Survival among Patients with Kidney Failure in Jalisco, Mexico
Guillermo Garcia-Garcia*,
Gregorio Briseño-Rentería*,
Victor H. Luquín-Arellan*,
Zhiwei Gao,
John Gill and
Marcello Tonelli
* Nephrology Service, Hospital Civil de Guadalajara, Guadalajara, Jalisco, Mexico; Department of Medicine, University of Alberta, Alberta, Edmonton, Canada; and Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
Address correspondence to: Dr. Guillermo Garcia-Garcia, Hospital Civil de Guadalajara, Hospital 278, 44280 Guadalajara, Jalisco, Mexico. Phone: +52-33-3614-7456, ext. 310; Fax: +52-33-3817-3514; garciagg{at}prodigy.net.mx
Received for publication December 20, 2006.
Accepted for publication March 19, 2007.
ESRD is a serious public health problem in the state of Jalisco,Mexico. This study evaluated mortality in poor patients whoinitiated dialysis at the Jalisco Health Secretariat, comparedwith Hispanic patients without medical insurance who initiateddialysis in the United States. All patients who received a diagnosiswith ESRD between February 1 and December 31, 2003, were studiedprospectively at a single institution that provides care tothe poor of Jalisco. Data from an American national dialysisregistry and Cox proportional hazards models were used to comparethe adjusted survival among Jalisco patients with that of acontemporaneous group of incident Hispanic patients who didnot have Medicare or private insurance cover and who initiatedperitoneal dialysis in the United States. Of 274 consecutivepatients who presented with a clinical diagnosis of ESRD inJalisco, mean estimated GFR at dialysis initiation was verylow (3.9 ± 2.4 ml/min per 1.73 m2), and <10% werepreviously known to a nephrologist. Of the 274 patients, 102(37.2%) did not initiate dialysis therapy, 71 (69.6%) of whomdied during follow-up. The majority (n = 49) of such deathsoccurred in-hospital before dialysis initiation. Of 172 patientswho initiated dialysis, 36 (20.9%) died within the first 90d of renal replacement therapy. An additional 31 (18.0%) patientsdied during a median follow-up of 186 d. When all 274 Jaliscopatients who presented with ESRD were considered, survival was49.6% at the end of follow-up. Unadjusted mortality rates amongthose who survived at least 90 d after dialysis initiation were19.2 (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 Americanpatients, respectively. After adjustment, the risk for deathremained nearly three-fold higher in Jalisco patients (hazardratio 2.7; 95% CI 1.5 to 4.7). Poor patients with kidney failurein Jalisco have very advanced disease at the time of first nephrologiccontact and have exceedingly high rates of mortality after dialysisinitiation. Our findings demonstrate a tremendous opportunityto reduce morbidity and mortality from kidney disease in Jaliscoand perhaps other regions of Mexico.
In the past 60 yr, Mexico has experienced significant economicprogress that has been accompanied by major societal change.As in other developing nations, life expectancy in Mexico hasincreased, and morbidity and mortality as a result of infectiousdiseases have fallen dramatically. However, these successeshave been offset by the emergence of chronic noncommunicablediseases, such as diabetes, hypertension, and chronic kidneydisease (CKD), which currently account for 56% of deaths inthe general population (1–3).
The state of Jalisco is located in western Mexico and has 6.3million inhabitants, approximately 60% of whom live in the statecapital of Guadalajara with the remainder in dispersed urbanand rural areas. Unemployment among adults who seek work islow (2%), and annual per capita income is approximately US$6000/yr.The chief employers in Jalisco are the service (31%) and industrial(25%) sectors, with only 11% of adults working in the agriculturalindustry. Despite this growing economic prosperity, 10% of Jaliscohouseholds do not have running water or sewage systems (4).
The public health care system in Jalisco (like elsewhere inMexico) is multitiered and highly centralized. Social securitybenefits (including access to dialysis) are available to individualswho are employed by corporations or the state. However, suchpeople represent less than half of the Jalisco population, and<2% can afford private health insurance. The remaining 56%do not have access to social security and cannot afford accessto private health care services. This segment of the populationseeks care at the facilities of the state’s Health Secretariat.
ESRD is a serious public health problem in Jalisco and is amongthe 10 leading causes of death, with an annual mortality rateof 12 deaths per 100,000 population (4). Diabetes is responsiblefor 56% of incident cases of ESRD in Jalisco, and the proportionis increasing over time (5). The public health care system hasbeen placed under tremendous strain by the epidemic of diabetesand its complications. Although access to predialysis care isalmost universal for those with social security benefits, itis severely restricted for the poor (6).
Clinical experience suggests that Jalisco patients who havekidney failure and do not have social security benefits presentvery late to nephrologic services, leading to adverse outcomes.We conducted this prospective study to examine mortality inpatients who initiated dialysis at the Jalisco Health Secretariat,compared with Hispanic patients who did not have medical insuranceand initiated dialysis in the United States.
Data Sources Jalisco, Mexico.
The Hospital Civil de Guadalajara is a large tertiary care facilitythat offers dialysis to patients without medical insurance andis funded by the state and federal governments. Unlike the situationin the United States, most Jalisco patients with ESRD starton continuous ambulatory peritoneal dialysis (CAPD). Becauseof limited resources, hemodialysis is mainly used as a back-uptherapy for PD failures. Every patient who is referred for renalreplacement therapy (RRT) is presented to a review board thatincludes a social worker, nurses, and physicians. The patient’ssocioeconomic and medical conditions are closely scrutinized,including housing conditions. When needed, recommendations forminor home adaptations are made. Patients are generally initiatedon treatment with weekly intermittent PD while being trainedfor CAPD. Once training is complete and the home environmenthas been optimized, patients initiate CAPD. Payment for home-delivereddialysis supplies is made in advance by those with sufficientfunds (approximately US$180/mo). The cost of treatment is whollyor partially borne by the hospital for patients who cannot affordthese charges, and no patient is denied access to dialysis becauseof inability to pay.
All patients who received a diagnosis of ESRD between February1 and December 31, 2003, were prospectively registered by oneof us (G.B.-R.). Patients who had acute renal failure, thosewho previously underwent dialysis, and those who had receiveda kidney transplant were excluded from the study.
Baseline data that were obtained from each patient includedage, gender, cause of renal failure, type of referral (self,physician), referring physician (nephrologist, other), typeof admission (emergency, elective), laboratory data (hematocrit,serum creatinine, serum albumin), appropriate or inappropriatehousing to permit CAPD, and the presence of a ready-to-use dialysisaccess. GFR was estimated using the Modification of Diet inRenal Disease (MDRD) study equation (7).
Patients who presented for dialysis because of uremic symptomsand without being referred by a physician were considered as"self-referred." For those who were referred by a physician,the distinction was made between nephrologists and other specialists."Inappropriate housing" was defined as a house with one or moreof the following conditions: Lack of plastered and painted walls,presence of a cardboard ceiling, or lack of an intact windowand/or a door. Acute dialysis was defined as the initiationof dialysis using an uncuffed temporary PD catheter. Long-termdialysis was considered to have commenced at the time a permanent,double-cuffed PD catheter was inserted. Vital status was ascertainedby data linkage with the Office of Vital Statistics at the stateHealth Secretariat.
United States.
We used data from the US Renal Data System (USRDS) to obtaina contemporaneous comparator group of patients who initiatedRRT in the United States. This cohort was composed of incidentHispanic PD patients who did not have Medicare, Medicaid, orprivate insurance coverage and who initiated RRT between April1, 1995, and October 3, 2001. Because Medicare data availabilityis inconsistent during the first 90 d of dialysis therapy (8),we restricted analyses that used USRDS data to patients whosurvived at least 90 d. Baseline demographic and clinical characteristicswere obtained from the Identification and Medical Evidence portionsof the Renal Beneficiary Utilization System of the Health CareFinancing Administration. The date of death for deceased patientswas obtained from the Renal Beneficiary Utilization System Identificationand Death Notification Files.
Statistical Analyses
Survival time was defined for all participants by the periodbeginning 90 d after dialysis inception and ending at death.Follow-up was censored in all participants at 1300 d, loss tofollow-up, or renal transplantation. We individually examinedthe association between region of treatment (United States versusJalisco) and other factors on survival after dialysis inceptionusing Cox proportional hazards models. We then determined whetherthese associations were statistically independent of other factorsusing multivariable Cox models that included variables thatshowed an association (P < 0.1) with survival in univariatemodels. Factors considered included age, gender, diabetic status,smoking status, weight, hematocrit, serum creatinine, and serumalbumin (all at baseline). We determined that the proportionalhazard assumption was satisfied by examining plots of the log-negative-logof the within-group survivorship functions versus log-time aswell as comparing Kaplan-Meier (observed) with Cox (expected)survival curves. Adjusted survival curves were produced usingthe mean of covariates method. Statistical analyses were performedwith SAS software version 8.2 (SAS Institute, Cary, NC) andStata software version 8.0 (Stata Corp., College Station, TX).This study was approved by the institutional review boards atthe Hospital Civil de Guadalajara and the University of Alberta.
Study Population
Of 274 consecutive Jalisco patients who presented with a clinicaldiagnosis of ESRD, the average age was 49.1 ± 18.4 yr,and approximately 85% were admitted through the emergency department.Residual kidney function at dialysis initiation was very poor(mean estimated GFR 3.9 ml/min per 1.73 m2), and severe metabolicacidosis, anemia, and abnormal calcium-phosphate metabolismwere common. Fewer than 10% of patients were previously knownto a nephrologist, and only seven (2.6%) had estimated GFR >10.5ml/min per 1.73 m2 at dialysis initiation.
Access to Dialysis Treatment
Of 274 Jalisco patients with ESRD, 102 (37.2%) did not initiatedialysis therapy. Of these, 49 (48%) died in hospital beforedialysis was initiated, 35 (34.3%) chose not to initiate dialysis,and 15 (14.7%) were not considered suitable for dialysis becausethey were moribund (n = 2) or lacked appropriate housing orfamily support (n = 13). An additional three patients transferredto another facility. Patients who initiated dialysis were morelikely to be younger; more likely to be female; and had slightlyless abnormal levels of serum phosphate, bicarbonate, and albuminthan patients who did not initiate dialysis (Table 1). AmongJalisco patients, markers of socioeconomic deprivation werecommon. However, within the population studied, there was norelation between socioeconomic characteristics and the likelihoodof initiating RRT (Table 2). Of those who did not initiate dialysis,71 (69.6%) of 102 died during follow-up.
Table 2. Socioeconomic characteristics of patients who were referred for dialysis treatmenta
Survival on Dialysis among Jalisco Patients
Of the 172 patients who initiated dialysis in Jalisco, 36 (20.9%)died within the first 90 d of RRT. An additional 31 (18.0%)patients who survived this period died during follow-up. Aftera median of 186 d of follow-up, 19.8% of patients had died (unadjustedmortality rate 11.0 per 100 patient-years; 95% confidence interval[CI] 6.8 to 17.7) among patients who initiated dialysis treatment.When all 274 patients who presented with ESRD were considered,survival was 49.6% at the end of follow-up.
Comparison with Patients Who Initiated PD in the United States
We restricted these analyses to the 106 patients with at least90 d of follow-up time on dialysis, excluding those who diedwithin the first 90 d or had <90 d of follow-up at studyend. In these analyses, treatment in Jalisco was associatedwith similar demographic characteristics (including age andthe likelihood of diabetes) but much poorer residual renal function,lower serum albumin, and more severe anemia at dialysis initiationthan treatment in the United States (Table 3).
Table 3. Demographic and clinical characteristics of patients who initiated dialysis treatment in Jalisco compared with the United Statesa
After a median follow-up of 865 d, survival in this group was70.8% in Jalisco patients and 86.1% in American patients (P= 0.001). Unadjusted mortality rates were 19.2 (95% CI 13.5to 27.3) and 5.9 (95% CI 4.6 to 7.7) per 100 patient-years,respectively. After adjustment for age and gender, the riskfor death after dialysis initiation remained approximately three-foldhigher in Jalisco patients than in American PD patients of Hispanicdescent (hazard ratio [HR] 3.2; 95% CI 2.1 to 5.1) and was similarin the fully adjusted model (HR 2.7; 95% CI 1.5 to 4.7; Figure 1).
Figure 1. Adjusted survival of patients who initiated peritoneal dialysis in Jalisco compared with patients who were treated in the United States. The figure shows survival among patients who survived on dialysis for 90 d, after adjustment for age, gender, body weight, diabetic status, hematocrit, serum creatinine, and serum albumin.
Sensitivity Analyses
We first performed sensitivity analyses to compare the Jaliscopatients with subsets of the 409 USRDS patients who were studiedin the primary analysis. Restricting analyses to compare the106 Jalisco patients with only the 252 American patients withGFR <6 ml/min per 1.73 m2 at dialysis initiation obtainedsimilar results to those in the primary analysis (adjusted HR3.0; 95% CI 1.5 to 6.1). When the subset of 228 American patientswho initiated PD in calendar years 1999 to 2001 was studiedinstead, results remained similar (adjusted HR 3.2; 95% CI 1.4to 7.3).
Because PD patients are a relatively select group in the UnitedStates, we performed an additional analysis that compared mortalityin Jalisco patients and all Hispanic USRDS patients who didnot have medical insurance and survived at least 90 d afterdialysis initiation, regardless of dialysis modality. Mortalityremained significantly higher among Jalisco patients in thisanalysis (HR 3.5; 95% CI 2.4 to 5.0).
Patients who are treated for kidney failure at the Jalisco HealthSecretariat are unlikely to receive predialysis nephrologiccare and have very severe metabolic derangements at the timeof dialysis initiation. By American standards, dialysis wasinitiated very late in this group of patients, and only 2.6%had estimated GFR >10.5 ml/min per 1.73 m2 at dialysis initiationas recommended by US guidelines (9).
Probably because delayed presentation was so common, nearly20% of patients died in hospital before dialysis could be initiated,and an additional 13% (21% of those who initiated dialysis)died within the first 3 mo of treatment. Even after exclusionof the relatively high proportion of patients with early death,adjusted survival of dialysis patients who were treated in Jaliscowas substantially lower than in seemingly comparable patientswho were treated in the United States, perhaps because of theiradvanced disease at presentation. An additional 18% of patientsdid not initiate dialysis for various reasons, leading to deathfrom uremia in the majority. Although choosing not to initiatedialysis may well have been appropriate in some cases, it ispossible that some patients would have chosen differently withadequate time to prepare for RRT.
BP reduction (10), tight glycemic control (11), interruptionof the renin/angiotensin system (12,13), and possibly treatmentof hypercholesterolemia (14,15) all delay or prevent progressionof CKD and reduce cardiovascular morbidity and mortality. Timelynephrologic care may permit introduction of these proven therapiesas well as dialysis access creation and control of metabolicbone disease and anemia (using low-cost therapies such as oralcalcium carbonate and iron) (16–22). Although earlierreferral to nephrologic services would probably have improvedoutcomes in the Jalisco patients, this will require specificresource allocation and recruitment of additional nephrologists.For instance, currently 10 dialysis programs (staffed by 31nephrologists) provide care to beneficiaries of Social Securitybut only three programs (nine nephrologists) in the Health Secretariatfacilities. All three of the dialysis facilities that are runby the Health Secretariat are located centrally in Guadalajara,despite that many of the poor reside outside the state capital.
Although we did not collect data to confirm our impression,clinical experience suggests that (with the exception of insulinand oral hypoglycemic agents) medication use at presentationamong the patients in our study was exceedingly rare. This suggeststhat multipronged interventions that target multiple cardiorenalrisk factors in patients with CKD have considerable potentialto improve health in Jalisco by delaying or preventing kidneyfailure and perhaps by reducing the burden of comorbidity atdialysis initiation.
Although recent articles highlighted the growing burden of kidneydisease in developing nations as a result of globalization andother factors (23–27), most have focused on whether provisionof RRT is possible or cost-effective in this setting. Our studydemonstrates that funding dialysis services is associated withvery poor clinical outcomes in the absence of therapies thataim to prevent progressive kidney disease and its complications.These data support current initiatives by the InternationalSociety of Nephrology and other organizations that target low-costtherapies for prevention (rather than treatment) of kidney failureand its causes (28–30).
Our study has several limitations that should be considered.Although data were prospectively collected according to a prioridefinitions, they were obtained from a single institution andtherefore may not be generalizable to all low- or middle-incomesettings. Second, because of widely known limitations of theUSRDS registry (8), we were unable to compare mortality in Jaliscopatients within the first 90 d of dialysis treatment with thatexperienced by patients who were treated in the United States.Data on early death in Americans with ESRD are sparse, but availablestudies suggest that the proportion of incident patients whodie within the first 3 mo of treatment ranges from 6 to 12%—substantiallylower than in Jalisco. Therefore, this limitation is unlikelyto have affected our conclusions (31–33). Third, <20%of incident patients in the United States initiate RRT on PD,raising the possibility that the seemingly better outcomes comparedwith Jalisco patients (all of whom were treated with PD) aredue to selection bias. However, results were similar when Americanhemodialysis patients were included in the comparator group,making this possibility less likely. Fourth, the US patientswere selected from a slightly earlier calendar period than theJalisco patients. However, we believe that this is unlikelyto have affected our outcomes because mortality rates amongUS dialysis patients have remained relatively constant duringthis period. Fifth, the MDRD equation may not perform well amongHispanic patients or those with kidney failure; therefore, conclusionsrelated to the precise level of GFR among the patients in ourstudy should be viewed with caution. However, because all patientsin the study were of Hispanic origin, this is unlikely to haveled to bias. Finally, although Jalisco patients without socialsecurity or private insurance are unlikely to have receivedcare for kidney failure at other institutions, we cannot excludethe possibility that some died without seeking any medical attention.Therefore, our results probably underestimate mortality as aresult of kidney failure among the poor of Jalisco.
We found that poor patients with kidney failure in Jalisco havevery advanced disease at the time of first nephrologic contactand have exceedingly high rates of mortality after dialysisinitiation. Our findings demonstrate a tremendous opportunityto reduce morbidity and mortality as a result of CKD in Jaliscoand perhaps other regions of Mexico.
This study was funded by a grant from the Foundation of theCivil Hospital de Guadalajara. The sponsor did not participatein analyses or influence the decision to submit for publication.M.T. was supported by a Population Health Investigator Awardfrom the Alberta Heritage Foundation for Medical Research andby a New Investigator Award from the Canadian Institutes ofHealth Research.
Data on patients from Jalisco who died after loss to follow-upwere provided by Teresa Garcia, Office of Vital Statistics,Secretaria de Salud (Jalisco, Mexico).
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Related Article
Renal Replacement Therapy in the Developing World: Are We on the Right Track, or Should There Be a New Paradigm?
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Abstract
Introduction
90 d, after adjustment for age, gender, body weight, diabetic status, hematocrit, serum creatinine, and serum albumin.