Glomerular diseases最新文献

Introduction: Preeclampsia, a leading cause of morbidity during pregnancy, is associated with glomerular endotheliosis, fibrin deposition, and thrombotic microangiopathy and is characterized by edema, proteinuria, and acute kidney injury. Preeclampsia has been described on a background of glomerular disease membranous nephropathy, IgA nephropathy, and focal segmental glomerulosclerosis, but biopsy studies have also described the de novo diagnosis of glomerulopathy as thrombotic microangiopathy, endotheliosis or collapsing glomerulopathy in the setting of preeclampsia.

Case presentations: We report 3 cases of preeclampsia-associated collapsing focal and segmental glomerulosclerosis in the third trimester of gestation, two of which were previously healthy and one with a history of chronic hypertension that presented with nephrotic-range proteinuria without secondary causes detected. It was decided to begin with antiproteinuric treatment after delivery, resulting in a complete response without the need for immunosuppressant drugs. The outcomes of these cases suggest that a favorable evolution is expected once preeclampsia had resolved and therefore the glomerular changes had been reversed.

Conclusion: A subgroup of pregnant patients can be managed without exposing the mother-child pair to adverse effects related to immunosuppression when preeclampsia is detected in the third trimester of gestation.

Introduction: There are few descriptions of glomerular calcification in patients with advanced or end-stage kidney disease (ESKD). There also are limited data on long-term outcomes for patients receiving complement factor 5 inhibitor (C5i) treatment for complement-mediated thrombotic microangiopathy (CM-TMA), previously termed atypical hemolytic uremic syndrome, associated with a complement factor I (CFI) mutation.

Case presentation: Here we report a case of ESKD from CM-TMA in a patient who developed tertiary hyperparathyroidism. Due to cerebral symptoms (focal paresthesias) of TMA, he received long-term treatment with a C5i. A nephrectomy subsequently was performed for renal cell carcinoma and showed diffuse glomerular, in addition to focal arterial and tubular basement membrane, calcification. There also was chronic TMA associated with continued C5i treatment, with no evidence of recurrent thrombosis consistent with quiescent systemic TMA activity.

Conclusion: Glomerular calcification is rare, and it is unknown if this is related to the treated hyperparathyroidism or other pathogenetic mechanisms. The nephrectomy findings also suggest that patients with pathogenic mutations in CFI may benefit from long-term, likely lifelong, complement inhibitory treatment.

Introduction: Patients with complement 3 glomerulopathy (C3G) have poor clinical outcomes, although new targeted therapies have very recently been approved. Here, we describe the burden and management of C3G in global clinical practice.

Methods: Retrospective analysis of data obtained from a cross-sectional survey (Adelphi Real World C3G Disease Specific Programme™) of nephrologists actively managing C3G (N = 195) and their patients (N = 385) in France, Germany, Italy, Spain, the UK (EU5), the USA, China, and Japan (July 2022-April 2023). Information on patient demographics, clinical characteristics, diagnosis journey, treatment patterns, dialysis and kidney transplant information, and patient-reported outcomes was collected from nephrologist-completed patient record forms (PRFs) and patient self-completion forms (PSCFs). Results were reported using descriptive statistics.

Results: Records for 385 patients with C3G were completed by 129 nephrologists. Most patients had moderate to severe disease at the time of diagnosis (85.1%), based on individual nephrologist assessment. At the time of PRF completion, 83.4% of patients were receiving pharmacological treatment, which included angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (70.4%) and corticosteroids (48.6%). In patients receiving treatment, proteinuria remained the most common nephrologist-reported sign of C3G (66.0%), irrespective of treatment duration; of patients with available data, 68.9% had proteinuria ≥1 g/day. At the time of PRF completion, 8.3% of patients were on dialysis, 41.6% of patients were considered eligible for a kidney transplant, and 6.5% were transplant recipients. Patients experienced anxiety/depression (73.7%), pain/discomfort (65.3%), fatigue (90.7%), and problems doing usual activities (62.7%) at the time of PSCF completion.

Conclusion: Despite most patients receiving current guideline-recommended standard of care, the burden of C3G remains high worldwide, demonstrating the need for more effective treatment options. In addition, most patients presented with advanced disease by the time of diagnosis, warranting a need to address significant diagnostic delays to facilitate earlier therapeutic intervention.

Background: Tropical regions, home to nearly 40% of the world's population, face a high burden of infectious diseases due to climate, socioeconomic factors, and limited healthcare access. Many tropical infections - including malaria, dengue, leptospirosis, schistosomiasis, filariasis, scrub typhus, and human immunodeficiency virus (HIV) - have been increasingly recognized as causes of glomerular disease. These infections can directly or indirectly affect the kidney, resulting in a diverse spectrum of glomerular pathologies.

Summary: This review highlights the epidemiology, clinical manifestations, pathophysiology, and renal histopathological findings associated with major tropical infections that involve the glomeruli. It describes how parasitic, bacterial, and viral pathogens trigger immune-mediated glomerular injury, contribute to acute kidney injury, or lead to chronic kidney disease. Specific glomerular lesions, including mesangioproliferative glomerulonephritis (GN), membranoproliferative GN, focal segmental glomerulosclerosis, and HIV-associated nephropathy, are detailed with mechanistic insights. The article also discusses diagnostic challenges; therapeutic approaches, including antiparasitic and antiretroviral therapy; and the role of preventive strategies such as vaccination, vector control, and mass drug administration.

Key message: Tropical infections are increasingly recognized as important yet underappreciated contributors to glomerular disease, particularly in low-resource settings. Early recognition and timely targeted treatment of infection-related GN can significantly reduce the risk of long-term kidney damage. To effectively mitigate the kidney disease burden, comprehensive public health measures - including enhanced surveillance, vaccination initiatives, and integrated vector control strategies - are essential.

Introduction: Immune checkpoint inhibitors have significantly improved the prognosis of patients with certain malignancies; however, they can also be associated with diverse autoimmune organ toxicities, including those affecting the kidney.

Case presentation: A 75-year-old man was referred to the nephrology team with a progressive decline in kidney function over a 3-month period. His medical history included a diagnosis of non-small cell lung cancer for which he had been treated with pembrolizumab immunotherapy for the past 18 months (15 cycles). At referral, serum creatinine had risen from a baseline of 140 µmol/L to 208 µmol/L. Urinalysis showed blood and protein, and his urine protein creatinine ratio was 457 mg/mmol. An autoimmune screen yielded a positive anti-glomerular basement membrane (anti-GBM) antibody result (23 IU/L, normal range <7). He underwent a kidney biopsy. Light microscopy demonstrated focal and necrotising crescentic glomerulonephritis and eosinophilic tubulointerstitial nephritis. Immunofluorescence revealed linear IgG deposition along glomerular basement membranes. The patient did not have any clinical or radiographic evidence of pulmonary haemorrhage. A diagnosis of anti-GBM glomerulonephritis was made, and the patient received treatment with corticosteroids, seven cycles of plasma exchange, oral cyclophosphamide (total dose 3.3 g) and two intravenous doses of 1 g rituximab. The patient achieved a negative anti-GBM status within 1 week of presentation. Despite treatment for anti-GBM disease and cessation of pembrolizumab, his kidney function continued to decline, and his cancer progressed. Six months after diagnosis, he presented unwell to the hospital and received treatment for a presumed chest infection. Unfortunately, his condition deteriorated during this inpatient stay, and he passed away peacefully (6.7 months after induction treatment).

Conclusion: This case demonstrates a rare but important diagnosis of anti-GBM disease during pembrolizumab therapy. It highlights the challenges of managing immunosuppression and chemotherapy options in patients who are frail and with impaired kidney function.

Introduction: Punctate IgG staining of podocytes ("dusting") identified by immunofluorescence recently has been described in a subset of minimal change disease (MCD), possibly correlating with anti-nephrin or other autoantibodies. Whether dusting is associated with other clinicopathologic features of MCD remains unclear, but identification of these associations could provide insight into MCD mechanisms, prognosis, and therapeutic strategies.

Methods: Cases with a diagnosis of MCD over 8.5 years at one institution were retrospectively reviewed, including reexamination of IgG immunofluorescence and electron microscopy when necessary. Demographic, clinical, and ultrastructural feature data were collected. Cases were divided into presumed primary and secondary MCD based on clinical associations and they were assessed for dusting frequency.

Results: A total of 371 cases were included, of which 73% were primary MCD and 16.4% were pediatric. Dusting frequency among MCD etiologies ranged from 45 to 63% and did not differ between children and adults, or in primary versus any secondary MCD association. Dusting was positively correlated with the degree of podocyte foot process effacement (p < 0.005) and actin cytoskeletal condensation (p = 0.001). Otherwise, dusting was not associated with other ultrastructural features of proteinuric kidney disease or with podocyte ballooning clusters.

Conclusion: Podocyte IgG dusting was not specific for any one etiologic trigger of MCD or age category. This suggests that autoantibodies may induce MCD irrespective of a primary (idiopathic) versus a presumed secondary cause, which may alter the diagnostic and therapeutic approach. Additionally, podocyte ultrastructural features associated with dusting may reflect mechanisms of autoantibody-induced injury, or may represent a feature of disease severity and/or temporal progression.

Introduction: Lupus nephritis (LN) is kidney inflammation that commonly occurs from systemic lupus erythematosus. NF-κB activity is increased in LN patients, leading to elevated circulating concentrations of immune modulators that contribute to LN pathophysiology. This study sought to investigate this phenomenon with the aim of discovering novel serum biomarkers for LN.

Methods: A multiplex antibody-based assay was performed with serum from 24 LN patients and 7 healthy controls (HCs) to determine if 48 NF-κB-regulated proteins were elevated in LN patients. Confirmation ELISAs were performed on stem cell factor (SCF), macrophage colony-stimulating factor (M-CSF), and interleukin-2 receptor alpha (IL-2Rα) subunit in a separate sample cohort of 27 LN patients and 10 HC. Follow-up ELISAs were performed on samples obtained from the same patients during LN remission to determine if these candidates were reliable predictors of disease activity. Comparisons of protein levels between LN patients and HC were performed using a series of 2-tailed Mann-Whitney tests. Paired samples were analyzed using a Wilcoxon matched pairs test. Two-tailed Spearman's correlation analyses were used to compare serum protein concentrations with LN clinical parameters. All p values were adjusted for multiple comparisons.

Results: SCF, M-CSF, and IL-2Rα were significantly elevated in LN serum. Elevated serum SCF and M-CSF were significantly correlated with elevated urine protein to creatinine ratio, decreased estimated glomerular filtration rate, and elevated serum creatinine. Elevated serum IL-2Rα was significantly correlated with elevated serum creatinine. Serum SCF concentration was significantly decreased during LN remission in paired samples from individuals, but it was not a good predictor at the population level (AUC = 0.6265).

Conclusion: We identified the NF-κB-regulated proteins SCF, M-CSF, and IL-2Rα as candidate serum biomarkers for consideration in monitoring LN activity. Our findings also indicate the importance for follow-up mechanistic studies pertaining to these inflammatory mediators.

Introduction: Intraglomerular malignancy (IGM) is a rare finding, with current data limited to case reports and small, often postmortem, series. This study aimed to characterize the clinicopathologic features of kidney biopsy cases with IGM.

Methods: Renal biopsy cases diagnosed with IGM from January 2000 to June 2023 at Cedars Sinai Medical Center were retrospectively reviewed. Demographic data, clinical characteristics, and pathologic data were collected, and cases were divided into hematologic (HEME) versus non-hematologic (non-HEME) malignancy.

Results: We identified 9 patients with IGM. Five were hematolymphoid in origin, and 4 were from metastatic solid tumor (2 carcinomas from the lung, 1 neuroendocrine tumor of likely lung origin, and 1 from the head and neck). All patients presented with proteinuria and hematuria, and 89% had renal dysfunction. The median serum creatinine was 2.9 (IQR 1.7-5.7) mg/dL. All non-HEME patients had an established malignant diagnosis at the time of kidney biopsy, whereas all HEME cases were initially or concurrently diagnosed at the time of biopsy. Two of the non-HEME biopsies showed extracapillary hypercellularity due to malignant cells, a feature not seen in HEME cases. Of the 8 patients with follow-up available, 7 (88%) died within a median of 69 (IQR 4-161) days.

Conclusion: IGM is a rare presentation of disseminated malignancy, often indicating advanced disease with poor prognosis. Nephropathologists should be aware of IGM as a histologic mimicker of endocapillary hypercellularity or cellular crescent formation. Similarly, the provision of complete clinical history is critical for accurate biopsy assessment and to avoid this diagnostic pitfall. Given its high mortality rate and the short interval between tissue diagnosis and death, the identification of IGM should prompt urgent medical attention.

Introduction: According to the Brazilian Dialysis Survey 2022 glomerular diseases are among the three main causes of chronic kidney disease in the elderly. The distribution and presentation of such kidney diseases specifically in elderly need additional and more recent data in Brazil.

Methods: Retrospective analysis of 613 native kidney biopsies from patients aged 60 years and above, in a single center, of the five regions of Brazil, performed from 2015 to 2020.

Results: Most patients were males with a mean age of 67.5 years. Nephrotic syndrome (NS) was the main clinical indication (52.4%), followed by asymptomatic urinary abnormalities (AUA, 21.4%), rapidly progressive glomerulonephritis (RPGN, 10.1%), and acute renal failure (ARF, 6.1%). In the group aged 80 years and over, indications were significantly increased due to acute conditions (ARF and RPGN) compared to other groups. Membranous nephropathy (MN) was the most common histopathological diagnosis, followed by pauci-immune glomerulonephritis (PIGN, 12.7%) and diabetic nephropathy (DN, 10.3%). DN was more frequent in the younger elderly, amyloidosis between 70 and 79 years old, and PIGN in those aged 80 or older. Younger men had higher frequencies of IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS); younger women had more PIGN, amyloidosis, and minimal change disease (MCD); 80 or more women had more PIGN and chronic glomerulonephritis. The clinical presentation of NS was mainly associated with the histopathological findings of MN and MCD. AUA was more associated with MN and IgAN.

Conclusion: In this study, the NS was the most frequent clinical presentation, and the most common histopathological finding was MN. We observed differences in glomerular disease frequencies between genders and age-groups in the elderly. Considering our findings, we emphasize the importance of kidney biopsy in this age-group due to the potential for improvement with specific treatments.

Introduction: Among patients with proteinuric glomerular diseases, there is a paucity of high-quality evidence and substantial variation in practice patterns among nephrologists. Our objective was to describe the clinical presentation, treatment patterns, and outcomes of patients with biopsy-proven glomerular diseases in a contemporary, well-phenotyped, diverse cohort.

Methods: The Nephrotic Syndrome Study Network (NEPTUNE) is a prospective observational cohort study of children and adults with proteinuric glomerular diseases enrolled at 23 centers in the USA and Canada since 2009. We included participants who underwent their first clinically indicated kidney biopsy demonstrating minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or membranous nephropathy (MN). We described demographic and clinical characteristics at the time of biopsy and baseline visits. We analyzed treatment patterns for participants with and without immunosuppressive therapy (IST) use prior to biopsy. We described clinical outcomes including complete remission (CR) and proteinuria, stratified by IST use, at biopsy and up to 36 months' follow-up.

Results: Among 507 NEPTUNE participants who underwent biopsy, 203 were classified as having FSGS, 193 as having MCD, and 111 as having MN. Corticosteroid exposure was high overall and highest among MCD patients. Substantial heterogeneity in treatment choices was evident, particularly among those initiating second-line therapy. The rate of kidney failure was highest, and CR rates were lowest, among patients with FSGS, who experienced ∼50% cumulative probability of first remission at 36 months after biopsy. At 36 months, 49.5% of all patients were not in CR; 19.3% were not in CR despite being on IST. Additionally, 20.2% of patients had proteinuria >1.5 g/g; among those on IST at their 36-month visit, 26.3% had UPCR >1.5 g/g.

Conclusion: A substantial proportion of patients were not in remission and had persistent proteinuria despite being on IST 3 years after their first biopsy.