| Objective:Alport syndrome is a typical inherited glomerular disease characterized by the presence of typical GBM lamellar ultrastructural changes,sensorineural hearing loss,ocular abnormalities and progressive renal failure.The inheritance of Alport syndrome is complex.X-linked dominant Alport syndrome accounts for 85% of patients with Alport syndrome.The mutation of COL4A5 gene located on chromosome X leads to the occurrence of X-linked dominant Alport syndrome.About 90% of male patients with X-linked dominant Alport syndrome progress to end-stage renal disease at the age of 40,mostly with hearing impairment,but only15% to 30% of women develop renal failure at the age of 60.In this study,we followed up a male patient with Alport syndrome with FSGS as the clinical pathological manifestation,recorded the treatment method of the combination of Chinese and Western medicine,and summarized the diagnosis and treatment of Alport syndrome,in order to improve the understanding of clinicians on Alport syndrome and provide the TCM ideas and solutions for genetic nephropathy.Methods:A case of Alport syndrome with FSGS as the pathological manifestation was followed up in the Nephrology Department of Hubei Provincial Hospital of Traditional Chinese Medicine.Medical history collection,physical examination and laboratory tests including routine urine test,routine blood test,24-h urine protein quantification,renal function,T lymphocyte subsets,liver function and coagulation function were performed.The symptoms,physical examination and laboratory tests were followed for 27 months.The definition,diagnosis and treatment of Alport syndrome in TCM and Western medicine were reviewed based on the relevant literature both in China and abroad.Results:1.Follow-up observation: The patient in this case was diagnosed with FSGS through kidney biopsy in a western hospital.After two months of treatment with medroxyprogesterone 48 mg,the curative effect was unsatisfactory.Hence,tacrolimus 1mg bid was added,and the 24-h urine protein quantity was gradually decreased,reaching a minimum of 0.236 g/24 h.When the hormone content was regularly reduced to 12 mg,the disease recurred,and it was slightly improved after the addition of 4mg,but when it was reduced again to 12 mg,the 24-h urine protein gradually increased,reaching3.534mg/24 h h.The outpatient physician recommended the patient go to our hospital for integrative Chinese and Western medicine treatment.Outpatient follow-up in our hospital so far.During our out-patient follow-up of 3 months,tacrolimus was discontinued based on his time of use and T-lymphocyte subsets.Later,the patient’s condition was controlled by using Medrol as well as symptomatic treatment in combination with traditional Chinese medicine treatment.During the follow-up period of 22 months,considering the possibility of genetic nephropathy in combination with the patient’s situation,the patient was recommended to undergo genetic testing and gradually stop using Medrol.Only the symptomatic treatment and TCM syndrome differentiation treatment were adopted,and the patients were treated with Qingxin Lianzi Decoction combined with Fangji Huangqi Decoction.As a result,the patient’s serum creatinine gradually decreased to normal.Genetic testing reports showed that this patient had a hemizygous mutation in the COL45 gene: a hemizygous mutation at nucleotide 1120,which changed from guanine G to adenine A（c.1120G> A）,resulting in glycine 374 to arginine（P.G374R）,which was a missense mutation.According to the ACMG guidelines,the mutation was tentatively identified as a pathogenic mutation: PS4+PM1+PM2+PM5+PP3.Family-validated analysis revealed no mutation at this locus in her father and a heterozygous mutation at this locus in her mother.2.Review of literature both in China and abroad: At present,there is no specific treatment method for patients with Alport syndrome in China and abroad.Many clinical studies have shown that ACEI/ARB drugs can control proteinuria and delay renal progressive development in patients.For patients with end-stage renal failure caused by Alport syndrome,the efficacy and survival of dialysis treatment and renal transplantation are not statistically significant compared with those of patients with end-stage renal disease caused by non-Alport syndrome.The former is even superior to the latter in efficacy and survival in a clinical study.In animal studies,multiple in vivo experiments proved that anti-fibrosis,anti-inflammation,anti-interstitial and control of cholesterol content had a significant inhibitory effect on mice with Alport syndrome,which could reduce urine protein and delay renal failure.In an in vitro experiment,pluripotent stem cells were successfully induced from the patient’s peripheral blood mononuclear cells.Conclusion:1.For hereditary nephropathy,there is no specific treatment in western medicine at present,and ACEI/ARB is the main treatment.In CNKI,CBM,Wanfang,Chinese Medical Association,NEJM,THE LANCET,Pubmed and other database,there are very few reports about the treatment of Alport syndrome with traditional Chinese medicine.The first manifestation of this case reported in this paper is refractory nephrotic syndrome,with FSGS as the pathological feature.Western medicine treatment is very difficult and the condition is repeated.After seeking the treatment of integrated traditional Chinese and western medicine,the hormone and immunosuppressant were successfully withdrawn.After the diagnosis of AS,the treatment of integrated Chinese and western medicine made the patient.2.With the popularization of gene testing,more and more patients with Alport syndrome,especially male patients caused by COL4A5 gene mutation,were found to have FSGS as their pathological features.3.When hereditary diseases have not been popularized,secondary nephrotic syndrome is investigated,and nephrotic syndrome with pathological characteristics of FSGS caused by hereditary diseases is often less investigated.With the popularization of genetic testing and the reduction of the cost of genetic testing,it is suggested that genetic testing should be started as soon as possible for patients with refractory nephrotic syndrome,those with rapidly progressive kidney development and those whose pathological reports suggest that genetic testing is necessary,so as to guide the follow-up treatment,and avoid unnecessary immunosuppressive therapy to reduce its side effects and reduce the economic burden.4.The first symptom of Alport syndrome patients is persistent microscopic hematuria,which mostly occurs in childhood.The first symptom and onset age of this patient are different from those of common Alport syndrome,and misdiagnosis of AS often occurs in clinic.This report is hereby made to raise clinicians’ attention to this disease. |
