Biomedical subjects

Geraldine Derby

Publications and source records attributed to Geraldine Derby.

3 recordsLinked to original sources

PubMed2006

Adaptive hyperfiltration in the aging kidney after contralateral nephrectomy.

We examined the magnitude of adaptive hyperfiltration in the remaining kidney of 16 aging (>57 yr) and 16 youthful (<55 yr) individuals who had undergone a contralateral nephrectomy. Healthy volunteers who were youthful (n = 143) or aging (n = 37) provided control values for the binephric condition. One-kidney glomerular filtration rate (GFR; +42%), renal plasma flow (+38%), plasma oncotic pressure (+2.8 mmHg), and mean arterial pressure (+7.0 mmHg) were all higher in youthful uninephric vs. binephric subjects. Corresponding excesses in aging uninephric vs. binephric subjects were by 38 and 36% and 1.4 and 14.0 mmHg, respectively. Modeling of these data revealed that an isolated increase in either the glomerular ultrafiltration coefficient (K(f)) by 110% or in the transcapillary hydraulic pressure gradient (DeltaP) by 7 mmHg, could account for the observed level of hyperfiltration in youthful uninephric subjects. Corresponding increases for aging uninephric subjects were 61% for K(f) and 5 mmHg for DeltaP. We conclude that the magnitude of adaptive hyperfiltration is similar in aging to that in youthful uninephric subjects, albeit at a lower absolute GFR level. Isolated increases in either K(f) or DeltaP or a combination of smaller increases in both can account for the hyperfiltration. Greater adaptive arterial hypertension in aging than youthful uninephric subjects raises the possibility of a disproportionate role for glomerular hypertension and DeltaP elevation in aging compared with youthful uninephric subjects. Glomerular hypertension could exacerbate the sclerosing glomerulopathy of senescence and lead to renal insufficiency. We recommend that living donors of a kidney transplantation in or beyond the seventh decade be used with caution.

Adaptation, Physiological↗

PubMed2003

Determinants of glomerular hypofiltration in aging humans.

BACKGROUND: The purpose of the present study was to confirm the extent to which glomerular filtration rate (GFR) is depressed in healthy, aging subjects and to elucidate the mechanism of such hypofiltration. METHODS: Healthy volunteers aged 18 to 88 years (N = 159) underwent a determination of GFR, renal plasma flow (RPF), afferent oncotic pressure, and arterial pressure. Glomeruli in renal biopsies of healthy kidney transplant donors aged 23 to 69 years (N = 33) were subjected to a morphometric analysis, so as to determine glomerular hydraulic permeability and filtration surface area. The aforementioned GFR determinants were then subjected to mathematical modeling to compute the glomerular ultrafiltration coefficient (Kf) for two kidneys and individual glomeruli. RESULTS: GFR was significantly depressed (P < 0.0001) by 22% in aging (>or=55 years old) compared to youthful subjects (<or=40 years old). Corresponding reductions of the following GFR determinants in the aging vs. youthful subsets were RPF by 28% (P < 0.0001), two-kidney Kf by 21% to 53% (P < 0.005), glomerular hydraulic permeability by 14% (P = 0.03), and the single-nephron Kf (SNKf) by 30% (P = 0.09). There were no significant differences between aging and youthful subsets for afferent oncotic pressure and filtration surface area per glomerulus. CONCLUSION: We conclude that a reduction in overall, two-kidney Kf contributes to GFR depression in aging subjects. We infer that this is due in part to structural changes that lower SNKf, and in part to the reduction in the actual number of functioning glomeruli that has been demonstrated by others at autopsy.

Adult↗

PubMed2002

Podocytopenia and disease severity in IgA nephropathy.

BACKGROUND: IgA nephropathy is a common form of progressive glomerular disease, associated with proliferation of mesangial cells and mesangial deposition of IgA. The present study was designed to investigate functional and morphological covariates of disease severity in patients with IgA nephropathy. METHODS: Glomerular hemodynamics, permselectivity and ultrastructure were studied in 17 adult patients with IgA nephropathy using inulin, para-aminohippuric acid (PAH) and 3H-Ficoll clearances and morphometric methods. A mathematical model of macromolecule permeation through a heteroporous membrane was used to characterize glomerular permselectivity. Controls consisted of 14 healthy living kidney donors and 12 healthy volunteers. RESULTS: The patients were heterogeneous in their disease severity, but as a group had a decreased glomerular filtration rate (GFR) and increased urinary protein excretion compared to controls [63 +/- 29 SD vs. 104 +/- 23 mL/min/1.73 m2, P < 0.001, and (median) 1.34 vs. 0.11 g/day, P < 0.0001, respectively). A multivariate analysis of structural and functional relationships revealed GFR depression to be most strongly correlated with the prevalence of global glomerular sclerosis (t = -4.073, P = 0.002). Those patients with the most severe glomerular dysfunction had a reduced number of glomerular visceral epithelial cells (podocytes) per glomerulus. The degree of podocytopenia was related to the extent of glomerular sclerosis and of impairment of permselectivity and GFR, with worsening injury below an apparent threshold podocyte number of about 250 cells per glomerulus. There were no corresponding correlations between these indices of injury and the number of mesangial and endothelial cells. CONCLUSIONS: Our findings show that podocyte loss is a concomitant of increasing disease severity in IgA nephropathy. This suggests that podocyte loss may either cause or contribute to the progressive proteinuria, glomerular sclerosis and filtration failure seen in this disorder.

Adult↗