Samra Abouchacra

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.

Under- treatment and under diagnosis of hypertension: a serious problem in the United Arab Emirates

BackgroundHypertension, notably untreated or uncontrolled, is a major risk factor for cardiovascular diseases (CVD) morbidity and mortality. In countries in transition, little is known about the epidemiology of hypertension, and its biochemical correlates. This study was carried out in Al Ain, United Arab Emirates, to characterize self-reported (SR) normotensives and hypertensives in terms of actual hypertension status, demographic variables, CVD risk factors, treatment, and sequalae.MethodsA sample, stratified by SR hypertensive status, of 349 SR hypertensives (Mean age ± SD; 50.8 ± 9.2 yrs; Male: 226) and 640 SR normotensives (42.9 ± 9.3 yrs, Male: 444) among nationals and expatriates was used. Hypertensives and normotensive subjects were recruited from various outpatient clinics and government organizations in Al-Ain city, United Arab Emirates (UAE) respectively. Anthropometric and demographic variables were measured by conventional methods.ResultsBoth under-diagnosis of hypertension (33%) and under-treatment (76%) were common. Characteristics of undiagnosed hypertensives were intermediate between normotensives and SR hypertensives. Under-diagnosis of hypertension was more common among foreigners than among nationals. Risk factors for CVD were more prevalent among SR hypertensives. Obesity, lack of exercise and smoking were found as major risk factors for CVD among hypertensives in this population.ConclusionHypertension, even severe, is commonly under-diagnosed and under-treated in the UAE. Preventive strategies, better diagnosis and proper treatment compliance should be emphasized to reduce incidence of CVD in this population.

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.

GFR estimation in the morbidly obese pre- and postbariatric surgery: one size does not fit all

BackgroundGlomerular hyperfiltration commonly associated with obesity is expected to improve postbariatric surgery. However, formula-based glomerular filtration rate (GFR) estimation in these patients is limited by body size confounders necessitating use of modified equations, the reliability of which remains uncertain.MethodsIn this study, various GFR-estimating formulae were compared in morbidly obese patients at baseline and postbariatric surgery. Through a retrospective chart review, we identified 220 patients who had undergone this procedure, with over 6-month follow-up, during which major weight reduction was achieved.ResultsA significant decrease in BP and glomerular hyperfiltration was observed, though there was large variability in GFR estimation using the different formulae. Gross over and underestimation was observed which improved with correction for body size confounders especially lean body weight (LBW). Postoperatively, significant attenuation in estimated GFR was demonstrated when LBW or body surface area-adjusted versions were used. In a subgroup of patients with chronic kidney disease, a significant improvement in GFR was seen postoperatively with the LBW-modified formula but there were again inconsistencies when using other equations.ConclusionThough clinicians must be critical in the application of GFR estimates to patient care, LBW adjustment appears to be the most practical solution to its estimation in the obese patients. This is particularly true for patients with normal renal function but appears to be also applicable to those with compromised kidney function. Future studies are needed to compare these equations with a gold standard GFR measure as well as to explore whether the renal benefits from bariatric surgery are sustained or seen in more advanced CKD stages.

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.

Potassium Binders in Hemodialysis Patients: A Friend or Foe?

There is insufficient evidence on the utility of potassium-binding resins in patients with end-stage renal disease on dialysis. In addition, their poor tolerability raises concerns of patient adherence. We aimed to assess the efficacy of calcium resonium and investigate the impact of counseling on adherence pattern as well as treatment response. Adult patients on hemodialysis receiving calcium resonium were enrolled with a control group not on treatment. Adherence patterns and adverse effects were recorded following patient interviews. Patients were stratified into 28 adherent (A), 42 non-adherent (NA), and 30 controls (C). Patient education was undertaken, and serum potassium levels were evaluated for 3 months pre- and post-counseling with inter- and intra-group comparison. A statistically significant difference was observed between potassium levels at baseline in A and NA groups but not post-education, which was related to worsening control in former and not due to improvement in NA patients. The poor effectiveness of calcium resonium in the control of hyperkalemia was likely related to non-compliance due to gastrointestinal (GI) intolerability. Dietary indiscretions as well as lack of consistent use of cathartics may have also contributed. No difference in dialysis adequacy was noted among groups, although the contribution of residual renal function was not assessed. These findings raise concern regarding cost-efficacy of this medication and lend credence to investing in traditional measures in hyperkalemia management, namely dietary compliance and adequate dialysis. Further long-term trials are awaited to better define the role of calcium resonium in the dialysis setting.

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.

Epidemiology and referral patterns of patients with chronic kidney disease in the Emirate of Abu Dhabi.

According to estimates, the dialysis prevalence in Abu Dhabi is around 370 per million population. The annual growth is 12-15% and the dialysis population is likely to double in the next five years. Most patients present to dialysis as an emergency and only 2.7% have an arteriovenous fistula at the first dialysis. The prevalence of chronic kidney disease (CKD) in the Emirate is undefined. A study of the epidemiology of CKD and referral patterns was undertaken. SEHA, the Abu Dhabi Health Service delivery company, has a unified computer system containing all measurements made in its laboratories. This study considered all serum creatinine measurements performed between 1 September 2011 and 31 October 2012 from outpatient departments or emergency rooms. The estimated glomerular filtration rate (eGRF) was calculated using the Modification of Diet in Renal Disease formula (the Schwartz formula was used for children). We identified 331,360 samples from 212,314 individuals. The mean serum creatinine was 61 ± 48 μmol/L in females (59 ± 43 μmol/L in Emiratis, 63 ± 54 μmol/L in expatriates) and 87 ± 69 μmol/L in males (80 ± 59 μmol/L in Emiratis, 92 ± 74 μmol/L in expatriates). Among Emiratis, 4.6% of males and 2.8% of females had an eGFR between CKD 3 and 5. Among expatriates, 4.2% of males and 3.2% of females had an eGFR between CKD 3 and 5. On average, eight months elapsed before a patient with CKD 3, and three months for a patient in CKD 5, to attend the nephrology clinic. This study has defined the prevalence of CKD within Abu Dhabi and demonstrated the need to improve identification and referral of CKD patients. Possible solutions include campaigns to increase public and physician awareness of CKD.

Encapsulating Peritoneal Sclerosis: A Rare Complication of Peritoneal Dialysis in Al-Ain, United Arab Emirates

Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis (PD) with devastating consequences. Although it can occur among patients on PD, it may present long after PD has been discontinued; thus, its diagnosis depends on a high index of suspicion. We present a rare case of EPS in the United Arab Emirates with a protracted course and delays in recognizing the condition until after resolution of the acute attack. This case highlights the need for early identification of risk factors as well as the subtle features of EPS for appropriate diagnosis and perhaps even prevention; this being worth a ton of cure. A review of the literature including the latest evidence-based treatment options is also highlighted.

Potential Benefits of Controlling Coronary Heart Disease Risk Factors in the United Arab Emirates

Background: Cardiovascular risk factors including obesity, diabetes, hypertension, and dyslipidemia, are highly prevalent in the United Arab Emirates. In spite of significant awareness initiatives, little is known about the potential benefits of controlling these risk factors. Aims: To assess the prevalence of preventable risk factors for coronary heart disease (CHD), and the likely benefits of controlling these risk factors. Methods: In a health survey stratified by self-reported hypertension, we enrolled 349 hypertensive and 641 normotensive subjects of diverse ethnicity in Al-Ain city, and measured CHD risk factors. We used the Framingham risk score to estimate the proportion of CHD potentially preventable by controlling hypertension, dyslipidemia, diabetes mellitus (DM), and smoking. Results: Smoking was similar in the two groups (hypertensives 13.2% vs. normotensives 14.2%). The prevalence of diabetes, dyslipidemia [mean (SD) triglycerides, high-density lipoprotein-cholesterol (HDL-C)], overweight/obesity, and thus the 10-year Framingham risk were all significantly (p < 0.001) higher among hypertensive than normotensives. Conclusion: Prevention of type 2 DM, aggressive control of hypertension and dyslipidemia, and smoking cessation could potentially reduce the 10-year incidence of CHD. Barriers include lack of awareness of this problem among the general population and health care providers.