Growing international evidence for urinary biomarker panels identifying lupus nephritis in children - verification within the South African Paediatric Lupus Cohort.

BACKGROUND: A urinary biomarker panel including alpha-1-acid-glycoprotein (AGP), lipocalin-like-prostaglandin-D-synthase (LPGDS), transferrin and ceruloplasmin demonstrates an 'excellent' ability for identifying active lupus nephritis in UK/US children. This study aimed to assess whether this panel identifies active lupus nephritis within the South African Paediatric Lupus Cohort. METHODS: Juvenile-onset-systemic lupus erythematosus (JSLE) patients aged < 19 years at diagnosis and healthy controls were recruited. Patients were categorized as having active lupus nephritis (renal BILAG score; A/B and previous histological confirmation) or inactive lupus nephritis (renal BILAG score: D/E). Urinary biomarkers were quantified by ELISA. Mann-Whitney U-test compared biomarker levels between groups. Binary logistic regression and receiver operating curve analysis assessed biomarker combinations. RESULTS: Twenty-three juvenile-onset-systemic lupus erythematosus patients were recruited with a median age of 13.5 years (interquartile range (IQR) 12.7-14.9) and disease duration of 2.6 years (IQR 1.8-4.0). Eighteen healthy controls had a median age of 11.0 years (IQR 10.0-12.0). AGP, LPGDS, transferrin, ceruloplasmin and VCAM-1 were significantly higher in active than in inactive lupus nephritis patients (corrected p-values, all pc < 0.05), with no difference between inactive lupus nephritis patients and healthy controls (all pc = 1.0). The optimal biomarker combination included AGP, ceruloplasmin, LPGDS and transferrin (area under the curve = 1.0). CONCLUSIONS: A urinary biomarker panel comprising AGP, ceruloplasmin, LPGDS and transferrin previously validated within UK/US cohorts also performed excellently within a racially distinct South African cohort which displayed more severe lupus nephritis.

Severe disease presentation and poor outcomes among pediatric systemic lupus erythematosus patients in South Africa.

Background Systemic lupus erythematosus (SLE) is a life-threatening multisystem autoimmune disease that is more severe in patients of African ancestry and children, yet pediatric SLE on the African continent has been understudied. This study describes a cohort of pediatric SLE (PULSE) patients in South Africa. Methods Patients with a diagnosis of SLE (1997 American College of Rheumatology criteria) diagnosed prior to age 19 years in Cape Town, South Africa, were enrolled in this cross-sectional study from September 2013 to December 2014. Information on clinical and serological characteristics was extracted from medical records. Results were compared to a well-described North American pediatric SLE cohort. Results Seventy-two South African patients were enrolled in the study; mean age 11.5 years; 82% were girls. The racial distribution was 68% Coloured, 24% Black, 5% White and 3% Asian/Indian. Most patients presented with severe lupus nephritis documented by renal biopsy (61%). Of patients with lupus nephritis, 63% presented with International Society of Nephrology/Renal Pathology Society class III or IV. Patients in the PULSE cohort were more likely to be treated with cyclophosphamide, methotrexate and azathioprine. The PULSE cohort had high disease activity at diagnosis (mean Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K) 20.6). The SLEDAI-2K at enrolment in the PULSE cohort (5.0) did not differ from the North American pediatric SLE cohort (4.8). Sixty-three per cent of the PULSE cohort had end organ damage with Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI) score >0 (mean SLICC-DI 1.9), compared to 23% in a previously reported US cohort. Within the PULSE cohort, nine (13%) developed end-stage renal disease with six (8%) requiring transplant, strikingly higher than North American peers (transplant rate <1%). Conclusions The PULSE cohort had highly active multiorgan disease at diagnosis and significant disease damage at enrolment in the South African registry. South African patients have severe lupus nephritis and poor renal outcomes compared to North American peers. Our study revealed a severe disease phenotype in the PULSE cohort resulting in poor outcomes in this high-risk population.

Untoward cardiac changes during CO2 insufflation in laparoscopic cholecystectomies in low-risk patients.

In the past decade, laparoscopic cholecystectomy has become the gold standard treatment for gallbladder disease. A debate has arisen about using CO2 to distend the abdomen because of negative effects on venous return to the heart and declining cardiac output. Some authors have supported the use of pulmonary artery catheters for intraoperative monitoring while others have recommended gasless techniques to avoid these negative effects for high-risk patients. In this study, four cases of bradycardia and/or asystole during CO2 pneumoinsufflation at the beginning of planned, elective laparoscopic cholecystectomies are described. These patients were ASA category II, without history of cardiac disease. To determine the frequency and any underlying common denominators, we analyzed these laparoscopic cholecystectomies. Each patient experienced bradycardia shortly after the start of the laparoscopic cholecystectomy. None had known cardiac disease or symptoms. Two were on antihypertensive medications, and one had experienced an episode of unexplained bradycardia 6 years earlier. These cases occurred during 725 laparoscopic cholecystectomies (0.6% approximately). Using the senior author's conversion rate of 10% to open cholecystectomies, the entire group would be approximately 800, and the risk of bradycardia upon induction of CO2 is 4 per 800, or 0.5%. Although cardiovascular changes were noted during laparoscopic gynecologic surgery approximately 20 years ago, only in the last few years have cardiovascular changes been reported during laparoscopic cholecystectomies. This study reviews four cases of bradycardia during CO2 insufflation in patients that were considered to be low-risk. Surgeons should be prepared to encounter such cardiovascular changes even with low-risk patients.