Urinary findings and renal function in adult Navajo Indians and associations with type 2 diabetes.

We screened a sample of adult Navajo Indians for signs of renal disease that might underlie their increasing rates of renal failure. Nondiabetics had modest rates of hypertension, which was more common in males and increased with age. Microscopic hematuria was very common, and only a fraction was associated with progressive nephropathy. Microalbuminuria, mostly undetected by routine dipstick, was present in 14.6% of subjects; overt albuminuria was present in 2%. Increasing albuminuria was related to renal insufficiency, which was more common in males. Hypertension was associated with greater then threefold increases in both albuminuria and renal insufficiency. Cardiovascular disease was uncommon and had no discernible relationship to albuminuria. Most diabetic patients (58.4%) had hypertension, with equal rates for males and females. Fully half of all diabetic patients had unsatisfactory blood pressure levels at screening. Rates and patterns of hematuria were like those of nondiabetics. Microalbuminuria was present in 36.1% and overt albuminuria in 17.9%, four and eight times the rates in matched nondiabetics, respectively; these differences persisted after controlling for blood pressure. Renal insufficiency was associated with progressive albuminuria and was present in 10.6%, with equal rates in males and females. Hypertension, albuminuria, and renal insufficiency, but not hematuria, increased with increasing diabetes duration. Hypertension was associated with a twofold increase in albuminuria, a threefold increase in overt albuminuria, and an eightfold increase in renal insufficiency. Cardiovascular disease had no detectable association with microalbuminuria, but had a strong relationship to overt albuminuria. The high rates of hematuria are not well explained. It probably has nonrenal as well as renal origins, the latter including mesangial proliferative glomerulonephritis. The impressive rates of albuminuria among diabetic patients mark a large reservoir of renal disease and fore-shadow even larger burdens of end-stage renal disease and cardiovascular disease in the near future. Improved detection and treatment of hypertension is needed to slow the progression of renal disease in nondiabetics and diabetics, together with screening and treatment protocols for albuminuric diabetic patients. Prevention of albuminuria probably involves population-based modification of blood pressure and metabolic profiles.

Cardiovascular disease in Navajo Indians with type 2 diabetes.

Rates of both type 2 diabetes and cardiovascular disease have risen sharply in recent years among Navajo Indians, the largest reservation-based American Indian tribe, but the association between the two conditions is not entirely clear. Rates of cardiovascular disease and some possible associations in several hundred diabetic and non-diabetic Navajos were estimated. Nearly one-third (30.9 percent) of those with diabetes had formal diagnoses of cardiovascular disease--25.3 percent had heart disease, 4.4 percent had cerebrovascular disease, and 4.1 percent had peripheral vascular disease. (The percentages exceed the total because some people had more than one diagnosis. Age-adjusted rates were 5.2 times those of nondiabetics for heart disease, 10.2 times for cerebrovascular disease, and 6.8 times for peripheral vascular disease. Accentuation of risk was most marked in young diabetics and in female diabetics. Hypertensive diabetics had a twofold increase in heart disease and more than a fivefold increase in cerebral and peripheral vascular disease over nonhypertensive diabetics. Age, blood pressure, cholesterol levels, and albumenuria were independent risk factors for cardiovascular disease. Triglyceride levels or body weight were not. Male sex and diabetes duration were independent risk factors for cerebral and peripheral vascular disease but not for heart disease. In view of the impressive segregation of cardiovascular disease in the diabetic Navajo population, the prevention of diabetes through population-based health promotion seems basic to its containment. Over the short term, vigorous treatment of hypertension in subjects who are already diabetic is mandatory.

Blood pressure in Navajo Indians and its association with type 2 diabetes and renal and cardiovascular disease.

In mid-1990 we evaluated blood pressure and its associations in 366 nondiabetic adult Navajos and 400 Navajos with type 2 diabetes attending Indian Health Service outpatient clinics in Tuba City, Arizona. In nondiabetics, systolic blood pressure (SBP) rose with increasing age while diastolic blood pressure (DBP) fell; 13.4% had hypertension by diagnosis or treatment. Female nondiabetics had lower blood pressures than males. SBP and DBP correlated with age, body mass index (BMI), and urinary albumin excretion (UAE). Hypertension was associated with a sixfold increase in nephropathy, a threefold increase in renal insufficiency, and an almost sixfold increase in cardiovascular disease. Diabetics had higher blood pressures than age- and sex-matched nondiabetics; 58.4% had hypertension by diagnosis or treatment, and, in spite of widespread antihypertensive treatment, blood pressures in almost 50% were suboptimal from the perspectives of cardiovascular and renal protection. Blood pressures of female diabetics were similar to those of males. Blood pressures correlated with age, BMI, and increasing UAE. Rates of nephropathy and cardiovascular disease were much higher in diabetics than nondiabetics, and within the diabetic population hypertension was associated with a greater than threefold increase in nephropathy, an eightfold increase in renal insufficiency, a five-fold increase in peripheral and cerebrovascular disease, and more than doubling of the rate of heart disease. The relationship of blood pressure to renal and cardiovascular disease suggest similar mechanisms in nondiabetics and diabetics, with diabetes contributing an accentuated susceptibility. Albuminuria and cardiac disease are generated at "subhypertensive" blood pressures, while established hypertension appears to drive overt renal, cerebrovascular, and peripheral vascular disease, and to further increase heart disease risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Mesangial proliferative glomerulonephritis in southwestern American Indians.

A series of 166 American Indian renal biopsy specimens from 1971 to 1989 showed a very high proportion with mesangial proliferative glomerulonephritis with mesangial immunoglobulin deposition (Ig-pos mesGN). This disease comprised 68.7% of all the biopsies and 83.8% of all primary GN, proportions much greater than those (23.5% and 37.7%, respectively) of a local contemporaneous biopsy series from non-Indians (P < 0.001). These proportions and the extrapolated population-based incidence rates of mesGN are the highest yet described in any population. Males and females were equally represented in the Indian Ig-pos mesGN series. Biopsy was most commonly performed in early adulthood, but duration of suspected disease prior to biopsy was often many years. Mesangial glomerulonephritis often occurred in family clusters. It was occasionally associated with rashes, arthralgias, and/or a history of alcohol abuse. Due to different surveillance and biopsy practices, the spectrum of severity was different in Zunis and Navajos, allowing examination of clinicopathologic correlations over a broad range of disease. Early disease was manifest by microscopic hematuria alone, but rates of severe disease, with hypertension, heavy proteinuria, and renal insufficiency, were very high. Clinical severity increased with age, with extension of pathology beyond the mesangium, and with scarring and vascular change. Changing patterns of deposition of mesangial immunoglobulin and of electron-dense deposits in sequential biopsy specimens, recurrence of disease in kidney transplants, and biopsy diagnosis of disease in asymptomatic relatives of afflicted subjects were all observed. Five-year renal failure rates were estimated at 41%, much higher than in most other series. This disease constituted most biopsied cases of GN-end stage renal disease in Navajos, and largely determined the young age of Navajo GN-end stage renal disease subjects compared with their US-wide counterparts. To reconcile the diversity of clinical and morphologic findings in such homogeneous ethnic groups, and in individual families within such groups, we propose a unifying hypothesis for a broader spectrum of mesGN than traditionally defined by immunoglobulin subtype deposition. We also argue against a major role for IgA aggregates or immune complexes in initiating or propagating the mesangial inflammatory process, and propose that mesangial pathology of another, independent cause might be primary. Hyperinsulinemia, or insulin resistance, which is common in these populations and in other transitional populations with similar GN and ESRD patterns, might be one such mesangiopathic factor.

Mesangiopathic glomerulonephritis in Zuni (New Mexico) Indians.

Zuni is a Pueblo Indian village having more than a sixfold greater incidence of nondiabetic end-stage renal disease than the rest of the United States. Renal biopsy specimens from 44 patients with nondiabetic renal disease were subdivided into two groups. In group 1, 21 patients with asymptomatic microscopic hematuria revealed a mild mesangiopathic glomerulonephritis in 18 cases. The predominantly staining immunoglobulin was IgM in ten specimens and IgA in eight specimens. In group 2, 23 patients with symptomatic renal disease presented with nephrotic range proteinuria (11), renal insufficiency (eight), and hypertension (four). A mesangiopathic glomerulonephritis was diagnosed in 16 cases, and in 11 was IgA predominant. Three cases of membranoproliferative glomerulonephritis occurred in group 2. Five cases revealed focal glomerulosclerosis without immune deposits (three in group 1 and two in group 2). More than half (57%) of the patients undergoing biopsy were related. Cases of symptomatic nondiabetic renal disease showed a significant tendency to cluster among the members of four families, suggesting a hereditary influence in the pathogenesis of immune-mediated glomerulonephritis in the Zuni.

Pathologic findings in mesangiopathic glomerulonephritis in Navajo Indians.

Immune complex-associated mesangiopathic glomerulonephritis was found in 64% of renal biopsies performed on Navajos over a 16-year period. It is characterized by mild mesangial expansion and predominant immunoglobulin (Ig) A and/or IgM deposits. Statistical analysis shows that glomerular deposits of IgG and C3, glomerular sclerosis, interstitial fibrosis, interstitial inflammation, and tubular atrophy are associated with renal insufficiency at the time of biopsy, and can be integrated into a pathologic index that has a high correlative value. Mesangiopathic glomerulonephritis is probably responsible for the high rates of non-diabetic end-stage renal disease seen in Navajo Indians.

Rates and causes of end-stage renal disease in Navajo Indians, 1971-1985.

The rates of end-stage renal disease are much increased in American Indians, but no longitudinal study of its rates and causes has been undertaken in any tribe. This 15-year study of rates and causes of treated end-stage renal disease in the Navajo, the largest Indian tribe, supplies an important model on which to base projections and plan interventions. Treated end-stage renal disease in Navajos has increased to an age-adjusted incidence 4 times that in whites in the United States. Diabetic nephropathy accounted for 50% of all new cases in 1985, with an incidence 9.6 times that in US whites, and was due entirely to type II disease. Glomerulonephritis caused end-stage renal disease in Navajos at a rate at least 1.8 times that in US whites and afflicted a much younger population. The predominant form was mesangial proliferative glomerulonephritis associated with an immune complex deposition. Renal disease of unknown etiology, which probably includes much silent glomerulonephritis, accounted for 20% of all new cases. The aggregate Navajo population with end-stage renal disease was 9 years younger than its US counterpart. These observations reflect the genesis of the epidemic of diabetic nephropathy afflicting many tribes. Urgent measures are needed to contain this. In addition, the etiology and control of mesangiopathic, immune-complex glomerulonephritis of unusual severity, a previously unrecognized problem, need to be addressed.

Epidemic renal disease of unknown etiology in the Zuni Indians.

An epidemic of renal disease is occurring among the Zuni Indians in western New Mexico. In 1985, 1.6% of Zunis had clinically recognized renal disease and 1% had renal insufficiency. The incidence of end-stage renal disease (ESRD) in 1984 and 1985 was 14 times the rate for US whites, and three times the rates of other Indians in ESRD network 6. One third of the cases of renal disease and ESRD is due to type 2 diabetes, but the etiology of disease in most of the remainder is unknown. Affected subjects range from early childhood to old age. Early signs are hematuria, mild to moderate proteinuria, normal BP, and low total hemolytic complement, normal or low C3 and C4 levels, in about 40% of the cases. The clinical course varies from benign to rapidly progressive renal failure. Biopsies usually reflect an immune-complex mediated mesangiopathic glomerulonephritis, with IgA, IgG, IgM, and C3 variably present in the mesangium. In some cases, there is a very strong familial pattern suggesting autosomal dominant inheritance or a marked communal exposure effect. This may be a genetic disease educed by the consanguinity in the ethnically homogeneous Zuni population. Mesangiopathic renal disease is common in some Oriental populations, and this phenomenon may reflect the American Indians' Oriental ancestry. This disease may also be due to toxic exposures related to jewelry-making, potting, Zuni water, Zuni salt, or herbal or other products used for medicinal or religious purposes. This epidemic is much morbidity and generating huge costs for ESRD treatment. Further study is needed to better understand its etiology.