Long term end-stage renal disease and death following acute renal replacement therapy in the ICU.

INTRODUCTION: In ICU the need for acute renal replacement therapy (RRT) associates with high mortality and risk of end-stage renal disease (ESRD), but there are limited long-term data. We investigated these outcomes and their risk factors. METHODS: Retrospective analysis of all adult patients admitted to a general, university hospital ICU 2005-2012, excluding chronic dialysis patients. ESRD was defined as need of RRT > 90 days or kidney transplant. RESULTS: Of 5766 patients included, 1004 (16%) received acute RRT; their 30-day mortality was 42% vs. 16% for those not requiring acute RRT (adjusted hazard ratio (HR) 1.13 (0.96-1.32)). The 90-day mortality was 55% for patients receiving acute RRT vs. 22% for those who did not (adjusted HR 1.32 (1.15-1.51)) and 1-year mortality was 63% vs. 30%, respectively, (adjusted HR 1.31 (1.16-1.48)). The 7-year risk of ESRD for ICU patients surviving 90 days was 10% for patients who received acute RRT vs. 0.5% among those who did not (adjusted HR 5.9 (2.9-12.4)). Independent risk factors for ESRD included pre-existing kidney disease, pre-existing peripheral vascular disease and use of acute RRT in ICU. CONCLUSIONS: The need of acute RRT was associated with markedly increased long term risk of death and ESRD; in contrast its use was not associated with 30-day mortality. In addition to acute RRT, decreased kidney function and peripheral vascular disease before ICU admission were risk factors for ESRD. It seems warranted offering medical follow-up to patients after acute RRT in ICU.

Is pancreatic polypeptide response to food ingestion a reliable index of vagal function in type 1 diabetes?

OBJECTIVE: The diagnosis of autonomic neuropathy in diabetic patients is based on cardiovascular reflex tests. Since cardiac function may be affected by arteriosclerosis and cardiomyopathy in type 1 diabetes mellitus, alternative tests reflecting vagal nerve function, in other organ systems, are needed. In this study the pancreatic polypeptide (PP) response to a mixed meal was evaluated in healthy subjects and in recently diagnosed type 1 diabetic patients. MATERIAL AND METHODS: The PP response was studied at different levels of the vagally mediated reflex arch by application of different stimuli: meal ingestion, i.v. edrophonium (a cholinesterase inhibitor) injection and arginine infusion. RESULTS: Meal ingestion (stimulation of cerebral/vagal level) resulted in a significant and similar PP response in the two groups; i.v. edrophonium injection (stimulating at the second neuron level) resulted in a smaller increase in PP concentrations in the type 1 diabetic patients as compared with the healthy subjects, whereas direct PP-cell stimulation by arginine infusion resulted in similar increments in PP concentrations in the two groups. Thus, in recently diagnosed type 1 diabetic patients with no known manifestations of diabetic neuropathy, the cholinergic second neuron function of the vagal arch to the pancreas is impaired, whereas intrinsic PP-cell function is unaffected. CONCLUSIONS: This abnormality in cholinergic second neuron function of the vagal reflex arch and the fact that three of the healthy subjects had no increase in PP concentrations at all during the meal test indicates that PP response to a mixed meal is unsuitable for the diagnosis of autonomic neuropathy in type 1 diabetes. The nature of the defect in the second neuron of the vagal innervation of the pancreas in type 1 diabetes remains to be elucidated.

Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients.

To elucidate the causes of the diminished incretin effect in type 2 diabetes mellitus we investigated the secretion of the incretin hormones, glucagon-like peptide-1 and glucose- dependent insulinotropic polypeptide and measured nonesterified fatty acids, and plasma concentrations of insulin, C peptide, pancreatic polypeptide, and glucose during a 4-h mixed meal test in 54 heterogeneous type 2 diabetic patients, 33 matched control subjects with normal glucose tolerance, and 15 unmatched subjects with impaired glucose tolerance. The glucagon-like peptide-1 response in terms of area under the curve from 0-240 min after the start of the meal was significantly decreased in the patients (2482 +/- 145 compared with 3101 +/- 198 pmol/liter.240 min; P = 0.024). In addition, the area under the curve for glucose-dependent insulinotropic polypeptide was slightly decreased. In a multiple regression analysis, a model with diabetes, body mass index, male sex, insulin area under the curve (negative influence), glucose-dependent insulinotropic polypeptide area under the curve (negative influence), and glucagon area under the curve (positive influence) explained 42% of the variability of the glucagon-like peptide-1 response. The impaired glucose tolerance subjects were hyperinsulinemic and generally showed the same abnormalities as the diabetic patients, but to a lesser degree. We conclude that the meal-related glucagon-like peptide-1 response in type 2 diabetes is decreased, which may contribute to the decreased incretin effect in type 2 diabetes.

Neuroendocrine responses to hypoglycaemia decrease within the first year after diagnosis of type 1 diabetes.

Neuroendocrine responses (adrenaline, noradrenaline and pancreatic polypeptide (PP)) to hypoglycaemia are often diminished in long-term diabetic patients, but the role of autonomic nervous system changes in these reductions is not yet fully clarified. In order to establish whether such changes in neuroendocrine responses occur early in the course of diabetes, we investigated the responses to insulin-induced hxypoglycaemia during the first year of type 1 diabetes. Autonomic and somatic nerve function tests were performed concomitantly. Six type 1 diabetes patients were studied 3 and 12 months after diagnosis of diabetes. Hypoglycaemia was induced by i.v. insulin infusion after an overnight normalization of blood glucose. Autonomic nerve function was evaluated by cardiovascular tests, and somatic nerve function by nerve conduction velocities A 50% reduction was found in adrenaline (p < 0.025) and noradrenaline (p < 0.05) responses to hypoglycaemia; PP, too, was significantly diminished at 12 months compared with 3 months after diagnosis of type 1 diabetes. Rate of glucose recovery did not differ at month 12 compared with month 3. Cardiovascular autonomic nerve function tests did not change and remained within the normal range throughout the study. Altered neuroendocrine responses to hypoglycaemia may occur early in the course of type 1 diabetes. These are unlikely to be due to structural changes (i.e. autonomic neuropathy), but rather to changes in central nervous system activity patterns, i.e. a higher threshold (i.e. a lower blood glucose level) for hypothalamic activation of the sympathoadrenal system.