Risk of Anal High-grade Squamous Intraepithelial Lesions Among Renal Transplant Recipients Compared With Immunocompetent Controls.

BACKGROUND: Renal transplant recipients (RTRs) have increased risk of human papillomavirus (HPV)-related cancers, including anal cancer. We investigated the prevalence of anal high-grade intraepithelial lesions (HSILs) in RTRs compared with immunocompetent controls and risk factors for anal HSIL in RTRs. METHODS: We included 247 RTRs and 248 controls in this cross-sectional study. We obtained anal samples for HPV testing with INNO-LiPA and performed high-resolution anoscopy on all participants. The participants completed a questionnaire on lifestyle and sexual habits. We used logistic regression to estimate odds ratios (ORs) of histologically confirmed anal HSIL in RTRs vs controls and risk factors for anal HSIL in RTRs, stratified by sex and anal high-risk (hr) HPV status, adjusting for age, smoking, lifetime sexual partners, and receptive anal sex. RESULTS: RTRs had higher anal HSIL prevalence than controls, both among men (6.5% vs 0.8%; adjusted OR [aOR], 11.21 [95% confidence interval {CI}, 1.46-291.17]) and women (15.4% vs 4.0%; aOR, 6.41 [95% CI, 2.14-24.10]). Among those with anal hrHPV, RTRs had higher anal HSIL prevalence than controls (33.8% vs 9.5%; aOR, 6.06 [95% CI, 2.16-20.27]). Having had receptive anal sex (aOR, 6.23 [95% CI, 2.23-19.08]) or genital warts (aOR, 4.21 [95% CI, 1.53-11.48]) were risk factors for anal HSIL in RTRs. All HSIL cases occurred in individuals with anal hrHPV. CONCLUSIONS: RTRs had increased risk of anal HSIL compared with immunocompetent controls, with particularly high prevalence in female RTRs. Receptive anal sex, previous genital warts, and anal hrHPV infection were risk factors for anal HSIL in RTRs. Screening for anal HSIL in RTRs should be considered. CLINICAL TRIALS REGISTRATION: NCT03018927.

Risk of Anogenital Warts in Renal Transplant Recipients Compared with Immunocompetent Controls: A Cross-sectional Clinical Study.

Renal transplant recipients have increased risk of human papilloma virus-related anogenital (pre)cancers. Less is known about their risk of anogenital warts. The aim of this study was to estimate the prevalence and odds of anogenital warts in renal transplant recipients compared with immunocompetent controls, and to assess risk factors for intra- and perianal warts in renal transplant recipients. The study examined 248 renal transplant recipients and 250 controls for cutaneous and mucosal anogenital warts. Participants completed a questionnaire on lifestyle and sexual habits. For external anogenital warts (including penile, vulvar and perianal warts), renal transplant recipients had higher prevalence and odds than controls, both in men (8.1% vs 1.6%, adjusted odds ratio (ORadjusted)=5.09, 95% confidence interval (95% CI), 1.03-25.04) and women (11.3% vs 1.6%, ORadjusted=8.09, 95% CI 1.69-38.82). For intra-anal warts, there was no clear pattern of higher odds in renal transplant recipients than controls. Current smoking and having had receptive anal sex increased the risk of intra-/perianal warts in renal transplant recipients. In conclusion, renal transplant recipients in this study had higher odds of external anogenital warts than controls.

Cancer risk and mortality after kidney transplantation: a population-based study on differences between Danish centres using standard immunosuppression with and without glucocorticoids.

BACKGROUND: Kidney recipients receive immunosuppression to prevent graft rejection, and long-term outcomes such as post-transplant cancer and mortality may vary according to the different protocols of immunosuppression. METHODS: A national register-based historical cohort study was conducted to examine whether post-transplant cancer and all-cause mortality differed between Danish renal transplantation centres using standard immunosuppressive protocols including steroids (Centres 2, 3, 4) or a steroid-free protocol (Centre 1). The Danish Nephrology Registry, the Danish Civil Registration System, the Danish National Cancer Registry and the Danish National Patient Register were used. A historical cohort of 1450 kidney recipients transplanted in 1995-2005 was followed up with respect to post-transplant cancer and death until 31 December 2011. RESULTS: Compared with Center 1 the adjusted post-transplant cancer risk was 6-39% lower in Centre 3 [hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.67-1.32], in Centre 2 (HR 0.72, 95% CI 0.52-0.98) and in Centre 4 (HR 0.61, 95% CI 0.44-0.83). Compared with Center 1, the adjusted post-transplant mortality was 21-55% higher in Centre 4 (HR 1.21, 95% CI 0.91-1.61), in Centre 3 (HR 1.35, 95% CI 0.98-1.86) and in Centre 2 (HR 1.55, 95% CI 1.17-2.05). On average, post-transplant cancer was associated with a 4-fold increase in the risk of death (HR 4.25, 95% CI 3.36-5.38). CONCLUSIONS: There was a tendency of a higher post-transplant cancer occurrence, but lower all-cause mortality, in the Danish transplantation centre that adhered to a standard steroid-free immunosuppressive protocol.

Pre-transplant levels of ficolin-3 are associated with kidney graft survival.

Ficolin-3 is an initiator of the lectin complement pathway. The complement system is a mediator of the pathophysiology of graft rejection in kidney transplantation, but the role of ficolin-3 in this process is unknown. Using a prospective study design, 527 kidney transplanted patients were included. 97 blood donors served as controls. Ficolin-3, C4 and C3 were measured in pre-transplant as well as in control serum samples. In controls, deposition of ficolin-3, C4, C3 and the terminal complement complex (TCC) was measured in an assay based on acetylated albumin as matrix. The ficolin-3 levels correlated with the serum levels of C4 and C3. The serum levels of ficolin-3 correlated with the deposition of ficolin-3, C4, C3 and TCC. Survival analyses showed that high pre-transplant serum levels of ficolin-3 were associated with decreased graft survival. These results suggest an important role of ficolin-3 in the pathophysiology of kidney graft rejection.

Plasma adiponectin before and after kidney transplantation.

The role of plasma adiponectin (ADPN) in patients with impaired kidney function and following kidney transplantation (Tx) is debated. We aimed to: (i) determine whether pretransplant ADPN level is an independent risk factor for deterioration of glucose tolerance including development of new-onset diabetes mellitus after Tx, (ii) describe which parameters that influence the ADPN concentration before and after Tx. Fifty-seven nondiabetic kidney allograft recipients and 40 nondiabetic uraemic patients were included. The Tx group was examined at baseline and 3 and 12 months after Tx. The uraemic control group was examined twice, separated by 12 months. ADPN levels declined significantly following Tx (P < 0.0001), while estimated glomerular filtration rate (eGFR) increased (P < 0.0005). eGFR, BMI and insulin sensitivity index were independently associated with ADPN in a multivariate regression analysis, whereas an ordinal logistic regression analysis revealed no predictive characteristic of ADPN for aggravation of the glucose tolerance after Tx. In conclusion, kidney transplantation is accompanied by a significant reduction in ADPN concentration. Several factors determine the ADPN concentration before and after Tx including kidney function, insulin resistance, use of immunosuppressive agents and BMI. Pretransplant ADPN level did not predict development of new-onset diabetes mellitus or even deterioration of the glucose tolerance following Tx.

Warts in a cohort of Danish kidney transplanted patients: impact on quality of life.

There are no published clinical studies evaluating the impact of warts on quality of life after transplantation. The aim of this study was to determine the frequency of self-reported skin warts and skin cancer and their impact on quality of life in kidney transplanted patients, as measured with the Dermatology Life Quality Index (DLQI). Of 740 patients with a functioning renal allograft and were free of dialysis who were surveyed, 568 returned the questionnaires. Patients were asked about general health issues, with a focus on transplantation history, cutaneous warts and whether they had ever had cutaneous cancer. A total of 285 (52%) patients replied that they had warts, and these increased with time since last transplantation, with a p-value < 0.0001. A total of 101 patients (18%) reported that they had ever had skin cancer. The median DLQI was 0 for patients not having warts, 1 for patients with warts, and 2 for patients having warts and skin cancer. In conclusion, renal transplant recipients experience increasing numbers of warts and skin cancer over time, and having skin cancer impairs patients' quality of life to a greater degree than warts.

Plasma neutrophil gelatinase associated lipocalin (NGAL) is associated with kidney function in uraemic patients before and after kidney transplantation.

BACKGROUND: Neutrophil gelatinase associated lipocalin (NGAL) is a biomarker of kidney injury. We examined plasma levels of NGAL in a cohort of 57 kidney allograft recipients (Tx group, 39 ± 13 years), a uraemic group of 40 patients remaining on the waiting list (47 ± 11 years) and a control group of 14 healthy subjects matched for age, sex and body mass index (BMI). The kidney graft recipients were studied at baseline before transplantation and 3 and 12 months after transplantation and the uraemic group at baseline and after 12 months. METHODS: NGAL was measured using a validated in-house Time-Resolved Immuno-flourometric assay (TRIFMA). Repeated measurements differed by < 10% and mean values were used for statistical analyses. Spearman rank order correlation analysis and the Kruskal-Wallis non-parametric test were used to evaluate the association of NGAL concentrations with clinical parameters. RESULTS: Plasma NGAL levels before transplantation in the Tx and uraemic groups were significantly higher than in the healthy controls (1,251 µg/L, 1,478 µg/L vs. 163 µg/L, p < 0.0001). In the Tx group NGAL concentrations were associated with serum creatinine (R = 0.51, p < 0.0001), duration of end-stage renal failure (R = 0.41, p = 0.002) and leukocyte count (R = 0.29, p < 0.026). At 3 and 12 months plasma NGAL concentrations declined to 223 µg/L and 243 µg/L, respectively and were associated with homocysteine (R = 0.39, p = 0.0051 and R = 0.47, p = 0.0007). CONCLUSIONS: Plasma NGAL is a novel marker of kidney function, which correlates to duration of end-stage renal failure (ESRD) and serum creatinine in uraemic patients awaiting kidney transplantation. Plasma NGAL is associated with homocysteine in transplanted patients. The prognostic value of these findings requires further studies.

Kidney transplantation improves arterial function measured by pulse wave analysis and endothelium-independent dilatation in uraemic patients despite deterioration of glucose metabolism.

BACKGROUND: The aim of this study is to investigate the effect of kidney transplantation on arterial function in relation to changes in glucose metabolism. METHODS: Included were 40 kidney recipients (Tx group, age 38 ± 13 years) and 40 patients without known diabetes remaining on the waiting list for kidney transplantation (uraemic control group, age 47 ± 11 years). Arterial function was estimated by the pulse wave velocity (PWV) of the carotid-femoral pulse wave, aortic augmentation index (AIX), flow-mediated (FMD) and nitroglycerin-induced vasodilatation (NID) of the brachial artery performed before transplantation and after 12 months. PWV recorded sequentially at the carotid and femoral artery is an estimate of arterial stiffness; AIX is an integrated index of vascular and ventricular function. FMD and NID are the dilatory capacities of the brachial artery after increased flow (endothelium dependent) and after nitroglycerin administration (endothelium independent). The insulin resistance was estimated by the insulin sensitivity index (ISI). RESULTS: AIX was reduced from 27% (17-33) to 14% (7-25) (P = 0.01) after 1 year in the Tx group and remained stable in uraemic controls (P = 0.001, between groups), and NID increased from 11% (7-16) to 18% (12-23) (P = 0.0005). At baseline, carotid-femoral PWV was similar in the Tx group, uraemic controls and healthy controls and it did not change significantly after transplantation. ISI deteriorated in the Tx group from 7.2 ± 4.0 to 5.0 ± 3.0 (P = 0.005) and remained stable in uraemic controls (7.9 ± 5.1 vs 8.5 ± 4.9, NS). Mean arterial blood pressure decreased from 105 ± 13 to 96 ± 11 mmHg (P = 0.005) in the Tx group despite a 20% lower use of antihypertensive agents. CONCLUSIONS: Arterial function measured by AIX and NID was improved 1 year after kidney transplantation. This was associated with a decline in blood pressure and seen inspite of an increase in insulin resistance.

Pre-diabetes and arterial stiffness in uraemic patients.

BACKGROUND: In order to address factors of relevance for new onset diabetes mellitus and cardiovascular disease after kidney transplantation, we investigated the presence of pre-diabetes, arterial stiffness and endothelial dysfunction in patients with end-stage renal disease (ESRD) accepted for kidney transplantation. METHODS: Pre-diabetes and an insulin sensitivity index were estimated by an oral glucose tolerance test in 66 consecutive uraemic patients, without diabetes, being on the waiting list for the first renal transplantation. Mean age was 43 +/- 13 years. Duration of ESRD was 32 +/- 27 months. A control group consisted of 14 healthy subjects. Arterial stiffness was measured by aorta pulse wave velocity (PWV) and aorta augmentation index (AIX). Endothelial function was evaluated by flow-mediated vasodilatation (FMD) and plasma concentrations of von Willebrand factor antigen (vWF). Mean arterial blood pressure (MAP) was measured in supine resting position. RESULTS: Twenty-seven uraemic patients (41%) had pre-diabetes (IFG+IGT), and 39 had normal glucose tolerance. The uraemic patients were more insulin resistant with lower insulin sensitivity index compared to healthy controls (6.1 +/- 3 vs. 15 +/- 7, P < 0.0001) but with no difference between patients with and without pre-diabetes. HbA1c and fasting plasma glucose was comparable in uraemic patients with and without pre-diabetes. PWV was higher in pre-diabetic compared to normoglycaemic uraemic patients (9.1 +/- 3 vs. 7.3 +/- 2 m/s, P = 0.03) and healthy controls (9.1 +/- 3 vs. 6.7 +/- 1, P = 0.01), while AIX did not differ (24.9 +/- 13 vs. 23.2 +/- 12 vs. 17 +/- 16, P = NS). Presence of pre-diabetes was positively associated to PWV in a univariate analysis. Multivariable analysis revealed age and MAP as independent predictors of PWV in uraemic patients. FMD and vWF were impaired in uraemic patients compared to healthy controls (3 +/- 4 vs. 7 +/- 3, P = 0.007 and 1.8 +/- 0.7 vs. 0.96 +/- 0.3 kIU/L, P = 0.0002, respectively) but with no difference between the two groups of uraemic patients. In conclusion, a high prevalence of pre-diabetes, impaired insulin resistance, increased arterial stiffness of aorta as well as impaired augmentation index and vasodilatation was demonstrated in uraemic patients prior to kidney transplantation. Increased arterial stiffness of aorta and augmentation index were independently associated with age and blood pressure.

New-onset diabetes mellitus after kidney transplantation in Denmark.

BACKGROUND AND OBJECTIVES: This study aimed to investigate the development of new-onset diabetes mellitus (NODM) in a prospective study of 97 nondiabetic uremic patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Included were 57 kidney recipients (Tx group, age 39 +/- 13 years) and 40 uremic patients remaining on the waiting list for kidney transplantation (uremic controls, age 47 +/- 11 years). All were examined at baseline before possible transplantation and after 12 months. The prevalence of diabetes, prediabetes, insulin sensitivity index (ISI), and insulin secretion index (Isecr) were estimated using an oral glucose tolerance test with measurements of plasma glucose and plasma insulin. RESULTS: One year after transplantation NODM was present in 14% (8 of 57) compared with 5% (2 of 40) in the uremic control group (P = 0.01). ISI in the Tx group deteriorated from 6.8 +/- 3.9 before transplantation to 4.9 +/- 2.8 at 12 months after transplantation (P = 0.005), and a slight increase in Isecr from 37 +/- 19 to 46 +/- 22 (P = 0.02) was seen. No significant changes occurred in the uremic controls (ISI was 7.9 +/- 5 and 8.5 +/- 5, and Isecr was 31 +/- 17 and 28 +/- 15). Using multivariate ordinal logistic regression, pre-Tx ISI and age predicted NODM (odds ratios: 0.82, P = 0.01 and 1.06, P = 0.02, respectively). CONCLUSIONS: One year after kidney transplantation, NODM was present in 14% of patients. This was mainly caused by an increase in insulin resistance and was observed despite improvement in insulin secretion.

[Kidney function and immunosuppression of kidney-transplanted patients]. / Enkeltcenteropgørelse af nyretransplanterede patienters nyrefunktion og immunsuppressive behandling.

INTRODUCTION: The number of kidney-transplanted patients is growing. This report describes the age, sex distribution, kidney function, graft age, and immunosuppressive drugs of kidney-transplanted patients followed at the outpatient clinic of the nephrology department at Copenhagen University Hospital, Herlev, Denmark. MATERIALS AND METHODS: Cross-sectional study of all living kidney-transplanted patients with a functioning graft followed at Copenhagen University Hospital, Herlev (n=241). Data were extracted from patient records during November 2005-March 2006. RESULTS: The sex distribution (131 males, 110 females) was equal. The average patient age was 52 years (SD 12), the average glomerular filtration rate 43 ml/min/1.73 m2 (range 6-114 ml/min/1.73 m2), and the average graft age was 8.3 years (range 0-28 years). Hyperparathyroidism was highly prevalent (64%). The majority of patients (74%) were treated with triple-drug immunosuppression, in most cases (46%) with the combination prednisolone-ciclosporine-azathioprine. During recent years, azathioprine has been increasingly replaced by mycophenolate mofetil. CONCLUSIONS: The majority of kidney-transplanted patients with a functioning graft have sufficient kidney function to keep the patients free of uremic symptoms. Hyperparathyroidism is frequent. The immunosuppressive regimens used for kidney-transplanted patients are currently changing.

[Laparoscopic donor nephrectomy at the Herlev University Hospital, Denmark]. / Erfaringer med laparoskopisk donornefrektomi på Herlev Hospital.

INTRODUCTION: The purpose of this investigation was to evaluate the morbidity and convalescence of donors after laparoscopic nephrectomy. Transperitoneal laparoscopy was initiated at Herlev University Hospital in November 2002. MATERIALS AND METHODS: All 24 records from patients who underwent laparoscopic donor nephrectomy were reviewed. Demographic data and perioperative data were collected. RESULTS: Median operation time was 162 min. Estimated blood loss was 200 ml and warm ischemia time 5 min. Postoperative side effects were nausea/vomiting (nine patients) and shoulder pain (two patients). Most serious complication was bleeding, leading to laparotomy the day of surgery in one patient. Other complications were ileus due to herniation of small intestine in porthole 1/24, wound infection 3/24, vaso-vagal episode 1/24, bronchospasms with CO2-retention 1/24, pneumonia 1/24. Length of stay was three days. Return to activities of daily life after 3-4 weeks. Typical analgesics were ketorolac and paracetamol. No laparoscopic procedures were converted to open surgery. There was no mortality. One year graft survival is 96%. CONCLUSION: Transperitoneal laparoscopic donor nephrectomy can be performed safely without serious complications. It is a good alternative to the conventional open approach. No laparoscopic procedures were converted to open nephrectomy. These results are similar to experiences from large centres.