Congenital anomalies of the kidney and urinary tract (CAKUT) represent a broad range of diseases with differing mechanisms, clinical presentations, and prognoses. With an estimated prevalence of between 4 and 60 per 10,000 births, CAKUT represents a sizable number of patients for pediatric and adult nephrologists as therapies have progressed, allowing longer life spans. Many CAKUT disorders are associated with genetic mutations, and with advances in genomic sequencing, these genes are being identified at an increasing rate. Understanding these mutations provides insight into these conditions’ molecular mechanisms and pathophysiology. In this article, we discuss the epidemiology, presentation, and outcomes of CAKUT in addition to our current understanding of genetic and molecular mechanisms in these diseases.

Inborn errors of metabolism (IEMs) are a group of disorders resulting from defects in enzymes in metabolic pathways. These disorders impact the processing of metabolites, leading to a wide array of effects on each organ system. Advances in genetic screening have allowed for the early identification and intervention of IEMs, traditionally in the form of enzyme replacement or vitamin supplementation. However, many IEMs disrupt essential metabolic pathways where simple supplementation proves ineffective, resulting in substantial disease burden. In the case of renal IEMs, metabolic pathway disruption leads to the onset of chronic kidney disease (CKD). For these diseases, genetic therapy provides hope. Over the past few decades, the technology for genetic therapy has emerged as a promising solution to these disorders. These therapies aim to correct the source of the defect in the genetic code so that patients may live full, unencumbered lives. In this review, we searched a large database to identify IEMs that affect the kidney and investigated the current landscape and progression of gene therapy technology. Multiple promising genetic therapies were identified for IEMs affecting the kidney, including primary hyperoxaluria, argininemia, glycogen storage diseases Ia and Ib, and Fabry disease. Emerging gene therapy approaches using adeno-associated virus (AAV) vectors, lentiviral vectors, and CRISPR/Cas9 techniques hold promising potential to provide curative treatments for additional single-mutation disorders.

Numerous studies support a mechanistic link between hearing loss and increased risks of cognitive decline and dementia. Hearing loss is widely viewed as a modifiable risk factor for Alzheimer's disease (AD). During normal aging the inferior colliculus (IC), a large auditory midbrain nucleus, undergoes numerous changes to neurotransmission, and these changes contribute to the development of central gain and presbycusis. Recent reports also implicate the IC as a nucleus that undergoes processing changes during AD. We used transmission electron microscopy (EM) to examine the synaptic ultrastructure of the central IC (ICc) in 3xTG mice during presymptomatic, emerging, and established disease stages. Synapses were identified by a collection of presynaptic vesicles, a clear synaptic cleft, and a postsynaptic density. Symmetric synapses had pre and postsynaptic membranes of similar thickness, whereas asymmetric synapses had postsynaptic densities were conspicuously thicker than the presynaptic densities. We also quantified the presynaptic profile areas, active zone lengths, and presynaptic mitochondria. The data demonstrate a significant loss of symmetric and asymmetric synapses in the emerging disease stage. In particular, the density of symmetric synapses in the ICc was reduced by ∼50%. As inhibitory neurotransmitters gamma‐aminobutyric acid (GABA), glycine, and neuropeptide Y are released from neurons that form symmetric synapses in the IC, the robust loss of these synapses may contribute to central gain and presbycusis during AD. Furthermore, as these synapses were lost well before the established disease stages, perhaps alterations in ICc represent an early biomarker for Alzheimer's progression.