COVID-19-associated acute renal failure in critically ill patients correlates with microthrombosis and renal loss of thrombomodulin (preprint)

Critically ill COVID-19 patients have a high degree of acute kidney injury which develops in up to 85% of patients. We have previously shown that circulating levels of angiopoietin-2 increased in critically ill COVID-19 patients correlated to kidney injury, coagulopathy, and mortality. Furthermore, our experiments showed a causal effect on coagulopathy from angiopoietin-2 binding and inhibition of thrombomodulin mediated anticoagulation. In the current study we hypothesize that renal microthrombi may be a mechanism for reduced renal function in critically ill COVID-19 patients, and that local dysregulation of thrombomodulin and angiopoietin-2 may be involved. To investigate our hypothesis, we utilized postmortem kidney tissue from seven COVID-19 patients treated at the intensive care unit. We evaluated kidney function, thrombosis, tubular injury, fibrosis, glomerulosclerosis, glomerular size as well as renal expression of thrombomodulin and angiopoietin-2. Proximity ligation assay was utilized to evaluate the presence of angiopoietin-2 binding to thrombomodulin. Normal kidney tissue came from the healthy part of six nephrectomies due to cancer. Our experiments show renal thrombosis in 6/7 COVID-19 patients, on average 14.7 (6.9-22.5) thrombi per mm2. Most COVID-19 kidneys had extensive kidney injury, especially tubular necrosis, but also glomerular enlargement, glomerulosclerosis, and tubulointerstitial fibrosis which in some cases most likely resulted from underlying disease. Thrombomodulin expression was reduced in glomeruli and peritubular capillaries in kidneys from COVID-19 patients, whereas no change was found for angiopoietin-2. In summary, our study describes a high degree of acute renal failure, renal microthrombosis, and loss of thrombomodulin in postmortem tissue from critically ill COVID-19 patients.

IFIH1 loss-of-function predisposes to inflammatory and SARS-CoV-2-related infectious diseases (preprint)

The IFIH1 gene, encoding melanoma differentiation-associated protein 5 (MDA5), is an indispensable innate immune regulator involved in the early detection of viral infections. Previous studies described MDA5 dysregulation linking it to weakened immunological responses, and increased susceptibility to microbial infections and autoimmune disorders. Monoallelic gain-of-function of the IFIH1 gene has been associated with multisystem disorders, namely Aicardi-Goutieres and Singleton-Merten syndromes, while biallelic loss of this gene causes immunodeficiency. In this study, nine patients suffering from different cases of recurrent infections, inflammatory diseases, severe COVID-19, or multisystem inflammatory syndrome in children (MIS-C) were identified with putative loss-of-function IFIH1 variants by whole exome sequencing. All patients revealed signs of lymphopenia and an increase in inflammatory markers, including CRP, amyloid A, ferritin, and IL-6. One patient with a pathogenic homozygous variant c.2807+1G>A was the most severe case showing immunodeficiency and glomerulonephritis. The c.1641+1G>C variant was identified in the heterozygous state in patients suffering from periodic fever, COVID-19, or MIS-C, while the c.2016delA variant was identified in two patients with inflammatory bowel disease or MIS-C. Expression analysis showed that PBMCs of one patient with a c.2016delA variant had a significant decrease in ISG15, IFNA and IFNG transcript levels, compared to normal PBMCs, upon stimulation with poly(I:C), suggesting that MDA5 receptor truncation disrupts the immune response. Our findings accentuate the implication of rare monogenic IFIH1 loss-of-function variants in altering the immune response, and severely predisposing patients to inflammatory and infectious diseases, including SARS-CoV-2 related disorders.

Rapidly progressive IgA nephropathy with membranoproliferative glomerulonephritis-like lesions in an elderly man following the third dose of an mRNA COVID-19 vaccine: a case report.

BACKGROUND: As messenger RNA (mRNA)-based vaccines for coronavirus disease 2019 (COVID-19) have been administered to millions of individuals worldwide, cases of de novo and relapsing glomerulonephritis after mRNA COVID-19 vaccination are increasing in the literature. While most previous publications reported glomerulonephritis after the first or second dose of an mRNA vaccine, few reports of glomerulonephritis occurring after the third dose of an mRNA vaccine currently exist. CASE PRESENTATION: We report a case of rapidly progressive glomerulonephritis in a patient following the third dose of an mRNA COVID-19 vaccine. A 77-year-old Japanese man with a history of hypertension and atrial fibrillation was referred to our hospital for evaluation of anorexia, pruritus, and lower extremity edema. One year before referral, he received two mRNA vaccines (BNT162b2) for COVID-19. Three months before the visit, he received a third mRNA vaccine (mRNA-1273) for COVID-19. On admission, the patient presented severe renal failure with a serum creatinine level of 16.29 mg/dL, which had increased from 1.67 mg/dL one month earlier, prompting us to initiate hemodialysis. Urinalysis showed nephrotic-range proteinuria and hematuria. Renal biopsy revealed mild mesangial proliferation and expansion, a lobular appearance, and double contours of the glomerular basement membrane. Renal tubules had severe atrophy. Immunofluorescence microscopy showed strong mesangial staining for IgA, IgM, and C3c. Electron microscopy exhibited mesangial and subendothelial electron-dense deposits, leading to a diagnosis of IgA nephropathy with membranoproliferative glomerulonephritis-like changes. The kidney function remained unchanged after steroid therapy. CONCLUSIONS: Although the link between renal lesions and mRNA vaccines remains unclear, a robust immune response induced by mRNA vaccines may play a role in the pathogenesis of glomerulonephritis. Further studies of the immunological effects of mRNA vaccines on the kidney are warranted.

De Novo Crescentic Glomerulonephritis Following COVID-19 Infection: A Pediatric Case Report.

As the global coronavirus disease 2019 (COVID-19) pandemic continues to sweep across the globe, reports of kidney involvement in adult patients infected with COVID-19 have been documented, and recently, cases in the pediatric population have also been reported. This report highlights the case of an 11-year-old boy who developed acute kidney injury presenting as gross hematuria, proteinuria, and hypertension immediately after a COVID-19 infection. A renal biopsy allowed us to diagnose the patient with post-COVID-19 infection-associated de novo crescentic immune-mediated glomerulonephritis. Oral prednisolone and cyclophosphamide treatments were initiated after methylprednisolone pulse therapy administration. Currently, the patient is receiving medical treatment for five weeks, and his renal function is gradually recovering. Previous studies have suggested that, although quite rare, a variety of kidney complications can occur after COVID-19 infection or vaccination, and it is recommended to monitor renal function through evaluation. Herein, we report a pediatric case of post-COVID-19 infection-associated de novo crescentic immune-mediated glomerulonephritis consistent with rapidly progressive glomerulonephritis.

Coronavirus disease 2019-associated nephropathy in an African American patient: a case report and review of the literature.

BACKGROUND: Acute kidney injury is now recognized as a common complication of coronavirus disease 2019, affecting up to 46% of patients, with acute tubular injury as the most common etiology. Recently, we have seen an increase in cases of collapsing glomerulonephritis in patients with coronavirus disease 2019, also known as coronavirus disease 2019-associated nephropathy. It has been noted to be seen with a higher incidence in African American patients who are carriers of the APOL1 variant allele. CASE PRESENTATION: A 47-year-old African American male with a past medical history of asthma presented to the emergency department with complaints of intermittent chest pain, shortness of breath, and worsening confusion. On admission, he was found to be hemodynamically stable, but labs were significant for elevated creatinine and blood urea nitrogen, signifying acute kidney injury. He was admitted and taken for emergent dialysis. During his hospitalization, he was found to be positive for coronavirus disease 2019. Renal biopsy was done, which showed collapsing glomerulopathy, and the patient continues to require outpatient dialysis after discharge. CONCLUSION: Collapsing glomerulonephritis has emerged as a complication in patients with coronavirus disease 2019. This condition should be particularly suspected in African American patients who present with acute kidney injury, nephrotic-range proteinuria, and who are positive for coronavirus disease 2019. Current treatment options are limited to supportive treatment and renal replacement therapy. More clinical cases and trials are needed to better understand and improve therapeutic outcomes in these patients.

An unusual form of kidney injury without glomerulonephritis in microscopic polyangiitis: a case report.

BACKGROUND: Microscopic polyangiitis (MPA), a kind of antineutrophil cytoplasmic autoantibody associated vasculitis (AAV), predominantly affects small-sized vessels. MPA is a significant cause of the pulmonary-renal syndrome. Pauci-immune necrotizing and crescentic glomerulonephritis is the typical renal histological feature of AAV. Tubulointerstitial lesions may occur and mostly form with inflammatory cell infiltration in the interstitium. However, a few cases reported only tubulointerstitial involvement without glomerular lesions in patients with MPA. CASE PRESENTATION: We present an MPA case, a 70-year-old male patient diagnosed with acute kidney injury accompanying the dialysis requirement. Only acute tubulointerstitial nephritis was revealed in kidney biopsy without evidence of glomerular injury. Also, interstitial pulmonary fibrosis was determined on computerized tomography, and myeloperoxidase antineutrophil cytoplasmic autoantibody was positive. Consequently, we have considered the main diagnosis as MPA. We did not prefer a standard tubulointerstitial nephritis treatment regimen due to the presence of life-threatening systemic vasculitis. Treatment was established like crescentic glomerulonephritis. Induction therapy consisted of pulse steroid, cyclophosphamide, and plasmapheresis. Unfortunately, severe SARS-CoV-2 infection caused death during induction therapy in this case. CONCLUSIONS: The lack of glomerular injury and solely interstitial inflammation is atypical regarding AAV involvement in the kidney. This diversity might be initially considered as only a simple histological elaboration. However, it is a significant entity for guiding the treatment of AAV.

Glomerulonephritis associated with systemic sclerosis: a case report.

BACKGROUND: Systemic sclerosis is a multiorgan autoimmune disease that can overlap with other rheumatologic disorders; however, co-occurrence with antineutrophil cytoplasmic antibody-associated vasculitis is rare. CASE PRESENTATION: A 39-year-old Persian female patient with systemic sclerosis according to American College of Rheumatology/European League Against Rheumatism 2013 criteria with a disease duration of 6 years was admitted to the hospital due to a rise in creatinine level in July 2021. She had complaints of nasal speech and feeling of nasal perforation. The first symptoms of antineutrophil cytoplasmic antibody-associated vasculitis had started 5 years earlier with palpable purpura in the lower limbs, hemoptysis, and positive perinuclear (p)-antibody-associated vasculitis level (> 300 AU/mL). Still, the diagnosis was not achieved due to the patient's reluctance to undergo a biopsy. She was treated with azathioprine (150 mg/day) and prednisolone (10 mg/day) during the 5-year follow-up. Her renal biopsy results showed cortical renal tissue with a cellular crescent in more than 50% of the specimen, rupture of the Bowman capsule and the glomerular basement membrane, peri-glomerular inflammation, and mild tubular atrophy in microscopic examinations. The immunofluorescence study resulted in a granular pattern of immune deposits along the glomerular basement membrane, mesangial tissue, and tubular basement membranes. CONCLUSION: We reported a rare case of comorbid systemic sclerosis and antineutrophil cytoplasmic antibody-associated vasculitis with nasal perforation. Her renal biopsy showed immune deposits along the glomerular basement membrane, mesangial tissue, and tubular basement membranes. Overlapping with other collagen vascular diseases can occur in rheumatology patients with uncommon manifestations. In systemic sclerosis, renal involvement in the form of glomerulonephritis is infrequent, and comorbid systemic lupus erythematosus or antineutrophil cytoplasmic antibody-associated vasculitis should be considered.

The presentation, etiologies, pathophysiology, and treatment of pulmonary renal syndrome: A review of the literature.

Pulmonary renal syndrome (PRS) is a constellation of different disorders that cause both rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage. While antineutrophil cytoplasmic antibody associated vasculitis and anti-glomerular basement membrane disease are the predominant causes of PRS, numerous other mechanisms have been shown to cause this syndrome, including thrombotic microangiopathies, drug exposures, and infections, among others. This syndrome has high morbidity and mortality, and early diagnosis and treatment is imperative to improve outcomes. Treatment generally involves glucocorticoids and immunosuppressive agents, but treatment targeted to the underlying disorder can improve outcomes and mitigate side effects. Familiarity with the wide range of possible causes of PRS can aid the clinician in workup, diagnosis and early initiation of treatment. This review provides a summary of the clinical presentation, etiologies, pathophysiology, and treatment of PRS.

Renal biopsy in systemic infections: expect the unexpected.

Infection-related glomerulonephritis is well recognized in patients with ongoing infections. It can be missed, however, if the infection is unusual or undetected. We present three cases where the renal biopsy findings prompted the identification or treatment of systemic infections.Case 1: A 84-year-old male presented with acute kidney injury (AKI) and IgA vasculitis on skin biopsy. A renal biopsy showed active glomerulonephritis with abundant neutrophils and predominantly mesangial immune complex deposits containing IgA. The findings prompted an infectious workup which was positive for COVID-19, suggesting exacerbation of IgA nephropathy by recent COVID-19 infection. Case 2: A 31-year-old female status post kidney transplant for granulomatosis with polyangiitis (GPA) had recent pregnancy with preterm delivery, disseminated herpes simplex virus (HSV) infection with HSV hepatitis, E. coli on urine culture, and AKI. A renal biopsy showed proliferative glomerulonephritis with subendothelial and mesangial immune complex deposits containing IgG and C3. The findings were most consistent with infection-related immune complex glomerulonephritis, most likely HSV-related. Case 3: A 78-year-old female presented with AKI, proteinuria, hematuria, and positive p-ANCA. Clinically, ANCA vasculitis was suspected, and renal biopsy did show focal, segmental, necrotizing glomerulonephritis. However, immunofluorescence and electron microscopy showed IgM-rich deposits in the mesangium. The unusual presentation prompted an infectious workup including a Bartonella antibody panel which showed very high titers, suggesting Bartonella endocarditis.Infection-related glomerulonephritis has a wide variety of presentations histologically and clinically. The three cases we present here emphasize the importance of recognizing these entities to help guide treatment and improve patient care.

Anti-glomerular Basement Membrane Disease Concomitant with MPO-ANCA Positivity Concurrent with High Serum Levels of Interleukin-26 Following Coronavirus Disease 2019 Vaccination.

As coronavirus disease 2019 (COVID-19) vaccine booster campaigns progress worldwide, new reports of complications following COVID-19 vaccination have emerged. We herein report a case of new-onset anti-glomerular basement membrane (GBM) disease concomitant with myeloperoxidase-antineutrophil cytoplasmic antibody positivity concurrent with high levels of interleukin (IL)-26 following the second dose of the Pfizer-BioNTech COVID-19 vaccine. The temporal association with vaccination in this case suggests that an enhanced neutrophilic immune response through IL-26 may have triggered necrotizing glomerulonephritis and a T-cell-mediated immune response to GBMs, leading to the development of anti-GBM antibodies, with an enhanced B-cell response after the vaccination triggering anti-GBM IgG and the onset of anti-GBM disease.

Diffuse proliferative glomerulonephritis in a patient with COVID-19 infection.

COVID-19 primarily presents with respiratory involvement. Extrapulmonary manifestations as the sole manifestation also occur although rare. The kidney, being one of the organs with the greatest number of ACE receptors, is usually reported as part of multiorgan involvement. We report an early adolescent boy who presented with nephrotic-nephritic syndrome with severe kidney dysfunction from COVID-19 infection. He had low C3 and undetected antineutrophil cytoplasmic antibodies, antinuclear antibody and antistreptolysin O. Kidney biopsy revealed findings consistent with diffuse proliferative glomerulonephritis with a focal glomerular crescent formation and thin basement nephropathy. Due to the rapidly progressive deterioration of kidney function, he was given pulse methylprednisolone therapy followed by oral prednisone. Complete recovery was documented 12 weeks after the onset of post-infectious glomerulonephritis. The possible pathogenesis of glomerulonephritis in a patient with COVID-19, its differential diagnosis and treatment are discussed.

Sibling cases of gross hematuria and newly diagnosed IgA nephropathy following SARS-CoV-2 vaccination.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has become a major part of the strategy to reduce Coronavirus disease 2019 (COVID-19) numbers worldwide. To date, vaccinations based on several mechanisms have been used clinically, although relapse of existent glomerulonephritis presenting as gross hematuria, and occurrence of de novo glomerulonephritis have been reported. CASE PRESENTATION: We report the first sibling cases newly diagnosed as immunoglobulin A (IgA) nephropathy after the second dose of SARS-CoV-2 vaccination. 15- and 18-year-old men presented with gross hematuria following the second dose of SARS-CoV-2 vaccine (Pfizer, BNT162b2) received on the same day. Pathological findings of each kidney biopsy specimen were consistent with IgA nephropathy. Gross hematuria in both cases spontaneously recovered within several days. CONCLUSIONS: These cases indicate that SARS-CoV-2 vaccination might trigger de novo IgA nephropathy or stimulate its relapse, and also highlight the necessity of understanding the immunological responses to the novel mRNA vaccines in patients with kidney diseases.

Glomerulonephritides associated with infections.

Glomerulonephritides associated with infections constitute an important group of diseases. Their occurrence is shifting from children and young people to elderly people. The rates of acute post-streptococcal glomerulonephritis, a condition with a good prognosis, are decreasing, and the rates of glomerulonephritides associated with various bacterial, viral, or parasitic infections, often with a poor prognosis, are increasing. Renal biopsy plays an important role in the diagnostic process. Manifestations of glomerulonephritis can be the initial sign of an occult infection. When evaluating renal biopsy specimens, certain signs may suggest this option, but it cannot be relied on completely. The search for an active infection is warranted in every patient with newly diagnosed glomerulonephritis. Hepatitis B and C serology is always performed, with other investigations depending on individual risk factors, clinical manifestations, and laboratory and histological findings. Failure to follow this rule may have serious consequences, in part because immunosuppressive therapy for glomerulonephritis can worsen the underlying infection and also because the progressive nature of parainfective glomerulonephritis cannot be reversed without eliminating the causative infection. Distinguishing between parainfective and autoimmune glomerulonephritis can be difficult, as there are no major differences in clinical manifestations, laboratory, and sometimes even histological findings. In the setting of the Czech Republic, important diseases include, in particular, staphylococcus infection-associated glomerulonephritis (SAGN) and, in general, infective endocarditis-associated glomerulonephritis, shunt nephritis, and other cases associated with foreign-material infection, such as catheters or electrodes. Among viral diseases, glomerulonephritides associated with the hepatitis B virus, hepatitis C virus, and the SARS CoV-2 virus are of major significance. The treatment of parainfectious glomerulonephritides involves elimination of the causative infection; only in rare cases, a combination of anti-infective treatment and mild immunosuppression can be indicated.

Relapse of Monoclonal Gammopathy of Renal Significance after mRNA Covid-19 vaccination: a case report (preprint)

Introduction This case report represents, to our knowledge, the first suspected case of Light Chain Deposition Disease (LCDD) relapse associated with mRNA COVID-19 vaccination. It must be made clear that timing is the only link between the vaccination and the relapse of LCDD, and since millions of individuals received these vaccines, an event like this may be due to chance. At the same time, this case report may be an entry point into further explorations of the pathogenesis of LCDD, given the mechanism of action of the vaccine and the pathophysiology of the disease, as it is currently understood. Case presentation The 75-year-old female patient of Greek ethnicity was admitted into our clinic for the investigation of worsening renal function that was detected on routine lab examinations two weeks after she received the second dose of the moderna COVID vaccine (mRNA-1273). Rapidly progressive glomerulonephritis and anemia were the most notable findings upon admission. She had a history of Light Chain Deposition Disease (LCDD) which had remained stable under management for four years. Serum protein electrophoresis was performed and showed monoclonal kappa zones, while bone marrow biopsy revealed 5% plasma cell infiltration. All the above, along with other investigations, established the diagnosis of LCDD recurrence. She was started on chemotherapy, which improved her immunological profile but not her renal function. The patient has remained on hemodialysis since. Conclusions The association between mRNA vaccinations and LCDD relapse may be ground for investigations into the pathophysiology of MGRS, given the patient’s previous long-term remission. In this context, we want to stress once again the importance of following standardized routine mandates on COVID vaccination, especially in immunocompromised patients. This case report is not intended to directly inform changes in clinical practice.

Renal Biopsy Diagnosis of Acute Tubular Injury After Pfizer-BioNTech COVID-19 Vaccination: A Case Report (preprint)

Recently, there have been reports of new cases of acute kidney injury (AKI) after coronavirus disease 2019 (COVID-19) vaccination. Podocytic damage, IgA nephropathy, vasculitis, tubulointerstitial damage, and thrombotic microangiopathy have been reported as the causes. However, there are no reports of acute tubular injury (ATI) as the sole cause of AKI. In this case, a 54-year-old man with type 2 diabetes visited a local physician. He was highly obese with a body mass index of 36 kg/m2. He was treated with metformin and insulin. Diabetic retinopathy, urinary protein, and occult blood were absent. He had received four COVID-19 vaccines; three were from Pfizer and one from Moderna. He was referred to our hospital 5 days after receiving the fourth dose of the Pfizer-BioNTech COVID-19 vaccine. He had stage 3 AKI. Urinary findings revealed the presence of new proteinuria and glomerular occult blood. Steroids were introduced on the day of admission for rapidly progressive glomerulonephritis. A renal biopsy was performed on the second day, with results obtained on the fifth day revealing no findings other than ATI. The patient was therefore deemed unamenable to steroids. After steroid discontinuation, renal function recovered spontaneously, and urinalysis abnormalities disappeared. In this case, ATI was the sole pathogenesis of COVID-19 vaccine-induced AKI, and treatment with immunosuppressive drugs was not necessary.

Incidence of new onset glomerulonephritis after SARS-CoV-2 mRNA vaccination is not increased.

Numerous cases of glomerulonephritis manifesting shortly after SARS-CoV-2 vaccination have been reported, but causality remains unproven. Here, we studied the association between mRNA-based SARS-CoV-2 vaccination and new-onset glomerulonephritis using a nationwide retrospective cohort and a case-cohort design. Data from all Swiss pathology institutes processing native kidney biopsies served to calculate incidence of IgA nephropathy, pauci-immune necrotizing glomerulonephritis, minimal change disease, and membranous nephropathy in the adult Swiss population. The observed incidence during the vaccination campaign (January to August 2021) was not different from the expected incidence calculated using a Bayesian model based on the years 2015 to 2019 (incidence rate ratio 0.86, 95% credible interval 0.73-1.02) and did not cross the upper boundary of the 95% credible interval for any month. Among 111 patients 18 years and older with newly diagnosed glomerulonephritis between January and August 2021, 38.7% had received at least one vaccine dose before biopsy, compared to 39.5% of the general Swiss population matched for age and calendar-time. The estimated risk ratio for the development of new-onset biopsy-proven glomerulonephritis was not significant at 0.97 (95% confidence interval 0.66-1.42) in vaccinated vs. unvaccinated individuals. Patients with glomerulonephritis manifesting within four weeks after vaccination did not differ clinically from those manifesting temporally unrelated to vaccination. Thus, vaccination against SARS-CoV-2 was not associated with new-onset glomerulonephritis in these two complementary studies with most temporal associations between SARS-CoV-2 vaccination and glomerulonephritis likely coincidental.

Epidemiological characteristics and pathological changes of primary glomerular diseases.

OBJECTIVE: By analyzing the pathological characteristics and clinical data of renal biopsy in our hospital in the past 20 years, to further understand the epidemic characteristics and pathological changes of primary glomerular disease, and to provide regional data for the big data of kidney disease in my country. METHODS: A retrospective analysis of 9448 patients with primary glomerular disease who were hospitalized in our hospital from January 1, 2000 to December 31, 2019, aged 18 years or older, and undergoing renal biopsy. Divided every 5 years into a group, a total of 4 groups (first group 2000.1.1-2004.12.31, second groups 2005.1.1-2009.12.31; third groups 2010.1.1-2014.12.31, fourth groups 2015.1.1-2019.12.31). RESULTS: ① There were more males than females, and male: female vs 1.53:1. The proportion of men in the past five years has increased compared with the previous 15 years. ② Mostly middle-aged, with a median age of 41.39 years old. The age is increasing over time. There are differences between the four groups, P <0.001; ③ The most common clinical manifestations are nephrotic syndrome, followed by chronic glomerulonephritis. Occult glomerulonephritis, the proportion of patients with nephrotic syndrome increases over time, first to fourth group (40.08%< 42.64% < 47.08%< 53.69%); ④ The most common pathology type from 2000 to 2009 was mesangial proliferative glomerulonephritis. IgA nephropathy was the most common type from 2010 to 2014, but the proportion of membranous nephropathy increased year by year, and it became the most common pathological type from 2015 to 2019; ⑤ The clinical and pathological manifestations of different genders are different, but there is no statistical difference. CONCLUSION: In the past 20 years, the primary glomerular disease is mainly middle-aged. There are more men than women. The most common type of clinical manifestation is nephrotic syndrome. The pathological type is mesangial proliferative glomerulonephritis. Over time, the average age is increasing, and the proportion of patients with renal syndrome is increasing. IgA nephropathy is the most common pathological type from 2010 to 2014, and membranous nephropathy has become the main pathological type in the past 5 years.