Scleroderma renal crisis: patient characteristics and long-term outcomes.

BACKGROUND: Scleroderma renal crisis (SRC) is an important complication of systemic sclerosis, causing acute renal failure, and usually hypertension. AIMS: To review the clinical and pathological features of SRC, and correlate them with renal outcomes and mortality. DESIGN: Retrospective case series. METHODS: We identified 110 cases of SRC managed at a single centre between 1990 and 2005. RESULTS: SRC occurred in 5% of scleroderma cases under follow-up. Cases were predominantly female (81%), with diffuse cutaneous disease (78%). RNA polymerase antibodies were found in 59% of cases tested. Almost all (108/110) received treatment with ACE inhibitors (ACEIs). Dialysis was not required in 36%, was required temporarily (for up to 3 years) in 23%, was required permanently in 41%. Patients not on dialysis showed improvement in estimated glomerular filtration rate after SRC (mean change +23 ml/min over 3 years). Poor renal outcome was associated with lower blood pressure at presentation, and with higher age in those requiring dialysis. Steroid use, microangiopathic haemolytic anaemia, and antibody profile were not related to renal outcome. In the 58 renal biopsies available for clinical correlation, acute changes of mucoid intimal thickening in arteries and fibrinoid necrosis in arterioles were associated with a poorer renal outcome. Mortality was high (59% survival at 5 years), and was higher in men. DISCUSSION: Despite the efficacy of ACEIs in managing SRC, the poor long-term outcome warrants evaluation for additional treatments for this devastating complication of systemic sclerosis.

Atrial thrombus and central venous dialysis catheters.

A native arteriovenous fistula is the first choice for hemodialysis access. Despite improved catheter designs and the use of internal jugular veins, thrombotic complications still occur when tunneled central venous catheters are used as an alternative. Although right atrial thrombus (RAT) is a well-characterized complication of long-term central venous cannulation, particularly when used for parenteral nutrition and chemotherapy in pediatric practice, only 9 reported cases previously have been associated with the long-term use of central venous catheters for hemodialysis. We report five cases of RAT seen at our unit between 1994 and 1998 in patients who had been dialyzed using tunneled catheters. In four of five cases, the diagnosis was made during the investigation of hemoptysis or dyspnea. In the fifth case, a screening transthoracic echocardiogram revealed the thrombus. Three of five of the patients suffered pulmonary emboli, and a fourth patient had an unexplained electromechanical dissociation cardiac arrest without definite evidence of pulmonary embolus. Our experience suggests that anticoagulated patients with RAT remain at risk of pulmonary embolism. One of our patients successfully underwent atrial thrombectomy. In four of five of our cases and four of nine cases in the literature, the central venous catheter tip was within the right atrium. Positioning of the central venous catheter tip low down in the superior vena cava or in the right atrium has been advocated to improve dialysis adequacy and to reduce the incidence of catheter thrombosis. However, placement of the catheter tip within the right atrium may be associated with an increased risk of RAT.

Pregnancy in renal transplant recipients: the Royal Free Hospital experience.

BACKGROUND: For women with end-stage renal failure of child-bearing age, renal transplantation offers a chance to start a family. Pregnancies in renal transplant recipients involve risks for graft and fetus, and need to be carefully managed. AIM: To identify graft, fetal and maternal outcomes in our patients, and compare our results with those of the large national transplant registries. DESIGN: Retrospective case-note review. METHODS: We assessed the outcomes of 48 pregnancies in 24 renal transplant recipients. Obstetric data and renal parameters were examined in 27-30 pregnancies that progressed to delivery. RESULTS: Mean time from transplantation to pregnancy was 6.5 years, with an unfavourable outcome in patients who conceived within 1 year. There was a 41% incidence of fetal growth restriction (FGR), and 33% of infants were small for gestational age. FGR was associated with maternal hypertension, a pre-pregnancy serum creatinine (SCr) >/= 133 micro mol/l (1.5 mg/dl), calcineurin inhibitors and the use of cardioselective beta blockers. Two patients with pre-pregnancy SCr > 200 micro mol/l lost their grafts within 3 years of delivery. A permanent significant decline in graft function occurred in 20%, by 6 months post delivery. DISCUSSION: FGR with SGA infants occurs frequently. Atenolol should be avoided in pregnancy and Metoprolol should not be combined with calcineurin inhibitors. Pregnancy appeared to have a deleterious effect on graft function in patients with SCr > 155 micro mol (1.75 mg/dl). Patients with pre-pregnancy SCr 200 micro mol/l are at greatest risk.

Membrane and centrifugal therapeutic plasma exchange: practical difficulties in anticoagulating the extracorporeal circuit.

Therapeutic plasma exchange (TPE) is a well-established treatment modality for nephrology patients, using two conventional methods: membrane (mTPE) or centrifugal TPE (cTPE). Although the efficacy of both treatments has been described, there are few reports that compare these methodologies. Here we describe three nephrology patients who were treated with both mTPE and cTPE. The mTPE method, but not the cTPE method, was associated with persistent difficulty anticoagulating the extracorporeal circuit in all three patients. In mTPE procedures, the doses of heparin bolus and infusion rate were important determinants of whether the circuit clotted. With a heparin bolus at or below 2000 IU, clotting occurred in 67% of treatments, dropping to 25% with a bolus of >2000 IU. Likewise, a heparin infusion rate during the procedure was indicative of clotting. With a maintenance infusion of <2000 IU/h, most circuits clotted. No clotting was observed during cTPE procedures using acid citrate dextrose formula A solution as an anticoagulant of the extracorporeal circuit. Overall, difficulties maintaining the extracorporeal circuit in mTPE required the use of additional disposable sets, high doses of heparin and nursing time. In addition, mTPE procedures took longer to perform than cTPE.

Radiotherapy for a pulmonary aspergilloma complicating p-ANCA positive small vessel vasculitis.

Life-threatening haemoptysis may complicate aspergillomas within pre-existing lung cavities. Treatment options have included lung resection, pulmonary or bronchial artery embolisation and antifungal therapy administered either systemically or by endobronchial or percutaneous instillation. We present a case of aspergilloma complicating small vessel vasculitis, and its successful treatment using radiotherapy.

Low plasma protein nitrotyrosine levels distinguish primary Raynaud's phenomenon from scleroderma.

OBJECTIVE: To investigate the hypothesis that increased formation of reactive nitrogen species may contribute to the vascular pathology that develops in patients with connective tissue disease such as scleroderma. PATIENTS AND METHODS: The level of protein-bound nitrotyrosine in plasma was measured by stable isotope dilution gas chromatography/negative ion chemical ionisation mass spectrometry in 11 patients with primary Raynaud's phenomenon, 37 with scleroderma, 13 with chronic renal impairment, and in 23 healthy controls. RESULTS: Plasma protein-bound nitrotyrosine was markedly decreased in patients with primary Raynaud's phenomenon (mean (SEM) 0.60 (0.06) ng/mg dry protein) compared with patients with scleroderma (1.78 (0.21) ng/mg protein), chronic renal impairment (1.42 (0.17) ng/mg protein) or healthy controls (1.63+/-0.15 ng/mg protein, ANOVA p<0.001). CONCLUSION: These data suggest that there is decreased nitration of plasma proteins, or increased degradation of nitrated proteins from the circulation of patients with primary but not secondary Raynaud's phenomenon.

The safety and efficacy of MMF in lupus nephritis: a pilot study.

Inducing and maintaining remission in patients with lupus nephritis may be difficult. Current treatments have significant toxicity. Mycophenolate mofetil (MMF) limits damage in murine models of lupus nephritis. We have assessed the efficacy and tolerability of MMF in the treatment of patients with long-standing or resistant lupus nephritis. We have treated 13 patients with biopsy proven lupus nephritis (two membranous nephropathy, four membranous nephropathy with superimposed proliferative changes, seven with proliferative glomerulonephritis). All patients had relapsed on conventional treatment or there were pressing indications to minimise steroid dosage or avoid alkylating agents. Nine out of 13 were treated with MMF and prednisolone, 3/10 with MMF alone and 1/10 with MMF, prednisolone and cyclosporine. Thirteen patients were treated with MMF for up to 37 months (median 25 months). Three patients were withdrawn from MMF during the first 8 months of treatment. The remainder tolerated MMF (median dose 1 g/day). Serological improvements were observed in 9/13 and steroid dosage was reduced in 8/10 patients. Infections occurred in 3/13. One patient relapsed. MMF significantly reduced the rate of decline of renal function. MMF should be considered in the treatment of long-standing or resistant lupus nephritis. Controlled clinical trials are required to confirm these findings.

Calculated glomerular filtration rate is a useful screening tool to identify scleroderma patients with renal impairment.

OBJECTIVES: Although it only occurs in a minority of patients, renal involvement is a life-threatening complication of scleroderma (SSc). We have investigated the utility of two formulae to calculate glomerular filtration rate (GFR) in a population of SSc patients. METHODS: Twenty-six patients (20 female, 6 male, median age 58 yr, age range 12-80 yr) satisfied our criteria for inclusion in a retrospective comparison of measured and calculated GFR. GFR was measured using (51)Cr-EDTA. The modified Cockcroft and Gault formula and equation 7 from the Modification of Diet in Renal Disease (MDRD) were used to calculate GFR. RESULTS: Eighteen out of 19 patients analysed with a serum creatinine concentration less than the upper limit of the normal range had a measured GFR outside the normal range. Three patients with a normal creatinine concentration had a measured GFR <60 ml/min and in each of these the calculated GFR was also abnormal. All patients with a measured GFR <60 ml/min were identified using both the MDRD and the modified Cockcroft and Gault formula to calculate GFR. The greatest correlation between measured and calculated GFR was seen when the MDRD formula, which employs demographic and serum variables, was used in patients with body surface area (BSA) >1.4 m(2) who were not taking Iloprost (r=0.91). Use of the Cockcroft and Gault formula to calculate creatinine clearance with a correction factor for GFR, the inclusion of patients taking Iloprost and the inclusion of patients with BSA <1.4 m(2) were all associated with a lower degree of correlation. CONCLUSION: Serum creatinine is a poor marker of renal function in SSc patients. Calculating GFR from demographic and serum variables is a simple technique to identify SSc patients who have abnormal renal function. The authors recommend the use of the MDRD formula.