Lysozyme Excretion as a Measure of Renal Tubular Dysfunction in Children

1. Activity of the low molecular weight enzyme lysozyme was measured in the plasma and urine of healthy adults and children and of children with renal disease. 2. No difference was detected between lysozyme excretion (expressed as the lysozyme/creatinine clearance ratio) of healthy adults and neonates, implying that the proximal tubular function of protein reabsorption is mature in the neonate. 3. The lysozyme/creatinine clearance ratio was not elevated in the nephrotic syndrome: thus a heavy load of filtered albumin does not interfere with low molecular weight protein reabsorption. 4. Very high values of lysozyme/creatinine clearance were observed in children with the Fanconi syndrome; there was no overlap with any other group studied. 5. Children with pyuria had a very slight increase in urine lysozyme/creatinine concentration ratio.

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Tinzaparin Safety in Patients With Cancer and Renal Impairment: A Systematic Review

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029620979592 ◽

2021 ◽

Vol 27 ◽

pp. 107602962097959

Author(s):

I. A. Vathiotis ◽

N. K. Syrigos ◽

E. P. Dimakakos

Keyword(s):

Systematic Review ◽

Molecular Weight ◽

Renal Impairment ◽

Creatinine Clearance ◽

Cancer Patients ◽

Major Bleeding ◽

Severe Renal Impairment ◽

Special Populations ◽

Low Molecular Weight ◽

Patients With Cancer

Low-molecular-weight heparins are approved for primary and secondary venous thromboembolism prevention. Tinzaparin is the low-molecular-weight heparin with the highest average molecular weight. The purpose of this systematic review is to provide an update regarding the safety profile of tinzaparin, prescribed either as a prophylactic or as a therapeutic regimen for venous thromboembolism in special populations, including cancer patients and patients with renal impairment. We identified prospective studies up to August 2020 reporting safety outcomes for cancer patients and patients with renal impairment on tinzaparin regimens. In patients with cancer major bleeding rates fluctuated between 0.8% and 7%. Patients on tinzaparin exhibited significantly lower rates of clinically relevant nonmajor bleeding events in comparison with those on vitamin K antagonists. Bioaccumulation of tinzaparin was not correlated with age, body weight or creatinine clearance. Periodic administration of either prophylactic or therapeutic doses of tinzaparin did not result in bioaccumulation, even in patients with severe renal impairment and creatinine clearance < 20 ml/min. Major bleeding rates for non-cancer patients with renal impairment on prophylactic tinzaparin regimens were 0%. Non-cancer patients with renal impairment on therapeutic tinzaparin regimens exhibited major bleeding in 0 to 3.4% of cases; major bleeding rates were higher for cancer patients with renal impairment on therapeutic tinzaparin regimens (4.3 to 10%). Tinzaparin can be used without dose adjustment in patients with severe renal impairment and creatinine clearance > 20 ml/min. Tinzaparin represents a safe choice for special populations at increased risk for thrombosis and bleeding.

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MYOHEMOGLOBINURIA

Journal of Experimental Medicine ◽

10.1084/jem.74.3.187 ◽

1941 ◽

Vol 74 (3) ◽

pp. 187-196 ◽

Cited By ~ 36

Author(s):

Charles L. Yuile ◽

William F. Clark

Keyword(s):

Molecular Weight ◽

Plasma Concentration ◽

Creatinine Clearance ◽

Glomerular Filtration ◽

Renal Clearance ◽

Renal Excretion ◽

Clearance Ratio ◽

A Value ◽

Blood Hemoglobin

When myohemoglobin is injected intravenously into dogs, in amounts ranging from 0.75 to 1.50 gm., it is rapidly eliminated from the plasma and approximately 65 per cent is excreted by the kidneys in from 1½ to 2½ hours. Myohemoglobin does not appear in the urine below a threshold plasma concentration which is slightly under 20 mg. per 100 cc. but above this level the rate of renal excretion is directly proportional to the plasma concentration. The maximum myohemoglobin/creatinine clearance ratio averages 0.58 contrasted with a value of 0.023 for blood hemoglobin. This indicates that the rate of renal clearance of myohemoglobin is twenty-five times more rapid than that of blood hemoglobin. Evidence is presented that the excretory mechanism is essentially similar for the two substances but that differences in molecular weight account for different rates of glomerular filtration.

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An enhanced chemiluminescence detection system combined with a modified immunoblot technique for the detection of low molecular weight IgM in sera from healthy adults and neonates

Journal of Immunological Methods ◽

10.1016/0022-1759(92)90233-j ◽

1992 ◽

Vol 146 (2) ◽

pp. 241-247 ◽

Cited By ~ 6

Author(s):

H.J. Xu ◽

K. Umapathysivam ◽

J. McNeilage ◽

T.P. Gordon ◽

P.J. Roberts-Thomson

Keyword(s):

Molecular Weight ◽

Detection System ◽

Healthy Adults ◽

Low Molecular Weight ◽

Chemiluminescence Detection ◽

Enhanced Chemiluminescence ◽

Immunoblot Technique

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Stop-flow analysis of creatinine excretion in the dog

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1962.203.6.980 ◽

1962 ◽

Vol 203 (6) ◽

pp. 980-984 ◽

Cited By ~ 21

Author(s):

Robert E. Swanson ◽

Ali A. Hakim

Keyword(s):

Creatinine Clearance ◽

Competitive Inhibition ◽

Flow Analysis ◽

High Plasma ◽

Free Flow ◽

Inulin Clearance ◽

Plasma Creatinine ◽

Clearance Ratio ◽

Creatinine Concentration ◽

Stop Flow

Urinary excretion patterns of creatinine and inulin under stop-flow conditions in male mongrel dogs were compared. Evidence for a weak creatinine secretory mechanism at the proximal tubule level include the following: 1) Exogenous creatinine in the stop-flow samples appears prior to inulin when both are injected midway during a 10-min ureteral clamping period. 2) The ratio of creatinine/inulin U/P values (creatinine clearance ratio) shows a peak and a distribution coextensive with PAH/inulin clearance ratios. 3) Self-depression of the peak stop-flow creatinine clearance ratio was obtained at high plasma creatinine concentrations. 4) High plasma p-aminohippuric acid levels depressed the free-flow and peak stop-flow creatinine clearance ratios and, conversely, high plasma creatinine concentration depressed free-flow and peak stop-flow PAH clearance ratios (competitive inhibition). 5) Probenecid reduced free-flow and peak stop-flow creatinine clearance ratios (creatinine secretory mechanism blocked). The mean free-flow creatinine/inulin clearance ratios in 44 clearance periods was 1.2±0.1 (sd), compared to the peak stop-flow ratio of 1.8±0.4 (sd) (N = 20) at plasma creatinine concentrations less than 20 mg/100 ml.

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Use of Therapeutic Dose Low Molecular Weight Heparin in Patients with Renal Insufficiency: Analysis of Anti-Xa Levels and Creatinine Clearance.

Blood ◽

10.1182/blood.v108.11.884.884 ◽

2006 ◽

Vol 108 (11) ◽

pp. 884-884

Author(s):

Wendy Lim ◽

Manasa Sridhara ◽

Luqi Wang ◽

Krystyna Kinnon ◽

James Douketis ◽

...

Keyword(s):

Molecular Weight ◽

Renal Function ◽

Renal Insufficiency ◽

Creatinine Clearance ◽

Therapeutic Dose ◽

Low Molecular Weight Heparin ◽

Dose Adjustment ◽

Low Molecular Weight ◽

Recurrent Vte ◽

Dependent Patient

Abstract Low molecular weight heparin (LMWH) is predominantly eliminated by the kidneys. In patients with severe renal impairment, use of therapeutic dose LMWH may be associated with accumulation and a resultant bleeding risk. Tinzaparin may be less dependent on renal clearance due to its higher molecular mass and greater negative charge compared to other LMWHs. The objective of this prospective cohort study was to serially measure the anti-Xa anticoagulant effect of therapeutic dose tinzaparin over 5–7 days, used for the initial treatment of venous thromboembolism (VTE) in patients with varying degrees of renal insufficiency. We present the anti-Xa results from the first 78 patients enrolled in the study, correlated with renal function. In this study, consecutive in- and outpatients with objectively confirmed VTE requiring anticoagulation were enrolled and stratified into 4 groups based on the calculated Cockcroft-Gault creatinine clearance (CrCl): > 60 mL/min, 30–60 mL/min, ≤ 30 mL/min and hemodialysis-dependent. Tinzaparin 175 IU/kg was administered subcutaneously once daily for 5–7 days or until the INR ≥ 2.0 with warfarin therapy. Trough anti-Xa levels were measured prior to the 3rd, 5th and/or 7th tinzaparin doses. Patients with anti-Xa level > 0.5 IU/mL received tinzaparin dose adjustment using a standardized nomogram. Bleeding and recurrent VTE events were recorded. The relationship between anti-Xa levels and CrCl is shown in Figure 1. Based on our predefined anti-Xa threshold of 0.5 IU/mL, 5 of 78 patients (6.4%) required dose adjustment; 1 hemodialysis dependent patient, 2 patients with CrCl < 30 mL/min, 1 patient each with CrCl 30–60 and > 60 mL/min, respectively. None of these patients developed bleeding or recurrent VTE. Among all 78 patients, 1 hemodialysis-dependent patient developed a hematoma following a traumatic line insertion, and no patients developed recurrent VTE. In conclusion, in a cohort of 78 patients with differing degrees of renal function including patients requiring hemodialysis, use of therapeutic-dose tinzaparin for the initial treatment of VTE resulted in accumulation (defined by trough anti-Xa > 0.5 IU/mL) in 6% of patients. There appears to be a weak inverse relationship between renal function and trough anti-Xa levels, but does not result in clinically significant accumulation when tinzaparin is used for up to 7 days. Further evaluation of tinzaparin in patients with severe renal insufficiency is required. Figure Figure

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Reversibility of renal tubular dysfunction in streptozotocin-induced diabetes in the rat

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y92-134 ◽

1992 ◽

Vol 70 (7) ◽

pp. 977-982 ◽

Cited By ~ 8

Author(s):

S. Chouinard ◽

C. Viau

Keyword(s):

Molecular Weight ◽

Urinary Excretion ◽

Insulin Treatment ◽

Diabetic Rats ◽

Control Group ◽

Low Molecular Weight ◽

Tubular Dysfunction ◽

Alanine Aminopeptidase ◽

Group A ◽

Streptozotocin Induced Diabetes

Enzymuria and specific proteinuria were examined over a period of 19 days in 4 groups of 5 rats: a control group, a non-diabetic polyuric group, a group of streptozotocin-induced diabetic rats treated with insulin as of the 10th day after the injection of the drug, and a similar group of untreated diabetic rats. Increased urinary excretion of β-N-acetyl-D-glucosaminidase, lactate dehydrogenase, and alanine aminopeptidase was observed shortly after the induction of diabetes. It was partly or totally reversible following insulin treatment. Nondiabetic polyuria had a slight effect on the excretion of alanine aminopeptidase only. The urinary excretion of β2-microglobulin also rapidly increased after the onset of diabetes to a level approximately 50 times the control values. This effect was largely reversible with insulin treatment and was absent in the nondiabetic polyuric group. A small but significant 3-fold increase in albumin excretion was also noted but was not affected by insulin treatment. We conclude that streptozotocin-induced diabetes causes an early tubular dysfunction that is unrelated to polyuria and is reversible upon insulin treatment. This tubular dysfunction is best revealed by the urinary excretion of the low molecular weight protein β2-microglobulin. Our results suggest that it would be of interest to further examine the usefulness of sensitive markers of tubular dysfunction, especially low molecular weight proteinuria, in the detection of early stages of diabetic nephropathy.Key words: diabetic nephropathy, enzyme, urine, proteinuria, β2-microglobulin, streptozotocin, insulin, rat.

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Donnai–Barrow syndrome in nephrology practice

Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) ◽

10.21508/1027-4065-2021-66-1-106-112 ◽

2021 ◽

Vol 66 (1) ◽

pp. 106-112

Author(s):

M. E. Aksenova ◽

N. M. Zaikova ◽

T. V. Lepaeva ◽

V. V. Dlin

Keyword(s):

Molecular Weight ◽

Patient Management ◽

Clinical Manifestations ◽

Low Molecular Weight ◽

Tubular Dysfunction ◽

Progressive Myopia ◽

Endosomal Transport ◽

System Disorder ◽

Variable Combination ◽

Degrees Of Severity

Donnai–Barrow syndrome is a multi-system disorder characterized by a variable combination of congenital anomalies, progressive myopia, sensorineural hearing loss, intellectual disability and renal disease. The article describes clinical cases of children with different phenotypes of the syndrome, including different renal disorders. One patient had isolated low-molecular-weight proteinuria, another patient suffered from proteinuria, hypercalciuria, nephrocalcinosis. Disruption of megaline-mediated endocytosis, retrograde endosomal transport of ligands, mitochondrial dysfunction, stress of the endoplasmic reticulum can lead to a different spectrum and various degrees of severity of tubular dysfunction in Donnai-Barrow syndrome. A variety of clinical manifestations of the disease can lead to a low diagnosis of Donnai-Barrow syndrome and inadequate patient management.

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Assay of N-Acetyl-β-D-Glucosaminidase in Urine from Neonates: Comparison of Two New Colorimetric Methods Using MNP-GlcNAc and VRA-GlcNAc as Substrates

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/000456329202900307 ◽

1992 ◽

Vol 29 (3) ◽

pp. 292-295 ◽

Cited By ~ 4

Author(s):

István Pócsi ◽

László Csáthy ◽

V Anna Oláh ◽

Robert G Price

Keyword(s):

Molecular Weight ◽

Gel Filtration ◽

Low Molecular Weight ◽

Creatinine Concentration ◽

Significant Change ◽

Normal Neonates ◽

Colorimetric Methods

The NAG activity present in urine from newborn babies was assayed using two colorimetric procedures with either MNP-GlcNAc or VRA-GlcNAc as substrate and compared with data obtained with the well established PNP-GlcNAc procedure. Both new assays were easy to perform and reproducible. The MNP-GlcNAc method has the advantage that it is now available as a kit; however, the VRA-GlcNAc procedure is more sensitive. NAG activity, creatinine concentration and NAG-index values were determined in normal neonates and within-run imprecision calculated. Excellent correlations were found between MNP-GlcNAc-ase and VRA-GlcNAc-ase indices ( r = 0·984) and between PNP-GlcNAc-ase and VRA-GlcNAc-ase indices ( r = 0.952). When low molecular weight urinary components were removed by gel filtration no significant change in VRA-GlcNAc-ase activity was observed.

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Tubular Dysfunction Mimicking Dent’s Disease in 2 Infants Born with Extremely Low Birth Weight

Case Reports in Nephrology and Dialysis ◽

10.1159/000455828 ◽

2017 ◽

Vol 7 (1) ◽

pp. 13-17 ◽

Cited By ~ 3

Author(s):

Midori Awazu ◽

Mie Arai ◽

Shoko Ohashi ◽

Hirotaka Takahashi ◽

Takashi Sekine ◽

...

Keyword(s):

Molecular Weight ◽

Birth Weight ◽

Low Birth Weight ◽

Extremely Low Birth Weight ◽

Low Molecular Weight ◽

Tubular Dysfunction ◽

Low Molecular Weight Proteinuria ◽

Proximal Tubular Dysfunction ◽

Dent's Disease ◽

Proximal Tubular

Two preterm infants, with extremely low birth weight born at gestational weeks 24 and 25, showed generalized proximal tubular dysfunction during their stay in the neonatal intensive care unit, including glucosuria, low molecular weight proteinuria, phosphaturia, uricosuria, enzymuria (elevated urine N-acetyl-β-D-glucosaminidase), panaminoaciduria, and hypercalciuria, associated with renal calcification. Renal tubular acidosis was not present in either patient. DNA mutation analysis for Dent’s disease, performed in patient 1, was negative. Although both patients had rickets of prematurity, tubular dysfunction persisted after its resolution. Patient 2, who had severe chronic lung disease, also had elevated serum creatinine, proteinuria, and hypertension, suggesting glomerular damage. In patient 1, low molecular weight proteinuria, enzymuria, panaminoaciduria, hypercalciuria, and renal calcification were still present at the age of 8 years. In patient 2, tubular dysfunction resolved except for β2 microglobulinuria at the age of 5 years. While a reduced nephron number resulting in focal segmental glomerulosclerosis is well-known, generalized proximal tubular dysfunction can also occur in infants born preterm and/or with extremely low birth weight.

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