Drugs and the Kidneys: Clinical Pharmacology Perspectives

Vincent, John

doi:10.1002/cpt.775

Cited by 6 publications

(5 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Measurement of kidney function is essential in daily clinical practice. Precise and unbiased measurement of kidney function is particularly crucial in the decision of the following situations: adjustment of drug dosages [21] , diagnosis of CKD [22] , and suitability as a living donor for kidney transplantation [23] . C-in is the gold standard measurement of GFR [1] , and additional methods using a variety of radioactive ( 99 mTc-DTPA, 125 I-iothalamate, and 51 Cr-EDTA) and nonradioactive (iohexol and iothalamate) tracers have been developed thus far [24] .…”

Section: Discussionmentioning

confidence: 99%

Measurement of glomerular filtration rate using endogenous d-serine clearance in living kidney transplant donors and recipients

et al. 2022

View full text Add to dashboard Cite

Background Endogenous molecules that provide an unbiased and a precise evaluation of kidney function are still necessary. We explored the potential of clearance of D-serine, a rare enantiomer of serine and a biomarker of kidney function, as a measure of glomerular filtration rate (GFR).Methods This was a cross-sectional observational study of 200 living kidney transplant donors and recipients enrolled between July 2019 and December 2020 in a single Japanese center, for whom GFR was measured by clearance of inulin (C-in). Clearance of D-serine (C-DSer) was calculated based on blood and urine levels of D-serine, as measured by two-dimensional high-performance liquid chromatography. Analytical performance was assessed by calculating biases. Utilizing data from 129 participants, we developed equations for C-in based on C-DSer and C-cre using a linear regression model, and the performance was validated in 68 participants.Findings The means of C-in and C-DSer were 66.7 and 55.7 mL/min/1.73 m 2 of body surface area, respectively, in the entire cohort. C-DSer underestimated C-in with a proportional bias of 22.0% (95% confidence interval, 14.2 −29.8%) and a constant bias of -1.24 (-5.78−3.31), whereas the proportional bias was minor to that of C-cre (34.6% [31.1−38.2%] and 2.47 (-1.18−6.13) for proportional and constant bias, respectively). Combination of C-DSer and Ccre measured C-in with an equation of 0.391 £ C-DSer + 0.418 £ C-cre + 3.852, which reduced the proportional bias (6.5% [-0.2−13.1%] and -4.30 [-8.87−0.28] for proportional and constant bias, respectively). In the validation dataset, this equation performed well with median absolute residual of 3.5 [2.3−4.8], and high ratio of agreement (ratios of 30% and 15% different from C-in [P 30 and P 15 ] of 98.5 [91.4−100] and 89.7 [80.0−95.2], respectively).Interpretation The smaller proportional bias compared to that of C-cre is an advantage of C-DSer as a measure of Cin. Combinational measurement of D-serine and creatinine, two endogenous molecules, has the potential to serve as a measure of GFR with precision and minor biases and can support important clinical decisions.

show abstract

Section: Discussionmentioning

confidence: 99%

Measurement of glomerular filtration rate using endogenous d-serine clearance in living kidney transplant donors and recipients

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Las lesiones medulares provocan múltiples alteraciones metabólicas y sistémicas que pueden afectar la eficacia y seguridad del uso de algunas drogas 6 . El riñón es el principal regulador del ambiente fluido interno 10 . Los cambios fisiológicos asociados con la disfunción renal pueden tener efectos pronunciados en el rendimiento de gran cantidad de fármacos 6,10,11 , en particular de aquellos eliminados principalmente por vía renal, como los aminoglucósidos y las quinolonas, que son ampliamente utilizados después de una lesión medular 6 .…”

Section: Consecuencias De La Disfunción Renal En La Farmacoterapia Del Paciente Con Lesión Medularunclassified

“…El riñón es el principal regulador del ambiente fluido interno 10 . Los cambios fisiológicos asociados con la disfunción renal pueden tener efectos pronunciados en el rendimiento de gran cantidad de fármacos 6,10,11 , en particular de aquellos eliminados principalmente por vía renal, como los aminoglucósidos y las quinolonas, que son ampliamente utilizados después de una lesión medular 6 . La detección temprana de disfunción renal es de vital importancia 11,12 , ya que la excreción renal de los fármacos y sus metabolitos se lleva a cabo mediante una combinación de tres procesos: filtración glomerular, secreción tubular y reabsorción tubular 6,11 .…”

Section: Consecuencias De La Disfunción Renal En La Farmacoterapia Del Paciente Con Lesión Medularunclassified

“…Por lo tanto, las alteraciones de la TFG dan como resultado una disminución del aclaramiento del fármaco 12 . La función renal deteriorada obliga a ajustar la dosis del fármaco, en particular los excretados por filtración glomerular, que son potencialmente tóxicos, como los aminoglucósidos 6,10,12 .…”

Section: Consecuencias De La Disfunción Renal En La Farmacoterapia Del Paciente Con Lesión Medularunclassified

See 1 more Smart Citation

Falla renal en el paciente con lesión medular aguda

et al. 2019

View full text Add to dashboard Cite

Las lesiones medulares constituyen un evento catastrófico relacionado con discapacidades físicas significativas y grandesimplicaciones socioeconómicas. Entre sus complicaciones, la insuficiencia renal, se encuentra relacionada con mayor morbilidad y mortalidad. De todos los mecanismos fisiopatológicos propuestos de la enfermedad, destacan el desequilibrio en las funciones reguladoras del sistema nervioso autónomo, el estado inflamatorio sistémico producto de la activación exponencial de las células inflamatorias circulantes, y la rabdomiólisis producto del trauma. Estos cambios fisiológicos que llevan a la insuficiencia renal afectan el metabolismo de diferentes fármacos, en particular de aquellos con eliminación renal. Los componentes intracelulares de la maquinaria inflamatoria, incluidas enzimas y factores de transcripción, también pueden servir como dianas terapéuticas para resolver la inflamación en múltiples órganos posterior a una lesión medular.

show abstract

“…Drug injury assessment relies heavily on experimental animal models, and it is difficult to precisely reflect the same predictive capacity in humans. Current human two-dimensional (2D) in vitro models are limited in accurately replicating the in vivo organ system 10,11 . Organoids are considered as complex three-dimensional (3D) structures that develop from stem cells or organ-specific progenitors through a self-organization process 12 .…”

Section: Introductionmentioning

confidence: 99%

Three-Dimensional Renal Organoids from Whole Kidney Cells: Generation, Optimization, and Potential Application in Nephrotoxicology In Vitro

et al. 2020

View full text Add to dashboard Cite

The kidney function of patients with chronic kidney disease (CKD) is impaired irreversibly. Organ transplantation is the only treatment to restore kidney function in CKD patients. The assessment of new potential therapeutic procedures relies heavily on experimental animal models, but it is limited by its human predictive capacity. In addition, the frequently used two-dimensional in vitro human renal cell models cannot replicate all the features of the in vivo situation. In this study, we developed a three-dimensional (3D) in vitro human renal organoid model from whole kidney cells as a promising drug screening tool. At present, the renal tissue generated from human pluripotent stem cells (hPSCs) exhibits intrinsic tumorigenicity properties. Here we first developed a 3D renal organoid culture system that originated from adult differentiated cells without gene modification. Renal organoids composed of multiple cell types were created under optimal experimental conditions and evaluated for morphology, viability and erythropoietin production. As a novel screening tool for renal toxicity, 3D organoids were exposed to three widely used drugs: aspirin, penicillin G and cisplatin. The study results showed this 3D renal organoid model can be used as a drug screening tool, a new in vitro 3D human kidney model, and provide hope for potential regenerative therapies for CKD.

show abstract

Drugs and the Kidneys: Clinical Pharmacology Perspectives

Cited by 6 publications

References 16 publications

Measurement of glomerular filtration rate using endogenous d-serine clearance in living kidney transplant donors and recipients

Measurement of glomerular filtration rate using endogenous d-serine clearance in living kidney transplant donors and recipients

Falla renal en el paciente con lesión medular aguda

Three-Dimensional Renal Organoids from Whole Kidney Cells: Generation, Optimization, and Potential Application in Nephrotoxicology In Vitro

Contact Info

Product

Resources

About