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BackgroundSchool urinary screening has been performed in Japan.MethodsIkeda 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.Results14,606 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.ConclusionSchool 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.

Objective: To calculate the cut off value of the spot urine protein/creatinine ratio (PCR) for predicting significant proteinuria in our population of patients with HTN (hypertension) in pregnancy, and study its correlation with total urine estimation in 24 hour collection of urine. Materials and Methods: We conducted a prospective observational study among pregnant women with HTN attending Department of Obstetrics and Gynaecology, Lok Nayak Hospital, Maulana Azad Medical College, New Delhi. Two hundred patients with singleton pregnancy with hypertension and gestational age >20 weeks were included in the study. Both 24-hour urine protein measurement and a spot urine PCR was done for every patient. Follow up was performed till delivery and outcomes were noted. Results: Significant proteinuria was found in 64 (32%) patients. The study suggested moderate degree of correlation between spot urine PCR and 24 hour urine protein, with a correlation coefficient of 0.47, p higher i.e. 0.776 for nonambulatory patients. The ROC curve analysis revealed an excellent sensitivity of 96.3% and specificity of 84.2% with AUC 0.91 (excellent) for a cut-off value of spot PCR >0.19 to detect significant proteinuria in our population. The negative predictive value was 98.4% and positive predictive value was 69.3%. Conclusion: The spot urine Protein Creatinine ratio can be considered an excellent ruling out test. However, women with abnormally high spot urine PCR should undergo 24-hour urine protein measurement before clinical intervention is done. Keywords: High risk obstetrics, Preeclampsia, PCR, Proteinuria.

Aim School urine screening has been established in several countries of Asia, including Japan, Korea and Taiwan. In Osaka prefectural schools, the urine screening system had some problematic issues including an unclear referral procedure for students with abnormal urinary findings. Therefore, the school urine screening system was reviewed and restructured in 2004. The aim of this study was to assess the improvement in school urine screening through evaluation of the restructured Osaka prefectural school urinary screening system. Methods The Osaka prefectural school urinary screening system was reviewed, mainly considering two points. One was the incorporation of standard urinary protein/creatinine ratio measurement instead of the traditional urine dipstick and urine sediment tests; the second point was that all students requiring further examination were referred to regional nephrologists. Results After restructuring, the number of students who were referred to a medical institute for detailed examinations decreased to 10%, although the number of students newly diagnosed with kidney disease and the types of diagnosis did not change. The positive predictive value of screening increased to about 8 times the value before the system restructuring. The reductions enabled students who required further examination to be referred to regional nephrologists and has contributed to a decreased cost for these examinations. Conclusion Incorporating urinary protein/creatinine ratio measurement into the school urinary screening system, and updating the guiding principles, including referral to nephrology specialists, has enabled the school urinary screening system in Osaka Prefecture to become more efficient and have better cost performance.

The aim was to investigate the diagnostic efficacy of urinary protein/creatinine ratio (UPCR) and factors influencing its substitutability of 24-h urine protein (24hUP) in children with proteinuria. A total of 356 children were recruited, including 149 with non-nephrotic-range proteinuria and 207 with nephrotic-range proteinuria which were further divided into Henoch–Schonlein purpura nephritis (HSPN), lupus nephritis (LN), and primary nephrotic syndrome (PNS). The urine protein and creatinine were measured by routine methods. Bland–Altman analysis was used to test the agreement. Spearman correlation was performed to evaluate the relevance. The receiver operating characteristic curve was used to analyze the diagnostic efficacy of UPCR. Bland–Altman analysis showed there was an excellent agreement between UPCR and 24hUP in each group. Correlations between UPCR and 24hUP were strong in 356 children (r = 0.869) and in the non-nephrotic-range proteinuria group (r = 0.806), but moderate in nephrotic-range proteinuria group (r = 0.586). With the increase of nephrotic-range proteinuria, the correlations between UPCR and 24hUP were decreased further, however, after UPCR was adjusted by 24-h urine creatinine (24hUCr), the correlation coefficient was improved (r = 0.682). In three subgroups with nephrotic-range proteinuria, high correlation coefficient (r = 0.731) was observed in HSPN, but not in LN (r = 0.552) and PNS (r = 0.563). The sensitivity and specificity of UPCR for diagnosing nephrotic-range proteinuria were 89.9 % and 92.2%. UPCR is competent in evaluating proteinuria. The degree of proteinuria, 24hUCr and the underlying pathological types of renal disease may be the important influencing factors in the correlation between UPCR and 24hUP in children with nephrotic-range proteinuria.

Background: Quantification of proteinuria is usually predicted upon 24-hour urine collection. Multiple factors influence urine collection and the rate of protein and creatinine excretion. A spot urine protein-creatinine (P-C) ratio has been shown over the years to be a reliable alternative to the 24-hour collection for detection and follow up of proteinuria. The objective of the study was to evaluate the accuracy of urine protein creatinine ratio (UP/UC) in a spot sample for quantitative measurement of proteinuria in comparison with 24 hours urinary protein excretion in children of nephrotic syndrome having normal Glomerular Filtration Rate (GFR). Methodology: This was a prospective study conducted in the department of paediatrics, Sir Salimullah Medical College & Mitford Hospital Dhaka over a period of six months from January 2003. Fifty cases of Nephrotic syndrome were included who were on initial attack and relapse cases noted down into the proforma with respect to history, examination and investigation. All the patients were advised regarding 24 hours urine collection. They were asked to give a 24 hours urine sample starting at 9.00 am for total protein excretion rate. A spot urine sample was obtained and urine protein/creatinine ratio was calculated. The data was analyzed by linear regression and by calculating the correlation coefficient between urinary protein/ creatinine ratio and 24-hour urinary protein. Results: Sample size was fifty. Urine total protein in a timed 24-hour sample of nephrotic syndrome patients was in the range of 300-3150mg/m2/hour with the mean value of 1725 mg/m2/hour. While as U(Pr/Cr) ratio ranged from 3.1-27.5 with the mean value of 15.2. A significant correlation was found between timed 24-hour urinary protein and UP/UC ratio (r=0.622, p=

Introduction: Nephrotic Syndrome is the commonest glomerular disease in children and is often characterized by multiple relapses. 24 hour urinary protein excretion is the accepted method used in quantification of proteinuria, but it's a time consuming, inconvenient and cumbersome method and difficult in very young children. Spot urine examination would be a simpler, easy, acceptable, and less time consuming method for detection of proteinuria in children. Aim: To evaluate the utility of protein: Creatinine ratio in random urine samples as a reliable diagnostic tool to quantify proteinuria and to determine the correlation of protein: Creatinine ratio to 24 hour protein excretion which is the gold standard reference method. Materials and Methods: The study was done on forty pediatric patients with nephrotic syndrome admitted in relapse, or presenting for the first time. Nephrotic syndrome was diagnosed on the basis of massive proteinuria (>40 mg/m2/hr), hypoalbuminemia (

Three main tests are commonly employed for the measurement of proteinuria: the dipstick test, the urinary protein/creatinine ratio (P/C) and the 24-h urine collection. The aim of this study was to evaluate the correlation between these methods, comparing linear regression and ROC curve data.A total of 297 consecutive outpatients with different renal diseases were included in the study. Twenty-four-hour proteinuria was considered the reference test.A high degree of correlation was observed between all the tests (p0.0001), the highest regression coefficient being between 24-h proteinuria and P/C (R=0.82), and the lowest between P/C and the dipstick test (R=0.72). The dipstick test failed to detect pathological proteinuria in 94 patients (31.6%). Therefore, in these subjects, the patterns of proteinuria were assessed by immunofixation and sodium dodecyl sulphate (SDS) electrophoresis.Our data strongly support the use of urinary P/C for the detection of proteinuria, at least in nephrology units, where the prevalence of proteinuria is likely to be high.

Objective To systematically review literature on the utility of spot urinary protein-creatinine ratio (PCR) as a screening test for proteinuria and its ability to accurately measure proteinuria compared with 24-hour urine collection (24H-P) in patients with systemic lupus erythematosus (SLE). Methods We conducted a literature search (1900-2015) for articles comparing PCR and 24H-P in SLE patients in the databases Medline, Web of Science, and Embase. Included studies and their results were critically appraised and analyzed. Results Thirteen studies (1,001 patients; 84.01% women) were included. Ten studies reported on Pearson's correlation (range 0.67-0.94), and 3 studies reported on Spearman's correlation (range 0.78-1.00). The meta-analysis of studies with Pearson's correlation showed a high overall correlation of 0.80 between 24H-P and PCR, yet with high heterogeneity (I(2) = 97.2%). Correlation analysis is not sufficient to evaluate the utility of a new test against the gold standard test, and analysis on agreement is required. Seven studies reported on agreement: 3 studies analyzed concordance correlation coefficient (0.48-0.94), 3 analyzed intraclass correlation coefficient (0.66-0.95), and 1 analyzed kappa coefficient (0.58). These results confirmed that the agreement between 24H-P and PCR was inappropriate. Three studies included Bland-Altman plots, and the results also demonstrated poor agreement between both tests. Conclusion The PCR has a utility as a screening test for proteinuria in SLE patients. The studies' results of 24H-P and PCR showed poor agreement between both tests, signifying that PCR should not be a substitute for the gold standard test (24H-P) to accurately measure proteinuria.

To explore the correlation between urinary protein:creatinine ratio and 24-h excretion of protein, we studied 149 women referred to a day assessment unit for investigations for suspected preeclampsia. Paired samples were obtained for measurement of urinary protein:creatinine ratio and 24-h protein excretion. Collection of a 24-h urine sample was validated by the daily creatinine excretion. The outcome measure was proteinuria of 300 mg/day or more. Inaccurate 24-h collection was observed in 17% of women. All women (n = 56) with a protein:creatinine ratio >60 mg/mM had significant proteinuria. No woman with protein:creatinine ratio

Context: Glomerulonephritis is an important cause of morbidity and mortality among all age group in Bangladesh. This cross sectional study was carried out with an aim to observe the comparison of 24 hour urinary protein and spot urinary protein- creatinine ratio in patients with glomerulonephritis in 3 group: on basis of 24 hour total protein, GFR level and serum albumin level.Methods: A total number of 128 consecutive patients having glomerulonephritis with 18 to 70 years who came in the Nephrology Unit, Dhaka Medical College Hospital, Dhaka, during the period of January to December of 2011 were included in this study. Patients with proteinuria other than glomerulonephritis like DM, UTI and Hypertension and 6 gm. A significant positive correlation was also found between 24 hour Urine Protein (gm/24 hour) with Protein Creatinine Ratio, which were in patients having GFR 30gm/dl and 20-30 gm/dl respectively. But because of only one sample in the group having

Background: Preeclampsia (PE) is heterogeneous disorder. The aim of the study was to observe the role of a spot urinary protein - creatinine ratio (UPCR) and uterine artery doppler velocimetry measured between 20-24 weeks of gestation in prediction of preeclampsia.Methods: Prospective observational study conducted on 120 pregnant mothers with singleton pregnancy between 20-24 weeks of gestational age in two tertiary teaching hospitals in eastern India. A spot urinary protein creatinine ratio (UPCR) was determined in a mid- stream urine sample and estimation of protein was done by immunoturbidimetric micro albumin method and creatinine by modified Jaffe’s method. Doppler velocimetry was also determined at 20-24 weeks of gestation. A notch in uterine artery, unilateral or bilateral; or RI > 0.7 and PI of > 1.45 were considered to have an abnormal result. Women were followed-up and relationship between variables was assessed by Chi- square test.Results: Women who subsequently developed preeclampsia had significantly higher UPCR (median 44.8 mg/mmol) when compared with women of unaffected groups (median 26.6 mg/mmol). The optimum spot urinary UPCR to predict preeclampsia was 35.5 mg/mmol and the cut-off value >35.5 mg/mmol had a test sensitivity (80%), specificity (94.06%), PPV (66.76%) and NPV (96.94%).The area under curve (AUC) of spot UPCR in ROC curve was 0.949 (95% CI,0.891 - 1.000). For predicting preeclampsia, the mean uterine artery RI had to be >0.7 having sensitivity (60%), specificity (97.03%), PPV (75%) and NPV (94.23%). The area under curve (AUC) was 0.856 (95% CI, 0.742 - 0.971).Conclusions: Second trimester UA doppler is a useful screening test for prediction of preeclampsia. This test works best when combined with a spot UPCR and accuracy of both the methods for prediction of preeclampsia was 92.24%.

INTRODUÇÃO: Tem-se defendido a utilização do índice urinário proteína e creatinina em substituição à determinação de proteinúria de 24 horas para acompanhamento de doenças glomerulares, considerando-se as vantagens de maior facilidade na coleta e o menor custo. Entretanto, há dúvidas quanto à pertinência de usar este índice tanto numa avaliação isolada como no seguimento de pacientes com nefrite lúpica. OBJETIVO: Avaliar as determinações de proteinúria de 24 horas e proteinúria em amostra isolada de urina, fazendo a correção pela creatinina urinária, relação proteinúria/creatininúria, em indivíduos com nefrite lúpica. MÉTODOS: Determinações de proteinúria de 24 horas e relação proteinúria/creatininúria por métodos convencionais (Pirogalol automatizado para proteinúria e picrato alcalino para creatinina). RESULTADOS: Foram comparadas 78 amostras de urina de 41 pacientes com diagnóstico de lúpus eritematoso sistêmico, segundo os critérios da Associação Americana de Reumatologia, com nefrite lúpica, constatando-se uma boa correlação entre proteinúria de 24 horas e relação proteinúria/creatininúria (r = 0,9010 e r² = 0,813). Não se observou, entretanto, uma boa correlação entre proteinúria em amostra isolada (sem correção pela creatinina urinária) versus aquela de 24 horas (r = 0,635 e r² = 0,403) ou versus relação proteinúria/creatininúria (r = 0,754 e r² = 0,569). CONCLUSÃO: Os marcadores de proteinúria de 24 horas e relação proteinúria/creatininúria isoladamente mostraram-se úteis no acompanhamento de cada caso. Porém, observou-se que os seus valores absolutos são diferentes, não possibilitando a substituição de um pelo outro ao longo do seguimento, particularmente quando este resultado é usado para definição de atividade da doença. Se necessário, sugere-se um período de intersecção (duas a três determinações pelos dois métodos) para mudança de um para outro e escolha de um único marcador preferencial para seguimento da proteinúria. INTRODUCTION: The urinary protein/creatinine ratio has been used instead of 24-hour proteinuria in Nephrology practice for the follow-up of glomerular diseases, considering the advantages of collection and the low cost. However, there are still doubts as to its applicability both for an isolated evaluation and for the follow-up of patients with lupus nephritis. OBJECTIVE: To evaluate 24-hour proteinuria determinations and random urine samples, performing urinary creatinine correction and urinary protein/creatinine ratio in subjects with lupus nephritis. METHODS: 24-hour proteinuria and urinary protein/creatinine ratio were determined by conventional methods (automated Pyrogallol for proteinuria and alkaline picrate for creatinine). RESULTS: Seventy-eight urine samples of 41 patients diagnosed with systemic lupus erythematosus, according to the American Rheumatology Association, with lupus nephritis, were analyzed, and a good correlation between 24-hour proteinuria and urinary protein/creatinine ratio (r = 0.9010 and r² = 0.813) was observed. However, a poor correlation between random proteinuria (without creatinine correction) versus 24-hour proteinuria (r = 0.635 and r² = 0.403) or versus urinary protein/creatinine ratio (r = 0.754 and r² = 0.569) was seen. CONCLUSION: 24-hour proteinuria and urinary protein/creatinine ratio were useful in the follow-up of each case. However, we observed that the absolute values were different, which did not allow the replacement of one for the other during follow-up, especially when this result is used to define the activity of the disease. Based on these results, we suggest a period of intersection from one to the other (two to three determinations by both methods), and the choice of one marker for proteinuria follow-up, if necessary.

Background: Hypertensive disorders are the most common medical complications of pregnancy with an incidence of 12-22% and are rampant globally. To assess the diagnostic accuracy of spot urinary protein-creatinine ratio keeping 24 hr urinary protein as gold standard in pregnancy induced hypertension.Methods: Spot urinary protein-creatinine ratio was determined in a mid-stream urine sample. 24 hours, urine protein was measured. The correlation between the spot urinary protein-creatinine ratio and 24-hour urine protein amount was done. Sensitivity, specificity, positive predictive value and negative predictive value along with diagnostic accuracy was calculated from data.Results: There was a strong correlation between the spot urinary protein-creatinine ratio and 24-hour urine protein excretion (pearson’s correlation coefficient r = 0.824; P

Introduction: Early neonates (1-7-day-old) may develop acute kidney injury or acute renal failure due to functional (pre-renal, may be caused by decreased renal perfusion), intrinsic (renal, may be caused by acute insult), or obstructive (due to anatomic urinary tract obstruction) causes. Urinary protein estimation is important for diagnosis, follow-up and prognosis of disease. The Protein Creatinine Ratio (PCR) has been successfully used to establish proteinuria in different types of patients. Aim: This study was undertaken to establish normal PCR range in neonates, to rule out abnormal protein excretion in sick neonates. Materials and Methods: A total of 37 normal early neonates of age 0-3 days were enrolled for this study. Random spot urine samples were collected in paediatric urine bags for protein and creatinine estimation. Results: The urinary PCR varied between 0.1-0.8. The range of PCR values obtained was greater in 0-1 day old infants, compared to infants older than one day. Changes in PCR values were due to variations in the creatinine excretion. Conclusion: Urinary PCR values ≤ 0.8 indicate normal protein excretion. However, reference intervals of PCR should be established for narrow age groups in case of early neonates, e.g. 0-6h, 6-12h, 12-24h, 24-72h old babies.

Proteinuria assessment is important in pregnancy, particularly in determining whether or not a woman has pre-eclampsia. The random protein to creatinine ratio (PrCr) has been recommended as a confirmatory test for dipstick proteinuria in pregnancy, defined as random PrCr ⩾30mg/mmol. However, it has been our clinical impression that women with normal pregnancy outcomes have fluctuating or persistently elevated PrCr values.As the primary goal of proteinuria testing in pregnancy should be to identify women at increased risk of adverse outcomes, we sought to explore our clinical impression that an elevated PrCr is seen not infrequently in pregnancies with normal outcome.In this prospective cohort study, consecutive inpatients or outpatients (attending high-risk maternity clinics) were evaluated at a tertiary care facility. Random midstream urine samples were obtained as part of normal clinical care. Urine protein was measured using a pyrocatechol violet molybdate dye-binding method, and urine creatinine by an enzymatic method, both on an automated analyser (Vitros® 5.1 FS or Vitros® 5600, Ortho-Clinical Diagnostics, Rochester, NY) followed by PrCr calculation. Maternal and perinatal outcomes were abstracted from the hospital case notes.160 women (81.9% outpatients) were screened at one/more antenatal visits providing a total of 233 samples for analysis. Ninety one (39.1%) samples had a random PrCr ⩾30 mg/mmol. This result was more common when urinary creatinine concentration was3mM [64 (94.1%)] compared with ⩾3mM [27 (16.4%)], even among the 32 (20.0%) women with known normal pregnancy outcome [(13 (92.9%) vs. 0 (0%), respectively] (Panel A). In dilution studies using the same automated analyser, urinary protein (at a concentration of 0.12g/L) was 'detected' in deionised, double-distilled water. Method-specific re-analysis of data from two other published cohorts from our centre revealed substantially less inflation of PrCr values in dilute 24h urine samples tested using a pyrogallol red dye-binding based protein assay. When results were categorized according to urinary creatinine3mM vs. ⩾3mM, PrCr ⩾30mg/mmol occurred in 12 (66.7%) vs. 99 (55.3%) respectively (p=0.35) in a 24-h urine completeness cohort and 92 (73.6%) vs. 313 (64.9%) respectively (p=0.07) in a cohort of women hospitalised for pre-eclampsia (Panel B).Random urinary PrCr results may be inflated in dilute urines because of overestimation of proteinuria in a common pyrocatechol violet dye-based method. This inflation was reduced but not eliminated when the dye used was pyrogallol red. Analytical methods do matter in the assessment of proteinuria in pregnant women. It may be prudent to consider the potential for falsely positive PrCr ⩾30mg/mmol in dilute urine, and to order PrCr testing on first voided (concentrated) urines whenever possible.

Introduction: Diagnosis of preeclampsia relies on protein quantification in a 24-hour urine collection, a procedure wrought with pitfalls and errors. There are growing claims that urine protein/creatinine ratios (PCR) on single voided urines are valid alternatives that should replace the timed collections, and decrease the time needed for decision making when triaging patients suspected to have preeclampsia. However the validity of such claims requires a demonstration that the ratio remains unchanged throughout the day (i.e. both creatinine and protein are excreted at a nearly constant rate), and this requirement does not appear to have been accurately studied nor evaluated. Objectives: This study is performed to study the correlation of PCR in single voided urine at different times of the day with 24-hour protein excretion. Furthermore we investigated the variation of PCR during the day. Methods: 105 patients, admitted to the Erasmus Medical Center to rule out preeclampsia underwent 24 hour urine collections with aliquots from 8.00 am, 12.00 and 5.00 pm void saved separately. Creatinine and protein levels were measured in each specimen along with the 24 hour collection whose volume was also recorded. Results: Figure shows the individual PCR data on 8.00 am, 12.00 and 5.00 pm. Each line represents an individual patient (N = 105). As shown in figure the variations of spot PCR as mg/mmol varied little the exceptions being women with high nephritic range proteinuria. Otherwise, the spot urinary PCR at all three times of the day correlated strongly with each other as well as with the 24-hour protein excretion. Receiver operating characteristics curves to discriminate between

Background The spot urine protein/creatinine ratio (UPCR) is proposed to be a substitute for 24-hour urinary protein (24 h-UP). This study is aimed to determine whether the predictive accuracy of 24 h-UP using UPCR can be improved by simply multiplying estimated daily urine creatinine excretion (eUCr) and UPCR together. Methods This study enrolled 120 participants to investigate the correlation between spot UPCR and 24 h-UP. Three sets of spot urine samples were randomly collected throughout the day and night, along with the first morning void. UPCR was weighted by eUCr to investigate the improvement of accuracy in using spot urine samples to predict 24 h-UP. Results There were strong correlation and concordance between UPCR and 24 h-UP irrespective of the time of spot urine sampling, and the correlation, concordance and agreement were improved after multiplying the UPCR value by the eUCr. Greater improvement was found in the subgroups with measured daily urine creatinine excretion ≤ 0.8 g/d and ≥ 1.2 g/d. Conclusions This investigation demonstrated that multiplying UPCR by eUCr can improve the accuracy of only using UPCR to predict 24 h-UP.

To determine the correlation between the protein/creatinine ratio and 24-h proteinuria; to estimate the sensitivity and specificity of this ratio for the diagnosis of significant proteinuria; to establish its cutoff point with the best predictive value for the diagnosis of significant proteinuria in patients with systemic arterial hypertension.A cross-sectional study of 47 hypertensive patients who had been pregnant for 20 weeks or more seen at the Maternity of the University Hospital of Porto Alegre. The studied factor was the protein/creatinine ratio measured in a single random urine sample and the outcome was protein determination in 24-h urine. The level of significance was set at 0.05.The correlation coefficient between the protein/creatinine ratio and 24-h proteinuria was 0.94 when urine was properly collected. A receiver-operator characteristic curve was constructed to determine the sensitivity and specificity of the ratio for the diagnosis of significant proteinuria (or = 300 mg in 24 h). Specificity and predictive positive value were 100% for a ratioor = 0.8. The best values for sensitivity, specificity, positive predictive value, and negative predictive value in the diagnosis of proteinuriaor = 300 mg in 24 h were obtained when the protein/creatinine ratio was 0.5 (0.96, 0.96, 0.96, and 0.96, respectively).The protein/creatinine ratio measured in a single urine sample taken at random from hypertensive pregnant women showed good sensitivity and specificity for the diagnosis of 24-h proteinuriaor = 300 mg and was strongly correlated with 24-h proteinuria. A ratio of 0.5 mg/mg is predictive of significant proteinuria and can be used for the diagnosis and follow-up of hypertensive pregnant women.

Preeclampsia is a big problem in obstetrics. The diagnosis relies mainly on the detection of both hypertension and proteinuria. The gold standard for the determination of proteinuria is 24 h urinary protein creatinine ratio; however, this approach is inconvenient and it is a considerable time consuming process that might bring a delayed diagnosis which might result in delayed treatment. Although spot urine measurement can be done, it has very poor prediction. The use of periodic urinary protein creatinine ratio is proposed as a possible alternative to solve this problem. Here, the author tries to perform a time effectiveness analysis for reported models on periodical urinary protein creatinine ratio for predicting significant proteinuria in preeclampsia. Data from previously published reports on this topic are used for further analysis. It seems that the alternative, 4 h, gives the most effectiveness in the shortest period of turnaround time. Hence, this alternative is recommended for screening proteinuria.

Background For clinicians, it is important to rely on accurate laboratory results for patient care and optimal use of health care resources. We sought to explore our observations that urine protein:creatinine ratios (PrCr) ≥30 mg/mmol are seen not infrequently associated with normal pregnancy outcome. Methods Urine samples were collected prospectively from 160 pregnant women attending high-risk maternity clinics at a tertiary care facility. Urinary protein was measured using a pyrocatechol violet assay and urinary creatinine by an enzymatic method on Vitros analysers. Maternal/perinatal outcomes were abstracted from hospital records. Results 91/233 (39.1%) samples had a PrCr ≥30 mg/mmol, especially when urinary creatinine concentration was Conclusions Random urinary PrCr was overestimated in dilute urine when tested using a common pyrocatechol violet dye-based method. This effect was reduced in cohorts when pyrogallol red assays were used. False positive results can impact on diagnosis and patient care. This highlights the need for both clinical and laboratory quality improvement projects and standardization of laboratory protein measurement.

Quantitation of urinary protein excretion has traditionally involved collection of a 24-hour urine specimen. Recent reports have suggested that the ratio of protein to creatinine in a single-voided urine specimen may be used as a screening test of proteinuria, obviating the need for a 24-hour urine collection. This study was undertaken to determine whether the urinary protein/creatinine ratio was correlated with 24-hour protein excretion in women with diabetes, to determine whether pregnancy had any effect on the correlation, and to test the accuracy of estimates of 24-hour protein excretion on the basis of the protein/creatinine ratio. We studied 329 24-hour urine specimens from 133 women with classes B through RF diabetes. The protein/creatinine ratio was highly correlated with total protein excretion (r = 0.977, p less than 0.0001). The correlation was not affected by pregnancy, trimester, or preeclampsia. Three methods were used to predict protein excretion on the basis of the ratio. Compared with actual protein excretion, predicted values had mean errors of 19% to 27%; 6% to 13% of predictions were in error by greater than or equal to 50%. Because of these large errors, we conclude that this method of estimating protein excretion has limited value in pregnant women with diabetes.

To assess the urine protein/creatinine ratio in urine samples of pregnant women with hypertension in regard to: 1) the presence of significant variation at different periods of the day; 2) the differences if they exist, to identify the most reliable period of the day for sampling; and 3) whether the first sample, obtained when the patient arrives at the clinic, correlates with the same accuracy, with the 24-hour proteinuria.Cross-sectional study.Obstetrics Emergency Department, Hospital de Clínicas de Porto Alegre, a teaching hospital in Porto Alegre, Brazil.Seventy-five women with hypertension with 20-week gestation or over.Urine samples for determination of the protein/creatinine ratio were obtained on arrival (first specimen) and every 6 hours thereafter, totaling four samples in 24 hours. Four sampling periods were established: 1) from 8 am to 2 pm, 2) from 2 pm to 8 pm, 3) from 8 pm to 2 am, and 4) from 2 am to 8 am. The protein/creatinine ratio in the four different day periods were compared with the 24-hour proteinuria obtained simultaneously. The results were analyzed by the Spearman correlation and the receiver-operator characteristic (ROC) curve.The urine protein/creatinine ratio is strongly correlated (Spearman correlation equal to 0.8 or greater) with the 24-hour proteinuria at all four periods of the day (p0.001), as well as the first sample obtained on arrival (p=0.003). These findings were corroborated by the ROC curve in which the values of four day periods and that of the first sample were equal to or greater than 0.930.In hypertensive pregnant women, the single voided urine sample protein/creatinine ratio, irrespective of sampling time, is strongly correlated with the 24-hour proteinuria, as is the sample obtained on arrival.

Background: Nephrotic Syndrome (NS) is very common in children. The typical laboratory finding is high urinary protein creatinine ratio. Apart from it low serum albumin, high cholesterol contribute to hyper coagulable states. Due to this the risk of thromboembolism in both arterial and venous circulation is significant in children and adults. Patients at risk for thromboembolism traditionally have to be screened by ventilation/perfusion scans and Dopplers for the definitive diagnosis of thromboembolic disease. There are several studies performed on adult nephrotic syndrome and thromboembolic events in them worldwide. We wanted to look for simple, affordable tests, that can be performed even when state of the art technology is not available, and can point towards at risk thromboembolic patients. Methods: The study was conducted in 17 nephrotic syndrome children in active disease, 13 nephrotic syndrome children in remission and 15 healthy children as controls, all between 4-14 years age group. Study included both male and female children. Results: Our results revealed prolonged. APTT in NS with active disease when compared to remission and control groups. High fibrinogen levels in relapse group indicated hypercoagulative state, along with routine parameters such as high cholesterol and low albumin. Both relapse and remission groups had proteinuria, with very high P/C ratio in relapse group, indicating at risk group for thromboembolic complications along with basic coagulation parameters. Conclusion: We suggest that when there are indications of hypercoagulable state antiplatelet drugs such as a low dose aspirin 75 mg or low dose warfarin may be given as prophylactic treatment for thromboembolic disease.

Objectives Mycophenolate mofetil (MMF)has become the primary induction therapy for lupus nephritis (LN). The purpose of this study was to look at the timing of the protein creatinine ratio reaching 500mg after starting Mycophenolate mofetil (MMF) for class III, IV or V lupus nephritis. Methods 21 SLE patients began mycophenolate mofetil (MMF) shortly after a biopsy-confirmed diagnosis of LN. The baseline urine protein ranged between 0.635 to 11.91grams, with only 1 patient being below 1 gram at baseline. They consisted of 18 females, 3 males, 9 African Americans, 8 Caucasians, and 4 other ethnicities. Ages ranged from 18 to 70 with a mean age of 37 (SD=15).The mycophenolate mofetil (MMF) dose ranged between 250 to 3000 mg per day. We estimated the survival function time until the urine protein reached 0.5 grams or less after starting mycophenolate mofetil (MMF) using an approach that accommodates interval censored data. Results The graph shows an estimate of the probability that patients would still have urine protein above 500 mg by various time points after starting mycophenolate mofetil (MMF). We estimate that 50% of patients will have reached 0.5 grams of protein with 51 days of starting mycophenolate mofetil (MMF), and 77% will have reached 0.5 grams within 180 days. Conclusions This study demonstrates that the majority of patients with lupus nephritis (77%) can reach a urine protein creatinine ratio of 0.5 grams or less by 6 months after initiation of mycophenolate mofetil (MMF). These data can be used to determine sample sizes for clinical trials in lupus nephritis; but also suggest that a more stringent goal should be considered. Disclosure of Interest None Declared

Objective To determine the diagnostic accuracy of the albumin creatinine ratio (ACR) and protein creatinine ratio (PCR) compared to the 24 h total urine (24 h TU) and how well they predict adverse outcomes for mother and baby in women with suspected pre-eclampsia (PE). Methods Systematic searches in electronic databases, reference lists and contact with experts. All studies reporting on ACR and/or PCR in hypertensive pregnant women with suspected PE compared to 24 h TU or to predict adverse outcome and with data for a 2×2 table. No language restrictions. Bivariate meta-analysis was conducted. Results 3111 citations were identified, 103 papers for detailed evaluation. 20 papers were included in the review, 2978 women. 15 studies examined the PCR compared to 24 hTU, 4 looked at ACR compared to 24 hTU and one at ACR compared to adverse outcomes. A PCR of 0.3 had a sensitivity of 0.93 (95% CI 0.85 to 0.97) and specificity of 0.90 (95%CI 0.71 to 0.97) to predict significant proteinuria on 24 hTU (>0.3 g/day). For ACR meta-analysis was not possible due to different thresholds and study characteristics. Thus the results from one of the studies in a hypertensive pregnant population were sensitivity 0.94 (95% CI 0.85 to 0.98) and specificity 0.94 (95% CI 0.88 to 0.94). Conclusion The results suggest that PCR and in particular, ACR, may be valuable point of care tests in the management of suspected PE. Further work needs to be performed to look at their role in the management of this condition in the prediction of adverse outcomes for mother and baby and which is the most cost-effective threshold to use.

Background Up to 25% of elderly humans have proteinuria, often associated with underlying lesions. Data concerning the presence of proteinuria in elderly dogs is scarce. Objectives To describe the presence and persistence of proteinuria and to compare urinary protein : creatinine ratio (UPC) between free catch and cystocentesis urine samples in apparently healthy elderly dogs. Animals Hundred apparently healthy elderly dogs. Methods Prospective study. Owners of 100 elderly dogs were asked to collect 2 free catch urine samples. Dogs were considered healthy based on owner's perception and an age chart, based on ideal bodyweight, was used to define dogs as senior or geriatric. UPC of urine collected by free catch and cystocentesis were compared. Overt proteinuria and borderline proteinuria were defined as UPC >0.5 and between 0.2 and 0.5, respectively, if examination of sediment did not explain proteinuria. Proteinuria was considered persistent if present at both sampling times. Results At baseline, 71 owners succeeded in collecting urine. Eleven percent of dogs had overt proteinuria, 14% were borderline proteinuric, and 75% nonproteinuric. Thirty-seven repeated urine samples, with a median time interval of 31 days (range 10–90), were available. Nineteen percent of dogs had a persistently increased UPC (>0.2), with persistent overt proteinuria present in 8%. A strong correlation (ρ = 0.88) was found between UPC of urine collected by free catch and cystocentesis. Conclusions and Clinical Importance As 19% of study dogs had persistent proteinuria, our findings emphasize that measurement of proteinuria should be part of geriatric health screening. For UPC in dogs, free catch urine provides a good alternative to cystocentesis.

Doença renal crônica (DRC) é a forma mais comum de doença renal em gatos. Vários fatores têm sido citados como importantes na progressão da doença, dentre eles a proteinúria. A relação proteína-creatinina (RPC) urinária em uma única amostra de urina apresenta boa correlação com a perda de proteína urinária em 24 horas. O objetivo dessa investigação foi determinar a RPC urinária em gatos com DRC adquirida naturalmente. A determinação da RPC foi realizada em nove gatos saudáveis (Grupo I) e em trinta gatos com DRC (Grupo II). Os gatos do Grupo I apresentaram RPC de 0,16±0,10 e os gatos do Grupo II apresentaram RPC de 0,53± 0,59. No Grupo II encontrou-se correlação positiva e significante da RPC com o nível de creatinina sérica. Os resultados deste estudo demonstram que a RPC urinária em gatos com DRC é bastante variável e que, à semelhança do que já havia sido previamente descrito, aproximadamente um terço dos gatos com DRC são considerados proteinúricos segundo critérios estabelecidos pela literatura (RPC urinária >0,4).Chronic renal disease (CRD) is the most common form of renal disease in cats. Several factors contribute to disease progression. Proteinuria is an important marker of renal disease progression. The protein-creatinine ratio in a single urine sample correlates well with urinary protein loss in 24 hours. The aim of this investigation was to determine the urine protein-creatinine (UPC) ratio in cats with natural acquired chronic renal disease. The UPC ratio was performed in nine clinically normal cats and in 30 cats with chronic renal disease. Mean UPC ratio in normal cats was 0.16±0.10, and mean UPC ratio in the cats with chronic renal disease was 0.53± 0.59. In the group with renal disease there was positive correlation between UPC ratio and serum creatinine levels. The results obtained from this study demonstrate that UPC ratio in cats with CRD is variable and that, in accordance to what has previously been described, approximately one third of the cats with CRD are considered proteinuric according to the criteria established in literature (UPC ratio > 0.4).

Background: Diagnosis of familial amyloidosis (FA) in Abyssinian cats usually is made on postmortem examination. Hypothesis/Objectives: Sequential analysis of serum SAA (sSAA), urinary SAA (uSAA), urinary protein:creatinine (UPC) ratio, or sodium-dodecylsulfate agarose gel electrophoresis (SDS-AGE) may facilitate early identification of cats with FA. Animals: Twenty-three Abyssinian cats belonging to cattery A or B (low and high prevalence of FA, respectively). Methods: Prospective longitudinal study using 109 blood and 100 urine samples collected over 4-year period every 4 months, if possible, or more frequently in case of illness. Cats that died during study were necropsied. Health status of live cats was checked 5 years after enrollment. Serum amyloid A (sSAA) and urinary SAA (uSAA) were measured using ELISA kit. The UPC ratio and SDS-AGE also was performed. Results: Familial amyloidosis was not identified in cattery A, whereas 7/14 cats from cattery B had FA. Serum amyloid A concentrations were not significantly different between cats in catteries A and B or between cats with or without FA, despite frequent peaks in cats from cattery B. Conversely, uSAA was significantly higher in cattery B, especially in the terminal phases of FA. Proteinuria occasionally was found in cats from both catteries, especially in those with FA. Urine protein electrophoresis identified mixed proteinuria only in cats with FA. Conclusions and Clinical Importance: Serum amyloid A and UPC ratio are not helpful for early identification of Abyssinian cats with FA. Conversely, increases in uSAA with or without mixed proteinuria may be found before onset of clinical signs in cats with FA.

Background Annual urinary screening is conducted at municipal kindergartens, elementary schools, and junior high schools in Ikeda City, Osaka, Japan (Ikeda City School System), and the results are reviewed by a general physician, but standards for when to recommend specialist referral have not been clear. Methods In all children attending the Ikeda City School System in 2012, dipstick urinalysis of a first-morning urine specimen was recommended once or twice, and if a second urinalysis showed proteinuria (≥1+), the urinary protein/creatinine ratio was measured. If this showed ≥0.2 g/g of creatinine (g/gCr), it was recommended that the child be evaluated by a specialist at Ikeda City Hospital. Results Urinary screening was performed in about 20% (388) of kindergarten, about 90% (5363) of elementary school, and about 86% (2523) of junior high school children living in Ikeda City. Urine samples were obtained from 387, 5349, and 2476 children, respectively. The urinary protein/creatinine ratio was ≥0.2 g/gCr in 13 children, including 1 elementary and 12 junior high children. In these 13 children, chronic nephritic syndrome (CNS) was suspected in 6 junior high school children, and of these, this was a new finding in 5, and renal biopsy was indicated in 3. In Ikeda City, the prevalence of CNS in elementary school children was

This study aimed to evaluate the renal function of six bitches of various breeds and ages, with open pyometra, attended in the Small Animal Medical Clinic sector of the Veterinary Hospital from Federal University of Campina Grande, through the measurement of laboratory tests: urea and creatinine serum, dosage of the urinary Protein-Creatinine Ratio (PCR), urinary gamma-glutamyltransferase (GGT) and determination of the renal resistivity index (RI). The levels of urea and creatinine were elevated in 16.6% (1/6) of the female dogs; the urinary protein-creatinine ratio was increased in 66.6% (4/6), while the urinary gamma-glutamyltransferase value was elevated in 50% (3/6). The renal resistivity index was increased in the right and left kidneys by 66.6% (4/6) of bitches, with no statistical difference between them. It was concluded that the renal resistivity index was a practical and effective method to assist in the diagnosis of acute kidney injury, along with other early markers, such as PCR and urinary GGT.

Objectives: Nephrotic syndrome is a common renal disorder seen in children, with proteinuria as the hallmark. Growth retardation is a known feature of nephrotic syndrome, either due to the disease or treatment with steroids. Thyroid hormone strongly inuences growth of the body. So, the present study was undertaken with the objective to assess the thyroid prole in children with nephrotic syndrome Methods: The study involved 41 cases of nephrotic syndrome and 41 age and sex matched controls. Serum total triiodothyronine (T3), total thyroxine (T4), free triiodothyronine (T3), free thyroxine (T4) and thyroid stimulating hormone (TSH) were assessed in these subjects. The thyroid hormones were correlated with urinary protein creatinine ratio. The cases were followed up after one month and the levels of thyroid hormones were reassessed. Results: Total T3, total T4, free T3 and free T4 are signicantly decreased and TSH signicantly increased among cases when compared to controls. TSH is positively correlating with urinary protein creatinine ratio in cases. After one month of treatment, total T3 and total T4 are signicantly increased in cases. Conclusions: The thyroid hormone levels are altered in children with nephrotic syndrome during the episode. A state of subclinical hypothyroidism exists during the nephrotic stage. The alteration is normalized with remission and does not require treatment.

Introduction Progressive proteinuria and glomerulosclerosis characterize chronic allograft nephropathy. Podocytes are fundamental cells for maintaining the functionality of glomerular filtration barrier. Failure to achieve this task due to reduced podocyte number and results in progressive glomerular dysfunction, causing proteinuria and glomerulosclerosis and ultimately leading to end-stage kidney disease. Assessment of podocyturia and its correlation with other renal parameters could help with the diagnosis and definition of prognosis of the glomerulopathies, thus contributing to risk reduction. Objective To evaluate podocyturia and others renal parameters as functional markers in pregnant women with kidney grafts. Methods In this cross-sectional and prospective study, 43 pregnant women with kidney grafts had their Mid-stream urine samples collected to determine proteinuria, including retinol-binding protein (enzyme immunoassay using monoclonalantibodies), albumin/creatinine ratio (immunoturbidimetry), protein/creatinine ratio (the alkaline picrate colorimetric method), and podocyturia (indirect immunofluorescence). Results 43 women who got pregnant after renal transplantation were included. Podocyturia was not significantly correlated with other renal function markers. A gradual increase was observed in the following parameters during pregnancy and puerperium: serum creatinine levels (P Conclusion Proteinuria, urinary protein/creatinine ratio, and retinol-binding protein levels were elevated in patients with preeclampsia. Proteinuria (or more specifically, urinary protein/creatinine ratio) and albumin/creatinine ratio has also used as a marker of CKD progression. We observed that urinary podocyte excretion occurs in pregnant women with kidney transplant. Using these markers to assess renal function during pregnancy may be clinically useful for early diagnosis and follow-up of glomerular injury, eventually preeclampsia. It may be also associated to its severity or activity.

Background/Introduction Heart Failure with preserved ejection fraction (HFpEF) is a major cause of death worldwide with currently no approved treatment. Diastolic dysfunction, dyspnea, intolerance to effort, high cardiac filling pressure, and lung congestion coexist with normal ejection fraction in this clinical syndrome. Ageing, obesity, type 2 diabetes, hypertension and renal dysfunction are the main comorbidities found in this heterogeneous group of patients. Microvascular endothelial dysfunction, driven by these risk factors, may be a common link with other aspects of the HFpEF pathogenesis that include oxidative stress, inflammation, cardiomyocyte stiffness/hypertrophy, and myofibroblast accumulation. Sphingosine-1-phosphate type-1 receptor (S1P1), a G protein–coupled receptor highly expressed in endothelial cells, regulates vascular integrity, vascular development and immune cell trafficking. Compound A is a novel G protein-biased S1P1 agonist that lacks functional antagonism and has endothelial-protective properties. Purpose S1P1 activation could promote phosphorylation of endothelial nitric oxide synthase, restoration of endothelial structure and function, and thus diminish cardiac and vascular stiffness, hypertrophy and fibrosis. The aim of this study was to investigate if compound A could improve renal and cardiac functions in a rat model of HFpEF with metabolic syndrome. Methods 65-week-old obese ZSF1 rats were fed a chow diet containing compound A (8 mg/kg/day) or no compound for 4 weeks. Lean ZSF1 and Wistar rats were included in the study as control groups. Urinary protein/creatinine ratio was measured as an index of glomerular injury. Cardiac hypertrophy and function were assessed by two-dimensional and Doppler echocardiography. Total cardiac and atrial weights and pulmonary edema were assessed. Results The obese ZSF1 rat was confirmed as a relevant model of HFpEF with advanced renal dysfunction. These rats showed severe glomerular filtration impairment, left ventricular and atrial hypertrophy and pulmonary edema. Cardiac systolic function, cardiac output and chamber volumes were preserved, diastolic function was impaired, and left ventricular posterior walls and septal thicknesses were increased compared to control groups. Four weeks of compound A treatment reduced urinary protein/creatinine ratio, blunted cardiac and atrial hypertrophy, and partially restored diastolic function. Circulating lymphocytes were not reduced by compound A, confirming that these pharmacological effects were not associated with S1P1 desensitization. Conclusion Compound A, a novel S1P1 agonist with endothelial properties, improves cardiac and renal functions in a rat model of metabolic syndrome-associated HFpEF. Sustained S1P1 activation with compound A may be a promising strategy for HFpEF treatment.

Rationale & Objective Remission of proteinuria has been shown to be associated with lower rates of kidney disease progression among people with focal segmental glomerulosclerosis (FSGS). The goal of this study was to evaluate whether reductions in proteinuria after treatment are associated with greater kidney survival. Study Design Cohort analysis of clinical trial participants. Setting & Participants Patients with steroid-resistant FSGS enrolled in a randomized treatment trial that compared cyclosporine with mycophenolate mofetil plus dexamethasone. Predictors Reduction in proteinuria measured during 26 weeks after initiating treatment. Outcomes Repeated assessments of estimated glomerular filtration rate (eGFR) and time to a composite outcome of kidney failure or death assessed between 26 weeks and 54 months after randomization. Analytical Approach Multivariable linear mixed-effects models with participant-specific slope and intercept to estimate the association of change in proteinuria over 26 weeks while receiving treatment with the subsequent slope of change in eGFR. Multivariable time-varying Cox proportional hazards models were used to estimate the association of changes in proteinuria with time to the composite outcome. Results 138 of 192 trial participants were included. Changes in proteinuria over 26 weeks were significantly related to eGFR slope. A 1-unit reduction in log-transformed urinary protein-creatinine ratio was associated with a 3.90 mL/min/1.73 m2 per year increase in eGFR (95% CI, 2.01-5.79). This difference remained significant after adjusting for complete remission. There was an analogous relationship between time-varying proteinuria and time to the composite outcome: the HR per 1-unit reduction in log-transformed urinary protein-creatinine ratio was 0.23 (95% CI, 0.12-0.44). Limitations Limited to individuals with steroid-resistant FSGS followed up for a maximum of 5 years. Conclusions These findings provide evidence for the benefit of urinary protein reduction in FSGS. Reductions in proteinuria warrant further evaluation as a potential surrogate for preservation of kidney function that may inform the design of future clinical trials.

Background. Despite enzyme replacement therapy, Fabry nephropathy still progresses. Podocyturia is an irreversible event that antedates proteinuria and leads to chronic renal failure. We evaluated a potential mechanism of podocyte detachment via the expression of the urokinase-type Plasminogen Activator Receptor (uPAR) in urinary podocytes of Fabry patients.Methods. This is a cross-sectional study that included controls (n=20) and Fabry patients (n=44) either untreated (n=23) or treated with agalsidase-β(n=21).Variables. Variables are estimated glomerular filtration rate (eGFR), urinary protein : creatinine ratio, and urinary uPAR+ podocyte : creatinine ratio. uPAR mRNA expression in response to lyso-Gb3, a bioactive glycolipid accumulated in Fabry disease, was studied in cultured human podocytes.Results. Controls and Fabry patients had similar age, gender, and renal function. Urinary uPAR+ podocytes were higher in patients than in controls. Untreated patients were significantly younger; had more females, and presented lower urinary protein : creatinine ratios and significantly higher urinary uPAR+ podocytes than treated subjects. In treated patients, urinary uPAR+ podocytes correlated with urinary protein : creatinine ratio (ρ=0.5;p=0.02). Lyso-Gb3 at concentrations found in the circulation of Fabry patients increased uPAR expression in cultured podocytes.Conclusions. Urinary podocytes expressing uPAR are increased in Fabry patients, especially in untreated patients. The potential contribution of uPAR expression to podocyte detachment merits further studies.

Background:Lupus nephritis (LN) remains a significant cause of morbidity and mortality in subjects with Systemic Lupus Erythematosus (SLE). The gold standard for evaluation of LN remains the kidney biopsy, whereas renal function is usually evaluated by eGFR and urinary protein:creatinine ratio. More effective and sensitive methodology is needed to assess LN and also the response to treatment. Functional imaging of the kidney using quantitative techniques has great potential, as it can assess kidney function and pathologic changes non-invasively by evaluating perfusion, oxygenation, cellular density and fibrosis.Objectives:The objective of this study was to develop a multi-modality imaging approach for the evaluation of the spectrum of pathologic changes in LN and to determine when imaging data correlated with renal functionMethods:In this multi-center study (NCT03180021), subjects who were having a standard of care renal biopsy for LN were asked to participate in the imaging evaluation. Local Institutional Review Board approval was obtained, and subjects signed an Informed Consent Form. Dynamic contrast enhanced MRI (DCE-MRI) was employed to detect changes in vascularization and perfusion, Diffusion Weighted Imaging (DWI) to assess interstitial diffusion, T2*Map/BOLD to evaluate tissue oxygenation and T1rho to evaluate fibrosis (Figure 1). Regions of interest were identified in the imaged kidneys and imaging parameters were correlated with measures of renal function, including eGFR and urinary protein: creatinine ratio. In DCE-MRI, we specifically focused on mean Maximum Enhancement (ME), mean Time to Peak Enhancement (TTP) and mean Time of Washout (Twashout) as indicators of renal perfusion.Results:Nine subjects have been evaluated to date and their imaging data assessed for quality. Evaluation of mean data from DCE-MRI has shown a significant correlation between renal perfusion and renal function. For example, as shown in the figure, the 24 hour protein concentration negatively correlated with ME (rs=-0.81, p=0.015), TTP (rs=-0.83, p=0.01) and Twashout (rs=-0.81.p=0.01, Spearman rank correlation). In addition, the protein:creatinine ratio also negatively correlated with ME (rs=-0.79, p=0.02), TTP (rs=-0.74, p=0.04) and Twashout (rs=-0.79, p=0.02, Spearman rank correlation).Conclusion:These initial results have established the feasibility of multi-modality imaging as a tool to evaluate LN in a multi-center study. Moreover, changes in perfusion detected by DCE-MRI significantly correlate with proteinuria and urinary protein:creatinine ratio. These results suggest that multiparameter imaging may contribute useful data in the evaluation of subjects with LN.Figure:Disclosure of Interests:Claire Dykas: None declared, Brad H Rovin Grant/research support from: GSK, Consultant of: GSK, Mikael Boesen Consultant of: AbbVie, AstraZeneca, Eli Lilly, Esaote, Glenmark, Novartis, Pfizer, UCB, Paid instructor for: IAG, Image Analysis Group, AbbVie, Eli Lilly, AstraZeneca, esaote, Glenmark, Novartis, Pfizer, UCB (scientific advisor)., Speakers bureau: Eli Lilly, Esaote, Novartis, Pfizer, UCB, Olga Kubassova Shareholder of: IAG, Image Analysis Group, Consultant of: Novartis, Takeda, Lilly, Employee of: IAG, Image Analysis Group, Peter Lipsky Consultant of: Horizon Therapeutics

Women with hypertensive forms of pregnancy such as hemolysis-elevated liver enzymes-low platelet syndrome have increased circulating endothelin 1; however, the relationship between hypertension and endothelin 1 has not been studied. Using an animal model, we sought to determine whether there was an increased activation/dysfunction of endothelin 1, the effect of endothelin 1 receptor-A blockade on hypertension and other manifestations of hemolysis, elevated liver enzymes, and low platelets syndrome. On gestational day 12, timed-pregnant rats were infused with soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEndoglin; 4.7 and 7 µg/kg) via mini-osmotic pumps for 8 days. A subset of rats were treated with receptor-A antagonist (ABT-627, 5mg/kg) for 8 days. Rats with hemolysis-elevated liver enzymes-low platelet syndrome had significantly increased hypertension (P = .0001), circulating endothelin 1 (P = .03), and a significant 3.3- and 7.2-fold increase in preproendothelin messenger RNA (mRNA) expression in the placenta and liver (P = .01 and .04). Urinary protein:creatinine ratio was significantly increased in these animals (P = .0007), and circulating factors from these rats stimulated a significant increase in endothelial cell secretion of endothelin 1 (P = .001) in an in vitro assay. Blockade of the endothelin 1 receptor A significantly decreased hypertension (P = .001), circulating endothelin 1, and interleukin 17 (P = .004 and .003), placental preproendothelin mRNA expression (P = .016), and urinary protein:creatinine ratio (P = .007) in rats with hemolysis-elevated liver enzymes-low platelet syndrome. Blockade of the endothelin 1 receptor A significantly decreased hemolysis (P = .009), liver enzymes (P = .011), and significantly increased platelet levels (P = .03) and decreased circulating CD4+ and CD8+ T lymphocytes (P = .0004 and .0001) in rats infused with sFlt-1 and sEndoglin. These data support the hypothesis that endothelin 1 activation has a critical role in pathophysiology of as hemolysis-elevated liver enzymes-low platelet syndrome.

Background Few studies have prospectively evaluated the progression of chronic kidney disease (CKD) in children and adolescents, as well as factors associated with progression. Study Design Prospective multicenter observational cohort study. Setting & Participants 496 children and adolescents with CKD enrolled in the Chronic Kidney Disease in Children (CKiD) Study. Predictors Proteinuria, hypoalbuminemia, blood pressure, dyslipidemia, and anemia. Outcomes Parametric failure-time models were used to characterize adjusted associations between baseline levels and changes in predictors and time to a composite event of renal replacement therapy or 50% decline in glomerular filtration rate (GFR). Results 398 patients had nonglomerular disease and 98 had glomerular disease; of these, 29% and 41%, respectively, progressed to the composite event after median follow-ups of 5.2 and 3.7 years, respectively. Demographic and clinical characteristics and outcomes differed substantially according to the underlying diagnosis; hence, risk factors for progression were assessed in stratified analyses, and formal interactions by diagnosis were performed. Among patients with nonglomerular disease and after adjusting for baseline GFR, times to the composite event were significantly shorter with urinary protein-creatinine ratio > 2mg/mg, hypoalbuminemia, elevated blood pressure, dyslipidemia, male sex, and anemia, by 79%, 69%, 38%, 40%, 38%, and 45%, respectively. Among patients with glomerular disease, urinary protein-creatinine ratio >2mg/mg, hypoalbuminemia, and elevated blood pressure were associated with significantly reduced times to the composite event by 94%, 71%, and 67%, respectively. Variables expressing change in patient clinical status over the initial year of the study contributed significantly to the model, which was cross-validated internally. Limitations Small number of events in glomerular patients and use of internal cross-validation. Conclusions Characterization and modeling of risk factors for CKD progression can be used to predict the extent to which these factors, either alone or in combination, would shorten the time to renal replacement therapy or 50% decline in GFR in children with CKD.