Spot Urine Samples Research Articles

EVALUATION OF PHYSIOLOGICAL BIOMARKERS AS POSSIBLE PREDICTIVE FACTORS AND PROGNOSIS MARKERS OF KIDNEY INJURY IN DOGS NATURALLY INFECTED WITH LEISHMANIA INFANTUM

Impaired renal function is one of the main characteristics of dogs infected with Leishmania infantum. Early diagnosis of kidney injury is essential for improving patient’s prognosis. This study aims to evaluate physiological biomarkers as predictors of kidney injury and prognostic markers. Medical records of fifty-nine dogs of different breed, age, and sex, naturally infected with L. infantum, were analyzed. Red blood cells, leucocytes, platelets count, hematocrit, total plasma proteins, plasma globulin, plasma albumin, serum creatinine, serum urea, serum phosphorus, serum symmetrical dimethyl arginine, urine analysis, urinary density, urinary protein creatinine ratio, urinary creatinine, urinary protein, and systemic blood pressure were examined in trial 0. Six months after trial 0, twenty-four dogs returned for clinical and laboratory examination. The second medical record analysis was identified as trial 1. The twenty-four dogs were examined using the same tests performed in trial 0. The physiological biomarker such as platelets and leukocyte count, hematocrit, serum phosphorus, urinary density, and systemic blood pressure, showed a significant correlation as prognostic and predictive factors of kidney injury in dogs. The platelet count was used as the physiological biomarker to show the value as a predictive factor and prognostic marker related to biomarkers of kidney injury in dogs naturally infected with L. infantum.

Proteinuria in predicting adverse outcomes in women with severe features of pre-eclampsia from a developing country: Aprospective cohort study.

To study the adverse maternal and perinatal outcomes in women with severe pre-eclampsia (SPE) among different ranges of proteinuria. This prospective cohort study was conducted in Jawaharlal Institute of Postgraduate Medical Education and Research, India. After obtaining informed written consent, the 202 singleton women fulfilling the criteria of severe features of pre-eclampsia were stratified based on the value of urine protein-creatinine ratio (UPCR) as mild, moderate, severe, and massive proteinuria during pregnancy. Clinical outcomes were assessed and patients were followed up until 12 weeks postpartum to identify persistent proteinuria and hypertension. Of the 202 women with SPE, adverse maternal outcomes were seen in 34.65% (n = 70) and adverse perinatal outcomes in 75.74% (n = 153). The demographic and clinical factors were similar among women with increasing severity of proteinuria, except for mean systolic blood pressure, serum creatinine and total serum protein. UPCR was found to have a significant correlation with composite adverse perinatal outcome (P < 0.001) and individual outcomes of neonatal intensive care unit admission for >48 h (P = 0.01) and neonatal sepsis (P = 0.02) but not adverse maternal outcomes (P = 0.201). The optimum UPCR cutoff for adverse perinatal outcomes was 1.6 (sensitivity, 73.2%; specificity, 52.7%). In addition, 14.85% of the women had a persistently elevated UPCR and 3.96% had hypertension at 3 months postpartum. In women with SPE, severe and massive proteinuria were related to composite adverse perinatal outcome but not composite adverse maternal outcome. Moreover, antenatal 24-h proteinuria was significantly associated with persistent proteinuria. Significant proteinuria in women with SPE poses a risk for chronic renal dysfunction, requiring follow-up.

Renal biomarkers, clinical parameters, and renal Doppler velocimetry in bitches with cystic endometrial hyperplasia-pyometra complex.

Cystic endometrial hyperplasia (CEH)-pyometra complex is the most common uterine infection in adult and elderly bitches and can cause renal dysfunction. The aim of this study was to measure and compare urinary creatinine, urea, symmetric dimethylarginine (SDMA), urinary protein-creatinine ratio (UPC), measurement of systolic blood pressure (SBP), and Doppler velocimetry of renal arteries in patients with CEH-pyometra complex before and after an average of 6 months of treatment, evaluating the possibility of the changes persisting. The evaluation was conducted at two moments: M1 (at the diagnosis of CEH-pyometra, n = 36) and M2 (after an average of six months of treatment, n = 16). For the control group, eight bitches with no changes in blood tests or history of conditions underwent Doppler ultrasound evaluation of the renal arteries. At both M1 and M2, we measured creatinine, urea, and serum SDMA, UPC, SBP, and Doppler ultrasound of the renal arteries. Patients were evaluated according to the following groups: azotemic (AZO) and non-azotemic (NAZO), and open and closed cervix pyometra. The parameters were compared between animals present in both moments presented as M1R (bitches that were in M1 and M2) and M2. Statistical significance was considered when p < .05. The medians found for creatinine in M1 were as follows: 1.15 mg/dL, being 1.8 mg/dL for AZO (12/36) and 0.95 mg/dL for NAZO (24/36); and in M2: 0.85 mg/dL (16/16), being 1.15 mg/dL for AZO (4/16) and 0.8 mg/dL for NAZO (12/36). For urea, in M1 it was 36 mg/dL (32/36), with AZO being 103 mg/dL (11/32) and 33 mg/dL in NAZO (21/32); and in M2 32 mg/dL (16/ 16), being 29 mg/dL for AZO (4/36), and 31 mg/dL for NAZO (3/15). The median SDMA measured in M1R was 17 μg/dL (15/16), with AZO being 31 μg/dL (3/15), and NAZO being 16.5 μg/dL (12/15); and in M2, SDMA was 12 μg/dL (16/16), with AZO being 12.5 μg/dL (4/16), and NAZO being 12 μg/dL (12/16). The median UPC measured in M1 was 1.15 (10/36), with AZO being 0.25 (1/10), and NAZO being 1.38 (9/10); and in M2, it was 0.2 (13/16), being 0.1 in AZO (4/13), and 0.2 (9/16) in NAZO. For SBP, in M1, it was 118 mmHg (30/36), with AZO being 102 mmHg (10/30) and 133 mmHg in NAZO (20/30); and in M2 142.5 mmHg (12/16), being 155 mmHg for AZO (4/12), and 140 mg/dL for NAZO (8/12). When comparing animals with open and closed cervixes, a difference was found between SDMA measurements (p = .001). There was a distinction between PI and RI of the left and right kidneys consecutively (p = .007; p = .033; p = .019; p = .041). Correlations found in M1: SDMA × PI RIM DIR (r = 0.873; p = .002), SDMA × PSV RIM ESQ (r = 0.840; p = .004), SDMA × EDV RIM ESQ (r = 0.675; p = .046). With this study, we conclude a return to normality of renal biomarkers and clinical parameters after six months. Yet, there is a persistence of Doppler velocimetric measurements between the two moments. Thus, this parameter is not suitable for identifying and classifying chronic kidney injury in bitches with pyometra.

The correlation of spot urinary protein-to-creatinine ratio with 24-h urinary protein excretion in various glomerulopathies.

Proteinuria is an important and well-known biomarker of many forms of kidney injury. Its quantitation is of particular importance in the diagnosis and management of glomerular diseases. Its quantification can be done by several methods. Among these, the measurement of 24-h urinary protein excretion is the gold standard method. However, it is cumbersome, time-consuming, and inconvenient for patients and is not completely foolproof. Many alternative methods have been tested over time albeit with conflicting results. Among the latter, the measurement of urine protein-to-creatinine ratio (uPCR) in single-voided urinary samples is widely used. The majority of studies found a good correlation between uPCR in single urine samples with 24-h urinary protein estimation, whereas others did not. To investigate the correlation of spot uPCR with 24-h urinary protein estimation in patients suffering from different forms of glomerulopathies at a single large-volume nephrological center in Pakistan. This cross-sectional, observational study was conducted at the Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan from September 2017 to March 2018. All newly presenting adult patients with proteinuria who were being investigated for suspected glomerulonephritis and persistent proteinuria with ages between 18 to 60 years were enrolled. All patients were given detailed advice regarding 24-h urine collection starting at 7:00 AM for total protein and creatinine excretion estimations. A spot urine sample was collected the next day at the time of submission of a 24-h urine sample for measuring uPCR along with a blood sample. The data of patients were collected in a proforma. SPSS version 20.0 was used for statistical analysis. A total of 157 patients were included. Their mean age was 30.45 ± 12.11 years. There were 94 (59.8%) males and 63 (40.2%) females. The mean 24-h urinary protein excretion was 3192.78 ± 1959.79 mg and the mean spot uPCR was 3.16 ± 1.52 in all patients. A weak but significant correlation was observed between spot uPCR and 24-h urinary protein excretion (r = 0.342, P = 0.01) among all patients. On subgroup analysis, a slightly better correlation was found in patients older than 47 years (r = 0.78), and those with body mass index > 25 kg/m2 (r = 0.45). The Bland and Altman's plot analysis comparing the differences between spot uPCR and 24-h protein measurement also showed a wide range of the limits of agreement between the two methods. Overall, the results from this study showed a significant and weakly positive correlation between spot uPCR and 24-h urinary protein estimation in different forms of glomerulopathies. The agreement between the two methods was also poor. Hence, there is a need for careful interpretation of the ratio in an unselected group of patients with kidney disease.

Iodine intake in the Swiss population 100years after the introduction of iodised salt: a cross-sectional national study in children and pregnant women.

The Swiss voluntary salt iodisation programme has successfully prevented iodine deficiency for 100years, but dietary habits are changing and todayonly one-third of processed foods contain iodised salt. We aimed to monitor the current iodine status in childrenand pregnant women. We conducted a nationwide cross-sectional study in children (6-12years) and pregnant women and measured the urinary iodine concentration (UIC) in spot urine samples. We estimated the iodine intake using UIC and urinary creatinine concentration (UCC) and determined the prevalence of intakes below the average requirement (AR) using the SPADE method. We measured dried blood spot (DBS) thyroglobulin (Tg), TSH and total T4 in pregnant women. The median UIC was 127μg/L (bootstrapped 95% CI 119, 140, n = 362) in children and 97μg/L (bootstrapped 95% CI 90, 106, n = 473) in pregnant women. The estimated prevalence of inadequate iodine intake (< 65μg/day) was 5.4% (bootstrapped 95% CI 0.0, 14.6) in children. Half (47%) of the women consumed iodine-containing multivitamin and mineral supplements (≥ 150μg/day). Compared to non-users, users had higher median UIC (129 vs. 81μg/L, P < 0.001), lower prevalence of inadequacy (< 160μg/day; 0.2 vs. 31%) and lower DBS-Tg (23 vs. 29μg/L, P < 0.001). All women were euthyroid. The Swiss diet and current salt fortification provides adequate iodine intake in children, but not in all pregnant women. Iodine supplements cover the dietary gap in pregnancy but are not universally consumed. Therefore, improved use of iodised salt in processed foods is desired to ensure adequate iodine intake in all population groups. This trial was registered at clinicaltrials.gov as NCT04524013.

Exploring the Utility of Urinary Creatinine Adjustment for KIM-1, NGAL, and Cystatin C for the Assessment of Kidney Function: Insights from the C-KidnEES Cohort.

Normalization of urinary biomarkers of kidney injury is a common practice in clinical and research settings to account for variations in urine concentration, and urinary creatinine is often used as a reference. However, to date, there is no consensus on the adjustment of urinary biomarkers with creatinine, and both absolute and creatinine-adjusted biomarker levels are adopted for making interpretations of kidney health. Hence, the present study aimed to investigate the associations of urinary creatinine with three widely used kidney injury biomarkers, KIM-1, NGAL, and cystatin C, to validate the applicability of urinary creatinine as a reference for normalization. A cross-sectional study was performed with 2100 students, 10-18 years of age in the Children's Kidney Environmental Exposure Study (C-KidnEES) cohort established in Sri Lanka. As identified in linear regression analyses, normalization of urinary KIM-1, NGAL, and Cys-C to urinary creatinine did not result in significant under-adjustment or over-adjustment to the absolute urinary concentrations, giving no specific rationale for creatinine adjustment. Hence, absolute urinary concentrations of the above biomarkers can be adopted for the characterization of subclinical kidney injury in adolescents in community studies where early morning urine sampling is practiced. However, for spot urine samples, consideration of both absolute and creatinine-adjusted biomarker levels would be a better approach.

Dietary Magnesium Intake and Proteinuria: Is There a Relationship?

The possible relationship between dietary magnesium status and proteinuria has been suggested by a number of previous studies. However, human studies on this association are limited. Therefore, the present study aimed to investigate the independent relationship between dietary magnesium intake and urinary protein excretion. The present study was a post hoc analysis of the previous randomized clinical trial that evaluated the effect of dietary phosphorus restriction on proteinuria. The baseline data of 90 participants with proteinuria and chronic kidney disease was used to measure the association between dietary magnesium intake and proteinuria. Participants were asked to record their 24-h food intake for three days a week in a questionnaire. Urinary protein to creatinine ratio (UPCR) in a random urine sample was measured to be a marker for proteinuria. Out of 90 patients included in the study, 47 were men and 43 were women. The mean ± standard deviation of age and body mass index were 59.05 ± 14.16 years and 29.02 ± 5.54 kg/m2, respectively. The patients' average daily dietary intake of energy and magnesium were 2183 kcal and 169.44 mg, respectively. A significant inverse correlation was found between the dietary intake of magnesium and UPCR (r = - 0.219, p = 0.042). This association remained significant even after adjusting for confounding variables (β = - 0.222, p = 0.028). The findings of the present study showed a significant inverse relationship between the magnesium intake and proteinuria. Although, the design of the current research was cross-sectional, it has provided a basis for conducting future longitudinal studies and trials to better elucidate such a relationship.

Association between parental smoking and child exposure to environmental tobacco smoke in Israel

BackgroundEnvironmental tobacco smoke (ETS) exposure in children can cause delayed lung development and lifelong cardiovascular damage. The aim of this study was to measure ETS exposure in children in Israel in 2020–2021 using urinary cotinine (UC) measurements and to assess correlates of ETS exposure, including parental smoking.MethodsIn the framework of the National Human Biomonitoring Program, spot urine samples and questionnaire data were collected from 166 children aged 4–12 years, during the years 2020–2021. We collected urine samples in 233 adults, 69 of whom were parents of children included in the study. Parents of participating children were asked about parental smoking, child’s exposure to ETS and smoking policy at home. Cotinine and creatinine were measured in urine. Creatinine-adjusted and unadjusted urine cotinine (UC) geometric means were calculated. Associations between potential correlates and UC concentrations were analyzed in univariate and multivariate analyses. For 69 child-parent pairs, correlation between child and parental UC was analyzed.ResultsBased on urinary cotinine measurement, 65.2% of children of smokers are exposed to ETS, compared to 20.7% of children in non-smoking families. Greater numbers of smokers living in the home (beta = 1.27, p < 0.01), and low maternal education (beta = − 2.32, p < 0.01) were associated with higher levels of UC in a multivariate analysis. Spearman correlations showed a positive moderate correlation between UC in 69 child–parent pairs (r = 0.52, p < 0.01).ConclusionsIn order to reduce child exposure to ETS, smoking parents should be urgently targeted for smoking cessation and smoke-free home interventions. Further interventions are needed to protect all children from ETS.

Metabolomic Insights on Potassium Excretion, Blood Pressure, and Glucose Homeostasis: The African-PREDICT Study

BackgroundLow-potassium intake is associated with a higher risk of type 2 diabetes and hypertension. Both conditions occur more frequently in Black populations, who also consume less potassium-rich foods. ObjectivesUsing metabolomics to identify dysregulated metabolic pathways associated with low-potassium excretion may procure more accurate entry points for nutritional prevention and intervention for type 2 diabetes and hypertension. MethodsA total of 440 White and 350 Black adults from the African-PREDICT study (aged 20–30 y) were included. Twenty-four-hour blood pressure (BP) was measured. Potassium, sodium, and fasting glucose concentrations were analyzed in 24-h urine and plasma samples. Liquid chromatography-tandem mass spectrometry-based metabolomics included the analyses of amino acids and acylcarnitines in spot urine samples. ResultsBlack participants had lower urinary potassium concentrations than Whites (36.6 compared with 51.1 mmol/d; P < 0.001). In White but not Black adults, urinary potassium correlated positively with 2-aminoadipic acid (2-AAA) (r = 0.176), C3-[propionyl]carnitine (r = 0.137), C4-[butyryl]carnitine (r = 0.169) and C5-[isovaleryl]carnitine (r = 0.167) in unadjusted and 2-AAA (r = 0.158) and C4-carnitine (r = 0.160) in adjusted analyses (all P < 0.05 and q < 0.05). Elevated C0-, C3-, and C5-carnitine in turn were positively associated with systolic BP (Black and White groups), diastolic BP (Black group), and glucose (White group) (all P < 0.05). ConclusionsRacial differences are an important consideration when investigating nutrient–metabolite relationships and the role thereof in cardiovascular disease. Only in White adults did urinary potassium associate with 2-AAA and short-chain acylcarnitines. These metabolites were positively related to BP and fasting plasma glucose concentrations. In White adults, the metabolomic profiles related to potassium excretion may contribute to BP regulation and glucose homeostasis.This trial was registered at clinicaltrials.gov as NCT03292094.

The East Bay Diesel Exposure Project: a biomonitoring study of parents and their children in heavily impacted communities

BackgroundDiesel exhaust (DE) exposures pose concerns for serious health effects, including asthma and lung cancer, in California communities burdened by multiple stressors.ObjectiveTo evaluate DE exposures in disproportionately impacted communities using biomonitoring and compare results for adults and children within and between families.MethodsWe recruited 40 families in the San Francisco East Bay area. Two metabolites of 1-nitropyrene (1-NP), a marker for DE exposures, were measured in urine samples from parent–child pairs. For 25 families, we collected single-day spot urine samples during two sampling rounds separated by an average of four months. For the 15 other families, we collected daily spot urine samples over four consecutive days during the two sampling rounds. We also measured 1-NP in household dust and indoor air. Associations between urinary metabolite levels and participant demographics, season, and 1-NP levels in dust and air were evaluated.ResultsAt least one 1-NP metabolite was present in 96.6% of the urine samples. Detection frequencies for 1-NP in dust and indoor air were 97% and 74%, respectively. Results from random effect models indicated that levels of the 1-NP metabolite 6-hydroxy-1-nitropyrene (6-OHNP) were significantly higher in parents compared with their children (p-value = 0.005). Urinary 1-NP metabolite levels were generally higher during the fall and winter months. Within-subject variability was higher than between-subject variability (~60% of total variance versus ~40%, respectively), indicating high short-term temporal variability.ImpactBiomonitoring, coupled with air monitoring, improves understanding of hyperlocal air pollution impacts. Results from these studies will inform the design of effective exposure mitigation strategies in disproportionately affected communities.

Urinary concentrations of bisphenol A, parabens and benzophenone-type ultra violet light filters in relation to sperm DNA fragmentation in young men: A chemical mixtures approach

People are daily exposed to multiple endocrine disruptor compounds (EDCs) that may interfere with different molecular and cellular processes, promoting a potential estrogenic, androgenic, or anti-androgenic state. However, most epidemiological studies attempting to establish relationships between EDCs exposure and health effects are still considering individual compounds. A few studies have shown associations between exposure to individual non-persistent EDCs and sperm DNA fragmentation (SDF) in different male populations. Thus, the aim of this study was to investigate associations between combined exposure to non-persistent EDCs and SDF index in young men. A cross-sectional study was conducted with 158 healthy university students from Southeaster Spain. The participants provided spot urine and semen samples on the same day. The concentrations of urinary bisphenol A (BPA), benzophenones [2,4-dihydroxybenzophenone (BP-1); 2,2′,4,4′-tetrahydroxybenzophenone (BP-2), 2-hydroxy-4-methoxybenzophenone (BP-3), 2,2′-dihydroxy-4-methoxybenzophenone (BP-8), 4-hydroxybenzophenone (4OHBP)], and parabens (methylparaben, ethylparaben, propylparaben, butylparaben) were measured by dispersive liquid-liquid microextraction and ultrahigh-performance liquid chromatography with tandem mass spectrometry detection. SDF was analysed using a Sperm Chromatin Dispersion test. Statistical analyses were carried out using Bayesian Kernel Machine Regression models to evaluate associations between combined exposure to these compounds and SDF index while adjusting by relevant covariates. The increase in urinary concentration of 4OHBP was found to be the most important contributor to the negative association between urinary EDCs concentrations and SDF index, being of −5.5 % [95 % CI: −10.7, −0.3] for those in percentile 50, and − 5.4 % [95 % CI: −10.8, −0.1] for those in percentile 75. No significant associations were observed between other EDCs and SDF index. Our findings show that urinary 4OHBP levels may be associated with a decrease in the SDF index. Nonetheless, the effects we observed were likely to be small and of uncertain clinical significance. Further research is needed to replicate our findings in other male populations.

Diagnostic value of random urine protein/creatinine ratio for preeclampsia

ObjectiveThe 24-h urine protein remains the gold standard to diagnose proteinuria in suspected preeclamptic patients. However, this test is time consuming and sometimes inaccurate. In this study, we aimed to analyse the correlation between the random urine protein/creatinine ratio (UPCR) and 24-h urine protein and to explore the clinical value of UPCR in the diagnosis of preeclampsia. MethodWe retrospectively evaluated 109 pregnant women from our hospital who had hypertensive diseases. They were grouped according to time of urine collection and disease severity to compare differences in random urine protein, urine creatinine, and UPCR. The correlation between the UPCR and 24-h urine protein was determined by Pearson's linear correlation. ResultsWe found no statistically significant differences in random urine protein, urine creatinine, or UPCR among the four time of sampling groups. Further, random urine protein, UPCR, and 24-h urine protein between the gestational hypertension and preeclampsia groups differed significantly (P < 0.001). Correlation analysis showed significant positive correlation between random urine protein, and 24-h urine protein, and UPCR and 24-h urine protein, with r values of 0.789 and 0.810, respectively. According to the receiver operating characteristic (ROC) curve, the optimal threshold, sensitivity, specificity, and area under the curve of UPCR for the diagnosis of preeclampsia were 0.456 g/mmol, 67.8 %, 78.3 %, and 0.747, respectively (95 % confidence interval [CI], 0.65–0.844). ConclusionThis study indicated that UPCR is significantly correlated with 24-h urine protein and is expected to replace the 24-h urine protein test as a diagnostic indicator of preeclampsia.

Validating the association of Oxford classification and renal function deterioration among Taiwanese individuals with Immunoglobulin A nephropathy

Validation of the Oxford classification (MEST and MEST-C) for Immunoglobulin A nephropathy (IgAN) in the Taiwanese population is lacking. Our study aimed to validate this classification and assess individual lesion impact. We conducted a retrospective cohort study at Taichung Veterans General Hospital, Taiwan (Jan 2011–Jul 2023). Composite renal outcomes were evaluated using clinical conditions and estimated glomerular filtration rate (eGFR). We used Kaplan–Meier, univariable/multivariable logistic regression and ROC curves. Subgroup analysis considered eGFR < or ≥ 30.0 ml/min/1.73 m2. In 366 renal biopsies, serum creatinine was 1.34 mg/dl, eGFR 53.8 ml/min/1.73 m2, urine protein–creatinine ratio 1159 mg/g. T1/T2 lesions had lowest baseline eGFR (39.6/11.5 ml/min/1.73 m2), correlating with poorest renal survival (median survival 54.7/34.4 months). Univariable analysis linked all individual variables to worse renal outcomes. Multivariable analysis (MEST/MEST-C) showed only T1/T2 linked to worse outcomes. T score had highest predictive power (AUC 0.728, sensitivity 60.2%, specificity 83.6%), with MEST having high AUC (0.758). No extra predictive power was seen transitioning MEST to MEST-C. Subgroup analysis (eGFR < 30.0 ml/min/1.73 m2) associated C1 with improved renal outcomes (odds ratio 0.14, 95% CI 0.03–0.65). T lesion correlated with worse outcomes across subgroups. The T lesion consistently correlated with worse renal outcomes across all groups and baseline statuses. Integrating the C lesion into the transition from MEST to MEST-C did not enhance predictive power. Importantly, the C1 lesion was linked to improved renal outcomes in the eGFR < 30.0 ml/min/1.73 m2 subgroup, likely due to treatment effects.

The epidemiology of primary FSGS including cluster analysis over a 20-year period

IntroductionFocal segmental glomerulosclerosis (FSGS) is one of the leading causes of nephrotic syndrome in adults. This epidemiological study describes a renal centre’s 20-year experience of primary FSGS.MethodsPatients were identified with a diagnosis of primary FSGS after exclusion of known secondary causes. In this retrospective observational study, data was collected for baseline demographics, immunosuppression and outcomes. A two-step cluster analysis was used to identify natural groupings within the dataset.ResultsThe total cohort was made up of 87 patients. Those who received immunosuppression had lower median serum albumin than those who did not- 23g/L vs 40g/L (p<0.001) and higher median urine protein creatinine ratios (uPCR)- 795mg/mmol vs 318mg/mmol (p <0.001). They were more likely to achieve complete remission (62% vs 40%, p=0.041), but relapsed more 48.6% vs 22% (p=0.027). Overall 5 year mortality was 10.3% and 5 year progression to RRT was seen in 17.2%. Complete remission was observed in 49.4%. The 2-step cluster analysis separated the cohort into 3 clusters: cluster 1 (n=26) with ‘nephrotic-range proteinuria’; cluster 2 (n=43) with ‘non-nephrotic-range proteinuria’; and cluster 3 (n=18) with nephrotic syndrome. Immunosuppression use was comparable in clusters 1 and 3, but lower in cluster 2 (77.8% and 69.2% vs 11.6%, p<0.001). Rates of complete remission were greatest in clusters 1 and 3 vs cluster 2: 57.7% and 66.7% vs 37.2%.ConclusionPeople who received immunosuppression had lower serum albumin and achieved remission more frequently, but were also prone to relapse. Our cluster analysis highlighted 3 FSGS phenotypes: a nephrotic cluster that clearly require immunosuppression; a cohort with preserved serum albumin and non-nephrotic range proteinuria who will benefit from supportive care; and lastly a cluster with heavy proteinuria but serum albumin > 30g/L. This group may still have immune mediated disease and thus could potentially benefit from immunosuppression.Trial registrationThis study protocol was reviewed and approved by the ‘Research and Innovation committee of the Northern Care Alliance NHS Group’, study approval number (Ref: ID 22HIP54).

Rituximab as add-on therapy in patients with resistant lupus nephritis who have failed induction or maintenance therapy with other agents: A real-world experience from a single center in Mumbai.

Lupus nephritis (LN) is associated with poor outcomes and a significant risk of progression to end-stage renal disease (ESRD). Some patients with resistant LN do not respond adequately to current treatment options and need alternative strategies or therapies. The objective is to evaluate the efficacy and safety of rituximab as a re-induction therapy (Re-RTX) followed by maintenance therapy for patients with resistant LN. Twenty-four patients with resistant LN (failed initial induction therapy or severe relapse after remission) were analyzed. Re-RTX was co-administered with other immunosuppressants. The primary KDIGO criteria outcomes included renal response (complete and partial), disease progression, relapses, and infections. The median age was 28years (IQR 24.5-42), and the female-to-male ratio was 11:1. All patients had active LN, and 91.3% had proliferative LN. Baseline creatinine was 1.075mg% (IQR 0.7-1.38), and mean urine protein-to-creatinine ratio (UPCR) was 4.9 (IQR 2.8-6.65). Of the patients receiving RTX as re-induction therapy, 66.6% (16/24) had failed initial induction therapy with other immunosuppressants, whereas 33.3% (8/24) had severe relapse during maintenance therapy.Re-RTX had a favorable renal response at 6months, with 91.7% of the patients responding (20.8% complete response and 70.8% partial response). At 12months, 58.3% of the patients maintained a renal response (25% complete response and 33.3% partial response). Approximately one-third of patients relapsed within a year.Fourteen patients (58.3%) continued RTX maintenance therapy with two different treatment regimens. At 6months, Regimen-1 (500mg every 6months) resulted in a partial response in 43% (3/7) and relapse in 57% (4/7) of patients. Regimen 2 (1g dose per year) achieved a complete response in 28.5% (2/7) and a partial response in 71.5% (5/7) with no relapses at 6months.At a median follow-up of 29months, adverse renal outcomes were observed in 29.16% of the patients with progression to advanced chronic kidney disease (CKD) or end-stage renal disease (ESRD). The overall use of Re-RTX was considered safe, with a reported infection prevalence of 16%, which is comparable to the existing data. Re-RTX demonstrated efficacy and safety as an induction therapy for resistant LN. However, the response waned after 1year, underscoring the need for optimized maintenance therapy.

A competing risk predictive model for kidney failure in patients with advanced chronic kidney disease

Background/purposePredictive modeling aids in identifying patients at high risk of adverse events. Using routinely collected data, we report a competing risk prediction model for kidney failure. MethodsA total of 5138 patients with CKD stages 3b–5 were included and randomized into the development and validation cohorts at a ratio of 7:3. The outcome was end-stage kidney disease, defined as the initiation of dialysis or kidney transplantation. All patients were followed-up until December 31, 2020. A Fine and Gray model was applied to estimate the sub-hazard ratio of kidney failure, with death as a competing event. ResultsIn the development cohort, the mean age was 67.6 ± 13.9 years and 60 % were male. The mean index eGFR and median urinary protein-creatinine ratio (UPCR) were 26.5 ± 12.8 mL/min/1.73 m2 and 1051 mg/g, respectively. The median follow-up duration was 1051 days. The proportion of patients with kidney failure and death was 25.4 % and 14.1 %, respectively. Four models were applied, including eGFR, age, sex, UPCR, systolic and diastolic blood pressure, serum albumin, phosphate, uric acid, haemoglobin, and potassium levels had the best goodness of fit. All models had good discrimination with time-to-event c statistics of 0.89–0.95 in the development cohort and 0.86–0.95 in the validation cohort. The prediction models showed excellent and fairly good calibration at 2 and 5-year risk, respectively. ConclusionUsing real-world data, our competing risk model can accurately predict progression to kidney failure over 2 years in patients with advanced CKD.

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.

Optimizing Albuminuria Assessment in Patients with Sickle Cell Disease: Insights from the Sikamic Study

Background Patients with sickle cell disease (SCD) are at increased risk of developing renal complications, making early detection and management of these issues critical. Albuminuria has been identified as a relevant biomarker associated with chronic kidney disease (CKD) progression in SCD, as demonstrated in several studies (Gonzalez et al., 2017; Guasch et al., 2018). Quantification of albuminuria is typically performed using the urine albumin-to-creatinine ratio (ACR). However, this measurement is not without its challenges, as variability in results can occur due to several factors, including analytical method, varying sampling conditions, and biological and medical factors such as physical activity, diurnal changes, diet, and hydration, which require the collection of multiple consecutive first morning samples. Studies have shown that the use of ACR from first morning urine samples provides results comparable to the gold standard 24-hour urine collection, with improved precision and less intra-individual variability than random urine samples typically collected during clinic visits (Witte 2009, Jermendy 2001, Lambers 2008). Collecting more urine samples generally improves precision and statistical power, but Kröpelin et al (2025) showed that collecting more than three consecutive urine samples does not significantly improve precision. Material and method The ongoing SIKAMIC study is a phase IIb, international (France and Africa), double-blind, randomized, placebo-controlled trial. The study aims to determine the effect of hydroxycarbamide on albuminuria level after 6 months of treatment in SCD adult patients. Here, we analyzed the variability of ACR in all patients pre-selected for the study. Microalbuminuria is commonly considered the first clinical indicator of glomerular damage in SCD. As per the KDIGO (Kidney Disease: Improving Global Outcomes), microalbuminuria is characterized by an ACR ranging from 3 to 30 mg/mmol, while macroalbuminuria refers to an ACR greater than 30 mg/mmol. For SIKAMIC study, patients with an ACR above 3 mg/mmol and below 100 mg/mmol were included. ACR was measured in first morning urine samples over three consecutive days. Patients were instructed to collect these samples at home, which were either collected by a hospital courier or brought to the hospital/laboratory by the patient for analysis. Estimated glomerular filtration rate (eGFR) was calculated using the CKD EPI formula without ethnic criteria. Means and standard deviations of the three measurements were calculated per patient, and a reproducibility test was performed using Mixed Effect Model and Bland Altman analyses (Graphpad Prism 9). Results Out of the initial 179 patients pre-selected for the study (59 from France and 120 from Africa) 99 patients (34 in France and 65 in Africa) met the inclusion criteria and were enrolled in the SIKAMIC study. Pre-selected patients from Africa were younger than patients from France with a mean age of 28.3 years and 33.8 years respectively (p&amp;lt;0.001). However, the mean ACR did not differ between groups (11.8 vs 12.7 mg/mmol; p=0.8) as observed for the mean eGFR value (123 vs 120.9; p=0.75). Additionally, the sex ratio was similar between groups (0.62 vs 0.67). For all patients, the mean ACR was 14.6, 17.3 and 15.6 mg/mmol on days 1, 2 and 3, respectively, with no significant difference (p=0.43; Figure 1 : A). The mean standard deviation of ACR between day 1, 2 and 3 was 6.8 mg/mmol, suggesting good consistency and reproducibility of the ACR measurements over the three days. Bland-Altman plots are shown in Figure 1 for the total population (n=161; 1B), microalbuminuric (1C; n=86) and macroalbuminuric (1D; n=11) patients, illustrating the agreement of ACR measurements within these subgroups. Conclusion : The SIKAMIC study contributes valuable insights into the evaluation of albuminuria in SCD patients. The reproducibility of the ACR appears to be sufficient to allow satisfactory monitoring on a single morning measurement in SCD routine care, both in Africa and Europe population of SCD patients.

The Feasibility of Japanese Histological Grade Classification for Predicting Renal Function Deterioration among Taiwanese Individuals with IgA Nephropathy

Background: We aimed to validate the Japanese histological grading classification (JHGC) in our population of IgA immunoglobulin (IgAN) cases. Methods: We conducted a retrospective cohort study at Taichung Veterans General Hospital in Taiwan from January 2011 to December 2023. The process involved assessing JHGC’s clinical, histological, and merged grading system. Composite renal outcomes based on glomerular filtrate rate (eGFR) were considered. Results: The study included 359 IgAN by renal biopsies. Kidney function at the time of biopsy was suboptimal, with average SCr of 1.3 mg/dL, eGFR of 54.0 mL/min/1.732 m2, and urine protein–creatinine ratio (UPCR) of 1.2 mg/mg. JHGC effectively identified different severity levels of histological and clinical aspects in Taiwanese IgAN. Initial 4-histological classification showed significantly higher MEST-C scores (p &lt; 0.001). Merging grade III and IV was reasonable in Japanese and Taiwanese populations. The clinical grading system (3C) was associated with histological status and proteinuria, but there was no significant trend with SCr, eGFR, and blood urea nitrogen. Significant differences were found among the three groups (log-rank p &lt; 0.01), but C-grade I and II lacked significant difference in long-term renal outcomes. We separated UPCR &lt; 0.5 mg/mg into two groups: eGFR≥ and &lt;60 mL/min/1.732 m2. The new grading system effectively differentiated risk factors for renal outcomes (log-rank p &lt; 0.01), suggesting the need for separation in Taiwanese IgAN. Conclusions: Our study externally validated JHGC in non-Japanese IgAN. Despite applicability to our population, we recommend a new classification specifically for Taiwanese IgAN patients with increased case numbers in eGFR ≥ 60 mL/min/1.732 m2 and UPCR &lt; 0.5 g/day group.

The Jamaica Salt Consumption Study Protocol: Sodium Intake; Sodium Content in Restaurant Foods; Knowledge, Attitudes, and Practices; Spot Urine Sodium Validation.

Excess dietary salt consumption is a major contributor to hypertension and cardiovascular disease. Public education programs on the dangers of high salt intake, and population level interventions to reduce the salt content in foods are possible strategies to address this problem. In Jamaica, there are limited data on the levels of salt consumption and the population's knowledge and practices with regards to salt consumption. This study therefore aims to obtain baseline data on salt consumption, salt content in foods sold in restaurants, and evaluate knowledge, attitudes, and practices of Jamaicans regarding salt consumption. The study is divided into four components. Component 1 will be a secondary analysis of data on urinary sodium from spot urine samples collected as part of a national survey, the Jamaica Health and Lifestyle Survey 2016-2017. Component 2 will be a survey of chain and non-chain restaurants in Jamaica, to estimate the sodium content of foods sold in restaurants. Component 3 is another national survey, this time on a sample 1,200 individuals to obtain data on knowledge, attitudes and practices regarding salt consumption and estimation of urinary sodium excretion. Component 4 is a validation study to assess the level of agreement between spot urine sodium estimates and 24-hour urinary sodium from 120 individuals from Component 3. This study will provide important baseline data on salt consumption in Jamaica and will fulfil the first components of the World Health Organization SHAKE Technical Package for Salt Reduction. The findings will serve as a guide to Jamaica's Ministry of Health and Wellness in the development of a national salt reduction program. Findings will also inform interventions to promote individual and population level sodium reduction strategies as the country seeks to achieve the national target of a 30% reduction in salt consumption by 2025.