Aminu K. Bello

Systematic Review: Kidney Transplantation Compared With Dialysis in Clinically Relevant Outcomes

Individual studies indicate that kidney transplantation is associated with lower mortality and improved quality of life compared with chronic dialysis treatment. We did a systematic review to summarize the benefits of transplantation, aiming to identify characteristics associated with especially large or small relative benefit. Results were not pooled because of expected diversity inherent to observational studies. Risk of bias was assessed using the Downs and Black checklist and items related to time‐to‐event analysis techniques. MEDLINE and EMBASE were searched up to February 2010. Cohort studies comparing adult chronic dialysis patients with kidney transplantation recipients for clinical outcomes were selected. We identified 110 eligible studies with a total of 1 922 300 participants. Most studies found significantly lower mortality associated with transplantation, and the relative magnitude of the benefit seemed to increase over time (p < 0.001). Most studies also found that the risk of cardiovascular events was significantly reduced among transplant recipients. Quality of life was significantly and substantially better among transplant recipients. Despite increases in the age and comorbidity of contemporary transplant recipients, the relative benefits of transplantation seem to be increasing over time. These findings validate current attempts to increase the number of people worldwide that benefit from kidney transplantation.

Association Between Glycemic Control and Adverse Outcomes in People With Diabetes Mellitus and Chronic Kidney Disease: A Population-Based Cohort Study

BACKGROUND Better glycemic control as reflected by lower hemoglobin A(1c) (HbA(1c)) level may prevent or slow progression of nephropathy in people with diabetes mellitus (DM). Whether a lower HbA(1c) level improves outcomes in people with DM and chronic kidney disease (CKD) is unknown. METHODS From all people with serum creatinine measured as part of routine care in a single Canadian province from 2005 through 2006, we identified those with CKD based on laboratory data (estimated glomerular filtration rate [eGFR], <60.0 mL/min/1.73 m(2)]) and DM using a validated algorithm applied to hospitalization and claims data. Patients were classified based on their first HbA(1c) measurement; Cox regression models were used to assess independent associations between HbA(1c) level and 5 study outcomes (death, progression of kidney disease based on a doubling of serum creatinine level, or new end-stage renal disease [ESRD], cardiovascular events, all-cause hospitalization). RESULTS We identified 23,296 people with DM and an eGFR lower than 60.0 mL/min/1.73 m(2). The median HbA(1c) level was 6.9% (range, 2.8%-20.0%), and 11% had an HbA(1c) value higher than 9%. Over the median follow-up period of 46 months, 3665 people died, and 401 developed ESRD. Regardless of baseline eGFR, a higher HbA(1c) level was strongly and independently associated with excess risk of all 5 outcomes studied (P < .001 for all comparisons). However, the association with mortality was U-shaped, with increases in the risk of mortality apparent at HbA(1c) levels lower than 6.5% and higher than 8.0%. The increased risk of ESRD associated with a higher HbA(1c) level was attenuated at a lower baseline eGFR (P value for interaction, <.001). Specifically, among those with an eGFR of 30.0 to 59.9 mL/min/1.73 m(2), the risk of ESRD was increased by 22% and 152% in patients with HbA(1c) levels of 7% to 9% and higher than 9%, respectively, compared with patients with an HbA(1c) level lower than 7% (P < .001), whereas corresponding increases were 3% and 13%, respectively, in those with an eGFR of 15.0 to 29.9 mL/min/1.73 m(2). CONCLUSIONS A hemoglobin A(1c) level higher than 9% is common in people with non-hemodialysis-dependent CKD and is associated with markedly worse clinical outcomes; lower levels of HbA(1c) (<6.5%) also seemed to be associated with excess mortality. The excess risk of kidney failure associated with a higher HbA(1c) level was most pronounced among people with better kidney function. These findings suggest that appropriate and timely control of HbA(1c) level in people with DM and CKD may be more important than previously realized, but suggest also that intensive glycemic control (HbA(1c) level <6.5%) may be associated with increased mortality.

CKD Prevalence Varies across the European General Population

CKD prevalence estimation is central to CKD management and prevention planning at the population level. This study estimated CKD prevalence in the European adult general population and investigated international variation in CKD prevalence by age, sex, and presence of diabetes, hypertension, and obesity. We collected data from 19 general-population studies from 13 European countries. CKD stages 1-5 was defined as eGFR<60 ml/min per 1.73 m(2), as calculated by the CKD-Epidemiology Collaboration equation, or albuminuria >30 mg/g, and CKD stages 3-5 was defined as eGFR<60 ml/min per 1.73 m(2) CKD prevalence was age- and sex-standardized to the population of the 27 Member States of the European Union (EU27). We found considerable differences in both CKD stages 1-5 and CKD stages 3-5 prevalence across European study populations. The adjusted CKD stages 1-5 prevalence varied between 3.31% (95% confidence interval [95% CI], 3.30% to 3.33%) in Norway and 17.3% (95% CI, 16.5% to 18.1%) in northeast Germany. The adjusted CKD stages 3-5 prevalence varied between 1.0% (95% CI, 0.7% to 1.3%) in central Italy and 5.9% (95% CI, 5.2% to 6.6%) in northeast Germany. The variation in CKD prevalence stratified by diabetes, hypertension, and obesity status followed the same pattern as the overall prevalence. In conclusion, this large-scale attempt to carefully characterize CKD prevalence in Europe identified substantial variation in CKD prevalence that appears to be due to factors other than the prevalence of diabetes, hypertension, and obesity.

Kidney stones and kidney function loss: a cohort study

Objective To investigate whether the presence of kidney stones increase the risk of end stage renal disease (ESRD) or other adverse renal outcomes. Design A registry cohort study using validated algorithms based on claims and facility utilisation data. Median follow-up of 11 years. Setting Alberta, Canada, between 1997 and 2009. Participants 3 089 194 adult patients without ESRD at baseline or a history of pyelonephritis. Of these, 1 954 836 had outpatient serum creatinine measurements and were included in analyses of chronic kidney disease and doubling of serum creatinine level. Exposure One or more kidney stones during follow-up. Main outcome measures Incident ESRD, development of stage 3b–5 chronic kidney disease (estimated glomerular filtration rate <45 mL/min/1.73 m2), and sustained doubling of serum creatinine concentration from baseline. Results 23 706 (0.8%) patients had at least one kidney stone, 5333 (0.2%) developed ESRD, 68 525 (4%) developed stage 3b–5 chronic kidney disease, and 6581 (0.3%) experienced sustained doubling of serum creatinine. Overall, one or more stone episodes during follow-up was associated with increased risk of ESRD (adjusted hazard ratio 2.16 (95% CI 1.79 to 2.62)), new stage 3b–5 chronic kidney disease (hazard ratio 1.74 (1.61 to 1.88)), and doubling of serum creatinine (hazard ratio 1.94 (1.56 to 2.43)), all compared with those without kidney stones during follow-up. The excess risk of adverse outcomes associated with at least one episode of stones seemed greater in women than in men, and in people aged <50 years than in those aged ≥50. However, the risks of all three adverse outcomes in those with at least one episode of stones were significantly higher than in those without stones in both sexes and age strata. The absolute increase in the rate of adverse renal outcomes associated with stones was small: the unadjusted rate of ESRD was 2.48 per million person days in people with one or more episodes of stones versus 0.52 per million person days in people without stones. Conclusion Even a single kidney stone episode during follow-up was associated with a significant increase in the likelihood of adverse renal outcomes including ESRD. However, the increases were small in absolute terms.

Global kidney health 2017 and beyond: a roadmap for closing gaps in care, research, and policy

The global nephrology community recognises the need for a cohesive plan to address the problem of chronic kidney disease (CKD). In July, 2016, the International Society of Nephrology hosted a CKD summit of more than 85 people with diverse expertise and professional backgrounds from around the globe. The purpose was to identify and prioritise key activities for the next 5-10 years in the domains of clinical care, research, and advocacy and to create an action plan and performance framework based on ten themes: strengthen CKD surveillance; tackle major risk factors for CKD; reduce acute kidney injury-a special risk factor for CKD; enhance understanding of the genetic causes of CKD; establish better diagnostic methods in CKD; improve understanding of the natural course of CKD; assess and implement established treatment options in patients with CKD; improve management of symptoms and complications of CKD; develop novel therapeutic interventions to slow CKD progression and reduce CKD complications; and increase the quantity and quality of clinical trials in CKD. Each group produced a prioritised list of goals, activities, and a set of key deliverable objectives for each of the themes. The intended users of this action plan are clinicians, patients, scientists, industry partners, governments, and advocacy organisations. Implementation of this integrated comprehensive plan will benefit people who are at risk for or affected by CKD worldwide.

Quality of care and mortality are worse in chronic kidney disease patients living in remote areas

Many patients with non-dialysis dependent chronic kidney disease (CKD) live far from the closest nephrologist; although reversible, this might constitute a barrier to optimal care. In order to evaluate outcomes, we selected 31,452 outpatients older than 18 years with an estimated glomerular filtration rate (eGFR) less than 45 ml/min per 1.73 m² who had serum creatinine measured at least once during 2005 in Alberta, Canada. We then used logistic regression to examine the association between outcomes of 6545 patients who lived more than 50 km from the nearest nephrologist. Over a median follow-up of 27 months, 7684 participants died and 15,075 were hospitalized at least once. Compared with those living within 50 km, those further away were significantly less likely to visit a nephrologist or a multidisciplinary CKD clinic within 18 months of the index measurement of the eGFR. Similarly, remote dwellers with diabetes were significantly less likely to have hemoglobin A1c evaluated within 1 year of the index eGFR measurement, to have urinary albumin assessed biannually, or to receive an angiotensin converting enzyme inhibitor or receptor blocker in the setting of diabetes or proteinuria. Remote-dwelling participants were also significantly more likely to die or be hospitalized during follow-up than those living closer. Thus, among people with CKD, remote dwellers were less likely to receive specialist care, recommended laboratory testing, and appropriate medications, and were more likely to die or be hospitalized compared with those living closer to a nephrologist.

Associations among Estimated Glomerular Filtration Rate, Proteinuria, and Adverse Cardiovascular Outcomes

BACKGROUND AND OBJECTIVES Most studies of chronic kidney disease (CKD) and outcomes focus on mortality and ESRD, with limited data on other adverse outcomes. This study examined the associations among proteinuria, eGFR, and adverse cardiovascular (CV) events. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a population-based longitudinal study with patients identified from province-wide laboratory data from Alberta, Canada, between 2002 and 2007. Selected for this study from a total of 1,526,437 patients were 920,985 (60.3%) patients with at least one urine dipstick measurement and 102,701 patients (6.7%) with at least one albumin-creatinine ratio (ACR) measurement. Time to hospitalization was considered for one of four indications: congestive heart failure (CHF), coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI), peripheral vascular disease (PVD), and stroke/transient ischemic attacks [TIAs] (cerebrovascular accident [CVA]/TIA). RESULTS After a median follow-up of 35 months, in fully adjusted models and compared with patients with estimated GFR (eGFR) of 45 to 59 ml/min per 1.73 m(2) and no proteinuria, patients with heavy proteinuria by dipstick and eGFR ≥ 60 ml/min per 1.73 m(2) had higher rates of CABG/PCI and CVA/TIA. Similar results were obtained in patients with proteinuria measured by ACR. CONCLUSIONS Risks of major CV events at a given level of eGFR increased with higher levels of proteinuria. The findings extend current data on risk of mortality and ESRD. Measurement of proteinuria is of incremental prognostic benefit at every level of eGFR. The data support use of proteinuria measurement with eGFR for definition and risk stratification in CKD.

Socioeconomic status and chronic kidney disease at presentation to a renal service in the United Kingdom.

BACKGROUND AND OBJECTIVES Low socioeconomic status (SES) is associated with both development and progression of chronic kidney disease (CKD). The impact of SES on severity of CKD at presentation to a renal service is less well known. This study investigated the relationship between SES and severity of CKD in a retrospective, cross-sectional analysis involving 1657 patients at the Sheffield Kidney Institute (Sheffield, UK). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS SES was assigned to each patient according to electoral ward of residence by postcode and ranked according to the corresponding British Index of Multiple Deprivation score, which comprises five deprivation quintiles (Q1, least deprived; Q5, most deprived). National Kidney Foundation Kidney Disease Outcomes Quality Initiative classification of CKD was used for stratification and analysis. Binary logistic regression analysis was applied for the association of variables/risk factors with CKD (lower GFR) at presentation. RESULTS The age-adjusted prevalence of diagnosed CKD at presentation by area of residence, across the five deprivation quintiles, per million population was Q1 = 1495, Q2 = 3530, Q3 = 3398, Q4 = 3989, and Q5 = 19,599. Logistic regression models showed that living in the lowest SES quintile area (Q5) as compared with the highest SES (Q1) was associated with a greater risk for presenting with a lower estimated GFR, after adjustment for sociodemographic, lifestyle, and clinical variables. CONCLUSIONS Low SES is related to severity of CKD at presentation. Further studies are needed to examine this issue across the various SES categories in the United Kingdom.

Higher estimated glomerular filtration rates may be associated with increased risk of adverse outcomes, especially with concomitant proteinuria

The estimated glomerular filtration rate (eGFR) is a powerful predictor of adverse outcomes, but most attention has focused on studies in the setting of reduced eGFR. Here we tested whether patients with an eGFR higher than 60-89.9 ml/min per 1.73 m(2) could also be at elevated risk of adverse outcomes. Further, we tested whether concomitant proteinuria further increases the risk of outcomes among individuals with an eGFR equal to or above 90 ml/min per 1.73 m(2), as it does for those with reduced eGFR. Using data from a population-based outpatient laboratory data set of 1,526,437 patients, we measured adjusted associations between eGFR calculated by the modification of diet in renal disease equation, urine dipstick proteinuria, and adverse clinical outcomes. The adjusted risk of all-cause mortality was lowest at an eGFR of 60-74.9 ml/min per 1.73 m(2) (referent) and increased at both lower and higher levels of eGFR. Specifically, the hazard ratio of death was 3.7 and 1.8 among patients with an eGFR equal to or above 105 and 90-104.9 ml/min per 1.73 m(2), respectively, compared to the referent group. Similar results were seen when the CKD-EPI equation (sensitivity analyses) was used to assess eGFR. Higher levels of eGFR were not associated with the risk of kidney failure or myocardial infarction. Thus, the presence and severity of proteinuria was significantly associated with graded increases in the risk of clinical outcomes for both lower and higher eGFR. We do not know, however, whether the finding at higher eGFR could be due to inadequacies of the eGFR formula at low serum creatinine levels.

Chronic Kidney Disease in Older People: Physiology, Pathology or Both?

The global population is aging due to a reduction in youthful deaths and an extension of the later stages of life. With aging comes a decline in the physiologic functions of various organs and systems. Vascular aging is associated with structural and functional changes of the arterial wall leading to loss of elasticity and compliance. Renal vasculature is not spared as aging is associated with arterial, arteriolar and capillary, glomerular changes (glomerulosclerosis). It is likely that age-related vascular changes are linked to the decline in renal function observed with aging. These changes occur at varying stages of aging depending on predisposing genetic factors and associated life course exposure to cardiovascular risk factors including hypertension and diabetes. The decline in renal function with ‘normal’ aging in the absence of associated progressive cardiovascular disease is slow and does not seem to be of major clinical significance. The current definition of chronic kidney disease (CKD), including microalbuminuria, and the method of estimation of glomerular filtration rate have inadvertently resulted in an exaggerated prevalence of CKD in the elderly. This is combined with the fact that most of the studies showing decline in renal function with aging are limited by the absence of a correction for associated comorbid confounding factors, resulting in difficulty separating the effect of physiological aging on kidney function from pathological aging due to comorbidities. Such a correction is difficult, if not impossible, to objectively construct. We suggest that only those fractions of older patients with underlying progressive vascular pathology likely to involve the kidneys will, in the future, warrant attention to reduce vascular risk and the associated kidney damage.