This study assessed hemodialysis adequacy in pediatric centers. Monthly adequacy data were requested in NAPRTCS enrollees on hemodialysis for at least 6 mo. Data forms were returned for 147 children from 32 centers. Data are presented for the 138 children (57% boys, 45% black) that were dialyzed 3 times/wk, representing 2282 patient-months of follow-up. Pre- and postdialysis BUN levels were reported in all children. Kt/V values were reported in 76 children; however, sufficient data were obtained to calculate Kt/V in 129 children. On average, 14.9 Kt/V and 15.2 urea reduction ratio (URR) values were calculated per child. Aggregate dialysis dose was defined as adequate if Kt/V was >1.2 in at least 75% of calculated Kt/V measures within a subject. Mean +/- SD age was 11.3 +/- 3.7 yr (median, 12.0 yr). Hemodialysis dose was variable within subjects (median CV%: URR 8.2, Kt/V 16.9). Aggregate dialysis dose was adequate in 70% of subjects. Multivariate logistic regression showed male gender (OR, 0.41; 95% CI, 0.16 to 0.98), black race (OR, 0.28; 95% CI, 0.11 to 0.67), larger body surface area (fourth versus first quartile: OR, 0.22; 95% CI, 0.05 to 0.80), and absence of reported Kt/V at the treating center (OR, 0.26; 95% CI, 0.10 to 0.62) were significant predictors of inadequate dialysis dose. Age, renal diagnosis, and center size were not associated with adequacy. Racial and gender disparities in hemodialysis dose existed among children at specialized academic pediatric centers and a substantial proportion received inadequate hemodialysis.
Background. The metabolism of tacrolimus is influenced by several medications when they are given concurrently. We report the interaction between tacrolimus and chloramphenicol in a renal transplant recipient. Methods. An adolescent with vancomycin-resistant Enterococcus was given standard doses of chloramphenicol. Tacrolimus trough levels increased, and the dose was adjusted to maintain the target trough level. Pharmacokinetic studies were obtained during chloramphenicol administration and 14 days after its discontinuation. Results. Toxic levels of tacrolimus were seen on the second day of chloramphenicol administration, requiring an 83% reduction in the tacrolimus dose. The dose-adjusted area under the curve value for tacrolimus was 7.5-fold greater while the patient was on chloramphenicol. These data are consistent with inhibition of tacrolimus clearance by chloramphenicol Conclusions. Chloramphenicol interferes with tacrolimus metabolism. Careful monitoring of tacrolimus trough levels during concomitant chloramphenicol therapy is recommended to avoid toxicity.
An 11-year-old African-American girl presented with fever, joint pain, fatigue, rash, and hypertension and was diagnosed with systemic lupus erythematosus (SLE). Her paternal grandmother and several paternal aunts also had SLE. Laboratory evaluation included a urinalysis with 21 protein and occasional red blood cells (RBCs) on microscopic examination; serum creatinine, 0.7 mg/dL; albumin, 4.2 g/dL; 24-hour urinary protein excretion, 1 g; C3, 60 mg/dL (normal, 88 to 201 mg/dL); C4, 10 mg/dL (normal, 15 to 45 mg/dL); and an anti-DNA titer of 1:80. The patient underwent percutaneous renal biopsy, which showed focal proliferative lupus glomerulonephritis (World Health Organization [WHO] type III). There were fibrin thrombi in the lumina of several arteries and arterioles, consistent with thrombotic microangiopathy. The patient was treated with three monthly doses of cyclophosphamide, 1 g intravenously; prednisone on a tapered schedule; and quinapril, 5 mg daily. The proteinuria resolved, and serum complement levels nearly normalized (C3, 131 mg/dL; C4, 13 mg/dL). Her anti-DNA titer remained elevated at $1:160. The prednisone was continued at 5 mg daily, and the cyclophosphamide was discontinued. Eleven months after presentation, the patient developed hypertension. Laboratory studies included a urinalysis with no protein and 8 to 30 RBCs/high-powered field; serum creatinine, 0.6 mg/dL; white blood cells (WBCs), 3.8 3 1,000/mm3; hemoglobin, 10.5 g/dL; platelet count, 300,000/ mm3; and depressed C3 and C4 levels, 42 mg/dL and 5 mg/dL. Over the next month, the patient’s blood pressure increased, and C3 and C4 levels decreased further to 25 mg/dL and 4 mg/dL. The quinapril dose was increased to 10 mg twice a day. One month later, the patient developed nausea, abdominal pain, and fever and was evaluated at a local hospital. She was dehydrated on examination, and her initial laboratory tests were notable for hemoglobin, 5.3 g/dL; blood urea nitrogen, 58 mg/dL; creatinine, 5.3 mg/dL; albumin, 3.3 g/dL; and urinalysis with 31 protein, 20 to 50 WBCs/highpowered field, and 4 to 8 RBCs/high-powered field. The patient was treated with intravenous methylprednisolone, 1 g daily for 3 days, and intravenous hydration; quinapril was discontinued; and she was transferred to this institution for further evaluation and treatment. At this institution, the physical examination was notable for a blood pressure of 138/78 mm Hg, periorbital edema, clear lungs, normal heart sounds with a II/VI systolic murmur, a soft abdomen with right upper quadrant tenderness without guarding or rebound, and nonpitting peripheral edema. The patient had no joint swelling or tenderness and no rash. Laboratory studies included blood urea nitrogen, 88 mg/dL; creatinine, 8.3 mg/dL; WBCs, 13,200/mm3; hemoglobin, 6.4 g/dL; platelet count, 515,000/mm3; and reticulocytes, 11.6%. The peripheral blood smear showed schistocytes, spherocytes, anisocytosis, and poikilocytosis. Urinalysis showed specific gravity of 1.015, pH 5, 11 protein, 11 blood, 2 to 5 RBCs/high-powered field, rare WBCs, granular casts, and rare tubular epithelial cells. Additional laboratory tests included albumin, 2.4 g/dL; lactate dehydrogenase, 1,672 U/L (normal, 372 to 744 U/L); C3, 52 mg/dL; C4, 11 mg/dL; rheumatoid factor, less than 11 IU/mL (normal, 0 to 15 IU/mL); antinuclear antibody (ANA) titer, greater than or equal to 1:160 in a smooth/speckled pattern; anti-DNA titer, greater than or equal to 1:160; negative antineutrophil cytoplasmic autoantibody (ANCA); negative cryoglobulins; negative lupus anticoagulant panel; fibrinogen, 565 mg/dL (normal, 185 to 400 mg/dL); and a negative direct Coombs’ test. On renal ultrasound, the kidneys measured 10 cm in length with normal echogenicity and no hydronephrosis. On Doppler examination, the renal arteries and veins were patent with diminished diastolic flow. The patient was started on methylprednisolone, 100 mg intravenously daily. During the next 2 days, she remained markedly oliguric, creatinine increased to 9.7 mg/ dL, and she underwent a second percutaneous renal biopsy.
Data from the North American Pediatric Renal Transplant Cooperative Study were analyzed to determine the effects of alternate-day (QOD) steroid dosing on growth, graft survival, and graft function in children with functioning grafts 12 months after transplantation. At 12 months after transplantation, 16.8% (337/2001) of transplant recipients were receiving QOD dosing. The basis for the selection of a steroid dosing regimen cannot be determined from registry data; however, the frequency of QOD dosing differed by donor source, race, age at transplant, and the occurrence of rejection episodes in the first year. The effect of the steroid dosing pattern on growth was evaluated in children continuously on either QOD or daily (QD) steroid dosing. The mean change in the standardized height scores from 1 month to 24 months after transplantation was significantly greater in those on QOD dosing(+0.5±0.06) than in those on QD dosing (+0.1±0.03). Using multiple regression analyses, better growth was associated with QOD dosing, recipient age less than 13 years, lower total steroid dose over 48 hr, and lower serum creatinine (all P<0.001). Graft survival did not differ on the basis of the steroid dosing pattern. In a proportional hazards model for survival of living donor grafts after 12 months, graft survival was negatively associated with the use of QD dosing, black race, rejection episodes in the first year, and a higher serum creatinine at 12 months. The survival of cadaver grafts was negatively associated with the use of QD steroid dosing, recipient age less than 2 years, rejection episodes in the first year, and a higher serum creatinine at 12 months. In addition, the decline in graft function did not differ between those on QOD steroid therapy and those on QD therapy. We conclude that selected pediatric renal transplant recipients receiving QOD dosing have better growth than those receiving QD dosing without compromising allograft survival or function.
Kinins promote natriuresis in vivo, at least in part by altering Na+ transport in the collecting duct. Using freshly prepared suspensions of rabbit inner medullary collecting duct (IMCD) cells, we have examined the effects of kinins on Na+ transport using measurements of oxygen consumption (QO2) and isotopic Na+ uptake. Bradykinin (BK) inhibited IMCD cell QO2 by 24.7 +/- 0.9% without significantly reducing QO2 in cells derived from the outer medullary collecting duct. BK and kallidin half-maximally inhibited QO2 at concentrations in the 10(-12)-10-(-11) M range; beta 1-receptor agonists did not alter QO2, and beta 1-receptor antagonism did not reduce the effect of kinins. These observations indicate that the actions of kinins on IMCD cells are mediated by beta 2-receptors or a distinct subclass. Several observations indicate that kinins reduce QO2 by inhibiting Na+ entry: in the absence of Na+, BK did not reduce QO2; BK inhibition of QO2 was not additive with ouabain, amiloride, atrial natriuretic peptide (ANP), or 8-bromoguanosine 3',5'-cyclic monophosphate and was abolished in the presence of the cation ionophore amphotericin B. Measurements of isotopic Na+ uptake demonstrated that BK reduced the initial rate of Na+ entry by 58%; BK inhibited the amiloride-sensitive component of conductive Na+ uptake. Because ANP inhibits conductive Na+ entry in IMCD cells via stimulation of cGMP accumulation, the effect of BK on cGMP levels was determined. Unlike ANP, BK did not increase cGMP levels, indicating that transport effects of kinins in IMCD are not mediated by cGMP. Thus kinins directly inhibit conductive Na+ entry in IMCD cells at concentrations suggestive of a physiological effect.(ABSTRACT TRUNCATED AT 250 WORDS)
