Diagnostic Value of Type IV Collagen Expression in Renal Glomeruli at Alport’s Syndrome

The Alport’s syndrome is the hereditary multisystem disease characterized by the development of the progressive nephropathy. The early diagnosis and subsequent prescription of nephroprotective therapy improves significantly the nephrological prognosis. Purpose of the Study. Determine the value of the immunohistochemical method for the Alport’s syndrome diagnosis. Material and methods. The clinical, laboratory and morphological data of 35 patients with suspected Alport’s syndrome (13 years of age [11; 16]; 18 boys and 17 girls) examined in the Nephrology Department in 2013–2019 were summarized. The study of the renal tissue included the light, immunofluorescence, electron microscopy of the kidney biopsy sample, determination of the expression of α1, α3 and α5 chains of type IV collagen in the renal glomeruli using the immunohistochemical method; the genetic testing was carried out for 26 patients. The children were divided into groups depending on the glomerular expression of α5 chain of type IV collagen: normal (group 1, n=18), decreased (group 2, n=4), negative (group 3, n=13). Results are as the following: The disorder of the expression of α5 chain was detected in ¾ (q = 0.78) patients with genetically confirmed Alport’s syndrome and in almost all children with the X-linked variant of the disease (q = 0.94). Results. Based on the genetic testing, the Alport’s syndrome was confirmed in ¼ of the children of the 1st group (the children with the heterozygous variants of COL4A3, COL4A5 genes) and in all children of the 2nd and 3rd groups (COL4A5 variants). The sensitivity/ specificity of the immunohistochemical study for the Alport’s syndrome diagnosis was 78% /100%, that of the electron microscopy – 93% /87%. The predictive value of the positive/negative result of the immunohistochemical study was 100% /66%, that of the electron microscopy – 95% / 88% compared with 100% / 88% with the combine use of two methods. Conclusion. The determination of the expression of α5 chain of type IV collagen in the renal glomeruli has the independent diagnostic value, but it is inferior to the electron microscopy in the heterozygous variants of the Alport’s syndrome. The high specificity of the immunohistochemical method makes it possible to confirm the Alport’s syndrome in the case of the change in the expression of α5 chain of type IV collagen in the renal glomeruli.

Renal involvement in genetic disease

There are more than 200 inherited disorders in which the kidney is affected and which display a wide range of renal features. Autosomal dominant polycystic kidney disease— affects about 1/1000 individuals and accounts for 7% of cases of endstage renal failure in Western countries. Inheritance is autosomal dominant, with mutations in polycystin 1 responsible for 75% of cases and mutations in polycystin 2 accounting for most of the remainder. May present with renal pain, haematuria, urinary tract infection, or hypertension, or be discovered incidentally on physical examination or abdominal imaging, or by family screening, or after routine measurement of renal function. Commonly progresses to endstage renal failure between 40 and 80 years of age. Main extrarenal manifestations are intracranial aneurysms, liver cysts, and mitral valve prolapse. Alport’s syndrome—X-linked dominant inheritance in 85% of kindreds, with molecular defects involving the gene encoding the α‎-5 chain of the type IV collagen molecule. Males typically present with visible haematuria in childhood, followed by permanent nonvisible haematuria, and later by proteinuria and renal failure. Extrarenal manifestations include perceptive deafness of variable severity and ocular abnormalities. Carrier women often have slight or intermittent urinary abnormalities, but may develop mild impairment of renal function late in life, and a few develop endstage renal disease. In the autosomal recessive form of Alport’s syndrome, renal disease progresses to endstage before 20 to 30 years of age at a similar rate in both affected men and women. Other disorders covered in this chapter include hereditary tubulointerstitial nephritis, hereditary tumours, glomerular structural diseases, metabolic diseases with glomerular involvement (Fabry’s disease), congenital anomalies of the kidney and urinary tract, and other genetic diseases with kidney involvement.

Incidentally Diagnosed Alport Syndrome in a Patient with Drug-Induced Vasculitis

A 53-year-old woman is admitted with a serum creatinine of 16 mg/dl. Seven months earlier, she was diagnosed with heart failure and started on several medications, including Hydralazine. Laboratory studies revealed the presence of dual Anti-Neutrophil Cytoplasmic Antibodies (anti-MPO and anti-PR3), anti-nuclear and anti-histone antibodies. The clinical diagnosis was Drug-Induced ANCA Vasculitis (DIAV). Kidney histology, however, did not reveal crescents, but showed characteristic features of Alport’s syndrome.

Alport’s syndrome and intracranial aneurysm: mere coincidence or undiscovered causal relationship

A 44-year-old Caucasian man with a history of deceased donor renal transplant for end-stage renal disease from Alport’s syndrome (AS), presented with a spontaneous subarachnoid haemorrhage and hydrocephalus. Following an external ventricular drain for the hydrocephalus, a CT angiography revealed a dissection of the left vertebral artery extending into vertebro-basilar junction necessitating a bypass between left occipital artery to left posterior inferior cerebellar artery. He had a posterior fossa Craniectomy, C1 laminectomy and coiling off, of the left vertebral artery. Postprocedure course was prolonged but uneventful with complete recovery and normal renal function 18 months postpresentation. AS, a disease caused by abnormalities in the synthesis of type IV collagen, can cause aneurysms with severe and permanent neurological sequalae. We present a case of AS with intracranial arterial dissection with potential life-threatening consequences and discuss the genetic and molecular basis of AS along with review of the relevant literature.