The perception of sleep quality in kidney transplant patients during the first year of transplantation

OBJECTIVE: Poor sleep quality is one of the factors that adversely affects patient quality of life after kidney transplantation, and sleep disorders represent a significant cardiovascular risk factor. The objective of this study was to investigate the prevalence of changes in sleep quality and their outcomes in kidney transplant recipients and analyze the variables affecting sleep quality in the first years after renal transplantation. METHODS: Kidney transplant recipients were evaluated at two time points after a successful transplantation: between three and six months (Phase 1) and between 12 and 15 months (Phase 2). The following tools were used for assessment: the Pittsburgh Sleep Quality Index; the quality of life questionnaire Short-Form-36; the Hospital Anxiety and Depression scale; the Karnofsky scale; and assessments of social and demographic data. The prevalence of poor sleep was 36.7% in Phase 1 and 38.3% in Phase 2 of the study. RESULTS: There were no significant differences between patients with and without changes in sleep quality between the two phases. We found no changes in sleep patterns throughout the study. Both the physical and mental health scores worsened from Phase 1 to Phase 2. CONCLUSION: Sleep quality in kidney transplant recipients did not change during the first year after a successful renal transplantation.

Oral Lesions in Renal Transplant

To prevent rejection of kidney transplants, patients must be kept in immunosuppressive therapy for a long time, which includes the use of drugs such as cyclosporine, azathioprine, cyclophosphamide, and prednisone. The action of these drugs reduces the general immune response of transplant patients and thus increases their susceptibility to infections. Moreover, these drugs increase the potential of developing lesions. Therefore, oral hygiene in kidney transplant recipients contributes to maintenance of the transplanted organ and its function. Thus, an investigation of oral lesions could be counted as a notable work. The aim of this study was to investigate oral lesions in a group of 21 kidney transplant patients under immunosuppressive therapy attended during a 1-year period in the Nephrology Department of the Federal University of Sergipe, Brazil. Data related to sex, age, etiology of renal disease, types of renal transplant, time elapsed after transplantation, immunosuppressive treatment, use of concomitant agents, and presence of oral lesions were obtained. All patients received a kidney transplant from a living donor, and the mean posttransplantation follow-up time was 31.6 months; 71.5% used triple immunosuppressive therapy with cyclosporine A, azathioprine, and prednisone. Ten patients were also treated with calcium-channel blockers. Of the 21 transplant patients, 17 (81%) presented oral lesions. Gingival overgrowth was the most common alteration, followed by candidiasis and superficial ulcers. One case of spindle cell carcinoma of the lower lip was observed. Oral cavity can harbor a variety of manifestations related to renal transplantation under immunosuppressive therapy.

De Novo Thrombotic Microangiopathy After Kidney Transplantation: Clinical Features, Treatment, and Long-Term Patient and Graft Survival

Introduction. Posttransplant thrombotic microangiopathy (TMA)/hemolytic uremic syndrome (HUS) can occur as a recurrent or de novo disease. Methods. A retrospective single-center observational study was applied in order to examine the incidence and outcomes of de novo TMA/HUS among transplantations performed between 2000 and 2010. Recurrent HUS or antibody-mediated rejections were excluded. Results. Seventeen (1.1%) among 1549 kidney transplant recipients fulfilled criteria for de novo TMA. The mean follow-up was 572 days (range, 69-1769). Maintenance immunosuppression was prednisone, tacrolimus (TAC), and mycophenolic acid in 14 (82%) patients. Mean age at onset was 40 +/- 15 years, and serum creatinine was 6.1 +/- 4.1 mg/dL. TMA occurred at a median of 25 days (range, 1-1755) after transplantation. Nine (53%) patients developed TMA within 1 month of transplantation and only 12% after 1 year. Clinical features were anemia (hemoglobin < 10 g/dL) in 9 (53%) patients, thrombocytopenia in 7 (41%), and increased lactate dehydrogenase in 12 (70%). Decreased haptoglobin was observed in 64% and schistocytes in 35%. Calcineurin inhibitor (CM) withdrawal or reduction was the first step in the management of 10/15 (66%) patients, and 6 (35%) received fresh frozen plasma (FFP) and/or plasmapheresis. TAC was successfully reintroduced in six patients after a median of 17 days. Eight (47%) patients needed dialytic support after TMA diagnosis and 75% remained on dialysis. At 4 years of follow-up, death-censored graft survival was worse for TMA group (43.0% versus 85.6%, log-rank = 0.001; hazard ratio = 3.74) and there was no difference in patient survival (53.1% versus 82.2%, log-rank = 0.24). Conclusion. De novo TMA after kidney transplantation is a rare but severe condition with poor graft outcomes. This syndrome may not be fully manifested, and clinical suspicion is essential for early diagnosis and treatment, based mainly in CM withdrawal and FFP infusions and/or plasmapheresis.

Current outcome of prioritized patients for kidney transplantation

Purpose: To analyze the outcome of deceased donor recipients given priority in allocation due to lack of access for dialysis and compare this data to the one obtained from non-prioritized deceased donor kidney transplant recipients. Materials and Methods: we reviewed electronic charts of 31 patients submitted to kidney transplantation that were given priority in transplantation program due to lack of access for dialysis from January 2005 to December 2008. Immunological and surgical complications rates, and grafts and patients survival rates were analyzed. These data were compared to those obtained from 100 regular patients who underwent kidney transplantation without allocation priority during the same period. Results: Overall surgical complication rate was 25.8% and 27% in the patients with priority in allocation and in the non-prioritized patients, respectively. There was no statistical significant difference for surgical complications (p = 1.0), immunological complications (p = 0.21) and graft survival (p = 0.19) rates between the groups. However, patient survival rate was statistically significant worse in prioritized patients (p = 0.05). Conclusions: patients given priority in allocation owing to lack of access for dialysis have higher mortality rate when compared to those non-prioritized.

Malakoplakia after renal transplantation in the current era of immunosuppressive therapy: case report and literature review

Malakoplakia is a rare chronic granulomatous disease of unknown cause. It is thought to be caused by an acquired bactericidal defect of macrophages. Malakoplakia is associated with chronic infections and immunosuppression. Although it occurs mainly in the urinary tract, it has already been reported in almost every organ system. The isolation of bacteria, especially Escherichia coli, is common in malakoplakia patients. Here, we present a case of primary cutaneous malakoplakia in a kidney transplant recipient who had been taking prednisone, tacrolimus, and mycophenolate. Culture of a lesion grew Burkholderia cepacia complex. Treatment with high doses of trimethoprim-sulfamethoxazole was successful. We also present a systematic review of the literature, identifying 4 previously reported cases of malakoplakia after renal transplantation under similar immunosuppressive therapy, most occurring in the urinary tract or perineum and following benign courses to cure. Data in the literature suggest that malakoplakia has become even rarer since changes were made in the immunosuppressive therapy employed after kidney transplantation.

Immunogenicity and Reactogenicity of 2009 Influenza A (H1N1) Inactivated Monovalent Non-Adjuvanted Vaccine in Elderly and Immunocompromised Patients

Background Immunosuppressed individuals present serious morbidity and mortality from influenza, therefore it is important to understand the safety and immunogenicity of influenza vaccination among them. Methods This multicenter cohort study evaluated the immunogenicity and reactogenicity of an inactivated, monovalent, non-adjuvanted pandemic (H1N1) 2009 vaccine among the elderly, HIV-infected, rheumatoid arthritis (RA), cancer, kidney transplant, and juvenile idiopathic arthritis (JIA) patients. Participants were included during routine clinical visits, and vaccinated according to conventional influenza vaccination schedules. Antibody response was measured by the hemagglutination-inhibition assay, before and 21 days after vaccination. Results 319 patients with cancer, 260 with RA, 256 HIV-infected, 149 elderly individuals, 85 kidney transplant recipients, and 83 with JIA were included. The proportions of seroprotection, seroconversion, and the geometric mean titer ratios postvaccination were, respectively: 37.6%, 31.8%, and 3.2 among kidney transplant recipients, 61.5%, 53.1%, and 7.5 among RA patients, 63.1%, 55.7%, and 5.7 among the elderly, 59.0%, 54.7%, and 5.9 among HIV-infected patients, 52.4%, 49.2%, and 5.3 among cancer patients, 85.5%, 78.3%, and 16.5 among JIA patients. The vaccine was well tolerated, with no reported severe adverse events. Conclusions The vaccine was safe among all groups, with an acceptable immunogenicity among the elderly and JIA patients, however new vaccination strategies should be explored to improve the immune response of immunocompromised adult patients. (ClinicalTrials.gov, NCT01218685)

Lithiasis in 1,313 Kidney Transplants: Incidence, Diagnosis, and Management

Background. Renal transplantation remains the optimal treatment of patients with end-stage renal disease. Urinary lithiasis represents an unusual urologic complication in renal transplantation, with an incidence of <1%. Today, recipients of kidneys from deceased donors are more likely to receive grafts with undiagnosed lithiasis, which does not occur in patients from living donors, owing to screening with computerized tomography. Objective. The aim of this study was to evaluate the incidence, diagnosis, and therapeutic management of renal lithiasis in transplanted kidneys at a single institution. Methods. We reviewed the medical records for 1,313 patients who underwent kidney transplantation from February 1968 to February 2011. Results. Among the grafts, 17 patients (1.29%) had nephrolithiasis: 9 women and 8 men. Ages ranged from 32 to 63 years (mean = 45.6 years). Fifteen patients received kidneys from cadaveric and only 2 from living related donors. Two stones, both located inside the ureter, were identified during transplant surgery (11.7%). Three instances of lithiasis were incidentally diagnosed by ultrasound during graft evaluation, within 7 days after surgery (17.6%); all 3 were in the calyces. The 12 remaining patients had the stones diagnosed later (70.58%): 6 in the calyces, 3 in the renal pelvis, and 3 inside the ureter. Conclusions. Urinary lithiasis is a rare complication in renal transplantation. In most patients the condition occurs without pain. The diagnosis and treatment options for graft urolithiasis are similar to those patients with nephrofithiasis in the general population. Extracorporeal shock wave lithotripsy (ESWL) was the most common treatment method.

Cellular Infiltrates and NF kappa B Subunit c-Rel Signaling in Kidney Allografts of Patients With Clinical Operational Tolerance

Background. Nuclear factor kappa B (NF kappa B) plays a potential role in tolerance by orchestrating onset and resolution of inflammation and regulatory T cell differentiation through subunit c-Rel. We characterized cellular infiltrates and expression of NF kappa B1, c-Rel and its upstream regulators phosphatidylinositol 3-kinase/RAC-alpha serine/threonine kinase, in allograft biopsies from patients with spontaneous clinical operational tolerance (COT). Methods. Paraffin-fixed kidney allograft biopsies from 40 patients with COT (n=4), interstitial rejection (IR; n=12), borderline changes (BC; n=12), and long-term allograft function without rejection (NR; n=12) were used in the study. Cellular infiltrates and immunohistochemical expression of key proteins of the NF kappa B pathway were evaluated in the cortical tubulointerstitium and in cellular infiltrates using digital image analysis software. Results were given as mean +/- SEM. Results. Biopsies from patients with COT exhibited a comparable amount of cellular infiltrate to IR, BC, and NR (COT, 191 +/- 81; IR, 291 +/- 62; BC, 178 +/- 45; and NR, 210 +/- 42 cells/mm(2)) but a significantly higher proportion of forkhead box P3-positive cells (COT, 11%+/- 1.7%; IR, 3.5%+/- 0.70%; BC, 3.4%+/- 0.57%; and NR, 3.7%+/- 0.78% of infiltrating cells; P=0.02). c-Rel expression in cellular infiltrates was significantly elevated in IR, BC, and NR when analyzing the number of positive cells per mm(2) (P=0.02) and positive cells per infiltrating cells (P=0.04). In contrast, tubular PI3K and c-Rel expression were significantly higher in IR and BC but not in NR compared with COT (P=0.03 and P=0.006, respectively). With RAC-alpha serine-threonine kinase, similar tendencies were observed (P=0.2). Conclusions. Allografts from COT patients show significant cellular infiltrates but a distinct expression of proteins involved in the NF kappa B pathway and a higher proportion of forkhead box P3-positive cells.

The role of myocardial scintigraphy in the assessment of cardiovascular risk in patients with end-stage chronic kidney disease on the waiting list for renal transplantation

The usefulness of stress myocardial perfusion scintigraphy for cardiovascular (CV) risk stratification in chronic kidney disease remains controversial. We tested the hypothesis that different clinical risk profiles influence the test. We assessed the prognostic value of myocardial scintigraphy in 892 consecutive renal transplant candidates classified into four risk groups: very high (aged epsilon 50 years, diabetes and CV disease), high (two factors), intermediate (one factor) and low (no factor). The incidence of CV events and death was 20 and 18, respectively (median follow-up 22 months). Altered stress testing was associated with an increased probability of cardiovascular events only in intermediate-risk (one risk factor) patients [30.3 versus 10, hazard ratio (HR) 2.37, confidence interval (CI) 1.693.33, P 0.0001]. Low-risk patients did well regardless of scan results. In patients with two or three risk factors, an altered stress test did not add to the already increased CV risk. Myocardial scintigraphy was related to overall mortality only in intermediate-risk patients (HR 2.8, CI 1.55.1, P 0.007). CV risk stratification based on myocardial stress testing is useful only in patients with just one risk factor. Screening may avoid unnecessary testing in 60 of patients, help stratifying for risk of events and provide an explanation for the inconsistent performance of myocardial scintigraphy.

Recipient of kidney from donor with asymptomatic infection by Paracoccidioides brasiliensis

The increase in solid organ transplantations may soon create a rise in the occurrence of endemic fungal diseases, such as paracoccidioidomycosis, due to the lack of rigorous screening of donors from endemic areas. Here we present the first case of an immunocompetent and asymptomatic kidney donor who had Paracoccidioides brasiliensis infected-adrenal tissue but no glandular dysfunction.

Diagnosis and treatment of coronary artery disease in hemodialysis patients evaluated for transplant

We present a review of current strategies for the diagnosis and treatment of coronary artery disease (CAD) in patients with advanced chronic kidney disease who are on the waiting list for transplants, based on data from the literature and originated from a single-center cohort of 1,250 patients with maximum follow-up of 12 years. We discuss the best way to select patients to be tested for CAD, how to choose the more adequate screening test for CAD and cardiovascular disease, how to select patients for invasive treatment studies and how to treat patients with significant CAD. We also suggest new research avenues to be explored to resolve some problems in this area.

Prevention of Intradialytic Hypotension in Patients with Acute Kidney Injury Submitted to Sustained Low-Efficiency Dialysis

Objectives: This study evaluated the effects of a protocol aiming to reduce hypotension in acute kidney injury (AKI) patients submitted to sustained low-efficiency dialysis (SLED). Methods: Patients were randomly assigned to two SLED prescriptions-control group, dialysate temperature was 37.0 degrees C with a fixed sodium concentration [138 mEq/L] and ultrafiltration (UF) rate; and profiling group, dialysate temperature was 35.5 degrees C with a variable sodium concentration [150-138 mEq/L] and UF rate. Results: Sixty-two SLED sessions were evaluated (34 in profiling and 28 in control). Patients (n = 31) were similar in terms of gender, age, and Sequential Organ Failure Assessment (SOFA) score. Dialysis time, dialysis dose, and post-dialysis serum sodium were similar in both groups. The profiling group had significantly less hypotension episodes (23% vs. 57% in control, p = 0.009) and achieved higher UF volume (2.23 +/- 1.25 L vs. 1.59 +/- 1.03 L in control, p = 0.04) when compared with control group. Conclusions: SLED protocol with modulation of dialysate temperature, sodium, and UF profiling showed similar efficacy but less intradialytic hypotension when compared with a standard SLED prescription.

Oxidative Stress and Modification of Renal Vascular Permeability Are Associated with Acute Kidney Injury during P. berghei ANKA Infection

Malaria associated-acute kidney injury (AKI) is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. However, the causes that lead to a framework of malaria-associated AKI are still poorly characterized. Some clinical studies speculate that oxidative stress products, a characteristic of Plasmodium infection, as well as proinflammatory response induced by the parasite are involved in its pathophysiology. Therefore, we aimed to investigate the development of malaria-associated AKI during infection by P. berghei ANKA, with special attention to the role played by the inflammatory response and the involvement of oxidative stress. For that, we took advantage of an experimental model of severe malaria that showed significant changes in the renal pathophysiology to investigate the role of malaria infection in the renal microvascular permeability and tissue injury. Therefore, BALB/c mice were infected with P. berghei ANKA. To assess renal function, creatinine, blood urea nitrogen, and ratio of proteinuria and creatininuria were evaluated. The products of oxidative stress, as well as cytokine profile were quantified in plasma and renal tissue. The change of renal microvascular permeability, tissue hypoxia and cellular apoptosis were also evaluated. Parasite infection resulted in renal dysfunction. Furthermore, we observed increased expression of adhesion molecule, proinflammatory cytokines and products of oxidative stress, associated with a decrease mRNA expression of HO-1 in kidney tissue of infected mice. The measurement of lipoprotein oxidizability also showed a significant increase in plasma of infected animals. Together, our findings support the idea that products of oxidative stress, as well as the immune response against the parasite are crucial to changes in kidney architecture and microvascular endothelial permeability of BALB/c mice infected with P. berghei ANKA.

Chronic VEGF Blockade Worsens Glomerular Injury in the Remnant Kidney Model

VEGF inhibition can promote renal vascular and parenchymal injury, causing proteinuria, hypertension and thrombotic microangiopathy. The mechanisms underlying these side effects are unclear. We investigated the renal effects of the administration, during 45 days, of sunitinib (Su), a VEGF receptor inhibitor, to rats with 5/6 renal ablation (Nx). Adult male Munich-Wistar rats were distributed among groups S+V, sham-operated rats receiving vehicle only; S+Su, S rats given Su, 4 mg/kg/day; Nx+V, Nx rats receiving V; and Nx+Su, Nx rats receiving Su. Su caused no change in Group S. Seven and 45 days after renal ablation, renal cortical interstitium was expanded, in association with rarefaction of peritubular capillaries. Su did not worsen hypertension, proteinuria or interstitial expansion, nor did it affect capillary rarefaction, suggesting little angiogenic activity in this model. Nx animals exhibited glomerulosclerosis (GS), which was aggravated by Su. This effect could not be explained by podocyte damage, nor could it be ascribed to tuft hypertrophy or hyperplasia. GS may have derived from organization of capillary microthrombi, frequently observed in Group Nx+Su. Treatment with Su did not reduce the fractional glomerular endothelial area, suggesting functional rather than structural cell injury. Chronic VEGF inhibition has little effect on normal rats, but can affect glomerular endothelium when renal damage is already present.

Silent Ureteral Stones: Impact on Kidney Function-Can Treatment of Silent Ureteral Stones Preserve Kidney Function?

OBJECTIVE To report our experience with silent ureteral stones and expose their true influence on renal function. METHODS We analyzed 506 patients who had undergone ureterolithotripsy from January 2005 to May 2010. Silent ureteral stones were calculi found in the absence of any specific or subjective ureteral stone-related symptoms. Of the 506 patients, 27 (5.3%) met these criteria (global cohort). All patients were assessed postoperatively with dimercaptosuccinic acid scintigraphy (DMSA). A difference in relative kidney function of >10% was considered abnormal. Pre- and postoperative comparative DMSA analyses were electively obtained for 9 patients (kidney function cohort). A t test was used to assess the numeric variables, and the chi-square test or Fisher's exact test was used for categorical variables. Two-tailed P < .05 was considered statistically significant. RESULTS Stones were diagnosed by radiologic abdominal evaluation for nonurologic diseases in 40% and after previous nephrolithiasis treatment in 33%. The primary therapy was ureterolithotripsy in 88%. The mean follow-up time was 23 months. The overall ureteral stone-free rate after 1 and 2 procedures was 96% and 100%, respectively. In the global cohort, the mean pre- and postoperative serum creatinine levels were similar (P = .39), and the mean postoperative function on DMSA was 31%. In the kidney function cohort, no difference was found between the pre-and postoperative DMSA findings (22% +/- 12.1% vs 20% +/- 11.8%; P = .83) and serum creatinine (0.8 +/- 0.13 mg/dL vs 1.0 +/- 0.21 mg/dL; P = .45). CONCLUSION Silent ureteral stones are associated with decreased kidney function present at the diagnosis. Hydronephrosis tends to diminish after stone removal, and kidney function remains unaltered. UROLOGY 79: 304-309, 2012. (C) 2012 Elsevier Inc.