Stanley M.H. Yeung

Background Observational studies suggest that adequate dietary potassium intake (90–120 mmol/day) may be renoprotective, but the effects of increasing dietary potassium and the risk of hyperkalemia are unknown. Methods This is a prespecified analysis of the run-in phase of a clinical trial in which 191 patients (age 68±11 years, 74% males, 86% European ancestry, eGFR 31±9 ml/min per 1.73 m 2 , 83% renin-angiotensin system inhibitors, 38% diabetes) were treated with 40 mmol potassium chloride (KCl) per day for 2 weeks. Results KCl supplementation significantly increased urinary potassium excretion (72±24 to 107±29 mmol/day), plasma potassium (4.3±0.5 to 4.7±0.6 mmol/L), and plasma aldosterone (281 [198–431] to 351 [241–494] ng/L), but had no significant effect on urinary sodium excretion, plasma renin, BP, eGFR, or albuminuria. Furthermore, KCl supplementation increased plasma chloride (104±3 to 105±4 mmol/L) and reduced plasma bicarbonate (24.5±3.4 to 23.7±3.5 mmol/L) and urine pH (all P <0.001), but did not change urinary ammonium excretion. In total, 21 participants (11%) developed hyperkalemia (plasma potassium 5.9±0.4 mmol/L). They were older and had higher baseline plasma potassium. Conclusions In patients with CKD stage G3b–4, increasing dietary potassium intake to recommended levels with potassium chloride supplementation raises plasma potassium by 0.4 mmol/L. This may result in hyperkalemia in older patients or those with higher baseline plasma potassium. Longer-term studies should address whether cardiorenal protection outweighs the risk of hyperkalemia. Clinical trial number: NCT03253172

<b><i>Background/Aims:</i></b> Dietary potassium (K<sup>+</sup>) has beneficial effects on blood pressure and cardiovascular (CV) outcomes. Recently, several epidemiological studies have revealed an association between urinary K<sup>+</sup> excretion (as proxy for dietary intake) and better renal outcomes in subjects with chronic kidney disease (CKD). To address causality, we designed the “K<sup>+</sup> in CKD” study. <b><i>Methods:</i></b> The K<sup>+</sup> in CKD study is a multicenter, randomized, double blind, placebo-controlled clinical trial aiming to include 399 patients with hypertension, CKD stage 3b or 4 (estimated glomerular filtration rate [eGFR] 15–44 mL/min/1.73 m<sup>2</sup>), and an average eGFR decline > 2 mL/min/1.73 m<sup>2</sup>/year. As safety measure, all included subjects will start with a 2-week open-label phase of 40 mmol potassium chloride daily. Patients who do not subsequently develop hyperkalemia (defined as serum K<sup>+</sup> >5.5 mmol/L) will be randomized to receive potassium chloride, potassium citrate (both K<sup>+</sup> 40 mmol/day), or placebo for 2 years. The primary end point is the difference in eGFR after 2 years of treatment. Secondary end points include other renal outcomes (> 30% decrease in eGFR, doubling of serum creatinine, end-stage renal disease, albuminuria), ambulatory blood pressure, CV events, all-cause mortality, and incidence of hyperkalemia. Several measurements will be performed to analyze the effects of potassium supplementation, including body composition monitoring, pulse wave velocity, plasma renin and aldosterone concentrations, urinary ammonium, and intracellular K<sup>+</sup> concentrations. <b><i>Conclusion:</i></b> The K<sup>+</sup> in CKD study will demonstrate if K<sup>+</sup> sup­plementation has a renoprotective effect in progressive CKD, and whether alkali therapy has additional beneficial effects.

PURPOSE The phase III RESILIENT trial compared second-line liposomal irinotecan with topotecan in patients with small cell lung cancer (SCLC). PATIENTS AND METHODS Patients with SCLC and progression on or after first-line platinum-based chemotherapy were randomly assigned (1:1) to intravenous (IV) liposomal irinotecan (70 mg/m 2 every 2 weeks in a 6-week cycle) or IV topotecan (1.5 mg/m 2 daily for 5 consecutive days, every 3 weeks in a 6-week cycle). The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS) and objective response rate (ORR). RESULTS Among 461 randomly assigned patients, 229 received liposomal irinotecan and 232 received topotecan. The median follow-up was 18.4 months. The median OS was 7.9 months with liposomal irinotecan versus 8.3 months with topotecan (hazard ratio [HR], 1.11 [95% CI, 0.90 to 1.37]; P = .31). The median PFS per blinded independent central review (BICR) was 4.0 months with liposomal irinotecan and 3.3 months with topotecan (HR, 0.96 [95% CI, 0.77 to 1.20]; nominal P = .71); ORR per BICR was 44.1% (95% CI, 37.6 to 50.8) and 21.6% (16.4 to 27.4), respectively. Overall, 42.0% and 83.4% of patients receiving liposomal irinotecan and topotecan, respectively, experienced grade ≥3 related treatment-emergent adverse events (TEAEs). The most common grade ≥3 related TEAEs were diarrhea (13.7%), neutropenia (8.0%), and decreased neutrophil count (4.4%) with liposomal irinotecan and neutropenia (51.6%), anemia (30.9%), and leukopenia (29.1%) with topotecan. CONCLUSION Liposomal irinotecan and topotecan demonstrated similar median OS and PFS in patients with relapsed SCLC. Although the primary end point of OS was not met, liposomal irinotecan demonstrated a higher ORR than topotecan. The safety profile of liposomal irinotecan was consistent with its known safety profile; no new safety concerns emerged.

OBJECTIVE: To study whether fibroblast growth factor 23 (FGF23) is associated with adverse outcomes in patients with type 2 diabetes and normal or mildly impaired kidney function. RESEARCH DESIGN AND METHODS: . Associations of FGF23 with all-cause mortality and major adverse cardiovascular events (MACE) were studied by Cox regression. RESULTS: During a follow-up of 5.8 years (3.3-6.5), 47 patients developed MACE and 28 patients died. FGF23 was associated with an increased risk of all-cause mortality (age- and sex-adjusted hazard ratio 2.78 [95% CI 1.76-4.40]) and MACE (1.67 [1.12-2.49]). Results were similar after additional adjustment for other potential confounders and were consistent upon replication in an independent cohort. CONCLUSIONS: In patients with type 2 diabetes and normal or mildly impaired kidney function, FGF23 is associated with an increased risk of cardiovascular events and mortality.