Rapid determination of renal filtration function using an optical ratiometric imaging approach

2007 ◽  
Vol 292 (6) ◽  
pp. F1873-F1880 ◽  
Author(s):  
Weiming Yu ◽  
Ruben M. Sandoval ◽  
Bruce A. Molitoris

Glomerular filtration rate (GFR), which measures the amount of plasma filtered through the kidney within a given time, is an essential and clinically important indicator of kidney function. Here, we report a new ratiometric measurement technique based on intravital fluorescence microscopy that allows rapid evaluations of renal function in rodent models. By using this technique, plasma clearance rates of a fluorescent GFR marker can be measured in less than 5 min following a bolus infusion of a fluorescent dye mixture into the bloodstream. The plasma clearance kinetics of the GFR marker showed consistent values when measured in healthy animals at locations both in the kidney and from the skin. In addition, by using this technique, we were able to rapidly determine renal function with acute renal failure animal models and with other animal models where kidney filtration functions were altered. The measured plasma clearance kinetics using this technique correlated with expected changes in kidney function. We found this ratiometric approach offers improved accuracy and speed for quantifying renal function compared with the approach using single fluorescent probes, and the measurement can be done noninvasively from the skin. This approach also offers a high sensitivity for determining plasma clearance rate of a fluorescent compound. This feature is important for rapidly quantifying small differences in plasma clearance when kidney function is changing.

Author(s):  
Mandy Turner

Glomerular filtration rate is a measure of the kidney’s ability to filter blood. In animal models of early kidney failure, there is no routine method to accurately measure GFR. The expensive gold standard of GFR measurement is exogenous inulin clearance. The commonly used method, endogenous plasma creatinine concentration, is unreliable and insensitive, especially at normal levels of renal function. This study investigates the utility of iohexol, an inexpensive radio-contrast agent as a promising exogenous marker for plasma clearance kidney function evaluation in rats. Early stages of progressive kidney failure were induced with a 0.25% adenine diet in male Sprague Dawley rats (N=8) over 5 weeks. Both plasma clearance of iohexol and inulin and creatinine concentration were evaluated following weekly venous injections and blood sampling. Plasma iohexol clearance and plasma inulin clearance strongly correlate (R2=0.95). However, plasma creatinine concentration correlated weakly with iohexol(R2=0.53) and inulin(R2=0.58). Iohexol plasma clearance accurately measures changes in kidney function, especially in in comparison to creatinine analysis. The data demonstrates creatinine is an inappropriate marker for renal function in early adenine-induced CKD rat models. Ongoing analysis of this data suggests refinement of the protocol will yield a simple method for routine measure of kidney function in murine lab animals. This tool will facilitate advancement in kidney disease onset and allow for more accurate interpretation of kidney function in the various animal models.


Author(s):  
Mariia D. Ivanova ◽  
Anatoliy I. Gozhenko ◽  
Tommy Crestanello ◽  
Dmytro D. Ivanov

<b><i>Introduction:</i></b> In observational studies, increased water intake improves kidney function but not in adults with CKD stage 3 and more. CKD WIT trial has shown a nonsignificant gradual decline in kidney function after 1 year of coaching to increase water intake (CIWI) [<xref ref-type="bibr" rid="ref1">1</xref>]. We propose that CIWI may benefit in CKD stage 1–2 (G1 and G2) and depends on functional renal functional reserve (RFR) [<xref ref-type="bibr" rid="ref2">2</xref>, <xref ref-type="bibr" rid="ref3">3</xref>]. <b><i>Objective:</i></b> Parallel-group randomized trial was aimed to determinate the effectiveness of CIWI dependence of estimated glomerular filtration rate (eGFR) stage and RFR in adults with CKD 1–2 stages. <b><i>Methods:</i></b> CKD WIT trial was taken as the basis for prospective multicenter randomized trial named “Early Coaching to Increase Water Intake in CKD (ECIWIC).” The primary outcome was the change in kidney function by eGFR from baseline to 12 months. Secondary outcomes included 1-year change in urine albumin/Cr ratio, and patient-reported overall quality of health (QH) ranged from 0 (worst possible) to 10 (best possible). CIWI aimed to have the diuresis being 1.7–2 L. There were 4 groups with nondiet sodium restriction which consisted of 31 patients each: 2 groups with CKD G1 and CKD G2, undergoing CIWI and 2 others with CKD G1 and CKD G2 without CIWI (Fig. 1a). Overall checks were made at 0, 6, and 12 months. RFR evaluation was performed using 0.45% sodium chloride oral solution. <b><i>Results:</i></b> Of our randomized 124 patients (mean age 53.2 years; men 83 [67%], 0 died), mean change in 24-h urine volume was 0.6 L per day in G1 with CIWI group and 0.5 L in G2. No statistically significant data on eGFR depending CIWI were obtained (Fig. <xref ref-type="fig" rid="f01">1</xref>b). However, the trend suggests that CIWI improves eGFR in CKD G1 (from 95 to 96 mL/min/1.73 m<sup>2</sup>) and preserves eGFR decline in CKD G2 (78–78). The QH values were also preserved (from 7 to 7 in G1 and G2 groups). Although coaching to maintain the same water intake did not preserve physiological and pathological eGFR decreasing in CKD G1-2 (G1 from 96 to 93, G2 from 76 to 73; <i>t</i> = 0.6, <i>p</i> = 0.29, and <i>p</i> ≤ 0.05 in all groups) and the QH was declined (from 7 to 6 in both groups). An individual analysis of the RFR has shown that patients with RFR more than 50% (G1 19 patients, 61%, and G2 13 patients, 42%) had reliable preservation of eGFR with its increase of 1.5 mL/min on CIWI, while patients with low functional renal reserve had a drop of eGFR at 1.1 mL/min/m<sup>2</sup> within 12 months. Patients with low normal serum sodium levels have shown worse results on CIWI. <b><i>Conclusions:</i></b> With CKD G1, the CIWI leads to the preservation of the renal function with its increase of GFR per 1 mL/min/m<sup>2</sup>/per year in comparison with the same water intake. In CKD G2, the CIWI prevents physiological and pathological loss of renal function, and RFR above 50% aids restoration of eGFR both in CKD G1-2. ECIWIC trial demonstrates benefit of CIWI in patients with CKD 1–2 and preserved RFR.


2021 ◽  
Vol 8 ◽  
pp. 205435812110180
Author(s):  
Orit Kliuk-Ben Bassat ◽  
Sapir Sadon ◽  
Svetlana Sirota ◽  
Arie Steinvil ◽  
Maayan Konigstein ◽  
...  

Background: Transcatheter aortic valve replacement (TAVR), although associated with an increased risk for acute kidney injury (AKI), may also result in improvement in renal function. Objective: The aim of this study is to evaluate the magnitude of kidney function improvement (KFI) after TAVR and to assess its significance on long-term mortality. Design: This is a prospective single center study. Setting: The study was conducted in cardiology department, interventional unit, in a tertiary hospital. Patients: The cohort included 1321 patients who underwent TAVR. Measurements: Serum creatinine level was measured at baseline, before the procedure, and over the next 7 days or until discharge. Methods: Kidney function improvement was defined as the mirror image of AKI, a reduction in pre-procedural to post-procedural minimal creatinine of more than 0.3 mg/dL, or a ratio of post-procedural minimal creatinine to pre-procedural creatinine of less than 0.66, up to 7 days after the procedure. Patients were categorized and compared for clinical endpoints according to post-procedural renal function change into 3 groups: KFI, AKI, or preserved kidney function (PKF). The primary endpoint was long-term all-cause mortality. Results: The incidence of KFI was 5%. In 55 out of 66 patients patients, the improvement in kidney function was minor and of unclear clinical significance. Acute kidney injury occurred in 19.1%. Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 was a predictor of KFI after multivariable analysis (odds ratio = 0.93 to develop KFI; confidence interval [95% CI]: 0.91-0.95, P < .001). Patients in the KFI group had a higher Society of Thoracic Surgery (STS) score than other groups. Mortality rate did not differ between KFI group and PKF group (43.9% in KFI group and 33.8% in PKF group) but was significantly higher in the AKI group (60.7%, P < .001). Limitations: The following are the limitations: heterozygous definitions of KFI within different studies and a single center study. Although data were collected prospectively, analysis plan was defined after data collection. Conclusions: Improvement in kidney function following TAVR was not a common phenomenon in our cohort and did not reduce overall mortality rate.


Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Ashlyn C Harmon ◽  
Ashley C Johnson ◽  
Santosh Atanur ◽  
Klio Maratou ◽  
Tim Aitman ◽  
...  

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.


2020 ◽  
Vol 1 (2) ◽  
pp. 65-70
Author(s):  
Esa Indah Ayudia ◽  
Huntari Harahap ◽  
Irfannuddin Irfannuddin

  Obesity is a condition in which the ratio of body weight and height exceeds the specified standards. Obesity is an increase in total body fat, that is, if you are found to be overweight> 20% in men and 25% in women because of fat. The intermittent fasting diet is a calorie restriction method that is widely used for health or weight loss reasons. Overall kidney function is based on nephron function and impaired function is caused by decreased nephron action. Several laboratory tests have been developed to evaluate kidney function and identify the disorder early on. This can help clinicians to take early prevention and management in order to prevent the progression of kidney disorders to kidney failure. Renal function tests are carried out by examining the levels of urea and cretinin.    


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Sara Núñez Delgado ◽  
Miren Iriarte-Abril ◽  
Júlia Farrera-Núñez ◽  
Sergi Pascual-Sánchez ◽  
Laia Sans-Atxer ◽  
...  

Abstract Background and Aims Acute renal failure (AKI) associated to rhabdomyolysis conditions a worse prognosis in short-term, its implication in the long-term renal function has been less evaluated. Method Retrospective analysis of patients diagnosed with rhabdomyolysis defined by creatinine kinase &gt; 5000 IU/L between 2015-2019. Basal and 12-month renal function was evaluated. AKI was classified as either non-severe (AKI-KDIGO 1/2) or severe (AKI-KDIGO 3). Results Eighty-seven patients were included, 25 (28.74%) had some degree of chronic kidney disease (CKD) on admission. 56 (64.37%) had AKI on admission, 17 of which were severe (6 required hemodialysis). The patients with AKI had more cardiovascular disease (CVD) and worse analytical parameters on admission (table). Patients with severe AKI showed no difference in CVD from those with non-severe AKI but were younger and had more hyperkalemia. There were no significant differences between patients with severe AKI who required hemodialysis and those who did not. Inpatient mortality was 8%, higher in patients with AKI but without differences according to severity. In 45 patients kidney function was available 12 months after the episode, loss of eGF was -4.90 ± 14.35 ml/min-1.73m2 (p=0.007). There was no difference between patients who developed AKI and those who did not (-4.10 ± 14.4 vs. -5.39 ± 14.57 ml/min-1.73m2; p=0.67), nor between non-severe and severe AKI (-5.50 ± 14.76 vs. -5.12 ± 15.08ml/min-1.73m2; p=0.98). Of the 33 patients without previous CKD, 5 developed CKD, with greater decrease in eGF than those who did not (-22.69 ± 6.04 vs. -2.63 ± 13.92 ml/min-1.73m2; p=0.003). Female sex (60% vs. 12%; p=0.031) and previous basal eGF (72.22 ± 4.37 vs. 95.6±19.97 ml/min-1.72m2; p=0.016) were related to this deterioration. Conclusion After an episode of rhabdomyolysis, the loss of eGF is similar in patients who develop AKI compared to those who do not.


2020 ◽  
Author(s):  
Benedict Morath ◽  
Andreas Meid ◽  
Johannes Rickmann ◽  
Jasmin Soethoff ◽  
Markus Verch ◽  
...  

Abstract Background: Fluid management is an everyday challenge in intensive care units worldwide. Data from recent trials suggest that the use of hydroxyethyl starch leads to a higher rate of acute kidney injury and mortality in septic patients. Evidence on the safety of hydroxyethyl starch used in postoperative cardiac surgery patients is lacking Methods: The aim was to determine the impact of postoperatively administered hydroxyethylstarch 130/0.42 on renal function and 90-day mortality compared to with or without balanced crystalloids in patients after elective cardiac surgery. A retrospective cohort analysis was performed including 2245 patients undergoing elective coronary artery bypass grafting or, aortic valve replacement, or a combination of both between 2015 - 2019. Acute kidney injury was defined according to the ‘kidney disease improving global outcomes’ criteria. Multivariate logistic regression yielded adjusted associations of postoperative hydroxyethyl starch administration with acute kidney injury during hospital stay and 90-day mortality. Linear mixed-effects models predicted trajectories of estimated glomerular filtration rates over the postoperative period to explore the impact of dosage and timing of hydroxyethyl starch administration.Results: A total of 1009 patients (45.0 %) suffered from acute kidney injury. Significantly less acute kidney injury of any stage occurred in patients receiving hydroxyethyl starch compared to patients receiving only crystalloids for fluid resuscitation (43.7 % vs. 51.2 % p=0.008). In multivariate analysis, the administration of hydroxyethyl starch showed a protective effect (OR 0.89 95% confidence interval (CI) (0.82-0.96)) which was less prominent in patients receiving only crystalloids (OR 0.98, 95% CI (0.95-1.00)). No association between hydroxyethyl starch and 90-day mortality (OR 1.05 95% CI (0.88-1.25)) was detected. Renal function trajectories were dose-dependent and biphasic and hydroxyethyl starch could even slow down the late postoperative decline of kidney function.Conclusion: This study showed no association between hydroxyethyl starch and the postoperative occurrence of acute kidney injury and may add evidence to the discussion about the use of hydroxyethyl starch in cardiac surgery patients. In addition, hydroxyethyl starch administered early after surgery in adequate low doses might even prevent the decline of the kidney function after cardiac surgery.


2015 ◽  
Vol 69 (8) ◽  
pp. 782-788 ◽  
Author(s):  
Xianhui Qin ◽  
Yuejuan Wang ◽  
Youbao Li ◽  
Di Xie ◽  
Genfu Tang ◽  
...  

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