Heterozygous Urinary Abnormality–Causing Variants of COL4A3 and COL4A4 Affect Severity of Autosomal Recessive Alport Syndrome

BackgroundAutosomal recessive Alport syndrome (ARAS) is an inherited renal disorder caused by homozygous and compound heterozygous mutations in COL4A3 or COL4A4, but the prognostic predictors for this disorder are not yet fully understood. Recently, the magnitude of the clinical spectrum of the COL4A3 and COL4A4 heterozygous state has attracted attention. This spectrum includes asymptomatic carriers of ARAS, benign familial hematuria, thin basement membrane disease, and autosomal dominant Alport syndrome.MethodsWe retrospectively analyzed 49 patients with ARAS from 41 families with a median age of 19 years to examine the clinical features and prognostic factors of ARAS, including the associated genotypes.ResultsThe median age of patients with ARAS at ESKD onset was 27 years. There was no significant association between the presence or absence of hearing loss or truncating mutations and renal prognosis. However, there was a statistically significant correlation between renal prognosis and heterozygous variants that cause urinary abnormalities. Where the urinary abnormality–causing variant was absent or present in only one allele, the median age of ESKD onset was 45 years, whereas the same variant present on both alleles was associated with an age of onset of 15 years (P<0.001).ConclusionsThis study was the first to demonstrate the clinical importance in ARAS of focusing on variants in COL4A3 or COL4A4 that cause urinary abnormalities in both the homozygous or heterozygous state. Although heterozygous mutation carriers of COL4A3 and COL4A4 comprise a broad clinical spectrum, clinical information regarding each variant is important for predicting ARAS prognosis.

Microalbuminuria in Healthy Adolescents: A Comparative Study at High Altitude and at Sea Level

Background : High altitude is associated with hypobaric hypoxia and increased risk for microalbuminuria in adults. We hypothesized that healthy adolescents at higher altitude might have an increased frequency of microalbuminuria in comparison with a group of adolescents living at sea level. Methods : We evaluated the presence of microalbuminuria in adolescents at sea level (n=68, altitude 130 meters) and at high altitude (n=114, altitude 3200 meters) living in Peru. Each subject was evaluated for body mass index, Blood Pressure, microalbuminuria, proteinuria, hematuria and leukocyturia in a first morning urine sample. Subjects with a positive test for microalbuminuria underwent repeat testing one or two weeks after the initial screening. Results : Subjects at sea level and high altitude had similar age, weight, height and blood pressure (p=NS). Microalbuminuria without any other urinary abnormality, was higher in the first screening among adolescents residing at high altitude compared to those living at sea level (42 vs15, p: 0.0215). In the second screening the results were similar in both groups (31 vs 11, p: 0.0879). Conclusion : Persistent microalbuminuria was observed in more than one-quarter of adolescents living at high altitude. This study suggests that subtle renal injury may occur early in subjects living at high altitude.

Indices of Kidney Damage and Cardiovascular Disease Risk Factors in a Semiurban Community of Iloye, South-West Nigeria

Health screening exercises are important, as they enable early detection of diseases in individual subjects and also enable data collection, useful in estimating disease burden in the community. This paper describes the findings of a health screening exercise conducted in a semiurban population of Iloye, by the Rotary Club of Ota, Ogun State, Western Nigeria, as a part of its community-oriented services and projects. Three hundred and twenty six community members were screened during the exercise. There were 189 (57.97%) females and 137 (42.03%) males, with a mean age of 43.5 ± 14.88 yrs. Urinary abnormality and/or creatinine clearance less than 90 mls/min was detected in 147 (45.09%) participants. 99 (30.37%) participants had proteinuria, 16 (4.91%) had haematuria, and 5 (1.53%) participants had both haematuria and proteinuria. Eight (2.45%) participants had GFR less than 60 mls/min. Elevated blood pressure was found in 152 (46.63%), while 3 (0.9%) participants had diabetes, 71 (21.8%) were obese, 16 (4.9%) had hypercholesterolaemia, and 3 (0.9%) had hypertriglyceridaemia. Prevalence of both smoking and alcohol consumption was 6 (1.84%). It was concluded that the prevalence of indices of kidney damage and cardiovascular risk factors is high in Iloye community.