scholarly journals Plasma oxalate and eGFR are correlated in primary hyperoxaluria patients with maintained kidney function—data from three placebo-controlled studies

2021 ◽  
Author(s):  
Dawn S. Milliner ◽  
Pierre Cochat ◽  
Sally-Anne Hulton ◽  
Jerome Harambat ◽  
Ana Banos ◽  
...  
Keyword(s):  
Kidney Function ◽  
Primary Hyperoxaluria ◽  
Correlation Coefficients ◽  
Inverse Correlation ◽  
Individual Study ◽  
Severe Chronic Kidney Disease ◽  
Urinary Oxalate Excretion ◽  
The Relationship ◽  
Spearman’S Correlation

Abstract Background In patients with primary hyperoxaluria (PH), endogenous oxalate overproduction increases urinary oxalate excretion, leading to compromised kidney function and often kidney failure. Highly elevated plasma oxalate (Pox) is associated with systemic oxalate deposition in patients with PH and severe chronic kidney disease (CKD). The relationship between Pox and estimated glomerular filtration rate (eGFR) in patients with preserved kidney function, however, is not well established. Our analysis aimed to investigate a potential correlation between these parameters in PH patients from three randomized, placebo-controlled trials (studies OC3-DB-01, OC3-DB-02, and OC5-DB-01). Methods Baseline data from patients with a PH diagnosis (type 1, 2, or 3) and eGFR > 40 mL/min/1.73 m2 were analyzed for a correlation between eGFR and Pox using Spearman’s rank and Pearson’s correlation coefficients. Data were analyzed by individual study and additionally were pooled for Studies OC3-DB-02 and OC5-DB-01 in which the same Pox assay was used. Results A total of 106 patients were analyzed. A statistically significant inverse Spearman’s correlation between eGFR and Pox was observed across all analyses; correlation coefficients were − 0.44 in study OC3-DB-01, − 0.55 in study OC3-DB-02, − 0.51 in study OC5-DB-01, and − 0.49 in the pooled studies (p < 0.0064). Conclusions Baseline evaluations showed a moderate and statistically significant inverse correlation between eGFR and Pox in patients with PH already at early stages of CKD (stages 1–3b), demonstrating that a correlation is present before substantial loss in kidney function occurs. Graphical abstract

scholarly journals Nasal Morphology and Its Correlation to Craniofacial Morphology in Lateral Cephalometric Analysis

2021 ◽  
Vol 18 (6) ◽  
pp. 3064
Author(s):  
Agnieszka Jankowska ◽  
Joanna Janiszewska-Olszowska ◽  
Katarzyna Grocholewicz
Keyword(s):  
Soft Tissue ◽  
Nasal Bone ◽  
Correlation Coefficients ◽  
Craniofacial Morphology ◽  
Base Angle ◽  
Nasolabial Angle ◽  
Orthodontic Patients ◽  
Nose Shape ◽  
The Relationship ◽  
Spearman’S Correlation

Nose shape, size, and inclination influence facial appearance, but few studies concern the relationship between the nasal profile and craniofacial structures. The objective of this study was to analyze association of nasal cephalometric variables with skeletal structures, age, and sex. Cephalometric and nasal analysis was performed in 386 Polish orthodontic patients (aged 9–25 years). Student t-test and Mann–Whitney test were used to compare quantitative variables and Pearson’s or Spearman’s correlation coefficients—to find correlations. Soft tissue facial convexity angle correlates to Holdaway ratio, ANB (A-Nasion-B), and Wits appraisal. Nasal dorsum axis, nose length, nose depth (1) and nose depth (2), nose hump, lower dorsum convexity, and columella convexity increase with age. Nasal base angle, nasolabial angle, nasomental angle, soft tissue facial convexity and nasal bone angle decrease with age. Nasal base angle and nasomental angle are smaller in females. Thus, a relationship exists between nasal morphology and sagittal jaw configuration. Nasal parameters significantly change with age. Sexual dimorphism characterizes nasal bone angle and nasomental angle.

scholarly journals The Dependence of Renal 68Ga[Ga]-DOTATOC Uptake on Kidney Function and Its Relevance for Peptide Receptor Radionuclide Therapy with 177Lu[Lu]-DOTATOC

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1216
Author(s):  
Falk Gühne ◽  
Alexander Heinzig ◽  
Philipp Seifert ◽  
Robert Drescher ◽  
Martin Freesmeyer
Keyword(s):  
Kidney Function ◽  
Specific Binding ◽  
Correlation Coefficients ◽  
Inverse Correlation ◽  
Peptide Receptor Radionuclide Therapy ◽  
Tracer Uptake ◽  
Significant Inverse Correlation ◽  
Peptide Receptor ◽  
Pet Ct ◽  
Induced Changes

Background: In addition to its SSTR-specific binding in tumors and healthy tissues, DOTATOC analogues accumulate in kidney parenchyma. Renal tracer uptake might be a surrogate of kidney function or dysfunction. This study aimed to evaluate if kidney function can be estimated from 68Ga[Ga]-DOTATOC uptake in PET/CT and its impact on the nephrotoxicity of 177Lu[Lu]-DOTATOC PRRT. Methods: Two cohorts of patients (A: 128 diagnostic patients; B: 32 PRRT patients) were evaluated retrospectively. SUV values of the kidneys, physiologically SSTR-expressing organs and in background compartments were assessed. Kidney function was calculated as eGFR by CKD-EPI creatinine equation. Pearson’s correlation coefficients and treatment-induced changes of uptake and kidney function were assessed and compared. Results: Kidney function and renal DOTATOC uptake showed a significant inverse correlation (R2 = 0.037; p = 0.029). Evaluated models of PET/CT measurements were not able to predict kidney function sufficiently. The uptake of other organs did not depend on eGFR. While the renal uptake increased after PRRT (p < 0.001), the kidney function did not change significantly (p = 0.382). Neither low pre-therapeutic eGFR nor high pre-therapeutic kidney uptake were risk factors of PRRT-induced deterioration in kidney function. Conclusion: The relevance of kidney function for renal 68Ga[Ga]-DOTATOC uptake is limited. The nephrotoxicity of 177Lu[Lu]-DOTATOC PRRT might be low and cannot be reliably predicted by pre-therapeutic measurements.

MO047STABLE EGFR IN PATIENTS WITH PRIMARY HYPEROXALURIA TYPE 1 TREATED WITH LUMASIRAN, REGARDLESS OF KIDNEY FUNCTION AT START OF TREATMENT

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Wesley Hayes ◽  
Sander Garrelfs ◽  
David Sas ◽  
John Lieske ◽  
Taylor Ngo ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Kidney Function ◽  
Primary Hyperoxaluria ◽  
Small Sample ◽  
Primary Hyperoxaluria Type 1 ◽  
Primary Hyperoxaluria Type ◽  
The Mean ◽  
Over Time ◽  
Hyperoxaluria Type

Abstract Background and Aims Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder characterized by hepatic oxalate overproduction. Excess oxalate is excreted by the kidneys, leading to recurrent kidney stones, nephrocalcinosis, and progressive kidney disease. Patients with PH1 generally experience a slow decline in kidney function over time that can be punctuated by abrupt worsening precipitated by infection, obstructing stones, or dehydration. Approximately half of patients with PH1 progress to kidney failure by early adulthood, and nearly all by 60 years of age. Lumasiran is an RNAi therapeutic indicated for the treatment of PH1 in all age groups. In clinical trials, treatment with lumasiran resulted in substantial reductions in urinary and plasma oxalate in pediatric and adult patients, with an acceptable safety profile. This analysis evaluates the change in kidney function of patients with PH1 with an eGFR of ≥30 mL/min/1.73m2 enrolled in clinical trials of lumasiran. Method We analyzed kidney function from 75 patients with PH1, age ≥12 months old, eGFR ≥30 mL/min/1.73m2, enrolled in 3 clinical trials of lumasiran (Phase 2 open-label extension, and Phase 3 ILLUMINATE-A and ILLUMINATE-B). In these trials, eGFR was calculated with the Modification of Diet in Renal Disease (MDRD) Study equation in adults or the bedside Schwartz equation in children. The effect of lumasiran on eGFR was assessed by baseline eGFR subgroup: ≥90, &lt;90, 60 to &lt;90, 45 to &lt;60, and 30 to &lt;45 mL/min/1.73m2. Results Of 75 patients available for analysis, 46 were treated with lumasiran from the start of the study through the Month 12 visit. eGFR remained stable in all eGFR subgroups. Patients with eGFR ≥90 mL/min/1.73m2 at baseline (N=16) demonstrated fluctuations in mean values by timepoint, with a mean change (95% CI) from baseline of -1 (-8, 6) mL/min/1.73m2 at Month 12. In patients with eGFR &lt;90 mL/min/1.73m2 (N=30), no change in mean eGFR from baseline was observed at Month 12; the mean change (95% CI) was 0 (-3, 3). When evaluating subgroups with impaired kidney function, variations in the mean change were observed at Month 12 due to small sample sizes. For patients with eGFR 60 to &lt;90 mL/min/1.73m2 (N=22), the mean change (95% CI) was -2 (-5, 1). For patients with eGFR 45 to &lt;60 mL/min/1.73m2 (N=5), the mean change (95% CI) was 3 (-8, 14). For patients with eGFR 30 to &lt;45 mL/min/1.73m2 (N=3), the mean change (95% CI) was 9 (7, 11). Conclusion Patients with PH1 had stable kidney function over time with lumasiran treatment, regardless of kidney function at baseline. Given the progressive kidney function decline that is characteristic of PH1, the eGFR stability observed during 12 months of treatment with lumasiran is encouraging. Kidney function will continue to be monitored for the duration of the lumasiran clinical trials.

scholarly journals Time in range, especially overnight time in range, is associated with sudomotor dysfunction in patients with type 1 diabetes

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Zhou-qin Feng ◽  
Qing-yu Guo ◽  
Wei Wang ◽  
Yan-yu Yuan ◽  
Xu-guang Jin ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Microvascular Complications ◽  
Correlation Coefficients ◽  
Sweat Glands ◽  
Sudomotor Function ◽  
Time In Range ◽  
Logistic Regressions ◽  
Independent Association ◽  
The Relationship

Abstract Background Time in range (TIR) is advocated as key metric of glycemic control and is reported to be associated with microvascular complications of diabetes. Sudomotor dysfunction is among the earliest detectable diabetic peripheral neuropathy (DPN). We set about to research the relationship between TIR including overnight TIR and sudomotor function detected by SUDOSCAN with the intention of exploring the correlation of TIR including overnight TIR and early DPN in type 1 diabetes (T1D). Methods 95 patients with T1D were enrolled. TIR including nocturnal TIR of 3.9–10.0 mmol/L was evaluated with CGM. SUDOSCAN measured feet electrochemical skin conductance (FESC) and sudomotor dysfunction was defined as average FESC < 60µS. Logistic regressions were applied to examine the independent association of TIR and overnight TIR with sudomotor function. Results The overall prevalence of sudomotor dysfunction was 28.42%. Patients with sudomotor dysfunction had significantly lower TIR for the whole recorded phase and for nighttime. The sudomotor dysfunction prevalence progressively declined with the ascending tertiles of TIR and nocturnal TIR (P for trend < 0.05). Correlation analysis showed that the relationship between nocturnal TIR and FESC was stronger than that between TIR and FESC with correlation coefficients were respectively 0.362 and 0.356 (P < 0.001). Finally, logistic regression analysis indicated the independently negative relation between TIR and nocturnal TIR and sudomotor dysfunction (P < 0.05), and the correlation between nocturnal TIR and sudomotor dysfunction was more statistically significant. Conclusions TIR is negatively correlated with sudomotor dysfunction in T1D independent of HbA1c. Furthermore, decreased nocturnal TIR is more closely related to the impaired function of sudomotor nerves in sweat glands.

scholarly journals Cosmological effects on Size Evolution of some Extragalactic Radio Sources and Quasar/Galaxy Unification

2021 ◽  
pp. 21-24
Author(s):  
Ezeugo Jeremiah Chukwuemerie
Keyword(s):  
Empirical Relation ◽  
Correlation Coefficients ◽  
Inverse Correlation ◽  
Radio Sources ◽  
Simple Linear Regression ◽  
Extragalactic Radio Sources ◽  
Empirical Relations ◽  
Size Evolution ◽  
The Relationship ◽  
Quasars And Radio Galaxies

We use analytical methods to develop a mathematical model that expresses the relationship between the linear size  of some extragalactic radio sources (EGRS) and their redshift . Result shows that , where . For the purpose of obtaining an empirical relation of similar form, we carry out simple linear regression analyses of the observed linear sizes of these EGRS in our sample against their respective observed redshifts. We obtain an empirical relation of the form, , where  and  for radio-loud quasars and radio galaxies respectively, with correlation coefficients given by,  for each of the sources. The correlation is marginal/slight. Comparing the theoretical and empirical relations, we find that the  data show an inverse correlation which is similar to the theory. This suggestively indicates presence of cosmological effects on the size evolution of the radio sources. Moreover, we find that similarity in the behavior of the two sources in the  plane, simply supports quasar/galaxy unification scheme in which the different observable properties that characterize these two subclasses of radio sources are aspect-dependent.

scholarly journals Lysosomal Exoglycosidase Profile and Secretory Function in the Salivary Glands of Rats with Streptozotocin-Induced Diabetes

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Mateusz Maciejczyk ◽  
Agnieszka Kossakowska ◽  
Julita Szulimowska ◽  
Anna Klimiuk ◽  
Małgorzata Knaś ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Inverse Correlation ◽  
Salivary Flow ◽  
Diabetic Rats ◽  
Secretory Function ◽  
Submandibular Glands ◽  
Streptozotocin Induced Diabetes ◽  
And Control ◽  
The Relationship

Before this study, there had been no research evaluating the relationship between a lysosomal exoglycosidase profile and secretory function in the salivary glands of rats with streptozotocin- (STZ-) induced type 1 diabetes. In our work, rats were divided into 4 groups of 8 animals each: control groups (C2, C4) and diabetic groups (STZ2, STZ4). The secretory function of salivary glands—nonstimulated and stimulated salivary flow,α-amylase, total protein—and salivary exoglycosidase activities—N-acetyl-β-hexosaminidase (HEX, HEX A, and HEX B),β-glucuronidase,α-fucosidase,β-galactosidase, andα-mannosidase—was estimated both in the parotid and submandibular glands of STZ-diabetic and control rats. The study has demonstrated that the activity of most salivary exoglycosidases is significantly higher in the parotid and submandibular glands of STZ-diabetic rats as compared to the healthy controls and that it increases as the disease progresses. Reduced secretory function of diabetic salivary glands was also observed. A significant inverse correlation between HEX B,α-amylase activity, and stimulated salivary flow in diabetic parotid gland has also been shown. Summarizing, STZ-induced diabetes leads to a change in the lysosomal exoglycosidase profile and reduced function of the salivary glands.

scholarly journals The Relationship Between Demographic and Occupational Characteristics and Disability Severity in Patients With Knee Osteoarthritis

2020 ◽  
Vol 10 (1) ◽  
pp. 1-6
Author(s):  
Maryam Abdoos ◽  
◽  
Mahyar Salavati ◽  
Zahra Mosallanezhad ◽  
Hoda Fasihnia ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Knee Osteoarthritis ◽  
Pain Intensity ◽  
Educational Level ◽  
Functional Disability ◽  
Correlation Coefficients ◽  
Pain Severity ◽  
History Of ◽  
The Relationship ◽  
Spearman’S Correlation

Purpose: Osteoarthritis is a progressive disease and the most common form of joint inflammation. Moreover, it is the most common cause of functional disability in the elderly. Among the multiple and predisposing factors influencing the disease are demographic indicators and occupational factors. The present study aimed to investigate the relationship between age, pain severity, Body Mass Index (BMI), occupation, and educational level, and the severity of functional disability in patients with Knee Osteoarthritis (KO). Methods: This descriptive study was performed on 97 KO patients referring to the Novin private physiotherapy clinic of Semnan University of Medical Sciences from April to March 2017. The study participants were selected through a simple nonprobability sampling technique. Literate individuals with the educational level of guidance school and above and diagnosed with KO were included in the study. Individuals with a history of inflammatory arthritis diseases, such as rheumatoid arthritis, soft tissue rheumatoid arthritis, fibromyalgia syndrome, bursitis, tendonitis, the neurological and vascular conditions of the lower extremity, mental problems, and malignancy were excluded from this research. The data related to the variables such as age, gender, occupation, history of osteoarthritis, pain intensity, involved side, educational level, and the Knee Injury and Osteoarthritis Outcome Score (KOOS) for knee disability were collected by a self-report questionnaire. This study was approved by the Research Ethics Committee of the University of Social Welfare and Rehabilitation Sciences. Using SPSS, Spearman’s correlation coefficients were calculated to examine the relationship between the study variables. Results: Spearman’s correlation coefficients revealed no significant correlation between the KOOS scores and age, occupation, and educational level. The obtained results suggested a poor significant association between KOOS and BMI; however, there was a strong significant correlation between KOOS and pain intensity Visual Analogue Scale (VAS) (P<0.05). Conclusion: The severity of functional disability in patients with KO based on KOOS questionnaire scores, was well correlated with pain severity, but poorly associated with age and BMI. The obtained data indicated no significant relationship between disability and occupation and educational level.

scholarly journals Phase 1/2 Study of Lumasiran for Treatment of Primary Hyperoxaluria Type 1

2021 ◽  
pp. CJN.14730920
Author(s):  
Yaacov Frishberg ◽  
Georges Deschênes ◽  
Jaap W. Groothoff ◽  
Sally-Anne Hulton ◽  
Daniella Magen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase 1 ◽  
Primary Hyperoxaluria ◽  
Urinary Oxalate ◽  
Primary Hyperoxaluria Type 1 ◽  
Primary Hyperoxaluria Type ◽  
Urinary Oxalate Excretion ◽  
Healthy Participants ◽  
Hyperoxaluria Type

Background and objectivesIn the rare disease primary hyperoxaluria type 1, overproduction of oxalate by the liver causes kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. Lumasiran, an RNA interference therapeutic, suppresses glycolate oxidase, reducing hepatic oxalate production. The objective of this first-in-human, randomized, placebo-controlled trial was to evaluate the safety, pharmacokinetic, and pharmacodynamic profiles of lumasiran in healthy participants and patients with primary hyperoxaluria type 1.Design, setting, participants, & measurementsThis phase 1/2 study was conducted in two parts. In part A, healthy adults randomized 3:1 received a single subcutaneous dose of lumasiran or placebo in ascending dose groups (0.3–6 mg/kg). In part B, patients with primary hyperoxaluria type 1 randomized 3:1 received up to three doses of lumasiran or placebo in cohorts of 1 or 3 mg/kg monthly or 3 mg/kg quarterly. Patients initially assigned to placebo crossed over to lumasiran on day 85. The primary outcome was incidence of adverse events. Secondary outcomes included pharmacokinetic and pharmacodynamic parameters, including measures of oxalate in patients with primary hyperoxaluria type 1. Data were analyzed using descriptive statistics.ResultsThirty-two healthy participants and 20 adult and pediatric patients with primary hyperoxaluria type 1 were enrolled. Lumasiran had an acceptable safety profile, with no serious adverse events or study discontinuations attributed to treatment. In part A, increases in mean plasma glycolate concentration, a measure of target engagement, were observed in healthy participants. In part B, patients with primary hyperoxaluria type 1 had a mean maximal reduction from baseline of 75% across dosing cohorts in 24-hour urinary oxalate excretion. All patients achieved urinary oxalate levels ≤1.5 times the upper limit of normal.ConclusionsLumasiran had an acceptable safety profile and reduced urinary oxalate excretion in all patients with primary hyperoxaluria type 1 to near-normal levels.Clinical Trial registry name and registration number:Study of Lumasiran in Healthy Adults and Patients with Primary Hyperoxaluria Type 1, NCT02706886

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