Can pulsatile cardiopulmonary bypass prevent perioperative renal dysfunction during myocardial revascularization in elderly patients?

BACKGROUNDS/AIMS: We recently demonstrated that pulsatile cardiopulmonary bypass (CPB) versus standard linear CPB is associated with better perioperative renal function. Since older subjects have a higher risk of acute renal failure, we have extended our study to evaluate the specific impact of pulsatile CPB on the perioperative renal function in elderly patients. METHODS: We enrolled 50 patients with normal preoperative renal function: they were stratified by age (65-75 vs. 50-64 years) and randomized to nonpulsatile (group A) or pulsatile CPB (group B). Twenty-seven patients aged > or =50 years and <65 years were randomized to group A (n = 12) or to group B (n = 15) and 23, aged > or =65 years and < or =75 years, to group A (n = 13) or to group B (n = 10). Glomerular filtrate rate (GFR), daily diuresis, lactatemia and other parameters were measured during the pre- and perioperative period. RESULTS: The percent perioperative decrease in GFR was lower in group A than in group B (p < 0.001), without differences between older and younger patients. By contrast, perioperative plasma lactate levels were higher in group A than in group B (p < 0.001), both in older and younger patients. No difference was observed for 24 h urine output and blood urea nitrogen. CONCLUSIONS: Pulsatile CPB preserves renal function better than standard CPB even in patients older than 65. CPB could be adopted as the procedure of choice in this subgroup of patients.

A randomized trial of pulsatile perfusion using an intra-aortic balloon pump versus nonpulsatile perfusion on short-term changes in kidney function during cardiopulmonary bypass during myocardial reperfusion.

BACKGROUND: Nonpulsatile perfusion during cardiopulmonary bypass can induce renal damage. We evaluated whether pulsatile perfusion using an intra-aortic balloon pump preserves renal function in patients undergoing myocardial revascularization. STUDY DESIGN: Randomized controlled trial, nonmasked parallel-group design. SETTING & PARTICIPANTS: 100 patients undergoing preoperative perfusion using an intra-aortic balloon pump; 64 with baseline estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m(2) or greater (>or=1 mL/s/1.73 m(2); stage 1 or 2) and 36 with eGFR of 30 to 59 mL/min/1.73 m(2) (0.5 to 0.98 mL/s/1.73 m(2); stage 3). INTERVENTION: Patients were randomly assigned to nonpulsatile perfusion during cardiopulmonary bypass (group A) or automatic intra-aortic balloon pump-induced pulsatile perfusion during cardiopulmonary bypass (group B). OUTCOMES & MEASUREMENTS: Renal function, daily diuresis, complications, serum lactate levels, and other biochemical indices at 24 and 48 hours. RESULTS: GFR, adjusted for baseline eGFR, was 16 mL/min/1.73 m(2) [0.27 mL/s/1.73 m(2)] less in group A (58.1 mL/min/1.73 m(2); 95% confidence interval [CI], 56.1 to 60.1 mL/min/1.73 m(2) [0.97 mL/s/1.73 m(2); 95% CI, 0.94 to 1.0 mL/s/1.73 m(2)]) than in group B (74.0 mL/min/1.73 m(2); 95% CI, 72.0 to 76.1 mL/min/1.73 m(2) [1.23 mL/s/1.73 m(2); 95% CI, 1.20 to 1.27 mL/s/1.73 m(2)]; P < 0.001). Plasma lactate levels were +3.9 mg/dL (+0.43 mmol/L) higher in group A (19.5 mg/dL; 95% CI, 18.4 to 20.5 mg/dL [2.16 mmol/L; 95% CI, 2.04 to 2.28 mmol/L]) than in group B (16.7 mg/dL; 95% CI, 14.4 to 16.7 mg/dL [1.73 mmol/L; 95% CI, 1.60 to 1.85 mmol/L]; P < 0.001). No significant difference between the 2 groups was observed for 24-hour diuresis. Patients with eGFR stage 3 had a greater decrease in GFR and daily diuresis and greater increase in lactate levels than those with eGFR stages 1 to 2. LIMITATIONS: Short-term change in kidney function as a surrogate outcome for "hard" clinical outcomes of mortality, morbidity, and length of hospitalization. Other limitations are short-term follow-up and absence of measurement of hemodynamic parameters or inflammatory mediators. CONCLUSIONS: Use of automatic pulsatile intra-aortic balloon pumps during cardiopulmonary bypass is associated with better renal function during myocardial reperfusion. More studies are needed to verify the effects of pulsatile intra-aortic balloon pumps.

Prevalence and severity of anaemia in patients with type 2 diabetic nephropathy and different degrees of chronic renal insufficiency.

BACKGROUND/AIM: Type 2 diabetes mellitus is the single most common cause of chronic kidney disease (CKD); however its real impact on renal anaemia has not been established. The aim of this study was to evaluate whether onset, severity, and prevalence of anaemia during the course of CKD is different between type 2 diabetic and non-diabetic patients. METHODS: We enrolled 281 patients with: (1) type 2 diabetes and no CKD (n = 75); (2) type 2 diabetes plus CKD (n = 106), and (3) CKD without type 2 diabetes (n = 100). According to K/DOQI guidelines, the patients with renal insufficiency (i.e., those with a glomerular filtration rate <60 ml/min) were subgrouped into three tertiles of CKD: (1) stage 3 (creatinine clearance 60-30 ml/min); (2) stage 4 (creatinine clearance 29-15 ml/min), and (3) stage 5 (creatinine clearance <15 ml/min). RESULTS: Anaemia was observed in 16% of the diabetic patients without CKD; it was more frequent in the diabetic patients with CKD than in the non-diabetic patients with CKD (61.7 vs. 52%, p < 0.05). The comparison among the tertiles showed that the prevalence of anaemia was significantly higher only in diabetic CKD patients of stages 4 and 5. The prevalence was higher in females independently of type 2 diabetes mellitus. In diabetics with a normal renal function, the haemoglobin levels were higher than in diabetics and non-diabetics with CKD, but the diabetics showed lower levels of haemoglobin than non-diabetics at stage 3 and stage 4 of CKD. CONCLUSIONS: Diabetic patients with CKD of stages 4 and 5 have a higher prevalence of anaemia than non-diabetic patients with comparable glomerular filtration rate. A higher awareness of this risk will allow earlier diagnosis and treatment.

Radiocontrast media cause dephosphorylation of Akt and downstream signaling targets in human renal proximal tubular cells.

Radiocontrast medium induced nephrotoxicity is a major clinical problem. There is considerable interest in reducing the incidence of acute renal failure due to the use of radiocontrast media (RCM). Reduction of renal blood flow and direct toxic effect on renal tubular epithelial cells have been postulated as major causes of RCM nephropathy. Understanding the molecular mechanisms by which RCM cause cell damage may allow the development of pharmacological therapy to prevent their nephrotoxicity. In this work we have investigated the signaling pathways that may be affected by RCM. The incubation of human renal tubular proximal cells with sodium diatrizoate, iopromide and iomeprol caused a marked dephosphorylation of the kinase Akt on Ser473 within 5min of incubation. RCM also caused a decrease in cell viability, which was substantially alleviated by transfecting the cells with a constitutively active form of Akt. Further downstream targets of Akt, including the Forkhead family of transcription factors FKHR and FKHRL1, were also dephosphorylated by RCM at Thr24 and Thr32, respectively. The P70S6 kinase was also dephosphorylated at Thr389 and Ser371 by RCM. However there was a more dramatic decrease in phosphorylation of the phosphorylated form of mammalian target of rapamycin (mTOR) and of the extracellular-signal regulated kinases (ERK) 1/2 caused by sodium diatrizoate than by iopromide. These results demonstrate the effect of RCM on some intracellular signaling pathways that may allow understanding of the mechanism of their toxicity and may allow the development of strategies to overcome their adverse effects.

A case report of plasma exchange therapy in non-paraneoplastic cerebellar ataxia associated with anti-Yo antibody.

A 71-year-old-woman was admitted to the S. Eugenio Hospital for a history of progressively impaired standing and gait. Anamnesis revealed systemic hypertension, gastric polyposis and juvenile pulmonary tuberculosis. Neurological examination showed a severe truncal and gait ataxia, without any sensory-motor impairment. Motor and somato-sensory evoked potentials were normal. Brain Magnetic Resonance Imaging (MRI) showed minimal signs of chronic ischemia only at a supratentorial level. Cerebral Single Photon Emission Computed Tomography, spinal MRI, total body computed tomography, Esophagogastroduodenoscopy, and finally total body Positron Emission Tomography resulted negative for neoplasms. Oncological serum markers were negative. Serum antibody against Purkinje's cells (Anti-Yo) was detected and titer was 1:80, while normally it should be undetectable. Other autoantibodies (Anti-Hu, Anti-Ri) were undetectable. Two sessions of plasma exchange (PE) were thus performed, leading to a rapid, marked and durable improvement of standing and gait and to a reduction of the autoantibody, which became undetectable. No serious adverse effect was noted. Although no definite therapy for autoimmune cerebellar ataxia has been established, PE should be considered as one of the main therapeutic choices.

Adequate protein dietary restriction in diabetic and nondiabetic patients with chronic renal failure.

OBJECTIVE: To evaluate whether a dietary protein restriction is useful for slowing the progression of chronic renal failure (CRF) in diabetic and nondiabetic patients and to analyze the possible risk of malnutrition after such a dietary regimen. DESIGN: Prospective, randomized case-control clinical trial. SETTING: Nephrology outpatients. PATIENTS AND OTHER PARTICIPANTS: A total of 169 patients, 89 affected with CRF and chronic hypertension and 80 affected with overt diabetic nephropathy (24 suffering from type 1 and 56 from type 2 diabetes) and chronic hypertension. INTERVENTION: Diabetic patients and nondiabetic patients were randomly divided into 2 groups: 40 diabetic patients received a low-protein diet (0.8 g/kg/day) and 40 were maintained on a free protein diet; similarly, 44 nondiabetic patients received a low-protein diet (0.6 g/kg/day) and 45 were maintained on a free protein diet. The investigation lasted 1 year. MAIN OUTCOME MEASURE: Renal function and nutritional status. RESULTS: At the end of the study, there were no statistically significant differences in renal function between treated and nontreated diabetic patients, whereas treated nondiabetic patients showed a lower decrease in renal function compared with the nontreated group. In both diabetic and nondiabetic patients, the mean body weight and obesity index decreased significantly in treated patients compared with nontreated ones. Serum albumin and prealbumin were stable in all patients during the whole study time, and there were no other signs of malnutrition. CONCLUSION: An adequate dietary protein restriction is accepted by patients, and it is well tolerated during a 12-month follow-up. Without any sign of malnutrition, it is possible to get near the ideal body weight and to reduce the obesity index and the body mass index, which are both well-established risk factors for developing cardiovascular pathology. In nondiabetic patients only, we observed a significant slowing of the progression of renal damage.

Anti-inflammatory effects of combined treatment with acetyl salicylic acid and atorvastatin in haemodialysis patients affected by Normal Weight Obese syndrome.

Low-grade inflammation is a common feature of chronic kidney disease (CKD) and persistent systemic inflammation is thought to be a strong predictor of cardiovascular events. Inflammation plays a role in determining the serum albumin levels in haemodialysis patients (HD) independently of the nutritional status. Increased cardiovascular mortality in CKD has been associated with the increased incidence of obesity in uremic patients. Ingenbleek suggested a prognostic inflammation and nutritional index (PINI), based on serum albumin, pre-albumin, C-reactive protein, and alpha1 acid glycoprotein, to identify and to follow up acutely ill patients at risk of major complications. The aims of the present study were: to verify the incidence of Normal Weight Obese (NWO) syndrome; to evaluate by PINI the effect of 8 weeks acetyl salicylic (100 mg/die) and atorvastatin (10 mg/die) combined treatment on chronic inflammation in 52 selected HD patients. Laboratory evaluation, anthropometric and body composition measurements were detected. At baseline the 56.25% of non-obese, the 84.21% of pre-obese-obese, and the 41.17% of NWO women showed PINI values >1 (normal status PINI<1). After the pharmacological treatment, high significant (P<0.001) reduction in lipid profile, an elevated increase of HDL levels, and a significant reduction of inflammatory markers were obtained. Firstly, our results showed that ASA and atorvastatin combined treatment was effective in reducing inflammatory status in HD patients independently of body composition: at the end of the study only 7.49% of the patients exhibited PINI>1. Further studies will be necessary to understand the causes of inflammation in non-responder patients.

Severe dietary protein restriction in overt diabetic nephropathy: benefits or risks?

OBJECTIVE: To evaluate whether restricting protein intake may delay the progression of chronic renal failure caused by overt diabetic nephropathy and also whether this increases the risk of malnutrition. DESIGN: Prospective clinical trial. SETTING: Nephrology outpatients. PATIENTS: Sixty-nine patients (32 affected by type 1 and 37 by type 2 diabetes, all treated with insulin) affected by both overt diabetic nephropathy and hypertension. INTERVENTION: The study was started once hypertension and glycemia had been under control for at least 3 months. Two groups of patients, matched for similar mean glomerular filtration rate value and nutritional status, were studied: a low-protein diet (0.6 g/kg/d) was randomly prescribed to 35 patients, whereas in the other 34 patients a free diet intake was maintained for 12 months. MAIN OUTCOME MEASURE: Renal function and nutritional status. RESULTS: The protein intake was significantly different in the 2 groups of patients, whereas the average decline of glomerular filtration rate during the follow-up was comparable. In the low-protein diet group, serum prealbumin concentration significantly decreased after 9 months, whereas serum albumin decreased at the end of the study. CONCLUSION: Severe dietary protein restriction does not seem to delay the progression of renal disease in patients with overt diabetic nephropathy, whereas it may induce malnutrition.