RAF, arterial spin labeling to measure perfusion, and both changes in transverse relaxation time (T2*) and dynamic blood oxygenation level–dependent imaging to measure blood oxygenation.ResultsHandgrip exercise induced a significant decrease in RAF. In the renal medulla, this was accompanied by an increase of oxygenation (reflected by an increase in T2*) despite a significant drop in medullary perfusion; the renal cortex showed a significant decrease in both perfusion and oxygenation. We also found a significant correlation (R2=0.8) between resting systolic BP and the decrease in RAF during handgrip exercise.ConclusionsRenal MRI measurements in response to handgrip exercise were consistent with a sympathetically mediated decrease in RAF. In the renal medulla, oxygenation increased despite a reduction in perfusion, which we interpreted as the result of decreased GFR and a subsequently reduced reabsorptive workload. Our results further indicate that the renal flow response’s sensitivity to sympathetic activation is correlated with resting BP, even within a normotensive range.