Renal impairment resulting from hypothyroidism--or impaired estimated glomerular filtration rate in a patient with hypothyroidsm

Renal impairment (RI) is common in patients with multiple myeloma (MM) and new therapies that can improve renal function are needed. The Phase 3 IKEMA study (NCT03275285) investigated isatuximab (Isa) with carfilzomib and dexamethasone (Kd) vs Kd in relapsed MM. This subgroup analysis examined results from patients with RI, defined as estimated glomerular filtration rate

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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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Predictors of estimated glomerular filtration rate progression, stabilization or improvement after chronic renal impairment in HIV-positive individuals

AIDS ◽

10.1097/qad.0000000000001464 ◽

2017 ◽

Vol 31 (9) ◽

pp. 1261-1270 ◽

Cited By ~ 13

Author(s):

Lene Ryom ◽

Amanda Mocroft ◽

Ole Kirk ◽

Peter Reiss ◽

Michael Ross ◽

...

Keyword(s):

Glomerular Filtration Rate ◽

Renal Impairment ◽

Glomerular Filtration ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

Hiv Positive ◽

Chronic Renal Impairment

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Strength of evidence for labeled dosing recommendations in renal impairment

Clinical Trials ◽

10.1177/1740774516673818 ◽

2016 ◽

Vol 14 (2) ◽

pp. 219-221 ◽

Cited By ~ 1

Author(s):

Joshua J Gagne ◽

Nazleen F Khan ◽

Tara S Raj ◽

Lajja R Patel ◽

Niteesh K Choudhry

Keyword(s):

United States ◽

Glomerular Filtration Rate ◽

Renal Impairment ◽

Glomerular Filtration ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

The United States ◽

Phase Iii ◽

Pharmacokinetic Studies ◽

Kidney Impairment

Background/Aims: Renally excreted medications often require dose adjustment in patients with kidney impairment. While drug development and approval in the United States are typically based on several Phase I and II studies and one or more larger Phase III randomized trials, the basis for labeled dosing recommendations for patients with renal impairment is less well known. In response, we aimed to quantify the level of evidence used to recommend labeled dosing adjustments for newly approved drugs in patients with renal impairment. Methods: We reviewed publicly available drug labels and approval packages for new molecular entities approved in the United States between 2012 and 2014. The sample was restricted to 29 renally excreted new molecular entities that were not granted orphan drug status. We extracted data regarding approved indications, normal dosing, dosing adjustments for patients with mild (estimated glomerular filtration rate >60 mL/min/1.73 m2), moderate (estimated glomerular filtration rate 30–<60 mL/min/1.73 m2), and severe (estimated glomerular filtration rate <30 mL/min/1.73 m2) renal impairment, characteristics of studies used to justify dosing adjustments, and numbers of subjects in each study. Results: In all, 14 of 29 (48%) new molecular entities had labels that recommended dosing adjustments for patients with mild, moderate, and/or severe renal impairment. Among these 14 new molecular entities, 4 (29%) used only pharmacokinetic studies to justify the recommendations, with no examination of clinical outcomes for patients with renal impairment. Where data were available, the median number of patients with renal impairment evaluated in studies used for dosing adjustment was 34 (range, 4–5976). Of the 15 new molecular entities with no recommended dosing adjustments for this population, 2 (13%) did not report assessing the effects of renal impairment. Conclusion: Nearly half of newly approved renally excreted drugs include dosing adjustments for kidney impairment on the label, but the recommendations are usually based on very small numbers of patients and often utilize pharmacokinetic studies alone. More research is needed to understand the benefits and risks of new drugs in patients with renal impairment.

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Sunitinib versus sorafenib for patients with advanced renal cell carcinoma with renal impairment before the immune-oncology therapy era

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyz127 ◽

2019 ◽

Vol 49 (12) ◽

pp. 1164-1171

Author(s):

Tatsuya Takayama ◽

Taro Kubo ◽

Masahiro Yamazaki ◽

Saki Takeshima ◽

Maiko Komatsubara ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Glomerular Filtration Rate ◽

Renal Impairment ◽

Cell Carcinoma ◽

Glomerular Filtration ◽

Renal Cell ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

Advanced Renal Cell Carcinoma ◽

Long Term Treatment

Abstract Objectives The efficacy and safety of sunitinib versus sorafenib in patients with advanced renal cell carcinoma with renal impairment remains poorly documented. Patients and methods We assessed the efficacy and safety of sunitinib and sorafenib in patients with advanced renal cell carcinoma with an estimated glomerular filtration rate of 15–60 mL/min/1.73 m2 by reviewing the medical records of patients treated at Jichi Medical University Hospital, Japan, between May 2008 and August 2016. Results Twenty-seven patients were treated with sunitinib and 14 with sorafenib. Median progression-free survival in sunitinib- and sorafenib-treated patients was comparable, at 6.6 vs 5.8 months, respectively (HR, 1.618; 95% CI, 0.689–3.798; P = 0.2691). Median overall survival was also comparable, at 65.9 vs 58.0 months (HR, 0.985; 95% CI, 0.389–2.479; P = 0.9748). Grade 3 or higher adverse events were significantly more frequent in the sunitinib-treated than sorafenib-treated patients (P = 0.0357). Compared to pre-treatment values, estimated glomerular filtration rate at the discontinuation of treatment was not decreased in either group. In contrast, estimated glomerular filtration rate was decreased on long-term treatment, particularly in previously nephrectomized patients. Conclusions Sunitinib and sorafenib had similar efficacy in patients with advanced renal cell carcinoma and severe renal impairment. Although renal function was not markedly impaired in either group, close attention to decreased renal function may be necessary in previously nephrectomized patients on long-term treatment.

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561-P: Serum C-Peptide Concentrations Are Inversely Associated with Cardiovascular Autonomic Neuropathy in Type 2 Diabetic Individuals With and Without Renal Impairment Independently of Estimated Glomerular Filtration Rate

Diabetes ◽

10.2337/db19-561-p ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 561-P

Author(s):

JIN OOK CHUNG ◽

SEON-YOUNG PARK ◽

DONG HYEOK CHO ◽

DONG JIN CHUNG ◽

MIN YOUNG CHUNG

Keyword(s):

Glomerular Filtration Rate ◽

Renal Impairment ◽

Glomerular Filtration ◽

Autonomic Neuropathy ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

Cardiovascular Autonomic Neuropathy ◽

C Peptide ◽

Type 2 Diabetic

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Determinants of Risk Factors for Renal Impairment among HIV-Infected Patients Treated with Tenofovir Disoproxil Fumarate-Based Antiretroviral Regimen in Southern Vietnam

BioMed Research International ◽

10.1155/2020/7650104 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Cuong Q Hoang ◽

Hai D Nguyen ◽

Huy Q Vu ◽

Khai T Nguyen ◽

Linh T Hoang ◽

...

Keyword(s):

Risk Factors ◽

Glomerular Filtration Rate ◽

Renal Impairment ◽

Glomerular Filtration ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

Cross Sectional Survey ◽

Serological Tests ◽

Cross Sectional ◽

Increased Risk

Background. The situation of renal impairment among HIV-infected patients treated with TDF-based antiretroviral (ARV) regimen greater than 3 years is little known when TDF use has been promptly increasing in Vietnam. Methods. We analyse demographic and clinical data from a cross-sectional survey of 400 HIV-infected patients aged ≥18 years, who were treatment-naive or switched TDF regimen within over 3 years between November 2018 and March 2019. Serological tests for serum creatinine, ALT, and AST were performed. Renal impairment was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Multivariate regression analyses were used to explore the risk factors associated with renal impairment. Results. At the baseline, 7.8% of respondents had estimated glomerular filtration rate (eGFR) of 30–59 mL/min/1.73 m2 and 0.8% had eGFR of 15–29 mL/min/1.73 m2, out of 34 (8.5%) of participants who had renal impairment. Multivariate analysis showed that participants who had preexposure to isoniazid (adjusted PR [aPR] = 0.35 Cl: 0.14–0.91) compared with nonexposure to isoniazid who had a BMI from 18.5 up to 25 kg/m2 (aPR = 0.31 Cl: 0.15–0.62) compared with BMI below 18.5 kg/m2 were less likely to suffer from renal impairment. Patients aged greater than 60 years (aPR = 26.75, 95% Cl: 3.38–211.62) compared with those aged 20–29 years were more likely to have increased risk of renal impairment. Conclusion. Our findings underscore the need for longitudinal studies to assess the influence of TDF on maintaining the low prevalence of renal impairment among HIV-infected patients in Vietnam.

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Effect of severe renal impairment on the pharmacokinetics of brigatinib

Investigational New Drugs ◽

10.1007/s10637-021-01095-5 ◽

2021 ◽

Author(s):

Neeraj Gupta ◽

Michael J. Hanley ◽

David Kerstein ◽

Meera Tugnait ◽

Narayana Narasimhan ◽

...

Keyword(s):

Renal Function ◽

Glomerular Filtration Rate ◽

Renal Impairment ◽

Protein Binding ◽

Healthy Volunteers ◽

Glomerular Filtration ◽

Normal Renal Function ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

Severe Renal Impairment

SummaryBackground Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, targets activated, mutant forms of ALK and overcomes mechanisms of resistance to the ALK inhibitors crizotinib, ceritinib, and alectinib. Brigatinib is approved in multiple countries for treatment of patients with ALK-positive non–small cell lung cancer. Based on population pharmacokinetic (PK) analyses, no dosage adjustment is required for patients with mild or moderate renal impairment. Methods An open-label, single-dose study was conducted to evaluate the PK of brigatinib (90 mg) in patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m2; n = 8) and matched healthy volunteers with normal renal function (estimated glomerular filtration rate ≥ 90 mL/min/1.73 m2; n = 8). Plasma and urine were collected for the determination of plasma protein binding and estimation of plasma and urine PK parameters. Results Plasma protein binding of brigatinib was similar between patients with severe renal impairment (92 % bound) and matched healthy volunteers with normal renal function (91 % bound). Unbound brigatinib exposure (area under the plasma concentration-time curve from time zero to infinity) was approximately 92 % higher in patients with severe renal impairment compared with healthy volunteers with normal renal function. The renal clearance of brigatinib in patients with severe renal impairment was approximately 20 % of that observed in volunteers with normal renal function. Conclusions These findings support a brigatinib dosage reduction of approximately 50 % in patients with severe renal impairment.Trial registry: Not applicable.

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