Prospective Multicenter Study on Early Proximal Tubular Injury in COVID-19-Related Acute Respiratory Distress Syndrome.

Introduction: During COVID-19, renal impairment is associated with poor prognosis in intensive care unit (ICU). We aimed to assess the existence and incidence of early renal dysfunction and its prognostic value in patients with COVID-19-related acute respiratory distress syndrome (ARDS). Methods: In this prospective multicenter study, patients aged over 18 years with invasive mechanical ventilation (MV) for ARDS were enrolled in 3 ICUs. Precise evaluation of renal dysfunction markers, including urinary protein electrophoresis (UPE) and quantification, was performed within 24 hours after MV onset. Results: From March 2020 to December 2021, 135 patients were enrolled as follows: 100 with COVID-19 ARDS and 35 with non-COVID-19 ARDS. UPE found more tubular dysfunction in patients with COVID-19 (68% vs. 21.4%, P < 0.0001) and more normal profiles in patients without COVID-19 (65.0% vs. 11.2%, P = 0.0003). Patients with COVID-19 significantly displayed early urinary leakage of tubular proteins such as beta-2-microglobulin (ß2m) and free light chains, tended to display acute kidney injury (AKI) more frequently (51.0% vs. 34.3%, P = 0.088), had longer MV (20 vs. 9 days, P < 0.0001) and longer ICU stay (26 vs. 15 days, P < 0.0001). In COVID-19 ARDS, leakage of free lambda light chain was associated with the onset of Kidney Disease: Improving Global Outcomes (KDIGO) ≥2 AKI (odds ratio [OR]: 1.014, 95% confidence interval [CI] 1.003-1.025, P = 0.011). Conclusion: Patients with COVID-19-related ARDS display a proximal tubular dysfunction before the onset of AKI, which predicts AKI. Proximal tubular damage seems an important mechanism of COVID-19-induced nephropathy. Analysis of urinary proteins is a reliable noninvasive tool to assess proximal tubular dysfunction in the ICU.

Sprayed Urine Emits a Pungent Odor due to its Increased Adhesion to Vertical Objects via Urinary Proteins Rather Than to Changes in its Volatile Chemical Profile in Domestic Cats.

Spraying urine on vertical objects by raising the tail is a commonly observed functional behavior for chemical communication in Felidae species, including domestic cats (Felis silvestris catus). The sprayed urine is recognized as a chemical signal for territorial ownership of their habitats. Previous studies reported that sprayed urine emits a more pungent odor than urine excreted from a squatting position. However, little is known about how sprayed urine acts as a strong scent mark in the environment. Here, we showed that sprayed urine originates only from bladder urine without any secretions, such as anal sac secretions, but it can effectively emit volatile organic compounds (VOCs) when smeared on vertical objects due to its strong adhesion. Chemical profiles of VOCs and odor qualities were similar between fresh sprayed urine and bladder urine sampled immediately after spraying from the same individuals. Meanwhile, feline-specific proteinuria arising from excretion of a carboxylesterase that produces a precursor of cat-specific odorants resulted in reduced surface tension of the urine and increased adhesion to vertical surfaces, which kept sprayed urine on the surfaces and led to the emission of large amounts of VOCs. In conclusion, proteinuria contributes to the emission of a strong odor through its enhanced adhesion to vertical objects without other secretions containing malodorous substances. These findings improve our understanding of the mechanism of scent marking via the spraying of urine for chemical communication in cats.

Urinary protein and coagulation-fibrinolysis indicators in preeclampsia: Expression and significance.

This study investigates the expression and significance of urinary protein and coagulation-fibrinolysis indicators in preeclampsia, categorized into mild preeclampsia (109 cases) and severe preeclampsia (97 cases) based on disease severity. Additionally, 110 patients with gestational hypertension (gestational hypertension group) were included for comparative analysis. General information, laboratory indicators, urinary protein, and coagulation-fibrinolysis indicator levels were collected for each group. Significant differences were observed in blood pressure among groups (P < .05), while uric acid, serum creatinine, aspartate transaminase, alanine transaminase, and triglycerides showed no significant differences (P > .05). Total cholesterol, triglycerides, and low-density Lipoprotein levels in severe preeclampsia were higher than those in mild preeclampsia and gestational hypertension groups, whereas high-density lipoprotein, albumin, and platelet levels were lower in severe preeclampsia. No significant differences were observed in prothrombin time or D-dimer levels among groups (P > .05). Urinary protein, urinary protein quantification, activated partial thromboplastin time, thrombin time, and fibrinogen were identified as influencing factors for adverse maternal and infant outcomes in severe preeclampsia patients. The study concludes that urinary protein and coagulation-fibrinolysis indicators are elevated in preeclampsia, particularly in severe preeclampsia cases, suggesting their potential use as diagnostic influencing factors for severe preeclampsia.

The Strategy for Peptidomic LC-MS/MS Data Analysis: The Case of Urinary Peptidome Study.

The study of urinary peptidome is an important area of research, which concerns the characterization of endogenous peptides, as well as the identification of biomarkers for a wide range of socially significant diseases. First of all, this relates to renal and genitourinary pathologies and/or pathologies associated with proteinuria, such as kidney diseases, bladder, prostate and ovarian cancers, diabetic nephropathy, and pre-eclampsia. Unlike proteins, peptides do not require proteolytic hydrolysis, can be analyzed in their native form and can provide certain information about occurring (patho)physiological processes. Mass spectrometry (MS)-based approaches are the most unbiased and sensitive instruments with high multiplexing capacity and provided most of the current information about endogenous urine peptides. However, despite the large number of urine peptidomic studies, there are certain issues related to the insufficient comparability of their results due to the lack of consistent approaches to their interpretation. Also the development of a custom project-specific protein library for endogenous peptides search and identification is another important point that should be noted in the context of high-throughput peptidomic analysis. Here we propose the custom-specific urinary protein database and the grouping of endogenous urinary peptides with overlapping sequences as useful tools, which can facilitate the acquisition and analysis of LC-MS peptidomic data, as well as the comparison of results of different studies, which should facilitate their more efficient further application.

Nonlinear association between proteinuria levels and the risk of cardiovascular disease events and all-cause mortality among chronic kidney disease patients.

BACKGROUND: The association between proteinuria levels and cardiovascular disease (CVD) development and all-cause mortality in chronic kidney disease (CKD) patients remains controversial. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Fractional excretion of total protein in patients with nephrotic syndrome.

BACKGROUND: The urine protein to creatinine ratio (UPCR) correlates well with the 24-h urine protein test (24-h UPT) and is a reliable indicator of proteinuria. However, in nephrotic syndrome, the correlation between the UPCR and the 24-h UPT tends to decrease. To address this, we introduced the fractional excretion of total protein (FETP), which reflects serum total protein and creatinine levels because severe hypoproteinemia and/or elevated serum creatinine levels tend to occur under these conditions. The 24-h UPT corrected for body surface area (BSA) (24-h UPT/BSA) was used to take body size into consideration. The correlation coefficients for 24-h UPT/BSA and FETP and 24-h UPT/BSA and UPCR were calculated. The statistical significance of the differences between these coefficients was also calculated. METHODS: Thirty-six pediatric patients with nephrotic syndrome were included in this study. The FETP was calculated as total protein clearance/creatinine clearance (%). Correlation coefficients were calculated for 24-h UPT/BSA and FETP and 24-h UPT/BSA and UPCR. The statistical significance of the differences between these coefficients was also calculated. RESULTS: The mean ± standard error of FETP was 0.11% ± 0.013%. The correlation coefficients of FETP and UPCR with 24-h UPT/BSA were 0.91 and 0.81, respectively. The FETP demonstrated a significantly stronger correlation with 24-h UPT/BSA than with UPCR (p = 0.01). CONCLUSIONS: The FETP correlated more strongly with 24-h UPT/BSA than with UPCR in patients with nephrotic syndrome. The FETP is a reliable indicator of proteinuria in nephrotic syndrome, especially in patients with severe hypoproteinemia or elevated serum creatinine levels.

Reference values for urinary protein, albumin, beta 2-microglobulin, and the alpha 1-microglobulin-to-creatinine ratio in Japanese children.

BACKGROUND: The importance of the ratio of creatinine to urinary protein, albumin, and low-molecular weight protein as a urinary marker in chronic kidney disease patients is widely recognized. However, no reference values have hitherto been established for these markers in Japanese children. The present study aimed to establish the reference values for these urinary markers in Japanese children. METHODS: The first morning urine was randomly collected from 1712 pupils aged ≥ 3 to < 18 years during school and kindergarten mass urinary screenings. The upper limit of the reference values was set at the 97.5th percentile of the creatinine ratio per marker. RESULTS: The urinary protein-to-creatinine ratio (PCR), urinary albumin-to-creatinine ratio (ACR), urinary beta 2-microglobulin-to-creatinine ratio (BMCR), and urinary alpha 1-microglobulin-to-creatinine ratio (AMCR) showed an age-related decrease at the 50th percentile reflecting an age-related increase in urinary creatinine. The appropriate reference value for the PCR and ACR was 0.12 g/gCr and 35 mg/gCr, respectively, in the entire cohort. The appropriate reference value for the BMCR was 0.5 µg /mgCr for age ≥ 3 to < 6 years and 0.35 µg/mgCr for age 6 years or older. The appropriate reference value for the AMCR was 5.0 µg/mgCr for age ≥ 3 to < 6 years and 3.5 µg /mgCr for age 6 years or older. CONCLUSION: The present study was the first to determine appropriate reference values for the PCR, ACR, BMCR, and AMCR based on an analysis of the first morning urine samples of a large number of children.

Study on the efficacy, safety, and biomarkers of nusinersen in type II and III spinal muscular atrophy in children.

Introduction/aims: The time span for the approval of nusinersen to treat SMA remains short. Most studies on the efficacy and safety of this drug within clinical trials, are lacking real-world research data. This study is based on real-world studies of SMA patients in children with type II and III SMA and is committed to objectively evaluating the effectiveness and safety of this drug. Methods: A retrospective analysis was conducted on the clinical data of 18 children with type II and III SMA from January 2022 to June 2023. The motor function assessment scale, SMN protein, platelet, liver and kidney function, and other laboratory indicators of all patients before and after treatment were collected for statistical analysis. Results: After load dose treatment (after 64 days of treatment), compared with baseline, the Revised Upper Limb Module (RULM) of SMA patients showed significant improvement (improvement rate: 44%), confirming the short-term effectiveness of the drug. The increase in cerebrospinal fluid SMN protein was greater in patients with significant improvement in motor function than in patients without improvement in motor function. Compared with baseline, there was no significant increase in AST and ALT levels in SMA patients, indicating that the drug had almost no effect on the liver. After each treatment, thrombocytopenia and partial urinary protein positivity may occur, but it could recover before the next treatment. This indicates that nusinersen is potentially harmful to platelet and renal function, although the effect is weak and reversible. Discussion: Nusinersen has shown good efficacy and overall safety, but platelets and urinary protein are still indicators that require long-term monitoring. The increase in cerebrospinal fluid SMN protein was greater in patients with significant improvement in motor function than in patients without improvement in motor function.

Urinary Liver-Type Fatty Acid Binding Protein, a Biomarker for Disease Progression, Dialysis and Overall Mortality in Chronic Kidney Disease.

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.

Increased paternal corticosterone exposure influences offspring behaviour and expression of urinary pheromones.

BACKGROUND: Studies have shown that paternal stress prior to conception can influence the innate behaviours of their offspring. The evolutionary impacts of such intergenerational effects are therefore of considerable interest. Our group previously showed in a model of daily stress that glucocorticoid treatment of adult male mouse breeders prior to conception leads to increased anxiety-related behaviours in male offspring. Here, we aimed to understand the transgenerational effects of paternal stress exposure on the social behaviour of progeny and its potential influence on reproductive success. RESULTS: We assessed social parameters including social reward, male attractiveness and social dominance, in the offspring (F1) and grand-offspring (F2). We report that paternal corticosterone treatment was associated with increased display of subordination towards other male mice. Those mice were unexpectedly more attractive to female mice while expressing reduced levels of the key rodent pheromone Darcin, contrary to its conventional role in driving female attraction. We investigated the epigenetic regulation of major urinary protein (Mup) expression by performing the first Oxford Nanopore direct methylation of sperm DNA in a mouse model of stress, but found no differences in Mup genes that could be attributed to corticosterone-treatment. Furthermore, no overt differences of the prefrontal cortex transcriptome were found in F1 offspring, implying that peripheral mechanisms are likely contributing to the phenotypic differences. Interestingly, no phenotypic differences were observed in the F2 grand-offspring. CONCLUSIONS: Overall, our findings highlight the potential of moderate paternal stress to affect intergenerational (mal)adaptive responses, informing future studies of adaptiveness in rodents, humans and other species.

A case of renal vein thrombosis associated with autoimmune hemolytic anemia and eosinophilic granulomatous polyangiitis.

Only a few cases of renal vein thrombosis (RVT) occurring in patients with vasculitis have been reported. RVT associated with vasculitis and hemolytic anemia has not been reported yet. We describe here a patient with RVT complicated by pulmonary embolism, autoimmune hemolytic anemia, and eosinophilic granulomatous polyangiitis. A 69-year-old Japanese man who had been treated with corticosteroids was referred to our department for severe proteinuria (4.32 g/gCr). Abdominal ultrasonography showed bilateral RVT, and contrast-enhanced computed tomography showed bilateral pulmonary embolism. Therefore, the patient was diagnosed with RVT complicated by pulmonary embolism. Anticoagulation therapy with heparin followed by apixaban was started. Thereafter, the D-dimer concentration decreased from 8.3 to 1.2 µg/mL, and urinary protein excretion improved to 0.62 g/gCr. Renal function was unchanged with an estimated glomerular filtration rate of 68.8 mL/minute/1.73 m2. The thrombi in both renal veins and pulmonary arteries gradually regressed. Clinicians should be aware of this complication when worsening proteinuria is observed during steroid therapy in patients with autoimmune hemolytic anemia and eosinophilic granulomatous polyangiitis.

Determinants on urinary excretion of oxalate and other key factors related to urolithiasis among patients with chronic kidney disease: a single center study.

PURPOSE: Urolithiasis is a known risk factor for chronic kidney disease (CKD). However, how CKD might affect the risk of incidence of urolithiasis is not widely studied. METHODS: Urinary excretion of oxalate as well as other key factors related to urolithiasis was analyzed in a single center study of 572 patients with biopsy-proven kidney disease. RESULTS: The mean age of the cohort was 44.9 years and 60% were males. The mean eGFR was 65.9 ml/min/1.73 m2. Median urinary excretion of oxalate was 14.7 (10.4-19.1) mg/24-h and associated with current urolithiasis (OR 12.744, 95% CI: 1.564-103.873 per one logarithm transformed unit of urinary oxalate excretion). Oxalate excretion was not associated with eGFR and urinary protein excretion. Oxalate excretion was higher in patients with ischemia nephropathy as compared with patients with glomerular nephropathy and tubulointerstitial nephropathy (16.4 vs 14.8 vs 12.0 mg, p = 0.018). And ischemia nephropathy (p = 0.027) was associated with urinary oxalate excretion on adjusted linear regression analysis. Urinary excretion of calcium and uric acid was correlated with eGFR and urinary protein excretion (all p < 0.001), with ischemia nephropathy and tubulointerstitial nephropathy associated with uric acid excretion (both p < 0.01) as well. Citrate excretion was correlated with eGFR (p < 0.001) on adjusted linear regression. CONCLUSION: Excretion of oxalate and other key factors related to urolithiasis was differentially associated with eGFR, urinary protein, and pathological changes in CKD patients. The influence of these intrinsic traits of the underlining kidney disease should be considered when evaluating urolithiasis risk in patients with CKD.

Serum homocysteine concentration as a marker for advanced diabetic nephropathy in a cohort of elderly patients.

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.

Withdrawal from Hemodialysis in a Patient with IgD Type Multiple Myeloma: A Case-based Review.

Several previous case reports have shown that patients with immunoglobulin D (IgD) multiple myeloma (MM) can be withdrawn from hemodialysis, however, the characteristics that can predict withdrawal in these patients have not yet been elucidated. A 57-year-old Japanese woman required hemodialysis because of renal dysfunction due to IgD-λ and Bence Jones protein-λ MM. Bortezomib-based chemotherapy nine days after admission led to her withdrawal from hemodialysis on Day 50. In our case-based review, younger age and early initiation of bortezomib-based chemotherapy emerged as possible predictors of successful hemodialysis withdrawal.

Component-Resolved Diagnosis Based on a Recombinant Variant of Mus m 1 Lipocalin Allergen.

Exposure to the Mus m 1 aeroallergen is a significant risk factor for laboratory animal allergy. This allergen, primarily expressed in mouse urine where it is characterized by a marked and dynamic polymorphism, is also present in epithelium and dander. Considering the relevance of sequence/structure assessment in protein antigenic reactivity, we compared the sequence of the variant Mus m 1.0102 to other members of the Mus m 1 allergen, and used Discotope 2.0 to predict conformational epitopes based on its 3D-structure. Conventional diagnosis of mouse allergy is based on serum IgE testing, using an epithelial extract as the antigen source. Given the heterogeneous and variable composition of extracts, we developed an indirect ELISA assay based on the recombinant component Mus m 1.0102. The assay performed with adequate precision and reasonable diagnostic accuracy (AUC = 0.87) compared to a routine clinical diagnostic test that exploits the native allergen. Recombinant Mus m 1.0102 turned out to be a valuable tool to study the fine epitope mapping of specific IgE reactivity to the major allergen responsible for mouse allergy. We believe that advancing in its functional characterization will lead to the standardization of murine lipocalins and to the development of allergen-specific immunotherapy.

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

BACKGROUND: 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. AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Quantitative vessel density analysis of macular and peripapillary areas by optical coherence tomography angiography in adults with primary nephrotic syndrome.

PURPOSE: To compare the microvascular parameters of macular and peripapillary areas in adults with primary nephrotic syndrome (PNS) and healthy controls (HCs). METHODS: In this cross-sectional study, optical coherence tomography angiography (OCTA) was used to evaluate the changes in retinal microvascular in 37 adult patients with PNS and 30 HCs in this study. All subjects underwent OCTA for measuring vascular density (VD), perfusion density (PD), and foveal avascular zone (FAZ) in the superficial capillary plexus (SCP) and optical coherence tomography (OCT) for measuring central macular thickness (CMT) and retinal nerve fiber layer (RNFL) thickness. The following clinical data of the PNS group were collected: hemoglobin, platelet, total protein, albumin, prealbumin, creatinine, urea nitrogen, glomerular filtration rate, blood lipid, urinary protein, urine microalbumin, urine microalbumin/creatinine, 24-h urine volume, and 24-h urine protein quantification. The OCTA data were compared between patients with PNS and HCs, and the correlation between the OCTA data and clinical data was analyzed in the PNS group. RESULTS: VD and PD in the macular area of the PNS group were significantly lower than those in the HC group (VD: 17.025 ± 2.229 vs. 18.290 ± 0.721, P = 0.001; PD: 0.417 ± 0.058 vs. 0.450 ± 0.019, P = 0.003). No significant differences in the FAZ area and perioptic disc microvascular parameters were observed between the two groups, and patients in the PNS group showed consistent changes in the left and right eyes. VD and PD in the central macular area were positively correlated with plasma prealbumin level (VD: ρ = 0.541, P = 0.001; PD: ρ = 0.562, P < 0.001) and negatively correlated with urinary protein level (VD: ρ = -0.579, P < 0.001; PD: ρ = -0.596, P < 0.001). CONCLUSIONS: In adult patients with PNS, the decrease in VD and PD was mainly occurred in the macular area. Partly vascular density of the macular area was positively correlated with plasma prealbumin level and negatively correlated with urinary protein level. OCTA provides a convenient, non-invasive and effective method for evaluating and monitoring retinal microcirculation damage in patients with PNS.

The Relevance of Screening for Vector-Borne Diseases in Dogs with Proteinuria Living in an Endemic Region: A Retrospective Study.

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.

Expression pattern and clinical significance of microRNA-let-7a and IFN-gamma in placental tissue of patients with preeclampsia with severe features.

OBJECTIVES: Preeclampsia with severe features (PECsf) is a common disease in pregnant women. let-7a and IFN-gamma (interferon-gamma) are involved in diagnosis and prognosis of preeclampsia. This study explored effects of let-7a and IFN-gamma on PECsf patients. METHODS: The placental tissue of 21 PECsf, 19 preeclampsia without severe features (PEC), and 20 normal pregnant women were collected, and clinical data were recorded. let-7a and IFN-gamma expressions in placental tissue were detected. The correlation between let-7a/IFN-gamma expression and clinical indexes was analyzed. According to let-7a and IFN-gamma expressions, PECsf patients were assigned into Hlet-7a group (let-7a high expression group), Llet-7a group (let-7a low expression group), HIFN-gamma group (IFN-gamma high expression group) and LIFN-gamma group (IFN-gamma low expression group). The incidence of adverse prognosis was compared. RESULTS: let-7a and IFN-gamma were highly expressed in placental tissue of preeclampsia patients, with significant differences between PEC and PECsf. The high expressions of let-7a and IFN-gamma were positively correlated with mean arterial pressure, lactate dehydrogenase, and 24 h urinary protein in placental tissues of PECsf patients. High let-7a and IFN-gamma expressions were correlated with adverse outcomes of PECsf. CONCLUSIONS: High let-7a and IFN-gamma expressions were correlated with clinical features, and could be used as biomarkers for treatment and poor prognosis of PECsf.

Association Between Urinary Protein-to-Creatinine Ratio and Chronic Kidney Disease Progression: A Secondary Analysis of a Prospective Cohort Study.

Objective: Studies on the association between urinary protein-to-creatinine ratio (UPCR) and chronic kidney disease (CKD) progression are limited. This study aimed to investigate the relationship between UPCR and CKD progression in a Japanese population. Methods: The present research was a secondary analysis of a prospective cohort study. Eight hundred and ninety-six subjects from the research of CKD-ROUTE in Japan were included. All the patients were new visitors or first referred to the participating centers of nephrology between October 2010 and December 2011. The target-independent variable was UPCR measured at baseline. The dependent variable was CKD progression and the estimated glomerular filtration rate (eGFR) changes during follow-up. We used Cox proportional hazards regression to investigate the association between UPCR and CKD progression risk. To address UPCR and CKD progression's non-linearity, a multivariate Cox proportional hazards regression analysis with cubic spline functions model and smooth curve fitting (penalized spline method) were conducted. We further used a generalized linear mixed model to explore the relationship between UPCR and the changes of eGFR. Result: The mean age of the included patients was 67.2 ± 13.4 years old. Two hundred and thirty-four people occurred CKD progression during follow-up. The present study showed that UPCR was independently associated with CKD progression in the multivariate analysis [HR = 1.164, 95% CI (1.116, 1.215)]. The non-linear relationship between UPCR and CKD progression was explored in a dose-dependent manner, with an obvious inflection point of 1.699. Furthermore, our findings indicated that the tendency of the effect sizes on both the left and right sides of the inflection point was not consistent [left HR: 4.377, 95% CI (2.956, 6.483); right HR: 1.100, 95% CI (1.049-1.153)]. Using the linear mixed-effects regression model, we found that UPCR was an independent predictor of the longitudinal changes in eGFR (p < 0.001 for the interaction term with time). Conclusion: This study demonstrates a nonlinear positive relationship between UPCR and CKD progression in the Japanese population. UPCR is also an independent predictor of the longitudinal changes in eGFR.