Linburg-Comstock anomaly: A comparison of the prevalence in women with and without clinical carpal tunnel syndrome.

We aimed to compare the prevalence of the Linburg-Comstock anomaly in women with and without a clinical diagnosis of carpal tunnel syndrome. The prevalence of the Linburg-Comstock anomaly was evaluated in 400 hands from 200 women over 40 years of age who were diagnosed clinically with carpal tunnel syndrome (CTS), designated as the CTS group. The volunteer group consisted of 400 hands from 200 healthy women over 40 years of age. The women from both groups were asked to carry out the clinical flexion and pain tests described by Linburg and Comstock (1979) as a basis for the clinical diagnosis. CTS patient ages ranged from 40 to 90 (mean 55.8) years, while volunteer group ages ranged from 40 to 93 (mean 55) years. The flexion test was positive in 305 (76%) hands in the CTS group and 242 (60%) hands in the volunteer group. The pain test was positive in 261 (65%) hands in the CTS group and 108 (27%) hands in the volunteer group. Both tests were positive in 244 (61%) hands in the CTS group and 98 (24%) hands in the volunteer group. All these differences were statistically significant. Based on clinical examination using the flexion and pain tests, the prevalence of Linburg-Comstock anomaly was statistically higher in the group of women with carpal tunnel syndrome than in healthy volunteers.

Ingestion of a moderate dose of alcohol enhances physical exercise-induced changes in blood lactate concentration.

The consumption of alcoholic beverages influences carbohydrate and lipid metabolism, although it is not yet clear whether metabolism during physical exercise at different intensities is also affected. This was the objective of the present study. Eight young and healthy volunteers performed a treadmill test to identify the running speed corresponding to a lactate concentration of 4 mM (S4mM). At least 48 h later, they were subjected to two experimental trials (non-alcohol or alcohol) in which they performed two 1-km running sessions at the following intensities: 1) S4mM; 2) 15% above S4mM. In both trials, blood lactate, triglycerides, and glucose concentrations were measured before and after exercise. The acute alcohol intake increased triglycerides, but not lactate concentration under resting conditions. Interestingly, alcohol intake enhanced the exercise-induced increase in lactate concentration at the two intensities: S4mM (non-alcohol: 4.2±0.3 mM vs alcohol: 4.8±0.9 mM; P=0.003) and 15% above S4mM trial (P=0.004). When volunteers ingested alcohol, triglycerides concentration remained increased after treadmill running (e.g., at S4mM - at rest; non-alcohol: 0.2±0.5 mM vs alcohol: 1.3±1.3 mM; P=0.048). In contrast, glucose concentration was not modified by either alcohol intake, exercise, or their combination. We concluded that an acute alcohol intake changed lactate and lipid metabolism without affecting blood glucose concentration. In addition, the increase in lactate concentration caused by alcohol was specifically observed when individuals exercised, whereas augmented triglycerides concentration was already observed before exercise and was sustained thereafter.

Ingestion of a moderate dose of alcohol enhances physical exercise-induced changes in blood lactate concentration

The consumption of alcoholic beverages influences carbohydrate and lipid metabolism, although it is not yet clear whether metabolism during physical exercise at different intensities is also affected. This was the objective of the present study. Eight young and healthy volunteers performed a treadmill test to identify the running speed corresponding to a lactate concentration of 4 mM (S4mM). At least 48 h later, they were subjected to two experimental trials (non-alcohol or alcohol) in which they performed two 1-km running sessions at the following intensities: 1) S4mM; 2) 15% above S4mM. In both trials, blood lactate, triglycerides, and glucose concentrations were measured before and after exercise. The acute alcohol intake increased triglycerides, but not lactate concentration under resting conditions. Interestingly, alcohol intake enhanced the exercise-induced increase in lactate concentration at the two intensities: S4mM (non-alcohol: 4.2±0.3 mM vs alcohol: 4.8±0.9 mM; P=0.003) and 15% above S4mM trial (P=0.004). When volunteers ingested alcohol, triglycerides concentration remained increased after treadmill running (e.g., at S4mM - at rest; non-alcohol: 0.2±0.5 mM vs alcohol: 1.3±1.3 mM; P=0.048). In contrast, glucose concentration was not modified by either alcohol intake, exercise, or their combination. We concluded that an acute alcohol intake changed lactate and lipid metabolism without affecting blood glucose concentration. In addition, the increase in lactate concentration caused by alcohol was specifically observed when individuals exercised, whereas augmented triglycerides concentration was already observed before exercise and was sustained thereafter.

Inter- and Intra-Individual Analysis of Post-Exercise Hypotension Following a Single Bout of High-Intensity Interval Exercise and Continuous Exercise: A Pilot Study.

Recently, post-exercise blood pressure (BP) has been considered a predictive tool to identify individuals who are responsive or not to BP reductions with exercise training (i. e., "high" and "low responders"). This study aimed to analyze the inter- and intra-individual BP responsiveness following a single bout of high-intensity interval exercise (HIIE) and continuous exercise (CE) in normotensive men (n=14; 24.5±4.2 years). Mean change in BP during the 60 min period post-exercise was analyzed and minimal detectable change (MDC) was calculated to classify the subjects as "low" (no post-exercise hypotension [PEH]) and "high responders" (PEH occurrence) following each exercise protocol (inter-individual analysis). The MDC for systolic and diastolic BP was 5.8 and 7.0 mmHg. In addition, a difference equal/higher than MDC between the exercise protocols was used to define an occurrence of intra-individual variability in BP responsiveness. There were "low" and "high" PEH responders following both exercise protocols (inter-individual variability) as well as subjects who presented higher PEH following a specific exercise protocol (intra-individual variability between exercise protocols). These results were observed mainly for systolic BP. In summary, PEH is a heterogeneous physiological phenomenon and, for some subjects, seems to be exercise-protocol dependent. Further investigations are necessary to confirm our preliminary findings.

Urinary MCP-1 and RBP: independent predictors of renal outcome in macroalbuminuric diabetic nephropathy.

BACKGROUND: Albuminuria has been considered a sine qua non condition for the diagnosis of diabetic nephropathy (DN) and has been widely used as a surrogate outcome of chronic kidney disease (CKD). However, recent data suggest that albuminuria may fail as a biomarker in a subset of patients, and the search for novel markers is intense. METHODS: We analyzed the role of urinary RBP and of serum and urinary cytokines (TGF-beta, MCP-1 and VEGF) as predictors of the risk of dialysis, doubling of serum creatinine or death (primary outcome, PO) in 56 type 2 diabetic patients with macroalbuminuric DN. RESULTS: Mean follow-up time was 30.7±10 months. Urinary RBP and MCP-1 were significantly higher in patients presenting the PO, whereas no difference was shown for TGF-ß or VEGF. In the Cox regression, urinary RBP, MCP-1 and VEGF were positively associated and serum VEGF was inversely related to the risk of the PO. However, after adjustments for creatinine clearance, proteinuria, and blood pressure only urinary RBP (OR 11.6; 95% CI 2.7-49.2, p=0.001 for log RBP) and urinary MCP-1 (OR 11.0; 95% CI 1.6-76.4, p=0.02 for log MCP-1) remained as significant independent predictors of the PO. CONCLUSION: Urinary RBP and MCP-1 are independently related to the risk of CKD progression in patients with macroalbuminuric DN. Whether these biomarkers have a role in the setting of normoalbuminuria and microalbuminuria in DN should be further investigated.

Renal evaluation in women with preeclampsia.

BACKGROUND/AIMS: Preeclampsia (PE) is a cause of glomerulopathy worldwide. Urinary retinol-binding protein (RBP) is a marker of proximal tubular dysfunction, albuminuria is an endothelial injury marker, urine protein:creatinine ratio (PCR) may have a predictive value for renal disease later in life, and, recently, podocyturia has been proposed as a sensitive tool in pregnancy, but it needs to be tested. The aim of this study was to evaluate renal involvement in PE and healthy pregnancy. METHODS: Case-control study with 39 pregnant women assessed after 20 weeks of gestation (25 in the control group, CG, and 14 in the PE group) by performing urinary tests. RESULTS: Mean (±SD) age and gestational age of the CG were 26.9 ± 6.4 years and 37.1 ± 5.0 weeks, and of the PE group 26.4 ± 6.9 years and 30.6 ± 5.6 weeks, respectively (p = 0.001). Mean (±SD) urinary RBP (p = 0.017), albuminuria (p = 0.002), and urinary albumin concentration (UAC) ratio (p = 0.006) of the CG were 0.4 ± 0.7 mg/l, 7.3 ± 6.9 mg/l, and 8.2 ± 6.7 mg/g and of the PE group 2.0 ± 4.4 mg/l, 2,267.4 ± 2,130.8 mg/l (p = 0.002), and 3,778.9 ± 4,296.6 mg/g (p = 0.006), respectively. Mean (±SD) urine PCR in the PE group was 6.7 ± 6.1 g/g (p < 0.001). No statistical differences were found between podocyturia in the CG and PE group (p = 0.258). CONCLUSIONS: Urinary RBP, PCR, albuminuria, and UAC ratio were elevated in the PE group in comparison to the CG. Podocyturia did not predict PE.

PP019 The role of renal markers in women with and without preeclampsia: Evaluation of urinary excretion of podocytes and proteins.

INTRODUCTION: Preeclampsia (PE) is an important cause of glomerulopathy. Assessment of renal markers during pregnancy may have a predictive value for glomerular disease later in life. The early detection of PE may prevent the complications of this syndrome. OBJECTIVES: Assess the glomerular involvement in PE and in normal pregnancy by evaluating renal markers such as podocyturia and proteinuria. METHODS: Case-control study with 39 pregnant women after 20 weeks of gestation (control group - CG with n=25 and PE with n=14), we assessed podocyturia (cytospin method) and proteinuria (albuminuria, urine protein:creatinine - PCR, urinary retinol protein - RBP and albumin/creatinine ratio - ACR). (Grant FAPESP 08/56338-1) RESULTS: Mean±standard deviation of age and mean gestational age of CG were 26.9±6.4years and 37.1±5.0weeks and of PE, 26.4±6.9 and 30.6±5.6, respectively (p=0.001). No statistical differences were found between podocyturia in CG and PE although it was more frequent in this last group (p=0.258). Podocyte cells and parietal epithelial cells were detected in the slides. Mean±standard deviation of urinary RBP (p=0.017), albuminuria (p=0.002) and UAC ratio (p=0.006) of CG were 0.4±0.7mg/L, 7.3±6.9mg/L and 8.2±6.7mg/g and of PE, 2.0±4.4mg/L, 2267.4±2130.8mg/L (p=0.002) and 3778.9±4296.6mg/g (p=0.006), respectively. Mean value±standard deviation of urine PCR in PE was 6.7±6.1g/g (p=< 0.001). CONCLUSION: Urinary RBP, PCR, albuminuria and UAC ratio were elevated in PE in comparison to CG indicating its glomerular involvement but there was no correlation between those renal parameters and podocyturia. RPC and UAC ratios were good predictors of PE, but not podocyturia. Either podocyte cells as parietal epithelial cells were detected in the urine, these findings may indicate a non-invasive marker for renal disease activity but more studies are required to determine its role in PE.

PP090. The contribution of podocyturia to the evaluation of ongoing glomerular disorder in pregnant women with kidney graft (preliminary results).

INTRODUCTION: Progressive proteinuria and glomerulosclerosis characterize chronic allograft nephropathy. However, the causes are not fully elucidated. Injury of parietal epithelial cells in glomeruli, the podocytes, is the initiating cause of many renal diseases, leading to proteinuria with possible progression to glomerulosclerosis. Podocytes are highly specialized cells, with an important role in maintaining the glomerular filtration barrier and producing growth factor for mesangial cells and endothelial cells. With their foot processes they cover the glomerular basement membrane, and form slit diaphragms with neighboring podocytes. The potential role of podocytes in the failing transplanted kidney is unknown. OBJECTIVES: To evaluate podocyturia as a functional marker in pregnant women with kidney grafts. METHODS: Twenty pregnant women with kidney grafts had their urine samples cytocentrifugated and evaluated by indirect immunofluorescence. The slide was incubated for 45' at room temperature with fluorescein (FITC) anti-rabbit IgG secondary antibody (Sigma-Aldrich, EUA). Then Vectashield (mounting medium for fluorescence) with DAPI (4'6-diamino-2-fenilindol dihidrocloreto) were applied H-1200 (Vector laboratories, inc, USA). The podocytes and the total number of cells were counted in 15 fields photographed under 400x magnification with a digital camera coupled to an epifluorescence microscope DM1000 (Leica, Germany) connected to a computer. The results were expressed as podocyte/total cells (%) per area of higher cell concentration (hot spots) in the field of 400x detected by staining of nuclei and cytoplasm. (Grant FAPESP 08/56338-1). RESULTS: The mean age of the women was 26years. The urinalysis was performed at the third trimester of gestation; 11 did not exhibit urinary podocytes and 9 had podocyturia. There was also a relationship between blood pressure levels, proteinuria and the excretion of podocytes. CONCLUSION: Urinary podocyte number, blood pressure and proteinuria were associated. We observed that urinary podocyte excretion occurs in pregnant women with kidney transplant almost synchronously with higher systolic and diastolic blood pressure and higher mean levels of proteinuria. The detection of podocyturia in these women could be useful for early diagnosis and follow-up of glomerular injury, eventually preeclampsia. It may be also associated to its severity or activity, although additional studies are necessary to confirm these aspects.

Acute resistance exercise is more effective than aerobic exercise for 24h blood pressure control in type 2 diabetics.

AIM: The study aimed to analyze blood pressure (BP) responses in individuals with type 2 diabetes (T2D) over a 24h period following resistance (RES) and aerobic (AER) exercise. METHODS: Ten adults with T2D (age: 55.8 ± 7.7 years; weight: 79.4 ± 14.0 kg; fasting glucose: 133.0 ± 36.7 mg.dL⁻¹) underwent: (1) AER: 20 min of cycling at 90% lactate threshold (90% LT); (2) RES: three laps of a circuit of six exercises with eight repetitions at 70% 1-RM and 40s of recovery; and (3) a control session of no exercise. Heart rate (HR), and systolic (SBP), diastolic (DBP), mean arterial (MAP) and pulse (PP) BP, as well as lactataemia (Lac), VO(2), respiratory exchange ratio (RER) and rate of perceived exertion (RPE) were measured at rest, during exercise and control (CON) periods, and 60min after interventions. After each session, BP was also monitored over a 24h period. RESULTS: Peak Lac (RES: 6.4 ± 1.4mM; AER: 3.8 ± 1.2mM), RER (RES: 1.1 ± 0.1; AER: 0.9 ± 0.1) and RPE (RES: 14.0 ± 1.3; AER: 11.0 ± 2.3) were higher following the RES session (P < 0.05). Similar VO2 (~70% VO(2peak)) was reached during AER and RES sessions (14.0 ± 3.0 vs 14.3 ± 1.6 mL.kg.min⁻¹; P > 0.05). Compared with CON, only RES elicited post-exercise BP reduction that lasted 8h after exercise. Also, in comparison to pre-exercise rest, the BP dip during sleep was greater following RES (P < 0.05). CONCLUSION: A single exercise bout decreases BP in T2D patients over a 24h period, with RES being more effective than AER exercise for BP control.

Effect of type 2 diabetes on plasma kallikrein activity after physical exercise and its relationship to post-exercise hypotension.

AIM: The present study was undertaken to determine the effects of type 2 diabetes (T2D) on plasma kallikrein activity (PKA) and postexercise hypotension (PEH). METHODS: Ten T2D patients (age: 53.6±1.3 years; body mass index: 30.6±1.0kg/m(2); resting blood glucose: 157.8±40.2mgdL(-1)) and 10 non-diabetic (ND) volunteers (age: 47.5±1.0 years; body mass index: 28.3±0.9kg/m(2); resting blood glucose: 91.2±10.5mgdL(-1)) underwent two experimental sessions, consisting of 20min of rest plus 20min of exercise (EXE) at an intensity corresponding to 90% of their lactate threshold (90LT) and a non-exercise control (CON) session. Blood pressure (BP; Microlife BP 3AC1-1 monitor) and PKA were measured during rest and every 15min for 135min of the postexercise recovery period (RP). RESULTS: During the RP, the ND individuals presented with PEH at 30, 45 and 120min (P<0.05) while, in the T2D patients, PEH was not observed at any time. PKA increased at 15min postexercise in the ND (P<0.05), but not in the T2D patients. CONCLUSION: T2D individuals have a lower PKA response to exercise, which probably suppresses its hypotensive effect, thus reinforcing the possible role of PKA on PEH.

Identificação do limiar anaeróbio em indivíduos com diabetes tipo-2 sedentários e fisicamente ativos / Identification of the anaerobic threshold in sedentary and physically active individuals with type 2 diabetes

OBJETIVO: Comparar intensidades de limiar anaeróbio (LA) obtidas a partir do lactato, ventilação e glicemia em diabéticos tipo-2 ativos (DA) e sedentários (DS) e não-diabéticos ativos (NDA), e correlacionar variáveis metabólicas, hemodinâmicas e de composição corporal com o LA. METODOLOGIA: Grupos de DS (n= 09, 56,7 ± 11,9 anos), DA (n= 09, 50,6 ± 12,7 anos) e NDA (n= 10, 48,1 ± 10,8 anos) foram submetidos a um teste em cicloergômetro com incrementos de 15W até a exaustão. Freqüência cardíaca, pressão arterial (PA), percepção de esforço, lactato, glicemia e variáveis ventilatórias foram mensuradas nos 20seg finais de cada estágio de 3min para determinação dos limiares de lactato, ventilatório e glicêmico. RESULTADOS: As intensidades associadas ao LA identificado pelos diferentes métodos não diferiram entre si (p> 0,05). As intensidades absolutas foram menores para o grupo DS em relação aos grupos ativos (p< 0,05), não sendo observadas diferenças entre os grupos para as intensidades relativas ao consumo máximo de oxigênio ( por centoVO2 pico) e potência máxima ( por centoPpico) de ocorrência do LA. Observou-se correlação significativa entre LA e o percentual de gordura (r= -0,52), com tendência à correlação entre o LA e a glicemia ambulatorial (r= -0,33). Variáveis hemodinâmicas e LA não demonstraram correlações. CONCLUSÃO: O LA foi identificado a partir das técnicas estudadas em diabéticos tipo-2 e não-diabéticos. Apesar das diferenças entre grupos para as intensidades absolutas (Watts), a patologia pareceu não influenciar as intensidades relativas em que o LA foi observado. O LA apresentou correlação com a composição corporal e tendência a se correlacionar com a glicemia ambulatorial, sugerindo-se, com isso, o LA como um parâmetro importante na avaliação clínica destes pacientes.

OBJECTIVE: To compare anaerobic threshold (AT) intensities determined from blood lactate, blood glucose and ventilatory responses among sedentary (SD) and physically active (AD) type-2 diabetics and active non-diabetics (AND), and to correlate metabolic, hemodynamic and body composition variables with the AT. METHOD: The SD (n= 9, 56.7 ± 11.9 years), AD (n= 9, 50.6 ± 12.7 years) and AND (n= 10, 48.1 ± 10.8 years) groups performed a cycle ergometer test with increases of 15 watts every three minutes until exhaustion. Heart rate, arterial pressure, perceived exertion, blood lactate, blood glucose and ventilatory variables were measured during the last 20 seconds of each incremental stage, to determine the lactate, ventilatory and glucose thresholds. RESULTS: The AT intensities identified by the different methods did not differ from each other (p> 0.05). However, the absolute intensities were lower for SD than for the active groups (p< 0.05). No differences in intensity were found between the groups in relation to maximum oxygen consumption ( percentVO2 peak) and maximum power ( percentPpeak) at which the AT was observed. There was a significant correlation between AT and percentage fat (r= -0.52), and there was a trend towards correlation between AT and ambulatory blood glucose (r= -0.33). The hemodynamic variables did not show any correlations with AT. CONCLUSION: The AT was identified by means of the techniques studied, among type 2 diabetics and non-diabetics. Despite the differences between the groups with regard to absolute intensities (watts), diabetes did not appear to influence the relative intensities at which the AT was observed. The AT presented a correlation with body composition and a trend towards correlation with ambulatory blood glucose, thus suggesting that the AT is an important parameter in clinical assessments for such patients.

Relationship of cyclosporin and sirolimus blood concentrations regarding the incidence and severity of hyperlipidemia after kidney transplantation.

The influence of drug concentrations on the development of persistent posttransplant hyperlipidemia was investigated in 82 patients who received cyclosporin A (CsA) and prednisone plus sirolimus (SRL) (52) or azathioprine (AZA) (30) during the first year after transplantation. Blood levels of CsA and SRL, daily doses of AZA and prednisone, and cholesterol, triglyceride, and glucose concentrations were determined during each visit (pretransplant and 30, 60, 90, 120, 180, and 360 days posttransplant). Persistent hyperlipidemia was defined as one-year average steady-state cholesterol (CavCHOL) or triglyceride (CavTG) concentrations above 240 and 200 mg/dL, respectively. Mean cholesterol and triglyceride concentrations increased after transplantation (P < 0.01) and were higher in patients receiving SRL compared to AZA (P < 0.001). Patients receiving SRL showed a significantly higher number of cholesterol (> 229 or > 274 mg/dL) and triglyceride (> 198 or > 282 mg/dL) determinations in the upper interquartile ranges. CsA and SRL interquartile ranges correlated with cholesterol concentrations (P = 0.001) whereas only SRL interquartile ranges correlated with triglyceride concentrations (P < 0.0001). Only pretransplant cholesterol concentration > 205 mg/dL was independently associated with development of persistent hypercholesterolemia (CavCHOL > 240 mg/dL, relative risk (RR) = 20, CI 3.8-104.6, P = 0.0004) whereas pretransplant triglyceride concentration > 150 mg/dL (RR = 7.2, CI 1.6-32.4, P = 0.01) or > 211 mg/dL (RR = 19.8, CI 3.6-107.9, P = 0.0006) and use of SRL (RR = 3, CI 1.0-8.8, P = 0.0049) were independently associated with development of persistent hypertriglyceridemia (CavTG > 200 mg/dL). Persistent hypercholesterolemia was more frequent among patients with higher pretransplant cholesterol concentrations and was dependent on both CsA and SRL concentrations. Persistent hypertriglyceridemia was more frequent among patients with higher pretransplant triglyceride concentrations and was dependent on SRL concentrations.

Impact of initial exposure to calcineurin inhibitors on kidney graft function of patients at high risk to develop delayed graft function.

We conducted a retrospective analysis of the influence of full doses of calcineurin inhibitors [8-10 mg kg-1 day-1 cyclosporine (N = 80), or 0.2-0.3 mg kg-1 day-1 tacrolimus (N = 68)] administered from day 1 after transplantation on the transplant outcomes of a high-risk population. Induction therapy was used in 13% of the patients. Patients also received azathioprine (2 mg kg(-1) day(-1), N = 58) or mycophenolate mofetil (2 g/day, N = 90), and prednisone (0.5 mg kg(-1) day(-1), N = 148). Mean time on dialysis was 79 +/- 41 months, 12% of the cases were re-transplants, and 21% had panel reactive antibodies > 10%. In 43% of donors the cause of death was cerebrovascular disease and 27% showed creatinine above 1.5 mg/dL. The incidence of slow graft function (SGF) and delayed graft function (DGF) was 15 and 60%, respectively. Mean time to last dialysis and to nadir creatinine were 18 +/- 15 and 34 +/- 20 days, respectively. Mean creatinine at 1 year after transplantation was 1.48 +/- 0.50 mg/dL (DGF 1.68 +/- 0.65 vs SGF 1.67 +/- 0.66 vs immediate graft function (IGF) 1.41 +/- 0.40 mg/dL, P = 0.089). The incidence of biopsy-confirmed acute rejection was 22% (DGF 31%, SGF 10%, IGF 8%). One-year patient and graft survival was 92.6 and 78.4%, respectively. The incidence of cytomegalovirus disease, post-transplant diabetes mellitus and malignancies was 28, 8.1, and 0%, respectively. Compared to previous studies, the use of initial full doses of calcineurin inhibitors without antibody induction in patients with SGF or DGF had no negative impact on patient and graft survival.

Impact of initial exposure to calcineurin inhibitors on kidney graft function of patients at high risk to develop delayed graft function

We conducted a retrospective analysis of the influence of full doses of calcineurin inhibitors [8-10 mg kg-1 day-1 cyclosporine (N = 80), or 0.2-0.3 mg kg-1 day-1 tacrolimus (N = 68)] administered from day 1 after transplantation on the transplant outcomes of a high-risk population. Induction therapy was used in 13 percent of the patients. Patients also received azathioprine (2 mg kg-1 day-1, N = 58) or mycophenolate mofetil (2 g/day, N = 90), and prednisone (0.5 mg kg-1 day-1, N = 148). Mean time on dialysis was 79 ± 41 months, 12 percent of the cases were re-transplants, and 21 percent had panel reactive antibodies >10 percent. In 43 percent of donors the cause of death was cerebrovascular disease and 27 percent showed creatinine above 1.5 mg/dL. The incidence of slow graft function (SGF) and delayed graft function (DGF) was 15 and 60 percent, respectively. Mean time to last dialysis and to nadir creatinine were 18 ± 15 and 34 ± 20 days, respectively. Mean creatinine at 1 year after transplantation was 1.48 ± 0.50 mg/dL (DGF 1.68 ± 0.65 vs SGF 1.67 ± 0.66 vs immediate graft function (IGF) 1.41 ± 0.40 mg/dL, P = 0.089). The incidence of biopsy-confirmed acute rejection was 22 percent (DGF 31 percent, SGF 10 percent, IGF 8 percent). One-year patient and graft survival was 92.6 and 78.4 percent, respectively. The incidence of cytomegalovirus disease, post-transplant diabetes mellitus and malignancies was 28, 8.1, and 0 percent, respectively. Compared to previous studies, the use of initial full doses of calcineurin inhibitors without antibody induction in patients with SGF or DGF had no negative impact on patient and graft survival.

Relationship of cyclosporin and sirolimus blood concentrations regarding the incidence and severity of hyperlipidemia after kidney transplantation

The influence of drug concentrations on the development of persistent posttransplant hyperlipidemia was investigated in 82 patients who received cyclosporin A (CsA) and prednisone plus sirolimus (SRL) (52) or azathioprine (AZA) (30) during the first year after transplantation. Blood levels of CsA and SRL, daily doses of AZA and prednisone, and cholesterol, triglyceride, and glucose concentrations were determined during each visit (pretransplant and 30, 60, 90, 120, 180, and 360 days posttransplant). Persistent hyperlipidemia was defined as one-year average steady-state cholesterol (CavCHOL) or triglyceride (CavTG) concentrations above 240 and 200 mg/dL, respectively. Mean cholesterol and triglyceride concentrations increased after transplantation (P < 0.01) and were higher in patients receiving SRL compared to AZA (P < 0.001). Patients receiving SRL showed a significantly higher number of cholesterol (>229 or >274 mg/dL) and triglyceride (>198 or >282 mg/dL) determinations in the upper interquartile ranges. CsA and SRL interquartile ranges correlated with cholesterol concentrations (P = 0.001) whereas only SRL interquartile ranges correlated with triglyceride concentrations (P < 0.0001). Only pretransplant cholesterol concentration >205 mg/dL was independently associated with development of persistent hypercholesterolemia (CavCHOL >240 mg/dL, relative risk (RR) = 20, CI 3.8-104.6, P = 0.0004) whereas pretransplant triglyceride concentration >150 mg/dL (RR = 7.2, CI 1.6-32.4, P = 0.01) or >211 mg/dL (RR = 19.8, CI 3.6-107.9, P = 0.0006) and use of SRL (RR = 3, CI 1.0-8.8, P = 0.0049) were independently associated with development of persistent hypertriglyceridemia (CavTG >200 mg/dL). Persistent hypercholesterolemia was more frequent among patients with higher pretransplant cholesterol concentrations and was dependent on both CsA and SRL concentrations. Persistent hypertriglyceridemia was more frequent among patients with higher pretransplant triglyceride concentrations and was dependent on SRL concentrations.