Guillermo Garcia-Garcia

Chronic kidney disease: global dimension and perspectives

Chronic kidney disease is defined as a reduced glomerular filtration rate, increased urinary albumin excretion, or both, and is an increasing public health issue. Prevalence is estimated to be 8-16% worldwide. Complications include increased all-cause and cardiovascular mortality, kidney-disease progression, acute kidney injury, cognitive decline, anaemia, mineral and bone disorders, and fractures. Worldwide, diabetes mellitus is the most common cause of chronic kidney disease, but in some regions other causes, such as herbal and environmental toxins, are more common. The poorest populations are at the highest risk. Screening and intervention can prevent chronic kidney disease, and where management strategies have been implemented the incidence of end-stage kidney disease has been reduced. Awareness of the disorder, however, remains low in many communities and among many physicians. Strategies to reduce burden and costs related to chronic kidney disease need to be included in national programmes for non-communicable diseases.

International Society of Nephrology's 0by25 initiative for acute kidney injury (zero preventable deaths by 2025): a human rights case for nephrology

Executive summary Acute kidney injury (AKI) is a major contributor to poor patient outcomes. AKI occurs in about 13·3 million people per year, 85% of whom live in the developing world, and, although no direct link between AKI and death has yet been shown, AKI is thought to contribute to about 1·7 million deaths every year. The course of AKI varies with the setting in which it occurs, and the severity and duration of AKI aff ects outcomes such as dialysis requirement, renal functional recovery, and survival. Recognition is increasing for the eff ect of AKI on patients, and the resulting societal burden from its longterm eff ects, including development of chronic kidney disease and end-stage renal disease needing dialysis or trans plantation. Few systematic eff orts to manage (prevent, diagnose, and treat) AKI have been put in place and few resources have been allocated to inform health-care professionals and the public of the importance of AKI as a preventable and treatable disease. Several factors have contributed to the paucity of information. Most importantly, there have been few population-level epidemiological studies in several regions of the world. Diffi culties in defi nition of the incidence of AKI are especially evident in searches for data from low-income and middle-income countries, where more than 85% of the world’s population resides. No nationwide data collection systems are available, and data are usually from isolated centres and probably largely underestimate the true extent of AKI because they mostly do not include patients with AKI who were not able to reach a hospital for treatment. A recent metaanalysis that included 312 cohort studies and more than 49 million patients shows a scarcity of data from Africa and large parts of southeast Asia. We did an updated meta-analysis that used the most recent KDIGO (Kidney Disease: Improving Global Outcomes) defi nitions, which confi rms the high incidence and resulting outcomes of AKI, particularly in Africa, Asia, and Latin America, for which data were previously absent. The strong relation between the severity of AKI and consequent mortality is reiterated by our fi ndings and is evident across heterogeneous populations and specifi c disease cohorts. However, large gaps remain in knowledge about the factors that aff ect the geographical variation of AKI and poor outcomes. Many diff erences exist in the aetiology, pathophysiology, and management of AKI across the world. In high-income countries, AKI develops mainly in patients in hospitals. In low-income and middle-income countries, AKI occurs mainly in the community setting in acute illness, usually in association with diarrhoeal states and dehydration, infections such as malaria, and toxins (venoms and poisons). Public health issues (eg, contaminated water, poor sanitation, endemic infections such as malaria and dengue fever, venomous snakes, and toxic traditional medicines) and socioeconomic factors (eg, availability of health-care facilities) aff ect the epidemiology of AKI. Additionally availability of trained personnel and access to diagnostic tests and dialysis aff ect practice patterns and impose barriers to care. The extent to which these factors contribute to mortality and non-recovery of renal function has not been quantifi ed. AKI is potentially preventable and treatable with timely intervention, but there continues to be a high human burden. Which specifi c factors account for the poor outcomes and to what extent variations in care delivery contribute are unclear. The ability to provide lifesaving treatments for AKI provides a compelling argument to consider therapy for AKI as much of a basic right as it is to give antiretroviral drugs to treat HIV in low-resource regions, especially because care needs only be given for a Published Online March 13, 2015 http://dx.doi.org/10.1016/ S0140-6736(15)60126-X

International Differences in Dialysis Mortality Reflect Background General Population Atherosclerotic Cardiovascular Mortality

Existing national, racial, and ethnic differences in dialysis patient mortality rates largely are unexplained. This study aimed to test the hypothesis that mortality rates related to atherosclerotic cardiovascular disease (ASCVD) in dialysis populations (DP) and in the background general populations (GP) are correlated. In a cross-sectional, multinational study, all-cause and ASCVD mortality rates were compared between GP and DP using the most recent data from the World Health Organization mortality database (67 countries; 1,571,852,000 population) and from national renal registries (26 countries; 623,900 population). Across GP of 67 countries (14,082,146 deaths), all-cause mortality rates (median 8.88 per 1000 population; range 1.93 to 15.40) were strongly related to ASCVD mortality rates (median 3.21; range 0.53 to 8.69), with Eastern European countries clustering in the upper and Southeast and East Asian countries in the lower rate ranges. Across DP (103,432 deaths), mortality rates from all causes (median 166.20; range 54.47 to 268.80) and from ASCVD (median 63.39 per 1000 population; range 21.52 to 162.40) were higher and strongly correlated. ASCVD mortality rates in DP and in the GP were significantly correlated; the relationship became even stronger after adjustment for age (R(2) = 0.56, P < 0.0001). A substantial portion of the variability in mortality rates that were observed across DP worldwide is attributable to the variability in background ASCVD mortality rates in the respective GP. Genetic and environmental factors may underlie these differences.

Prevalence of chronic kidney disease in the Kidney Early Evaluation Program (KEEP) México and comparison with KEEP US

The National Kidney Foundation Kidney Early Evaluation Program (KEEP) is a free community screening program aimed at early detection of kidney disease among high-risk individuals. A pilot phase of KEEP México began in 2008 in México City and Jalisco State. Adults with diabetes, hypertension, or family history of diabetes, hypertension, or chronic kidney disease (CKD) were invited to participate through advertising campaigns. All participants completed a questionnaire. Blood pressure, weight, and height were measured; blood and urine tests included albuminuria and serum creatinine to estimate glomerular filtration rate using the Modification of Diet in Renal Disease Study equation. Mean age of KEEP México City and KEEP Jalisco participants was 46 and 53 years, respectively; >70% were women. CKD prevalence was 22% in KEEP México City and 33% in KEEP Jalisco, not significantly different from reported KEEP US prevalence of 26%. CKD stages 1 and 2 were more frequent in KEEP México and stage 3 in KEEP US. In KEEP México City, CKD prevalence was higher than the overall prevalence among participants with diabetes (38%) or diabetes and hypertension (42%). Most KEEP México participants were unaware of the CKD diagnosis, despite that 71% in KEEP México City had seen a doctor in the previous year. CKD is highly prevalent, underdiagnosed, and underrecognized among high-risk individuals in México. KEEP is an effective screening program that can successfully be adapted for use in México.

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.

Recognition and management of acute kidney injury in the International Society of Nephrology 0by25 Global Snapshot: a multinational cross-sectional study

BACKGROUND Epidemiological data for acute kidney injury are scarce, especially in low-income countries (LICs) and lower-middle-income countries (LMICs). We aimed to assess regional differences in acute kidney injury recognition, management, and outcomes. METHODS In this multinational cross-sectional study, 322 physicians from 289 centres in 72 countries collected prospective data for paediatric and adult patients with confirmed acute kidney injury in hospital and non-hospital settings who met criteria for acute kidney injury. Signs and symptoms at presentation, comorbidities, risk factors for acute kidney injury, and process-of-care data were obtained at the start of acute kidney injury, and need for dialysis, renal recovery, and mortality recorded at 7 days, and at hospital discharge or death, whichever came earlier. We classified countries into high-income countries (HICs), upper-middle-income countries (UMICs), and combined LICs and LMICs (LLMICs) according to their 2014 gross national income per person. FINDINGS Between Sept 29 and Dec 7, 2014, data were collected from 4018 patients. 2337 (58%) patients developed community-acquired acute kidney injury, with 889 (80%) of 1118 patients in LLMICs, 815 (51%) of 1594 in UMICs, and 663 (51%) of 1241 in HICs (for HICs vs UMICs p=0.33; p<0.0001 for all other comparisons). Hypotension (1615 [40%] patients) and dehydration (1536 [38%] patients) were the most common causes of acute kidney injury. Dehydration was the most frequent cause of acute kidney injury in LLMICs (526 [46%] of 1153 vs 518 [32%] of 1605 in UMICs vs 492 [39%] of 1260 in HICs) and hypotension in HICs (564 [45%] of 1260 vs 611 [38%%] of 1605 in UMICs vs 440 [38%] of 1153 LLMICs). Mortality at 7 days was 423 (11%) of 3855, and was higher in LLMICs (129 [12%] of 1076) than in HICs (125 [10%] of 1230) and UMICs (169 [11%] of 1549). INTERPRETATION We identified common aetiological factors across all countries, which might be amenable to a standardised approach for early recognition and treatment of acute kidney injury. Study limitations include a small number of patients from outpatient settings and LICs, potentially under-representing the true burden of acute kidney injury in these areas. Additional strategies are needed to raise awareness of acute kidney injury in community health-care settings, especially in LICs. FUNDING International Society of Nephrology.

Survival among Patients with Kidney Failure in Jalisco, Mexico

ESRD is a serious public health problem in the state of Jalisco, Mexico. This study evaluated mortality in poor patients who initiated dialysis at the Jalisco Health Secretariat, compared with Hispanic patients without medical insurance who initiated dialysis in the United States. All patients who received a diagnosis with ESRD between February 1 and December 31, 2003, were studied prospectively at a single institution that provides care to the poor of Jalisco. Data from an American national dialysis registry and Cox proportional hazards models were used to compare the adjusted survival among Jalisco patients with that of a contemporaneous group of incident Hispanic patients who did not have Medicare or private insurance cover and who initiated peritoneal dialysis in the United States. Of 274 consecutive patients who presented with a clinical diagnosis of ESRD in Jalisco, mean estimated GFR at dialysis initiation was very low (3.9 +/- 2.4 ml/min per 1.73 m(2)), and <10% were previously known to a nephrologist. Of the 274 patients, 102 (37.2%) did not initiate dialysis therapy, 71 (69.6%) of whom died during follow-up. The majority (n = 49) of such deaths occurred in-hospital before dialysis initiation. Of 172 patients who initiated dialysis, 36 (20.9%) died within the first 90 d of renal replacement therapy. An additional 31 (18.0%) patients died during a median follow-up of 186 d. When all 274 Jalisco patients who presented with ESRD were considered, survival was 49.6% at the end of follow-up. Unadjusted mortality rates among those who survived at least 90 d after dialysis initiation were 19.2 (95% confidence interval [CI] 13.5 to 27.3) and 5.9 (95% CI 4.6 to 7.7) per 100 patient-years in Jalisco and American patients, respectively. After adjustment, the risk for death remained nearly three-fold higher in Jalisco patients (hazard ratio 2.7; 95% CI 1.5 to 4.7). Poor patients with kidney failure in Jalisco have very advanced disease at the time of first nephrologic contact and have exceedingly high rates of mortality after dialysis initiation. Our findings demonstrate a tremendous opportunity to reduce morbidity and mortality from kidney disease in Jalisco and perhaps other regions of Mexico.

Screening for CKD and Cardiovascular Disease Risk Factors Using Mobile Clinics in Jalisco, Mexico

BACKGROUND Chronic kidney disease (CKD) is a major cause of morbidity and mortality in Mexico. However, many residents of underserved areas may be unaware that they potentially are affected. STUDY DESIGN In an observational cross-sectional study, we examined the diagnostic yield of screening for CKD and cardiovascular disease risk factors using mobile units that traveled to poor communities in Jalisco, Mexico. SETTING & PARTICIPANTS We excluded individuals who were aware that they had CKD and those < 18 years of age. OUTCOMES Glomerular filtration rate, cardiovascular risk. MEASUREMENTS Demographic data, socioeconomic status, blood pressure, fasting glucose, and dipstick urinalysis. RESULTS 3,734 participants; 29.3% men and mean age of 57.4 +/- 13.0 years. Most (99.7%) had no history of cardiovascular disease; however, 43.5% had a history of diabetes, 11.4% had dipstick-positive proteinuria, 62.0% had blood pressure in the hypertensive range, and 15.8% had an estimated glomerular filtration rate compatible with stages 3-5 CKD. In patients with no history of cardiovascular disease, proportions with predicted 5-year risks of new cardiovascular events <5%, 5%-10%, 10.1%-20%, 20.1%-30%, and >30% were 10.0%, 11.7%, 26.6%, 20.7%, and 30.9%, respectively. Screening 18 participants aged < 40 years would be expected to detect 6 new cases of hypertension or 2 new cases of diabetes. LIMITATIONS Data may not be generalizable to all low-income settings or other regions of Mexico. CONCLUSIONS Impaired kidney function, proteinuria, and cardiovascular risk factors were detected frequently when mobile units were used to perform screening in poor areas of Jalisco, Mexico. This suggests that trials of targeted screening and intervention are feasible and warranted.

Latin American Dialysis and Transplant Registry: 2008 prevalence and incidence of end-stage renal disease and correlation with socioeconomic indexes.

In 2008, 563,294,000 people were living in Latin America (LA), of which 6.6% were older than 65. The region is going through a fast demographic and epidemiologic transition process, in the context of an improvement in socio-economic indices. The Latin American Dialysis and Renal Transplant Registry has collected data since 1991, through an annual survey completed by 20 affiliated National Societies. Renal replacement treatment (RRT) prevalence and incidence showed an increase year by year. The prevalence rate (in all modalities) correlated with the World Bank country classification by income and the epidemiologic transition stage the countries were experiencing. RRT prevalence and kidney transplantation rates correlated significantly with gross national income (GNI), health expenditure in constant dollars (HeExp), % older than 65, life expectancy at birth, and % of the population living in urban settings. Kidney transplantation increased also, year by year, with more than 50% of transplants performed using kidneys from deceased donors. Double transplants were performed in six countries. RRT prevalence and incidence increased in LA, and are associated with indexes reflecting higher and more evenly distributed national wealth (GNI and HeExp), and the stage of demographic and epidemiological transition.

Renal replacement therapy in Latin American end-stage renal disease

The Latin American Dialysis and Renal Transplant Registry (RLADTR) was founded in 1991; it collects data from 20 countries which are members of Sociedad Latinoamericana de Nefrología e Hipertension. This paper presents the results corresponding to the year 2010. This study is an annual survey requesting data on incident and prevalent patients undergoing renal replacement treatment (RRT) in all modalities: hemodialysis (HD), peritoneal dialysis (PD) and living with a functioning graft (LFG), etc. Prevalence and incidence were compared with previous years. The type of renal replacement therapy was analyzed, with special emphasis on PD and transplant (Tx). These variables were correlated with the gross national income (GNI) and the life expectancy at birth. Twenty countries participed in the surveys, covering 99% of the Latin American. The prevalence of end stage renal disease (ESRD) under RRT in Latin America (LA) increased from 119 patients per million population (pmp) in 1991 to 660 pmp in 2010 (HD 413 pmp, PD 135 pmp and LFG 111 pmp). HD proportionally increased more than PD, and Tx HD continues to be the treatment of choice in the region (75%). The kidney Tx rate increased from 3.7 pmp in 1987 to 6.9 pmp in 1991 and to 19.1 in 2010. The total number of Txs in 2010 was 10 397, with 58% deceased donors. The total RRT prevalence correlated positively with GNI (r2 0.86; P < 0.05) and life expectancy at birth (r2 0.58; P < 0.05). The HD prevalence and the kidney Tx rate correlated significantly with the same indexes, whereas the PD rate showed no correlation with these variables. A tendency to rate stabilization/little growth was reported in the most regional countries. As in previous reports, the global incidence rate correlated significantly only with GNI (r2 0.63; P < 0.05). Diabetes remained the leading cause of ESRD. The most frequent causes of death were cardiovascular (45%) and infections (22%). Neoplasms accounted for 10% of the causes of death. The prevalence of RRT continues to increase, particularly in countries with 100% public health or insurance coverage for RRT, where it approaches rates comparable to those displayed by developed countries with a better GNI. The incidence also continues to increase in both countries that have not yet extended its coverage to 100% of the population as well as in those that have an adequate program for timely detection and treatment of chronic kidney disease (CKD) and its associated risk factors. PD is still an underutilized strategy for RRT in the region. Even though renal Tx is feasible, its growth rate is still not as fast as it should be in order to compensate for the increased prevalence of patients on waiting lists. Diagnostic and prevention programs for hypertension and diabetes, appropriate policies promoting the expansion of PD and organ procurement as well as transplantation as cost-effective forms of RRT are needed in the region. Regional cooperation among Latin American countries, allowing the more developed to guide and train others in starting registries and CKD programs, may be one of the key initiatives to address this deficit.