Yousef Boobes

Gonadal dysfunction and infertility in kidney transplant patients receiving sirolimus

Sirolimus is an immunosupressor of the mammalian target of rapamycin inhibitors (mTOR-I) group. Recent studies have emphasized a potential impact of sirolimus on male gonadal function. We report our clinical experience with sirolimus-induced gonadal dysfunction and infertility in both male and female kidney transplant patients. Of the 170 kidney transplant patients, nine (5.3%) patients (six males and three females) were receiving sirolimus. Follow-up data for two male patients were not available. The one unmarried female patient developed amenorrhea post-transplantation and had resumption of her menstrual cycles after discontinuation of sirolimus. The remaining six married patients (four males and two females), who all had fathered or conceived children in the pre-transplantation period, developed gonadal dysfunction and infertility on average 5–12 months after transplantation. Sirolimus was discontinued in all four male patients with full recovery of the oligo/azospermia and restoration of fertility. Both married female patients developed amenorrhea post-transplantation. Sirolimus was discontinued in one female patient with resumption of her menstrual cycles. In this small population of patients treated with sirolimus, the prevalence rate of reversible gonadal dysfunction and infertility was significant in both males and females. Infertility secondary to sirolimus is under-diagnosed and should be studied further.

Plasma BNP in patients on maintenance haemodialysis: a guide to management?

The number of patients requiring long-term haemodialysis is increasing throughout the world. Cardiovascular disease is much more common in these patients than in the general population and accounts for the majority of deaths. New approaches to management are clearly needed to reduce this excessive cardiovascular burden. We propose that circulating levels of the cardiac natriuretic peptides, B-type natriuretic peptide (BNP) in particular, might provide a useful, objective guide to the management of their hydration status and pharmacotherapy. An overview of the literature shows that plasma levels of the cardiac natriuretic peptides are increased in this patient population and reflect cardiac preload and afterload along with cardiac pathology, thereby providing an index of cardiovascular (especially cardiac) stress and distress. Circulating levels of the cardiac peptides change in parallel with cardiac load, especially across haemodialysis. Furthermore, there is robust evidence that natriuretic peptide levels are predictive of cardiovascular outcome in these patients. Accordingly, we hypothesize that management of their haemodialysis, and pharmacotherapy designed specifically to lower plasma BNP levels to, or close to, the normal range, will reduce the excessive burden on the cardiovascular system and thereby ultimately lower the incidence of cardiovascular disease. We outline, in broad terms, how a trial to test this hypothesis might be designed.

Long-term use of low-molecular-weight heparin in hemodialysis patients: a 7-year experience.

Background: Low-molecular-weight-heparin (LMWH) is not routinely used as anticoagulant in hemodialysis (HD). The ideal dose and the safety of long-term use are not known. Methods: A prospective three-phase interventional study. Phase 1 involved dose titration, phase 2 safety and efficacy and phase 3 routine practice. Results: During 7 years of the use of the LMWH enoxaparin (EN), 236 patients were treated with a total number of 60,987 HD sessions. The mean dose used during the titration phase was 0.43 ± 0.16 mg/kg/session, which was subsequently reduced in phase 3 to 0.36 ± 0.14 mg/kg/session. The long-term effects of EN on the platelet count and lipid profile were comparable to unfractionated heparin. Conclusion: The long-term use of LMWH (EN) with a reduced dose in HD is practical and safe.

Renal biomarkers for assessment of kidney function in renal transplant recipients: how do they compare?

Accurate assessment of renal function is of key importance, given its prognostic value. However, gold standard measures are cumbersome, and serum creatinine itself is an insensitive predictor, especially in renal transplant recipients. Though GFR-estimating formulae have been relied upon, they do have their own limitations. Nevertheless, renal biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C, among others, are now emerging as potentially useful indicators of GFR. We aimed to evaluate the diagnostic performance of NGAL versus cystatin C and eGFR using CKD-EPI, MDRD and cystatin C in renal transplant recipients and non-transplant CKD patients. We found a significant correlation between NGAL, serum creatinine, cystatin C and eGFR. The latter parameters were also strong predictors of serum NGAL levels. However, performance of NGAL, based on receiver operating characteristic curves, was inferior to that of the reference tests. It appears that in renal transplant recipients NGAL correlates well with cystatin C and eGFR, most strongly with cystatin-based formula. Though this suggests potential use of NGAL as a screening test, its weaker diagnostic performance raises some concern about its clinical usefulness. Larger studies are needed to explore this further.

Prevalence of Polyomavirus Among United Arab Emirates Kidney Transplant Recipients: Results From a Single Center

BACKGROUND BK viremia and nephropathy are increasing problems in renal transplant recipients. The absence of a safe and effective antiviral therapy made screening-based prevention a recommended strategy. The prevalence of its reactivation among recipients of kidney transplants in the Middle East has not been well established. Our objective was to determine the prevalence of BK virus (BKV) infection for renal transplant recipients at our medical center. METHODS All renal transplant recipients followed up in our transplantation clinic between 2012 and 2013 (n = 116) were screened. Urine and blood quantitative real-time polymerase chain reaction (PCR) for the BKV were performed in all of the study patients. Renal biopsy was performed only in patients with deteriorating renal function associated with positive PCR. Patients who showed positive BKV PCR were followed up for 6 to 12 months. This included clinical and kidney function assessment along with BKV PCR viral load. RESULTS Among the 116 kidney transplant recipients studied, 65 (56%) were male, age 51 ± 15 years, with a transplantation vintage of 131 ± 61 months; 17 (14.7%) were positive for BKV PCR. Three (2.7%) showed viremia; 2 of them had deterioration of kidney function, renal biopsy confirmed the diagnosis of BK nephropathy (NP) in both cases. The 3 cases were managed by reducing the immunosuppressive treatment with stabilization of their kidney function. Cases with stable renal function and positive urine for BKV cleared the virus spontaneously during follow-up after minor reduction of the immunosuppressive treatment or without any intervention. None of our patients lost the graft due to BK NP. CONCLUSION Our study suggests that BKV is not uncommon in our kidney transplant recipients. Routine screening suggested by the KDIGO Guidelines could help minimize its detrimental impact on the transplant outcome.

Adaptation and Implementation of the "Kidney Disease: Improving Global Outcomes (KDIGO)" Guidelines for Evaluation and Management of Mineral and Bone Disorders in Chronic Kidney Disease for Practice in the Middle East Countries

This review presents the views of an expert group of nephrologists from the Middle East along with an international expert on adaptation and implementation of the 2009 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for evaluation and manage-ment of mineral and bone disorders in chronic kidney disease (CKD-MBD) for practice in the Middle East countries. The members of the panel examined the KDIGO guidelines and formulated recommendations that can be implemented practically for the management of CKD-MBD in the Middle East. There was a broad agreement on most of the recommendations made by the KDIGO work-group. However, the panelists commented on specific areas and amplified certain concepts that might help the nephrologists in the Middle East. The final document was reviewed by all participants as well as by members of the Middle East task force implementation group for KDIGO guidelines. Their comments were incorporated. The guideline statements are presented along with detailed rationale and relevant discussion as well as limitations of the evidence. The panel recognized the need to upgrade the suggestion of KDIGO related to lateral abdominal radiograph and echocardiogram in patients with CKD stages 3-5D into a stronger recommendation. The panel underlined the risk of hyper-phosphatemia to CKD-MBD and the importance of prompt initiation or modification of therapy according to rising trends in para-thyroid hormone level. They recommended the use of non-calcium-based phosphate binders as the first-line therapy in CKD patients with signs of vascular calcification. The panel agreed that all aspects of the KDIGO recommendations concerning bone biopsy, evaluation and treatment of bone disease after kidney trans-plantation should be implemented as such.