Kidney function, future health costs, and quality-adjusted life-years in kidney transplant recipients transplanted during the SARS-Cov-2 lockdown in Denmark - An observational study.

BACKGROUND: It is unknown whether lockdown due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may affect both clinical outcome in kidney transplant recipients and health care economics in Denmark. METHODS: We compared kidney transplant data at a tertiary university hospital before and during the lockdown period from March 13, 2020 until March 31, 2021, as well as kidney transplant data from Scandiatransplant for entire Denmark. Outcome variables included fall of plasma creatinine during the first postoperative day, and graft function three months posttransplant. We calculated the quality-adjusted life-years (QALYs) and costs which were caused by the lockdown recommendations. FINDINGS: The portion of living donation kidney transplantation was largely reduced during the lockdown period compared to before the lockdown: AB0-incompatible living donation declined from 14% to 7% (P < 0.01), and AB0-compatible living donation declined from 34% to 20% (p < 0.01).In entire Denmark during the lockdown period 78 living donor kidney transplants out of 268 kidney transplants (29%) were performed, whereas there were 878 living donor kidney transplants out of 2218 kidney transplants (39%) before the lockdown (P = 0.01).The observed reduction of living donor kidney transplants and consecutive reduction of graft survival will cause a loss of 5.04 QALYs.The additional costs in kidney transplant recipients who received a kidney transplant during the lockdown period will be 277,298 EUR. INTERPRETATION: SARS-CoV-2 lockdown period largely reduced living donation kidney transplants which will lead to reduced QALY as well as higher costs in kidney transplant recipients.

Thiazide-like diuretics attenuate agonist-induced vasoconstriction by calcium desensitization linked to Rho kinase.

Lowering blood pressure using thiazide-like diuretics, including chlorthalidone and hydrochlorothiazide, has been proven to be effective in clinical studies. However, the mechanisms by which thiazide-like diuretics lower blood pressure are still poorly understood. To evaluate whether thiazide-like diuretics cause calcium desensitization in smooth muscle cells, we measured their effects on agonist-induced increase of blood pressure in Wistar rats in vivo and on agonist-induced vasoconstriction of aortic rings, DNA synthesis, and protein synthesis, RhoA, Rho kinase, and intracellular calcium in vascular smooth muscle cells in vitro. Thiazide-like diuretics significantly attenuated angiotensin II-induced or norepinephrine-induced increase of systolic blood pressure in rats. Thiazide-like diuretics inhibited agonist-induced vasoconstriction of aortic rings in a concentration-dependent manner in the presence and absence of endothelium. The inhibitory effects of thiazide-like diuretics were similar to that of the specific Rho kinase inhibitor Y27632. RT-PCR and immunoblotting showed that RhoA and Rho kinase were significantly reduced in vascular smooth muscle cells after administration of thiazide-like diuretics. In contrast, thiazide-like diuretics did not affect protein tyrosine phosphatase-2 (SHP-2) expression. Agonist-induced changes of intracellular calcium were not affected by thiazide-like diuretics. The study indicates that thiazide-like diuretics inhibit agonist-induced vasoconstriction by calcium desensitization in smooth muscle cells linked to the Rho-Rho kinase pathway.