Clinical Response and Safety of Angiotensin Receptor and Neprilysin Inhibitor Combination in Advanced Chronic Kidney Disease and Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Though the combination of an angiotensin receptor blocker (ARB) and a neprilysin inhibitor (ARNi) has been shown to be useful in heart failure with reduced ejection fraction (HFrEF), its use has mostly been restricted to chronic kidney disease (CKD) patients with an estimated glomerular filtration rate (eGFR) >30 mL/minute/1.73 m2 . We studied the role of ARNi in advanced CKD. MATERIALS AND METHODS: Patients with HFrEF and advanced CKD with an eGFR of <30 mL/ minute/1.73 m2 were given ARNi (sacubitril with valsartan) and prospectively studied for changes in hospitalization rate for HF, clinical symptoms, levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP), eGFR, and potassium. RESULTS: Of 34 patients who received ARNi, five were excluded due to hyperkalemia and three due to a decrease in eGFR >30% occurring within 1 month. The remaining 26 patients included 17 with diabetes mellitus (DM) and 23 with underlying coronary artery disease. A total of eight patients had stage 4 and 18 stage 5 CKDs, amongst which eight required hemodialysis. Following ARNi, there was a significant decrease in the need for hospitalization for breathlessness (2.04 ± 1.03-0.23 ± 0.51; p < 0,05), New York Heart Association (NYHA) and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores (3.77 ± 0.43-2.19 ± 0.56 and 28.58 ± 9.04-64.81 ± 14.3, respectively, p < 0.001) and NT-pro-BNP levels (24761 ± 12157.51-20149.92 ± 13555.269, p < 0.05) without significant change in eGFR after 6 months. There were no significant differences in the need for hospitalization, changes in NT proBNP levels and eGFR between stages 4 and 5. CONCLUSION: Neprilysin inhibitor (ARNi) is effective and can be used with care even in patients with CKD stages 4 and 5 having HFrEF with monitoring of eGFR and potassium.

Clinical Response and Pattern of B cell Suppression with Single Low Dose Rituximab in Nephrology.

Background: There is no consensus regarding dose and frequency of rituximab in nephrology with extrapolation of doses used in treating lymphoproliferative disorders. There are no guidelines on targeting initial and subsequent doses on the basis of CD19+ B cells. Methods: Initially, 100 mg rituximab was given to 42 adults with steroid-dependent nephrotic syndrome (SDNS) and frequently relapsing nephrotic syndrome (FRNS), idiopathic membranous nephropathy (MN), and high-immunologic-risk kidney transplantation. Absolute and percentage levels of CD19 B cells and clinical status were assessed at baseline, days 30, 90, and 180, and at 1 year. Subsequent doses of rituximab were on the basis of CD19 B cell reconstitution and clinical response. Results: CD19 B cell percentage decreased from 16.3 ± 7.6 to 0.3 ± 0.3 (P≤0.001), 1.9 ± 1.7 (P≤0.001), and 4.0 ± 4.5 (P=0.005) by 30, 90, and 180 days, respectively. Suppression of CD19 B cell count below 1% at days 30, 90, and 180 was seen in 40 of 42 (95.2%), 18 of 42 (42.9%), and 7 of 42 (16.7%) patients, respectively. Of 30 with SDNS and FRNS followed up for 1 year, 29 (96.7%) went into remission at day 30. Remission was sustained in 23 (76.6%) at day 180 and 21 (70%) at 1 year. There was a significant decrease (P<0.001) in the dose of steroids needed to maintain remission at 180 days after rituximab (0.27 ± 0.02 mg/kg to 0.02 ± 0.00 mg/kg). CD19 B cell percentage at 90 days correlated with relapse (P=0.001; odds ratio 1.42; 95% confidence interval, 1.25 to 2.57). Eighteen (60%) required an additional dose. Of five with MN, four achieved remission by 6 months, which was sustained in three by 1 year. Of the seven kidney transplant recipients, two had antibody-mediated rejections, although CD19 B cells were suppressed even at 1 year. Conclusions: Low-dose rituximab induces sustained depletion of CD19 B cells for up to 90 days. Its role in preventing relapses in SDNS, FRNS, MN, and rejection needs further study.