Ten-Year Efficacy and Safety of Once-Daily Tacrolimus in Kidney Transplant: A Prospective Cohort Study.

Tacrolimus is a cornerstone in the immunosuppressive therapy of kidney transplantation. The once-daily formulation of tacrolimus has been shown to improve adherence of patients without affecting short-term efficacy. However, long-term proof of once-daily tacrolimus efficacy and safety is still lacking. From January 2009 to November 2013, 170 clinically stable kidney transplant patients were offered to change from the ongoing twice-daily tacrolimus (TDT) formulation to a once-daily tacrolimus (ODT) regimen. Kidney transplant recipients agreeing to the change to be treated with an ODT regimen (n = 105, estimated glomerular filtration rate [eGFR] 57.1 ± 1.6 mL/min/1.73 m2) and patients continuing on a TDT formulation (n = 65, eGFR 52.0 ± 2.2 mL/min/1.73 m2) were prospectively followed (median follow-up time 10.4 and 12.6 years in the ODT and TDT groups, respectively, P = not significant). At the end of the follow-up, patients in both groups experienced similar eGFR (50.4 ± 2.2 vs 48.0 ± 2.7 mL/min/1.73 m2 in the ODT and TDT groups, respectively, P = not significant). No differences were observed in biopsy-proven acute rejection, overall graft survival, doubling of serum creatinine, and new onset of proteinuria. The 2 groups also had a comparable rate of death, sepsis, and neoplasia. In conclusion, ODT appears safe and effective in stable kidney graft recipients even 10 years after transplantation. These findings support the use of ODT as a primary tacrolimus formulation in patients with kidney transplantation.

Ultrasound findings in dual kidney transplantation.

PURPOSE: This study was done to analyse colour Doppler ultrasound (CDUS) findings in patients with dual kidney transplantation (DKT) and to compare renal volume and resistive index (RI) values between DKT and single kidney transplantation (SKT). MATERIALS AND METHODS: We reviewed the clinical and imaging findings [30 CDUS, five magnetic resonance (MR) and one computed tomography (CT) examination] in 30 patients with DKT (23 men and seven women; median age 65 years; range 55-82). Three patients had clinical signs of graft malfunction. Renal volumes and RI were compared with those of 14 SKT patients and comparable levels of renal function. RESULTS: Three patients had graft dysfunction: one had chronic rejection and two had pathologies involving one kidney only (one encrusted pyeloureteritis of a left graft and one occluded main artery of a left graft). Asymptomatic unilateral pathologies were seen in six cases. In asymptomatic DKT patients, no significant differences in length, volume, cortical echogenicity and RI between the two kidneys were observed; DKTs were smaller (median volume 116.7 vs. 171.6 cc) and had higher RIs (0.76 vs. 0.68) (p<0.01) than SKTs. CONCLUSIONS: CDUS provides useful information in patients with DKT, allowing detection of clinically unsuspected unilateral diseases. At comparable levels of renal function, DKT patients had higher RI and lower volumes than SKT patients.

Abnormal arachidonic acid content of red blood cell membranes and main lithogenic factors in stone formers.

BACKGROUND: Increased arachidonic acid content in red blood cell membranes of stone formers (SF) has recently been reported and is hypothesized as representing the underlying causal factor for both hyperoxaluria and hypercalciuria. We performed the present study to see whether we could confirm this finding and to test whether any relationship exists between the fatty acid composition of red blood cell membranes and the main metabolic factors involved in stone formation. METHODS: In 21 SF and 40 healthy controls subjects the fatty acid composition of red blood cell membranes was assessed. In addition, the following parameters were evaluated in SF: daily and fasting urinary calcium excretion, fractional intestinal calcium absorption, 1,25-dihydroxy-vitamin D, intact parathyroid hormone, hydroxyproline in fasting urine, daily urinary excretion of oxalate, citrate, urate, electrolytes, urea, sulphate, relative supersaturation for calcium oxalate monohydrate. RESULTS: The red blood cell membrane of SF had a lower content of arachidonic acid, linoleic acid, and docosahexaenoic acid than that of control subjects. Arachidonic acid content was not correlated with any of the parameters studied. However, when patients were grouped according to the degree of oxalate excretion, hyperoxaluric SF had a higher arachidonic acid content and arachidonic/linoleic acid ratio than SF with normal oxalate excretion. CONCLUSIONS: Our results do not confirm the finding of an increased arachidonic acid content of red blood cell membrane in SF. On the contrary, reduced arachidonic acid levels were found in our patients. However, hyperoxaluric SF had a relatively higher arachidonic acid content than SF with normal urinary oxalate excretion.

Angiotensin-converting enzyme gene polymorphism and reversibility of uremic left ventricular hypertrophy following long-term antihypertensive therapy.

BACKGROUND: Prolonged antihypertensive therapy might be less effective in reversing the left ventricular hypertrophy (LVH) in uremics bearing the deleted (DD) allele of the angiotensin converting enzyme (ACE) gene than in patients with the inserted (II) allele or in those heterozygous (ID) for the gene. METHODS: Thirteen DD and 17 II + ID hemodialyzed uremics were followed-up with yearly echocardiography and 24-hour blood pressure (BP) monitoring over five years while on an antihypertensive therapy that included ACE inhibitors as first line drugs. RESULTS: In the II + ID group there were significant decreases of the left ventricular mass index (LVMi) and of both systolic and diastolic BPs. These changes were less pronounced in the DD group, but the difference was not statistically significant given the wide overlap between the two groups. Further analysis of the data revealed that the only factor associated to a decreased LVMi was the decrease of the systolic BP irrespective of the ACE gene genotype of each individual patient. CONCLUSIONS: The ACE-gene genotype does not necessarily predict the extent to which LVMi will be lowered by ACE-inhibitors therapy. The LVH of hypertensive uremics is amenable by long-term antihypertensive therapy provided that it results in significantly decreased systolic blood pressure.

Cardiac diastolic abnormalities and atrial natriuretic factor in essential hypertension.

Cardiac function and plasma levels of atrial natriuretic factor (ANF) were studied in a group of 38 patients with untreated essential hypertension and in a group of 31 well matched normotensive controls. ANF was slightly but significantly higher in hypertensives and was directly correlated with mean arterial pressure and inversely with plasma renin activity (PRA). Hypertensives showed normal systolic function and higher cardiac mass compared to controls. ANF was inversely correlated to echocardiographic indexes of left ventricular performance in the former group. At Doppler echocardiographic evaluation, hypertensives showed an impairment in diastolic function which was correlated to the increase in ANF levels. Stepwise multiple regression analysis performed with ANF as the dependent variable and several biohumoral and echocardiographic parameters as the independent variables showed that only cardiac diastolic function and PRA significantly affect ANF levels in hypertensives. In conclusion, an impairment in cardiac diastolic function may be responsible together with other factors for the increased ANF levels encountered in essential hypertension.

Changes in blood pressure, plasma triglyceride and aldosterone concentration, and red cell cation concentration in patients with hyperinsulinemia.

Blood pressure, plasma concentration of triglyceride, aldosterone, renin activity (PRA), and atrial naturietic peptide (ANP), and red blood cell, urine, and plasma sodium and potassium concentration were determined in 24 healthy individuals divided into two groups defined as being either hyperinsulinemic or normoinsulinemic. The results demonstrated that the hyperinsulinemic group had significantly higher values for both systolic (P less than .01) and diastolic (P less than .05) blood pressure. In addition, plasma concentrations of triglyceride (P less than .02), aldosterone (P less than .05) and potassium (P less than .05) were higher in hyperinsulinemic individuals as compared to those who were normoinsulinemic. Furthermore, red cell potassium was lower (P less than .01) and red cell sodium higher (P less than .01) in the hyperinsulinemic group. Finally, the magnitude of hyperinsulinemia correlated directly with systolic (r = 0.50, P less than .01) and diastolic (r = 0.44, P less than .05) blood pressure, concentration of plasma triglyceride (r = 0.55, P less than .01) and aldosterone (r = 0.46, p less than .05), and erythrocyte sodium concentration (r = 0.57, p less than .01). In contrast, plasma insulin response was negatively correlated with erythrocyte potassium concentration (r = 0.40, P less than 0.05). These observations provide further support for the view that hyperinsulinemia, presumably secondary to resistance to insulin-stimulated glucose uptake, is associated with a cluster of variables that may play important roles in the etiology and clinical course of hypertension.

Long-term minoxidil treatment in refractory hypertension and renal failure.

Twenty-two patients with severe or accelerated hypertension refractory to conventional hypotensive therapy have been treated with minoxidil for an extended period. Patients were divided in three groups according to different degrees of renal function or the presence of accelerated hypertension. In the first group (8 patients with normal or slightly decreased renal function) BP fell from 197 +/- 11/118 +/- 3 before minoxidil therapy to 157 +/- 7/98 +/- 2 after six months (p less than 0.001), and remained steady during the following eighteen months. In the second group (9 patients with creatinine clearance of 30 +/- 3 ml/min.1.73 m2) BP decreased from 192 +/- 9/119 +/- 4 to 147 +/- 6/91 +/- 4 at six months (p less than 0.001); renal function did not show any significant modification during the eighteen months of the study. In the third group (5 patients with accelerated hypertension) BP fell from 243 +/- 14/137 +/- 6 to 166 +/- 13/99 +/- 7 at six months (p less than 0.01). Seven patients, four in the first and three in the second group, were followed for more than six years; these patients, with mild renal insufficiency (creatinine clearance 50 +/- 4 ml/min) before minoxidil therapy, were on a protein unrestricted diet for the entire length of the study. In this group of patients BP fell from 182 +/- 9/115 +/- 3 to 150 +/- 6/96 +/- 2 after one year (p less than 0.01) and remained well controlled for the following six years or more. Renal function did not show any significant worsening over the years (monthly decrement in creatinine clearance 0.08 ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)