ANCA-associated renal vasculitis following anti-tumor necrosis factor alpha therapy.

We report the case of a 62-year-old woman with rheumatoid arthritis treated with adalimumab, an anti-tumor necrosis factor alpha drug, who presented with 4 weeks of lethargy, upper respiratory tract symptoms, a vasculitic skin rash, and rapidly deteriorating renal function. She had cytoplasmic antineutrophil cytoplasmic antibodies and skin and renal biopsy specimens diagnostic of small vessel vasculitis and necrotizing crescentic glomerulonephritis, respectively. After immunosuppressive therapy and discontinuation of adalimumab therapy, vasculitis resolved and renal function recovered. This is the first report of antineutrophil cytoplasmic antibody associated necrotizing glomerulonephritis with adalimumab.

Randomized study comparing cyclosporine with azathioprine one year after renal transplantation-15-year outcome data.

BACKGROUND: The introduction of cyclosporine (CsA) improved 1-year graft survival and reduced the incidence of acute rejection episodes after renal transplantation compared to azathioprine (Aza). However, CsA has many side effects and reducing exposure of this drug after the first year may benefit long-term patient and graft survival. METHODS: We report 15-year outcome data from a single center, randomized controlled study comparing CsA withdrawal and conversion to Aza with continuation of CsA 1-year posttransplant. RESULTS: Two hundred sixteen patients who showed a serum creatinine less than 300 mumol/L with no acute rejection episodes in the preceding 6 months were enrolled (CsA 114, Aza 102). There was no difference in patient survival at 15 years: 62.4% in the CsA group and 64.4% in the Aza group (P=0.6). Fifteen-year transplant survival was 41.9% for the CsA group and 48.8% for the Aza group (P=0.8). Fifteen-year graft survival censoring for death with a functioning graft was 58% in the CsA group and 72% in the Aza group (P=0.5). Predictors of patient survival were younger recipient age (P<0.001) and lower systolic blood pressure at randomization (P=0.01). Predictors of graft survival were older recipient age (P<0.001) and better renal function at randomization (P=0.01). Assigned drug showed no effect on graft or patient survival. Patients assigned to CsA showed significantly worse renal function up to 10 years posttransplantation and required more anti-hypertensive treatment throughout the study period. CONCLUSION: In a selected group of patients, either Aza or low-dose CsA is safe and effective. Despite lower estimated glomerular filtration rate (eGFR) up to 10 years posttransplantation and increased use of anti-hypertensive agents, low-dose CsA was not associated with a worse patient or graft survival.

Allocation of deceased donor kidneys for transplantation: opinions of patients with CKD.

BACKGROUND: Deceased donor kidney allocation schemes are designed to balance optimal utility with equity of access. The aim of this single-center survey is to seek patient opinion about the relative importance of factors used to determine the optimal transplant recipient in kidney allocation schemes. METHODS: In each of 8 scenarios, participants were invited to select which 1 of 2 hypothetical patients should receive a kidney. RESULTS: Two hundred thirty-two of 295 invited patients (78.6%) completed the questionnaire: 104 of 153 invited hemodialysis patients (68.0%) and 128 of 142 invited patients with functioning transplants (90.1%). Only 6.0% of participants agreed with current UK Transplant (UKT) and United Network for Organ Sharing (UNOS) allocation to a patient not yet on dialysis therapy who had been on the transplant waiting list longer than a patient already on dialysis therapy. Only 24.6% of participants agreed with the UKT and UNOS schemes that the transplant survival advantage associated with HLA matching warranted allocation of a kidney to a patient who had been waiting 2 years in preference to a patient waiting 7 years. Participants also were opposed to the use of recipient age and balance of exchange agreements (that reward centers with high rates of organ retrieval). The majority agreed with UKT and UNOS that recipient sex should not be used to allocate kidneys and allocation should favor recipients who have waited longer. CONCLUSION: Patients disagreed with several aspects of current allocation systems. Analysis of patient opinion should be taken into consideration when attempting to optimize the use of this scarce health resource.

A prospective open-label randomised trial of quinapril and/or amlodipine in progressive non-diabetic renal failure.

BACKGROUND: Treatment of hypertension slows the progression of non-diabetic nephropathies, but the optimal regimen is unknown. Angiotensin-converting enzyme inhibitors are more effective than beta-blockers, but their merits relative to calcium channel blockers are less clear. METHODS: 73 hypertensive patients with progressive non-diabetic nephropathies were prospectively randomised to open-label quinapril (Q, n = 28), amlodipine (A, n = 28) or both drugs (Q&A, n = 17). Therapy was increased to achieve a diastolic blood pressure < 90 mm Hg. Patients were followed for 4 years or until death. The primary outcome was the combined endpoint of doubling serum creatinine, starting renal replacement therapy or death. RESULTS: There was no significant difference in the primary outcome, or in the change of glomerular filtration rate. Blood pressure was equally controlled throughout the study period. 29 (40%) patients were withdrawn from the allocated therapy (Q 39%, A 36%, Q&A 47%). Because of the large crossover between trial arms, the data were re-analysed per protocol. The effect on preventing the need for renal replacement therapy then approached significance between the groups (p = 0.089) and the combined quinapril-containing groups were less likely than the amlodipine group to achieve the primary endpoint (p = 0.038), or the individual endpoints of renal replacement therapy (p = 0.030) or doubling creatinine (p = 0.051). CONCLUSIONS: Quinapril is more effective than amlodipine at reducing the incidence of dialysis in patients with progressive renal failure, but only if they can tolerate the drug. The tolerability of these drugs in patients with advanced renal failure is poor.

The influence of pre-operative electrocardiographic abnormalities and cardiovascular risk factors on patient and graft survival following renal transplantation.

Premature cardiovascular disease (CVD) is the leading cause of mortality and of graft loss in renal transplant recipients. However, the pattern of cardiovascular risk factors (specifically modifiable risk factors) is not well established and may be different from the general population. In this study we investigated the importance of electrocardiographic abnormalities and conventional cardiovascular risk factors present at the time of first renal transplantation in a longitudinal follow-up study of 515 patients. Overall, 45.8% were cigarette smokers, 13.0% were diabetic, 75.1% had "hypertension", 12.2% had symptoms of angina pectoris and 9.1% had a past history of myocardial infarction or stroke. Two thirds of ECG tracings were abnormal. 58.7% of men and 37.5% of women had left ventricular hypertrophy (LVH). Overall, 28.2% had simple LVH, 20.5% had LVH with repolarisation changes ('strain'). 434 patients had complete data for multivariate analyses of patient and graft survival. A Cox multivariate analysis of patient survival (patients whose graft failed were censored in the analysis) identified: age (hazard ratio 1.03/year), diabetes (2.72), smoking (1.81) and family history of premature CVD (2.17) as independent risk factors for patient survival. An abnormal ECG was also independently associated with outcome, with the exception of isolated left ventricular hypertrophy. Left ventricular hypertrophy with strain, or ischaemic changes were associated with adverse outcome with a hazard ratio of 1.96 and 3.30 respectively. A similar analysis of the determinants of graft survival (patients who died with a functioning graft were censored in the analysis) identified: acute rejection (hazard ratio 2.38), cigarette smoking (1.48) and age (1.04/year) as independent predictors of graft failure. These data demonstrate a high prevalence of ECG abnormalities and CV risk factors in renal transplant recipients. Moreover, ECG abnormalities and "conventional" cardiovascular risk factors are associated with poor graft and patient outcome and represent potentially remediable risk factors for renal transplant recipients.

Determinants of hypertension and left ventricular function in end stage renal failure: a pilot study using cardiovascular magnetic resonance imaging.

Cardiovascular disease is the principal cause of mortality in patients with renal failure. Left ventricular (LV) abnormalities are adverse prognostic indicators for cardiovascular outcome. The aim of this study was to use cardiac magnetic resonance scanning (CMR) to define LV functional abnormalities in haemodialysis (HD) patients and clarify the determinants of blood pressure (BP) and the effect of anaemia in this population. We studied 44 HD patients and 11 controls with CMR performed following dialysis. Forty patients and 11 controls completed the study. LV mass (P<0.001) and estimated systemic vascular resistance (SVR) (P = 0.002) were significantly higher in the dialysis group compared to controls. LV ejection fraction (P = 0.002) and SV (P = 0.043) were lower than controls. In the HD patients, BP correlated significantly with cardiac output (CO; r = 0.569, P<0.001) and end diastolic volume (EDV; r = 0.565, P<0.001) but there was no correlation between BP and SVR (r = 0.201, P = 0.594). Haemoglobin was inversely correlated with both CO (r = -0.531, P<0.001) and EDV (r = -0.493, P = 0.001) and positively with SVR (r = 0.402, P = 0.009). HD patients had a higher LV mass and lower ejection fraction than controls. The relationship of BP with CO, but not SVR, supports the theory that a major determinant of BP is intravascular volume and CO rather than vascular resistance although there was a fixed increase in SVR in this population. Improved understanding of the mechanisms underlying increased SVR and improved control of CO and intravascular volume may allow better therapeutic strategies. CMR provides insights into the pathophysiology of hypertension and LV dysfunction in HD patients.

Five-year outcomes after a change from a cyclosporin-based to a 'low-dose' tacrolimus-based primary immunosuppression regimen for incident kidney transplants--the Glasgow experience.

In January 2007, our centre changed from a cyclosporin (CyA)/azathioprine (Aza)/ prednisolone (Pred) primary immunosuppression regimen (with basiliximab induction and mycophenolate mofetil [MMF] for those at immunologically high risk) to a tacrolimus (Tac) (low dose)/MMF/Pred regimen with basiliximab induction, following presentation of Symphony trial results. This analysis assesses the impact of this change on 5-year outcomes. Three hundred consecutive renal-only transplants were identified: 140 from the 2005-06 era and 160 from the 2007-08 era. The proportions of living donor (37.5 vs. 22.9%; p = 0.04) and donors after circulatory death (11.9 vs. 5.0%; p = 0.03) were higher in the 2007-08 cohort. Five-year actuarial patient survival was higher in the 2007-08 cohort (96.8 vs. 87.1%; p = 0.003), with a trend toward higher 5-year transplant survival (84.7 vs. 76.3%; p = 0.08). Estimated glomerular filtration rate (eGFR) was higher than in the 2005-06 era at 1 (53.5 vs. 44.5 ml/min/1.73m2; p = 0.0006) and 3 years (50.9 vs. 43.4 ml/min/1.73m2; p = 0.02), with a trend toward higher eGFR at 5 years (41.8 vs. 49.6 ml/min/1.73m2; p = 0.09). Differences were consistent when living donor and deceased donor transplants were analysed separately. In a "real world" population, a change from a CyA-based to a Tac (low-dose)/MMF/Pred primary immunosuppression regimen has been associated with better 5-year outcomes.

A case of hepatitis C virus transmission acquired through sharing a haemodialysis machine.

Hepatitis C virus (HCV) infection is a significant problem among haemodialysis populations worldwide. 'Horizontal' cross-infection between patients can occur, predominately through direct environmental transmission of the virus. Current guidelines thus recommend universal barrier precautions, however they do not suggest using dedicated machines for HCV-positive patients to prevent the 'sequential' transmission of virus to those who subsequently use that machine. We report a case where sequential HCV transmission occurred from a patient of low HCV infectivity with no identifiable machine fault. We suggest that current guidelines should be reviewed to encourage the use of dedicated haemodialysis machines for HCV-positive patients.

A rare cause of nephrotic syndrome in autosomal-dominant polycystic kidney disease.

We report the case of a 49-year-old lady who presented with hypertension, breathlessness and malaise. She was thrombocytopenic, with polycystic kidneys on imaging, and was found to have nephrotic syndrome. Serological results were consistent with systemic lupus erythematosus (SLE) and a renal biopsy confirmed WHO class V lupus nephritis. This is the first reported case of nephrotic syndrome due to lupus nephritis in a patient with autosomal dominant polycystic kidney disease (ADPKD) and underlines the importance of renal biopsy in patients with ADPKD and nephrotic range proteinuria.

Diagnostic potential of circulating natriuretic peptides in chronic kidney disease.

BACKGROUND: Measurement of natriuretic peptides, particularly brain natriuretic peptide (BNP) is an established method for the diagnosis of cardiovascular disorders, chiefly left ventricular (LV) dysfunction. The influence of renal function on the diagnostic utility of natriuretic peptides is unclear. METHODS: We performed a cross-sectional study of 296 patients with renal disease but no history of cardiac disease using echocardiography to assess LV mass and function. Circulating levels of atrial natriuretic peptide (ANP) and BNP were also measured. RESULTS: The incidence of LV hypertrophy increased with progressive renal dysfunction; from 39% in patients with near-normal renal function, to 80% in renal transplant patients. There was a negative correlation between both ANP and BNP, and glomerular filtration rate (GFR) (ANP: r = -0.28, P<0.001; BNP: r = -0.40, P<0.001). Serum ANP and BNP had sensitivity and specificity for LV hypertrophy of 39.9%, 87.4% (ANP) and 61.4%, 67.6% (BNP) respectively. Sensitivity and specificity for LV dysfunction was 77.2%, 32.4% (ANP) and 71.8%, 40.0% (BNP). Significant confounders in determining serum ANP were haemoglobin, beta blockade and albumin, while serum BNP levels were significantly confounded by GFR, albumin, haemoglobin, beta blockade and age. CONCLUSIONS: Across a spectrum of renal dysfunction, GFR is a more important determinant of serum BNP than ventricular function, and several factors are predictors of natriuretic peptide levels. In chronic kidney disease, the use of natriuretic peptides to diagnose LV hypertrophy must be interpreted in light of these other factors. The use of these peptides in renal dysfunction to diagnose LV dysfunction may be of limited value.

Persistent dipstick haematuria following renal transplantation.

Despite widespread testing for dipstick haematuria following renal transplantation, there are no published series describing the prevalence and possible causes of this complication in an adult population. A cross-sectional study of 640 renal transplant recipients under review at our follow-up clinic was performed. Persistent haematuria was defined as a minimum of 1+ of blood on urinalysis stick testing detected at not fewer than 75% of clinic visits since its onset, or since the start of routine testing, present over a period of at least 4 weeks. The prevalence of persistent dipstick haematuria was 13.3%. Median serum creatinine was higher in patients with persistent haematuria but age, gender and length of time since transplantation were not significantly different. Potential explanations for persistent haematuria in 21 of 85 affected patients were chronic infection, ureteric stent without chronic infection, regular or intermittent self-catheterization, persistent menstrual bleeding, anticoagulant therapy, graft calculus, and allograft renal cell carcinoma. Recurrent or de novo glomerular disease was confirmed by graft biopsy in 10 of 85 patients. Among the 41 recipients whose original cause of renal failure was IgA nephropathy (IgAN), the prevalence of persistent haematuria was 31.7% compared with 12% in the remaining patients (relative risk 2.6, 95% CI: 1.6-4.3). Persistent haematuria in IgAN patients was not associated with gender, age or time since transplantation. After 29 months of follow-up, 20% of patients with haematuria had progressed to graft failure or death compared with 11.6% of the unaffected group (p = 0.029). However, despite the association with earlier graft failure, haematuria did not predict this endpoint independently of renal function.