A priori clinical diagnosis of CKD is defined as pre-WES clinical diagnosis per referral by primary nephrologist. CAKUT, congenital anomalies of the kidney and urinary tract; CKD, chronic kidney disease; ESKD, end-stage kidney disease; GN, glomerulonephritis; SRNS, steroid-resistant nephrotic syndrome; TIKD, tubulointerstitial kidney disease; WES, whole exome sequencing. a Age at first presentation to medical services with evidence of CKD. b Age at start of renal replacement therapy, i.e., dialysis or kidney transplantation. DM Connaughton et al.: Monogenic causation of chronic kidney disease in Ireland c l i n i c a l i n v e s t i g a t i o n Kidney International (2019) 95, 914-928 DM Connaughton et al.: Monogenic causation of chronic kidney disease in Ireland c l i n i c a l i n v e s t i g a t i o n

At 4°, the association reaction between bacterial ferric cytochrome P-450 and its substrate (/-camphor is second order with a rate constant of 4.1 X 106 m"1 sec"1, while the reverse, camphor-dissociation reaction exhibits firstorder kinetics with a rate constant of 6.0 sec"1. Over the temperature range 4-40°, the rate constant for dissociation shows the normal exponential dependence on reciprocal temperature.The equilibrium association constant for camphor binding depends exponentially on reciprocal temperature from 4°to about 13°, where it becomes temperature independent. The

1 We recently demonstrated the presence of phospholipase C-coupled bradykinin (BK) B 2 -receptors in human primary and SV40 virus-immortalized corneal epithelial (CEPI) cells. =8 ± 20 nM) in CEPI cells and both responses were inhibited in a concentration-dependent manner by 100 nM ± 10 mM Hoe-140, a selective B 2 -receptor antagonist, and also inhibited by the selective phospholipase C (PLC) inhibitor, U73122 (1-(6-((17b-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione) (IC 50 =3.0+1.6 mM). BK-induced [Ca 2+ ] i mobilization was reduced by about 30% in the presence of 4 mM EGTA, but was not signi®cantly a ected by 100 nM nifedipine. 5 BK (0.1 nM ± 10 mM) signi®cantly (P50.05 ± 0.001) stimulated [ 3 H]-thymidine incorporation into CEPI cellular DNA. However, while interleukin-1a (IL-1a; 10 ng ml 71 ) potently stimulated the release of IL-6, IL-8 and granulocyte macrophage colony-stimulating factor from CEPI cells, BK (0.1 nM ± 10 mM) was without e ect. 6 Whilst phorbol-12-myristate-13-acetate (PMA; 3 mg ml 71 ) and 10% foetal bovine serum (positive control agents) signi®cantly stimulated the release of both MMP-1 and PGE 2 from CEPI cells, BK (0.1 nM ± 10 mM) was without any signi®cant e ect under these conditions. 7 In conclusion, these data indicate that the CEPI cells express high-a nity [ 3 H]-BK binding sites representing B 2 -subtype BK receptors coupled to PI turnover and [Ca 2+ ] i mobilization which appear to stimulate [ 3 H]-thymidine incorporation into cellular DNA. In contrast, BK failed to elicit the release of PGE 2 , various cytokines and MMP-1 from CEPI cells. These results suggest that BK may have a potential role in corneal epithelium wound healing by stimulating cell proliferation.

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