Differential Determinants of Tubular Phosphate Reabsorption: Insights on Renal Excretion of Phosphates in Kidney Disease.

We assessed the tubular reabsorption of phosphate (TRP) and maximal renal threshold for phosphate reabsorption to glomerular filtration rate (TmPi/GFR) and their determinants in 64 stages 2-4 chronic kidney disease (CKD) patients in order to define the early changes in phosphate metabolism in CKD. In multivariable analysis, TmPi/GFR correlates were estimated GFR (eGFR), intact parathyroid hormone (iPTH), and hemoglobin (R2 = 0.417), while TRP correlates were eGFR, iPTH, 24-h phosphaturia, and calcitriol (R2 = 0.72). This suggests that TmPi/GFR and TRP, respectively, assess hemoglobin-phosphate and bowel-kidney phosphate regulation axis. Iron supplementation based on TmPi/GFR or earlier phosphate restriction based on TRP should be investigated in view of modifying clinical outcomes in CKD.

Perception of musical timbre by cochlear implant listeners: a multidimensional scaling study.

OBJECTIVES: Several studies have shown that the ability to identify the timbre of musical instruments is reduced in cochlear implant (CI) users compared with normal-hearing (NH) listeners. However, most of these studies have focused on tasks that require specific musical knowledge. In contrast, the present study investigates the perception of timbre by CI subjects using a multidimensional scaling (MDS) paradigm. The main objective was to investigate whether CI subjects use the same cues as NH listeners do to differentiate the timbre of musical instruments. DESIGN: Three groups of 10 NH subjects and one group of 10 CI subjects were asked to make dissimilarity judgments between pairs of instrumental sounds. The stimuli were 16 synthetic instrument tones spanning a wide range of instrument families. All sounds had the same fundamental frequency (261 Hz) and were balanced in loudness and in perceived duration before the experiment. One group of NH subjects listened to unprocessed stimuli. The other two groups of NH subjects listened to the same stimuli passed through a four-channel or an eight-channel noise vocoder, designed to simulate the signal processing performed by a real CI. Subjects were presented with all possible combinations of pairs of instruments and had to estimate, for each pair, the amount of dissimilarity between the two sounds. These estimates were used to construct dissimilarity matrices, which were further analyzed using an MDS model. The model output gave, for each subject group, an optimal graphical representation of the perceptual distances between stimuli (the so-called "timbre space"). RESULTS: For all groups, the first two dimensions of the timbre space were strikingly similar and correlated strongly with the logarithm of the attack time and with the center of gravity of the spectral envelope, respectively. The acoustic correlate of the third dimension differed across groups but only accounted for a small proportion of the variance explained by the MDS solution. Surprisingly, CI subjects and NH subjects listening to noise-vocoded simulations gave relatively more weight to the spectral envelope dimension and less weight to the attack-time dimension when making their judgments than NH subjects listening to unprocessed stimuli. One possible reason for the relatively higher salience of spectral envelope cues in real and simulated CIs may be that the degradation of local fine spectral details produced a more stable spectral envelope across the stimulus duration. CONCLUSIONS: The internal representation of musical timbre for isolated musical instrument sounds was found to be similar in NH and in CI listeners. This suggests that training procedures designed to improve timbre recognition in CIs will indeed train CI subjects to use the same cues as NH listeners. Furthermore, NH subjects listening to noise-vocoded sounds appear to be a good model of CI timbre perception as they show the same first two perceptual dimensions as CI subjects do and also exhibit a similar change in perceptual weights applied to these two dimensions. This last finding validates the use of simulations to evaluate and compare training procedures to improve timbre perception in CIs.

Malaria, Collapsing Glomerulopathy, and Focal and Segmental Glomerulosclerosis.

BACKGROUND AND OBJECTIVES: Malaria, a potentially life-threatening disease, is the most prevalent endemic infectious disease worldwide. In the modern era, the spectrum of glomerular involvement observed in patients after malarial infections remains poorly described. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We therefore performed a retrospective multicenter study to assess the clinical, biologic, pathologic, and therapeutic characteristics of patients with glomerular disease demonstrated by kidney biopsy in France within 3 months of an acute malaria episode. RESULTS: We identified 23 patients (12 men), all but 1 of African ancestry and including 10 patients with concomitant HIV infection. All of the imported cases were in French citizens living in France who had recently traveled back to France from an endemic area and developed malaria after their return to France. Eleven patients had to be admitted to an intensive care unit at presentation. Plasmodium falciparum was detected in 22 patients, and Plasmodium malariae was detected in 1 patient. Kidney biopsy was performed after the successful treatment of malaria, a mean of 24 days after initial presentation. At this time, all patients displayed AKI, requiring KRT in 12 patients. Nephrotic syndrome was diagnosed in 17 patients. Pathologic findings included FSGS in 21 patients and minimal change nephrotic syndrome in 2 patients. Among patients with FSGS, 18 had collapsing glomerulopathy (including 9 patients with HIV-associated nephropathy). In four patients, immunohistochemistry with an antibody targeting P. falciparum histidine-rich protein-2 demonstrated the presence of the malaria antigen in tubular cells but not in podocytes or parietal epithelial cells. An analysis of the apoL1 risk genotype showed that high-risk variants were present in all seven patients tested. After a mean follow-up of 23 months, eight patients required KRT (kidney transplantation in two patients), and mean eGFR for the other patients was 51 ml/min per 1.73 m2. CONCLUSIONS: In patients of African ancestry, imported Plasmodium infection may be a new causal factor for secondary FSGS, particularly for collapsing glomerulopathy variants in an APOL1 high-risk variant background.