Youssef M.K. Farag

Epidemiology and risk factors of chronic kidney disease in India - results from the SEEK (Screening and Early Evaluation of Kidney Disease) study.

BackgroundThere is a rising incidence of chronic kidney disease that is likely to pose major problems for both healthcare and the economy in future years. In India, it has been recently estimated that the age-adjusted incidence rate of ESRD to be 229 per million population (pmp), and >100,000 new patients enter renal replacement programs annually.MethodsWe cross-sectionally screened 6120 Indian subjects from 13 academic and private medical centers all over India. We obtained personal and medical history data through a specifically designed questionnaire. Blood and urine samples were collected.ResultsThe total cohort included in this analysis is 5588 subjects. The mean ± SD age of all participants was 45.22 ± 15.2 years (range 18–98 years) and 55.1% of them were males and 44.9% were females. The overall prevalence of CKD in the SEEK-India cohort was 17.2% with a mean eGFR of 84.27 ± 76.46 versus 116.94 ± 44.65 mL/min/1.73 m2 in non-CKD group while 79.5% in the CKD group had proteinuria. Prevalence of CKD stages 1, 2, 3, 4 and 5 was 7%, 4.3%, 4.3%, 0.8% and 0.8%, respectively.ConclusionThe prevalence of CKD was observed to be 17.2% with ~6% have CKD stage 3 or worse. CKD risk factors were similar to those reported in earlier studies.It should be stressed to all primary care physicians taking care of hypertensive and diabetic patients to screen for early kidney damage. Early intervention may retard the progression of kidney disease. Planning for the preventive health policies and allocation of more resources for the treatment of CKD/ESRD patients are imperative in India.

Kidney Pathological Changes in Metabolic Syndrome: A Cross- sectional Study

BACKGROUND The worldwide prevalence of metabolic syndrome is increasing and has been associated with chronic kidney disease. Kidney pathological findings in patients with metabolic syndrome have not been well described, as was explored in this study. STUDY DESIGN Cross-sectional study. SETTING & PARTICIPANTS We retrospectively screened clinical information for 146 patients who underwent elective nephrectomy for renal cell carcinoma between January 2005 and March 2007 at Brigham and Womens Hospital, Boston, MA. Twelve patients with metabolic syndrome were identified. Twelve age- and sex-matched patients who did not have any of the criteria for metabolic syndrome were used as controls. PREDICTOR Presence of metabolic syndrome defined by using Adult Treatment Panel III criteria. OUTCOMES Histological characteristics in each group, decrease in kidney function at 1-year follow-up. MEASUREMENTS Two pathologists blinded to the clinical diagnosis independently evaluated nephrectomy specimens using Banff criteria to objectively assess histological characteristics. RESULTS Baseline characteristics were similar between the 2 groups. On histopathologic examination, patients with metabolic syndrome compared with controls had a greater prevalence of tubular atrophy (P = 0.006), interstitial fibrosis (P = 0.001), and arterial sclerosis (P = 0.001), suggesting microvascular disease. Patients with metabolic syndrome had greater global (P = 0.04) and segmental glomerulosclerosis (P = 0.05). Glomerular volume and cross-sectional surface area were not different. The combined end point of tubular atrophy greater than 5%, interstitial fibrosis greater than 5%, and presence of arterial sclerosis was more prevalent in patients with metabolic syndrome (P = 0.003; odds ratio, 33; confidence interval, 2.9 to 374.3) than controls. After 1 year, estimated glomerular filtration rate was significantly lower in patients with metabolic syndrome compared with controls (P = 0.03). LIMITATIONS Small sample size, retrospective design. CONCLUSIONS We report a high prevalence of microvascular disease in patients with metabolic syndrome. There was a steeper decrease in kidney function over time in patients with metabolic syndrome, suggesting limited renal reserve. Aggressive screening and management may be warranted in patients with metabolic syndrome to protect kidney function.

Chronic Kidney Disease in the Arab World: A Call for Action

Chronic kidney disease (CKD) is an emerging non-communicable disease worldwide. The Arab countries have a high prevalence of CKD risk factors, e.g. diabetes, obesity and hypertension. Unfortunately, the magnitude of CKD in the Arab world has not been studied well. This review presents the current data on CKD in the Arab world and proposes a call for action to address this rising epidemic.

Diabetic nephropathy in the Arab Gulf countries.

While the prevalence of diabetes mellitus is increasing worldwide, one third of the diabetic patients will eventually develop chronic kidney disease. The aim of this review is to present the available data on diabetic nephropathy and its complications in the Arab Gulf countries. This will eventually help to raise the awareness of both government and healthcare systems towards the substantial value of prevention, early detection as well as proper management of both diabetes mellitus and chronic kidney disease. This could be achieved by funding large-scale longitudinal studies, improving training programs (both research and clinical) and increasing the role of media in fighting this epidemic.

Outcome of acute kidney injury in pediatric patients admitted to the intensive care unit

BACKGROUND Acute kidney injury (AKI) is common in the pediatric intensive care unit (PICU). We aimed to describe the etiology, clinical features, and outcome of AKI in pediatric patients and to determine the predictors for initiation of renal replacement and mortality. METHODS A retrospective chart review was performed of the medical records for all patients who were admitted to the PICU at King Abdulaziz University Hospital between January 1 and December 31, 2011. The pediatric-modified RIFLE criteria were used to classify AKI. RESULTS We included 102 children with AKI, aged 4 - 60 months. Oliguria (61.5%, p < 0.0001) and hypervolemic signs (38.5%, p = 0.03) were more common among patients with RIFLE class failure. They also had the highest mortality (53.9%, p = 0.01). Oliguric patients were ~ 23 times more likely than their non-oliguric counterparts to be initiated on renal replacement therapy (RRT) (RR = 23.38, 95% CI: 3.07 - 178.16). Diuretic infusion was also a strong predictor for RRT initiation (RR = 10.00, 95% CI: 2.77 - 36.12). Hypervolemic patients were twice more likely to die during hospitalization in both unadjusted and adjusted models (RR = 2.06, 95% CI: 1.09 - 3.90, and aRR = 2.45, 95% CI: 1.09 - 5.51, respectively). Mechanical ventilation and RRT initiation were associated with higher likelihood of death (ARR = 13.23, 95% CI: 1.90 - 92.04, and ARR = 2.20, 95% CI: 1.18 - 4.12, respectively). Patients with RIFLE class Failure were about thrice more likely than patients with RIFLE class Risk to die in both the unadjusted (RR = 2.76, 95% CI: 1.35 - 5.65), and adjusted models (ARR = 2.88, 95% CI: 1.38 - 6.04). Children with AKI had longer PICU stay (0.0003) and higher mortality (< 0.0001) than the non-AKI group. CONCLUSION Severe AKI predicted high mortality in critically ill children.

Renal impairment in children with posterior urethral valves

BackgroundPosterior urethral valves (PUV) are a common cause of end-stage renal failure in childhood. Our aim was to describe a cohort of patients with PUV and to investigate the predictors of renal impairment.MethodsWe performed a retrospective chart review of children with PUV who were followed at King Abdulaziz University hospital between 2002 and 2011.ResultsThe cohort comprised 68 boys. There was a significant difference in the duration of follow-up (p = 0.024), nadir serum creatinine (p < 0.001), and last known serum creatinine level (p = 0.001) between the patients with and without renal impairment. The duration of follow-up appeared to be a significant predictor for serum creatinine doubling (p = 0.003; odds ratio, 1.8). There was no difference in the age of presentation, age at the time of the study, and first or last serum creatinine between children who initially had vesicostomy and children who had ablation.ConclusionsAblation of PUV or vesicostomy did not influence kidney function in our study cohort. Children with a normal nadir serum creatinine who presented early had a better outcome.

Serum vitamin D and sex hormones levels in men and women: The Multi-Ethnic Study of Atherosclerosis (MESA)

INTRODUCTION 25-hydroxyvitamin D [25(OH)D] deficiency has been associated with low testosterone levels in men, but there are conflicting reports of its associations with sex hormones in women. Less is known about whether these associations are independent of adiposity and lifestyle factors, and whether they differ by race/ethnicity. AIM To examine associations of 25(OH)D concentrations with sex hormone levels. METHODS Cross-sectional analysis of 3017 men and 2929 women in a multi-ethnic cohort. MAIN OUTCOME MEASURES Testosterone, estradiol, dehydroepiandrosterone (DHEA), sex hormone binding globulin (SHBG), and free testosterone. RESULTS The mean (SD) levels of 25(OH)D in men and women were 25.7(10.4) and 26.1(12.0)ng/ml, respectively. In men, after adjusting for demographic and lifestyle variables, a 10ng/ml [25nmol/L] decrease in 25(OH)D was associated with an average difference of -0.70nmol/L (95%CI -1.36, -0.05) in SHBG and 0.02 percent (0.01, 0.04) in free testosterone, but was not associated with low total testosterone level (<10.41nmol/L). In women, a 10ng/ml decrease in 25(OH)D levels was associated with an average difference of -0.01nmol/L (-0.01, -0.00) for estradiol, -8.29nmol/L (-10.13, -6.45) for SHBG, 0.06 percent (0.04, 0.07) for free testosterone, and 0.40nmol/L (0.19, 0.62) for DHEA. There was no significant interaction by race/ethnicity. CONCLUSIONS Lower 25(OH)D concentrations were associated with lower SHBG levels and higher free testosterone levels in both men and women, and lower estradiol and higher DHEA levels in women, independent of adiposity and lifestyle. We observed no significant association of 25(OH)D with total testosterone in men. Future studies are needed to determine whether vitamin D supplementation influences sex hormone levels.

Predictors of diabetic nephropathy

Diabetic nephropathy (DN) is a leading cause of morbidity and mortality in diabetic patients representing a huge health and economic burden. Alarming recent data described diabetes as an unprecedented worldwide epidemic, with a prevalence of ∼6.4% of the world population in 2010, while the prevalence of CKD among diabetics was approximately 40%. With a clinical field hungry for novel markers predicting DN, several clinical and laboratory markers were identified lately with the promise of reliable DN prediction. Among those are age, gender, hypertension, smoking, sex hormones and anemia. In addition, eccentric left ventricular geometric patterns, detected by echocardiography, and renal hypertrophy, revealed by ultrasonography, are promising new markers predicting DN development. Serum and urinary markers are still invaluable elements, including serum uric acid, microalbuminuria, macroalbuminuria, urinary liver-type fatty acid-binding protein (u-LFABP), and urinary nephrin. Moreover, studies have illustrated a tight relationship between obstructive sleep apnea and the development of DN. The purpose of this review is to present the latest advances in identifying promising predictors to DN, which will help guide the future research questions in this field. Aiming at limiting this paramount threat, further efforts are necessary to identify and control independent modifiable risk factors, while developing an integrative algorithm for utilization in DN future screening programs.

De novo multifocal renal cell carcinoma in the renal allograft

A 30-year-old Caucasian male on chronic hemodialysis presents with a 4-day history of right flank pain accompanied by fever, nausea, and anorexia. On physical examination, he had a heart rate of 100 beats per minute and a blood pressure of 147/95 mm Hg. The abdomen was soft. There was no tenderness or guarding over the allograft, and lymph nodes were not enlarged. His remaining examination was unremarkable. Blood and urine cultures were negative. The patient had undergone ultrasonographic examination of the allograft every year since 1998 with evidence of simple cysts in the parenchyma (Figure la) and a persistent fluid collection adjacent to the lower pole representing a lymphocele. A CT scan of the abdomen showed two sub-centimeter low-density lesions within the enlarged right transplanted kidney, suspicious for an infectious or neoplastic process. A persistent and stable right lower quadrant lymphocele was also present. Aspiration of the lymphocele yielded sterile fluid without evidence of infection. A transplant nephrectomy was performed.

Modulation of Platelet Activation in Chronic Kidney Disease Patients on Erythropoiesis-Stimulating Agents:

Background: Clinical trials demonstrate either no benefit or increased risk of cardiovascular events and mortality in patients with chronic kidney disease (CKD) targeted for higher hemoglobin levels, who are treated with erythropoiesis-stimulating agents (ESAs). The mechanism underlying this observation remains unexplained. Methods and Results: We assessed platelet activation by measuring soluble P-selectin (sPsel), CD40 ligand (CD40L), and circulating microparticles (CMP) in patients with CKD. Higher hemoglobin levels were associated with increased Psel levels in patients on ESAs but not in ESA-naïve anemic and nonanemic patients. Psel positively correlated with CMP and CD40L in both anemic and nonanemic patients. Multivariate linear regression analysis revealed an association between increased Psel levels and hemoglobin concentration in patients receiving ESAs. Conclusions: Anemic CKD patients on ESAs demonstrate increased levels of markers of platelet activation. These observations suggest a potentially complex interplay between platelet activation, impaired kidney function, and treatment of CKD anemia with ESAs.