AZGP1 as a potential biomarker of IgA vasculitis with nephritis in a children­based urinary proteomics study by diaPASEF.

The present study aimed to screen for potential biomarkers in the urine of immunoglobulin A vasculitis with nephritis (IgAVN) using parallel accumulation­serial fragmentation combined with data­independent acquisition (diaPASEF) proteomic approach. Urine proteomes of eight children with IgAVN and eight healthy children were identified by diaPASEF and all differential proteins were analyzed by Gene Ontology and Kyoto Encyclopedia of Gene and Genome. Then, the specific biomarkers of urine samples from 10 children with IgAVN, 10 children with IgAV and 10 healthy children were verified by ELISA. The present study screened 254 differential proteins from the experiment, including 190 upregulated proteins and 64 downregulated proteins. The results of the ELISA showed that the concentration of urinary zinc­alpha­2­glycoprotein (AZGP1) in children with IgAVN was significantly higher compared with that in children with IgAV and healthy children. The present study provided the potential clinical application of AZGP1 as a helpful biomarker and a potential indicator for early diagnosis of the occurrence of IgAVN.

Two Cases of Acute Focal Bacterial Nephritis With Central Nervous System Manifestations in Children and Literature Review.

Acute focal bacterial nephritis (AFBN) is a kidney disease characterized by a localized bacterial infection that manifests as an inflammatory mass. Most children with AFBN have nonspecific symptoms including fever, vomiting, and abdominal discomfort, and some develop neurological symptoms such as meningeal irritation, unconsciousness, and seizures as their condition worsens. This was 2 cases of AFBN with central nervous system manifestations in children, and we analyzed its possible mechanisms of the clinical and radiographic features. We experience 2 very unusual cases of AFBN which were linked to central nervous system abnormalities. A 6-year-old boy with AFBN and clinically moderate ncephalitis/encephalopathy with a reversible splenial lesion (MERS) presented with neurological symptoms, including unconsciousness and convulsions. The second case involved an 8-year-old child with AFBN-associated acute encephalopathy who exhibited neurological symptoms, including unconsciousness. According to previous research, AFBN is linked to central nervous system impairment. As a result, when a clinician meets a patient with an inexplicable fever caused by a neurological condition, he should pay attention to this diagnosis of AFBN and follow it in the abdominal graph.

A Case of Acute Encephalopathy Associated with Acute Focal Bacterial Nephritis.

Acute encephalopathy is a syndrome characterized by an acute onset of disturbance of consciousness. Many acute encephalopathies are caused by viral infections; however, they can also be a result of bacterial infections. Acute focal bacterial nephritis (AFBN) can cause neurological symptoms, such as irritation, unconsciousness, and seizures. In some cases, AFBN-associated acute encephalopathy has also been reported. This report describes the first case of acute encephalopathy with AFBN without significant findings on brain MRI. The patient was a 3-year-old male, who had two episodes of febrile seizures at the ages of 1 and 2 years. He developed disturbance of consciousness, irritability, excitability, and neck stiffness on the day after admission. There were no abnormal findings on brain MRI; however, a generalized high-voltage slow wave was noted on electroencephalography (EEG). His urinary sediment count was elevated, and Morganella morganii and Enterococcus faecalis were detected in the urinary culture. A diagnosis of acute encephalopathy with urinary tract infection (UTI) was made. Intravenous (IV) antibiotics were administered to treat the UTI, while methylprednisolone pulse therapy and IV immunoglobulin were administered to treat acute encephalopathy. Additionally, AFBN was detected in both kidneys on contrast-enhanced CT. The patient received a second course of methylprednisolone pulse therapy due to the persistent high voltage slow wave noted on the EEG on day 8. Furthermore, contrast-enhanced CT revealed AFBN in both kidneys. The final diagnosis was acute encephalopathy with AFBN; however, we had initially diagnosed febrile seizures associated with UTI. It should be noted that acute encephalopathy is associated with AFBN.

Precipitation as a Possible Risk Factor for Development of Lyme Nephritis in Dogs.

To determine whether increased precipitation in the months before diagnosis is predictive of Lyme nephritis in dogs, a symmetrical bidirectional case-crossover study was performed on 87 dogs with presumptive Lyme nephritis. Cases were geographically linked to the nearest precipitation monitoring station, and monthly total precipitation for the 4 mo preceding diagnosis was compared to monthly total precipitation 1 yr before and 1 yr after. Breeds affected included Labrador retrievers (n = 31), mixed-breed dogs (n = 19), and golden retrievers (n = 10), with a possible seasonal bimodal peak in spring and fall. In age-adjusted analysis, each additional inch of precipitation 3 mo before diagnosis was associated with an increase in the odds of developing Lyme nephritis (odds ratio 1.13, 95% confidence interval 1.01-1.25). The results suggest that increased precipitation is a possible risk factor for Lyme nephritis in dogs. These findings may provide useful information for the accurate diagnosis of dogs with protein-losing nephropathy and may guide future studies of risk factors for Lyme nephritis. The methodology employed here reinforces the concept that case-crossover designs have utility beyond acute exposures and outcomes and offer an attractive alternative for studies in companion animals.

Skin-to-Renal Pelvis Distance Predicts Costovertebral Angle Tenderness in Adult Patients with Acute Focal Bacterial Nephritis.

OBJECTIVES: The aim of this study was to examine whether the distance between the skin and the renal pelvis affects the detection of costovertebral angle (CVA) tenderness in patients with acute focal bacterial nephritis (AFBN). METHODS: We retrospectively reviewed the charts of our patients between April 2013 and June 2019 who were diagnosed as having AFBN. Diagnosis was based on ultrasound or computed tomography with contrast, revealing at least one wedge-shaped area of decreased vascularity and confirmation of fever not attributable to another condition. RESULTS: We extracted 23 cases, all Japanese (mean age 60.0 years old [range 45-81 years], 7 males, 16 females). CVA tenderness was present in 8 of these 23 patients. Receiver operating characteristic curves were drawn to evaluate the ability to differentiate skin-to-renal pelvis distance (SPD), body mass index, and age. Only SPD was a useful predictor of CVA tenderness, and 66 mm was determined as the optimal cutoff point (area under the receiver operating characteristic curve 0.858, 95% confidence interval 0.70-1.00). Logistic regression analysis was performed with CVA tenderness as a dependent variable, and SPD, body mass index, and age as explanatory variables. SPD was an independent predictive variable of CVA tenderness (P = 0.038, odds ratio 0.76, 95% confidence interval 0.590-0.986). CONCLUSIONS: CVA tenderness showed low yield in the diagnosis of AFBN in patients with longer SPD. Its use for diagnosis in obese patients may therefore be limited.

Urinary complement proteins are increased in children with IgA vasculitis (Henoch-Schönlein purpura) nephritis.

BACKGROUND: Children with immunoglobulin A vasculitis (IgAV Henoch-Schönlein purpura) frequently encounter nephritis (IgAV-N) with 1-2% risk of kidney failure. The pathophysiology of IgAV-N is not fully understood with speculation that complement may contribute. The aim of this study was to identify whether urinary complement proteins are increased in children with IgAV-N. METHODS: A cross-sectional prospective cohort of children with IgAV were recruited together with controls including healthy children and children with systemic lupus erythematosus (SLE). Patients were subdivided according to the presence of nephritis. Urinary C3, C4, C5, and C5a were measured by enzyme-linked immunosorbent assay (ELISA) and corrected for urinary creatinine. RESULTS: The study included 103 children; 47 with IgAV (37 IgAV without nephritis, IgAVwoN; 10 IgAV-N), 30 SLE and 26 healthy children. Urinary complement C3, C4, and C5 were all statistically significantly increased in all children with IgAV compared to SLE patients (all p < 0.05). In patients with IgAV-N, urinary complement C3, C4, C5, C5a were all statistically significantly increased compared to IgAVwoN (C3 14.65 µg/mmol [2.26-20.21] vs. 2.26 µg/mmol [0.15-3.14], p = 0.007; C4 6.52 µg/mmol [1.30-9.72] vs. 1.37 µg/mmol [0.38-2.43], p = 0.04; C5 1.36 µg/mmol [0.65-2.85] vs. 0.38 µg/mmol [0.03-0.72], p = 0.005; C5a 101.9 ng/mmol [15.36-230.0] vs. 18.33 ng/mmol [4.27-33.30], p = 0.01). Using logistic regression, the urinary complement components produced an outstanding ability to discriminate between patients with and without nephritis in IgAV (AUC 0.92, p < 0.001). CONCLUSIONS: Children with IgAV-N have evidence of increased complement proteins present in their urine that may indicate a pathological role and may allow treatment stratification. A higher resolution version of the Graphical abstract is available as Supplementary information.

A simple nomogram for assessing the risk of IgA vasculitis nephritis in IgA vasculitis Asian pediatric patients.

A nomogram for assessing the risk of IgA vasculitis nephritis (originally termed Henoch-Schönlein purpura nephritis, HSPN) in IgA vasculitis (originally termed Henoch-Schönlein purpura, HSP) pediatric patients can effectively improve early diagnosis and prognosis of IgA vasculitis nephritis. However, currently, no nomogram is available. 246 IgA vasculitis and 142 IgA vasculitis nephritis Asian pediatric patients confirmed by renal biopsy were enrolled. Univariate and multivariate logistic regressions were performed to identify the independent risk factors and construct a series of predictive models. The receiver operating characteristic curve, calibration plot, decision curve analysis, net reclassification index and integrated discrimination index were used to screen the best model. Stratification analysis was applied to optimize model's clinical utility. An external validation set was introduced to verify the predictive efficiency. The final predictive model was converted to nomogram for visual use. We identified age, duration of rash (Dor), D-dimer and IgG as independent risk factors and constructed four models as follows: AIDD (Age + IgG + Dor + D-dimer), AIDi (Age + IgG + D-dimer), AIDo (Age + IgG + Dor) and ADD (Age + Dor + D-dimer), which achieved the receiver operator characteristic curve (AUROC) of 0.931, 0.920, 0.856 and 0.907, respectively. Finally, AIDi model with an AUROC of 0.956 and 0.897 in internal and external validating sets was proposed as a novel predictive model. In stratification analysis by gender and histological grade, the AUROC of AIDi was 0.949 in female, 0.926 in male, 0.933 in mild histological grades and 0.939 in severe histological grades, respectively. AIDi nomogram is an effective and visual tool for assessing the risk of nephritis in IgA vasculitis Asian pediatric patients, regardless of IgA vasculitis nephritis histological grades and gender.

Urinary T cells are detected in patients with immune checkpoint inhibitor-associated immune nephritis that are clonotypically identical to kidney T cell infiltrates.

Acute kidney injury (AKI) occurs in ~20% of patients receiving immune checkpoint inhibitor (ICI) therapy; however, only 2-5% will develop ICI-mediated immune nephritis. Conventional tests are nonspecific in diagnosing disease pathology and invasive procedures (i.e. kidney biopsy) may not be feasible. In other autoimmune renal diseases, urinary immune cells correlated with the pathology or were predictive of disease activity. Corresponding evidence and analysis are absent for ICI-mediated immune nephritis. We report the first investigation analyzing immune cell profiles of matched kidney biopsies and urine of patients with ICI-AKI. We demonstrated the presence of urinary T cells in patients with immune nephritis by flow cytometry analysis. Clonotype analysis of T cell receptor (TCR) sequences confirmed enrichment of kidney TCRs in urine. As ICI therapies become standard of care for more cancers, noninvasively assessing urinary immune cells of ICI therapy recipients can facilitate clinical management and an opportunity to tailor ICI-nephritis treatment.

Neutrophil-to-lymphocyte ratio as an independent inflammatory indicator for poor renal prognosis in adult IgA vasculitis with nephritis.

BACKGROUND: Skin-limited IgAV patients usually present self-limiting disease and good prognosis, while adult IgA vasculitis with nephritis (IgAV-N) present severe phenotype and poor prognosis. Previous studies showed that neutrophil-to-lymphocyte ratio (NLR) was an inflammatory indicator for predicting systemic involvement in children IgAV patients. In this study, we focused on adult IgAV-N patients to explore the relationship of NLR with disease phenotype and long-term renal prognosis. METHODS: In this study, 245 IgAV-N patients, 1151 IgAN patients and 251 healthy controls were recruited. Composite endpoint was defined as 30% eGFR declined or end stage kidney disease. RESULTS: IgAV-N patients presented increased white blood cells (WBC), neutrophils (NE), platelet-to-lymphocyte ratio (PLR), and NLR levels, while decreased lymphocyte (LY) than healthy controls. When compared to clinical and pathological features matched IgAN patients, IgAV-N patients still showed higher WBC, NE, and NLR levels. NLR showed the best performance for the diagnosis of IgAV-N with the highest area under the ROC curves (0.738). IgAV-N patients in high NLR group (>2.41) presented with sever baseline manifestations and more acute pathological lesions than low NLR group (≤2.41). 77 patients with regular follow-up were used for survival analysis. After adjusting some well-known risk factors, NLR levels remained as an independent risk factor for poor renal outcome in adult patients with IgAV-N (HR, 1.913; 95% CI, 1.314 to 2.787, P = 0.001). CONCLUSIONS: NLR levels were associated with the clinical and pathological phenotypes, and NLR may serve as an independent risk factor for poor renal outcome in adult IgAV-N patients.

Construction of Prediction Model of Renal Damage in Children with Henoch-Schönlein Purpura Based on Machine Learning.

Objective: The children with Henoch-Schönlein purpura (HSP) may suffer from renal insufficiency, which seriously affects the life and health of the children. This study aims to construct a prediction model of Henoch-Schönlein purpura nephritis (HSPN). Methods: A total of 240 children with HSP treated in dermatology and pediatrics in our hospital were selected. The general information, patients' clinical symptoms, and laboratory examination indicators were collected for feature selection, and the XGBoost algorithm prediction model was built. Results: According to the input feature indexes, the top ten crucial feature indicators output by the XGBoost model were urine N-acetyl-ß-D-aminoglucosidase, urinary retinol-binding protein, IgA, age, recurrence of purpura, purpura area, abdominal pain, 24-h urinary protein quantification, percentage of neutrophils, and serum albumin. The areas under the curves of the training set (0.895, 95% CI: 0.827-0.963) and test set (0.870, 95% CI: 0.799-0.941) models were similar. Conclusion: The prediction model based on XGBoost is used to predict HSP renal damage based on clinical data of children, which can reduce the harm caused by invasive examination for patients.

[Glomerular hematuria: an atypical presentation of anti-glomerular basement membrane nephritis]. / Glomerulaire hematurie.

BACKGROUND: Urologic diseases can cause hematuria, but dysmorphic erythrocytes directs to a glomerular disease. The latter might occur isolated or in the presence of systemic complaints, proteinuria or kidney failure. These factors determine the differential diagnosis that ranges from an innocent IgA nephropathy to a fatal anti-glomerular basement membrane (GBM) nephritis. CASE: A 30-year old patient attended the outpatient clinic because of glomerular hematuria and normal kidney function with working diagnosis IgA nephropathy. Three months later he presented to the emergency department with a severe acute kidney injury duo to an anti-GBM nephritis. In retrospect, the anti-GBM titer was already high during the outpatient clinic phase, but due to the preserved kidney function, anti-GBM nephritis was not added to the differential diagnosis. CONCLUSION: Glomerular hematuria with a preserved kidney function could in a rare instance be caused by a subclinical anti-GBM nephritis. Follow-up of the kidney function and comprehensive laboratory testing - or even a kidney biopsy - could potentially lead to an early diagnosis of anti-GBM nephritis.

Acute focal bacterial nephritis and prolonged fever.

Acute focal bacterial nephritis (AFBN) is characterised by a complicated upper urinary tract infection ranging from acute pyelonephritis to renal abscess. Timely diagnosis of AFBN is important because antibiotic therapy of longer duration is required. A 10-year-old boy presented with fever for 5 days and bilateral flank pain. He was oriented and cooperative but appeared ill. Physical examination did not reveal any oedema or costovertebral angle tenderness. Acute phase reactants such as erythrocyte sedimentation rate and C-reactive protein were raised, serum creatinine was 1.25 mg/dL (0.31-0.88) and leucocyte esterase was positive in the urine. Ultrasonographic examination demonstrated bilaterally enlarged kidneys with increased echogenicity. Because of the high creatinine level, abdominal magnetic resonance imaging (MRI) was performed instead of computed tomography (CT) for further evaluation. The MRI showed an increase in the size of both kidneys, renal cortical heterogeneity and multiple cortical nodular lesions with diffusion restriction (constrained Brownian movement of water molecules) on diffusion-weighted MRI. A negative urine culture result in children presenting with fever and abdominal pain may mislead the clinicians, causing them to miss a nephro-urological diagnosis. It is therefore recommended that patients in whom the cause of fever cannot be determined be scanned by ultrasound and examined by CT or MRI so that undiagnosed and/or suspected cases of AFBN might be detected.

Clinical predictive model for the 1-year remission probability of IgA vasculitis nephritis.

PURPOSE: Early remission of Immunoglobulin A vasculitis nephritis (IgAVN) substantially affects its prognosis. In this work, a multivariate model to predict the 1-year remission probability of patients with IgAVN was developed on the basis of clinical laboratory data. METHODS: Data of 187 patients with IgAVN confirmed by renal biopsy were retrospectively assessed. Least absolute shrinkage and selection operator regression analysis were conducted to establish a multivariate logistic regression model. A nomogram based on the multivariate logistic regression model was constructed for easy application in clinical practice. Concordance index, receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and clinical impact curves (CIC) were used to evaluate the predictive accuracy and clinical value of this nomogram. RESULTS: The predictive factors contained in the multivariate model included duration, gender, respiratory infection, arthritis, edema, estimated glomerular filtration rate, 24 h urine protein, uric acid, and renal ultrasound intensity. The area under the curves (AUC) of the nomogram in the training set and testing set were 0.814 and 0.822, respectively, indicating its good predictive ability. Moreover, the DCA curve and CIC revealed its clinical utility. CONCLUSION: The developed multivariate predictive model combines the clinical and laboratory factors of patients with IgAVN and is useful in the individualized prediction of the 1-year remission probability aid for clinical decision-making during treatment and management of IgAVN.

IgA vasculitis nephritis clinical course and kidney biopsy - national study in children.

The aim of the study was to investigate the relationship between the severity of typical clinical symptoms, severity of histopathological lesions in kidney biopsies in IgA vasculitis nephritis (IgAVN) and to propose indications for kidney biopsy in children. MATERIAL AND METHODS: This retrospective study enrolled 106 patients, included in the IgAVN registry of Polish children, diagnosed by kidney biopsy. Renal and extrarenal symptoms at onset of the disease were analyzed. Biopsy results were assessed using Oxford classifications (MEST-C). The patients were divided into 3 groups depending on the severity of proteinuria: A-nephrotic proteinuria with hematuria; B-non-nephrotic proteinuria with hematuria; C-isolated hematuria. RESULTS: The first symptoms of nephropathy were observed at the 0.7 (1-128.4) months from the onset of extrarenal symptoms. Kidney biopsy was performed on 39 (6-782) days after the onset of nephropathy symptoms. MEST-C score 4 or 5 was significantly more frequent in children from group A than in groups B and C. Significantly higher mean MEST-C score was found in patients with abdominal symptoms than without. In group A: S0 and T0 we found in significantly shorter time to kidney biopsy than in S1, T1-2 p < 0.05) and in group B the significantly shorter time in T0 compare to T1-2 p < 0.05). The ROC analysis shows that S1 changes appear in kidney biopsies in group A with cut off 21 days (AUC 0,702, p = 0.004, sensitivity 0.895 specificity 0.444) T1-2 changes after 35 days (AUC 0.685, p = 0.022, sensitivity 0.750, specificity 0.615), and in goupn B T1-2 cut off is 74 days (AUC 0,738, p = 0.002, sensitivity 0.667, specificity 0.833). CONCLUSIONS: In childhood IgAVN, the severity of changes in the urine is clearly reflected in the result of a kidney biopsy. The biopsy should be performed in patients with nephrotic proteinuria no later than 3 weeks after the onset of this symptom in order to promptly apply appropriate treatment and prevent disease progression. Accompanying abdominal symptoms predispose to higher MESTC score.

Targeting Enrichment and Correlation Studies of Glutathione and Homocysteine in IgAVN Patient Urine Based on a Core-Shell Zr-Based Metal-Organic Framework.

Aminothiols are closely related to chronic kidney disease, but little is known regarding levels of related aminothiols in the urine of immunoglobulin A vasculitis with nephritis (IgAVN) patients. Herein, a well-defined core-shell Zr-based metal-organic framework (Zr-MOF) composite SiO2@50Benz-Cys was constructed as a mercury ion affinity material via a solvent-assisted ligand exchange strategy for the selective extraction and enrichment of low-concentration aminothiols in IgAVN patient urine. SiO2@50Benz-Cys was competent to enrich the total glutathione (GSH) and total homocysteine (Hcy) in virtue of the excellent affinity after chelation with mercury ions. The extraction efficiencies were closely related to the pH, dithiothreitol amount, and the dose of functional Zr-MOF. Coupled with HPLC-MS/MS in optimized conditions, GSH and Hcy were determined with low detection limits of 0.5 and 1 nmol L-1, respectively. The recoveries of GSH and Hcy for the urine sample at three spiked levels were in the range of 85.3-105% and 79.5-103%, which showed good precision and accuracy. Benefiting from the matrix interference elimination in the process of extraction, the simultaneous detection of aminothiols in the urine of the healthy group and immunoglobulin A vasculitis (IgAV) and IgAVN patients was successfully carried out, suggesting that the Zr-MOF and the robust method together provided a potential application in the analysis of urinary biomolecules. The analysis of variance (ANOVA) showed that the levels of GSH and Hcy had significant differences between the patients and the control. This work is very valuable as it provides a better understanding of concentration alterations of GSH and Hcy in urine involved with IgAVN for clinical research.

A systematic review of urine biomarkers in children with IgA vasculitis nephritis.

BACKGROUND: Nephritis is a recognised complication of IgA vasculitis (IgAV, Henoch-Schönlein purpura) contributing to 1-2% of all chronic kidney disease (CKD) stage 5. Improved understanding may reduce irreversible damage in IgAV nephritis (IgAV-N). OBJECTIVE: The aim of this study was to perform a comprehensive systematic literature review to identify promising clinical and pre-clinical urine biomarkers in children with IgAV-N that could predict the presence of nephritis and/or determine its severity. METHODS: A systematic literature review was performed using four search engines and a predefined search term strategy. Promising biomarkers were divided in terms of clinical or pre-clinical and ability to predict the presence of nephritis or determine its severity. Results were described using statistical significance (p < 0.05) and area under the curve (AUC) values. RESULTS: One hundred twenty-one studies were identified; 13 were eligible. A total of 2446 paediatric patients were included: healthy controls (n = 761), children with IgAV-N (n = 1236) and children with IgAV without nephritis (IgAV-noN, n = 449). Fifty-one percent were male, median age 7.9 years. The clinical markers, 24-h protein quantity and urine protein:creatinine ratio, were deemed acceptable for assessing severity of nephritis (AUC < 0.8). Urinary albumin concentration (Malb) performed well (AUC 0.81-0.98). The most promising pre-clinical urinary biomarkers in predicting presence of nephritis were as follows: kidney injury molecule-1 (KIM-1) (AUC 0.93), monocyte chemotactic protein-1 (MCP-1) (AUC 0.83), N-acetyl-ß-glucosaminidase (NAG) (0.76-0.96), and angiotensinogen (AGT) (AUC not available). Urinary KIM-1, MCP-1, and NAG appeared to correlate with disease severity. CONCLUSIONS: Longitudinal studies are needed to assess whether pre-clinical biomarkers enhance standard of care in IgAV-N.

An extremely mild clinical course in a case with LAMB2-associated nephritis diagnosed with next-generation sequencing.

Biallelic pathogenic variants in the laminin ß2 (LAMB2) gene, which encodes laminin ß2, are associated with Pierson syndrome characterized by a congenital nephrotic syndrome that rapidly progresses to end-stage renal disease, distinct ocular maldevelopment with bilateral microcoria, and neurodevelopmental deficits. However, the phenotypic spectrum of LAMB2-associated disorder is broader than expected, and cases with milder phenotypes such as isolated congenital or infantile nephrotic syndrome have also been reported. We report a patient with LAMB2-associated renal disorder showing an extremely mild phenotype. A 5-year-old girl presented with asymptomatic proteinuria and hematuria detected by urinalysis screening. She had been previously healthy without any additional renal symptoms. The serum albumin and creatinine levels were normal. Renal biopsy revealed minor glomerular abnormalities with occasional focal mesangial proliferation. Electron microscopy showed no structural changes in the glomerular basement membrane. Targeted sequencing of podocyte-related genes using next-generation sequencing was performed. As a result, previously reported biallelic pathogenic variants of the truncating variant (c.5073_5076dupCCAG) and a splice site variant (c.3797 + 5G > A) in the LAMB2 gene were detected, and the patient was diagnosed with LAMB2-associated renal disorder. Interestingly, a previously reported case with this splicing variant also showed an atypically mild phenotype. We suggest that clinicians should consider LAMB2-associated nephritis as an important differential diagnosis in children with asymptomatic proteinuria and microscopic hematuria if there is no structural change in the glomerular basement membrane. A comprehensive gene-screening system using next-generation sequencing is useful for diagnosing these atypical cases with isolated urine abnormalities.

Flank pain and hematuria is not always a kidney stone.

BACKGROUND: Patients with flank pain and hematuria are common emergency department presentations of nephrolithiasis. We may anchor on this etiology and potentially miss other less common differentials. We present a case of a patient with hematuria and flank pain typical of nephrolithiasis who was diagnosed with a Page kidney causing secondary hypertension. A 50 year-old male with no significant past medical history presented to the Emergency Department with severe left-sided flank pain, vomiting, and blood-tinged urine. We pursued a diagnosis of nephrolithiasis and found a left renal subcapsular hematoma on non-contrast CT. A CTA was done with no active hemorrhage found. The patient had no history of recent trauma and was found to be hypertensive on evaluation. Urology was consulted and management for the patient's hypertension was initiated. He was diagnosed with Page Kidney and admitted to medicine for observation and hypertension management with an angiotensin-converting enzyme inhibitor. Page Kidney is a diagnosis that describes compression of the renal parenchyma by a hematoma or mass causing secondary hypertension through the activation of the renin-angiotensin-aldosterone system. Causes may include traumatic subcapsular hematoma, renal cyst rupture, tumor, hemorrhage, arteriovenous malformation, among others. Treatment may involve conservative measures including hypertension management, or more invasive measures like evacuation or nephrectomy. We describe the case of a patient presumed to have nephrolithiasis presenting with typical left-sided flank pain, diagnosed with Page kidney, and treated conservatively.

Expanding the phenotype of biallelic loss-of-function variants in the NSUN2 gene: Description of four individuals with juvenile cataract, chronic nephritis, or brain anomaly as novel complications.

The NSUN2 gene encodes a tRNA cytosine methyltransferase that functions in the maturation of leucyl tRNA (Leu) (CAA) precursors, which is crucial for the anticodon-codon pairing and correct translation of mRNA. Biallelic loss of function variants in NSUN2 are known to cause moderate to severe intellectual disability. Microcephaly, postnatal growth retardation, and dysmorphic facial features are common complications in this genetic disorder, and delayed puberty is occasionally observed. Here, we report four individuals, two sets of siblings, with biallelic loss-of-function variants in the NSUN2 gene. The first set of siblings have compound heterozygous frameshift variants: c.546_547insCT, p.Met183Leufs*13; c.1583del, p.Pro528Hisfs*19, and the other siblings carry a homozygous frameshift variant: c.1269dup, p.Val424Cysfs*14. In addition to previously reported clinical features, the first set of siblings showed novel complications of juvenile cataract and chronic nephritis. The other siblings showed hypomyelination and simplified gyral pattern in neuroimaging. NSUN2-related intellectual disability is a very rare condition, and less than 20 cases have been reported previously. Juvenile cataract, chronic nephritis, and brain anomaly shown in the present patients have not been previously described. Our report suggests clinical diversity of NSUN2-related intellectual disability.