scholarly journals Kidney Dysfunction among COVID-19 Patients in the United Arab Emirates

2021 ◽  
Vol 36 (1) ◽  
pp. e221-e221
Author(s):  
brahim Y. Hachim ◽  
Mahmood Y. Hachim ◽  
Kashif Bin Naeem ◽  
Haifa Hannawi ◽  
Issa Al Salmi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Renal Function ◽  
Renal Impairment ◽  
United Arab Emirates ◽  
Estimated Glomerular Filtration Rate ◽  
Severe Renal Impairment ◽  
Hematological Indices ◽  
Laboratory Markers ◽  
Function Impairment ◽  
Univariate Statistics

Objectives: We sought to determine the estimated glomerular filtration rate (eGFR) among patients with COVID-19 and to examine its correlation with different demographic, clinical, and laboratory characteristics. Methods: This study examined patients diagnosed with COVID-19 and enrolled at Al Kuwait Hospital, Dubai, UAE. eGFR was calculated using the Modification of Diet in Renal Disease equation, 186 × (SCr mg/dL)-1.154 × (age)-0203 × 0.742 [if female] × 1.212 [if black], and compared for 250 COVID-19 cases and 153 non-COVID-19 controls. Analysis were performed using univariate statistics. Results: The overall mean age of the cohort was 47.2±14.0 years, and 54.6% (n = 220) were males. The results showed that 45.3% of COVID-19 patients had mild-severe renal impairment, as reflected in the eGFR. When compared to patients with normal eGFR, those with severe renal impairment were older (62.5 vs. 40.2 years; p < 0.001), more likely to be male (100% vs. 71.1%; p = 0.016), and have comorbidities (90.9% vs. 40.0%; p < 0.001) including diabetes mellitus (72.7% vs. 21.5%; p < 0.001) and hypertension (72.7% vs. 25.2%; p = 0.003). They were also more likely to be associated with those that had severe (36.4% vs. 25.9%; p < 0.001) and critical (63.6% vs. 16.3%; p < 0.001) COVID-19 infection as well as intensive care unit admission (72.7% vs. 16.3%; p < 0.001). Correlational analysis showed a significant association between renal function indicators and different laboratory markers, including hematological indices and different liver enzymes. Conclusions: This is the first study to examine the renal function among COVID-19 cases in the Middle East. Nearly half of COVID-19 patients had moderate to severe renal impairment. Diabetes mellitus and hypertension were the most common underlying comorbidities associated with moderate-severe renal function impairment among COVID-19 patients.

scholarly journals Effect of severe renal impairment on the pharmacokinetics of brigatinib

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.

scholarly journals Pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with renal dysfunction.

1996 ◽  
Vol 40 (6) ◽  
pp. 1514-1519 ◽  
Author(s):  
A E Heald ◽  
P H Hsyu ◽  
G J Yuen ◽  
P Robinson ◽  
P Mydlow ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Renal Function ◽  
Renal Impairment ◽  
Normal Renal Function ◽  
Severe Renal Impairment ◽  
Moderate Renal Impairment ◽  
Pharmacokinetic Parameters ◽  
Geometric Means ◽  
Immunodeficiency Virus

The purpose of this study was to determine the safety and pharmacokinetics of lamivudine (3TC), a nucleoside analog that has shown potent in vitro and recent in vivo activity against human immunodeficiency virus. Sixteen human immunodeficiency virus-infected patients, six with normal renal function (creatinine clearance [CLCR], > or = 60 ml/min), four with moderate renal impairment (CLCR, 10 to 40 ml/min), and six with severe renal impairment (CLCR, < 10 ml/min), were enrolled in the study. After an overnight fast, patients were administered 300 mg of 3TC orally. Blood was obtained before 3TC administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, and 48 h afterward. Timed urine collections were performed for patients able to produce urine. Serum and urine were assayed for 3TC by reverse-phase high-performance liquid chromatography with UV detection. Pharmacokinetic parameters were calculated by using standard noncompartmental techniques. The peak concentration of 3TC increased with decreasing renal function; geometric means were 2,524, 3,538, and 5,684 ng/ml for patients with normal renal function, moderate renal impairment, and severe renal impairment, respectively. The terminal half-life also increased with decreasing renal function; geometric means were 11.5, 14.1, and 20.7 h for patients with normal renal function, moderate renal impairment, and severe renal impairment, respectively. Both oral and renal clearances were linearly correlated with CLCR. A 300-mg dose of 3TC was well tolerated by all three patient groups. The pharmacokinetics of 3TC is profoundly affected by impaired renal function. Dosage adjustment, by either dose reduction or lengthening of the dosing interval, is warranted.

scholarly journals Isatuximab plus carfilzomib and dexamethasone versus carfilzomib and dexamethasone in relapsed multiple myeloma patients with renal impairment: IKEMA subgroup analysis

Haematologica ◽  
2021 ◽  
Author(s):  
Marcelo Capra ◽  
Thomas Martin ◽  
Philippe Moreau ◽  
Ross Baker ◽  
Ludek Pour ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Renal Impairment ◽  
Glomerular Filtration ◽  
Subgroup Analysis ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Phase 3 ◽  
New Therapies

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

Abstract 11267: LX4211, a Dual Inhibitor of Sodium-Glucose Cotransporters 1 and 2, Reduces Systolic Blood Pressure in Patients With Type 2 Diabetes Mellitus and Moderate to Severe Renal Impairment

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Pablo Lapuerta ◽  
Paul Strumph ◽  
Philip Banks ◽  
Ikenna Ogbaa ◽  
Brian Zambrowicz ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Renal Impairment ◽  
Systolic Blood Pressure ◽  
Severe Renal Impairment ◽  
Postprandial Glucose ◽  
Dual Inhibitor

Introduction: Selective sodium-glucose cotransporter 2 (SGLT2) inhibitors target only the kidney, and they have reduced efficacy when patients with type 2 diabetes mellitus (T2DM) have renal impairment (RI). LX4211 blocks sodium and glucose absorption in the gastrointestinal tract by inhibition of SGLT1, and it enhances urinary sodium and glucose excretion in the urine through inhibition of SGLT2. The dual SGLT1/2 action of LX4211 was anticipated to reduce systolic blood pressure (SBP) in addition to improving glucose control in the setting of RI. Methods: This analysis explored the effect of LX4211 on SBP in a clinical trial of patients with T2DM and moderate to severe RI. Patients (N=31) were randomly assigned to be treated with LX4211 (400 mg, N=16) or placebo (N=15) qd for 7 consecutive days. Postprandial glucose levels after a standard high glucose meal served as the primary measure of pharmacodynamic activity. Baseline and Day 8 trough SBP measures were each an average of 3 seated assessments. Results: Mean baseline characteristics included age 66.4 years, estimated glomerular filtration rate (eGFR) 43.4 mL/min/1.73 m 2 , and SBP 130.9 mmHg. Postprandial glucose area under the curve (sampled from pre-dose to 4 hours post meal) was reduced from Baseline to Day 7 by 169.3 mg*hr/dL on LX4211 compared to placebo (p=0.003). Day 8 SBP reductions were 11.4 mmHg on LX4211 and 0.0 mmHg on placebo (p=0.045 for difference between groups). Patients with greater RI (eGFR <45 mL/min/1.73 m2) treated with LX4211 (N=6) had a 10.5 mmHg SBP reduction compared to 0.3 mmHg on placebo (N=9). The difference between seated and standing SBP did not change with LX4211 (0.0 mmHg change, Day 8 vs. Baseline). There were no reports of hypotension, hypovolemia, no serious adverse events, and no patient discontinued due to an adverse event. Mild hypoglycemia was reported in 1 LX4211 patient compared to 2 placebo patients. Conclusions: LX4211 may reduce SBP and enhance glycemic control in T2DM patients with moderate to severe RI.

Increased Potency and Decreased Elimination of Lamifiban, a GPIIb-IIIa Antagonist, in Patients with Severe Renal Dysfunction

1998 ◽  
Vol 79 (06) ◽  
pp. 1119-1125 ◽  
Author(s):  
Knut Nordal ◽  
Karsten Midtvedt ◽  
Timothy Goggin ◽  
Frank Brosstad ◽  
Gustav Lehne
Keyword(s):  
Renal Function ◽  
Renal Impairment ◽  
Ex Vivo ◽  
Severe Renal Impairment ◽  
Thrombus Formation ◽  
Drug Dosage ◽  
The Novel ◽  
Platelet Membrane Receptor ◽  
Group 3 ◽  
Group 2

SummaryActivation of the platelet membrane receptor glycoprotein (GP) IIb-IIIa is essential for thrombus formation. The novel nonpeptide GPIIb-IIIa antagonist, lamifiban, represents a promising approach for antiplatelet therapy in patients with cardiovascular disease. Since renal impairment frequently occurs in these patients, we designed a phase I study to assess the tolerability, pharmacodynamics and pharmacokinetics of lamifiban in patients with renal impairment. Four healthy volunteers (Group 1) with creatinine clearance (CLCR) >75 ml/min, eight patients (Group 2) with mild to moderately impaired renal function (CLCR 30-74 ml/min) and eight patients (Group 3) with severe renal impairment (CLCR 10-29 ml/min) were studied. They received stepwise increased doses of lamifiban intravenously (IV). There was a linear relationship between the systemic clearance of the drug and renal function (R2 = 0.86). The mean plasma concentration required for half-maximal inhibition of thrombin-receptor agonist peptide (TRAP) induced platelet aggregation (EC50) ex vivo was 21, 28 and 11 ng/ml in Groups 1, 2 and 3. The patients in Group 3 were sensitized to the anti-platelet effect allowing an 18-fold dosage reduction without compromising the pharmacodynamics. In conclusion, the decreased clearance of lamifiban may act in concert with increased potency of the drug in patients with severe renal impairment, and the drug dosage should be reduced accordingly.

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