Evaluation of a predictive model of end-stage kidney disease in a French-based cohort

Background

The risk of ESKD is highly heterogeneous among renal diseases, and risk scores were developed to account for multiple progression factors. Kidney failure risk equation (KFRE) is the most widely accepted, although external validation is scarce. The objective of this study was to evaluate the usefulness of this score in a French case–control cohort and test the pertinence of the proposed thresholds.

Methods

A retrospective case–control study comparing a group of patients starting renal replacement therapy (RRT) to a group of patients with CKD stages 3–5. Multivariate analysis to assess the predictors of ESKD risk. Discrimination of 4-, 6- and 8-variable scores using ROC curves and compared with eGFR alone and albumin/creatinine ratio (ACR) alone.

Results

314 patients with a ratio of 1 case for 1 control. In multivariate analysis, increasing age and higher eGFR were associated with a lower risk of ESKD (OR 0.62, 95% CI 0.48–0.79; and OR 0.72, 95% CI 0.59–0.86, respectively). The log-transformed ACR was associated with a higher risk of ESKD (OR 1.25 per log unit, 95% CI 1.02–1.55). The 4-variable score was significantly higher in the RRT group than in the CKD-ND group, and was more efficient than the eGFR (AUROC 0.66, 95% CI 0.60–0.72, p?=?0.018) and the log-transformed ACR (AUROC 0.63 95% CI 0.60–0.72, p?=?0.0087) to predict ESKD. The 6-variable score including BP metrics and diabetes was not more discriminant as the 4-variable score. The 8-variable score had similar performance compared with the 4-score (AUROC 8-variable score: 0.70, 95% CI 0.64–0.76, p?=?0.526). A 40% and 20% score thresholds were not superior to eGFR?<?15 and 20 mL/min/1.73 m², respectively. A 10% threshold was more specific than an eGFR?<?30 mL/min/1.73 m².

Conclusion

KFRE was highly discriminant between patients progressing to ESKD vs those non-progressing. The 4-variable score may help stratify renal risk and referral in the numerous patients with stage 3 CKD. Conversely, the proposed thresholds for creating vascular access or preemptive transplantation were not superior to eGFR alone.

     

Preliminary study of the deposition of aerosol in the maxillary sinuses using a plastinated model.

In spite of the widespread use of aerosols in respiratory diseases, very few studies have been performed in the field of ear, nose, and throat (ENT) disorders. The conditions for penetration of aerosols inside the sinus cavities are thus still not understood fully. The aim of this study was to investigate the penetration of aerosols inside maxillary sinuses in vitro, using plastinated models. Three plastinated specimens of the nose and sinuses were made from three different corpses. These specimens were validated by CT scans and were used to study deposition of aerosol in the maxillary sinuses. We performed scintigraphic images of the models in above, face, and profile views using a technetium (99mTc)-labelled solution to show aerosol deposition. We also counted the radioactivity deposited on gauze compresses placed inside the maxillary sinuses. In addition, we constructed a measuring unit with miniature humidity sensors placed inside the sinuses. We recorded the changes in relative humidity observed during nebulization. Results from these studies showed that scintigraphic images of the specimen, whatever the incidence of the views, were not accurate enough to differentiate the aerosol deposition in the maxillary sinuses from that in the nasal cavity. Using indirect counting on gauze compresses made possible the quantification of local aerosol deposition, and we found that aerosols entered into the sinuses. This confirmed that aerosols could reach the middle meatus, which is the main area for sinusitis disorders. The increased activity compared to background varied from 17 to 127%. The humidity sensors recorded changes in relative humidity during the nebulization. These humidity changes fitted a nonlinear model represented by the equation: y = b0 (1 - e(-b1t)), where b0 is the plateau and b1 is the speed to reach the plateau. These techniques may be useful in the future for in vitro characterization of aerosol penetration into the maxillary sinuses.     

In vivo tonic inhibition of spinal substance P (-like material) release by endogenous opioid(s) acting at delta receptors.

Although numerous data support the existence of a presynaptic inhibitory control by opioids of substance P-containing primary afferent fibres entering the dorsal horn of the spinal cord, the exact nature of the opioid receptor involved in this control is still a matter of debate. In the present study, the potential role of delta opioid receptors was investigated by looking for the possible effects of selective delta ligands on the in vivo release of substance P-like material from the whole spinal cord in halothane-anaesthetized rats. Perfusion of the intrathecal space allowed the collection of substance P-like material that was released at a constant rate of approximately 0.65 pg substance P equivalents/min for at least 135 min. The addition of Tyr-D-Thr-Gly-Phe-Leu-Thr (10 microM) or dermenkephalin (10 microM), two selective delta agonists, to the perfusing fluid produced a marked reduction (-50-65%) in substance P-like material outflow which could be prevented by the selective delta antagonist naltrindole (10 microM) but not by naloxone (10 microM), which acts preferentially on mu opioid receptors. Furthermore, naltrindole alone (or the association of this antagonist plus dermenkephalin) enhanced the outflow of substance P-like material (+ 170%) as expected from the blockade of a tonic inhibitory control due to the stimulation of delta receptors by endogenous opioids.(ABSTRACT TRUNCATED AT 250 WORDS)     

Abysmal prognosis of patients with type 2 diabetes entering dialysis.

INTRODUCTION: The importance of non-insulin-dependent diabetes mellitus (type II diabetes) as a leading cause of end-stage renal disease is now widely recognized. The purpose of this study was to assess life-prognosis and its predictors in a cohort of patients newly entering dialysis. MATERIAL AND METHODS: Eighty-four consecutive type II diabetes patients (40% of all patients) starting dialysis between 01/01/95 and 31/12/96 were studied retrospectively, focusing on clinical data at inception and life-prognosis after a mean follow-up of 211 days. Patients were divided into three groups, according to onset of renal failure: acute 11% (9/84), chronic 61% (51/84) and acutely aggravated chronic renal failure 28% (25/84). RESULTS: Patients (mean age 67 years) had long-standing diabetes (mean duration approximately 15 years), heavy proteinuria (approximately 3 g/24h) and diabetic retinopathy (67%). The average creatinine clearance (Cockcroft's formula) was 13 ml/min. Cardiovascular diseases were highly prevalent at the start of dialysis: history of myocardial infarction (26%), angina (36%) and acute left ventricular dysfunction (67%). More than 80% of the patients underwent the first session dialysis under emergency conditions, a situation in part related to late referral to the nephrology division (63% for chronic patients). A great majority of the patients were overhydrated when starting dialysis, as evidenced by the average weight loss of 6 kg, during the first month of dialysis, required to reach dry weight. Nearly 64% of the patients presented high blood pressure (> 140/90 mmHg) when starting dialysis despite antihypertensive therapy (mean: 2.3 drugs). The outcome of this type II diabetes population was dramatic: 32% (27/84) died after a mean follow-up of 211 days, mostly from cardiovascular diseases. The rate of recovery of renal function was low in both the acute and the acutely aggravated renal failure group (30% and 24%, respectively). Of note, iatrogenic nephrotoxic agents accounted for renal function impairment in nearly 30% of patients. CONCLUSION: Our observational study illustrates the high burden of cardiovascular diseases contrasting with sub-optimal cardiovascular therapeutic interventions in type II diabetes patients entering dialysis. Factors aggravating renal failure were mainly iatrogenic, and therefore largely avoidable. Late referral generally implied a poor clinical condition at the start of dialysis.