Renal function of patients with a failing Fontan circuit undergoing total cavopulmonary revision surgery.

This report characterizes renal dysfunction after total cavopulmonary (TCPC) revision surgery for atriopulmonary Fontan (APF) circulations, a known risk factor for a poor outcome. The perioperative data for 23 consecutively identified patients were reviewed. The preoperative mean glomerular filtration rate (GFR) was 101 +/- 30 ml/min/1.73 m(2), decreasing to 65 +/- 41 ml/min/1.73 m(2) early in the postoperative period. The preoperative GFR was highly correlated with age at APF (r = -0.5; p = 0.024), age at TCPC (r = -0.5; p = 0.01), and mixed venous saturation (r = 0.6; p = 0.01). Three of four patients requiring renal replacement therapy (RRT) died at a median age of 3 months (range, 18 days to 9 months). Determinants of early GFR and RRT were preoperative GFR (p = 0.016) and creatinine (p = 0.035). Younger age at primary Fontan (p = 0.008), higher preoperative mixed venous saturation (p = 0.019), and higher preoperative blood pressure (p = 0.006) independently predicted better GFRs at the latest follow-up evaluation. Renal function declines acutely after TCPC revision, often necessitating RRT. A requirement for RRT marks greater mortality. Higher preoperative creatinine levels identify those at greatest risk.

Decline in kidney function before and after nephrology referral and the effect on survival in moderate to advanced chronic kidney disease.

BACKGROUND: The burden of chronic kidney disease (CKD) is high, but its natural history and the benefit of routine nephrology care is unclear. This study investigated the decline in kidney function prior to and following nephrology referral and its association with mortality. METHODS: This study provides a retrospective review of the individual rates of glomerular filtration rate (GFR) decline (millilitre per minute per 1.73 m(2)/year) for the 5 years before and after referral in 726 new referrals with stages 3-5 CKD to one renal unit between 1997 and 2003. Blood pressures are averages at referral, 1 and 3 years post referral. Logistic regression and Cox's models tested factors predicting post-referral GFR decline and the impact on mortality. RESULTS: Mean (SD) age was 72 (14), and 389 (54%) patients had stages 4-5 CKD. GFR decline slowed significantly from -5.4 ml/min/1.73 m(2)/year (-13. to -2) before to -0.35 ml/min/1.73 m(2)/year (-3 to +3) after referral (P < 0.001). Blood pressure also reduced significantly (155/84 to 149/80, P < 0.05) with most changes occurring within 1 year of referral. Factors predicting a non-progressive post-referral decline included a lower systolic blood pressure at referral and 1 year after referral, a CKD diagnosis other than diabetic nephropathy, less baseline proteinuria and a non-progressive pre-referral GFR decline. A non-progressive post-referral GFR decline was independently associated with significantly better survival (hazard ratio 0.55, 95% CI 0.40-0.75, P

The second United Kingdom Heart and Renal Protection (UK-HARP-II) Study: a randomized controlled study of the biochemical safety and efficacy of adding ezetimibe to simvastatin as initial therapy among patients with CKD.

BACKGROUND: Evaluating the effects of decreasing low-density lipoprotein (LDL) cholesterol levels requires large randomized trials. In preparation for such a trial, we assessed the biochemical efficacy, safety, and tolerability of adding ezetimibe, 10 mg/d, to simvastatin, 20 mg/d, as initial therapy for such patients. METHODS: Two hundred three patients (152 predialysis patients with creatinine levels > or = 1.7 mg/dL [> or = 150 micromol/L], 18 patients on peritoneal dialysis therapy, and 33 patients on hemodialysis therapy) were randomly assigned to the administration of simvastatin, 20 mg/d, plus ezetimibe, 10 mg/d; or simvastatin, 20 mg, plus placebo ezetimibe daily. RESULTS: After 6 months, allocation to simvastatin monotherapy was associated with a 31-mg/dL (0.8-mmol/L) decrease in nonfasting LDL cholesterol levels compared with baseline. Allocation to simvastatin plus ezetimibe produced an additional 18-mg/dL (0.47-mmol/L) decrease in LDL cholesterol level, representing an incremental 21% reduction over that achieved with simvastatin monotherapy (P < 0.0001). There were no statistically significant effects of the addition of ezetimibe to simvastatin on triglyceride or high-density lipoprotein cholesterol levels. Ezetimibe was not associated with an excess risk of abnormal liver function test results or of elevated creatine kinase levels and did not impair absorption of fat-soluble vitamins. There were no serious adverse events caused by study treatment. CONCLUSION: This 6-month study shows that the addition of ezetimibe to simvastatin, 20 mg/d, as initial therapy for patients with chronic kidney disease was well tolerated and produced an additional 21% decrease in LDL cholesterol levels. The clinical efficacy and safety of combination therapy in this population are now being assessed in a large randomized trial.

An evaluation of a shared primary and secondary care nephrology service for managing patients with moderate to advanced CKD.

BACKGROUND: Chronic kidney disease (CKD) is common, and nephrology services may not cope with the comprehensive referral of patients with CKD. We evaluated a shared primary and secondary care nephrology scheme, hypothesizing that some patients with less progressive moderate to advanced CKD can be identified and safely managed without attending the renal unit. METHODS: A retrospective review of 949 new referrals with stages 3 to 5 CKD managed in either the hospital nephrology clinic (HC) or the shared care scheme (SCS), in which nephrologists review patients remotely by using regular biochemical tests and clinical data recorded in primary care. RESULTS: Two hundred sixty-six patients (28%) were enrolled in the SCS and 683 patients (72%) were managed solely in the HC. Median time to entering the SCS was 111 days (interquartile range, 0 to 328 days). Baseline factors independently predictive of enrollment in the SCS were increasing age, greater glomerular filtration rate (GFR) and serum albumin levels, and no diabetic nephropathy. Few SCS patients did not attend reviews. Forty-one patients (15%) required recall to the HC, mostly because of a decline in GFR. Beneficial changes were seen in blood pressure levels and prescribing of angiotensin-system inhibitors from first referral to 3 years in all patients. Those enrolled in the SCS had good prognosis, with a lower risk for death or renal replacement therapy than the HC group after adjustment for age, sex, GFR, diabetic nephropathy, and vascular disease (hazard ratio, 0.64; 95% confidence interval, 0.38 to 0.89; P = 0.003). CONCLUSION: In this setting, it was possible to select nearly 30% of patients with stages 3 to 5 CKD for management in the SCS. More than half enrolled within 4 months of nephrology referral. Systematic surveillance was effective, and most patients remained stable, with few progressing to renal replacement therapy or death.

First United Kingdom Heart and Renal Protection (UK-HARP-I) study: biochemical efficacy and safety of simvastatin and safety of low-dose aspirin in chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease are at increased risk for cardiovascular disease, but the efficacy and safety of simvastatin and aspirin are unknown in this patient group. METHODS: Patients were randomly assigned in a 2 x 2 factorial design to the administration of: (1) 20 mg of simvastatin daily versus matching placebo, and (2) 100 mg of modified-release aspirin daily versus matching placebo. RESULTS: Overall, 448 patients with chronic kidney disease were randomly assigned (242 predialysis patients with a creatinine level > or = 1.7 mg/dL [> or =150 micromol/L], 73 patients on dialysis therapy, and 133 patients with a functioning transplant). Compliance with study treatments was 80% at 12 months. Allocation to treatment with 100 mg of aspirin daily was not associated with an excess of major bleeds (aspirin, 4 of 225 patients [2%] versus placebo, 6 of 223 patients [3%]; P = not significant [NS]), although there was a 3-fold excess of minor bleeds (34 of 225 [15%] versus 12 of 223 patients [5%]; P = 0.001). Among those with predialysis renal failure or a functioning transplant at baseline, aspirin did not increase the number of patients who progressed to dialysis therapy (7 of 187 [4%] versus 6 of 188 patients [3%]; P = NS) or experienced a greater than 20% increase in creatinine level (63 of 187 patients [34%] versus 56 of 188 patients [30%]; P = NS). After 12 months of follow-up, allocation to 20 mg of simvastatin daily reduced nonfasting total cholesterol levels by 18% (simvastatin, 163 mg/dL [4.22 mmol/L] versus placebo, 196 mg/dL [5.08 mmol/L]; P < 0.0001), directly measured low-density lipoprotein cholesterol levels by 24% (89 mg/dL [2.31 mmol/L] versus 114 mg/dL [2.96 mmol/L]; P < 0.0001), and triglyceride levels by 13% (166 mg/dL [1.87 mmol/L] versus 186 mg/dL [2.10 mmol/L]; P < 0.01), but there was no significant effect on high-density lipoprotein cholesterol levels (2% increase; P = NS). Allocation to simvastatin therapy was not associated with excess risk for abnormal liver function test results or elevated creatine kinase levels. CONCLUSION: During a 1-year treatment period, simvastatin, 20 mg/d, produced a sustained reduction of approximately one quarter in low-density lipoprotein cholesterol levels, with no evidence of toxicity, and aspirin, 100 mg/d, did not substantially increase the risk for a major bleeding episode. Much larger trials are now needed to assess whether these treatments can prevent vascular events.

A population-based study of the incidence and outcomes of diagnosed chronic kidney disease.

BACKGROUND: This study aims to determine the incidence rate and prognosis of detected chronic kidney disease (CKD) in a defined population. METHODS: This is a retrospective cohort study of all new cases of CKD from Southampton and South-West Hampshire Health Authority (population base, 405,000) determined by a persistently increased serum creatinine (SCr) level (>or=1.7 mg/dL [>or=150 micromol/L] for 6 months) identified from chemical pathology records. Follow-up was for a mean of 5.5 years for survival, cause of death, and acceptance to renal replacement therapy (RRT). RESULTS: The annual incidence rate of detected CKD was 1,701 per million population (pmp; 95% confidence interval [CI], 1,613 to 1,793) and 1,071 pmp (95% CI, 1,001 to 1,147) in those younger than 80 years. There was a steep age gradient; median age was 77 years. The man-woman rate ratio was 1.6 (95% CI, 1.4 to 1.8), with a male excess in all age groups older than 40 years. Incidence increased in areas with greater socioeconomic deprivation. Median survival was 35 months. Age, SCr level, and deprivation index were all significantly associated with survival. Standardized mortality ratios were 36-fold in those aged 16 to 49 years, 12-fold in those aged 50 to 64 years, and more than 2-fold in those older than 65 years. Cardiovascular disease (CVD) was the most common cause of death (46%). Only 4% of patients were accepted to RRT. CONCLUSION: The incidence of diagnosed CKD is common, especially in the elderly, and is greater in more deprived areas. Prognosis is poor, with CVD prominent. More research is needed to assess the effectiveness and costs of increasing referral to nephrologists of patients with CKD.