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Both in the United States and many regions of the world, chronic kidney disease and end-stage renal disease (ESRD) in patients with diabetes mellitus have reached epidemic proportions in recent years. The large prevalent diabetic ESRD population in the US involves remarkable risk in African Americans and an increasing population of elderly diabetic patients, including many octogenarians. In the US and globally, over 90% of diabetic ESRD patients have type 2 diabetes. The multinational epidemic of diabetic ESRD has been linked to increases in the prevalence of diabetes in many populations, related to obesity, ageing, and physical inactivity. It is anticipated that the worldwide prevalence of diabetes over the next 20 years will reach a level twice that of the year 2000. The excessive morbidity and mortality of the diabetic ESRD population are well documented. However, the growth in incidence and prevalence rates for diabetic ESRD has remained somewhat stable in the US in recent years, and new data suggest that the incidence of ESRD expressed per diabetic population may finally be declining, suggesting that proven therapies are making “progress on progression.” [ABSTRACT FROM AUTHOR]

Persons with diabetes mellitus whose kidney disease progresses to end-stage requiring dialysis have poorer outcomes compared to nondiabetic patients who commence maintenance dialysis. In the diabetic patient without renal failure, sustained strict glycemic, lipid, and blood pressure (BP) control can retard or thwart diabetic complications such as retinopathy, neuropathy, coronary disease, and peripheral vascular disease. Achieving these outcomes requires multidisciplinary collaborative care. Best care of the diabetic person requires a dedicated clinician who knows the patient well, who closely follows the course of clinical problems, who provides frequent assessments and interventions, and who also directs care to other agencies, clinics, and specialized clinicians who provide expert focused evaluations and interventions aimed at specific clinical concerns. Diabetic patients who reach end-stage renal disease (ESRD) have even greater clinical need of a dedicated principal care clinician than the diabetic patient who has minimal or moderate kidney disease. The diabetic patient with ESRD exhibits greater fluctuations in glucose and BP due to dialysis-related diet patterns and fluid balances and has more active cardiovascular problems due to the combined influences of calcium, phosphorus, and lipid imbalances. These problems warrant exceptional care that includes frequent surveillance and monitoring with timely interventions if patient outcomes are to be improved. We present here a quality improvement model for optimizing care of the diabetic dialysis patient that relies on a dedicated practitioner who can evaluate and intervene on the multiple variables within and beyond the dialysis clinic that impact the patient’s health. We present three detailed clinical care pathways that the dedicated clinician can follow. We believe that patient outcomes can be improved with this approach that provides customized problem-focused care, collaborates with the dialysis-provider team, and extends and directs diabetic self-care, home-care, and specialized clinical care in the challenging areas of cardiac and peripheral vascular disease, glycemic control, lipid control, infection prevention, and BP management. [ABSTRACT FROM AUTHOR]

Summary: As kidney function declines, chronic kidney disease (CKD) becomes an increasingly systemic disorder. Most patients with CKD eventually develop subclinical or clinical abnormalities in bone and mineral metabolism. Recent observational and basic scientific studies have led to a new emphasis on the changes in phosphorus and calcium metabolism, parathyroid hormone, and vitamin D that lead to this complex systemic bone/mineral disorder (CKD/BMD). At the center of the disorder are relationships among all 4 factors that conspire to create a perfect storm, leading to secondary hyperparathyroidism (SHPT). Some key current issues that are reviewed here are as follows: (1) factors promoting SHPT, (2) the role of fibroblast growth factor-23 in CKD/BMD, (3) molecular mechanisms of SHPT, (4) mechanisms of vascular calcification, and (5) medical management of the disorder, including calcimimetics. Current therapies directed at correcting the primary abnormalities (ie, improve conditions to an imperfect storm) and minimizing the consequences of CKD/BMD are discussed. [ABSTRACT FROM AUTHOR]

Background: Taste bud cells transmit information regarding the contents of food from taste receptors embedded in apical microvilli to gustatory nerve fibers innervating basolateral membranes. In particular, taste cells depolarize, activate voltage-gated sodium channels, and fire action potentials in response to tastants. Initial cell depolarization is attributable to sodium influx through TRPM5 in sweet, bitter, and umami cells and an undetermined cation influx through an ion channel in sour cells expressing PKD2L1, a candidate sour taste receptor. The molecular identity of the voltage-gated sodium channels that sense depolarizing signals and subsequently initiate action potentials coding taste information to gustatory nerve fibers is unknown. Results: We describe the molecular and histological expression profiles of cation channels involved in electrical signal transmission from apical to basolateral membrane domains. TRPM5 was positioned immediately beneath tight junctions to receive calcium signals originating from sweet, bitter, and umami receptor activation, while PKD2L1 was positioned at the taste pore. Using mouse taste bud and lingual epithelial cells collected by laser capture microdissection, SCN2A, SCN3A, and SCN9A voltage-gated sodium channel transcripts were expressed in taste tissue. SCN2A, SCN3A, and SCN9A were expressed beneath tight junctions in subsets of taste cells. SCN3A and SCN9A were expressed in TRPM5 cells, while SCN2A was expressed in TRPM5 and PKD2L1 cells. HCN4, a gene previously implicated in sour taste, was expressed in PKD2L1 cells and localized to cell processes beneath the taste pore. Conclusion: SCN2A, SCN3A and SCN9A voltage-gated sodium channels are positioned to sense initial depolarizing signals stemming from taste receptor activation and initiate taste cell action potentials. SCN2A, SCN3A and SCN9A gene products likely account for the tetrodotoxin-sensitive sodium currents in taste receptor cells. [ABSTRACT FROM AUTHOR]

Preeclampsia is a serious complication during pregnancy that includes potentially life-threatening risks to the mother and fetus. It may be challenging to distinguish this from other causes of rapidly escalating hypertension, especially in women with end-stage renal disease, because current diagnostic criteria for preeclampsia cannot be easily applied. We report a woman undergoing hemodialysis who was considered to be preeclamptic when her blood pressure suddenly increased during her 29th week of gestation. At that time, she underwent emergent cesarean section. The presence of a normal-sized placenta with no histological evidence of preeclampsia and retrospective analyses of maternal antiangiogenic biomarkers (soluble fms-like tyrosine kinase-1 and soluble endoglin) that were within normal levels for pregnancy suggest an alternative diagnosis. There is growing evidence that circulating levels of these proteins cause the preeclamptic phenotypes and also are sensitive and specific predictors and markers of this disease, suggesting that measurements of soluble fms-like tyrosine kinase-1 and soluble endoglin be considered in such difficult diagnostic dilemmas as the cause of hypertension in pregnant dialysis patients. Additional studies in this particular group of patients are required. [ABSTRACT FROM AUTHOR]