[Cross-sectional associations between reproductive lifespan duration and urinary albumin-creatinine ratio].

Objective: To investigate the association between reproductive lifespan duration (RLD) and urinary albumin-creatinine ratio (UACR) in a Chinese postmenopausal population. Methods: This cross-sectional study included 11 055 naturally postmenopausal women from seven regions of China from May to December 2011. RLD was divided into four groups. Propensity score matching was performed to reduce bias, and logistic regressions and stratifications were conducted to investigate the association between RLD and increased UACR (≥30 mg/g). Mediation effect analysis was performed to quantify the effect of RLD on cardiovascular disease (CVD) induced by elevated UACR. Results: There were 2 373 participants with a RLD of 18-31 years, 2 888 participants with a RLD of 32-34 years, 2 472 participants with a RLD of 35-36 years, and 3 322 participants with a RLD of 37-50 years. The shortest RLD (18-31 years) group was characterized with older age (P<0.001), a higher incidence of CVD (P=0.025), and the highest level of UACR (P<0.001). After adjusting for confounders, women with a longer RLD (37-50 years group) exhibited a lower risk of UACR elevation compared with those with the shortest RLD (18-31 years group) (OR=0.72, 95%CI 0.64-0.82, P<0.001). Every 1-year extension in RLD was linked to a 2% reduction in the risk of UACR elevation (OR=0.98, 95%CI 0.97-0.99, P<0.001). Stratified analysis revealed a more significant association between RLD and UACR in women who were a normal weight (P=0.003) or overweight (P=0.001), in those without CVD history (P=0.001), and in those with impaired estimated glomerular filtration rate (P=0.004). The mediation casual analysis showed that 3.0% of proteinuria inducing CVD events was mediated by RLD (P=0.048). Conclusion: A longer RLD (37-50 years) is associated with a lower UACR in Chinese postmenopausal women.

Kidney dysfunction: prevalence and associated risk factors in a community-based study from the North West Province of South Africa.

BACKGROUND: Globally, the World Health Organization ranks chronic kidney disease (CKD) as one of the top 10 causes of mortality. In South Africa, where noncommunicable diseases have become leading causes of mortality, the true population prevalence of CKD is unknown and associated risk factors remain understudied. This study aimed to describe the prevalence of kidney dysfunction and associated risk factors in a community from the North West province of South Africa. METHODS: This cross-sectional study included 1999 participants older than 30 years. Kidney dysfunction was defined as (i) estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73m2, or (ii) urine albuminuria-to-creatinine ratio (uACR) ≥ 3.0 mg/mmol, or a combination (i and ii). Risk factors included age, sex, urban/rural locality, body mass index (BMI), blood pressure (BP), lipid profile, haemoglobin A1c (HbA1C), C-reactive protein (CRP), gamma-glutamyl transferase (GGT), tobacco use, and HIV status. RESULTS: Mean age of participants was 48 (42;56) years, and 655/1999 (33%) had eGFR < 90 ml/min/1.73m2 and/or uACR ≥ 3.0 mg/mmol. Compared to those with normal kidney function, participants with eGFR < 90 ml/min/1.73m2 and/or uACR ≥ 3.0 mg/mmol were older, female, had higher measures of adiposity, systolic, diastolic, and mean arterial blood pressure, serum lipids and C-reactive protein (CRP) (all p ≤ 0.024). In multiple regression analyses eGFR was associated with systolic BP (ß = 0.11) and HIV infection (ß = -0.09), and albuminuria was associated with elevated CRP (ß = 0.12) and HIV infection (ß = 0.11) (all p < 0.026). In both groups (individuals with and without kidney dysfunction respectively), eGFR was associated with age (ß = -0.29, ß = -0.49), male sex (ß = 0.35, ß = 0.28), BMI (ß = -0.12, ß = -0.09), low-density/high-density lipoprotein cholesterol ratio (ß = -0.17, ß = -0.09) and CRP (ß = 0.10, ß = 0.09) (all p < 0.005); and uACR was associated with female sex (ß = 0.10, ß = -0.14), urban locality (ß = -0.11, ß = -0.08), BMI (ß = -0.11, ß-0.11), and systolic BP (ß = 0.27, ß = 0.14) (all p < 0.017). CONCLUSION: In this study from the North West province, South Africa, eGFR < 90 ml/min/1.73m2 and/or uACR ≥ 3.0 mg/mmol was prevalent and associated with modifiable risk factors. The findings may inform screening strategies for kidney disease prevention, focusing on women, obesity, blood pressure control, dyslipidaemia, identifying and treating inflammation, and HIV diagnosis and treatment.

High-Density Lipoprotein Lipidomics in Chronic Kidney Disease.

BACKGROUND: Patients with chronic kidney disease (CKD) have dysfunctional high-density lipoprotein (HDL) particles as compared with the general population. Understanding the lipid composition of HDL may provide mechanistic insight. We tested associations of estimated glomerular filtration rate (eGFR) and albuminuria with relative HDL abundance of ceramides, sphingomyelins, and phosphatidylcholines in participants with CKD. METHODS: We studied 490 participants with CKD from the Seattle Kidney Study. HDL was isolated from plasma; targeted lipidomics was used to quantify the relative abundance of ceramides, sphingomyelins, and phosphatidylcholines per 10 µg of total HDL protein. We evaluated the associations of eGFR and albuminuria with levels of individual lipids and lipid classes (including 7 ceramides, 6 sphingomyelins, and 24 phosphatidylcholines) using multivariable linear regression, controlling for multiple comparisons via the false discovery rate. RESULTS: The mean (SD) eGFR was 45 (24) mL/min/1.73 m2; the median (IQR[interquartile range]) albuminuria was 108 (16, 686) mg/g (12.2 [1.8, 77.6] mg/mmol) urine creatinine. After adjusting for demographics, past medical history, laboratory values, and medication use, eGFR was not associated with higher relative abundance of any class of lipids or individual lipids. Greater albuminuria was significantly associated with a higher relative abundance of total ceramides and moderate-long R-chain sphingomyelins, ceramides 22:0 and 24:1, hexosylceramide 16:0, sphingomyelin 16:0, and phosphatidylcholines 29:0, 30:1, and 38:2; the strongest association was for hexosylceramide 16:0 (increase per doubling of urine albumin to creatinine ratio 0.022 (95% CI, 0.012-0.032). CONCLUSIONS: Greater albuminuria was significantly associated with specific alterations in the lipid composition of HDL in participants with CKD.

Positive association between urinary albumin-creatinine ratio and lower extremity peripheral arterial disease in Chinese diabetes patients: A cross-section study with propensity score matching analysis.

BACKGROUND AND AIMS: Elevated urinary albumin-creatinine ratio (ACR) is an established risk factor for lower extremity peripheral arterial disease (PAD) in non-diabetes individual. This study aimed to determine the relationship between urinary ACR level and PAD in diabetes population. METHODS AND RESULTS: A cross-section study with 1396 hospitalized diabetes participants from department of endocrinology and neurology were performed and the propensity score matching method was applied to reduce the effects of confounding factors between the matched PAD and Non-PAD groups. The relationship between urinary ACR and ankle-brachial index (ABI) was analyzed by linear curve fitting analyses and multiple logistic regression models. Our study showed that the prevalence of PAD (low ABI, ABI<0.9) was 7.09% in our diabetes patients. The ABI level was significantly lower in high ACR group compared with those in normal urinary ACR group (1.11 ± 0.17 vs 1.13 ± 0.15, p = 0.010). The prevalence of PAD was increased with the increased tertile's of log2-transformed ACR in total patients before and after propensity score matching (p < 0.001 and p = 0.007, respectively). The OR (95% CI) between log2-transformed ACR and PAD was 1.0 and 1.70 (1.08-2.69, p = 0.022) respectively in normal and high ACR levels in diabetes patients after adjusting for potential confounders. After propensity score matching, the OR (95% CI) between log2-transformed ACR and PAD was 1.0 and 1.85 (1.05-3.23, p = 0.031) respectively in normal and high ACR levels in diabetes patients after adjusting for potential confounders. CONCLUSION: The elevated urinary ACR level was associated with PAD in Chinese diabetes patients.

Impact of Albuminuria on the Prognosis After Transcatheter Aortic Valve Implantation.

The impact of preoperative albuminuria on the prognosis after transcatheter aortic valve implantation (TAVI) has not been studied. A total of 228 patients who underwent TAVI for severe aortic stenosis (AS) and for whom preoperative urinary data was available were retrospectively investigated. Patients were divided into two groups according to the urinary albumin-to-creatinine ratio (ACR): high (ACR≥ 30 mg/g) and low (ACR<30 mg/g). The urinary total protein-to-creatinine ratio (PCR) and dipstick proteinuria were also evaluated. The primary outcome was the composite outcome of all-cause death and readmission for heart failure. In total, 117 patients had a high ACR and 111 patients had a low ACR. During the median follow-up period of 467 days, patients with a high ACR had a higher incidence of the primary outcome than those with a low ACR (p<0.001). Patients with a high PCR or positive dipstick proteinuria were also at a higher risk for the primary outcome (p<0.001 and p=0.008, respectively). Multivariable Cox proportional hazards analysis showed a high ACR was independently associated with a primary outcome (hazard ratio, 4.98; 95% confidence interval, 1.84-13.49; p=0.002). In conclusion, preoperative albuminuria is an independent predictor of cardiac events in patients with severe AS undergoing TAVI.

Urine excretion of C3dg and sC5b-9 coincide with proteinuria and development of preeclampsia in pregnant women with type-1 diabetes.

OBJECTIVE: Pregnant women with type-1 diabetes have an increased risk of preeclampsia with kidney injury and cardiovascular complications. Urine excretion of plasmin and soluble membrane attack complex (sC5b-9) is elevated in severe preeclampsia. We hypothesized a coupling between these events and that active plasmin promotes intratubular complement activation and membrane deposition. METHODS: Stored urine and plasma samples from pregnant women with type-1 diabetes (n = 88) collected at gestational weeks 12, 20, 28, 32, 36 and 38 were used. In the cohort, 14 women developed preeclampsia and were compared with 16 nonpreeclampsia controls. RESULTS: Urine C3dg and sC5b-9-associated C9 neoantigen/creatinine ratios increased and were significantly higher in women who developed preeclampsia. Plasma concentrations did not change with gestation. Urine plasmin(ogen) correlated to urine C3dg (r = 0.51, P < 0.001) and C9 neoantigen (r = 0.68, P < 0.001); urine albumin correlated to C3dg (r = 0.44, P < 0.001) and C9 (r = 0.59, P < 0.001). Membrane-associated C3dg and C9 neoantigen was detected in urinary extracellular vesicles from patients but not controls at 36 weeks. Receiver operating characteristic curves showed that C3dg and C9 neoantigen were inferior to albumin as predictive biomarkers for preeclampsia. CONCLUSION: In preeclampsia, urinary excretion of activated complement relates significantly to albuminuria and to plasmin(ogen) but not to activation in plasma. Intratubular complement activation in preeclampsia is a postfiltration event tightly related to proteinuria/plasminogenuria and a possible mechanistic link to cellular damage and kidney injury.

Assessing gestational exposure to trace elements in an area of unconventional oil and gas activity: comparison with reference populations and evaluation of variability.

BACKGROUND: Located in Northeastern British Columbia, the Montney formation is an important area of unconventional oil and gas exploitation, which can release contaminants like trace elements. Gestational exposure to these contaminants may lead to deleterious developmental effects. OBJECTIVES: Our study aimed to (1) assess gestational exposure to trace elements in women living in this region through repeated urinary measurements; (2) compare urinary concentrations to those from North American reference populations; (3) compare urinary concentrations between Indigenous and non-Indigenous participants; and (4) evaluate inter- and intra-individual variability in urinary levels. METHODS: Eighty-five pregnant women participating in the Exposures in the Peace River Valley (EXPERIVA) study provided daily spot urine samples over 7 consecutive days. Samples were analyzed for 20 trace elements using inductively-coupled mass spectrometry (ICP-MS). Descriptive statistics were calculated, and inter- and intra-individual variability in urinary levels was evaluated through intraclass correlation coefficient (ICC) calculation for each trace element. RESULTS: When compared with those from North American reference populations, median urinary levels were higher in our population for barium (~2 times), cobalt (~3 times) and strontium (~2 times). The 95th percentile of reference populations was exceeded at least 1 time by a substantial percentage of participants during the sampling week for barium (58%), cobalt (73%), copper (29%), manganese (28%), selenium (38%), strontium (60%) and vanadium (100%). We observed higher urinary manganese concentrations in self-identified Indigenous participants (median: 0.19 µg/g creatinine) compared to non-Indigenous participants (median: 0.15 µg/g of creatinine). ICCs varied from 0.288 to 0.722, indicating poor to moderate reliability depending on the trace element. SIGNIFICANCE: Our results suggest that pregnant women living in this region may be more exposed to certain trace elements (barium, cobalt, copper, manganese, selenium, strontium, and vanadium), and that one urine spot sample could be insufficient to adequately characterize participants' exposure to certain trace elements. IMPACT STATEMENT: Unconventional oil and gas (UOG) is an important industry in the Peace River Valley region (Northeastern British Columbia, Canada). Information on the impacts of this industry is limited, but recent literature emphasizes the risk of environmental contamination. The results presented in this paper highlight that pregnant women living near UOG wells in Northeastern British Columbia may be more exposed to some trace elements known to be related to this industry compared to reference populations. Furthermore, our results based on repeated urinary measurements show that one urine sample may be insufficient to adequately reflect long-term exposure to certain trace elements.

Association of habitual coffee consumption and kidney function: A prospective analysis in the Rotterdam Study.

BACKGROUND & AIMS: Population-based studies have suggested a protective effect of coffee against development of chronic kidney disease (CKD), possibly through coffee's anti-inflammatory and antioxidant compounds. Studies on coffee and kidney function decline in the general population are scarce. We studied associations of habitual coffee consumption with repeated assessments of estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR). METHODS: We used data from 7,914 participants of the population-based Rotterdam Study. Baseline coffee consumption data (cups/day) were obtained from home interviews and validated food frequency questionnaires (1997-2008). Repeated assessments of eGFR (ml/min per 1.73 m2, 1997-2014) were calculated according to the creatinine-based CKD Epidemiology Collaboration equation of 2012. Repeated assessments of urinary albumin and creatinine were used to estimate ACR (mg/g, 2006-2014). Data were analyzed by applying linear mixed models, adjusted for sociodemographic, lifestyle and dietary factors, and cardiovascular disease risk factors. Predefined subgroup analyses were performed stratified by CKD risk factors. RESULTS: Participants' mean (SD) baseline age was 66 (10) years, 57% were women and median [IQR] coffee consumption was 3.0 [2.0, 5.0] cups/day. Those drinking more coffee were more likely to smoke, and to have type 2 diabetes (T2D) and obesity. Mean eGFR was 79 (15) ml/min per 1.73 m2. In the total study population, coffee was not associated with longitudinal eGFR during a median of 5.4 years of follow-up (ß = 0.04 ml/min per 1.73 m2 per one cup/day [95% CI: -0.10,0.18]). However, among those aged >70 years, one additional coffee cup/day was associated with on average 0.84 (0.51,1.18) ml/min per 1.73 m2 higher longitudinal eGFR. Among obese participants this estimate was 0.32 (0.01,0.63). A protective trend was also observed among former smokers (0.17 [-0.03,0.39]) and those with T2D (0.42 [-0.05,0.88]). Coffee was not associated with longitudinal ACR (0.01 mg/ml [-0.01,0.02]). CONCLUSION: While coffee was not associated with eGFR and ACR in the total population, more coffee consumption was associated with higher longitudinal eGFR among those at higher risk for CKD, i.e., among those aged 70+ and obese participants. These findings require confirmation in other prospective cohort studies.

Use of Estimated Glomerular Filtration Rate and Urine Albumin-to-Creatinine Ratio Based on KDIGO 2012 Guideline in a Thai Community Hospital: Prevalence of Chronic Kidney Disease and its Risk Factors.

BACKGROUND Kidney disease is hard to detect at its early stage; therefore, the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guideline was developed for improving care and outcomes of patients with kidney disease. This study aimed to determine clinical outcomes from applying this guideline in a community hospital service. MATERIAL AND METHODS The patients' data were extracted from their medical records and analyzed for outcomes of using the estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) for detecting kidney disease. RESULTS The eGFR was utilized in 36 172 patients aged ≥18 years, and 76.86% of them had normal kidney function. The prevalence of chronic kidney disease (CKD) was 8.20%; most patients (68%) with CKD were in stages 3a and 3b. The most common causes of CKD were diabetes and hypertension. The UACR was mainly used in patients with diabetes. The percentage of patients with UACR ≥3 mg/mmol creatinine alone was significantly higher than that of patients with eGFR.

Design and Engineering of a Palm-Sized Optical Immunosensing Device for the Detection of a Kidney Dysfunction Biomarker.

Creatinine is one of the most common and specific biomarkers for renal diseases, usually found in the serum and urine of humans. Its level is extremely important and critical to know, not only in the case of renal diseases, but also for various other pathological conditions. Hence, detecting creatinine in clinically relevant ranges in a simplistic and personalized manner is interesting and important. In this direction, an optical sensing device has been developed for the simple, point-of-care detection of creatinine. The developed biosensor was able to detect creatinine quantitatively based on optical signals measured through a change in color. The sensor has been integrated with a smartphone to develop a palm-sized device for creatinine analysis in personalized settings. The sensor has been developed following facile chemical modification steps to anchor the creatinine-selective antibody to generate a sensing probe. The fabricated sensor has been thoroughly characterized by FTIR, AFM, and controlled optical analyses. The quantitative analysis is mediated through the reaction between picric acid and creatinine which was detected by the antibody-functionalized sensor probe. The differences in color intensity and creatinine concentrations show an excellent dose-dependent correlation in two different dynamic ranges from 5 to 20 µM and 35 to 400 µM, with a detection limit of 15.37 (±0.79) nM. Several interfering molecules, such as albumin, glucose, ascorbic acid, citric acid, glycine, uric acid, Na+, K+, and Cl-, were tested using the biosensor, in which no cross-reactivity was observed. The utility of the developed system to quantify creatinine in spiked serum samples was validated and the obtained percentage recoveries were found within the range of 89.71-97.30%. The fabricated biosensor was found to be highly reproducible and stable, and it retains its original signal for up to 28 days.

A comparison of the utility of the urine dipstick and urine protein-to-creatinine ratio for predicting microalbuminuria in patients with non-diabetic lifestyle-related diseases -a comparison with diabetes.

BACKGROUND: The utility of dipstick proteinuria for predicting microalbuminuria in non-diabetic lifestyle-related diseases compared with the urine protein-to-creatinine ratio (uPCR) and the effect of dipstick proteinuria on the cut-off value (CO) and accuracy of uPCR are unclear. METHODS: The subjects included Japanese patients ≥ 18 years old with lifestyle-related diseases who had an estimated glomerular filtration rate of ≥ 15 ml/min/1.73 m2 and uPCR of < 0.5 g/gCr at initiation. Urine dipstick, uPCR and urine albumin-to-creatinine ratio (uACR) were measured three times per case. Microalbuminuria was defined as uACR of 30-299 mg/gCr for at least 2 of 3 measurements. Youden's Index was used as the optimal CO. Factors associated with microalbuminuria were analyzed using a logistic regression model. RESULTS: In 313 non-diabetic cases (median 70.8 years old), 3 dipstick proteinuria measurements were independently useful for detecting microalbuminuria, and the CO was set when a trace finding was obtained at least 1 of 3 times (sensitivity 0.56, specificity 0.80, positive predictive value [PPV] 0.73, negative predictive value [NPV] 0.65). A single uPCR measurement was more useful than 3 dipstick measurements, and was useful for detecting microalbuminuria even in cases with three consecutive negative proteinuria findings, indicating that the CO of the second uPCR with G1-3a (n = 136) was 0.06 g/gCr (sensitivity 0.76, specificity 0.84. PPV 0.68, NPV 0.89), while that with G3-b4 (n = 59) was 0.10 g/gCr (sensitivity 0.56, specificity 0.91. PPV 0.83, NPV 0.71). The sum of 3 uPCRs was useful for detecting microalbuminuria in cases with G1-3a (sensitivity 0.67, specificity 0.94, PPV 0.82, NPV 0.86) and G3b-4 (sensitivity 0.78, specificity 0.94, PPV 0.91 NPV 0.83), with both COs being 0.23 g/gCr. These COs of microalbuminuria did not change when trace or more proteinuria was included, although the sensitivity increased. A high uPCR and low urine specific gravity or creatinine level were independent factors for uACR ≥ 30 mg/gCr in cases with negative proteinuria, although the uPCR was a major predictive factor of a uACR ≥ 30 mg/gCr. CONCLUSIONS: The uPCR (preferably determined using early-morning urine), including in dipstick-negative proteinuria cases with non-diabetic lifestyle-related diseases, can aid in the early detection of microalbuminuria. TRIAL REGISTRATION: Retrospectively registered.

[Suitability of estimated urine protein using different estimated 24 h urine creatinine equations in children with glomerular diseases].

Objective: To assess the reliability of estimated urine protein to predict 24 h urine protein excretion in children with glomerular diseases. Methods: Four hundred and forty-three children with glomerular diseases, who were admitted to pediatric department of Peking University First Hospital from January 2001 to December 2021, were enrolled in the cross-sectional study. The 24 h estimated urine creatinine which calculated by 6 previously described equations, 24 h measured urine creatinine, measured urine protein-to-creatinine ratio(UPCR), 24 h urine protein (24 hUP) and urinary sediment analysis with microscopy were collected, estimated urine protein was computed as the product of measured UPCR and estimated or measured 24 h urine creatinine. Spearman correlation analysis, Bland-Altman analysis and linear regression analysis were used to compare the correlation, agreement and accuracy between estimated urine protein and 24 hUP, and the effect of urinary protein level and erythrocyte numbers on their relationship was analyzed. Results: Of 443 children with glomerular diseases (aged (11±4) years, 221 male, 222 female), there were 216 participants with nephrotic syndrome, 78 participants with IgA nephropathy, 47 participants with Alport syndrome, 42 participants with lupus nephritis, 58 participants with purpura nephropathy, and 2 participants with isolated proteinuria. Spearman correlation analysis showed a strong correlation between estimated urine protein and 24 hUP (r=0.90, P<0.05), and the correlation improved after multiplying the measured UPCR by 24 h measured urine creatinine (r=0.94, P<0.05). Improved correlation was also observed using the estimated urine creatinine which calculated by Hellerstein formula, Ghazali-Barratt formula, Ellam formula, Walser formula, Cockcroft-Gault formula, Ix formula (r=0.93, 0.94, 0.90, 0.90, 0.94, 0.93, all P<0.05).Bland-altman analysis showed that the difference between measured UPCR and 24 hUP was (-0.30±2.22) g, consistency limit was -4.65-4.04, and the consistency improved after 24 h measured urine creatinine correction (difference was (0.27±1.31) g, consistency limit -2.30-2.84). The consistency of estimated urine protein was further improved after correction by different formulas, and the Cockcroft-Gault formula showed the best consistency between estimated urine protein and 24 hUP (difference was (0.11±1.18)g, consistency limit was -2.20-2.42). Linear regression analysis showed that measured UPCR had poor accuracy in predicting 24 hUP (R2=0.55, α=0.48, ß=0.60, P<0.05), and the accuracy improved after 24 h measured urine creatinine correction, the accuracy of estimated urine protein for predicting 24 hUP was further improved by using different formulas, and Cockcroft-Gault formula was the best (R2=0.81, α=0.18, ß=0.96, P<0.05). With the increase of urinary protein level and the decrease of urinary erythrocyte numbers, the correlation, agreement and accuracy between estimated urine protein and measured UPCR and 24 hUP were improved(all P<0.05). Except Ellam and Ix formulas, estimated urine protein using the rest four formulas outperformed measured UPCR(all P<0.05). Conclusion: The 24 h urine creatinine excretion rate (obtained by the Cockcroft-Gault equation)-weighted urine protein-to-creatinine ratio more reliably predicts 24 hUP than measured UPCR alone in children with glomerular diseases.

Prevalence of aldosterone breakthrough in dogs receiving renin-angiotensin system inhibitors for proteinuric chronic kidney disease.

BACKGROUND: The influence of aldosterone breakthrough (ABT) on proteinuria reduction during renin-angiotensin system (RAS) inhibition for spontaneous proteinuric chronic kidney disease (CKDP ) has not been determined in dogs. OBJECTIVES: Determine whether ABT occurs in dogs with CKDP and if it is associated with decreased efficacy in proteinuria reduction during RAS inhibitor treatment. ANIMALS: Fifty-six client-owned dogs with CKDP and 31 healthy client-owned dogs. METHODS: Prospective, multicenter, open-label clinical trial. Dogs were treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker alone or in combination at the attending clinician's discretion and evaluated at 5 time points over 6 months. Healthy dogs were used to determine the urine aldosterone-to-creatinine ratio cutoff that defined ABT. The relationship of ABT (present at ≥50% of visits) and proteinuria outcome (≥50% reduction in urine protein-to-creatinine ratio from baseline at ≥50% of subsequent visits) was evaluated. Mixed effects logistic regression was used to evaluate the relationship between clinical variables and outcomes (either successful proteinuria reduction or ABT). RESULTS: Thirty-six percent (20/56) of dogs had successful proteinuria reduction. Between 34% and 59% of dogs had ABT, depending on the definition used. Aldosterone breakthrough was not associated with proteinuria outcome. Longer duration in the study was associated with greater likelihood of successful proteinuria reduction (P = .002; odds ratio, 1.6; 95% confidence interval [CI], 1.2-2.2). CONCLUSIONS AND CLINICAL IMPORTANCE: Aldosterone breakthrough was common in dogs receiving RAS inhibitors for CKDp but was not associated with proteinuria outcome.

Association between Elevated Iodine Intake and IQ among School Children in Portugal.

The goal of this work was to examine whether elevated iodine intake was associated with adverse effects on IQ among school-age children in Portugal. In a representative sample of children from the north of the country, IQ percentiles by age (assessed with Raven's Colored Progressive Matrices) were dichotomized to <50 ("below-average" IQs) and ≥50. Morning urine iodine concentrations, corrected for creatinine, were dichotomized to <250 µg/g and ≥250 µg/g, according to the European Commission/Scientific Committee on Food's tolerable upper level of daily iodine intake for young children. Data were examined with Chi-square tests, logistic regression, and GLM univariate analysis. The sample (N = 1965) was classified as generally iodine-adequate (median urinary iodine concentration = 129 µg/L; median iodine-to-creatinine ratio = 126 µg/g) according to the WHO's criteria. A greater proportion of children in the ≥250 µg/g group had below-average IQs, compared to children with less than 250 µg/g (p = 0.037), despite a sizable (though non-significant) proportion of children in the less-than-250 µg/g group also presenting below-average IQs, at the bottom of the iodine distribution (<50 µg/g). The proportion of below-average IQs increased with increasingly elevated iodine concentrations (p = 0.047). The association remained significant after the adjustment for confounders, with the elevated iodine group showing increased odds of having below-average IQs when compared with the non-elevated iodine group (OR 1.55; 95% CI 1.11-2.17; p = 0.011). Consistently, the former group presented a lower mean IQ than the latter (p = 0.006). High iodine intake was associated with lower IQs even in a population classified as iodine-adequate. These results bear on child cognition and on initiatives involving iodine supplementation.

Glutathione Peroxidase 4 Is a Predictor of Diabetic Kidney Disease Progression in Type 2 Diabetes Mellitus.

Background: Diabetic kidney disease (DKD) represents a heavy burden in type 2 diabetes mellitus (T2DM). Ferroptosis plays an important role in DKD, and it thus provides new perspectives to pursue more related biomarkers to assess the disease severity and prognosis. Glutathione peroxidase 4 (GPX4) is the mainstay in regulating ferroptosis. The current study investigated the predictive value of kidney GPX4 expression level in DKD progression. Methods: We measured GPX4 levels in kidney paraffin sections of 85 biopsy-proven DKD patients by immunohistochemistry staining. The associations between the GPX4 level and clinicopathological parameters as well as renal outcomes were analyzed. Results: GPX4 is mainly expressed in kidney tubulointerstitium, especially in tubular epithelial cells of DKD patients. The GPX4 expression level was significantly lower in DKD patients than healthy controls. Besides, GPX4 level significantly correlated with proteinuria (r = -0.42, p < 0.001), urinary albumin-to-creatinine ratio (uACR) (r = -0.40, p < 0.01), serum creatinine (Scr) (r = -0.59, p < 0.001), estimated glomerular filtration rate (eGFR) (r = 0.66, p < 0.001), and the percentage of sclerosed glomeruli (r = -0.42, p < 0.001) in renal specimens. During follow-up, the GPX4 level positively correlated with eGFR slope (r = 0.48, p < 0.001), and GPX4-low patients showed a significantly higher probability of developing end-stage kidney disease (ESKD) compared with GPX4-high patients (p < 0.01). Moreover, after adjusting for other potential predictors, the GPX4 level was still an independent predictor of developing ESKD (HR 2.15, 95% CI 1.08 to 4.28, p < 0.05). Conclusions: Kidney tubulointerstitial GPX4 expression level was associated with the disease severity and progression of DKD.

Urinary brain-derived neurotrophic factor and nerve growth factor as noninvasive biomarkers of overactive bladder in children.

Introduction: Overactive bladder (OAB) is the most common urinary disorder and the leading cause of functional daytime intermittent urinary incontinence in children. The aim of this study was to determine whether urinary brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) concentrations, normalized to urine creatinine, could be used as biomarkers for diagnosis and treatment monitoring of OAB in children. Materials and methods: Urine samples of 48 pediatric patients with OAB were collected at the start of anticholinergic therapy (baseline), at follow-up visits (3 and 6 months), and from 48 healthy controls. Urinary BDNF and NGF concentrations were determined by ELISA method (Merck, Darmstadt, Germany) and Luminex method (Thermo Fisher Scientific, Waltham, USA). Differences of frequency between quantifiable analyte concentrations between subject groups were determined using Fisher's exact test. Results: There was no statistically significant difference between quantifiable analyte concentrations between patients at baseline and the control group for BDNF and NGF by either the ELISA or Luminex method (P = 1.000, P = 0.170, P = 1.000, and P = N/A, respectively). There was a statistically significant difference between quantifiable BDNF by the ELISA method between patients at baseline and complete success follow-up (P = 0.027), while BDNF by Luminex method and NGF by both methods were not statistically significant (P = 0.078, P = 0.519, and P = N/A, respectively). Conclusions: This study did not demonstrate that urinary BDNF and NGF concentrations, can be used as biomarkers for diagnosis and therapy monitoring of OAB in children.

A Method for Estimating 24 h Urinary Sodium and Potassium Excretion by Spot Urine Specimen in Stroke Patients.

Spot urine specimens have been used to estimate 24 h urinary sodium (Na) excretion (24UNaV) and potassium (K) excretion (24UKV). However, the validity is limited for 24UNaV and unknown for 24UKV in stroke patients, using the existing formulas. Herein, we developed and validated a new formula for 24UNaV and 24UKV by spot urine specimens in stroke patients. Spot and 24 h urine samples were collected from 970 stroke patients. The models of 24UNaV and 24UKV were developed using stepwise multivariate linear regression in 689 patients. The performance of different formulas was internally validated in 281 patients at the population and individual levels. The obtained new formulas were: (1) estimated 24UNaV (mmol/day): -0.191 × Age + 4.349 × BMI + 0.229 × SpotNa + 1.744 × SpotNa/Spot creatinine (Cr) + 41.492 (for male); -1.030 × Age + 2.011 × BMI + 0.143 × SpotNa + 1.035 × SpotNa/SpotCr + 147.159 (for female); and (2) estimated 24UKV (mmol/day): -0.052 × Age + 0.410 × BMI + 0.031 × SpotK + 33.280 × Ln (spotK/spot Cr) - 5.789 × Ln (spotNa/spot Cr) - 1.035 (for male); -0.235 × Age + 0.530 × BMI + 0.040 × SpotK + 30.990 × Ln (spot K/spot Cr) - 7.837 × Ln (spotNa/spotCr) + 4.318 (for female). The new formula obtained the lowest mean bias (5.17 mmol/day for 24UNaV and 0.85 mmol/day for 24UKV) and highest proportion at the cutoff under the ±30% level for the estimation of 24UNaV (59.43%) and 24UKV (70.11%). The new formula provides a meaningful exploration to estimate 24UNaV and 24UKV in stroke patients by using spot urine specimens.

Progression of Chronic Kidney Disease Risk Categories and Risk of Cardiovascular Disease and Total Mortality: Coronary Artery Risk Development in Young Adults Cohort.

Background Previous studies of worsening chronic kidney disease (CKD) based on declining estimated glomerular filtration rate (eGFR) or increasing urine albumin-creatinine ratio (UACR) are limited to later middle-age and older adults. We examined associations of CKD progression and incident cardiovascular disease (CVD) and mortality in younger adults. Methods and Results We studied 4382 adults in CARDIA (Coronary Artery Risk Development in Young Adults) initially aged 27 to 41 years and prospectively over 20 years. Five-year transition probabilities across CKD risk categories were based on eGFR and UACR measured at each exam. Proportional hazards models predicted incident CVD and all-cause mortality by time-varying CKD risk category, adjusting for demographics and CVD risk factors. Progression of CKD risk categories over 20 years occurred in 28.7% (1256/4382) of participants, driven by increases in UACR, but including 5.8% (n=255) with eGFR<60 mL/min per 1.73 m2 or UACR ≥300 mg/g. Compared with eGFR ≥60 and UACR <10, demographic and smoking-adjusted hazard ratios for CVD were 1.62 (95% CI, 1.21-2.18) for low CKD risk (eGFR ≥60 with UACR 10-29) and 13.65 (95% CI, 7.52-24.79) for very high CKD risk (eGFR <30 or eGFR 30-44 with UACR 30-299; or eGFR 30-59 with UACR ≥300). Corresponding hazard ratios for all-cause mortality were 1.42 (95% CI, 1.08-1.88) and 14.75 (95% CI, 9.97-21.82). Although CVD associations were attenuated after adjustment for mediating CVD risk factors, all-cause mortality associations remained statistically significant. Conclusions Among young to middle-aged adults, progression to higher CKD risk category was common. Routine monitoring eGFR and UACR holds promise for prevention of CVD and total mortality.

Sysmex UN2000 detection of protein/creatinine ratio and of renal tubular epithelial cells can be used for screening lupus nephritis.

OBJECTIVES: This study is aimed to evaluate if automated urine sediment analysis UN2000 can be used to screen lupus nephritis. METHODS: UN2000 was used to examine 160 urine samples from patients with systemic lupus erythematosus and 124 urine samples from Lupus nephritis. The result of protein/creatinine ratio(P/C) and renal tubular epithelial cells (RTEC) were evaluated. With biochemical analysis and microscopic examination as the gold standard, the Kappa consistency test was used to analyze the accuracy of P/C and RTEC. Analysis was to evaluate the accuracy of P/C single item or RTEC single item and both screening lupusnephritis. RESULTS: The consistency of P/C and the gold standard, and that of RTEC and the gold standard are respectively strong and good (0.858 vs. 0.673). The specificity, positive predictive value, and coincidence were the highest when P/C ≥ 2 + was set as the only screening standard for lupus nephritis. When the standard was selected between P/C ≥ 2 + or RTEC > 2.8 cells/µl, the sensitivity and negative predictive value were the highest. CONCLUSION: UN 2000 can be used to screen lupus nephritis by detecting P/C and RTEC.

Evaluation of Early Renal Involvement in Essential Hypertension by Measuring Urinary Biomarkers.

Hypertensive kidney damage results in glomerular as well as tubular dysfunction. Albuminuria is a well-known marker of glomerular damage. On the other hand, urinary uromodulin is increasingly considered as a potential biomarker of early tubular dysfunction. The aim of the study was to assess glomerular and tubular function of the kidney by measuring urinary albumin and uromodulin excretion in hypertensive subjects. This cross-sectional study was conducted from July 2018 to June 2019 in Hypertension Clinic of Dhaka Medical College Hospital, Dhaka and Kidney Care and Research Centre, Sonargaon, Narayanganj, Bangladesh. In this study 122 hypertensive subjects with age >30 years, duration of hypertension <5 years, without accelerated or malignant BP, absence of dipstick proteinuria and eGFR >60ml/min were included. There were also 33 normotensive individuals included as healthy controls. Albumin-creatinine ratio (uACR mg/g), urine uromodulin-creatinine ratio (uUMODµg/g), urinary sodium-creatinine ratio (mEq/g) and potassium-creatinine ratio (mEq/g) were measured from single morning spot urine sample. Urinary uromodulin levels were measured by ELISA method. The hypertensive and normotensive subjects were age matched 49.0±12.0 vs. 48.0±11.0, years (p=NS). The mean uACR was 29.0±65.0 versus 5.6±2.7mg/g, (p<0.001) respectively. The median uUMOD in hypertensive subjects was 3.38 (1.73-9.06) and in normotensives 3.85(2.28-5.69) µg/g (p=non significant). Multivariate analysis showed significant inverse association between diastolic blood pressure and urinary uromodulin excretion. A uUMOD cut-off of 2.9 (25th percentile) showed eGFR, urinary sodium and potassium excretions were significantly lower at low uromodulin group. The glomerular involvement was found in 21.0% of hypertensive subjects as evidenced by albuminuria. No difference was observed in urinary uromodulin level between hypertensive and normotensive subjects. Low urinary uromodulin level was associated with lower eGFR, Na+ and K+ excretion which indicate simultaneous tubular and glomerular involvement.