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Lupus nephritis (LN) is a pathologically heterogenous autoimmune disease linked to end-stage kidney disease and mortality. Better therapeutic strategies are needed as only 30%-40% of patients completely respond to treatment. Noninvasive biomarkers of intrarenal inflammation may guide more precise approaches. Because urine collects the byproducts of kidney inflammation, we studied the urine proteomic profiles of 225 patients with LN (573 samples) in the longitudinal Accelerating Medicines Partnership in RA/SLE cohort. Urinary biomarkers of monocyte/neutrophil degranulation (i.e., PR3, S100A8, azurocidin, catalase, cathepsins, MMP8), macrophage activation (i.e., CD163, CD206, galectin-1), wound healing/matrix degradation (i.e., nidogen-1, decorin), and IL-16 characterized the aggressive proliferative LN classes and significantly correlated with histological activity. A decline of these biomarkers after 3 months of treatment predicted the 1-year response more robustly than proteinuria, the standard of care (AUC: CD206 0.91, EGFR 0.9, CD163 0.89, proteinuria 0.8). Candidate biomarkers were validated and provide potentially treatable targets. We propose these biomarkers of intrarenal immunological activity as noninvasive tools to diagnose LN and guide treatment and as surrogate endpoints for clinical trials. These findings provide insights into the processes involved in LN activity. This data set is a public resource to generate and test hypotheses and validate biomarkers.

Background: TRIM8-related neuro-renal syndrome (NRS), caused by pathogenic variants of the TRIM8 gene, is characterized by epilepsy, developmental delay (DD) and renal disorders. The severity of the neurological effects as well as the presence of renal disorders is variable among patients. Here, we report three additional patients with clinical features compatible with NRS and summarize the association between the variants' loci and phenotype of TIRM8-related NRS. Methods: A retrospective analysis was conducted for three Chinese children with NRS due to TRIM8 variants identified through whole-exome sequencing (WES). Previous reports of patients with TRIM8-related NRS were reviewed systematically. Demographic and clinical data were collected from these patients. Results: Two de novo TRIM8 truncating variants in three NRS patients were identified in our study, including c.1327_c.1328delCCinsTG (p. Arg443*) and c.1375C>T (p. Gln459*). Our three patients all exhibited drug-resistant epilepsy and early-onset DD, and two of whom developed electrical status epilepticus during sleep (ESES). Brain magnetic resonance imaging (MRI) showed periventricular leukomalacia in one patient and normal in the other two. All three patients demonstrated nephrotic range proteinuria (NRP) or nephrotic syndrome (NS) with normal renal function during follow-up. There was a total of 27 patients with TRIM8-related NRS have been identified to date. The most common clinical features are renal diseases (89%), DD (89%), followed by epilepsy (78%). 67% of patients eventually progressed to end-stage renal disease (ESRD). Focal seizure was the most frequent seizure type (57%). 52% of patients presented drug-resistant epilepsy. 64% of patients exhibited non-specific brain MRI abnormalities. Brain atrophy was the most common change (50%). Two patients with TRIM8 variants closer to the N-terminal had neurological diseases without renal damage. Five patients with TRIM8 variants closer to the C-terminal had no severe neurological diseases. Seven patients had Gln459* variant which is the most common variant (7/27, 25.9%). The severity of the renal and neurological damage of the seven patients was variable. Conclusion: This study expands the number of individuals with confirmed NRS due to pathogenic variants in TRIM8. Neurological and renal phenotype with the same variant locus differed in their severity. Further research is needed to explore the relationship between genotype and phenotype of TRIM8 variants. [ABSTRACT FROM AUTHOR]

Background: Assessing for significant proteinuria in pregnancy (SPIP) stands as a key indicator for diagnosing preeclampsia. However, the initial method typically employed for this assessment, the urine dipstick test, often yields inaccurate results. While a 24-h urine collection is considered the most reliable test, its implementation can lead to delays in diagnosis, potentially affecting both maternal and fetal well-being. The urine protein–creatinine (P/Cr) ratio can be used as an alternative to 24-h urine protein analysis, but its diagnostic accuracy has remained uncertain. There is a need to compare the diagnostic accuracy of urine P/Cr ratio and dipstick urinalysis for SPIP, especially in resource-poor settings. Objectives: To determine and compare the diagnostic accuracy of urine P/Cr ratio and dipstick urinalysis in a spot urine specimen for the diagnosis of SPIP among women evaluated for preeclampsia using 24-h urine protein excretions as a gold standard. Design: This is a comparative cross-sectional study. Methods: The study involved 82 singleton pregnant women evaluated for preeclampsia from 20 weeks of gestation who underwent dipstick and P/Cr ratio tests in the same urine sample. Women at risk of preeclampsia were given a specimen container for the collection of urine samples on an outpatient basis. Participants were trained and told to collect the urine sample 24 h prior to their next antenatal appointment. However, those on admission and evaluated for preeclampsia had their 24-h urine collected in the hospital. The outcome measures included sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio and accuracy for the two tests. Significant proteinuria was defined as a P/Cr ratio >0.27 or ⩾2+ of proteinuria on the dipstick test. Preeclampsia was confirmed in women with both high blood pressure and SPIP. Results: The mean age of participants was 28.65 ± 5.76 years. Comparatively, the diagnostic accuracy (91.46% (95% CI = 83.29–96.59) vs 59.76% (95% CI = 48.34–70.44), p = 0.001), sensitivity (94.74% vs 70.00%, p = 0.021), specificity (84.00% vs 43.75%, p = 0.001), negative predictive value (87.50% vs 48.28%, p = 0.003) and positive predictive value (93.10% vs 66.04%, p = 0.001), respectively, were higher for the spot urine P/Cr ratio than dipstick test. In addition, the positive likelihood ratio and the negative likelihood ratio for spot urine P/Cr ratio versus dipstick test were (1.93 vs 1.24) and (0.07 vs 0.69), respectively. Conclusion: The spot urine P/Cr has superior diagnostic accuracy in the determination of significant proteinuria in pregnant women being evaluated for preeclampsia than the widely used dipstick test. A more robust multicenter study is needed to compare the diagnostic accuracy of spot urine PCR with the standard 24-h urine protein in low-income settings. Plain language summary: Comparison of diagnostic tests for the detection of protein in the urine of pregnant women with preeclampsia • Preclampsia is one of the medical disorders that can complicate pregnancy, and it is a major cause of feto-maternal morbidity and mortality during pregnancy. • Preeclampsia is the development of elevated blood pressure beyond the normal value during the second half of pregnancy with a significant amount of protein in the urine. • The detection of a significant amount of protein in the urine is one of the criteria for the diagnosis of preeclampsia; however, there are limitations with the various methods of urine protein detection and estimation. • The study was conducted among women being evaluated for preeclampsia. We compared the diagnostic accuracy of the urine protein-creatinine ratio and dipstick urine test for the diagnosis of significant proteinuria in pregnancy using 24-hour urine protein excretions as a gold standard. • Our findings showed that the spot urine protein-creatinine ratio has superior diagnostic accuracy when compared to the regular dipstick urine tests for the detection of significant protein in the urine among pregnant women being evaluated for preeclampsia. [ABSTRACT FROM AUTHOR]

ABSTRACT Sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) have demonstrated a blood pressure (BP) reduction benefit despite other indications for use. We evaluated BP changes and antihypertensive medication use pre‐ and post‐SGLT2i initiation among 12 960 patients with treated hypertension and among subgroups with apparent treatment‐resistant hypertension (aTRH) and/or proteinuria. Post‐SGLT2i initiation, the mean (SD) systolic blood pressure (SBP) was reduced from 133.9 (16.4) to 128.6 (15.5) mmHg and the mean diastolic blood pressure (DBP) was reduced from 70.8 (11.8) to 68.3 (11.3) mmHg among all patients. The mean SBP/DBP reduction was 5.3/2.5, 6.2/2.8, and 6.1/2.9 mmHg among all patients, patients with aTRH, and patients with proteinuria, respectively. Achieved BP < 130/80 mmHg increased by 12.5%, 16.9%, and 11.1% for all patients, patients with aTRH, and patients with proteinuria, respectively. Discontinuation of ≥ 1 antihypertensive medication within 12 months of SGLT2i initiation occurred in 33.4% overall, 47.6% of patients with aTRH, and 38.7% of patients with proteinuria. [ABSTRACT FROM AUTHOR]

Soluble epoxide hydrolase (sEH) has previously been demonstrated to play an important part in kidney diseases by hydrolyzing renoprotective epoxyeicosatrienoic acids to their less active diols. However, little is known about the role of sEH in primary glomerular diseases. Here, we investigated the effects of sEH inhibition on proteinuria in primary glomerular diseases and the underlying mechanism. The expression of sEH in the renal tubules of patients with minimal change disease, IgA nephropathy, and membranous nephropathy was significantly increased. Renal sEH expression level was positively correlated with the 24 h urine protein excretion and negatively correlated with serum albumin. In the animal model of Adriamycin (ADR)-induced nephropathy, renal sEH mRNA and protein expression increased significantly. Pharmacological inhibition of sEH with AUDA effectively reduced urine protein excretion and attenuated renal pathological damage. Furthermore, sEH inhibition markedly abrogated the abnormal expressions of nephrin and desmin in glomerular podocytes induced by ADR. More importantly, AUDA treatment inhibited renal NF-κB activation and reduced TNF-α levels in rats with ADR-induced nephropathy. Overall, our findings suggest that sEH inhibition ameliorates renal inflammation and podocyte injury, thus reducing proteinuria and exerting renoprotective effects. Targeting sEH might be a potential strategy for the treatment of proteinuria in primary glomerular diseases. [ABSTRACT FROM AUTHOR]

Incident chronic kidney disease (CKD) varies in populations with hypertension of similar severity. Proteinuria promotes CKD progression in part due to activation of plasminogen to plasmin in the podocytes, resulting in oxidative stress‐mediated injury. Additional mechanisms include deficiency of renal alpha‐klotho, that inhibits Wnt/beta‐catenin, an up regulator of intra‐renal renin angiotensin system (RAS) genes. Alpha‐klotho deficiency therefore results in upregulation of the intra‐renal RAS via Wnt/beta‐catenin. In hypertensive, Dahl salt sensitive (DS) and spontaneously hypertensive rats (SHR), we investigated renal and vascular injury, miR‐155, AT1R, alpha‐klotho, and TNF‐α. Hypertensive high salt DS (DS‐HS), but not SHR developed proteinuria, plasminuria, and glomerulosclerosis. Compared to DS low salt (DS‐LS), in hypertensive DS‐HS alpha‐klotho decreased 5‐fold in serum and 2.6‐fold in kidney, whereas serum mir‐155 decreased 3.3‐fold and AT1R increased 52% in kidney and 77% in aorta. AT1R, alpha‐klotho, and miR‐155 remained unchanged in prehypertensive and hypertensive SHR. TNF‐α increased by 3‐fold in serum and urine of DS‐HS rats. These studies unveiled in salt sensitive DS‐HS, but not in SHR, a genetically conditioned dysfunction of the intermolecular network integrated by alpha‐klotho, RAS, miR‐155, and TNF‐α that is at the helm of their end‐organ susceptibility while plasminuria may participate as a second hit. [ABSTRACT FROM AUTHOR]

Proteinuria is a biomarker of kidney injury that typically results from glomerular and/or tubulointerstitial disease. Whereas kidney impairment with normal urinary protein excretion is usually less focused and understudied. We conducted a retrospective review of the renal histopathology of the patients with variable degrees of unexplained renal insufficiency but with normal range proteinuria between 2014 and 2024 of three university teaching hospitals in Shenzhen city of Southern China. Patients with kidney dysfunction of undetermined or uncertain etiology and with normal urinary protein excretion (defined by a 24hr urinary protein excretion < 150 mg or spot urinary protein to creatinine ratio [PCR] < 150 mg/g) were enrolled and analyzed. In a total of 2405 patients, 53 (2.2%) fulfilled the inclusion criteria (male/female 40/13, age 47.3 ± 14.3 years) with a mean eGFR of 46.6 ± 16.8 ml/min per 1.73 m2. Glomerular disease (GD) was the most frequent pathological finding identified in 23 (43.4%) patients, while 19 (35.8%) cases showed tubulointerstitial disease (TID) and 11 (20.8%) patients exhibited small vascular disease (SVD). Patients in the TID had the lowest mean eGFR and the highest numerical 24hr urinary protein excretion among the three groups. The incidence of acute kidney injury was significantly higher in TID than in other two groups. The patients in the SVD group had the highest fraction of underlying hypertension. Kidney dysfunction with normal range proteinuria may be related with, in descending order of probablity, glomerular, tubulointerstitial and small vascular diseases. Renal biopsies were proved useful in informing therapeutic choice, long-term management and in predicting prognosis in this setting. [ABSTRACT FROM AUTHOR]

Aims/Introduction: The time course of chronic kidney disease in young‐onset type 2 diabetes mellitus remains unclear. We compared the trajectories of proteinuria and estimated glomerular filtration rate (eGFR) decline between young‐onset (aged ≤40 years) and late‐onset (aged >40 years) type 2 diabetes mellitus in a Japanese multicenter cohort. Materials and Methods: Participants without diabetic kidney disease were divided into two groups according to age at diagnosis: young‐ and late‐onset. The primary endpoint was eGFR <60 mL/min/1.73 m2, proteinuria or both. Multivariable Cox proportional hazards were calculated to estimate incidence. Results: Among 626 participants with type 2 diabetes mellitus, 78 (12.4%) had young‐onset and 548 (87.6%) had late‐onset diabetes. The incidence of eGFR <60 mL/min/1.73 m2 was lower (16.7% vs 33.5%, P = 0.003), but that of proteinuria was higher (46.2% vs 28.9%, P = 0.002) in the young‐onset type 2 diabetes mellitus group. The Kaplan–Meyer curve showed that young‐onset type 2 diabetes mellitus was associated with a decreased hazard ratio (HR) for eGFR <60 mL/min/1.73 m2 and an increased HR for proteinuria compared with late‐onset type 2 diabetes mellitus. In the multivariate Cox analysis, young‐onset type 2 diabetes mellitus increased the HR (95% confidence interval) of proteinuria (1.53, 95% confidence interval 1.03–2.26), but did not change the eGFR <60 mL/min/1.73 m2 HR. Conclusions: Young‐onset type 2 diabetes mellitus has a lower HR of eGFR <60 mL/min/1.73 m2 and an increased HR of proteinuria compared with late‐onset type 2 diabetes mellitus, indicating that young‐onset type 2 diabetes mellitus has a different time course for the development of proteinuria and subsequent eGFR decline. [ABSTRACT FROM AUTHOR]

Purpose: Proteinuria can cause interindividual variability in the pharmacokinetics of therapeutic antibodies and may affect therapeutic efficacy. Here, we measured the serum and urinary concentrations of bevacizumab (BV) and nivolumab (NIVO) in patients with proteinuria and reported a case series of these patients. Methods: Thirty-two cancer patients who received BV every 3 weeks or NIVO every 2 weeks between November 2020 and September 2021 at Kyoto University Hospital were enrolled in this study. The serum and urinary concentrations of BV and NIVO were measured using liquid chromatography-tandem mass spectrometry. Results: We divided the BV-treated patients and the NIVO-treated patients into two groups based on the urine protein-creatinine ratio (UPCR): UPCR 1 g/g or higher (BV, n = 9; NIVO, n = 3) and UPCR less than 1 g/g (BV, n = 14; NIVO, n = 6). Serum concentrations of the therapeutic antibodies adjusted by their doses were significantly lower in both BV- and NIVO-treated patients with UPCR 1 g/g or higher compared to those with less than 1 g/g. In patients with UPCR 1 g/g or higher, urinary concentrations of the therapeutic antibodies adjusted by their serum concentrations and urinary creatinine concentrations tended to increase. Conclusion: This case-series study suggests a possibility of reduction in serum concentrations of BV and NIVO in patients with proteinuria by urinary excretion of these drugs. [ABSTRACT FROM AUTHOR]

Background and purpose: Reports of patients who have autoimmune nodopathies concurrent with nephrotic syndrome are increasing. We investigated whether proteinuria could be a biomarker of autoimmune nodopathies. Methods: Qualitative urinalysis results were retrospectively obtained from 69 patients who were diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) at a hospital in Japan. Proteinuria was graded as mild to severe (i.e., mild, 30–99; moderate, 100–299; severe, 300 mg/dL or more) according to the results of the urine dipstick test. Autoantibodies against the paranodal proteins contactin 1 (CNTN1), neurofascin 155 (NF155), and contactin‐associated protein 1 (Caspr1) and the nodal protein neurofascin 186 (NF186) were measured, and the predominant IgG subclass was determined by enzyme‐linked immunosorbent assay in sera from the 69 patients. Results: Four patients (6%), five patients (7%), and one (1%) patient were positive for anti‐CNTN1, anti‐NF155, and anti‐Caspr1 IgG4 antibodies, respectively. No patients had IgG4 antibodies against NF186. Proteinuria of mild or greater levels was found in three patients with anti‐CNTN1 IgG4 and two patients with anti‐NF155 IgG4 antibodies. The autoantibody‐positive patients more frequently had proteinuria of mild or greater levels than the seronegative patients (p = 0.01). Conclusions: Proteinuria is a possible biomarker of autoimmune nodopathies associated with autoantibodies targeting CNTN1 or NF155. Urinalysis results should be carefully checked for quick differentiation of autoimmune nodopathies from CIDP. Patients who present with nephrotic syndrome should be tested for anti‐CNTN1 IgG4 antibodies, and patients who exhibit mild proteinuria should be tested for anti‐NF155 IgG4 antibodies. [ABSTRACT FROM AUTHOR]

Objective: This paper was aimed at unveiling the effect of low-molecular-weight heparin calcium (LMWH) combined with magnesium sulfate and labetalol on coagulation, vascular endothelial function, and pregnancy outcome in early-onset severe preeclampsia (EOSP). Methods: Pregnant women with EOSP were divided into the control group and the study group, each with 62 cases. Patients in the control group were treated with labetalol and magnesium sulfate, and those in the study group were treated with LMWH in combination with the control grou Blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]), 24-h urine protein, coagulation indices [D-dimer (D-D), plasma fibrinogen (Fg), prothrombin time (PT), activated partial thromboplastin time (APTT), and prothrombin time (TT)], endothelial function [endothelin (ET-1) and nitric oxide (NO)], oxidative stress indices [oxidized low-density lipoproteins (ox-LDL), lipid peroxidation (LPO), superoxide dismutase (SOD), and malondialdehyde (MDA)], pregnancy outcome, and adverse effects occurred in the two groups were compared. Results: After treatment, lower SBP, DBP, and 24-h urine protein levels; lower Fg and D-D levels; higher PT, APPT, and TT levels; higher NO levels; lower ET-1 levels; lower ox-LDL, MDA, and LPO levels; higher SOD levels; and lower incidence of adverse pregnancy and adverse reactions were noted in the study group in contrast to the control group. Conclusion: EOSP patients given with LMWH combined with magnesium sulfate and labetalol can effectively reduce the patient's blood pressure and urinary protein level; improve coagulation function, oxidative stress, and vascular endothelial function indices; reduce the adverse pregnancy outcomes; and improve the safety of treatment. [ABSTRACT FROM AUTHOR]

Background: Steroid-resistant nephrotic syndrome is the second leading cause of chronic kidney disease among patients < 25 years of age. Through exome sequencing, identification of > 65 monogenic causes has revealed insights into disease mechanisms of nephrotic syndrome (NS). Methods: To elucidate novel monogenic causes of NS, we combined homozygosity mapping with exome sequencing in a worldwide cohort of 1649 pediatric patients with NS. Results: We identified homozygous missense variants in MYO1C in two unrelated children with NS (c.292C > T, p.R98W; c.2273 A > T, p.K758M). We evaluated publicly available kidney single-cell RNA sequencing datasets and found MYO1C to be predominantly expressed in podocytes. We then performed structural modeling for the identified variants in PyMol using aligned shared regions from two available partial structures of MYO1C (4byf and 4r8g). In both structures, calmodulin, a common regulator of myosin activity, is shown to bind to the IQ motif. At both residue sites (K758; R98), there are ion-ion interactions stabilizing intradomain and ligand interactions: R98 binds to nearby D220 within the myosin motor domain and K758 binds to E14 on a calmodulin molecule. Variants of these charged residues to non-charged amino acids could ablate these ionic interactions, weakening protein structure and function establishing the impact of these variants. Conclusion: We here identified recessive variants in MYO1C as a potential novel cause of NS in children. [ABSTRACT FROM AUTHOR]

Background: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and glomerulonephritis is uncommon in children. We sought to characterize the histological and clinical features of the disease and report on risk factors for adverse outcomes in a pediatric cohort. Methods: Retrospective single-center cohort of all pediatric (< 20 years) patients diagnosed with ANCA-associated glomerulonephritis (AAGN) by kidney biopsy between 2002 and 2022 at Johns Hopkins University. Histological and clinical features were extracted from the medical record. Clinical, laboratory, and histological findings were analyzed to determine the association with kidney failure (KF) and/or death. Results: A total of 17 patients were identified (GPA n = 7, MPA = 10) with a median age of 15 years (IQR 12–17) at presentation, a slight female predominance (59%), with seven patients reaching the composite outcome of death (n = 1) or kidney failure (n = 6). There was no difference in presenting clinical symptoms or extra-renal manifestations between the two groups. Univariable Cox regression identified several factors associated with an increased hazard of endpoint including the degree of global or segmental sclerosis, interstitial fibrosis and tubular atrophy (IFTA), C3 and C1q staining, presence of subendothelial deposits, and proteinuria. Multivariable regression was not performed due to the small sample size. We saw a trend towards increased utilization of plasma exchange and a decrease in cyclophosphamide utilization in the more recent era. There was no association between treatment modality and outcome. Conclusions: Pediatric AAGN is a rare disease associated with significant morbidity. We identified glomerulosclerosis and IFTA on histology, and proteinuria on initial presentation as risk factors for KF/death. [ABSTRACT FROM AUTHOR]

Background: Lupus nephritis (LN) is a very severe manifestation of lupus. There is no consensus on which treatment goals should be achieved to protect kidney function in children with LN. Methods: We retrospectively analyzed trends of commonly used laboratory biomarkers of 428 patients (≤ 18 years old) with biopsy-proven LN class ≥ III. We compared data of patients who developed stable kidney remission from 6 to 24 months with those who did not. Results: Twenty-five percent of patients maintained kidney stable remission while 75% did not. More patients with stable kidney remission showed normal hemoglobin and erythrocyte sedimentation rate from 6 to 24 months compared to the group without stable kidney remission. eGFR ≥ 90 ml/min/1.73m2 at onset predicted the development of stable kidney remission (93.8%) compared to 64.7% in those without stable remission (P < 0.00001). At diagnosis, 5.9% and 20.2% of the patients showed no proteinuria in the group with and without stable kidney remission, respectively (P = 0.0001). dsDNA antibodies decreased from onset of treatment mainly during the first 3 months in all groups, but more than 50% of all patients in both groups never normalized after 6 months. Complement C3 and C4 increased mainly in the first 3 months in all patients without any significant difference. Conclusions: Normal eGFR and the absence of proteinuria at onset were predictors of stable kidney remission. Significantly more children showed normal levels of Hb and erythrocyte sedimentation rate (ESR) from 6 to 24 months in the group with stable kidney remission. [ABSTRACT FROM AUTHOR]

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Secondary amyloidosis (AA) is a disorder of protein conformation associated with inflammatory disorders. Detailed reports of patients diagnosed with AA and inflammatory bowel disease (IBD) are limited. This study reports the cases of eight patients, across three tertiary medical centers, diagnosed with both IBD and AA between 2000 and 2020. Seven patients had a diagnosis of Crohn disease (CD), while one had ulcerative colitis (UC). All patients were diagnosed with AA after being diagnosed with IBD (median: 15 years later). The small bowel (62.5%) and the colon (62.5%) were the most common IBD locations. 4 patients had undergone TNF-alpha inhibitor therapy and all CD patients required surgical treatment of their IBD. A history of fistula or abscess was identified in 5 patients. The most common initial site of AA was the kidney (75%). All 8 patients presented with some form of renal dysfunction and proteinuria (median: 1500 mg/24 h). Hypoalbuminemia was found in most patients. Six patients developed chronic kidney disease and 4 required dialysis. Anti TNF-alpha antibody therapy led to rapid improvement of renal function in one of four patients who received it. Three patients required a renal transplant. Four patients had died upon the latest follow-up (5-year survival: 75%). The presence of proteinuria, fistula, or abscess should serve as indicators for potentially increased AA risk in CD patients. [ABSTRACT FROM AUTHOR]

Background: Imerslund-Gräsbeck syndrome (IGS) is an autosomal recessive disorder characterized by selective vitamin B12 malabsorption, resulting in vitamin B12 deficiency and impaired reabsorption of proximal tubular proteins.This case highlights a previously unidentified compound heterozygous variant in the Amnionless (AMN) gene that causes IGS syndrome and underscores the importance of long-term oral vitamin B12 replacement therapy in managing the condition. Case presentation: In this retrospective analysis, we present the clinical data of a 3-year and 6-month-old female child diagnosed with IGS at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China, in November 2018. The child was admitted to the hospital due to a history of anemia persisting for over a month. There was no previous significant medical history. The admission examination revealed megaloblastic anemia with proteinuria. Serum vitamin B12 levels were decreased, while folic acid and renal function were normal. The patient was diagnosed with megaloblastic anemia and started long-term oral vitamin B12 replacement therapy. Throughout the follow-up period, blood tests consistently showed normal results, while proteinuria persisted. In November 2019, the child and her parents underwent whole exome sequencing analysis, which revealed a novel compound heterozygous variant in the AMN gene: c.162 + 1G > A and c.922 C > T (p.Q308X) in the child, c.162 + 1G > A in the father, and c.922 C > T (p.Q308X) in the mother. Therefore, this child was further diagnosed with IGS. Conclusions: In this case, whole exome sequencing proves to be highly practical in daily healthcare for diagnosing and refining rare or ultra-rare diseases with ambiguous phenotypes or genetic diversity. It is also valuable for prognostic evaluation and personalized management. Additionally, the oral vitamin B12 treatment demonstrated positive clinical effects for the child, offering a new option for patients unable to undergo intramuscular vitamin B12 replacement therapy. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is one of the most common complications of diabetes mellitus (DM). Diabetes mellitus contributes to about 66% of CKD cases globally. CKD results in increased morbidity and mortality and advanced stages often require kidney replacement therapy that is unaffordable for the majority of the patients. Developing countries have scanty data regarding CKD burden in diabetic patients. Objectives: This study aimed at determining the prevalence of low estimated glomerular filtration rate (eGFR) and proteinuria and associated clinical and socio-demographic factors among adult diabetic patients attending the diabetic clinic of Mbale Regional Referral Hospital (MRRH). Methods: A cross-sectional study was conducted at the adult diabetic clinic of MRRH in Eastern Uganda. A total of 374 adult diabetic patients were enrolled. A urine sample for urine albumin creatinine ratio (UACR) determination and a venous blood sample for measurement of serum creatinine were obtained from each participant. The eGFR was determined using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and CKD was staged according to the Kidney Disease Improving Global Outcomes (KDIGO) classification. Results: A total of 318 (85%) participants had an eGFR of ≤ 60 mL/min/1.73m2, UACR of ≥ 30g/g, or both. Only 6.1% were aware. Age, duration of DM, hypertension, and dyslipidemia were associated with low eGFR and proteinuria. Conclusion: There is a high prevalence of low eGFR and proteinuria among DM patients, 85% of the participants had these markers of CKD and the majority of them were undiagnosed. Over half of the DM patients had an eGFR consistent with advanced CKD. Strengthening routine screening for CKD biomarkers and equipping DM clinics with more diagnostic resources is recommended. [ABSTRACT FROM AUTHOR]

Simple Summary: The most common adverse events (AEs) that occurred in response to targeted therapy for hepatocellular carcinoma were appetite loss (adverse event grade 0/1/2/3 = 97/23/55/12), general fatigue (102/31/44/6), hypertension (120/6/40/17), hand-foot syndrome (HFS) (135/21/24/3), proteinuria (140/13/16/14), and hypothyroidism (148/12/23/0). Among these, appetite loss and general fatigue negatively affect overall survival (OS) and progression-free survival (PFS). Increasing AE grades of hypertension, proteinuria, and hypothyroidism were associated with better OS, whereas hypertension, HFS, and hypothyroidism were associated with better PFS. To assess the impact of adverse event (AE) severity, caused by targeted therapy, on overall survival (OS) and progression-free survival (PFS) in patients with unresectable hepatocellular carcinoma (HCC), a total of 183 patients with HCC treated with atezolizumab plus bevacizumab (40), lenvatinib (57), sorafenib (79), cabozantinib (3), ramucirumab (3), and regorafenib (1) were included in this study. Age-, AFP-, and ALBI score-adjusted hazard ratios (HRs) of AE grades 1 to 3 versus grade 0 for OS and PFS were calculated using Cox proportional hazards models. The linear trend of the HRs was assessed by calculating the p values for this trend. The most common AEs were appetite loss (AE grade 0/1/2/3 = 97/23/55/12), general fatigue (102/31/44/6), hypertension (120/6/40/17), hand-foot syndrome (HFS) (135/21/24/3), proteinuria (140/13/16/14), and hypothyroidism (148/12/23/0). The adjusted HRs for OS of these AEs were 0.532–1.450–2.361 (p for trend 0.037), 1.057–1.691–3.364 (p for trend 0.004), 1.176–0.686–0.281 (p for trend 0.002), 0.639–0.759–1.820 (p for trend 0.462), 1.030–0.959–0.147 (p for trend 0.011), and 0.697–0.609 (p for trend 0.119), respectively. Those for PFS of the corresponding AEs were 0.592–1.073–2.811 (p for trend 0.255), 1.161–1.282–4.324 (p for trend 0.03), 0.965–0.781–0.655 (p for trend 0.095), 0.737–0.623–2.147 (p for trend 0.153), 1.061–0.832–0.800 (p for trend 0.391), and 1.412–0.560 (p for trend 0.081), respectively. Appetite loss and general fatigue negatively affected clinical outcomes, whereas hypertension, HFS, proteinuria, and hypothyroidism had positive effects. [ABSTRACT FROM AUTHOR]

The association between obstructive sleep apnea (OSA) and proteinuria is undetermined, with few studies on hypertension, a high-risk group for renal impairment. Therefore, we aimed to explore whether OSA is an independent risk factor for proteinuria in patients with hypertension. We investigated the cross-sectional association between OSA and proteinuria. Participants were divided into groups by apnea hypopnea index (AHI) category. Multivariable Logistic regression analysis was used to evaluate the association between OSA severity, objectively measured sleep dimensions, and proteinuria which is mainly defined by 24-h urine protein quantification > 300 mg/24 h. Sensitivity analyses were performed by excluding those with comorbidities (primary aldosteronism and homocysteine ≥ 15 μmol/L). Of the 2106 participants, the mean age was 47.57 ± 10.50 years, 67.2% were men, and 75.9% were OSA patients. In total participants, compared with those without OSA, patients with mild OSA, moderate OSA, and severe OSA showed 1.09 (95% CI 0.80–1.40), 1.24 (95% CI 0.89–1.74) and 1.47 (95% CI 1.04–2.08) fold risk for proteinuria with a trend test P trend < 0.05. Each 10-unit increase in the AHI, oxygen desaturation index (ODI), and time spent with oxygen saturation < 90% (T90) was found to be associated with 13%, 10%, and 2% higher likelihood of proteinuria in the crude model, significant in adjusted models. The more severe the OSA is, the higher the risk of proteinuria. AHI and T90 are independently associated with a higher risk of structural renal damage in the population with hypertension. [ABSTRACT FROM AUTHOR]

Summary Monoclonal Immunoglobulin deposition disease (MIDD) is characterised by deposits of intact monoclonal light chains in the kidney leading to renal dysfunction. In this study, we retrospectively investigated the underlying plasma cell cytogenetic abnormalities in MIDD. CyclinD1 (11;14) translocation was identified in 12/27 (45%) patients. Among the patients without translocation, del13q and hyperdiploidy were the most common abnormalities. Patients in the non‐t (11;14) group had a higher baseline light‐chain ratio, higher proteinuria and lower eGFR as compared to patients with t (11;14). Haematological VGPR or higher was seen in 58% of t (11;14), and 30% without t (11;14), possibly related to higher use of Daratumumab‐based therapy in the t (11;14) group. With a median follow‐up of 750 days, 30% (8/24) progressed to end stage renal disease (ESRD). eGFR <20 mL/min (HR 25, 95% CI 2.09–298, p = 0.01) and 24 urine protein >3 g/24 h (HR 9, 95% CI 1.27–63.90, p = 0.02) at diagnosis were significantly associated with progression to ESRD. Renal survival was better in t (11;14) as compared to the non‐t (11;14) group (HR 0.11, p = 0.06). Translocation (11;14) is a common abnormality in MIDD and affects the presentation and outcomes. Identification of this abnormality should lead to exploration of BCL2 inhibitors in this disease. [ABSTRACT FROM AUTHOR]

This mini‐review explores glucocorticoids, mycophenolate mofetil (MMF), and hydroxychloroquine (HCQ) in IgA nephropathy (IgAN). It discusses conflicting findings from pivotal trials like TESTING and STOP‐IgAN regarding glucocorticoid efficacy, emphasizing reduced‐dose protocols as potentially safer options. MMF's effectiveness varies among populations, demonstrating promise in Chinese cohorts but yielding inconclusive results elsewhere. HCQ shows potential in reducing proteinuria, with ongoing trials investigating its long‐term benefits. Summary at a glance: This mini‐review summarizes the evidence regarding glucocorticoids, mycophenolate mofetil (MMF), and hydroxychloroquine (HCQ) therapy in IgA nephropathy. It highlights the ongoing debate on the efficacy of glucocorticoids and MMF across different populations, and the potential effect of HCQ in IgA nephropathy. [ABSTRACT FROM AUTHOR]

There is growing evidence of endothelin receptor antagonists (ERAs) in renoprotection in proteinuric kidney disease including IgA nephropathy (IgAN). Here, we review current evidence, including the use of sparsentan, atrasentan and zibotentan in IgAN. Recent trails of combination therapy including SGLT2 inhibitors and ERAs suggest possible benefit in further reduction of proteinuria and reducing ERA fluid‐retention side effects although more evidence is needed for clinical applications. [ABSTRACT FROM AUTHOR]

When Berger et al. first reported IgA nephropathy in 1968, the prognosis was generally thought to be benign. However, as more case data were accumulated, it became evident that not all patients with IgA nephropathy necessarily had a good prognosis. IgA nephropathy has a significant morbidity, culminating in end‐stage kidney disease (ESKD) in about 40% of patients without treatment within 20 years of the diagnosis. Although almost 20% of patients remain stable in their renal function, 30%–40% of patients develop ESKD from its onset. The important factors of renal outcome in patients with IgA nephropathy is the severity of histopathological findings, heavy proteinuria, long duration of proteinuria, haematuria and hypertension. [ABSTRACT FROM AUTHOR]