Sexual Dysfunction in Patients With Chronic Renal Disease: Does It Improve With Renal Transplantation?

IntroductionCurrently in the medical literature there is controversy about the role and effects of renal transplantation (RTx) on the sexual functioning of patients with terminal chronic renal disease (TCRD). There is no clear evidence of the real impact of RTx on sexual functioning in these patients. This article makes a brief summary of the literature, describing the most important clinical concepts, evaluates results, and compares the impact of renal transplantation on sexual function before and after the procedure.Material and MethodsMedline and the Embase database were consulted; Medical Subject Headings used were “Kidney Failure, Chronic,” “Kidney Transplantation,” “Sexual Dysfunction,” “Pleasure,” “Sexual Behavior,” and “Quality of Life.” Search was limited to articles within the last 15 years.ResultsSexual dysfunction affects almost 87% of male and 60% to 80% of female patients; 40% to 78% of male patients with RTx report a sense of improvement on global sexual function, 25% to 30% of female patients of reproductive age with RTx report improvement in sexual performance and decreasing of menstrual cycle alterations. Fewer than 10% of patients receiving an RTx reported a decrease of sexual satisfaction.DiscussionDespite controversy, reviewed results show significant improvement of sexual functioning after receiving an RTx. Those who report no improvement of sexual functioning may have conditions attributable to implicit characteristics of TCRD (age, neuroendocrine/metabolic problems) and/or RTx (immunosuppressive therapy). RTx improves sexual functioning by improving sexual desire and overall sexual satisfaction.ConclusionIdentified determinants associated with improvement of sexual functioning are decreased prolactin serum level, age younger than 45 years, and onset of dialysis less than 6 months.     

Is Serum Cystatin C an Accurate Endogenous Marker of Glomerular Filteration Rate for Detection of Early Renal Impairment in Patients with Type 2 Diabetes Mellitus?

Background. Researches have recently reported that serum cystatin C is a more sensitive marker of changes in glomerular filtration rate (GFR) than serum creatinine. We conducted this study to evaluate the significance of serum cystatin C as a more sensitive marker of GFR for early detection of renal impairment in special groups of patients with type 2 diabetes mellitus (DM). Methods. The present study included 40 patients with type 2 DM divided into four equal groups based on their urinary albumin excretion and renal function: group 1 was normoalbuminuric, group 2 was microalbuminuric, group 3 was macroalbuminuric, and group 4 was macroalbuminuric with renal dysfunction. All patients underwent a thorough history, full clinical examination, fasting, and renal function tests. Post-prandial blood glucose levels, glycosylated hemoglobin A1c (HbA1c), proteins, albumin in 24 hr urine, and serum cystatin C were collected. Results. Serum cystatin C and creatinine were significantly higher in macrolbuminuric type 2 diabetic patients with renal dysfunction (group 4: 2.26 ± 1.28, 4.21 ± 2.38 mg/dl, respectively; p < 0.001) than macrolbuminuric type 2 diabetic patients with normal renal function (group 3: 1.04 ± 0.24, 0.96 ± 0.20 mg/dl, respectively), the microalbuminuric group (0.87 ± 0.28, 0.71 ± 0.12 mg/dl, respectively), as well as the normoalbuminuric group (0.55 ± 0.41, 0.60 ± 0.18 mg/dl, respectively). ROC plots demonstrated that area under the curve (AUC) of cystatin C (0.74) was greater than that for creatinine clearance (cr.cl) (0.67) and serum creatinine (s‐cr) (0.74); therefore, the sensitivity and diagnostic accuracy of cystatin c was better than cr. cl., and both were better than s-cr. Serum cystatin C showed significant correlation in groups 2–4 with s-cr, cr.cl, and 24 hr urine albumin, but no correlation was found in group 1. Conclusion. Serum cystatin C is a reliable and easily performed marker for GFR to detect renal impairment in patients with type 2 DM.     

Borderline Changes in Renal Transplantation: Are We Aware of the Real Impact in Graft Survival?

BackgroundBorderline changes suspicious for acute T-cell–mediated rejection (BC) are frequently seen on biopsy specimens, but their clinical significance and clinical management are still controversial. Our goal was to compare clinical outcomes of kidney transplant recipients with biopsy-proven BC vs acute T-cell–mediated rejection (aTCMR) and the influence of treating BC on graft outcomes.MethodsA retrospective cohort study was performed in all kidney transplant recipients with biopsy-proven BC and aTCMR between January 2012 and December 2018, according to Banff 2017 criteria; patients with concomitant antibody-mediated rejection were excluded.ResultsWe included 85 patients, 30 with BC (35.3%) and 55 with aTCMR (64.7%). There was no difference between groups regarding demographics, HLA matching and sensitization, immunosuppression, or time of transplant. Treatment with steroids was started in 15 patients with BC (50%) and in all patients with aTCMR, with 4 of the latter additionally receiving thymoglobulin (7.2%). At 1 year post biopsy, overall graft survival was 71%, and despite presenting better estimated glomerular filtration rate (eGFR) at biopsy (33.3 ± 23.4 vs 19.9 ± 13.2 mL/min/1.73 m², P = .008), patients in the BC group presented the same graft survival as the aTCMR group according to Kaplan-Meyer survival curves. When analyzing the BC group (n = 30) and comparing the patients who were treated (n = 15) vs a conservative approach (n = 15), graft survival at 1 year was 87% for treated patients and 73% for nontreated patients (P = .651), with no difference in eGFR for patients with functioning graft. However, at longer follow-up, survival curves showed a trend for better graft survival in treated patients (70.2 ± 9.2 vs 38.4 ± 8.4 months, P = .087).ConclusionOur study showed that patients with BC did not present better graft survival or graft function at 1 year after biopsy or at follow-up compared with the aTCMR group, despite better eGFR at diagnosis. We found a trend for better graft survival in patients with BC treated with steroids compared with a conservative approach. These results reinforce the importance of borderline changes in graft outcomes and that the decision to treat can influence long-term outcomes.     

Levofloxacin-Induced Delirium: Is It a Dangerous Drug in Patients with Renal Dysfunction?

The central nervous system (CNS) toxicity of fluoroquinolones is well known but usually occurs benign. In the literature, there are a few number of severe CNS toxicity cases related to fluoroquinolones. Levofloxacin is a third-generation fluorinated quinolone antibiotic, is the active levo stereoisomer of ofloxacin, and has one of the most favorable adverse reaction profiles. We describe a case of delirium associated with levofloxacin in a 55-year-old man who was hospitalized in our medical clinic for pneumonia.     

Molecular Marker for Predicting Treatment Response in Advanced Renal Cell Carcinoma: Does the Promise Fulfill Clinical Need?

Renal cell carcinoma (RCC) is largely diagnosed incidentally on imaging taken for unrelated reasons. The management of localized lesions is primarily extirpative with excellent results. Treatment of advanced RCC has evolved over recent years with the use of targeted therapies such as tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and antibody-mediated therapies. The treatment response to these targeted therapies is highly variable, with no clear clinical method of identifying patients who will benefit from or not tolerate therapy. The field of molecular markers has evolved significantly in the last decade, with a multitude of markers identified that predict treatment response and drug toxicity. The following review critically evaluates those molecular markers that have been assessed for their utility in predicting treatment response in patients with advanced/metastatic renal cell carcinoma (mRCC). Identifying the ideal treatment for these patients will improve responses to therapy, minimize morbidity, and save significant healthcare dollars.     

An Obituary for GFR as the Main Marker for Kidney Function?

This publication comments on the recently published findings of a study by Eloot et al. (cJASN, 6: 1266–1273, 2011) that evaluated the correlation between several formulae for calculating estimated GFR (eGFR) and different low molecular weight uremic toxins; eGFRs were based on serum creatinine (SCrea), cystatin C (Cys C), or a combination of both. Unexpectedly, the correlations for the different solutes were highly inconsistent, irrespective of the eGFR formula. On the other hand, the different eGFR formulae gave consistent results per solute. Correlation coefficients for some solutes were low (hippuric acid, p‐cresylsulfate, indole acetic acid, uric acid, asymmetric dimethylarginine) to nonsignificant (carboxy‐methyl‐propyl‐furanpropionic acid). These data point to the fact that eGFR is a deceiving predictor of uremic solute concentration and their biological action; this inconsistency is very likely the result of the impact of other factors affecting concentration, such as tubular secretion, generation by intestinal flora and metabolism.     

Serum Neutrophil Gelatinase-Associated Lipocalin as a Marker of Renal Function in Non-Diabetic Patients with Stage 2–4 Chronic Kidney Disease

The current Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines advocate creatinine-based equations for estimating GFR to identify patients with potential kidney disease and classify them into different stages due to the fact that serum creatinine is very insensitive to changes in the glomerular filtration rate. Very few biomarkers exist for monitoring chronic kidney disease. The aim of the study was to assess whether NGAL could represent a novel, sensitive marker of kidney function in adult patients with CKD. The study was performed on 92 non-diabetic patients with CKD stages 2–4. Serum and urinary NGAL as well as serum cystatin C were measured using commercially available kits. Serum NGAL was related, in univariate analysis, to serum creatinine, urinary NGAL, hemoglobin, hematocrit, leukocyte count, eGFR, and cystatin C. Urinary NGAL correlated with age, hemoglobin, hematocrit, serum creatinine, and eGFR. In multiple regression analysis, predictors of serum NGAL were creatinine (beta value = 0.97, p = 0.005), cystatin C (beta = 0.34, p = 0.01), and eGFR (beta value = 1.77, p = 0.001). In the healthy volunteers, serum NGAL correlated with age, serum creatinine, eGFR, leukocyte count, and cystatin C. Taking into consideration the fact that the recent DOQI (Dialysis Outcomes Quality Initiative) states that individuals with reduced GRF (glomerular filtration rate) are at greater risk for CVD and cardiac deaths, precise evaluation of renal function is important in order to select the appropriate strategy to reduce the cardiovascular risk. NGAL should be investigated as a potential early and sensitive marker of kidney impairment/injury.     

Acetabular Distraction: An Alternative for Severe Defects with Chronic Pelvic Discontinuity?

Background  

Stabilization of a pelvic discontinuity with a posterior column plate with or without an associated acetabular cage sometimes results in persistent micromotion across the discontinuity with late fatigue failure and component loosening. Acetabular distraction offers an alternative technique for reconstruction in cases of severe bone loss with an associated pelvic discontinuity.     

Are the Anticardiolipin Antibodies a Risk Factor for Coronary Artery Disease in Chronic Renal Failure Patients?

Objective. It has been proposed that anticardiolipin (aCL) antibodies are a risk factor for coronary artery disease (CAD) in recently studies. In this study, we aimed to investigate the existence of coronary artery disease in dialysis patients who were aCL positive and undergoing hemodialysis and peritoneal dialysis due to end stage renal failure and also to determine its relationship with risk factors in patients with coronary artery disease. Methods. This study has been conducted in the end stage renal failure in 140 hemodialysis patients, 18 peritoneal dialysis patients, and 38 healthy controls. The urea, creatinine, total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride, total protein, and albumin values are obtained. In all cases, aCL levels are investigated with ELISA method. Results. In the HD and CAPD patients, no significant relationship could be found between the age, gender, dialysis time, total cholesterol, HDL cholesterol, LDL cholesterol, total protein, and albumin values (p > 0.05). HD and CAPD vs. controls (aCL), 9.2% (13/140), 11.1% (2/18) vs. 2.6% (1/38), p = 0.002. No significant difference was noted between aCL-positive and -negative patients in serum urea, creatinine, total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride, total protein, and albumin levels. The coronary artery disease was determined in three patients out of 16 patients with aCL positivity. Conclusion. The prevalence of aCL antibodies positivity in our study was similar to the prevalence of aCL positivity in other studies. Therefore, we do not think aCL antibodies positivity is a risk factor for coronary artery disease.     

Early Sirolimus Therapy in Renal Transplant Recipients at High Risk: Is It Justified?

Background

We studied early sirolimus (SRL) therapy in renal transplant recipients at high risk after administration of antithymocyte globulin or interleukin-2 receptor blockade induction.

Patients and Methods

In 45 patients, SRL therapy was started within 1 month after transplantation. The primary indications for conversion of treatment from calcineurin inhibitors (CNIs)-mycophenolate mofetil (MMF)-steroid to SRL-MMF-steroid were biopsy-proved rejection (after treatment), CNI toxicity, CNI elimination, and acute tubular necrosis. Pediatric, geriatric, and other patients with medical comorbidities were not excluded.

Results

Post-SRL rejection episodes were reported in 22.2% of recipients including 15.6% who were resistant to steroid therapy. Mean (SD) follow-up after SRL therapy was 59.9 (8.1) months. Proteinuria greater than 2 g/d (P = .001), leukopenia (P < .001), hyperlipidemia (P < .001), and transaminases values (P = .02) increased significantly after SRL therapy. Graft survival was 88.8%, and patient survival was 93.3%. There was significant improvement in serum creatinine concentration and estimated creatinine clearance by the end of the study (P < .001). A high incidence of adverse effects and infections was noted post-SRL therapy, and the drug was discontinued in 31% of patients because of multiple adverse effects. At multivariate analysis, age, hypertension, nutritional status, bone marrow suppression, hyperlipidemia, and graft dysfunction were identified as risk factors for worse graft and patient outcome.

Conclusion

Early treatment with combined SRL-MMF-steroid may be effective as a CNI-free immunosuppression regimen in patients at high risk; however, there is a high rate of adverse effects during long-term follow-up.     

Complement Polymorphisms in Kidney Transplantation: Critical in Graft Rejection?

The complement system, as part of the innate immune system, plays an important role in renal transplantation. Complement is involved in the protection against foreign organisms and clearance of apoptotic cells but can also cause injury to the renal allograft, for instance, via antibody binding or in ischemia–reperfusion injury. Numerous polymorphisms in complement factors have been identified thus far; some of them result in different functionalities or alter complement levels. In this review, we provide an overview of the literature on the role of complement polymorphisms in renal transplantation. Furthermore, we discuss functional complement polymorphisms that have not yet been investigated in kidney transplantation. By investigating multiple polymorphisms both in donor and recipient at the same time, a complotype can be constructed. Because the combination of multiple polymorphisms is likely to have a greater impact than a single one, this could provide valuable prognostic information.