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S Y Woodford

Publications and source records attributed to S Y Woodford.

11 recordsLinked to original sources

Epidemiology of IgA nephropathy in central and eastern Kentucky for the period 1975 through 1994. Central Kentucky Region of the Southeastern United States IgA Nephropathy DATABANK Project.

Population-based incidence data for IgA nephropathy (IgAN) are available for some countries but not for the United States. The purpose of this study was to determine the incidence of IgAN in central and eastern Kentucky for 5- and 10-yr periods between 1975 and 1994 and to examine differences among patient groups between those periods. The incidence of IgAN was 5.4 cases per one million population per year (MPPY) for period 1A (1975 through 1979), increasing to 12.4 cases per MPPY for period 2B (1990 through 1994) (P < 0.001). Males had a 2.7 times higher incidence than females for period 1 (1975 through 1984) and 2.2 times higher for period 2 (1985 through 1994). For period 1A, the incidence for Fayette County, which includes the city of Lexington, was lower than that of the rest of the study area (P=0.26), whereas for period 2 the incidence was higher for Fayette County (P=0.052). During period 1, the highest incidence of IgAN for any age and gender group was 24.3 cases per MPPY for males ages 30 through 39. For period 2, the incidence for males was similar for each decade between ages 20 and 59 (approximately 19 cases per MPPY). No African-American was diagnosed during period 1, but in period 2 incidences for blacks and whites were similar (10.7 and 10.2 cases per MPPY, respectively). For the last 5 yr of the study (1990 through 1994), the incidence of end-stage renal disease (ESRD) due to IgAN was 5.5 cases per MPPY: 8.4 for males and 2.7 for females. The incidence of IgAN in Kentucky for period 2B was still much lower than that in European studies, but the incidence of ESRD due to IgAN may be similar. Thus, IgAN may be as important a condition with respect to ESRD in Kentucky as it is in other regions of the world.

Adolescent↗

IgA nephropathy: long-term prognosis for pediatric patients.

OBJECTIVE: The determination of the ultimate prognosis for patients with IgA nephropathy diagnosed in childhood requires long-term follow-up of identified patients. The purpose of this study was to obtain such follow-up for patients from two centers where the disease has been diagnosed for more than 20 years. METHODS: Clinical data at the apparent onset of symptoms and renal histologic data were obtained for 103 patients in whom IgA nephropathy was diagnosed before age 18 years. Clinical status at last follow-up was obtained from office records or from direct contact with the patient. Predicted kidney survival was determined by the Kaplan-Meier method. Follow-up of more than 10 years from the time of biopsy was available for 40 of the patients. RESULTS: Fourteen of the patients have progressed to end-stage renal disease; three others have progressive chronic renal insufficiency as defined by an estimated creatinine clearance of less than 50 ml/min per 1.73 m2. Severity of the renal histologic findings and the degree of proteinuria at the time of biopsy were associated with poor outcome. For all patients, predicted kidney survival from the time of apparent onset was 94% at 5 years, 87% at 10 years, 82% at 15 years, and 70% at 20 years. Age at clinical onset and gender were not associated with poor outcome, but black race and severity of renal histologic findings were. CONCLUSION: With follow-up into adulthood, the outcome for pediatric patients with IgA nephropathy appears to be as serious as that reported in adult patients. Follow-up of a pediatric patient with persistent clinical findings should be maintained after the patient's care is transferred to a physician caring for adults.

Adolescent↗

C4A deficiency and poor prognosis in patients with IgA nephropathy.

IgA nephropathy (Berger's disease) is an important cause of end-stage renal failure in persons of Asian and European descent. We performed C4 phenotyping on plasma from 123 patients with IgA nephropathy who resided in several different parts of the United States. All of these patients underwent diagnostic renal biopsy in adulthood. Six patients had a total deficiency for the C4A protein and all six had chronic renal insufficiency (serum creatinine concentration higher than 1.4 mg/dl at last follow-up). In contrast, 47% of the patients without C4A deficiency had chronic renal insufficiency (p = 0.001). The C4 gene defect was due to deletion of both C4A genes in only two individuals, whereas three patients were heterozygous for the C4A gene deletion. We speculate that the functional alteration of the complement system related to C4A deficiency might lead to expression of clinically severe disease in an individual with a genetic susceptibility to IgA nephropathy.

Chromosome Deletion↗

Familial clustering and immunogenetic aspects of IgA nephropathy.

IgA nephropathy (IgAN) has been assumed to develop sporadically in individuals. We review the recent clinical and laboratory evidence that supports a genetic influence in the immunopathogenesis in some patients. These data include (1) families with multiple members with the disease not sharing a known nephrotoxic factor, (2) clustering of the birthplaces of ancestors of large pedigrees with multiple affected members, suggesting a "founder effect," (3) DNA alleles and protein phenotypes associated with IgAN (or a clinical subset) in some patient populations or that cosegregate with the disease in families with multiple affected members, and (4) immunologic abnormalities of patients shared by relatives with renal disease. However, the lack of understanding the fundamental pathogenetic mechanisms hinders progress in the pursuit of genetically controlled process in this disease. Furthermore, the diagnosis requires a renal biopsy, and no therapy has been proven effective. Therefore, asymptomatic family members with IgAN may forego the invasive diagnostic procedure necessary to establish the diagnosis, and instances of familial disease may not be investigated. Nonetheless, the increasing awareness of families with multiple affected members offers an opportunity to investigate the hypothesized genetic influence in the pathogenesis of IgAN.

Genetic Markers↗

Regionalization in hereditary IgA nephropathy.

The genealogies of 80 patients with IgA nephropathy who were born in central or eastern Kentucky or whose parents were born in this region were researched. At a minimum, 48 of these patients were related to at least one other patient. On the basis of presence or absence of established kinships, the patients were divided into three groups. Twenty-nine patients in group 1 belonged to one large pedigree. Their birthplaces and those of their parents, grandparents, and great-grandparents clustered in the extreme eastern portion of the state. Seventeen other patients, group 2, were related to at least one other patient but not to a patient in group 1. Their birthplaces and those of their ancestors did not show significant clustering. With the exception of two siblings, the 34 patients of group 3 had no family members with IgA nephropathy. The birthplaces for these patients and ancestors were widely scattered. These data suggest that one or more genetically determined factors are important in the pathogenesis of IgA nephropathy in some patients. A founder effect, whereby a gene(s) conveying susceptibility to IgA nephropathy was carried into eastern Kentucky by one or more of the early settlers, would explain the geographic clustering of the birthplaces of the patients in group 1 and their ancestors. The characteristic immunopathology of IgA nephropathy may represent the histologic result of separate disease processes, one or more of which could be genetically influenced.

Consanguinity↗

Familial IgA nephropathy. Evidence of an inherited mechanism of disease.

The evaluation of familial glomerulonephritis in patients with IgA nephropathy who were from central and eastern Kentucky resulted in the discovery of potentially related pedigrees containing 14 patients. An additional 17 members of the pedigrees had clinical glomerulonephritis, and 6 had "chronic nephritis" noted on their death certificates. Six patients with IgA nephropathy had a common ancestor. In addition, both parents of six patients with the disease came from families with other cases of IgA nephropathy. No single HLA haplotype or antigen was found in all the patients with IgA nephropathy. Our data on these pedigrees strongly support an inherited mechanism in the pathogenesis of IgA nephropathy in some patients.

Female↗

Effect of alternate-day prednisone on plasma lipids in renal transplant recipients.

While numerous groups have reported high prevalences of plasma lipid abnormalities in their renal transplant recipients, we have been unable to confirm this finding. We have suggested that the routine use of alternate-day steroids (ADS) in our patients may be responsible. To test that hypothesis, a prospective controlled trial of equal total dose ADS versus daily steroids (DS) was conducted. Four months after transplant and before entering the trial, transplant study patients had significantly higher serum cholesterol (243 +/- 9 mg/dl) than either normal controls (cholesterol 200 +/- 7 mg/dl, alpha = 0.01) or hemodialysis patients (cholesterol 211 +/- 9 mg/dl, alpha = 0.01). They also had higher serum triglyceride than controls (129 +/- 7 mg/dl vs. 98 +/- 8 mg/dl, alpha = 0.01). After randomization to DS or ADS and 1 year of further followup study, the ADS group had a significant decrease in both serum triglyceride (139 +/- 9 to 100 +/- 7 mg/dl, P less than 0.01) and cholesterol (251 +/- 16 to 220 +/- 9 mg/dl, P less than 0.05) while the DS group's serum triglyceride and cholesterol values remained unchanged. Serum triglyceride and cholesterol in the ADS group had decreased to values that were not significantly different from 41 normal healthy controls. Dose spacing per se, and not the use of a lower total dose of prednisone, appears to result in a lower prevalence of abnormal plasma lipids after successful renal transplantation.

Adolescent↗

Comparison of daily and alternate-day prednisone during chronic maintenance therapy: a controlled crossover study.

To determine if dose spacing of low dose chronic suppressive corticosteroid therapy would result in different effects on circulating T lymphocytes and hypothalamic-pituitary-adrenal (HPA) axis suppression, a crossover trial of two maintenance steroid regimens was performed. Twenty stable renal allograft recipients were treated for 6 mo with daily prednisone (DS) and then the same patients were abruptly converted to alternate-day prednisone (ADS) for another 6 mo. Total prednisone dosage was identical during the 6-mo study periods and only dose spacing differed. Both circulating T lymphocyte numbers and responsiveness to mitogens were less on the DS regimen. Patients gained weight on DS and lost weight on ADS. Five of the 20 patients developed infections on DS. However, HPA suppression was not different on the two regimens. These findings suggest that dose spacing alters the immunosuppressive and metabolic response to prednisone, even at low dose.

Body Weight↗

Effect of prednisone dose spacing on plasma lipids.

We have previously reported a low prevalence of hyperlipidemia in renal transplant recipients who were treated with alternate-day corticosteroid. To determine whether alternate-day prednisone per se is associated with lower plasma lipids than is daily prednisone, we studied 14 renal transplant recipients with good allograft function (serum creatinine less than 2.5 mg/dl) who were normolipidemic on alternate-day prednisone. All patients were treated with 6 months of daily prednisone (10.9 +/- 0.4 mg, mean +/- S.E.) and then returned to 6 months of alternate-day prednisone (21.6 +/- 1.0 mg). Mean plasma triglyceride, cholesterol, and cholesterol fractions on either regimen were normal and not different. There were no differences in fasting or 2 hr postprandial glucose and insulin levels. Twelve patients gained weight on daily prednisone, and 11 patients lost weight on reversion to alternate-day prednisone. The changes in ideal body weight in both periods correlated (p less than 0.05) with changes in plasma triglycerides. These data suggest that a daily prednisone regimen per se as compared to an alternate-day regimen does not dispose normolipidemic patients to hyperlipidemia. The factors contributing to the low prevalence of hyperlipidemia in our renal transplant recipients remain obscure.

Adult↗