Fenoldopam and renal function after partial nephrectomy in a solitary kidney: a randomized, blinded trial.

OBJECTIVE: To test the hypothesis that fenoldopam administration ameliorates ischemic injury, preserving the glomerular filtration rate and serum creatinine postoperatively after partial nephrectomy in patients with a solitary kidney. MATERIALS AND METHODS: Fenoldopam is a short-acting dopamine-1 receptor agonist that might provide renal protection during ischemic stress. A total of 90 patients with a solitary functioning kidney who were undergoing partial nephrectomy were randomized to fenoldopam or placebo in a double-blind protocol. The patients assigned to fenoldopam received an infusion rate of 0.1 µg/kg/min for 24 hours. The effect of fenoldopam on renal function was assessed by comparing the groups on the change in glomerular filtration rate from baseline to the third postoperative day (primary outcome) and on the change in serum creatinine over time (secondary outcome). RESULTS: Of the 90 enrolled patients, 77 provided analyzable data (43 in fenoldopam and 44 in placebo group). Fenoldopam (vs placebo) did not reduce the mean percentage of change in the glomerular filtration rate from baseline to the third postoperative day (P = .15), with an estimated ratio of means of 0.89 (95% confidence interval 0.69-1.09) for fenoldopam vs placebo. The postoperative serum creatinine in the 2 groups changed at comparable rates from postoperative day 1 to 4 (group-by-time interaction, P = .72) after adjusting for baseline creatinine, with no difference in the mean serum creatinine over time (P = .78). CONCLUSION: Fenoldopam administration did not preserve renal function in the clinical setting of renal ischemia during solitary partial nephrectomy, as evidenced by changes in the glomerular filtration rate or serum creatinine.

Linkage analysis of genetic loci for kyphoscoliosis on chromosomes 5p13, 13q13.3, and 13q32.

Kyphoscoliosis, a three-dimensional deformity of spinal growth, is characterized by a curvature in the coronal plane (scoliosis) in conjunction with thoracic kyphosis in excess of the normal range in the sagittal plane. We identified kyphoscoliosis within members of seven families (53 individuals) originally ascertained as part of a large collaborative study of familial idiopathic scoliosis. Model-independent linkage analysis of a genome-wide microsatellite screen identified areas suggestive of linkage on chromosomes 2q22, 5p13, 13q, and 17q11. Single-point and multipoint analyses of an additional 25 flanking microsatellite markers corroborated linkage to these regions, with areas on chromosomes 5p13, 13q13, and 13q32 being the most significant (P < 0.005). Analyses of single nucleotide polymorphism (SNP) markers in the candidate region on chromosome 5 narrowed the region to approximately 3.5 Mb (P < 0.05), with the most significant P values (P < 0.01) occurring in approximately a 1.3-Mb region. Candidate loci in this region include IRX1, IRX2, and IRX4 of the Iroquois Homeobox protein family. On chromosome 13, single-point and multipoint analyses resulted in multiple SNPs having P values < 0.05 within five candidate genes: Osteoblast-specific factor 2 or periostin, forkhead box O1A, A-kinase anchor protein 11, TBC1 domain family member 4, and glypican 5, thus supporting the potential relevance of this region in the pathogenesis of kyphoscoliosis.