The incidence and outcome of AKI in patients with sepsis in the emergency department applying different definitions of AKI and sepsis.

BACKGROUND: Sepsis is often accompanied with acute kidney injury (AKI). The incidence of AKI in patients visiting the emergency department (ED) with sepsis according to the new SOFA criteria is not exactly known, because the definition of sepsis has changed and many definitions of AKI exist. Given the important consequences of early recognition of AKI in sepsis, our aim was to assess the epidemiology of sepsis-associated AKI using different AKI definitions (RIFLE, AKIN, AKIB, delta check, and KDIGO) for the different sepsis classifications (SIRS, qSOFA, and SOFA). METHODS: We retrospectively enrolled patients with sepsis in the ED in three hospitals and applied different AKI definitions to determine the incidence of sepsis-associated AKI. In addition, the association between the different AKI definitions and persistent kidney injury, hospital length of stay, and 30-day mortality were evaluated. RESULTS: In total, 2065 patients were included. The incidence of AKI was 17.7-51.1%, depending on sepsis and AKI definition. The highest incidence of AKI was found in qSOFA patients when the AKIN and KDIGO definitions were applied (51.1%). Applying the AKIN and KDIGO definitions in patients with sepsis according to the SOFA criteria, AKI was present in 37.3% of patients, and using the SIRS criteria, AKI was present in 25.4% of patients. Crude 30-day mortality, prolonged length of stay, and persistent kidney injury were comparable for patients diagnosed with AKI, regardless of the definition used. CONCLUSION: The incidence of AKI in patients with sepsis is highly dependent on how patients with sepsis are categorised and how AKI is defined. When AKI (any definition) was already present at the ED, 30-day mortality was high (22.2%). The diagnosis of AKI in sepsis can be considered as a sign of severe disease and helps to identify patients at high risk of adverse outcome at an early stage.

[A man with bulging eyes]. / Een man met uitpuilende ogen.

Graves' orbitopathy may cause multiple symptoms, such as proptosis, redness or inflammation of the conjunctiva, excessive tearing, swelling of the eyelids and pain. Smoking, male gender and old age are significant risk factors for a more severe and active disease.

Living Donor Kidney Transplantation in Atypical Hemolytic Uremic Syndrome: A Case Series.

BACKGROUND: The development of complement inhibitors has greatly improved the outcome of patients with atypical hemolytic uremic syndrome (aHUS), making kidney transplantation a more feasible option. Although prophylactic eculizumab therapy may prevent recurrent disease after transplantation, its necessity for all transplant recipients is debated. STUDY DESIGN: A case series. SETTING & PARTICIPANTS: Patients with aHUS who underwent living donor kidney transplantation after 2011 at 2 university centers, prospectively followed up with a protocol of eculizumab therapy limited to only recipients with documented posttransplantation recurrent thrombotic microangiopathy. In addition, the protocol emphasized lower target level tacrolimus and aggressive treatment of high blood pressure. OUTCOMES: Recurrence of aHUS, kidney function, acute kidney injury. RESULTS: We describe 12 female and 5 male patients with a mean age of 47 years. 5 patients had lost a previous transplant due to aHUS recurrence. 16 patients carried a pathogenic or likely pathogenic variant in genes encoding complement factor H, C3, or membrane cofactor protein, giving a high risk for aHUS recurrence. Median follow-up after transplantation was 25 (range, 7-68) months. One patient had aHUS recurrence 68 days after transplantation, which was successfully treated with eculizumab. 3 patients were treated for rejection and 2 patients developed BK nephropathy. At the end of follow-up, median serum creatinine concentration was 106 (range, 67-175) µmol/L and proteinuria was negligible. LIMITATIONS: Small series and short duration of follow-up. CONCLUSIONS: Living donor kidney transplantation in aHUS without prophylactic eculizumab treatment appears feasible.

The impact of renal protection clinics on prescription of and adherence to cardioprotective drug therapy in chronic kidney disease patients.

Background: The aim of this study was to assess the impact of follow-up in renal protection clinics on the prescription of and adherence to cardioprotective drugs in patients with chronic kidney disease (CKD). Methods: We studied stage 4 and 5 CKD patients who initiated follow-up in three renal protection clinics. The prescription pattern of antihypertensive agents (AHA) and lipid-lowering agents (LLAs) was measured as the percentage of patients who are prescribed the agents of interest at a given time. Adherence to drug therapy was defined as the percentage of days, during a pre-defined observation period, in which patients have an on-hand supply of their prescribed medications. Results: A total of 259 CKD patients were enrolled and followed for up to 1 year after referral to renal protection clinics. There was a significant increase in the prescription of angiotensin-converting enzyme inhibitors (34-39%), angiotensin II receptor blockers (11-14%), beta-blockers (40-51%), calcium channel blockers (62-74%), diuretics (66-78%) and LLAs (39-47%) during follow-up in the renal protection clinic compared with baseline (P-values <0.01 for all comparisons). The proportions of patients with good (≥ 80%) and poor (< 80%) adherence to AHA (P = 0.41) and LLAs (P = 0.11) were similar in the year preceding and the year following the first visit to the renal protection clinics. Conclusion: Our results suggest that referral and follow-up in a renal protection clinic may increase the prescription of cardioprotective agents in CKD patients, but does not appear to improve adherence to these medications.

Cost-effectiveness of eculizumab treatment after kidney transplantation in patients with atypical haemolytic uraemic syndrome.

Background: Kidney transplantation in patients with atypical haemolytic uraemic syndrome (aHUS) is frequently complicated by recurrence of aHUS, often resulting in graft loss. Eculizumab prophylaxis prevents recurrence, improving graft survival. An alternative treatment strategy has been proposed where eculizumab is administered upon recurrence. We combined available evidence and performed a cost-effectiveness analysis of these competing strategies. Methods: A cost-effectiveness analysis using a decision analytical approach with Markov chain analyses was used to compare alternatives for aHUS patients with end-stage renal disease (ESRD): (i) dialysis treatment, (ii) kidney transplantation, (iii) kidney transplantation with eculizumab therapy upon recurrence of aHUS, (iv) kidney transplantation with eculizumab induction consisting of 12 months of prophylaxis and (v) kidney transplantation with lifelong eculizumab prophylaxis. We assumed that all patients received a graft from a living donor and that recurrence probability was 28.4% within the first year of transplantation. Results: At 8.34 quality-adjusted life years (QALYs) gained and a cost of €402 412, kidney transplantation without eculizumab was the least costly alternative. By comparison, dialysis was more costly and resulted in fewer QALYs gained. Eculizumab upon recurrence resulted in 9.55 QALYs gained at a cost of €425 097. The incremental cost-effectiveness ratio (ICER) was €18 748 per QALY. Both eculizumab induction and lifelong eculizumab were inferior to eculizumab upon recurrence, as both resulted in fewer QALYs gained and higher costs. Conclusions: Kidney transplantation is more cost effective than dialysis to treat ESRD due to aHUS. Adding eculizumab treatment results in a substantial gain in QALYs. When compared with eculizumab upon recurrence, neither eculizumab induction nor lifelong eculizumab prophylaxis resulted in more QALYs, but did yield far higher costs. Therefore, eculizumab upon recurrence of aHUS is more acceptable.

A Multicenter Study of the Predictive Value of Crescents in IgA Nephropathy.

The Oxford Classification of IgA nephropathy does not account for glomerular crescents. However, studies that reported no independent predictive role of crescents on renal outcomes excluded individuals with severe renal insufficiency. In a large IgA nephropathy cohort pooled from four retrospective studies, we addressed crescents as a predictor of renal outcomes and determined whether the fraction of crescent-containing glomeruli associates with survival from either a ≥50% decline in eGFR or ESRD (combined event) adjusting for covariates used in the original Oxford study. The 3096 subjects studied had an initial mean±SD eGFR of 78±29 ml/min per 1.73 m2 and median (interquartile range) proteinuria of 1.2 (0.7-2.3) g/d, and 36% of subjects had cellular or fibrocellular crescents. Overall, crescents predicted a higher risk of a combined event, although this remained significant only in patients not receiving immunosuppression. Having crescents in at least one sixth or one fourth of glomeruli associated with a hazard ratio (95% confidence interval) for a combined event of 1.63 (1.10 to 2.43) or 2.29 (1.35 to 3.91), respectively, in all individuals. Furthermore, having crescents in at least one fourth of glomeruli independently associated with a combined event in patients receiving and not receiving immunosuppression. We propose adding the following crescent scores to the Oxford Classification: C0 (no crescents); C1 (crescents in less than one fourth of glomeruli), identifying patients at increased risk of poor outcome without immunosuppression; and C2 (crescents in one fourth or more of glomeruli), identifying patients at even greater risk of progression, even with immunosuppression.

Tonsillectomy in a European Cohort of 1,147 Patients with IgA Nephropathy.

BACKGROUND: Tonsillectomy has been considered a treatment for IgA nephropathy (IgAN). It is aimed at removing a source of pathogens, reducing mucosa-associated lymphoid tissue and decreasing polymeric IgA synthesis. However, its beneficial effect is still controversial. In Asia, favorable outcomes have been claimed mostly in association with corticosteroids. In Europe, small, single-center uncontrolled studies have failed to show benefits. METHODS: The European validation study of the Oxford classification of IgAN (VALIGA) collected data from 1,147 patients with IgAN over a follow-up of 4.7 years. We investigated the outcome of progression to end-stage renal disease (ESRD) and/or 50% loss of estimated glomerular filtration rate (eGFR) and the annual loss of eGFR in 61 patients who had had tonsillectomy. RESULTS: Using the propensity score, which is a logistic regression model, we paired 41 patients with tonsillectomy and 41 without tonsillectomy with similar risk of progression (gender, age, race, mean blood pressure, proteinuria, eGFR at renal biopsy, previous treatments and Oxford MEST scores). No significant difference was found in the outcome. Moreover, we performed an additional propensity score pairing 17 patients who underwent tonsillectomy after the diagnosis of IgAN and 51 without tonsillectomy with similar risk of progression at renal biopsy and subsequent treatments. No significant difference was found in changes in proteinuria, or in the renal end point of 50% reduction in GFR and/or ESRD, or in the annual loss of eGFR. CONCLUSION: In the large VALIGA cohort of European subjects with IgAN, no significant correlation was found between tonsillectomy and renal function decline.

Hepatocyte Nuclear Factor 1ß-Associated Kidney Disease: More than Renal Cysts and Diabetes.

Hepatocyte nuclear factor 1ß (HNF1ß)-associated disease is a recently recognized clinical entity with a variable multisystem phenotype. Early reports described an association between HNF1B mutations and maturity-onset diabetes of the young. These patients often presented with renal cysts and renal function decline that preceded the diabetes, hence it was initially referred to as renal cysts and diabetes syndrome. However, it is now evident that many more symptoms occur, and diabetes and renal cysts are not always present. The multisystem phenotype is probably attributable to functional promiscuity of the HNF1ß transcription factor, involved in the development of the kidney, urogenital tract, pancreas, liver, brain, and parathyroid gland. Nephrologists might diagnose HNF1ß-associated kidney disease in patients referred with a suspected diagnosis of autosomal dominant polycystic kidney disease, medullary cystic kidney disease, diabetic nephropathy, or CKD of unknown cause. Associated renal or extrarenal symptoms should alert the nephrologist to HNF1ß-associated kidney disease. A considerable proportion of these patients display hypomagnesemia, which sometimes mimics Gitelman syndrome. Other signs include early onset diabetes, gout and hyperparathyroidism, elevated liver enzymes, and congenital anomalies of the urogenital tract. Because many cases of this disease are probably undiagnosed, this review emphasizes the clinical manifestations of HNF1ß-associated disease for the nephrologist.

Strategies to increase living kidney donation: a retrospective cohort study.

BACKGROUND: Living kidney transplantation (LKT) offers the best medical outcomes for organ recipients. Historically, our centre had a low rate of LKT. In 2009, in an effort to increase living organ donation (LOD), a dedicated team was created. Its mandate was to promote LOD at our centre and at referring centres, to coordinate assessments of living organ donors, to facilitate the process, and to ensure long-term follow-up after the donation. In November 2010, our centre joined the national living donor paired exchange registry (LDPE). OBJECTIVE: To document the impact of the LOD team and LDPE registry on LOD rates at our centre. DESIGN: Retrospective cohort study. SETTING: Single center study in a university hospital with an adult kidney transplant program. PATIENTS: Using our electronic database, we included all potential living organ donors who contacted our centre from 01/01/2005 to 31/12/2008 and from 01/01/2009 to 31/12/2012. Follow-up was conducted until 31/12/2013. MEASUREMENTS: Number of transplantations from living donors, number of potential donors who contacted the centre, donor and recipient characteristics. METHODS: We compared the number of transplantations from living donors performed and the number of potential donors who contacted the centre before and after the creation of the LOD team and participation in the LDPE. RESULTS: A total of 50 renal transplantations were performed using organs from living donors during the first time period, whereas this increased to 73 in the 2009-2012 cohort (incidence rate difference (IRD): 0.030, 95% confidence interval (CI) 0.003-0.056). We also observed a significant increase in the number of individuals who contacted our centre to donate a kidney. During the 2005-2008 period (cohort 1), 191 individuals interested in donating a kidney contacted our centre, whereas this figure was 304 during the 2009-2012 period (cohort 2) (IRD: 0.143, 95% CI 0.091-0.196). LIMITATIONS: Single center study, relatively low sample size. CONCLUSION: The implementation of a LOD team, combined with our participation in the LDPE registry, was associated with a significant increase in the actual number of living kidney transplantations performed. These data support initiatives such as the creation of dedicated LOD teams and LDPE registry to increase LKT.

CONTEXTE: Le meilleur traitement pour les patients atteints d'insuffisance rénale est la transplantation rénale à partir d'un donneur vivant (DV). Historiquement, notre centre hospitalier réalisait une faible proportion de greffes rénales à partir de DV. En 2009, nous avons créé une équipe dédiée au don vivant afin d'augmenter le nombre de transplantations rénales à partir de DV. Cette équipe avait pour mandat de promouvoir le don vivant dans notre centre et dans les centres périphériques, de coordonner et faciliter l'évaluation des DV et s'assurer d'un suivi à long terme des DV. A partir de novembre 2010, notre centre s'est joint au registre canadien de donneurs vivants jumelés par échange de bénéficiaires (DVEB). OBJECTIF: Évaluer l'impact de l'équipe dédiée au don vivant et de la participation au registre canadien de DVEB sur le nombre de donneurs potentiels ayant contacté notre centre et le nombre de transplantation effectuées à partir de DV. TYPE D'ÉTUDE: Etude de cohorte rétrospective. LIEU DE L'ÉTUDE: Centre de santé universitaire offrant un programme de transplantation rénale adulte. PATIENTS: Tous les DV qui ont contacté notre centre entre le 01/01/2005 et le 31/12/2008 et entre le 01/01/2009 et le 31/12/2012. Nous avons effectué un suivi jusqu'au 31/12/2013. MESURES: Nombre de transplantations effectuées à partir de DV, nombre de donneurs potentiels ayant contacté notre centre, caractéristiques des donneurs et des receveurs. MÉTHODOLOGIE: Nous avons comparé le nombre de transplantations à partir de DV ainsi que le nombre de donneurs potentiels qui ont contacté notre centre avant et après la création d'une équipe dédiée au don vivant et la participation au registre de DVEB. RÉSULTATS: Nous avons réalisé 50 transplantations à partir de DV dans la première période, et 73 dans la deuxième (différence du taux d'incidence (DTI) : 0.030, intervalle de confiance de 95% (IC) 0.003-0.056). Entre 2005 et 2008, 191 individus ont manifesté un intérêt à être DV en contactant notre centre, alors que ce chiffre a augmenté à 304 pour la période 2009-2012 (DTI: 0.143, IC 95% 0.091-0.196). LIMITES: Étude avec un petit nombre de patients, provenant d'un seul centre de santé. CONCLUSION: La création d'une équipe de DV et la participation au registre canadien de DVEB sont associés à un accroissement du nombre de donneurs vivants effectifs. Ces données supportent l'efficacité d'initiatives telles la mise en place d'équipes dédiées au don vivant et le registre canadien de DVEB afin d'augmenter le nombre de transplantations à partir de DV.

[Cryptococcal meningitis]. / Cryptokokkenmeningitis.

Immunocompromised patients are at increased risk of disseminated cryptococcal infection, often presenting as a primary respiratory infection with yeast cells originating from bird excreta. Because Cryptococcus neoformans has a tropism for cerebrospinal fluid, most patients suffer from meningitis or meningoencephalitis. Symptoms of cryptococcal meningitis are non-specific: headache, fever, nausea, or altered mental state and behaviour. Case descriptions of a renal transplant recipient and an HIV patient illustrate the non-specific presentation of cryptococcal meningitis. Lumbar puncture seemed to be critical in establishing the diagnosis. Cerebrospinal fluid, blood and other tissues were tested for C. neoformans by microscopy, culture and antigen tests. The patients were successfully treated with amphotericin B or liposomal amphotericin B intravenously and flucytosine intravenously or orally, followed by long-term fluconazole. The mortality rate for cryptococcal meningitis is 41% among renal transplant recipients and 20% in HIV patients.

Corticosteroids in IgA Nephropathy: A Retrospective Analysis from the VALIGA Study.

Current guidelines suggest treatment with corticosteroids (CS) in IgA nephropathy (IgAN) when proteinuria is persistently ≥1 g/d despite 3-6 months of supportive care and when eGFR is >50 ml/min per 1.73 m(2). Whether the benefits of this treatment extend to patients with an eGFR≤50 ml/min per 1.73 m(2), other levels of proteinuria, or different renal pathologic lesions remains unknown. We retrospectively studied 1147 patients with IgAN from the European Validation Study of the Oxford Classification of IgAN (VALIGA) cohort classified according to the Oxford-MEST classification and medication used, with details of duration but not dosing. Overall, 46% of patients received immunosuppression, of which 98% received CS. Treated individuals presented with greater clinical and pathologic risk factors of progression. They also received more antihypertensive medication, and a greater proportion received renin angiotensin system blockade (RASB) compared with individuals without immunosuppressive therapy. Immunosuppression was associated with a significant reduction in proteinuria, a slower rate of renal function decline, and greater renal survival. Using a propensity score, we matched 184 subjects who received CS and RASB to 184 patients with a similar risk profile of progression who received only RASB. Within this group, CS reduced proteinuria and the rate of renal function decline and increased renal survival. These benefits extended to those with an eGFR≤50 ml/min per 1.73 m(2), and the benefits increased proportionally with the level of proteinuria. Thus, CS reduced the risk of progression regardless of initial eGFR and in direct proportion to the extent of proteinuria in this cohort.

Novel aspects of atypical haemolytic uraemic syndrome and the role of eculizumab.

The haemolytic uraemic syndrome (HUS) is part of a spectrum of thrombotic microangiopathies. The most common etiologies of HUS are the ones seen in childhood caused by an infection of Shiga toxin-producing Escherichia coli, HUS caused by an infection with Streptococcus pneumoniae and HUS due to abnormalities in the alternative pathway of the complement system. In the past decade, enormous progress has been made in understanding the pathogenesis in the latter group of patients. The analysis of genes that encode for complement regulatory proteins and the development of assays for measuring the activity of ADAMTS13 and the detection of antibodies against factor H contributed significantly to the diagnostic tools in patients with HUS. These assays have made it possible to clearly differentiate between thrombotic thrombocytopenic purpura and various forms of HUS. With the introduction of eculizumab, a monoclonal anti-C5 inhibitor, in the clinical arena as effective treatment of most complement-mediated forms of HUS, a new era of treatment in HUS has begun. We review the recent advances in HUS, with the focus on treatment. We discuss unsolved questions, which should be addressed in future studies.

The incidence, management, and evolution of rapamycin-related side effects in kidney transplant recipients.

Conversion from a calcineurin-inhibitor-based immunosuppression to a rapamycin-based immunosuppression may preserve kidney graft function. The side effects of rapamycin can limit its usefulness, but their management and evolution are rarely reported in clinical trials. We performed a retrospective cohort study in patients transplanted before December 31, 2008 and who received rapamycin to replace calcineurin inhibitors. In 219 patients studied, 98% presented ≥1 side effects after starting rapamycin. Side effects occurring in ≥10% of patients were dyslipidemia (52%, 95% confidence interval (CI): 45-59%), peripheral edema (37%, 95%CI: 31-43%), cytopenia (36%, 95% CI: 30-42%), acne (29%, 95% CI: 23-35%), proteinuria (23%, 95% CI: 17-29%), and oral ulcers 14% (95% CI: 10-18%). Proteinuria, ulcers, and edema were difficult to manage and were more likely to cause cessation of rapamycin. Rapamycin was discontinued in 46% of patients (95% CI: 40-52%). Age (odds ratio [OR] per 10-yr increase: 1.29, 95% CI: 1.05-1.59) and obesity (OR: 2.57, 95% CI: 1.10-6.01) were independently associated with cessation of rapamycin. We conclude that successful control of dyslipidemia and cytopenia can be achieved without discontinuing rapamycin. Most other side effects are harder to manage. Leaner and younger patients are less likely to discontinue rapamycin due to side effects.

The risk of thromboembolic events in kidney transplant patients.

Little is known about the risk of venous thrombosis following kidney transplant. To determine this we estimated the risk of thromboembolic events (TEs) in a cohort of consecutive patients who underwent kidney transplantation at a single tertiary care center over an 11-year period and calculated standardized incidence ratios (SIRs) for a first TE in kidney transplant recipients compared with the general population. We then performed a nested case-control study and compared patients with and without TEs to identify risk factors for thrombosis. Among 913 kidney transplant recipients (KTRs), 68 patients developed these events. The SIR for TEs in KTRs compared with the general population was 7.9 over the duration of follow-up. The risk was particularly higher in the first post-transplant year (SIR 26.1) but remained elevated afterward (SIR 5.2). Hospitalization, use of sirolimus, low hemoglobin level, and use of renin-angiotensin system inhibitors were independently associated with these events. When cases of TEs that occurred during hospitalization were excluded, the risk of these events remained elevated. The risk of TEs in KTRs was eightfold higher than in the general population but not fully explained by the increased risk associated with hospitalization. Our results underscore the important risk of thrombosis in patients who received a kidney transplant, making vigilance mandatory especially during hospitalization.

Prevalence, awareness, and management of CKD and cardiovascular risk factors in publicly funded health care.

BACKGROUND AND OBJECTIVES: It is uncertain how many patients with CKD and cardiovascular risk factors in publicly funded universal health care systems are aware of their disease and how to achieve their treatment targets. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The CARTaGENE study evaluated BP, lipid, and diabetes profiles as well as corresponding treatments in 20,004 random individuals between 40 and 69 years of age. Participants had free access to health care and were recruited from four regions within the province of Quebec, Canada in 2009 and 2010. RESULTS: CKD (Chronic Kidney Disease Epidemiology Collaboration equation; <60 ml/min per 1.73 m(2)) was present in 4.0% of the respondents, and hypertension, diabetes, and hypercholesterolemia were reported by 25%, 7.4%, and 28% of participants, respectively. Self-awareness was low: 8% for CKD, 73% for diabetes, and 45% for hypercholesterolemia. Overall, 31% of patients with hypertension did not meet BP goals, and many received fewer antihypertensive drugs than appropriately controlled individuals; 41% of patients with diabetes failed to meet treatment targets. Among those patients with a moderate or high Framingham risk score, 53% of patients had LDL levels above the recommended levels, and many patients were not receiving a statin. Physician checkups were not associated with greater awareness but did increase the achievement of targets. CONCLUSION: In this population with access to publicly funded health care, CKD and cardiovascular risk factors are common, and self-awareness of these conditions is low. Recommended targets were frequently not achieved, and treatments were less intensive in those patients who failed to reach goals. New strategies to enhance public awareness and reach guideline targets should be developed.