<b><i>Introduction:</i></b> In observational studies, increased water intake improves kidney function but not in adults with CKD stage 3 and more. CKD WIT trial has shown a nonsignificant gradual decline in kidney function after 1 year of coaching to increase water intake (CIWI) [<xref ref-type="bibr" rid="ref1">1</xref>]. We propose that CIWI may benefit in CKD stage 1–2 (G1 and G2) and depends on functional renal functional reserve (RFR) [<xref ref-type="bibr" rid="ref2">2</xref>, <xref ref-type="bibr" rid="ref3">3</xref>]. <b><i>Objective:</i></b> Parallel-group randomized trial was aimed to determinate the effectiveness of CIWI dependence of estimated glomerular filtration rate (eGFR) stage and RFR in adults with CKD 1–2 stages. <b><i>Methods:</i></b> CKD WIT trial was taken as the basis for prospective multicenter randomized trial named “Early Coaching to Increase Water Intake in CKD (ECIWIC).” The primary outcome was the change in kidney function by eGFR from baseline to 12 months. Secondary outcomes included 1-year change in urine albumin/Cr ratio, and patient-reported overall quality of health (QH) ranged from 0 (worst possible) to 10 (best possible). CIWI aimed to have the diuresis being 1.7–2 L. There were 4 groups with nondiet sodium restriction which consisted of 31 patients each: 2 groups with CKD G1 and CKD G2, undergoing CIWI and 2 others with CKD G1 and CKD G2 without CIWI (Fig. 1a). Overall checks were made at 0, 6, and 12 months. RFR evaluation was performed using 0.45% sodium chloride oral solution. <b><i>Results:</i></b> Of our randomized 124 patients (mean age 53.2 years; men 83 [67%], 0 died), mean change in 24-h urine volume was 0.6 L per day in G1 with CIWI group and 0.5 L in G2. No statistically significant data on eGFR depending CIWI were obtained (Fig. <xref ref-type="fig" rid="f01">1</xref>b). However, the trend suggests that CIWI improves eGFR in CKD G1 (from 95 to 96 mL/min/1.73 m²) and preserves eGFR decline in CKD G2 (78–78). The QH values were also preserved (from 7 to 7 in G1 and G2 groups). Although coaching to maintain the same water intake did not preserve physiological and pathological eGFR decreasing in CKD G1-2 (G1 from 96 to 93, G2 from 76 to 73; <i>t</i> = 0.6, <i>p</i> = 0.29, and <i>p</i> ≤ 0.05 in all groups) and the QH was declined (from 7 to 6 in both groups). An individual analysis of the RFR has shown that patients with RFR more than 50% (G1 19 patients, 61%, and G2 13 patients, 42%) had reliable preservation of eGFR with its increase of 1.5 mL/min on CIWI, while patients with low functional renal reserve had a drop of eGFR at 1.1 mL/min/m² within 12 months. Patients with low normal serum sodium levels have shown worse results on CIWI. <b><i>Conclusions:</i></b> With CKD G1, the CIWI leads to the preservation of the renal function with its increase of GFR per 1 mL/min/m²/per year in comparison with the same water intake. In CKD G2, the CIWI prevents physiological and pathological loss of renal function, and RFR above 50% aids restoration of eGFR both in CKD G1-2. ECIWIC trial demonstrates benefit of CIWI in patients with CKD 1–2 and preserved RFR.

Introduction and aim. There is evidence in the literature about a change in the effectiveness of inhibitors of the renin-angiotensin system (iRAS) in people with COVID-19. Considering different mechanisms of pressure reduction by different iRAS groups, one can expect differences in people with COVID-19 receiving these drugs. The aim of angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB) and direct renin inhibitors (DRi) usage in COVID-19 (BIRCOV study) was to pinpoint clinical and laboratory differences in people with hypertension who received iRAS and suffered coronavirus infection. Material and methods. An open prospective trial of 108 patients was performed in subjects suffering from COVID-19 who have been receiving iRAS: ACEi, ARB or DRi as basic antihypertensive therapy. The disease follow-up was 12 and 24 weeks. A blood pressure (BP) measurement was performed the week before COVID-19 and up to 24 weeks from the disease onset. Subanalysis in patients with chronic kidney disease (CKD) was performed. Results. In patients with COVID-19, a change in the effectiveness of antihypertensive therapy depending on the type of drug in the iRAS group has been documented in the first 4 weeks from the onset of the disease. The use of ACEi had significantly increased the risk of severe hypotension, unlike ARBs that do not cause hypotension. The synchronous decline of estimated glomerular filtration rate (eGFR) and systolic BP was more pronounced in CKD patients followed by albuminuria incidence. The greatest decrease in eGFR was in people taking ACEi. Conclusion. People with grade 1-2 hypertension who are constantly receiving RAS inhibitors suffering from COVID-19 may develop hypotension with ACEi. COVID-19 leads to transient albuminuria and decreased glomerular filtration rate, which is especially dangerous for people with CKD 4-5.

Background. The question of the possible effect of the inhibitors of the renin-angiotensin system (iRAS) on hypertensive subjects who fell ill with COVID-19 has been discussed in the literature. SARS-CoV-2 is well-known to use an angiotensin-converting enzyme 2 receptors facilitating virus entry into host cells. There are three possible mechanisms of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) effect in COVID-19 in clinical practice: with worsening, neutral, or helpful function. Considering the different mechanisms of blood pressure reduction by iRAS, one can expect differences in people with COVID-19 receiving these drugs. The purpose of the BIRCOV study is to pinpoint possible clinical and laboratory differences in hypertensive people who received iRAS and suffered from coronavirus infection. Materials and methods. Patient-Oriented Evidence that Matters (POEM) intervention was designed as an open prospective randomized two medical centers trial in subjects suffering from COVID-19 who have been receiving iRAS, either ACEi, ARB, or direct renin inhibitor (DRi) as basic antihypertensive therapy. One hundred and twenty people with stage 1–2 hypertension have been screened, 108 subjects were enrolled in the BIRCOV study. COVID-19 was confirmed by a PCR test; the disease follow-up was divided into 2 periods: up to 12 weeks and up to 24 weeks. The primary outcome measure was as follows: blood pressure (BP) was known one week before COVID-19 onset and was measured during the disease on weeks 2, 4, 12, 24. The secondary outcome measures were clinical features. Subanalysis in patients with chronic kidney disease (CKD) was performed. Results. All patients were randomized into 3 groups who received: ACEi — 42 (39 %), ARB — 35 (32 %), or DRi — 31 (29 %). The BIRCOV trial documented the trend of BP lowering in the first two weeks of the COVID-19 disease with its gradual return to baseline values up to the 12th week. Twenty-three (21 %) patients have withdrawn medicine for up to 2 weeks due to severe hypotension. However, the BP values after COVID-19 in most subjects remained lower than the baseline ones for 4 weeks. The use of ACE inhibitors significantly increased the risk of withdrawal compared to DRi (RR 1.648; 95% CI 0.772–3.519; NNT 7.0) and ARB (RR 13.023; 95% CI 1.815–93.426; NNT 2.9) due to COVID-19. The synchronous decline of estimated glomerular filtration rate (eGFR) and systolic BP was more pronounced in CKD patients. The greatest decrease in eGFR was noted in people who have been taking ACEi. The drop in eGFR ranged from 23 % in CKD stage 1 to 45 % in CKD stage 4. Two people required short-term dialysis. The analysis of secondary outcome points demonstrated that in 23 % of people without preceding albuminuria it developed in the A2 range. During 12 weeks of observation, 81 % of patients had spontaneous albuminuria reduction. Post-COVID-19 (above 12 weeks) albuminuria remained in 19 % of patients, 90 % of them had a history of CKD. Patients with preceding CKD had an increase in albuminuria in 78 % of cases, and its return to the baseline was observed only in 24 % of patients by the 12th week and in 49 % of individuals in 24 weeks. Conclusions. People with stage 1–2 hypertension who are receiving chronic iRAS and suffer from COVID-19 may develop hypotension with ACE inhibitors. COVID-19 leads to transient albuminuria and decreased glomerular filtration rate, which is especially dangerous for people with CKD.

Parallel two-group prospective multicentre randomized trial named “HYD45 — Hydration in CKD 4–5 stages” that enrolled 62 patients with CKD G4–5 was aimed at evaluating of estimated glomerular filtration rate (eGFR) with coaching to increase water intake (CIWI) with the achievement of minimally higher diuresis by 400 mL in 31 patients compared with the CKD G4–5 group without CIWI. The stated duration was 12 months, and the trial was terminated in 6 months due to a more pronounced eGFR drop in the CIWI group, namely –3.3 ml vs. 2 ml in the group without CIWI. eGFR, renal functional reserve (RFR), albumin-to-creatinine ratio, and patient’s quality of life were additionally analyzed in this trial. Finally, three randomized clinical trials were analyzed in which patients with CKD 1–2, 3, and 4–5 received hydration. The results of studies demonstrate the possible efficacy of CIWI in stage 1–2 CKD in patients with normal or increased renal functional reserve. In stage 3 CKD, CIWI showed no benefits, and in stage CKD 4–5, forced hydration resulted in greater renal function loss. Summarizing these data, the authors concluded that it is probably appropriate for healthy people to consume the amount of fluid that provides physiological diuresis of 1.2–1.8 L and urine normal osmolarity. CIWI is often excessive, forced excessive hydration may not promote a healthy lifestyle. CIWI becomes forced excess hydration as kidney function decreases. Possibly, the benefits of CIWI are lost in CKD with the progression of renal function reduction. The effect of CIWI for 12 months may be positive for stage 1 CKD and stage 2 CKD with normal functional renal reserve. CIWI is probably impractical for chronic stages 3–5 CKD. In CKD 4–5, RFR is not preserved, which probably explains the negative effect of CIWI. With CKD G1, the CIWI leads to the optimal preservation of the renal function with the increase of GFR per 1 ml/min/1.73 m2 per year in comparison with the same water intake. In CKD G2, CIWI prevents physiological and pathological loss of renal function, RFR above 50 % provides restoration of eGFR in CKD G1–2. Early Coaching to Increase Water Intake in CKD (ECIWIC) trial demonstrates benefits of CIWI in patients with CKD G1–2 and preserved RFR and may be recommended to delay the CKD worsening.