Renal Biopsy Research Articles

Measurement Matters: A Metrological Approach to Renal Preimplantation Biopsy Evaluation to Address Uncertainty in Organ Selection.

Preimplantation biopsy combines measurements of injury into a composite index to inform organ acceptance. The uncertainty in these measurements remains poorly characterized, raising concerns variability may contribute to inappropriate clinical decisions. We adopted a metrological approach to evaluate biopsy score reliability. Variability was assessed by performing repeat biopsies (n = 293) on discarded allografts (n = 16) using 3 methods (core, punch, and wedge). Uncertainty was quantified using a bootstrapping analysis. Observer effects were controlled by semi-blinded scoring, and the findings were validated by comparison with standard glass evaluation. The surgical method strongly determined the size (core biopsy area 9.04 mm2, wedge 37.9 mm2) and, therefore, yield (glomerular yield r = 0.94, arterial r = 0.62) of each biopsy. Core biopsies yielded inadequate slides most frequently. Repeat biopsy of the same kidney led to marked variation in biopsy scores. In 10 of 16 cases, scores were contradictory, crossing at least 1 decision boundary (ie, to transplant or to discard). Bootstrapping demonstrated significant uncertainty associated with single-slide assessment; however, scores were similar for paired kidneys from the same donor. Our investigation highlights the risks of relying on single-slide assessment to quantify organ injury. Biopsy evaluation is subject to uncertainty, meaning each slide is better conceptualized as providing an estimate of the kidney's condition rather than a definitive result. Pooling multiple assessments could improve the reliability of biopsy analysis, enhancing confidence. Where histological quantification is necessary, clinicians should seek to develop new protocols using more tissue and consider automated methods to assist pathologists in delivering analysis within clinical time frames.

Application of spatial-omics to the classification of kidney biopsy samples in transplantation.

Improvement of long-term outcomes through targeted treatment is a primary concern in kidney transplant medicine. Currently, the validation of a rejection diagnosis and subsequent treatment depends on the histological assessment of allograft biopsy samples, according to the Banff classification system. However, the lack of (early) disease-specific tissue markers hinders accurate diagnosis and thus timely intervention. This challenge mainly results from an incomplete understanding of the pathophysiological processes underlying late allograft failure. Integration of large-scale multimodal approaches for investigating allograft biopsy samples might offer new insights into this pathophysiology, which are necessary for the identification of novel therapeutic targets and the development of tailored immunotherapeutic interventions. Several omics technologies - including transcriptomic, proteomic, lipidomic and metabolomic tools (and multimodal data analysis strategies) - can be applied to allograft biopsy investigation. However, despite their successful application in research settings and their potential clinical value, several barriers limit the broad implementation of many of these tools into clinical practice. Among spatial-omics technologies, mass spectrometry imaging, which is under-represented in the transplant field, has the potential to enable multi-omics investigations that might expand the insights gained with current clinical analysis technologies.

DOT1L protects against podocyte injury in diabetic kidney disease through phospholipase C-like 1

BackgroundPodocyte injury causes proteinuria and accelerates glomerular sclerosis during diabetic kidney disease (DKD). Disruptor of telomeric silencing 1-like (DOT1L), an evolutionarily conserved histone methyltransferase, has been reported in preventing kidney fibrosis in chronic kidney disease models. However, whether DOT1L exerts beneficial effects in diabetes induced podocyte injury and the underlying molecular mechanisms need further exploration.MethodsThe expression of DOT1L was confirmed by Western blotting in MPC-5 cells and cortex of kidney from db/db mice, as well as immunofluorescence staining in human renal biopsy samples. The effect of DOT1L on podocyte injury was obtained using MPC-5 cells and db/db mice. The potential target genes regulated by DOT1L was measured by RNA-sequencing. Then, a series of molecular biological experiments was performed to investigate the regulation of PLCL1 by DOT1L in MCP-5 cells and db/db mice. Lipid accumulation was assessed by UPLC-MS/MS analysis and Oil Red O staining.ResultsDOT1L expression was significantly declined in high glucose (HG)-treated MPC-5 cells, podocyte regions of kidney tissues from db/db mice and human renal biopsy samples. Subsequent investigations revealed that upregulation of DOT1L ameliorated HG-induced cell apoptosis in MPC-5 cells as well as primary podocytes. Furthermore, podocyte-specific DOT1L overexpression inhibited diabetic podocyte injury in db/db mice. Mechanistically, we revealed that DOT1L upregulated phospholipase C-like 1 (PLCL1) expression by mediating H3K79me2 at its promoter and PLCL1 silencing suppressed the protective role of DOT1L on podocyte injury. Moreover, DOT1L improved diabetes induced abnormal fatty acid metabolism in podocytes and PLCL1 knockdown reversed its protective effects.ConclusionsTaken together, our results indicate that DOT1L protects podocyte injury via PLCL1-mediated fatty acid metabolism and provides new insights into the therapeutic target of DKD.

Clinicopathological characteristics and outcomes of patients with unexplained renal impairment: a single center study

Background: Chronic kidney disease (CKD) is a growing health problem. About 20% of CKD patients have undetermined causes. Data describing histopathological patterns of unexplained impaired kidney functions in Egypt are lacking. We aimed to identify the clinicopathological characteristics and short-term outcomes of adult cases with unexplained impaired kidney functions.Methods: We conducted a prospective study in Assiut University Hospital from August 2018 to May 2022. It included patients with unexplained elevated serum creatinine (serum creatinine > 115 µmol/L) who underwent renal biopsies. Descriptive statistics were used to summarize data on patient demographics, histopathological patterns, and outcomes after three months. Clinical trial registration number: NCT03586531.Results: Overall, 210 native renal biopsies were included in the analysis. Glomerular diseases were the most common pathological finding (n=88, 44.9 %), amyloidosis and FSGS were the most prevalent glomerular pathology (15.2%, 14.3%, respectively). Chronic kidney disease of unknown etiology (CKDu) was diagnosed in 8.1% of the cases; histology suggestive of genetic origin was found in 2.5%, and LECT amyloidosis was found in 3.8% of the cases. Poor outcomes were observed in 43.6% of the patients i.e., renal replacement therapy or death. Treatment strategies were changed based on the biopsy findings in 86 patients (40%).Conclusion: Amyloidosis and FSGS were the most common causes of unexplained renal impairment. CKDu is not uncommon in Egypt, and more preventive measures are needed. This study supports the irreplaceable role of renal biopsy in disease diagnosis, treatment decisions, and predicting prognosis even in advanced stages.

Shear-Wave Elastography Improves Diagnostic Accuracy in Chronic Kidney Disease Compared to Conventional Ultrasound.

Non-invasive tests are increasingly demanded for diagnosing and prognostication of chronic kidney disease (CKD). Shear-wave elastography (SWE), an emerging technique for measuring tissue stiffness, shows promise for distinguishing between individuals with different stages of renal fibrosis. This study aimed to compare the diagnostic accuracy of two-dimensional SWE (2D-SWE) and conventional ultrasound for detecting CKD, employing renal biopsy as the gold standard. From May 2020 to October 2023, this prospective study included 30 healthy volunteers and 169 patients with CKD who had undergone 2D-SWE and conventional ultrasound of both kidneys. Cortical and medullary stiffness, cortical pixel intensity, renal length, parenchymal and cortical thickness, interlobar artery peak systolic velocity, end-diastolic velocity (EDV), and resistive index were measured. The diagnostic accuracy of 2D-SWE and conventional ultrasound was compared using the receiver operating characteristic curve (ROC) and Delong test. For diagnosing CKD, the area under the ROC (AUC) of cortical stiffness (0.96 [95% CI, 0.93, 0.99]) was significantly higher than that of all conventional ultrasound parameters, including EDV (0.78 [95% CI, 0.71, 0.86]) and cortical thickness (0.74 [95% CI, 0.67, 0.80]). The sensitivity of cortical stiffness (91%) was significantly higher than that of EDV (68%) and cortical thickness (53%). No significant difference was found in the specificity of cortical stiffness (96%) compared to that of EDV (79%) and cortical thickness (100%). Two-dimensional SWE showed higher diagnostic accuracy than that of conventional ultrasound for detecting CKD.

Native kidney biopsy in pregnancy and postpartum: A single centre experience from India

Native kidney biopsy in pregnancy and postpartum: A single centre experience from India

C/EBPα-mediated ACSL4-dependent ferroptosis exacerbates tubular injury in diabetic kidney disease

Diabetic kidney disease (DKD) is a prevalent and debilitating complication of diabetes characterized by progressive renal function decline and a lack of effective treatment options. Here, we investigated the role of the transcription factor CCAAT/enhancer binding protein alpha (C/EBPα) in DKD pathogenesis. Analysis of renal biopsy samples revealed increased C/EBPα expression in patients with DKD. Using RNA sequencing and proteomics, we explored the mechanisms through which the C/EBPα contributes to DKD. Our findings demonstrated that C/EBPα exacerbated tubular injury by promoting acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. We identified that C/EBPα upregulated ACSL4 expression by binding to its transcription regulatory sequence (TRS), leading to elevated lipid peroxidation and ferroptosis. Furthermore, inhibition or genetic ablation of C/EBPα attenuated ferroptosis and mitigated tubular injury in DKD. These results highlighted the C/EBPα-ACSL4-ferroptosis pathway as a promising therapeutic target for DKD treatment.

Tubulointerstitial nephritis with IgM-positive plasma cells complicated by liver failure.

Tubulointerstitial nephritis (TIN) is characterized by inflammation of the renal interstitium with the infiltration of immune cells, mainly consisting of T cells. Recently, patients with TIN with the predominant infiltration of immunoglobulin M (IgM)-positive plasma cells were reported, coined IgMPC-TIN. Here we report the case of a 70-year-old woman diagnosed with Fanconi syndrome and renal tubular acidosis. Renal biopsy revealed IgMPC-TIN. Her renal dysfunction and clinical findings improved after corticosteroid therapy. However, the patient died of progressive liver failure and spontaneous bacterial peritonitis. In laboratory tests, viral hepatitis was excluded, and autoantibodies associated with liver diseases were negative. Generally, IgMPC-TIN is often complicated by primary biliary cholangitis (PBC), whereas her autopsy revealed the local infiltration of IgM-positive plasma cells, obliterative portal venopathy, and nodular regenerative hyperplasia in liver. This case is the first demonstration that IgMPC-TIN is also seen in liver disease with nodular regenerative hyperplasia, although IgMPC-TIN is more common in anti-M2 antibody-positive disease.

Male systemic lupus erythematosus, rapidly progressive glomerulonephritis, and iatrogenic acute bone marrow failure: a case report

Lupus nephritis (LN) is a significant complication of systemic lupus erythematosus (SLE), marked by kidney inflammation due to autoimmune activity, leading to proteinuria, hematuria, and potentially renal failure. Rapidly progressive glomerulonephritis (RPGN) is a rare, critical manifestation of LN characterized by a rapid decline in kidney function. This condition can lead to irreversible renal damage and is often fatal without prompt treatment. In this case, a 62-year-old man initially presented with fever, cough, and body aches, which were treated as an acute upper respiratory infection. Despite initial improvement, he developed persistent nausea, vomiting, and signs of renal dysfunction. Laboratory investigations revealed anemia, high erythrocyte sedimentation rate (ESR), electrolyte imbalances, and elevated creatinine. Imaging and endoscopy ruled out malignancy, and a differential diagnosis of multiple myeloma was excluded through plasma protein electrophoresis. Serological tests confirmed SLE, and subsequent renal biopsy revealed LN with RPGN features. Despite aggressive treatment with corticosteroids and cyclophosphamide, the patient’s condition rapidly deteriorated, leading to respiratory distress and intensive care unit (ICU) admission. He ultimately succumbed to his illness, underscoring the unpredictable and severe nature of RPGN in LN. This case highlights the importance of early diagnosis and intensive management to prevent rapid disease progression and improve patient outcomes.

Archetypal Analysis of Kidney Allograft Biopsies Using Next-generation Sequencing Technology.

In kidney transplantation, molecular diagnostics may be a valuable approach to improve the precision of the diagnosis. Using next-generation sequencing (NGS), we aimed to identify clinically relevant archetypes. We conducted an Illumina bulk RNA sequencing on 770 kidney biopsies (540 kidney recipients) collected between 2006 and 2021 from 11 European centers. Differentially expressed genes were determined for 11 Banff lesions. An ElasticNet model was used for feature selection, and 4 machine learning classifiers were trained to predict the probability of presence of the lesions. NGS-based classifiers were used in an unsupervised archetypal analysis to different archetypes. The association of the archetypes with allograft survival was assessed using the iBox risk prediction score. The ElasticNet feature selection reduced the number of the genes from a range of 859-10 830 to a range of 52-867 genes. NGS-based classifiers demonstrated robust performances (precision-recall area under the curves 0.708-0.980) in predicting the Banff lesions. Archetypal analysis revealed 8 distinct phenotypes, each characterized by distinct clinical, immunological, and histological features. Although the archetypes confirmed the well-defined Banff rejection phenotypes for T cell-mediated rejection and antibody-mediated rejection, equivocal histologic antibody-mediated rejection, and borderline diagnoses were reclassified into different archetypes based on their molecular signatures. The 8 NGS-based archetypes displayed distinct allograft survival profiles with incremental graft loss rates between archetypes, ranging from 90% to 56% rates 7 y after evaluation (P < 0.0001). Using molecular phenotyping, 8 archetypes were identified. These NGS-based archetypes might improve disease characterization, reclassify ambiguous Banff diagnoses, and enable patient-specific risk stratification.

Adult-Onset Female Focal Segmental Glomerulosclerosis with Nephrotic Syndrome Caused by a TBC1D8B Variant: a Case Report

Abstract We report the case of a 49-year-old Chinese woman with nephrotic syndrome, characterized by normal kidney function but poor response to hormonal and immunosuppressive therapy, indicative of steroid-resistant nephrotic syndrome (SRNS). Through renal biopsy, the patient was diagnosed as FSGS (perihilar type), and subsequent whole exome sequencing (WES) identified a pathogenic frameshift variant concerning the TBC domain of the TBC1D8B gene. This patient represents the first late-onset Chinese female who was found to carry a novel, pathogenic variant in the gene TBC1D8B.

Attenuated kidney oxidative metabolism in young adults with type 1 diabetes.

In type 1 diabetes (T1D), impaired insulin sensitivity may contribute to the development of diabetic kidney disease (DKD) through alterations in kidney oxidative metabolism. Young adults with T1D (n = 30) and healthy controls (HC, n = 20) underwent hyperinsulinemic-euglycemic clamp studies, MRI, 11C-acetate PET, kidney biopsies, single-cell RNA sequencing, and spatial metabolomics to assess this relationship. Participants with T1D had significantly higher glomerular basement membrane thickness compared to HC. T1D participants exhibited lower insulin sensitivity and cortical oxidative metabolism, correlating with higher insulin sensitivity. Proximal tubular transcripts of TCA cycle and oxidative phosphorylation enzymes were lower in T1D. Spatial metabolomics showed reductions in tubular TCA cycle intermediates, indicating mitochondrial dysfunction. The Slingshot algorithm identified a lineage of proximal tubular cells progressing from stable to adaptive/maladaptive subtypes, using pseudotime trajectory analysis, which computationally orders cells along a continuum of states. This analysis revealed distinct distribution patterns between T1D and HC, with attenuated oxidative metabolism in T1D attributed to a greater proportion of adaptive/maladaptive subtypes with low expression of TCA cycle and oxidative phosphorylation transcripts. Pseudotime progression associated with higher HbA1c, BMI, GBM, and lower insulin sensitivity and cortical oxidative metabolism. These early structural and metabolic changes in T1D kidneys may precede clinical DKD. gov NCT04074668.

New-onset complement-mediated thrombotic microangiopathy during the COVID-19 pandemic.

The coronavirus disease-19 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus is alleged to enable a proinflammatory state, that leads to the activation of the coagulation and the complement cascade. In this study, we aimed to establish the impact of the COVID-19 pandemic on patients with new onset of cTMA/aHUS in the Vienna TMA cohort and whether COVID-19 or SARS-CoV-2 vaccinations would pose a greater risk of initial manifestation of cTMA/aHUS. We used the Vienna TMA cohort database to examine the prevalence of COVID-19 related and of SARS-CoV-2 vaccination-related aHUS/cTMA during the first 3 years of the COVID-19 pandemic in a large single-center cohort. Between March 2020 and May 2023, a total of 7 patients experienced their first aHUS/cTMA episode. No patient experienced a TMA relapse or more than one episode during the follow-up period. Three TMA episodes were attributable to either COVID-19 (n=1; 33%) or SARS-CoV-2 vaccination (n=2; 66%), respectively. All three patients had systemic signs of TMA and TMA was confirmed by kidney biopsy in all cases. Among the seven patients we recorded five infections that triggered one TMA episode (20%) and 19 vaccinations triggered two TMA episodes (10%; p=0.52, odds ratio 0.47; 95% CI 0.04-8.39). We speculate, that both SARS-CoV-2 vaccinations and COVID-19 episodes can represent a triggering factor for aHUS/cTMA episodes in (genetically) vulnerable individuals. However, COVID-19 might have a stronger association and might be a stronger trigger than the SARS-CoV-2 vaccines. The incidence of new aHUS cases did not differ from the pre-pandemic era in a large tertiary care centre cohort.

Circulating proteins linked to apoptosis processes and fast development of end-stage kidney disease in diabetes.

Many circulating proteins are associated with risk of ESKD, but their source and the biological pathways/disease processes they represent are unclear. Using OLINK proteomics platform, concentrations of 455 proteins were measured in plasma specimens obtained at baseline from 399 individuals with diabetes. Elevated concentrations of 46 circulating proteins were associated (P < 1 × 10-5) with development of ESKD (n = 143) during 7-15 years of follow-up. Twenty of these proteins enriched apoptosis/TNF receptor signaling pathways. A subset of 20 proteins (5-7 proteins), summarized as an apoptosis score, together with clinical variables accurately predicted risk of ESKD. Expression of genes encoding the 46 proteins in peripheral WBCs showed no difference between cells from individuals who did or did not develop ESKD. In contrast, plasma concentration of many of the 46 proteins differed by this outcome. In single-nucleus RNA-Seq analysis of kidney biopsies, the majority of genes encoding for the 20 apoptosis/TNF receptor proteins were overexpressed in injured versus healthy proximal tubule cells. Expression of these 20 genes also correlated with the overall index of apoptosis in these cells. Elevated levels of circulating proteins flagging apoptotic processes/TNF receptor signaling pathways - and likely originating from kidney cells, including injured/apoptotic proximal tubular cells - preceded the development of ESKD.

The clinical course of SARS-CoV-2 infection in patients with glomerular diseases and evaluation of the subsequent risk of relapse

IntroductionThis study aimed to describe the clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with glomerular diseases (GDs) and its impact on the probability of relapse.MethodsPatients with biopsy-proven GD and positive PCR test for SARS-CoV-2 from glomerular clinics across Greece were studied retrospectively. Those who received the GD diagnosis after the SARS-CoV-2 vaccination or coronavirus disease 2019 (COVID-19) or ended in ESKD prior to infection were excluded. Demographics, histopathological diagnoses, past medical history, immunosuppression, and GD activity status were recorded.ResultsA total of 219 patients with GDs and documented SARS-CoV-2 infection were included. The mean time from the diagnostic kidney biopsy to SARS-CoV-2 infection was 67.6 ( ± 59.3) months. Among the participants, 82.5% had been vaccinated against SARS-CoV-2 with three doses (range: 2.5–3) without subsequent GD reactivation in 96.2% of them. Twenty-two patients (10%) were hospitalized for COVID-19 and one (0.5%) required mechanical ventilation. Four (1.8%) died due to COVID-19 and one (0.5%) had long COVID-19 symptoms. Among patients in remission prior to SARS-CoV-2 infection, 22 (11.2%) experienced a GD relapse within 2.2 (range: 1.5–3.7) months from the diagnostic test. The relapse-free survival after COVID-19 was significantly shorter for patients with minimal change disease, pauci-immune glomerulonephritis, and focal segmental glomerulosclerosis. No difference was observed in the relapse-free survival post-COVID-19 based on the history of SARS-CoV-2 vaccination.ConclusionsSARS-CoV-2 infection appears to have a symptomatic but uncomplicated sequence in vaccinated patients with GDs, with a significant impact on the clinical course of GD, associated with an increased probability of relapse in certain histopathological types.

Renal involvement in solid cancers: epidemiological, clinical and histological characteristics study of 154 onconephrology patients.

Onconephrology is a growing discipline that aims to improve the management of patients with cancer and kidney disease. If kidney histology is an essential key, the anatomopathological data remain weak although essential to this complex management. Patients with active cancer who had a kidney biopsy (KB) between 2014 and 2020 were included, and their clinicobiological and histological data were analyzed retrospectively. Our cohort consisted of 154 patients (83 women) with a mean age of 58 years. One hundred twelve patients presented with proteinuria, 95 with acute kidney injury, and 59 with arterial hypertension. Histologically, interstitial fibrosis was found in 74% of KBs, tubular atrophy in 55.1%, arteriolar hyalinosis in 58.4%, and fibrous endarteritis in 54.4%. Regarding the main acute lesions, thrombotic microangiopathy (TMA) was found in 29.9% of biopsies, acute tubular necrosis (ATN) in 51.3%, and acute interstitial nephritis in 24.8%. The etiological diagnosis most often made was the nephrotoxicity of anticancer drugs (87 patients), followed by a pre-renal (15 patients) and kidney disease unrelated to cancer (13 patients). Sixty-seven patients presented with at least 2 associated diagnoses reflecting the complexity of kidney damage in cancer. Different clusters were found, highlighting that immunotherapy and anti-VEGF were the most commonly involved drugs. During onconephrology practice, kidney toxicity of treatments is the most common etiology. Several mechanisms can be involved, underscoring the importance of kidney biopsy and the complexity of its management. Chronic histological lesions were very common.

Slowly progressive autosomal dominant Alport Syndrome due to COL4A3 splicing variant.

Alport syndrome is a rare genetic kidney disease caused by variants in the COL4A3/A4/A5 genes. It's characterised by progressive kidney failure, though therapies targeting Renin-Angiotensin System can delay its progression. Additionally, extrarenal manifestations may sometimes coexist. Recent advances in genetic analysis and the necessity to better clarify genotype-phenotype correlations in affected patients raises the importance of detecting even cryptic splicing variants, lying in both canonical and non-canonical splice sites variants such as last exonic nucleotide variants. These variants, often, do not cause an amino acid change but alter the snRNP proteins binding. We studied a big Italian family with Alport syndrome showing a clear dominant pattern of transmission with younger family members having only haematuria and older individuals presenting with End-Stage Kidney Failure (ESKF). Kidney biopsy showed the typical disease hallmarks. We deeply mined the data for SNV and CNV through exome sequencing on DNA from both peripheral blood samples and patients' podocytes-lineage cells. We identified an already reported synonymous variant, c.765G>A (p.(Thr255Thr)), in the last exonic nucleotide of exon 13 of the COL4A3 gene. Employing the patient's podocytes we demonstrated that this variant results in exon skipping leading to an in-frame deletion of 28 amino acids without leaky effect. According to the pattern of transmission, to the kidney biopsy and to the exome data analysis we provided further evidence that autosomal dominant Alport syndrome is a well-defined clinical entity. We also confirmed the pathogenicity of the synonymous COL4A3 variant for the first time demonstrating its role in a dominant pattern of transmission.

The Usefulness of Lordosis Load Test and Urinary Biochemistry in the Diagnosis of Orthostatic Proteinuria.

Introduction Renal disease is commonly suspected in patients with proteinuria. Renal biopsy might be considered based on the patient's clinical history and the results of diagnostic tests. However, as orthostatic proteinuria is benign and requires no treatment, it is important to obtain a diagnosis without renal biopsy whenever possible. Therefore, up to now, for the diagnosis of orthostatic proteinuria, in addition to resting urinalysis evaluation (disappearance of proteinuria), we have performed the lordosis load test and urine biochemistry of the samples showing peak proteinuria in a lordosis load test. Method We retrospectively enrolled all patients who visited the pediatric department and underwent the lordosis load test at Kanazawa Medical Center between 2011 and 2020. In the present study, samples with the highest concentrations of protein after the lordosis load test were subjected to general urinary biochemistry and urinary sediment analysis. Patients were followed up with the lordosis load test for several years. Results Enrolled in the study were 68 patients with OP. The mean age at the time of diagnosis was 11.5 years (range, six to 16 years). General urinary tests, urinary sediment, and urinary biochemistry including N-acetyl-beta-D-glucosaminidase (NAG), alpha1-microglobulin(α1MG), and beta 2-microglobulin (β2MG) were normal in all patients with orthostatic proteinuria except one case who was a premature baby. Conclusion If proteinuria disappears after two hours of rest, and urinary biochemistry of the samples showing peak proteinuria in the lordosis load test is normal, orthostatic proteinuria can be diagnosed more accurately.

Sex differences in mortality among patients with lupus nephritis

ObjectiveTo evaluate the prognostic importance of sex in lupus nephritis (LN).MethodsA retrospective cohort of 1048 biopsy-confirmed LN patients, diagnosed between January 1, 1996, and December 31, 2018, was analyzed. Demographics, clinical characteristics, laboratory findings, and renal pathology were assessed. The primary outcome was mortality, and the secondary outcomes included doubling of serum creatinine and end-stage renal disease (ESRD). Sex-associated risks were evaluated using Cox regression models.ResultsAmong the1048 patients, 178 (17%) were male and 870 (83%) were female. Male patients exhibited more aggressive features: higher blood pressure, earlier disease onset, and elevated levels of serum creatinine (Scr), uric acid, blood urea nitrogen. Intriguingly, male patients also displayed more severe histopathological alterations, such as more total crescents, cellular crescents formations, higher level of glomerular leukocyte infiltration and Activity Index (AI), even when overall renal pathology was comparable between sexes. During a median follow-up of 112 months, mortality was registered in 141 patients (15.3%). Mortality rates were conspicuously higher in males (24.2% males vs. 13.4% females, p = 0.0029). Secondary outcomes did not show significant sex differences. Cox regression analysis highlighted male, age of renal biopsy, eGFR, and Chronicity Index (CI) as independent risk factors for survival in LN patients. Notably, infections emerged as the leading cause of mortality among LN patients, with a significant higher rate in male patients.ConclusionIn our cohort with LN, there was a higher rate of all-cause mortality and proportion of infection-related death in male. Recognizing and further exploring these sex disparities is crucial for optimized LN patients care.Graphical

Establishing a Risk Model for Diabetic Nephropathy and Addressing the Therapeutic Effect of Combined Epalrestat- Dapagliflozin Regimen.

To explore the construction of a diagnostic prediction model of diabetic nephropathy (DN) in type 2 diabetic patients for prognostic risk prediction and observe the therapeutic effect of Epalrestat combined with Dapagliflozin on DN. The study consisted of two phases, phase I: A retrospective analysis was conducted on the case information and clinical treatment related data of a total of 460 patients who underwent kidney biopsy from June 2018 to June 2021. They were randomly divided into validation queue and training queue. The predictive factors of the diagnostic prediction model were obtained through multivariate logistic regression. An interventional study of 94 patients with DN admitted between January 2022 and August 2023 was conducted, and they were randomized into a control group (n = 47) receiving Dapagliflozin and a research group (n = 47) receiving Epalrestat combined with Dapagliflozin. The glucose metabolism, renal function, and treatment safety of the two groups before and after treatment were compared. In addition, the adverse reactions during the treatment of the two groups were counted. In the phase I of the study, the DN risk model established showed a good performance in the diagnosis and risk assessment of patients with DN and could provide certain reference opinions for future clinical practice. In the phase II of the study, the research group showed better glucose metabolism and renal function than the control group after treatment (P < .05), but no statistical difference was identified between groups in the incidence of adverse reactions (P > .05). Conclusion. Epalrestat combined with Dapagliflozin is significantly effective in the treatment of DN, which can effectively improve glucose metabolism and renal function in DN patients.