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1.
Physiol Rev ; 102(2): 993-1024, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-34486394

RESUMEN

Over the course of more than 500 million years, the kidneys have undergone a remarkable evolution from primitive nephric tubes to intricate filtration-reabsorption systems that maintain homeostasis and remove metabolic end products from the body. The evolutionarily conserved solute carriers organic cation transporter 2 (OCT2) and organic anion transporters 1 and 3 (OAT1/3) coordinate the active secretion of a broad range of endogenous and exogenous substances, many of which accumulate in the blood of patients with kidney failure despite dialysis. Harnessing OCT2 and OAT1/3 through functional preservation or regeneration could alleviate the progression of kidney disease. Additionally, it would improve current in vitro test models that lose their expression in culture. With this review, we explore OCT2 and OAT1/3 regulation from different perspectives: phylogenetic, ontogenetic, and cell dynamic. Our aim is to identify possible molecular targets both to help prevent or compensate for the loss of transport activity in patients with kidney disease and to enable endogenous OCT2 and OAT1/3 induction in vitro in order to develop better models for drug development.


Asunto(s)
Riñón/metabolismo , Proteína 1 de Transporte de Anión Orgánico/metabolismo , Transportadores de Anión Orgánico Sodio-Independiente/metabolismo , Transportador 2 de Cátion Orgánico/metabolismo , Animales , Humanos , Enfermedades Renales/metabolismo , Filogenia
2.
Brief Bioinform ; 25(5)2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39082652

RESUMEN

The development of omics technologies has driven a profound expansion in the scale of biological data and the increased complexity in internal dimensions, prompting the utilization of machine learning (ML) as a powerful toolkit for extracting knowledge and understanding underlying biological patterns. Kidney disease represents one of the major growing global health threats with intricate pathogenic mechanisms and a lack of precise molecular pathology-based therapeutic modalities. Accordingly, there is a need for advanced high-throughput approaches to capture implicit molecular features and complement current experiments and statistics. This review aims to delineate strategies for integrating multi-omics data with appropriate ML methods, highlighting key clinical translational scenarios, including predicting disease progression risks to improve medical decision-making, comprehensively understanding disease molecular mechanisms, and practical applications of image recognition in renal digital pathology. Examining the benefits and challenges of current integration efforts is expected to shed light on the complexity of kidney disease and advance clinical practice.


Asunto(s)
Enfermedades Renales , Aprendizaje Automático , Humanos , Enfermedades Renales/genética , Enfermedades Renales/metabolismo , Genómica/métodos , Biología Computacional/métodos , Proteómica/métodos , Multiómica
3.
Curr Issues Mol Biol ; 46(5): 4595-4608, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38785547

RESUMEN

Proteogenomics represents a transformative intersection in nephrology, uniting genomics, transcriptomics, and proteomics to unravel the molecular intricacies of kidney diseases. This review encapsulates the methodological essence of proteogenomics and its profound implications in chronic kidney disease (CKD) research. We explore the proteogenomic pipeline, highlighting the integrated analysis of genomic, transcriptomic, and proteomic data and its pivotal role in enhancing our understanding of kidney pathologies. Through case studies, we showcase the application of proteogenomics in clear cell renal cell carcinoma (ccRCC) and Autosomal Recessive Polycystic Kidney Disease (ARPKD), emphasizing its potential in personalized treatment strategies and biomarker discovery. The review also addresses the challenges in proteogenomic analysis, including data integration complexities and bioinformatics limitations, and proposes solutions for advancing the field. Ultimately, this review underscores the prospective future of proteogenomics in nephrology, particularly in advancing personalized medicine and providing novel therapeutic insights.

4.
Kidney Int ; 105(2): 364-375, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37914088

RESUMEN

Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplant. This is partly because doctors give very large volumes of artificial fluids to keep the new kidney working. When severe, fluid imbalance can lead to seizures, cerebral edema and death. In this pragmatic, open-label, randomized controlled trial, we randomly assigned (1:1) pediatric kidney transplant recipients to Plasma-Lyte-148 or standard of care perioperative intravenous fluids (predominantly 0.45% sodium chloride and 0.9% sodium chloride solutions). We then compared clinically significant electrolyte and acid-base abnormalities in the first 72 hours post-transplant. The primary outcome, acute hyponatremia, was experienced by 53% of 68 participants in the Plasma-Lyte-148 group and 58% of 69 participants in the standard fluids group (odds ratio 0·77 (0·34 - 1·75)). Five of 16 secondary outcomes differed with Plasma-Lyte-148: hypernatremia was significantly more frequent (odds ratio 3·5 (1·1 - 10·8)), significantly fewer changes to fluid prescriptions were made (rate ratio 0·52 (0·40-0·67)), and significantly fewer participants experienced hyperchloremia (odds ratio 0·17 (0·07 - 0·40)), acidosis (odds ratio 0·09 (0·04 - 0·22)) and hypomagnesemia (odds ratio 0·21 (0·08 - 0·50)). No other secondary outcomes differed between groups. Serious adverse events were reported in 9% of participants randomized to Plasma-Lyte-148 and 7% of participants randomized to standard fluids. Thus, perioperative Plasma-Lyte-148 did not change the proportion of children who experienced acute hyponatremia compared to standard fluids. However fewer fluid prescription changes were made with Plasma-Lyte-148, while hyperchloremia and acidosis were less common.


Asunto(s)
Acidosis , Hiponatremia , Trasplante de Riñón , Desequilibrio Hidroelectrolítico , Humanos , Niño , Cloruro de Sodio/efectos adversos , Hiponatremia/epidemiología , Hiponatremia/etiología , Electrólitos/efectos adversos , Acidosis/etiología , Acidosis/inducido químicamente , Desequilibrio Hidroelectrolítico/etiología , Desequilibrio Hidroelectrolítico/inducido químicamente , Fluidoterapia/efectos adversos , Soluciones Isotónicas/efectos adversos , Gluconatos , Cloruro de Potasio , Cloruro de Magnesio , Acetato de Sodio
5.
Kidney Int ; 105(2): 259-268, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38008159

RESUMEN

Health care on a global scale significantly contributes to carbon emissions, with high-income countries being the primary culprits. Within health care, dialysis plays a significant role as a major source of emissions. Low- and middle-income countries have a high burden of kidney disease and are facing an increasing demand for dialysis. This reality presents multiple opportunities to plan for environmentally sustainable and quality kidney care. By placing a stronger emphasis on primary and secondary prevention of kidney disease and its progression, within the framework of universal health coverage, as well as empowering patients to enhance self-care, we can significantly reduce the need for costly and environmentally detrimental kidney replacement therapy. Mandating the adoption of lean and innovative low-carbon dialysis practices while also promoting the growth of kidney transplantation would enable low- and middle-income countries to take the lead in implementing environmentally friendly nephrology practices and reducing costs, thus optimizing sustainability and the well-being of individuals living with kidney disease.


Asunto(s)
Enfermedades Renales , Nefrología , Humanos , Países en Desarrollo , Diálisis Renal , Enfermedades Renales/terapia , Carbono
6.
Kidney Int ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38959996

RESUMEN

Patient navigators enable adult patients to circumnavigate complex health systems, improving access to health care and outcomes. Here, we aimed to evaluate the effects of a patient navigation program in children with chronic kidney disease (CKD). In this multi-center, randomized controlled trial, we randomly assigned children (aged 0-16 years) with CKD stages 1-5 (including children on dialysis or with kidney transplants), from low socioeconomic status backgrounds, and/or residing in remote areas, to receive patient navigation at randomization (immediate) or at six months (waitlist). The primary outcome was self-rated health (SRH) of participating children at six months, using intention to treat analysis. Secondary outcomes included caregivers' SRH and satisfaction with health care, children's quality of life, hospitalizations, and missed school days. Repeated measures of the primary outcome from baseline to six months were analyzed using cumulative logit mixed effects models. Semi-structured interviews were thematically evaluated. Of 398 screened children, 162 were randomized (80 immediate and 82 waitlist); mean age (standard deviation) of 8.8 (4.8) years with 64.8% male. SRH was not significantly different between the immediate and wait-listed groups at six months. There were also no differences across all secondary outcomes between the two groups. Caregivers' perspectives were reflected in seven themes: easing mental strain, facilitating care coordination, strengthening capacity to provide care, reinforcing care collaborations, alleviating family tensions, inability to build rapport and unnecessary support. Thus, in children with CKD, self-rated health may not improve in response to a navigator program, but caregivers gained skills related to providing and accessing care.

7.
Am J Transplant ; 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39047976

RESUMEN

Posttransplant diabetes mellitus (PTDM) and prediabetes represent serious complications after kidney transplantation and are associated with increased cardiovascular morbidity and mortality. We assessed the predictive performance of continuous glucose monitoring (CGM) compared with plasma glucose and hemoglobin A1c in 46 kidney transplant recipients (KTRs) without known preexisting diabetes mellitus. CGM (14-day recording duration) was performed on days 8, 30, 45, 60, 90, and 180 posttransplant. Eight patients (17%) developed PTDM and nine (20%) impaired glucose tolerance (IGT), as diagnosed by oral glucose tolerance test (oGTT)-derived 2-hour plasma glucose (2hPG) or glucose-lowering therapy on day 90. CGM-readouts percent of time >140 mg/dL (%TAR (140 mg/dL)) and percent of time >180 mg/dL (%TAR (180 mg/dL)) showed excellent in-sample test characteristics regarding PTDM from day 8 onward (days 8-90 receiver operating characteristic area under the curve: 0.88-0.99) and regarding PTDM/IGT with the commencement of maintenance immunosuppression from day 30 onward (days 30-90 receiver operating characteristic area under the curve: 0.88-0.91). Exploratory CGM-%TAR (140 mg/dL)-screening thresholds of 31.8% on day 8 and 13.2% on day 30 yielded sensitivities/specificities of 88%/83% for PTDM and 94%/78% for PTDM/IGT on day 90, respectively. Although our findings need to be replicated in studies with larger sample sizes, CGM bears promising potential to facilitate clinical practice and research regarding PTDM.

8.
Am J Transplant ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39029874

RESUMEN

The Banff 2022 consensus introduced probable antibody-mediated rejection (AMR), characterized by mild AMR histologic features and human leukocyte antigen (HLA) donor-specific antibody (DSA) positivity. In a single-center observational cohort study of 1891 kidney transplant recipients transplanted between 2004 and 2021, 566 kidney biopsies were performed in 178 individual HLA-DSA-positive transplants. Evaluated at time of the first HLA-DSA-positive biopsy of each transplant (N = 178), 84 of the 178 (47.2%) of first biopsies were scored as no AMR, 22 of the 178 (12.4%) as probable AMR, and 72 of the 178 (40.4%) as AMR. The majority (77.3%) of probable AMR cases were first diagnosed in indication biopsies. Probable AMR was associated with lower estimated glomerular filtration rate (mL/min/1.73m2) than no AMR (20.2 [8.3-32.3] vs 40.1 [25.4-53.3]; P = .001). The one-year risk of (repeat) AMR was similar for probable AMR and AMR (subdistribution hazard ratio (sHR), 0.99; 0.42-2.31; P = .97) and higher than after no AMR (sHR, 3.05; 1.07-8.73; P = .04). Probable AMR had a higher five-year risk of transplant glomerulopathy vs no AMR (sHR, 4.29; 0.92-19.98; P = 06), similar to AMR (sHR, 1.74; 0.43-7.04; P = .44). No significant differences in five-year risk of graft failure emerged between probable AMR and AMR (sHR, 1.14; 0.36-3.58; P = .82) or no AMR (sHR, 2.46; 0.78-7.74; P = .12). Probable AMR is a rare phenotype, however, sharing significant similarities with AMR in this single-center study. Future studies are needed to validate reproducible diagnostic criteria and associated clinical outcomes to allow for defining best management of this potentially relevant phenotype.

9.
Am J Transplant ; 24(7): 1172-1179, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38215981

RESUMEN

Renal ex vivo normothermic machine perfusion (NMP) is under development as an assessment tool for high-risk kidney grafts and as a means of achieving more physiologically accurate organ preservation. On-going hemolysis has been reported during NMP, as this technique relies on red blood cells for oxygen delivery. In this study, we confirm the occurrence of progressive hemolysis during 6-hour kidney NMP. NMP-associated erythrostasis in the glomeruli and in peri-glomerular vascular networks points to an interaction between the red blood cells and the graft. Continuous hemolysis resulted in prooxidative changes in the perfusate, which could be quenched by addition of fresh frozen plasma. In a cell-based system, this hemolysis induced redox stress and exhibited toxic effects at high concentrations. These findings highlight the need for a more refined oxygen carrier in the context of renal NMP.


Asunto(s)
Eritrocitos , Trasplante de Riñón , Preservación de Órganos , Oxígeno , Perfusión , Eritrocitos/metabolismo , Preservación de Órganos/métodos , Oxígeno/metabolismo , Humanos , Hemólisis , Animales , Masculino , Riñón/metabolismo
10.
Am J Kidney Dis ; 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38640993

RESUMEN

In 1988, the American Board of Internal Medicine (ABIM) defined essential procedural skills in nephrology, and candidates for ABIM certification were required to present evidence of possessing the skills necessary for placement of temporary dialysis vascular access, hemodialysis, peritoneal dialysis, and percutaneous renal biopsy. In 1996, continuous renal replacement therapy was added to the list of nephrology requirements. These procedure requirements have not been modified since 1996 while the practice of nephrology has changed dramatically. In March 2021, the ABIM Nephrology Board embarked on a policy journey to revise the procedure requirements for nephrology certification. With the guidance of nephrology diplomates, training program directors, professional and patient organizations, and other stakeholders, the ABIM Nephrology Board revised the procedure requirements to reflect current practice and national priorities. The approved changes include the Opportunity to Train standard for placement of temporary dialysis catheters, percutaneous kidney biopsies, and home hemodialysis, which better reflects the current state of training in most training programs, and the new requirements for home dialysis therapies training will align with the national priority to address the underuse of home dialysis therapies. This perspective details the ABIM process for considering changes to the certification procedure requirements and how ABIM collaborated with the larger nephrology community in considering revisions and additions to these requirements.

11.
Am J Kidney Dis ; 83(4): 531-545, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38108672

RESUMEN

Ultrasonography is increasingly being performed by clinicians at the point of care, and nephrologists are no exception. This Core Curriculum illustrates how ultrasonography can be incorporated into clinical decision making across the spectrum of kidney disease to optimize the care nephrologists provide to patients. Sonography is valuable in outpatient and inpatient settings for the diagnosis and management of acute and chronic kidney disease, evaluation of cystic disease, urinary obstruction, pain, hematuria, proteinuria, assessment of volume status, and in providing guidance for kidney biopsy. As kidney disease advances, ultrasound is useful in the placement and maintenance of temporary and permanent access for dialysis. After kidney transplantation, ultrasonography is critical for evaluation of allograft dysfunction and for biopsies. Sonography skills expedite patient care and enhance the practice of nephrology and are relatively easily acquired with training. It is our hope that this curriculum will encourage nephrologists to learn and apply this valuable skill.


Asunto(s)
Nefrología , Insuficiencia Renal Crónica , Humanos , Nefrología/educación , Ultrasonografía , Diálisis Renal , Curriculum , Insuficiencia Renal Crónica/diagnóstico por imagen , Insuficiencia Renal Crónica/terapia
12.
Am J Kidney Dis ; 83(3): 277-287, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38142396

RESUMEN

The Kidney Disease: Improving Global Outcomes (KDIGO) guideline for diabetes management in chronic kidney disease (CKD) was updated in 2022, just 2 years after the previous update. The need for this rapid update is reflective of the recent and unprecedented positive results of numerous clinical trials aimed at reducing kidney and cardiovascular morbidity and mortality in people with diabetes. The Kidney Disease Outcomes Quality Initiative (KDOQI) work group for diabetes in CKD, convened by the National Kidney Foundation, provides herein a commentary on these changes, particularly the implications for health care in the United States. Changes to the KDIGO guideline mirror the evolution of sodium/glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists from purely antihyperglycemic agents to cardiorenal-metabolic therapeutics, and the lower estimated glomerular filtration rate of≥20mL/min/1.73m2 for SGLT2 inhibitor initiation. New data have also brought the addition of the first-in-class, Federal Drug Administration-approved nonsteroidal mineralocorticoid receptor antagonist finerenone as an agent to reduce cardiorenal end points. While there has been significant progress in innovation, there remain serious challenges to implementation, particularly in the United States where inequities in insurance coverage and high costs limit their use, particularly in vulnerable populations, ultimately widening health care disparities.


Asunto(s)
Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Insuficiencia Renal Crónica , Humanos , Estados Unidos , Insuficiencia Renal Crónica/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Progresión de la Enfermedad , Riñón , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico
13.
Artículo en Inglés | MEDLINE | ID: mdl-39020254

RESUMEN

Patients with kidney disease have an uncertain future with prognosis varying greatly per patient. To get a better idea of what the future holds and tailor interventions to the individual patient, prediction models can be of great value. Before a prediction model can be applied in practice, its performance should be measured in target populations of interest (i.e., external validation) and whether it helps improve clinical practice (i.e., whether it impacts clinical practice) should be determined. The impact would ideally be determined using an impact trial, but such a trial is often not feasible, and the impact of prediction models is therefore rarely assessed. As a result, prediction models that may not be so impactful may end up in clinical practice and impactful models may not be implemented due to a lack of impact studies. Ultimately, many prediction models end up never being implemented, resulting in much research waste. To allow researchers to get an indication of a prediction model's impact on clinical practice, alternative methods to assess a prediction model's impact are important. In this paper, we discuss several alternatives, including interviews, case-based surveys, decision comparisons, outcome modelling, before-after analyses, and decision curve analyses. We discuss the general idea behind these approaches, including what information can be gathered from such studies and important pitfalls. Lastly, we provide examples of the different alternatives.

14.
Artículo en Inglés | MEDLINE | ID: mdl-39182157

RESUMEN

BACKGROUND AND HYPOTHESIS: Young adults starting kidney replacement therapy (KRT) during childhood and reaching their 18th birthday (i.e. adult survivors of childhood KRT) form a challenging population of interest to nephrologists treating adults, as during this period there will be a transition to adult renal centres. Nonetheless, few studies have focused on the epidemiology of KRT in this group. We aimed to provide an update on these patients' characteristics, treatment history, graft and patient survival, to report their 5-year prognosis, and expected remaining lifetime. METHODS: Data on KRT patients reaching their 18th birthday in 2008-2019 were collected from 21 European countries/regions providing individual patient data to the European Renal Association (ERA) Registry. Patient characteristics and treatment trajectories were examined before and after turning 18 years. Kaplan-Meier and Cox proportional hazards regression were used for patient and graft survival analyses. RESULTS: In total, 2944 patients were included. The proportion of adult survivors initiating KRT at a very young age (0-4 years), and undergoing pre-emptive kidney transplantation increased. Unadjusted 5-year patient survival was 96.9% (95% CI: 96.2-97.5). Dialysis patients had a higher risk of death than kidney transplant recipients (adjusted hazard ratio 5.44 (95% CI: 3.34-8.86)). Between ages 18 and 23 years, about 21% of the adult survivors lost their kidney transplant and 34% of the dialysis patients continued this treatment. Compared with the general population, life expectancy for eighteen-year-old kidney transplant and dialysis patients was 17 and 40 years shorter, respectively. CONCLUSION: Life expectancy of 18-year-old kidney transplant recipients was lower compared with the general population. Yet, having a functioning kidney graft at age 18 years resulted in better outcomes than being on dialysis. Nevertheless, between ages 18 and 23 years, about one-fifth of the kidney grafts failed and one-third of the patients remained on dialysis.

15.
Artículo en Inglés | MEDLINE | ID: mdl-39152048

RESUMEN

While the native arterio-venous fistula (AVF) remains the first choice in vascular access for most hemodialysis patients, tunneled hemodialysis catheters (tHDC) continue to be an option in selected patients. Since timely access to vascular surgery-due to delayed referral or resource limitations-is not always possible, nephrologists have to become more actively involved in planning, creation and monitoring of vascular access. Moreover, this approach could also strengthen patient-centered care in nephrology. This manuscript reviews the current standard in tHDC creation, patient selection and strategies to mitigate the risk of infectious complications and catheter thrombosis. Presentation of novel developments in catheter placement with ultrasound-guided or ECG-guided positioning, their benefits and possible disadvantages emphasizes the complexity of vascular access planning. We offer an approach for choice of insertion method, depending on selected side and existing resources and set focus on the necessity and required resources of 'interventional nephrology' training programs.

16.
Artículo en Inglés | MEDLINE | ID: mdl-39138117

RESUMEN

Over the last 13 years, the use of immune checkpoint inhibitor (ICI) therapy has grown remarkably, owing to their unprecedented anti-tumor efficacy in certain tumor groups. With increased use of ICIs, we are seeing immune-related adverse events (irAE's) more frequently. Renal irAE's, such as ICI-associated acute kidney injury (ICI-AKI), are reported in 2-5% of patients treated with ICIs, with acute tubulointerstitial nephritis (ATIN) as the most common histopathologic lesion, though various forms of glomerulonephritis have also been reported. Modifiable risk factors for ICI-AKI include concurrent use of ATIN-associated drugs, like proton pump inhibitors, non-steroidal anti-inflammatory drugs and antibiotics, and dual ICI therapy with both CTLA-4 and PD1/PDL-1 blockade. Kidney biopsies remain the diagnostic modality of choice, though several promising non-invasive biomarkers, which have not yet been broadly clinically validated have emerged. The treatment of ICI-AKI involves holding ICIs, discontinuation of ATIN-associated drugs, and initiation of immunosuppression with corticosteroids as first-line therapy. With prompt treatment initiation, most patients achieve full or partial renal recovery, allowing for re-challenge with ICI. However, a subset of patients will require additional steroid-sparing therapies for corticosteroid-dependent or refractory ICI-AKI. Here we review developments in our understanding of the pathophysiology of ICI-AKI, the approach to diagnosis (with a focus on the emergence of novel diagnostic tools), prognostic factors and the current evidence for establishing treatment standards for ICI-AKI. As the evidence base remains largely retrospective, we identify questions that would benefit from future prospective studies in the diagnosis, management, and prognostication of ICI-AKI.

17.
Br J Clin Pharmacol ; 90(7): 1677-1687, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38599658

RESUMEN

AIMS: Prednisolone is the cornerstone of treatment for idiopathic nephrotic syndrome in children, but is associated with marked side-effects. Therapeutic drug monitoring using saliva would be a patient-friendly option to monitor prednisolone treatment. To assess the feasibility of saliva monitoring, we described the pharmacokinetics (PK) of unbound prednisolone in plasma and saliva of children with first onset steroid-sensitive nephrotic syndrome (SSNS). METHODS: Children (age 2-16 years) with SSNS participating in a randomized, placebo-controlled trial with levamisole were treated with an 18-week tapering schedule of prednisolone. Five serial samples were collected at 4 (saliva) and 8 weeks (saliva and plasma) after first onset. A nonlinear mixed-effects model was used to estimate the PK parameters of unbound prednisolone and the saliva-to-plasma ratio. Monte Carlo simulations were performed to assess the predictive performance of saliva monitoring. RESULTS: From 39 children, 109 plasma and 275 saliva samples were available. Estimates (relative squared error) of unbound plasma clearance and volume of distribution were 93 (5%) L h-1 70 kg-1 and 158 (7%) L 70 kg-1, respectively. Typical saliva-to-plasma ratio was 1.30 (8%). Monte Carlo simulations demonstrated that on basis of 4 saliva samples and a single plasma sample unbound plasma area-under-the-concentration-time curve can be predicted within 20% imprecision in 79% of the patients compared to 87% based on 4 plasma samples. CONCLUSION: Saliva proved to be a reliable and patient-friendly option to determine prednisolone plasma exposure in children with SSNS. This opens opportunities for further PK and pharmacodynamics studies of prednisolone in a variety of paediatric conditions.


Asunto(s)
Monitoreo de Drogas , Síndrome Nefrótico , Prednisolona , Saliva , Humanos , Prednisolona/farmacocinética , Prednisolona/administración & dosificación , Niño , Síndrome Nefrótico/tratamiento farmacológico , Saliva/química , Preescolar , Adolescente , Masculino , Femenino , Monitoreo de Drogas/métodos , Levamisol/farmacocinética , Levamisol/administración & dosificación , Levamisol/análisis , Levamisol/uso terapéutico , Glucocorticoides/farmacocinética , Glucocorticoides/administración & dosificación , Método de Montecarlo
18.
Br J Clin Pharmacol ; 90(4): 1066-1080, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38031322

RESUMEN

AIMS: We propose using glomerular filtration rate (GFR) as the physiological basis for distinguishing components of renal clearance. METHODS: Gentamicin, amikacin and vancomycin are thought to be predominantly excreted by the kidneys. A mixed-effects joint model of the pharmacokinetics of these drugs was developed, with a wide dispersion of weight, age and serum creatinine. A dataset created from 18 sources resulted in 27,338 drug concentrations from 9,901 patients. Body size and composition, maturation and renal function were used to describe differences in drug clearance and volume of distribution. RESULTS: This study demonstrates that GFR is a predictor of two distinct components of renal elimination clearance: (1) GFR clearance associated with normal GFR and (2) non-GFR clearance not associated with normal GFR. All three drugs had GFR clearance estimated as a drug-specific percentage of normal GFR (gentamicin 39%, amikacin 90% and vancomycin 57%). The total clearance (sum of GFR and non-GFR clearance), standardized to 70 kg total body mass, 176 cm, male, renal function 1, was 5.58 L/h (95% confidence interval [CI] 5.50-5.69) (gentamicin), 7.77 L/h (95% CI 7.26-8.19) (amikacin) and 4.70 L/h (95% CI 4.61-4.80) (vancomycin). CONCLUSIONS: GFR provides a physiological basis for renal drug elimination. It has been used to distinguish two elimination components. This physiological approach has been applied to describe clearance and volume of distribution from premature neonates to elderly adults with a wide dispersion of size, body composition and renal function. Dose individualization has been implemented using target concentration intervention.


Asunto(s)
Antibacterianos , Vancomicina , Recién Nacido , Adulto , Humanos , Masculino , Anciano , Antibacterianos/farmacocinética , Vancomicina/farmacocinética , Amicacina/farmacocinética , Gentamicinas/farmacocinética , Tasa de Filtración Glomerular , Tasa de Depuración Metabólica , Creatinina
19.
Ann Pharmacother ; : 10600280241240409, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38563565

RESUMEN

OBJECTIVE: The objective was to explore and describe the role of pharmacists in providing postdischarge care to patients with kidney disease. DATA SOURCES: PubMed, Embase (Elsevier), CINAHL (Ebscohost), Web of Science Core Collection, and Scopus were searched on January 30, 2023. Publication date limits were not included. Search terms were identified based on 3 concepts: kidney disease, pharmacy services, and patient discharge. Experimental, quasi-experimental, observational, and qualitative studies, or study protocols, describing the pharmacist's role in providing postdischarge care for patients with kidney disease, excluding kidney transplant recipients, were eligible. STUDY SELECTION AND DATA EXTRACTION: Six unique interventions were described in 10 studies meeting inclusion criteria. DATA SYNTHESIS: Four interventions targeted patients with acute kidney injury (AKI) during hospitalization and 2 evaluated patients with pre-existing chronic kidney disease. Pharmacists were a multidisciplinary care team (MDCT) member in 5 interventions and were the sole provider in 1. Roles commonly identified include medication review, medication reconciliation, medication action plan formation, kidney function assessment, drug dose adjustments, and disease education. Some studies showed improvements in diagnostic coding, laboratory monitoring, medication therapy problem (MTP) resolution, and patient education; prevention of hospital readmission was inconsistent. Limitations include lack of standardized reporting of kidney disease, transitions of care processes, and differences in outcomes evaluated. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review identifies potential roles of a pharmacist as part of a postdischarge MDCT for patients with varying degrees of kidney disease. CONCLUSIONS: The pharmacist's role in providing postdischarge care to patients with kidney disease is inconsistent. Multidisciplinary care teams including a pharmacist provided consistent identification and resolution of MTPs, improved patient education, and increased self-awareness of diagnosis.

20.
Pediatr Transplant ; 28(3): e14762, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38650537

RESUMEN

Antibodies to angiotensin II type 1 receptor (AT1R-Abs) are among the most well-studied non-HLA antibodies in renal transplantation. These antibodies have been shown to be common in pediatric kidney transplantation and associated with antibody-mediated rejection (AMR), vascular inflammation, development of human leukocyte donor-specific antibodies (HLA DSA), and allograft loss. As AT1R-Ab testing becomes more readily accessible, evidence to guide clinical practice for testing and treating AT1R-Ab positivity in pediatric kidney transplant recipients remains limited. This review discusses the clinical complexities of evaluating AT1R-Abs given the current available evidence.


Asunto(s)
Rechazo de Injerto , Trasplante de Riñón , Receptor de Angiotensina Tipo 1 , Humanos , Receptor de Angiotensina Tipo 1/inmunología , Rechazo de Injerto/inmunología , Niño , Antígenos HLA/inmunología , Autoanticuerpos/inmunología , Isoanticuerpos/inmunología
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