A case of severe osteomalacia secondary to phosphate diabetes in a renal transplant recipient

Transient hypophosphatemia is frequently observed during the first months after renal transplantation and is usually asymptomatic. Phosphate diabetes is defined as inadequate tubular phosphorus reabsorption leading to persistent renal phosphorus wasting, which is an important but overlooked cause of osteodystrophy in the post-renal transplantation population. We report the case of a 58-year-old male who presented with severe multiple osteoarticular pains within 3 months after successful first kidney transplantation. Bone disease was attributed initially to mild hyperparathyroidism secondary to vitamin D deficiency. Despite the correction of the hyperparathyroidism, the withdrawal of corticosteroids, and the reduction of immunosuppressive treatment to tacrolimus-based monotherapy, the osteoarticular pains persisted. Skeletal investigations at month 9 post-transplantation demonstrated a significant bone mineral density loss associated with osteomalacia and osteoporosis on the bone biopsy. Laboratory data showed persistent hypophosphatemia, and phosphate diabetes was then diagnosed explaining the post-transplant bone disease. A tacrolimus-induced renal tubular disorder was suspected to contribute to the excessive renal phosphorus wasting. The replacement of tacrolimus by sirolimus, in addition to oral phosphorus and vitamin D supplementations, led to the disappearance of pains, the normalization of urinary and plasma phosphate level, and a significant improvement of bone mineralization.     

Coercion,dissatisfaction, and social stigma: an ethnographic study of compensated living kidney donation in Iran

International Urology and Nephrology - This article updates the qualitative research on Iran reported in the 2012 article by Tong et al. “The experiences of commercial kidney donors: thematic...     

Predictive Modeling of Tacrolimus Dose Requirement Based on High‐Throughput Genetic Screening

Any biochemical reaction underlying drug metabolism depends on individual gene–drug interactions and on groups of genes interacting together. Based on a high‐throughput genetic approach, we sought to identify a set of covariant single‐nucleotide polymorphisms predictive of interindividual tacrolimus (Tac) dose requirement variability. Tac blood concentrations (Tac C₀) of 229 kidney transplant recipients were repeatedly monitored after transplantation over 3 mo. Given the high dimension of the genomic data in comparison to the low number of observations and the high multicolinearity among the variables (gene variants), we developed an original predictive approach that integrates an ensemble variable‐selection strategy to reinforce the stability of the variable‐selection process and multivariate modeling. Our predictive models explained up to 70% of total variability in Tac C₀ per dose with a maximum of 44 gene variants (p‐value <0.001 with a permutation test). These models included molecular networks of drug metabolism with oxidoreductase activities and the multidrug‐resistant ABCC8 transporter, which was found in the most stringent model. Finally, we identified an intronic variant of the gene encoding SLC28A3, a drug transporter, as a key gene involved in Tac metabolism, and we confirmed it in an independent validation cohort.     

Determination of short-term exposure with a direct reading photoionization detector

The use of a direct reading photoionization detector (PID) to determine short-term solvent exposures is described in the present paper. To assess the relevance of such a total exposure evaluation it was necessary to compare it with the real concentration of pollutants. This comparison was made by measuring in parallel with the PID determination the concentration of each pollutant using a standard technique, i.e. sampling on charcoal tubes and subsequent analysis by gas chromatography. Laboratory tests showed that the linearity of the answer of the PID is good for many compounds and for a mixture of these compounds. Similar tests were carried out for painters in workplaces with the same good correlations (determination coefficient r2 close to 1) between the PID response and the real concentration of the pollutants measured on the sampling tubes. The use of PID also allowed determination of the exposure profile of the workers and comparison of the short-term exposure to the corresponding limit values. Many cases of the short-term limit values being exceeded were revealed by use of the PID, although very few cases of the long-term limit values have been found by the usual sampling (charcoal tube) and analytical (gas chromatography) methods.     

Structure-activity relationships and binding mode of styrylquinolines as potent inhibitors of HIV-1 integrase and replication of HIV-1 in cell culture

Our prior studies showed that polyhydroxylated styrylquinolines are potent HIV-1 integrase (IN) inhibitors that block the replication of HIV-1 in cell culture at nontoxic concentrations. To explore the mechanism of action of these inhibitors, various novel styrylquinoline derivatives were synthesized and tested against HIV-1 IN and in cell-based assays. Regarding the in vitro experiments, the structural requirements for biological activity are a carboxyl group at C-7, a hydroxyl group at C-8 in the quinoline subunit, and an ancillary phenyl ring. However the in vitro inhibitory profile tolerates deep alterations of this ring, e.g. by the introduction of various substituents or its replacement by heteroatomic nuclei. Regarding the ex vivo assays, the structural requirements for activity are more stringent than for in vitro inhibition. Thus, in addition to an o-hydroxy acid group in the quinoline, the presence of one ortho pair of substituents at C-3' and C-4', particularly two hydroxyl groups, in the ancillary phenyl ring is imperatively required for inhibitory potency. Starting from literature data and the SARs developed in this work, a putative binding mode of styrylquinoline inhibitors to HIV-1 IN was derived.