Cholesterol synthesis, cholesterol absorption, and mortality in hemodialysis patients.

BACKGROUND AND OBJECTIVES: Recent clinical trials on cholesterol-lowering in patients with CKD yielded conflicting results, which might have resulted from different treatment strategies. Serum cholesterol levels are determined by endogenous synthesis and intestinal absorption, which are differentially influenced by various classes of cholesterol-lowering agents. Assessing markers of cholesterol metabolism has thus been proposed for guidance of lipid-lowering therapy. This study analyzed surrogate markers of cholesterol absorption and synthesis in hemodialysis (HD) patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In 113 HD patients, lathosterol was measured as a marker of cholesterol synthesis and cholestanol was measured as a marker of cholesterol absorption via gas chromatography. Controls were 229 healthy persons. Overall survival in HD patients was recorded over 3.4-year follow-up. RESULTS: Compared with controls, HD patients had lower lathosterol and higher cholestanol levels (P<0.001 for both). During follow-up, 58 patients died; higher cholestanol (indicating higher cholesterol absorption) predicted poor outcome among HD patients in multivariate Cox regression analysis after adjustment for potential confounders (hazard ratio for cholestanol above median, 2.24 [95% confidence interval (CI), 1.29-3.89]; P=0.004), whereas lower lathosterol (indicating lower cholesterol synthesis) did not (hazard ratio for lathosterol below median, 1.43 [95% CI, 0.81-2.50]; P=0.22). CONCLUSIONS: This analysis of markers of cholesterol metabolism characterizes HD patients as cholesterol absorbers. In longitudinal analysis, higher levels of cholestanol were associated with all-cause mortality.

Ultrasound renal resistive index is not an organ-specific predictor of allograft outcome.

BACKGROUND: Ultrasound-measured renal resistive index (RRI) has been suggested to predict allograft survival in renal transplant recipients. Based on experimental and clinical data, we objected to the theory that RRI specifically mirrors allograft characteristics. Instead, we hypothesized that RRI rather represents a marker of systemic vascular damage than an organ-specific marker. In order to refute this hypothesis, RRI should override the resistive index measured in other abdominal parenchymatous organs-such as the spleen-as predictor of allograft outcome. We therefore set out to simultaneously measure renal and splenic ultrasound resistive index in kidney allograft recipients. METHODS: Eighty-seven stable transplant recipients were recruited. We measured RRI, splenic resistive index (SRI) and an established marker of systemic vascular damage, namely common carotid intima-media thickness (IMT). During a follow-up of 4.9 ± 0.5 years, the occurrence of the combined primary end point, defined as a decrease of ≥ 50% in estimated glomerular filtration rate (eGFR), need for dialysis treatment or death, was recorded. RESULTS: At baseline, both RRI and SRI correlated with common carotid IMT [RRI: r = 0.203 (P = 0.006); SRI: r = 0.315 (P < 0.001)], but not with allograft-specific markers such as eGFR or proteinuria. Elevated RRI was a weak non-significant predictor of the combined primary end point. Notably, RRI did not surpass SRI as outcome predictor. When analysing individual components of the combined primary end point separately, elevated RRI failed to predict strictly renal events (decrease of ≥ 50% in eGFR/need for dialysis treatment), while it predicted total mortality. CONCLUSIONS: Our findings support the notion that RRI is not a specific indicator of allograft damage. Similar to SRI, RRI is rather associated with systemic vascular damage markers and mortality.

Indices of systemic atherosclerosis are superior to ultrasound resistance indices for prediction of allograft survival.

BACKGROUND: In renal allograft recipients, ultrasound resistance indices (RI) have been discussed as predictors of transplant survival. RI measurements are correlated with subclinical atherosclerosis. It is thus unclear whether RI measurements represent specific markers of allograft damage or merely reflect systemic vascular damage. We studied whether RI are superior outcome predictors compared to markers of subclinical atherosclerosis and global cardiovascular risk. METHODS: In 105 renal transplant patients, intrarenal RI and common carotid intima-media thickness (IMT) were measured. Risk for coronary heart disease was determined by Framingham risk scoring (FRS). Patients were followed up for 5.4 +/- 0.4 years. The combined end point was a decrease of > or =50% in estimated glomerular filtration rate, need for dialysis or death. RESULTS: Both an increased IMT and a high FRS were predictors of the combined end point. In contrast, increased RI did not significantly predict the combined end point in the entire cohort. Only among low-risk patients with either normal IMT or FRS < or =20%, high RI measurements were associated with allograft loss. CONCLUSIONS: Compared to markers of cardiovascular risk or systemic atherosclerosis, renal RI are inferior outcome predictors in unselected transplant recipients. Only in patients with mild or moderate cardiovascular risk may RI measurements allow additional risk stratification.

Renal Doppler resistance indices are associated with systemic atherosclerosis in kidney transplant recipients.

BACKGROUND: In kidney transplant recipients, increased intrarenal resistance indices measured by duplex ultrasound are associated with poor subsequent allograft performance. It remains unclear whether high resistance indices rather reflect local renal damage or systemic vessel disease. We hypothesized that resistance indices are associated with cardiovascular risk factors and with subclinical systemic atherosclerosis in transplant recipients. METHODS: In 105 renal transplant recipients, categories of risk for coronary heart disease were determined by Framingham risk scoring. Intrarenal resistive index (RI) and pulsatility index (PI) were measured in segmental arteries at five representative locations. For assessment of subclinical atherosclerosis, common carotid intima-media thickness, and ankle-brachial blood pressure index (ABI) were determined. RESULTS: Transplant recipients with high coronary risk had higher intrarenal resistance indices than low-risk patients. Higher age, female gender, and lower body mass index were independently associated with increased resistance indices. Renal resistance indices were correlated with common carotid intima-media thickness [RI: r= 0.270 (P= 0.005); PI: r= 0.355 (P < 0.001)]. This association remained significant after adjusting for renal function. Renal resistance indices were increased in patients with pathologic ankle-brachial-indices compared to patients with physiologic ankle-brachial-indices [RI: 73.3 +/- 7.1 vs. 70.2 +/- 6.9 (P= 0.03); PI: 146.4 +/- 29.9 vs. 131.4 +/- 25.9 (P= 0.01)]. Renal resistance indices were neither significantly correlated with glomerular filtration rate (GFR), nor with donor age. CONCLUSION: Intrarenal resistance indices are a complex integration of arterial compliance, pulsatility, and peripheral resistance. They are associated with traditional cardiovascular risk factors as well as with subclinical atherosclerotic vessel damage and should thus not be considered specific markers of renal damage.