Renal function in patients with chronic kidney disease and hypertension degree 1–2 against the background of SARS-CoV-2

Abstract

Background. SARS-CoV-2 infection in patients with chronic kidney disease (CKD) and hypertension degree 1–2 worsens the state of the cardiovascular system and may contribute to cardiovascular events and adverse renal risks. The presence of CKD in combination with hypertension degree 1–2 and its medical correction with renin-angiotensin-aldosterone system (RAAS) inhibitors causes a significant impact on the health of patients infected with SARS-CoV-2. SARS-CoV-2 uses RAAS, namely the receptor for angiotensin-converting enzyme (ACE) 2, as a tool to enter the cell. To choose further approaches and treatment, this combination of three pathological conditions requires careful analysis and research. Objective: to study the functional state of the kidneys in patients with CKD and hypertension infected with SARS-CoV-2. Materials and methods. The article is a fragment of the BIRCOV (ARB, ACE inhibitors, DRi in COVID-19) trial, which was designed according to the POEM (Patient-Oriented Evidence that Matters). The BIRCOV (two-center, open-label, initiative-randomized, in three parallel arms) prospective study enrolled 120 patients with CKD and hypertension degree 1–2, it lasted for 1 year and was registered at ClinicalTrials.gov (NCT03336203). One hundred and twelve outpatients with degree 1–2 hypertension, 83 with combination with CKD, were selected. At the end of the study, 108 patients remained, their results are presented in the article with subsequent statistical processing. Division into groups occurred depending on the drugs received (ACE inhibitors, angiotensin receptor blockers (ARBs) or direct renin inhibitor (DRIs)). Endpoints were: estimated glomerular filtration rate (eGFR), average blood pressure, albuminuria level. In 24 patients, the urine albumin to creatinine ratio was analyzed at the beginning of SARS-CoV-2, then 2, 4, 12, 24 weeks after the onset of the disease. Mathematical processing and statistical evaluation of the research results was done in the medical statistics package. Results. All patients were divided into 3 groups depending on the drug: 35 (32 %) of them received ARBs, 42 (39 %) ACE inhibitors, 31 (29 %) DRIs. At the manifestation of SARS-CoV-2, a decrease in blood pressure was recorded during the first two weeks, with the subsequent return to baseline on week 12 in the group of people who received ACE inhibitors, the lowest indicator was in the DRI group. The use of ACE inhibitors (risk ratio (RR) 1.648, 95% confidence interval (CI) 0.772–3.519, number needed to treat (NNT) 7.0) and ARBs (RR 13.023, 95% CI 1.815–93.426, NNT 19) in the treatment of hypertension significantly increased the risk of withdrawal compared to DRIs. Patients with CKD had similar dynamics of blood pressure during 24 weeks of observation. In CKD, higher mean blood pressure values were obtained compared to other participants of the BIRCOV trial. A simultaneous decrease in eGFR and systolic blood pressure was documented, it was most pronounced in patients with CKD. The lowest results were in people who took ACE inhibitors for 0–24 weeks: the correlation coefficient was 0.815. A decrease in eGFR correlated with the degree of CKD. There was a decrease in eGFR of less than 60 ml/min during the first 4 weeks from the onset of SARS-CoV-2 in 28 people who took ACE inhibitors versus 22 who used ARBs or DRIs: absolute risk was 0.667 (RR 2.00, 95% CI 1.337–2.92, NNT 3.0). The relative risk of eGFR reduction was 16.6 (95% CI 5.263–52.360, NNT 1.774) for people receiving ACE inhibitors versus all patients with CKD, 2.049 for ARBs (95% CI 0.361–11.22, NNT 1.774) and 1.064 for DRIs versus the entire sample of people with CKD (95% CI 0.116–9.797, NNT 431.6). After 12 weeks of follow-up, eGFR almost returned to baseline in CKD stage 2–3a. An increase in the urine albumin to creatinine ratio (which did not reach the baseline within 24 weeks from the onset of the disease) was recorded in CKD patients with stable renal function during the first 12 weeks from the onset of SARS-CoV-2 (the mean values of eGFR were not statistically different within 2–24 weeks). Males had a higher risk of CKD progression to end-stage renal disease. In people with SARS-CoV-2, on the second week from the onset of the disease, a decrease in eGFR was observed with a reciprocal increase in the level of blood uric acid, which differed significantly from the baseline values. The use of dexamethasone was accompanied by a decrease in eGFR (Р ≤ 0.05) and the preservation of these disorders in people with CKD stage 3b-4 up to 24 weeks of observation (RR 0.686, 95% CI 0.264–1.780, NNT 7.636). Conclusions. The course of SARS-CoV-2 in people with hypertension degree 1–2 was characterized by the development of significant hypotension among those taking ACE inhibitors, and in patients with CKD and hypertension taking ACE inhibitors — by a decrease in GFR, hypotension, an increase in albuminuria and in the urine albumin to creatinine ratio, which was transient in most cases. Albuminuria increased less significantly in patients taking ARBs and was practically unchanged when using DRIs. Patients with CKD stage 4 and hypertension degree 2 had the greatest risks of an unfavorable prognosis. The authors hypothesized about the mechanism of SARS-CoV-2 effect when using ACE inhibitors that was similar to that of ARBs (ARB effect), i.e., in people who took ACE inhibitors, the effect of reducing blood pressure was comparable to that of the dual RAAS blockade with ACE inhibitors and ARBs.

Effect of ACE inhibitors on the course of SARS-CoV-2 in a patient with pre-existing chronic kidney disease: a clinical case

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Клінічне спостереження

Clinical Observation

ВступСерцево-судинні захворювання, як і хронічна хвороба нирок (ХХН), входять до четвірки основних факторів ризику тяжкого перебігу COVID-19 [1]. Нерідко люди з артеріальною гіпертензією (АГ) не знають про наявність у них зниженої функції нирок, яка стає випадковою знахідкою на тлі вірусної інфекції [1-10].

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“…Нерідко люди з артеріальною гіпертензією (АГ) не знають про наявність у них зниженої функції нирок, яка стає випадковою знахідкою на тлі вірусної інфекції [1-10]. Зменшення розрахункової швидкості клубочкової фільтрації (рШКФ) у такій ситуації може мати транзиторний характер або ставати погіршуючим фактором вже існуючої, можливо, раніше не діагностованої хронічної хвороби нирок [1,7,8,[11][12][13][14][15][16][17]. Аналіз ниркових подій на тлі COVID-19 показав велику складність проблеми коронавірусної інфекції, що назвали синдемією.…”

“…Аналіз ниркових подій на тлі COVID-19 показав велику складність проблеми коронавірусної інфекції, що назвали синдемією. «Синдемія» -термін, запропонований у 1990-х роках антропологом Мерріл Зінгер: «Дві або більше хвороби взаємодіють таким чином, що завдають більшої шкоди, ніж проста сума двох захворювань» [1]. Інфекція SARS-CoV-2 викликає генералізоване запалення ендотелію та вазодилатацію, що підтверджує причинність COVID-19 як судинного захворювання.…”