Candiduria in renal transplant recipients: incidence, clinical repercussion, and treatment indication.

INTRODUCTION: The incidence of candiduria in renal transplant recipients is unknown. In clinical practice, the indications for antifungal therapy are not well established. Furthermore, there is the problem of the choice of the antifungal drug since some of them may select resistant Candida species, or interact with immunosuppressive agents or only be used intravenously. AIM: We sought to study the incidence, clinical repercussions and effectiveness of antifungal treatment to prevent recurrence of candiduria. MATERIALS AND METHODS: We examined all episodes of Candida-positive urine cultures (>50,000 cfu/mL) in 996 recipients over 2 years. We considered the Candida species, administered treatment, presence of fever, requirement for hospital admission versus outpatient case, occurrence of simultaneous bacterial urinary tract infection (UTI), antibiotic use during the week before candiduria, and presence of an indwelling urinary catheter. RESULTS: Among 996 subjects, 34 displayed 83 episodes of candiduria, yielding an accumulated incidence of 3.4% after 2 years. The frequency was higher among women (6.3% vs 1.7%, P<.001). Of the 45 outpatient episodes (54.2%), 17 were treated and one required hospitalization (5.9%). Of the 28 nontreated outpatients, two were hospitalized (7.1%, P=.68 vs treated patients). All cases of hospital admission presented simultaneous bacterial UTI, none developed candidemia, and two patients did not receive any antifungal therapy. With respect to the first episodes of each patient (n=34), 5/11 treated (45.5%) and 4/23 untreated (17.4%) patients developed recurrences (P=.095). Selection of more resistant Candida species was not observed. Fifty cases (60%) were associated with antibiotic therapy and 34 (41%) the presence of a urinary catheter. CONCLUSIONS: It does not seem necessary to treat candiduria in this setting. Antifungal therapy was not associated with either a reduction in recurrence or the appearance of more resistant species in this study. We observed no important clinical repercussions.

Aportación de la dinamometría isocinética de columna lumbar en una mutua laboral / Contribution of isokinetic dynamometry of the lumbar spine in an occupational mutual insurance company

Objetivo: Conocer la discordancia entre la clínica y las pruebas complementarias en la patología del raquis lumbar. Pacientes y metodología: Estudiamos 64 pacientes (50 hombres, 14 mujeres), con una edad media de 45 años (rango: 33–55), que fueron evaluados con un dinamómetro para conocer la fuerza concéntrica y excéntrica de los músculos extensores de la columna lumbar. Padecían de lumbalgia, 36 procedían de accidente laboral y 28 de contingencia común. La mayoría de los hombres realizaban trabajos en la construcción y las mujeres trabajos de manipulación o en cadenas de montaje. Se obtuvo la sinceridad del esfuerzo mediante REC (índice excéntrico / concéntrico) y DEC (diferencia entre REC a velocidad alta y REC a velocidad baja). Resultados: La media de días desde la baja hasta realizar la prueba fue de 280 días en accidentes laborales y 157 días en las contingencias. En el 68% de las pruebas se registraron parámetros indicativos de esfuerzo máximo. En ellos se registraron unos valores deficitarios de extensores en modalidad excéntrica (50%) y concéntrica (60%). Conclusiones: La dinamometría isocinética de columna lumbar permite hacer una estimación sobre la funcionalidad de la columna (AU)

Objetive: To determine the discrepancy between the clinical manifestations and complementary test findings in lumbar spine disorders. Patients and methods: A total of 64 patients (50 males, 14 females) with a mean age of 45 years (range: 33-55) were subjected to dynamometric testing to determine concentric and eccentric strength of the extensor muscles of the lumbar spine. The patients presented lumbar disorders; 36 had suffered occupational accidents and 28 common contingencies. Most of the males worked in construction, while the women were involved in processing or assembly operations. Exertion sincerity was determined by REC (eccentric / concentric ratio) and DEC (difference between REC at high velocity and REC at low velocity). Results: The mean days from the start of sick leave to the moment of testing was 280 days in the case of occupational accidents and 157 days in the case of contingencies. Most of the tests (68%) registered parameters indicative of maximum exertion. These tests showed extensor deficiencies in the eccentric (50%) and concentric modalities (60%). Conclusions: Isokinetic dynamometry of the lumbar spine offers an estimation of spinal functionality (AU)

Sirolimus and everolimus induced pneumonitis in adult renal allograft recipients: experience in a center.

Mammalian target of rapamycin (mTOR) inhibitors induce pneumonitis, an unusual but potentially fatal side effect of this drug group. We retrospectively collected the cases of pneumonitis induced by sirolimus or everolimus among 1471 adult cadaveric renal transplant recipients who were grafted at our institution from 1980-2008. Due to chronic transplant dysfunction or tumor, 205 patients were switched from calcineurin inhibitors to sirolimus (n = 88) or to everolimus (n = 117). Six patients (2.9%) developed pneumonitis: 1 was associated with sirolimus and 5 with everolimus (5 males and 1 female; median age, 60 years [range, 47-73 years]). Median times from conversion to pneumonitis onset were 34 days in 4 patients (range, 24-46 days) and 491 days in 2 subjects (range, 454-528 days). The mean drug trough level at presentation was 8.2 microg/L (range, 5.5-13.8 microg/L). The most common symptoms were dry cough (n = 6), fever (n = 5), and dyspnea (n = 4). Imaging tests revealed lower lobe involvement in all patients. Bronchoalveolar lavage performed in 4 patients showed lymphocytic alveolitis. All patients completely recovered after drug withdrawal. Five patients received steroids, 5 were switched to a calcineurin inhibitor, and 1 was switched to the other mTOR inhibitor. In conclusion, mTOR inhibitor-associated pneumonitis is a rare disease. Sirolimus did not cause more cases of pneumonitis than everolimus. Pneumonitis development was not dependent upon the drug blood level. Lower lobe involvement and lymphocytic alveolitis were usually present. Discontinuation of the mTOR inhibitor with steroid prescription resulted in adequate outcomes. A change to the other mTOR inhibitor should be contemplated if patient circumstances require this type of immunosuppression.

Treatment of persistent hyperparathyroidism in renal transplant patients with cinacalcet improves control of blood pressure.

Persistent hyperparathyroidism is observed in 17% to 50% of patients at 1 year after renal transplantation. In 10% of these patients, hypercalcemia is also present. This condition increases the risk of vascular calcification, correlating with inferior graft function among patients with interstitial calcification in the renal allograft. Hypertension is appears in 60% to 90% of patients after transplantation, favoring progressive graft dysfunction. Hypercalcemia per se causes hypertension. Parathyroid hormone can potentiate the pressor effects of hypercalcemia. Fourteen renal transplant recipients were included based upon: total serum calcium > 10.0 mg/dL, intact parathyroid hormone levels > 70 pg/mL, graft function > 6 months, creatinine clearance > 50 mL/min, and stable immunosuppressive therapy. We also examined blood pressure and antihypertensive treatment. Initially patients received 30 mg of cinacalcet once a day. The follow-up was up to 6 months. The mean cinacalcet dose was 40 mg/24 h. Five patients received 60 mg/24 h. Both serum calcium and iPTH decreased significantly from 10.6 (DE 0.4) to 9.8 (DE Both serum calcium and iPTH decreased significantly from 10.6 (DE 0.4)to 9.8 (DE 0.6) mg/dL (P < .001) and from 195.0 (DE 140.0) to 118.62 (DE 102.2; P < .0001). There were no significant changes in renal function, proteinuria, or tacrolimus levels. Mean blood pressure diminished from 94.1 (DE 12.0) to 88.0 (DE 7.5) mm Hg (P < .019) with no changes in antihypertensive treatment. Cinacalcet was suspended in one patient because of gastrointestinal discomfort and in another one because the iPTH was reduced to 51 pg/mL. Cinacalcet is an effective treatment for persistent hyperparathyroidism associated with hypercalcemia among renal transplant patients and may be helpful for hypertension control.

Kidney transplantation complications related to psychiatric or neurological disorders.

Defining absolute psychiatric or neurological contraindications among kidney transplantation candidates is controversial, especially taking into account that graft outcomes are similar to other groups of patients. The social support network should be exhaustively evaluated to ensure adherence to immunosuppressive therapy and minimization of complications resulting from the neuropsychiatric disorder. We reviewed transplants (n = 668) in our center between January 2001 and August 2008 searching for patients with a diagnosis of neurological or psychiatric disease before renal transplantation. We also reviewed demographic data, social support networks, patient and graft survivals as well as transplant complications. Twelve patients were transplanted with neurological or psychiatric disorders: seven with cognitive impairment and five with psychiatric diseases. Nine patients had good social support networks. The mean follow-up time was 2.65 +/- 2.42 years. The graft loss rate was 34% (n = 4), including only one attributed to a mental disorder, namely, nonadherence to immunosuppressive therapy. Regarding complications, four were related to the neuropsychiatric disorder: hypoglycemia due to insulin overdose, aspiration pneumonia because of altered pharynx-larynx motility, hyponatremia related to diuretic abuse, and malnutrition plus dehydration. Patient survival in this period was 91.7%. The one patient died due to multiple organ failure secondary to respiratory sepsis with a functioning graft. In summary, neuropsychiatric disorders should not be considered to be contraindications for kidney transplantation although a social support network is essential and must be carefully evaluated.

Preemptive kidney transplant from deceased donors: an advantage in relation to reduced waiting list.

BACKGROUND: Preemptive living donor kidney transplantation is associated with better allograft and recipient survival. However, it remains unclear whether preemptive transplantation from deceased donors is beneficial too. An increased number of deceased donors has reduced the waiting list in our hospital in the last years allowing preemptive deceased donor kidney transplantation (PDDKT). AIM: We compared our experience with preemptive transplantation with patients who underwent dialysis before transplantation. PATIENTS AND METHODS: Thirty-three PDDKT, including 77.5% male patients of overall mean age of 48 +/- 14 years, were performed in our hospital between January 1999 and December 2004 (8% of transplantations). We compared the outcomes of these patients with those of renal transplants in subjects who had undergone dialysis. The donors for both groups had similar characteristic; they were paired donor kidneys in most cases. RESULTS: The types of donors in both groups were: non-heart-beating (49%), heart-beating deceased (27%) or en bloc pediatric (24%). The serum creatinine of the recipients was 6.9 +/- 1.8 mg/dL prior to transplantation, and the creatinine clearance was 14.6 +/- 3.6 mL/min (estimated by the Cockroft-Gault formula). The Charlson comorbidity index adapted for patients with advanced chronic kidney disease (ACKD) was 0.8 +/- 0.2 in the preemptive group versus 1.7 +/- 0.4 in the dialysis group (P < .05). Delayed graft function rates were 0% versus 25% in preemptive vs dialysis groups, respectively. No differences in 1-month or 1-year renal function as determined by serum creatinine were observed between the groups. We did not observe differences in the incidence of acute rejection or 1- and 2-year graft and patient survivals. CONCLUSION: PDDKT is the treatment of choice for ACKD. It is associated with less delayed graft function and similar 2-year graft and patient survivals than kidney transplantation after dialysis. The Charlson index reflected less comorbidity among patients with PDDKT, a finding that must influence long-term outcomes.

Effect of the brain-death process on acute rejection in renal transplantation.

INTRODUCTION: Growing experimental evidence suggests that the state of brain death (BD) activates surface molecules on peripheral organs by the massive release of macrophage- and T cell-associated cytokines as well as adhesion molecules into the circulation. The question is whether the sequelae of the BD process substantially influences the quality of the donor organ, the ensuing host response, or the ultimate transplant outcome. Our aim was to compare explosive BD with gradual-onset injury in terms of a trigger of the host immune mechanisms accelerating acute rejection processes. MATERIALS AND METHODS: This retrospective study included 149 cadaveric donors whose kidneys were transplanted in to 264 recipients. Exclusion criteria were previous transplants and hyperimmmunized patients. Donor variables were: sex, age, etiology of death, and hemodynamic conditions during the 24 hours prior to death. The recipient variables included, all possible conditions known to induce rejection. RESULTS: Cox analysis revealed the following factors to be predictive of acute vascular rejection: initial immunosuppression without induction (risk ratio [RR] 1.83; 95% confidence interval [CI] 1.02 to 3.25; P = .039) which there was a trend to an impact of a regimen without tacrolimus (RR 1.84; 95% CI 0.85 to 3.98; P = .099), or of recipient age < 30 years (RR 2.17; 95% CI 1.06 to 4.48); P = .053) or lower mean donor blood pressure during the 3 hours prior to death (RR 1.17; 95% CI 1.00 to 1.37; P = .054). CONCLUSIONS: Greater sympathetic activity during brain death produces nonspecific endothelial damage and increases organ immunogenicity, promoting rejection.

Varicella infection in adult renal allograft recipients: experience at one center.

Disseminated varicella-zoster virus (VZV) infection in adult renal allograft recipients is a rare but potentially fatal illness. We retrospectively collected the cases of VZV infection that occurred in 812 adult renal transplant recipients, performed between 1995 and 2004 at our institution. Eight patients developed varicella (1%), seven men and one woman. The overall median age was 38 years (range = 31 to 64). The median time from transplantation to infection was 32 months (range = 2 to 92). Four cases were primary infections and four disseminated VZV reactivations. Immunosuppression consisted of prednisone (PDN) + cyclosporine (CSA) + mycophenolate (MF; n = 4); PDN + CSA + azathioprine (n = 1); PDN + tacrolimus (FK) + MF (n = 1); FK + MF (n = 1); PDN + rapamycin + MF (n = 1). Seven patients (87%) required hospital admission for a median duration of 11 days (range = 3 to 21). Four patients were previously diagnosed with chronic hepatitis virus infection: two type B (HBV) and two type C (HCV). The last cohort required longer admission than the negative patients (11.5 +/- 3 vs 7.5 +/- 9 days; P = .1). The only clinical manifestation in four patients was general malaise, fever, and a disseminated vesicular rash; the other four patients also showed visceral involvement: two pneumonitis, one hepatitis, and thrombotic microangiopathy, and one developed multiorgan failure and died due to a delayed diagnosis in a patient positive for HBVs. The diagnosis was established according to the symptoms, IgG-IgM seroconversion and VZV polymerase chain reaction quantification in vesicle contents. Treatment consisted of reduced immunosuppression, antiviral drugs (acyclovir or gancyclovir), and in six patients, a varicella-zoster immunoglobulin dose. We concluded that varicella infection in adult renal allograft recipients is unusual but highly morbid. A vaccination program in seronegative pretransplant candidates should be attempted. Early diagnosis and treatment may improve the prognosis. Although further studies are required, chronic HBV or HCV infection seemed to be a risk factor for the disease.

Conversion to sirolimus in renal transplant patients with tumors.

BACKGROUND: Conversion from calcineurin inhibitors (CNI) to sirolimus (SRL) is an option for renal transplant patients who develop a tumor. This strategy, however, may be associated with an increased risk of rejection. AIM: We sought to evaluate a series of renal transplant patients who underwent conversion from CNI to SRL because they developed a tumor during the posttransplant period. METHODS: This prospective study of 29 patients included 2 patients with skin cancer (1 melanoma and 1 squamous cell carcinoma) and 27 patients who developed other tumors: lung (n = 6), prostate (n = 4), lymphoma (n = 2), colon adenocarcinoma (n = 2), kidney (n = 2), Kaposi sarcoma (n = 2), urothelium (n = 1), parotid (n = 1), larynx (n = 1), gastric (n = 1), breast (n = 1), tongue (n = 1), liver (n = 1), xanthoastrocytoma (n = 1), and aggressive angiomyxoma of the perineum (n = 1). RESULTS: CNI were withdrawn in 28 patients and reduced in the remaining patient. Renal function was better when CNI were rapidly or abruptly suspended, with maintenance of cyclosporine (CsA) + SRL for more than 3 months being especially detrimental. Proteinuria worsened in patients whose preconversion levels were >0.5 g/d, particularly those treated with CsA. There was no episode of rejection. CONCLUSIONS: SRL is a promising option for the management of posttransplant tumors. The switch in immunosuppression should be undertaken quickly, especially in patients under treatment with CsA.

Daclizumab induction as an immunosuppressive regimen for renal transplant recipients from non-heart-beating donors.

BACKGROUND: Recent reports have demonstrated the efficacy of interleukin-2-receptor blockers in lowering the incidence of early acute rejection. The present study aimed to test the hypothesis that the use of daclizumab induction (DAC) plus low-dose tacrolimus, mycophenolate mofetil, and steroid diminishes the incidence of delayed graft function (DGF) in renal transplants from non-heart-beating donors (NHBD). METHODS: We compared the incidence of DGF and rejection in 185 renal transplants from NHBD treated as follows: Group-I: quadruple sequential therapy with antithymocyte globulin, cyclosporine, azathioprine, and steroids (n=22); Group-II: cyclosporine (8 mg/kg/d) plus azathioprine plus steroid (n=26); Group-III: low-dose cyclosporine (5 mg/kg/d) plus mycophenolate mofetil plus steroid (n=68); Group-IV: low-dose tacrolimus (0.1 mg/kg/d) plus mycophenolate mofetil plus steroid (n=17); and Group-V: DAC plus low-dose tacrolimus plus mycophenolate mofetil plus steroid (n=43). RESULTS: The incidences of DGF were 72.7% in Group-I, 73.1% in Group-II, 69.1% in Group-III, 76.5% in Group-IV, and 44.2% in Group-V. Acute rejection was higher in Group-IV. CONCLUSIONS: The combination of DAC, low-dose tacrolimus, mycophenolate mofetil, and steroids is effective in lowering the incidence of DSF in NHBD kidney transplant recipients without any increase in acute rejection.

Prevalence of hypertension in renal disease.

BACKGROUND: Hypertension (HTN) is very frequent in patients with renal disease and its prevalence increases as renal failure progresses. METHODS: We studied the prevalence of HTN in 1921 patients with different nephropathies. Patients on dialysis and renal transplant patients were not included in the study. HTN was defined as SBP>140 and/or DBP>90 mmHg, or requiring antihypertensive therapy. RESULTS: The prevalence of HTN in the total group of patients with renal diseases was 60.5%, but this prevalence varied widely depending upon the type of underlying nephropathy. The prevalence of HTN was practically universal in patients with renal vascular disease (93%) and in patients with established diabetic nephropathy (87%), and 74% of the patients with polycystic kidney disease, 63% of the patients with chronic pyelonephritis and 54% of the patients diagnosed with glomerulonephritis were hypertensive. The prevalence of HTN in patients with renal insufficiency (80%) is significantly higher than that in patients without renal insufficiency (43% P<0.001). In a multiple logistic regression analysis, the independent risk factors defining HTN in renal patients were: renal failure, age, the presence of diabetes, hypertriglyceridaemia and proteinuria. Antihypertensive treatment consisted of diet alone in 4% of the patients, one drug in 45%, two drugs in 36%, three medications in 13% and more than three drugs in 2.5%. The angiotensin-converting enzyme (ACE) inhibitors were the most frequently prescribed drug (39% of the patients treated in monotherapy) followed by calcium channel blockers (27%), diuretics (18%) and beta-blockers (9%). The most common combined therapy was a diuretic plus an ACE inhibitor. The percentage of patients with BP controlled according to current recommendations for renal patients (BP<130/85) was very low; SBP in only 49% and DBP in 24%. Control of both was only achieved in 10% of the patients. CONCLUSIONS: There is a high prevalence of HTN in renal patients, which depends on the type of nephropathy and the degree of renal failure. Other independent risk factors for HTN in patients with renal disease are: advanced age, the presence of diabetes, hypertriglyceridaemia and the severity of proteinuria. BP control in renal patients is quite poor and should be improved to reduce progression of the renal disease.

Effect of strict blood pressure control on proteinuria in renal patients treated with different antihypertensive drugs.

BACKGROUND: The severity of proteinuria is the main predictive factor in the progression of renal failure in chronic nephropathies. Therefore, action aimed at reducing proteinuria should be a priority in the treatment of these patients. Various antihypertensive drugs, in particular the angiotensin-converting enzyme inhibitors (ACEIs), have a greater antiproteinuric effect, although it is difficult to establish whether this is due only to their effect on arterial blood pressure (BP) or to other mechanisms associated with blockade of the renin-angiotensin system (RAS). METHODS: The evolution of proteinuria after two successive treatment periods was studied prospectively for 2 years in 22 patients with chronic glomerulonephritis. In period I, which lasted for 12 months, BP was strictly controlled (<125/75 mmHg) and the patients received random and double-blind treatment with a beta-blocker (betaB), atenolol; a non-dihydropyridine calcium channel blocker (CCB), verapamil; an ACEI, trandolapril; or a fixed combination of the latter two. In period II, all of the patients received treatment openly for an additional 12 months with a fixed combination of verapamil+trandolapril at half the dose of the preceding period, to obtain conventional control of BP at <140/90 mmHG: RESULTS: The mean level for basal SBP/DBP was 136+/-14/86+/-7 mmHg, which decreased in period I to 121+/-15/76+/-8 mmHg (P=0.01) and to 124+/-5/78 +/-8 mmHg (P<0.05) at 6 and 12 months of treatment, respectively. There were no differences in the BP reached in the four therapy groups; however, proteinuria only decreased in the patients treated with trandolapril alone or in combination with verapamil. In period II, BP levels rose to 134+/-10/84+/-8 mmHg (P<0.05); this increase in BP was accompanied by an increase in proteinuria in those patients who had received the ACEI alone or in combination in the previous period, while in patients previously treated with a betaB or a CCB, proteinuria decreased, in spite of the increase in BP. CONCLUSIONS: With equal BP control, treatment with the ACEI trandolapril alone, or in combination with a CCB, has a greater antiproteinuric effect than that obtained with other antihypertensive drugs, but this effect is attenuated if BP is not strictly controlled.