scholarly journals The Effect of Cadmium on GFR Is Clarified by Normalization of Excretion Rates to Creatinine Clearance

2021 ◽  
Vol 22 (4) ◽  
pp. 1762
Author(s):  
Soisungwan Satarug ◽  
David A. Vesey ◽  
Muneko Nishijo ◽  
Werawan Ruangyuttikarn ◽  
Glenda C. Gobe ◽  
...  
Keyword(s):  
Creatinine Clearance ◽  
Tubular Injury ◽  
Creatinine Concentration ◽  
Thai Subjects ◽  
Urine Creatinine ◽  
Wide Range ◽  
Nephron Loss ◽  
Urine Cadmium ◽  
Excretion Rates ◽  
Cd Exposure

Erroneous conclusions may result from normalization of urine cadmium and N-acetyl-β-D-glucosaminidase concentrations ([Cd]u and [NAG]u) to the urine creatinine concentration ([cr]u). In theory, the sources of these errors are nullified by normalization of excretion rates (ECd and ENAG) to creatinine clearance (Ccr). We hypothesized that this alternate approach would clarify the contribution of Cd-induced tubular injury to nephron loss. We studied 931 Thai subjects with a wide range of environmental Cd exposure. For x = Cd or NAG, Ex/Ecr and Ex/Ccr were calculated as [x]u/[cr]u and [x]u[cr]p/[cr]u, respectively. Glomerular filtration rate (GFR) was estimated according to the Chronic Kidney Disease (CKD) Epidemiology Collaboration (eGFR), and CKD was defined as eGFR < 60 mL/min/1.73m2. In multivariable logistic regression analyses, prevalence odds ratios (PORs) for CKD were higher for log(ECd/Ccr) and log(ENAG/Ccr) than for log(ECd/Ecr) and log(ENAG/Ecr). Doubling of ECd/Ccr and ENAG/Ccr increased POR by 132% and 168%; doubling of ECd/Ecr and ENAG/Ecr increased POR by 64% and 54%. As log(ECd/Ccr) rose, associations of eGFR with log(ECd/Ccr) and log(ENAG/Ccr) became stronger, while associations of eGFR with log(ECd/Ecr) and log(ENAG/Ecr) became insignificant. In univariate regressions of eGFR on each of these logarithmic variables, R2 was consistently higher with normalization to Ccr. Our tabular and graphic analyses uniformly indicate that normalization to Ccr clarified relationships of ECd and ENAG to eGFR.

scholarly journals The Source and Pathophysiologic Significance of Excreted Cadmium

Toxics ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 55 ◽  
Author(s):  
Soisungwan Satarug ◽  
David A. Vesey ◽  
Werawan Ruangyuttikarn ◽  
Muneko Nishijo ◽  
Glenda C. Gobe ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Filtration Rate ◽  
Cellular Damage ◽  
Tubular Injury ◽  
Estimated Gfr ◽  
Tubular Cells ◽  
Thai Subjects ◽  
Urine Concentrations ◽  
Excretion Rates ◽  
Cd Exposure

In theory, the identification of the source of excreted cadmium (Cd) might elucidate the pathogenesis of Cd-induced chronic kidney disease (CKD). With that possibility in mind, we studied Thai subjects with low, moderate, and high Cd exposure. We measured urine concentrations of Cd, ([Cd]u); N-acetyl-β-d-glucosaminidase, a marker of cellular damage ([NAG]u); and β2-microglobulin, an indicator of reabsorptive dysfunction ([β2MG]u). To relate excretion rates of these substances to existing nephron mass, we normalized the rates to creatinine clearance, an approximation of the glomerular filtration rate (GFR) (ECd/Ccr, ENAG/Ccr, and Eβ2MG/Ccr). To link the loss of intact nephrons to Cd-induced tubular injury, we examined linear and quadratic regressions of estimated GFR (eGFR) on ECd/Ccr, eGFR on ENAG/Ccr, and ENAG/Ccr on ECd/Ccr. Estimated GFR varied inversely with both ratios, and ENAG/Ccr varied directly with ECd/Ccr. Linear and quadratic regressions of Eβ2MG/Ccr on ECd/Ccr and ENAG/Ccr were significant in moderate and high Cd-exposure groups. The association of ENAG/Ccr with ECd/Ccr implies that both ratios depicted cellular damage per surviving nephron. Consequently, we infer that excreted Cd emanated from injured tubular cells, and we attribute the reduction of eGFR to the injury. We suggest that ECd/Ccr, ENAG/Ccr, and eGFR were associated with one another because each parameter was determined by the tubular burden of Cd.

Melatonin protects against cadmium-induced oxidative damage in different tissues of rat: a mechanistic insight

2019 ◽  
Vol 2 (2) ◽  
pp. 1-21 ◽  
Author(s):  
Elina Mitra ◽  
Bharati Bhattacharjee ◽  
Palash Kumar Pal ◽  
Arnab Kumar Ghosh ◽  
Sanatan Mishra ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Oxidative Damage ◽  
Protein Carbonyl ◽  
Environmental Pollutant ◽  
Glutathione S Transferase ◽  
Protein Carbonyl Content ◽  
Wide Range ◽  
Liver And Kidney ◽  
Nadh Cytochrome ◽  
Cd Exposure

Cadmium (Cd) is a notorious environmental pollutant known for its wide range of toxicities to organisms. Thus, the present study is designed to examine whether melatonin, a potent antioxidant, protects against Cd-induced oxidative damage in the heart, liver and kidney of rats. Cd treatment at a dose of 0.44 mg/kg for 15 days caused severe damage in all these organs. These included significantly increased activities of SGPT, SGOT, lactate dehydrogenase- 1 and 5 and ALP and levels of total lactate, creatinine, lipid peroxidation, protein carbonyl content and reduced glutathione while the activities of superoxide dismutases, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase along with mitochondrial pyruvate dehydrogenase, isocitrate dehydrogenase, α-keto glutarate dehydrogenase, succinate dehydrogenase, NADH-cytochrome-c-oxidoreductase and cytochrome-c-oxidase were significantly reduced by Cd. However, if melatonin was given orally 30 min before Cd injection, all these alterations induced by Cd were significantly preserved by melatonin. Histological observations also demonstrated that Cd exposure caused cellular lesions, promoting necrotic or apoptotic changes. Notably, all these changes were significantly protected by melatonin. The results suggest that melatonin is a beneficial molecule to ameliorate Cd-induced oxidative damage in the heart, liver and kidney tissues of rats with its powerful antioxidant capacity, heavy metal chelating activity and competition of binding sites with Cd to the GSH and catalase.

scholarly journals Non-Albumin Proteinuria (NAP) as a Complementary Marker for Diabetic Kidney Disease (DKD)

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 224
Author(s):  
Jaehyun Bae ◽  
Young Jun Won ◽  
Byung-Wan Lee
Keyword(s):  
Kidney Disease ◽  
Filtration Rate ◽  
Diabetic Kidney Disease ◽  
Estimated Glomerular Filtration Rate ◽  
Early Stage ◽  
Screening Tools ◽  
Tubular Injury ◽  
Current Standard ◽  
Diabetic Kidney ◽  
Wide Range

Diabetic kidney disease (DKD) is one of the most common forms of chronic kidney disease. Its pathogenic mechanism is complex, and it can affect entire structures of the kidney. However, conventional approaches to early stage DKD have focused on changes to the glomerulus. Current standard screening tools for DKD, albuminuria, and estimated glomerular filtration rate are insufficient to reflect early tubular injury. Therefore, many tubular biomarkers have been suggested. Non-albumin proteinuria (NAP) contains a wide range of tubular biomarkers and is convenient to measure. We reviewed the clinical meanings of NAP and its significance as a marker for early stage DKD.

scholarly journals Proteinuria in COVID-19: prevalence, characterization and prognostic role

2021 ◽  
Author(s):  
Justine Huart ◽  
Antoine Bouquegneau ◽  
Laurence Lutteri ◽  
Pauline Erpicum ◽  
Stéphanie Grosch ◽  
...  
Keyword(s):  
Urinary Catheter ◽  
Single Center ◽  
Tubular Injury ◽  
Tubular Proteinuria ◽  
Prognostic Role ◽  
Urine Creatinine ◽  
Single Center Study ◽  
Center Study

Abstract Background Proteinuria has been commonly reported in patients with COVID-19. However, only dipstick tests have been frequently used thus far. Here, the quantification and characterization of proteinuria were investigated and their association with mortality was assessed. Methods This retrospective, observational, single center study included 153 patients, hospitalized with COVID-19 between March 28th and April 30th, 2020, in whom total proteinuria and urinary α1-microglobulin (a marker of tubular injury) were measured. Association with mortality was evaluated, with a follow-up until May 7th, 2020. Results According to the Kidney Disease Improving Global Outcomes staging, 14% (n = 21) of the patients had category 1 proteinuria (< 150 mg/g of urine creatinine), 42% (n = 64) had category 2 (between 150 and 500 mg/g) and 44% (n = 68) had category 3 proteinuria (over 500 mg/g). Urine α1-microglobulin concentration was higher than 15 mg/g in 89% of patients. After a median follow-up of 27 [14;30] days, the mortality rate reached 18%. Total proteinuria and urinary α1-microglobulin were associated with mortality in unadjusted and adjusted models. This association was stronger in subgroups of patients with normal renal function and without a urinary catheter. Conclusions Proteinuria is frequent in patients with COVID-19. Its characterization suggests a tubular origin, with increased urinary α1-microglobulin. Tubular proteinuria was associated with mortality in COVID-19 in our restropective, observational study.

Renal Injury in Sick Newborn Infants: A Prospective Evaluation Using Urinary β2-Microglobulin Concentrations

PEDIATRICS ◽  
1988 ◽  
Vol 81 (3) ◽  
pp. 432-440
Author(s):  
Eric D. Tack ◽  
Jeffrey M. Perlman ◽  
Alan M. Robson ◽  
Cathy Hausel ◽  
Charles C. T. Chang
Keyword(s):  
Renal Injury ◽  
Confidence Limit ◽  
Newborn Infants ◽  
Tubular Injury ◽  
Creatinine Concentration ◽  
Term Infants ◽  
Urinary Creatinine ◽  
Β2 Microglobulin ◽  
Sick Newborn ◽  
Healthy Infants

Urinary concentrations of β2-microglobulin and creatinine were measured serially in 140 sick infants, of whom 109 were asphyxiated, and in 35 healthy preterm and term infants. First voided urines and samples from days 3 and 7 postpartum were studied. Urinary β2-microglobulin concentrations in healthy infants averaged 1.34 ± 1.34 mg/L (mean ± SD) in first voided specimens and 1.32 ± 0.98 mg/L in day 3 samples; the calculated upper limit of normal (95% confidence limit) was 4.00 mg/L. Elevated values (those exceeding the 95% confidence limit) occurred most often in the sick asphyxiated patients (56%); the first voided sample value in these patients was 10.0 ± 10.4 mg/L. The equivalent value in the sick nonasphyxiated infants was 8.32 ± 7.27 mg/L. Values were significantly and persistently elevated in the sick infants on days 3 and 7. Factoring β2-microglobulin levels by urinary creatinine concentration did not affect the significance of the findings. The increased urinary β2-microglobulin levels were not (1) related to gestational age; low β2-microglobulin values occurred at all gestational ages for both healthy and sick infants; (2) a consequence of urine flow rate; urinary β2-microglobulin did not correlate with urinary creatinine concentration or with urine to plasma creatinine ratio; and (3) a consequence of increased production of β2-microglobulin; urinary and serum β2-microglobulin values did not correlate (r = .03). Thus, we propose that the elevated levels of urinary β2-microglobulin in the sick infants were the consequence of tubular injury. This was associated with hematuria but not with a high incidence of azotemia or oliguria. In the most premature infants (&lt;32 weeks), elevated urinary β2-microglobulin concentrations were associated with significantly increased urinary concentrations of sodium and potassium. These data suggest a higher prevalence of acute tubular injury in sick newborn infants than has been reported in previous studies in which more traditional indices of renal injury were used.

scholarly journals The relation between oestrus signs and probability of ovulation at dubious oestrus in gilts.

1989 ◽  
Vol 37 (2) ◽  
pp. 165-168
Author(s):  
H. Boer ◽  
L.A. den Hartog ◽  
K. Boode ◽  
H.A.M. van der Steen ◽  
W.C. Melger ◽  
...  
Keyword(s):  
Urine Samples ◽  
Creatinine Concentration ◽  
Urine Creatinine

680 gilts were studied from 168 days of age. Urine samples were collected 10-12 days after a "dubious" 1st oestrus. Of 188 gilts showing a dubious 1st oestrus, 14 produced urine samples with a creatinine concentration of 0.25 mg/ml, 99 and 75 samples had a high and a low pregnanediol concentration resp. It was concluded that 99 (57%) of gilts had an ovulatory 1st oestrus as indicated by high urine creatinine and pregnanediol concentrations. (Abstract retrieved from CAB Abstracts by CABI’s permission)

Establishment of creatinine clearance reference values for older women

1994 ◽  
Vol 40 (12) ◽  
pp. 2276-2281 ◽  
Author(s):  
L J Sokoll ◽  
R M Russell ◽  
J A Sadowski ◽  
F D Morrow
Keyword(s):  
Serum Creatinine ◽  
Creatinine Clearance ◽  
Older Women ◽  
Research Unit ◽  
Reference Ranges ◽  
Prediction Formula ◽  
Urine Creatinine ◽  
Gault Formula ◽  
Modification Factor ◽  
Metabolic Research Unit

Abstract Age-adjusted reference ranges for creatinine clearance were determined in 279 women, ages 40-95 years, who were housed in a metabolic research unit and consumed a meat-free diet. Creatinine clearance, but not serum creatinine, declined with age by 0.63 mL/min per 1.73 m2 per year. Serum and urine creatinine concentrations, used to calculate clearances, were analyzed by a kinetic Jaffé procedure. In a subset of 100 subjects, fasting serum creatinine values averaged 8.3 +/- 5.2 (SD) mumol/L higher when measured by the kinetic Jaffé procedure than by an enzymatic method (creatinine PAP). The Cockcroft-Gault formula for estimating creatinine clearance from serum creatinine in women was validated, and the modification factor for the male equation was determined to be 0.84 (95% confidence interval 0.83-0.86) confirming the suggested 15% correction. A prediction formula derived from this population was similar in accuracy to the Cockcroft-Gault formula.

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