L’estimation du débit de filtration glomérulaire en 2012 : quelle valeur ajoutée pour la nouvelle équation CKD-EPI ?

Measuring or estimating glomerular filtration rate (GFR) is still considered as the best way to apprehend global renal function. In 2009, the new Chronic Kidney Disease Epidemiology (CKD-EPI) equation has been proposed as a better estimator of GFR than the Modification of Diet in Renal Disease (MDRD) study equation. This new equation is supposed to underestimate GFR to a lesser degree in higher GFR levels. In this review, we will present and deeply discuss the performances of this equation. Based on articles published between 2009 and 2012, this review will underline advantages, notably the better knowledge of chronic kidney disease prevalence, but also limitations of this new equation, especially in some specific populations. We eventually insist on the fact that all these equations are estimations and nephrologists should remain cautious in their interpretation.     

An automated procedure for the assessment of white matter hyperintensities by multispectral (T1, T2, PD) MRI and an evaluation of its between-centre reproducibility based on two large community databases

Introduction An automated procedure for the detection, quantification, localization and statistical mapping of white matter hyperintensities (WMH) on T2-weighted magnetic resonance (MR) images is presented and validated based on the results of a between-centre reproducibility study. Methods The first step is the identification of white matter (WM) tissue using a multispectral (T1, T2, PD) segmentation. In a second step, WMH are identified within the WM tissue by segmenting T2 images, isolating two different classes of WMH voxels – low- and high-contrast WMH voxels, respectively. The reliability of the whole procedure was assessed by applying it to the analysis of two large MR imaging databases (n = 650 and n= 710, respectively) of healthy elderly subjects matched for demographic characteristics. Results Average overall WMH load and spatial distribution were found to be similar in the two samples, (1.81 and 1.79% of the WM volume, respectively). White matter hyperintensity load was found to be significantly associated with both age and high blood pressure, with similar effects in both samples. With specific reference to the 650 subject cohort, we also found that WMH load provided by this automated procedure was significantly associated with visual grading of the severity of WMH, as assessed by a trained neurologist. Conclusion The results show that this method is sensitive, well correlated with semi-quantitative visual rating and highly reproducible.     

Living-related liver transplantation and vena cava reconstruction after total hepatectomy including the vena cava for hepatoblastoma.

BACKGROUND: In most cases of total hepatectomy (TH) required for hepatoblastoma (HB), the retrohepatic inferior vena cava (IVC) has to be removed with the native liver for complete tumor excision. Because the liver graft procured by living donation has no IVC, a reconstruction of the recipient IVC is needed. We report our experience with living-related liver transplantation (LRLT) and IVC replacement in such cases. METHODS: Between May 1998 and December 1999, four children underwent TH, including IVC and LRLT with IVC replacement for otherwise irresectable HB after chemotherapy (SIOPEL 2 and 3 protocols). IVC reconstruction used an allogenic iliac vein procured from a cadaveric donor (bank graft) in two cases and an internal jugular vein procured from the donor parent in two cases. Median age and weight at surgery were 17 months (range 10-60) and 9.6 kg (range 8.3-17.9). RESULTS: In the living donors, there were two complications of the procurement: one intra-abdominal biliary collection and one subcutaneous abscess. In all four children, complete excision of the tumor could be achieved without any intra-operative complication. One patient died 5 months after LRLT due to lung metastases. Three patients were alive and well with no evidence of tumor recurrence 13-24 months after surgery. Reconstructed IVC was patent in two patients, and asymptomatic thrombosis occurred 2 years after operation in one patient. CONCLUSION: Total hepatectomy including the retrohepatic IVC is not a technical obstacle to LRLT. Therefore, scheduled surgery, at the best time after chemotherapy, can be considered in all patients with otherwise irresectable HBs.     

Long-term kidney graft survival across a positive historic but negative current sensitized cross-match

BACKGROUND: The sensitive cross-match (XM) techniques that have been introduced for clinical transplantation can detect anti-donor immune reactivity despite a negative standard National Institute of Health (NIH) cross-match. One of them uses anti-kappa human light chain globulins (AHG). But there is some discussion about the clinical consequences of a positive AHG-XM in the historical sera that became negative in the sera collected just before the transplantation (pretransplant sera). This study was intended to assess the risk of kidney graft failure associated with a positive historic but negative pretransplant AHG-XM in allosensitized patients having a negative historic NIH-XM. METHODS: This retrospective study includes 90 consecutive renal transplants in immunized patients performed at one center between 1985 and 1991. All of the patients had negative historical and pretransplant standard NIH lymphocytotoxic cross-matches and received the same immunosuppressive regimen. The AHG-XMs were done retrospectively using peak historic and sera collected on the day of the transplantation. RESULTS: The AHG cross-match (AHG-XM) was positive in 17 patients, although the standard NIH cross-match was negative. Fourteen of them had a positive historical but negative pretransplant AHG-XM. The actuarial graft survival in this group of 14 patients was 100% at 1 year and 78% at 9 years compared with 90 and 67%, respectively, in patients with negative historical AHG-XM. In addition, the number of rejection episodes per patient as well as renal function at 1, 2, and 5 years were similar in the two groups. IgG anti-donor HLA class I accounted for the XM positivity in 12 of the 14 patients; most rapidly lost all antibody reactivity by NIH technique in an average time of 8 months before the transplantation. In conclusion, this study suggests that transplant patients having a negative historic NIH-XM but a positive historic AHG-XM may not be at high risk of graft failure especially if there is a well-documented sera history showing a marked decrease in PRA level before transplantation and a negative pretransplant AHG-XM.     

Treatment of reverse oblique and transverse intertrochanteric fractures with use of an intramedullary nail or a 95 degrees screw-plate: a prospective, randomized study

BACKGROUND: Intertrochanteric fractures are composed of different anatomic patterns that vary in their degree of stability following open reduction and internal fixation. A particularly unstable group is classified as AO/OTA 31-A3, with the fracture pattern described as reverse oblique or transverse. The purpose of this study was to compare the results of intramedullary fixation with those of plate fixation for these intertrochanteric fractures in elderly patients. METHODS: Thirty-nine elderly patients with AO/OTA 31-A3 intertrochanteric fractures of the femur were randomized into two treatment groups and were followed for a minimum of one year. The nineteen patients in Group I were treated with a 95 fixed-angle screw-plate (Dynamic Condylar Screw), and the twenty patients in Group II were treated with an intramedullary nail (Proximal Femoral Nail). The treatment groups were comparable with regard to all demographic and injury variables. RESULTS: Patients treated with an intramedullary nail had shorter operative times, fewer blood transfusions, and shorter hospital stays compared with those treated with a 95 screw-plate. Implant failure and/or nonunion was noted in seven of the nineteen patients who had been treated with the 95 screw-plate. Only one of the twenty fractures that had been treated with an intramedullary nail did not heal. CONCLUSION: The results of our study support the use of an intramedullary nail rather than a 95 screw-plate for the fixation of reverse oblique and transverse intertrochanteric fractures in elderly patients.     

Enterolith ileus due to jejunal diverticulosis

Jejunal diverticulosis is a rare malformation that is often asymptomatic. Complications might be similar to those occurring in large-bowel diverticula but also include a much more particular event: intestinal obstruction due to migration and impaction of enterolith formed inside diverticula. This is a very uncommon entity; diagnosis and management are thus often delayed. Mostly surgical exploration is necessary because obstruction symptoms are unresponsive to medical treatment. The authors report a new case of enterolith ileus in a 74-year-old man, due to jejunal diverticulosis, and its successful surgical management in emergency. Only 39 similar cases have ever been reported in the literature.     

Ventromedial Hypothalamic Nitric Oxide Production Is Necessary for Hypoglycemia Detection and Counterregulation

OBJECTIVE

The response of ventromedial hypothalamic (VMH) glucose-inhibited neurons to decreased glucose is impaired under conditions where the counterregulatory response (CRR) to hypoglycemia is impaired (e.g., recurrent hypoglycemia). This suggests a role for glucose-inhibited neurons in the CRR. We recently showed that decreased glucose increases nitric oxide (NO) production in cultured VMH glucose-inhibited neurons. These in vitro data led us to hypothesize that NO release from VMH glucose-inhibited neurons is critical for the CRR.

RESEARCH DESIGN AND METHODS

The CRR was evaluated in rats and mice in response to acute insulin-induced hypoglycemia and hypoglycemic clamps after modulation of brain NO signaling. The glucose sensitivity of ventromedial nucleus glucose-inhibited neurons was also assessed.

RESULTS

Hypoglycemia increased hypothalamic constitutive NO synthase (NOS) activity and neuronal NOS (nNOS) but not endothelial NOS (eNOS) phosphorylation in rats. Intracerebroventricular and VMH injection of the nonselective NOS inhibitor N^G-monomethyl-l-arginine (l-NMMA) slowed the recovery to euglycemia after hypoglycemia. VMH l-NMMA injection also increased the glucose infusion rate (GIR) and decreased epinephrine secretion during hyperinsulinemic/hypoglycemic clamp in rats. The GIR required to maintain the hypoglycemic plateau was higher in nNOS knockout than wild-type or eNOS knockout mice. Finally, VMH glucose-inhibited neurons were virtually absent in nNOS knockout mice.

CONCLUSIONS

We conclude that VMH NO production is necessary for glucose sensing in glucose-inhibited neurons and full generation of the CRR to hypoglycemia. These data suggest that potentiating NO signaling may improve the defective CRR resulting from recurrent hypoglycemia in patients using intensive insulin therapy.Intensive insulin therapy significantly reduces the onset and progression of hyperglycemia-related complications in patients with type 1 and advanced type 2 diabetes. However, intensive insulin therapy also causes a clinically adverse effect: hypoglycemia (1). Powerful neuroendocrine and autonomic counterregulatory mechanisms protect the brain from hypoglycemia (2,3). These protective mechanisms, known as the counterregulatory response (CRR) to hypoglycemia, involve the release of hormones (e.g., glucagon, epinephrine) that restore euglycemia by stimulating hepatic glucose production and inhibiting peripheral glucose uptake (3). Although the physiology of the CRR is well understood, the underlying cellular mechanisms by which the brain senses hypoglycemia and initiates the CRR remain elusive.During hypoglycemia, central and peripheral glucose sensors detect declining glucose levels (4). In the brain, the ventromedial hypothalamus, which includes the arcuate nucleus and the ventromedial nucleus (VMN), is important in the initiation of the CRR (5–7). This region contains specialized glucose-sensing neurons (GSNs). Ventromedial hypothalamic (VMH) GSN electrical activity is regulated by physiologically relevant changes in extracellular glucose levels (8–11). Glucose-excited neurons decrease, whereas glucose-inhibited neurons increase, their input resistance, membrane potential, and action potential frequency when extracellular glucose is reduced (10). Many studies suggest that VMH glucose-inhibited neurons play a critical role in the control of the CRR (4). For example, the response of VMH glucose-inhibited neurons to decreased glucose is impaired under conditions where the CRR is impaired (e.g., recurrent hypoglycemia) (12,13).Nitric oxide (NO) is a gaseous messenger produced by NO synthase (NOS). Two classes of NOS have been identified in the brain: the inducible NOS (iNOS) and the constitutive NOS, which includes the neuronal NOS (nNOS) and endothelial NOS (eNOS) isoforms (14). Hypothalamic NO is involved in the regulation of food intake and glucose homeostasis (15–18). In support of this, we have recently shown that VMH glucose-inhibited neurons produce NO via nNOS in response to decreased extracellular glucose levels (19,20). Therefore, in this study, we test the hypothesis that NO production by VMH glucose-inhibited neurons is necessary for the CRR to hypoglycemia. We tested this hypothesis using a combination of in vivo and in vitro techniques in wild-type rats and mice as well as in transgenic nNOS and eNOS knockout mice.     

Novel Lamp-2 gene mutation and successful treatment with heart transplantation in a large family with Danon disease

Lysosome-associated membrane protein-2 deficiency (LAMP-2 deficiency), or Danon disease, is a rare X-linked lysosomal disease characterized by cardiomyopathy, vacuolar myopathy, and mental retardation. Less than 20 families with mutations of the Lamp-2 gene have been reported. We describe a family from Sardinia with eight affected patients (4 females and 4 males) and a novel mutation in exon 2 of the Lamp-2 gene (c.102_103delAG). Females developed isolated cardiomyopathy in adulthood, whereas males presented with cardiomyopathy, myopathy, and mental retardation before the age of 20 years. Cardiomyopathy was lethal in three females in their 40s and in three males before the age 20 years. One patient was successfully treated by heart transplantation with more than 5-year follow-up. This study demonstrates that Danon disease is a frequently fatal condition that is potentially treatable with heart transplantation.