Renal Hyperfiltration and the Development of Microalbuminuria in Type 1 Diabetes

OBJECTIVE

The purpose of this study was to examine prospectively whether renal hyperfiltration is associated with the development of microalbuminuria in patients with type 1 diabetes, after taking into account known risk factors.

RESEARCH DESIGN AND METHODS

The study group comprised 426 participants with normoalbuminuria from the First Joslin Kidney Study, followed for 15 years. Glomerular filtration rate was estimated by serum cystatin C, and hyperfiltration was defined as exceeding the 97.5th percentile of the sex-specific distribution of a similarly aged, nondiabetic population (134 and 149 ml/min per 1.73 m² for men and women, respectively). The outcome was time to microalbuminuria development (multiple albumin excretion rate >30 μg/min). Hazard ratios (HRs) for microalbuminuria were calculated at 5, 10, and 15 years.

RESULTS

Renal hyperfiltration was present in 24% of the study group and did not increase the risk of developing microalbuminuria. The unadjusted HR for microalbuminuria comparing those with and without hyperfiltration at baseline was 0.8 (95% CI 0.4–1.7) during the first 5 years, 1.0 (0.6–1.7) during the first 10 years, and 0.8 (0.5–1.4) during 15 years of follow-up. The model adjusted for baseline known risk factors including A1C, age at diagnosis of diabetes, diabetes duration, and cigarette smoking resulted in similar HRs. In addition, incorporating changes in hyperfiltration status during follow-up had minimal impact on the HRs for microalbuminuria.

CONCLUSIONS

Renal hyperfiltration does not have an impact on the development of microalbuminuria in type 1 diabetes during 5, 10, or 15 years of follow-up.The glomerular filtration rate (GFR), the volume of water filtered out of the plasma per unit of time, is indicative of overall kidney function. However, measuring GFR with the gold standard technique is an intensive process and difficult for both the operator and the participant. Thus, it has not been practical to determine GFR in large epidemiological studies. Instead, serum creatinine has been widely used to estimate low levels of GFR when loss of kidney function has already occurred. However, serum creatinine is not sensitive enough to detect changes when renal function is normal or abnormally elevated (1). A laboratory test to estimate GFR based on serum cystatin C levels has been developed recently. Cystatin C assays are easy to perform and have been shown to yield accurate estimates even in the normal or elevated ranges of filtration (2,3). This development has created a new opportunity for studying early diabetic renal function abnormalities in large epidemiological studies.Hyperfiltration has been suggested as a risk factor for the development of microalbuminuria (4). The increase in pressure and flow may lead to functional and structural changes in the kidney (5,6). In several small studies, hyperfiltration was associated with the development of microalbuminuria in type 1 diabetes, but results have been inconsistent. Some studies were conducted in children beginning at diagnosis or early in the course of diabetes, and usually a few events of microalbuminuria were observed (7–11). Yip et al. (12) found no association between hyperfiltration and microalbuminuria in a 10-year prospective case control study of 25 adult pairs who had diabetes duration between 1 and 19 years. None of these studies adequately addressed confounders. Little subsequent research in large cohorts has been conducted on the role of hyperfiltration, primarily due to difficulties in determining GFR.Scott et al. (13) studied microalbuminuria onset in the First Joslin Study on the Natural History of Microalbuminuria (First Joslin Kidney Study) during the first 4 years of follow-up (13). They found that younger age at diabetes diagnosis, longer diabetes duration, poorer glycemic control, and cigarette smoking were associated with the development of microalbuminuria. Serum cystatin C measurements (to estimate GFR) were not available at the time of that work. The current project builds upon this prior study by examining whether hyperfiltration, as measured by cystatin C, is associated with the development of microalbuminuria during 15 years of follow-up, after taking into account known risk factors.     

Role of National Immunization Technical Advisory Group on improvement of immunization programmes in the Islamic Republic of Iran

The National Immunization Technical Advisory Group (NITAG) was established in Iran in 1982 and has made many important technical recommendations (e.g., regarding polio eradication, introduction of new vaccines, organizing special studies) that have contributed to a dramatic decline in vaccine preventable disease burden. The NITAG consists of experts from the Ministry of Health and Medical Education (MOHME), vaccine manufacturers, and medical universities with national Expanded Program of Immunization (EPI) staff serving as the secretariat. It is not completely independent from MOHME or EPI. It meets on a quarterly basis, and publishes national guidelines and immunization schedules that are updated regularly. Although primarily an advisory body, representation from MOHME members, including the EPI manager, ensures almost universal implementation of NITAG recommendations.     

HER2/neu expression in head and neck squamous cell carcinoma patients is not significantly elevated

Background: HER2/neu, a member of EGFR family, is over expressed in some tumors .The purpose of thisstudy was to determine the salivary level and tissue expression of HER2/neu in patients with head and necksquamous cell carcinoma (HNSCC) and any correlation with clinicopathologic parameters. Methods: An enzymelinkedimmunosorbent assay (ELISA) was used to evaluate the salivary level and immunohistochemistry (IHC) toassess tissue expression of HER2/neu in 28 patients with HNSCC and 25 healthy controls. Results: The salivarylevels of HER2/neu in HNSCC patients was not significantly higher than in the healthy controls (p>0.005). Therewas no apparent correlation in salivary HER2/neu level with clinicopathological features such as age, sex, grade,tumor size and nodal status. All HNSCC specimens were positive (membranous or/and cytoplasmic) for HER2/neu, except one sample. Only one HNSCC specimen was stained in cytoplasm purely. All control specimens weremembranous and cytoplasmic positive for HER2/neu. There was a significant difference between cytoplasmicstaining in case and control groups (p-value<0.05). Conclusion: In our cases, no overexpression of HER2/neuwas observed. Thus, our findings suggested that the use of Her-2 as a salivary marker of HNSCC cannot berecommended.     

Renoportal anastomosis in liver transplantation and its impact on patient outcomes: a systematic literature review

Portal vein thrombosis (PVT) is commonly encountered during liver transplantation (LT). Depending on the grade of thrombosis, varied management strategies are indicated. The aims of this study are to clarify the contemporary role of renoportal anastomosis (RPA) in patients with splanchnic vein thrombosis (SVT) undergoing LT and to systematically analyze all reported cases of RPA. A systematic literature search was performed according to Preferred Reporting Items for Systematic Reviews and Meta‐ Analyses statement guidelines. The study was limited to studies reported in English between January 1997 and May 2017. Only retrospective single center studies were included in the analysis. A total of 66 patients with SVT were reported to have undergone RPA during LT. Transient renal dysfunction was reported in 12 patients (18.1%), variceal hemorrhage in 2 patients (3%), early portal vein (PV) re‐thrombosis in 2 patients (3%), chronic renal dysfunction in 2 patients (3%), and late PV re‐thrombosis in 1 patient (1.5%). The overall patient and graft survival were each 80%. This analysis illustrates the decades‐long evolution of a technique practiced across the field of transplantation. Postoperative complications and graft survival appear to be encouraging, even in the setting of SVT.     

Involvement of NMDA receptors in morphine state-dependent learning in mice

In the present study, the effects of intracerebroventricular (i.c.v.) injection of NMDA receptor agonist and antagonist on impairment of memory formation and the state-dependent learning by morphine have been investigated in mice. Pretraining administration of morphine (5 mg/kg; s.c.) decreased the learning of one-trial passive avoidance task. Pretest administration of morphine (5 mg/kg) induced state-dependent learning acquired under pretraining morphine influence. Pretest administration of NMDA receptor agonist, L-glutamate (0.00001 and 0.0001 and 0.001 microg/mouse, i.c.v.) following pretraining saline treatment did not affect retention. Amnesia induced by pretraining morphine was significantly reversed by pretest administration of L-glutamate (0.0001 and 0.001 microg/mouse, i.c.v.). Pretest administration of noncompetitive NMDA receptor antagonist, MK-801 (0.5, 1, and 2 microg/mouse, i.c.v.) significantly impaired memory formation. Amnesia induced by pretraining morphine was increased by pretest administration of MK-801 (2 microg/mouse, i.c.v.). Pretest coadministration of L-glutamate (0.0001 and 0.001 microg/mouse, i.c.v.) or MK-801 (0.5, 1, and 2 microg/mouse, i.c.v.) with morphine (5 mg/kg, s.c.) increased and decreased morphine state-dependent learning, respectively. The results suggest that NMDA receptors are involved in morphine state-dependent learning in mice.     

Antinociceptive effect of spinally administered cannabinergic and 2-adrenoceptor drugs on the formalin test in rat: possible interactions

The current experiments were designed to study the antinociceptive effects of intrathecal (i.t.) administration of cannabinoid CB1 receptor and 2-adrenoceptor drugs in the nociceptive processing and also their receptor interactions. Different doses of a cannabinoid receptor agonist, CP 55,940, and an 2-adrenoceptor agonist, clonidine induced a dose-dependent antinociception in both phases of the formalin test.CP 55,940-induced antinociception was reduced by pretreatment of a selective cannabinoid CB1 receptor antagonist, SR 141716A, but not by pretreatment with an 2-adrenoceptor antagonist, yohimbine in both phases of the test. However, yohimbine and SR 141716A attenuated the antinociception induced by clonidine in the early phase but not in the late phase of the test. While SR 141716A by itself did not influence pain behaviour, the reversal effect of clonidine by SR 141716A indicate that clonidine stimulate the release of endocannabinoid(s).In conclusion, our findings may suggest that: (1) spinal cannabinoid and 2-adrenoceptor systems are able to induce antinociception in both phases of formalin test, and (2) the cannabinoid system may be involved in the antinociception induced by adrenoceptors in the early phase.