Urinary Clearance Research Articles

SUB-CLINICAL DAMAGE TO THE TARGET ORGANS (TOD) IN HYPERTENSIVE PATIENTS, ABOUT 300 PATIENTS

Objective: HTA is considered to be a silent killer. TOD is an indicator of cardiovascular risk in people with hypertension. The main objective of our study is to describe the sub-clinical TOD in hypertensive patients. Design and method: This is a descriptive study, conducted between October 2016 and October 2019. It included all asymptomatic hypertensive patients over the age of 35 of both sexes. Screening for infraclinical cardiac, vascular and renal damage is carried out with; the evaluation of the left ventricular hypertrophy (LVH) ultrasound and electric. Intima media thickness measurement by 2D carotid ultrasound and screening and evaluation of plaques. The measurement of pulsed pressure. Measuring the ABI for obliterating arterial disease. And finally, the estimate of urinary albumin excretion (UEA) and creatinine clearance according to MDRD. Results: 300 patients included in our series, these are 120 men and 180 women. The average age is 59.75 years. The prevalence of TOD is estimated at 72.3%, the prevalence of electrical LVH is 17.3%, the ultrasound LVH is 29%. Carotid hypertrophy is observed in 34.9% and the presence of stenotic plaques affect 9.1% of patients AOMI is found in 9%. Pathological pulsed pressure is found in 34.3%. UAE is pathological in 23.30% of our patients for A2 and 5.7% for A3. The creatinine clearance is less than 60 ml / min in 11%. The main independent risk factors associated with TOD are the value of SBP and Age. Pulse pressure> 60 mmHg is associated with all TOD and the IMT is correlated with all screening tests for TOD. The SCORE score is predictive only for carotid lesions, it is not predictive for LVH or albuminuria. The SCORE score is not very predictive for AOMI and renal failure. Conclusions: Subclinical TOD is frequent in our series. The major modifiable independent risk factor is the value of SBP. Special attention to pulse pressure as a cardiovascular risk factor and marker of arterial stiffness A strategy for screening for target organ damage coupled with effective therapy targeting SBP is the only way to prevent cardiovascular, neurovascular and renal complications.

Comparison of Plasma Clearance With Early-Compartment Correction Equations and Urinary Clearance in High GFR Ranges

IntroductionGlomerular filtration rate (GFR) is measured from the late plasma disappearance curve of an exogenous tracer, after correction for the early decay—corresponding to the distribution of the tracer—using various equations. These equations display the highest discrepancies in the GFR range above 90 ml/min per 1.73 m2, and their respective performances against a reference, urinary GFR measurement are unclear.MethodsIn patients with mGFR >90 ml/min per 1.73 m2 from 6 different cohorts, we compared GFR obtained from the plasma clearance of iohexol or 51Cr-ethylenediamine tetraacetic acid (EDTA), after correction using Chantler (C), Bröchner-Mortensen (BM), Fleming (F), Jodal-Bröchner-Mortensen (JBM), and Ng (N) equations, with urinary clearance of the same tracers or inulin.ResultsIn 438 participants (median age 41 [39–42] years, 43% women), the median urinary clearance was 100.8 (94.7–112.6) ml/min per 1.73 m2. Plasma clearances using the correction equations were 105.7 (96.8–119.2), 102.4 (95.2–112.9), 100.7 (93.6–111.1), 102.6 (95.2–113.4), and 106.0 (98.2–117.6) ml/min per 1.73 m2 for C, BM, F, JBM, and N, respectively. Concordance correlation coefficients between plasma and urinary clearances were poor for all equations. Compared with urinary clearances, BM, F, and JBM displayed the best accuracy within 10% (73%, 72%, and 71%, respectively, vs. 63% and 66% for C and N), whereas BM and JBM had the lowest median biases. Accuracy of all equations was especially low in the hyperfiltration range (urinary clearance >130 ml/min per 1.73 m2).ConclusionThe BM and JBM equations displayed the best overall performances to correct for the early disappearance curve. Results of these equations should be interpreted with caution, especially in the highest GFR range.

Distribution of creatinine and estimated glomerular filtration rate in healthy schoolchildren: The Health Oriented Pedagogical Project (HOPP)

Glomerular filtration rate (GFR) measured by urinary clearance of inulin is considered the gold standard for assessment of kidney function in both adults and children. Because the procedure is cumbersome, GFR is estimated (eGFR) using algorithms based on the observed relationship between measured GFR (mGFR) and more accessible biomarkers such as creatinine and cystatin C. In children, most of the data on this relationship is retrieved from patients with reduced kidney function. Nonetheless, eGFR equations are widely in use in healthy children to evaluate kidney status and diagnose kidney disease. The aim of the present study was to compare the distribution of eGFR using two established pediatric eGFR equations incorporating age, height and serum creatinine (Schwartz-Lyon and Full Age Spectrum-height) and two recently published equations restricted to age and serum creatinine (Lund-Malmö Revised 18 and European Kidney Function Consortium equation) in 1200 healthy schoolchildren age 6–12 years. In addition, we present 2.5th, median and 97.5th percentiles for serum creatinine stratified by age and gender. Depending on the equation used, mean eGFR ranged from 101.6 to 115.4 mL/min/1.73 m2. The lower 2.5th percentile ranged from 83.3 to 89.0 mL/min/1.73 m2 and the fraction of children with eGFR < 90 mL/min/1.73 m2 ranged from 2.9% to 9.8%. In conclusion, expected values of eGFR in healthy children are significantly dependent on the equation used. When decision limits for diagnosis or classification are applied to eGFR results, the related equation should be clearly stated.

Impact of paclitaxel, cisplatin, and gemcitabine as first-line chemotherapy in cisplatin-fit and -unfit patients with advanced/metastatic urothelial carcinoma

PurposeThis study aimed to clarify the efficacy and toxicity of first-line combination treatment with paclitaxel, cisplatin, and gemcitabine (PCG) for advanced/metastatic urothelial carcinoma (UC) in cisplatin-unfit patients compared with cisplatin-fit patients. MethodsWe conducted a retrospective study of patients who received first-line PCG. Using international consensus criteria, patients were classified into cisplatin-fit and -unfit groups. Cisplatin-unfit patients received PCG with adjustment of the cisplatin dose after assessing 24-hour urinary creatinine clearance, without modifying the administration interval. ResultsFrom 2008 to 2017, 50 patients received first-line PCG, of whom 30 and 20 were classified into the cisplatin-fit and -unfit groups. After a median follow-up of 15.0 months, the median overall survival (OS) and progression-free survival (PFS) were 15.0 and 9.8 months in all patients, 15.0 and 10.0 months in the cisplatin-fit group, and 13.2 and 9.3 months in the cisplatin-unfit group, respectively. There was no significant difference in OS (hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 0.69–2.54) or PFS (HR: 1.38, 95% CI: 0.74–2.55) between the groups. The overall response rate and complete response rate were 58% (95% CI: 43.2–71.8) and 32% (95% CI: 19.5–46.7) in all patients, and 55% (95% CI: 31.5–76.9) and 35% (95% CI: 15.4-59.2) in the cisplatin-unfit group, respectively. The common grade 3 of 4 adverse events experienced were neutropenia (78%), followed by thrombocytopenia (56%), anemia (46%), and febrile neutropenia (16%). The 24-hour urinary creatinine clearance did not differ significantly between the groups after one, two, or three courses of PCG. ConclusionsWe found no significant difference regarding OS and PFS between the cisplatin-fit patients with a full dose of cisplatin and -unfit patients with cisplatin-dose-adjusted chemotherapy. In select cisplatin-unfit patients, PCG with dose adjustment of cisplatin may be useful for treating advanced/metastatic UC without any significant adverse events or impaired renal function compared with cisplatin-fit patients with a full dose of cisplatin.

Nutritional Secondary Hyperparathyroidism in the Equines of Jammu Region

A study was undertaken on 29 equines with a history of lameness, difficulty in mastication, reduced feed intake, and swelling of facial bones. Feeding history was recorded and clinical examination of all horses was performed. Radiographs of the head of some horses were taken. Blood samples were collected from 14 osteodystrophic and 6 healthy horses to estimate plasma levels of Ca, P, ALP, BUN, and creatinine. Urine samples were collected for a routine examination, sulkowitch test, urine calcium, and phosphorus estimation, and fractional urinary clearance of phosphorus was calculated. Mean values of P, ALP and UFCP was significantly higher in NSHP affected horse than healthy horses. Radiographs of the head revealed decreased bone density, loosened teeth in alveolar sockets, and increased osteoid thickening of maxillae and mandible bones. Young horses were more susceptible than older horses. All the animals were treated by supplementation of 40 gm of calcium carbonate orally for 2 months, resulting in the disappearance of lameness and returning animals to normal work.

Kinetic Glomerular Filtration Rate Equations in Patients With Shock: Comparison With the Iohexol-Based Gold-Standard Method.

Static glomerular filtration rate formulas are not suitable for critically ill patients because of nonsteady state glomerular filtration rate and variation in the volume of distribution. Kinetic glomerular filtration rate formulas remain to be evaluated against a gold standard. We assessed the most accurate kinetic glomerular filtration rate formula as compared to iohexol clearance among patients with shock. Retrospective multicentric study. Three French ICUs in tertiary teaching hospitals. Fifty-seven patients within the first 12 hours of shock. On day 1, we compared kinetic glomerular filtration rate formulas with iohexol clearance, with or without creatinine concentration correction according to changes in volume of distribution and ideal body weight. We analyzed three static glomerular filtration rate formulas (Cockcroft and Gault, modification of diet in renal disease, and Chronic Kidney Disease-Epidemiology Collaboration), urinary creatinine clearance, and seven kinetic glomerular filtration rate formulas (Jelliffe, Chen, Chiou and Hsu, Moran and Myers, Yashiro, Seelhammer, and Brater). We evaluated 33 variants of these formulas after applying corrective factors. The bias ranged from 12 to 47 mL/min/1.73 m2. Only the Yashiro equation had a lower bias than urinary creatinine clearance before applying corrective factors (15 vs 20 mL/min/1.73 m2). The corrected Moran and Myers formula had the best mean bias, 12 mL/min/1.73 m2, but wide limits of agreement (-50 to 73). The corrected Moran and Myers value was within 30% of iohexol-clearance-measured glomerular filtration rate for 27 patients (47.4%) and was within 10% for nine patients (15.8%); other formulas showed even worse accuracy. Kinetic glomerular filtration rate equations are not accurate enough for glomerular filtration rate estimation in the first hours of shock, when glomerular filtration rate is greatly decreased. They can both under- or overestimate glomerular filtration rate, with a trend to overestimation. Applying corrective factors to creatinine concentration or volume of distribution did not improve accuracy sufficiently to make these formulas reliable. Clinicians should not use kinetic glomerular filtration rate equations to estimate glomerular filtration rate in patients with shock.

Improving glomerular filtration rate estimation by semi-supervised learning: a development and external validation study.

Accurate estimating glomerular filtration rate (GFR) is crucial both in clinical practice and epidemiological survey. We incorporated semi-supervised learning technology to improve GFR estimation performance. AASK [African American Study of Kidney Disease and Hypertension], CRIC [Chronic Renal Insufficiency Cohort] and DCCT [Diabetes Control and Complications Trial] studies were pooled together for model development, whereas MDRD [Modification of Diet in Renal Disease] and CRISP [Consortium for Radiological Imaging Studies of Polycystic Kidney Disease] studies for model external validation. A total of seven variables (Serum creatinine, Age, Sex, Black race, Diabetes status, Hypertension and Body Mass Index) were included as independent variables, while the outcome variable GFR was measured as the urinary clearance of 125I-iothalamate. The revised CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration] creatinine equations was selected as benchmark for performance comparisons. Head-to-head performance comparisons from four-variable to seven-variable combination were conducted between revised CKD-EPI equations and semi-supervised models. In each independent variables combination, the semi-supervised models consistently achieved superior results in all three performance indicators compared with corresponding revised CKD-EPI equations in the external validation data set. Furthermore, compared with revised four-variable CKD-EPI equation, the seven-variable semi-supervised model performed less biased (mean of difference: 0.03 [- 0.28, 0.34] vs 1.53 [1.28, 1.85], P < 0.001), more precise (interquartile range of difference: 7.94 [7.37, 8.50] vs 8.28 [7.76, 8.83], P = 0.1) and accurate (P30: 88.9% [87.4%, 90.2%] vs 86.0% [84.4%, 87.4%], P < 0.001. The superior performance of the semi-supervised models during head-to-head comparisons supported the hypothesis that semi-supervised learning technology could improve GFR estimation performance.

Mesenchymal stromal cell treatment of donor kidneys during ex vivo normothermic machine perfusion: A porcine renal autotransplantation study.

Normothermic machine perfusion (NMP) of injured kidneys offers the opportunity for interventions to metabolically active organs prior to transplantation. Mesenchymal stromal cells (MSCs) can exert regenerative and anti-inflammatory effects in ischemia-reperfusion injury. The aims of this study were to evaluate the safety and feasibility of MSC treatment of kidneys during NMP using a porcine autotransplantation model, and examine potential MSC treatment-associated kidney improvements up to 14days posttransplant. After 75min of kidney warm ischemia, four experimental groups of n=7 underwent 14h of oxygenated hypothermic machine perfusion. In three groups this was followed by 240min of NMP with infusion of vehicle, 10million porcine, or 10million human adipose-derived MSCs. All kidneys were autotransplanted after contralateral nephrectomy. MSC treatment did not affect perfusion hemodynamics during NMP or cause adverse effects at reperfusion, with 100% animal survival. MSCs did not affect plasma creatinine, glomerular filtration rate, neutrophil gelatinase-associated lipocalin concentrations or kidney damage assessed by histology during the 14days, and MSCs retention was demonstrated in renal cortex. Infusing MSCs during ex vivo NMP of porcine kidneys was safe and feasible. Within the short posttransplant follow-up period, no beneficial effects of ex vivo MSC therapy could be demonstrated.

Comparison of 51Cr-EDTA and 99mTc-DTPA for glomerular filtration rate measurement.

The production of 51Cr-labelled ethylenediaminetetraacetic acid (51Cr-EDTA), a validated and widely used radio-isotopic tracer for glomerular filtration rate (GFR) measurement in Europe, was recently halted by the manufacturer. Technetium-99m-diethylenetriaminepentaacetic acid (99mTc-DTPA) clearance has so far mostly been restricted to assessment of separate renal function by scintigraphy, but scarcely used and validated for GFR measurement. We compared the performances of 51Cr-EDTA and 99mTc-DTPA for GFR and extracellular fluid measurement. In a multi-centre prospective study, 51Cr-EDTA and 99mTc-DTPA were simultaneously injected into 88 patients, and their urinary and plasma clearances, as well as their volumes of distribution, were measured during seven 30-min periods after a 90-min equilibrium time. Mean age was 52.2 ± 14.5years, 59% were men. Urinary clearances of 51Cr-EDTA and 99mTc-DTPA were 64.1 ± 27.6 and 66.1 ± 28.0mL/min, respectively, with a mean bias of 2.00 ± 2.25mL/min, an accuracy within 10% of 95% [95% CI 91-99], and a coefficient of determination (R2) of 0.994. Plasma clearances of 51Cr-EDTA and 99mTc-DTPA were 66.1 ± 25.8 and 68.1 ± 26.6mL/min, respectively, with a mean bias of 1.96 ± 3.32mL/min, an accuracy within 10% of 91% [95% CI 85-97] and a R2 of 0.985. Distribution volumes were 17.3 ± 4.6 L for 51Cr-EDTA and 16.6 ± 4.6 L for 99mTc-DTPA (R2 0.930). The accuracy and precision of 99mTc-DTPA clearance, compared to 51Cr-EDTA clearance, was excellent for both urinary and plasma clearance methods, despite an approximate 2mL/min overestimation, showing that the tracer is a reliable alternative to 51Cr-EDTA for GFR measurement.

Head-to-Head Comparison of 68Ga-NOTA (68Ga-NGUL) and 68Ga-PSMA-11 in Patients with Metastatic Prostate Cancer: A Prospective Study.

68Ga-NOTA Glu-Urea-Lys (NGUL) is a novel prostate-specific membrane antigen (PSMA)-targeting tracer used for PET/CT imaging. This study aimed to compare performance in the detection of primary and metastatic lesions and to compare biodistribution between 68Ga-NGUL and 68Ga-PSMA-11 in the same patients with prostate cancer. Methods: Eleven patients with metastatic prostate cancer were prospectively recruited. The quantitative tracer uptake was determined in normal organs and in primary and metastatic lesions. Results:68Ga-NGUL showed significantly lower normal-organ uptake and rapid urinary clearance. The number and sites of detected PSMA-positive primary and metastatic lesions were identical, and no significant quantitative uptake difference was observed. 68Ga-NGUL showed a relatively lower tumor-to-background ratio than 68Ga-PSMA-11. Conclusion: In a head-to-head comparison with 68Ga-PSMA-11, 68Ga-NGUL showed lower uptake in normal organs and similar performance in detecting PSMA-avid primary and metastatic lesions. 68Ga-NGUL could be a valuable option for PSMA imaging.

Clarifying Optimal Sodium InTake In Cardiovasular and Kidney (COSTICK) Diseases: a study protocol for two randomised controlled trials

Background: While low sodium intake (<2.3g/day) is recommended for all, there is uncertainty about feasibility and net cardiovascular effects. In COSTICK, we evaluated the effects of a dietary counselling intervention (reduced sodium intake) on intermediate cardiorenal outcomes in patients with(STICK) and without (COSIP) mild/moderate kidney disease. Methods: This is a protocol for two phase IIb randomised, two-group, parallel, open-label, controlled, single centre trials. Participants were aged >40 years with stable blood pressure, unchanged anti-hypertensive medications, willing to modify diet and provided written informed consent. Participants were excluded for abnormal sodium handling, heart failure, high dose diuretics, immunosuppression, pregnancy/lactation, postural hypotension, cognitive impairment, high or low body mass index (BMI) or inclusion in another trial. STICK participants had estimated glomerular filtration rate (eGFR) 30-60ml/min/1.73m 2 and were excluded for acute kidney Injury, rapidly declining eGFR; known glomerular disease or current use of non-steroidal anti-inflammatory drugs. For COSIP, participants were excluded for known kidney or cardiovascular disease. Participants were randomized to usual care only (healthy eating) or an additional sodium lowering intervention (target <100mmol/day) through specific counseling (sodium use in foods, fresh over processed foods, sodium content of foods and eating outside of home). In STICK the primary outcome is change in 24-hour urinary creatinine clearance. In COSIP, the primary outcome is change in five biomarkers (renin, aldosterone, high sensitivity troponin T, pro-B-type natriuretic peptide and C-reactive protein). Our primary report (COSTICK), reports six biomarker outcome measures in the entire population at 2 years follow-up. Discussion: These Phase II trials will explore uncertainty about low sodium intake and cardiovascular and kidney biomarkers, and help determine the feasibility of low sodium intake. Trial results will also provide preliminary information to guide a future definitive clinical trial, if indicated. Trial registration: STICK: ClinicalTrials.gov NCT02738736 (04/04/2016); COSIP: ClinicalTrials.gov NCT02458248 (15/05/2016).

Secreted Phosphoprotein 24 is a Biomarker of Mineral Metabolism.

The 24kD form of secreted phosphoprotein (SPP-24), a cytokine-binding bone matrix protein with various truncated C-terminal products, is primarily synthesized by the liver. SPP-24 shares homology with fetuin-A, a potent vascular and soft tissue calcification inhibitor and SPP-24 is one component of calciprotein particles (CPPs), a circulating fetuin-mineral complex. The limited molecular evidence to date suggests that SPP-24 may also function as an inhibitor of bone formation and ectopic vascular calcification, potentially through bone morphogenic protein 2 (BMP-2) and Wnt-signaling mediated actions. The C-terminal products of SPP-24 bind to BMP-2 and attenuate BMP-2-induced bone formation. The aim of this study was to assess circulating SPP-24 in relation to kidney function and in concert with markers of mineral metabolism in humans. SPP-24 was measured in the serum of total of 192 subjects using ELISA-based measurements. Subjects were participants of one of two cohorts: (1) mGFR Cohort (n = 80) was participants of a study of measured GFR (mGFR) using inulin urinary clearance, recruited mostly from a chronic kidney disease clinic with low-range kidney function (eGFR 38.7 ± 25.0mL/min/1.73m2) and (2) CaMOS Cohort (n = 112) was a subset of randomly selected, community-dwelling participants of year 10 of the Canadian Multicentre Osteoporosis Study with eGFR in the normal range of 75.0 ± 15.9mL/min/1.73m2. In the combined cohort, the mean SPP-24 was 167.7 ± 101.1ng/mL (range 33.4-633.6ng/mL). The mean age was 66.5 ± 11.3, 57.1% female and mean eGFR (CKD-EPI) was 59.9 ± 27.0mL/min/1.73m2 (range 8-122mL/min/1.73m2). There was a strong inverse correlation between SPP-24 and eGFR (R = -0.58, p < 0.001) that remained after adjustment for age. Following adjustment for age, eGFR, and sex, SPP-24 was significantly associated with phosphate (R = -0.199), PTH (R = 0.298), and the Wnt-signaling inhibitor Dickkopf-related protein 1 (R = -0.156). The results of this study indicate that SPP-24 is significantly altered by kidney function and is the first human data linking levels of SPP-24 to other biomarkers involved in mineral metabolism. Whether there is a role for circulating SPP-24 in bone formation and ectopic mineralization requires further study.

Population Pharmacokinetics of Levetiracetam in Patients with Traumatic Brain Injury and Subarachnoid Hemorrhage Exhibiting Augmented Renal Clearance.

Patients with severe trauma exhibit augmented renal clearance, which can alter the dosing requirement of renally eliminated drugs. This study aimed to develop a population pharmacokinetic model for levetiracetam in patients with severe traumatic brain injury and aneurysmal subarachnoid hemorrhage, and use it to describe optimal dosing regimens. This was a prospective open-label observational study. Critically ill adult patients with severe traumatic brain injury or aneurysmal subarachnoid hemorrhage without renal dysfunction and receiving levetiracetam were eligible. Serial levetiracetam plasma concentrations were analyzed to develop a population pharmacokinetic model and perform dosing simulations. A two-compartment model best described the concentration-time data from 30 patients. The mean ± standard deviation parameter estimates were bioavailability (F) of 0.8 ± 0.2, absorption rate constant of 2.4 ± 2 h-1, clearance 2.5 ± 1.1 L/h, central volume of distribution 8.9 ± 3.0 L/h, and transfer rate constraints of 1.8 ± 1.1 h-1 from central to peripheral compartments and 0.7 ± 0.3 h-1 from peripheral to central compartments. For the simulated intermittent dosing regimens, on average, the median trough concentration reduced by 50% for every 40-mL/min/1.73m2 increase in urinary creatinine clearance. Simulated doses of at least 6 g/day were required for some levels of augmented renal clearance. Patients with severe traumatic brain injury and aneurysmal subarachnoid hemorrhage with augmented renal clearance are at risk of not achieving target levetiracetam plasma concentrations. We suggest dose titration guided by measured creatinine clearance, and/or, therapeutic drug monitoring if available, to minimize the risk of seizures.

Targeted design of a recombinant tracer for SPECT renal imaging.

Rationale: A robust radiopharmaceutical has high uptake in the target and low retention in non-target tissues. However, traditional tracers for renal imaging that chemically chelate 99mTc are excreted through the renal route with transient resident time in the kidney. Following a rational design approach, we constructed a protein-based radiotracer, designated PBT-Fc, to sequentially bind tubular neonatal Fc-receptor and subsequently proximal tubular basement membrane for its targeted sequestration in kidney parenchyma. In this process, the tracer participates in physiologic glomerular filtration and tubular reabsorption while escaping lysosomal catabolism and urinary clearance.Methods: To specifically target renal receptors in navigating the urinary passage in the kidney, we produced a recombinant fusion protein with two separate functional parts: a polybasic PBT segment derived from human Vascular Endothelial Growth Factor and Fc segment of IgG1. The chimeric fusion of PBT-Fc was labeled with radionuclide 99mTc and tested in rodent models of kidney diseases. Planar scintigraphy and single-photon emission computerized tomography (SPECT) were performed to evaluate renal-specificity of the tracer.Results: When injected in mouse and rat, following a brief 10 - 15 min dynamic redistribution phase in circulation, ~ 95% of the [99mTc]-PBT-Fc signal was concentrated in the kidney and lasted for hours without urinary loss or surrounding tissue activities. Long-lasting tracer signals in the kidney cortex in conjunction with SPECT greatly augmented the image quality in detecting pathological lesions in a variety of disease models, including ischemic acute kidney injury, drug-induced renal toxicity, and chronic kidney disease from renin-angiotensin system (RAS) overactivation.Conclusion: Exclusive renal retention of the recombinant radiotracer greatly facilitated static-phase signal acquisition by SPECT and achieved submillimeter spatial resolution of kidney alternations in glomerular and tubular disease models.

Evaluation of Response to Treatment in Children with Nephrotic Syndrome over a 10-Year Period: A Retrospective Study

Background Nephrotic syndrome (NS), defined as massive loss of urinary protein results in a triad of hypoalbuminemia, hyperlipidemia and edema. We aimed to determine the frequency of clinical symptoms, laboratory findings and treatment response in children with Nephrotic Syndrome. Materials and Methods: We conducted a longitudinal retrospective study from 2009 to 2019 at a single regional pediatric center, Zahedan, Iran, on 206 children (up to 14 years) with NS that were selected from all clinical records files. Parameters extracted included age, sex, presenting symptoms, blood pressure. Laboratory information included complete blood count, urine analysis, 24-hour urinary protein excretion, creatinine clearance, serum electrolytes, serum urea and creatinine levels, total protein and albumin, triglyceride and cholesterol, acute phase reactant, treatment and outcome. All the data extracted were recorded in pre-prepared forms. Results: A total of 107 men (52%) and 99 women (49%) participated in the study. Edema was most commonly found in 197 (95.6%), respiratory distress in 2 (0.9%), abdominal pain in 45 (21.8%), nausea and vomiting in 28 (13.5%), and gross hematuria in 6 (2.9%). Leukopenia was seen in 0.5% followed by 42.4% of normal white blood cells (WBCs) and 57.1% leukocytosis. 74.4% of all patients had anemia in their laboratory tests in spite of thrombocytopenia only seen in 1.7%. 49% had pyuria and hematuria was seen in 41%. The mean level of serum albumin was 2.5 g/l, cholesterol was 381 mg/dl, triglyceride was 287 mg/dl and the mean level of 24-hour urinary protein excretion was 2084 mg/dl. Conclusion The most common clinical symptom in nephrotic syndrome was edema followed by nausea and vomiting and abdominal pain.

Comparison of various predictive equations for glomerular filtration rate in healthy individuals and chronic kidney disease patients from North India.

A noninvasive and accurate estimate of the glomerular filtration rate (GFR) is an essential prerequisite for medical professionals. In the absence of 24-h urinary creatinine clearance, various predictive equations can be utilized for estimating GFR. A cross-sectional observational study was conducted on healthy adults as well as adult chronic kidney disease (CKD) Indian population. In normal males and females, Modification of Diet in Renal Disease-4 (MDRD-4) and Cockcroft- Gault (CG) were the best equations respectively, which showed the best correlation and best precision in CKD stage 1 males and females, MDRD-4 and MDRD-6 were the best equations respectively In CKD stage 2 males and females, CKD-Epidemiology Collaboration (CKD-EPI) was adjudged the best equation, which showed the best correlation, best precision, and least bias. In CKD stage 3 males and females, CG and CKD-EPI were the best equation respectively, with the best correlation, best precision, least biased, and most accuracy. In CKD stage 4 males and females, MDRD-6 and MDRD-4 showed the best correlation, best precision and most accuracy respectively. In CKD stage 5, CKD-EPI demonstrated the best results in both sexes. We observed that all the predictive equations were good estimates of GFR in one or other stages of CKD, but no single predictive equation showed consistent results when compared among normal subjects and CKD sub-groups.

Heparin length in the coating of extremely small iron oxide nanoparticles regulates in vivo theranostic applications.

The positive contrast of extremely small iron oxide nanoparticles (ESIONP) in magnetic resonance imaging (MRI) rejuvenates this class of metal nanoparticles (NP).Yet, the current synthesis often lacks the possibility of adjusting the core size (while it is a key element for ESIONP-based MRI contrast behaviour), and also involved multiple complex steps before obtaining a ready-to-use probe for medical applications. In this study, we faced these challenges by applying heparin oligosaccharides (HO) of different lengths as coatings for the preparation of HEP-ESIONP with a one-pot microwave method. We demonstrated that the HO length could control the core size during the synthesis to achieve optimal positive MRI contrast, and that HEP-ESIONP were endowed directly with anticoagulant properties and/or a specific antitumor activity, according to the HO used. Relevantly, positron emission tomography (PET)-based in vivo biodistribution study conducted with 68Ga core-doped HEP-ESIONP analogues revealed significant changes in the probe behaviours, the shortening of HO promoting a shift from hepatic to renal clearance. The different conformations of HO coatings and a thorough in vitro characterisation of the probes' protein coronas provided insight into this crucial impact of HO length on opsonization-mediated immune response and elimination. Overall, we were able to identify a precise HO length to get an ESIONP probe showing prolonged vascular lifetime and moderate accumulation in a tumor xenograft, balanced with a low uptake by non-specific organs and favourable urinary clearance. This probe met all prerequisites for advanced theranostic medical applications with a dual MRI/PET hot spot capability and potential antitumor activity.

Association of cardiovascular morbidity with residual renal function in twice weekly versus thrice weekly hemodialysis patients

Background: Chronic kidney disease is a non-communicable global problem. In patients of chronic kidney disease especially in hemodialysis patient mortality and morbidity due to atherosclerosis induced cardiovascular complications is very high despite the advances of hemodialysis procedure. Residual renal function contributes significantly to the overall health and cardiovascular morbidity of dialysis patients. So, the loss of residual renal function, especially in patients on hemodialysis, is a powerful predictor of mortality. Preserving residual renal function is the goal of nephrologists. Objective: To find the association between residual renal function and cardiovascular morbidity in twice weekly and thrice weekly hemodialysis patient. Methodology: This cross sectional study was conducted on 72 hemodialysis patients received dialysis more than three months in the dialysis centre of BSMMU and DMCH, Dhaka, Bangladesh during the period of October 2018 to September 2019. Study populations were divided into two groups on the basis of residual renal function (RRF). RRF was defined by interdialytic 24 hours urine volume and average of urinary urea and creatinine clearance. Preserved RRF was defined 24 hours urine volume more than 100 ml. Chi-square test (χ2), Student’s paired t-test and multiple regression analysis were used to find association between cardiovascular morbidity and RRF. Result: A significant difference of diastolic dysfunction, systolic dysfunction, LVH (p=0.001, p=0.001, p=0.004 respectively) was seen in between preserved RRF and without preserved RRF group but the difference of regional wall motion abnormality and valvular heart disease was found to be non-significant. In regression analysis, loss of RRF was found to be a significant predictor of cardiovascular morbidity. Conclusion: Preserved RRF was significantly associated with less frequent diastolic dysfunction, left ventricular hypertrophy and higher level of left ventricular ejection fraction compared to without preserved residual renal function in both twice weekly and thrice weekly HD patient.

Does renal function matter for polymyxin B?

Does renal function matter for polymyxin B?

A New Panel-Estimated GFR, Including β2-Microglobulin and β-Trace Protein and Not Including Race, Developed in a Diverse Population

Glomerular filtration rate (GFR) estimation based on creatinine and cystatin C (eGFRcr-cys) is more accurate than estimated GFR (eGFR) based on creatinine or cystatin C alone (eGFRcr or eGFRcys, respectively), but the inclusion of creatinine in eGFRcr-cys requires specification of a person's race. β2-Microglobulin (B2M) and β-trace protein (BTP) are alternative filtration markers that appear to be less influenced by race than creatinine is. Study of diagnostic test accuracy. Development in a pooled population of 7 studies with 5,017 participants with and without chronic kidney disease. External validation in a pooled population of 7 other studies with 2,245 participants. Panel eGFR using B2M and BTP in addition to cystatin C (3-marker panel) or creatinine and cystatin C (4-marker panel) with and without age and sex or race. GFR measured as the urinary clearance of iothalamate, plasma clearance of iohexol, or plasma clearance of [51Cr]EDTA. Mean measured GFRs were 58.1 and 83.2 mL/min/1.73 m2, and the proportions of Black participants were 38.6% and 24.0%, in the development and validation populations, respectively. Indevelopment, addition of age and sex improved the performance of all equations compared with equations without age and sex, but addition of race did not further improve the performance. In validation, the 4-marker panels were more accurate than the 3-marker panels (P< 0.001). The 3-marker panel without race was more accurate than eGFRcys (percentage of estimates greater than 30% different from measured GFR [1 - P30] of 15.6% vs 17.4%; P= 0.01), and the 4-marker panel without race was as accurate as eGFRcr-cys (1 - P30 of 8.6% vs 9.4%; P= 0.2). Results were generally consistent across subgroups. No representation of participants with severe comorbid illness and from geographic areas outside of North America and Europe. The 4-marker panel eGFR is as accurate as eGFRcr-cys without requiring specification of race. A more accurate race-free eGFR could be an important advance.