Martin A. Turman

Use of ionic dialysance to calculate Kt/V in pediatric hemodialysis

Online clearance (OLC) monitor measures conductivity difference between dialysate entering and leaving the dialyser. Derived ionic dialysance (ID) represents effective urea clearance from which Kt/V is calculated, allowing Kt/V monitoring at every treatment without blood sampling. We tested ID accuracy in children and provide recommendations for its use. Using Fresenius machines 2008 K with built‐in OLC monitors, we studied 45 hemodialysis (HD) sessions and 168 calculated Kt/V results in 11 patients. Urea distribution volume (V), needed to calculate Kt/V from ID, was estimated using three methods: Mellits and Cheek (MC), KDOQI recommended total body water nomograms (TBWN) and OLC‐derived independent from tested HD sessions. Reference spKt/V from pre‐ and post‐HD BUN (Daugirdas) was compared with Kt/V calculated from ID using three different estimated Vs. ID was accurate in calculating Kt/V in children when V derived from OLC was used (P = 0.42), with absolute error 0.14 ± 0.12. If TBWN‐derived V was used, Kt/V was consistently underestimated by 0.32 ± 0.22. TBWN‐derived V can still be recommended for use with OLC for monitoring trend in Kt/V, if underestimation of spKt/V of average 0.3 is accounted for. MC‐derived V results in even greater underestimation of spKt/V and therefore cannot be recommended for use with OLC.

Comparison of cystatin C and Beta‐2‐microglobulin kinetics in children on maintenance hemodialysis

Middle‐molecules (MM) are not monitored in children on hemodialysis (HD), but are accumulated and increase the risk of cardiovascular disease and mortality. Molecular properties of Cystatin C (CyC), 13 kDa, potentially make it a preferred MM marker over Beta‐2‐Microglobulin (B2M), 12 kDa. We compared CyC and B2M kinetics to investigate if CyC can be used as preferred MM marker. CyC (mg/L) and B2M (μg/mL) were measured in 21 low‐flux HD sessions in seven children. Blood samples were taken at HD start (pre), 1 and 2 hours into HD and at end of HD (post) for all sessions and 60 minutes after the first HD (Eq). PreCyC (9.85 ± 2.15) did not differ (P > 0.05) from postCyC (10.04 ± 2.83). PostB2M (38.87 ± 7.12) was higher (P < 0.05) than preHD B2M (33.27 ± 7.41). There was no change in CyC at 1 and 2 hours into HD, while B2M progressively increased. CyC or B2M changes did not significantly correlate with spKt/V (2.09 ± 0.86), ultrafiltration (4.61 ± 1.98%) or HD duration (218 ± 20 minutes). EqCyC was not different from postCyC (11.07 ± 3.14 vs. 10.71 ± 2.85, P > 0.05), while EqB2M was lower than postB2M (36.48 ± 7.68 vs. 41.09 ± 8.99, P < 0.05). MMs as represented by B2M and CyC are elevated in children on standard HD. Intensified HD modalities would be needed for their removal. B2M is affected by the dialytic process with a rise during HD independent of ultrafiltration and decrease 1 hour after, while CyC remains unchanged. We suggest that CyC be used as preferred marker of MM removal and as a marker of adequacy of intensified HD regimens.

Clindamycin-Associated Hyperphosphatemia in a Child with Renal Dysfunction

Objective: To report a case of hyperphosphatemia associated with administration of intravenous clindamycin phosphate in a child with renal dysfunction. Case Summary: We describe the case of a 12-year-old boy who developed hyperphosphatemia while receiving intravenous clindamycin phosphate. The child had a history of asthma but was otherwise healthy. He was transferred to our facility for management of methicillin-resistant Staphylococcus aureus bacteremia, periorbital cellulitis, osteomyelitis, and necrotizing pneumonia. He received intravenous vancomycin and clindamycin 930 mg administered every 8 hours. Concurrently, he developed acute kidney injury. His baseline phosphorus concentration was within the normal range but increased as high as 11.7 mg/dL while he received clindamycin. Despite receiving oral phosphate binder therapy and a low phosphorus diet, he had little reduction in serum phosphorus values. Intravenous clindamycin was suspected as a potential cause for hyperphosphatemia, and a recommendation was made to switch from intravenous to oral clindamycin solution since it contains a different salt formulation. Given the severity of the childs disseminated infection and questions of whether he could absorb the enteral formulation, the decision was made to continue intravenous clindamycin and he was ultimately transferred to a rehabilitation facility for further care on intravenous clindamycin. Discussion: Excess oral or intravenous intake of phosphorus can result in hyperphosphatemia, as the bodys plasma phosphate concentration exceeds the kidneys diminished filtration capacity. In this patient, use of the Naranjo probability scale indicated a possible adverse event associated with clindamycin. Phosphate intake from intravenous clindamycin and decreased glomerular filtration rate may have contributed to the childs hyperphosphatemia. Conclusions: While intravenous clindamycin was not the sole cause for this patients hyperphosphatemia, health care professionals should be aware of the potential for increased phosphate load when administering this drug to a patient with renal dysfunction.

Infant with gross hematuria and nephrotic syndrome: answers

Our differential diagnosis was acute glomerulonephritis due to infections known to cause nephrotic syndrome (NS) in the first year of life, including syphilis, toxoplasmosis, cytomegalovirus (CMV), rubella, hepatitis B, hepatitis C, human immunodeficiency virus (HIV), parvovirus, Epstein-Barr virus (EBV), herpes simplex virus (HSV), hemolytic–uremic syndrome (HUS), autoimmune disease [systemic lupus erythematosus (SLE), vasculitis], malignancy, and primary (genetic) NS with later presentation at 9 months of age (Table 1). Due to severe gross hematuria, NS and decreased renal function on admission, percutaneous renal biopsy was performed on hospital day 1 without complications. Renal ultrasonography with Doppler flow showed no evidence of renal vein thrombosis. Histologic laboratory tests showed complement levels C3 and C4 were within normal limits [120 (85–157) and 27 (15–38) mg/dl respectively], as well as total complement CH50 46 (40–70). All tests for infectious causes were negative, including antibodies to HSV, Rubella, toxoplasmosis, EBV, hepatitis C, HIV, parvovirus; polymerase chain reaction (PCR) for EBV and parvovirus; hepatitis B antigen; rapid plasma reagin test for syphilis; and nasopharyngeal viral culture including adenovirus, influenza A and B, parainfluenza, meta-pneumovirus, and respiratory syncytial virus. Stool culture for Escherichia coli O157 was negative. Serologic tests to look for SLE (antinuclear antibodies, antibodies to double-stranded DNA) and vasculitis (antineutrophil cytoplasmic antibodies) were also negative. A peripheral blood smear was done to evaluate for HUS and malignancy. The smear showed normocytic anemia without red blood cell morphologic abnormalities and no evidence of microangiopathic hemolysis. For possibility of Denys-Drash syndrome (DDS) in an infant with female phenotype, karyotype was tested and showed normal 46 XX female. Genetic testing for gene mutations in PLCE1, LAMB2, WT1, NPHS1, and NPHS2 genes for early-onset NS showed DNA sequence variants in NPHS1 (heterozygous transition G>A, nucleotide position IVS9+8) and WT1 (heterozygous, transition T>C, nucleotide position 844, codon position 282, amino acid change cysteine>arginine), which were of unknown clinical significance and have not been associated with NS (Athena Diagnostics Inc., Worchester, MA, USA). This refers to the article that can be found at http://dx.doi.org/10.1007/ s00467-011-1965-z

Infant with gross hematuria and nephrotic syndrome: questions

A 9-month old girl presented to the emergency room with brown urine and generalized edema. She had been born at full term with normal growth and development. Her parents were unrelated and had no other children. She had been in good health until she developed brown urine 4 days prior to presentation and was noted to have edema 1 day prior to being seen in emergency department. Her physical exam was remarkable for moderate generalized edema, mild pallor, and irritability. Vital signs were within normal limits except for elevated blood pressure (115/63 mmHg). Her urine specimen was turbid and brown. Microscopic exam showed red blood cells (RBC) too numerous to count, 2–5 white blood cells (WBC), and 5–10 squamous epithelial cells per high power field. No RBC casts were seen. Urine protein/creatinine ratio was 17. Renal function panel revealed normal electrolytes, elevated serum creatinine at 0.49 mg/dl (estimated glomerular filtration rate Schwartz 63 ml/min/1.73 m), and low serum albumin at 1.9 g/dl. Complete blood count showed mild anemia with hemoglobin 8.9 g/dl, platelet count 273,000/mm, and WBC 13,900/ mm. Renal ultrasound showed bilaterally enlarged kidneys with increased cortical echogenicity. Chest X-ray was within normal limits. The infant was admitted to the hospital.