Endstage Renal Disease ESRD

Prevalence and incidence. Among both African Americans and whites with ESRD, diabetes accounts for 30% of ESRD (139,140). Data from the Michigan Kidney Registry, from 1974 to 1983 (470 African American and 861 white diabetics with ESRD) shows an annual age-adjusted rate of 127.8/100 000 African American diabetics and 50.2/100 000 white diabetics, with an African American:white incidence ratio of 2.55 (141). Figure 9A.7 shows that the incidence in African Americans is bimodal with peaks at age 20 and 60 years (2) while whites have a single peak at age 30 years. Thus, the excess incidence of diabetic ESRD is attributable to Type 2 diabetes and not to Type 1 diabetes (African American:white incidence ratio 4.31 [95% CI 3.6-5.52], and 1.03 [95% CI 0.731.36], respectively). Stephens reported similar data (142). Most African Americans with diabetic ESRD had Type 2 diabetes (776) while most whites had Type 1 diabetes (58%) (141). Pugh confirms these data in African Americans with ESRD (84% Type 2 diabetes, 13% Type 1 diabetes) but differs in whites (59% Type 2 diabetes, 39% Type 1 diabetes) (143).

The risk of diabetic ESRD depends on type of diabetes and race (141). The estimated 10-year risk of diabetic ESRD, for African Americans and whites combined, is 5.2% for Type 1 diabetes and 0.50% for Type 2 diabetes (African Americans have an 8-fold higher and whites have a 20-fold higher risk). The 10-year risk of diabetic ESRD is four times greater in African Americans than whites with Type 2 diabetes (1.06% vs 0.27%) and 1.62 times greater with Type 1 diabetes (8.7% vs 5.38%).

Overall, the 5-year survival with diabetes and ESRD is 24-30% compared to 48% with non-diabetic ESRD (139). Paradoxically, despite a higher prevalence of hypertension and incidence of diabetic ESRD, African Americans have better survival on dialysis treatment than whites (144-146). Data from the Michigan kidney registry in patients with age of onset of ESRD < 65 years during the years 1974-1983 and followed through 1988 (284 African American and 311 white patients), showed the median survival time was 27 months for Africans with Type 2 diabetes and 16 months for whites (45% longer in African

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Figure 9A.7 Age-specific rates of the incidence of diabetic end-stage renal disease among blacks and whites in Michigan, 1974-1983 Panel A shows the incidence per 100 000 general population and panel B the incidence per 100 000 diabetic patients Source: Reproduced from (141), Figure 1, page 1076, by permission

15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65- 70- 75- 60» 19 24 29 34 39 44 49 54 S9 64 69 74 79

Figure 9A.7 Age-specific rates of the incidence of diabetic end-stage renal disease among blacks and whites in Michigan, 1974-1983 Panel A shows the incidence per 100 000 general population and panel B the incidence per 100 000 diabetic patients Source: Reproduced from (141), Figure 1, page 1076, by permission

Americans than whites). In contrast, transplantation was associated with equal and lower death rate than dialysis for both races without significant differences by type of diabetes (147). This advantage in survival persists after adjusting for various co-morbidities known to affect survival, including type of diabetes. Data from this study showed that at the time of ESRD African Americans had a significantly higher prevalence of LVH and higher blood pressure but interestingly, lower frequency of CHF (58.5 vs 71.5 p<0.05), lower frequency of MI (23.5% vs 33.1%, p<0.10) and a longer duration between first MI and ESRD (56.3 vs 34.9 months, p < 0.10).

The reason for the higher rates of ESRD in African Americans is not known. Variations in blood pressure, glycemic control, socio-economic status and access to health care are reported not to account for the observed 4-fold increase in African Americans versus whites with Type 2 diabetes (148). For example, after controlling for the increased prevalence of Type 2 diabetes, glucose, BP, male sex and CHF, the likelihood of a serum creatinine > 2 mg/dl was 91% higher in African Americans than whites (149).

Inherited or genetic factors may account for the higher rates of ESRD. Freedman reports a familial predisposition for ESRD among African Americans with Type 2 diabetes (150) with an 8-fold greater increase in ESRD in individuals with a close relative with ESRD independent of glycemic control (after adjusting for smoking, hypertension and cholesterol levels). The susceptibility to ESRD is independent of the presence of Type 2 diabetes in African Americans and is similar to data from the Pima Indians and whites with Type 1 diabetes (151,152). HLA associations may mark African American Type 2 diabetes patients with hypertension at risk for nephropathy compared to those without hypertension (153).

Early diabetic nephropathy. Since ESRD takes years to develop and itself causes hypertension, it is difficult to determine the relative roles of antecedent vs subsequently developing hypertension, glycemic control, duration of diabetes, microalbuminuria and hyperfiltration in the pathogenesis of diabetic nephropathy (154-156). In cross-sectional and longitudinal studies Chaiken reports the natural history of early nephropathy in terms of duration of diagnosed diabetes and hypertension in 194 African American Type 2 diabetes subjects (155). Overt nephropathy (albumin excretion rates or AER > 300 mg/24 h) was correlated with: (1) duration of diabetes; (2) decrease in glomerular filtration rates (GFR, measured with 125I-iothalamate infusion) and increase in serum creatinine, and all these patients were hypertensive. Incipient nephropathy (AER 30-300 mg/24 h) was correlated with duration of diabetes and 80% of this group were hypertensive. Analysis in terms of the duration of diabetes and the presence or absence of hypertension showed that subjects who remained normotensive had normal renal function regardless of duration of diabetes (normal GFR and serum creatinine). In hypertensive subjects with Type 2 diabetes, Chaiken found: (1) a decrease in GFR with duration of diabetes of greater than 1 year; and (2) with Type 2 diabetes > 10 years, 36% had impaired renal function (GFR < 80 ml/m2 and/or serum creatinine > 1.4 mg/dl; 75% of these subjects have microalbuminuria or proteinuria. Within the group with longstanding diabetes, subjects who developed their hypertension after the diagnosis of diabetes were more likely to have nephropathy compared to those who developed hypertension prior to or at the time of diagnosis of diabetes (17/20 [85%] vs 7/13 [54%] respectively, p < 0.05), suggesting that nephropathy resulted in hypertension.

Within the first year of diagnosis of Type 2 diabetes in African Americans, Chaiken (157) showed an absence of microalbuminuria in subjects (mean age 47 years) with or without hypertension. In contrast, Goldschmid (154) reported 30% to have microalbuminuria (mean age 52 years). The reason for this difference is unknown but may be due to the older age, or delay in presentation of diabetes in Goldschmid's patients. Similarly to Chaiken, he found the risk factors for nephropathy were duration of diabetes and hypertension; multivariate analysis showed HbAlC did not predict nephropathy. Dasmahap-tra (156) reported 50 t of 116 African American clinic-based patients had increased AER, but did not report data for new-onset patients. AER correlated with age of onset, hypertension and BMI but not with duration of diabetes, age, HbA1C or lipids.

Thus, early diabetic nephropathy, characterized by microalbuminuria, is associated with duration of diabetes and hypertension. The role of glycemia is not clear. It is not known whether urinary microalbumin excretion rates are associated with cardiovascular risk as in some groups (158,159).

Early glomerular hyperfiltration has been variably associated with subsequent nephropathy in Type 1 (160-163) but not Type 2 diabetes (164-167). Chaiken reports hyperfiltration in 36% (15/42) of newly diagnosed (<1 years) African American Type 2 diabetic subjects in good glycemic control (GFRs > 140 ml/min/m2 measured using a constant infusion of 125I-iothalamate) (168-170). Hyperfiltration occurred mostly in younger patients and up to age 62 years and persisted up to 10 years after the diagnosis of diabetes in 14-20% of subjects. It did not predict deterioration of renal function (170).

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