David B. Bernard

Acute regional circulatory and renal hemodynamic effects of converting-enzyme inhibition in patients with congestive heart failure.

The acute effects of the angiotensin converting-enzyme inhibitor captopril on regional blood flow, renal hemodynamics and sodium excretion were studied in 12 patients with severe congestive heart failure. Converting-enzyme inhibition decreased systemic vascular resistance by 27% and increased cardiac index by 16%. Estimated hepatic blood flow decreased 17%, but renal blood flow increased 60%. The ratio of renal-systemic blood flow increased from 0.10 ± 0.01 to 0.14 ± 0.02 (p = 0.031). Although renal plasma flow increased from 202.8 ± 28.8 to 323.7 ± 42.7 mI/min (p = 0.008), the glomerular filtration rate did not change significantly from the mean pretreatment value of 82.1 ± 12.3 mI/min. The filtration fraction decreased from 41.3 ± 3.8% to 33.4 ± 4.5% (p = 0.050), while urinary sodium excretion doubled, from 34.5 ± 9.6 to 68.2 ± 19.6 uEq/min. The plasma renin activity increased from 12.6 ± 5.0 to 29.9 ± 8.4 ng/ml/hr (p = 0.030) as plasma aldosterone concentration decreased from 30.5 ± 6.5 to 11.3 ± 1.2 ng/dl (p = 0.010) and norepinephrine concentrations decreased from 774 ± 105 to 618 ± 85 pg/nl (p = 0.020). We conclude that converting-enzyme inhibition reverses renal vasoconstriction in congestive heart failure and redistributes regional blood flow. The natriuresis may be mediated by one or more of the following: improved renal plasma flow, reduction in filtration fraction, suppression of hyperaldosteronism, and lowering of circulatory catecholamine concentrations.

Lipid Abnormalities in the Nephrotic Syndrome: Causes, Consequences, and Treatment

Hyperlipidemia so commonly complicates heavy proteinuria that it has come to be regarded as an integral feature of the nephrotic syndrome (NS). Characteristically, total plasma cholesterol and triglyceride levels are elevated, as are very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterol. Although high-density lipoprotein (HDL) concentrations may be normal, HDL subtypes are abnormally distributed, with a reduction of HDL2 and an increase in HDL3. In addition, lipoprotein (a) [Lp (a)] levels may be elevated. The mechanisms underlying these abnormalities are multifactorial, involving both increased rates of lipoprotein synthesis and defective clearance and catabolism of circulating particles. Although recent dietary and therapeutic studies have demonstrated that nephrotic hyperlipidemia can be effectively treated, the need for such intervention has not been clearly established. This pattern of lipoprotein abnormality is associated with an increased risk of cardiovascular disease in the general population, and several studies have suggested that nephrotic individuals are more likely to develop atherosclerosis. However, no prospective trials have evaluated the relationship between deranged lipid metabolism and coronary or cerebral artery disease in patients with NS. In addition, although recent experimental studies suggest that lipid abnormalities may accelerate renal injury and that lipid-lowering agents may protect renal function, there is little current evidence to suggest that such intervention is of value in preserving residual renal function in humans. Further studies are clearly required to assess the potential long-term benefits of lipid-lowering intervention in individuals with NS. In the meantime, based on data generated from other population groups, a rational approach to the clinical management of hyperlipidemia in these patients is presented.

The Role of Urea Kinetic Modeling, TACurea, and Kt/V in Achieving Optimal Dialysis: A Critical Reappraisal

The National Cooperative Dialysis Study (NCDS) established the importance of the time-averaged concentration of blood urea nitrogen (BUN) (TACurea) as a determinant of morbidity among patients maintained on hemodialysis. Although urea is not itself toxic, it serves as a surrogate for those low-molecular weight products of protein catabolism that do contribute to uremic toxicity. The NCDS also reported an association between low protein catabolic rates (a measure of dietary protein intake) and increased morbidity, but the validity of this result has been questioned. On the basis of a retrospective re-analysis of the data, Gotch and Sargent have proposed following the normalized whole-body urea clearance, Kt/V, as a more fundamental index of the level of dialytic therapy. In this review, a comparison is made between these two measures of adequate dialysis, namely, midweek predialysis urea concentration and Kt/V. At least for the cellulosic membranes used in the NCDS, they seem to be equivalent. Furthermore, each prescription defines adequate nutrition as a dietary protein intake (DPI) of 1.0 g/kg/d. At this DPI, a time-averaged concentration of BUN of 17.9 mmol/L (50 mg/dL) (corresponding roughly to a midweek predialysis BUN of 21.4 to 28.6 mmol/L (60 to 80 mg/dL), as recommended by the NCDS, is equivalent to a Kt/V of 1.0, as recommended by Gotch and Sargent. Based on ease and accuracy of measurement, TACurea would seem the more reliable marker for monitoring the adequacy of dialysis. Extrapolation of the utility of TACurea and/or Kt/V to noncellulosic membranes remains to be established. Urea kinetic modeling constitutes a powerful mathematical tool for implementing these recommendations. Urea kinetic modeling may also be used as a means of monitoring DPI and thereby ensuring adequate nutrition.

Redistribution of regional blood flow following angiotensin-converting enzyme inhibition: Comparison of normal subjects and patients with heart failure

The systemic and regional circulatory effects of angiotensin-converting enzyme inhibition were investigated in 30 normal subjects and in 36 patients with severe congestive heart failure. Regional blood flow was measured in individual patient groups. Cardiac index rose and systemic vascular resistance fell in normal subjects after angiotensin-converting enzyme inhibition. In the patients with heart failure, a similar rise in cardiac index and fall in systemic resistance occurred. In addition, right and left ventricular filling pressures decreased. The fall in systemic vascular resistance correlated with plasma renin activity (r = 0.57, p less than or equal to 0.001). Of the regional circulations investigated in normal subjects, only forearm blood flow increased after angiotensin-converting enzyme inhibition. Although over-all there was no change in renal or coronary blood flow, coronary flow dramatically increased in some patients and the increase in flow correlated with plasma renin activity (r = 0.939, p less than or equal to 0.001). In patients with heart failure, forearm, splanchnic, and coronary flow were unaffected by angiotensin-converting enzyme inhibition, whereas renal blood flow estimated from para-aminohippurate clearance increased 60 percent and accounted for 50 percent of the increase in cardiac output seen in these patients. Thus, redistribution of flow occurs in congestive heart failure with a significant reduction in the fraction flow to the kidneys when compared with normal flow. The contribution of the renin-angiotensin system to the regulation of regional blood flow is different in normal subjects and in patients with heart failure. Angiotensin-converting enzyme inhibition augments skeletal flow in normal subjects whereas it increases renal blood flow in patients with heart failure.

Reflex Sympathetic Dystrophy Syndrome of the Hand After Placement of an Arteriovenous Graft for Hemodialysis

Reflex sympathetic dystrophy syndrome (RSDS), a complex clinical syndrome characterized by pain and swelling of an affected extremity, is most commonly seen after trauma. We report the case of a woman with diabetes mellitus and chronic renal failure who presented with RSDS 5 months after placement of an arteriovenous (AV) graft for hemodialysis. The temporal relationship between RSDS and the vascular surgery suggests AV graft placement as the precipitating event for the development of RSDS. Treatment with systemic corticosteroids successfully relieved the patients symptoms. We believe that RSDS should be included in the differential diagnosis of unexplained limb pain and swelling after AV graft placement.