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Biomedical subjects

B A Kiberd

Publications and source records attributed to B A Kiberd.

At least 19 recordsLinked to original sources
PubMed1998

Routine treatment of insulin-dependent diabetic patients with ACE inhibitors to prevent renal failure: an economic evaluation.

The objective of this study was to determine how effective angiotensin-converting enzymes (ACEs) must be in preventing diabetic nephropathy to warrant routine administration to insulin-dependent diabetic patients. A Markov model was used to compare three strategies designed to prevent the development of end-stage renal disease in insulin-dependent diabetic patients. Strategy I, screening for microalbuminuria and treatment of incipient nephropathy as currently recommended, was compared with strategy II, a protocol in which patients were routinely administered an ACE inhibitor 5 years after diagnosis of diabetes, and strategy III, in which patients at high risk for nephropathy were routinely treated and low-risk patients followed a protocol in which patients were treated with an ACE inhibitor if they developed hypertension and/or macroproteinuria. The model predicted that strategy II would produce as many quality-adjusted life-years as strategy I at nearly the same cost if routine drug therapy reduced the rate of development of microalbuminuria by 26% in all patients. Strategy III produced as many quality-adjusted life-years at less cost than strategy I if a high-risk cohort could be identified with a rate of developing microalbuminuria at four times the rate of low-risk patients and if drug therapy reduced the rate of developing microalbuminuria in this high-risk group by 20%. In conclusion, routine ACE inhibitor therapy could prove to be cost-effective, especially if high-risk individuals could be identified. A prospective trial examining this goal should be considered.

Adult↗
PubMed1997

A patient centered approach to the treatment of renal vascular disease to prevent end stage renal failure.

Atherosclerotic renal vascular disease (RVD) is a cause of renal failure especially in the elderly. There has never been a clinical trial to determine how effective invasive therapy is over medical therapy to prevent end stage renal disease. The objective of this study was to determine how effective invasive therapy for RVD to prevent renal failure should be from the perspective of the patient to warrant implementation. Subjects included 28 elderly dialysis patients and 26 renal health care workers (HCW). Subjects were asked directly how effective invasive therapy should be if they were to undertake the procedure. Invasive therapy would have to eliminate the need for dialysis permanently by 41 +/- 6% for the dialysis patients and 21 +/- 4% for the HCW to be acceptable. This difference in efficacy between the two groups was statistically significant (P = 0.014). Efficacy was also determined using a medical decision analysis model that incorporated patient health related quality of life status for dialysis and non-dialysis. To be cost-effective (< $50,000 incremental cost/quality adjusted life year) invasive therapy had to reduce the development of end stage renal failure by 35 +/- 1% (M +/- SE) for dialysis patients and 15 +/- 1% for HCW. These results show that patients demand better efficacy rates than their providers and that this difference appears to be appropriate based on their perceptions of health and projected outcomes. Both patient and health care workers are more conservative than predicted by the medical decision analysis model. Since the range of patient responses was large, methods of documenting patient perspectives for risky procedures may help clinicians determine how aggressively to investigate and treat patients with RVD.

Aged↗
PubMed1995

Screening to prevent renal failure in insulin dependent diabetic patients: an economic evaluation.

OBJECTIVE: To examine the conditions necessary to make screening for microalbuminuria in patients with insulin dependent diabetes mellitus cost effective. DESIGN: This economic evaluation compared two strategies designed to prevent the development of end stage renal disease in patients with insulin dependent diabetes with disease for five years. Strategy A, screening for microalbuminuria as currently recommended, was compared with strategy B, a protocol in which patients were screened for hypertension and macroproteinuria. INTERVENTION: Patients identified in both strategies were treated with an angiotensin converting enzyme inhibitor. SETTING: Computer simulation. MAIN OUTCOME MEASURES: Strategy costs and quality adjusted life years (QALYs). RESULTS: The model predicted that strategy A would produce an additional 0.00967 QALYs at a present value cost of $261.53 (1990 US$) per patient (or an incremental cost/QALY of $27,041.69) over strategy B. The incremental cost/QALY for strategy A over B was sensitive to several variables. If the positive predictive value of screening for microalbuminuria (impact of false label and unnecessary treatment) is < 0.72, the effect of treatment to delay progression from microalbuminuria to macroproteinuria is < 1.6 years, the cumulative incidence of diabetic nephropathy falls to < 20%, or > 64% of patients demonstrate hypertension at the onset of microalbuminuria, then the incremental costs/QALY will exceed $75,000. CONCLUSION: Whether microalbuminuria surveillance in this population is cost effective requires more information. Being aware of the costs, recommendation pitfalls, and gaps in our knowledge should help focus our efforts to provide cost effective care to this population.

Albuminuria↗
PubMed1995

Established murine lupus nephritis does not respond to exogenous interleukin-1 receptor antagonist; a role for the endogenous molecule?

Interleukin 1 beta (IL-1 beta) is a potent inflammatory cytokine and IL-1 beta gene expression is elevated in the kidneys of mice with lupus nephritis. This study was designed to examine whether pharmacological administration of the IL-1 receptor antagonist (IL-1ra) would reduce the inflammation in MRL lpr/lpr mice with lupus nephritis. Human recombinant IL-1ra (RA) or saline (SA) was infused by intraperitoneal osmotic minipumps in 16 week old mice (n = 9, group RA or n = 12, group SA, respectively). Age matched MRL +/+ mice served as normal controls. At the end of 4 weeks of treatment glomerular filtration rates (5.4 +/- 0.4 vs 5.6 +/- 0.4 ml/min/kg BW), proteinuria (6.0 +/- 1.0 vs 5.5 +/- 1.2 micrograms IgG/day) glomerular volumes (571 +/- 30 vs 509 +/- 25 microns3 x 10(3)), mesangial volumes (172 +/- 23 vs 158 +/- 17 microns3 x 10(3)), and cells/glomerulus (519 +/- 51 vs 506 +/- 47) were not significantly different between RA and SA groups respectively. There was also no significant differences in spleen sizes, plasma IgG and anti-dsDNA antibody levels despite achieving levels of IL-1ra of over 0.8 microgram/ml in RA mice. Circulating IL-1 was not detected by bioassay in the plasma of diseased or normal mice. In fact, diseased, saline treated mouse plasma inhibited the cell proliferation assay in the presence of IL-1, and dilution studies showed that the endogenous inhibitors were of high titre. Although IL-1 may play a role in the renal injury of lupus nephritis, pharmacological inhibition with IL-1ra in animals with established injury is without effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Should hepatitis C-infected kidneys be transplanted in the United States?

Over the past several years, the issue of hepatitis C virus (HCV) infection in renal transplantation has generated considerable interest. With the availability of a test for HCV, some but not all physicians have advocated that all HCV-infected kidneys be discarded. An economic appraisal was carried out to examine 3 theoretical policies of organ allocation for HCV-infected kidneys: (a) discard all infected kidneys, (b) transplant infected kidneys into infected donors only, or (c) transplant regardless of HCV status. Using probabilities, costs, and patient outcomes from the literature/best estimate, a cost-utility analysis was performed. Patients free of infection transplanted with an infected organ were assigned higher treatment costs and poorer outcomes compared with all other combinations. Assuming a potential to transplant 8100 kidneys per year, option A was predicted to produce the fewest total quality-adjusted life years (QALYs) and incur the highest costs (largely due to patients left on dialysis). Option B was projected to produce the most QALYs, whereas option C incurred the lowest costs (no need to screen for HCV). The incremental cost utility of option B over C was $13,954 (present value 1990)/QALY. This economic appraisal suggests that transplanting HCV-infected kidneys into infected recipients is superior to a discard policy from both a cost and patient outcome perspective. However, other overriding factors, such as the ethical dilemma of transplanting an infected organ, must be addressed by both physician and patient/public before a consensus can be reached.

Costs and Cost Analysis↗
PubMed1994

Modulation of glomerular structure and function in murine lupus nephritis by methylprednisolone and cyclophosphamide.

The effects of methylprednisolone and cyclophosphamide were examined in a murine model of lupus nephritis (MRL-1pr/1pr). Animals were assigned to four groups at 12 weeks of age. Mice in the control group received intraperitoneal saline solution either daily or weekly. Animals in the low-dose methylprednisolone (MPLD) group received 6 mg/kg/day intraperitoneal methylprednisolone; those in the high-dose methylprednisolone (MPHD) group received 12 mg/kg/day intraperitoneal methylprednisolone. Animals in the cyclophosphamide group received 50 mg/kg/wk intraperitoneal cyclophosphamide. Animals surviving to 24 weeks were examined. MPHD and cyclophosphamide treatments were associated with maintenance of normal glomerular filtration rates and the development of only minimal proteinuria. However, detailed morphometric evaluation of the glomerulus revealed glomerular enlargement and mesangial matrix expansion in both groups. Unlike MPHD-treated mice, cyclophosphamide-treated animals demonstrated a marked reduction in the number of osmophilic dense deposits along the glomerular capillary walls. MPLD had little effect on function, despite significant reductions in cell proliferation and anti-double-strand DNA antibodies. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels were dramatically increased in plasma of control animals. Treatment with methylprednisolone and cyclophosphamide dramatically reduced TNF-alpha but not IL-6. Treatment also reduced renal IL-1 beta, TNF-alpha and transforming growth factor-beta mRNA levels compared with untreated mice. Despite minimal serologic activity and preservation of renal function, neither cyclophosphamide nor methylprednisolone was able to completely suppress disease activity, as measured by increased cytokine production and glomerular structural injury. The inability of treatment to reduce IL-6 levels may explain the resistance to treatment in this model.

Animals↗
PubMed1993

Interleukin-6 receptor blockage ameliorates murine lupus nephritis.

The therapeutic effects of a neutralizing monoclonal antibody (mAb) to the interleukin-6 receptor (IL-6R) were examined in the MRL-lpr/lpr murine lupus nephritis model. Animals (15 wk old) were treated with ip mAb IL-6R for 5 wk. GFR in these mice at the end of this treatment period were comparable to those of congenic strain disease-resistant MRL-(+)/+ controls treated with rat immunoglobulin G (IgG) (254 +/- 61 versus 285 +/- 26 microL/min; P = not significant). GFR was significantly (P < 0.05) lower in lpr/lpr mice receiving ip rat IgG (disease controls) at the same time (165 +/- 76 microL/min). The fractional mesangial volume (Mv) and surface density of open glomerular capillaries (Sv) in mAb II-6R-treated lpr/lpr and IgG-treated +/+ mice (Mv, 0.21 +/- 0.04 and 0.19 +/- 0.04 micron3/micron3; Sv, 0.18 +/- 0.01 and 0.20 +/- 0.01 micron/micron2, respectively) were similar. However, Mv (0.40 +/- 0.04) was significantly higher (P < 0.001) and Sv (0.13 +/- 0.04) was lower (P < 0.01) in IgG-treated lpr/lpr animals. Treatment with mAb IL-6R significantly reduced anti-dsDNA antibody levels after Week 2 of treatment, but these values rebounded at Week 4. The late development of neutralizing antibodies and the increased secretion of IL-6 at Week 4 were likely responsible. Despite these events, neutralizing mAb to the IL-6R proved to be effective therapeutically, as demonstrated by preserved glomerular function and structure.

Animals↗
PubMed1993

Organ procurement.

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Cost-Benefit Analysis↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

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↗