Volume 84, Issue 5, Pages 980-988 (November 2013) Subcutaneous interstitial pressure and volume characteristics in renal impairment associated with edema  Leonard M. Ebah, Helge Wiig, Idalia Dawidowska, Charlotte O'Toole, Angela Summers, Milind Nikam, Anuradha Jayanti, Beatrice Coupes, Paul Brenchley, Sandip Mitra  Kidney International  Volume 84, Issue 5, Pages 980-988 (November 2013) DOI: 10.1038/ki.2013.208 Copyright © 2013 International Society of Nephrology Terms and Conditions

Figure 1 Comparison of and bioimpedance-derived body fluid volumes between patients and healthy volunteers. Mean (+s.d.) (a) total body water (TBW), (b) extracellular fluid volume (ECFV), and (c) interstitial fluid volume (IFV) were significantly higher in the edematous patients with renal dysfunction compared with the healthy volunteers. The mean difference (9.95l) in ECFV between patients and controls (23.96±6.69 vs. 14.01±1.55l; P=0.0008) is almost entirely accounted for by differences in IFV (mean difference 8.9l; 19.96±6.07 vs. 11.09±1.29l; P=0.0009). Kidney International 2013 84, 980-988DOI: (10.1038/ki.2013.208) Copyright © 2013 International Society of Nephrology Terms and Conditions

Figure 2 Comparison of interstitial pressure (ISP) measurements between patients with manifest edema and healthy volunteers. (a) A dot plot comparing (t-test) ISP of all patients (squares, n=17) and all healthy volunteers (circles, n=10). ISP was high (positive; 4.62±4.2mmHg) in edematous chronic kidney disease (CKD) patients and low (negative; -0.9±1.3mmHg) in healthy volunteers. (b) The patient and healthy volunteers groups are separated by gender. HV F, female healthy volunteers; HV M, male healthy volunteers; Patients F, female patients; Patients M, male patients. aA Kruskal–Wallis test showed an overall difference across the groups. bDunn’s post-hoc multiple testing adjustment shows a persistent difference of ISP between female patients and female healthy volunteers (P=0.03). The small number of male healthy volunteers precludes comparisons with this group. Kidney International 2013 84, 980-988DOI: (10.1038/ki.2013.208) Copyright © 2013 International Society of Nephrology Terms and Conditions

Figure 3 Linear regression graphs of interstitial pressure (ISP) and bioimpedance body fluid volumes. The graphs depict the linear relationships between interstitial pressure and (a) total body water (TBW), (b) segmental extracellular fluid volume (ECFV), and (c) ECFV/TBW (Bio-ratio) in the study patient group (n=15). Significant positive linear relationships are seen between ISP and TBW, and ISP and segmental ECFV, whereas the relationship between ISP and ECFV/TBW is negative (R2=0.40, r=-0.63, P=0.01). Square data points denote female patients, whereas triangles denote male patients. Kidney International 2013 84, 980-988DOI: (10.1038/ki.2013.208) Copyright © 2013 International Society of Nephrology Terms and Conditions

Figure 4 Comparison of interstitial pressure (ISP) measurements between short- and long-duration edema. Edema of up to 2 weeks of duration was categorized as ‘short duration (SD),’ whereas those of >2 weeks as ‘long duration (LD).’ The box-and-whisker plot shows that the mean (±s.d. and 95% confidence interval (CI)) ISP in patients with LD (2.13±1.56; 95% CI 0.77–7.69mmHg) is significantly lower than in SD (6.36±4.65; 95% CI 0.31–8.15mmHg; P=0.03). Kidney International 2013 84, 980-988DOI: (10.1038/ki.2013.208) Copyright © 2013 International Society of Nephrology Terms and Conditions

Figure 5 The nonlinear pressure–volume relationship in the subcutaneous interstitial compartment with varying states of hydration. The relationship between interstitial pressure (ISP) and interstitial fluid volume (IFV) in all subjects in whom both measurements were available (8 controls and 16 chronic kidney disease (CKD) patients). The second-order polynomial y=-7.9+0.8x-0.009x2 (R2=0.56, P<0.0001) depicts a change in the rate of rise of ISP with changing IFV. All controls (depicted in circles) cluster at baseline with negative pressure measurements. The patients are depicted in squares, and a separate regression line for this group (broken line, R2=0.32, P=0.03) follows a similar pattern as the curve for the whole cohort (solid line). Kidney International 2013 84, 980-988DOI: (10.1038/ki.2013.208) Copyright © 2013 International Society of Nephrology Terms and Conditions

Figure 6 Linear regression graphs of the determinants of edema refill time. (a) Total body water (TBW), (b) interstitial fluid volume (IFV), and (c) segmental extracellular fluid volume (ECFV) exhibited significant linear correlations with edema refill time (ERT; n=18). Kidney International 2013 84, 980-988DOI: (10.1038/ki.2013.208) Copyright © 2013 International Society of Nephrology Terms and Conditions