J. Clin. Med.2015, 4(7), 1518-1535; doi:10.3390/jcm4071518 - published 22 July 2015 Show/Hide Abstract
Abstract: Background: In order to reduce the cardiovascular risk, morbidity and mortality of peritoneal dialysis (PD), a minimal level of small-solute clearances as well as a sodium and water balance are needed. The peritoneal dialysis solutions used in combination have reduced the complications and allow for a long-time function of the peritoneal membrane, and the preservation of residual renal function (RRF) in patients on peritoneal dialysis (PD) is crucial for the maintenance of life quality and long-term survival. This retrospective cohort study reviews our experience in automatic peritoneal dialysis (APD) patients, with end-stage renal disease (ESRD) secondary to diabetic nephropathy (DN) in comparison to non-diabetic nephropathy (NDN), using different PD solutions in combination. Design: Fifty-two patients, 29 diabetic and 23 non-diabetic, were included. The follow-up period was 24 months, thus serving as their own control. Results: The fraction of renal urea clearance (Kt) relative to distribution volume (V) (or total body water) (Kt/V), or creatinine clearance relative to the total Kt/V or creatinine clearance (CrCl) decreases according to loss of RRF. The loss of the slope of RRF is more pronounced in DN than in NDN patients, especially at baseline time interval to 12 months (loss of 0.29 mL/month vs. 0.13 mL/month, respectively), and is attenuated in the range from 12 to 24 months (loss of 0.13 mL/month vs. 0.09 mL/month, respectively). Diabetic patients also experienced a greater decrease in urine output compared to non-diabetic, starting from a higher baseline urine output. The net water balance was adequate in both groups during the follow up period. Regarding the balance sodium, no inter-group differences in sodium excretion over follow up period was observed. In addition, the removal of sodium in the urine output decreases with loss of renal function. The average concentration of glucose increase in the cycler in both groups (DN: baseline 1.44 ± 0.22, 12 months 1.63 ± 0.39, 24 months 1.73 ± 0.47; NDN: baseline 1.59 ± 0.40, 12 months 1.76 ± 0.47, 24 months 1.80 ± 0.46), in order to maintain the net water balance. The daytime dwell contribution, the fraction of day and the renal fraction of studies parameters provide sustained benefit in the follow-up time, above 30%. Conclusions: The wet day and residual renal function are determinants in the achievement of the objective dose of dialysis, as well as in the water and sodium balance. The cause of chronic kidney disease (CKD) does not seem to influence the cleansing effectiveness of the technique.
J. Clin. Med.2015, 4(7), 1498-1517; doi:10.3390/jcm4071498 - published 17 July 2015 Show/Hide Abstract
Abstract: Microalbuminuria provides the earliest clinical marker of diabetic nephropathy among patients with Type 1 diabetes, yet it lacks sensitivity and specificity for early histological manifestations of disease. In recent years microRNAs have emerged as potential mediators in the pathogenesis of diabetes complications, suggesting a possible role in the diagnosis of early stage disease. We used quantiative polymerase chain reaction (qPCR) to evaluate the expression profile of 723 unique microRNAs in the normoalbuminuric urine of patients who did not develop nephropathy (n = 10) relative to patients who subsequently developed microalbuminuria (n = 17). Eighteen microRNAs were strongly associated with the subsequent development of microalbuminuria, while 15 microRNAs exhibited gender-related differences in expression. The predicted targets of these microRNAs map to biological pathways known to be involved in the pathogenesis and progression of diabetic renal disease. A microRNA signature (miR-105-3p, miR-1972, miR-28-3p, miR-30b-3p, miR-363-3p, miR-424-5p, miR-486-5p, miR-495, miR-548o-3p and for women miR-192-5p, miR-720) achieved high internal validity (cross-validated misclassification rate of 11.1%) for the future development of microalbuminuria in this dataset. Weighting microRNA measurements by their number of kidney-relevant targets improved the prognostic performance of the miRNA signature (cross-validated misclassification rate of 7.4%). Future studies are needed to corroborate these early observations in larger cohorts.
J. Clin. Med.2015, 4(7), 1480-1497; doi:10.3390/jcm4071480 - published 14 July 2015 Show/Hide Abstract
Abstract: While hypopituitarism after traumatic brain injury (TBI) was previously considered rare, it is now thought to be a major cause of treatable morbidity among TBI survivors. Consequently, recommendations for assessment of pituitary function and replacement in TBI were recently introduced. Given the high incidence of TBI with more than 100 pr. 100,000 inhabitants, TBI would be by far the most common cause of hypopituitarism if the recently reported prevalence rates hold true. The disproportion between this proposed incidence and the occasional cases of post-TBI hypopituitarism in clinical practice justifies reflection as to whether hypopituitarism has been unrecognized in TBI patients or whether diagnostic testing designed for high risk populations such as patients with obvious pituitary pathology has overestimated the true risk and thereby the disease burden of hypopituitarism in TBI. The findings on mainly isolated deficiencies in TBI patients, and particularly isolated growth hormone (GH) deficiency, raise the question of the potential impact of methodological confounding, determined by variable test-retest reproducibility, appropriateness of cut-off values, importance of BMI stratified cut-offs, assay heterogeneity, pre-test probability of hypopituitarism and lack of proper individual laboratory controls as reference population. In this review, current recommendations are discussed in light of recent available evidence.
J. Clin. Med.2015, 4(7), 1463-1479; doi:10.3390/jcm4071463 - published 13 July 2015 Show/Hide Abstract
Abstract: Pituitary dysfunction following traumatic brain injury (TBI) is significant and rarely considered by clinicians. This topic has received much more attention in the last decade. The incidence of post TBI anterior pituitary dysfunction is around 30% acutely, and declines to around 20% by one year. Growth hormone and gonadotrophic hormones are the most common deficiencies seen after traumatic brain injury, but also the most likely to spontaneously recover. The majority of deficiencies present within the first year, but extreme delayed presentation has been reported. Information on posterior pituitary dysfunction is less reliable ranging from 3%–40% incidence but prospective data suggests a rate around 5%. The mechanism, risk factors, natural history, and long-term effect of treatment are poorly defined in the literature and limited by a lack of standardization. Post TBI pituitary dysfunction is an entity to recognize with significant clinical relevance. Secondary hypoadrenalism, hypothyroidism and central diabetes insipidus should be treated acutely while deficiencies in growth and gonadotrophic hormones should be initially observed.
J. Clin. Med.2015, 4(7), 1448-1462; doi:10.3390/jcm4071448 - published 13 July 2015 Show/Hide Abstract
Abstract: Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in many age groups. Neuroendocrine dysfunction has been recognized as a consequence of TBI and consists of both anterior and posterior pituitary insufficiency; water and electrolyte abnormalities (diabetes insipidus (DI) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH)) are amongst the most challenging sequelae. The acute head trauma can lead (directly or indirectly) to dysfunction of the hypothalamic neurons secreting antidiuretic hormone (ADH) or of the posterior pituitary gland causing post-traumatic DI (PTDI). PTDI is usually diagnosed in the first days after the trauma presenting with hypotonic polyuria. Frequently, the poor general status of most patients prevents adequate fluid intake to compensate the losses and severe dehydration and hypernatremia occur. Management consists of careful monitoring of fluid balance and hormonal replacement. PTDI is associated with high mortality, particularly when presenting very early following the injury. In many surviving patients, the PTDI is transient, lasting a few days to a few weeks and in a minority of cases, it is permanent requiring management similar to that offered to patients with non-traumatic central DI.
J. Clin. Med.2015, 4(7), 1428-1447; doi:10.3390/jcm4071428 - published 9 July 2015 Show/Hide Abstract
Abstract: Although there are many etiologies for diabetic nephropathy (DN), one common characteristic of all cases involves mitochondrial oxidative stress and consequent bioenergetic dysfunction. As the predominant low-molecular-weight, intramitochondrial thiol reductant, the mitochondrial glutathione (mtGSH) pool plays important roles in how this organelle adapts to the chronic hyperglycemia and redox imbalances associated with DN. This review will summarize information about the processes by which this important GSH pool is regulated and how manipulation of these processes can affect mitochondrial and cellular function in the renal proximal tubule. Mitochondria in renal proximal tubular (PT) cells do not appear to synthesize GSH de novo but obtain it by transport from the cytoplasm. Two inner membrane organic anion carriers, the dicarboxylate carrier (DIC; Slc25a10) and 2-oxoglutarate carrier (OGC; Slc25a11) are responsible for this transport. Genetic modulation of DIC or OGC expression in vitro in PT cells from diabetic rats can alter mitochondrial function and susceptibility of renal PT cells to oxidants, with overexpression leading to reversion of bioenergetic conditions to a non-diabetic state and protection of cells from injury. These findings support the mtGSH carriers as potential therapeutic targets to correct the underlying metabolic disturbance in DN.