scholarly journals 1543. Ceftaroline Model-based Dose Individualization in an Infant with Kidney Disease and Mediastinitis

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S563-S563
Author(s):  
Mark Murphy ◽  
Sonya Tang-Girdwood ◽  
Peter Tang ◽  
Brady C Rebecca ◽  
Tomoyuki Mizuno ◽  
...  
Keyword(s):  
Renal Function ◽  
Kidney Disease ◽  
Renal Dysfunction ◽  
Drug Exposure ◽  
Kidney Injury ◽  
Dosing Regimen ◽  
Dose Individualization ◽  
Model Based ◽  
First Case ◽  
High Concentrations

Abstract Background Options for the treatment of infections caused by resistant gram-positive bacteria are limited in children with kidney disease. Ceftaroline (CFD) may be an attractive option but dosing recommendations are not available for children with renal dysfunction. We present a case of pharmacokinetics (PK) model-based individualization of CFD in an infant with kidney disease and mediastinitis. A 5-week-old infant with a hypoplastic left side of the heart developed mediastinitis following a Norwood and BT shunt. Blood and chest washout cultures grew S. epidermidis. Vancomycin therapy led to acute kidney injury (AKI) (eGFR ~15mL/minute) and therefore, CFD was initiated at 8 mg/kg every 12 hours. The model-based clinical service was consulted to assist with dosing. Methods Plasma levels were drawn on day 2 and 10 of CFD. CFD concentrations were determined by HPLC. The pharmacodynamic (PD) target used the MIC of the isolate, 1 µg/mL, and assumed drug diffusion into the mediastinum at 20% of plasma. The PD target was ƒT>MIC at 100%. Individual PK parameters were estimated using Bayesian estimation with MWPharm++ (Mediware, the Netherlands). Results CFD dosing of 8 mg/kg every 12 hours resulted in concentrations well above the target. The trough level was 10 times higher than levels seen in clinical trials. Repeat levels were checked on day 10 due to improved renal function (eGFR 30 mL/minute) and changes in volume status. Changes in both clearance and volume were noted. ƒT>MIC was maintained 100% during dosing intervals. We dose optimized CFD to achieve the target while minimizing potential toxicity with long-term use. A new dosing regimen, 5.4 mg/kg every 8 hours, was started on day 12 and continued for 6 weeks. Conclusion This is the first case report of CFD use in a child with AKI. Though initial dosing resulted in high concentrations, no adverse effects were noted. Successful treatment was completed with a final dosing regimen of 5.3 mg/kg every 8 hours, below the recommended 8 mg/kg every 8 hours. Lower dosing was needed to decrease high drug exposure due to the decreased clearance. This case also demonstrated the feasibility of PK model-based precision dosing within 48 hours, and documented utility in the setting of changes in renal function. Further PK/PD studies are needed in children with renal dysfunction. Disclosures All authors: No reported disclosures.

Histomorphometry of Feline Chronic Kidney Disease and Correlation With Markers of Renal Dysfunction

2012 ◽  
Vol 50 (1) ◽  
pp. 147-155 ◽  
Author(s):  
S. Chakrabarti ◽  
H. M. Syme ◽  
C. A. Brown ◽  
J. Elliott
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Image Analysis ◽  
Renal Function ◽  
Kidney Disease ◽  
Renal Dysfunction ◽  
Interstitial Fibrosis ◽  
Glomerular Hypertrophy ◽  
Renal Lesions ◽  
Postmortem Examinations

Chronic kidney disease is common in geriatric cats, but most cases have nonspecific renal lesions, and few studies have correlated these lesions with clinicopathological markers of renal dysfunction. The aim of this study was to identify the lesions best correlated with renal function and likely mediators of disease progression in cats with chronic kidney disease. Cats were recruited through 2 first-opinion practices between 1992 and 2010. When postmortem examinations were authorized, renal tissues were preserved in formalin. Sections were evaluated by a pathologist masked to all clinicopathological data. They were scored semiquantitatively for the severity of glomerulosclerosis, interstitial inflammation, and fibrosis. Glomerular volume was measured using image analysis; the percentage of glomeruli that were obsolescent was recorded. Sections were assessed for hyperplastic arteriolosclerosis and tubular mineralization. Kidneys from 80 cats with plasma biochemical data from the last 2 months of life were included in the study. Multivariable linear regression ( P < .05) was used to assess the association of lesions with clinicopathological data obtained close to death. Interstitial fibrosis was the lesion best correlated with the severity of azotemia, hyperphosphatemia, and anemia. Proteinuria was associated with interstitial fibrosis and glomerular hypertrophy, whereas higher time-averaged systolic blood pressure was associated with glomerulosclerosis and hyperplastic arteriolosclerosis.

Abstract 161: Identification of Genetic Variants Associated with Kidney Injury That Leads to Increased Blood Pressure

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Ashlyn C Harmon ◽  
Ashley C Johnson ◽  
Santosh Atanur ◽  
Klio Maratou ◽  
Tim Aitman ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Bone Marrow ◽  
Immune Response ◽  
Renal Function ◽  
Kidney Disease ◽  
Kidney Function ◽  
Genetic Variants ◽  
Kidney Injury ◽  
Chromosome 11 ◽  
Genomic Locus

Hypertension, diabetes and obesity, along with genetic predisposition, contribute to the growing number of chronic kidney disease patients. Our novel congenic model [S.SHR(11)] was developed through genetic modification of the Dahl salt-sensitive (S) rat, a model of hypertension related renal disease. The S.SHR(11) strain exhibits accelerated kidney injury compared to the already highly susceptible S rat. On either a low or high-salt diet, the S.SHR(11) model predominately exhibited more tubulointerstitial fibrosis compared to the S rat (17.1±1.29% vs. 12.9±1.22%). Increased α-SMA and macrophage infiltration was also observed. The S and S.SHR(11) had similar blood pressure (week 12), despite an early reduction in renal function in the S.SHR(11); however at an advanced age the S.SHR(11) demonstrated significantly higher blood pressure than the S (215±6.6 mm Hg vs. 183±5.9, respectively). This suggests that increased kidney injury is driving the development of hypertension later in life. Since these two animal models are identical with exception of chromosome 11, the causative genetic variants contributing to decreased renal function must reside within this region. The Dahl S and SHR genomes have been sequenced; this data provides a catalog of all the genetic variants between the two models. The 95% confidence interval of the genomic locus contains 28 non-synonymous SNP, with 15 of these SNP occurring within only three genes: Retnlg , Trat1 and Myh15. Two of these genes, Retnlg and Trat1, are known to play a role in immune response leading to our hypothesis that genetic variants in these genes alter protein function and lead to an increased immune response. Bone marrow transplant studies have been initiated to test our hypothesis and preliminary data shows that S rats who receive S.SHR(11) bone marrow have kidney function measurements similar to the S.SHR(11). The sequencing information has also lead to the development of nine new, more refined congenic strains. Through functional analysis of these new congenic animals, identification of the causative genetic variations will be expedited. In summary, we are employing a model of accelerated kidney disease to identify genes or genetic variants responsible for reduced kidney function and hypertension.

scholarly journals Impact of Cardiac Function Improvement on Cardiac Surgery Associated Acute Kidney Injury for Patients with Preoperative Renal Dysfunction

2020 ◽  
Author(s):  
Jiarui Xu ◽  
Xin Chen ◽  
Jing Lin ◽  
Yang Li ◽  
Bo Shen ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Cardiac Surgery ◽  
Cardiac Function ◽  
Renal Dysfunction ◽  
Significant Risk ◽  
Kidney Injury ◽  
Normal Function ◽  
Function Group ◽  
Postoperative Aki

Abstract Background: We aim to investigate whether the postoperative cardiac function improve or not would affect the risk of cardiac surgery associated acute kidney injury (AKI) for patients with preoperative renal dysfunction. Method: Data from patients underwent cardiac surgery from April 2012 to February 2016 were collected. Renal dysfunction was defined as preoperative SCr >1.2 mg/dL (females) or >1.5 mg/dL (males). Patients were grouped as normal renal function group, renal dysfunction with chronic kidney disease (CKD group), and non CKD group. △LVEF=postoperative LVEF - preoperative LVEF. Cardiac function improved was defined as △LVEF ≥10. Patients were further divided into non CKD & cardiac function improved (non CKD+), non CKD & cardiac function not improved (non CKD-), CKD & cardiac function improved (CKD+) and CKD & cardiac function not improved (CKD-) subgroups.Results: A total of 8,661 patients were allocated as normal renal function (n=7,903), non CKD(n = 662) and CKD (n = 136) groups. Both non CKD and CKD groups had higher AKI incidence than normal function group (39.5% vs 30.0%, P < 0.001; 61.8% vs 30.0%, P<0.001), and non CKD+ group had the similar AKI incidence with normal function group (30.9% vs 30.0%, P=0.729). Multivariate logistic regression analysis revealed that non CKD-, CKD+ and CKD- were significant risk factors, whereas non CKD+ was not a significant risk factor for postoperative AKI. The SCr at discharge in non CKD+ subgroup was significantly lower than its preoperative SCr (1.4 ± 0.8 vs 1.7 ± 0.9 mg/dL, P = 0.020).Conclusions: For renal dysfunction patients with no CKD, the risk of postoperative AKI did not exist if the cardiac function improved after surgery. For CKD patients, the risk of postoperative AKI increase regardless whether the cardiac function improved or not.

Use of Pamidronate for Hypercalcemia of Malignancy in Renal Dysfunction

2019 ◽  
pp. 089719001988316 ◽  
Author(s):  
Sarah J. Norman ◽  
David J. Reeves ◽  
Lindsay M. Saum
Keyword(s):  
Renal Function ◽  
Renal Dysfunction ◽  
Chart Review ◽  
Kidney Injury ◽  
Retrospective Chart Review ◽  
Primary Objective ◽  
Limited Impact ◽  
Hypercalcemia Of Malignancy ◽  
Baseline Renal Function ◽  
Community Teaching

Background: Few studies have been conducted investigating the use of bisphosphonates in hypercalcemia of malignancy (HCM) in the setting of renal dysfunction. Objective: The primary objective was to compare the incidence of acute kidney injury (AKI) within 7 days of receiving pamidronate for the treatment of HCM with pre-existing renal dysfunction versus normal renal function at the time of pamidronate administration. The secondary objectives explored the effects of pamidronate doses and infusion rates on the safety and efficacy in those with pre-existing renal dysfunction for the treatment of HCM. Methods: A retrospective chart review was conducted on patients who received pamidronate for the treatment of HCM at a community teaching hospital in Indianapolis, Indiana, from January 1, 2013, to May 31, 2017. Results: A total of 141 pamidronate administrations were included (116 patients had normal baseline renal function, and 25 patients had pre-existing renal dysfunction before pamidronate administration for the treatment of HCM). Two (8%) patients developed AKI in the pre-existing renal dysfunction group, compared with 4 (3.4%) patients in those without pre-existing renal dysfunction ( P = .288). For those with pre-existing renal dysfunction, the incidence of AKI did not differ based on the dosage of pamidronate given ( P = .762) or infusion rates ( P = .373). Conclusion: Pamidronate appears to have limited impact on renal function at doses up to 90 mg in the setting of pre-existing renal dysfunction for the treatment of HCM.

scholarly journals Adult Nesidioblastosis in Chronic Kidney Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Eduardo Lozano-Melendez ◽  
Mercedes Aguilar-Soto ◽  
Luis Eugenio Graniel-Palafox ◽  
Laura Elena Ceceña-Martínez ◽  
Rafael Valdez-Ortiz ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Case Report ◽  
Kidney Disease ◽  
Kidney Failure ◽  
Hyperinsulinemic Hypoglycemia ◽  
Histopathological Diagnosis ◽  
Insulin Levels ◽  
First Case ◽  
End Stage

Context. Nesidioblastosis is a rare cause of hyperinsulinemic hypoglycemia in adults. The diagnosis is further complicated in patients with kidney failure, since impaired renal function can cause hypoglycemia by itself and diagnostic criteria for this clinical scenario have not been developed yet. Case Description. We present the case report of a 36-year-old patient with end stage chronic kidney disease who presented to the emergency department because of hypoglycemia. However, the patient’s hypoglycemia did not respond well to medical treatment; the diagnosis of hyperinsulinemic hypoglycemia was made due to the presence of inappropriately high levels of insulin, proinsulin, and C-peptide during an episode of hypoglycemia. Imaging studies were performed without any conclusive findings; so selective intra-arterial pancreatic stimulation with hepatic venous sampling (SACTS) was done. Based on the results of this study the patient was referred for subtotal pancreatectomy. Classic criteria for the diagnosis of insulinoma with SACTS required a 2-fold increase in insulin levels but newer criteria suggest thresholds that are useful in the differential diagnosis of insulinoma and nesidioblastosis. In our patient, the former criteria were positive; however, the new criteria were not compatible with insulinoma but with nesidioblastosis, which was the final histopathological diagnosis. Conclusion. This seems to be the first case report of a patient with end stage chronic kidney disease and nesidioblastosis, as well as the first case of hyperinsulinemic hypoglycemia in the context of kidney failure diagnosed by SACTS. We consider this method to be very useful in patients with renal impairment because peripancreatic insulin levels do not depend on the renal function.

scholarly journals The Effect of Renal Dysfunction on Circulating Sclerostin Level in Patients with Type 2 Diabetes

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Se Hwa Kim ◽  
Soo Young Yoon ◽  
Sung-Kil Lim ◽  
Yumie Rhee
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Renal Dysfunction ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Cross Sectional ◽  
Sclerostin Level

Objective. Sclerostin is a Wnt inhibitor produced specifically by osteocytes. However, it is not currently clear whether renal dysfunction has an effect on circulating sclerostin level in patients with type 2 diabetes. The aim of the study was to evaluate this relationship. Design and Patients. We conducted a cross-sectional observational study of 302 type 2 diabetic patients with or without chronic kidney disease. Serum sclerostin level was analyzed by ELISA, and renal function was assessed by estimated glomerular filtration rate (eGFR) using chronic kidney disease epidemiology collaboration (CKD-EPI) equation. Results. There was a strong correlation between sclerostin level with renal function presented as serum creatinine (r=0.745, P<0.001) and eGFR (r=-0.590, P<0.001). Serum sclerostin level was significantly higher in patients with CKD-G3 stage than those with CKD-G1/2 stages after adjusting for age, sex, and BMI (P=0.011). Patients with CKD-G4/5 stages had dramatically increased level of circulating sclerostin. Multiple regression analyses found that age, sex, and eGFR were independent determining factors for circulating sclerostin level. Conclusion. Our data showed that serum sclerostin levels start to increase in diabetic patients with CKD-G3 stage. Further studies are needed to establish the potential role of elevated sclerostin in diabetic patients with CKD.

scholarly journals Developing better mouse models to study cisplatin-induced kidney injury

2017 ◽  
Vol 313 (4) ◽  
pp. F835-F841 ◽  
Author(s):  
Cierra N. Sharp ◽  
Leah J. Siskind
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Therapeutic Interventions ◽  
Low Doses ◽  
Dosing Regimen ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Novel Therapeutic

Cisplatin is a potent chemotherapeutic used for the treatment of many types of cancer. However, its dose-limiting side effect is nephrotoxicity leading to acute kidney injury (AKI). Patients who develop AKI have an increased risk of mortality and are more likely to develop chronic kidney disease (CKD). Unfortunately, there are no therapeutic interventions for the treatment of AKI. It has been suggested that the lack of therapies is due in part to the fact that the established mouse model used to study cisplatin-induced AKI does not recapitulate the cisplatin dosing regimen patients receive. In recent years, work has been done to develop more clinically relevant models of cisplatin-induced kidney injury, with much work focusing on incorporation of multiple low doses of cisplatin administered over a period of weeks. These models can be used to recapitulate the development of CKD after AKI and, by doing so, increase the likelihood of identifying novel therapeutic targets for the treatment of cisplatin-induced kidney injury.

scholarly journals Drug-induced renal disorder-A Mini Review

2020 ◽  
Vol 11 (1) ◽  
pp. 166-172 ◽  
Author(s):  
Divya M ◽  
Nivetha S. R. ◽  
Lekshmi Mohan ◽  
Arul B* ◽  
Kothai R
Keyword(s):  
Risk Factors ◽  
Renal Function ◽  
Renal Dysfunction ◽  
Renal Scarring ◽  
Kidney Injury ◽  
Drug Induced ◽  
Related Factors ◽  
Renal Disorder ◽  
Renal Obstruction ◽  
Renal Tubular Cells

Drug-induced kidney disorder/disease (DKID) is an origin of kidney disease followed by acute renal failure. Drug-induced renal toxicity is more common in infants and young children in certain clinical circumstances where underlying renal dysfunction and cardiovascular diseases. Sometimes, administered drugs may cause acute renal injury, intra-renal obstruction, interstitial nephritis, nephrotic syndrome, and acid-base and fluid electrolytes disorders in patients. Certain drugs may cause alterations in intra-glomerular hemodynamics, inflammatory changes in renal tubular cells, leading to acute kidney injury (AKI), interstitial tubule disease, and renal scarring. Common risk factors include; pre-existing renal dysfunction, volume-depleted state, old age, and use of nephrotoxic drugs. Therefore, the prevention from the disease includes the knowledge about the nephrotoxicity, assessing considering the patient-related, kidney-related, and drug-related factors while prescribing medicines, using of alternative drugs, which are non-nephrotoxic, assessing the baseline of renal function before starting the treatment, monitor the renal function during the treatment and avoid the nephrotoxic drug combinations and withdrawing the offending drugs due to toxicity. The ADRs of the prescribed/ administered are identified at the earliest to prevent the development of the last-stage renal disorder. This review discusses the risk factors associated with drug-induced renal disease, estimation of renal function, mechanism of drug-induced nephrotoxicity, and certain drugs that cause nephrotoxicity.

scholarly journals Lipid spectrum and function of kidneys before and after liver transplantation

Kardiologiia ◽  
2019 ◽  
Vol 59 (6S) ◽  
pp. 17-23
Author(s):  
E. D. Kosmacheva ◽  
A. E. Babich
Keyword(s):  
Chronic Kidney Disease ◽  
Liver Transplantation ◽  
Renal Function ◽  
Lipid Metabolism ◽  
Kidney Disease ◽  
Total Cholesterol ◽  
Renal Dysfunction ◽  
Inverse Correlation ◽  
Study Results ◽  
Lipid Spectrum

Background. In patients after liver transplantation cardiovascular complications is the third main reason of death afer allograf failure and infections. The most important factors in the development of cardiovascular diseases are dyslipidemia and impaired renal function. The aim of the study was to investigate the lipid spectrum and renal function in liver recipients in real clinical practice and the correspondence of their correction to current clinical recommendations for the diagnosis and treatment of dyslipidemia and chronic kidney disease (CKD). Methods. A retrospective analysis of lipid spectrum and renal function in patients who underwent OLT in Research Institute – Regional Clinical Hospital №1, Krasnodar was performed. The level of creatinine, GFR and lipid spectrum was studied before and 36 months after liver transplantation. The GFR was calculated using the formula CKD‑EPI (Chronic Kidney Disease Epidemiology Collaboration). Statistical analysis of the study results was made using the program Statistica 10. Results. Liver recipients have a significantly higher total cholesterol by 31.0% (p<0.01) in comparison with the baseline before surgery. Total cholesterol was increased in 13.7% (p<0.01), triglycerides in 12.3% (p<0.01) before transplantation. Tree years after transplantation, the increasion in cholesterol was registered in 42.6% (p<0.01) and triglycerides in 37.9% (p <0.01), respectively. 3 years after transplantation reduction of GFR was observed in comparison with the baseline by 22.6% (p=0.00006). Verification of chronic kidney disease and statin administration in patients were carried out in some cases. The levels of total cholesterol and triglycerides had a reliable inverse correlation with GFR (r = ‑0.42; p<0.01 and r = ‑0.36; p<0.05). Conclusions. In the long‑term postoperative period there was an impaired lipid metabolism and decreased level of GFR. Dyslipidemia was closely related to the progression of renal dysfunction in liver recipients, an inverse correlation was established between the glomerular filtration rate and the increasion in cholesterol and triglyceride levels. It is necessary to increase the attention of physicians with regard to timely correction of lipid metabolism disorders and detection of initial manifestations of renal dysfunction.

scholarly journals Rivaroxaban-related acute kidney injury in a patient with IgA vasculitis

2019 ◽  
Vol 12 (1) ◽  
pp. e227756 ◽  
Author(s):  
Yoshihiko Fujino ◽  
Chisato Takahashi ◽  
Kensuke Mitsumoto ◽  
Takashi Uzu
Keyword(s):  
Atrial Fibrillation ◽  
Acute Kidney Injury ◽  
Renal Function ◽  
Systemic Vasculitis ◽  
Kidney Injury ◽  
Close Monitoring ◽  
Iga Vasculitis ◽  
Direct Oral Anticoagulant ◽  
Macroscopic Haematuria ◽  
First Case

Anticoagulants have recently been recognised as a cause of acute kidney injury (AKI). We describe the case of a 75-year-old man with IgA vasculitis and atrial fibrillation treated with rivaroxaban, who presented with macroscopic haematuria and an acute decline in renal function. Two months before referral, he noted palpable purpuric lesions and was diagnosed with IgA vasculitis based on skin biopsy findings; the skin lesion disappeared following treatment with a steroid external preparation. Renal biopsy revealed glomerular haemorrhage and red blood cell casts. Although rivaroxaban was withdrawn, his kidney function worsened and he was started on haemodialysis. His renal function did not recover. To the best of our knowledge, this is the first case of direct oral anticoagulant (DOAC)-related AKI in systemic vasculitis. During DOAC therapy, close monitoring of a patient’s urinalysis results and their renal function may be required for patients with systemic vasculitis to avoid AKI.

Sign in / Sign up

Export Citation Format

Share Document