Kidney Function

Background: Critically ill children with hemodynamic instability and acute kidney injury often develop fluid overload. Continuous renal replacement therapy (CRRT) has emerged as a favored modality in the management of such children. This study investigated the association between fluid overload and mortality in children receiving CRRT.Study Design: Prospective observational study.Setting & Participants: 297 children from 13 centers across the United States participating in the Prospective Pediatric CRRT Registry.Predictor: Fluid overload from intensive care unit (ICU) admission to CRRT initiation, defined as a percentage equal to (fluid in [L] − fluid out [L])/(ICU admit weight [kg]) × 100%.Outcome & Measurements: The primary outcome was survival to pediatric ICU discharge. Data were collected regarding demographics, CRRT parameters, underlying disease process, and severity of illness.Results: 153 patients (51.5%) developed < 10% fluid overload, 51 patients (17.2%) developed 10%-20% fluid overload, and 93 patients (31.3%) developed ≥ 20% fluid overload. Patients who developed ≥ 20% fluid overload at CRRT initiation had significantly higher mortality (61/93; 65.6%) than those who had 10%-20% fluid overload (22/51; 43.1%) and those with < 10% fluid overload (45/153; 29.4%). The association between degree of fluid overload and mortality remained after adjusting for intergroup differences and severity of illness. The adjusted mortality OR was 1.03 (95% CI, 1.01-1.05), suggesting a 3% increase in mortality for each 1% increase in severity of fluid overload. When fluid overload was dichotomized to ≥ 20% and < 20%, patients with ≥ 20% fluid overload had an adjusted mortality OR of 8.5 (95% CI, 2.8-25.7).Limitations: This was an observational study; interventions were not standardized. The relationship between fluid overload and mortality remains an association without definitive evidence of causality.Conclusions: Critically ill children who develop greater fluid overload before initiation of CRRT experience higher mortality than those with less fluid overload. Further goal-directed research is required to accurately define optimal fluid overload thresholds for initiation of CRRT.

Toxic nephropathies are an important and relatively common category of kidney damage. Although they generally are reversible when detected early, they may be permanent, leading to chronic kidney disease (CKD). Toxic nephropathies are defined primarily as kidney injury caused by any number of medications, diagnostic agents, alternative products, herbal adulterants, or other toxin exposures, which includes environmental agents and chemicals. Because the kidney performs a number of essential bodily functions, including clearance of endogenous waste products, control of volume status, maintenance of electrolyte and acid-base balance, and modulation of endocrine activity, loss of kidney function leads to a number of clinical problems. Furthermore, metabolism and excretion of exogenously administered medications and environmental exposures is a critically important function. In its role as the primary eliminator of exogenous drugs and toxins, the kidney is vulnerable to develop various forms of injury.

Background: There are few anecdotal reports of circulating antineutrophil cytoplasmic autoantibodies (ANCAs) in patients with immunoglobulin A (IgA) nephropathy.Study Design: Retrospective case series.Setting & Participants: We studied 8 patients with crescentic IgA nephropathy associated with ANCAs against myeloperoxidase (n = 5) and proteinase 3 (n = 3) followed up for 2.4 ± 1.7 years. They were compared with 26 patients with IgA nephropathy with > 10% crescentic glomeruli, but negative for ANCAs.Outcomes: We analyzed clinical and histologic features of patients and their response to treatment.Measurements: Screening for ANCAs was performed using indirect immunofluorescence, and positive results were verified using enzyme-linked immunosorbent assay.Results: All patients with crescentic IgA nephropathy and positive for ANCAs, compared with only one-third of ANCA-negative patients, presented with the clinical syndrome of rapid progressive glomerulonephritis. ANCA-positive patients reached a higher peak serum creatinine level within the first 3 months (4.2 ± 2.2 vs 2.5 ± 1.9 mg/dL; estimated glomerular filtration rate, 19.3 ± 10.2 vs 45.9 ± 30.1 mL/min/1.73 m2). ANCA-positive patients with IgA nephropathy had a higher percentage of crescentic glomeruli (54.3% ± 18%) compared with ANCA-negative patients with crescentic IgA nephropathy (34.5% ± 26%). ANCA-positive patients were treated using cyclophosphamide and corticosteroids. Kidney function improved in all these patients: serum creatinine level decreased from the peak of 4.2 ± 2.2 to 1.7 ± 0.7 mg/dL at the end of follow up (estimated glomerular filtration rate, 19.3 ± 10.2 to 44.6 ± 11.1 mL/min/1.73 m2). In contrast, no significant improvement was achieved in ANCA-negative patients.Conclusion: Patients with IgA nephropathy, crescents, and positive for ANCAs represent a clinical entity with a diverse more exaggerated clinical and histologic picture. However, disease in these patients responded well to aggressive immunosuppressive therapy.