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INTRODUCTION: Antibrush border antibody disease (ABBA) is an autoimmune tubulointerstitial kidney disease that primarily affects older individuals and results in progressive kidney failure. It is rare with only 20 reported cases. Here, we describe a case series to further define the clinicopathologic spectrum and natural history, and to inform management. METHODS: We identified 67 patients with ABBA who underwent kidney biopsy, including 65 native and 2 transplants. Demographics, clinical findings, and laboratory data were obtained. Histopathologic data included light microscopy, immunofluorescence, electron microscopy and immunostaining for LRP2, CUBN, and AMN. Follow-up data, including treatment(s), laboratory values, and outcomes, were available from 51 patients. RESULTS: Patients with ABBA were predominantly male with a median age of 72 years. Median serum creatinine was 2.7 mg/dl, proteinuria was 2.8 g/day, and hematuria was present in two-thirds of the patients. Tubular injury with LRP2-positive tubular basement membrane (TBM) deposits were seen in 94.2% of patients. Thirty-eight patients (56.7%) had a second kidney disease, commonly glomerular diseases with high-grade proteinuria. These diseases included podocytopathies, membranous nephropathy (MN), IgA nephropathy, diabetic glomerulopathy, lupus nephritis (LN), crescentic glomerulonephritis (GN), tubulointerstitial nephritis, and involvement by lymphoma. The majority of patients were treated with immunosuppression. Of those patients with follow-up, 29.4% achieved remission, 70.6% had no response, and 52.8% required dialysis or were deceased. Untreated patients were at the highest risk. CONCLUSION: ABBA is a rare autoimmune kidney disease that often occurs with other kidney diseases. Although the overall prognosis of ABBA is poor, there is potential benefit from immunosuppression.

Background Renal flare in lupus nephritis (LN) is a crucial contributing factor to poor kidney outcomes. This study aimed at evaluating the predictive value of residual active histologic lesions on renal flare in proliferative LN patients with clinical remission. Methods We retrospectively enrolled LN patients with class III/IV ± V (biopsy 1) who had undergone a protocol repeat biopsy (biopsy 2) at 7.3 (IQR: 6.5, 8.4) months after induction therapy with clinical remission and experienced renal flare within 3 years or had been followed up for at least 3 years without renal flare after biopsy 2 with maintenance therapy from two kidney units in China. Results A total of 114 eligible patients were included, 28 (24.6%) of whom developed a renal flare. Activity index (AI) at biopsy 2 was significantly associated with LN flare (P < .0001). If AI > 1, the OR for LN flare was 23.1 (95%CI, 5.1–103.8, P < .001). For patients with partial clinical remission compared with those with complete clinical remission, the OR for LN flare was 3.0 (95%CI: 1.1–8.3, P = .029). Multivariate analysis showed that anti-dsDNA positivity, presence of cellular/fibrocellular crescent, and endocapillary hypercellularity at biopsy 2 were independent risk factors for LN flare. When residual active histologic lesions were added to clinical variables, the area under the curve of the prediction model for LN flare significantly increased and the misclassification rate significantly decreased. Conclusions Renal flare in LN patients with clinical remission is strongly associated with the residual active histologic lesions. [ABSTRACT FROM AUTHOR]

Background: Despite extensive research on proteinuria's impact on chronic kidney disease progression, there is no direct comparison of outcomes in biopsy-diagnosed glomerular disease (GD) patients with nephrotic syndrome (NS) or nephrotic range proteinuria (NRP). Our study addresses this gap, comparing long-term outcomes between NS and NRP. Methods: We conducted a retrospective study on 240 kidney biopsy-proven GD patients, tracked from 2010 to 2015 until end-stage kidney disease (ESKD), death, or the study end in January 2022. Results: The median follow-up was 8.8 years. Diagnoses were predominantly nonproliferative (53%), proliferative (25%) nephropathies, diabetic nephropathy (12%), and paraprotein diseases (10%). NS was observed in 141 (59%) patients, presenting more frequently with arterial hypertension, higher eGFR, increased proteinuria, and dyslipidemia than NRP patients. NRP patients often had proliferative GD and diabetic nephropathy; their renal chronicity score was higher. The ESKD endpoint occurred in 35% NS and 39% NRP patients (p 0.4). The cohort's mean kidney survival time was 8.2 years. In a multivariate analysis, NS, lower eGFR, a higher renal chronicity score, and diabetic nephropathy were associated with ESKD. A total of 64 patients (27%) died, 73% post-kidney replacement therapy initiation, and mostly from cardiovascular disease (63%). Mortality between proteinuria forms showed no difference. The multivariate analysis found lower eGFR, a higher Charlson comorbidity score, and diabetic nephropathy associated with mortality. Conclusions: Our study found no difference in all-cause mortality between NS and NRP in glomerular diseases. However, an adjusted analysis revealed poorer kidney survival for NS patients, emphasizing the need for personalized management to improve renal prognoses. [ABSTRACT FROM AUTHOR]

Background and Aim: Glomerular diseases affecting pediatric patients differ from conditions encountered in adults. Additionally, the pattern of glomerular disease varies in different regions of the world. In the Mediterranean region, data on glomerular diseases in children patients remain sparse. Therefore, we conducted a study to assess glomerulonephritis disease patterns at our institute and assess for recent incidence trends. Methods: A retrospective study conducted at a university affiliated tertiary hospital located in the capital city of Amman. We included native kidney biopsy reports of patients who fulfilled our age criterion of < 15 years old. Results: Our study showed a total of 178 kidney biopsies, of which 71 patient fulfilled our inclusion criteria. The average age of studied patients was 7.6 ± 4.1 years. Our study had more males compared to females, 56% and 44%, respectively. In nephritic syndrome, IgA nephropathy was the most common cause (13%), which was followed by Post-Infectious glomerulonephritis (8%). In children with nephrotic syndrome, MCD was exceedingly more common in male children when compared to females, 14 versus 8 patients, respectively. While FSGS was more common among females compared to males, 5 versus 2 patients, respectively. [ABSTRACT FROM AUTHOR]

Objective: Cast nephropathy (CN) is the leading cause of acute kidney injury (AKI) in multiple myeloma (MM). Since it is sparsely documented why some patients with CN do achieve a renal response while others do not, we describe a single-center cohort of patients with multiple myeloma and biopsy-confirmed CN to evaluate potential markers of renal response. Methods: The data was collected as a retrospective, single-center analysis of CN-patients treated at the Medical University Vienna between 01/01/2004 and 01/01/2022. Baseline parameters and clinical outcome was compared between renal responders and non-responders. Results: Among 28 patients with CN, n = 23 were assessed for renal response (14 responders; 9 non-responders). Renal responders were younger (median age: 61 years; 77 years, p = 0.039), showed higher overall survival (153months; 58months, p = 0.044) and achieved hematologic response (≥PR) to first-line therapy (p = 0.029), and complete hematologic response (CR) at any time (p = 0.025) significantly more often. Further, we could show that rapid initiation of anti-myeloma therapy after initial presentation correlated significantly with renal response (median 9 days; 27 days, p = 0.016). Analyses of kidney biopsy specimens revealed that patients with a high IF/TA score showed end stage renal disease (dialysis ≥ 3 months) significantly more often (p = <0.001). Discussion: In summary, our data suggests, that a rapid start with systemic hematologic treatment in patients with MM and CN is crucial and achieving an early hematologic response is important for renal recovery. Moreover, achieving a deep hematologic response and subsequent renal recovery improves clinical outcome as reflected by an overall survival benefit. [ABSTRACT FROM AUTHOR]

Background: The course of kidney function and outcomes of severe malaria infection in pregnant women is poorly understood. The indications for renal replacement therapy in pregnant patients with AKI are similar to the general population. This is the case of a pregnant patient with severe Plasmodium falciparum infection that caused cerebral malaria, acute kidney injury (AKI) who required renal replacement therapy and kidney biopsy during her hospitalization. Case presentation: A 29-year-old pregnant woman from Equatorial Guinea was admitted to the hospital with haemolytic anaemia, hyperbilirubinaemia and thrombocytopenia. During hospitalization, a thick blood smear was performed where parasitaemia by P. falciparum were observed and confirmed by real-time PCR assay. The patient developed cerebral malaria secondary to an ischaemic-type cerebral vascular event, hypotension and severe. After confirming diagnosis of P. falciparum infection, artesunate, artemether/lumefantrine and primaquine were started. Kidney biopsy revealed an active tubulointerstitial nephritis with acute tubular lesion and pigment tubulopathy with negative immunofluorescence. After CVVHDF, the patient received intermittent haemodialysis until the recovery of kidney function. After discharge, follow-up was carried until the successful resolution of the pregnancy by cesarean delivery and not shown deterioration in kidney function or proteinuria. Conclusion: In this case, intensive dialysis was started and dialysis intensity progressively reduced when kidney function improved. Due to the evolution of kidney function, a kidney biopsy was performed which showed tubulointerstitial nephritis as a manifestation of the infection. While the kidney biopsy was of interest for discriminating between tubular and glomerular involvement, the availability of placental biomarkers (sflt1-PlGF) would have been of help for ruling out preeclampsia and placental damage. The multidisciplinary approach to AKI during pregnancy should be the rule, with diligent care of maternal–fetal well-being during pregnancy and monitoring of kidney function after delivery. [ABSTRACT FROM AUTHOR]

Kidney allograft rejection is one of the main limitations to long-term kidney transplant survival. The diagnostic gold standard for detecting rejection is a kidney biopsy, an invasive procedure that can often give imprecise results due to complex diagnostic criteria and high interobserver variability. In recent years, several additional diagnostic approaches to rejection have been investigated, some of them with the aid of machine learning (ML). In this review, we addressed studies that investigated the detection of kidney allograft rejection over the last decade using various ML algorithms. Various ML techniques were used in three main categories: (a) histopathologic assessment of kidney tissue with the aim to improve the diagnostic accuracy of a kidney biopsy, (b) assessment of gene expression in rejected kidney tissue or peripheral blood and the development of diagnostic classifiers based on these data, (c) radiologic assessment of kidney tissue using diffusion-weighted magnetic resonance imaging and the construction of a computer-aided diagnostic system. In histopathology, ML algorithms could serve as a support to the pathologist to avoid misclassifications and overcome interobserver variability. Diagnostic platforms based on biopsy-based transcripts serve as a supplement to a kidney biopsy, especially in cases where histopathologic diagnosis is inconclusive. ML models based on radiologic evaluation or gene signature in peripheral blood may be useful in cases where kidney biopsy is contraindicated in addition to other non-invasive biomarkers. The implementation of ML-based diagnostic methods is usually slow and undertaken with caution considering ethical and legal issues. In summary, the approach to the diagnosis of rejection should be individualized and based on all available diagnostic tools (including ML-based), leaving the responsibility for over- and under-treatment in the hands of the clinician. [ABSTRACT FROM AUTHOR]

This epidemiological study aimed to identify the primary categories of kidney pathology diagnosis and their prevalence among patients admitted to Shahid Labbafinezhad Teaching Hospital. We included 1006 kidney biopsy findings from 2019 to 2022. The majority of kidney patients (78%) were between the ages of 20 and 60 years. Nephrotic syndrome made up 62% of the patient population. The findings revealed that primary glomerulonephritis, secondary glomerulonephritis, tubular/interstitial nephritis, end-stage kidney disease, and unclassified cases accounted for 63%, 17%, 12%, 6%, and 2% of kidney disease cases, respectively. The inclusion of a large number of patients from various regions across the country, combined with the expertise of the laboratory staff, underscores the reliability and significance of the results obtained in this study. [ABSTRACT FROM AUTHOR]

Kidney biopsy plays a crucial role in the diagnosis and management of several glomerular diseases. While it is generally considered a routine and safe procedure in children, it should be conducted with the primary objective of addressing the following question: do the prognosis and treatments vary based on the findings of kidney biopsy? In children presenting with idiopathic nephrotic syndrome (INS), guidelines suggest to consider kidney biopsy for individuals older than 12 years, primarily due to the possible increased incidence of different glomerulonephritis compared to younger patients, who predominantly manifest with minimal change disease. However, these guidelines also advocate for uniform therapeutic strategies, typically steroids, irrespective of the age or histological findings. Whether the age of more than 12 years may be a recommendation for performing kidney biopsy at presentation of INS is debatable. Instead, kidney biopsy could be reserved for steroid-resistant cases. On the other hand, when kidney biopsy is performed in INS, particularly in focal segmental glomerulosclerosis, histology may reveal additional lesions, that are strongly associated with a poorer response to treatment and worse clinical outcomes. Therefore, current guidelines on treatments of nephrotic syndrome may appear overly restrictive, despite the relevant findings provided by kidney biopsy. Therefore, in the present manuscript, which is part of a pro–con debate on the management of nephrotic syndrome in adolescents, we emphasize the potential role of performing a kidney biopsy before initiating corticosteroid treatment. [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]

Unilateral kidney hypoplasia is a congenital condition characterized by the underdevelopment of one kidney. Although often asymptomatic, it can cause severe renal complications in patients combined with contralateral renal injury, leading to acute renal failure. This case report describes a patient with unilateral kidney hypoplasia who underwent a kidney biopsy on the contralateral normal‐sized kidney and subsequently developed oliguric acute kidney injury. This report discusses the challenges encountered while diagnosing and managing this rare case, highlighting the importance of awareness and recognition to perform timely intervention and optimize the patient's outcome. [ABSTRACT FROM AUTHOR]

The field of genetic testing has experienced significant growth in medical practice since 1956, when the first genetic analysis was introduced. Persistent proteinuria has long been considered a strong risk factor for the progression of chronic renal failure, though, paradoxically, it can also be a benign process, as seen in individuals with mutations in the cubilin (CUBN) protein, specifically the C-terminal. CUBN is a peripheral protein that plays a crucial role in the receptor-mediated endocytotic reabsorption of albumin in the proximal tubule. In the past, there have been misinterpretations of CUBN variants with isolated proteinuria as glomerular injury, leading to unnecessary kidney biopsies and ineffective treatments. This paper discusses two siblings with a homozygous variant of (p.Tyr3018Ser) in the C-terminal of the CUBN protein, inherited from both heterozygous carrier parents. This case presents an opportunity to question our typical approach to proteinuria in an effort to avoid unnecessary kidney biopsies and the subsequent side effects of treatments, particularly for those with proteinuria. [ABSTRACT FROM AUTHOR]

Gastric cancer ranks fourth among the most commonly diagnosed cancers, with over a million new cases diagnosed worldwide each year. Acute and chronic kidney damage are common in patients with malignant diseases and are associated with increased risk of complications and mortality. Rarely, acute renal insufficiency may result from bilateral infiltration of renal parenchyma by tumor cells from another organ. We present a case of a patient with clinical suspected gastric cancer and metastases to the kidneys leading to acute renal failure requiring hemodialysis. Despite gastric biopsies, no tumor cells were found, while histopathological examination of enlarged intra-abdominal lymph node biopsy material confirmed adenocarcinoma of signet ring cell originating from the digestive system. Stomach cancer was identified as the most likely primary site after the kidney biopsy was performed. To the best of our knowledge, no case of gastric cancer leading to kidney metastases and acute renal failure requiring renal replacement therapy was yet described. Multidisciplinary collaboration among oncologists, urologists, radiologists, pathologists, and nephrologists is essential for the optimal treatment outcome of these patients, who generally have a poor prognosis. [ABSTRACT FROM AUTHOR]

Research regulations around the world do not impose any limits on the risks to which consenting adults may be exposed. Nonetheless, most review committees regard some risks as too high, even for consenting adults. To justify this practice, commentators have appealed to a range of considerations which are external to informed consent and the risks themselves. Most prominently, some argue that exposing consenting adults to very high risks has the potential to undermine public trust in research. This justification assumes that it is not the magnitude of the risks themselves which raises concern, but the way in which the public might respond to them. This justification thus depends on the possibility that the public will find out about the risks and respond to them in the specified way. Like the other proposed external justifications, it thereby fails to offer a reason to think that exposing consenting adults to very high risks is problematic in itself. In the present paper, we describe and endorse a different justification. Rather than appealing to external factors, we argue that limits on risks for consenting adults trace to internal limits on informed consent, to limits on the things consent can and cannot make ethically permissible. In doing so, we aim to provide a firmer conceptual basis for the view that some research risks are unacceptably high, no matter how the research is conducted. [ABSTRACT FROM AUTHOR]

Background: C4d deposits are present in a substantial proportion of patients with IgA nephropathy (IgAN), indicating the activation of the lectin pathway (LP) of the complement system. It seems that patients with activated LP have worse renal prognosis. The aim of this study was to investigate the prevalence and prognostic significance of C4d in our cohort of patients with primary IgA nephropathy (pIgAN). Methods: Patients with pIgAN were recruited from a hospital register of kidney biopsies of the Department of Nephrology and Dialysis, Dubrava University Hospital, Zagreb. Additional immunohistochemistry staining for C4d was performed on paraffin-embedded kidney tissue, and patients were stratified into being C4d positive or C4d negative. The clinical and histologic features of patients were analyzed and compared regarding C4d positivity. The primary outcome was defined as kidney failure (KF), and predictor variables of KF and renal survival were analyzed. Results: Of a total of 95 patients with pIgAN included in the study, C4d was present in 43 (45.3%). C4d-positive patients had a higher value of systolic (p = 0.039) and diastolic (p = 0.006) blood pressure at diagnosis as well as higher 24 h proteinuria (p = 0.018), serum urate (p = 0.033), and lower eGFR (p < 0.001). C4d-positive patients had worse renal survival (p < 0.001), higher rates of disease progression to KF (p < 0.001), and higher proteinuria (p < 0.001) and lower eGFR (p < 0.001) at the last follow-up. Glomerular C4d was an independent predictor of disease progression to KF (HR = 5.87 [0.95 CI 1.06–32.44], p = 0.032). Conclusions: C4d is an independent predictor of disease progression in patients with pIgAN. C4d may be used as an additional marker of progressive disease course in IgAN. The therapeutic implications of C4d status in IgAN, particularly in terms of complement inhibitors application, are not yet known. [ABSTRACT FROM AUTHOR]

Primary glomerular diseases are rare entities. This has hampered efforts to better understand the underlying pathobiology and to develop novel safe and effective therapies. NEPTUNE is a rare disease network that is focused on patients of all ages with minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy. It is a longitudinal cohort study that collects detailed demographic, clinical, histopathologic, genomic, transcriptomic, and metabolomic data. The goal is to develop a molecular classification for these disorders that supersedes the traditional pathological features-based schema. Pediatric patients are important contributors to this ongoing project. In this review, we provide a snapshot of the children and adolescents enrolled in NEPTUNE and summarize some key observations that have been made based on the data accumulated during the study. In addition, we describe the development of NEPTUNE Match, a program that aims to leverage the multi-scalar information gathered for each individual patient to provide guidance about potential clinical trial participation based on the molecular characterization and non-invasive biomarker profile. This represents the first organized effort to apply principles of precision medicine to the treatment of patients with primary glomerular disease. NEPTUNE has proven to be an invaluable asset in the study of glomerular diseases in patients of all ages including children and adolescents. [ABSTRACT FROM AUTHOR]

Purpose: Diabetes mellitus (DM) is the leading cause of chronic kidney disease (CKD) in the population. In patients with diabetes mellitus, the incidence of non-diabetic nephropathy (NDNP) has been estimated to range from 3% to 69.5%. Personal judgment is frequently employed while deciding whether or not to do a kidney biopsy (KB) on diabetic patients. NDNP alters the prognosis and course of treatment for people with DM. In our study, we examined the incidence of NDNP concurrent with the progression of diabetes mellitus, as well as the laboratory and clinical indicators that could be utilized to forecast it. Methods: A retrospective analysis of 76 diabetic patients who underwent KB was conducted. Based on the pathological diagnoses of these patients, they were categorized as DNP (diabetic nephropathy) or NDNP. The definition of HbA1c variability was determined by calculating the mean HbA1c and the average value of the HbA1c measurements, as well as the standard deviation (SD) for each participant. Results: NDNP was detected in 50% of 76 patients. Among patients with NDNP, 36.8% had focal segmental glomerulosclerosis (FSGS), 23.6% had membranous glomerulonephritis, and 7.8% had IgA nephritis. The NDNP group exhibited significantly higher rates of female gender, absence of diabetic retinopathy, shorter time to diagnosis of diabetes mellitus, chronic kidney disease, and proteinuria, less intensive medication for diabetes mellitus, presence of hematuria and leukociduria, immunological serological marker positivity, and non-HbA1C variability. Risk factors for predicting non-diabetic nephropathy, as determined by multivariate analysis, included female gender, the absence of diabetic retinopathy, non-HbA1c variability and a positive immunological serological test. Conclusion: In this study, a significant number of diabetic patients with chronic kidney disease were diagnosed with NDNP. Identifying these patients allows for treatment of the specific underlying disease. Factors such as the absence of DR, non-HbA1c variability, female gender, and immunological serological test positivity can predict NDNP and guide the clinician's decision on kidney biopsy. Further prospective studies are warranted to validate the efficacy of potential predictive factors like HbA1c variability. [ABSTRACT FROM AUTHOR]

Introduction: Patients with systemic lupus erythematosus are prone to develop cardiovascular disease (CVD), and have increased morbidity and mortality. Methods: We conducted a retrospective analysis on lupus nephritis patients to assess the occurrence and predictors of major adverse cardiovascular events (MACE). Data were collected from patients who underwent kidney biopsy between 2005 and 2020. Statistical analysis was performed to unveil correlations. Results: 91 patients were analyzed in this period, with a mean age of 37.3 ± 12.3 years and 86% being female. The mean follow-up time was 62 ± 48 months. 15.38% of the patients underwent at least one MACE. Two patients deceased of CVD. Increased age (35.81 ± 11.14 vs 45.5 ± 15.11 years, p=0.012) entailed a higher occurrence of MACEs. Neutrophil count (5.15 ± 2.83 vs 7.3 ± 2.99 Giga/L, p=0.001) was higher, whereas diastolic blood pressure (DBP) was lower (89.51 ± 10.96 vs 78.43 ± 6.9 mmHg, p<0.001) at the time of the biopsy in patients with MACE. Age, neutrophil count, and DBP proved to be independent predictors of MACEs. We propose a new model (CANDE – Cardiovascular risk based on Age, Neutrophil count, and Diastolic blood pressure Estimation score) calculated from these variables, which predicts the probability of MACE occurrence. Conclusion: This study underscores the importance of actively screening for cardiovascular risks in this vulnerable patient population. Age, neutrophil count, and diastolic blood pressure have been established as independent risk factors for MACE in lupus nephritis. The CANDE score derived from these parameters may serve as a prompt, cost-effective, and easily accessible estimation tool for assessing the likelihood of major adverse cardiovascular risk. These findings emphasize the necessity for comprehensive management strategies addressing both immune dysregulation and cardiovascular risk factors in systemic lupus erythematosus to mitigate adverse outcomes. [ABSTRACT FROM AUTHOR]

Background This study validates the application of Systematized Nomenclature of Medicine second edition (SNOMED II) codes used to describe medical kidney biopsies in Denmark in encoded form, aiming to support robust epidemiological research on the causes, treatments and prognosis of kidney diseases. Methods Kidney biopsy reports from 1 January 1998 to 31 December 2018 were randomly extracted from the Danish National Patobank, using SNOMED codes. A 5% sample was selected, and nephrologists assessed the corresponding medical records, assigning each case the applied clinical diagnoses. Sensitivity, specificity, positive predictive values (PPV), negative predictive values and Cohen's kappa coefficient for the retrieved SNOMED codes were calculated. Results A total of 613 kidney biopsies were included. The primary clinical disease groups were glomerular disease (n  = 368), tubulointerstitial disease (n  = 67), renal vascular disease (n  = 51), diabetic nephropathy (n  = 51) and various renal disorders (n  = 40). Several SNOMED codes were used to describe each clinical disease group and PPV for the combined SNOMED codes were high for glomerular disease (94%), diabetic nephropathy (85%) and systemic diseases affecting the kidney (96%). Conversely, tubulointerstitial disease (62%), renal vascular disease (60%) and other renal disorders (17%) showed lower PPV. Conclusions SNOMED codes have a high PPV for glomerular diseases, diabetic nephropathy and systemic diseases affecting the kidney, in which they could be applied for future epidemiological research. [ABSTRACT FROM AUTHOR]

This study investigates the potential of quantitative Contrast-Enhanced Ultrasound (CEUS) parameters to distinguish between graft dysfunction due to rejection and non-rejection in kidney transplant recipients. In this retrospective study, 50 kidney transplant patients who presented elevated serum creatinine or proteinuria were analyzed. They were categorized as rejection or non-rejection based on biopsy outcomes. These classifications were applied in both derivation (n = 33) and validation cohorts (n = 17). Prior to the biopsy, all patients underwent a CEUS. Quantitative parameters derived from the CEUS were further analyzed for their consistency and reliability. Additionally, the relationship between the Banff scores, a standard for diagnosing transplant rejections, and these CEUS parameters was explored. Significant differences between rejection and non-rejection groups were observed in the CEUS parameters of derivation cohorts. Specifically, Peak Intensity (PI), 1/2 Descending Time (DT/2), Area Under Curve (AUC), and Mean Transit Time (MTT) stood out. Sensitivity and specificity for these parameters were 76.5% and 87.5% for PI, 76.5% and 81.2% for DT/2, 76.5% and 87.5% for AUC, and 68.8% and 94.1% for MTT, respectively. DT/2 and MTT showed superior interobserver agreement compared to PI and AUC. When extrapolating the cutoff values from the derivation cohort to the validation group, DT/2 and AUC exhibited optimal diagnostic precision with positive and negative predictive values being 91.7% vs. 100% and 100% vs. 85.7%, respectively. Additionally, DT/2 effectively differentiated between mild and moderate to severe microvascular inflammation, pivotal in diagnosing antibody-mediated renal transplant rejection. DT/2 from CEUS parameters presents as a reliable tool to differentiate rejection from non-rejection causes in renal transplant dysfunction. Yet, large-scale, multi-center studies are essential for further validation. [ABSTRACT FROM AUTHOR]

Acute kidney injury secondary to methotrexate therapy for hematologic malignancies is relatively uncommon. Methotrexate crystals in these cases are rarely seen on kidney biopsy, and in particular, their appearance in tissue prepared for transmission electron microscopy has not been described. A male patient with recurrent primary central nervous system lymphoma received high-dose methotrexate and rituximab for treatment. On day 2 of cycle 3, one day after the infusion of high-dose methotrexate, the patient was found to have high levels of serum methotrexate. Shortly after, he developed acute kidney injury. A kidney biopsy was performed, which showed methotrexate crystals only on tissue submitted for electron microscopy. To our knowledge, this is the first report to characterize methotrexate crystals on toluidine blue-stained thick sections and their ultrastructure on transmission electron microscopy.

Background: Kidney biopsy is the gold-standard for diagnosing medical renal diseases, but the accuracy of the diagnosis greatly depends on the quality of the biopsy specimen, particularly the amount of renal cortex obtained. Inadequate biopsies, characterized by insufficient cortex or predominant medulla, can lead to inconclusive or incorrect diagnoses, and repeat biopsy. Unfortunately, there has been a concerning increase in the rate of inadequate kidney biopsies, and not all medical centers have access to trained professionals who can assess biopsy adequacy in real time. In response to this challenge, we aimed to develop a machine learning model capable of assessing the percentage cortex of each biopsy pass using smartphone images of the kidney biopsy tissue at the time of biopsy. Methods: 747 kidney biopsy cores and corresponding smartphone macro images were collected from five unused deceased donor kidneys. Each core was imaged, formalin-fixed, sectioned, and stained with Periodic acid–Schiff (PAS) to determine cortex percentage. The fresh unfixed core images were captured using the macro camera on an iPhone 13 Pro. Two experienced renal pathologists independently reviewed the PAS-stained sections to determine the cortex percentage. For the purpose of this study, the biopsies with less than 30% cortex were labeled as inadequate, while those with 30% or more cortex were classified as adequate. The dataset was divided into training (n=643), validation (n=30), and test (n=74) sets. Preprocessing steps involved converting High-Efficiency Image Container iPhone format images to JPEG, normalization, and renal tissue segmentation using a U-Net deep learning model. Subsequently, a classification deep learning model was trained on the renal tissue region of interest and corresponding class label. Results: The deep learning model achieved an accuracy of 85% on the training data. On the independent test dataset, the model exhibited an accuracy of 81%. For inadequate samples in the test dataset, the model showed a sensitivity of 71%, suggesting its capability to identify cases with inadequate cortical representation. The area under the receiver-operating curve (AUC-ROC) on the test dataset was 0.80. Conclusion: We successfully developed and tested a machine learning model for classifying smartphone images of kidney biopsies as either adequate or inadequate, based on the amount of cortex determined by expert renal pathologists. The model's promising results suggest its potential as a smartphone application to assist real-time assessment of kidney biopsy tissue, particularly in settings with limited access to trained personnel. Further refinements and validations are warranted to optimize the model's performance.

The management of immune-mediated nephropathies in the elderly presents unique challenges due to age-related physiological changes, comorbidities, and frailty. This review addresses the clinical workup, diagnostic evaluation, and treatment strategies for this rapidly growing patient population. We highlight the inadequacies of current classification systems and the lack of evidence-based guidelines tailored to individuals ≥75 years. The review discusses the specific considerations in diagnosing and treating common conditions such as minimal change disease, focal and segmental glomerulosclerosis, membranous nephropathy, ANCA-associated vasculitis, infection-related and post-infectious glomerulonephritis, and anti-GBM disease. Managing these diseases requires a nuanced approach due to age-related changes in the immune system and the presence of multiple comorbidities. Immunosuppressive therapy, including corticosteroids, rituximab, and cyclophosphamide, remains a cornerstone of treatment, but the choice and dosage of drugs must be carefully balanced to avoid severe side effects. Comorbidity management, regular monitoring of kidney function, and a patient-centered approach are crucial for improving outcomes and quality of life. A multidisciplinary team can provide comprehensive care, addressing all aspects of the patient’s health. Supportive care, the role of kidney biopsy, and the balance between immunosuppressive therapy and the risk of complications are emphasized. Collaborative, individualized care approaches are recommended to improve outcomes and quality of life for elderly patients with immune-mediated kidney diseases. Future research should focus on including older patients in clinical trials to establish robust, age-specific guidelines.

Abstract Background Proteinuria is a prevalent symptom of pediatric nephrology, while kidney biopsy remains the gold standard for kidney tissue analysis, and it is currently controversial. We report the rare case that the mutation in the AMN gene was considered to cause chronically isolated proteinuria and also suggest that renal biopsy should be chosen with caution in children with chronic isolated non-nephrotic levels of proteinuria and that genetic testing may be feasible for the early precise diagnosis. Case presentation A 35-month-old boy presented with excessive urine foaming for more than half a month; his proteinuria was considered non-nephrotic range and urine protein electrophoresis was suggestive of mixed proteinuria; other than that, the investigations are non-specific. Given the child’s chronic isolated proteinuria and good renal function, we chose to refine the genetic test rather than a renal biopsy; a compound heterozygous variant was found in the AMN gene of this child which was caused by a point mutation in the father, and a partial chromosomal deletion in the mother. Conclusions Cubilin(encoded by CUBN), amnionless(encoded by AMN), and megalin form a multiligand receptor complex; CUBN or AMN gene variants have been implicated as a hereditary cause of megaloblastic anemia, proteinuria, and neurological impairment. In the past few decades, chronic isolated proteinuria caused by CUBN gene variants is benign, non-progressive, and has normal renal function. However, the child is the first reported case of isolated proteinuria of AMN gene mutation, indicating that the earlier diagnostic genetic sequencing in an otherwise well, not nephrotic proteinuria child may be a convenient, cost-effective, and harmless option, challenging the traditional paradigm.

Aim: Kidney disease is common in older adults due to age-related structural and functional changes in the kidneys, higher rates of chronic disease, and increased drug use. As societies age, there is a rise in the prevalence of renal disease and the number of kidney biopsies being performed in older patients. This study aimed to investigate renal biopsy indications, complications, pathology results, and subsequent treatment among older adults in Turkey. Materials and Methods: We retrospectively analyzed data from patients aged 65 and over who underwent renal biopsy in a university nephrology department between 2004 and 2023. The patients’ demographic information, chronic comorbidities, biopsy indications, pre-biopsy laboratory values, post-biopsy complications, pathology results, and post-biopsy treatments were obtained by reviewing their medical records and biopsy reports. Results: A total of 66 patients were included in the study. The median age was 73.0 years (IQR: 68.8-79.0 years) and 66.7% of the patients were men. The most common comorbidities were hypertension (83.3%), diabetes mellitus (24.3%), coronary artery disease (22.7%), and chronic kidney disease (21.2%). The most common indication for renal biopsy was nephrotic-range proteinuria (56.1%), followed by acute kidney injury (24.2%). When the pathology results were examined, primary glomerulonephritis (62.1%) was the most common result, followed by secondary glomerulonephritis (21.2%) and tubulointerstitial nephritis (12.1%). The most common histopathological diagnoses in primary glomerulonephritis were membranous glomerulonephritis (39.4%) and focal segmental glomerulosclerosis (12.1%), while those in secondary glomerulonephritis were secondary amyloidosis (9.1%) and lupus nephritis (4.5%). After biopsy, 54.5% of the patients received immunosuppressive therapy and 34.8% received renal replacement therapy. No post-biopsy complications were observed. Conclusion: Although the most common indication for kidney biopsy in older adults is nephrotic-range proteinuria. Kidney biopsy is the gold standard method for the diagnosis of renal parenchymal diseases and is a safe procedure in older patients, with low complication rates. Kidney biopsy should not be avoided in geriatric patients if deemed clinically necessary.

Polyomaviruses, particularly BK virus, are ubiquitous latent infections that may reactivate with immunosuppression during kidney transplantation, resulting in polyomavirus nephropathy (PVN). The levels of viruria and viremia serve as tools for screening and making a presumptive diagnosis of PVN, respectively, while a definitive diagnosis requires a kidney biopsy. There are histologic classifications of PVN based on the extent of tubular cell viral infection, interstitial fibrosis, and interstitial inflammation. These classifications correlate to some degree with graft function and loss, aiding in determining treatment efficacy and prognostication. PVN has histologic overlap with acute cell-mediated rejection, making the differential diagnosis challenging, although there are suggestive features for these different causes of graft dysfunction. This article reviews the diagnosis, histologic findings, and classifications of PVN, and discusses how to differentiate viral nephropathy from acute rejection.

Abstract Background Medullary sponge kidney (MSK)is rare in association with glomerulonephritis. We report a patient with medullary sponge kidney, and the kidney biopsy revealed a diagnosis of IgA nephropathy. Case presentation A 27-year-old female presented with hematuria and proteinuria, and imaging studies indicated the presence of medullary spongy kidney. With appropriate preparation, a kidney biopsy was performed. Considering the patient’s clinical and pathological characteristics, the final diagnosis was determined to be medullary sponge kidney associated by IgA nephropathy. The combination of corticosteroids and angiotensin receptor blockers (ARBs) proved to be significantly effective in reducing proteinuria in the current case. To the best of our knowledge, this is the first reported case that demonstrates the coexistence of MSK and IgA nephropathy. Conclusions Administering precise therapy based on renal pathology can potentially enhance outcomes for patients with renal conditions, necessitating the need for clinicians to be vigilant about differential diagnosis in order to reduce the rates of missed diagnoses and misdiagnosis.

Abstract IgA nephropathy progresses to kidney failure, making early detection important. However, definitive diagnosis depends on invasive kidney biopsy. This study aimed to develop non-invasive prediction models for IgA nephropathy using machine learning. We collected retrospective data on demographic characteristics, blood tests, and urine tests of the patients who underwent kidney biopsy. The dataset was divided into derivation and validation cohorts, with temporal validation. We employed five machine learning models—eXtreme Gradient Boosting (XGBoost), LightGBM, Random Forest, Artificial Neural Networks, and 1 Dimentional-Convolutional Neural Network (1D-CNN)—and logistic regression, evaluating performance via the area under the receiver operating characteristic curve (AUROC) and explored variable importance through SHapley Additive exPlanations method. The study included 1268 participants, with 353 (28%) diagnosed with IgA nephropathy. In the derivation cohort, LightGBM achieved the highest AUROC of 0.913 (95% CI 0.906–0.919), significantly higher than logistic regression, Artificial Neural Network, and 1D-CNN, not significantly different from XGBoost and Random Forest. In the validation cohort, XGBoost demonstrated the highest AUROC of 0.894 (95% CI 0.850–0.935), maintaining its robust performance. Key predictors identified were age, serum albumin, IgA/C3, and urine red blood cells, aligning with existing clinical insights. Machine learning can be a valuable non-invasive tool for IgA nephropathy.

Introduction: Diabetic kidney disease (DKD) affects 30–40% of patients with diabetes. The prevalence of nondiabetic kidney disease (NDKD) in patients with type 2 diabetes mellitus (T2D) in Egypt is unknown. This study aimed to assess the prevalence of NDKD in patients with T2D in Egypt. Methods: In this cross-sectional study, we searched the data of patients with T2D who underwent a native kidney biopsy between January 2010 and December 2020 in a kidney pathology laboratory in Egypt. Results: Of 12,006 patients who underwent kidney biopsy, 677 patients had T2D. NDKD was found in 285 patients (42.7%), DKD in 220 patients (33%), and mixed DKD and NDKD in 162 patients (24.3%). The total prevalence of NDKD was 67% in patients with T2D in our study group. Membranous nephropathy was the most common histopathological disease in patients with NDKD (20.6%) followed by acute tubular injury (ATI) (19.2%) and focal segmental glomerulosclerosis (15.2%). The presence of ATI in a kidney biopsy was associated with a significantly higher mean serum creatine level (p < 0.001). Minimal change disease was associated with a significantly higher proteinuria level (p < 0.001). In binary logistic regression analysis, combining NDKD and mixed groups, the duration of diabetes was a negative predictor of NDKD, with a longer duration decreasing the likelihood of NDKD. Conclusion: NDKD is prevalent among patients with T2D who underwent a kidney biopsy. Kidney biopsy remains the gold standard for diagnosing NDKD in patients with T2D.

Introduction: Kimura’s disease (KD) is a rare chronic inflammatory disorder characterized by subcutaneous lymphoid hyperplasia with peripheral eosinophilia. Kidney involvement is reported in 15%–18% of adult patients with KD, in many cases as nephrotic syndrome. We present a case of overlapping membranous nephropathy and IgA nephropathy associated with KD. Case report: A 27-year-old man was admitted with a history of bilateral leg edema for the last 2 months and concomitant progressive increase of cervical mass and fever. Laboratory findings were as follows: peripheral leukocyte count, 10,080/mm³; eosinophils, 3,200/mm³ (31.7%); serum creatinine, 0.83 mg/dL; and eGFR: 140 mL/min per 1.73 m². Urinalysis revealed the presence of hematuria and proteinuria and the following results: 24-h proteinuria, 12.9 g; serum albumin, 1.3 g/dL; and elevated IgE level, 750 kU/L. Serologies for hepatitis B, hepatitis C, HIV, and VDRL were all negative. Complement C3 and C4 levels were normal. No monoclonal protein was detected in blood and urine. Parasite infestation was discarded. A biopsy of the cervical lymph node revealed eosinophilic lymphoid hyperplasia, suggesting KD. A kidney biopsy revealed findings consistent with the overlapping of membranous nephropathy with IgA nephropathy. The patient was treated for KD with prednisone 1 mg/kg/d with progressive dose tapering and posterior association of methotrexate 15 mg/week. A renin–angiotensin system inhibitor was prescribed for nephrotic syndrome. The cervical mass regressed, and proteinuria achieved partial remission, with an increase in serum albumin level and normalization of eosinophils and IgE levels. Conclusion: Although uncommon, kidney involvement must be considered in patients with KD. Glomerular diseases are the most frequent form of kidney injury. [ABSTRACT FROM AUTHOR]

Background: IgA nephropathy (IgAN) is a significant contributor to chronic kidney disease (CKD). Renal arteriolar damage is associated with IgAN prognosis. However, simple tools for predicting arteriolar damage of IgAN remain limited. We aim to develop and validate a nomogram model for predicting renal arteriolar damage in IgAN patients. Methods: We retrospectively analyzed 547 cases of biopsy-proven IgAN patients. Least absolute shrinkage and selection operator (LASSO) regression and logistic regression were applied to screen for factors associated with renal arteriolar damage in patients with IgAN. A nomogram was developed to evaluate the renal arteriolar damage in patients with IgAN. The performance of the proposed nomogram was evaluated based on a calibration plot, ROC curve (AUC) and Harrell's concordance index (C-index). Results: In this study, patients in the arteriolar damage group had higher levels of age, mean arterial pressure (MAP), serum creatinine, serum urea nitrogen, serum uric acid, triglycerides, proteinuria, tubular atrophy/interstitial fibrosis (T1-2) and decreased eGFR than those without arteriolar damage. Predictors contained in the prediction nomogram included age, MAP, eGFR and serum uric acid. Then, a nomogram model for predicting renal arteriolar damage was established combining the above indicators. Our model achieved well-fitted calibration curves and the C-indices of this model were 0.722 (95%CI 0.670-0.774) and 0.784 (95%CI 0.716-0.852) in the development and validation groups, respectively. Conclusion: With excellent predictive abilities, the nomogram may be a simple and reliable tool to predict the risk of renal arteriolar damage in patients with IgAN. [ABSTRACT FROM AUTHOR]

Background: Proteinuria is a prevalent symptom of pediatric nephrology, while kidney biopsy remains the gold standard for kidney tissue analysis, and it is currently controversial. We report the rare case that the mutation in the AMN gene was considered to cause chronically isolated proteinuria and also suggest that renal biopsy should be chosen with caution in children with chronic isolated non-nephrotic levels of proteinuria and that genetic testing may be feasible for the early precise diagnosis. Case presentation: A 35-month-old boy presented with excessive urine foaming for more than half a month; his proteinuria was considered non-nephrotic range and urine protein electrophoresis was suggestive of mixed proteinuria; other than that, the investigations are non-specific. Given the child's chronic isolated proteinuria and good renal function, we chose to refine the genetic test rather than a renal biopsy; a compound heterozygous variant was found in the AMN gene of this child which was caused by a point mutation in the father, and a partial chromosomal deletion in the mother. Conclusions: Cubilin(encoded by CUBN), amnionless(encoded by AMN), and megalin form a multiligand receptor complex; CUBN or AMN gene variants have been implicated as a hereditary cause of megaloblastic anemia, proteinuria, and neurological impairment. In the past few decades, chronic isolated proteinuria caused by CUBN gene variants is benign, non-progressive, and has normal renal function. However, the child is the first reported case of isolated proteinuria of AMN gene mutation, indicating that the earlier diagnostic genetic sequencing in an otherwise well, not nephrotic proteinuria child may be a convenient, cost-effective, and harmless option, challenging the traditional paradigm. [ABSTRACT FROM AUTHOR]

Changes over time in prevalence of glomerulopathies (GP) have been reported worldwide, but given the scarcity of data from Romania, we assessed the frequency of biopsy-proven GP over a 10-year period. This single-centre retrospective study enrolled 1 254 adults with GP on native kidneys diagnosed between 01.01.2008 – 31.12.2017, whose cases were extracted from the kidney biopsy (KB) registry of the hospital. Those with repeated KB and insufficient tissue sample or missing data were all excluded. Demographic, clinical, laboratory and histological data were analyzed and compared between subjects who underwent KB in the first and last five years (2008-2012, n=355 vs. 2013-2017, n=899). Even if nephrotic syndrome was the main reason for KB, its frequency decreased from one in two to one in three cases (p<0.001). During the second period, older subjects with lower glomerular filtration rate and proteinuria were found. Also, KB was prescribed for chronic kidney function decline three times more often (p<0.001), while acute nephritic syndrome almost doubled its prevalence among biopsies (p=0.005). IgA nephropathy and membranous nephropathy were similarly the two most frequent histological patterns in both time intervals. However, between 2013-2017, diabetic nephropathy was more commonly detected (12.3% vs. 4.8%, p<0.001), probably because more diabetics underwent KB, but also the crescentic glomerulonephritis showed higher prevalence over time (6.6% vs. 3.1%, p=0.02). Subject to the limitations of our retrospective single-centre study, its findings suggested rather a change in the diagnostic approach than an actual different GP prevalence in adults, as KB were performed in patients with more advanced age, lower kidney function and less proteinuria. [ABSTRACT FROM AUTHOR]

Background: Class III obesity, formerly known as morbid obesity, is a known risk factor for chronic kidney diseases. Due to outdated information suggesting that morbid obesity is a contraindication for kidney biopsy and the misconception that proteinuria in obese patients is solely related to hyperfiltration, necessiating only conservative treatment, the vast majority of primary glomerulonephritis in these patients remains undiagnosed and untreated. Here, the clinical characteristics, treatments and results of patients who had class III obesity and needed a kidney biopsy are presented. Methods: Two hundred thirty-one native kidney biopsies conducted between 2015 and 2021 were retrospectively reviewed, identifying 12 patients with a body mass index =40 kg/m². Results: Ten patients presented with nephrotic syndrome, 8 of these patients underwent immunosuppressive therapy. Membranous nephropathy and focal segmental glomerulosclerosis were the most common diagnoses. Seven patients went into remission during follow-up. Our results indicated that class III obesity alone is not a detrimental morbidity when it comes to diagnosing and treating glomerular diseases. Conclusion: If a primary glomerulonephritis is diagnosed through a safe biopsy procedure, there is no reason to avoid considering immunosuppressive therapy for these patients. [ABSTRACT FROM AUTHOR]

Background: Kidney biopsy (KB) is the gold standard in the diagnosis of kidney diseases. Ultrasound (USG)-guided and automatic biopsy guns have decreased the complications. In our study, we examined the complications of KB performed using the routine kidney USG protocol performed during and 24 hours after the procedure. We also examined risk factors that may predict complications. Methods: Major complications after biopsy were defined as bleeding requiring transfusion or surgical intervention. Minor complications were defined as hematoma not requiring transfusion, accompanied by hemoglobin (Hb) decrease of more than 1 g/dL. Ultrasound-guided automatic biopsy device and 18-gauge needle were used. Control USG was performed immediately after the biopsy and 24 hours after the procedure. Results: Two hundred fifty-nine biopsy procedures were analyzed. Major complications were found in 15 (5.8%), minor complications in 22 (8.5%) patients. Of the 62 patients who developed hematoma after biopsy, 24 hematomas (38.7%) occurred immediately, and 38 hematomas (61.3%) were detected after 24 hours by the control USG. The low Hb and serological marker (antinuclear antibody, antineutrophil cytoplasmic antibody, and anti-glomerular basement membrane antibody) positivity were statistically significant in terms of major complications after KB. Conclusion: Clinical follow-up for at least 24 hours, routine 24-hour control USG and early intervention (transfusion) may have prevented more severe clinical findings and complications. The low complication rate and the ability to obtain sufficient tissue make smaller-gauge needles advantageous. Low hemoglobin levels before biopsy and serological marker positivity were found to be independent risk factors for major complications. [ABSTRACT FROM AUTHOR]

Introduction This study aimed to analyze the clinical course of TAFRO syndrome in patients through extended follow-up, focusing on recurrent cases and long-term remission. Methods This was a retrospective case series study. We assessed the clinical course of patients diagnosed with TAFRO syndrome between January 2012 and September 2022 at Toranomon Hospital or Toranomon Hospital Kajigaya, excluding those patients who died during the initial hospitalization. Results Twelve patients were included. Baseline characteristics, laboratory findings, treatment modalities, and outcomes were assessed. During the median follow-up period of 1474 days, two patients experienced recurrence following a reduction in tocilizumab (TCZ) dose, whereas two achieved remission for >400 days without TCZ treatment. The remaining eight patients maintained remission under the continued TCZ therapy. Recurrence diagnosis was complicated by the non-simultaneous presentation of the five manifestations of TAFRO syndrome. The patients who experienced recurrence showed milder manifestations and faster recovery than the initial onset. Glomerular endotheliopathy was evident in kidney biopsies during recurrence, which was similar to the initial presentation. In a case where only inflammation preceded other manifestation, a kidney biopsy was pivotal in distinguishing TAFRO syndrome relapse from other inflammatory conditions such as infection. Pretreatment serum IL-6 levels were within the reference range only in patients who experienced long-term remission without TCZ treatment. Conclusions This is the first study to perform kidney biopsies on recurrent TAFRO cases, highlighting recurrence after TCZ dosage reduction, non-simultaneous manifestation of symptoms, the utility of kidney biopsies in recurrence diagnosis, and potential non-IL-6 pathogenesis factors. Pretreatment serum IL-6 levels may help identify patients suitable for maintenance therapy without TCZ. Further investigation is warranted to identify stratified treatment approaches based on individual etiologic factors. [ABSTRACT FROM AUTHOR]

Steroid resistant nephrotic syndrome (SRNS) accounts for 30% of all cases of nephrotic syndrome (NS) in children and frequently leads to end stage kidney disease (ESKD). About 30% of children with SRNS demonstrate causative mutations in podocyte- associated genes. Early identification of genetic forms of SRNS is critical to avoid potentially harmful immunosuppressive therapy. A 2-year-old male patient with NS and no family history of renal disease did not respond to 4-week steroid treatment. Kidney biopsy demonstrated mesangial proliferative glomerulopathy with basement membrane dysmorphism. Tacrolimus and Lisinopril were added to therapy pending results of genetic testing. Kidney Gene panel showed a NPHS2 c.413G>A (p.Arg138Gln) homozygous pathogenic variant. This missense variant is considered a common pathogenic founder mutation in European populations. A diagnosis of autosomal-recessive form of nonsyndromic SRNS due to NPHS2 causative variant was made. Immunosuppresive therapy was stopped, Lizinopril dose was increased and weekly infusions of Albumin/furosemide were initiated to manage edema. This case demonstrates that early genetic testing in children with SRNS avoids prolonged potentially harmful immunosuppressive therapy, allows for timely genetic family counseling, and allows earlier consideration for future living related donor kidney transplantation. [ABSTRACT FROM AUTHOR]

Objective: This study aims to develop and validate machine learning models to predict proliferative lupus nephritis (PLN) occurrence, offering a reliable diagnostic alternative when renal biopsy is not feasible or safe. Methods: This study retrospectively analyzed clinical and laboratory data from patients diagnosed with SLE and renal involvement who underwent renal biopsy at West China Hospital of Sichuan University between 2011 and 2021. We randomly assigned 70% of the patients to a training cohort and the remaining 30% to a test cohort. Various machine learning models were constructed on the training cohort, including generalized linear models (e.g., logistic regression, least absolute shrinkage and selection operator, ridge regression, and elastic net), support vector machines (linear and radial basis kernel functions), and decision tree models (e.g., classical decision tree, conditional inference tree, and random forest). Diagnostic performance was evaluated using ROC curves, calibration curves, and DCA for both cohorts. Furthermore, different machine learning models were compared to identify key and shared features, aiming to screen for potential PLN diagnostic markers. Results: Involving 1312 LN patients, with 780 PLN/NPLN cases analyzed. They were randomly divided into a training group (547 cases) and a testing group (233 cases). we developed nine machine learning models in the training group. Seven models demonstrated excellent discriminatory abilities in the testing cohort, random forest model showed the highest discriminatory ability (AUC: 0.880, 95% confidence interval(CI): 0.835-0.926). Logistic regression had the best calibration, while random forest exhibited the greatest clinical net benefit. By comparing features across various models, we confirmed the efficacy of traditional indicators like anti-dsDNA antibodies, complement levels, serum creatinine, and urinary red and white blood cells in predicting and distinguishing PLN. Additionally, we uncovered the potential value of previously controversial or underutilized indicators such as serum chloride, neutrophil percentage, serum cystatin C, hematocrit, urinary pH, blood routine red blood cells, and immunoglobulin M in predicting PLN. Conclusion: This study provides a comprehensive perspective on incorporating a broader range of biomarkers for diagnosing and predicting PLN. Additionally, it offers an ideal non-invasive diagnostic tool for SLE patients unable to undergo renal biopsy. [ABSTRACT FROM AUTHOR]

Background: Acute post-streptococcal glomerulonephritis (APSGN) is a common cause of acute kidney injury (AKI) in children; however, in a small subgroup, the presentation is one of rapidly progressive glomerulonephritis (RPGN) deteriorating kidney function associated with severe oligo-anuria or a mixed nephritic-nephrotic picture. This study reviewed potential clinical and laboratory factors which may assist the treating clinician to identify patients at high risk of severe disease. Methods: All kidney biopsies for APSGN performed between 1996 and 2020 were obtained from a departmental biopsy database. Clinical and laboratory data were extracted from the patients' clinical records. Kidney biopsies were reviewed and scored independently by a renal histopathologist. Results: Thirty of 53 (56.6%) patients had stage 3 AKI at initial presentation with a median estimated glomerular filtration rate (eGFR) 27 (IQR 11–41), falling to 20 ml/min/1.73 m2 (IQR 13.3–43) at time of biopsy. Patients who had either a pre-biopsy eGFR < 35 ml/min/1.73 m2 or a ≥ 25% fall in eGFR between admission and biopsy were more likely to have glomerular crescents (p = 0.004). Multivariate regression analysis and receiver operating curve showed the pre-biopsy eGFR most accurately predicted glomerular crescents (p = 0.047, ROC 0.757). There were no significant predictors of nephrotic proteinuria or nephrotic syndrome during the acute phase. Conclusions: Severe APSGN is associated with a pronounced reduction in eGFR. Calculation of eGFR in this small group of patients may assist in identifying which patient should have an urgent kidney biopsy to facilitate a more accurate clinical diagnosis and management plan. [ABSTRACT FROM AUTHOR]

Background: Diabetic nephropathy may begin in childhood, but clinical kidney disease ascribable to this is uncommon in children with type 1 (insulin dependent) diabetes mellitus. Methods: We reviewed our experience of kidney biopsies in children with type 1 diabetes mellitus. Results: Between 1995 and 2022, there were biopsies in 17 children, with various clinical indications for kidney biopsy, making this the largest series of biopsies in diabetic children with clinical kidney abnormalities. Four biopsies showed diabetic nephropathy, three showed the combination of diabetic nephropathy and IgA nephropathy, and ten showed a variety of conditions other than diabetic nephropathy: minimal change disease (2), membranous nephropathy (2), thin glomerular basement membrane lesion (2), non-glomerular chronic damage in Wolcott–Rallison syndrome (2), acute pauciimmune necrotizing crescentic glomerulonephritis (1) and IgA nephropathy (1). Clinical clues of something other than diabetic nephropathy included acute kidney injury, microscopic haematuria or chronic kidney impairment with little or no proteinuria and the nephrotic syndrome after a short duration of diabetes. Conclusions: We confirm that changes better known in adults with either type 1 or type 2 diabetes mellitus can occur in children with type 1 diabetes mellitus: overt diabetic nephropathy either on its own or combined with other conditions and kidney disorders other than diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Glomerular diseases (GDs), significant causes of end-stage kidney disease, are better understood through epidemiological studies based on kidney biopsies (KBs), which provide important insights into their prevalence and characteristics. This study aims to analyze the clinicopathological features of GDs diagnosed from 2008 to 2017 at Romania's largest reference center. In this decade-long study, 1254 adult patients diagnosed with GDs were included. The local previously validated renal histopathological prognostic score was calculated for each KB using four histopathologic lesions: global glomerulosclerosis, tubular atrophy, interstitial fibrosis and fibrocellular/fibrous crescents. The mean patient age was 50 years, with a male predominance (57%). The primary referral reasons were nephrotic syndrome (46%), nephritic syndrome (37%), chronic kidney disease (12%), asymptomatic urinary abnormalities (4%), and acute kidney injury (1%). Immunoglobulin A nephropathy (IgAN) was the most frequently diagnosed GD (20%), aligning with frequencies reported in European registries. Diabetic glomerular nephropathy was the most common secondary GD (10%). It also presented the highest median renal histopathological prognostic score (2), indicating a poorer prognosis. Lower eGFR and higher proteinuria were independently associated with higher scores. This decade-long study highlights IgAN as the most frequent GD diagnosed by KB. Diabetic glomerular nephropathy was identified as the most common secondary GD. The renal histopathological prognostic score, notably high in diabetic glomerular nephropathy patients, was correlated with lower eGFR and higher proteinuria, underlining its clinical relevance. [ABSTRACT FROM AUTHOR]