Renal manifestations in toddlers with Takayasu's arteritis and malignant hypertension.

Three children under the age of 3 years presented with malignant hypertension, proteinuria, and acute kidney injury. Takayasu's arteritis was diagnosed on the basis of clinical symptoms of weight loss and low grade fever in conjunction with elevated sedimentation rate and radiographic evidence of aortic and renal artery stenosis. One patient had a renal biopsy which showed arteriolar sclerosis and focal glomerulosclerosis. All three patients required multiple antihypertensive agents, ultimately including angiotensin receptor blockers and/or angiotensin converting enzyme inhibitors. The vasculitis was treated with pulse corticosteroids followed by cyclophosphamide in one patient and mycophenolate mofetil as maintenance therapy in all. Follow-up has ranged from 2 to 8 years. Although global renal function has normalized in each patient, two have unilateral non-function of one kidney. The last patient has persistent aortic and renal artery stenosis with complex collateralization requiring ongoing medical and anticipated surgical management.

Comparison of tissue plasminogen activator-antibiotic locks with heparin-antibiotic locks in children with catheter-related bacteraemia.

BACKGROUND: An accepted pathogenesis of catheter-related bacteraemia (CRB) is the seeding of microorganisms from the intraluminal biofilm of central venous catheters. Antibiotic locks (ABL) are solutions containing high concentrations of antimicrobials with or without anticoagulants that aim to destroy the biofilm. METHODS: In this study, two different ABL solutions, tissue plasminogen activator (TPA)-based and heparin-based ABL, used in conjunction with systemic antibiotics, were prospectively compared in the treatment of CRB. RESULTS: A total of 42 children on chronic haemodialysis with 11,016 catheter-days were observed for signs and symptoms of CRB over a period of 10 months. Twenty-four CRBs were diagnosed in 18 children (2.2 CRB/1000 catheter-days) and were treated with the protocol. Symptoms of CRB resolved in 83% within 48 h of treatment. None of the infected catheters required early emergent exchange or removal for poorly controlled CRB. Six children had recurrence of CRB within 6 weeks, of which four required catheter exchange. There was no specific microorganism or type of CRB that predisposed to higher recurrence rates. The mean infection-free survival of the catheters following TPA-ABL treatment was shorter than that following heparin-ABL treatment, but was not statistically significant by the log-rank test (126.8 +/- 81.6 days versus 154.5 +/- 70.4 days). CONCLUSION: Both TPA-ABL and heparin-ABL used in conjunction with systemic antibiotics can effectively clear CRB without significant late recurrence at 6 weeks. Early use of ABL for management of CRB can potentially decrease the need for catheter removal, thus salvaging vascular access sites.

Rituximab therapy for juvenile-onset systemic lupus erythematosus.

Rituximab (RTX), an anti-CD20 monoclonal antibody, has been proposed for use in the therapy of systemic lupus erythematosus (SLE). We present the initial long-term experience of the safety and efficacy of rituximab for treatment of SLE in children. Eighteen patients (mean age 14 +/- 3 years) with severe SLE were treated with rituximab after demonstrating resistance or toxicity to conventional regimens. There was a predominance of female (16/18) and ethnic African (13/18) patients. All had lupus nephritis [World Health Organization (WHO) classes 3-5] and systemic manifestations of vasculitis. Clinical disease activity of the SLE was scored with the SLE-disease activity index 2K (SLEDAI-2K). Patients were followed-up for an average of 3.0 +/- 1.3 years (range 0.5 to 4.8 years). B-cell depletion occurred within 2 weeks in all patients and persisted for up to 1 year in some. Clinical activity scores, double-stranded DNA (dsDNA) antibodies, renal function and proteinuria [urine protein to creatinine ratio (Upr/cr)] improved in 93% of the patients. Five patients required multiple courses of RTX for relapse, with B-cell repopulation. One died of infectious endocarditis related to severe immunosuppression. In conclusion, our data support the efficacy of rituximab as adjunctive treatment for SLE in children. Although rituximab was well tolerated by the majority of patients, randomized controlled trials are required to establish its long-term safety and efficacy.

Treatment of catheter-related bacteremia with tissue plasminogen activator antibiotic locks.

This retrospective study was completed to investigate the effectiveness of tissue plasminogen activator (TPA) antibiotic locks (ABL) along with systemic antibiotics (AB) to clear catheter-related bacteremia (CRB) in children on chronic hemodialysis. There were 76 CRBs in 37 children. CRBs were successfully cleared with AB/ABL in 63/76 (83%) cases. Ten of 76 (13%) CRBs were symptomatic at 48 h of treatment. These were seven polymicrobial, two gram-negative, and one Candida CRB. 13/76 (17%) episodes required catheter exchange, and all were wire-guided exchanges. TPA-ABL/AB cleared gram-positive and gram-negative CRBs significantly better than polymicrobial CRBs (p < 0.01). The infection-free survival and the rate of recurrence at 45 days was not statistically different between the TPA-ABL/AB group and the catheter-exchange group. If CRB was symptomatic at 48 h of treatment, recurrence at 6 weeks was more frequent with persistent use of TPA-ABL/AB (p < 0.05). There were no episodes of metastatic infections, catheter malfunction from occlusion, or catheter breakdown during the course of TPA-ABL treatments. In conclusion, TPA-ABL can be safely and effectively used in the management of CRB, increasing the probability of catheter survival and preserving the vascular access site. With the exception of polymicrobial CRB, there is no disadvantage in using TPA-ABL/AB over catheter exchange, as the infection-free survival and the rate of recurrence are comparable.

Paricalcitol versus calcitriol treatment for hyperparathyroidism in pediatric hemodialysis patients.

Secondary hyperparathyroidism (SHPT) remains a treatment dilemma in pediatric dialysis patients. Recent experience with paricalcitol (P), a vitamin D analogue, in adults with SHPT has shown equal efficacy and improved survival compared to traditional treatment with calcitriol (C). We present our experience with (C) compared to (P) treatment in our pediatric dialysis patients with SHPT. Twenty-one patients (mean age 11.5+/-5 years) with SHPT (intact parathyroid hormone (iPTH) averaging 1,228+/-496 pg/ml) were studied. Seventeen received (C) followed by (P); while an additional four were treated with either (C=1) or (P=3) alone. After 26+/-8 weeks, average percent (%) decrease in iPTH was similar with (C) and (P) (-60.4+/-34% versus -65.4+/-28%, respectively; p=0.6). In the (P) group, the effective dose in children was greater than in adult trials based on kilogram weight. Episodes of hypercalcemia between the treatment groups were not different. However, episodes of elevated calcium x phosphorus product (CaxP)> or =70 mg(2)/dl(2) occurred more frequently in the (C) group (odds ratio=1.5; p=0.01). Paricalcitol appears to be safe and effective in pediatric patients. Data suggest that dosing should be gauged according to degree of SHPT. This should serve as impetus for future pharmacokinetic studies in pediatric dialysis patients.

Profiling proteinuria in pediatric patients.

This study was designed to characterize proteinuria in children with kidney disease. Random urine samples from 250 pediatric patients were examined by quantitative measures of total protein (pr), albumin (Alb), and creatinine (cr). Patient diagnoses were subjectively categorized as "Glomerular" (GD) or "Tubulo-interstitial" disease (TD) in origin. Proteinuria was quantitated by the random urine protein-to-creatinine (Upr/cr) ratio, and glomerular proteinuria was assessed as the albumin-to-creatinine ratio (Ualb/cr) and percentage albuminuria (%Alb=Alb/pr*100). The non-albumin fraction (1-Alb/pr) includes low-molecular-weight proteins and micro- and macroglobulins. Of the 250 patients, 112 (45%) had GD and 138 (55%) had TD. Both proteinuria and albuminuria correlated with a decline in glomerular filtration rate (GFR) (r=-0.4; p<0.0001). Those with GD averaged significantly greater %Alb than those with TD at all levels of proteinuria (p<0.0001). With loss in GFR, %Alb increased significantly in patients with TD (18+/-13 to 47+/-30%; p<0.001) and GD (56+/-26 to 74+/-15%; p<0.01), respectively. The %Alb at all levels of GFR averaged <50% in those with TD and >50% in those with GD. In conclusion, random Ualb/cr, Upr/cr, and %Alb provide a simple and inexpensive assessment of proteinuria and may profile renal disease activity and response to therapy in pediatric patients.

Novel anticoagulant activity of polyamino acid offsets bacterial endotoxin-induced extrinsic hypercoagulation: downregulation of monocytic tissue factor-dependent FVII activation.

The extrinsic hypercoagulation often resulting from sepsis could contribute to disseminated intravascular coagulation and cardiovascular complications. The effective prevention and intervention remained largely complex and unclear. In a cell model of human leukemia THP-1 monocytes following bacterial endotoxin (LPS) exposure, we show the novel anticoagulant ability of polyamino acid (polyAA) to suppress the extrinsic hypercoagulation. LPS-induced monocytic tissue factor (mTF) procoagulation was readily offset by poly-L-lysine (PLK), poly-L-arginine (PLR), or poly-L-ornithine (POR) included in single-stage clotting assays. IC50 was estimated at 0.35, 0.30, or 0.58 microM for PLR, POR, or PLK, respectively, whereas, poly-L-asparatic acid (PLD) remained ineffective. In a separate approach, inclusion of cationic polyAA in human plasma significantly prolonged prothrombin time, confirming the depressed extrinsic coagulation. In chromogenic assays dissecting the extrinsic pathway, we further determined the inhibitory site(s). PLK, PLR, or POR significantly inhibited LPS-induced FVII activation, which was consistent with the diminished FVIIa formation shown on Western blotting analysis. In contrast, polyAA did not show any additional effect on either FVIIa/FXa amidolytic activities or mTF/FVIIa-catalyzed FX activation. Nor did polyAA show any effect on FVII activation directly catalyzed by FXa. Taken together, PLK, PLR, or POR preferentially inhibited mTF-dependent FVII activation, accounting for their novel anticoagulant activities. PolyAA might present the specific antagonists to arrest the extrinsic hypercoagulation following inflammation.