De novo CMV-associated collapsing focal segmental glomerulosclerosis in a kidney transplant recipient.

Collapsing focal segmental glomerulosclerosis (FSGS) is a variant of FSGS and is associated with severe nephrotic syndrome and acute kidney injury and can occur after kidney transplantation. The exact mechanism of collapsing FSGS after kidney transplantation is unknown, but potential causes include autoimmune diseases, certain malignancies, bisphosphonates, m-TOR inhibitors, interferon-alpha, HIV infection, and other viruses. We describe a case of de novo Cytomegalovirus (CMV)-associated collapsing FSGS in a kidney transplant recipient with a UL97 phosphotransferase mutation that was successfully treated with intravenous ganciclovir, intravenous immunoglobulin, and steroids.

An Update on Viral Infection-Associated Collapsing Glomerulopathy.

The COVID-19 era has been a reminder to clinicians around the world of the important role that viral infections play in promoting glomerular disease. Several viral infections including human immunodeficiency virus (HIV), severe acute respiratory syndrome coronavirus 2, Epstein-Barr virus, cytomegalovirus, and parvovirus B19 can cause podocyte injury and present with a collapsing glomerulopathy (CG) variant of focal segmental glomerulosclerosis or minimal change disease. CG associated with COVID-19 has been termed COVID-19-associated nephropathy due to its striking resemblance to HIV-associated nephropathy. Host susceptibility is a major determinant of viral infection-associated CG, and the presence of two APOL1 risk variants explains most of the racial predilection to viral-associated CG observed in individuals of African ancestry. Interactions between APOL1 risk variants, viral genes, and the systemic inflammatory response to viral infection all contribute to kidney injury. This review will summarize our current knowledge of viral infection-associated CG, focusing primarily on the clinical presentation, histological features, mechanisms, and disease course of HIV-associated nephropathy and COVID-19-associated nephropathy.

Stabilization of hepatitis C associated collapsing focal segmental glomerulosclerosis with interferon alpha-2a and ribavirin.

Hepatitis C virus (HCV) infection is associated with a variety of glomerular diseases, most notably cryoglobulin associated membranoproliferative glomerulonephritis Type I. Focal segmental glomerulosclerosis has only rarely been reported in association with HCV. More striking are multiple reports of de novo collapsing focal segmental glomerulosclerosis (cFSGS) developing during administration of interferon for treatment of HCV. Herein is presented a case of HCV associated cFSGS stabilized with combination therapy of interferon α-2a and ribavirin in a patient with advanced kidney disease.

Long-term response to peginterferon in hepatitis C virus-associated nephrotic syndrome from focal segmental glomerulosclerosis.

Hepatitis C virus (HCV) infection is a global public health problem. Chronic HCV infection is an important cause of chronic liver disease. Since the first reported association between HCV and membranoproliferative glomerulonephritis (MPGN) in 1993, HCV has been described with other types of glomerular diseases, although less frequently. Focal segmental glomerulosclerosis (FSGS) is one such glomerular disease that has been rarely reported in association with HCV. Antiviral therapy with interferon and ribavirin has been shown to be beneficial in HCV-associated MPGN. The optimal therapy of HCV-associated FSGS is not currently known. To our knowledge, long-term response to pegylated interferon monotherapy in treatment of HCV-associated FSGS has not been reported. We report an adult patient with HCV-associated FSGS who presented with nephrotic syndrome and renal failure. Treatment with pegylated interferon alfa-2a monotherapy resulted in sustained virological response with a clinical remission of nephrotic syndrome and stabilization of renal function. Patient continued to remain in clinical remission of nephrotic syndrome with stable renal function, 5 years after treatment. We also briefly review the literature on HCV-associated glomerular diseases, particularly HCV-associated FSGS.

[Glomerular diseases in HIV-infected patients: clinical and morphological evaluation].

AIM: To evaluate the clinical and morphological variants of kidney abnormalities in HIV-infected patients. SUBJECTS AND METHODS: Thirty HIV-infected patients (60% men and 40% women) aged 26 to 54 years (mean age 31.6 +/- 4.7 years) who had undergone diagnostic needle renal biopsy were examined. The indication for the biopsy was nephrotic syndrome (NS) (isolated or concurrent acute nephritic syndrome) and/or decreased renal function. The morphological study of biopsy specimens included light microscopy and immunofluorescence assay. RESULTS: In the examined HIV-infected patients, the histological variants of kidney abnormalities presented with immune complex glomerulonephritis (ICGN) in 26 cases and with focal segmental glomerulosclerosis (FSGS) in 4 cases. The clinical manifestations of ICGN were as follows: NS (61.5%), acute nephritic syndrome (in more than one third of the patients) concurrent with hematuria, as well as mainly grades 2-3 arterial hypertension (AH) (12/14) and renal dysfunction. Immune complex glomerulopathies were marked by polymorphism in the renal morphological pattern with fluorescence during immunofluorescence microscopy in most cases of virtually all classes of immunoglobulins (IgA, IgM, IgG) and complement system fragments (C3, C1q). FSGS was clinically characterized by NS concurrent with AH, hematuria. The morphological subtypes of FSGS were exhibited by apical, perihilar, and nonspecific variants in 1, 1, and 2 cases, respectively. By the time the signs of renal dysfunction appeared, the HIV-infected patients with glomerulopathy were found to have a high viral load (HIV RNA >100 000 copies/ml) and low CD4 lymphocyte levels (< or = 200 in 1 microl). CONCLUSION: In our study, the morphological pattern of chronic glomerulonephritis showed a preponderance of immune complex nephropathies with the clinical manifestations of acute nephritic syndrome and/or NS concurrent with hematuria. High viremia and depressed immune system may be risk factors for nephropathy.

[Kidney damage in COVID-19]. / Les atteintes rénales de la COVID-19.

COVID-19 is a disease caused by the RNA virus SARS-CoV-2. It is characterised by an attack mainly affecting the respiratory system. There is renal involvement which is characterised by three main types of damage, acute tubular necrosis occurring in the most severe cases, proximal tubulopathy which is a prognostic marker of the disease and segmental and focal hyalinosis occurring in a genetically predisposed terrain. The pathophysiology of SARS-CoV-2 renal involvement is not yet defined. The direct role of the virus is debated, whereas the cytokine storm and the hypoxic and thrombotic complications seem more important. The long-term outcome of the renal damage appears to be quite good. Long-term follow-up will allow us to say whether the renal damage is part of the long COVID.

Collapsing Focal Segmental Glomerulosclerosis in Viral Infections.

Collapsing glomerulopathy represents a special variant of the proteinuric kidney disease focal segmental glomerulosclerosis (FSGS). Histologically, the collapsing form of FSGS (cFSGS) is characterized by segmental or global condensation and obliteration of glomerular capillaries, the appearance of hyperplastic and hypertrophic podocytes and severe tubulointerstitial damage. Clinically, cFSGS patients present with acute kidney injury, nephrotic-range proteinuria and are at a high risk of rapid progression to irreversible kidney failure. cFSGS can be attributed to numerous etiologies, namely, viral infections like HIV, cytomegalovirus, Epstein-Barr-Virus, and parvovirus B19 and also drugs and severe ischemia. Risk variants of the APOL1 gene, predominantly found in people of African descent, increase the risk of developing cFSGS. Patients infected with the new Corona-Virus SARS-CoV-2 display an increased rate of acute kidney injury (AKI) in severe cases of COVID-19. Besides hemodynamic instability, cytokine mediated injury and direct viral entry and infection of renal epithelial cells contributing to AKI, there are emerging reports of cFSGS associated with SARS-CoV-2 infection in patients of mainly African ethnicity. The pathogenesis of cFSGS is proposed to be linked with direct viral infection of podocytes, as described for HIV-associated glomerulopathy. Nevertheless, there is growing evidence that the systemic inflammatory cascade, activated in acute viral infections like COVID-19, is a major contributor to the impairment of basic cellular functions in podocytes. This mini review will summarize the current knowledge on cFSGS associated with viral infections with a special focus on the influence of systemic immune responses and potential mechanisms propagating the development of cFSGS.

APOL1 risk variants and the development of HIV-associated nephropathy.

HIV-associated nephropathy (HIVAN) remains a concern among untreated HIV patients, notably of African descent, as patients can reach end-stage renal disease within 3 years. Two variants (G1 and G2) of the APOL1 gene, common in African populations to protect against African sleeping sickness, have been associated with an increased risk of several glomerular disorders including HIVAN, hypertension-attributed chronic kidney disease, and idiopathic focal segmental glomerulosclerosis and are accordingly named renal risk variants (RRVs). This review examines the mechanisms by which APOL1 RRVs drive glomerular injury in the setting of HIV infection and their potential application to patient management. Innate antiviral mechanisms activated by chronic HIV infection, especially those involving type 1 interferons, are of particular interest as they have been shown to upregulate APOL1 expression. Additionally, the downregulation of miRNA 193a (a repressor of APOL1) is also associated with the upregulation of APOL1. Interestingly, glomerular damage affected by APOL1 RRVs is caused by both loss- and gain-of-function changes in the protein, explicitly characterizing these effects. Their intracellular localization offers a further understanding of the nuances of APOL1 variant effects in promoting renal disease. Finally, although APOL1 variants have been recognized as a critical genetic player in mediating kidney disease, there are significant gaps in their application to patient management for screening, diagnosis, and treatment.

COVID-19 Recovery Without B Cells or Antibodies in Patients Receiving Rituximab for Autoimmune Disease.

No Abstract.

HIV-1 and kidney cells: better understanding of viral interaction.

HIV-associated nephropathy (HIVAN) is the most common disease affecting untreated seropositive patients of African descent. Besides genetic (African descent) and HIV-1 infection (environmental), specific host factors such as activation of renin-angiotensin-aldosterone system (RAAS) have also been demonstrated to play a role in the manifestation of HIVAN. The recent identification of MYH9 as susceptible allele is a key step forward in our understanding for the pathogenesis of focal glomerulosclerosis in people of African-American descent. HIV-1 transgenic models have significantly advanced our knowledge base in terms of role of HIV-1 genes in general and individual gene in particular in the development of renal lesions mimicking HIVAN. These studies suggest that viral replication is not needed for the development of renal lesions. Renal biopsy data from HIVAN patients suggest that renal epithelial cells express HIV-1 genes and thus it may be sufficient to invoke HIVAN phenotype in the presence of specific host and genetic factors. On the other hand, immune response to infection may be required to induce HIV-1 associated immune complex kidney disease (HIVICK). Since renal cell lack conventional HIV-1 receptors, HIV-1 entry into renal cells has been a mystery. Recently, non-conventional pathways have been demonstrated to facilitate HIV-1 entry into renal cells in in vitro studies. These include presence of DEC-205 receptors in renal tubular cells and lipid rafts in podocytes. However, HIV-1 entry through these pathways only allows non-productive infection. It appears that the presence of specific genetic and host factors in in vivo conditions may be facilitating the development of the productive HIV-1 infection in kidney cells.

Hepatitis C virus-related kidney disease: various histological patterns.

BACKGROUND: Although hepatitis C virus (HCV) infection is known to be associated with Type 2 cryoglobulinemic glomerulopathy (CG), only a few reports about other types of nephropathy have been published. METHODS: 68 HCV antibody positive patients in whom renal biopsy had been performed for persistent proteinuria, hematuria, and/or renal dysfunction between 1992 and 2008 at our institute were included. The histological, clinical and laboratory characteristics including the age, gender, hypertension, diabetes mellitus, liver histology (chronic hepatitis or liver cirrhosis), HCV-RNA, HCV genotype, splenomegaly, gastroesophageal varices, serum creatinine, hemoglobin, platelet count, rheumatoid factor, cryoglobulin, IgG, IgA, IgM, CH50, C3, C4, creatinine clearance, 24-h protein excretion, and hematuria, between their nephropathy with and without immune deposition were compared. RESULTS: Nephropathy was classified into two groups based on the detection of immune deposits by immunofluorescence microscopy: i.e., a positive group (n = 39) and a negative group (n = 29). The former group was further classified into three types of nephropathy: IgG dominant group (n = 10) (including membranous nephropathy (MN)), IgA dominant group (n = 20) (including IgA nephropathy (IgAN)), membranoproliferative glomerulonephritis (MPGN) (IgA type)), and IgM dominant group (n = 9) (MPGN apart from the IgA type). The latter group included diabetic nephropathy (n = 13), focal glomerular sclerosis (n = 4), and benign nephrosclerosis (n = 3), malignant nephrosclerosis (n = 1), tubulointerstitial nephritis (TIN) (n = 2), minimal change nephrotic syndrome (n = 1), cast nephropathy (n = 1), granulomatous TIN (n = 1), and others (n = 3). An increased serum IgM level, hypocomplementemia, splenomegaly, thrombocytopenia, liver cirrhosis, hematuria, and a high HCV RNA level were features of patients with MPGN of IgM dominant group (consistent with "CG"). CONCLUSIONS: Our results showed various histological patterns of HCV-related kidney disease and the specificity of CG, and revealed that a minority of HCV patients (n = 7) presented typical CG, while IgAN, MN, and diabetic nephropathy were more frequent.

Hepatitis B virus associated focal and segmental glomerular sclerosis: report of two cases and review of literature.

The hepatitis B virus (HBV) is estimated to have infected about 350 million people worldwide, making it one of the most common human pathogens. Renal involvement is among its most common extra hepatic manifestations and usually manifests in the form of immune complex mediated glomerulopathy, such as membranous glomerulonephritis (MGN), membranoproliferative glomerulonephritis (MPGN), mesangioproliferative glomerulonephritis and immunoglobulin A (IgA) nephropathy. Occurrence of focal and segmental glomerular sclerosis (FSGS) with HBV infection is rare and only five cases have been reported earlier. We report two cases of hepatitis B associated FSGS. In both the cases, HBsAg was demonstrated in the renal tissue and both the cases showed response to treatment with lamivudine, thus indicating a possible causal association between the viral infection and occurrence of nephrotic syndrome.

[Focal segmental glomerulosclerosis related to BK virus in a child with nephrotic syndrome. A case report]. / Glomerulopatía colapsante asociada a virus BK en un niño con síndrome nefrótico idiopático. Informe de un caso.

BACKGROUND: focal segmental glomerulosclerosis (FSGS) is observed in about 10 % of children with idiopathic nephrotic syndrome; this disorder is usually resistant to corticoid therapy. In the last few years, five histological types of FSGS have been recognized; the collapsing nephropathy type is characterized by a rapid evolution to chronic renal failure. CLINICAL CASE: a four-year-old boy presented with an irrelevant past history; eight months before admission he developed idiopathic nephrotic syndrome. He was treated with steroids without improvement, and a renal biopsy was performed in which minimal glomerular changes were found. Despite combined immunosuppressive treatment, he developed renal failure, septic shock and death. Collapsing nephropathy was demonstrated by immunohistochemistry, light and electron microscopy; renal new human papovirus (BK) infection was also found in the postmortem study. CONCLUSIONS: collapsing nephropathy is an aggressive disorder resistant to immunosuppressive treatment, as occurred in our patient. Although some viral diseases have been associated with collapsing nephropathy, to our knowledge, BK infection has not been previously described in those patients.

[Collapsing focal segmental glomerulosclerosis induced by cytomegalovirus: A case report]. / Hyalinose segmentaire et focale collapsante secondaire au cytomégalovirus : à propos d'un cas.

Focal segmental glomerulosclerosis (FSGS) is a common cause of nephrotic syndrome in child and adult. The collapsing forms are of poor renal prognosis and are usually secondary to viral infections with, first and foremost, the human immunodeficiency virus. Among other viral etiologies, cytomegalovirus (CMV) is an uncommon cause. We report a case of a 32years-old patient with collapsing focal segmental glomerulosclerosis induced by cytomegalovirus with initial acute renal failure and proteinuria at 12.4g/24h. The treatment associated ganciclovir during 7days followed by valganciclovir during 14days and steroids at 1mg/kg/day. Renal function improved and proteinuria decreased with this treatment. Proteinuria increase again 3weeks after valganciclovir discontinuation while CMV Polymerase chain reaction (PCR) was positive. Therefore, valganciclovir has been resumed allowing renal function normalization and decrease in proteinuria to 4g/24h after negative CMVPCR assay after 15weeks. Anti-CMV therapy combined with steroids seems to provide a renal response in case of FSGS induced by CMV even if long-term prognosis stays uncertain.

Infection-Related Focal Segmental Glomerulosclerosis in Children.

Focal segmental glomerulosclerosis (FSGS) is the most common cause of steroid resistant nephrotic syndrome in children. It describes a unique histological picture of glomerular damage resulting from several causes. In the majority of patients the causing agent is still unknown, but in some cases viral association is evident. In adults, the most established FSGS causing virus is the human immune-deficiency virus, which is related to a collapsing variant of FSGS. Nevertheless, other viruses are also suspected for causing a collapsing or noncollapsing variant, for example, hepatitis B virus, parvovirus B19, and Cytomegalovirus. Although the systemic infection mechanism is different for these viruses, there are similarities in the pathomechanism for the induction of FSGS. As the podocyte is the key structure in the pathogenesis of FSGS, a direct infection of these cells or immediate damage through the virus or viral components has to be considered. Although viral infections are a very rare cause for FSGS in children, the treating pediatric nephrologist has to be aware of a possible underlying infection, as this has a relevant impact on therapy and prognosis.

Renal manifestations of sexually transmitted diseases: sexually transmitted diseases and the kidney.

The adolescent population is particularly vulnerable to STDs. Those that cause significant kidney disease are of viral origin. The primary VVD are HIV-1, HBV, and HCV. Screening of high-risk populations should include quantitation of proteinuria, including total protein and microalbumin, to assess severity of renal damage and potential for progression. Renal biopsy is indicated for diagnosis and for planning important treatment interventions if there is significant proteinuria or decreased renal function. Causes of acute renal failure are frequently reversible and should be treated aggressively. These include HUS, vaso-motor or ischemic acute tubular necrosis, and drug toxicities. The spectrum of chronic kidney disease associated with VVD is broad and may include systemic manifestations of vasculitis. HIV-associated nephropathy is the prototype, with the most prevalent lesion remaining FSGS. Progression occurs in up to 15% of the patients, who are overwhelmingly of African lineage. Significant advances in management include ongoing development of HAART, angiotensin antagonists to control proteinuria, and novel immune-modulating drugs such as MMF, CsA, and rituximab. Dialysis therapies have offered improved survival, especially in pediatric patients. Moreover, transplantation is no longer considered experimental and should be offered to select patients.

[Collapsing variant of focal segmental glomerulosclerosis by parvovirus B19: case report]. / Glomeruloesclerose segmentar e focal (GESF) colapsante associada ao parvovírus B19: relato de caso.

OBJECTIVE: To describe the clinical and laboratory profile of focal segmental glomerulosclerosis (FSGS) of the collapsing subtype in association with infection by parvovirus B19 (PVB19). CASE REPORT: Female patient, 37 years old, mulatto, developed pharyngalgia and fever with partial improvement after penicillin. After one week we observed reduced urinary output and lower limb edema. Smoker, family and personal history negative for hypertension, diabetes or kidney disease. Patient presented with olyguria, hypertension and edema, also hypochromic microcytic hypoproliferative anemia, nephritic range proteinuria, microscopic hematuria and renal dysfunction. All rheumatologic investigation, HIV and hepatitis serology were negative. Unremarkable renal ultrasound. PCR positive for PVB19 in bone marrow aspirate and blood and renal biopsy conclusive of collapsing FSGS subtype. Spontaneous remission occurred within two weeks of the profile. The blood PVB19 PCR was repeated within a month and resulted negative. This finding demonstrated PVB19 acute infection or viral reactivation in association with collapsing FSGS. CONCLUSION: There is demonstrated the temporal association of PVB19 viremia and collapsing FSGS, due primary infection or viral reactivation. The association of collapsing FSGS and PVB19 is described in the literature, demonstrating virus presence in kidney tissue, but the real relationship of virus in the pathogenesis of this glomerulopathy remains unclear.