Acute kidney injury in patients with chronic liver disease.

Acute kidney injury (AKI) is a frequent clinical event in patients with liver disease, compounding their prognosis. Furthermore, it is likely that the occurrence of AKI has a detrimental impact on the subsequent renal function and the long-term survival of these patients. Recently, some authors advocated the use of new diagnostic criteria for detecting acute kidney injury in patients with cirrhosis. These criteria are based on the rapidity and extent of the creatinine increase comparing to the basal creatinine and also on the kinetics of diuresis decrease. Although their validity in this population requires further studies to be clearly established, these new criteria could have two advantages: (1) to allow earlier diagnosis of AKI and, thus, hepatorenal syndrome for which earlier intervention could improve patients' survival; and (2) to promote more intensive monitoring of renal function in these patients with high risk of AKI. Finally, recent practice guidelines about the prevention and treatment of general AKI have been published which should be useful in optimising the management of AKI in cirrhotic patients.

Postconditioning with cyclosporine a reduces early renal dysfunction by inhibiting mitochondrial permeability transition.

BACKGROUND: Ischemia-reperfusion (IR) injury leads to mitochondrial permeability transition pore opening, which contributes to cell death. The aim of this study is to determine whether ischemic or pharmacological postconditioning with cyclosporine A (CsA) might protect the kidney from lethal reperfusion injury. METHODS: Male mice underwent a unilateral (right) nephrectomy followed by 30 minutes of contralateral (left) clamping of the renal artery. We studied 4 groups at 20 minutes and 24 hours of reperfusion: a sham group (n = 4), an ischemic group (n = 6), CsA-postconditioned group (postcond-CsA, injection of 3 mg/kg of CsA 5 minutes before the end of ischemia, (n = 6), and an ischemic postconditioning (IPC) group (n = 6), consisting of 3 cycles of 30 seconds of renal ischemia with 30 seconds intervening reperfusion. After 24 hours of reperfusion, we measured plasma creatinine, urea, and histological kidney injury. The kidney mitochondria were isolated to assess the mitochondria calcium retention capacity and oxidative phosphorylation. RESULTS: At 24 hours after reperfusion, serum creatinine decreased in postcond-CsA and IPC compared to ischemic group. The histological score was also significantly improved with postcond-CsA and IPC. At 20 minutes and 24 hours of reperfusion, calcium retention capacity was decreased significantly in the ischemic group. The mitochondrial respiration stay decreased in the ischemic group at 24 hours of reperfusion, whereas the respiration was improved significantly in the postcond-CsA and IPC group. Bax and cleaved caspase 3 decreased in PostCsA and IPC group. CONCLUSIONS: Our results suggest that IPC and CsA, administered immediately before reperfusion, protect the kidney from lethal injury.

Early mortality in dialysis and adequacy of predialysis renal care: the picture is more complex than we thought.

Two new studies examine clinical events during early dialysis. Foley et al. underline a probable ascertainment bias affecting the mortality rate during the first 6 weeks and find that age is the major risk factor for very early mortality, which can be amplified by short time of predialysis nephrology care. Singhal et al. show that adequacy of predialysis renal care is determined not only by the timing of the nephrology referral but also by the number and timing of visits.

To live with normal GFR: when higher is not better.

Eriksen et al. unmask an independent link between a high glomerular filtration rate (GFR) and subclinical cardiovascular damage in a large cohort of nondiabetic middle-aged people in Tromsø, Norway. Although others have previously reported an association between estimated GFR and cardiovascular risk factors, the present work is remarkable in that it relies on measured GFR, thus overcoming potential bias of the limited accuracy of common GFR estimates in individuals with high GFR values.

Evaluation of renal function in patients with cirrhosis: where are we now?

In the clinical context of the patients with liver cirrhosis, accurate evaluation of the renal function is potentially crucial. Indeed, it can lead to early diagnosis of both acute kidney injury and chronic kidney disease and to reliable characterization of the renal status of the patient before performing a liver transplantation. Despite some limitations, the assay of serum creatinine (SCr) is universally used to estimate glomerular filtration rate (GFR) because of its wide availability, its simplicity and because it is inexpensive. Nevertheless, several reports show that the value of this assay to estimate GFR is strongly challenged in cirrhotic patients, especially in patients with liver failure and/or severely impaired renal function. This has led to seek new alternatives to estimate more reliably the GFR in these patients. Although the reference methods, based on the utilization of exogenous markers, allow measuring GFR and thereby constitute the "gold standard" to evaluate renal function, they are not feasible in routine clinical practice. Several studies have shown that a cystatin C (CysC) based formula perform better than the SCr-based estimates in cirrhotic patients and the estimation of GFR by these formulas could therefore lead to optimize the management of the patients. A new estimate based on CysC has been recently developed using a large number of patients and the first results regarding the evaluation of its performance are promising, making this new formula the best candidate for a reference estimate of the renal function in cirrhotic patients.

[Physical activity and chronic kidney disease: an update in 2013?]. / Activité physique et maladie rénale chronique : quelles relations en 2013 ?

The practice of physical activity is now a subject of special attention in public health. Indeed, the expected benefits in terms of cardiovascular morbidity and mortality suggest that all physicians should promote it. However, there are few data on the impact of physical activity on the health of patients with chronic kidney disease before the dialysis stage. This review focuses on the relationship between chronic kidney disease and the practice of physical activity. Different tools to assess the level of physical activity helped to highlight a marked deterioration in physical capacity of patients with chronic kidney disease, including during the earliest stages. Although there is currently no specific recommendations regarding the practice of physical activity in patients with renal impairment, it seems desirable to promote it in an appropriate way, based on what is currently advocated for cardiovascular prevention in the general population.

Creatinine- versus cystatine C-based equations in assessing the renal function of candidates for liver transplantation with cirrhosis.

UNLABELLED: Renal dysfunction is frequent in liver cirrhosis and is a strong prognostic predictor of orthotopic liver transplantation (OLT) outcome. Therefore, an accurate evaluation of the glomerular filtration rate (GFR) is crucial in pre-OLT patients. However, in these patients plasma creatinine (Pcr) is inaccurate and the place of serum cystatine C (CystC) is still debated. New GFR-predicting equations, based on standardized assays of Pcr and/or CystC, have been recently recommended in the general population but their performance in cirrhosis patients has been rarely studied. We evaluated the performance of the recently published Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPI-Pcr, CKD-EPI-CystC, and CKD-EPI-Pcr-CystC) and the more classical ones (4- and 6-variable MDRD and Hoek formulas) in cirrhosis patients referred for renal evaluation before OLT. Inulin clearance was performed in 202 consecutive patients together with the determination of Pcr and CystC with assays traceable to primary reference materials. The performance of the GFR-predicting equations was evaluated according to ascites severity (no, moderate, or refractory) and to hepatic and renal dysfunctions (MELD score ≤ or >15 and KDOQI stages, respectively). In the whole population, CystC-based equations showed a better performance than Pcr-based ones (lower bias and higher 10% and 30% accuracies). CKD-EPI-CystC equation showed the best performance whatever the ascites severity and in presence of a significant renal dysfunction (GFR <60 mL/min/1.73 m(2)). CONCLUSION: Pcr-based GFR predicting equations are not reliable in pre-OLT patients even when an IDMS-traceable enzymatic Pcr assay is used. Whenever a CystC-assay traceable to primary reference materials is performed and when a true measurement of GFR is not possible, CystC-based equations, especially CKD-EPI-CystC, may be recommended to evaluate renal function and for KDOQI staging.

[Kidney aging: a predictable and partly avoidable fragility]. / Le vieilissement rénal : une fragilité prévisible et en partie évitable.

The 9th World Kidney Day, on 13 March 2014, was devoted to the topic of renal aging. The proportion of older people in the general population is increasing steadily worldwide, with the most rapid growth in developing countries. This demographic upheaval is a consequence of socioeconomic development and increasing life expectancy. Chronic kidney disease is an important public health problem characterized by poor health outcomes and very high healthcare costs. Chronic kidney disease is a major risk multiplier in patients with diabetes, hypertension, heart disease and stroke, all of which are key causes of death and disability among older people. The prevalence of chronic kidney disease is higher in the elderly, in whom it contributes to the effects of aging. The decrease in renal function with age also compounds the effects of renal disease, whether primary or secondary to systemic or urinary tract disorders. This physiological reduction in functional capacity affects the glomerular filtration rate and renal tubular functions, including water and salt regulation and also the elimination of many drugs. The aging kidney is much more sensitive to toxic insults, especially those due to nonsteroidal antiinflammatory drugs and iodinated contrast agents. Prevention of renal deterioration in the elderly is based on monitoring renal function, adapting medications, and maintaining a regular supply of water and salt.

Impact of prior CKD management in a renal care network on early outcomes in incident dialysis patients: a prospective observational study.

BACKGROUND: Effective therapeutic strategies are available to prevent adverse outcomes in patients with chronic kidney disease (CKD) but their clinical results are hindered by unplanned implementation. Coordination of care emerges as a suitable way to improve patient outcomes. In this study, we evaluated the effect of planned and coordinated patient management within a dedicated renal care network comparatively to standard renal care delivered in nephrology departments of teaching hospitals. METHODS: This observational matched cohort study included 40 patients with CKD stage 4-5 in the network group as compared with a control group of 120 patients matched for age, sex and diabetic status. Main outcome was a composite endpoint of death from cardiovascular cause and cardiovascular events during the first year after dialysis initiation. RESULTS: There was no difference between the two groups neither for the primary outcome (40% vs 41%) nor for the occurrence of death from cardiovascular cause or cardiovascular events. Whereas the proportion of patients requiring at least one hospitalization was identical (83.3% vs 75%), network patients experienced less individual hospitalizations than control patients (2.3 ± 2.0 vs 1.6 ± 1.7) during the year before dialysis start. Patients of the network group had a slower renal function decline (7.7 ± 2.5 vs 4.9 ± 1.1 ml/min/1,73 m(2) per year; p=0.04). CONCLUSIONS: In this limited series of patients, we were unable to demonstrate a significant impact of the coordinated renal care provided in the network on early cardiovascular events in incident dialysis patients. However, during the predialysis period, there were less hospitalizations and a slower slope of renal function decrease.

[Comparison of methods estimating a quantitative parameter: evaluation of the agreement]. / Comparaison des méthodes d'estimation d'un paramètre quantitatif : évaluation de la concordance.

Many quantitative clinical, biological and radiological parameters are useful in medicine for guiding diagnosis and therapy. The nephrologists use such parameters on a daily basis, particularly to assess renal function. In order to use the measurement methods of these parameters in clinical practice, it is mandatory to establish the agreement of the values provided, comparatively to the value obtained by using the reference measurement method of this parameter. This review details the methodology for the validation of methods for estimating quantitative parameters.

[Evaluation of renal oxygen content by BOLD MRI]. / Évaluation du contenu tissulaire rénal en oxygène par la technique IRM BOLD.

Blood Oxygen Level-Dependent (BOLD) MRI signal is a new method of renal functional imaging which allows renal cortical and medullary oxygen contents measurement in a noninvasive way and without injection of potentially nephrotoxic contrast product. Several clinical and experimental studies showed its potential interest in measuring renal oxygen content and its variation during different renal injuries, allowing new progress in the comprehension of the pathophysiology of several nephropathies.

[Natural course of chronic kidney disease]. / Histoire naturelle de la maladie rénale chronique.

The natural history of chronic kidney disease describes a progressive decrease in renal function assessed by glomerular filtration rate. After the initial phase, this decrease is related to the occurence of physiological adaptation mechanisms independent of the primary renal disease. It is accompanied by the gradual appearance of clinical and metabolic abnormalities that can be largely prevented by early management including careful monitoring and appropriate treatments. The main determinants of the risk of progression to end-stage renal failure requiring the use of replacement therapy are initial glomerular filtration rate, as an index of residual renal mass, the amount of proteinuria, and the level of blood pressure. The last two factors are the main targets of nephroprotective treatment based on the blockade of the renin-angiotensin system. Other elements of nephroprotective treatment are parts of a multifactorial approach that identifies and corrects individual factors present in each patient, and prevents acute exacerbations related to intercurrent events or inappropriate interventions. Such a treatment strategy significantly reduces the risk of progression to end-stage renal disease, and of cardiovascular events to which these patients are particularly exposed.

[Contribution of X-ray computed tomography in the evaluation of kidney performance]. / Apport de la tomodensitométrie par rayons X dans l'évaluation de la performance rénale.

X-ray computer assisted tomography scanner is an imaging method based on the use of X-ray attenuation in tissue. This attenuation is proportional to the density of the tissue (without or after contrast media injection) in each pixel image of the image. Spiral scanner, the electron beam computed tomography (EBCT) scanner and multidetector computed tomography scanner allow renal anatomical measurements, such as cortical and medullary volume, but also the measurement of renal functional parameters, such as regional renal perfusion, renal blood flow and glomerular filtration rate. These functional parameters are extracted from the modeling of the kinetics of the contrast media concentration in the vascular space and the renal tissue, using two main mathematical models (the gamma variate model and the Patlak model). Renal functional imaging allows measuring quantitative parameters on each kidney separately, in a non-invasive manner, providing significant opportunities in nephrology, both for experimental and clinical studies. However, this method uses contrast media that may alter renal function, thus limiting its use in patients with chronic renal failure. Moreover, the increase irradiation delivered to the patient with multi detector computed tomography (MDCT) should be considered.

Renal perfusion: noninvasive measurement with multidetector CT versus fluorescent microspheres in a pig model.

PURPOSE: To validate the measurement of renal perfusion with multidetector computed tomography (CT) with a low-rate injection of contrast medium (ie, 3 mL/sec) through a catheter placed peripherally with gamma variate extended modeling in a pig model, compared with a reference method of fluorescent microspheres. MATERIALS AND METHODS: This study was approved by the Institutional Animal Care and Use Committee. Renal perfusion was measured in 10 anesthetized pigs simultaneously with multidetector CT and with fluorescent microspheres, which are the reference standard for measuring regional renal perfusion. In each pig, measurements were obtained under three conditions. These were dopamine infusion, dopamine infusion with vascular expansion, and angiotensin II infusion. Aortic and cortical time-attenuation curves were modeled to measure renal perfusion with the gamma variate model. The renal perfusion measurements with the multidetector CT and that with microspheres were compared with least squares regression analysis and Bland-Altman plots. RESULTS: Perfusion as measured with multidetector CT and that as measured with microspheres were strongly correlated (ρ = 0.93, P < .0001). Multidetector CT renal perfusion with dopamine infusion (3.13 mL/min/g ± 0.53) was not changed after volume expansion (3.37 mL/min/g ± 0.75, P = .35) but was significantly decreased after angiotensin II injection (2.01 mL/min/g ± 0.57, P = .0001). CONCLUSION: Multidetector CT provides reliable measurements of single-kidney perfusion with peripheral low-rate contrast medium injection.

Performance of the chronic kidney disease epidemiology collaboration equation to estimate glomerular filtration rate in diabetic patients.

OBJECTIVE: The best method to estimate glomerular filtration rate (GFR) in diabetic patients is still largely debated. We compared the performance of creatinine-based formulas in a European diabetic population. RESEARCH DESIGN AND METHODS: We compared the performance of Cockcroft and Gault, simplified Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equations in 246 diabetic patients by calculating the mean bias and the interquartile range (IQR) of the bias, 10% (P10) and 30% (P30) accuracies, and Bland-Altman plots. GFR was measured by inulin clearance. RESULTS: For the whole population, the IQR was slightly lower for CKD-EPI, but the mean bias was lower and P10 and P30 were higher for MDRD. Similar results were observed in specific subgroups, including patients with mild renal insufficiency, obese patients, or type 2 diabetic patients. CONCLUSIONS: In our population, the CKD-EPI formula does not exhibit better performance than the simplified MDRD formula for estimating GFR.

Which creatinine and cystatin C equations can be reliably used in children?

BACKGROUND AND OBJECTIVES: Estimation of GFR in children is challenging; reference methods are cumbersome, and formulas have limitations. The aims of this study were to evaluate (1) the new creatinine-based formula recently proposed by Schwartz using a kinetic colorimetric compensated Jaffe technique; (2) some cystatin C-derived formulas (Hoek, Le Bricon, Larsson, Rule, Filler, and Zappitelli) using a nephelemetric technique; and (3) combined formulas using both cystatin and creatinine (Zappitelli and Bouvet). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: These formulas were evaluated in a cross-sectional cohort of 252 children with moderate CKD or normal GFR, in comparison with the reference standard (inulin clearance, iGFR). Mean age, body weight, height, creatinine, and cystatin C were 10.7 ± 4.0 years, 35 ± 15 kg, 137 ± 20 cm, 55 ± 30 µmol/L, and 0.91 ± 0.35 mg/L, respectively. RESULTS: Mean ± SD iGFR was 101 ± 32 ml/min per 1.73 m². When evaluating agreement between these formulas and iGFR (e.g. correlation, Bland Altman plots, bias, and accuracies), there was a good correlation between iGFR and all Le Bricon, Larsson, Rule, and Zappitelli (both) and locally adapted Schwartz and 2009 Schwartz formulas; by contrast, Filler and original 1976 Schwartz formulas overestimated iGFR, whereas Hoek and Bouvet formulas underestimated iGFR. CONCLUSION: Different cystatin C-derived formulas (at least Larsson and Le Bricon) for estimating GFR as well as the Zappitelli combined formula are accurate in addition to the new Schwartz bedside formula in a general pediatric population.

Evolution of renal oxygen content measured by BOLD MRI downstream a chronic renal artery stenosis.

BACKGROUND: A decrease in renal oxygen content can be measured non-invasively by the increase of the R2* value derived from blood oxygen level-dependent magnetic resonance imaging (BOLD MRI). The aim of this study was to test if renal hypoxia occurs in kidneys downstream a chronic and unilateral renal artery stenosis. METHODS: Chronic renal ischaemia was induced in rats using a calibrated clip inserted on the right renal artery. R2* was determined, using a multiple recalled gradient-echo sequence, before and once a week after a clip insertion over 4 weeks, in a group of clipped (n = 8) and sham-operated (n = 7) rats. RESULTS: At baseline, in stenotic kidneys, R2* was higher in the outer stripe of outer medulla (105 ± 4.6) and the outer medulla (99 ± 2.5) than in the cortex (84 ± 2.5; P < 0.002 for comparison with both areas). R2* was unchanged in the cortex, the outer stripe of outer medulla and the outer medulla in stenotic kidneys, sham-operated kidneys and contralateral kidneys during the 4 weeks. Mean blood pressure was higher in rats with clipped kidney than in sham-operated rats from Day 11 and remained increased thereafter. The renal volume increased progressively in sham-operated kidneys and contralateral kidneys, whereas it slightly decreased in stenotic kidneys. CONCLUSIONS: Our study shows that after 4 weeks, no renal hypoxia can be detected in the kidney downstream to a renal artery stenosis, suggesting that atrophy could be induced by other factors.

Hemodynamic responses to acute and gradual renal artery stenosis in pigs.

BACKGROUND: Reduction of renal blood flow (RBF) due to a renal artery stenosis (RAS) can lead to renal ischemia and atrophy. However in pigs, there are no data describing the relationship between the degree of RAS, the reduction of RBF, and the increase of systemic plasma renin activity (PRA). Therefore, we conducted a study in order to measure the effect of acute and gradual RAS on RBF, mean arterial pressure (MAP), and systemic PRA in pigs. METHODS: RAS was induced experimentally in six pigs using an occluder placed around the renal artery downstream of an ultrasound flow probe. The vascular occluder was inflated gradually to reduce RBF. At each inflation step, percentage of RAS was measured by digital subtraction angiography (DSA) with simultaneous measurements of RBF, MAP, and PRA. Data were normalized to baseline values obtained before RAS induction. Piecewise regression analysis was performed between percentage of RAS and relative RBF, MAP, and PRA, respectively. RESULTS: In all pigs, the relationship between the degree of RAS and RBF was similar. RBF decreased over a threshold of 42% of RAS, with a rapid drop in RBF when RAS reached 70%. PRA increased dramatically over a threshold of 58% of RAS (+1,300% before occlusion). MAP increased slightly (+15% before occlusion) without identifiable threshold. CONCLUSIONS: This study emphasizes that the relation between the degree of RAS and RBF and systemic PRA is not linear and that a high degree of RAS must be reached before the occurrence of significant hemodynamic and humoral effects.

What is the best alternative to inulin clearance to estimate GFR in patients with decompensated alcoholic cirrhosis?

BACKGROUND: Accurate evaluation of the glomerular filtration rate (GFR) in patients awaiting liver transplantation is important because they have a greater risk of impaired renal function. A major percentage of these patients have alcoholic cirrhosis, and the accuracy of bedside used GFR estimates have not been specifically evaluated in this group. The aim of this study was to evaluate the validity of the simplified Modification of Diet in Renal Diseases (MDRD) and Cockcroft and Gault (CG) formulas in patients with decompensated alcoholic cirrhosis in comparison to inulin clearance as the reference method. METHODS: GFR estimated by the simplified MDRD and CG formulas were retrospectively compared to the true GFR measured by inulin clearance in a single-centre cohort of 148 patients with decompensated alcoholic cirrhosis. RESULTS: Mean ± standard deviation of age, body mass index, inulin clearance and MDRD and CG estimates were 54.4 ± 6.9 years, 26.5 ± 4.7 kg/m(2), 76.9 ± 28.0 mL/min per 1.73 m(2), 99.4 ± 34.0 mL/min per 1.73 m(2) and 98.7 ± 32.0 mL/min per 1.73 m(2), respectively; 70% of the patients had a GFR, measured by inulin clearance, below 90 mL/min per 1.73 m(2). The difference between estimated GFR and true GFR were 23 ± 23 mL/min per 1.73 m(2) for MDRD and 22 ± 20 mL/min per 1.73 m(2) for Cockcroft and Gault. CONCLUSIONS: The simplified MDRD and CG formulas largely overestimated GFR in patients with decompensated alcoholic cirrhosis. Results of such bedside formulas should be interpreted with caution in these patients.

Early impairment of trabecular microarchitecture assessed with HR-pQCT in patients with stage II-IV chronic kidney disease.

Bone fragility is a complication of chronic kidney disease (CKD). The aim of this study was to assess whether volumetric bone mineral density (vBMD) and microarchitecture could be impaired early in the course of CKD. Bone microarchitecture was examined with a noninvasive 3D imaging technique [high-resolution peripheral quantitative computed tomography (HR-pQCT)] at the tibia and radius in 70 stage II-IV CKD patients older than 50 years of age; controls belonged to two cohorts of healthy subjects comparable for age and gender (OFELY cohort in women and STRAMBO cohort in men). We examined 46 men and 24 women; 19 patients were diabetic. Mean age was 70.8 +/- 8.5 years, mean glomerular filtration rate (GFR) was 34 +/- 12 mL/min per 1.73 m(2), and mean serum parathyroid hormone (PTH) level was 87 +/- 59 pg/mL. Both CKD men and women experienced a moderate but significant trabecular (Tb) impairment, positioning CKD patient values between those of normal and osteopenic controls (e.g., CKD men versus healthy controls: Tb vBMD 172 +/- 35 versus 188 +/- 34 mg HA/cm(3); Tb number 1.75 +/- 0.27 versus 1.86 +/- 0.26 mm(-1), and Tb separation 503 +/- 94 versus 465 +/- 78 microm; p < .05). Cortical thickness (Ct.Th) in men also was significantly decreased compared with healthy controls (e.g., CKD men versus healthy controls: tibial Ct.Th 1171 +/- 331 versus 1288 +/- 283 microm; p < .05). In conclusion, this study, using a noninvasive bone-imaging device, shows for the first time an early impairment of trabecular microarchitecture in stage II-IV CKD patients. Further longitudinal studies should be performed to validate HR-pQCT as a tool for predicting the fracture risk in CKD.