Serum homocysteine concentration as a marker for advanced diabetic nephropathy in a cohort of elderly patients.

BACKGROUND: Hyperhomocysteinemia has been linked with chronic kidney disease (CKD). The present study investigated whether homocysteine (Hcy) serum levels might serve as a marker for the advancement of diabetic nephropathy (DN). METHODS: Clinical and laboratory indicators including Hcy, vitamin D (VD), urine protein, estimated glomerular filtration rate (eGFR) and the urinary protein/creatinine ratio in subjects > 65 years with DN (n = 1,845), prediabetes (n = 1,180) and in a non-diabetes (control) group (n = 28,720) were analyzed. RESULTS: DN patients had elevated Hcy concentrations, decreased VD and higher urinary protein levels, a reduced eGFR and a higher urinary protein/creatinine ratio compared with prediabetic and control subjects. After correcting for urinary protein quantitation, multivariate analysis revealed that both the Hcy concentration (P < 0.010) and urinary protein/creatinine ratio (P < 0.001) were risk factors, while the VD2 + VD3 serum concentration (P < 0.001) was a protective factor for DN. Moreover, Hcy > 12 µmol/L was a cut-off value for predicting advanced DN. CONCLUSION: Hcy serum concentration is a potential marker for the advancement of CKD in DN but not prediabetes patients.

Evaluation of proteinuria monitoring practice patterns and treatment implications in patients with cancer receiving bevacizumab products.

INTRODUCTION: Proteinuria is a well-known toxicity of bevacizumab which can lead to kidney injury or nephrotic syndrome. There is little guidance on the frequency of monitoring and management of those that experience bevacizumab-induced proteinuria. Previous literature has suggested routine monitoring with every dose has limited clinical significance. Currently, there is no standardization of proteinuria monitoring at OhioHealth. METHODS: This retrospective descriptive study included 100 adult patients who received at least 3 doses of a bevacizumab product for a malignant condition at any OhioHealth facility from April 15, 2022 to October 15, 2022. The primary outcome was to describe the average number of proteinuria tests ordered over the course of therapy. RESULTS: Of the 100 patients evaluated, 91 received proteinuria monitoring during treatment with bevacizumab. The overall average number of tests completed per patient per month based on treatment period of bevacizumab was 1.51. Twenty-two of 91 patients (24%) developed grade 2+ proteinuria. Average time to first grade 2+ proteinuria event was 5.7 months. A history of baseline renal dysfunction or chronic kidney disease was the only predefined factor found to be significantly associated with developing grade 2+ proteinuria. The most common treatment modification following a grade 2+ proteinuria result was a delay in therapy. CONCLUSION: Proteinuria monitoring may not be necessary for short definitive courses of bevacizumab and closer monitoring should be considered in patients with baseline renal dysfunction or CKD. Future direction includes evaluating the cost of varying proteinuria tests and developing a recommendation for OhioHealth to standardize testing.

Time-Updated Changes in Estimated GFR and Proteinuria and Major Adverse Cardiac Events: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Evaluating repeated measures of estimated glomerular filtration rate (eGFR) and urinary protein-creatinine ratio (UPCR) over time may enhance our ability to understand the association between changes in kidney parameters and cardiovascular disease risk. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Annual visit data from 2,438 participants in the Chronic Renal Insufficiency Cohort (CRIC). EXPOSURES: Average and slope of eGFR and UPCR in time-updated, 1-year exposure windows. OUTCOMES: Incident heart failure, atherosclerotic cardiovascular disease events, death, and a composite of incident heart failure, atherosclerotic cardiovascular disease events, and death. ANALYTICAL APPROACH: A landmark analysis, a dynamic approach to survival modeling that leverages longitudinal, iterative profiles of laboratory and clinical information to assess the time-updated 3-year risk of adverse cardiovascular outcomes. RESULTS: Adjusting for baseline and time-updated covariates, every standard deviation lower mean eGFR (19mL/min/1.73m2) and declining slope of eGFR (8mL/min/1.73m2 per year) were independently associated with higher risks of heart failure (hazard ratios [HRs] of 1.82 [95% CI, 1.39-2.44] and 1.28 [95% CI, 1.12-1.45], respectively) and the composite outcome (HRs of 1.32 [95% CI, 1.11-1.54] and 1.11 [95% CI, 1.03-1.20], respectively). Every standard deviation higher mean UPCR (136mg/g) and increasing UPCR (240mg/g per year) were also independently associated with higher risks of heart failure (HRs of 1.58 [95% CI, 1.28-1.97] and 1.20 [95% CI, 1.10-1.29], respectively) and the composite outcome (HRs of 1.33 [95% CI, 1.17-1.50] and 1.12 [95% CI, 1.06-1.18], respectively). LIMITATIONS: Limited generalizability of annual eGFR and UPCR assessments; several biomarkers for cardiovascular disease risk were not available annually. CONCLUSIONS: Using the landmark approach to account for time-updated patterns of kidney function, average and slope of eGFR and proteinuria were independently associated with 3-year cardiovascular risk. Short-term changes in kidney function provide information about cardiovascular risk incremental to level of kidney function, representing possible opportunities for more effective management of patients with chronic kidney disease.

Decision making for anti-VEGF inhibitor continuation: dip stick? or urine protein/creatinine ratio? (VERSiON UP study).

BACKGROUND: Monitoring proteinuria is important for the management of patients with cancer treated with anti-vascular endothelial growth factor (VEGF) or anti-VEGF receptor (VEGFR) inhibitors (VEGF/Ri). Here we investigated the difference between the urine protein/creatinine ratio (UPCR) and a qualitative value test (QV) on the decision making of treatment continuation and the usefulness of UPCR testing in patients with gastrointestinal cancer treated with anti-VEGF/Ri. METHODS: From January 2017 to December 2018, a survey was conducted based on the medical records of patients with gastrointestinal cancer with a QV of ≥2+ during the use of anti-VEGF/Ri at seven Japanese institutions participating in the Onco-nephrology Consortium. The primary endpoint was the ratio of the worst UPCR < 2.0 (low UPCR) in cases with a QV2+ at the point of the first proteinuria onset. The secondary endpoints were a comparison of low UPCR and worst UPCR ≥2.0 (high UPCR), the concordance rate between UPCR and QV in the Common Terminology Criteria for Adverse Events (CTCAE) grading, and the differences in the decision making for anti-VEGF/Ri continuation. RESULTS: Among the 71 patients enrolled, the proportion of low UPCR in onset QV2+ (n = 53) was 66% (n = 35). In a comparison between low (n = 36) and high UPCR cases (n = 24), body weight (P = 0.036), onset QV status (P = 0.0134), and worst QV status (P < 0.0001) were significantly associated with UPCR levels. The concordance rate for CTCAE Grade 2 of both the QV and UPCR was 83%. Regarding the judgment of anti-VEGF/Ri continuation, treatment was continued in 42.4% of cases when the QV became 3+, whereas only 25% continued treatment when the UPCR value became high. CONCLUSION: Urine dipstick test results may overestimate proteinuria, and the UPCR result tended to be more critical than the QV when deciding the treatment policy. TRIAL REGISTRATION: This study is a multiple institutional retrospectively registered observational trial. CLINICAL TRIAL NUMBER: University Hospital Medical Information Network (UMIN) Clinical Trials Registry (protocol ID UMIN000042545 ).

Renal effects of long-term lithium therapy, revisited.

OBJECTIVE: The aim of this study was to investigate the effect of lithium treatment on renal function and to determine influencing factors. In addition, the utility of spot urine protein/creatinine ratio in detection of lithium induced nephropathy was also investigated. METHODS: Serum concentrations of lithium, blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR), and urinalysis including protein/creatinine ratio were measured in 375 patients using lithium. RESULTS: Patients taking lithium for ≥8 years had higher BUN, creatinine levels, percentage of proteinuria, percentages of stage 2 and 3 chronic kidney disease (CKD); lower urine density and eGFR compared to patients taking lithium <8 years. Urine density was lower in groups with >0.8 and 0.6-0.8 mmol/L lithium level than <0.6 mmol/L. Predictors of CKD were serum level of lithium, dose of lithium, cumulative duration of lithium use, age at onset of illness, and caffeine consumption. CONCLUSIONS: Detrimental effects of lithium on renal functions were detected after lithium use for ≥8 years. Proteinuria measured by spot urine protein/creatinine ratio can be detected even when eGFR is >90 ml/min/1.73 m2 . Spot urine protein/creatinine ratio, which is a cost-effective and practical laboratory test, can be used to monitor lithium-treated patients.

Clinical value and cost analysis of the sFlt-1/PlGF ratio in addition to the spot urine protein/creatinine ratio in women with suspected pre-eclampsia: PREPARE cohort study.

BACKGROUND: This study investigated the clinical value of adding the sFlt-1/PlGF ratio to the spot urine protein/creatinine ratio (PCr) in women with suspected pre-eclampsia. METHODS: This was a prospective cohort study performed in a tertiary referral centre. Based on the combination of PCr (< 30) and sFlt-1/PlGF (≤38) results, four groups were described: a double negative result, group A-/-; a negative PCr and positive sFlt-1/PlGF, group B-/+; a positive PCr and negative sFlt-1/PlGF, group C+/-; and a double positive result, group D+/+. The primary outcome was the proportion of false negatives of the combined tests in comparison with PCr alone in the first week after baseline. Secondary, a cost analysis comparing the costs and savings of adding the sFlt-1/PlGF ratio was performed for different follow-up scenarios. RESULTS: A total of 199 women were included. Pre-eclampsia in the first week was observed in 2 women (2%) in group A-/-, 12 (26%) in group B-/+, 4 (27%) in group C+/-, and 12 (92%) in group D+/+. The proportion of false negatives of 8.2% [95% CI 4.9-13.3] with the PCr alone was significantly reduced to 1.6% [0.4-5.7] by adding a negative sFlt-1/PlGF ratio. Furthermore, the addition of the sFlt-1/PlGF ratio to the spot urine PCr, with telemonitoring of women at risk, could result in a reduction of 41% admissions and 36% outpatient visits, leading to a cost reduction of €46,- per patient. CONCLUSIONS: Implementation of the sFlt-1/PlGF ratio in addition to the spot urine PCr, may lead to improved selection of women at low risk and a reduction of hospital care for women with suspected pre-eclampsia. TRIAL REGISTRATION: Netherlands Trial Register (NL8308).

An equation to estimate 24-hour total urine protein excretion rate in patients who underwent urine protein testing.

BACKGROUND: The urine protein-creatinine ratio (UPCR) in a spot first-morning urine sample is used to estimate 24-h urine proteinuria (24hUP) in patients who underwent urine protein testing. UPCR cannot be directly compared with 24-h proteinuria. Thus, an equation to estimate 24-h total protein excretion rate, using age, gender, and the UPCR may improve its bias and accuracy in patients who underwent urine protein testing. METHODS: We simultaneously measured 24-h urine protein and the same day's first-morning spot urine from patients with kidney disease. Generalized linear and no-linear models, using age, gender, and UPCR, were constructed to estimate for 24-h urine protein and the best model (NJ equation) was selected to estimated 24 hUP (e24hUP). RESULTS: A total of 5435 paired samples (including a training cohort of 3803 patients and a validation cohort of 1632 patients) were simultaneously measured for UPCR and 24-h urine protein. In the training cohort, the unadjusted UPCR obviously underestimated 24-h urine protein when UPCR ≤1.2 g/g (median bias - 0.17 g/24 h) and overestimated 24-h urine protein when UPCR > 1.2 g/g (median bias 0.53 g/24 h). In the validation cohort, the NJ equation performed better than the unadjusted UPCR, with lower root mean square error (0.81 vs. 1.02, P < 0.001), less bias (median difference between measured and estimated urine protein, - 0.008 vs. 0.12), improved precision (interquartile range of the differences, 0.34 vs. 0.50), and greater accuracy (percentage of estimated urine protein within 30% of measured urine protein, 53.4% vs. 32.2%). Bland-Altman plot indicated that the agreement of spot and daily estimates was less pronounced with 24 hUP > 2 g than lower values. CONCLUSIONS: The NJ e24hUP equation is more accurate than unadjusted UPCR to estimate 24 hUP in patients with kidney disease and could be used for laboratory application.

Frequency of kidney dysfunction in patients with acute stroke and the relationship with the type, severity and outcome.

Background/Aim: Kidney dysfunction is an established risk factor for cardiovascular diseases including stroke. The study aimed at assessing the frequency of kidney dysfunction in patients with acute stroke and to evaluate the relationship to the type, severity and outcome of stroke. To establish a relationship, which has not been explained in past studies. Materials and Methods: This was a cross-sectional analytical study on acute stroke patients and matched controls, evaluating for kidney dysfunction using both estimated glomerular filtration rate (GFR) and the spot urine protein creatinine ratio. The type of stroke was observed by neuroimaging. The National Institute of Health Stroke Score was used to assess the severity of stroke at presentation and outcome after 7 days. Data analysis was done using Statistical Package for Social Sciences (SPSS) application version 23.0 (SPSS Inc., Chicago, IL, USA). Results: : Ninety-eight patients and 100 controls were recruited, with a mean age of 64.7 ± 15.5 and 64.8 ± 15.1 years, respectively. The patients with stroke had a statistically significant higher frequency of kidney dysfunction compared to the controls (85.9% vs. 62.0%, P ≤ 0.001). Patients with haemorrhagic stroke had a higher frequency of kidney dysfunction compared with those with ischaemic stroke (93.8% vs. 77.3%, P = 0.048). The proportion of patients with kidney dysfunction was seen to increase from those with mild to those with severe stroke symptoms, both at presentation and after 7 days. Estimated GFR was seen to be an independent predictor of poor outcome in patients with stroke (odds ratio 0.955, 95% confidence interval 0.924 - 0.986, P = 0.005). Conclusion: The study demonstrated that in patients with acute stroke there is a high frequency of kidney dysfunction. Haemorrhagic stroke, increasing stroke severity and poor outcome were seen to be associated with kidney dysfunction. Thus, recommending the need for kidney care as an important part of stroke management.

Elevated Creatinine Clearance in Lupus Nephritis patients with Normal Creatinine.

Objectives: The present study aimed to observe the differences in creatinine clearance (Ccr) in systemic lupus erythematosus (SLE) patients with normal serum creatinine at different levels of urinary protein. Method: The present cross-sectional study included 177 SLE patients with normal serum creatinine from Qilu Hospital of Shandong University between January 2010 and April 2020. The following data were collected: blood urea nitrogen (BUN), serum creatinine (Cr), serum total protein, serum albumin, immunoglobulin (Ig) G, IgA, IgM, complement 3, complement 4, anti-ds-DNA antibody, routine urine test, urine protein/creatinine ratio (UPCR) (g/g), and the SLE disease activity index. The estimated Ccr was calculated according to the Cockcroft formula. Results: 123 patients were with positive urinary protein (Lupus Nephritis, LN group) and 54 patients were with negative urinary protein (Non-LN group). Compared with the Non-LN group, the LN group had higher BUN (5.76±3.22 vs. 4.78±1.58, P=0.007) and Cr (62.36±19.53 vs. 54.83±11.09, P=0.001). There was a strong correlation between the UPCR and the semi-quantitative determination of urine protein in LN patients (r=0.9583, P=0.0417). The serum creatinine levels were significantly higher in patients with urine protein 3+ (72.97±25.16) or massive proteinuria (62.32±19.66) than the other groups. Patients with urinary protein ± exhibited a significantly elevated Ccr when compared to patients with urinary protein 3+ (130.6±44.15 vs. 110.5±33.50, P=0.02), and patients with UPCR<0.15 g/g had higher Ccr than other groups and showed significantly increased Ccr compared with patients with UPCR≥0.15 g/g (132.44±21.02 vs. 115.14±35.89, P=0.007). Conclusions: Early renal function impairment may be present in LN patients. The kidneys of LN patients with urinary protein ± or UPCR<0.15 g/g are in a state of hyperfunction.

Reference values of urine protein/creatinine ratio in healthy Dalian adults.

BACKGROUND: The urine protein/creatinine ratio (UPCR) is commonly used in current clinical practice. However, there are only few published clinical data on UPCR from large cohorts of Chinese adults. This study aimed to determine the overall and age- and sex-specific UPCR reference values for healthy Dalian adults. METHODS: According to the Clinical & Laboratory Standards Institute EP28-A3c guidelines, 1321 healthy Dalian adults (646 men and 675 women) aged 20-69 years were enrolled. Urine protein and creatinine levels were analyzed in the random morning spot urine samples, and UPCR was calculated. The 95th percentile of the UPCR was used as the normal upper limit. The Mann-Whitney U test was used to test differences among groups. RESULTS: The UPCR reference value was 141.7 mg/g for the entire cohort, 128.7 mg/g for men, and 150.8 mg/g for women. In addition, women had relatively higher UPCR values than men in the same age group. We also compared the UPCR reference values between different estimated glomerular filtration rate (eGFR) groups and found that women had significantly higher UPCR values than men in the normal eGFR groups. CONCLUSIONS: This study provides the overall and age- and sex-specific UPCR reference values for healthy Dalian adults.

Correlation of urine protein/creatinine ratios to 24-h urinary protein for quantitating proteinuria in children.

BACKGROUND: The purpose of this study was to evaluate the correlation and consistency between urine protein/creatinine ratio (UPCR) and 24-h urine protein (24HUPr) in children, and to determine cutoff values of UPCR relative to 24HUPr at 100 mg/m2/d (≥ 100 mg/m2/d as pathological proteinuria) and 1000 mg/m2/d (≥ 1000 mg/m2/d as nephrotic-range proteinuria). METHODS: Three hundred sixty-six children were enrolled, including 81 controls, 109 with Henoch-Schönlein purpura nephritis, 167 with nephrotic syndrome, 5 with IgA nephropathy, and 4 with lupus nephritis. Patients were divided into three groups: normal group; non-nephrotic-range proteinuria group; nephrotic-range proteinuria group. The cutoff values of UPCR in predicting the different levels of proteinuria were determined using ROC curve analysis. RESULTS: UPCR was positively correlated with 24HUPr (r = 0.915, p < 0.01). Bland-Altman diagrams showed that UPCR and 24HUPr had good consistency, and > 95% spots of UPCR and 24HUPr were within 95% confidence intervals. Relative to 24HUPr at 100 mg/m2/d, the cutoff value of UPCR (0.18 g/g Cr) had the highest sensitivity (94%) and specificity (98.8%) which is close to 0.2 g/g Cr as proposed by the American College of Rheumatology. Relative to 24HUPr at 1000 mg/m2/d, the cutoff value of UPCR (2.09 g/g Cr) had the highest sensitivity (92.1%) and specificity (92.1%) which is close to the 2.0 g/g Cr proposed in KDIGO guidelines. CONCLUSIONS: UPCR showed strong correlation and consistency with 24HUPr for evaluating levels of proteinuria in children. UPCR < 0.2 g/g Cr can be considered a criterion for normal-range proteinuria. Instead of 24HUPr ≥ 1000 mg/m2/d, UPCR ≥ 2.0 g/g Cr can be considered a criterion for nephrotic-range proteinuria or nephrotic syndrome in children.

Identification of children with chronic kidney disease through school urinary screening using urinary protein/creatinine ratio measurement: an observational study.

BACKGROUND: School urinary screening has been performed in Japan. METHODS: Ikeda City and Toyono Town introduced, in 2012 and 2013, urinary protein/creatinine (Cr) ratio measurement into the urine-screening protocols designed for students aged between 4 and 15 years. For each student whose urinary protein/Cr ratio was ≥ 0.15 g/gCr (positive case), an appointment was made with a specialist at Ikeda City Hospital. The results of these screening urinalyses conducted through 2018 are summarized. RESULTS: 14,606 junior high and elementary school students aged between 6 and 15 years were included. On average, they underwent 4.16 screening tests. 77 positive cases were detected, and seven students were diagnosed with high-risk chronic kidney disease (CKD). Of these, four underwent renal biopsy, and two, one, and one were diagnosed with IgA nephropathy, MPGN, and FSGS, respectively. In three students, detection of CKD would have been difficult without urinary screening. Incident rates of high-risk CKD and IgA nephropathy are estimated as 11.5 and 3.3 cases/100,000 students/year. 78.0% of positive cases without high-risk CKD showed no urinary abnormality after one year. 2301 kindergarten students aged between 4 and 6 years received an average of 1.74 screening urinalyses; none was positive or high-risk CKD. The estimated cost of detecting one high-risk CKD student whose detection would have been difficult without this screening was 3,156,711 Japanese yen. CONCLUSION: School urinary screening using the urinary protein/Cr ratio can efficiently refer to a specialist. It detects a few children with high-risk CKD early with spending high cost.

Proteinuria from an internists point of view.

A basal level of proteinuria is about 30-100 mg/day, the upper limit of basal proteinuria does not exceed 150 mg/day which is considered non-pathology. Albumin accounts approximately 15 % of basal protein in the urine, other plasma proteins (immunoglobulins, β-2 microglobulin, Tamm-Horsfall mucoprotein) comprise the remaining 85 % of total quantity non-pathology proteinuria. Persistent proteinuria present for more than three months already meets the definition of chronic kidney disease independently of the stage of the estimated glomerular filtration rate. Patients are classified as A1-A3 based on the level of albuminuria. Examination of the albumin in the urine is one of the single sensitive indicators of chronic kidney disease. Proteinuria is an independent risk factor for cardiovascular disease, overall mortality and end stage renal failure both in general population and in population with chronic kidney disease. Presence of the urinary protein is associated with a higher mortality rate in critically ill patients. The degree of proteinuria after kidney transplantation predicts graft and patient survival in this population. Pharmacological and non-pharmacological treatments that attenuate proteinuria have been associated with better prognosis of kidney disease.

Proteinuria from an internists point of view.

A basal level of proteinuria is about 30-100 mg/day, the upper limit of basal proteinuria does not exceed 150 mg/day which is considered non-pathology. Albumin accounts approximately 15 % of basal protein in the urine, other plasma proteins (immunoglobulins, β-2 microglobulin, Tamm-Horsfall mucoprotein) comprise the remaining 85 % of total quantity non-pathology proteinuria. Persistent proteinuria present for more than three months already meets the definition of chronic kidney disease independently of the stage of the estimated glomerular filtration rate. Patients are classified as A1-A3 based on the level of albuminuria. Examination of the albumin in the urine is one of the single sensitive indicators of chronic kidney disease. Proteinuria is an independent risk factor for cardiovascular disease, overall mortality and end stage renal failure both in general population and in population with chronic kidney disease. Presence of the urinary protein is associated with a higher mortality rate in critically ill patients. The degree of proteinuria after kidney transplantation predicts graft and patient survival in this population. Pharmacological and non-pharmacological treatments that attenuate proteinuria have been associated with better prognosis of kidney disease.

Treatment of Membranous Nephropathy in Patients With THSD7A Antibodies Using Immunoadsorption.

Antibodies against THSD7A (thrombospondin type 1 domain-containing protein 7A) have been proposed to play a causal role in the development of nephrotic syndrome in patients with THSD7A antibody-positive membranous nephropathy. We hypothesized that removal of these antibodies from plasma could lead to a rapid reduction in proteinuria. Using immunoadsorption to reduce THSD7A antibodies led to a rapid reduction in proteinuria in 2 patients with THSD7A antibody-positive membranous nephropathy. Moreover, our findings support and strengthen the pathogenic role of the antibodies in the development of nephrotic syndrome in patients with THSD7A antibody-positive membranous nephropathy. Taken together, these 2 cases suggest that immunoadsorption could be a useful tool in the treatment of patients with THSD7A antibody-positive membranous nephropathy.

Estimating Time to ESRD in Children With CKD.

RATIONALE & OBJECTIVE: The KDIGO (Kidney Disease: Improving Global Outcomes) guideline for chronic kidney disease (CKD) presented an international classification system that ranks patients' risk for CKD progression. Few data for children informed guideline development. STUDY DESIGN: Observational cohort study. SETTINGS & PARTICIPANTS: Children aged 1 to 18 years enrolled in the North American Chronic Kidney Disease in Children (CKiD) cohort study and the European Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) trial. PREDICTOR: Level of estimated glomerular filtration rate (eGFR) and proteinuria (urine protein-creatinine ratio [UPCR]) at study entry. OUTCOME: A composite event of renal replacement therapy, 50% reduction in eGFR, or eGFR<15mL/min/1.73m2. eGFR was estimated using the CKiD-derived "bedside" equation. ANALYTICAL APPROACH: Accelerated failure time models of the composite outcome using a conventional generalized gamma distribution. Likelihood ratio statistics of nested models were used to amalgamate levels of similar risk. RESULTS: Among 1,232 children, median age was 12 (IQR, 8-15) years, median eGFR was 47 (IQR, 33-62) mL/min/1.73m2, 60% were males, and 13% had UPCRs>2.0mg/mg at study entry. 6 ordered stages with varying combinations of eGFR categories (60-89, 45-59, 30-44, and 15-29mL/min/1.73m2) and UPCR categories (<0.5, 0.5-2.0, and >2.0mg/mg) described the risk continuum. Median times to event ranged from longer than 10 years for eGFRs of 45 to 90mL/min/1.73m2 and UPCRs<0.5mg/mg to 0.8 years for eGFRs of 15 to 30mL/min/1.73m2 and UPCRs>2mg/mg. Children with glomerular disease were estimated to have a 43% shorter time to event than children with nonglomerular disease. Cross-validation demonstrated risk patterns that were consistent across the 10 subsample validation models. LIMITATIONS: Observational study, used cross-validation rather than external validation. CONCLUSIONS: CKD staged by level of eGFR and proteinuria characterizes the timeline of progression and can guide management strategies in children.

Renal Function and exposure to Bisphenol A and phthalates in children with Chronic Kidney Disease.

RATIONALE AND OBJECTIVE: Exposure to Bisphenol A (BPA) and phthalates is ubiquitous among adults and children in the United States. Among children and adolescents, those with chronic kidney disease (CKD) are potentially at greater risk of adverse effects from BPA and phthalate exposure. The objective of this study was to evaluate BPA and phthalate exposure among children with CKD and evaluate associations with three measures of kidney function. STUDY DESIGN: Cross sectional study. SETTING, PARTICIPANTS, AND MEASUREMENTS: The CKD population was represented by the Chronic Kidney Disease in Children (CKiD) Study, a multicenter, prospective cohort study of children with impaired kidney function in the US. The main outcome was assessment of the relationship between chemical exposures and clinical laboratory findings at enrollment into CKiD. Data collected at baseline from participants 1 to 17 years old (N = 538) were analyzed. Urinary BPA and phthalate levels were evaluated at this time point. Data from the National Health and Nutrition Examination Survey (NHANES), a nationally representative pediatric population, were used for comparison to the CKiD cohort. RESULTS: Urinary BPA and phthalate levels in the CKiD population were consistently lower than levels detected in healthy children. Additionally, BPA was not significantly associated with blood pressure, proteinuria, or estimated glomerular filtration rate (eGFR). Within the CKiD population, for select individual and combined phthalates, there was an inverse relationship with the urinary protein:creatinine ratio (LMW phthalates, - 9.53% change; 95% CI: - 14.21, - 4.21; p = 0.001), and in most cases, a positive relationship with eGFR (LMW phthalates, a 3.46 unit increase in eGFR, 95% CI: 1.85, 5.07; p < 0.001). LIMITATIONS: Lack of longitudinal data, limited assessment of diet and nutritional status. CONCLUSION: In the study cohort, children with CKD did not have increased exposure to BPA and phthalates. Longitudinal studies with repeated measures are likely to be more informative about the possible health effects of prolonged exposure to BPA and phthalates in pediatric patients with CKD.

The effect of ethnicity on the performance of protein-creatinine ratio in the prediction of significant proteinuria in pregnancies at risk of or with established hypertension: an implementation audit and cost implications.

INTRODUCTION: The replacement of 24-h urine collection by protein-creatinine ratio (PCR) for the diagnosis of preeclampsia has been recently recommended. However, the literature is conflicting and there are concerns about the impact of demographic characteristics on the performance of PCR. MATERIAL AND METHODS: This was an implementation audit of the introduction of PCR in a London Tertiary obstetric unit. The performance of PCR in the prediction of proteinuria ≥300 mg/day was assessed in 476 women with suspected preeclampsia who completed a 24-h urine collection and an untimed urine sample for PCR calculation. Multivariate logistic regression was used to assess the independent predictors of significant proteinuria. RESULTS: In a pregnant population, ethnicity and PCR are the main predictors of ≥300 mg proteinuria in a 24-h urine collection. A PCR cut-off of 30 mg/mmol would have incorrectly classified as non-proteinuric, 41.4% and 22.9% of black and non-black women, respectively. Sensitivity of 100% is achieved at cut-offs of 8.67 and 20.56 mg/mmol for black and non-black women, respectively. Applying these levels as a screening tool to inform the need to perform a 24-h urine collection in 1000 women, would lead to a financial saving of €2911 in non-black women and to an additional cost of €3269 in black women. CONCLUSIONS: Our data suggest that a move from screening for proteinuria with a 24-h urine collection to screening with urine PCR is not appropriate for black populations. However, the move may lead to cost-saving if used in the white population with a PCR cut-off of 20.5.

Spot Urine Protein-to-Creatinine Ratio to Predict the Magnitude of 24-Hour Total Proteinuria in Preeclampsia of Varying Severity.

OBJECTIVE: The predictive value of spot urine protein-to-creatinine ratio (PCR) for estimating total 24-hour proteinuria in severe preeclampsia is unclear. This study aimed to assess the diagnostic accuracy of spot urine PCR for ascertaining the magnitude of proteinuria in women with preeclampsia of varying severity. METHODS: A total of 205 patients with prediagnosed preeclampsia were included in this prospective cohort study. Patients were allocated into one of the three groups categorized by severity of disease, as follows: gestational hypertension, group 1 (n = 41); preeclampsia, group 2 (n = 88); and severe preeclampsia, group 3 (n = 76). We assessed the spot urine PCRs to determine significant proteinuria and the magnitude of proteinuria in these groups. RESULTS: The spot urine PCR was 0.53, with 81% sensitivity and 93% specificity to detect significant proteinuria. A significant correlation was found between PCR and 24-hour total proteinuria in group 1 (r = 0.473, P = 0.002). There were also significant correlations in group 2 (r = 0.814, P < 0.001) and group 3 (r = 0.912, P < 0.001). The established formula using spot urine PCR to estimate 24-hour total proteinuria in severe preeclampsia was Y = 832.02X + 378.74 mg (r2 = 0.8304). CONCLUSION: Although 24-hour urine collection remains a merely reliable test to determine the degree of total proteinuria, our findings suggest that it is likely to assess the magnitude of proteinuria by the spot urine PCR, especially in severe preeclampsia. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.govNCT01623791.

Effect of urine creatinine level during pregnancy on dipstick test.

AIM: Dipstick results for proteinuria are affected by urine concentration, and thus urine creatinine concentration ([Cr]). This study was performed to determine whether spot urine [Cr] changes significantly during pregnancy, leading to a significantly different false-negative rate (FNR) on dipstick test between trimester. METHODS: The [Cr] and protein concentrations ([P]) were analyzed in 631 spot urine samples with negative/equivocal dipstick from 425 pregnant women. False-negative dipstick was defined as [P] : [Cr] ratio (P/Cr) > 0.27 mg/mg. RESULTS: Median [Cr] was 117 mg/dL (range, 6.5-326 mg/dL), 72 mg/dL (range, 4.3-477 mg/dL), and 73 mg/dL (range, 8.4-396 mg/dL) in the first (n = 96), second (n = 344), and third (n = 191) trimester urine samples, respectively (P = 0.000, Kruskal-Wallis). Both [P] and P/Cr increased significantly with advancing gestation. FNR 9.4% (18/191) in the third trimester was significantly higher than that of 0.0% (0/96) in the second trimester and that of 0.5% (2/344) in the third trimester. In the 20 urine samples with false-negative dipstick, median [Cr] was 47.0 mg/dL (range, 11.0-358 mg/dL) and the proportion of samples with dilute urine, that is, [Cr] <47 mg/dL, was significantly higher than in the remaining 611 urine samples (50%, 10/20 vs 28%, 174/611, respectively, P = 0.046). CONCLUSIONS: Urine samples in the second and third trimesters were more likely to be diluted compared with the first trimester. This was associated with high FNR in third trimester urine samples.