Fibronectin glomerulopathy (FGP), also known as fibronectin deposition glomerulopathy (GFND), is a rare hereditary autosomal dominant glomerular disease. Its clinical manifestations are proteinuria, hematuria, hypertension, and hyperkalemic distal renal tubular acidosis, which often progresses slowly to end-stage renal disease. We report a 21-year-old woman with fibronectin glomerulopathy who underwent renal puncture at the age of 10. The pathology was considered to be thrombotic microangiopathy, and it was not treated regularly. This time, renal puncture was performed again due to proteinuria combined with elevated serum creatinine. Light microscopy showed severe mesangial matrix hyperplasia of glomeruli with dense deposition and foam cell aggregation in capillary loops. Fibrinogen immunostaining was positive. Electron microscope showed severe hyperplasia of mesangial matrix, and a large amount of electron-dense matter deposited in mesangial area. Perfect genetic testing suggested that the FN1 gene was heterozygous for NM_212482.4 (c.2918A>G), that is, Y973C mutation. Therefore, she was diagnosed with fibronectin glomerulopathy and was given sacubitril valsartan sodium tablets 200 mg b.i.d. orally. We report a case of a patient with fibronectin glomerulopathy and review the literature of this disease. The disease often has insidious onset, and fibronectin deposition is a typical pathological change that can result. The disease slowly progresses to end-stage renal disease. At present, there is no specific treatment. It is advocated to use reninangiotensin-aldosterone system blockers to strictly control blood pressure and proteinuria, and the overall prognosis is poor. Genetic testing techniques may be helpful in early diagnosis of the disease.

Fibronectin glomerulopathy (FG) is caused by fibronectin 1 (FN1) gene mutations. A renal biopsy was performed on a 4-year-old girl with incidentally discovered proteinuria (150 mg/dL); her family history of renal disease was negative. Markedly enlarged glomeruli (mean glomerular diameter: 196 μm; age-matched controls: 140 μm), α-SMA-positive and Ki-67-positive mesangial cell proliferation (glomerular proliferation index 1.76), the mild expansion of mesangial areas, no immune or electron-dense deposits, normal glomerular basement membrane, and diffusely effaced foot processes were observed. Genetic testing identified a de novo heterozygous mutation (Gly417Val) in the collagen-binding site of the FN II-2 domain, prompting fibronectin immunostaining. Strong mesangial positivity was noted, hence FG was diagnosed. The follow-up period of 29 months revealed nephrotic range proteinuria, intermittent microhematuria, glomerular hyperfiltration, and preserved renal function. The biopsy features of early childhood-onset FG were compared to a case of FG with a lobular pattern diagnosed in a 44-year-old patient with undulating proteinuria, microhematuria, hypertension known for a year, and a positive family history. Early childhood-onset FG was characterized by glomerular enlargement, mesangial proliferation, and no changes that suggested fibronectin deposition disease. In summary, the novel aspects of the case were that the mutation was located at the collagen-binding site of the FN1 gene, not identified earlier, and the histologic spectrum of FG was expanded by the observed mesangial proliferative pattern and striking glomerulomegaly. Now, FG should also be considered among the monogenic causes of proteinuric kidney diseases in pediatric nephrology practice.

Fibronectin glomerulopathy is a rare autosomal dominant disorder characterized by abnormal deposition of fibronectin within the kidney. It is associated with several variant mutations in the FN1 gene. It is a disorder predominantly characterized by proteinuria that can reach the nephrotic range, and it has been primarily described in Asian and White populations. Here, we report a case of fibronectin glomerulopathy from Ethiopia, which, to our knowledge, is the first ever reported in Africa. A 17-year-old Ethiopian female presented with generalized body swelling and nephrotic range proteinuria. Secondary causes of nephrotic syndrome were ruled out, but kidney biopsy was not performed early because of financial constraints. The patient received initial treatments with RASi (renin-angiotensin system inhibitor) and diuretics followed by steroids and tacrolimus, but lacked a clear response. Eventually, a kidney biopsy and examination at a pathology laboratory in India revealed extensive periodic acid Schiff-positive but Jones' methenamine silver-negative and Congo red-negative mesangial and capillary wall deposits, which stained strongly for fibronectin on immunohistochemistry. A diagnosis of fibronectin glomerulopathy was made. Diagnosing fibronectin glomerulopathy could be challenging in many developing nations due to a lack of proper pathological and genetic testing infrastructure. Improving local health infrastructure for kidney tissue diagnosis could improve diagnostic accuracy, better guide management, and help avoid the administration of unnecessary medications with a potential for serious adverse events.

Fibronectin glomerulopathy (FNG) is a rare autosomal dominant inherited disease characterized by extensive deposits of fibronectin in the mesangium and subendothelial space of the glomeruli with membranoproliferative glomerulonephritis (MPGN)-like pattern. Currently, ten exonic and one intronic pathogenic variants in the fibronectin 1 gene have been identified; however, genotype-phenotype correlation data are lacking. We herein report a familial FNG caused by a splice site variant in intron 36 (c.5888-2A > G). The gene mutation was recently found, but to our knowledge, this is the first case report of a familial FNG with the intronic variant that describes the clinicopathological characteristics. In the current study, Case 1 is a previously healthy 29-year-old woman with nephrotic syndrome. Treatment with glucocorticoids, combined with the immunosuppressant mizoribine and an angiotensin II receptor blocker (ARB), resulted in an incomplete remission of nephrotic syndrome; however, renal function has been preserved. Case 2, the mother of Case 1, is a 49-year-old woman with vasculo-Behçet's disease with mild proteinuria and renal dysfunction. Due to the administration of azathioprine, aspirin, and ARB, renal function and proteinuria have been stable over 10 years. The kidney biopsy revealed MPGN-like histological features in both the mother and the daughter; however, the mesangial area exhibited a milder expansion in the mother than in the daughter. Accumulating genotype-phenotype correlation data will be essential for managing FNG.

Fibronectin glomerulopathy (FNG) is a rare autosomal dominant glomerulopathy that can lead to nephrotic syndrome. Here we report the case of an elderly patient diagnosed with FNG, exhibiting nephrotic-range proteinuria, with a 2-year follow-up. A 75-year-old Korean female visited the nephrology clinic after experiencing generalized edema for 2 months. Her serum creatinine was 1.36 mg/dL, and urine protein-to-creatinine ratio was 3.99 g/g. Kidney biopsy revealed mesangial and subendothelial dense deposits, and immunohistochemistry for fibronectin showed strong positivity in the glomerulus. The patient's family history included non-specific renal disease in her mother and two siblings. Genetic testing of the fibronectin 1 (FN1) gene showed Y973C mutation. She received conservative treatment, including angiotensin II receptor blockers (ARB). Two years after biopsy, the patient has preserved renal function and reduced proteinuria. We report the case of a 75-year-old patient with nephrotic-range proteinuria, who was diagnosed with FNG, and found to harbor a FN1 gene mutation. In this case, conservative treatment including ARB yielded reduction of proteinuria and preservation of renal function.