Table 2.

Mitochondrial function and energetic coupling deficits in CKD progression in T2DM

	Stages 1 and 2 (≥60 mL/min)	Stage 3 (30–59 mL/min)	Stages 4 and 5 (<29 mL/min)	P value
Participants, n	5	5	3
LEAK (L) respiration (pmol/s/mg)	0.325 (0.06)	0.44 (0.06)	0.82 (0.12)	<0.05^ #
Complex 1 respiration (pmol/s/mg)	4.3 (0.54)	3.46 (0.46)	2.9 (0.6)	0.018^
Maximal oxidative phosphorylation capacity (P) (pmol/s/mg)	7.52 (0.87)	5.7 (0.72)	5.4 (0.55)	0.004* ^
Maximal ETS capacity (E) (pmol/s/mg)	9.3 (1.3)	6.9 (0.97)	7.2 (0.31)	0.001^ #
Oxidative phosphorylation control ratio (P/E)	0.79 (0.07)	0.81 (0.036)	0.67 (0.15)	0.017^ #
RCR (P/L)	22 (4.3)	13.1 (2.4)	7.9 (3.2)	<0.001* ^ #
	eGFR
Correlations	r		P value
LEAK (normalized to CS)	−0.75		<0.001
Complex 4 enzyme activity	0.53		<0.001
Complex 1 respiration	0.82		<0.001
Maximal oxidative phosphorylation	0.81		<0.001

Data are mean (SD) unless otherwise indicated. Top: mitochondrial respiration normalized to mitochondrial content (CS activity) performed on a 13-participant subset of the study population was compared across stage groups using one-way ANOVA. Low oxidative phosphorylation control ratio values indicate intrinsic mitochondrial deficits within the phosphorylation system. Bottom: Pearson bivariate correlations were calculated to compare respiration measures/states normalized to mitochondrial content (CS activity) and mitochondrial ETC complex 4 enzyme activity with renal filtration rate (eGFR). RCR is an index in which larger values reflect better coupling between phosphorylation system and ATP production.

^*P < 0.05, post hoc pairwise comparison between stages 1 and 2 and stage 3.

^{^}P < 0.05, post hoc pairwise comparison between stages 1 and 2 and stages 4 and 5.

^#P < 0.05, post hoc pairwise comparison between stage 3 and stages 4 and 5.