Untimed Urine Specimens Research Articles

Hyperfiltration during early childhood precedes albuminuria in pediatric sickle cell nephropathy.

In patients with diabetes mellitus, hyperfiltration precedes the development of albuminuria. Pediatric sickle cell anemia (SCA) patients have a high prevalence of hyperfiltration and albuminuria during early childhood and adolescence. We tested the hypothesis that hyperfiltration precedes the development of albuminuria in a longitudinal pediatric SCA cohort. We identified 91 participants with HbSS or SB0 thalassemia 5-21 years of age enrolled in a longitudinal sickle cell nephropathy cohort study who had a cystatin C measured during early childhood (4-10 years of age). Early hyperfiltration was defined as a mean eGFR >180 mL/min/1.73m2 using cystatin C obtained from 4 to 10 years of age. Persistent albuminuria was defined as an albumin to creatinine ratio > 30 mg/g on two of three untimed urine specimens. Time to event analysis estimated survival curves for participants with and without hyperfiltration using Kaplan-Meier curves and used logrank test for categorical variables to assess the association with time to development of the first episode persistent albuminuria. Persistent albuminuria occurred more often and at an earlier age in participants with early hyperfiltration compared to those without early hyperfiltration (log-rank, P = .004). Participants who developed albuminuria have a significant increase in their eGFR during childhood (P = .003) as compared to participants who have not yet progressed to albuminuria (P = .26). For every 1 g/dL increase in hemoglobin, the hazard ratio for developing persistent proteinuria decreased by 0.56 (95% CI: 0.3, 1.06, P = .07). Hyperfiltration precedes the development of persistent proteinuria in pediatric SCA patients. Intervention strategies should target lowering eGFR during early childhood.

Physician and Patient Attitudes Toward Screening for Kidney Complications in Type 2 Diabetes: Is There A Role for Patient Self-Advocacy?

Urine protein screening rates among patients with type 2 diabetes are suboptimal despite evidence supporting its efficacy in preventing or slowing the progression of diabetic kidney disease (DKD) [1]. Testing of untimed urine specimens to quantify albumin (urine albumin-creatinine, or uACR)-the recommended screening test based on combination of simplicity, cost, and cardiovascular and renal prognostic value-is particularly underutilized, despite longitudinal efforts to improve awareness and screening among physicians [2].

Urine protein-to-creatinine ratio in an untimed urine collection is a reliable measure of proteinuria in lupus nephritis

To evaluate the accuracy of urine protein-to-creatinine (P/C) ratio in an untimed urine specimen as compared with 24 h total protein excretion for measurement of proteinuria in patients with lupus nephritis. Proteinuria in patients with lupus nephritis was assessed by 24 h total protein excretion and spot urine P/C ratio. Correlation and limits of agreement between the two methods were evaluated. The discriminant cutoff values for spot urine P/C ratio in predicting 24 h protein 'threshold' excretion of > or =0.3, > or =0.5, > or =1.0 and > or =3.5 g/day were determined using receiver operating characteristic curves. A total of 165 samples were available for assessment with 21.8% excluded due to inadequate collection. A strong correlation (r = 0.91, P < 0.0001) was found between spot urine P/C ratio and 24 h urine protein excretion. Bland-Altman plot showed the two tests had acceptable limits of agreement in low level of protein excretion (-0.86 to +0.92 g/day when protein excretion was <2.0 g/day). The limits became wider as the protein excretion increased. The spot urine P/C ratios of 0.45 (sensitivity 0.92; specificity 0.88), 0.7 (0.92; 0.89) and 1.84 (1.0; 0.86) mg/mg reliably predicted 24 h urine total protein equivalent 'thresholds' at > or =0.5, 1.0 and 3.5 g/day. This study supports the recommendation of using spot urine P/C ratio in screening and monitoring proteinuria in patients with lupus nephritis. However, in assessing the exact amount of proteinuria, the urine P/C ratio may have unacceptably wide limits of agreement in high protein excretion range.

Utility of untimed urinary albumin measurements in assessing albuminuria in black NIDDM subjects.

To determine the usefulness of an untimed morning urine specimen in screening a black NIDDM population attending an urban diabetes clinic for microalbuminuria. Untimed morning specimens were provided by 218 black NIDDM subjects. Of the 218 subjects, 123 also provided 24-h urine specimens. The 24-h specimens were assayed for albumin excretion rate (AER) in milligrams per 24 h, and the albumin-to-creatinine ratio (A-to-C) in micrograms per milligram was determined on the untimed morning urine specimen. Correlation between the A-to-C ratio and the 24-h AER was 0.96 (P = 0.0001). In the range of clinical proteinuria, r was 0.92 (P = 0.003, n = 7). In the range of microalbuminuria, r was 0.55 (P = 0.005, n = 26), and in the normal range, r was 0.59 (P < or = 0.0001, n = 90). Analysis of the untimed urine specimens from 218 black NIDDM subjects showed that 171 had A-to-C < 30 micrograms/mg, 38 had A-to-C 30-300 micrograms/mg, and 9 had A-to-C > 300 micrograms/mg. Data were grouped according to duration of NIDDM and the presence or absence of hypertension. None of the newly diagnosed NIDDM patients (< 1 year) (n = 40) had microalbuminuria. The frequency of microalbuminuria and clinical proteinuria increased with 1) duration of NIDDM 5-10 years (odds ratio [OR], 3.39; 95% CI 1.17-9.82),2) duration of NIDDM > 10 years (OR, 11.03; 95% CI 4.16-29.25), and 3) presence of hypertension (OR, 2.59; 95% CI I.20-5.61). The A-to-C ratio obtained from an untimed morning urine specimen correlates with the AER from a 24-h collection. In black subjects with newly diagnosed NIDDM, microalbuminuria is not present to a significant degree. Duration of NIDDM > 5 years is associated with increased prevalence of microalbuminuria, and hypertension is associated with microalbuminuria and clinical proteinuria in this population.

Prediction of siabetic nephropathy from untimed urine specimens

Source Citation Nelson RG, Knowler WC, Pettitt DJ, et al. Assessment of risk of overt nephropathy in diabetic patients from albumin excretion in untimed urine specimens. Arch Intern Med. 1991 Sep;1...

Assessment of Risk of Overt Nephropathy in Diabetic Patients From Albumin Excretion in Untimed Urine Specimens

The ability of an albumin-to-creatinine ratio, measured in a single untimed urine specimen, to indicate the likelihood of developing overt diabetic nephropathy was determined in 439 Pima Indians (134 men, 305 women) aged 25 years or older with non-insulin-dependent diabetes. During a mean follow-up period of 4.2 years, 59 (13%) of the subjects developed overt nephropathy, 47 (80%) of whom had albumin-to-creatinine ratios of 30 mg/g or greater at baseline. Subjects with albumin-to-creatinine ratios of 30 to 299 mg/g (a level of excretion often termed "microalbuminuria") had 9.2 times (95% confidence interval, 4.4 to 21.4) the incidence of overt nephropathy of those with ratios of less than 30 mg/g. Furthermore, the albumin-to-creatinine ratio remained a strong predictor of overt nephropathy even when controlled for age, sex, diabetes duration, mean blood pressure, and 2-hour postload plasma glucose concentration with a proportional-hazards function analysis. Thus, an albumin-to-creatinine ratio measured in a single untimed urine specimen is an effective means of identifying diabetic subjects who are at risk of developing overt nephropathy that could replace the more traditional timed urine collections.

Assessment of risk of overt nephropathy in diabetic patients from albumin excretion in untimed urine specimens

Assessment of risk of overt nephropathy in diabetic patients from albumin excretion in untimed urine specimens

Improved kinetic rate assay of urinary N-acetyl-beta-D-glucosaminidase with 2-chloro-4-nitrophenyl-N-acetyl-beta-D-glucosaminide as substrate

We have improved the kinetic rate assay method for determining N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30; NAG) activity in urine with use of the synthetic substrate, 2-chloro-4-nitrophenyl-N-acetyl-beta-D-glucosaminide (CNP-NAG), reported previously (Clin Chem 1988;34:2140-2). To increase the solubility of this substrate, we used crown ether (15-crown-5-ether) and ethylene glycol. In addition, we used for the standard solution NAG from human placenta, with specificity corresponding to that of human urine, so that values obtained with the CNP-NAG method and a p-nitrophenyl-NAG method ("MEI Assay NAG") correlated almost completely (r = 0.995, n = 29). Reference values for urinary NAG activity determined by the CNP-NAG method were established for untimed urine specimens from 674 healthy volunteers. The normal reference interval (mean +/- 2 SD) for NAG: 1.6-15.0 (mean 4.9) U per gram of creatinine.

Biological variation of urinary N-acetyl-beta-D-glucosaminidase: practical and clinical implications.

The analytical, within-subject, and between-subject components of variation of N-acetyl-beta-D-glucosaminidase (NAG) were estimated from duplicate assays of 10 timed first morning and 10 untimed urine specimens collected from each of 15 ostensibly healthy individuals. Results were expressed in terms of activity, NAG/creatinine ratio, and excretion rate. Current analytical methods can achieve desirable performance standards. NAG has little individuality, and conventional population-based reference intervals are therefore useful. In view of the practicability and relatively low within-subject variation, for routine clinical purposes we prefer assay of NAG in first morning urine, expressing the results in terms of activity. Using the results of assays of different specimens, we found that the correlation between urinary albumin and NAG varied considerably, owing to the large intrinsic variability of both analytes; this might explain previous conflicting results.

Urinary lipoperoxides quantified by liquid chromatography, and determination of reference values for adults.

Urinary lipoperoxides, measured as the malondialdehyde-thiobarbituric acid adduct, were quantified by adapting to urine the liquid-chromatographic method of Wong et al. (Clin Chem 1987;33:214-20) to plasma. Reference intervals for untimed urine specimens from 121 men, ages 16 to 67 years, and 107 women, ages 15 to 55, were determined. Their concentrations differed significantly (P = 0.015), males having a mean (and SD) of 0.89 (0.35) nmol of malondialdehyde per milligram of creatinine, females 0.78 (0.30). In both groups, the values were slightly skewed to the higher values. Our early studies suggest that measuring urinary lipoperoxide may have advantages over plasma in studying certain disorders. The presence of other urinary chromophores or TBA-reactive substances stresses the need for chromatographic techniques when lipoperoxides are measured in biological samples.

Urinary albumin/creatinine ratio and untimed urine specimens.

Urinary albumin/creatinine ratio and untimed urine specimens.

The value of catecholamine metabolite determination on untimed urine collections in the diagnosis of neural crest tumours in children.

There is still controversy regarding the relative merits of catecholamine metabolite estimations on 24 h versus untimed urine collections. The former has the advantage of taking into account diurnal variation in the rate of metabolite excretion but has the disadvantages of delaying results and of being affected by errors in collection. In this study percentile values were established for a reference population of 181 children for urinary 4-hydroxy-3-methoxyphenylacetic acid (HVA)/creatinine and 163 children for 4-hydroxy-3-methoxymandelic acid (VMA)/creatinine, using untimed urine collections. Results of similar determinations performed as part of the diagnostic work up of 23 consecutive children subsequently proven to have neural crest tumours showed that all patients had the value of at least one metabolite concentration at or above the highest reference value. In neuroblastoma all patients' VMA/creatinine exceeded the highest reference value and in neural crest tumours overall, this ratio was greater than the highest reference value in 96% of patients. These results are as good as, or better than, previously published results and demonstrate the practical value of using catecholamine metabolite determinations expressed as 'creatinine equivalents' on untimed urine specimens in the diagnosis of neuroblastoma and related tumours in children.

Quantitation of urinary normetanephrine and metanephrine by reversed-phase extraction and mass-fragmentographic analysis.

Hydrolyzed urine with added ring-trideuterated normetanephrine and metanephrine is applied to wet C18-reversed-phase minicolumns. The "metanephrines" are eluted, dried, derivatized with pentafluoropropionic anhydride, and analyzed with the gas chromatograph-mass spectrometer. Ions for the nondeuterated and trideuterated compounds are monitored at ml z 458 and 461, respectively. For both normetanephrine and metanephrine, the standard curve is linear over the range 10-2000 micrograms/L and the procedure has adequate precision both within-run (CV less than 3%) and between-day (CV less than 7%). Alkaline pH in the extraction is important for optimal analytical recovery. We have examined the potential value of untimed urine specimens for screening purposes and compared 24-h urine concentrations of these analyses in normotensive and hypertensive persons.

Spectral analysis of urinary reactions: a preliminary study based on a novel concept.

The concept of spectral analysis of urinary reactions (a range of simple chemical tests combined with pattern analysis) is described. A preliminary study in which we used 10 nonspecific tested on untimed urine specimens from 20 controls and 20 diabetics, matched for age and sex, suggested that a combination of these tests could be used to separate diabetics from healthy subjects. This combination, however, did not prove satisfactory for a further group of 13 diabetics. Closer examination revealed that factors such as therapy and glycosuria affected the results of these tests. This approach, which should extend the usefulness of urinalysis, may prove viable when larger groups, and possibly a different set of tests, are used to establish a more robust combination of tests.

Variation in urinary creatinine concentration and Schistosoma haematobium egg count

Variation in urinary creatinine concentration was studied in a Gambian community. Whilst there was appreciable day to day variation there were also differences between subjects and between different times of year. Day to day changes in creatinine concentration correlated with changes in egg count, which were, in proportion, smaller. While there are difficulties in the use of creatinine as a reference index, it is suggested that knowledge of creatinine concentrations may eliminate some of the ambiguities arising in the interpretation of Schistosoma haematobium egg counts in random, untimed urine specimens. The relation between the two variables and the extent of seasonal changes in creatinine concentration suggest that changes in the mean egg count of a group of subjects due to changes in urine flow are usually small and seldom of the magnitude which some have assumed.