Validation of a continuous infusion of low dose Iohexol to measure glomerular filtration rate: randomised clinical trial

1. The effect of a single dose of lithium on renal function before and during intravenous infusion of dopamine (3 μg min−1 kg−1) was investigated in 12 healthy males. In a double-blind and randomized design, 450 mg or 600 mg of lithium carbonate or placebo was administered orally at 22.00 hours on three different occasions. After an overnight fast, the subjects were water-loaded and clearance studies were started at 09.00 hours with a 1 h baseline period and three 1 h periods during dopamine infusion. 2. Baseline sodium clearance with placebo was 0.65 ± 0.35 ml/min, but with lithium it increased to 1.25 ± 0.44 (P < 0.001) and 1.17 ± 0.46 ml/min (P < 0.01) after 450 and 600 mg, respectively. Urine flow rates were unchanged compared with placebo. Lithium did not significantly affect glomerular filtration rate, but both doses slightly increased effective renal plasma flow by 7% (P < 0.05) and 10% (P < 0.01), respectively. 3. The maximal natriuretic and diuretic effects of dopamine were not reduced by lithium, but the percentage increases in sodium clearance were significantly diminished after 450 mg (P < 0.01) and 600 mg (P < 0.001) of lithium. Lithium had no effect on dopamine-induced changes in effective renal plasma flow, glomerular filtration rate or osmolal clearance. Neither lithium nor dopamine influenced plasma concentrations of renin, aldosterone or atrial natriuretic peptide. 4. In conclusion, single test doses of lithium, as normally used in lithium clearance studies, increase baseline values of sodium clearance and effective renal plasma flow. Although these effects of lithium do not reduce the maximal renal responses to low-dose dopamine, they result in an underestimation of the percentage increase in sodium excretion.

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Pomalidomide Plus Low-Dose Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma and Renal Impairment: Results From a Phase II Trial

Journal of Clinical Oncology ◽

10.1200/jco.2017.76.1742 ◽

2018 ◽

Vol 36 (20) ◽

pp. 2035-2043 ◽

Cited By ~ 23

Author(s):

Meletios Dimopoulos ◽

Katja Weisel ◽

Niels W.C.J. van de Donk ◽

Karthik Ramasamy ◽

Barbara Gamberi ◽

...

Keyword(s):

Multiple Myeloma ◽

Glomerular Filtration Rate ◽

Adverse Events ◽

Renal Impairment ◽

Glomerular Filtration ◽

Phase Ii ◽

Filtration Rate ◽

Low Dose ◽

Estimated Glomerular Filtration Rate ◽

Phase Ii Trial

Purpose Renal impairment (RI) limits treatment options in patients with relapsed/refractory multiple myeloma (RRMM). Here, we prospectively studied pomalidomide plus low-dose dexamethasone (LoDEX) in patients with RRMM and moderate or severe RI, including those receiving hemodialysis. Patients and Methods MM-013, a noncomparative, European phase II trial, enrolled three patient cohorts: moderate RI (cohort A; estimated glomerular filtration rate, 30 to < 45 mL/min/1.73 m2); severe RI (cohort B; estimated glomerular filtration rate, < 30 mL/min/1.73 m2); and severe RI that requires hemodialysis (cohort C). Patients received pomalidomide 4 mg/d on days 1 to 21 and LoDEX 20 or 40 mg once per week in 28-day cycles. The primary end point was overall response rate. Results Of 81 enrolled patients (33, 34, and 14 patients in cohorts A, B, and C, respectively), 13 were still receiving treatment at data cutoff (January 28, 2017). Overall response rates were 39.4%, 32.4%, and 14.3%, with a median duration of response of 14.7 months, 4.6 months, and not estimable, respectively. Of importance, 100%, 79.4%, and 78.6% of patients, respectively, achieved disease control. With a median follow-up of 8.6 months, median overall survival was 16.4 months, 11.8 months, and 5.2 months, respectively. Complete renal responses were observed only in cohort A (18.2%), and no patients in cohort C became hemodialysis independent. Grade 3 and 4 hematologic treatment-emergent adverse events and pomalidomide discontinuations as a result of treatment-emergent adverse events occurred more frequently in cohort C. Pomalidomide pharmacokinetics were comparable among the three renal cohorts. Conclusion Pomalidomide 4 mg/d plus LoDEX is efficacious in patients with RRMM with moderate or severe RI, including those who had more advanced disease and required hemodialysis. The safety profile was acceptable among the three groups, and no new safety signals were observed.

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