Population-based screening for chronic kidney disease (CKD) is sometimes recommended based on the assumption that detecting CKD is associated with beneficial changes in treatment. However, the ...treatment of CKD is often similar to the treatment of hypertension or diabetes, which commonly coexist with CKD.
To determine the frequency with which population-based screening for CKD is associated with a change in recommended treatment compared with a strategy of measuring blood pressure and assessing glycemia.
This cohort study was conducted using data obtained from studies that evaluated CKD in population-based samples from China (2007-2010), India (2010-2014), Mexico (2007-2008), Senegal (2012), and the United States (2009-2014), including a total of 126 242 adults screened for CKD. Data were analyzed from January 2020 to March 2021.
The primary definition of CKD was estimated glomerular filtration rate less than 60 mL/min/1.73 m2. For individuals with CKD, the need for a treatment change was defined as not taking an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker or having blood pressure levels of 140/90 mm Hg or greater. For individuals with CKD who also had diabetes, the need for a treatment change was also defined as having hemoglobin A1c levels of 8% or greater or fasting glucose levels of 178.4 mg/dL (9.9 mmol/L) or greater. Case finding was defined as testing for CKD only in adults with hypertension or diabetes.
Among 126 242 adults screened for CKD, there were 47 204 patients in the China cohort, 9817 patients in the India cohort, 51 137 patients in the Mexico cohort, 2441 patients in the Senegal cohort, and 15 643 patients in the US cohort. The mean age of participants was 49.6 years (95% CI, 49.5-49.7 years) in the China cohort, 42.9 years (95% CI, 42.6-43.2 years) in the India cohort, 51.6 years (95% CI, 51.5-51.7 years) in the Mexico cohort, 48.2 years (95% CI, 47.5-48.9 years) in the Senegal cohort, and 47.3 years (95% CI, 46.6-48.0 years) in the US cohort. The proportion of women was 57.3% (95% CI, 56.9%-57.7%) in the China cohort, 53.4% (95% CI, 52.4%-54.4%) in the India cohort, 68.8% (95% CI, 68.4%-69.2%) in the Mexico cohort, 56.0% (95% CI, 54.0%-58.0%) in the Senegal cohort, and 51.9% (51.0%-52.7%) in the US cohort. The prevalence of CKD was 2.5% (95% CI, 2.4%-2.7%) in the China cohort, 2.3% (95% CI, 2.0%-2.6%) in the India cohort, 10.6% (95% CI, 10.3%-10.9%) in the Mexico cohort, 13.1% (95% CI, 11.7%-14.4%) in the Senegal cohort, and 6.8% (95% CI, 6.2%-7.5%) in the US cohort. Screening for CKD was associated with the identification of additional adults whose treatment would change (beyond those identified by measuring blood pressure and glycemia) per 1000 adults: China: 8 adults (95% CI, 8-9 adults); India: 5 adults (95% CI, 4-7 adults); Mexico: 26 adults (95% CI, 24-27 adults); Senegal: 59 adults (95% CI, 50-69 adults); and the US: 19 adults (95% CI, 16-23 adults). Case finding was associated with the identification of 46.2% (95% CI, 45.1%-47.4%) to 86.4% (95% CI, 85.4%-87.3%) of individuals with CKD depending on the country, an increase in the proportion of individuals requiring a treatment change by as much 89.6% (95% CI, 80.4%-99.3%) in the US, and a decrease in the proportion of individuals needing GFR measurements by as much as 57.8% (95% CI, 56.3%-59.3%) in the US.
This study found that most additional individuals with CKD identified by population-based screening programs did not need a change in treatment compared with a strategy of measuring blood pressure and assessing glycemia and that case finding was more efficient than screening for early detection of CKD.
To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk.
Network ...meta-analysis.
Medline, Embase, and Cochrane CENTRAL up to 11 August 2020.
Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias.
Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review.
764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 3 to 40 fewer deaths in 1000 patients over five years; see interactive decision support tool (https://magicevidence.org/match-it/200820dist/#!/) for all outcomes.
In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with some differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review.
PROSPERO CRD42019153180.
Numerous glucose-lowering drugs are used to treat type 2 diabetes.
To estimate the relative efficacy and safety associated with glucose-lowering drugs including insulin.
Cochrane Library Central ...Register of Controlled Trials, MEDLINE, and EMBASE databases through March 21, 2016.
Randomized clinical trials of 24 weeks' or longer duration.
Random-effects network meta-analysis.
The primary outcome was cardiovascular mortality. Secondary outcomes included all-cause mortality, serious adverse events, myocardial infarction, stroke, hemoglobin A1c (HbA1C) level, treatment failure (rescue treatment or lack of efficacy), hypoglycemia, and body weight.
A total of 301 clinical trials (1,417,367 patient-months) were included; 177 trials (56,598 patients) of drugs given as monotherapy; 109 trials (53,030 patients) of drugs added to metformin (dual therapy); and 29 trials (10,598 patients) of drugs added to metformin and sulfonylurea (triple therapy). There were no significant differences in associations between any drug class as monotherapy, dual therapy, or triple therapy with odds of cardiovascular or all-cause mortality. Compared with metformin, sulfonylurea (standardized mean difference SMD, 0.18 95% CI, 0.01 to 0.34), thiazolidinedione (SMD, 0.16 95% CI, 0.00 to 0.31), DPP-4 inhibitor (SMD, 0.33 95% CI, 0.13 to 0.52), and α-glucosidase inhibitor (SMD, 0.35 95% CI, 0.12 to 0.58) monotherapy were associated with higher HbA1C levels. Sulfonylurea (odds ratio OR, 3.13 95% CI, 2.39 to 4.12; risk difference RD, 10% 95% CI, 7% to 13%) and basal insulin (OR, 17.9 95% CI, 1.97 to 162; RD, 10% 95% CI, 0.08% to 20%) were associated with greatest odds of hypoglycemia. When added to metformin, drugs were associated with similar HbA1C levels, while SGLT-2 inhibitors offered the lowest odds of hypoglycemia (OR, 0.12 95% CI, 0.08 to 0.18; RD, -22% -27% to -18%). When added to metformin and sulfonylurea, GLP-1 receptor agonists were associated with the lowest odds of hypoglycemia (OR, 0.60 95% CI, 0.39 to 0.94; RD, -10% 95% CI, -18% to -2%).
Among adults with type 2 diabetes, there were no significant differences in the associations between any of 9 available classes of glucose-lowering drugs (alone or in combination) and the risk of cardiovascular or all-cause mortality. Metformin was associated with lower or no significant difference in HbA1C levels compared with any other drug classes. All drugs were estimated to be effective when added to metformin. These findings are consistent with American Diabetes Association recommendations for using metformin monotherapy as initial treatment for patients with type 2 diabetes and selection of additional therapies based on patient-specific considerations.
Many nephrology observational studies use renal registries, which have well known limitations. The Canadian Kidney Disease Cohort Study (CKDCS) is a large prospective observational study of patients ...commencing hemodialysis in five Canadian centers. This study focuses on delineating potentially reversible determinants of adverse outcomes that occur in patients receiving dialysis for end-stage renal disease (ESRD).
The CKDCS collects information on risk factors and outcomes, and stores specimens (blood, dialysate, hair and fingernails) at baseline and in long-term follow-up. Such specimens will permit measurements of biochemical markers, proteomic and genetic parameters (proteins and DNA) not measured in routine care. To avoid selection bias, all consenting incident hemodialysis patients at participating centers are enrolled, the large sample size (target of 1500 patients), large number of exposures, and high event rates will permit the exploration of multiple potential research questions.
Data on the baseline characteristics from the first 1074 subjects showed that the average age of patients was 62 (range; 50-73) years. The leading cause of ESRD was diabetic nephropathy (41.9%), and the majority of the patients were white (80.0%). Only 18.7% of the subjects received dialysis in a satellite unit, and over 80% lived within a 50 km radius of the nearest nephrologist's practice.
The prospective design, detailed clinical information, and stored biological specimens provide a wealth of information with potential to greatly enhance our understanding of risk factors for adverse outcomes in dialysis patients. The scientific value of the stored patient tissue will grow as new genetic and biochemical markers are discovered in the future.
Since 2015, the International Society of Nephrology (ISN) Global Kidney Health Atlas (ISN-GKHA) has spearheaded multinational efforts to understand the status and capacity of countries to provide ...optimal kidney care, particularly in low-resource settings. In this iteration of the ISN-GKHA, we sought to extend previous findings by assessing availability, accessibility, quality, and affordability of medicines, kidney replacement therapy (KRT), and conservative kidney management (CKM).
A consistent approach was used to obtain country-level data on kidney care capacity during three phases of data collection in 2016, 2018, and 2022. The current report includes a detailed literature review of published reports, databases, and registries to obtain information on the burden of chronic kidney disease and estimate the incidence and prevalence of treated kidney failure. Findings were triangulated with data from a multinational survey of opinion leaders based on the WHO's building blocks for health systems (ie, health financing, service delivery, access to essential medicines and health technology, health information systems, workforce, and governance). Country-level data were stratified by the ISN geographical regions and World Bank income groups and reported as counts and percentages, with global, regional, and income level estimates presented as medians with interquartile ranges.
The literature review used information on prevalence of chronic kidney disease from 161 countries. The global median prevalence of chronic kidney disease was 9·5% (IQR 5·9–11·7) with the highest prevalence in Eastern and Central Europe (12·8%, 11·9–14·1). For the survey analysis, responses received covered 167 (87%) of 191 countries, representing 97·4% (7·700 billion of 7·903 billion) of the world population. Chronic haemodialysis was available in 162 (98%) of 165 countries, chronic peritoneal dialysis in 130 (79%), and kidney transplantation in 116 (70%). However, 121 (74%) of 164 countries were able to provide KRT to more than 50% of people with kidney failure. Children did not have access to haemodialysis in 12 (19%) of 62 countries, peritoneal dialysis in three (6%) countries, or kidney transplantation in three (6%) countries. CKM (non-dialysis management of people with kidney failure chosen through shared decision making) was available in 87 (53%) of 165 countries. The annual median costs of KRT were: US$19 380 per person for haemodialysis, $18 959 for peritoneal dialysis, and $26 903 for the first year of kidney transplantation. Overall, 74 (45%) of 166 countries allocated public funding to provide free haemodialysis at the point of delivery; use of this funding scheme increased with country income level. The median global prevalence of nephrologists was 11·8 per million population (IQR 1·8–24·8) with an 80-fold difference between low-income and high-income countries. Differing degrees of health workforce shortages were reported across regions and country income levels. A quarter of countries had a national chronic kidney disease-specific strategy (41 25% of 162) and chronic kidney disease was recognised as a health priority in 78 (48%) of 162 countries.
This study provides new information about the global burden of kidney disease and its treatment. Countries in low-resource settings have substantially diminished capacity for kidney care delivery. These findings have major policy implications for achieving equitable access to kidney care.
International Society of Nephrology.
Successful management of chronic kidney disease (CKD) in Latin America (LA) continues to represent a challenge due to high disease burden and geographic disparities and difficulties in terms of ...capacity, accessibility, equity, and quality of kidney failure care. Although LA has experienced significant social and economic progress over the past decades, there are still important inequities in health care access. Through this third iteration of the International Society of Nephrology Global Kidney Health Atlas, the indicators regarding kidney failure care in LA are updated. Survey responses were received from 22 of 31 (71%) countries in LA representing 96.5% of its total population. Median CKD prevalence was 10.2% (interquartile range: 8.4%–12.3%), median CKD disability-adjusted life year was 753.4 days (interquartile range: 581.3–1072.5 days), and median CKD mortality was 5.5% (interquartile range: 3.2%–6.3%). Regarding dialysis modality, hemodialysis continued to be the most used therapy, whereas peritoneal dialysis reached a plateau and kidney transplantation increased steadily over the past 10 years. In 20 (91%) countries, >50% of people with kidney failure could access dialysis, and in only 2 (9%) countries, people who had access to dialysis could initiate dialysis with peritoneal dialysis. A mix of public and private systems collectively funded most aspects of kidney replacement therapy (dialysis and transplantation) with many people incurring up to 50% of out-of-pocket costs. Few LA countries had CKD/kidney replacement therapy registries, and almost no acute kidney injury registries were reported. There was large variability in the nature and extent of kidney failure care in LA mainly related to countries’ funding structures and limited surveillance and management initiatives.
The South Asia region is facing a high burden of chronic kidney disease (CKD) with limited health resources and low expenditure on health care. In addition to the burden of CKD and kidney failure ...from traditional risk factors, CKD of unknown etiologies from India and Sri Lanka compounds the challenges of optimal management of CKD in the region. From the third edition of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA), we present the status of CKD burden, infrastructure, funding, resources, and health care personnel using the World Health Organization’s building blocks for health systems in the ISN South Asia region. The poor status of the public health care system and low health care expenditure resulted in high out-of-pocket expenditures for people with kidney disease, which further compounded the situation. There is insufficient country capacity across the region to provide kidney replacement therapies to cover the burden. The infrastructure was also not uniformly distributed among the countries in the region. There were no chronic hemodialysis centers in Afghanistan, and peritoneal dialysis services were only available in Bangladesh, India, Nepal, Pakistan, and Sri Lanka. Kidney transplantation was not available in Afghanistan, Bhutan, and Maldives. Conservative kidney management was reported as available in 63% (n = 5) of the countries, yet no country reported availability of the core CKM care components. There was a high hospitalization rate and early mortality because of inadequate kidney care. The lack of national registries and actual disease burden estimates reported in the region prevent policymakers’ attention to CKD as an important cause of morbidity and mortality. Data from the 2023 ISN-GKHA, although with some limitations, may be used for advocacy and improving CKD care in the region.
The highest financial and symptom burdens and the lowest health-related quality-of-life scores are seen in people with kidney failure. A total of 11 countries in the International Society of ...Nephrology (ISN) Middle East region responded to the ISN-Global Kidney Health Atlas. The prevalence of chronic kidney disease (CKD) in the region ranged from 4.9% in Yemen to 12.2% in Lebanon, whereas prevalence of kidney failure treated with dialysis or transplantation ranged from 152 per million population (pmp) in the United Arab Emirates to 869 pmp in Kuwait. Overall, the incidence of kidney transplantation was highest in Saudi Arabia (20.2 pmp) and was lowest in Oman (2.2 pmp). Chronic hemodialysis (HD) and peritoneal dialysis (PD) services were available in all countries, whereas kidney transplantation was available in most countries of the region. Public government funding that makes acute dialysis, chronic HD, chronic PD, and kidney transplantation medications free at the point of delivery was available in 54.5%, 72.7%, 54.5%, and 54.5% of countries, respectively. Conservative kidney management was available in 45% of countries. Only Oman had a CKD registry; 7 countries (64%) had dialysis registries, and 8 (73%) had kidney transplantation registries. The ISN Middle East region has a high burden of kidney disease and multiple challenges to overcome. Prevention and detection of kidney disease can be improved by the design of tailored guidelines, allocation of additional resources, improvement of early detection at all levels of care, and implementation of sustainable health information systems.
The International Society of Nephrology Global Kidney Health Atlas charts the availability and capacity of kidney care globally. In the North America and the Caribbean region, the Atlas can identify ...opportunities for kidney care improvement, particularly in Caribbean countries where structures for systematic data collection are lacking. In this third iteration, respondents from 12 of 18 countries from the region reported a 2-fold higher than global median prevalence of dialysis and transplantation, and a 3-fold higher than global median prevalence of dialysis centers. The peritoneal dialysis prevalence was lower than the global median, and transplantation data were missing from 6 of the 10 Caribbean countries. Government-funded payments predominated for dialysis modalities, with greater heterogeneity in transplantation payor mix. Services for chronic kidney disease, such as monitoring of anemia and blood pressure, and diagnostic capability relying on serum creatinine and urinalyses were universally available. Notable exceptions in Caribbean countries included non-calcium-based phosphate binders and kidney biopsy services. Personnel shortages were reported across the region. Kidney failure was identified as a governmental priority more commonly than was chronic kidney disease or acute kidney injury. In this generally affluent region, patients have better access to kidney replacement therapy and chronic kidney disease–related services than in much of the world. Yet clear heterogeneity exists, especially among the Caribbean countries struggling with dialysis and personnel capacity. Important steps to improve kidney care in the region include increased emphasis on preventive care, a focus on home-based modalities and transplantation, and solutions to train and retain specialized allied health professionals.
Delivery of care for kidney failure (KF) globally has a significant disparity; even in some countries, it means end of life for the person. The International Society of Nephrology Global Kidney ...Health Atlas (ISN-GKHA) tries to address gaps in KF care and standardize global nephrology care. From the third iteration of the ISN-GKHA, we present data for countries in the ISN Eastern and Central Europe region. The median prevalences of chronic kidney disease (12.8%) and treated KF (873.5 pmp) were higher than the global rates, respectively. Hemodialysis was the most preferred modality for KF in adults, whereas kidney replacement therapy was more balanced in children. Although most of the countries in the region had lower-middle–income and upper-middle–income levels, health expenditures for kidney health care were almost generally covered publicly. Nephrologists were responsible for the medical kidney care of people with KF in all countries. There was adequate infrastructure to provide all kinds of treatment for kidney care in the region. Regional characteristics such as high levels of obesity, smoking, and Balkan nephropathy as an endemic disease coupled with a shortage of workforce and finance continued to affect kidney care in the region negatively. By making organizational and legislative arrangements, partnerships with national authorities and societies may accelerate the improvement of kidney health care in the region.
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