Kidney International, Vol. 63, Supplement 83 (2003), pp. S22–S26

End-stage renal disease and acute glomerulonephritis inGoajiro Indians

JOSE HERRERA and BERNARDO RODRIGUEZ-ITURBE

Renal Service, Hospital Universitario, Instituto de Investigaciones Biomedicas, FUNDACITE-Zulia,Universidad del Zulia, Maracaibo, Venezuela

End-stage renal disease and acute glomerulonephritis in Goa- (in their native language “person” or “people”, in con-jiro Indians. trast with alijuna or “foreign” or “white”) have occupied

Background. Goajiro Indians are a semi-nomad tribe that livethe Goajira peninsula since pre-Hispanic times and areon the Goajiro peninsula, in the northwestern part of Vene-assumed to have migrated originally from the Amazonszuela. We investigated the incidence of end-stage renal dis-

ease (ESRD) and post-streptococcal glomerulonephritis (PSGN) [1]. Together with the Lohars of India, the Al Murrahamong Goajiros and to determine if it was increased and whe- Bedouins of Arabia, the Bajau boat dwellers of Phillip-ther congenital endowment of low number of nephrons (as

ines, the Qashqai sheperds from Iran, the Tuaregs fromindicated by low birth weight) was a contributing factor in theirthe Sahara, the Bambuti from the Ituri forest in Africa,predisposition to chronic renal failure (CRF).

Methods. The incidence of ESRD and the attack rate of post- and the Bororos for the Niger River, the Goajiros arestreptococcal glomerulonephritis (PSGN) among Goajiros dur- considered to be one of the remaining nomad tribes of theing the period December 1991 through December 1998 were

world [2]. Initially the Goajiros were hunters and fish-evaluated from the records of the University Hospital, in Mara-ermen, but they have evolved into a society of shepherdscaibo, which is the referral center for Goajiro Indians. Demo-

graphic characteristics and birth weight were obtained from that tend to mobilize less frequently and, therefore, arethe records of the Regional Public Health Service. Subclini- presently considered “transient” nomads or semi-nomadscal reduction in renal functioning mass was investigated in 11

[1]. In Venezuela, they occupy the northern part of Zuliahealthy Goajiros with a standardized tubular stress test thatstate and increasingly conduct commerce and trade withdetermines the increment in tubular secretion of creatinine

(TSCr) resulting from the intravenous administration of a bolus the cities in that region, particularly Maracaibo.of creatinine. The health system on the Venezuelan side of the Goa-

Results. The incidence of ESRD among Goajiros was 220jira Peninsula includes a loose web of ambulatory centerspatients per million inhabitants per year, 1.7 times higher thanthat use the University Hospital in Maracaibo as theirthe incidence for the country. The attack rate of post-strepto-

coccal glomerulonephritis is nearly double among Goajiro Indi- principal referral medical center. There are no publishedans (2.9 � 1.3 cases/100,000 inhabitants/year) than in the gen- data on the incidence of chronic renal failure among theeral population in the neighboring Maracaibo city (1.5 � 0.3,

Goajiro tribes, but anecdotal reports suggest that theyP � 0.02). Low weight birth was common among Goajiros; ashave a high incidence of acute glomerulonephritis and end-many as 23% of newborns weigh less than 1000 g. The stimu-

lated TSCr in healthy Goajiros was 30% lower than in controls stage renal disease (ESRD). Difficult access to qualified(P � 0.001). nephrology services, lack of coverage by the national So-

Conclusions. Goajiro Indians have a high incidence of ESRD.cial Security Health System, and traditional reliance onA high attack rate of PSGN and low nephron endowment inlocal empiric healers are some of the reasons for thesecombination may be responsible, at least in part, for the in-

creased risk of ESRD in this population. deficiencies.The present work documents a high incidence of ESRD,

post-streptococcal glomerulonephritis (PSGN) and lowGoajiro Indians are a tribe that gives its name to a birth weight among Goajiro Indians. The latter is thought

relatively uninhabited peninsula that lies between Co- to be associated with a low number of nephron units. Welombia and Venezuela in the Caribbean sea in the upper- evaluated healthy Goajiros with a recently described tu-most part of South America. The Goajiro Indians or wayuu bular stress test that may disclose subclinical reductions

of nephron units and found abnormal results [3]. Thedata obtained are consistent with the possibility that theKey words: Aborigines, streptococcal nephritis, tubular stress test,

newborn weight, nephron endowment. high incidence of ESRD among Goajiros results, at leastin part, from of a high attack rate of acute glomerulo- 2003 by the International Society of Nephrology

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Herrera and Rodrıguez-Iturbe: ESRD in Goajiros S-23

nephritis affecting a population endowed with a low the University Hospital. Forty to 51 of them had ESRDnumber of nephrons. that required chronic renal replacement therapy. There-

fore, it may be conservatively estimated that GoajiroIndians have an incidence of ESRD of about 220 patientsMETHODSper million population (pmp) per year, 1.7 times higher

Patients than the incidence for the country as a whole, estimatedData concerning the incidence of ESRD and PSGN at 132 pmp per year [6]. Disturbingly, only 3 to 5% of

were obtained from the records of the University Hospi- the patients included in the chronic dialysis program oftal in a seven year period from December 1991 to Decem- the University Hospital are Goajiros.ber 1998. Epidemiological and demographic data wereobtained from the Annual Reports of the Public Health Post-streptococcal glomerulonephritisSystem [4]. Birth weight information was only available In the period analyzed, there were 335 cases of acutefor the year 2000 and was graciously supplied by the of- glomerulonephritis admitted with an acute nephritic syn-fice of the Regional Public Health System (Director, Dr. drome. Of them, 241 (72%) had serological evidence ofFelix Gruber).

recent streptococcal infection and in the rest a strepto-The tubular stress test (TST) studies were done in 11

coccal etiology was suspected but not proven. Neverthe-paid Goajiro volunteers with no history of previous renalless, for the purposes of this survey, all the cases, averag-disease, and normal routine hematology and biochemicaling 48 cases per year, were considered to be PSGN. Thestudies (serum creatinine, fasting blood sugar, uric acid,incidence of PSGN in the different regions of the statecholesterol), normal renal ultrasound study and normal(Fig. 1) demonstrates that Goajiro Indians have an inci-urine analysis. Control subjects were 20 age-matched paiddence of PSGN (2.9 � 1.3 cases/100,000 inhabitants pernon-Goajiro volunteers representing the normal TSTyear), which is nearly double the incidence in the centralvalues of our population [3, 5]. The weight at birth wasregions of the state (P � 0.01). The values shown in thenormal in the non-Goajiro population but it was not ob-southern (0.02 � 0.02 cases/100,000 inhabitants per year)tainable in the Goajiro Indians. The studies were carriedand eastern (0.4 � 0.30) regions of the state are underes-out following a research protocol approved by the Ethi-timates because the patients in these areas are rarelycal Committee of our institution and reported in detailreferred to the University Hospital in Maracaibo due toin a recent communication [3].the long distances involved.Essentially, the TST required three baseline clearance

determinations followed by a bolus intravenous injectionBirth weight and demographic characteristics of theof creatinine (10 mg per kg body weight). This amount ofGoajiro Indiansexogenous creatinine injected over a 10-minute period,

resulted in serum creatinine (SCr) levels of 600 to 700 The population and several epidemiological indices of�mol/L, which were known to induce the maximum stim- the Goajira region are compared with the rest of the stateulation of TSCr. Fifteen minutes after the end of the cre- in Table 1. The population density varies considerablyatinine load (to avoid a rapid exponential decrease of SCr within Zulia state, ranging from almost 3500 inhabitantsafter the end of the infusion), three successive 30-minute per km2 in the city of Maracaibo to 30 to 40 inhabitantsclearance periods (Period A, B and C) were done. Glo- per km2 in the municipalities of the Goajira region.merular filtration rate (GFR), creatinine clearance (CCr), The incidence of low birth weight is higher in amongurinary creatinine excretion (UCrV) and tubular secretion Goajiros than in the rest of the state. As shown in Table 2,of creatinine (TSCr) were calculated for the baseline and nearly one-quarter of the Goajiro children weight lessstimulated periods. A single subcutaneous injection of ra- than 1000 kg at birth.dioactive iothalamate was used for GFR determinationsin all clearance periods; TSCr was calculated as the differ- Stimulation of tubular functionence between the urinary creatinine excretion (UCrV)

Table 3 shows the results of the TST. In baseline stud-and the filtered creatinine (GFR � SCr). Stimulated ories, Goajiro Indians had a lower systolic blood pressure“test” TSCr is calculated separately for the first period af-(P � 0.05) than the non-Goajiro control population. Theter creatinine infusion (Period A) and for the mean of theremaining baseline studies are not significantly differentthree post-infusion periods (Periods A�B�C/3) [3, 5].from the control population (Table 3). At the end of thecreatinine infusion, Goajiros and non-Goajiro individu-

RESULTS als had similar SCr values (SCr at time 0 in Test Values inIncidence of end-stage renal disease Table 3). Yet, as shown in Table 3, Goajiro Indians have

30% impairment in the TSCr response after the intrave-During the period of analysis, chronic renal failurewas diagnosed in 62 to 71 Goajiro Indians every year in nous creatinine load.

Herrera and Rodrıguez-Iturbe: ESRD in GoajirosS-24

Fig. 1. Map of Zulia state, showing the attackrate of acute post-streptococcal glomerulone-phritis (PSGN) referred to the University Hos-pital in Maracaibo in the period December1991–December 1998. The values correspondto cases per 100,000 population (mean � SD).The attack rates in the Goajira and centralregions of the state are representative of theincidence of PSGN, but the value listed forthe southern and western regions are an un-derestimation because only a minority of casesin these regions are referred to Maracaibo.

Table 1. Demographic indices for year 2000

Maternal mortality Infant mortalityPopulation Illiteracy Severe Mortalitymillions % rate �1000 malnutrition �1000 �100,000

Zulia State 3.21 (100) 6.9 4.6 4.34 1.84 23.3Goajira region 0.23 (7.3)

M. Mara 0.15 (4.6) 24.6 16.8 5.46 4.70 35.7M. Paez 0.08 (2.4) 35.0 6.6 2.33 5.27 26.3M. Padilla 0.01 (0.3) 24.9 19.2 4.04 28.8 32.4

The Goajiro Indians represent about 80% of the population in the Mara and Paez municipalities. The Padilla municipality is primarily inhabited by a differentIndian tribe, the Paraujanos or Anu Indians.

DISCUSSION communities needing renal replacement therapy are re-ferred to this center. Therefore, the incidence of ESRDThere is no reliable information on the incidence ofpresented here, while un underestimation, represents aESRD among Goajiro Indians. Even though there is areasonable approximation of the problem and indicatessignificant concern to preserve their cultural specificitythat Goajiro Indians have an incidence of ESRD that isand to include aboriginal representatives in the politicalat least 1.7 times higher than the general population.decision-making process, no separate health records areEven more troublesome, only a minority of these pa-kept. The largest chronic dialysis program of the publictients is in fact included in chronic dialysis programs; inhealth system is located in the University Hospital of

Maracaibo and, consequently, most patients of minority the University Hospital program only 3 to 5% of the

Herrera and Rodrıguez-Iturbe: ESRD in Goajiros S-25

Table 3. Tubular stress testTable 2. Incidence of low birth weight in Zulia Statein the year 2000

Control Goajiro IndiansBaseline values (N � 20) (N �11)Weight at birth

Live birthsN �2500 g �2500 g �1000 g Age years 25.3 �7.1 24.4�7.4

Systolic BP mm Hg 127 �13 117�7b

Zulia State 69,127 91.1% 8.9% 1.9% Diastolic BP mm Hg 71.4 �9.9 65.0�8.7Goajira Regiona 1,179 74.5% 35.7% 23.7% SCr lmol/L 85.7 �10.2 79.5�14.5

GFRa mL/min 111 �17 116.0�13There were a total of 69,127 live births in Zulia State in 2000, 33,762 of whichwere in the Region of Maracaibo City. The information given in the table was CCr mL/min 123 �16 118�8provided by the office of the Regional Public Health System. UCrV nmol/kg/min 144 �19 141�23

a Data correspond to Municipio Paez TSCr nmol/kg/min 35.9 �15.8 24.8�16.7

Test valuesScr (�mol/l) Time 0 621�155 628�163GFRa

Period A 101�17 112�7patients are Goajiros. The reasons for the gross underMean Post 103�19 110�10representation of Goairos Indians in renal replacement

CCra

programs include the lack of National Social Security or Period A 160�24 150�16Mean Post 143�17 129�10private insurance coverage, and difficulties of access to

UCrVdialysis units, all of which are located within the city.Period A 568�137 476�63b

The vast majority of cases of PSGN are admitted to Mean Post 424�71 368�30b

TSCrthe University Hospital [7]. We have previously reportedPeriod A 286�93 198�30c

in detail the epidemiological and clinical characteristics Mean Post 180�50 125�20c

of acute PSGN in Maracaibo [7, 8]. In the larger study,Serum creatinine time 0 corresponds to the end of creatinine infusion (10

concerning the period between January 1967 and Janu- mg/kg body weight in 10 minutes). Period A values in the first post-infusionperiod and Mean are the mean values for the 3 stimulated clearance periodsary 1983, there were 2006 cases of PSGN admitted in the(see text).

University Hospital [7]. This number of patients includes a Corrected for BSA 1.72 m2

b P � 0.05two epidemics, one in 1968 (384 patients) and anotherc P � 0.001

one in 1975 to 1976 (304 patients) [7]. The attack rate of48 cases per year, observed during the seven years re-ported in our current study, is less than the attack rateof 101 cases per year that, excluding the epidemics, we tured that they are born with a low nephron number.reported earlier [7]. Therefore, the incidence of PSGN The correlation between birth weight and number ofis decreasing in our region, as in other countries, proba- nephrons has been demonstrated in several animal stud-bly as a result of the earlier diagnosis and treatment of ies [reviewed in 9] as well as in clinical investigationsstreptococcal impetigo and throat infections. [10, 11]. In young Caucasians, low birth weight is not

From the earlier reports, it was suspected that acute associated with renal functional impairment [12], but inminority groups and aboriginal communities a relation-PSGN was more frequent among Goajiro Indians than

in the rest of the population. We found that 11.2% of ship between low birth weight and prevalence of chronicrenal disease has been found in several studies [13–16].the cases were from Goajiro region [7], and when the

cases were related to the corresponding population, the Therefore, congenital endowment with a low numberof nephron units may be a contributing factor to theGoajira region had higher attack rate of acute PSGN

(103 cases per 100,000 inhabitants) than Maracaibo city increased incidence of ESRD among Goajiro Indians,particularly in association with a high attack rate of acute(82 cases/100,000 inhabitants), which, in addition, in-

cluded significant numbers of Goajiro children living in glomerulonephritis.To gain some insight into the functional nephron massthe city. This relative predominance of cases among

Goajiros was similar in sporadic and epidemic cases, of the Goajiro population, we carried out a tubular stresstest (TST) that measures the capacity of the renal tubulesince the endemic and the epidemic attack rate of PSGN

are closely related in our region [8]. The increased inci- to increase creatinine secretion in response to an intrave-nous creatinine load [3]. The TST discriminates betweendence of PSGN among Goajiro Indians is more pro-

nounced in recent years, since the attack rate of PSGN normal subjects and groups of individuals—such as kid-ney donors, transplant recipients with good graft func-in Goajiros is now double the attack rate in the general

population (Fig. 1). This finding is probably related to tion and young patients with sickle cell anemia—whohave subclinical reductions of nephron mass that do nota more significant reduction of the incidence of PSGN

in the general population than in the Goajiros, for whom modify the serum creatinine or the GFR [3, 5]. There-fore, we reasoned that the TST test would be abnormalaccessibility to medical care remains difficult.

Since a high proportion of Goajiro Indians have a in Goajiro Indians with normal serum creatinine andGFR if they were, in fact, born with a reduced numbermarkedly low birth weight (Table 2), it may be conjec-

Herrera and Rodrıguez-Iturbe: ESRD in GoajirosS-26

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260, 1999E-mail: bri@iamnet.com