Mouse Brain MRI: Including In Vivo, Ex Vivo, and fcMRI for the Study of Microcephaly.

With its sensitivity to soft tissue, MRI is a powerful tool for the study of the neuroanatomical manifestations of a variety of conditions, such as microcephaly-related morbidities that are not easily visualized by other imaging techniques, such as CT. In addition to structural imaging, more recently, researchers have found changes in brain function in a wide range of neurological conditions-highlighting the utility of MRI for the study of microcephaly.In this methods chapter, basic mouse preparation and the acquisition of data for in vivo anatomical MRI will be discussed. Additionally, we will provide our protocol for the perfusion and fixation of brain tissue with gadolinium contrast agent. Following that, the process of optimization of system parameters will be shown for anatomical imaging of in vivo and ex vivo brain tissue. Lastly, the chapter will detail a protocol for fcMRI along with a discussion of considerations specific to functional imaging.

Treatment of Mild Hyperkalemia in Hospitalized Patients: An Unnecessary Practice?

BACKGROUND: Sodium polystyrene sulfonate (SPS) is one of the most commonly used treatments for mild hyperkalemia. Other treatments include insulin, sodium bicarbonate, and salbutamol, which may be given alone or in combination. The results of research examining treatment effectiveness for mild hyperkalemia (e.g., the ability of SPS to achieve normokalemia) thus far have been inconsistent. Given that the effectiveness of treatment for mild hyperkalemia is debatable, new research is needed. OBJECTIVE: To determine whether treatment of hospitalized patients with mild hyperkalemia (using SPS or another approach, relative to no treatment) was associated with achievement of normokalemia (serum potassium < 5.1 mmol/L). METHODS: For this retrospective, quasi-experimental study, hospitalized patients with index serum potassium level between 5.1 and 6.4 mmol/L were identified. Post-index serum potassium level within 24 hours was dichotomized (< 5.1 or ≥ 5.1 mmol/L). Pre-index serum creatinine and serum potassium levels were recorded as the average of the first 5 values immediately before the index potassium value. For each patient, treatment was categorized as no treatment, SPS treatment, or other treatment strategy. RESULTS: Among the 1944 patients included in the analysis, the average age was 66.8 (standard deviation 13.5) years; 605 (31.1%) of the patients were women and 1339 (68.9%) were men. Logistic regression results indicated that patients who were female and/or had higher pre-index serum potassium were less likely to return to normokalemia within 24 hours after the time of the index serum potassium value. Treatment category was not a statistically significant predictor of the achievement of normokalemia. Most patients with mild hyperkalemia (> 74.5% in each treatment category) achieved normokalemia, whether or not they received treatment. CONCLUSIONS: The findings of this study suggest that although follow-up is required for mild hyperkalemia in hospitalized patients, active treatment may be unnecessary.

CONTEXTE: Le sulfonate de polystyrène de sodium (SPS) est l'un des traitements les plus communément utilisés pour l'hyperkaliémie légère. D'autres traitements comprennent l'insuline, le bicarbonate de sodium et le salbutamol, qui peuvent être administrés seuls ou ensemble. Les résultats des recherches se penchant sur l'efficacité des traitements de l'hyperkaliémie légère (p. ex., la capacité du SPS à rétablir la normokaliémie) sont contradictoires jusqu'à présent. Étant donné que l'efficacité du traitement de l'hyperkaliémie légère est discutable, de nouvelles recherches sont nécessaires. OBJECTIF: Déterminer si le traitement des patients hospitalisés, présentant une hyperkaliémie légère, (à l'aide de SPS ou d'une autre approche, comparativement à l'absence de traitement) était associé à l'atteinte de la normokaliémie (potassium sérique < 5,1 mmol/L). MÉTHODES: Des patients hospitalisés, dont l'indice de concentration sérique de potassium se situait entre 5,1 et 6,4 mmol/L, ont été identifiés pour participer à cette étude rétrospective quasi expérimentale. La concentration sérique de potassium mesurée dans les 24 heures après le diagnostic d'hyperkaliémie légère a été dichotomisée (< 5,1 ou ≥ 5,1 mmol/L). Les indices de concentrations sériques de créatinine et de potassium avant le diagnostic d'hyperkaliémie légère ont été obtenus par la moyenne des cinq premières valeurs situées immédiatement avant celle de la concentration de potassium. Le classement du traitement de chaque patient était le suivant: Aucun traitement, Traitement par SPS ou Autre stratégie de traitement. RÉSULTATS: L'âge moyen des 1944 patients inclus dans l'analyse était de 66,8 ans (écart type 13,5); 605 (31,1 %) d'entre eux étaient des femmes et 1339 (68,9 %) des hommes. Les résultats de la régression logistique indiquaient que les patientes, donc les femmes, qui avaient un indice sérique de potassium plus élevé au moment du diagnostic, avaient moins de chances de retourner à la normokaliémie dans les 24 heures après l'instant de la mesure de la valeur de l'indice sérique de potassium. La catégorie de traitement n'était pas une variable prédictive statistiquement significative de l'atteinte de la normokaliémie. La plupart des patients présentant une hyperkaliémie légère (> 74,5 % dans chaque catégorie de traitement) atteignaient la normokaliémie, qu'ils aient reçu ou non un traitement. CONCLUSIONS: Les résultats de cette étude laissent entendre que, malgré la nécessité d'un suivi des patients hospitalisés en cas d'hyperkaliémie légère, un traitement actif pourrait s'avérer inutile.

Superoxide free radical spin-lattice relaxivity: A quench-assisted MR study.

PURPOSE: QuEnch-assiSTed (QUEST) MRI provides a unique biomarker of excessive production of paramagnetic free radicals (oxidative stress) in vivo. The contribution from superoxide, a common upstream species found in oxidative stress-based disease, to the QUEST metric is unclear. Here, we begin to address this question by measuring superoxide spin-lattice relaxivity (r1) in phantoms. METHODS: Stable superoxide free radicals were generated in water phantoms of potassium superoxide ( KO2) . To measure r1, 1/T1 of different concentration solutions of KO2 in the presence and absence of the antioxidant superoxide dismutase were measured. The 1/T1 confounding factors including acquisition sequence, pH, and water source were also evaluated. RESULTS: The T1 -weighted signal intensity increased with KO2 concentration. No contribution from pH, or reaction products other than superoxide, noted on 1/T1 . Superoxide r1 was measured to be 0.29 mM-1  s-1 , in agreement with that reported for paramagnetic molecular oxygen and nitroxide free radicals. CONCLUSION: Our first-in-kind measurement of superoxide free radical r1 suggests a detection sensitivity of QUEST MRI on the order of tens of µM, within the reported level of free radical production during oxidative stress in vivo. Similar studies for other common free radicals are needed.

Evaluation of a Pharmacist-Dietician-Led Patient-Centered Approach to Managing CKD-MBD: A Mixed-Method Study.

Chronic kidney disease mineral and bone disorder (CKD-MBD) is a common complication in end-stage renal disease (ESRD). To improve prescribing consistency and patient outcomes, a patient-centered, pharmacist-dietician-led approach to managing CKD-MBD was developed. The purpose of this study was to evaluate if the new approach impacted serum markers of CKD-MBD and medication burden, and to evaluate patient satisfaction. A single-arm, pre-post, mixed-methods study was conducted. Serum markers of CKD-MBD and medication data were collected pre- and post-intervention, and a patient survey administered post-intervention. Focus groups were conducted, transcribed, and analyzed thematically. No statistically significant differences in serum markers of CKD-MBD or medication burden were found. Eighty-seven percent of patients were satisfied with their care, however, 31% were very dissatisfied with medical explanations provided to them and 48% felt their allotted time with healthcare professionals was too short. Four major themes identified from focus groups included lack of privacy, knowledge and perceptions of blood work rounds, issues with taking phosphate binders, and areas for increased patient education. Patients would prefer more information regarding their blood work results and more time with the healthcare team. Areas for expanded education include renal diet, phosphate binders, and consequences of abnormal bloodwork.

An Adjustable Dalteparin Sodium Dose Regimen for the Prevention of Clotting in the Extracorporeal Circuit in Hemodialysis: A Clinical Trial of Safety and Efficacy (the PARROT Study).

BACKGROUND: Dalteparin sodium, a low-molecular-weight heparin, is indicated for prevention of clotting in the extracorporeal circuit during hemodialysis (HD). Product labeling recommends a fixed single-bolus dose of 5000 international units (IU) for HD sessions lasting up to 4 hours, but adjustable dosing may be beneficial in clinical practice. OBJECTIVE: The aim of the PARROT study was to investigate the safety and efficacy of an adjustable dose of dalteparin in patients with end-stage renal disease requiring 3 to 4 HD sessions per week. DESIGN: A 7-week, open-label, multicenter study with a single treatment arm, conducted between October 2013 and March 2016. SETTING: Ten sites in Canada. PATIENTS: A total of 152 patients with end-stage renal disease requiring 3 to 4 HD sessions per week. MEASUREMENTS: The primary outcome was the proportion of HD sessions completed without premature termination due to inadequate anticoagulation. METHODS: All participants initially received a dose of 5000 IU dalteparin, which could be adjusted at subsequent HD sessions when clinically indicated, by increment or decrement of 500 or 1000 IU, with no specified dose limits. RESULTS: Patients were followed for 256 patient-months. Nearly all (99.9%; 95% confidence interval [CI]: 99.7-100) evaluable HD sessions were completed without premature clotting. Dose was adjusted for more than half (52.3%) of participants, mostly owing to clotting or access compression time >10 minutes. Median dalteparin dose was 5000 IU (range: 500-13 000 IU). There were no major bleeds, and minor bleeding was reported in 2.3% of all HD sessions. There was no evidence of bioaccumulation. LIMITATIONS: This short-term study, with a single treatment arm, was designed to optimize dalteparin dose using a flexible dosing schedule; it was not designed to specifically evaluate dalteparin dose minimization, provide a direct comparison of dalteparin versus unfractionated heparin, or provide information on long-term safety for flexible dalteparin dosing. Patients were excluded if they were at high risk of bleeding, including those on anticoagulants and those on antiplatelet agents other than aspirin <100 mg/d. CONCLUSIONS: Overall, an adjustable dalteparin sodium dose regimen allowed safe completion of HD, with clinical benefits over fixed dosing. TRIAL REGISTRATION: ClinicalTrials.gov NCT01879618, registered June 13, 2013.

CONTEXTE: La daltéparine sodique, une héparine de faible poids moléculaire, est indiquée pour prévenir la formation de caillots dans le circuit extracorporel durant l'hémodialyse (HD). Pour une séance de dialyse d'une durée maximale de quatre heures, l'étiquette du produit recommande une dose fixe de 5 000 unités internationales (U.I.) administrée en bolus. Cependant, il est possible qu'il puisse être bénéfique d'ajuster la dose en pratique. OBJECTIF: Le but de l'étude PARROT était d'analyser l'innocuité et l'efficacité d'une dose ajustable de daltéparine chez des patients atteints d'insuffisance rénale terminale (IRT) et nécessitant trois à quatre séances d'HD par semaine. TYPE D'ÉTUDE: Il s'agit d'une étude ouverte et multicentrique à traitement unique d'une durée de sept semaines couvrant la période entre octobre 2013 et mars 2016. CADRE: L'étude a eu lieu dans dix centres de dialyse au Canada. SUJETS: L'étude a inclus 152 patients atteints d'IRT et nécessitant trois à quatre séances d'HD par semaine. MESURES: Le résultat principal était la proportion de séances d'HD complétées, non interrompues de manière prématurée en raison d'une anticoagulation inadéquate. MÉTHODOLOGIE: Tous les participants ont initialement reçu 5000 U.I. de daltéparine, dose qui a pu être ajustée lors des séances subséquentes, lorsqu'indiqué par le contexte clinique, à raison d'augmentation ou de réduction de 500 ou 1 000 U.I., sans spécification quant aux doses limites. RÉSULTATS: Les patients ont été suivis sur une période de 256 mois-patients. Pratiquement toutes les séances d'HD évaluables (99,9 %; IC 95 % : 99,7-100) ont été complétées sans coagulation prématurée. La dose de daltéparine a été ajustée pour plus de la moitié (52,3 %) des participants, essentiellement en raison de coagulation ou d'un besoin de procéder à une compression de l'accès vasculaire au-delà de 10 minutes. La dose médiane de daltéparine était de 5 000 U.I. (entre 500 et 13 000 U.I.). Aucune hémorragie majeure n'a été rapportée, mais une hémorragie mineure est survenue dans 2,3 % de toutes les séances d'HD analysées. Aucune bioaccumulation n'a été détectée. LIMITES: Cette étude de courte durée à traitement unique a été conçue pour optimiser le dosage de daltéparine à l'aide d'un schéma de posologie flexible. Elle ne visait pas à évaluer spécifiquement la minimisation de la dose ou à fournir des informations sur l'innocuité à long terme d'une posologie flexible pour la daltéparine. Également, les patients à haut risque d'hémorragie ont été exclus de l'étude, notamment ceux qui prenaient des anticoagulants ou des antiplaquettaires autres qu'une dose quotidienne de moins de 100 mg d'aspirine. CONCLUSION: Dans l'ensemble, un schéma posologique flexible pour la daltéparine sodique a permis de compléter les séances d'HD de façon sécuritaire, en plus de fournir des avantages cliniques par rapport à une dose fixe.

Development and examination of a rubric for evaluating point-of-care medical applications for mobile devices.

The rapid development and updates of mobile medical resource applications (apps) highlight the need for an evaluation tool to assess the content of these resources. The purpose of the study was to develop and test a new evaluation rubric for medical resource apps. The evaluation rubric was designed using existing literature and through a collaborative effort between a hospital and an academic librarian. Testing found scores ranging from 23% to 88% for the apps. The evaluation rubric proved able to distinguish levels of quality within each content component of the apps, demonstrating potential for standardization of medical resource app evaluations.

Canadian Society of Nephrology commentary on the 2012 KDIGO clinical practice guideline for the management of blood pressure in CKD.

The KDIGO (Kidney Disease: Improving Global Outcomes) 2012 clinical practice guideline for the management of blood pressure (BP) in chronic kidney disease (CKD) provides the structural and evidence base for the Canadian Society of Nephrology (CSN) commentary on this guideline's relevancy and application to the Canadian health care system. While in general agreement, we provide commentary on 13 of the 21 KDIGO guideline statements. Specifically, we agreed that nonpharmacological interventions should play a significant role in the management of hypertension in patients with CKD. We also agreed that the approach to the management of hypertension in elderly patients with CKD should be individualized and take into account comorbid conditions to avoid adverse outcomes from excessive BP lowering. In contrast to KDIGO, the CSN Work Group believes there is insufficient evidence to target a lower BP for nondiabetic CKD patients based on the presence and severity of albuminuria. The CSN Work Group concurs with the Canadian Hypertension Education Program (CHEP) recommendation of a target BP for all non-dialysis-dependent CKD patients without diabetes of ≤140 mm Hg systolic and ≤90 mm Hg diastolic. Similarly, it is our position that in diabetic patients with CKD and normal urinary albumin excretion, raising the threshold for treatment from <130 mm Hg systolic BP to <140 mm Hg systolic BP could increase stroke risk and the risk of worsening kidney disease. The CSN Work Group concurs with the CHEP and the Canadian Diabetic Association recommendation for diabetic patients with CKD with or without albuminuria to continue to be treated to a BP target similar to that of the overall diabetes population, aiming for BP levels < 130/80 mm Hg. Consistent with this, the CSN Work Group endorses a BP target of <130/80 mm Hg for diabetic patients with a kidney transplant. Finally, in the absence of evidence for a lower BP target, the CSN Work Group concurs with the CHEP recommendation to target BP<140/90 mm Hg for nondiabetic patients with a kidney transplant.

Programmatic variation in home hemodialysis in Canada: results from a nationwide survey of practice patterns.

BACKGROUND: Over 40% of patients with end stage renal disease in the United States were treated with home hemodialysis (HHD) in the early 1970's. However, this number declined rapidly over the ensuing decades so that the overwhelming majority of patients were treated in-centre 3 times per week on a 3-4 hour schedule. Poor outcomes for patients treated in this fashion led to a renewed interest in home hemodialysis, with more intensive dialysis schedules including short daily (SDHD) and nocturnal (NHD). The relative infancy of these treatment schedules means that there is a paucity of data on 'how to do it'. OBJECTIVE: We undertook a systematic survey of home hemodialysis programs in Canada to describe current practice patterns. DESIGN: Development and deployment of a qualitative survey instrument. SETTING: Community and academic HHD programs in Canada. PARTICIPANTS: Physicians, nurses and technologists. MEASUREMENTS: Programmatic approaches to patient selection, delivery of dialysis, human resources available, and follow up. METHODS: We developed the survey instrument in three phases. A focus group of Canadian nephrologists with expertise in NHD or SDHD discussed the scope the study and wrote questions on 11 domains. Three nephrologists familiar with all aspects of HHD delivery reviewed this for content validity, followed by further feedback from the whole group. Multidisciplinary teams at three sites pretested the survey and further suggestions were incorporated. In July 2010 we distributed the survey electronically to all renal programs known to offer HHD according to the Canadian Organ Replacement Registry. We compiled the survey results using qualitative and quantitative methods, as appropriate. RESULTS: Of the academic and community programs that were invited to participate, 80% and 63%, respectively, completed the survey. We observed wide variation in programmatic approaches to patient recruitment, human resources, equipment, water, vascular access, patient training, dialysis prescription, home requirements, patient follow up, medications, and the approach to non-adherent patients. LIMITATIONS: Cross-sectional survey, unable to link variation to outcomes. Competition for patients between HHD and home peritoneal dialysis means that case mix for HHD may also vary between centres. CONCLUSIONS: There is wide variation between programs in all domains of HHD delivery in Canada. We plan further study of the extent to which differences in approach are related to outcomes.

PROBLÉMATIQUE: Au début des années 70, plus de 40% des patients en insuffisance rénale terminale aux États-Unis étaient traités par hémodialyse à domicile (HDD). Cette proportion a décliné rapidement au cours des décennies suivantes, de sorte que le mode de suppléance pour la majorité des patients est maintenant l'hémodialyse 3 fois par semaine à raison de 3 à 4 heures par séance. Les mauvais résultats obtenus avec cette méthode ont renouvelé l'intérêt pour l'HDD, notamment pour les dialyses intensives incluant la dialyse quotidienne courte (DQC) et l'hémodialyse nocturne (HDN). Étant donné leur nouveauté, il y a peu de données sur les façons de faire avec ces modes de suppléance. OBJECTIF: Afin de décrire les pratiques actuelles, nous avons réalisé un questionnaire systématique auprès des programmes d'HDD au Canada. DESIGN: Développement et déploiement d'un outil qualitatif. CADRE: Programmes d'HDD académiques et communautaires au Canada. PARTICIPANTS: Médecins, infirmières et technologues. VARIABLES MESURÉES: Approches pour la sélection des patients, le mode de suppléance, les ressources humaines disponibles et le mode de suivi pour chaque programme. MÉTHODOLOGIE: Nous avons développé un outil en trois phases. Un groupe de discussion composé de néphrologues canadiens ayant une expertise en DQC ou HDN ont échangé sur le contenu de l'étude et ont rédigé des questions sur 11 domaines. Trois néphrologues familiers avec tous les aspects de l'HDD ont révisé la validité des questions, puis ont demandé un nouvel avis à tout le groupe de discussion. Des équipes multidisciplinaires provenant de trois sites ont ensuite évalué le questionnaire et ont apporté des suggestions. En juillet 2010, le questionnaire a été distribué électroniquement à tous les programmes qui offrent l'HDD d'après le Registre canadien des insuffisances et des transplantations d'organes. Les résultats ont été compilés au moyen de méthodes qualitatives ou quantitatives, le cas échéant. RÉSULTATS: 80% des centres académiques et 63% des centres communautaires invités ont répondu au questionnaire. Nous avons observé des variations importantes entre les programmes quant au recrutement des patients, aux ressources humaines, à l'équipement, à l'eau, aux accès vasculaires, à l'entraînement des patients, à la prescription de dialyse, aux exigences du domicile, au suivi des patients, à la médication et à l'approche face aux patients non-adhérents. LIMITATIONS: Étude transversale, incapacité d'associer les variations aux issues cliniques. La compétition entre l'HDD et la dialyse péritonéale pour le recrutement des patients entraîne peut-être une variabilité entre les centres dans la composition des groupes de patients en HDD. CONCLUSIONS: Il y a de grandes variations entre les programmes dans tous les domaines concernant l'HDD au Canada. Nous planifions d'étudier dans le futur jusqu'à quel point ces différences sont reliées aux issues cliniques.

Tinzaparin versus dalteparin for periprocedure prophylaxis of thromboembolic events in hemodialysis patients: a randomized trial.

BACKGROUND: Low-molecular-weight heparin (LMWH) is cleared predominantly by the kidneys and hence there is uncertainty about the safety of its use in hemodialysis (HD) patients. Our primary objective was to compare whether tinzaparin and dalteparin differentially accumulate in HD patients. STUDY DESIGN: Open-label randomized controlled trial. SETTING & PARTICIPANTS: HD patients undergoing periprocedure bridging anticoagulation. INTERVENTION: After warfarin therapy was discontinued, participants were randomly assigned to either 3 daily doses of tinzaparin (175 IU/kg) or dalteparin (200 IU/kg), with 2 intervening HD treatments between the first dose of study drug and their procedure. OUTCOMES: The primary outcome was predialysis anti-Xa levels 20 to 24 hours after the third LMWH dose (therapeutic target, <0.2 IU/mL). Secondary outcomes included thromboembolic events and major bleeding. RESULTS: Of 29 eligible and consenting patients, 17 patients received tinzaparin and 12 patients received dalteparin. Mean predialysis anti-Xa level 20-24 hours after the third LMWH dose was 0.37 ± 0.23 (SD) IU/mL for tinzaparin and 0.62 ± 0.41 IU/mL for dalteparin (P = 0.1), indicating clinically important accumulation for both drugs. No invasive procedures were canceled due to study drug accumulation. 4 patients experienced serious adverse events (1 major bleed after traumatic arteriovenous fistula puncture in the tinzaparin arm, 2 non-ST-elevation myocardial infarctions [1 in each group], and 1 upper-extremity deep venous thrombosis [dalteparin group]). LIMITATIONS: Small sample size. CONCLUSIONS: Dalteparin and tinzaparin significantly accumulate in HD patients at therapeutic doses. "Bridging therapy" with LMWHs at therapeutic doses in HD patients who require temporary interruption of warfarin therapy has the potential for complications and is of uncertain benefit. Other anticoagulation strategies, including no bridging therapy or intravenous heparin, need comparative evaluation in this unique patient population.

Combination therapy with an angiotensin receptor blocker and an ACE inhibitor in proteinuric renal disease: a systematic review of the efficacy and safety data.

Blockade of the renin-angiotensin system with either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) was shown to decrease urinary protein excretion and slow the progression of both diabetic and nondiabetic proteinuric renal disease. The safety and efficacy of combined ACE-inhibitor and ARB therapy is not well established. We conducted a systematic review and meta-analysis of randomized trials evaluating the combination of an ACE inhibitor and an ARB in patients with chronic proteinuric renal disease. Twenty-one randomized controlled studies (n = 654 patients) were identified using MEDLINE, EMBASE, and Cochrane Central databases. Five trials had a parallel-group design and 16 trials used a crossover design. Combination therapy with an ACE inhibitor and an ARB resulted in a small, but significant, increase in serum potassium levels (weighted mean difference, 0.11 mEq/L [0.11 mmol/L]; 95% confidence interval [CI], 0.05 to 0.17) and a nonsignificant decrease in glomerular filtration rate (weighted mean difference, 1.4 mL/min [0.02 mL/s]; 95% CI, -2.6 to 0.2). Addition of an ARB resulted in a further decrease in proteinuria (weighted mean difference, 440 mg/d; 95% CI, 289 to 591) compared with an ACE inhibitor alone. This effect was observed in patients with diabetic (210 mg/d; 95% CI, 84 to 336) and nondiabetic (582 mg/d; 95% CI, 371 to 793) renal disease. In conclusion, the combination of ACE-inhibitor and ARB therapy in patients with chronic proteinuric renal disease is safe, without clinically meaningful changes in serum potassium levels or glomerular filtration rates. Combination therapy also was associated with a significant decrease in proteinuria, at least in the short term. Additional trials with longer follow-up are needed to determine whether the decrease in proteinuria will result in significant preservation of renal function.

Cystatin-C and beta trace protein as markers of renal function in pregnancy.

OBJECTIVE: To assess the validity of Cystatin-C (Cys-C) and beta trace protein (BTP) as clinical markers of glomerular filtration rate (GFR) in pregnant women. DESIGN: Prospective cross sectional study. SETTING: Obstetric unit of a tertiary care hospital. POPULATION: One hundred and thirty-seven normal pregnant women and 13 women postpartum. METHODS: Twenty-four hour creatinine clearance (CrCl), serum creatinine, Cys-C and BTP concentrations were measured on normal pregnant women in the first trimester (n= 5), second trimester (n= 68) and third trimester (n= 64) and in 13 women postpartum. Data are given as median (2.5th centile, 97.5th centile). MAIN OUTCOME MEASURES: Serum concentrations of Cys-C and BTP compared with creatinine clearance and serum creatinine. RESULTS: The median serum creatinine throughout gestation was 53 micromol/L (39, 71), and median CrCl was 143 mL/minute (91 to 216). Postpartum, creatinine rose to 74 micromol/L (58, 86) and CrCl decreased to 104 mL/minute (71, 159). For Cys-C, the median concentration was 0.70 mg/L (0.46, 1.32), and 0.54 mg/L (0.36, 0.96) for BTP. Comparing the second and third trimesters, there was no significant difference between CrCl (median 145 vs 141 mL/minute) and BTP concentrations (median 0.51 vs 0.55 mg/L), while median Cys-C was significantly higher in the third trimester (0.61 vs 0.88 mg/L; P < 0.001). Unlike creatinine and BTP, Cys-C levels decreased to 0.72 mg/L (0.57, 0.95) postpartum. The only significant relationship of either of these markers to the standard used for GFR was between Cys-C and CrCl in the third trimester, and the correlation was weak (r= 0.27 for 1/Cys-C vs CrCl). CONCLUSION: These data demonstrate that despite claims to the contrary, Cys-C is a poor marker of GFR during pregnancy. Similarly, BTP shows little promise.

Does ALLHAT change the management of hypertension in chronic kidney disease?

ALLHAT was designed to test the hypothesis that "newer" antihypertensive agents are superior to a thiazide diuretic for cardiovascular outcomes. Pre-specified secondary outcomes included the development of end-stage renal disease (ESRD) (dialysis, renal transplantation, or death from renal cause) and estimated glomerular filtration rate (GFR). ALLHAT showed no differences in the overall rates of ESRD between those randomized to chlorthalidone, amlodipine, or lisinopril. It showed a slower rate of decline of GFR among those randomized to amlodipine in both diabetics and nondiabetics, and in the composite end point (ESRD or > or = 50% decline in GFR) in nondiabetics. The results of ALLHAT are consistent with other studies that, for the patient population studied (presumably largely nonalbuminuric patients with and without diabetes), at systolic BP > 130 mm Hg, there is no difference for renal outcomes between a thiazide diuretic, dihydropyridine calcium channel blocker, and ACEI-initiated treatment for 5 to 6 years of follow-up. These results suggest that BP control per se remains the most important objective for this patient population.

Zopiclone-induced acute interstitial nephritis.

Zopiclone, a relatively new nonbenzodiazepine short-acting hypnotic medication is prescribed frequently for insomnia. The authors report a case of zopiclone-induced acute interstitial nephritis in a young, otherwise healthy man. The patient presented with anuric acute renal failure requiring hemodialysis. Kidney biopsy results showed acute interstitial nephritis with a prominent eosinophilic infiltrate in the interstitium. He recovered his renal function after stopping the medication and receiving corticosteroids.