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N Muirhead

Publications and source records attributed to N Muirhead.

At least 19 recordsLinked to original sources
PubMed2006

Proteinuria and reduced kidney function in living kidney donors: A systematic review, meta-analysis, and meta-regression.

We reviewed any study where 10 or more healthy adults donated a kidney, and proteinuria, or glomerular filtration rate (GFR) was assessed at least 1 year later. Bibliographic databases were searched until November 2005. 31 primary authors provided additional information. Forty-eight studies from 27 countries followed a total of 5048 donors. An average of 7 years after donation (range 1-25 years), the average 24 h urine protein was 154 mg/day and the average GFR was 86 ml/min. In eight studies which reported GFR in categories, 12% of donors developed a GFR between 30 and 59 ml/min (range 0-28%), and 0.2% a GFR less than 30 ml/min (range 0-2.2%). In controlled studies urinary protein was higher in donors and became more pronounced with time (three studies totaling 59 controls and 129 donors; controls 83 mg/day, donors 147 mg/day, weighted mean difference 66 mg/day, 95% confidence interval (CI) 24-108). An initial decrement in GFR after donation was not accompanied by accelerated losses over that anticipated with normal aging (six studies totaling 189 controls and 239 donors; controls 96 ml/min, donors 84 ml/min, weighted mean difference 10 ml/min, 95% CI 6-15; difference not associated with time after donation (P=0.2)). Kidney donation results in small increases in urinary protein. An initial decrement in GFR is not followed by accelerated losses over a subsequent 15 years. Future studies will provide better estimates, and identify those donors at least risk of long-term morbidity.

Adolescent↗
PubMed2003

Effect of valsartan on urinary protein excretion and renal function in patients with chronic renal allograft nephropathy.

Chronic allograft nephropathy (CAN) remains a significant cause of late renal allograft loss. Although many factors may be involved in pathogenesis, the hemodynamic and fibrogenic consequences of long-term therapy with cyclosporine (CsA) have been implicated as important potentially reversible causes. CsA's effect on CAN is mediated in part through increased renal expression of TGF-beta, which can be modified by administration of angiotensin receptor blockers (ARBs). A pilot study was undertaken to evaluate the safety and efficacy of the ARB valsartan on renal function and proteinuira in patients with CAN. Ten patients on CsA-based therapy with evidence of CAN received valsartan in an initial dose of 80 mg/d, force titrated to 160 mg/d after 4 weeks, for a total of 52 weeks. Renal function was evaluated by serum creatinine, 24-hour creatinine clearance (CrCl), and isotope, GFR and urinary protein by 24-hour protein excretion. The 10 patients were aged 20 to 71 years and had been transplanted for 88.2 +/- 64.8 months at the time of study. After 52 weeks of valsartan therapy mean blood pressure (BP) fell from 152/88 mm Hg to 138/77 mm Hg (P =.06); serum creatinine rose from 206 +/- 55 micromol/L to 238 +/- 81 micromol/L (P =.22.); GFR fell from 39.8 +/- 17.6 to 31.9 +/- 19 mL/min (P =.23); and urine protein fell from 2.16 +/- 2.7 to 1.12 +/-.095 g/24 hours (P =.13). Side effects of valsartan therapy were few and included transient hyperkalemia in 2/10 patients. The small rise in serum creatinine and fall in GFR observed were not statistically significant. Urine protein fell by more than 50%, though the small patient numbers in this pilot study prevent this from achieving statistical significance. It is concluded that valasartan reduces BP and proteinuria in CAN patients without inducing a serious worsening in renal function. Valsartan may have a role to play in the management of patients with CAN.

Adult↗
PubMed2003

A comparison between cyclosporine and tacrolimus-based immunosuppression for renal allografts: renal function and blood pressure after 5 years.

The choice of initial immunosuppressive therapy (IST) following solid organ transplant remains a source of some controversy. Cyclosporine A (CsA) has been the basis of most IST protocols over the past two decades but has recently been supplanted in many centers by the use of tacrolimus (TAC)-based protocols. Renal allograft recipients in London may receive either CsA or TAC based IST, along with prednisone and azathioprine or (since 1999) mycophenolate mofetil (MMF). The decision is based on criteria such as age, gender, diabetic status, and lipid levels, which are felt to be impacted by the delivery of CsA or TAC based IST. The present analysis focuses on the results of BP and renal function in renal transplant patients receiving CsA or TAC based initial therapy during the period January 1, 1996 to June 30, 2002. Patients receiving TAC based IST were significantly younger than those receiving CsA (44 +/- 13.9 vs 50.5 +/- 12.3 years; P < .004). Mean arterial pressure (MAP) was lower in the TAC patients at 1 month (97.8 +/- 13.1 vs 103.2 +/- 11.8 mm Hg; P = .035), but became equivalent to CsA-treated patients for the balance of the follow-up period of up to 60 m. Serum creatinine was not significantly different between groups at any time during up to 60 months of follow-up. Based on these results, it seems apparent that the choice of calcineurin inhibitor may not influence renal function or blood pressure in long-term renal allograft survivors.

Adult↗
PubMed2003

Eletriptan for the treatment of migraine in patients with previous poor response or tolerance to oral sumatriptan.

To determine the tolerability and efficacy of eletriptan in patients who had discontinued oral sumatriptan due to lack of efficacy or intolerable adverse events (AEs) during previous clinical treatment (not a controlled trial). Eletriptan is a potent, selective 5-HT1B/1D receptor agonist with beneficial pharmacokinetic properties compared with sumatriptan. In a double-blind, parallel group, placebo-controlled multicentre study, patients with and without aura (n = 446) were randomized to 40 mg eletriptan (E40, n = 188), 80 mg eletriptan (E80, n = 171) or placebo (n = 87) for treatment of up to three migraine attacks. Two-hour headache response, based on first-dose, first-attack data, was 59% for eletriptan 40 mg, 70% for eletriptan 80 mg, and 30% for placebo (P < 0.0001 for both doses of eletriptan vs. PBO; P < 0.05 for E80 vs. E40). Onset of action was rapid, with 1-h headache response rates significantly superior for E40 and E80 vs. placebo (40%, 48%, 15%; P < 0.0005). Both E40 and E80 were significantly superior to placebo, based on first-dose, first-attack data, for 2-h pain-free response (35%, 42%, and 7%; P < 0.0001). Both E40 and E80 demonstrated significant consistency of response, with headache relief rates at 2 h on at least two of three attacks in 66% and 72% vs. 15% on placebo (P < 0.001). AEs were mild to moderate in severity and dose related. The most commonly reported AEs included nausea, vomiting, asthenia, and chest symptoms. E40 and E80 produce an effective response in patients who had previously discontinued treatment with sumatriptan due to lack of efficacy or side-effects.

Administration, Oral↗
PubMed2002

Canadian survey of clinical status at dialysis initiation 1998-1999: a multicenter prospective survey.

AIMS: The current growth in end-stage kidney disease populations has led to increased efforts to understand the impact of status at dialysis initiation on long-term outcomes. Our main objective was to improve the understanding of current Canadian nephrology practice between October 1998 and December 1999. METHODS: Fifteen nephrology centers in 7 provinces participated in a prospective data collection survey. The main outcome of interest was the clinical status at dialysis initiation determined by: residual kidney function, preparedness for chronic dialysis as measured by presence or absence of permanent peritoneal or hemodialysis access, hemoglobin and serum albumin. Uremic symptoms at dialysis initiation were also recorded, however, in some cases these symptom data were obtained retrospectively. RESULTS: Data on 251 patients during 1-month periods were collected. Patients commenced dialysis at mean calculated creatinine clearance levels of approximately 10 ml/min, with an average of 3 symptoms. 35% of patients starting dialysis had been known to nephrologists for less than 3 months. These patients are more likely to commence without permanent access and with lower hemoglobin and albumin levels. Even of those known to nephrologists, only 66% had permanent access in place. CONCLUSIONS: Patients commencing dialysis in Canada appear to be doing so in relative concordance with published guidelines with respect to timing of initiation. Despite an increased awareness of kidney disease, a substantial number of patients continues to commence dialysis without previous care by a nephrologist. Of those who are seen by nephrologists, clinical and laboratory parameters are suboptimal according to current guidelines. This survey serves as an important baseline for future comparisons after the implementation of educational strategies for referring physicians and nephrologists.

Adult↗
PubMed2001

The rationale for early management of chronic renal insufficiency.

Several strategies are available to delay progression of renal disease and the development of associated co-morbidities. Hypertension is a strong independent risk factor for end-stage renal disease (ESRD) and there is consensus that blood pressure (BP) management is an important aspect of care in patients with chronic renal insufficiency (CRI). Clinical studies have shown that angiotensin-converting enzyme (ACE) inhibitors have renoprotective properties, independent of their antihypertensive effects, which can delay the onset of ESRD. Studies have also shown that intensive therapy of both type 1 and type 2 diabetes patients, to give near normal blood glucose concentrations, can reduce the incidence of progressive clinical proteinuria and may, therefore, protect against ESRD. Additionally, data are emerging that treatment of renal anaemia with epoetin can reduce mortality and delay the onset of dialysis in CRI patients, but these encouraging results need to be confirmed in large prospective studies. In conclusion, control of BP and hyperglycaemia, as well as use of ACE inhibitors and anaemia treatment, all have potential in delaying the progression of CRI or improving patient outcomes. If benefit is proven in future studies, these strategies will be most effective if implemented early in the course of CRI.

Anemia↗
PubMed2001

Chronic kidney disease: why is current management uncoordinated and suboptimal?

Morbidity and mortality associated with chronic kidney disease (CKD) is higher than that of the normal population, and the incidence of end-stage renal disease (ESRD) continues to increase. Several factors contribute to the uncoordinated and suboptimal management of CKD, including the attitude and behaviour of nephrologists, referring physicians and patients, and economic constraints on healthcare systems. Late referral of at-risk patients to specialist care is an area of particular concern, as this denies nephrologists adequate opportunity to prevent progression of CKD and associated complications such as anaemia. Due to the ageing population and advances in technology, the costs of treating CKD and ESRD continue to escalate and represent another barrier to the delivery of optimal care. Optimizing the care provided to CKD patients requires a coordinated approach to the management of the condition. Closer collaboration and improved communication across specialities is important for the timely referral of patients and for efficient utilization of available resources. A multidisciplinary approach may facilitate patient identification and improve the management of CKD.

Anemia↗
PubMed2000

Comparative mortality of hemodialysis and peritoneal dialysis in Canada.

BACKGROUND: Comparisons of mortality rates in patients on hemodialysis versus those on peritoneal dialysis have been inconsistent. We hypothesized that comorbidity has an important effect on differential survival in these two groups of patients. METHODS: Eight hundred twenty-two consecutive patients at 11 Canadian institutions with irreversible renal failure had an extensive assessment of comorbid illness collected prospectively, immediately prior to starting dialysis therapy. The cohort was assembled between March 1993 and November 1994; vital status was ascertained as of January 1, 1998. RESULTS: The mean follow-up was 24 months. Thirty-four percent of patients at baseline, 50% at three months, and 51% at six months used peritoneal dialysis. Values for a previously validated comorbidity score were higher for patients on hemodialysis at baseline (4.0 vs. 3.1, P < 0.001), three months (3.7 vs. 3.2, P = 0.001), and six months (3.6 vs. 3.2, P = 0.005). The overall mortality was 41%. The unadjusted peritoneal dialysis/hemodialysis mortality hazard ratios were 0.65 (95% CI, 0. 51 to 0.83, P = 0.0005), 0.84 (95% CI, 0.66 to 1.06, P = NS), and 0. 83 (95% CI, 0.64 to 1.08, P = NS) based on the modality of dialysis in use at baseline, three months, and six months, respectively. When adjusted for age, sex, diabetes, cardiac failure, myocardial infarction, peripheral vascular disease, malignancy, and acuity of renal failure, the corresponding hazard ratios were 0.79 (95% CI, 0. 62 to 1.01, P = NS), 1.00 (95% CI, 0.78 to 1.28, P = NS), and 0.95 (95% CI, 0.73 to 1.24, P = NS). Adjustment for a previously validated comorbidity score resulted in hazard ratios of 0.74 (95% CI, 0.58 to 0.94, P = 0.01), 0.94 (95% CI, 0.74 to 1.19, P = NS), and 0.88 (95% CI, 0.68 to 1.13, P = NS) at baseline, three months, and six months. There was no survival advantage for either modality in any of the major subgroups defined by age, sex, or diabetic status. CONCLUSIONS: The apparent survival advantage of peritoneal dialysis in Canada is due to lower comorbidity and a lower burden of acute onset end-stage renal disease at the inception of dialysis therapy. Hemodialysis and peritoneal dialysis, as practiced in Canada in the 1990s, are associated with similar overall survival rates.

Canada↗
PubMed2000

Comparative hospitalization of hemodialysis and peritoneal dialysis patients in Canada.

BACKGROUND: Most comparisons of hemodialysis (HD) and peritoneal dialysis (PD) have used mortality as an outcome. Relatively few studies have directly compared the hospitalization rates, an outcome of perhaps equal importance, of patients using these different dialysis modalities. METHODS: Eight hundred twenty-two consecutive patients at 11 Canadian institutions with irreversible renal failure had an extensive assessment of comorbid illness and initial mode of dialysis collected prospectively immediately prior to starting dialysis therapy. The cohort was assembled between March 1993 and November 1994. The mean follow-up was 24 months. Admission data were used to compare hospitalization rates in HD and PD. RESULTS: Thirty-four percent of patients at baseline and 50% at three months used PD. Twenty-five percent of HD and 32% of PD patients switched dialysis modality at least once after their first treatment (P = NS). Nine percent of HD patients and 30% of PD patients switched modality after three months (P < 0. 001). Total comorbidity was higher in HD patients at baseline (P < 0. 001) and at three months (P = 0.001). The overall hospitalization rate was 40.2 days per 1000 patient days after baseline and 38.0 days per 1000 patient days after three months. When an adjustment was made for baseline comorbid conditions, patients on PD had a lower rate of hospitalization in intention-to-treat analysis according to the type of dialysis in use at baseline (RR 0.85, 95% CI, 0.82 to 0.87, P < 0.001), but a higher rate according to the type of dialysis in use three months after study entry (RR 1.31, 95% CI, 1.27 to 1.34, P < 0.001). In analyses based on the amount of time actually spent on each treatment modality, PD was associated with a higher rate of hospitalization when analyzed according to the type of dialysis in use at baseline (RR 1.10, 95% CI, 1.07 to 1.13, P < 0.001) and according to the type of dialysis in use three months after study entry (RR 1.26, 95% CI, 1.23 to 1.30, P < 0.001). CONCLUSIONS: Conclusions regarding comparative hospitalization rates are heavily dependent on the analytic starting point and on whether intention-to-treat or treatment-received analyses are used. When early treatment switches are accounted for, HD is associated with a lower rate of hospitalization than PD, but the effect is modest.

Canada↗
PubMed2000

Effect of hemoglobin levels in hemodialysis patients with asymptomatic cardiomyopathy.

BACKGROUND: Hemoglobin levels below 10 g/dL lead to left ventricular (LV) hypertrophy, LV dilation, a lower quality of life, higher cardiac morbidity, and a higher mortality rate in end-stage renal disease. The benefits and risks of normalizing hemoglobin levels in hemodialysis patients without symptomatic cardiac disease are unknown. METHODS: One hundred forty-six hemodialysis patients with either concentric LV hypertrophy or LV dilation were randomly assigned to receive doses of epoetin alpha designed to achieve hemoglobin levels of 10 or 13.5 g/dL. The study duration was 48 weeks. The primary outcomes were the change in LV mass index in those with concentric LV hypertrophy and the change in cavity volume index in those with LV dilation. RESULTS: In patients with concentric LV hypertrophy, the changes in LV mass index were similar in the normal and low target hemoglobin groups. The changes in cavity volume index were similar in both targets in the LV dilation group. Treatment-received analysis of the concentric LV hypertrophy group showed no correlation between the change in mass index and a correlation between the change in LV volume index and mean hemoglobin level achieved (8 mL/m2 per 1 g/dL hemoglobin decrement, P = 0.009). Mean hemoglobin levels and the changes in LV mass and cavity volume index were not correlated in patients with LV dilation. Normalization of hemoglobin led to improvements in fatigue (P = 0.009), depression (P = 0.02), and relationships (P = 0.004). CONCLUSIONS: Normalization of hemoglobin does not lead to regression of established concentric LV hypertrophy or LV dilation. It may, however, prevent the development of LV dilation, and it leads to improved quality of life.

Adult↗
PubMed1999

Idiopathic thrombocytopenia after cytomegalovirus infection in a renal transplant recipient.

Infection with cytomegalovirus (CMV) is a frequent complication of organ transplantation and presents a spectrum of disease ranging from asymptomatic viremia to life-threatening tissue-invasive disease. CMV is also lymphotrophic, with the potential to induce autoimmune disease, although immunosuppressive therapy may prevent or attenuate the clinical course in transplant patients. We report a case of idiopathic thrombocytopenic purpura occurring in a renal transplant recipient after primary CMV infection and discuss the possible mechanisms involved.

Cytomegalovirus Infections↗
PubMed1999

Erythropoietin and renal transplantation.

The advent of erythropoietin (rHuEPO) has revolutionized the treatment of anemia in end-stage renal disease. While many studies indicate beneficial effects of rHuEPO in hemodialysis, peritoneal dialysis and predialysis patients, the impact of the drug in renal transplantation is less clear. Treatment with rHuEPO may reduce the degree of allosensitization produced by random blood transfusion while still allowing the possibility of the transplant survival benefit derived from deliberate transfusion. Recovery from anemia post-transplantation is hastened by treatment with rHuEPO, while patients with failing allografts respond to rHuEPO in a fashion similar to dialysis patients, despite the concomitant use of immunosuppressives. The erythropoietic response to rHuEPO is abrogated during episodes of acute rejection, and restored when successful treatment of rejection has occurred. Iron therapy is a critical factor for support of erythropoiesis and prevention of absolute iron deficiency posttransplantation. In patients presenting for renal transplant, the balance of evidence suggests that there is no increase in the rate of delayed graft function, graft loss or vascular thrombosis for patients who had received prior rHuEPO therapy.

Anemia↗
PubMed1999

Management of idiopathic membranous nephropathy: evidence-based recommendations.

Membranous nephropathy is a frequent cause of nephrotic syndrome in adults, and in one third of these patients, it leads to end-stage renal disease. Based on an extensive critical review of the literature, the following recommendations are offered. Oral high-dose corticosteroids are ineffective in producing either a sustained remission of nephrotic syndrome or in preserving renal function in patients with membranous nephropathy, and should not be used as the sole therapy (grade A recommendation). The use of azathioprine is not associated with any significant benefits, so its use is not justified (grade C). The alkylating agents cyclophosphamide and chlorambucil are both effective in the management of membranous nephropathy. Because of growing concern about long-term toxicity, especially with cyclophosphamide, these drugs should be reserved for patients who exhibit clinical features, such as severe or prolonged nephrosis, renal insufficiency, or hypertension, that predict a high likelihood of progression to end-stage renal disease. Chlorambucil in conjunction with oral steroids is the drug of first choice (grade A). Cyclophosphamide and oral steroids are alternatives (grade B). Cyclosporine may, in the future, become the agent of choice for membranous nephropathy. Currently, it is recommended (grade B) that cyclosporine use be considered in patients at high risk for progression in membranous nephropathy or if alkylating agents are contraindicated or ineffective.

Adult↗
PubMed1999

The effect of valsartan and captopril on lipid parameters in patients with type II diabetes mellitus and nephropathy.

The study compared valsartan 80 mg or 160 mg o.d. with captopril 25 mg t.i.d. or placebo on plasma lipids in normotensive and treated hypertensive patients with type II diabetes and microalbuminuria. One hundred and twenty-two adult outpatients were randomised to receive either valsartan 80 mg or 160 mg, captopril 25 mg or placebo for 360 days. Changes from baseline to endpoint in plasma lipid parameters were measured. The primary criterion for tolerability was the incidence of adverse events. All treatment groups showed minor changes in lipid parameters. Triglyceride increased by 2.7% (valsartan 160 mg) to 9.1% (placebo). Total cholesterol decreased under valsartan 80 mg, while other groups showed increases of up to 0.031 mmol/l. Decreases in total cholesterol (p = 0.018), apolipoprotein B (p = 0.042) and apolipoprotein A1 (p = 0.025), were significant for the comparison of 80 mg valsartan and captopril. Valsartan 80 mg or 160 mg o.d. does not cause deleterious changes in the diabetic lipid profile and, unlike captopril, is not associated with dry cough.

Adult↗