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Background Borderline proteinuria is associated with decreased survival in cats with azotemic chronic kidney disease (CKD). Objectives Determine the clinical importance of borderline proteinuria in nonazotemic cats. Animals A total of 201 healthy client‐owned cats ≥7 years of age; 150 nonproteinuric (urinary protein : creatinine ratio [UPC] <0.2) and 51 borderline proteinuric (UPC 0.2‐0.4). Methods Prospective study. Cats were thoroughly screened and subsequently examined every 6 months for 2 years. Kaplan‐Meier curves were compared between nonproteinuric and borderline proteinuric cats. Univariable and multivariable Cox models were fit to determine the relationship between development of renal disease and potential risk factors such as age, sex, breed, weight, dental disease, blood pressure, serum creatinine concentration (sCrea), serum symmetric dimethylarginine concentration (sSDMA), blood urea nitrogen concentration, urine specific gravity (USG), and UPC. Results Significantly more cats with borderline proteinuria at inclusion developed renal disease (International Renal Interest Society [IRIS] ≥ stage 2 CKD or renal proteinuria; log‐rank P = .004) or died (log‐rank P = .02) within 2 years, compared with nonproteinuric cats. In the multivariate analysis, IRIS stage 1 CKD (persistent USG <1.035 or sSDMA >14 μg/dL; hazard ratio [HR], 4.2; 95% confidence interval [CI], 2.0‐8.8; P < .001), sCrea ≥1.6 mg/dL (≥140 μmol/L; HR, 2.6; 95% CI, 1.1‐6.4; P = .04), borderline proteinuria (HR, 2.5; 95% CI, 1.2‐5.2; P = .01), and age at inclusion (HR, 1.3; 95% CI, 1.2‐1.5; P < .001) were significantly associated with diagnosis of renal disease 6 months later. Conclusions and Clinical Importance Borderline proteinuria should receive more attention in healthy mature adult and senior cats because it is associated with renal disease and death.

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

Objective We evaluated the interaction of urinary protein-to-creatinine ratio (UPCR) with diabetes on the risk of cardiovascular events in a cohort study. Methods The study population consisted of 639 participants with chronic kidney disease (CKD) stages 2–5, enrolled between 2010 and 2011 in Japan. Cox proportional hazards models were used to evaluate the independent and combined effects of the UPCR and diabetes on cardiovascular events. Results During a median follow-up of 3 years, 59 participants developed cardiovascular events during follow-up. A notably higher risk of cardiovascular events was found in participants with proteinuria [hazards ratio (HR): 2.16, 95% confidence interval (95% CI): 1.17–3.97] compared to those without proteinuria at UPCR levels. In addition, the participants with diabetes had a higher risk of cardiovascular events (HR: 2.53, 95% CI: 1.49–4.30) than those without diabetes. Moreover, an interaction was found between UPCR and diabetes on cardiovascular events ( P for interaction = 0.04). Participants with both proteinuria (UPCR ≥ 0.5 g/gCr) and diabetes had a 4.09 times higher risk of cardiovascular events (HR: 4.09, 95% CI: 1.97–8.47) compared with those without proteinuria (UPCR < 0.5 g/gCr) and diabetes. Conclusions In summary, among participants with CKD stages 2–5, proteinuria and diabetes were found to independently and jointly affect the risk of cardiovascular events. Participants with proteinuria and diabetes had the highest risk of cardiovascular events compared with other groups.

Background Hyperhomocysteinemia has been linked with chronic kidney disease (CKD). The present study investigated whether homocysteine (Hcy) serum levels might serve as a marker for the advancement of diabetic nephropathy (DN). Methods Clinical and laboratory indicators including Hcy, vitamin D (VD), urine protein, estimated glomerular filtration rate (eGFR) and the urinary protein/creatinine ratio in subjects > 65 years with DN (n = 1,845), prediabetes (n = 1,180) and in a non-diabetes (control) group (n = 28,720) were analyzed. Results DN patients had elevated Hcy concentrations, decreased VD and higher urinary protein levels, a reduced eGFR and a higher urinary protein/creatinine ratio compared with prediabetic and control subjects. After correcting for urinary protein quantitation, multivariate analysis revealed that both the Hcy concentration ( P  < 0.010) and urinary protein/creatinine ratio ( P  < 0.001) were risk factors, while the VD2 + VD3 serum concentration ( P  < 0.001) was a protective factor for DN. Moreover, Hcy > 12 µmol/L was a cut-off value for predicting advanced DN. Conclusion Hcy serum concentration is a potential marker for the advancement of CKD in DN but not prediabetes patients.

By using spectral domain optical coherence tomography (SD-OCT) to measure retinal blood vessels. The correlation between the changes of retinal vascular structure and the degree of diabetic nephropathy is analyzed with a full-pixel Semantic segmentation method. A total of 120 patients with diabetic nephropathy who were treated in the nephrology department of Quzhou People's Hospital from March 2023 to March 2024 were selected and divided into three groups according to the urinary albumin creatinine ratio (UACR). The groups included simple diabetes group (UACR < 30 mg/g), microalbuminuria group (30 mg/g ≤ UACR <300 mg/g) and macroalbuminuria group (UACR ≥300 mg/g). SD-OCT was used to scan the arteries and veins in the superior temporal area B of the retina. The semantic segmentation method built into the SD-eye software was used to automatically identify the morphology and structure of the vessels and calculate the parameters of arteriovenous vessels. The parameters of arteriovenous vessels are as follows: outer diameter of the retinal artery (RAOD); inner diameter of the retinal artery (RALD); arterial wall thickness (AWT); arterial wall to lumen ratio (AWLR); cross sectional area of arterial wall (AWCSA); retinal vein outer diameter (RVOD); retinal vein inner diameter (RVLD); vein wall thickness (VWT); vein wall to lumen ratio (VWLR); cross sectional area of vein wall (VWCSA). Statistical analysis software was used to compare and analyze the parameters of retinal arteriovenous vessels of the three groups. The study revealed statistically significant differences in RAOD and RALD among the three groups (  < 0.05) with the RAOD and RALD of the macroalbuminuria group and microalbuminuria group being lower than those of the simple diabetes group. Conversely, there were no significant differences in AWT, AWLR and AWCSA among the three groups (  > 0.05). Additionally, the differences in RVOD and RVLD among the three groups were found to be statistically significant (  < 0.05) with the RVOD and RVLD of the simple diabetes group being lower than those of the microalbuminuria group and macroalbuminuria group. No significant differences were observed in VWT and VWL among the groups. Additionally, RVOD and RVLD were weakly associated with UACR (  = 0.247,  = 0.007;  = 0.210,  = 0.021). Full-pixel semantic segmentation method combined with OCT images is a new retinal vascular scanning technology, which can be used as a new method for early diagnosis of diabetic nephropathy. The structural changes of retinal vessels can be used to predict the severity of diabetic nephropathy during the development of diabetic nephropathy.

The association between proteinuria levels and cardiovascular disease (CVD) development and all-cause mortality in chronic kidney disease (CKD) patients remains controversial. In this investigation, we conducted a retrospective analysis involving 1138 patients who were registered in the CKD-Research of Outcomes in Treatment and Epidemiology (ROUTE) study. The primary outcome of this study was the composite of cardiovascular events or all-cause death. Cox proportional hazards regression, smooth curve fitting, piecewise linear regression, and subgroup analyses were used. The mean age of the included individuals was 67.3 ± 13.6 years old. Adjusted hazard ratios (HRs) for UPCR in middle and high groups, compared to the low group, were 1.93 (95% CI: 1.28-2.91) and 4.12 (95% CI: 2.87-5.92), respectively, after multivariable adjustment. Further adjustments maintained significant associations; HRs for middle and high groups were 1.71 (95% CI: 1.12-2.61) and 3.07 (95% CI: 2.08-4.54). A nonlinear UPCR-primary outcome relationship was observed, with an inflection point at 3.93 g/gCr. Among non-dialyzed patients with stage G2-G5 CKD, a nonlinear association between UPCR and the primary outcome was observed. A higher UPCR (when UPCR < 3.93 g/gCr) was an independent predictor of the primary outcome. Importantly, our study predates SGLT2 inhibitor use, showcasing outcomes achievable without these medications. Future research considerations will involve factors like SGLT-2 inhibitor utilization.

Albuminuria is a well-known predictor of chronic kidney disease in patients with type 2 diabetes mellitus (DM). However, proteinuria is associated with chronic complications in patients without albuminuria. In this retrospective cohort study, we explored whether non-albumin proteinuria is associated with all-cause mortality and compared the effects of non-albumin proteinuria on all-cause mortality between patients with and without albuminuria. We retrospectively collected data from patients with type 2 DM for whom we had obtained measurements of both urinary albumin-to-creatinine ratio (UACR) and urinary protein-to-creatinine ratio (UPCR) from the same spot urine specimen. Urinary non-albumin protein-creatinine ratio (UNAPCR) was defined as UPCR–UACR. Of the 1809 enrolled subjects, 695 (38.4%) patients died over a median follow-up of 6.4 years. The cohort was separated into four subgroups according to UACR (30 mg/g) and UNAPCR (120 mg/g) to examine whether these indices are associated with all-cause mortality. Compared with the low UACR and low UNAPCR subgroup as the reference group, multivariable Cox regression analyses indicated no significant difference in mortality in the high UACR and low UNAPCR subgroup (hazard ratio [HR] 1.189, 95% confidence interval [CI] 0.889–1.589, P = 0.243), but mortality risks were significantly higher in the low UACR and high UNAPCR subgroup (HR 2.204, 95% CI 1.448–3.356, P < 0.001) and in the high UACR with high UNAPCR subgroup (HR 1.796, 95% CI 1.451–2.221, P < 0.001). In the multivariable Cox regression model with inclusion of both UACR and UNAPCR, UNAPCR ≥ 120 mg/g was significantly associated with an increased mortality risk (HR 1.655, 95% CI 1.324–2.070, P < 0.001), but UACR ≥ 30 mg/g was not significantly associated with mortality risk (HR 1.046, 95% CI 0.820–1.334, P = 0.717). In conclusion, UNAPCR is an independent predictor of all-cause mortality in patients with type 2 DM.

BackgroundSchool urinary screening has been performed in Japan.MethodsIkeda City and Toyono Town introduced, in 2012 and 2013, urinary protein/creatinine (Cr) ratio measurement into the urine-screening protocols designed for students aged between 4 and 15 years. For each student whose urinary protein/Cr ratio was ≥ 0.15 g/gCr (positive case), an appointment was made with a specialist at Ikeda City Hospital. The results of these screening urinalyses conducted through 2018 are summarized.Results14,606 junior high and elementary school students aged between 6 and 15 years were included. On average, they underwent 4.16 screening tests. 77 positive cases were detected, and seven students were diagnosed with high-risk chronic kidney disease (CKD). Of these, four underwent renal biopsy, and two, one, and one were diagnosed with IgA nephropathy, MPGN, and FSGS, respectively. In three students, detection of CKD would have been difficult without urinary screening. Incident rates of high-risk CKD and IgA nephropathy are estimated as 11.5 and 3.3 cases/100,000 students/year. 78.0% of positive cases without high-risk CKD showed no urinary abnormality after one year. 2301 kindergarten students aged between 4 and 6 years received an average of 1.74 screening urinalyses; none was positive or high-risk CKD. The estimated cost of detecting one high-risk CKD student whose detection would have been difficult without this screening was 3,156,711 Japanese yen.ConclusionSchool urinary screening using the urinary protein/Cr ratio can efficiently refer to a specialist. It detects a few children with high-risk CKD early with spending high cost.

This study aims to assess the main causes of proteinuria in dogs from the region of Lisbon (Portugal), estimating the relevance of screening for canine vector-borne diseases (CVBDs). A cross-sectional retrospective study was conducted. Medical records from proteinuric dogs (urinary protein–creatinine ratio > 0.5) presented to a Veterinary Teaching Hospital over a two-year period were reviewed for signalment, established diagnosis, proteinuria origin, and CVBD screening results. A total of 106 dogs were included. The median age was 9.5 years old (IQR: 7–12). Proteinuria was considered of renal origin in 76% of cases (46% of them had a presumptive diagnosis of glomerulonephritis secondary to CVBD, 27% chronic kidney disease, 26% systemic disease possible to induce proteinuria, and 1% leptospirosis). Proteinuria was classified as post-renal or mixed-origin in 17% and 7% of cases, respectively. About 35% of proteinuric dogs were positive for at least one CVBD. Of them, 84% were seropositive for one CVBD, while 16% tested positive for two or more. Among dogs testing positive for CVBD, 89% were seropositive for Leishmania infantum. This study showed that about one-third of proteinuric dogs tested positive for CVBDs, highlighting the relevance of their screening in dogs with proteinuria living in endemic regions.

Chronic kidney disease (CKD) is a major public health concern with an increasing proportion of sufferers progressing to renal replacement therapy (RRT). Early identification of those at risk of disease progression could be key in improving outcomes. We hypothesise that urinary liver-type fatty acid binding protein (uL-FABP) may be a suitable biomarker for CKD progression and can add value to currently established biomarkers such as the urinary protein-to-creatinine ratio (uPCR). A total of 583 participants with CKD 1–5 (not receiving renal replacement therapy) entered a 2 yr prospective longitudinal study. UPCR and uL-FABP were measured at baseline and CKD progression was defined as either (i) a decline in eGFR of >5 mL/min/1.73 m2 or an increase in serum creatinine by 10% at 1 yr; (ii) a decline in eGFR of >6 mL/min/1.73 m2 or an increase in serum creatinine by 20% at 2 yrs; or (iii) the initiation of RRT. A combined outcome of initiating RRT or death was also included. Approximately 40% of participants showed CKD progression. uL-FABP predicted CKD progression at both years 1 and 2 (OR 1.01, p < 0.01). Sensitivity and specificity were comparable to those of uPCR (AUC 0.623 v 0.706) and heat map analysis suggested that uL-FABP in the absence of significant proteinuria can predict an increase in serum creatinine of 10% at 1 yr and 20% at 2 yrs. The risk of the combined outcome of initiating RRT or death was 23% higher in those with high uL-FABP (p < 0.01) independent of uPCR. uL-FABP appears to be a highly sensitive and specific biomarker of CKD progression. The use of this biomarker could enhance the risk stratification of CKD and its progression and should be assessed further.