Mycophenolate mofetil in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis: a prospective pharmacokinetics and clinical study.

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) treatment strategy is based on immunosuppressive agents. Little information is available concerning mycophenolic acid (MPA) and the area under the curve (AUC) in patients treated for AAV. We evaluated the variations in pharmacokinetics for MPA in patients with AAV and the relationship between MPA-AUC and markers of the disease. MPA blood concentrations were measured through the enzyme-multiplied immunotechnique (C(0), C(30), C(1), C(2), C(3), C(4), C(6) and C(9)) to determine the AUC. Eighteen patients were included in the study. The median (range) MPA AUC(0-12) was 50·55 (30·9-105·4) mg/h/l. The highest coefficient of determination between MPA AUC and single concentrations was observed with C(3) (P < 0·0001) and C(2) (P < 0·0001) and with C(4) (P < 0·0005) or C(0) (P < 0·001). Using linear regression, the best estimation of MPA AUC was provided by a model including C(30), C(2) and C(4): AUC = 8·5 + 0·77 C(30) + 4·0 C(2) + 1·7 C(4) (P < 0·0001). Moreover, there was a significant relationship between MPA AUC(0-12) and lymphocyte count (P < 0·01), especially CD19 (P < 0·005), CD8 (P < 0·05) and CD56 (P < 0·05). Our results confirm the interindividual variability of MPA AUC in patients treated with MMF in AAV and support a personalized therapy according to blood levels of MPA.

The influence of sex on renal function decline in people with Type 2 diabetes.

AIMS: Several reports have suggested a relationship between male sex and albuminuria in Type 2 diabetes, but impact on renal function decline has not been established. Our aim was to describe the influence of sex on renal function decline in Type 2 diabetes. METHODS: SURDIAGENE, an inception cohort, consisted in 1470 people with Type 2 diabetes. Patients without renal replacement therapy and with ≥ 3 serum creatinine determinations during follow-up prior to end-stage renal disease were included in the study. Estimated glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Primary outcome was steep estimated glomerular filtration rate (eGFR) decline, defined as a yearly slope value lower than -3.5 ml min(-1) 1.73 m(-2). Secondary outcomes were estimated glomerular filtration rate trajectories according to sex and occurrence of end-stage renal disease. RESULTS: A total of 22 914 serum creatinine determinations were considered in 1146 participants (60% men), aged 65 ± 11 years, with a median follow-up duration of 5.7 years (range 0.1-10.2). Median yearly estimated glomerular filtration rate slope was -1.31 ml min(-1) 1.73 m(-2) in women and -1.77 ml min(-1) 1.73 m(-2) in men (P < 0.001). Men were more likely than women to develop end-stage renal disease (22 men vs. 7 women; P(log-rank) = 0.03). Male sex was an independent risk factor of steep estimated glomerular filtration rate decline [adjusted odds ratio = 1.33 (1.02-1.76), P = 0.04] after adjustment for age, time from diagnosis of Type 2 diabetes, glycated haemoglobin, systolic blood pressure and urinary albumin:creatinine ratio. A multivariable linear mixed-effects model showed a significant difference of estimated glomerular filtration rate trajectories between men and women (P < 0.001). CONCLUSION: Male sex is an important independent factor associated with renal function decline in Type 2 diabetes.

CMV infection in the donor and increased kidney graft loss: impact of full HLA-I mismatch and posttransplantation CD8(+) cell reduction.

Despite a large body of literature, the impact of chronic cytomegalovirus (CMV) infection in donor on long-term graft survival remains unclear, and factors modulating the effect of CMV infection on graft survival are presently unknown. In this retrospective study of 1279 kidney transplant patients, we analyzed long-term graft survival and evolution of CD8(+) cell population in donors and recipients by CMV serology and antigenemia status. A positive CMV serology in the donor was an independent risk factor for graft loss, especially among CMV-positive recipients (R(+) ). Antigenemia was not a risk factor for graft loss and kidneys from CMV-positive donors remained associated with poor graft survival among antigenemia-free recipients. Detrimental impact of donor's CMV seropositivity on graft survival was restricted to patients with full HLA-I mismatch, suggesting a role of CD8(+) cells. In R(+) patients with positive CMV antigenemia during the first year, CD8(+) cell count did not increase at 2 years posttransplantation, in contrast to R(-) recipients. In addition, marked CD8(+) -cell decrease was a risk factor of graft failure in these patients. This study identifies HLA-I full mismatch and a decrease of CD8(+) cell count at 2 years as important determinants of CMV-associated graft loss.

New sampling strategy using a Bayesian approach to assess iohexol clearance in kidney transplant recipients.

BACKGROUND: Glomerular filtration rate (GFR) measurement is a major issue in kidney transplant recipients for clinicians. GFR can be determined by estimating the plasma clearance of iohexol, a nonradiolabeled compound. For practical and convenient application for patients and caregivers, it is important that a minimal number of samples are drawn. The aim of this study was to develop and validate a Bayesian model with fewer samples for reliable prediction of GFR in kidney transplant recipients. METHODS: Iohexol plasma concentration-time curves from 95 patients were divided into an index (n = 63) and a validation set (n = 32). Samples (n = 4-6 per patient) were obtained during the elimination phase, that is, between 120 and 270 minutes. Individual reference values of iohexol clearance (CL(iohexol)) were calculated from k (elimination slope) and V (volume of distribution from intercept). Individual CL(iohexol) values were then introduced into the Bröchner-Mortensen equation to obtain the GFR (reference value). A population pharmacokinetic model was developed from the index set and validated using standard methods. For the validation set, we tested various combinations of 1, 2, or 3 sampling time to estimate CL(iohexol). According to the different combinations tested, a maximum a posteriori Bayesian estimation of CL(iohexol) was obtained from population parameters. Individual estimates of GFR were compared with individual reference values through analysis of bias and precision. A capability analysis allowed us to determine the best sampling strategy for Bayesian estimation. RESULTS: A 1-compartment model best described our data. Covariate analysis showed that uremia, serum creatinine, and age were significantly associated with k(e), and weight with V. The strategy, including samples drawn at 120 and 270 minutes, allowed accurate prediction of GFR (mean bias: -3.71%, mean imprecision: 7.77%). With this strategy, about 20% of individual predictions were outside the bounds of acceptance set at ± 10%, and about 6% if the bounds of acceptance were set at ± 15%. CONCLUSIONS: This Bayesian approach can help to reduce the number of samples required to calculate GFR using Bröchner-Mortensen formula with good accuracy.

Mothers without HLA antibodies before transplantation have a low risk of alloimmunization post-transplantation.

Human leukocyte antigen antibodies (HLA Abs) are associated with poor renal graft outcome. We selected 134 first kidney transplant recipients without HLA Ab (LABScreen® Luminex) before transplantation despite previous allogeneic exposure whether through blood transfusion (BT) and/or pregnancy (PR). We screened these patients for HLA Ab post-transplantation (yearly) and determined the risk of HLA Ab and donor-specific antibody (DSA) appearance according to BT/PR in a univariate and a multivariate model. Among the 134 patients (43 males/91 females), 56 were BT+/PR-, 41 BT-/PR+ and 37 BT+/PR+. Median delay between last PR or BT and transplantation were 25.9 years (0.5-47.8) and 8 months (0.8-128.0), respectively. Median number of PR and BT were 2 (1-11) and 3 units (1-28), respectively. After transplantation (median follow-up: 47.5 months), 13 patients (9.7%) had HLA Ab and 10 DSA, mainly directed against class II HLA (HLA Ab: 10/13, DSA: 9/10). The risk of HLA Ab and DSA appearance was significantly lower in patients with PR before transplantation (P = 0.032 and P = 0.009, respectively). The risk of DSA appearance (hazard ratio = 0.17, P = 0.027) remained significantly lower after adjustment on donor age, acute rejection and number of class I/II HLA mismatches. In conclusion, we show that parous women non-immunized are at low risk of HLA Ab production after transplantation.

Prognostic value of absent end-diastolic flow within the first week following renal transplantation.

BACKGROUND: Doppler sonogram of the graft is used as a routine assessment in renal transplantation. When the resistance index (RI) equals 1, absent end-diastolic flow (AEDF) is observed; the prognostic value of AEDF is presently unknown. PATIENTS AND METHODS: Between 1988 and 1996, 342 patients received a first cadaveric kidney transplant in our ward. AEDF was observed in 30 patients who were compared with 60 controls who showed an RI < 0.75 within the first 7 days after transplantation. They were matched for year of transplantation (+/-1 year); recipient age (+/-2 years); recipient sex; and HLA antibodies (3 classes: 0%, 1-75%, >75%). The follow-up was 4 years. RESULTS: AEDF was observed at day 1 in 64%, at day 3 in 96%, and at day 7 in 28%. Recipient age, donor age, recipient sex, cold and warm ischemia durations, HLA A, B, and DR mismatches, and cytomegalovirus (CMV) status were not different between the 2 groups. Immediate graft function and 3- to 24-month creatinine levels were better in the control than the AEDF group. However, there was no difference in serum creatinine at 3 and 4 years or in patient and graft survivals during follow-up. CONCLUSIONS: AEDF observed within the first week following transplantation is associated with impaired renal functional recovery. However, whether AEDF is a prognostic marker of poor long-term graft function or survival remains to be proven.

Impact of a polymorphism in the IL-12p40 gene on the outcome of kidney transplantation.

A number of factors interfere with the outcome of renal transplantation. Revealing genetic factors that impact on graft outcome may have consequences for clinical practice. Interleukin-12 (IL-12), by stimulating interferon gamma (IFNgamma) production, plays a crucial role in immune responses against both graft and viral agents. An A-to-C single nucleotide polymorphism (SNP) within the 3'-untranslated region (3'UTR) of the IL-12p40 gene has been reported to be both functionally and clinically relevant. Since the impact of this SNP on kidney graft outcome has never been reported, we investigated the impact of the 3'UTR polymorphism on clinical events after transplantation among 253 kidney recipients transplanted between 1995 and 2003. The polymorphism was genotyped using the restriction fragment length polymorphism method. Our results showed that the 3'UTR polymorphism affected neither graft survival (P = .768) nor the occurrence of delayed graft function (DGF; P = .498). C allele carriers in our study displayed more acute rejections in the first year than patients with the A/A genotype, but it did not reach statistical significance (P = .108). In contrast, the C allele appeared to be a significant risk factor for cytomegalovirus infection (odds ratio = 1.77; P = .027). In conclusion, IL12B 3'UTR polymorphism did not affect graft survival, DGF, or acute rejection episodes, but had an impact on the occurrence of cytomegalovirus infection.

Early pulse pressure and low-grade proteinuria as independent long-term risk factors for new-onset diabetes mellitus after kidney transplantation.

Risk factors for new-onset diabetes after transplantation (NODAT) need to be assessed in large cohorts. We retrospectively evaluated the impact of early (3 and 6 months after transplantation) proteinuria, urinary albumin excretion (UAE) and arterial pressure on NODAT in 828 Caucasian renal transplant recipients (median follow-up: 5.3 years; 5832 patient-years). The 10- and 20-year incidence of NODAT was 15.0% and 22.0%, respectively. Low-grade (<1 g/day) (HR: 2.04 [1.25-3.33], p = 0.0042) and very low-grade (<0.3 g/day) (HR: 2.21 [1.32-3.70], p = 0.0025) proteinuria were independent risk factors for NODAT. There was a dose-dependent relationship across UAE categories (increasing risk from normoalbuminuria to macroalbuminuria) with NODAT. Tacrolimus, sirolimus and beta-blockers (HR: 1.86 [1.07-3.22], p = 0.0277) were significantly associated with NODAT even after multiple adjustments, but not diuretics, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Systolic arterial pressure (HR per 10 mmHg: 1.16 [1.03-1.29], p = 0.0126) and pulse pressure (HR: 1.26 [1.12-1.43], p = 0.0002) were associated with NODAT. Only pulse pressure remained significant after adjustments. Patients at highest risks had early proteinuria and pulse pressure >60 mmHg. Early low-grade proteinuria and pulse pressure (in addition to beta-blockers) constitute independent risk factors for NODAT; they may be markers of the metabolic syndrome and/or vascular damage in renal transplant recipients.

[BIRD: a large database using renal function parameters in France]. / BIRD: base de données sur la fonction rénale en région Centre.

The incidence of End-stage renal disease increases in most Western countries including in France. Few data regarding the incidence of mild renal dysfunction are scarce in the general population. The aim of the present study (BIRD study) was to collect in a database the results of creatinine measurements in the general population from a large area (Région Centre), and assess the percentage of patients with mild renal dysfunction (using the Cockcroft formula). This database was financed by the URCAM (social security from the Région Centre). Data from laboratories were regularly sent to the database through an automatic process. Regular ou emails then were sent to physicians in charge of the patient in order to collect information on patient's history of renal and cardiovascular disease. We were able to collect more than 100,000 creatinine measurements (in roughly 70,000 patients) with the participation of 27 laboratories in the Région Centre. The percentage of patients with glomerular filtration rate < 60 mL/min was 10% in patients 60 and older, 25% in patients with 70 and older and 75% in patients 75 and older. Data coming from the physicians indicated that patients with renal risk were also at high cardiovascular risk. However, these patients are not systematically identified as having renal dysfunction, which explains why diagnosis and appropriate management often are delayed (sonogram was performed in only 25% of patients and 75% of patients never saw a nephrologist). Information regarding assessment of renal function and appropriate management should improve this situation.

[Microalbuminuria and urinary albumin excretion: French guidelines]. / Microalbuminurie et excrétion urinaire d'albumine: recommandations pour la pratique clinique.

UNLABELLED: Measurement of urinary albumin excretion (UAE) may be done on a morning urinary sample or on a 24 hour-urine sample. Values defining microalbuminuria are: - 24-hour urine sample: 30-300 mg/24 hours - Morning urine sample: 20-200 mg/mL or 30-300 mg/g creatinine or 2.5-25 mg/mmol creatinine (men) or 3.5-35 mg/mol (women). - Timed urine sample: 20-200 mug/min. The optimal use of semi-quantitative urine test-strip is not clearly defined. It is generally believed that microalbuminuria reflects a generalized impairment of the endothelium; however, no definite proof has been shown in humans. In diabetic subjects, microalbuminuria is a marker of increased risk of cardiovascular (CV) and renal morbidity and mortality in type 1 and type 2 diabetic subjects. The increase in UAE during follow-up is also a marker of CV and renal risk in type 1 and type 2 diabetic subjects; its decrease during follow-up is associated with lower risks. In non-diabetic subjects, microalbuminuria is a marker of increased risk for diabetes mellitus, deterioration of the renal function, CV morbidity and all-cause mortality. It is a marker of increased risk for the development of hypertension in normotensive subjects, and is associated with unfavorable outcome in patients with cancer and lymphoma. Persistence or elevation of UAE overtime is associated with deleterious outcome in some hypertensive subjects. Measurement of UAE may be recommended in hypertensive subjects with 1 or 2 CV risk factors in whom CV risk remains difficult to assess, and in those with refractory hypertension: microalbuminuria indicates a high CV risk and must lead to strict control of arterial pressure. Studies focused on microalbuminuria in non-diabetic, non-hypertensive subjects are limited; most of them suggest that microalbuminuria predicts CV complications and deleterious outcome as it is in diabetic or hypertensive subjects. Subjects with a history of CV or cerebrovascular disease have an even greater CV risk if microalbuminuria is present than if it is not; however, in all cases, therapeutic intervention must be aggressive regardless of whether microalbuminuria is present or not. It is not recommended to measure UAE in non-diabetic non-hypertensive subjects in the absence of history of renal disease. Monitoring of renal function (UAE, serum creatinine and estimation of GFR) is annually recommended in all subjects with microalbuminuria. MANAGEMENT: in patients with microalbuminuria, weight reduction, sodium restriction (< 6 g/day), smoking cessation, strict glucose control in diabetic subjects, strict arterial pressure control are necessary; in diabetic subjects: use of maximal doses of ACEI or ARB are recommended; ACEI/ARB and thiazides have synergistic actions on arterial pressure and reduction of UAE; in non-diabetic subjects, any of the five classes of anti-hypertensive medications (ACEI, ARB, thiazides, calcium channel blockers or beta-blockers) can be used.

Five-year predictive factors of type 2 diabetes in men with impaired fasting glucose.

AIM: The outcome of 743 French men (age 20-60) with impaired fasting glucose (IFG) [blood glucose 6.1-6.9 mmol/l] at T1 was evaluated 5 years later, at T2. METHODS: Personal and family medical history, smoking, nutritional habits, physical activity, blood pressure, body mass index (BMI) and waist girth, fasting biological data were collected at T1 and T2. Predictive factors for developing diabetes were compared between those who returned to normal fasting glucose and those who had diabetes, before and after adjustment for age, BMI, glucose and triglyceride (TG) levels. RESULTS: At T2, 44%, 39%, 17% were classified as normal fasting plasma glucose (FPG), IFG or diabetic, respectively. Odd ratios for diabetes were 4.2 for men with a family history of diabetes (FHD), 3.4 if BMI > or = 25 kg/m(2), 2.9 if waist girth > or = 90 cm, 2.8 if TG > or = 2 mmol/l and 1.9 if no daily dairy products were eaten. Still significant after adjustment for age, BMI, glucose and TG levels were: FHD (P=0.001), no daily dairy products (P=0.001), high alcohol intake (P=0.02) and low physical activity (P = 0.02). CONCLUSION: No daily dairy products, high alcohol intake and low physical activity were independent predictive factors of a 5-year onset of diabetes after adjusting for BMI, FHD, triglyceride and glucose levels at baseline. For a better prevention of diabetes, these findings give clues for behaviour modifications as soon as IFG is detected.

Microalbuminuria and urinary albumin excretion: French clinical practice guidelines.

Urinary albumin excretion (UAE) may be assayed on a morning urinary sample or a 24 h-urine sample. Values defining microalbuminuria are: 1) 24-h urine sample: 30-300 mg/24 h; 2) morning urine sample: 20-200 mg/ml or 30-300 mg/g creatinine or 2.5-25 mg/mmol creatinine (men) or 3.5-35 mg/mmol (women); 3) timed urine sample: 20-200 mug/min. The optimal use of semi-quantitative urine test-strip is not clearly defined. It is generally believed that microalbuminuria reflects a generalized impairment of the endothelium; however, no definite proof has been obtained in humans. IN DIABETIC SUBJECTS: Microalbuminuria is a marker of increased risk of cardiovascular (CV) and renal morbidity and mortality in type 1 and type 2 diabetic subjects. The increase in UAE during follow-up is associated with greater CV and renal risks in type 1 and type 2 diabetic subjects; its decrease during follow-up is associated with lower risks. IN NON-DIABETIC SUBJECTS: Microalbuminuria is a marker of increased risk for diabetes mellitus, deterioration of renal function, CV morbidity and all-cause mortality. It is a marker of increased risk for the development of hypertension in normotensive subjects, and is associated with unfavorable outcome in patients with cancer and lymphoma. Persistence of elevated UAE during follow-up is associated with poor outcome in some hypertensive subjects. Measurement of UAE may be recommended in hypertensive medium-risk subjects with 1 or 2 CV risk factors in whom CV risk remains difficult to assess, and in those with refractory hypertension: microalbuminuria indicates a high CV risk and must lead to strict control of arterial pressure. Studies focused on microalbuminuria in non-diabetic non-hypertensive subjects are limited; most of them suggest that microalbuminuria predicts CV complications and deleterious outcome. Subjects with a history of CV or cerebrovascular disease have an even greater CV risk if microalbuminuria is present than if it is not; however, in all cases, therapeutic intervention must be aggressive regardless of whether microalbuminuria is present or not. It is not recommended to measure UAE in non-diabetic non-hypertensive subjects in the absence of history of renal disease. Monitoring of renal function (UAE, serum creatinine and estimation of GFR) is recommended annually in all subjects with microalbuminuria. MANAGEMENT: In patients with microalbuminuria, weight reduction, sodium restriction (<6 g per day), smoking cessation, strict glucose control in diabetic subjects, strict arterial pressure control are necessary; in diabetic subjects: use of maximal doses of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are recommended; ACEI/ARB and thiazides have synergistic actions on arterial pressure and reduction of UAE; in non-diabetic subjects, any of the five classes of anti-hypertensive medications (ACEI, ARB, thiazides, calcium channel blockers or beta-blockers) can be used.

[French as 2005-recommendations on the management of arterial hypertension]. / Les recommandations HAS 2005(1) sur la prise en charge des adultes atteints d'hypertension artérielle quelles nouveautés?

Self blood pressure measurements (home BP) and/or ambulatory BP measurements are recommended in mild to moderate hypertension (140/90 - 179/109 mmHg) in order to confirm sustained hypertension and identify white coat and masked hypertension. The evaluation of target organ damages (TOD) has to be integrated in cardiovascular risk estimate and taken into account in the management of hypertensive patients. Beside echocardiography, there is a place for the screening of microalbuminuria in non diabetic hypertensive patients, but these investigations should not be performed systematically. Arterial stiffness evaluation and carotid intima-media thickness quantification are not yet recommended. Cardiovascular risk (CV risk) estimate plays a pivotal role in the therapeutic decision and strategy. The cardiovascular risk grade is based on [1] the list of cardiovascular risk factors (same list AFSSAPS recommendations on dyslipidemia), [2] the presence or absence of TOD and [3] cardiovascular complications: "low", "medium", and "high" CV risk. Lifestyle modifications are recommended in all hypertensive patients. Five antihypertensive drugs are recommended for first line therapy: beta-blockers, thiazide diuretics, ACEIs, ARA II and CCBs (and fixed low dose combinations with AFSSAPS agreement for first line). In order to initiate the treatment, Evidence-based therapy (according to clinical trials conducted in different clinical situations), certain comorbid conditions (compelling indications), efficacy and side-effects in a previous experience, and the cost are the determinants of the first choice. Most hypertensive patients require more than one agent to achieve target blood pressure and for second line therapy the recommended combinations are: betablockers-diuretics, ACEIs-diuretics, ARAII-diuretics, betablockers-CCBs (DHP), ACEIs-CCBs, ARA II-CCBs and CCBs-diuretics. The delay to establish a combination therapy depend on CV risk. The BP goals are those recommended by ESH-ESC 2003: BP<140/90 mmHg in all, BP<130/80 mmHg in diabetic patients and in patients with chronic renal failure. Beside lowering BP, the reduction in proteinuria <500 mg/24 h is a new goal in these high risk patients. These guidelines provide a tool for every day practice and applicability should be evaluated.

[Ten-year incidence of high blood pressure in the general population: influence of clinical parameters, and implication for screening strategies]. / Incidence à 10 ans de l'HTA dans la population générale: rôle des paramètres démographiques et cliniques, et implication pour la surveillance des normotendus.

BACKGROUND: International guidelines recommend to modulate the periodicity of hypertension screening according to the initial level of blood pressure (BP). The aim of our study was to evaluate other factors that could be useful to optimise the screening for hypertension. METHODS: 9777 normotensive volunteers (4151 men, 5626 women) aged 16 to 68, studied at a 10 year interval during systematic health check ups (standardised questionnaire, clinical examination, biological tests) were included. We determined the 10-year incidence of high BP (systolic BP >or=140 mmHg and/or diastolic BP >or=90 mmHg and/or anti-hypertensive treatment). The role of potential risk factors for hypertension was assessed. RESULTS: The 10 year incidence of high BP was 19.9%. It was associated with the initial level of BP (OR=2.02 and 1.81 per +10 mmHg of systolic and diastolic BP, respectively, p<0.0001). Initial age and BMI were strongly associated with the incidence of a high BP (OR=1.88 / + 10 years and 1.18 / + 1 kg/m2, p<0.0001) after adjustment for the initial systolic BP. In men, a low reported physical activity level, alcohol consumption, and current smoking were independent risk factors (Table1). [table: see text] CONCLUSION: These results suggest that the recommendations for the screening of hypertension should not be based solely on the initial level of BP.

Sex hormone levels are not associated with progression of renal disease in male patients with T2DM.

BACKGROUND: Greater renal function decline (RFD) in type 2 diabetes (T2DM) has been suggested in men compared with women, and imbalances in estrogen/androgen levels have been associated with cardiovascular disease mortality in elderly men, but it remains unclear whether sex hormone disequilibrium is related to diabetic nephropathy (DN) in men with T2DM. OBJECTIVE: This study examined the relationship between sex steroid concentrations and renal outcomes in male T2DM patients. POPULATION AND METHODS: Total testosterone (T), total estradiol (E2), sex hormone-binding globulin (SHBG), and total and calculated free (cf) E2/T ratios were compared in 735 male T2DM patients with (n=513) and without (n=222) DN, using a cross-sectional approach. Also, in a pilot complementary prospective nested case-control cohort, total E2/total T and cfE2/cfT were evaluated according to a hard renal outcome (HRO): end-stage renal disease/doubling of baseline serum creatinine (36 HRO cases, 72 HRO controls) and rate of eGFR decline (68 rapid vs 68 slow RFD). RESULT: With the cross-sectional approach, E2 and cfE2 were higher in DN cases vs DN controls (95.5 vs 86.8pmol/L [P=0.0246] and 2.59 vs 2.36pmol/L [P=0.005], respectively). The difference in E2 persisted on multivariate analysis. In the prospective approach, E2 and T concentrations, and total E2/total T and cfE2/cfT2 ratios did not differ in HRO cases vs controls or in patients with rapid vs slow RFD. CONCLUSION: Although positively related to DN in the cross-sectional analysis, progression of renal disease in male patients with T2DM was not related to either sex hormone levels or aromatase index as reflected by E2/T ratio.

Estimation of the glomerular filtration rate through different methods in kidney transplant recipients: correlation with the creatinine clearance measurement.

The measurement of the glomerular filtration rate (GFR) is an important tool for physicians to follow kidney transplant recipients. Indeed, renal function has been shown to be predictive of graft outcome in retrospective studies. Several methods have been proposed to measure GFR. In the present study we evaluated the correlation of GFR between a reference method (calculation through the urine to plasma ratio of creatinine [UV/P] formula) and three estimation equations (Cockcroft and Gault; Nankivell; modification of diet in renal disease) in 81 kidney transplant recipients at 3 and 12 months posttransplantation. We showed a significant correlation between the three predictive formulas and UV/P, but none of the predictive equations showed an excellent correlation. The best correlation between an estimation equation and the UV/P formula was the CG formula. Further studies are required to compare the estimated GFR with better reference methods, such as the use of isotopic markers in kidney graft recipients.

[Larger waist circumference is a predictive factor for the occurrence of microalbuminuria in a non-diabetic population]. / Un tour de taille élevé est un facteur prédictif de survenue d'une microalbuminurie dans une population non diabétique.

Obesity and insulin resistance are directly associated with the presence of microalbuminuria. However, the prospective relationship between abdominal adiposity and the occurrence of micro-albuminuria has been little studied in a non-diabetic population. From the DESIR cohort, we examined whether waist circumference was associated with the incidence of micro-albuminuria at 6 years (D6). The study evaluated 2738 non-diabetic subjects without micro-albuminuria at inclusion who were then followed prospectively. At 6 years, 254 individuals (9.3%) had developed pathological micro-albuminuria (> or =20 mg/l) measured at micturation. In both sexes, the incidence of micro-albuminuria was associated with increased waist circumference and blood pressure, but not with blood glucose levels, lipid parameters or body mass index. Subjects with a higher waist circumference at inclusion were at a higher risk of having micro-albuminuria at 6 years compared to those with a normal waist circumference. Logical regression analysis showed that waist circumference as a continuous value, or greater than 94 cm for males and 88 cm for females, were predictive factors for the incidence of micro-albuminuria, after adjustment for age, hypertension, ACE inhibitor usage, fibrinogen, and blood glucose level. Abdominal adiposity is thus linked in both sexes to the development of microalbuminuria, which underlines the importance of measuring waist circumference when assessing risk factors for renal lesions in non-diabetic hypertensives.

Urinary and genital infections in patients with diabetes: How to diagnose and how to treat.

Diabetes is a predisposing factor for urinary tract and genital infections in both women and men. Sodium-glucose cotransporter-2 (SGLT2) inhibitors constitute a novel therapeutic class indicated for type 2 diabetes (T2D) patients, and are already on the market in a few countries in Europe. They decrease glycaemia mainly by enhancing glucose excretion in urine by reducing renal glucose reabsorption via the action of SGLT2 in the kidneys. In general, they are well tolerated, but their mode of action results in specific side effects as well as an increased risk of genital (vulvovaginitis and balanitis) and urinary tract infections, for which T2D patients are already at high risk, reported within the first 6 months of treatment. Usually these infectious events are successfully treated with standard therapies, but diabetologists are not accustomed to dealing with them. The aim of this review is to describe the different types of lower urinary tract and genital infections, and the treatment strategies currently available for patients with diabetes.

Management of resistant hypertension: expert consensus statement from the French Society of Hypertension, an affiliate of the French Society of Cardiology.

To improve the management of resistant hypertension, the French Society of Hypertension, an affiliate of the French Society of Cardiology, has published a set of eleven recommendations. The primary objective is to provide the most up-to-date information based on the strongest scientific rationale and that is easily applicable to daily clinical practice. Resistant hypertension is defined as uncontrolled blood pressure on office measurements and confirmed by out-of-office measurements despite a therapeutic strategy comprising appropriate lifestyle and dietary measures and the concurrent use of three antihypertensive agents including a thiazide diuretic, a renin-angiotensin system blocker (ARB or ACEI) and a calcium channel blocker, for at least 4 weeks, at optimal doses. Treatment compliance must be closely monitored, as must factors that are likely to affect treatment resistance (excessive dietary salt intake, alcohol, depression, drug interactions and vasopressor drugs). If the diagnosis of resistant hypertension is confirmed, the patient should be referred to a hypertension specialist to screen for potential target organ damage and secondary causes of hypertension. The recommended treatment regimen is a combination therapy comprising four treatment classes, including spironolactone (12.5-25 mg per day). In the event of a contraindication or a non-response to spironolactone, or if adverse effects occur, a ß-blocker, an α-blocker, or a centrally acting antihypertensive drug should be prescribed. Because renal denervation is still undergoing assessment for the treatment of hypertension, this technique should only be prescribed by a specialist hypertension clinic.

Prorenin in diabetes mellitus.

A rise in plasma prorenin often precedes the onset of vascular injury in patients with diabetes mellitus. Plasma prorenin measurements may be useful for predicting which patients will develop vascular injury and for monitoring the progression of the disease. A hypothesis is presented that accounts for these relationships and for the cosecretion of prorenin and renin into the circulation.