Urinary non-albumin protein-creatinine ratio is an independent predictor of mortality in patients with type 2 diabetes: a retrospective cohort study.

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.

Urinary Proteomics and Outcomes in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Although several studies have addressed plasma proteomics in heart failure with preserved ejection fraction, limited data are available on the prognostic value of urinary proteomics. The objective of our study was to identify urinary proteins/peptides associated with death and heart failure admission in patients with heart failure with preserved ejection fraction. METHODS AND RESULTS: The study population included participants enrolled in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial). The relationship between urine protein levels and the risk of death or heart failure admission was assessed using Cox regression, in both nonadjusted analyses and adjusting for urine creatinine levels, and the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) score. A total of 426 (12.4%) TOPCAT participants had urinary protein data and were included. There were 40 urinary proteins/peptides significantly associated with death or heart failure admission in nonadjusted analyses, 21 of which were also significant adjusted analyses. Top proteins in the adjusted analysis included ANGPTL2 (angiopoietin-like protein 2) (hazard ratio [HR], 0.5731 [95% CI, 0.47-0.7]; P=3.13E-05), AMY2A (α amylase 2A) (HR, 0.5496 [95% CI, 0.44-0.69]; P=0.0001), and DNASE1 (deoxyribonuclease-1) (HR, 0.5704 [95% CI, 0.46-0.71]; P=0.0002). Higher urinary levels of proteins involved in fibrosis (collagen VI α-1, collagen XV α-1), metabolism (pancreatic α-amylase 2A/B, mannosidase α class 1A member 1), and inflammation (heat shock protein family D member 1, inducible T cell costimulatory ligand) were associated with a lower risk of death or heart failure admission. CONCLUSIONS: Our study identifies several novel associations between urinary proteins/peptides and outcomes in heart failure with preserved ejection fraction. Many of these associations are independent of clinical risk scores and may aid in risk stratification in this patient population.

A phase 2b, randomized, double-blind, placebo-controlled, clinical trial of atacicept for treatment of IgA nephropathy.

Atacicept is a first-in-class, dual anti-B-cell Activation Factor-A Proliferation-Inducing Ligand fusion protein in clinical evaluation for treatment of IgA nephropathy. To compare efficacy and safety of atacicept versus placebo in patients with IgAN, this randomized, double-blind, placebo-controlled phase 2b clinical trial ORIGIN enrolled 116 individuals with biopsy-proven IgA nephropathy. Participants were randomized to atacicept 150, 75, or 25 mg versus placebo once weekly for up to 36 weeks. Primary and key secondary endpoints were changes in urine protein creatinine ratio based on 24-hour urine collection at weeks 24 and 36, respectively, in the combined atacicept 150 mg and 75 mg group versus placebo. The primary endpoint was met at week 24 as the mean urine protein creatinine ratio was reduced from baseline by 31% in the combined atacicept group versus 8% with placebo, resulting in a significant 25% reduction with atacicept versus placebo. At week 36, the key secondary endpoint was met as the mean urine protein creatinine ratio reduced from baseline by 34% in the combined atacicept group versus a 2% increase with placebo, resulting in a significant 35% reduction with atacicept versus placebo. The reduction in proteinuria was accompanied by stabilization in endpoint eGFR with atacicept compared to a decline with placebo at week 36, resulting in significant between-group geometric mean difference of 11%, approximating an absolute difference of 5.7 mL/min/1.73m2. Endpoint galactose deficient IgA1 levels significantly decreased from baseline by 60% versus placebo. The safety profile of atacicept was like placebo. Thus, our results provide evidence to support a pivotal, phase 3 study of atacicept in IgA nephropathy.

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.

Urinary podocyte markers of disease activity, therapeutic efficacy, and long-term outcomes in acute and chronic kidney diseases.

A critical degree of podocyte depletion causes glomerulosclerosis, and persistent podocyte loss in glomerular diseases drives the progression to end-stage kidney disease. The extent of podocyte injury at a point in time can be histologically assessed by measuring podocyte number, size, and density ("Biopsy podometrics"). However, repeated invasive renal biopsies are associated with increased risk and cost. A noninvasive method for assessing podocyte injury and depletion is required. Albuminuria and proteinuria do not always correlate with disease activity. Podocytes are located on the urinary space side of the glomerular basement membrane, and as they undergo stress or detach, their products can be identified in urine. This raises the possibility that urinary podocyte products can serve as clinically useful markers for monitoring glomerular disease activity and progression ("Urinary podometrics"). We previously reported that urinary sediment podocyte mRNA reflects disease activity in both animal models and human glomerular diseases. This includes diabetes and hypertension which together account for 60% of new-onset dialysis induction patients. Improving approaches to preventing progression is an urgent priority for the renal community. Sufficient evidence now exists to indicate that monitoring urinary podocyte markers could serve as a useful adjunctive strategy for determining the level of current disease activity and response to therapy in progressive glomerular diseases.

Evaluation of a urine dipstick protein to urine specific gravity ratio for the detection of proteinuria in dogs and cats.

BACKGROUND: The utility of urine dipsticks for the quantification of proteinuria is limited because of the influence of urine specific gravity (USG). To circumvent the need for urine protein creatinine ratios (UPCR) some have proposed a calculated dipstick urine protein to USG ratio (DUR) for the detection of proteinuria. However, the performance of DUR has not been evaluated in veterinary patients. OBJECTIVES: Evaluate the correlation between DUR and UPCR, while also assessing the effect of urine characteristics on this relationship and evaluating the performance of DUR in detecting proteinuria. ANIMALS: Urine samples from 308 dogs and 70 cats. METHODS: Retrospective cohort study of urinalyses and UPCRs from dogs and cats collected between 2016 and 2021. RESULTS: Both canine and feline urine samples showed a positive moderate correlation between the UPCR and DUR. The correlation was not influenced by the presence of active urine sediment, glucosuria, or urine pH. In detecting canine urine samples with a UPCR >0.5, an optimal DUR of 1.4 had sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 89%, 83%, 96%, and 63%, respectively. In detecting feline urine samples with a UPCR >0.4, an optimal DUR of 2.1 had sensitivity, specificity, PPV, and NPV of 70%, 100%, 100%, and 75%, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Use of the DUR can be a relatively reliable method for identification of proteinuria. However, given its poor NPV, the DUR cannot be recommended for exclusion of proteinuric patients.

Development of a Quantitative Digital Urinalysis Tool for Detection of Nitrite, Protein, Creatinine, and pH.

This paper presents a cost-effective, quantitative, point-of-care solution for urinalysis screening, specifically targeting nitrite, protein, creatinine, and pH in urine samples. Detecting nitrite is crucial for the early identification of urinary tract infections (UTIs), while regularly measuring urinary protein-to-creatinine (UPC) ratios aids in managing kidney health. To address these needs, we developed a portable, transmission-based colorimeter using readily available components, controllable via a smartphone application through Bluetooth. Multiple colorimetric detection strategies for each analyte were identified and tested for sensitivity, specificity, and stability in a salt buffer, artificial urine, and human urine. The colorimeter successfully detected all analytes within their clinically relevant ranges: nitrite (6.25-200 µM), protein (2-1024 mg/dL), creatinine (2-1024 mg/dL), and pH (5.0-8.0). The introduction of quantitative protein and creatinine detection, and a calculated urinary protein-to-creatinine (UPC) ratio at the point-of-care, represents a significant advancement, allowing patients with proteinuria to monitor their condition without frequent lab visits. Furthermore, the colorimeter provides versatile data storage options, facilitating local storage on mobile devices or in the cloud. The paper further details the setup of the colorimeter's secure connection to a cloud-based environment, and the visualization of time-series analyte measurements in a web-based dashboard.

Diagnostics of preeclampsia based on Congo red binding to urinary components: Rationales and limitations.

Preeclampsia is a disorder that can occur during pregnancy and is one of the leading causes of death among pregnant women. This disorder occurs after the 20th week of pregnancy and is characterized by arterial hypertension, proteinuria, fetoplacental, and multiple organ dysfunctions. Despite the long history of studying preeclampsia, its etiology and pathogenesis remain poorly understood, and therapy is symptomatic. One of the factors of the disorder is believed to be misfolded proteins that are prone to form amyloid aggregates. The CRD tests, utilizing the binding of the amyloid-specific dye Congo red to urine components, demonstrate high efficiency in diagnosing preeclampsia. However, these tests have also been found to be positive in other disorders with proteinuria, presumably associated with concomitant amyloidosis. To assess the limitations of the CRD tests, we examined urine congophilia and protein components mediating Congo red positivity in patients with proteinuria, including preeclampsia, amyloid and non-amyloid nephropathies. We stained the urine samples and calculated congophilia levels. We also assessed the contribution of large protein aggregates to congophilia values using ultracentrifugation and determined the molecular weights of congophilic urinary proteins using centrifugal concentrators. All proteinuric groups demonstrate positive results in the CRD tests and congophilia levels were more than two times higher compared with the control non-proteinuric groups (p <0.01). There was a strong correlation between urine protein excretion and congophilia in amyloid nephropathy (rs = 0.76), non-amyloid nephropathies (rs = 0.90), and preeclampsia (rs = 0.90). Removal of large aggregates from urine did not affect the congophilia levels. Separation of urine protein fractions revealed congophilic components in the range of 30-100 kDa, including monomeric serum albumin. Our results indicate limitations of CRD tests in preeclampsia diagnostics in women with renal disorders and underscore the need for further research on the mechanisms of Congo red binding with urine components.

The diagnostic Accuracy of Visual versus automated dipstick proteinuria testing in Pregnancy: A systematic review and Meta-Analysis.

OBJECTIVE: To evaluate the diagnostic accuracy of point-of-care (POC) tests for detecting proteinuria in pregnant women. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE and EMBASE databases were searched from inception to 13 November 2020. ELIGIBILITY CRITERIA AND DATA ANALYSIS: Included studies measured the sensitivity and specificity ofPOC proteinuria testing compared to laboratory reference standards (protein-creatinine ratio (PCR), 24-hour urine collection). Bivariate meta-analyses determined pooled sensitivity and specificity. Random-effects inverse-variance model determinedheterogeneity. MAIN OUTCOME MEASURES: The primary outcome was overall sensitivity and specificity, stratified by method of POC testing and reference standard. Secondary outcomes were sensitivity and specificity within thesubgroupstest brand, reference standard, and hypertension status. RESULTS: 1078 studies were identified, 17 studies comprising 23 comparisons were included. The meta-analysis included 13 studies with 19 comparisons. Pooled sensitivity and specificity of visual dipsticks against PCR was 72 % (95 % CI: 56 % to 84 %) and 92 % (95 % CI: 76 % to 98 %), respectively. Pooled sensitivity and specificity of visual dipsticks against 24-hour collection was 69 % (55 % to 80 %) and 70 % (51 % to 84 %), respectively. Pooled sensitivity and specificity for automated readers against PCR was 73 % (53 % to 86 %) and 91 % (83 % to 95 %), respectively. Pooled sensitivity and specificity of automated readers against 24-hour collection was 65 % (42 % to 83 %) and 82 % (46 % to 96 %), respectively. CONCLUSION: Visual dipsticks have comparable accuracy to automated readers, yet are notadequate as a rule-out test for proteinuria. Proteinuria POC testing maybe beneficial inantenatal care when repeatfollow-up tests are performed. PROSPERO Registration Number: CRD42021231914.

Urine albumin-to-creatinine ratio diurnal variation rate predicts outcomes in idiopathic membranous nephropathy.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is a leading cause of end-stage renal disease (ESRD). The purpose of this study was to evaluate whether urinary albumin-to-creatinine ratio (UACR) diurnal variation rate calculated by spot urinary protein test predicts 1-year nephrotic outcomes as a biomarker of proteinuria severity in patients with IMN. METHODS: Patients' baseline demographics, blood and urinary biomarkers, and clinical and pathological characteristics were collected retrospectively. Urine samples were collected at 7:00 (before breakfast) and 19:00 (after dinner) to calculate the UACR diurnal variation rate. A prediction model for no remission (NR) was developed statistically based on differences between prognosis groups. Receiver operating characteristic curve (ROC) analysis was performed to evaluate prediction abilities and determine optimal cut-off points of the model and UACR diurnal variation rate alone. RESULTS: The formula for calculating the probability of NR was exp(L)/(1 + exp(L)), where the linear predictor L = - 22.038 + 0.134 × Age (years) + 0.457 × 24-h urinary protein + 0.511 × blood urea nitrogen (BUN) + 0.014 × serum uric acid (SUA) + 2.411 if glomerular sclerosis + 0.816 × fasting blood glucose (FBG)-0.039 × UACR diurnal variation rate (%). Optimal cut-off points for NR prediction by the final model and UACR diurnal variation rate alone were 0.331 and 58.5%, respectively. Sensitivity and specificity were 0.889 and 0.859 for the final model, and 0.926 and 0.676 for UACR diurnal variation rate alone. CONCLUSION: UACR diurnal variation using spot urinary protein is a simpler way to predict nephrotic outcomes and is a highly sensitive screening tool for identifying patients who should undergo further comprehensive risk assessment.

Proteinuria, measured or estimated albuminuria for risk prediction in patients with chronic kidney disease?

BACKGROUND: Although albuminuria is the gold standard for defining chronic kidney disease (CKD), total proteinuria has also been widely used in real-world clinical practice. Moreover, the superiority of the prognostic performance of albuminuria over proteinuria in patients with CKD remains inconclusive. Therefore, we aimed to compare the predictive performances of albuminuria and proteinuria in these patients. METHODS: From the Korean Cohort Study for Outcome in Patients with CKD we included 2099 patients diagnosed with CKD grades 1-5 who did not require kidney replacement therapy. We measured the spot urine albumin:creatinine ratio (mACR) and protein:creatinine ratio (PCR) and estimated the ACR (eACR) using the PCR. Kidney failure risk equation (KFRE) scores were calculated using the mACR, PCR and eACR. The primary outcome was the 5-year risk of kidney failure with replacement therapy (KFRT). RESULTS: The eACR significantly underestimated mACR in patients with low albuminuria levels. The time-dependent area under the receiver operating characteristics curve showed excellent predictive performance for all KFRE scores from the mACR, PCR and eACR. However, eACR was inferior to mACR based on the continuous net reclassification index (cNRI) and integrated discrimination improvement index (IDI) in all CKD cause groups, except for the group with an unclassified aetiology. Moreover, the cNRI and IDI statistics indicated that both eACR and PCR were inferior to mACR in patients with low albuminuria (<30 mg/g). Conversely, the predictive performance of PCR was superior in severe albuminuria and nephrotic-range proteinuria, in which the IDI and cNRI of the PCR were greater than those of the mACR. CONCLUSIONS: The mACR, eACR and PCR showed excellent performance in predicting KFRT in patients with CKD. However, eACR was inferior to mACR in patients with low albuminuria, indicating that measuring rather than estimating albuminuria is preferred for these patients.

Withstanding the test of time: Morning versus afternoon/evening urine protein-to-creatinine ratios in preeclampsia.

OBJECTIVE: There are mixed findings regarding time preference for measuring spot urine protein to creatinine ratios (UPCR) in renal patients but no such literature among pregnant patients. We compare AM versus PM measurements for UPCR among pregnant patients with preeclampsia. STUDY DESIGN: This retrospective study included 163 patients diagnosed with preeclampsia. Laboratory tests of UPCR, urine specificity gravity, and uric acid were collected for these patients during the morning (AM) 12:00 AM (00:00) through 11:59 AM (11:59) and afternoon/evening (PM) 12:00 PM (12:00) through 11:59 PM (23:59). MAIN OUTCOME MEASURES: Outcomes were UPCR percentages indicative of preeclampsia, UPCR median values, abnormal uric acid, and normal urine specific gravity indicative of a quality sample for measuring UPCR. RESULTS: UPCR ≥ 0.3 indicative of preeclampsia significantly differed (p < 0.001) where the AM group (76.7 %) had a greater percentage than the PM group (52.8 %). Median UPCR significantly differed (p < 0.001) where the AM group had a greater median (0.44) than the PM group (0.32). None of the uric acid or urine specific gravity comparisons significantly differed between the AM and PM groups. Similar patterns occurred for subgroups of those with hypertension, nulliparous, and preeclampsia with severe features. CONCLUSION: We found that UPCR had greater median values and more values indicative of preeclampsia for AM measurements than PM measurements. Clinicians who use spot urine measurements and not 24-hour urine measurements should preferably measure UPCR in the AM rather than the PM.

Effects of exercise on urinary biochemical parameters and proteins in a group of well-trained military working dogs.

Exercise-induced proteinuria has been widely investigated in humans, also in relation to intensity and duration of activity. Instead, there are only limited publications regarding urinary biochemical parameters and urinary proteins before and after physical activity in dogs. This paper aimed to investigate the effects of exercise on urinary biochemistry and proteins in military dogs. Twenty-four dogs were enrolled in this study. All the dogs were clinically sound, and they were examined before and after activity. Pulse rates (PR) and respiratory rate (RR) were monitored. Urine was sampled before and after a training session of search activity. Standard urinalysis was carried out, urine total proteins and creatinine were measured and the urinary protein:creatinine ratio was calculated; finally, the urinary proteins were separated using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Clinical examination before and after activity did not reveal any pathological finding. After activity, the PR was slightly increased, while the RR was notably increased (p < 0.05). Total proteins, albumin, and their ratio with creatinine were significantly higher after exercise when considering all the dogs included or only the females while, when considering only the males no significant difference was detected. The clinical relevance of this study was related to the possibility of using urine as a non-invasive sample for monitoring health status after training activity and exercise in dogs. An increase in microalbuminuria after search activity, measured using SDS-PAGE could be considered an early biomarker of renal function during training sessions.

Comparison of cystocentesis versus home sampling to determine urinary protein: Creatinine ratio and urine specific gravity in cats.

BACKGROUND: Urinalysis is necessary for the diagnostic evaluation of chronic kidney disease in cats. Performing cystocentesis is not always feasible, but data comparing urine obtained by cystocentesis in the clinic with voided samples collected at home are lacking in cats. OBJECTIVES: To compare urinary protein:creatinine ratio (UPC) and urine specific gravity (USG) and to detect clinically relevant changes in proteinuria substage or urine concentration between urine collected at home and in-clinic by cystocentesis in cats. ANIMALS: Ninety-two healthy and diseased client-owned cats. METHODS: Prospective study. Owners collected voided urine at home and within 1 to 15 hours, cystocentesis was performed in the clinic. RESULTS: In a subset of motivated owners, 55% succeeded in collecting urine at home. Overall, UPC was higher (mean ±SD difference = 0.09 ±0.22; P < .001) and USG was lower (mean ±SD difference = -0.006 ±0.009; P < .001) in cystocentesis samples than in voided urine. Substantial agreement existed between sampling methods for UPC (weighted к = 0.68) and USG (к = 0.64) categories. A different proteinuria substage (UPC < 0.2, 0.2-0.4, >0.4) was present in paired urine samples from 28% of cats. In 18% of cats, urine concentrating ability (USG < or ≥1.035) differed between both samples. CONCLUSIONS AND CLINICAL IMPORTANCE: Home sampling of urine is a valid alternative to cystocentesis in cats. However, because clinically relevant differences in UPC and USG were present in 28% and 18% of cats, respectively, by the same collection method for monitoring each cat is advised.

Generation of a human induced pluripotent stem cell line from a patient with dent disease.

Dent disease, an X-linked tubular disorder, is a rare condition that leads to low-molecular-weight proteinuria, hypercalciuria, kidney stones, and chronic kidney disease. Here, we successfully established a human induced pluripotent stem cells (hiPSC) line from peripheral blood mononuclear cells of 10-year-old male with Dent disease 1 caused by the mutation of Chloride Voltage-Gated Channel 5 gene. This hiPSCs displayed features similar to human embryonic stem cells, including pluripotency-associated markers expression, normal karyotype, and the ability to differentiate into cells representing all three germ layers. The implications of this research extend to the potential development of novel treatments for Dent disease.

Proteinuria and Renal Dysfunction Due to Extremely Low Birth Weight in a Patient with Silver-Russell Syndrome.

A 36-year-old woman diagnosed with Silver-Russell syndrome during childhood presented to our department after a primary care physician suspected renal dysfunction. At birth, she had an extremely low weight (1210 g), and in childhood, she was diagnosed with Silver-Russell syndrome. At the age of 14 she was found to have proteinuria; however, the condition was never further examined. One month prior to her presentation to our department, the following were noted: 3+ urinary protein, 3.9 urinary protein/creatinine ratio, and 48 mL/min/1.73 m2 estimated glomerular filtration rate. Abdominal computed tomography revealed small kidneys difficult to visualize using ultrasound. Therefore, an open renal biopsy was performed. The renal biopsy revealed no significant findings in the glomerulus except glomerular hypertrophy, and the glomerular density in the cortical area was low (0.6/mm2). The patient was diagnosed with oligomeganephronia. Proteinuria and renal dysfunction were likely due to glomerular hyperfiltration resulting from a low nephron count caused by low birth weight. Silver-Russell syndrome is characterized by intrauterine growth retardation and additional developmental disorders after birth. Here, we detected oligomeganephronia following kidney biopsy in a patient with Silver-Russell syndrome. We suspect that a reduced number of nephrons due to low birth weight caused proteinuria and renal dysfunction.

Machine-learning enhancement of urine dipstick tests for chronic kidney disease detection.

OBJECTIVE: Screening for chronic kidney disease (CKD) requires an estimated glomerular filtration rate (eGFR, mL/min/1.73 m2) from a blood sample and a proteinuria level from a urinalysis. We developed machine-learning models to detect CKD without blood collection, predicting an eGFR less than 60 (eGFR60 model) or 45 (eGFR45 model) using a urine dipstick test. MATERIALS AND METHODS: The electronic health record data (n = 220 018) obtained from university hospitals were used for XGBoost-derived model construction. The model variables were age, sex, and 10 measurements from the urine dipstick test. The models were validated using health checkup center data (n = 74 380) and nationwide public data (KNHANES data, n = 62 945) for the general population in Korea. RESULTS: The models comprised 7 features, including age, sex, and 5 urine dipstick measurements (protein, blood, glucose, pH, and specific gravity). The internal and external areas under the curve (AUCs) of the eGFR60 model were 0.90 or higher, and a higher AUC for the eGFR45 model was obtained. For the eGFR60 model on KNHANES data, the sensitivity was 0.93 or 0.80, and the specificity was 0.86 or 0.85 in ages less than 65 with proteinuria (nondiabetes or diabetes, respectively). Nonproteinuric CKD could be detected in nondiabetic patients under the age of 65 with a sensitivity of 0.88 and specificity of 0.71. DISCUSSION AND CONCLUSIONS: The model performance differed across subgroups by age, proteinuria, and diabetes. The CKD progression risk can be assessed with the eGFR models using the levels of eGFR decrease and proteinuria. The machine-learning-enhanced urine-dipstick test can become a point-of-care test to promote public health by screening CKD and ranking its risk of progression.

Effect of laboratory and sample storage factors on urinary protein:creatinine ratios and clinical decision making in cats.

BACKGROUND: Urinary protein:creatinine ratio (UPC) results affect the diagnosis, prognosis, and therapy of chronic kidney disease in cats. OBJECTIVES: To investigate the interlaboratory and intralaboratory variability and the effect of storage on UPC and International Renal Interest Society (IRIS) proteinuria substaging in cats. ANIMALS: Healthy and diseased client-owned cats. METHODS: Prospective study. Urine of 60 cats was randomly sent to 4 (of 9) participating laboratories (to assess interlaboratory variability) and per cat, 2 laboratories each received 2 aliquots (to determine intralaboratory variability). Samples of 23 cats were analyzed in the same laboratory the day of collection, after preservation at 22°C for 1 day and at 4°C during 1-7 days (short-term storage) and at -24°C and -80°C for 6-12 months (long-term storage). Storage conditions were compared by equivalence testing. RESULTS: UPCs showed good interclass correlation (ICC-inter, 0.90) and excellent intraclass correlation (ICC-intra, 0.99). However, in 30/60 (50%) cats at least 1 of 4 laboratories assigned a different IRIS proteinuria substage. Urinary protein:creatinine ratio remained stable with short-term storage, but not after 6 months storage at -24°C and after 12 months storage at -24°C or -80°C. Long-term storage caused a change in IRIS proteinuria substage in 27% of cats, whereas a shift occurred only in 4% of cats during short-term storage. CONCLUSIONS AND CLINICAL IMPORTANCE: Laboratory choice for UPC measurement can result in different IRIS substaging for the same cat, whereas urine storage at room temperature for 1 day or in the refrigerator for up to 7 days does not clinically affect UPC.

Modified Sipjeondaebo-tang (JAROTANG) for Henoch-Schonlein purpura nephritis (HSPN): Two case reports.

INTRODUCTION: Henoch-Schönlein purpura (HSP) is a disease commonly manifesting purpura, joint pain, and gastrointestinal symptoms. It can lead to glomerulonephritis (Henoch-Schönlein purpura nephritis, HSPN), which is directly associated with mortality and progression to chronic kidney disease (CKD). While HSP occurs more commonly in children, deadly outcomes occur at a higher rate in adult patients. Previous studies have not reported effective treatment of HSPN by Western or traditional medicine. Here, we report two cases of adult HSPN patients treated with the herbal medicine Jarotang (JRT, modified Sipjeondaebo-tang, modified SJDBT). CASE SUMMARY: Two female patients (Cases 1 and 2), who were 26 and 27 years old, respectively, came to visit us complaining mainly of cutaneous purpura. Both women were diagnosed with HSP, and the results of urinalysis indicated that the HSP had already progressed to renal involvement (3+ proteinuria with 3+ urine occult blood in case 1; 100-120 RBC/HPF with 2+ urine occult blood in Case 2). Both patients were given modified SJDBT in the name of JRT, with some herbs added to disperse and circulate stagnant qi, relieve indigestion, and clear heat. After treatment, patient 1 showed only a trace level of urine occult blood, with disappearance of purpura and proteinuria. Patient 2 showed complete remission of purpura and hematuria. CONCLUSIONS: Modified SJDBT, namely, JRT was effective in treating 2 cases of adulthood HSP and subsequent nephritis. This may be due to the ability of this therapy to replenish qi and blood and/or its immunological effect on T cells. The medication can serve as an effective cure for HSPN.