Biopsy Registry Research Articles

A Descriptive Study of a New Mexico-Based Kidney-Allograft Biopsy Registry

A Descriptive Study of a New Mexico-Based Kidney-Allograft Biopsy Registry

Natural Language Processing for Extracting Kidney Biopsy Pathology Diagnoses: The Houston Methodist Hospital Kidney Biopsy Registry

Natural Language Processing for Extracting Kidney Biopsy Pathology Diagnoses: The Houston Methodist Hospital Kidney Biopsy Registry

Anatomo-clinical and Etiological Profile of Nephropathies Biopsied in the Nephrology Department of the Thies Regional Hospital (Senegal)

Introduction: In many developing countries, particularly in Africa, the use of renal biopsy (RB) in clinical nephrology is severely lacking. The objectives were to describe the anatomoclinical and etiological profile of these biopsied nephropathies, as well as the factors associated with the etiology of the nephropathies. Patients and method: This was a retrospective descriptive and analytical study from 1 April 2020 to 30 October 2022. The patients were selected from the renal biopsy register of the nephrology department of the Thiès Regional Hospital. Sociodemographic, clinical, biological, and histological parameters were studied. Results: 75 renal biopsies were included. The mean age was 33.3 ± 14.8 years, with a male predominance (65.3%). The main indications were nephrotic syndrome in 50.67% of cases. RB was adequate in 82.7%, inadequate in 13.3%, and borderline in 4%. Glomerular nephropathies predominated, with focal segmental glomerulosclerosis (FSGS) in 34.7%, membranous nephropathy (MN) in 17.3%, minimal change disease (MCD) in 10.67%, extracapillary glomerulonephritis (ECGN) in 5.3% and lupus nephritis (LN) in 3.9%. Thrombotic microangiopathy (TMA) was found in 9.3%. Chronic tubulointerstitial nephropathy (CTIN) accounted for 5.3% of all RB and acute tubular necrosis (ATN) for 4%. The etiologies were primary in 48%, secondary in 28%, and undetermined in 24%. In the bivariate analysis, the etiology was correlated with the mean SBP (p = 0.023), the mean level of hemoglobin (p = 0.028), the levels of GFR (p = 0.017), and the type of kidney disease (p = 0.000). Conclusion: Glomerular nephropathy was more frequent and FSGS was the most common histological lesion found. Primary causes predominated. Associated factors were identified to improve patient management.

Multiple Acyl-Coenzyme A Dehydrogenase Deficiency Is Associated with Sertraline Use - Is There an Acquired Form?

Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is a disorder of fatty acid oxidation and considered an inborn error of metabolism. In recent years, we have diagnosed an increasing number of patients where, despite extensive investigation, no disease-causing mutations have been found. We therefore investigated a cohort of consecutive patients, with the objective to detect possible non-genetic causes. We searched the patient records and the registry of muscle biopsies, for patients with MADD, diagnosed within the past 10 years. The patient records were reviewed regarding symptoms, clinical findings, comorbidities, drugs, diagnostic investigations, and response to treatment. In addition, complementary investigations of muscle tissue were performed. We identified 9 patients diagnosed with late-onset MADD. All presented with muscle weakness and elevated levels of creatine kinase. A lipid storage myopathy was evident in the muscle biopsies, as was elevated acylcarnitines in blood. Despite thorough genetic investigations, a probable genetic cause was found in only 2 patients. Remarkably, all 7 patients without disease-causing mutations were treated with sertraline. In some cases, a deterioration of symptoms closely followed dose increase, and discontinuation resulted in an improved acylcarnitine profile. All 9 patients responded to riboflavin treatment with normalization of creatine kinase and muscle biopsy findings, and in 8 patients the clinical symptoms clearly improved. Our findings strongly suggest that sertraline may induce an acquired form of MADD in some patients. Importantly, riboflavin treatment seems to be similarly effective as in genetic MADD, but discontinuation of sertraline is reasonably warranted. ANN NEUROL 2024.

Hemato-Renal Profile of Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits

Background Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a rare entity classified under the umbrella of monoclonal gammopathy of renal significance. The clinical implications of circulating monoclonal immunoglobulin (MIg), light chain restriction on immunofluorescence (IF) microscopy, histopathological pattern, and type of therapy on renal outcomes are not clearly defined. Materials and Methods Sixteen patients of PGNMID diagnosed between 2013 and 2020 were included from a biopsy registry of 11,459 patients at a single center. Follow-up data was collected from electronic medical records until June 2021. Results The mean age of the cohort was 41.7 ± 13.5 years. Forty-four (7/16) percent showed monoclonal protein on serum or urine electrophoresis, 25% (3/12) had IgG kappa by serum immunofixation electrophoresis (IFE) and 38% (5/13) had abnormal kappa: lambda free light chain (FLC) ratio. The predominant light microscopy pattern, membranoproliferative glomerulonephritis (MPGN) was seen in 7/16 (43.7%) patients. The predominant heavy chain detected by IF microscopy was IgG (13/16, 81.3%). Kappa and lambda light chain restriction were seen in 56.3 (9/16) and 43.8 (7/16) percent of patients respectively. Circulating monoclonal kappa light chains were detected in 50 and 29% of kappa-PGNMID patients by IFE and FLC assay respectively. None of the lambda-PGNMID patients had detectable circulating monoclonal lambda light chains. Patients with circulating MIg had more proteinuria, lower estimated glomerular filtration rate, and a higher percentage of plasma cells on bone marrow biopsy. Thirty-eight percent of our cohort (5/13) progressed to kidney failure over a median (range) period of 3 (IQR, 1-7) months. Of these, 4/5 received immunosuppression, and 1/5 were treated with plasma cell-targeted chemotherapy. Conclusion PGNMID is a rare disease with a biopsy incidence of 0.1%. Only a quarter of patients with PGNMID have circulating MIg. Presence of circulating MIg, type of monoclonal light chain restriction in kidney biopsy, and type of therapy did not predict renal outcomes. Patients with MPGN pattern had favorable renal outcomes despite a higher degree of proteinuria at presentation.

Renal osteodystrophy and clinical outcomes: a prospective cohort study.

Renal osteodystrophy (ROD) refers to a group of bone morphological patterns that derive from distinct pathophysiological mechanisms. Whether the ROD subtypes influence long-term outcomes is unknown. Our objective was to explore the relationship between ROD and clinical outcomes. This study is a subanalysis of the Brazilian Registry of Bone Biopsies (REBRABO). Samples from individual patients were classified as having osteitis fibrosa (OF), mixed uremic osteodystrophy (MUO), adynamic bone disease (ABD), osteomalacia (OM), normal/minor alterations, and according to turnover/mineralization/volume (TMV) system. Patients were followed for 3.4 yrs. Clinical outcomes were: bone fractures, hospitalization, major adverse cardiovascular events (MACE), and death. We enrolled 275 participants, of which 248 (90%) were on dialysis. At follow-up, 28 bone fractures, 97 hospitalizations, 44 MACE, and 70 deaths were recorded. ROD subtypes were not related to outcomes. The incidence of clinical outcomes did not differ between the types of ROD.

#2555 C4d—a novel predictor of the disease progression and treatment failure in primary focal segmental glomerulosclerosis?

Abstract Background and Aims Complement system seems to play a role in the pathogenesis of primary focal segmental glomerulosclerosis (pFSGS) where, due to unpredictable clinical course and outcome, novel prognostic factors are sought. The split product of C4 and tissue marker of complement activation, C4d, is a potential candidate whose prognostic significance was determined in this study. Method Patients >18 years with features consistent with pFSGS (full blown nephrotic syndrome, diffuse podocyte foot processes effacement and exclusion of known causes of FSGS), were recruited from our Hospital registry of kidney biopsies, from 2003 to 2021. Patients with end-stage renal disease (ESRD) defined as eGFR <15 ml/min/1.73 m2 were not included. Every renal biopsy specimen was analyzed by light, immunofluorescence and electron microscopy with additional immunochemistry for C4d performed on paraffin-embedded tissue using monoclonal rabbit antibody (detection system Ventana BenchMark Ultra). Samples with at least one non-globally sclerosed glomerulus (GSG) were examined by two renal pathologists who classified every non-GSG into C4d positive and negative. Based on ratio of C4d+ non-GGS/total N of non-GSG and C4d+ nonsclerotic glomeruli (NSG)/total N of NSG, patients were stratified into two groups: <50% and ≥50%. Primary outcome was defined as composite of ESRD and initial eGFR declining >50%. Failure to meet criteria for at least partial remission at the last follow-up visit according to KDIGO 2021 Guidelines was defined as treatment failure. Numeric variables are shown as median with interquartile range (IQR) and P value <0.05 was considered as significant. Results Relevant data of 58 included patients with renal outcomes are shown in Table. Median follow up was 90.7 (IQR 48-167) months. Patients with ≥50% of C4d+ non-GSG had higher proportion of treatment failure (Table) and worse renal survival (log-rank test, p = 0.006). In multivariate Cox regression analysis, after inclusion of age, sex, initial eGFR and 24-h proteinuria, IFTA, serum albumin and C4d category, only C4d ≥50% (HR = 4.077, 95% CI 1.101-15.09, p = 0.035) and IFTA (HR = 1.052, 95% CI 1.019-1.085, p = 0.002) remained independent predictors of progression to defined endpoint. Likewise, patients with ≥50% of C4d+ NSG/total N of NSG had higher proportion of treatment failure (chi-square, p = 0.03) and worse renal survival (log-rank, p = 0.037). Conclusion C4d deposition is an independent predictor of disease progression, treatment failure and renal survival in pFSGS. Significant influence of NSG-C4d deposition on disease progression may indicate pathophysiological role of the complement system activation in pFSGS independently of the presence of glomerular sclerosis.

#1883 SUrvey of renal Biopsy database and Anti-cancer dRUg therapy in Japan (SUBARU-J study)

Abstract Background and Aims The frequency of consultations for renal complications associated with anti-cancer drug therapy has greatly increased in recent years, but the actual situations remain yet to be fully understood. We aimed to investigate the clinical outcomes of anti-cancer drug therapy-associated renal complications, using the Japan Renal Biopsy Registry (J-RBR), a nationwide registry system in Japan. Method This nationwide survey was performed in 449 cases with “drug-induced” checked in J-RBR database from 2018 to 2021. In total 449 subjects, top-ranked histopathological diagnoses were as follows, TIN (49.8%), TMA (14.5), MN (10.0), MCNS (6.5), FSGS (4.4), Vasculitis (2.2) and others (12.2). Regardless of the causative agent, TIN was the most common diagnosis. Though, it was followed by TMA or MN in anti-cancer drug (n = 139)- or non-anticancer drug (n = 190)-related cases, respectively. Because there was also TMA included as 2nd highest in causative-agent unidentified cases (n = 120), we employed total 259 subjects of anti-cancer drug-related and causative-agent unidentified for this survey. Our surveillance files investigating on renal pathology, medications and cancer prognosis were distributed. Of the 224 cases with a file uploaded, a total of 135 anti-cancer drug-related cases confirmed by the information were analyzed. Patients’ clinical data collected at pre- and post-biopsy as well as histopathological diagnoses were used for epidemiological and clinicopathological analyses. Mann-Whitney U test or chi-square test was used for continuous or categorical variables. Overall survival (OS) was estimated using Kaplan–Meier method and compared by log-rank test. Results In total 135 subjects, top-ranked histopathological diagnoses were as follows: tubulointerstitial nephritis (TIN; 64 cases), thrombotic microangiopathy (TMA; 48), focal segmental glomerulosclerosis (FSGS; 5), IgA nephropathy (IgAN; 4), acute tubular necrosis (ATN; 3), minimal change nephrotic syndrome (MCNS; 3), crescentic glomerulonephritis (CrGN; 2), membranoproliferative glomerulonephritis (MPGN; 2) and others (4). 80% of TIN and 75% of TMA, the most frequent diagnoses in our survey, were associated with immune-checkpoint inhibitors (ICI) and anti-angiogenic therapy (AAG), respectively. All IgAN, MCNS and CrGN cases were ICI-related. Proton pump inhibitors and antibiotics were used concomitantly in TIN (p = 0.054) and TMA (p < 0.001), respectively. Among cases with TIN, their OS in the subgroups of targeted therapy (Tx), and the combination with Tx and conventional cytotoxic agents (Combi) seemed to be worse than that of cytotoxic agents alone (CTx); it may be due to more cases in the Tx and Combi subgroups with treatment response category of progressive disease (by RECIST criteria). In contrast, among TMA cases, OS in each of the three subgroups of Tx, CTx, and Combi seemed to be overlapped, suggesting the prognostic impact of TMA on OS. The serum LDH level was higher in TMA associated with CTx (CTx-TMA) than that with others (Fig. 1: 393.2 vs. 225.1 U/L, p = 0.06). Of note, Kaplan-Meier curves for OS in TMA cases with increased LDH (>220 U/L) showed poor prognosis in CTx-TMA than in others-TMA (Fig. 2: p = 0.018). Conclusion Our nationwide survey using J-RBR registry database with renal biopsy data provides a snapshot of kidney complications associated with anti-cancer drug therapy. Higher LDH in CTx-TMA cases may be associated with systemic TMA, probably leading to the poor prognosis. To explore the detail of anti-cancer drug-associated TMA and other complications, further research employing more sample size is warranted in the future.

#978 Interstitial fibrosis and tubular atrophy of immune checkpoint inhibitor-related interstitial nephritis associate mortality and kidney prognosis

Abstract Background and Aims Several studies have been conducted on immune checkpoint inhibitor (ICI)-associated nephrotoxicity. However, current clinical analyses for nephrotoxicity are inadequate owing to the diagnostic criteria, which are mostly based on an increase in serum Cre levels rather than on renal pathology. In addition, many studies have focused on the incidence of ICI-associated nephrotoxicity, and few have focused on its prognosis and effects on overall survival. One of the major pathological findings of ICI-associated nephrotoxicity is known to show tubulointerstitial nephritis (TIN). Therefore, this study aimed to clarify the clinical and pathological characteristics of biopsy-proven ICI-TIN and their effects on the clinical remission of kidney injury and renal or cancer prognosis using the nationwide database of the Japan Renal Biopsy Registry (J-RBR) of the Japanese Society of Nephrology. Method This is a multicenter study using J-RBR named “SUrvey of renal Biopsy database and Anti-cancer dRUg therapy in Japan (SUBARU-J)”. Fifty-four patients with renal biopsy-proven ICI-TIN, registered in the J-RBR between 2018 and 2021 was analyzed. We collected patient clinical characteristics, pathological scores of renal biopsy including glomerulosclerosis, interstitial fibrosis, tubular atrophy (IFTA), and cellular infiltration, as well as data on the clinical remission of kidney injury during the acute phase, defined as a recovery of serum Cre to <1.5 × above baseline within 90 days from renal biopsy, then performed a multivariable analysis to investigate factors associated with clinical remission of kidney, and finally calculated the adjusted hazard ratio of each factor for overall survival, progression-free survival (PFS) of cancer, and major kidney adverse events (MAKE), consisting of the composite endpoint of death, renal replacement therapy dependence, or a decrease in estimated glomerular filtration rate to <50% of baseline. Results The median (interquartile range) time from the initiation of immune checkpoint inhibitors to renal biopsy was 134 (IQR: 56.5–364) days. Extrarenal immune-related adverse events occurred in 10 (18.5%) patients and 44 (81.5%) patients were treated with steroids. Clinical remission of kidney injury was achieved in 28 (51.8%) patients. A shorter interval (within seven days) between renal biopsy and steroid treatment was independently associated with the clinical remission of kidney injury (OR 35.3, p = 0.0301). The observation period from renal biopsy was 415 (IQR 140-844) days, with one-year overall survival of 62.5% and two-year overall survival of 42.4%. Hypertension (aHR 0.37, 95% CI: 0.17-0.82, p = 0.0144), IFTA (aHR 2.50, 95% CI: 1.12-5.57, p = 0.0251), and clinical remission of kidney injury (aHR 0.43, 95% CI: 0.19-0.94, p = 0.0355) were independently associated with overall survival. Hypertension (aHR 0.31, 95% CI: 0.15-0.64, p = 0.0018) and clinical remission of kidney injury (aHR 0.47, 95% CI: 0.23-0.96, p = 0.0391) also had a significant association with PFS although IFTA did not (aHR 2.03, 95% CI: 0.98-4.21, p = 0.0560). Furthermore, Hypertension (aHR 0.37, 95% CI: 0.18-0.77, p = 0.0075), IFTA (aHR 2.40, 95% CI: 1.14-5.06, p = 0.0210), and clinical remission of kidney injury (aHR 0.39, 95% CI: 0.19-0.81, p = 0.0123) were independently associated with the incidence of MAKE. Conclusion These data suggested that the pathological IFTA score of ICI-TIN, along with hypertension and clinical remission of kidney injury during the acute phase, could be associated not only with kidney prognosis but also with overall survival.

#2800 AL amyloidosis with renal involvement: TAPSE and new therapies

Abstract Background and Aims Light chain (LA) deposition amyloidosis is the most common type of renal amyloidosis. It may be associated with monoclonal gammopathy of uncertain significance (MGUS), meeting criteria for monoclonal gammopathy of renal significance (MGRS), or present in the course of multiple myeloma. The therapy of choice is autologous hematopoietic stem cell transplantation (TAPSE), although given the associated risks, not all patients are considered candidates, and different therapeutic regimens may be used as an alternative or induction prior to TAPSE (Bortezomib/dexamethasone, daratumumab/bortezomib, cyclophosphamide-bortezomib-Dexamethasone (CyBorD). Method Retrospective observational study of a cohort of patients with AL amyloidosis evidenced by renal biopsy by spectrometry or immunohistochemistry. Data extracted from the HUVM biopsy registry (2017-2022). Results 12 patients. Median age: 64 years. 6 women and 6 men. Mean creatinine 1.14 ± 0.6 mg/dl and proteinuria 3.8 ± 2.9 g/24 h. Median monoclonal peak 0.348 g/dl. Light chain involved: 7 Lambda and 5 Kappa. 2 patients met criteria for MM. 2 Bence-Jones positive. The 4 patients who did not have a renal response achieved a renal response, while of the 6 who did have a response, only 3 had a response (p = 0.091), 2 of them with previous induction with DARATUMUMAB, representing 100% of the total number of patients with this scheme. 3 patients died, with a median from diagnosis of 508 days. 1 of them had previously received TAPSE, out of a total of 6, while among the 5 patients who did not undergo this therapy, we found 2 exitus (p = 0.387). Conclusion The most common form of presentation in our sample was as MSG, with only 2 patients with MM criteria at the time of diagnosis. It also associated a reduced monoclonal component, and the Bence-Jones study was mostly negative. We did not find significant prognostic differences between the different therapeutic groups, although it is worth noting the worse renal response in the TAPSE group (p = 0.091) and the better data associated with the DARATUMUMAB group.

#2724 Renal amyloidosis cohort registry in our health area

Abstract Background and Aims Renal amyloidosis is the pathological phenomenon of amyloid deposition in the kidney with marked differences in renal function impairment, proteinuria, need for renal replacement therapy (RRT) and exitus, depending on the protein involved. Light chain amyloidosis (AL) and serum protein A (AA) amyloidosis are the most common. Typical symptoms are severe proteinuria, nephrotic syndrome, and end-stage chronic kidney disease (ESRD). Method Retrospective study of a cohort of patients with renal amyloidosis. Data extracted from the biopsy registry of the HUVM Nephrology Service (2013-2022). We collected demographic, clinical, analytical, histological and clinical outcome variables (RTT, Exitus). Results are analyzed using Mayo Clinic staging criteria. Results 19 patients with a mean age of 63.4a; 57.9% male. Mean laboratory values at diagnosis: creatinine (Cr) 1.56 mg/dl and proteinuria 3.9 g/24 h. Abdominal fat biopsy in 13 cases; 3 (23%) tested positive. Comparative analysis of AL vs non-AL forms, Cr values (1.14 vs 2.27 mg/dl respectively) (p=0.57) differed. Proteinuria according to the histological location of the amyloid: 4.6 g/24 h in glomerular involvement vs. 0.3 g/24 h in those who did not present it (p<0.05). 31.6% required RTT with a mean onset time of 250.6 d from biopsy. Exitus of 21.1%: average time of 426.5 d. (See analysis in attached table). Conclusion We did not observe significant deterioration of renal function, which is greater in non-AL forms of amyloidosis. Fat biopsy was less cost-effective than reported in the literature. Significantly lower levels of proteinuria were found in the amyloidosis group without glomerular involvement. In our series, the prognostic capacity associated with the MAYO staging was confirmed.

#1982 Transcriptomic approach to predict drug targets in late-stage hypertensive nephropathy

Abstract Background and Aims Hypertensive nephropathy (HN) is a significant contributor to chronic kidney disease, yet the factors influencing the disease progression remains elusive. Notably, late-stage chronic kidney disease significantly impacts patient outcome. This project aims to unveil novel therapeutic targets for late-stage of HN using transcriptomic approach. Method A cohort of adult patients (n = 21; n = 9 females, mean age 57 years) with biopsy-confirmed HN were selected from the Norwegian Kidney Biopsy Registry (NKBR). Patients were classified as late-stage if eGFR≤45 ml/min/1.73 m2 at the time of biopsy. Patients were thereafter divided into “stable” (eGFR decline <3 ml/min/year) or “progressive” (eGFR decline ≥3 ml/min/year or start of renal replacement therapy) after a median follow-up of 9 years (5-15). TruSeq Exome sequencing was performed post-RNA extraction (miRNeasy FFPE kit, Qiagen) at Novogene, Cambridge, UK. R Studio (v4.2.0) and drug CTD repository in ShinyGO 0.80 facilitated data and drug interaction analysis. Results We focused on two distinct subgroups of HN patients: late stable (LS, n = 9) and late progressive (LP, n = 12). A total of n = 674 of differentially expressed genes (DEG, p-value < 0.05 and fold change (FC) ≥1.5) was identified in LS vs. LP. The subsequent drug interactive analysis of these DEGs unveiled 336 pathways with false discovery rate (FDR) < 0.05. Notably, the probenecid-related pathway demonstrated significant fold enrichment (FE=9, FDR = 1.5E-04), as depicted in Fig. 1. Particularly, key members of the SLC22 family, including SLC22A6 (FC=2.49, p-value = 0.002), SLC22A8 (FC=2.65, p-value = 0.004), SLC22A11 (FC=1.65, p-value = 0.036) and SLC22A12 (FC=1.97, p-value = 0.009) were prominently featured in this pathway. Besides their role as sole transporters, it is postulated that these proteins have central role in modulating local and systemic physiology, such as blood pressure, suggesting a potential significance of probenecid in the context of hypertensive nephropathy. Conclusion Transcriptomic profiling of kidney biopsies has strong potential to discover novel therapeutic targets, such as the probenecid-related pathway, in hypertensive nephropathy patients.

WCN24-474 Dominican renal biopsy registry: 24 years of experience in the Caribbean

WCN24-474 Dominican renal biopsy registry: 24 years of experience in the Caribbean

The Impact of a Pandemic on a Military Oral and Maxillofacial Pathology Biopsy Service.

Coronavirus disease 2019 (COVID-19) and the resulting societal reaction presented new challenges to the medical community by limiting patient access to care in 2020 and 2021. The Navy Postgraduate Dental School (NPDS) oral and maxillofacial pathology biopsy service is dependent on in-office physician or dentist appointments and patient biopsies. The purpose of this study was to understand the regulatory and societal impacts of COVID-19 restrictions on biopsy service submissions by assessing NPDS biopsy submission quantities and disease distribution. All NPDS oral and maxillofacial pathology biopsy submissions from calendar years 2015 to 2016 and 2019 to 2021 were evaluated, and patient demographics and biopsy diagnoses were recorded in a biopsy registry. Data collected included age, sex, biopsy site, and diagnosis. Data from 2015, 2016, and 2019 were defined as pre-COVID and 2020 and 2021 as COVID. Biopsy reports for each year were organized in quarters. Diagnoses were categorized as malignant, pre-malignant, or benign. Categorical and continuous data were evaluated and presented as counts with percentages and means or medians with standard deviations, respectively. Significant differences in proportions or means were assessed using chi-square analysis or Student t-test, respectively. Cases were aggregated by quarter and year and assessed for temporal trends using linear regression analysis. The study evaluated 9,351 biopsy submission reports. The annual pre-COVID count mean (± standard deviation) and yearly counts for 2020 and 2021 were 2,063 ± 33.3, 1,421, and 1,742, respectively. The mean (± standard deviation) percentage of diagnoses classified as malignant from pre-COVID, 2020, and 2021 were 2.46 ± 0.005%, 3.59%, and 3.04%, respectively. Case counts and representation as a percentage of all biopsy diagnoses for Human Papillomavirus (HPV)-associated squamous cell carcinoma increased significantly during COVID compared to pre-COVID years (P < .05). Overall, preventative COVID-19 health measures and protocols resulted in a reduction in biopsy submission frequency, particularly during the second quarter (April to June) of 2020. However, case counts for malignant biopsies remained consistent between pre-COVID and COVID time intervals, suggesting that the identification and analysis of cases requiring follow-on care were unaffected by COVID-19 protocols.

Heterogeneous nuclear ribonucleoprotein F deficiency in mouse podocyte promotes podocytopathy mediated by methyltransferase-like 14 nuclear translocation resulting in Sirtuin 1 gene inhibition

Heterogeneous nuclear ribonucleoprotein F (HnRNP F) is a key regulator for nucleic acid metabolism; however, whether HnRNP F expression is important in maintaining podocyte integrity is unclear. Nephroseq analysis from a registry of human kidney biopsies was performed. Age- and sex-matched podocyte-specific HnRNP F knockout (HnRNP FPOD KO) mice and control (HnRNP Ffl/fl) were studied. Podocytopathy was induced in male mice (more susceptible) either by adriamycin (ADR)- or low-dose streptozotocin treatment for 2 or 8 weeks. The mouse podocyte cell line (mPODs) was used in vitro. Nephroseq data in three human cohorts were varied greatly. Both sexes of HnRNP FPOD KO mice were fertile and appeared grossly normal. However, male 20-week-old HnRNP FPOD KO than HnRNP Ffl/fl mice had increased urinary albumin/creatinine ratio, and lower expression of podocyte markers. ADR- or diabetic- HnRNP FPOD KO (vs. HnRNP Ffl/fl) mice had more severe podocytopathy. Moreover, methyltransferase-like 14 (Mettl14) gene expression was increased in podocytes from HnRNP FPOD KO mice, further enhanced in ADR- or diabetic-treated HnRNP FPOD KO mice. Consequently, this elevated Mettl14 expression led to sirtuin1 (Sirt1) inhibition, associated with podocyte loss. In mPODs, knock-down of HnRNP F promoted Mettl14 nuclear translocation, which was associated with podocyte dysmorphology and Sirt1 inhibition-mediated podocyte loss. This process was more severe in ADR- or high glucose- treated mPODs. Conclusion: HnRNP F deficiency in podocytes promotes podocytopathy through activation of Mettl14 expression and its nuclear translocation to inhibit Sirt1 expression, underscoring the protective role of HnRNP F against podocyte injury.

EPIDEMIOLOGY OF BIOPSY CONFIRMED GLOMERULONEPHRITIS IN THE REPUBLIC OF MOLDOVA: PILOT STUDY

Renal biopsy is an important tool for the diagnosis of renal pathologies and for the choice of subsequent treatment tactics. Objectives: To report the epidemiology of glomerulonephritis in the Republic of Moldova, based on histological diagnosis, and set up the premises for the creation of the National Renal Biopsy Registry. Material and methods: The histological results of percutaneous renal ultrasound-guided biopsies, performed from March 30 to February 19, 2023, were evaluated in the Timofei Moșneaga Republican Clinical Hospital, Chisinau. Demographic characteristics, paraclinical parameters (serum creatinine, serum urea, glomerular filtration rate, nictemeral protein), and histological results were analyzed. Results: The outcomes of kidney biopsies performed on fifty-three patients were examined. The prevalence of renal pathologies in young and mature adults was observed, with the average age being 46.2 years. Most of the examined patients were men (71.70%). The main indication for performing renal biopsy was nephrotic syndrome, present in 64.15% of patients. The most common types of primary glomerulonephritis were membranous glomerulonephritis (50% of cases) and membranoproliferative glomerulonephritis (20% of cases). The most frequent types of secondary glomerulonephritis were lupus nephropathy (40%) and renal amyloidosis (30%). Conclusions: This study provides the first image of the current spectrum of glomerular kidney disease in the Republic of Moldova. It also serves as the basis for the development of the National Renal Biopsy Registry, which can serve as a useful resource for health policy development

Preliminary Renal Biopsy Registry: Dominican Republic

Preliminary Renal Biopsy Registry: Dominican Republic

A New Mexico-Based Kidney Biopsy Registry Data Analysis

A New Mexico-Based Kidney Biopsy Registry Data Analysis

General prognostic models may neglect vulnerable subgroups in ANCA-associated vasculitis

BackgroundANCA-associated vasculitis is an organ and life-threatening disease with the highest incidence in elderly patients. However, few studies have focussed on characteristics and treatment outcomes in a direct comparison of elderly and younger patients.MethodsIn a retrospective, single-centre, renal biopsy-cohort, patients were dichotomized by age ≥ 65 years to analyse baseline clinical, histological, laboratory and immunological characteristics and outcome differences in elderly and younger patients as regard to mortality, renal recovery from dialysis and eGFR after two years.ResultsIn the biopsy registry, n = 774 patients were identified, of whom 268 were ≥ 65 years old. Among them, ANCA-associated vasculitis was the most prevalent kidney disease (n = 54 ≈ 20%). After a follow-up of 2 years, overall mortality was 13.4%, with 19% and 4% in patients ≥ and < 65 years of age, respectively. While 41% of elderly and 25% of younger patients were dialysis-dependent at the time of biopsy, renal recovery was achieved in 41% and 57% of patients, respectively. The accuracy of prediction differed significantly between the whole cohort and elderly patients as regard to mortality (sensitivity 46% vs. 90%, respectively) and between younger and elderly patients as regard to eGFR (r2 = 0.7 vs. 0.46, respectively). Age-group-wise analysis revealed patients above 80 years of age to have particularly dismal renal outcome and survival.ConclusionIn our cohort, ANCA-associated vasculitis is the single most frequent histopathological diagnosis among the elderly patients in our cohort. Elderly and younger patients have comparable chances of recovering from dialysis-dependent renal failure, with comparable residual independent kidney function after two years. This study suggests (1) relevant predictors differ between age groups and hence (2) models involving all patients with ANCA-associated vasculitis neglect important features of vulnerable subgroups, i.e., patients above 80 years old.Graphical abstract

Regional differences in the incidence of lymphocytic and collagenous colitis over time

Background In microscopic colitis (MC), the incidence has increased over the last decades. The aim of the present study was to determine the incidence of lymphocytic (LC) and collagenous colitis (CC) in the county Skåne (Scania), southern Sweden, during the period 2010–20 with focus both on the temporal and spatial variations. Methods The MC diagnosis was retrieved from the biopsy registries at the Departments of Pathology. Established diagnostic criteria (increased lymphocyte count, inflammation in lamina propria and in CC a collagen band) were used for diagnosis. Age, gender, date for diagnosis and municipality of residence were retrieved for all patients. Results In total 1985 patients could be identified with a mean age of 62.9 years (SD 15.7) whereof 1415 were women. The incidence for CC was stable with a total age-standardized rate (ASR) per 100 000 person-years of 6.34, (range 4.6–8.1). In LC the ASR was 7.90 (range 1.7–15.2) but increased markedly 2015–20 reaching 15.2 in 2019. Also, the northwest part of the region showed significantly higher ASR:s of LC during the last part of the decade in comparation to the whole region. Conclusions The incidence of CC was stable during the period while LC differed substantially in a way that indicates that it most probably must be two different disease entities. In LC, in view of the marked and rapid increase, although no definitive explanation could be found, causative environmental factors could be contemplated, why further studies are indicated.