R. Stuart C. Rodger

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.

ANCA-Associated Renal Vasculitis Following Anti–Tumor Necrosis Factor α 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.

IgA anticardiolipin antibodies associated with Henoch-Schönlein purpura

Henoch-Schönlein purpura is associated with the deposition of immune complexes containing IgA. The nature of the antigen in these immune complexes is uncertain but in some reported cases has included autoantigens such as IgA rheumatoid factor and IgA antineutrophil cytoplasmic antibody. We report the finding of an IgA class anticardiolipin antibody in a 51-year-old patient with Henoch-Schönlein purpura. A potential role for IgA autoantibodies in Henoch-Schönlein purpura needs to be further explored.

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 &mgr;mol/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.

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 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 β-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.

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.

Persistent dipstick haematuria following renal transplantation.

Abstract:  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.