Measurement Of Urinary Protein Research Articles

The interference and elimination of nitrite on determination of total urinary protein by Pyrogallol Red–Molybdate method

BackgroundSome urine samples showed negative values of total urinary protein by Pyrogallol red–molybdate (PRM) method. Interestingly, these samples showed notably high levels of nitrite in the urine dipstick test. MethodsA total of 120 urine samples were collected and categorized into four groups (0 - < 100, 100-<500, 500-<1000, ≥1000 mg/L) based on total urinary protein concentration. Various concentrations of nitrite (2, 10, 50, 100, and 200 mg/L) were added to urine samples to investigate potential interference of nitrite in total urinary protein measurement by the PRM method. Additionally, different concentrations of L-ascorbic acid (100, 500, 1000, and 2000 mg/L) were added to urine-nitrite mixtures to explore the possibility of reversing the interference effects. Results2 mg/L nitrite had no impact on the test results.10 mg/L nitrite only showed significant effects on the detection results among the groups with 0 - < 100 and 100-<500 mg/L (P < 0.05). 200 mg/L nitrite caused a noticeable decrease in the urinary protein detection results of the four groups (0 - < 100, 100-<500, 500-<1000, ≥1000 mg/L), and the concentrations were reduced to 2.7 %, 26.85 %, 75.22 %, and 89.33 % of their original levels, respectively. 500 mg/L L-ascorbic acid effectively eliminated the interference from 200 mg/L nitrite and almost had no effect on detection. ConclusionsNitrite had negative effect on the detection of total urinary protein by PRM method and L-ascorbic acid was effective in counteracting the interference caused by nitrite.

CYSTOCENTESIS AND URINALYSIS IN ZOOMEDICINE: AN UNDERESTIMATED TOOL FOR LARGE FELID STANDARD HEALTH CHECKS.

Chronic kidney disease (CKD) is a prevalent disease among felids; yet its origin is still poorly understood, and the disease often remains asymptomatic for years, underscoring the need for early diagnosis. This study aimed to investigate the diagnostic value of urinalysis in accurately staging CKD, particularly as routine health checks in large felids often overlook its significance. In this research, ultrasound-guided cystocentesis (UGC) was performed on 50 captive nondomestic felids during routine veterinary health checks under general anesthesia. Urinalysis included microscopic examination of the sediment, measurement of urine specific gravity (USG) and protein to creatinine ratio (UPC). Additional serum kidney markers, such as creatinine and symmetric dimethylarginine, were compared with USG and UPC to assess their diagnostic value as urinary biomarkers. The results demonstrated proteinuria (UPC > 0.4) or borderline proteinuria (UPC 0.2-0.4) in 49% of the animals. Among these cases, 62% were of renal origin, and 38% were postrenal causes. USG was significantly higher in felids with borderline proteinuria compared to those with proteinuria. A moderate, but significant negative correlation between serum parameters and USG was observed, emphasizing the importance of assessing both diagnostic parameters during kidney evaluations. Additionally, felids with CKD have an increased risk of urinary tract infections, necessitating microscopic urinalysis and bacterial culture analysis. Abnormalities, including hematuria, pyuria, crystalluria, and bacteriuria, were found in approximately 38% of cases through microscopical examination of urine. No complications associated with UGC were observed and abnormal findings were detected in 60% of the cases. Based on these results, the authors recommend the inclusion of UGC and urinalysis as standard diagnostic tools in general health checks for nondomestic felids. This approach provides valuable insights into the early detection and staging of CKD, supporting early intervention and supportive medical care to prolong renal health in these animals.

APOL1 High-Risk Genotype is Not Associated With New or Worsening of Proteinuria or Kidney Function Decline Following COVID-19 Vaccination

SARS-CoV-2 infection increases systemic inflammatory cytokines which act as a second-hit driver of Apolipoprotein L1 (APOL1)-mediated collapsing glomerulopathy. SARS-CoV-2 vaccination also increases cytokines. Recent reports of new glomerular disease in individuals with APOL1 high-risk genotype (HRG) following SARS-CoV-2 vaccination raised the concern SARS-CoV-2 vaccination may also act as a second-hit driver of APOL1-mediated glomerulopathy. We screened 1507 adults in the Duke's Measurement to Understand Reclassification of Disease of Cabarrus and Kannapolis (MURDOCK) registry and enrolled 105 eligible participants with available SARS-CoV-2 vaccination data, prevaccination and postvaccination serum creatinine, and urine protein measurements. Paired data were stratified by number of APOL1 risk alleles (RAs) and compared within groups using Wilcoxon signed rank test and across groups by analysis of variance. Among 105 participants, 30 (28.6%) had 2, 39 (37.1%) had 1, and 36 (34.3%) had 0 APOL1 RA. Most of the participants (94%) received at least 2 doses of vaccine. Most (98%) received the BNT162B2 (Pfizer) or mRNA-1273 (Moderna) vaccine. On average, the prevaccine and postvaccine laboratory samples were drawn 648 days apart. There were no detectable differences between pre- and post-serum creatinine or pre- and post-urine albumin creatinine ratio irrespective of the participants' APOL1 genotype. Finally, most participants with APOL1 RA had the most common haplotype (E150, I228, and K255) and lacked the recently described protective N264K haplotype. In this observational study, APOL1 HRG is not associated with new or worsening of proteinuria or decline in kidney function following SARS-CoV-2 vaccination. Validation of this result in larger cohorts would further support the renal safety of SARS-CoV-2 vaccine in individuals with APOL1 HRG.

The EFLM European Urinalysis Guideline 2023.

The EFLM Task and Finish Group Urinalysis has updated the ECLM European Urinalysis Guidelines (2000) on urinalysis and urine bacterial culture, to improve accuracy of these examinations in European clinical laboratories, and to support diagnostic industry to develop new technologies. Graded recommendations were built in the following areas. Strategies of urine testing are described to patients with complicated or uncomplicated urinary tract infection (UTI), and high or low-risk to kidney disease. Patient preparation, and urine collection are supported with two quality indicators: contamination rate (cultures), and density of urine (chemistry, particles). Measurements of both urine albumin and α1-microglobulin are recommended for sensitive detection of kidney disease in high-risk patients. Performance specifications are given for urine protein measurements and quality control of multiproperty strip tests. Procedures for microscopy are reviewed for diagnostic urine particles, including urine bacteria. Technologies in automated particle counting and visual microscopy are updated with advice how to verify new instruments with the reference microscopy. Chromogenic agar is recommended as primary medium in urine cultures. Limits of significant growth are reviewed, with an optimised workflow for routine specimens, using leukocyturia to reduce less important antimicrobial susceptibility testing. Automation in bacteriology is encouraged to shorten turn-around times. Matrix assisted laser desorption ionization time-of-flight mass spectrometry is applicable for rapid identification of uropathogens. Aerococcus urinae, A. sanguinicola and Actinotignum schaalii are taken into the list of uropathogens. A reference examination procedure was developed for urine bacterial cultures.

Retrospective study assessing the use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers to reduce toxicity from tyrosine kinase inhibitors in metastatic renal cell carcinoma.

411 Background: The main toxicities associated with tyrosine-kinase inhibitors (TKIs) in the treatment of renal cell carcinoma (RCC) are proteinuria and hypertension. Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have established reno-protective and anti-hypertensive effects and can help with toxicity in mRCC. We hypothesize that use of ACEIs/ARBs is an effective method to decrease the degree of proteinuria and hypertension in patients treated with TKIs for metastatic/advanced renal cell carcinoma (mRCC). Methods: Single Institution retrospective study; mRCC patients (pts) who received TKI and ACEIs/ARBs and had urine protein measurements available at baseline and at 4-6 wk follow up post ACEs/ARBs were included in the analysis. Primary endpoints included improvement in grade of proteinuria and BP in mRCC pts on TKI treatment at baseline and with addition of ACEIs/ARBs. Secondary endpoints included number of dose interruptions (DI), BUN and creatinine changes. Paired statistical tests were used to compare the selected outcome variables between baseline and post ACE/ARB measures: for example, nonparametric Wilcoxon Signed-rank test for paired quantitative data and McNemar test for paired binary data. Results: Out of 71 screened patients between 2020-2023, N of 22 mRCC (N=22, 72.7% male, 77.3% white; 9% Hispanic; N=14 for TKI+ immunotherapy; N=8 TKI alone) pts were selected. ACEIs/ARBs treatment was associated with significantly reduced levels of proteinuria at 4–6wk follow-up. At baseline vs. follow-up, pts were found to have significantly lower proteinuria overall after ACEI/ARBs (p=0.0147), and 45.4% of pts had clinically insignificant proteinuria vs. 22.7% at baseline. Additionally, DI rates for TKI were significantly lower for pts placed on ACEIs/ARBs, with an 81% chance that pts with prior DI would not experience similar event in the follow-up period (p=0.003). Reductions in BP, creatinine, and TKI dosing were seen but not statistically significant (p&gt;0.05 for all measures). Conclusions: In our small study, degree of proteinuria was notably reduced with administration of ACEIs/ARBs. Further findings show fewer DI of TKIs with ACEIs/ARBs use. Our findings suggest a potential role for ACEIs/ARBs in managing toxicity in patients undergoing TKI based therapy for mRCC. Future studies are needed to evaluate the use of ACE/ARB from the time of initiation of TKI based therapy to reduce the toxicities and improve the adherence to mRCC treatment which may result in better outcomes.

Proteinuria among Pregnant Women Admitted to the Department of Obstetrics and Gynaecology of a Tertiary Care Centre.

Proteinuria is usually related with preeclampsia during pregnancy, although it can also be caused by other conditions such as renal disease or isolated proteinuria. Proteinuria during pregnancy can result in adverse fetomaternal outcomes. The study aimed to find the prevalence of proteinuria among pregnant women admitted to the Department of Obstetrics and Gynaecology of a tertiary care centre. A descriptive cross-sectional study was carried out among pregnant women in the Department of Obstetrics and Gynaecology after obtaining ethical approval from the Institutional Review Committee. Data of 14 April 2022 to 13 April 2023 was collected from 9 June 2023 to 9 September 2023 from medical records. The study included pregnant women aged 18-45 years, who were past 28 weeks of gestation and had a 24-hour urine protein measurement. Pregnant women who had insufficient medical records were excluded from the study. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Among 3,914 pregnant women, proteinuria was seen in 61 (1.56%) (1.17-1.95, 95% Confidence Interval). The mean proteinuria in the study group was 1.5±2.75 gm/24 hr. In pregnant women with proteinuria, maternal complications were seen in 51 (83.60%) and foetal complications in 34 (55.73%) cases. A total of 47 (77.05%) underwent emergency lower-section caesarean section. The prevalence of proteinuria among pregnant women was found to be similar as compared to studies done in similar settings. preeclampsia; pregnancy complications; proteinuria.

The Renal Protective Effect of Sickle Cell Disease-Modifying Drugs

Background Patients affected by sickle cell disease (SCD) often present with renal impairment due to the deleterious effects of polymerized red blood cells at the level of the nephron. The resulting glomerular damage leads to proteinuria as well as increased tubular secretion of creatinine, which in turn allows for the use of the urine protein:creatinine ratio (PCR) to monitor disease progression in SCD patients. Aim We aimed to evaluate the renal protective effect of various disease-modifying therapies via changes in urine PCR. Method This was a retrospective cohort study of patients with SCD (all genotyped, ≥16 years old) at UT Comprehensive Sickle Cell Center during the study period of 2019-2023. Demographics, clinical, and laboratory findings were collected and analyzed. Both the albumin:creatinine ratio (ACR) and PCR are comparable measures of kidney function. We measured PCR at our center due to test availability, and it also allowed the measurement of non-albumin urinary proteins that maybe important for prognosis. PCR was measured once or twice annually. Descriptive statistics are presented in percentages, medians, and interquartile ranges. Changes in urine PCR were calculated based on the difference in initial and recent urine PCR. A positive change means that there was improvement in the most recent urine PCR (i.e., measuring less than the initial urine PCR) or vice versa. An unpaired Student's t test was used to determine the level of significance in differences between initial and recent urine PCR for various disease-modifying drugs, with p &amp;lt;0.05 considered to be statistically significant. Data was analyzed using GraphPad Prism version 9.0.2. Results There was a total of 90 study participants eligible for analysis during the study period. Forty-three (47.8%) were male and 47 (52.2%) were female; the median age was 30 (IQR 24-35.3) years. The most common genotype was HbSS (81.1%), followed by HbSC (10%), and HbSB null (8.9%). Patient with sickle cell trait were excluded from this study. The majority of the patients (81.1%) received at least one treatment, and 24 (26.7%) were on combination therapy. Among the various SCD-modifying therapies, hydroxyurea was the most common therapy (64.4%) used, followed by voxelotor (13.3%), crizanlizumab (12.2%), and L-glutamine (11.1%). A detailed analysis is given in Table 1. The median initial urine PCR was 140 (IQR 90.0-242.5) mg/g. The median recent urine PCR of the study cohort was 135 mg/g (IQR 88.5-287.5), and the median change was 0 (IQR -45.0 to 43.5) mg/g. In stratifying by different disease-modifying drugs, the median change in urine PCR for hydroxyurea was -106.3 mg/g, L-glutamine 5.5 mg/g, voxelotor 19 mg/g, and crizanlizumab -22 mg/g. There was a statistically significant difference in the change in urine PCR for voxelotor and L-glutamine, compared with hydroxyurea (p=0.0361 and 0.0423, respectively) (Figure 1). Conclusion This is one of the first retrospective analyses to evaluate the renal protective effect of disease-modifying drugs at our comprehensive sickle cell center. The SCD-modifying therapies voxelotor and pharmaceutical-brand L-glutamine had the highest renal protective abilities and were associated with significant changes in urine PCR, compared with hydroxyurea. Larger studies are needed to corroborate these findings.

A correlation of 8-hour and 12-hour with 24-hour urinary protein among pregnant women with preeclampsia in a teaching hospital in South-Western Nigeria

Background and Objective: Proteinuria is one of the cardinal features of preeclampsia, which is a common and potentially severe complication of pregnancy. This study sought to determine how the quantitative measurement of urine protein from 8-hour and 12- hour samples correlate with that of a 24-hour sample in diagnosing preeclampsia.&#x0D; Materials and Methods: 52 eligible pregnant women with preeclampsia were recruited between April 2017 and April 2018. For each patient, having emptied the bladder at 0 hour, urine was collected into three different containers (containers 1, 2, 3) at 8th hour, 12th hour and 24th hour ensuring that the bladder was emptied into each container at hours 8, 12 and 24. Volumes of 8 hours urine (volume in container 1), 12 hours urine (total volume in containers 1 and 2), and 24 hours urine (total volumes in containers 1, 2 and 3) were measured and 5 ml aliquot respectively obtained from each sample for colorimetric analysis of urinary protein. Data was analyzed using the EPI Info software&#x0D; Results: A total of 52 patients completed the study. The mean gestational age was 33+ 2.82weeks. The mean 8-hour, 12-hour and 24-hour urinary protein values were 2.1+1.53, 2.3+1.52 and 3.1+1.89 respectively. There were significant correlations between the protein values of 8-and 12-hour urine samples with those of 24-hour urine samples&#x0D; Conclusion: 8-hour and 12-hour values of urine protein correlated positively with values in 24-hour samples and may be useful for initial assessment of cases of preeclampsia for prompt interventions.

Comparison of three spot proteinuria measurements for pediatric nephrotic syndrome: based on the International pediatric Nephrology Association 2022 Guidelines

Background Pediatric nephrotic syndrome (NS) requires routine proteinuria monitoring, which is costly and affects patients’ quality of life. The gold-standard 24-h urine protein (UP) measurement is challenging in children, and first-morning urine collection requires specific conditions, making it difficult in outpatient settings. Studies have reported comparability of second or random morning urine sample to the first-morning specimen. This study aimed to compare outcomes of random morning proteinuria measurements to 24-h UP and the roles of the urinary protein creatinine ratio (UPCR) and dipstick tests in pediatric NS, based on International Pediatric Nephrology Association (IPNA) 2022 Guidelines. Method Twenty-four-hour and morning urine samples were collected from 92 pediatric NS patients. These were subjected to automated analyses for 24-h UP, UPCR, and semi-automated dipstick analysis. A blinded doctor performed manual dipstick analysis. Results UPCR had a stronger correlation with 24-h UP than with automated and manual urine dipstick tests. UPCR had the highest sensitivity and specificity for predicting no remission/relapse and high sensitivity but low specificity for complete remission. The optimal UPCR cutoff for remission was 0.44 mg/mg and for no remission/relapse was 2.08 mg/mg. Automated and manual dipstick tests demonstrated limited sensitivity but high specificity and similar AUC values for remission/relapse. Conclusion UPCR was sensitive and specific for diagnosing no remission/relapse and sensitive but not specific for detecting remission. Manual and automated urine dipstick tests were comparable for remission and no remission/relapse detection. This study supports the IPNA 2022 Guidelines, as 2 mg/mg was the optimal UPCR cutoff for no remission/relapse, while for remission the optimal cutoff was 0.4 mg/mg.

Follow-up Care of Critically Ill Patients With Acute Kidney Injury: A Cohort Study

To evaluate follow-up care of critically ill patients with acute kidney injury (AKI). Retrospective cohort study. Patients admitted to the intensive care unit (ICU) with AKI in Alberta, Canada from 2005 to 2018, who survived to discharge without kidney replacement therapy or estimated glomerular filtration rate<15mL/min/1.73m2. AKI (defined as≥50% or≥0.3mg/dL serum creatinine increase). The primary outcome was the cumulative incidence of an outpatient serum creatinine and urine protein measurement at 3 months postdischarge. Secondary outcomes included an outpatient serum creatinine or urine protein measurement or a nephrologist visit at 3 months postdischarge. Patients were followed from hospital discharge until the first of each outcome of interest, death, emigration from the province, kidney replacement therapy (maintenance dialysis or kidney transplantation), or end of study period (March 2019). We used non-parametric methods (Aalen-Johansen) to estimate the cumulative incidence functions of outcomes accounting for competing events (death and kidney replacement therapy). There were 29,732 critically ill adult patients with AKI. The median age was 68 years (IQR, 57-77), 39% were female, and the median baseline estimated glomerular filtration rate was 72mL/min/1.73m2 (IQR, 53-90). The cumulative incidence of having an outpatient creatinine and urine protein measurement at 3 months postdischarge was 25% (95% CI, 25-26). At 3 months postdischarge, 64% (95% CI, 64-65) had an outpatient creatinine measurement, 28% (95% CI, 27-28) had a urine protein measurement, and 5% (95% CI, 4-5) had a nephrologist visit. We lacked granular data, such as urine output. Many critically ill patients with AKI do not receive the recommended follow-up care. Our findings highlight a gap in the transition of care for survivors of critical illness and AKI.

Comparison of random urine protein/creatinine ratio with 24-hour urine protein in suspected pre-eclampsia

IntroductionProteinuria is one of the classical criteria for the diagnosis of pre-eclampsia. The gold standard remains the measurement of 24-h urine protein which is time consuming and prone to preanalytical errors. Random urine protein creatinine ratio (UPCR) is endorsed by clinical practice guidelines as a faster alternative. The aim of this study was to evaluate the correlation between the 24-h urine protein excretion and UPCR in the identification of proteinuria in suspected preeclamptic patients. MethodA total of 51 women with suspected pre-eclampsia from the maternal fetal clinic of our institution were retrospectively studied. The correlation between the UPCR in random urine samples and protein excretion in the 24-h urine collection was determined by Deming Regression analysis and Pearson correlation on EP evaluator and SPSS respectively. ResultThere was a significant positive correlation between the numerical values obtained by 24-h urine protein and the UPCR (R = 0.88, P < 0.001). Concordance analysis showed 81.1% positive agreement for proteinuria between methods (>300 mg/24hr and >0.3) and 71.4% negative agreement. The clinical sensitivity and specificity of the UPCR was 74% and 69% respectively. ConclusionOverall, UPCR was well correlated with 24-h urine protein and could be an effective and compliant screening tool to indicate proteinuria in preeclamptic patients.

#3428 DEPLETED HDAC3 ATTENUATES HYPERURICEMIA-INDUCED RENAL INTERSTITIAL FIBROSIS VIA MIR-19B-3P/SF3B3 AXIS

Abstract Background and Aims Hyperuricemia (HN) is a threat for the occurrence of renal interstitial fibrosis (RIF). Dysfunctional histone deacetylase 3 (HDAC3) elicit renal fibrosis and damage. This study aimed to explore the role of HDAC3 in HN-induced RIF from microRNA-19b-3p/splicing factor 3b subunit 3 (miR-19b-3p/SF3B3) axis. Method 1. The HN model was established on rats to induce RIF by oral administration of adenine and potassium oxalate; 2. HN rats were injected with related vectors (sh-HDAC3, mimic-miR-19b-3p, sh-HDAC3+miR-19b-3p inhibitor) to suppress and/or promote HDAC3 and/or miR-19b-3p; The detection indicators are listed as follows: (1) Blood samples and urine samples were collected for UA, BUN, Scr and 24 h urine protein measurement; (2) Renal pathological damages, RIF index and renal cell apoptosis were measured by HE, Masson and TUNEL staining; (3) α-SMA, TGF-β1 and FN contents in renal tissues were detected by IHC staining; (4) mRNA and protein levels of HDAC3, miR-19b-3p and SF3B3 in renal tissues were detected by RT-qPCR and/or WB. (5) Interaction of HDAC3 and miR-19b-3p was detected by ChIP and dual luciferase reporter gene assay; (6) Interaction of miR-19b-3p and SF3B3 was predicted/detected by bioinformatics website/dual luciferase reporter gene assay. Results 1. HN induced renal dysfunction, renal pathological damages, RIF and renal cell apoptosis of rats; HN rats showed elevated HDAC3, SF3B3 and reduced miR-19b-3p in renal tissues. 2. Suppressed HDAC3 or promoted miR-19b-3p relieved HN-induced renal dysfunction, renal pathological damages, RIF and renal cell apoptosis; HDAC3 bound to the promoter of miR-19b-3p; miR-19b-3p negatively regulated SF3B3; miR-19b-3p depletion abrogated down-regulated HDAC3-induced effects on HN-induced RIF. Conclusion HDAC3 bound to the promoter of miR-19b-3p to regulate SF3B3. Depressed HDAC3 relived HN-induced RIF by restoring miR-19b-3p and knocking down SF3B3. Targeting HDAC3 and miR-19b-3p/SF3B3 axis may be a promising therapeutic strategy for preventing HN-induced RIF.

The Correlation of Urine Protein/osmolality and Protein/creatinine Ratio as Predictor of 24-hour Urinary Protein Excretion.

The drawback of 24-hour urine collection is that it is troublesome, takes a lot of time, and is inaccurate because of collection errors and improper timing. The research in the Indian adult population about the correlation of spot urine protein/osmolality ratio (UPOR) and spot urine protein/creatinine ratio (UPCR) as a predictor of 24-hour urinary protein excretion is lacking. To study the correlation of spot UPOR and spot UPCR as the prognosticator of 24-hour urinary protein excretion. The present cross-sectional observational study was undertaken on 50 patients &gt;18 years of age and of either sex who presented with proteinuria (dipstick test or urine routine) and were advised 24-hour urine protein examination. A 24-hour urine was collected for protein analysis starting from any time of day. Random urine samples were collected and processed for protein, creatinine, and osmolality. The spot UPOR and UPCR were calculated. The sensitivity and specificity were determined. Pearson's correlation was used to find the correlation. There was a statistically significant positive correlation of UPOR and UPCR (r = 0.418 and r = 0.512, respectively) with 24-hour urinary protein excretion. The sensitivity and specificity of UPOR to predict 24-hour urinary protein at cutoff point 1.32 was 82.3% and 81%, respectively. The sensitivity and specificity of UPCR to predict 24-hour urinary protein at cutoff point 1.09 was 87 and 86%, respectively. For the medical determination of proteins in urine, spot UPOR and UPCR are suitable, cheap, and dependable methods that can substitute the measurement of 24-hour urine protein.

Association of eGFR and mortality with use of a joint model: results of a nationwide study in Iceland.

Prior studies on the association of estimated glomerular filtration rate (eGFR) and mortality have failed to include methods to account for repeated eGFR determinations. The aim of this study was to estimate the association between eGFR and mortality in the general population in Iceland employing a joint model. We obtained all serum creatinine and urine protein measurements from all clinical laboratories in Iceland in the years 2008-16. Clinical data were obtained from nationwide electronic medical records. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation and categorized as follows: 0-29, 30-44, 45-59, 60-74, 75-89, 90-104 and >104mL/min/1.73 m2. A multiple imputation method was used to account for missing urine protein data. A joint model was used to assess risk of all-cause mortality. We obtained 2 120 147 creatinine values for 218 437 individuals, of whom 84 364 (39%) had proteinuria measurements available. Median age was 46 (range 18-106) years and 47% were men. Proteinuria associated with increased risk of death for all eGFR categories in persons of all ages. In persons ≤65years, the lowest risk was observed for eGFR of 75-89mL/min/1.73 m2 without proteinuria. For persons aged >65years, the lowest risk was observed for eGFR of 60-74mL/min/1.73 m2 without proteinuria. eGFR of 45-59mL/min/1.73 m2 without proteinuria did not associate with increased mortality risk in this age group. eGFR >104mL/min/1.73 m2 associated with increased mortality. These results lend further support to the use of age-adapted eGFR thresholds for defining chronic kidney disease. Very high eGFR needs to be studied in more detail with regard to mortality.

444. Effect of multidisciplinary management of CKD on proteinuria in people with HIV

Abstract Background Optimizing management of chronic kidney disease in people with HIV has become a more pressing priority both to minimize morbidity and preserve HIV antiretroviral options. Part of standard care is employing the beneficial effects of angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARB) in patients with clinically significant proteinuria. Our analysis looks at the proteinuria outcomes of PWH with CKD co-managed by a multidisciplinary team of infectious disease and nephrology physicians nested in a Ryan White-funded clinic in New Orleans. Methods Patients with HIV and at least grade 3 CKD or with significant proteinuria were referred to the multidisciplinary clinic. Patients were evaluated by an HIV specialist and nephrologist at the initial visit for a jointly developed management plan. Renal function and proteinuria were measured at baseline and longitudinally per standard of care. Change in proteinuria and GFR over time were calculated. Patients were also assessed for whether they were prescribed ACE/ARB therapy, if appropriate. Patients included in this analysis were evaluated between January 1, 2021 and March 31, 2022. Results During the analysis period, 46 patients with at least CKD 3 or proteinuria were evaluated. 35 patients were Black non-Hispanic, 9 were White non-Hispanic, and 2 were Hispanic. 39 were male, and 7 were female. 35 had a previous diagnosis of hypertension, and 10 had diabetes mellitus. Of the 42 with a recorded baseline urine protein measurement, 24 were found to have clinically significant proteinuria. Of those with proteinuria, 16 were on an ACE or ARB at their baseline evaluation. 20 were on ACE/ARB’s the end of the analysis period (p=0.058). Average baseline proteinuria was 1,158 mg/g, while average final was 938 mg/g, which was less but not significantly different (p=0.54). Mean baseline GFR was not significantly different from final GFR (50.8 mL/min vs 50.5 mL/min, p=0.67). Conclusion A multidisciplinary model of managing CKD among people with HIV may improve adherence with management guidelines and limit progression of proteinuria and decrease in GFR. In general, the natural history of kidney disease with proteinuria is to worsen over time, so while not significant, proteinuria in this cohort did decrease over time Disclosures All Authors: No reported disclosures.

Measurement of urinary protein in children

Proteinuria is an early hallmark of kidney disease and a major risk factor for systemic cardiovascular diseases. There are several methods to measure proteinuria, such as the urine dipstick test, 24-hour urinary protein excretion method, and spot urine for the protein-to-creatinine ratio. The urine dipstick test is simple but inaccurate. The 24-hour urinary protein excretion method is the gold standard; however, it is cumbersome, especially in children. Spot urine for the protein-to-creatinine ratio is simple and accurate, but has limitations. Specific urinary protein such as albumin can be measured instead of the total protein content. Tests should be avoided in situations that cause transient proteinuria or false-positive results. It should be performed correctly, and its limitations should be recognized and interpreted accurately.

Diabetes and Inflammation; Association Between C-Reactive Protein and Diabetic Nephropathy in Rawalpindi

Objective: To determine the frequency of elevated C-reactive protein in type 2 diabetics and to compare the levels of C-reactive protein between people with diabetes and non-diabetics nephropathy among the population of Rawalpindi, Pakistan. Methodology: This cross-sectional study Diabetic and Medical OPD of Fauji Foundation Hospital, Rawalpindi from January 2019 to July 2019. A total of 150 patients who had type 2 diabetes, aged between 35 to 60 years, irrespective of gender, were included. Blood samples were collected for blood sugar random, fasting, renal function test, WBC count, and C-reactive protein. Urine samples were collected for the measurement of 24-hour urinary proteins. The presence or absence of proteinuria was used to categorize patients into two groups. Group A consisted of 58 patients with type 2 diabetes who did not have nephropathy, and Group B consisted of 92 patients with type 2 diabetes who had nephropathy (proteinuria greater than 30 mg/dl in 24 hours). Results: The mean age in our study was 49.41+7.66. Ninety-two patients (61.3%) presented with diabetic nephropathy. CRP levels (&gt; 8200 ng/ml) were raised in 50 (54.3%) patients of group B and 19 (32.8%) patients of group A. The difference was statistically significant (p-value 0.010). Conclusion: This study showed a higher prevalence of raised CRP in type 2 diabetics with nephropathy. This reinforces the idea that low-grade inflammation has an essential role in the inception and evolution of diabetic renal disease.

Exploring urine:serum fractional excretion ratios as potential biomarkers for lupus nephritis.

ObjectivesThe goal of this exploratory study is to determine if urine:serum fractional excretion ratios can outperform the corresponding urinary biomarker proteins in identifying active renal disease in systemic lupus erythematosus (SLE).MethodsThirty-six adult SLE patients and twelve healthy controls were examined for serum and urine levels of 8 protein markers, namely ALCAM, calpastatin, hemopexin, peroxiredoxin 6 (PRDX6), platelet factor 4 (PF4), properdin, TFPI and VCAM-1, by ELISA. Fractional excretion of analyzed biomarkers was calculated after normalizing both the urine and serum biomarker levels against creatinine. A further validation cohort of fifty SLE patients was included to validate the initial findings.ResultsThe FE ratios of all 8 proteins interrogated outperformed conventional disease activity markers such as anti-dsDNA, C3 and C4 in identifying renal disease activity. All but VCAM-1FE were superior to the corresponding urine biomarkers levels in differentiating LN activity, exhibiting positive correlation with renal SLEDAI. ALCAMFE, PF4FE and properdinFE ratios exhibited the highest accuracy (AUC>0.9) in distinguishing active LN from inactive SLE. Four of the FE ratios exhibited perfect sensitivity (calpastatin, PRDX6, PF4 and properdin), while ALCAMFE, PF4FE and properdinFE exhibited the highest specificity values for active LN. In addition, several of these novel biomarkers were associated with higher renal pathology activity indices. In the validation cohort ALCAMFE, PF4FE and properdinFE once again exhibited higher accuracy metrics, surpassing corresponding urine and serum biomarkers levels, with ALCAMFE exhibiting 95% accuracy in distinguishing active LN from inactive SLE.ConclusionsWith most of the tested proteins, urine:serum fractional excretion ratios outperformed corresponding urine and serum protein measurements in identifying active renal involvement in SLE. Hence, this novel class of biomarkers in SLE ought to be systemically evaluated in larger independent cohorts for their diagnostic utility in LN assessment.

Trends in nephrology referral patterns for patients with chronic kidney disease: Retrospective cohort study.

IntroductionInformation on early, guideline discordant referrals in nephrology is limited. Our objective was to investigate trends in referral patterns to nephrology for patients with chronic kidney disease (CKD).MethodsRetrospective cohort study of adults with ≥1 visits to a nephrologist from primary care with ≥1 serum creatinine and/or urine protein measurement <180 days before index nephrology visit, from 2006 and 2019 in Alberta, Canada. Guideline discordant referrals were those that did not meet ≥1 of: Estimated glomerular filtration rate (eGFR) ˂ 30 mL/min/1.73m2, persistent albuminuria (ACR ≥ 300 mg/g, PCR ≥ 500 mg/g, or Udip ≥ 2+), or progressive and persistent decline in eGFR until index nephrology visit (≥ 5 mL/min/1.73m2).ResultsOf 69,372 patients with CKD, 28,518 (41%) were referred in a guideline concordant manner. The overall rate of first outpatient visits to nephrology increased from 2006 to 2019, although guideline discordant referrals showed a greater increase (trend 21.9 per million population/year, 95% confidence interval 4.3, 39.4) versus guideline concordant referrals (trend 12.4 per million population/year, 95% confidence interval 5.7, 19.0). The guideline concordant cohort were more likely to be on renin-angiotensin system blockers or beta blockers (hazard ratio 1.14, 95% confidence interval 1.12, 1.16), and had a higher risk of CKD progression (hazard ratio 1.09, 95% confidence interval 1.06, 1.13), kidney failure (hazard ratio 7.65, 95% confidence interval 6.83, 8.56), cardiovascular event (hazard ratio 1.40, 95% confidence interval 1.35,1.45) and mortality (hazard ratio 1.58, 95% confidence interval 1.52, 1.63).ConclusionsA significant proportion nephrology referrals from primary care were not consistent with current guideline-recommended criteria for referral. Further work is needed to identify quality improvement initiatives aimed at enhancing referral patterns of patients with CKD.

Multiplex LC-MS/MS Testing for Early Detection of Kidney Injury: A Next-Generation Alternative to Conventional Immunoassays?

LC-MS/MS has enabled the translation of many novel biomarkers to the clinical laboratory, but its potential for measurement of urinary proteins is still unexplored. In this study we examined the correlation and agreement between immunoassay and LC-MS/MS in the quantitation of kidney injury biomarkers and evaluated the application of technical LC-MS/MS meta-data assessment to ensure test result validity. NGAL, IGFBP7, TIMP2, and KIM-1 were quantified in 345 urine samples with one multiplex lab-developed test that combines immunocapture with mass spectrometry read-out and 4 singleplex sandwich-type immunoassays. Assay performance and imprecision were monitored by 2 urine-based quality controls. Ion ratios, signal intensity, and retention time were monitored over all study samples. The LC-MS/MS retention time drift was ≤1.2%, ion ratios were within 20% of the target values at concentrations of >100 pmol/L, and peptides originating from the same protein were in agreement (slopes between 1.03 and 1.41). The interassay CV was between 9.3% and 19.1% for LC-MS/MS analysis and between 4.2% and 10.9% for immunoassay. Direct LC-MS/MS analysis was correlated with immunoassay in the quantitation of NGAL (r = 0.93; range: 0.01-37 nmol/L), IGFBP7 (r = 0.80; range: 0.01-2.6 nmol/L), TIMP2 (r = 0.85; range: 0.01-6.3 nmol/L), and KIM-1 (r = 0.70; range 0.01-0.4 nmol/L), but the analytical methodologies differed in measurands and calibration strategies. LC-MS/MS is explored as a next-generation technology for multiplex urinary protein measurement. It has great potential to overcome nonselectivity and lack of standardization because of its capability of directly measuring well-defined molecular proteins.