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Chronic kidney disease (CKD) affects over 850 million people globally, and the need to prevent its development and progression is urgent. During the past decade, new perspectives have arisen related to the quality and precision of care for CKD, owing to the development of new tools and interventions for CKD diagnosis and management. New biomarkers, imaging methods, artificial intelligence techniques, and approaches to organizing and delivering healthcare may help clinicians recognize CKD, determine its etiology, assess the dominant mechanisms at given time points, and identify patients at high risk for progression or related events. As opportunities to apply the concepts of precision medicine for CKD identification and management continue to be developed, an ongoing discussion of the potential implications for care delivery is required. The 2022 KDIGO Controversies Conference on Improving CKD Quality of Care: Trends and Perspectives examined and discussed best practices for improving the precision of CKD diagnosis and prognosis, managing the complications of CKD, enhancing the safety of care, and maximizing patient quality of life. Existing tools and interventions currently available for the diagnosis and treatment of CKD were identified, with discussion of current barriers to their implementation and strategies for improving the quality of care delivered for CKD. Key knowledge gaps and areas for research were also identified., (Copyright © 2023 KDIGO: Kidney Disease Improving Global Outcomes. Published by Elsevier Inc. All rights reserved.)

It is unknown whether initiating diuretics on top of renin-angiotensin system inhibitors (RASi) is superior to alternative antihypertensive agents such as calcium channel blockers (CCBs) in patients with chronic kidney disease (CKD). For this purpose, we emulated a target trial in the Swedish Renal Registry 2007-2022 that included nephrologist-referred patients with moderate-advanced CKD and treated with RASi, who initiated diuretics or CCB. Using propensity score-weighted cause-specific Cox regression, we compared risks of major adverse kidney events (MAKE; composite of kidney replacement therapy [KRT], experiencing over a 40% eGFR decline from baseline, or an eGFR under 15 ml/min per 1.73m 2 ), major cardiovascular events (MACE; composite of cardiovascular death, myocardial infarction or stroke), and all-cause mortality. We identified 5875 patients (median age 71 years, 64% men, median eGFR 26 ml/min per 1.73m 2 ), of whom 3165 started a diuretic and 2710 a CCB. After a median follow-up of 6.3 years, 2558 MAKE, 1178 MACE and 2299 deaths occurred. Compared to CCB, diuretic use was associated with a lower risk of MAKE (weighted hazard ratio 0.87 [95% confidence interval: 0.77-0.97]), consistent across single components (KRT: 0.77 [0.66-0.88], over 40% eGFR decline: 0.80 [0.71-0.91] and eGFR under 15ml/min/1.73m 2 : 0.84 [0.74-0.96]). The risks of MACE (1.14 [0.96-1.36]) and all-cause mortality (1.07 [0.94-1.23]) did not differ between therapies. Results were consistent when modeling the total time drug exposure, across sub-groups and a broad range of sensitivity analyses. Thus, our observational study suggests that in patients with advanced CKD, using a diuretic rather than a CCB on top of RASi may improve kidney outcomes without compromising cardioprotection., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Despite recognized geographic and sex-based differences in hemoglobin in the general population, these factors are typically ignored in patients with chronic kidney disease (CKD) in whom a single therapeutic range for hemoglobin is recommended. We sought to compare the distribution of hemoglobin across international nondialysis CKD populations and evaluate predictors of hemoglobin., Methods: In this cross-sectional study, hemoglobin distribution was evaluated in each cohort overall and stratified by sex and estimated glomerular filtration rate (eGFR). Relationships between candidate predictors and hemoglobin were assessed from linear regression models in each cohort. Estimates were subsequently pooled in a random effects model., Results: A total of 58,613 participants from 21 adult cohorts (median eGFR range of 17-49 ml/min) and 3 pediatric cohorts (median eGFR range of 26-45 ml/min) were included with broad geographic representation. Hemoglobin values varied substantially among the cohorts, overall and within eGFR categories, with particularly low mean hemoglobin observed in women from Asian and African cohorts. Across the eGFR range, women had a lower hemoglobin compared to men, even at an eGFR of 15 ml/min (mean difference 5.3 g/l, 95% confidence interval [CI] 3.7-6.9). Lower eGFR, female sex, older age, lower body mass index, and diabetic kidney disease were all independent predictors of a lower hemoglobin value; however, this only explained a minority of variance (R 2 7%-44% across cohorts)., Conclusion: There are substantial regional differences in hemoglobin distribution among individuals with CKD, and the majority of variance is unexplained by demographics, eGFR, or comorbidities. These findings call for a renewed interest in improving our understanding of hemoglobin determinants in specific CKD populations., (© 2023 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.)

The availability of electronic health records and access to a large number of routine measurements of serum creatinine and urinary albumin enhance the possibilities for epidemiologic research in kidney disease. However, the frequency of health care use and laboratory testing is determined by health status and indication, imposing certain challenges when identifying patients with kidney injury or disease, when using markers of kidney function as covariates, or when evaluating kidney outcomes. Depending on the specific research question, this may influence the interpretation, generalizability, and/or validity of study results. This review illustrates the heterogeneity of working definitions of kidney disease in the scientific literature and discusses advantages and limitations of the most commonly used approaches using 3 examples. We summarize ways to identify and overcome possible biases and conclude by proposing a framework for reporting definitions of exposures and outcomes in studies of kidney disease using routinely collected health care data., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: The identification of patients with chronic kidney disease (CKD) at risk of progressing to kidney failure (KF) is important for clinical decision-making. In this study we assesed whether urinary peptidome (UP) analysis may help classify patients with CKD and improve KF risk prediction., Methods: The UP was analyzed using capillary electrophoresis coupled to mass spectrometry in a case-cohort sample of 1000 patients with CKD stage G3 to G5 from the French CKD-Renal Epidemiology and Information Network (REIN) cohort. We used unsupervised and supervised machine learning to classify patients into homogenous UP clusters and to predict 3-year KF risk with UP, respectively. The predictive performance of UP was compared with the KF risk equation (KFRE), and evaluated in an external cohort of 326 patients., Results: More than 1000 peptides classified patients into 3 clusters with different CKD severities and etiologies at baseline. Peptides with the highest discriminative power for clustering were fragments of proteins involved in inflammation and fibrosis, highlighting those derived from α-1-antitrypsin, a major acute phase protein with anti-inflammatory and antiapoptotic properties, as the most significant. We then identified a set of 90 urinary peptides that predicted KF with a c-index of 0.83 (95% confidence interval [CI]: 0.81-0.85) in the case-cohort and 0.89 (0.83-0.94) in the external cohort, which were close to that estimated with the KFRE (0.85 [0.83-0.87]). Combination of UP with KFRE variables did not further improve prediction., Conclusion: This study shows the potential of UP analysis to uncover new pathophysiological CKD progression pathways and to predict KF risk with a performance equal to that of the KFRE., (© 2022 Published by Elsevier Inc. on behalf of the International Society of Nephrology.)

Introduction: Incidence of kidney replacement therapy (KRT) varies widely across countries. Its relations to individual characteristics, nephrology practices for slowing chronic kidney disease (CKD) progression, and KRT access remain unclear., Methods: We investigated intercountry differences in kidney failure (KF) rate, defined by a sustained estimated glomerular filtration rate (eGFR) <15 ml/min per 1.73 m 2 , and separately in KRT incidence, before and after adjusting for risk factors and blood pressure (BP) control or renin-angiotensin-aldosterone system inhibitor (RAASi) prescription practices in the CKD Outcomes and Practice Patterns Study (CKDopps) cohort study., Results: Among 7381 patients with CKD stage 3 to 4 at enrollment, 1297 progressed to KF and 947 initiated KRT over a 3-year follow-up period. Compared to the United States, demographic-adjusted and eGFR-adjusted hazard ratios (HRs) (HRs, 95% confidence intervals [CI]) for a sustained low eGFR were 0.77 (95% CI, 0.57-1.02) in Brazil, 0.90 (95% CI, 0.75-1.08) in France, and 1.03 (95% CI, 0.86-1.03) in Germany. Further adjustment for comorbidities, albuminuria, systolic BP, and RAASi prescription did not substantially change these HRs. In contrast, compared with the United States, the fully-adjusted HR for KRT remained significantly lower in Brazil (0.55, 95% CI 0.39-0.79), higher in Germany (95% CI, 1.36, 1.09-1.69), and similar in France (95% CI, 1.07, 0.81-1.39)., Conclusion: Individual risk factors for CKD progression in nephrology patients appeared to explain most intercountry variations in KF but not KRT incidence. This suggests a prominent role for differences in practices related to KRT initiation or access, but not those for slowing disease progression. This study also shows that using KRT as a KF surrogate may bias estimates of associations with CKD progression risk factors., (© 2022 International Society of Nephrology. Published by Elsevier Inc.)

Objectives: Renin-angiotensin system inhibitors (RASi) are recommended for slowing chronic kidney disease (CKD) progression to kidney failure. Their effectiveness and tolerance as patients age remain uncertain because older patients have often been excluded from clinical trials., Design: CKD-REIN cohort study., Setting and Participants: We studied 2762 patients with CKD stages 3 and 4 and a clinical indication for RASi enrolled between 2013 and 2016 in 40 nephrology clinics nationally representative in France., Methods: The primary outcome was the occurrence of kidney failure or death. The secondary outcomes were the occurrence of cardiovascular events and hospitalizations with acute kidney injury (AKI) or hyperkalemia. A propensity score analysis was performed. We used Cox models to estimate hazard ratios (HRs) for each outcome associated with RASi prescription and tested interactions with age., Results: Patients' mean age was 67 years, including 841 (30%) aged 75 years and older; 2178 (79%) were prescribed RASi's. During a median follow-up of 4.6 years, 33% of patients reached kidney failure or died. RASi prescription was associated with a lower risk of kidney failure or death (HR 0.79, 95% CI 0.66, 0.95), an association not modified by age (P for interaction = .72). It was not significantly associated with cardiovascular events. During the first 3 years of follow-up, 14% of patients were hospitalized with AKI or hyperkalemia, but risk was not higher among those prescribed RASi's (HR 0.75, 95% CI 0.55-1.02) and age did not modify its effect (P for interaction = .28)., Conclusions and Implications: This study shows that aging does not appear to modify either RASi's beneficial effects on major CKD outcomes or their potential adverse effects., (Copyright © 2021 AMDA — The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Several clinical settings require an accurate estimation of the physiologically expected extracellular fluid volume (ECFV). We aimed to analyze the performances of existing ECFV-estimating equations and to develop a new equation., Methods: The performances of 11 ECFV-estimating equations were analyzed in 228 healthy kidney donor candidates (Bichat Hospital, Paris, France) who underwent ECFV measurement using the distribution volume of 51 Cr-labeled EDTA ( 51 Cr-EDTA). An equation was developed using a penalized linear modeling approach (elastic net regression) and externally (Tenon Hospital, Paris, France, N =  142) validated., Results: Participants from Bichat (mean age 45.2 ± 12.0 years, 43.0% men) and Tenon (47.8 ± 10.3 years, 29.6% men) hospitals had a mean measured ECFV of 15.4 ± 2.8 l and 15.1 ± 2.1 l, respectively. Available ECFV-estimating formulae have highly variable precision and accuracy. The new equation incorporating body weight, height, sex, and age had better precision and accuracy than all other equations in the external validation cohort, with a median bias of -0.20 (95% CI: -0.35 to -0.05) l versus -2.63 (-2.87 to -2.42) l to -0.57 (- 0.83 to -0.40) l and 0.21 (0.12 to 0.43) l to 2.89 (2.65 to 3.11) l, for underestimating and overestimating equations, respectively, an interquartile range for the bias of 0.88 (0.70 to 1.08) l versus 0.91 (0.71 to 1.20) l to 1.93 (1.67 to 2.25) l, and an accuracy within 10% of 90.9% (83.8 to 94.4) versus 88.0% (81.0 to 92.3) to 8.5% (4.2 to 13.4). These results were consistent across subgroups defined by sex, body mass index (BMI), body surface area (BSA), age, and ethnicity., Conclusion: We developed and validated a new equation to estimate the individual reference value of ECFV, which is easily usable in clinical practice. Further validation in cohorts including individuals of extreme age and corpulence remains needed., (© 2022 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: More men than women start kidney replacement therapy (KRT) although the prevalence of chronic kidney disease (CKD) is higher in women than men. We therefore aimed at analyzing sex-specific differences in clinical outcomes among 8237 individuals with CKD in stages 3 to 5 from Brazil, France, Germany, and the United States participating in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps)., Methods: Fine and Gray models, evaluating the effect of sex on time to events, were adjusted for age, Black race (model A); plus diabetes, cardiovascular disease, albuminuria (model B); plus estimated glomerular filtration rate (eGFR) slope during the first 12 months after enrollment and first eGFR after enrollment (model C)., Results: There were more men than women at baseline (58% vs. 42%), men were younger than women, and men had higher eGFR (28.9 ± 11.5 vs. 27.0 ± 10.8 ml/min per 1.73 m 2 ). Over a median follow-up of 2.7 and 2.5 years for men and women, respectively, the crude dialysis initiation and pre-emptive transplantation rates were higher in men whereas that of pre-KRT death was more similar. The adjusted subdistribution hazard ratios (SHRs) between men versus women for dialysis were 1.51 (1.27-1.80) (model A), 1.32 (1.10-1.59) (model B), and 1.50 (1.25-1.80) (model C); for pre-KRT death, were 1.25 (1.02-1.54) (model A), 1.14 (0.92-1.40) (model B), and 1.15 (0.93-1.42) (model C); for transplantation, were 1.31 (0.73-2.36) (model A), 1.44 (0.76-2.74) (model B), and 1.53 (0.79-2.94) (model C)., Conclusion: Men had a higher probability of commencing dialysis before death, unexplained by CKD progression alone. Although the causal mechanisms are uncertain, this finding helps interpret the preponderance of men in the dialysis population., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Populations in the high-income countries of Western Europe are aging due to increased life expectancy. As the prevalence of diabetes and obesity has increased, so has the burden of kidney failure. To determine the global capacity for kidney replacement therapy and conservative kidney management, the International Society of Nephrology conducted multinational, cross-sectional surveys and published the findings in the International Society of Nephrology Global Kidney Health Atlas. In the second iteration of the International Society of Nephrology Global Kidney Health Atlas, we aimed to describe the availability, accessibility, quality, and affordability of kidney failure care in Western Europe. Among the 29 countries in Western Europe, 21 (72.4%) responded, representing 99% of the region's population. The burden of kidney failure prevalence varied widely, ranging from 760 per million population (pmp) in Iceland to 1612 pmp in Portugal. Coverage of kidney replacement therapy from public funding was nearly universal, with the exceptions of Germany and Liechtenstein where part of the costs was covered by mandatory insurance. Fourteen (67%) of 21 countries charged no fees at the point of care delivery, but in 5 countries (24%), patients do pay some out-of-pocket costs. Long-term dialysis services (both hemodialysis and peritoneal dialysis) were available in all countries in the region, and kidney transplantation services were available in 19 (90%) countries. The incidence of kidney transplantation varied widely between countries from 12 pmp in Luxembourg to 70.45 pmp in Spain. Conservative kidney care was available in 18 (90%) of 21 countries. The median number of nephrologists was 22.9 pmp (range: 9.47-55.75 pmp). These data highlight the uniform capacity of Western Europe to provide kidney failure care, but also the scope for improvement in disease prevention and management, as exemplified by the variability in disease burden and transplantation rates., (© 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Chronic kidney disease (CKD) exposes to an increased incidence of fragility fractures. International guidelines recommend performing bone mineral density (BMD) if the results will impact treatment decisions. It remains unknown where bone loss occurs and what would preclude the longitudinal loss in patients with CKD. Here, we aimed to investigate factors influencing BMD and to analyze the longitudinal BMD changes., Methods: In the NephroTest cohort, we measured BMD at the femoral neck, total hip, lumbar spine, and proximal radius, together with circulating biomarkers and standardized measured glomerular filtration rate (mGFR) by 51 Cr-EDTA in a subset of patients with CKD stage 1 to 5 followed during 4.3 ± 2.0 years. A linear mixed model explored the longitudinal bone loss and the relationship of associated factors with BMD changes. A total of 858 patients (mean age 58.9 ± 15.2 years) had at least 1 and 477 had at least 2 BMD measures., Results: At baseline, cross-sectional analysis showed a significantly lower BMD at femoral neck and total hip and a significant higher serum parathyroid hormone (PTH) along with CKD stages. Baseline age, gender, tobacco, low body mass index (BMI), and high PTH levels were significantly associated with low BMD. Longitudinal analysis during the mean 4.3 years revealed a significant bone loss at the radius only. BMD changes at the femoral neck were associated with BMI, but not CKD stages or basal PTH levels., Conclusions: CKD is associated with low BMD and high PTH in the cross-sectional analysis. Longitudinal bone loss occurred at the proximal radius after 4.3 years., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: The uptake of the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 chronic kidney disease (CKD) Guideline is not fully described in real-world nephrology practice across the world., Methods: We used baseline data from the CKD Outcomes and Practice Patterns Study (2013-2017), a 4-country cohort of patients with estimated glomerular filtration rate <60 ml/min per 1.73 m 2 recruited from national samples of nephrology clinics, to describe adherence to measures for monitoring and delaying CKD progression. Data were collected as in clinical practice, except laboratory measures per protocol in France., Results: The mean age ranged from 65 years in Brazil to 72 years in Germany. Albuminuria (mostly proteinuria) was measured routinely in 36% to 43% of patients in Brazil, Germany, and the United States. Blood pressure control (≤140/90 mm Hg) ranged from 49% in France to 76% in Brazil; <40% of patients had blood pressure ≤130/80 mm Hg everywhere but Brazil (52%). More than 40% of nephrologists in Brazil reported a systolic blood pressure target ≤130 mm Hg for nondiabetic patients without proteinuria, but only 19% to 24% elsewhere. Prescription of renin-angiotensin aldosterone system inhibitors ranged from 52% in the United States to 81% in Germany. Dietary advice was more frequent for salt than protein intake; dietitian visits were uncommon. In nondiabetic patients, achievement of all 3 targets including blood pressure ≤130/80 mm Hg, renin-angiotensin aldosterone system inhibition, and dietary advice, ranged from 10% in the United States to 32% in Brazil; in treated diabetic patients, this ranged from 6% to 11% after including hemoglobin A1c target., Conclusion: Adherence to recommendations to slow CKD progression is low in typical practice settings, and substantial variation among countries for some indicates opportunities for improvement., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: The incidence of kidney replacement therapy (KRT) for kidney failure varies internationally much more than chronic kidney disease (CKD) prevalence. This ecologic study investigated the relation of CKD prevalence to KRT and mortality risks by world region., Methods: We used data from Global Burden of Disease and KRT registries worldwide with linear models to estimate the percentages of variance in KRT incidence and all-cause mortality explained by age-adjusted prevalence of CKD stages 3 to 5, overall and by gender, in 61 countries classified in 3 regions: high income ( n  = 28), Eastern and Central Europe ( n  = 15), and other ( n  = 18)., Results: The incidence of KRT ranged from 89 to 378 per million population in high-income regions, 32 to 222 per million population in Central and Eastern Europe, and 22 to 493 per million population in the other region; age-adjusted CKD prevalence ranged from 5.5% to 10.4%, 7.6% to 13.7%, and 7.4% to 13.1%, respectively. The relation between these indicators was positive in high-income countries, negative in Central and Eastern Europe, and null in the other region. Age-adjusted CKD prevalence explained 40% of the variance in KRT incidence ( P  < 0.001) in high-income countries. The explained variance of age-adjusted mortality was close to 0 in high-income countries and positive at 19% ( P  = 0.10) in Central and Eastern Europe and at 11% ( P  = 0.17) in the other region. Results were consistent by gender., Conclusion: This study raises awareness on the significant part of the gaps in KRT incidence across countries not explained by the number of individuals with CKD, even in high-income countries where access to KRT is not limited., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: In the general population, urinary sodium-to-potassium (uNa/K) ratio associates more strongly with high blood pressure (BP) than either urinary sodium or potassium alone. Whether this is also the case among patients with chronic kidney disease (CKD) is unknown., Methods: We studied the associations of spot urine sodium-to-creatinine (uNa/Cr), potassium-to-creatinine (uK/Cr), and uNa/K ratios with a single office BP reading in 1660 patients with moderate to severe CKD at inclusion in the CKD-REIN cohort., Results: Patients' median age was 68 (interquartile range [IQR], 59-76) years; most were men (65%), had moderate CKD (57%), and albuminuria (72%). Mean systolic and diastolic BP was 142/78 mm Hg. Spot uNa/Cr and uNa/K ratios were positively associated with systolic, mean arterial, and pulse pressures. The mean adjusted difference in systolic BP between the highest and the lowest quartile (Q4 vs . Q1) was 4.24 (95% confidence interval [CI], 1.53-6.96) mm Hg for uNa/Cr and 4.79 (95% CI, 2.18-7.39) mm Hg for uNa/K. Quartiles of spot uK/Cr were not associated with any BP index. The higher the quartile of uNa/K, the higher the prevalence ratio of uncontrolled (Q4 vs. Q1, 1.43; 95% CI, 1.19-1.72) or apparently treatment-resistant hypertension (Q4 vs. Q1, 1.35; 95% CI, 1.14-1.60). Findings were consistent in a subset of 803 individuals with 2 BP readings., Conclusion: In patients with CKD, higher urinary sodium excretion is associated with higher BP, but unlike in general population, lower potassium excretion is not. Urinary Na/K does not add significant value in assessing high BP risk, except perhaps for hypertension control assessment., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)

Volume overload has been shown to be an independent risk factor for mortality in patients receiving chronic dialysis, but data in non-dialysis patients are scarce. Therefore we evaluated the prognostic value of extracellular fluid (ECF) volume for chronic kidney disease (CKD) progression and mortality in a prospective hospital-based cohort with CKD stage 1-4 (NephroTest Study). ECF (scaled to body surface area) and the measured glomerular filtration rate (mGFR) were determined using the distribution volume and clearance of 51Cr-EDTA, respectively. Cause-specific Cox and linear mixed-effect regression models were used to analyze the association of ECF with end-stage kidney disease (ESKD) and mortality, and with mGFR decline, respectively. The 1593 patients were mean age 58.8 years, 67% were men, mean mGFR of 43.6 mL/min/1.73m 2 and mean ECF 15.1 L/1.73m 2 . After a median follow-up of 5.3 years, ESKD occurred in 324 patients and 185 patients died before ESKD. In multivariable analysis, ECF was significantly associated with the risk of ESKD (hazard ratio per 1L/1.73m 2 increase: 1.14; 95% confidence interval [1.07; 1.21]) and with a faster GFR decline (adjusted mean difference in mGFR slope per 1L/1.73m 2 increase -0.14 [-0.23; -0.05] mL/min/year). The relationship of ECF with mortality was non-linear and not significant (per 1L/1.73m 2 increase 0.92, [0.73; 1.16]), below 15L/1.73m 2 , but significant (1.28; [1.14-1.45]) above 15L/1.73m 2 . Thus, in this large cohort of carefully phenotyped patients with CKD, ECF was an independent risk factor of CKD progression and mortality. Hence, close monitoring and treatment of fluid overload are important for the clinical management of patients with non-dialysis CKD., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Although blood pressure control is a major goal in chronic kidney disease, no worldwide overview of either its achievement or antihypertensive prescriptions is currently available. To evaluate this we compared crude prevalence of uncontrolled blood pressure among 17 cohort studies, including 34 602 individuals with estimated glomerular filtration rate under 60 ml/min/1.73 m 2 and treated hypertension across four continents, and estimated observed to expected prevalence ratios, adjusted for potential confounders. Crude prevalence of blood pressure of 140/90 mm Hg or more varied from 28% to 61% and of blood pressure of 130/80 or more from 54% to 84%. Adjusted prevalence ratios indicated poorer hypertension control than expected in cohorts from European countries, India, and Uruguay, and better control in patients from North American and high-income Asian countries. Four antihypertensive drug classes or more were prescribed to more than 30% of participants in North American and some European cohorts, but this practice was less common elsewhere. Renin angiotensin-aldosterone system inhibitors were the most common antihypertensive drugs, prescribed for 54% to 91% of cohort participants. Differences for other drug classes were much stronger, ranging from 11% to 79% for diuretics, 22% to 70% for beta-blockers, and 27% to 75% for calcium-channel blockers. The confounders studied explain only a part of the international variation in blood pressure control among individuals with chronic kidney disease. Thus, considerable heterogeneity in prescription patterns worldwide calls for further investigation into the impact of different approaches on patient outcomes., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: We describe the characteristics of patients with moderate/advanced chronic kidney disease (CKD) according to receipt of lipid-lowering therapy (LLT), and whether they achieved low-density lipoprotein cholesterol (LDL-C) targets for high- and very high-risk patients., Methods: CKD-REIN (NCT03381950), a prospective cohort study conducted in 40 nephrology clinics in France, enrolled 3033 patients with moderate (stage G3) or advanced (stage G4/G5) CKD (2013-2016) who had not been on chronic dialysis or undergone kidney transplantation. Data were collected from patients' interviews and medical records. Patients were followed up at 1 year., Results: Among 2542 patients (mean [SD] age 67 [13] years, 34% women) with LDL-C measurements at baseline (mean [SD] LDL-C 2.7 [1.1] mmol/l; cholesterol 4.8 [1.3] mmol/l), 63% were on LLT; 24% were at high (CKD stage G3, no cardiovascular disease [CVD] or diabetes) and 74% at very high (CKD stage G3 with diabetes or CVD, or CKD stage G4/5) cardiovascular risk. Among high-risk patients, 45% of those on statin and/or ezetimibe achieved the LDL-C treatment target (<2.6 mmol/l). Among very high-risk patients, the percentage at goal (<1.8 mmol/l) was 38% for CKD stage G3 and 29% for stage G4/5. There was a trend toward higher achievement of LDL-C targets with increasing LLT intensity (adjusted odds ratios for moderate vs. low intensity 1.20; 95% confidence interval 0.92-1.56; high vs. low intensity 1.46; 1.02-2.09; P trend  = 0.036)., Conclusion: Many patients with CKD stage G3-G5 who are eligible for LLT are not treated, and those on LLT rarely achieve LDL-C targets., (© 2019 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: Clipping and selective removal of initially suspicious axillary lymph nodes in breast cancer patients who have been sonographically down-staged by primary systemic therapy improves the accuracy of surgical staging and provides the opportunity for more conservative axillary surgery. This study evaluated whether preoperative ultrasound-guided wire localization of the clipped node is useful for routine clinical practice., Material and Methods: This prospective, single-center feasibility trial included patients with invasive breast cancer (cT1-3N1-3M0) treated by primary systemic therapy. They underwent ultrasound-guided core needle biopsy and clip placement into the most suspicious axillary lymph node prior to chemotherapy. After primary systemic therapy the clipped lymph node was localized by a wire. All patients underwent target lymph node biopsy, completion axillary lymph node dissection and, if yiN0, axillary sentinel lymph node biopsy. The primary study endpoint was the identification rate of the target lymph node., Results: All patients (n = 30) underwent successful clip insertion into the lymph node. After chemotherapy, the clipped target lymph node was visible by ultrasound in 83.3% (25/30). Wire localization was possible in 24 cases (80%), and the clipped node identification rate was 70.8% (17/24 cases). In 9/30 patients (30%) clipped node removal was not confirmed by intraoperative radiography., Conclusion: Ultrasound-guided wire localization of the target lymph node is not suitable for clinical practice because of limitations regarding clip visibility and selective surgical preparation of the target lymph node. Further prospective evaluation of alternative techniques is needed., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Patients with chronic kidney disease and severely decreased glomerular filtration rate (GFR) are at high risk for kidney failure, cardiovascular disease (CVD) and death. Accurate estimates of risk and timing of these clinical outcomes could guide patient counseling and therapy. Therefore, we developed models using data of 264,296 individuals in 30 countries participating in the international Chronic Kidney Disease Prognosis Consortium with estimated GFR (eGFR)s under 30 ml/min/1.73m 2 . Median participant eGFR and urine albumin-to-creatinine ratio were 24 ml/min/1.73m 2 and 168 mg/g, respectively. Using competing-risk regression, random-effect meta-analysis, and Markov processes with Monte Carlo simulations, we developed two- and four-year models of the probability and timing of kidney failure requiring kidney replacement therapy (KRT), a non-fatal CVD event, and death according to age, sex, race, eGFR, albumin-to-creatinine ratio, systolic blood pressure, smoking status, diabetes mellitus, and history of CVD. Hypothetically applied to a 60-year-old white male with a history of CVD, a systolic blood pressure of 140 mmHg, an eGFR of 25 ml/min/1.73m 2 and a urine albumin-to-creatinine ratio of 1000 mg/g, the four-year model predicted a 17% chance of survival after KRT, a 17% chance of survival after a CVD event, a 4% chance of survival after both, and a 28% chance of death (9% as a first event, and 19% after another CVD event or KRT). Risk predictions for KRT showed good overall agreement with the published kidney failure risk equation, and both models were well calibrated with observed risk. Thus, commonly-measured clinical characteristics can predict the timing and occurrence of clinical outcomes in patients with severely decreased GFR., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Major temporal changes in the case mix of patients accepted for renal replacement therapy impede analysis of long-term mortality trends in end-stage renal disease patients. A record linkage study of 2 large electronic hospital inpatient data sets with national mortality data used standardization by age, sex, and comorbidity to uncover a 50% decline in 3-year mortality in English patients starting renal replacement therapy between 1970 and 2008, a faster drop than that seen in the general population., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

High-quality clinical trials are the cornerstone of evidence-based prevention and treatment of a disease, but nephrology has a strikingly weak base of such trials. Building the evidence base to improve outcomes for people with a kidney disease, therefore, requires both greater quantity and quality of clinical trials. To address these issues, we propose that we aim to enroll 30% of people with chronic kidney disease in trials by 2030. Goal 1: Strongly encourage and promote the conduct of clinical trials in people with chronic kidney disease to increase the number of clinical trials conducted. Goal 2: Optimize the design of clinical trials in people with chronic kidney disease. Goal 3: Increase the capacity for conducting clinical trials in people with chronic kidney disease.

Chronic kidney disease (CKD) continues to remain high globally, up to 13.4% by one estimate. Although the number, geographic distribution, size, and quality of the studies examining CKD prevalence and incidence have increased over the past decade, the global capacity for CKD surveillance is still far less developed than that for hypertension, diabetes, and cardiovascular disease. Estimating CKD prevalence is constrained by inadequate standardization of serum creatinine and urine albumin assays, heterogeneity in study designs, lack of national registries in many countries, incomplete adoption of disease classification guidelines, and inconsistent use of evidence-based equations for estimating glomerular filtration rate. Goal 1: Improve monitoring of CKD prevalence. To achieve this, disseminate the rationale for CKD prevalence monitoring, achieve uniform measurement of CKD markers, promote inclusion of CKD measurements in all large chronic disease cohorts and health surveys, harness administrative claims data for CKD surveillance, and incorporate the new CKD classification system in the International Classification of Diseases. Goal 2: Improve CKD monitoring of populations underrepresented in studies to date. To achieve this, establish registries of chronic dialysis and transplantation in all countries; establish registries for special CKD groups, such as children, patients with rare diseases, and patients with special etiologies of CKD. Goal 3: Improve identification of individuals with CKD. To achieve this, implement the Kidney Disease: Improving Global Outcomes guidelines for screening and testing, carry out randomized studies on screening strategies, ensure that estimated glomerular filtration rate is reported with all reports of serum creatinine, and leverage new software for identification and follow-up of CKD cases.

Introduction: Reducing protein intake is recommended for slowing chronic kidney disease (CKD) progression, but assessment of its true effectiveness is sparse., Methods: Using the Maroni formula, we assessed dietary protein intake (DPI) from 24-hour urinary urea excretion in 1594 patients (67% men and 33% women) with CKD, 784 of whom also had 7-day food records. Cause-specific hazard ratios (HRs) and 95% confidence intervals for the competing risks of DPI-associated end-stage renal disease (ESRD) or death were estimated in 1412 patients with baseline glomerular filtration rate ≥15 ml/min per 1.73 m 2 , measured by 51 Cr-EDTA renal clearance (mGFR)., Results: Overall, mean DPI estimated from urea excretion was 1.09 ± 0.30 g/kg of body weight per day (range = 0.34-2.76); 20% of patients had values > 1.3 g/kg per day, and 1.9% had values < 0.6 g/kg per day. Urea excretion and food records produced similar estimates of mean DPI. The lower the mGFR, the lower the mean DPI. Over a median follow-up of 5.6 years, there were 319 ESRD events and 189 pre-ESRD deaths. After adjusting for relevant covariates, each 0.1 g/kg daily higher baseline urea excretion-based DPI or food record-based DPI was associated with an HR for ESRD of 1.05 (95% confidence interval 1.01-1.10) or 1.09 (95% confidence interval 1.04-1.14), respectively. HRs were stronger in patients with baseline mGFR < 30 ml/min per 1.73 m 2 . There was no association with mortality. The mean age of the patients was 59 ± 15 years, and mean body mass index was 26.6 ± 5.2 kg/m 2 ., Conclusion: In this prospective observational study, the lower the baseline DPI, the slower the progression toward ESRD. Most importantly, the absence of threshold for the relation between DPI and ESRD risk indicates that there is no optimal DPI in the range observed in this cohort.

Introduction: Chronic kidney disease (CKD) is often associated with poor hypertension control and treatment resistance, but whether CKD modifies the effect of hypertension control on outcomes is unknown., Methods: We studied 10-year mortality and cardiovascular events according to hypertension control status and CKD (glomerular filtration rate <60 ml/min/1.73m 2 ) in 4262 community-dwelling individuals (40% men) more than 65 years of age., Results: At baseline, 19% had CKD, and 31.2% had controlled hypertension on ≤3 antihypertensive drugs, 62.3% uncontrolled hypertension ≥140/90 mm Hg on ≤2 drugs, and 6.5% apparent treatment-resistant hypertension (aTRH) ≥140/90 mm Hg with ≥3 drugs or use of ≥4 drugs regardless of level. There were 1115 deaths (305 total cardiovascular deaths) and 274 incident nonfatal or fatal strokes or coronary events. Compared to the reference group (controlled hypertension and no CKD), participants without CKD and with uncontrolled hypertension or aTRH had adjusted hazard ratios for all-cause mortality of 0.86 (0.74-1.01) and 1.09 (0.82-1.46), and those with CKD and controlled or uncontrolled hypertension, or aTRH, of 1.33 (1.06-1.68), 1.14 (0.93-1.39), and 1.34 (0.98-1.85), respectively. Participants with aTRH and CKD had a risk of coronary death more than 3 times higher than that of the reference group; participants with aTHR, with or without CKD, had a risk of stroke more than twice as high, and those with CKD but controlled hypertension a 2 times higher risk for cardiovascular deaths from other causes., Discussion: CKD does not appear to amplify the risk of stroke and coronary events associated with aTRH in this older population. The reasons for excess cardiovascular mortality from other causes associated with controlled hypertension require further study.

Eriksen et al. report a lack of association between baseline blood pressure and subsequent decline of iohexol measured glomerular filtration rate in a representative sample of over 1500 people from the general population in Norway. This is an innovative contribution to the ongoing debate on whether mild to moderate hypertension causes chronic kidney disease. While waiting for final clarification of the interconnection, one must keep in mind that absence of evidence is not evidence of absence., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Resistant hypertension is defined as blood pressure above goal despite adherence to a combination of at least three optimally dosed antihypertensive medications, one of which is a diuretic. Chronic kidney disease is the most frequent of several patient factors or comorbidities associated with resistant hypertension. The prevalence of resistant hypertension is increased in patients with chronic kidney disease, while chronic kidney disease is associated with an impaired prognosis in patients with resistant hypertension. Recommended low-salt diet and triple antihypertensive drug regimens that include a diuretic, should be complemented by the sequential addition of other antihypertensive drugs. New therapeutic innovations for resistant hypertension, such as renal denervation and carotid barostimulation, are under investigation especially in patients with advanced chronic kidney disease. We discuss resistant hypertension in chronic kidney disease stages 3-5 (ie, patients with an estimated glomerular filtration rate below 60 mL/min per 1·73 m(2) and not on dialysis), in terms of worldwide epidemiology, outcomes, causes and pathophysiology, evidence-based treatment, and a call for action., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Recent studies suggest that alkalinizing treatments improve the course of chronic kidney disease (CKD), even in patients without overt metabolic acidosis. Here, we tested whether a decreased ability in excreting urinary acid rather than overt metabolic acidosis may be deleterious to the course of CKD. We studied the associations between baseline venous total CO2 concentration or urinary ammonia excretion and long-term CKD outcomes in 1065 patients of the NephroTest cohort with CKD stages 1-4. All patients had measured glomerular filtration rate (mGFR) by (51)Cr-EDTA renal clearance. Median mGFR at baseline was 37.6 ml/min per 1.73 m(2). Urinary ammonia excretion decreased with GFR, whereas net endogenous acid production did not. After a median follow-up of 4.3 years, 201 patients reached end-stage renal disease (ESRD) and 114 died before ESRD. Twenty-six percent of the patients had mGFR decline rate greater than 10% per year. Compared with patients in the highest tertile of urinary ammonia excretion, those in the lowest tertile had a significantly increased hazard ratio for ESRD, 1.82 (95% CI, 1.06-3.13), and a higher odds ratio of fast mGFR decline, 1.84 (0.98-3.48), independent of mGFR and other confounders. Patients in the lowest tertile of venous total CO2 had significantly increased risk of fast mGFR decline but not of ESRD. None of these biomarkers was associated with mortality. Thus, these results suggest that the inability to excrete the daily acid load is deleterious to renal outcomes.

Genome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, single-nucleotide polymorphisms (SNPs) at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1, and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus, which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFR decline of 3 ml/min per 1.73 m(2) or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11, and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 h after gentamicin treatment compared with controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline.

Background: Ductal carcinoma in situ (DCIS) often accompanies invasive ductal carcinoma (IDC). The presence of co-existing DCIS is postulated to present as a less aggressive phenotype than IDC alone., Patients and Methods: Patients diagnosed with hormone receptor-positive breast cancer receiving mastectomy were evaluated. Only patients without adjuvant radio- and chemotherapy were included to decrease treatment bias on local recurrence (LR)., Results: Of 2239 breast cancer patients, 198 fulfilled the inclusion criteria. The overall LR rate was 11.6%. Tumor stage (p = 0.002), nodal status (pN2 vs. pN0, p = 0.023) and pure IDC compared with IDC-DCIS (p = 0.029) were multivariate independent factors for increased LR risk. Patients with IDC-DCIS were significantly younger (p < 0.001), had smaller tumors (p = 0.001), less lymph node involvement (p = 0.012). The LR rate was significantly increased in patients with pure IDC (p = 0.012). The time to distant metastases was decreased in patients with pure IDC compared with that observed in patients with IDC-DCIS (log rank = 0.030)., Conclusion: Invasive ductal carcinoma accompanied by DCIS is associated with lower LR. The prognostic value of co-existing DCIS in the adjuvant decision-making process may be considered a new independent prognostic marker. This finding needs further studies to evaluate its usefulness in premenopausal women., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Cystic kidney diseases and toxic interstitial nephritis may be complicated by renal tumors. Long-term lithium intake is associated with tubulointerstitial nephritis and renal cysts but to date such an association with tumors has not been determined. We evaluated this in a retrospective study to determine whether lithium-treated patients were at higher risk of renal tumors compared with lithium-free patients with chronic kidney disease (CKD), and to the general population. Over a 16-year period, 14 of 170 lithium-treated patients had renal tumors, including seven malignant and seven benign tumors. The mean duration of lithium exposure at diagnosis was 21.4 years. The renal cancers included three clear-cell and two papillary renal cell carcinomas, one hybrid tumor with chromophobe and oncocytoma characteristics, and one clear-cell carcinoma with leiomyomatous stroma. The benign tumors included four oncocytomas, one mixed epithelial and stromal tumor, and two angiomyolipomas. The percentage of renal tumors, particularly cancers and oncocytomas, was significantly higher in lithium-treated patients compared with 340 gender-, age-, and estimated glomerular filtration rate (eGFR)-matched lithium-free patients. Additionally, the Standardized Incidence Ratio of renal cancer was significantly higher in lithium-treated patients compared with the general population: 7.51 (95% confidence interval (CI) (1.51-21.95)) and 13.69 (95% CI (3.68-35.06)) in men and women, respectively. Thus, there is an increased risk of renal tumors in lithium-treated patients.

Background: Hypertension is the most prevalent comorbidity in individuals with chronic kidney disease. However, whether the association of the kidney disease measures, estimated glomerular filtration rate (eGFR) and albuminuria, with mortality or end-stage renal disease (ESRD) differs by hypertensive status is unknown., Methods: We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and ESRD associated with eGFR and albuminuria in individuals with and without hypertension., Findings: We analysed data for 45 cohorts (25 general population, seven high-risk, and 13 chronic kidney disease) with 1,127,656 participants, 364,344 of whom had hypertension. Low eGFR and high albuminuria were associated with mortality irrespective of hypertensive status in the general population and high-risk cohorts. All-cause mortality risk was 1·1-1·2 times higher in individuals with hypertension than in those without hypertension at preserved eGFR. A steeper relative risk gradient in individuals without hypertension than in those with hypertension at eGFR range 45-75 mL/min per 1·73 m(2) led to much the same mortality risk at lower eGFR. With a reference eGFR of 95 mL/min per 1·73 m(2) in each group to explicitly assess interaction, adjusted HR for all-cause mortality at eGFR 45 mL/min per 1·73 m(2) was 1·77 (95% CI 1·57-1·99) in individuals without hypertension versus 1·24 (1·11-1·39) in those with hypertension (p for overall interaction=0·0003). Similarly, for albumin-creatinine ratio of 300 mg/g (vs 5 mg/g), HR was 2·30 (1·98-2·68) in individuals without hypertension versus 2·08 (1·84-2·35) in those with hypertension (p for overall interaction=0·019). We recorded much the same results for cardiovascular mortality. The associations of eGFR and albuminuria with ESRD, however, did not differ by hypertensive status. Results for chronic kidney disease cohorts were similar to those for general and high-risk population cohorts., Interpretation: Chronic kidney disease should be regarded as at least an equally relevant risk factor for mortality and ESRD in individuals without hypertension as it is in those with hypertension., Funding: US National Kidney Foundation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We studied here the independent associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality and end-stage renal disease (ESRD) in individuals with chronic kidney disease (CKD). We performed a collaborative meta-analysis of 13 studies totaling 21,688 patients selected for CKD of diverse etiology. After adjustment for potential confounders and albuminuria, we found that a 15 ml/min per 1.73 m² lower eGFR below a threshold of 45 ml/min per 1.73 m² was significantly associated with mortality and ESRD (pooled hazard ratios (HRs) of 1.47 and 6.24, respectively). There was significant heterogeneity between studies for both HR estimates. After adjustment for risk factors and eGFR, an eightfold higher albumin- or protein-to-creatinine ratio was significantly associated with mortality (pooled HR 1.40) without evidence of significant heterogeneity and with ESRD (pooled HR 3.04), with significant heterogeneity between HR estimates. Lower eGFR and more severe albuminuria independently predict mortality and ESRD among individuals selected for CKD, with the associations stronger for ESRD than for mortality. Thus, these relationships are consistent with CKD stage classifications based on eGFR and suggest that albuminuria provides additional prognostic information among individuals with CKD.

Starting patients on dialysis early has been increasing in incidence in several countries. However, some studies have questioned its utility, finding a counter-intuitive effect of increased mortality when dialysis was started at a higher estimated glomerular filtration rate (eGFR). To examine this issue in more detail we measured mortality hazard ratios associated with Modification of Diet in Renal Disease eGFR at dialysis initiation for 11,685 patients from the French REIN Registry, with sequential adjustment for a number of covariates. The eGFR was analyzed both quantitatively by 5-ml/min per 1.73 m(2) increments and by demi-decile (i.e., 5 percentiles of the distribution); the 15th demi-decile, including values around 10 ml/min per 1.73 m(2), was our reference point. The patients more likely to begin dialysis at a higher eGFR were older male patients; had diabetes, cardiovascular diseases, or low body mass index and level of albuminemia; or were started with peritoneal dialysis. During a median follow-up of 21.9 months, 3945 patients died. The 2-year crude survival decreased from 79 to 46%, with increasing eGFR from less than 5 to over 20 ml/min per 1.73 m(2). Each 5-ml/min/1.73 m(2) increase in eGFR was associated with a 40% increase in crude mortality risk, which weakened to 9%, but remained statistically significant after adjusting for the above covariates. Analysis by demi-decile showed only the highest to be at significantly higher risk. Hence we found that age and patient condition strongly determine the decision to start dialysis and may explain most of the inverse association between eGFR and survival.

The association between membranous nephropathy (MN) and cancer is often mentioned in textbooks but poorly substantiated, and the characteristics of cancer-associated MN are unknown. To address these questions, we studied a cohort of 240 patients with MN, among them 24 had malignancy at the time of renal biopsy or within a year thereafter. The incidence of cancer was significantly higher in these patients than in the general population (standardized incidence ratio 9.8 [5.5-16.2] for men and 12.3 [4.5-26.9] for women). The frequency of malignancy increased with age. At the time of diagnosis, clinical presentation did not differ between the patients with cancer-associated MN and those with idiopathic MN, but smoking was more frequent among patients with cancer. Analysis of renal biopsies revealed that the number of inflammatory cells infiltrating the glomeruli was significantly higher in patients with cancer-associated MN (P = 0.001). The best cutoff value for distinguishing malignancy-related cases from controls was eight cells per glomerulus. Using this threshold led to a diagnosis of cancer-associated MN with a specificity of 75% and a sensitivity of 92%. In patients with cancer-associated MN, there was a strong relationship between reduction of proteinuria and clinical remission of cancer (P < 0.001). In conclusion, our study provides epidemiologic evidence of an excess of cancer risk in patients with MN. It also shows that age, smoking, and the presence of glomerular leukocytic infiltrates strongly increase the likelihood of malignancy in MN patients.

Background: There is concern about the rising prevalence of type 2 diabetes mellitus and of the resultant nephropathy. This study uses data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry to provide information on the epidemiology and outcome of renal replacement therapy (RRT) for end-stage renal disease (ESRD) due to diabetic nephropathy (DN)., Methods: Data from the following 10 registries: Austria, French-speaking Belgium, Denmark, Finland, Greece, Norway, Scotland (UK), Catalonia (Spain), Sweden, and The Netherlands were combined. Average annual changes (%) were estimated by Poisson regression. Analyses of mortality were performed by Cox regression., Results: An increase in patients with type 2 DN entering RRT has been observed (+11.9% annually, P < 0.05), while large differences in RRT incidence in this disease continue to exist between countries in Europe. There was a reduction in mortality during the first 2 years on dialysis therapy among patients with type 2 DN (AHR 0.96, 95%CI 0.94-0.97 annually). The mortality among transplant recipients decreased for both type 1 DN and nondiabetic ESRD (non DN) within the 1995-1998 cohort (type 1 DN: AHR 0.49, 95% CI 0.35-0.68; non DN: AHR 0.79, 95% CI 0.69-0.90) compared to the 1991-1994 cohort., Conclusion: This report has shown that during the last decade there has been a marked increase in the incidence of RRT for type 2 DN. Survival analysis showed that over the period 1991-1999 the mortality rates of all dialysis patients and of type 1 diabetic and nondiabetic renal transplant recipients have fallen.

Background: Long-term lithium administration in humans may lead to chronic tubulointerstitial nephritis, which develops very slowly. Its progression to end-stage renal disease (ESRD) has been rarely reported. The aim of this study is to document the rate of progression of lithium-induced nephropathy and its prognostic factors, and to provide an estimation of the percentage of lithium-induced ESRD in France., Methods: Two groups have been studied: 54 patients with lithium-induced renal failure, nine of whom underwent renal biopsy; and 20 patients who were referred for systematic renal biopsy, 14 of whom were subsequently followed up. In addition, a survey of lithium-induced ESRD was conducted in French dialysis centers., Results: The mean annual loss of creatinine clearance in patients with lithium-induced nephropathy was 2.29 mL/min. Among 74 patients, 12 reached ESRD at a mean age of 65 years. Creatinine clearance at referral and at last follow-up was inversely related to the duration of lithium therapy in both univariate and multivariate analyses adjusting for age, gender, hypertension, and proteinuria. The degree of interstitial fibrosis on renal biopsy was also related to the lithium duration and cumulative dose. It was predictive of the final creatinine clearance. About 35% of the patients tested had moderate hypercalcemia, due to hyperparathyroidism. The prevalence of lithium-related ESRD in France was estimated as two per 1000 dialysis patients. The average latency between onset of lithium therapy and ESRD was 20 years., Conclusion: Lithium-induced chronic renal disease is slowly progressive. Its rate of progression is related to the duration of lithium administration. Lithium-related ESRD represents 0.22% of all causes of ESRD in France. Regular monitoring of estimated creatinine clearance is mandatory in long-term lithium-treated patients.

Background: Smoking is a known risk factor for renal damage in diabetic patients, but its relationship to other renal diseases is less clear. To assess its effect in primary glomerular nephropathy (GN), we used data from a case control study designed to assess several environmental risk factors., Methods: This study included 295 biopsy-proven GN cases, 80 membranous nephropathy, 116 IgA nephropathy, and 99 nephrotic syndrome with either minimal change nephropathy or focal segmental hyalinosis, and 242 matched hospital controls, with diseases unrelated to smoking. Subjects were interviewed about their smoking history. Chronic renal failure (CRF), defined by serum creatinine> 150 micromol/L, was present in 74 cases (57 men and 17 women). Logistic regression was used to estimate odds ratios (ORs) adjusted for age and social class., Results: In men, the percentage of ever-smokers did not differ between GN cases (60%) and controls [65%, OR = 0.9 (95% Confidence Interval 0.6-1.4)], but was significantly higher among cases with CRF (75%) than those without [55%, OR = 2.4 (1.2-4.5)]. Dose-effect relationships were observed with both the daily and cumulative dose; this relationship was stronger in the comparison of cases with CRF and those without CRF than in the comparison of cases with CRF with controls: OR = 1.9 versus 1.3 (20 cigarettes/day); OR = 1.9 versus 1.4 (15 pack years). Interactions between age, hypertension, and smoking were observed in the risk of CRF: smoking was significantly related to CRF among cases who were older than 40 years and/or hypertensive, but not among those cases younger than 40 or normotensive. The results did not significantly differ among the three histologic types. No relationship was shown between smoking and CRF in women., Conclusion: This study provides additional support for the hypothesis that smoking is related to GN severity, particularly in the at-risk groups of men older than 40 and/or hypertensive patients. These findings should be corroborated by further observations in other populations.

The aim of this study was to answer the question: is it possible to save motor nerves when dissecting tissue with the hydro-jet dissector? In order to study the influence of the hydro-jet on motor nerves the function of the sciatic nerves of 10 Wistar rats was evaluated. The sciatic nerves were dissected bilaterally and only the left one was exposed to the hydro-jet. The water-jet emerged from a nozzle with a diameter of 0.1 mm and was applied to the nerve for 2, 5 or 10 s and with jet pressures of 80, 85 and 90 bar, respectively. After the operation the animals were observed for 5 months in order to monitor the degree of limping using a scale with 10 clinical grades of function. Five months postoperatively the animals were sacrificed and the sciatic nerves were studied by light and electron microscopy. It was found that hydro-jet pressures of 80 bar and exposure times of 2 s had already lead to irreversible damage to the sciatic nerve. Therefore further studies with lower pressures or shorter exposure times are required before considering hydro-jet cutting for parotid gland surgery. It must be confirmed as harmless to motor nerves before applying this method in humans.

Objectives: To quantify and identify sources of within- and between-subject variability of microalbumin, N-acetyl-beta-D-glucosaminidase (NAG) and alanine aminopeptidase (AAP), three biomarkers used for early detection of renal injury, and to assess the consequences of this variability for the design and power of epidemiological studies., Methods: Urinary excretion of microalbumin, NAG, AAP and creatinine as well as blood pressure (BP) were measured three times over a 2-year period among 142 healthy male workers. To minimise physiopathological and analytical sources of variation, standardised methods were used for urine collection and assays, and severe exclusion criteria were applied. At the first and third examinations, subjects completed the same questionnaire, providing information about their personal characteristics, tobacco and alcohol consumption, and health. A linear mixed model was used to estimate the within- and between-subject variance components and to analyse the relation between subjects' characteristics and the biomarkers., Results: No change in the mean value of any of the biomarkers was observed over the 2-year period. Intra-class correlation coefficients between repeated measurements were 0.53, 0.57 and 0.56 for microalbumin, NAG and AAP, respectively; the between-subject variance was slightly higher than the within-subject variance. Subjects' age, BP, body mass index and smoking and drinking habits explained 7.2%, 12.5% and 4.2% of the total variance of microalbumin, NAG and AAP, respectively., Conclusions: In this healthy population of male workers, day-to-day differences in biomarker values appeared to be nearly as great as differences between subjects. The within-subject variance of these biomarkers is not high enough to justify systematic repeated measurements in epidemiological surveys. But, in some situations where the number of subjects is limited, measuring the subjects twice may improve study power by reducing the total variance by about 25% for each biomarker. Taking the above covariates into account would slightly improve study power and the accuracy of parameter estimates for NAG, but would add little to the analysis of microalbumin and AAP.

From national surveys on representative samples of births, in France, in 1972 and in 1981, prenatal care and outcome of pregnancy among immigrant women--having been born outside continental France--have been studied. In spite of an increase in the number of prenatal visits, between 1972 and 1981, foreign women born in North Africa or in other non-European countries in 1981 had still less prenatal visits than women born in continental France. Few differences in outcome of pregnancy according to the women's birthplace in 1981 are shown, preterm deliveries' and birthweight less than 2,500 g rates had decreased between 1972 and 1981 among most groups of women. Nevertheless, in 1981 stillbirth was more frequent among foreign women, especially women born in North Africa.