Cystic Diseases of the Kidneys: From Bench to Bedside.

Exploration into the causes of hereditary renal cystic diseases demonstrates a deep-rooted connection with the proteomic components of the cellular organelle cilia. Cilia are essential to the signaling cascades, and their dysfunction has been tied to a range of renal cystic diseases initiating with studies on the oak ridge polycystic kidney (ORPK) mouse model. Here, we delve into renal cystic pathologies that have been tied with ciliary proteosome and highlight the genetics associated with each. The pathologies are grouped based on the mode of inheritance, where inherited causes that result in cystic kidney disease phenotypes include autosomal dominant and autosomal recessive polycystic kidney disease, nephronophthisis (Bardet-Biedl syndrome and Joubert Syndrome), and autosomal dominant tubulointerstitial kidney disease. Alternatively, phakomatoses-, also known as neurocutaneous syndromes, associated cystic kidney diseases include tuberous sclerosis (TS) and Von Hippel-Lindau (VHL) disease. Additionally, we group the pathologies by the mode of inheritance to discuss variations in recommendations for genetic testing for biological relatives of a diagnosed individual.

Obesity-related glomerulopathy in children: connecting pathophysiology to clinical care.

Obesity has continued to emerge as a worldwide pandemic and has been associated with a significant increase in associated comorbidities. These include well-known conditions such as hypertension and diabetes, as well as lesser-known conditions such as obesity-related glomerulopathy (ORG). The main etiology of ORG is podocyte damage, but contributing theories include dysfunctional renin-angiotensin-aldosterone system activation, hyperinsulinemia and lipid deposition. Recent advances have made strides in understanding the complex pathophysiology of ORG. The key to treating ORG is weight loss and proteinuria reduction. Lifestyle modification, pharmacological interventions and surgery are mainstays of management. A special focus on obese children is required, as childhood obesity tracks into adulthood and primary prevention is key. In this review we discuss the pathogenesis, clinical features and established and newer treatment modalities of ORG.

Age-related ultrastructural changes in the lateral cortex of the inferior colliculus.

Temporal precision, a key component of sound and speech processing in the inferior colliculus (IC), depends on a balance of inhibition and excitation, and this balance degrades during aging. The cause of disrupted excitatory-inhibitory balance in aging is unknown, however changes at the synapse are a likely candidate. We sought to determine whether synaptic changes occur in the lateral cortex of the IC (IClc), a multimodal nucleus that processes lemniscal, intrinsic, somatosensory, and descending auditory input. Using electron microscopic techniques across young, middle age and old Fisher Brown Norway rats, our results demonstrate minimal loss of synapses in middle age, but significant (∼28%) loss during old age. However, in middle age, targeting of GABAergic dendrites by GABAergic synapses is increased and the active zones of excitatory synapses (that predominantly target GABA-negative dendrites) are lengthened. These synaptic changes likely result in a net increase of excitation in the IClc during middle age. Thus, disruption of excitatory-inhibitory balance in the aging IClc may be due to synaptic changes that begin in middle age.

A case of Fournier's gangrene following a large-volume hydrocelectomy in a diabetic patient managed with SGLT-2 inhibitor therapy.

Dapagliflozin (Farxiga), is an SGLT-2 inhibitor commonly indicated for the treatment of diabetes mellitus type 2 (DM 2), heart failure, and chronic kidney disease. One rare side effect associated with SGLT-2 inhibitors is bacterial infection of the genitalia. There are several case reports highlighting the incidence of Fournier's gangrene (FG) in patients who take medications within this drug class. We report a case of FG in a diabetic patient on dapagliflozin who presented following scrotal hydrocelectomy for a large-volume hydrocele. The patient was urgently taken to the operating room for scrotal debridement and recovered well in the post-operative period.

GABAergic and glutamatergic cells in the inferior colliculus dynamically express the GABAAR γ1 subunit during aging.

Age-related hearing loss may result, in part, from declining levels of γ-amino butyric acid (GABA) in the aging inferior colliculus (IC). An upregulation of the GABAAR γ1 subunit, which has been shown to increase sensitivity to GABA, occurs in the aging IC. We sought to determine whether the upregulation of the GABAAR γ1 subunit was specific to GABAergic or glutamatergic IC cells. We used immunohistochemistry for glutamic acid decarboxylase and the GABAAR γ1 subunit at 4 age groups in the IC of Fisher Brown Norway rats. The percentage of somas that expressed the γ1 subunit and the number of subunits on each soma were quantified. Our results show that GABAergic and glutamatergic IC cells increasingly expressed the γ1 subunit from young age until expression peaked during middle age. At old age (∼77% of life span), the number of GABAAR γ1 subunits per cell sharply decreased for both cell types. These results, along with previous studies, suggest inhibitory and excitatory IC circuits may express the GABAAR γ1 subunit in response to the age-related decline of available GABA.