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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.

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 (

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.

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.

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.

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.

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.

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

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.

A 41 year old woman (gravida 1 para 0) presented to the antenatal day unit at 32 weeks’ gestation with a blood pressure of 157/93 mm Hg. Her first recorded BMI in pregnancy was 32. She was a non-smoker and had no known drug allergies. Her history included a thoracic spine fracture and two lumbar disc protrusions that had been asymptomatic since 2002. Earlier in the day, she had a headache that was relieved by paracetamol. Urinalysis showed 1+protein and a urinary protein creatinine ratio of 19 mg/mmol. Further measurements found a blood pressure of 163/96 mm Hg. The patient was admitted to the antenatal ward and started on an antihypertensive. Once her blood pressure was stable she was discharged with regular follow-up. At 34 weeks’ gestation she presented to labour ward triage with a blood pressure of 158/98 m Hg despite antihypertensive treatment. She was admitted to the antenatal ward, her antihypertensive therapy was increased, and a second line agent was started. Urinary protein creatinine ratio was 39 mg/mmol; 24 hour urine collection showed 540 mg/24 hour of protein. An ultrasound scan for growth, liquor volume, and umbilical cord dopplers was normal. Induction of labour was arranged at 37 weeks’ gestation. ### 1. What is the most likely diagnosis and what are the risk factors in this case? #### Short answer Gestational hypertension developing into pre-eclampsia. Risk factors include nulliparity, maternal age >40 years, and body mass index >25. #### Discussion Hypertension can be graded according to severity (box 1).1 The National Institute for Health and Care Excellence (NICE) classifies hypertensive disorder of pregnancy as chronic hypertension, gestational hypertension, or pre-eclampsia.1 Chronic hypertension is defined as pre-existing hypertension or hypertension diagnosed before 20 weeks’ gestation. Gestational hypertension is new …

Introduction Steroid-resistant focal segmental glomerulosclerosis (SR-FSGS) is a common glomerulopathy associated with nephrotic range proteinuria. Treatment goals are reduction in proteinuria, which can delay end-stage renal disease. Methods Patients with SR-FSGS were enrolled in a randomized, double-blind placebo-controlled trial of fresolimumab, a monoclonal anti−transforming growth factor−β antibody, at 1 mg/kg or 4 mg/kg for 112 days, followed double-blind for 252 days (NCT01665391). The primary efficacy endpoint was the percentage of patients achieving partial (50% reduction) or complete (< 300 mg/g Cr) remission of proteinuria. Results Of 36 enrolled patients, 10, 14, and 12 patients received placebo, fresolimumab 1 mg/kg, and fresolimumab 4 mg/kg, respectively. The baseline estimated glomerular filtration rate (eGFR) and urinary protein/creatinine ratio were 63 ml/min/1.73 m2 and 6190 mg/g, respectively. The study was closed before reaching its target of 88 randomized patients. None of the prespecified efficacy endpoints for proteinuria reduction were achieved; however, at day 112, the mean percent change in urinary protein/creatinine ratio (a secondary efficacy endpoint) was –18.5% (P = 0.008), +10.5% (P = 0.52), and +9.0% (P = 0.91) in patients treated with fresolimumab 1 mg/kg, fresolimumab 4 mg/kg, and placebo, respectively. There was a nonsignificant trend toward greater estimated glomerular filtration rate decline in the placebo group compared to either of the fresolimumab-treated arms up to day 252. Discussion The study was underpowered and did not meet the primary or secondary endpoints. However, fresolimumab was well tolerated and is appropriate for continued evaluation in larger studies with adequate power.

Background: The nephrotic syndrome is associated with an increased risk of venous and arterial thrombosis. There are little published data on the distribution, interpretation or determinants of serum D-dimer levels in patients with the nephrotic syndrome. We aimed to describe this relationship. Methods: This was a cross-sectional study of 100 patients with the nephrotic syndrome. Multivariate linear regression was used to evaluate for independent predictors of elevated D-dimer levels. Patients were observed for a period of 2 years after the baseline measurement of D-dimer level to assess for subsequent clinically evident thrombosis. Results: On univariate linear regression, D-dimer elevation was associated with age in years β (95% CI) 0.02 (0.016, 0.03), log-transformed urinary protein:creatinine ratio in g/g 0.439 (0.32, 0.558) and inversely with serum albumin in g/l –0.05 (–0.073, –0.035) and estimated glomerular filtration rate (eGFR) in ml/min/1.73 m2 –0.01 (–0.016, –0.003). On multivariate linear regression, age in years β (95% CI) 0.019 (0.012, 0.026), serum albumin in g/l –0.023 (–0.043, –0.003), and log-transformed urinary protein:creatinine ratio in g/g 0.266 (0.124, 0.408) were independently associated with elevated D-dimer levels. Conclusion: D-dimer levels are commonly raised in the nephrotic syndrome in the absence of clinically evident thrombosis, and are independently associated with age, degree of proteinuria and serum albumin, but not with eGFR. Baseline levels of D-dimer did not predict subsequent episodes of clinically evident thrombosis after 2 years of follow-up.

Catheter-based renal nerve ablation (CBRNA) is a promising new approach to reducing blood pressure in human patients with drug-resistant hypertension.1 The concept behind the method was derived from many decades of work in laboratory animals that showed the significant effect of renal nerves on blood pressure regulation in experimental hypertension and the physiological mechanisms underlying that effect.2 Early indications of efficacy of CBRNA in human trials, however, led to an explosion of interest in the procedure and its rapid application to thousands of patients worldwide.3 Most studies have appropriately focused on the clinical efficacy and safety of the procedure. On the other hand, comparatively little attention has been paid to identifying the specific physiological mechanisms responsible for the persistent fall in blood pressure seen in some (but not all) patients. A highly publicized recent report4 on the first prospective, double-blind, randomized, sham-controlled trial in patients with severe resistant hypertension (Symplicity HTN-3) showed that CBRNA failed to lower blood pressure significantly more than a sham procedure. The report has re-energized consideration of the physiological conditions under which the renal nerves are most likely to affect blood pressure in hypertension and the mechanisms responsible. It also has brought to the foreground questions about precisely how much renal nerve damage is necessary to meaningfully affect blood pressure in hypertensive subjects. Two articles appearing in this issue of the Journal, one by Henegar et al. 5 and one by Linz et al.,6 report data from experimental animal studies that shed significant new light on these issues. The most directly germane is the study by Henegar et al.5 These investigators used a well-characterized dog model of hypertension and a catheter device designed for human applications (St. Jude Medical EnligHTN system) to investigate the acute and chronic effects of renal denervation on blood pressure and other relevant physiological variables. Several valuable features of the study design deserve mention. First, renal denervation was performed in dogs with established hypertension. In most previous work on renal denervation in laboratory animals, denervation was done before the onset of hypertension. The approach used by Henegar et al. is more clinically relevant and recognizes the well-known fact that many interventions that mitigate hypertension development have little or no effect on blood pressure once hypertension is established. Second, the dogs were made hypertensive by high-fat feeding; this has clinical relevance because many patients with drug-resistant hypertension are overweight.7 Third, the investigators did a thorough job of quantifying the damage to the renal nerves caused by the ablation procedure using both histology and measurement of renal content of norepinephrine. This is important because at present it is not clear how much damage to the renal nerves is necessary to affect blood pressure, and similar quantification is not possible on a routine basis in the clinical setting. Last, but not least, blood pressure measurements were performed using repeated sampling for 18 hours a day for the duration of the study. This kind of recording (roughly equivalent to ambulatory measurements in humans) is critical to detect the small changes in blood pressure typically seen after renal denervation. The main findings of the Henegar et al. study were that CBRNA lowered BP significantly and persistently in obese hypertensive dogs without a major change in renal function and that this was associated with relatively modest damage to the renal nerves (approximately 42% loss as assessed by histology or norepinephrine content). Although the experiments were not designed specifically to explore the mechanisms responsible for the fall in blood pressure, some of the data collected are informative. No significant changes in heart rate, glomerular filtration rate, plasma renin activity, extracellular fluid volume, plasma volume (estimated from plasma protein concentration), plasma aldosterone, or plasma cortisol were found after CBRNA. Interestingly, the fall in blood pressure did not reach a peak steady-state value until several days after the procedure, suggesting the involvement of more slowly acting blood pressure control mechanisms. Similarly detailed time-course data are virtually absent from clinical studies. It is of substantial importance that only partial loss of renal nerve integrity was required to significantly reduce blood pressure in this study. Moreover, there was a trend (although not statistically significant) for the antihypertensive effect of CBRNA to correlate with the degree of denervation. A noteworthy limitation of all human trials of CBRNA to date (including Symplicity HTN-3) is a lack of data on the completeness of denervation. The little evidence we have in human patients indicates that denervation is far from complete, even when the procedure is performed by experts.8 This could be a major factor in explaining why blood pressure responses vary widely between patients. A logical (although not necessarily correct) assumption is that the magnitude of fall in blood pressure after CBRNA in any given subject will depend on the degree to which their blood pressure is being controlled by physiological mechanisms responsive to renal sympathetic nerve activity (RSNA) (e.g., renin release, sodium reabsorption, and renal vascular resistance). Elegant investigations in human subjects by Esler and colleagues reveal that RSNA is increased in some, but not all, patients with essential hypertension.9 To our knowledge there is no direct evidence for renal sympathetic overactivity in drug-resistant hypertension, but such patients often are obese, and many obese individuals have elevated RSNA.10 One clear link between obesity, sympathetic overactivity, and hypertension is obstructive sleep apnea (OSA),11 a prevalent condition in patients with drug-resistant hypertension.12 Therefore it is important to determine the impact of the renal sympathetic nerves on physiological responses to OSA, including systemic blood pressure. This was the goal of a paper by Linz et al. 6 They used an acute model of OSA in anesthetized pigs that involved repetitive obstruction of the trachea with negative pressure (NTP) every 15 minutes for 4 hours. They continuously recorded blood pressure and renal and femoral blood flow and determined plasma renin activity, plasma aldosterone, urinary protein/creatinine ratio, and glomerular filtration rate several times during the 4-hour protocol. In a subgroup of pigs, the effects of NTP were investigated after renal denervation was performed using the standard surgical approach of stripping away visible nerves and applying a phenol solution to the perivascular region. Another group of pigs was pretreated with the angiotensin receptor blocker irbesartan before being subjected to NTP. The results were striking: although the interapneic values of the measured variables were not affected by renal denervation, the marked postapneic increases in blood pressure and renal vascular resistance seen in untreated pigs were significantly attenuated by renal denervation (but not by irbesartan). Likewise, the gradual increments in plasma renin activity, plasma aldosterone, and urinary protein/creatinine ratio seen in control pigs during repetitive NTP were nearly eliminated in pigs with renal denervation. Although this was an acute protocol and renal denervation was surgical rather than by catheter, the results highlight some important issues discussed earlier. First, the findings support the common-sense view that the magnitude of any physiological response to renal denervation will depend on the level of renal sympathetic activity at the time of denervation. Accordingly, identification of patients likely to respond to CBRNA should include consideration of other pathologies (such as obesity and OSA) that are associated with increased RSNA. Second, it is notable that a large component of the systemic blood pressure response to NTP appears to depend on neurogenic changes in renal vascular resistance (femoral resistance changed very little). This suggests that under some conditions the mechanism of the antihypertensive response to CBRNA may simply be a reduced contribution of the renal vasculature to total peripheral resistance. Of course the impact of renal denervation on hormones and renal injury in this study also identify other potential mechanisms by which renal nerves could influence long-term blood pressure regulation. Collectively these articles show that well-designed, animal-based experimental physiology can importantly complement the results of clinical trials and clinical research in our efforts to establish the clinical utility (if any) of CBRNA in treating hypertension.

Background Measurement of protein excretion is not only used for diagnostic purpose but also to monitor disease severity and prognosis in children with nephrotic syndrome (NS). The common method to measure proteinuria is 24-hour urine collection. However, 24-hour urine collection is cumbersome, time consuming, and tedious. An alternative simplified method is the measurement of protein/creatinine ratio in single-voided urine specimens. Objective The aim of this study was to determine whether urine protein/creatinine ratio is accurate to predict pathologic (> 100 mg/m2/day) and massive proteinuria (> 1 g/m2/day). Methods Seventy single voided and 24-hour urine specimens were collected from children aged 3-18 years. The relationship between urinary protein/creatinine ratio and total daily protein excretion was calculated using correlation and linear regression analysis. Diagnostic test was conducted to estimate the accuracy of protein/creatinine ratio for the diagnosis of pathologic and massive proteinuria in NS. Results Correlation coefficient between quantity of protein in 24-hour urine specimens and protein/creatinine ratio in singlevoided urine specimens was 0.96 (R2=0.93). Both sensitivity and specificity of urinary protein/creatinine ratio were 87% in diagnosing pathologic proteinuria, whereas the sensitivity and specificity of the ratio to predict massive proteinuria were 88% and 91%, respectively. Conclusion The urinary protein/creatinine ratio in single voided urine specimen has a good accuracy to predict pathologic and massive proteinuria in children with NS aged 3-18 years.

Hypertension causes proteinuria and is an important factor in the progress of renal dysfunction. Increases in various proteins in urine are caused by malfunction of the glomerulus and the renal tubules. In the present study, the effects of hypertension on urinary excretion levels of various proteins were investigated to show the tubular cell malfunction in hypertensive patients.The subjects included 55 non-diabetic hypertensive patients without previous treatment and 42 normotensive individuals without microalbuminuria. Total urinary protein/creatinine ratio was measured, and urinary proteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).Total urinary protein/creatinine ratio was higher in hypertensive patients than in normotensive individuals (122.0+/-11.0 vs. 60.6+/-3.1 mg/gCr; p0.001). SDS-PAGE resolved 15 protein fractions from the urine of both groups. Thirteen fractions were more intensely stained in samples from the hypertensive than from the normotensive. Two fractions did not differ between the groups. Hypertension increased the urinary excretion of various proteins including proteins of less than 40 kDa, called tubular proteins, in addition to albumin.Hypertension differently influenced the excretion of each urinary protein fraction. Tubular malfunction should be considered in hypertensive patients in addition to glomerular malfunction.

Increased severity of glomerulonephritis in C-C chemokine receptor 2 knockout mice. Background The C-C chemokine receptor 2 (CCR2) is expressed on monocytes and facilitates monocyte migration. CCR2 is a prominent receptor for monocyte chemoattractant protein-1 (MCP-1). This chemokine recruits monocytes to sites of inflammation. It has been suggested that CCR2 and its ligand, MCP-1, play a role in the pathogenesis of glomerulonephritis. The goal of this study was to determine the contribution of CCR2 in a murine model of accelerated nephrotoxic nephritis. We measured the extent of development of renal disease in CCR2 wild-type and knockout mice after the administration of antiglomerular basement membrane antibody. Methods Eight groups of animals were treated ( N = 10 per group). Four days after IgG immunization, CCR2 wild-type and knockout mice received control serum or nephrotoxic serum. The urinary protein/creatinine ratio was measured on days 1 and 3; plasma and kidneys were collected on days 4 and 7. Kidneys were evaluated by light microscopy, immunohistochemistry, and immunofluorescence. The genotype of mice was confirmed by tissue analysis. Results Protective effects of CCR2 knockout on the urinary protein/creatinine ratio were observed on day 1, as values for this parameter were significantly lower (35 ± 3.6) than in nephritic wild-type mice (50 ± 6.8). There was a marked increase in proteinuria in nephritic wild-type mice on day 1 compared with vehicle-treated, wild-type animals (5 ± 1.0). On day 3, the ameliorative effects of CCR2 knockout were not observed; the increase in the urinary protein/creatinine ratio was similar in nephritic CCR2 wild-type (92 ± 11.2) and knockout mice (102 ± 9.2). Plasma markers of disease were evaluated on days 4 and 7. At these time points, there were no beneficial effects of CCR2 receptor knockout on plasma levels of urea nitrogen, creatinine, albumin, or cholesterol. On day 7, blood urea nitrogen (248 ± 19.9 mg/dL) and plasma cholesterol were higher in nephritic CCR2 knockout mice than in wild-type mice (142 ± 41.7 mg/dL) that received nephrotoxic serum. Histopathologic injury was more severe in nephritic CCR2 knockout mice than nephritic wild-type mice on day 4 (3.1 ± 0.3 vs. 2.0 ± 0.3) and day 7 (3.6 ± 0.2 vs. 2.9 ± 0.3). By immunohistochemical analysis at day 4, there were significantly fewer mac-2–positive cells, representative of macrophages in the glomeruli of nephritic CCR2 knockout (2.1 ± 0.6) mice than nephritic wild-type (3.9 ± 0.5) animals. By indirect immunofluorescence, there was a moderate, diffuse linear IgG deposition of equivalent severity present in glomeruli of both wild-type and CCR2 knockout nephritic mice. Conclusion These results suggest that our strategy was successful in reducing macrophage infiltration, but this model of glomerulonephritis is not solely dependent on the presence of CCR2 for progression of disease. After a transient ameliorative effect on proteinuria, CCR2 knockout led to more severe injury in nephritic mice. This raises the intriguing possibility that a CCR2 gene product ameliorates glomerulonephritis in this murine model. Although effects that occur in chemokine knockout mice are not equivalent to those expected with prolonged use of a chemokine antagonist, this study may nevertheless have implications for consideration of long-term use of chemokine antagonists in renal disease.

BACKGROUND: Podocyte depletion causes glomerulosclerosis, and persistent podocyte loss drives progression to ESKD. Urinary sediment podocin (u-sed Pod) mRNA excretion and urinary supernatant podocalyxin (u-sup PCX) protein have been used to monitor disease activity in glomerular diseases. However, the differences in these markers among pathologies have not been investigated. We examined the roles of these markers in kidney diseases. METHODS: From January 2013 to March 2016, early morning urine samples were collected from 12 healthy controls and 172 patients with kidney disease (n=15 patients with minor glomerular abnormality with mild proteinuria and/or microscopic hematuria, n=15 with minimal change nephrotic syndrome [MCNS], n=15 with membranous nephropathy [MN], n=60 with IgA nephropathy [IgAN], n=19 with crescentic GN [Cres GN], n=10 with lupus nephritis [LN], and n=38 with other kidney diseases). We examined u-sed Pod mRNA excretion, u-sup PCX protein, and the urinary protein-creatinine ratio (u-PCR). RESULTS: u-sed Pod mRNA excretion was significantly correlated with u-sup PCX protein (r=0.37, P

We present a case of pseudo–acute kidney injury (AKI) following capmatinib therapy in an 84-year-old man with combined non–small cell (adenocarcinoma) and small cell lung cancer with MET exon 14–skipping mutation. His past medical history was significant for chronic kidney disease stage 3 with a baseline serum creatinine (Scr) of 1.6 mg/dL rising to 2.44 mg/dL (estimated glomerular filtration rate [GFR] 24 mL/min/1.73 m2) while on capmatinib. Scr improved to 1.84 mg/dL with the cessation of capmatinib but rose again to 2.22 mg/dL upon resumption of therapy. Further investigation with cystatin C and renal iothalamate clearance showed that despite fluctuation in Scr levels, there was not much variation in GFR calculated using these methods. Urinalysis and urinary protein-creatinine ratio were unremarkable. Treatment with capmatinib was continued at reduced dose and a third instance of rise in Scr was observed, followed by a spontaneous return to baseline. Thus, MET inhibitor therapy can result in an asymptomatic rise in Scr, and it must be distinguished from AKI with more accurate non–creatinine-based methods to evaluate GFR. This could spare such patients from invasive diagnostic tests, such as a kidney biopsy, and premature cessation of prognostically important cancer therapies.

Nephrotic syndrome (NS) is a glomerular disease that is most often found in children with proteinuric as clinical manifestation. Gambier extract is a traditional medicine that has antioxidant effect. Its use to treat proteinuric has never been done. Therefore, we conducted an analytical study on the effect of gambier on proteinuric and superoxide dismutase (SOD) activity in proteinuric Wistar rat’s model. This research is an experimental study with a posttest control group design. The aim is analyzing the effect of giving gambier extract in decreasing urinary protein creatinine ratio and increasing SOD activity. Male Wistar rats were given an injection of puromycin aminonucleoside 1.5mg/100g body weight (BW), subcutaneously for 5 consecutive days for being nephrosis. The experimental animals in this study were divided into four groups: K1, the control group, consist of group of rats that were injected with 0.15ml/100 g BW of aquabidest and not given gambier extract. While K2 group consist of rats induced by Puromycin and given 1 ml of aquabidest. K3 consist of groups of rats induced by Puromycin and then given gambier extract 26mg/200g BW. Group K4 consist of rats induced by Puromycin and then given 80mg/200g BW of gambier extract. The four groups were given treatment for 14 days, after which the rats were placed in a metabolic cage for 24 hours to collect urine samples and then knocked down with ketamine for intra-cardiac blood collection. The results of this study showed differences between the four groups of rats in terms of the mean urine protein/creatinine ratio (p=0.015) and SOD activity (p=0.036). Groups of rats that were given gambier extracts 80mg/200g BW had lower urine protein / creatinine ratio and higher SOD activity. Therapy of gambier 80 mg/200g BW is better in managing proteinuric compared to 26mg/200g.

Introduction. Percentage of galactose-deficient IgA1 (Gd-IgA1) relative to total IgA in serum was recently reported to correlate with proteinuria at time of sampling and during follow-up for pediatric and adult patients with IgA nephropathy. We sought to determine whether this association exists in another cohort of pediatric patients with IgA nephropathy.Methods. Subjects were younger than 18 years at entry. Blood samples were collected on one or more occasions for determination of serum total IgA and Gd-IgA1. Gd-IgA1 was expressed as serum level and percent of total IgA. Urinary protein/creatinine ratio was calculated for random specimens. Spearman’s correlation coefficients assessed the relationship between study variables.Results. The cohort had 29 Caucasians and 11 African-Americans with a male : female ratio of 1.9 : 1. Mean age at diagnosis was 11.7 ± 3.7 years. No statistically significant correlation was identified between serum total IgA, Gd-IgA1, or percent Gd-IgA1 versus urinary protein/creatinine ratio determined contemporaneously with biopsy or between average serum Gd-IgA1 or average percent Gd-IgA1 and time-average urinary protein/creatinine ratio.Conclusion. The magnitude of proteinuria in this cohort of pediatric patients with IgA nephropathy was influenced by factors other than Gd-IgA1 level, consistent with the proposed multi-hit pathogenetic pathways for this renal disease.

The study was carried out to evaluate the possible effects of hormone replacement therapy (HRT) on renal functions in postmenopausal women.A total of 85 postmenopausal women without a history of medical illness were enrolled in the study. They were divided into HRT users and control groups. After 30 weeks of HRT use, the changes in serum urea, creatinine, uric acid, urinary protein, urinary creatinine, urinary protein/creatinine ratio and glomerular filtration rate (GFR) (mL/min/1.73 m(2)) were evaluated.HRT was associated with statistically significant increases in glomerular filtration rate (p0.01), while serum urea, creatinine, uric acid, urinary protein, urinary creatinine and urinary protein/creatinine ratio did not change significantly in both groups.In our study, we suggested that usage of hormone replacement therapy appeared to affect renal functions in postmenopausal women. There were beneficial effects of HRT on GFR in our postmenopausal patients. HRT may have possible protective mechanisms for kidney against adverse effects of aging.

Data reproducibility and single-center bias are concerns in preclinical research and compromise translation from animal to human. Multicenter preclinical randomized controlled trials (pRCT) may reduce the gap between experimental studies and RCT and improve the predictability of results, for example Jak1/2 inhibition in lupus nephritis. To evaluate this, we conducted the first pRCT in the kidney domain at two Spanish and two German academic sites. Eligible MRL/MpJ-Faslpr mice (female, age13-14 weeks, stress scores of less than two and no visible tumor or signs of infection) were equally randomized to either oral treatment with the Jak1/2 inhibitor baricitinib or vehicle for four weeks. Central blinded histology analysis was performed at an independent fifth site. The primary endpoint was the urinary protein/creatinine ratio. Baricitinib treatment did not significantly affect proteinuria, histological markers of activity and chronicity, or the glomerular filtration rate but significantly improved plasma autoantibody levels and lymphadenopathy. Data heterogeneity was noted across the different centers referring in part to phenotype differences between MRL/MpJ-Faslpr mice bred at different sites, mimicking well patient phenotype diversity in lupus trials. Multicenter pRCT can overcome single-center bias at the cost of increasing variability and reducing effect size. Thus, our pRCT predicts a low effect size of baricitinib treatment on human lupus nephritis in heterogeneous study populations.

We examined the relative feasibility of using random urinary dipstick testing and urinary protein/creatinine ratios in the quantitation of proteinuria. Sixty-four children with relapsing nephrotic syndrome, ranging in age from 1 1/2 to 16 years, contributed 145 timed urine collections and 150 random specimens, which were analyzed by urinary protein dipstick, quantitation of protein and creatinine, or both. Total protein excretion was expressed as grams per surface area per day and the urinary protein/creatinine ratio as milligrams of protein per milligram of creatinine. Degrees of proteinuria were designated as physiologic (less than 0.1 gm/m2/day), intermediate (greater than 0.1 and less than 1.0 gm/m2/day), or nephrotic (greater than 1.0 gm/m2/day). The log regression analysis of the 24-hour urinary protein/creatinine ratio (y) and total protein excretion (x) was highly significant (r = 0.97; p less than 0.001). The upper and lower confidence limits of the urinary protein/creatinine ratio (1.0 and 0.1, respectively) closely approximated the designations for nephrotic and physiologic proteinuria, respectively. These values were therefore used to classify degrees of proteinuria by the urine protein/creatinine ratio. The validity of these tests was assessed by sensitivity, specificity, and predictive value, and compared with that of random testing by urinary dipstick. The urinary protein/creatinine ratio offered good reliability as a test for classifying degrees of proteinuria and accurately predicting nephrotic and physiologic proteinuria. The random dipstick testing was reliable only when results were distinctly positive and when sensitivity and specificity were low. The error in the total protein excretion value that was imposed by collection errors with high and low variations in the creatinine value (57% of samples) was largely corrected by normalization of the data by log transformation. When controlled for creatinine excretion, linear regression analysis allowed calculation of total protein excretion (TP) from the urinary protein/creatinine ratio (U P/Cr) by the following equation: TP (gm/m2/day) = 0.63 (U P/Cr) at all levels of proteinuria. The random urinary protein/creatinine ratio appeared to offer the most sensitive test for classification of proteinuria in children with nephrosis, with the advantages of ease and expediency not afforded by the 24-hour urine quantitation.

Diabetic nephropathy (DN) is one of the major complications of diabetes and contributes significantly towards end-stage renal disease. Previous studies have identified the gene encoding carnosinase (CN-1) as a predisposing factor for DN. Despite this fact, the relationship of the level of serum CN-1 and the progression of DN remains uninvestigated. Thus, the proposed study focused on clarifying the relationship among serum CN-1, indicators of renal function and tissue injury, and the progression of DN. A total of 14 patients with minimal changes disease (MCD) and 37 patients with DN were enrolled in the study. Additionally, 20 healthy volunteers were recruited as control. Further, DN patients were classified according to urinary albumin excretion rate into two groups: DN with microalbuminuria (n = 11) and DN with macroalbuminuria (n = 26). Clinical indicators including urinary protein components, serum carnosine concentration, serum CN-1 concentration and activity, and renal biopsy tissue injury indexes were included for analyzation. The serum CN-1 concentration and activity were observed to be the highest, but the serum carnosine concentration was the lowest in DN macroalbuminuria group. Moreover, within DN group, the concentration of serum CN-1 was positively correlated with uric acid (UA, r = 0.376, p = 0.026) and serum creatinine (SCr, r = 0.399, p = 0.018) and negatively correlated with serum albumin (Alb, r = − 0.348, p = 0.041) and estimated glomerular filtration rate (eGRF, r = − 0.432, p = 0.010). Furthermore, the concentration of serum CN-1 was discovered to be positively correlated with indicators including 24-h urinary protein–creatinine ratio (24 h-U-PRO/CRE, r = 0.528, p = 0.001), urinary albumin-to-creatinine ratio (Alb/CRE, r = 0.671, p = 0.000), urinary transferrin (TRF, r = 0.658, p = 0.000), retinol-binding protein (RBP, r = 0.523, p = 0.001), N-acetyl-glycosaminidase (NAG, r = 0.381, p = 0.024), immunoglobulin G (IgG, r = 0.522, p = 0.001), cystatin C (Cys-C, r = 0.539, p = 0.001), beta-2-microglobulin (β2-MG, r = 0.437, p = 0.009), and alpha-1-macroglobulin (α1-MG, r = 0.480, p = 0.004). Besides, in DN with macroalbuminuria group, serum CN-1 also showed a positive correlation with indicators of fibrosis, oxidative stress, and renal tubular injury. Taken together, our data suggested that the level of CN-1 was increased as clinical DN progressed. Thus, the level of serum CN-1 might be an important character during the occurrence and progression of DN. Our study will contribute significantly to future studies focused on dissecting the underlying mechanism of DN.

Background: Lupus nephritis (LN) is a common and serious manifestation of SLE, occurring in more than half of patients with SLE during their course of illness, in 10–25% of such patients, kidney disorder progresses to end-stage renal disease (ESRD). Objective: To determine the predictors of remission in patients with biopsy-proven lupus nephritis, and to assess the long-term renal remission rate in our lupus nephritis patients. Patients and Methods: This is a retrospective observational study carried out at the Rheumatology and Nephrology Units, Internal Medicine Department, Menoufia and Mansoura Universities Hospitals, Egypt for a 1-year duration between 1 June 2019 and 1 June 2020. A total of 60 patients with biopsy-proven LN were studied. Results: In the current study, after six months of follow-up, about two-thirds of patients achieved remission. The urinary protein creatinine ratio (UPCR) of 4.9 g/g, systemic lupus erythematosus disease activity index (SLEDAI) of 20 and Hb of 8.8 g/dl at the third month are valuable for predicting remission at the sixth month in active lupus nephritis. On multivariate analysis, serum creatinine (SCr) at the time of diagnosis is the only independent predictor of remission (complete or partial) at 6 months. According to the receiver operating characteristic curve, the cut-off value of SCr ≤ 2.9 mg/dL with 100% specificity and 98 % sensitivity was a predictor for renal remission. Conclusion:The UPCR of 4.9 g/g, SLEDAI of 20 and Hb of 8.8 g/dl at the third month are valuable for predicting remission at the sixth month in active lupus nephritis. Serum creatinine level ≤2.9 mg/dL at the time of diagnosis was the only independent predictor of complete remission at 6 months.

Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and diuretics may exert synergistic antiproteinuric effects. Eighteen patients with a proteinuria >1 g/24 h after 6 mo of treatment with ramipril at 5 mg/d were assigned to receive in random order ramipril at 10 mg/d, valsartan at 160 mg/d, or combined ramipril at 5 mg/d and valsartan at 80 mg/d in addition to their antihypertensive treatment. The treatment periods lasted 4 wk and were separated by a 4-wk washout with ramipril at 5 mg/d. At the end of this crossover sequence, patients received combined ramipril at 5 mg/d, valsartan at 80 mg/d, and an increased furosemide dosage for an additional 4-wk period. The primary end point was the urinary protein/creatinine ratio for two 24-h urine collections at the end of each treatment period. No significant differences were noted between the study end points of the ramipril 10, valsartan 160, and combined ramipril 5 and valsartan 80 treatment groups. However, the urinary protein/creatinine ratio was lower with combined ramipril 5 and valsartan 80-increased furosemide dosage than with valsartan 160 and combined ramipril 5 and valsartan 80, with a similar tendency compared with ramipril 10. Combined ramipril 5 and valsartan 80-increased furosemide dosage decreased systolic home BP and increased serum creatinine but did not significantly increase the number of symptomatic hypotension cases compared with the other three treatments. Thus, in patients with severe proteinuria and hypertension, a cautious increase in diuretic dosage in addition to combined angiotensin-converting enzyme inhibitors and angiotensin receptor blockers decreases proteinuria and BP but may expose the patient to prerenal failure.

Background: Angiotensin II-Receptor Blockers (ARBs) has a questionable nephroprotective effect especially in diabetic nephropathy. Nephrin protein molecules exist in the slit diaphragm of the glomerular filtration membrane and control the passage of plasma protein. Aim of Study: To examine the possible role of Nephrin in the pathogenesis of diabetic nephropathy and the protective effect of ATII-RB (candesartan) on diabetic nephropathy. Material and Methods: Thirty-two male rats were used in this experiment. Half of the rats were fed a high-fat diet (HFD) and the other half were fed a standard diet for 4 weeks. A model of diabetic nephropathy (DN) was created by a 35mg/kg intraperitoneal dose of Streptozotocin (STZ) in the HFD-fed rats. Then the rats were divided into four groups (8 rats/group). (1) Normal control (NC) group; (2) Diabetic nephropathy (DN) group; (3) ARB-treated NC group: Normal rats were treated with the ARB (Candesartan Cilexetil), in a dose 0.1mg/kg; (4) ARB-treated DN group: The rats with DN and received the above dose of candesartan for 4 weeks. The urine was collected to measure the urine flow rate, urinary concentrations of Nephrin, creatinine, and protein. Blood samples were used to measure urea, creatinine, glucose, insulin, and the homeostatic model assessment (HOMA-IR). Then renal tissue samples were used to measure Superoxide dismutase (SOD) activity and Malondialdehyde (MDA) in addition to histopathological examination. The mean arterial blood pressure (MABP) was also recorded. Results: Candesartan treatment in the DN group showed significant reductions of glucose, HOMA-IR, amelioration of renal antioxidant system, reductions in creatinine, reduction of proteinuria, reduction of urinary Nephrin, and MABP. Histological improvement was also detected in the form of mild glomerulosclerosis and interstitial fibrosis. The urinary Nephrin was 90 times high in the condition of DN. This huge rise of urinary Nephrin was significantly reduced by Cande-sartan treatment. Moreover, in the DN group the urinary Nephrin level showed a significant correlation with glucose level, serum creatinine, urinary protein-creatinine ratio, and MABP.Conclusion: ATII-RB could reduce urinary Nephrin ex-cretion and possibly alters its expression through its inhibitory effect on the reactive oxygen species, the Renin-Angiotensin-Aldosterone system and subsequently maintains the normal physiological activity of podocytes in rats with STZ-induced diabetic nephropathy.

Chronic kidney disease (CKD) is a disease characterized by the gradual and functional loss of renal mass, affecting its physiology leading to clinical manifestations. The CKD reaches dogs of several breeds causing important clinical alterations. Some laboratory tests are determinant for the correct diagnosis and thus for the implementation of the most appropriate treatment. The urinalysis, urinary protein-creatinine ratio (UPC) evaluation, urea, and creatinine dosage together with the symmetric dimethylarginine dosage (SDMA), urinary tract ultrasonography and blood pressure monitoring, are the main methods used for diagnosis. In this way, this work aimed to report a case of CKD in a Teckel dog attended at the Veterinary Hospital of the Federal University of Jataí (UFJ), discussing the main clinical manifestations, laboratory, and image alterations, as well as the correct staging according to IRIS (Interest Renal International Society), from which the best treatment option to be adopted is determined.