Cardiovascular remodelling and extracellular fluid excess in early stages of chronic kidney disease.

BACKGROUND: Patients with a mild to moderate decrease of glomerular filtration rate (GFR) are at risk of cardiovascular (CV) events and CV remodelling has been demonstrated in patients with advanced chronic kidney disease (CKD). However, early stages of CKD and the mechanisms involved in these modifications have not been studied. METHODS: A total of 104 patients with early CKD (mean GFR 60+/-21 ml/min/1.73 m(2)) had cardiac and vascular ultrasound study and measurement of extracellular fluid by multifrequence spectroscopic bioimpedance. RESULTS: GFR decline was associated with left ventricular (LV) remodelling or hypertrophy in 58 and 68% of DOQI-2 and DOQI-3 patients, respectively and impaired LV diastolic function. GFR decrease was also associated with common carotid remodelling and increased aorta stiffness. Cardiac and vascular remodelling were significantly associated with an excess of extracellular fluid (ECFe) evidenced as early as DOQI-2 stage. In multivariate analysis with adjustment for GFR, ECFe, age and systolic blood pressure (sBP), GFR was no longer independently associated with cardiac and vascular remodelling, whereas ECFe was an independent determinant of LV hypertrophy, left atrium enlargement, common carotid diameter and intima media thickness. CONCLUSION: This study shows that CV remodelling and ECF excess occurred at a very early stage of CKD. The independent association between ECF excess and cardiac and vascular remodelling and hypertrophy may be instrumental in the increased cardiovascular risk in CKD patients. Early therapeutic control of ECF may reduce CV events in CKD patients.

Dramatic effect of sirolimus on renal angiomyolipomas in a patient with tuberous sclerosis complex.

Angiomyolipomas are very common in patients with tuberous sclerosis complex (TSC) and cause substantial morbidity. Until now, arterial embolization has been the recommended treatment for symptomatic patients. We report the case of a woman with TSC and giant angiolipomas in whom sirolimus induced a dramatic reduction in bilateral renal tumors.

Effects of intravenous polymaltose iron on oxidant stress and non-transferrin-bound iron in hemodialysis patients.

BACKGROUND: The use of intravenous iron to correct anemia in end-stage renal diseases (ESRD) has been suspected of catalyzing the production of activated oxygen species and promoting oxidative damage. We investigated the pro-oxidative potential of injected iron in hemodialysis patients. METHODS: In study A, 65 patients with ESRD were studied. 20 patients received weekly infusions of iron polymaltose (maltofer), whereas 45 patients had been off iron therapy for more than 2 months. In study B, 12 patients were investigated during two consecutive hemodialysis sessions, one session without and one session with infusion of 100 mg of maltofer over 4 h. Serum iron status, non-transferrin-bound iron (NTBI) and markers of oxidative stress were studied in blood samples from these patients. RESULTS: In study A, NTBI was detected in 41% of the patients and the proportion of NTBI-positive patients was the same whether or not they received iron therapy. In study B, the serum iron and transferrin saturation index increased during iron infusion and NTBI transiently appeared in some patients but markers of oxidative stress were not significantly affected. CONCLUSION: Although ESRD patients have a high prevalence of NTBI in their serum, no correlation could be established between the presence of NTBI and an increased oxidative stress. The slow infusion of maltofer does not promote a significant increase in the plasma concentration of oxidative stress markers. It may therefore be considered as a safe complement to erythropoietin therapy.

Lithium-induced nephropathy: Rate of progression and prognostic factors.

BACKGROUND: Long-term lithium administration in humans may lead to chronic tubulointerstitial nephritis, which develops very slowly. Its progression to end-stage renal disease (ESRD) has been rarely reported. The aim of this study is to document the rate of progression of lithium-induced nephropathy and its prognostic factors, and to provide an estimation of the percentage of lithium-induced ESRD in France. METHODS: Two groups have been studied: 54 patients with lithium-induced renal failure, nine of whom underwent renal biopsy; and 20 patients who were referred for systematic renal biopsy, 14 of whom were subsequently followed up. In addition, a survey of lithium-induced ESRD was conducted in French dialysis centers. RESULTS: The mean annual loss of creatinine clearance in patients with lithium-induced nephropathy was 2.29 mL/min. Among 74 patients, 12 reached ESRD at a mean age of 65 years. Creatinine clearance at referral and at last follow-up was inversely related to the duration of lithium therapy in both univariate and multivariate analyses adjusting for age, gender, hypertension, and proteinuria. The degree of interstitial fibrosis on renal biopsy was also related to the lithium duration and cumulative dose. It was predictive of the final creatinine clearance. About 35% of the patients tested had moderate hypercalcemia, due to hyperparathyroidism. The prevalence of lithium-related ESRD in France was estimated as two per 1000 dialysis patients. The average latency between onset of lithium therapy and ESRD was 20 years. CONCLUSION: Lithium-induced chronic renal disease is slowly progressive. Its rate of progression is related to the duration of lithium administration. Lithium-related ESRD represents 0.22% of all causes of ESRD in France. Regular monitoring of estimated creatinine clearance is mandatory in long-term lithium-treated patients.

A three-arm study comparing immediate tacrolimus therapy with antithymocyte globulin induction therapy followed by tacrolimus or cyclosporine A in adult renal transplant recipients.

BACKGROUND: Induction therapy with antithymocyte globulin (ATG) reduces the incidence of acute rejection after transplantation. A study was undertaken to assess the efficacy and safety of ATG induction on tacrolimus-based and cyclosporine A (CsA)-based therapies compared with immediate tacrolimus triple therapy in kidney transplant recipients. METHODS: In a 6-month, open-label, randomized, prospective study conducted in 30 European centers, 555 renal transplant patients were randomly assigned to tacrolimus triple therapy (Tac triple, n=185), ATG induction with tacrolimus (ATG-Tac, n=186), or ATG induction with CsA microemulsion (ATG-CsA, n=184); all were combined with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection episode confirmed by biopsy. RESULTS: Patient demographics and clinical parameters at baseline were similar. Patient and graft survival rates were similar in all groups. The incidence of clinically apparent acute rejection was significantly higher (P=0.003) for Tac triple (33.0%) compared with ATG-Tac (22.6%) and the incidence for ATG-Tac was significantly lower (P=0.004) than for ATG-CsA (37.0%). The incidences of acute rejection confirmed by biopsy (primary endpoint) were 25.4%, 15.1%, and 21.2% for Tac triple, ATG-Tac, and ATG-CsA, respectively (Tac triple vs. ATG-Tac, P=0.004). The incidences of corticosteroid-resistant acute rejection were 7.0% (Tac triple), 4.8% (ATG-Tac), and 10.9% (ATG-CsA) (ATG-Tac vs. ATG-CsA, P=0.038). In the ATG groups, the incidences of leukopenia, thrombocytopenia, serum sickness, fever, and cytomegalovirus infection were significantly higher (P<0.05). CONCLUSIONS: Acute rejection was significantly lower in the ATG-Tac group compared with the ATG-CsA and Tac triple groups. Significantly more hematologic and infectious adverse events were observed in both ATG induction groups.

Upper limb vein anatomy before hemodialysis fistula creation: cross-sectional anatomy using MR venography.

Preoperative imaging is indicated to discriminate patent, adequate superficial veins of the upper limbs undetectable by clinical inspection that could be anastomosed for the creation of a durable and functional hemodialysis fistula. The aim of this pictorial review is to provide a venous anatomic map of the upper limbs using MR venography (MRV) which could help surgeons before creation of hemodialysis access fistulas (AVF). At the level of the forearm, the antebrachial cephalic vein is the most commonly identified as patent. At the level of the elbow and distal arm, the cephalic vein is patent in 80% of normal subjects, and less often patent (23-26%) than basilic vein (33-38%) in patients. Overall, reading transaxial MR views can help for assessing upper limb vein anatomy before creation of a hemodialysis access fistula.

Combined dipyridamole-exercise stress echocardiography for detection of myocardial ischemia in hemodialysis patients: an alternative to stress nuclear imaging.

BACKGROUND: Stress nuclear imaging is the noninvasive technique currently used to detect coronary artery disease (CAD) in dialysis patients. Stress echocardiography is recognized as an alternative to stress nuclear imaging for the general population. The aim of this study is to assess the diagnostic accuracy of stress echocardiography for detecting myocardial ischemia in hemodialysis patients. METHODS: Stress echocardiography and stress technetium-99m-tetrofosmin (Myoview; Amersham International Plc) imaging were performed simultaneously for 66 asymptomatic hemodialysis patients in a single session, using a combination of high-dose dipyridamole and symptom-limited exercise. Coronary angiography was performed in 44 patients with at least one abnormal noninvasive test result or who were considered high-risk despite normal noninvasive test results. RESULTS: Results for stress echocardiography were abnormal in 15 patients (22%); stress Myoview, in 14 patients (21%); and coronary angiography, in 12 patients (18%). The sensitivity of stress echocardiography for detecting myocardial ischemia (defined as stress Myoview defect) was 86%; specificity, 94%; positive predictive value, 80%; negative predictive value, 96%; and overall accuracy, 92%. The sensitivity of stress echocardiography for detecting CAD (defined as abnormal coronary angiography result) was 83%; specificity, 84%; positive predictive value, 67%; negative predictive value, 93%; and overall accuracy, 84%. Stress echocardiography and stress Myoview did not differ significantly in overall accuracy for detecting CAD (84% versus 91%; P = not significant). CONCLUSION: In hemodialysis patients, combined dipyridamole-exercise echocardiography is an accurate method to detect both myocardial ischemia and CAD and represents an alternative to stress nuclear imaging.

Survival of elderly patients on peritoneal dialysis: retrospective study of 292 patients, from 1982 to 1999.

BACKGROUND: Dialysis is becoming increasingly frequent in patients over 75 years of age. Age is a superimposed comorbid factor commonly associated with poor prognosis in these patients. OBJECTIVE: To analyze the survival of 292 patients aged over 75 years on initiation of peritoneal dialysis (PD) from September 1982 to September 1999. DESIGN: Retrospective study. SETTING: Nephrology department in a University Hospital. RESULTS: Mean age was 81.5 years (range 75-92 years); 178 patients were over 80 years and 60 patients were over 85 years. Sex ratio was 136F/156M. Ninety-day mortality rate was 12%. Excluding the first 3 months, median patient survival was 21.6 months; 226 patients died on PD and 24 were shifted to hemodialysis. Survival was inversely correlated with the Charlson combined comorbidity index (CCI), but independent of predialysis hemoglobin and serum albumin levels. Over three selected periods, 1982-1989, 1989-1995, and 1995-1999, an increase was found in mean age (79.7 +/- 3.3, 82.6 +/- 3.9, and 81.8 +/- 4.4 years; p < 0.001), CCI (7.6 +/- 1.59, 8.0 +/- 1.52, and 8.5 +/- 1.63; p = 0.01), and predialysis creatinine clearance (6.2 +/- 2.3, 6.4 +/- 2.4, and 9.8 +/- 3.8 mL/minute; p < 0.001). Median survival was similar in the various selected periods (21.0, 21.5, and 25.4 months). The incidence of peritonitis decreased from 0.63 to 0.21 episodes per patient year. CONCLUSION: From 1982 to 1999, mean age and comorbidity increased on initiation of dialysis in elderly patients, with no increase in mortality. Survival in elderly patients on PD was related to the age-comorbidity index.