Anti-Neuronal IgG4 Autoimmune Diseases and IgG4-Related Diseases May Not Be Part of the Same Spectrum: A Comparative Study

BackgroundIgG4 is associated with two emerging groups of rare diseases: 1) IgG4 autoimmune diseases (IgG4-AID) and 2) IgG4-related diseases (IgG4-RLD). Anti-neuronal IgG4-AID include MuSK myasthenia gravis, LGI1- and Caspr2-encephalitis and autoimmune nodo-/paranodopathies (CNTN1/Caspr1 or NF155 antibodies). IgG4-RLD is a multiorgan disease hallmarked by tissue-destructive fibrotic lesions with lymphocyte and IgG4 plasma cell infiltrates and increased serum IgG4 concentrations. It is unclear whether IgG4-AID and IgG4-RLD share relevant clinical and immunopathological features.MethodsWe collected and analyzed clinical, serological, and histopathological data in 50 patients with anti-neuronal IgG4-AID and 19 patients with IgG4-RLD.ResultsA significantly higher proportion of IgG4-RLD patients had serum IgG4 elevation when compared to IgG4-AID patients (52.63% vs. 16%, p = .004). Moreover, those IgG4-AID patients with elevated IgG4 did not meet the diagnostic criteria of IgG4-RLD, and their autoantibody titers did not correlate with their serum IgG4 concentrations. In addition, patients with IgG4-RLD were negative for anti-neuronal/neuromuscular autoantibodies and among these patients, men showed a significantly higher propensity for IgG4 elevation, when compared to women (p = .005). Last, a kidney biopsy from a patient with autoimmune paranodopathy due to CNTN1/Caspr1-complex IgG4 autoantibodies and concomitant nephrotic syndrome did not show fibrosis or IgG4+ plasma cells, which are diagnostic hallmarks of IgG4-RLD.ConclusionOur observations suggest that anti-neuronal IgG4-AID and IgG4-RLD are most likely distinct disease entities.

The role of kidney biopsy in Immune Checkpoint Inhibitor-associated AKI

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Biopsy Proven Kidney Disease From A Rural Tertiary Care Centre — A Social And Epidemiological Perspective

The prevalence of chronic kidney disease (CKD) is rising in rural areas. Screening of high risk cases, early detection and referral by the physicians reduces the prevalence of kidney disease in the population. Hereditary disorders, Glomerular diseases, Obstructive nephropathies are common causes in CKD in rural areas. Kidney biopsy is an essential diagnostic tool in to diagnose glomerular diseases. This prospective study done at tertiary care teaching hospital between 2017 and 2020 to understand the profile of glomerular diseases in rural area. Forty patients were included in the Study. Primary glomerular disease (PGD) was present in 26 patients and Secondary glomerular disease (SGD) in 10 and primary tubulointerstitial pathology in 4 patients. The most common Secondary glomerular disease was lupus. Glomerular diseases are amenable to immunomodulatory therapy leading to change in clinical outcome of the disease. However, Kidney biopsy is underutilized particularly in elderly patients, hypertensive nephropathy patients, suspected non diabetic kidney disease and lupus patients. Financial and social issues play dominant role in the treatment plan of chronic diseases in rural areas. Regional registry of kidney biopsy of urban and rural areas separately helps in paving a way of understanding the profile of glomerular diseases and its prevention.

Renal biopsy in diabetic patients: Histopathological and clinical correlations

Introduction: Diabetes is the leading cause of chronic kidney disease and end-stage kidney disease worldwide. A kidney biopsy in a diabetic patient must be considered when non-diabetic renal disease is suspected, such as in the presence of a rapid decline in renal function or severe unexplained proteinuria. However, the timing and criteria of a biopsy remain controversial in these patients. We aimed to identify clinical and histological markers that could help differentiate diabetic and non-diabetic renal disease and decide if this invasive approach is needed or not. Subjects and Methods: We reviewed 30 years of biopsies from diabetic patients performed at a tertiary hospital. We collected patient demographic data, biopsy indications, histological findings, and clinical and analytical data both at the moment of the biopsy and extensive followup. Based on kidney biopsy findings, patients were categorized as isolated diabetic nephropathy, non-diabetic kidney disease, or non-diabetic kidney disease superimposed on diabetic nephropathy (diabetic kidney disease). Results and Discussion: We enrolled 92 patients, mostly with type 2 diabetes, with a mean age of 62.9 ± 13.2 years. Nearly half of them had isolated diabetic nephropathy (53.3%), and 15.2% had diabetic nephropathy superimposed on non-diabetic kidney disease, comprising a total of 63 patients (68.5%) with diabetic kidney disease. Twenty-nine patients (31.5%) were considered to have non-diabetic kidney disease. These last patients were significantly less likely to need insulin therapy (p=0.002), had more frequently an acute deterioration of renal function (p=0.01), lower albumin levels (p=0.03), and a higher prevalence of microhematuria (p=0.001). We found the latter to be an independent predictor of non-diabetic kidney disease. Further, patients with the primary diagnosis of diabetic nephropathy had higher survival than those who had nondiabetic kidney disease, contradicting published data. Conclusions: The criteria for performing a biopsy in diabetic patients still lack consensus, although the priority to identify non-diabetic kidney disease prevails. We believe the non-diabetic kidney disease predictors we describe may prove helpful for determining the need for a histological assessment in diabetic patients.

From membranoproliferative glomerulonephritis to a final diagnosis: Hypocomplementemic urticarial vasculitis syndrome

Membranoproliferative glomerulonephritis describes a glomerular-injury pattern common to a heterogeneous group of diseases. Evaluation based on clinical and laboratory presentation and immunofluorescence staining on kidney biopsy allows identification of underlying pathophysiological processes and may facilitate proper diagnosis and treatment. Hypocomplementemic urticarial vasculitis syndrome is a rare autoimmune disease of multi-organ involvement. The diagnosis is based on well-defined clinical and laboratory criteria. The pathophysiology is not completely understood but the presence of anti-C1q antibody seems to be involved. Renal involvement occurs in up to 50% of cases. It can be heterogeneous and can be indistinguishable from lupus nephritis. Serological findings and skin involvement distinguish these two entities. We report the case of a 40-year-old female who presented with urticarial skin lesions, hypocomplementemia and nephrotic syndrome. Kidney biopsy showed membranoproliferative glomerulonephritis with full house immune complex deposits. The diagnosis of hypocomplementemic urticarial vasculitis syndrome was made and the patient was successfully treated with prednisolone and mycophenolate mofetil.

A Novel Homozygous Mutation in the COL4A4 Gene (Gly1436del) Causing Alport Syndrome Exposed by Pregnancy: A Case Report and Review of the Literature

Background. Alport syndrome results from a hereditary defect of collagen IV synthesis. This causes progressive glomerular disease, ocular abnormalities, and inner ear impairment. Case Presentation. Herein, we present a case of Alport syndrome in a 28-year-old woman caused by a novel mutation (Gly1436del) in the COL4A4 gene that was not unveiled until her first pregnancy. Within the 29th pregnancy week, our patient presented with massive proteinuria and nephrotic syndrome. Light microscopic examination of a kidney biopsy showed typical histological features of segmental sclerosis, and electron microscopy revealed extensive podocyte alterations as well as thickness of glomerular basement membranes with splitting of the lamina densa. One and a half years after childbirth, renal function deteriorated to a preterminal stage, whereas nephrotic syndrome subsided quickly after delivery. Conclusion. This case report highlights the awareness of atypical AS courses and emphasizes the importance of genetic testing in such cases.

Morning Glory Syndrome associated with Autosomal Dominant Alport Syndrome with a Heterozygous COL4A4 Mutation

Morning glory syndrome (MGS) is a rare congenital optic disc anomaly with a characteristic fundal finding with severe visual impairment. It may occur in association with various systemic manifestations, even though most of the reported cases were isolated. A 6-year-old male visited the nephrology clinic with a history of microscopic hematuria and at the age of 12 years, he was diagnosed thin glomerular basement membrane nephropathy by kidney biopsy. After the following years, the patient had progressive deterioration of visual acuity, and diagnosed as MGS. Whole Exome Sequencing of this patient and his mother revealed heterozygous COL4A4 mutations [c.81_86del (p.Ile29_Leu30del)]. It is more reasonable to consider MGS seen in this patient as a coincidental finding of autosomal dominant Alport syndrome. To our knowledge, this case represents the first case report of autosomal dominant Alport syndrome associated with MGS.

Pathogenesis and methods of diagnosis of chronic kidney disease in cats: retrospective analysis (1981–2007)

The aim: to conduct a retrospective analysis of literature sources on the pathogenesis and methods of diagnosis of chronic kidney disease in cats. Materials and methods. The research was conducted by the method of scientific literature open-source analysis: PubMed, Elsevier, electronic resources of the National Library named after V.I. Vernadsky (1981–2007). Results. Chronic kidney disease is a common reason for cat owners to go to veterinary clinics. The term “chronic kidney disease” has a broader meaning than the more limited and not very specific name – chronic renal failure; it is also used to indicate the preazotemic stage of the disease. Chronic kidney disease is characterized by a gradual deterioration of the clinical condition of animals due to progressive decline in renal function. An idea of the pathogenesis and methods of diagnosis of chronic kidney disease in the period from 1981 to 2007 is presented. Conclusions. According to the results of retrospective analysis of literature sources for the period from 1981 to 2007, the basis was identified aspects of the pathogenesis of chronic kidney disease in domestic cats, which have not lost relevance today. The main link during chronic kidney disease in cats is the development of hyperazotemia and, as a consequence, endogenous intoxication of the body, which develops gradually and leads to the death of the animal. The morphological basis of chronic kidney disease in cats is the development of diffuse nephrosclerosis, which is reflected in the results of clinical, biochemical and instrumental studies. According to biochemical analysis of blood, in cats recorded an increase in urea and creatinine, the results of clinical studies of urine showed a decrease in its relative density, as well as the development of proteinuria, the appearance of erythrocytes and cylinders. According to the results of hematological research, anemic syndrome develops due to decreased erythropoietin synthesis. With age in cats, ultrasound examination of the kidneys reveals a decrease in their volume due to uniform sclerosis of the parenchyma: it is determined by its thinning and increased echogenicity due to the accumulation of connective tissue components, which is a sign of nephrosclerosis. Although kidney biopsy is the most informative method of diagnosing chronic kidney disease, it has many contraindications, which does not allow its use in the routine diagnosis of nephropathy in domestic cats. its thinning and increase in echogenicity due to the accumulation of connective tissue components, which is a sign of nephrosclerosis, is determined. Although kidney biopsy is the most informative method of diagnosing chronic kidney disease, it has many contraindications, which does not allow its use in the routine diagnosis of nephropathy in domestic cats. Its thinning and increase in echogenicity due to the accumulation of connective tissue components, which is a sign of nephrosclerosis, is determined