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Biomedical subjects

B A Kiberd

Publications and source records attributed to B A Kiberd.

9 recordsLinked to original sources

The functional and structural changes of the glomerulus throughout the course of murine lupus nephritis.

The glomerular functional and structural changes in a murine model (MRL-lpr/lpr) of progressive lupus nephritis were studied. Animals were grouped into three age categories. (I, 14 wk; II, 20 wk; and III, 26 wk). GFR fell with age (257 +/- 43, 178 +/- 50, and 150 +/- 40 microL/min for Groups I through III, respectively). Similarly, the ultrafiltration coefficient (Kf) measured on isolated glomeruli fell with time (0.030 +/- 0.006, 0.023 +/- 0.006, and 0.013 +/- 0.002 nL/s/mm Hg, respectively). Both indomethacin and a selective thromboxane receptor antagonist L-670,596 significantly improved GFR in Group II animals to values seen in Group I animals. Neither agent had any effect to increase GFR in older group III animals. L-670,596 had no effect on Kf in Group II or III animals. Glomerular morphometric evaluation demonstrated a progressive rise in glomerular tuft volume, mesangial matrix expansion, proliferation in cells, and a reduction in open capillary loops and epithelial filtration slits with age. However, because of the increase in glomerular volume, calculated surface area remained well preserved over the three respective groups (61 +/- 18, 76 +/- 15, and 71 +/- 13 microns2 x 10(3)). Therefore, the fall in Kf is likely due to a fall in hydraulic permeability (Lp). The ultrastructural component of the glomerular capillary wall that correlated best with Lp was the epithelial filtration slit number per micrometer of glomerular basement length (r = 0.73; P < 0.0001), which suggests that the structural correlate Kf is in the filtration slit length (FSL). Despite the cell proliferation and mesangial matrix expansion in early disease (Group II), the overall FSL remains stable because of a slight increase in filtration surface area and a slight reduction in epithelial slits per micrometer of glomerular basement membrane. The fall in GFR appears to be hemodynamically mediated by thromboxane A2. In older Group III animals, the fall in GFR appears to be due to a 40% reduction in FSL rather than being hemodynamically based. Thus, the early improvement in function with pharmacological agents is deceptive because considerable disease may be present because of adaptive structural changes. Eventually, with disease progression, compensating hemodynamic and structural factors fail to maintain GFR within normal limits.

6-Ketoprostaglandin F1 alpha

Nursing attitudes towards organ donation, procurement, and transplantation.

This survey was carried out to examine the attitudes of nurses towards organ donation, transplantation, and procurement from the perspective of their nursing unit affiliation in a tertiary care center. Overall, 62% of nurses have already signed an organ donor card or driver's license. Those nurses willing to donate, compared with those not willing to donate, perceive renal transplants as cost effective (90% vs 38%, p less than 0.001) and successful (66% vs 47%, p less than 0.001, for estimated cadaver 1 year success rate). Nurses from some units (i.e., renal dialysis nurses), perceiving renal transplantation as being cost effective and successful, were more likely to personally report signing organ donor cards or driver's license. On the other hand, nurses from other units (i.e., the operating room) perceiving lower cost effectiveness and lower renal transplant success rates were, as a group, significantly less likely to sign organ donor cards or driver's license. Across the nursing units surveyed, both perceived transplant success and support for procurement correlated with the percent of nurses who have already signed organ donor cards/license (r = 0.94, p less than 0.02). We suspect that the nursing environment and the exposure to follow-up information on transplantation greatly influences personal attitudes towards donation. Efforts must be directed from the medical staff and within nursing to correct these shortcomings in order that all units may participate fully in the procurement-transplantation process.

Attitude of Health Personnel

Murine lupus nephritis. A structure-function study.

This report examines the correlation between glomerular injury and glomerular dysfunction in murine lupus nephritis. Glomerular filtration rate was measured by the clearance of inulin in conscious NZB/W female mice and shown to vary 12-fold in the animals tested. Detailed morphometric measurements were made on the perfused fixed kidneys. As disease progressed the surface density (Sv) of the open capillary loops decreased by 73%. This drop in Sv correlated with a 4-fold increase in mean glomerular volume (MGV, r = -0.79, p less than 0.0001). The "compensating" increase in MGV maintained or increased filtration surface area despite the loss of some capillary loops to proliferating and/or infiltrating cells. Filtration slit length/glomerulus and the filtration slit number/micron glomerular basement membrane varied 10-fold and were found to correlate directly with glomerular filtration rate (r = 0.64, p less than 0.0007 and r = 0.70, p less than 0.0001, respectively). When linear and multiple regression analyses were applied, all other structural measures, including filtration surface area, correlated with glomerular filtration rate poorly if at all. Glomerular permselective dysfunction (proteinuria) was measured as the fractional clearance of albumin (fractional clearance of albumin) and of IgG. Stepwise multiple regression analysis revealed the percentage of the glomerular basement membrane occupied by dense deposits, slit number/glomerular basement membrane, and glomerular basement membrane thickness statistically explained most (81%) of the variation in fractional clearance of albumin and IgG. These results suggest that epithelial slit length is the most important structural determinant of GFR and that the increase in MGV maintains filtration surface area despite evidence of an extensive inflammatory insult. The mechanism(s) of proteinuria in this model of lupus nephritis are consistent with either a focal increase in GBM permeability due to immune deposits and/or a diffuse increase in permeability due to GBM charge neutralization. The study provides insight as to why previous structure-function reports failed to find correlates of glomerular injury to glomerular dysfunction.

Animals

Cyclosporine-induced renal dysfunction in human renal allograft recipients.

Cyclosporine-treated renal allograft recipients frequently suffer CsA-related nephrotoxicity and hypertension. This study demonstrates that glomerular filtration rate is reduced acutely by 13% (P less than 0.02) and renal vascular resistance increased by 30% (P less than 0.05), immediately after patients take their CsA dose. The reduction in GFR is directly related to their trough CsA level (r = 0.82; P less than 0.01). The lower the trough CsA level the greater the fall in GFR after the CsA dose. Plasma renin activity does not increase after the CsA dose (pre-CsA 0.6 +/- 0.2 ng/L/sec vs. post-CsA 0.4 +/- 0.1 ng/L/sec; P = NS), and therefore cannot be responsible for the reduction in renal function. Short-term nifedipine treatment is effective in preventing the acute reduction in GFR (P less than 0.05). This occurred despite no apparent effect of nifedipine in altering trough or post-dose CsA levels. Furthermore nifedipine was effective in lowering both the mean arterial blood pressure (109 mmHg to 94 mmHg; P less than 0.01) and the elevated renal vascular resistance (25% reduction; P less than 0.02) observed in these patients. These results suggest that nifedipine may be a suitable agent for limiting acute CsA nephrotoxicity and for treating CsA-associated hypertension in renal allograft recipients.

Cyclosporins

Outcome of the acute glomerular injury in proliferative lupus nephritis.

Treatment with total lymphoid irradiation (TLI) and corticosteroids markedly reduced activity of systemic lupus erythematosis in 10 patients with diffuse proliferative lupus nephritis (DPLN) complicated by a nephrotic syndrome. Physiologic and morphometric techniques were used serially before, and 12 and 36 mo post-TLI to characterize the course of glomerular injury. Judged by a progressive reduction in the density of glomerular cells and immune deposits, glomerular inflammation subsided. A sustained reduction in the fractional clearance of albumin, IgG and uncharged dextrans of radius greater than 50 A, pointed to a parallel improvement in glomerular barrier size-selectivity. Corresponding changes in GFR were modest, however. A trend towards higher GFR at 12 mo was associated with a marked increase in the fraction of glomerular tuft area occupied by patent capillary loops as inflammatory changes receded. A late trend toward declining GFR beyond 12 mo was associated with progressive glomerulosclerosis, which affected 57% of all glomeruli globally by 36 mo post-TLI. Judged by a parallel increase in volume by 59%, remaining, patent glomeruli had undergone a process of adaptive enlargement. We propose that an increasing fraction of glomeruli continues to undergo progressive sclerosis after DPLN has become quiescent, and that the prevailing GFR depends on the extent to which hypertrophied remnant glomeruli can compensate for the ensuing loss of filtration surface area.

Acute Disease

Treatment of lupus nephritis with total lymphoid irradiation. Observations during a 12-79-month followup.

Seventeen patients with intractable lupus nephritis and nephrotic syndrome were treated with total lymphoid irradiation. Statistically significant improvement in mean renal disease and serologic activity parameters occurred within 3 months and persisted for at least 3 years. Although there was a marked reduction of T helper cell numbers and function after total lymphoid irradiation, recovery of these parameters was not associated with a return of disease activity. Risks of sterility, severe infections, and hematologic malignancy appeared to be lower than with alkylating agents.

Adolescent

Effect of atrial natriuretic peptide on vasa recta blood flow in the rat.

To determine whether synthetic atrial natriuretic peptide (ANP) increases renal medullary blood flow and if so whether the increase mediates the diuresis and natriuresis induced by ANP, inner medullary vasa recta blood flow in the exposed left renal papilla of anesthetized Munich Wistar rats weighing between 102 and 161 g was measured by fluorescence videomicroscopy. The rats were maintained in a euvolemic state by the infusion of albumin. Synthetic ANP (Auriculin B) was administered intravenously as 2.5 micrograms/kg body wt prime and as a continuous infusion of 0.2 microgram X min-1 X kg body wt-1 to the experimental group (n = 7). Within 2 min after ANP was given, urine flow and sodium excretion increased (29.4 +/- 3.8 to 50.4 +/- 5.8 microliter X min-1 X kidney wt-1, P less than 0.01, and 3.39 +/- 0.57 to 6.05 +/- 0.95 mueq X min-1 X g kidney wt-1, P less than 0.01, respectively), but vasa recta blood flow in descending (DVR) or ascending (AVR) vasa recta did not change significantly (9.5 +/- 2.3 to 10.0 +/- 2.8 nl/min in DVR and 5.3 +/- 1.0 to 6.1 +/- 1.2 nl/min in AVR). Forty-five minutes after ANP was begun, urine flow and sodium excretion increased further (77.1 +/- 11.1 microliter X min-1 X g kidney wt-1 and 12.0 +/- 2.15 mueq X min-1 X g kidney wt-1, respectively), and by this time vasa recta blood flow had increased significantly to 14.0 +/- 2.6 in DVR, P less than 0.01, and 9.8 +/- 1.2 in AVR, P less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals