• Antitubercular therapy
• Collapsing glomerulopathy
• Immune dysregulation
• Renal recovery
• Tuberculosis

• APOL1
• children
• focal segmental glomerulosclerosis
• genetic ancestry
• monogenic chronic kidney disease
• steroid-resistant nephrotic syndrome

• Molecular biology
• Nephrology

• Animals
• Female
• Humans
• Mice
• B-Lymphocytes/immunology
• B-Lymphocytes/pathology
• Class I Phosphatidylinositol 3-Kinases/genetics
• Class I Phosphatidylinositol 3-Kinases/antagonists & inhibitors
• Class I Phosphatidylinositol 3-Kinases/metabolism
• Disease Models, Animal
• Glomerulonephritis/pathology
• Glomerulonephritis/immunology
• Glomerulonephritis/genetics
• Glomerulonephritis/enzymology
• Glomerulonephritis/drug therapy
• Lupus Nephritis/pathology
• Lupus Nephritis/immunology
• Lupus Nephritis/genetics
• Lupus Nephritis/enzymology
• Phosphoinositide-3 Kinase Inhibitors/pharmacology
• Podocytes/pathology
• Podocytes/immunology
• Podocytes/metabolism
• T-Lymphocytes/immunology
• T-Lymphocytes/pathology
• Thiazoles

• European Research Council
• Agence Nationale de la Recherche

• APOL1
• Mendelian variants
• collapsing glomerulopathy
• genetic ancestry
• genetically admixed population
• nephrotic syndrome

• Adult
• Child
• Humans
• Apolipoprotein L1/genetics
• Genotype
• Kidney/pathology
• Renal Insufficiency, Chronic/epidemiology
• Renal Insufficiency, Chronic/genetics
• Renal Insufficiency, Chronic/pathology
• Risk Factors
• Adolescent
• Young Adult

• Collapsing glomerulopathy
• Poncet’s disease
• nephrotic syndrome
• proteinuria
• tuberculosis

• C3 glomerulopathy
• collapsing FSGS

• Animals
• Humans
• Kidney Diseases/pathology
• Glomerulosclerosis, Focal Segmental/genetics
• Kidney Glomerulus/pathology
• Nephrotic Syndrome/genetics
• Podocytes/pathology

• R01 DK130386 NIDDK NIH HHS

• Male
• Humans
• Glomerulosclerosis, Focal Segmental/complications
• Glomerulosclerosis, Focal Segmental/pathology
• Kidney Transplantation/adverse effects
• RNA, Viral
• COVID-19/complications
• SARS-CoV-2
• Proteinuria/etiology

• collapsing focal segmental glomerulosclerosis
• cyclosporin
• low-density lipoprotein apheresis
• nephrotic syndrome
• steroid

• Adult
• Female
• Glomerulosclerosis, Focal Segmental/complications
• Glomerulosclerosis, Focal Segmental/therapy
• Humans
• Kidney Glomerulus/pathology
• Nephritis, Interstitial/complications
• Nephritis, Interstitial/therapy
• Nephrotic Syndrome/complications
• Nephrotic Syndrome/therapy
• Proteinuria/complications

Collapsing glomerulopathy (CG) is a rare variant of focal segmental glomerulosclerosis (FSGS) that commonly presents as nephrotic syndrome in patients. CG is almost always associated with human immunodeficiency virus (HIV) infection but is rarely from other infectious sources such as parvovirus, Epstein-Barr virus, cytomegalovirus, and SARS-CoV-2. CG has also been reported to be related to other etiologies such as genetic disorders, lupus, malignancy, and post-renal transplant but is exceedingly rare when related to hepatitis C virus (HCV). In this report, we describe the case of a patient presenting with nephrotic syndrome secondary to CG caused by newly diagnosed HCV.

Collapsing glomerulopathy (CG) is a clinicopathologic entity characterized by segmentar or global collapse of the glomerulus and hypertrophy and hyperplasia of podocytes. The Columbia classification of 2004 classified CG as a histological subtype of focal segmental glomerulosclerosis (FSGS). A growing number of studies have demonstrated a high prevalence of CG in many countries, especially among populations with a higher proportion of people with African descent. The present study is a narrative review of articles extracted from PubMed, Medline, and Scielo databases from September 1, 2020 to December 31, 2021. We have focused on populational studies (specially cross-sectional and cohort articles). CG is defined as a podocytopathy with a distinct pathogenesis characterized by strong podocyte proliferative activity. The most significant risk factors for CG include APOL1 gene mutations and infections with human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2. CG typically presents with more severe symptoms and greater renal damage. The prognosis is notably worse than that of other FSGS subtypes.

• Kidney transplantation
• genomic
• glomerular diseases
• immunopathology

Introduction: COVID-19 infections resulting in pathological kidney manifestations have frequently been reported in adults since the onset of the global COVID-19 pandemic in December 2019. Gradually, there have been an increased number of COVID-19-associated intrinsic kidney pathologies in children and adolescents reported as well. The pathophysiological mechanisms between COVID-19 and the onset of kidney pathology are not fully known in children; it remains a challenge to distinguish between intrinsic kidney pathologies that were caused directly by COVID-19 viral invasion, and cases which occurred as a result of multisystem inflammatory syndrome due to the infection. This challenge is made more difficult in children, due to the ethical limitations of performing kidney biopsies to reach a biopsy-proven diagnosis. Although previous systematic reviews have summarized the various pathological kidney manifestations that have occurred in adults following acute COVID-19 infection, such reviews have not yet been published for children and adolescents. We describe the results of a systematic review for intrinsic kidney pathology following COVID-19 infection in children and adolescents. Methods: A systematic literature search of published data up until 31 October was completed through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Research articles reporting new-onset or relapsed intrinsic kidney pathology in children or adolescents (≤18 years) following acute COVID-19 infection were included for qualitative review. COVID-19 infection status was defined by a positive result from a RT-PCR, or nuclear antibody testing. Only full-text articles published in the English language were selected for review. Results: Twenty-nine cases from fifteen articles were included in the qualitative synthesis of this systematic review. Nephrotic syndrome, as an umbrella condition, appeared as the most frequently observed presentation (20 cases) with disease remission noted in all cases with steroid treatment. Other cases included numerous glomerulonephritides, such as acute necrotizing glomerulonephritis, MPO vasculitis and collapsing glomerulopathy, and thrombotic microangiopathies, such as aHUS. For patients with transplanted kidneys, T-cell-mediated rejection and mild tubular interstitial infiltration were noted following testing positive for COVID-19. There were no mortalities reported in any of the included cases, although two patients remained dialysis dependent at hospital discharge. Conclusion: This systematic review highlights the various intrinsic pathological kidney manifestations in children and adolescents as a result of acute COVID-19 infection. The clinical timeline and presentation of these cases support the mechanistic hypothesis between COVID-19 infection and the onset of intrinsic kidney pathologies within this context. The progressive introduction of vaccination programs for children and adolescents may hopefully reduce the severity of COVID-19-associated illnesses, and pathological kidney manifestations in this population.

• COVID-19
• SARS-CoV-2
• adolescents
• children
• intrinsic kidney pathology

• Acute kidney injury
• Focal segmental glomerulosclerosis collapsing variant
• Low-density lipoprotein apheresis
• Nephrotic syndrome

• Blood Component Removal
• Female
• Glomerulosclerosis, Focal Segmental/drug therapy
• Humans
• Lipoproteins, LDL
• Male
• Nephrologists
• Nephrotic Syndrome/therapy
• Steroids

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can result in clinically significant multi-system disease including involvement in the kidney. The underlying histopathological processes were unknown at the start of the pandemic. As case reports and series have been published describing the underlying renal histopathology from kidney biopsies, we have started to gain an insight into the renal manifestations of this novel disease.

To provide an overview of the current literature on the renal histopathological features and mechanistic insights described in association with coronavirus disease 2019 (COVID-19) infection.

A systematic review was performed by conducting a literature search in the following websites-‘PubMed’, ‘Web of Science’, ‘Embase’ and ‘Medline-ProQuest’ with the following search terms-“COVID-19 AND kidney biopsy”, “COVID-19 AND renal biopsy”, “SARS-CoV-2 AND kidney biopsy” and “SARS-CoV-2 AND renal biopsy”. We have included published data up until February 15, 2021, which includes kidney biopsies (native, transplant and postmortem) from patients with COVID-19. Data on clinical presentation, histopathological features, management and outcome was extracted from the reported studies.

The total number of biopsies reported on here is 288, of which 189 are postmortem, 84 native and 15 transplants. The results are varied and show underlying pathologies ranging from collapsing glomerulopathy and acute tubular injury (ATI) to anti-nuclear cytoplasmic antibody associated vasculitis and pigment nephropathy. There was variation in the specific treatment used for the various renal conditions, which included steroids, hydroxychloroquine, eculizumab, convalescent plasma, rituximab, anakinra, cyclophosphamide and renal replacement therapy, amongst others. The pathological process which occurs in the kidney following COVID-19 infection and leads to the described biopsy findings has been hypothesized in some conditions but not others (for example, sepsis related hypoperfusion for ATI). It is important to note that this represents a very small minority of the total number of cases of COVID-19 related kidney disease, and as such there may be inherent selection bias in the results described. Further work will be required to determine the pathogenetic link, if any, between COVID-19 and the other renal pathologies.

This report has clinical relevance as certain renal pathologies have specific management, with the implication that kidney biopsy in the setting of renal disease and COVID-19 should be an early consideration, dependent upon the clinical presentation.

• COVID-19
• Histopathology
• Kidney biopsy
• Transplant
• SARS-CoV-2

• epidemiology
• focal segmental glomerulosclerosis
• glomerulonephritis
• histologic variant
• nephrotic syndrome
• survival analysis

Collapsing glomerulopathy (CG) is a distinct morphologic pattern of proliferative renal parenchymal injury. It differ from focal segmental glomerulosclerosis (FSGS) by clinicopathologic pattern and its adverse outcome. The clinical significance of CG in renal allograft biopsies is not yet clear due to scant data and less occurrence of CG in renal transplant recipients. We conducted this single-center retrospective study to evaluate the prevalence, clinicopathological features, and outcome of post renal transplant CG.

We studied 127 renal allograft biopsies performed over a period of 45 months (Jan 2015–Oct 2018). A diagnosis of CG was made if at least one glomerulus demonstrated global or segmental collapse of the glomerular capillary walls, associated marked hyperplasia, and hypertrophy of the overlying visceral epithelial cells. We analyzed clinical, biochemical, and pathological characteristics and its impact on renal allograft outcome. Statistical analysis was performed and continuous variables were expressed as means ± standard deviation (SD) or medians (interquartile range and noncontinuous data were expressed in percentage and numerical values.

The prevalence of CG was 5.3% (7/127) of allograft biopsies. Out of the seven patients, six patients had undergone live donor transplant and one patient had undergone deceased donor renal transplant. The native kidney disease was unknown in these patients except one (IgA nephropathy). The median duration of diagnosis for CG was 17 months after transplantation (range 5–132months). Presenting symptoms were pedal edema and hypertension in 71.4% (5) patients each. All patients had proteinuria of more than 1 gm and renal allograft dysfunction and median serum creatinine of 3.05 mg/dl (1.5–4.8 mg/dl). All patients received standard triple immunosuppression. Over a period of 2–20 months, 57.14% (4) patients developed a graft failure and 43% (3) of the other patients had functioning grafts with serum creatinine of 1.5–4.2 mg/dl.

CG presents with moderate to severe proteinuria and may lead to rapid graft dysfunction and subsequent graft failure in most of the patients.

• CG-collapsing glomerulopathy
• CNI-calcineurin inhibitors
• GD-graft dysfunction
• GF-graft failure

• acute renal failure
• oncology
• pathology
• proteinurea

• Aged
• Antibodies, Monoclonal, Humanized/adverse effects
• Humans
• Male
• Proteinuria/chemically induced
• Renal Insufficiency
• Thrombotic Microangiopathies/chemically induced
• Ramucirumab

• APOL1
• COVID-19
• COVID-associated nephropathy
• acute kidney injury
• collapsing glomerulopathy
• nephrotic syndrome

• acute kidney injury
• collapsing focal segmental glomerulosclerosis
• focal segmental glomerulosclerosis
• human immunodeficiency virus
• obesity‐related glomerulopathy
• trimethoprim‐sulfamethoxazole

• Autoimmune lymphoproliferative disorder
• Collapsing glomerulopathy
• Double negative T cell
• Focal segmental glomerulosclerosis
• Interferon gamma

• Autoimmune disorder
• Collapsing FSGS
• Collapsing glomerulopathy
• Mixed connective tissue disease

• Acute kidney injury
• COVID-19
• Collapsing glomerulopathy
• Kidney biopsy
• Transplant

• Betacoronavirus/isolation & purification
• COVID-19
• Case-Control Studies
• Coronavirus Infections/complications
• Coronavirus Infections/virology
• Glomerulonephritis/complications
• Humans
• Kidney Transplantation
• Male
• Middle Aged
• Pandemics
• Pneumonia, Viral/complications
• Pneumonia, Viral/virology
• SARS-CoV-2

• AKI
• COVID-19
• Collapsing GN
• Kidney failure
• Pathology

• Acute Kidney Injury/etiology
• Acute Kidney Injury/metabolism
• Acute Kidney Injury/pathology
• Acute Kidney Injury/physiopathology
• Anti-Bacterial Agents/adverse effects
• Antiviral Agents/adverse effects
• Apolipoprotein L1/genetics
• Ascorbic Acid/adverse effects
• Azotemia/metabolism
• Azotemia/pathology
• Azotemia/physiopathology
• COVID-19/metabolism
• COVID-19/pathology
• COVID-19/physiopathology
• Cytokines/metabolism
• Disease Progression
• Glomerulonephritis/metabolism
• Glomerulonephritis/pathology
• Glomerulonephritis/physiopathology
• Glomerulonephritis, Membranous/metabolism
• Glomerulonephritis, Membranous/pathology
• Glomerulonephritis, Membranous/physiopathology
• Hospital Mortality
• Humans
• Kidney Tubules, Proximal/injuries
• Length of Stay
• Myoglobin/metabolism
• Nephritis, Interstitial/metabolism
• Nephritis, Interstitial/pathology
• Nephritis, Interstitial/physiopathology
• Nephrosis, Lipoid/metabolism
• Nephrosis, Lipoid/pathology
• Nephrosis, Lipoid/physiopathology
• Renal Insufficiency, Chronic
• Rhabdomyolysis/metabolism
• SARS-CoV-2
• Severity of Illness Index
• Thrombotic Microangiopathies/metabolism
• Thrombotic Microangiopathies/pathology
• Thrombotic Microangiopathies/physiopathology
• Vitamins/adverse effects
• COVID-19 Drug Treatment

• K23 DK117014 NIDDK NIH HHS

• endstage kidney disease
• lupus nephritis
• rapid progression

• collapsing focal segmental glomerulosclerosis
• rituximab
• steroid dependent nephrotic syndrome
• steroid resistant nephrotic syndrome

• cathepsin
• collapsing FSGS
• extracellular matrix
• focal segmental glomerulosclerosis
• glomerular epithelial cells

Collapsing glomerulopathy is an aggressive form of focal segmental glomerulosclerosis with diverse causes. The presence of the apolipoprotein L1 (APOL1) high-risk genotype is a major risk factor for collapsing glomerulopathy in African Americans. Coronavirus disease 2019 (COVID-19) is an emerging pandemic with predominant respiratory manifestations. However, kidney involvement is being frequently noted and is associated with higher mortality. Currently, kidney pathology data for COVID-19 are scant and mostly come from postmortem findings. We report 2 African American patients who developed acute kidney injury and proteinuria in temporal association with COVID-19 infection. Kidney biopsy specimens showed collapsing glomerulopathy, endothelial tubuloreticular inclusions, and acute tubular injury, without evidence by electron microscopy or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in situ hybridization of viral infection of kidney cells. Both patients had the APOL1 high-risk genotype. We propose that collapsing glomerulopathy represents a novel manifestation of COVID-19 infection, especially in people of African descent with APOL1 risk alleles.

• collapsing glomerulopathy, focal segmental glomerulosclerosis, COVID-19, acute kidney injury, proteinuria, APOL1 genotype

• Minimal change disease
• electron microscopy
• focal segmental glomerulosclerosis

• Collapsing glomerulopathy
• Dedifferentiation podocytes
• Desdiferenciación podocitaria
• Glomerulopatía colapsante
• Nephrotic range proteinuria
• Podocitopatía
• Podocytopathy
• Proteinuria nefrótica

• FSGS
• Glomerulus
• Microsphere
• Podocyte

• APOL1 genotypes
• African Americans
• acute rejection
• acute vasoocclusion
• collapsing glomerulopathy
• kidney transplantation

• Adult
• Allografts/pathology
• Apolipoprotein L1/genetics
• Case-Control Studies
• Female
• Genotype
• Glomerulosclerosis, Focal Segmental/diagnosis
• Glomerulosclerosis, Focal Segmental/epidemiology
• Glomerulosclerosis, Focal Segmental/genetics
• Glomerulosclerosis, Focal Segmental/pathology
• Graft Rejection/diagnosis
• Graft Rejection/epidemiology
• Graft Rejection/genetics
• Graft Rejection/pathology
• Graft Survival/genetics
• Humans
• Incidence
• Kidney/pathology
• Kidney Failure, Chronic/surgery
• Kidney Transplantation/adverse effects
• Male
• Middle Aged
• Prognosis
• Tissue Donors
• Transplantation, Homologous/adverse effects

• R01 DK070941 NIDDK NIH HHS
• R01 DK084149 NIDDK NIH HHS
• R01 DK114893 NIDDK NIH HHS
• U01 DK116066 NIDDK NIH HHS

The glomerular diseases after renal transplantation can occur de novo, i.e., with no relation to the native kidney disease, or more frequently occur as a recurrence of the original disease in the native kidney. There may not be any difference in clinical features and histological pattern between de novo glomerular disease and recurrence of original glomerular disease. However, structural alterations in transplanted kidney add to dilemma in diagnosis. These changes in architecture of histopathology can happen due to: (1) exposure to the immunosuppression specifically the calcineurin inhibitors (CNI); (2) in vascular and tubulointerstitial alterations as a result of antibody mediated or cell-mediated immunological onslaught; (3) post-transplant viral infections; (4) ischemia-reperfusion injury; and (5) hyperfiltration injury. The pathogenesis of the de novo glomerular diseases differs with each type. Stimulation of B-cell clones with subsequent production of the monoclonal IgG, particularly IgG3 subtype that has higher affinity to the negatively charged glomerular tissue, is suggested to be included in PGNMID pathogenesis. De novo membranous nephropathy can be seen after exposure to the cryptogenic podocyte antigens. The role of the toxic effects of CNI including tissue fibrosis and the hemodynamic alterations may be involved in the de novo FSGS pathophysiology. The well-known deleterious effects of HCV infection and its relation to MPGN disease are frequently reported. The new concepts have emerged that demonstrate the role of dysregulation of alternative complement pathway in evolution of MPGN that led to classifying into two subgroups, immune complex mediated MPGN and complement-mediated MPGN. The latter comprises of the dense deposit disease and the C3 GN disease. De novo C3 disease is rather rare. Prognosis of de novo diseases varies with each type and their management continues to be empirical to a large extent.

• De novo glomerulonephritis
• Renal transplantation
• New concepts of therapy

• Bardet-Biedl
• Kidney Defects
• Primary Cilium

Collapsing glomerulopathy (CG) is a well-recognized distinct morphological pattern of proliferative parenchymal injury leading to rapid graft failure. We conducted a single-center retrospective study to evaluate the prevalence, clinicopathological features, and prognosis of CG in renal transplant recepient. We analyzed 2518 renal allograft biopsies performed from 2007 to 2015 and correlated their clinicopathological features. The prevalence of CG was 0.83% (21 out of 2518) of allograft biopsies with a higher prevalence of 1.4% during the period from 2012 to 2015. Out of 21 patients, 18 (85.71%) patients had undergone live donor and 3 (14.28%) patients had undergone deceased donor renal transplant. Hypertension was observed in 3 (14.28%) patients. The mean duration of diagnosis for CG was 1.85 ± 1.91 years. Urinalysis revealed microhematuria in 5 (23.8%) patients. The mean 24 h urinary protein excretion was 4.77 ± 5.3 g and serum creatinine was 2.12 ± 1.5 mg/dl. The predominant native kidney diseases in recipients were chronic glomerulonephritis of unknown etiology in 12 (57.14%) patients and hypertensive nephropathy in 3 (14.28%) patients. CG was associated with rejection in 9 (42.85%), calcineurin-inhibitor toxicity in 2 (9.5%), and BK virus nephropathy in 1 patient. All patients received standard triple immunosuppression. Eleven (52.38%) patients developed graft failure over a mean period of 2.2 ± 1.7 years and 6 (28.57%) patients recovered with stable graft function. CG can coexist with viral infection, drug toxicity, rejection, microvascular injury, etc. CG usually presents with moderate to severe proteinuria and may lead to rapid graft dysfunction and subsequent graft failure in most of the patients.

• Collapsing glomerulopathy
• end-stage renal disease
• hypertension
• podocyte
• proteinuria

• Metabolism
• Nephrology

To compare the clinico-pathological features of collapsing glomerulopathy (CG) at a tertiary hospital in Saudi Arabia with the world literature.

In a retrospective study, all biopsy-diagnosed cases of CG between 2004-2015 were identified and analyzed, at King Khalid University Hospital, King Saud University, Riyadh. The clinico-pathological findings along with prognosis were reviewed and compared with the reported literature.

Thirty-one CG patients were identified, most were adult males. All the CG cases were idiopathic, all Arabs, none HIV positive, none of African descent, and none with a history of drug abuse. The number of glomeruli with collapsing lesions per biopsy ranged from 1 to 9. Other types of FSGS lesions (not otherwise specified and perihilar) were also noted. There was extensive podocyte effacement. Upon treatment, remission (complete/partial) was noted in almost half the patients; around one fourth did not respond to treatment; and one fourth progressed to end stage kidney disease (ESKD). The median time taken to develop ESKD from the time of biopsy diagnosis was 23 months.

The clinico-pathological and prognostic correlates of CG in Saudi Arabia are comparable with that of the world literature. The management protocol at our center is the same as that practiced in different parts of the world, and the prognosis is overall poor.

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Child
• Child, Preschool
• Female
• Glomerulosclerosis, Focal Segmental/pathology
• Humans
• Male
• Middle Aged
• Prognosis
• Saudi Arabia
• Young Adult

• Adult
• Diagnosis, Differential
• Glomerulosclerosis, Focal Segmental/diagnosis
• Glomerulosclerosis, Focal Segmental/etiology
• HIV Infections/complications
• HIV Infections/diagnosis
• Humans
• Kidney/diagnostic imaging
• Kidney/pathology
• Kidney Diseases/diagnosis
• Male
• Nephrotic Syndrome/diagnosis
• Tomography, X-Ray Computed
• Ultrasonography
• Urinalysis