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Thursday, December 27, 2018

Kidney Diseases and Transplantation

Spectrum of glomerular diseases in Arab countries: A systematic review
Nasar Yousuf Alwahaibi, Halima Khalfan Al Issaei, Buthaina Saif Al Dhahli

Saudi Journal of Kidney Diseases and Transplantation 2018 29(6):1256-1266

According to the best of our knowledge, there is no review compiling incidence of glomerular disease in all Arab countries. Most of the Arab countries do not have a national renal biopsy registry. In addition, there is scanty data available on the epidemiology of glomerular diseases in Arab countries. In this review, we performed a systematic review analyzing the incidence of glomerular disease in all Arab countries. Relevant manuscripts in all 22 Arab countries found through searches of Medline, Science Direct, Embase, and Google Scholar were evaluated. The time was from January 1990 to March 2018. A total of 36 manuscripts containing 10,727 biopsies from 11 countries were analyzed. The male-to-female ratio was 1.2:1. Saudi Arabia had the largest number of published studies with 14 papers followed equally by Iraq, Jordan, and Sudan with three papers each. The average period of study was 8.17 years. Retrospective studies represented 86.11%. Focal and segmental glomerulosclerosis (FSGS) (27%), minimal change disease (14%), membranoproliferative glomerulonephritis (13%), mesangioproliferative glomerulonephritis (13%), and membranous glomerulopathy (11%) were the main types of primary glomerular diseases. The most common types of secondary glomerular diseases were lupus nephritis (LN) (58%), amyloidosis (10.19%), diabetic nephropathy (9.89%), hypertension (4.84%) and poststreptococcal glomerulonephritis (2.72%). In conclusion, FSGS and LN are the most common types of primary and secondary glomerular diseases, respectively, in all evaluated Arab countries. The trend of all types of glomerular diseases has not changed in the last three decades. We strongly recommend that each Arab country should have its own renal biopsy registry.


Comparative analysis for optimizing the modified release tacrolimus (Advagraf) after kidney transplantation: A prospective randomized trial
Mohamed Adel Bakr, Ayman Maher Nagib, Ahmed Farouk Donia, Ahmed Abdelfattah Denewar, Mohamed Megahid Abu-Elmagd, Mohamed Hamed Abbas, Ahmed Mansour Abdel-Rahman, Mohamed Elsayed Mashaly, Mohamed Mohamed Elsaftawy, Mohamed Ahmed Ghoneim

Saudi Journal of Kidney Diseases and Transplantation 2018 29(6):1267-1273

Immunosuppression management in clinical transplantation aims to balance delivery of efficacy against adverse reactions using therapeutic drug monitoring. Adherence to posttransplant immunosuppressive medications and minimizing variability in drug exposure are important considerations in preventing rejection and maximizing overall transplant outcomes. The availability of once-daily tacrolimus may add a potential benefit by simplifying immunosuppressive regimens, though improving compliance among transplant recipients. The aim of our study is to investigate the safety and efficacy of the once-daily formulation of tacrolimus (Advagraf) against the usually used twice daily tablets (Prograf). A prospective randomized trial 1:2 was designed for 99 consecutive live-related renal transplant recipients who received their grafts at a single center (study group, Advagraf, 33 recipients and control group, Prograf, 66 recipients). The demographic data were homogeneous among both groups regarding donors and patients’ characteristics. Posttransplant hypertension, infection, malignancy, and diabetes mellitus were comparable among both groups. Renal function and rejection episodes showed no statistical significance among recipients of both groups. Despite slight higher Advagraf unit doses, there was no statistical difference regarding the tacrolimus trough levels, between the two groups. Our singlecenter experience revealed that the availability of once-daily tacrolimus formulation could give potential benefit of improved medication compliance and better allograft outcomes by decreasing pill burden and thereby simplifying dosing schedule, Advagraf was non-inferior to twice-daily tacrolimus regarding safety and efficacy. Although being nonsignificant, a trend for better kidney function was noted in this short-term study in the Advagraf group, so long-term follow-up is needed to verify this.


Effect of thyroid function status in hemodialysis patients on erythropoietin resistance and interdialytic weight gain
Fatemah Saleh Bin Saleh, Marriam Nasser Naji, Abdalla A. Eltayeb, Fayez Faleh Hejaili, Abdulla Ahmed Al Sayyari

Saudi Journal of Kidney Diseases and Transplantation 2018 29(6):1274-1279

Thyroid function abnormalities are common in hemodialysis (HD) patients. Here, we investigated their frequency and impact on intradialytic hemodynamics and erythropoietin resistance index (ERI). Demographic and laboratory data including thyroid-stimulating hormone (TSH), interdialytic weight gain, and intradialytic blood pressure (BP) changes were measured, and ERI was calculated. The prevalence and causes of abnormities in TSH and free thyroxine (FT4) and their effects on ERI and intradialytic hemodynamics were then assessed. One hundred and thirty patients (mean age, 57.1 ± 19.2 years; 66.4% diabetic, 86.7% hypertensive) were enrolled. Among them, 16.7% had hypothyroidism, 2.3% had hyperthyroidism, and 10.9% had subclinical hypothyroidism. TSH level was significantly associated with higher BP (P <0.05), lower albumin (3.6 ± 4.4 and 2.6 ± 1.8, respectively; P = 0.05), lower dialysis hours (3.9 ± 5.3 and 2.6 ± 1.8, respectively), and lower ERI (3.7 ± 4.4 and 2.4 ± 1.9, respectively; P = 0.05). FT4 was significantly associated with higher interdialytic weight gain (13.4 ± 4.3 and 11.8 ± 2.2 pmol/L, respectively; P = 0.009) and higher pre-HD diastolic BP (13.2 ± 4.0 and 12.0 ± 2.9 pmol/L, respectively; P = 0.05). A negative correlation was seen between TSH level and urea reduction ratio (r = 0.29, P = 0.002), serum albumin (r = 0.304, P = 0.001), hemoglobin level (r = 0.26, P = 0.005), and ERI (r = 0.2, P = 0.002). A higher TSH level was associated with hypertension, lower albumin level, fewer dialysis hours, and increased resistance to erythropoietin. TSH level was negatively correlated with dialytic adequacy, serum albumin level, hemoglobin level, and ERI.


Assessment of left ventricular mass changes after arteriovenous fistula surgical banding in end-stage renal disease
Camilo Cortesi, Juan C Duque, Sedki Mai, Laisel Martinez, Adriana Dejman, Roberto Vazquez-Padron, Loay Salman, Marwan Tabbara

Saudi Journal of Kidney Diseases and Transplantation 2018 29(6):1280-1289

Left ventricular hypertrophy (LVH) is a multifactorial complication frequently seen in patients with advanced chronic kidney disease. An arteriovenous fistula (AVF) is the preferred method for hemodialysis access. Once functional, AVFs demonstrate better patency rates and fewer complications when compared to other forms of vascular access. AVFs have been implicated in cardiac remodeling, but it is controversial whether those changes can be reversed by surgical ligation or blood flow reduction. In this study, we describe a cohort of asymptomatic patients with LVH who underwent AVF banding with a two-dimensional-echocardiogram done before and after the intervention to evaluate the association between AVF surgical banding and left ventricular mass (LVM) changes. Our results show that AVF surgical banding did not alter the left ventricular mass index (LVMI) with a mean prebanding LVMI of 70.3 ± 57.5 g/m2 and mean postbanding LVMI of 81.9 ± 55.9 g/m2, (P = 0.4). Our study shows that AVF flow reduction by surgical banding did not alter LVMI, and therefore LVH, in end-stage renal disease patients who have not yet shown clinical manifestations of cardiac disease.


Clinical and laboratory findings of patients with diabetes undergoing kidney biopsy
Ehab Mohammed, Ahmed Atris, Issa Al Salmi, Lubna Al-Menawi, Faisal Shaheen, Suad Hannawi

Saudi Journal of Kidney Diseases and Transplantation 2018 29(6):1290-1302

Diabetic kidney disease (DKD), one of the most frequent microvascular complications of diabetes mellitus (DM), is the leading cause of end-stage kidney disease worldwide. We reviewed all kidney biopsies performed at the Royal Hospital, Muscat, Oman, between January 2005 and December 2016, and data of 51 DM patients were analyzed. Of the 51 patients, 54.9% were male and 45.1% were female. The mean age was 50.8 (47.1–55.2) years; 86% were between 25 and 64 years old. Edema was the main clinical presentation (70.6%) with clinical urine changes in 84.3%. Diabetic retinopathy was present in 62.2% in ophthalmological examination of 44 patients. Majority (67.5%) of patients were in advanced chronic kidney disease Stages III, IV, and V. About one-quarter underwent hemodialysis at the time of admission. Majority (76.9%) were obese and hypertensive (78.4%). Low hemoglobin (51%), high triglyceride (35.7%), high total cholesterol (56.8%), low serum albumin (78.4%), nephrotic-range proteinuria (75.6%), and microscopic hematuria (77.1%) were the main laboratory findings. In addition, immunological investigations were examined and immunoglobulin A was the most common findings (35.7%) of serological investigations. About 24.4% had positive antinuclear antibody, 20.8% had positive anti-dsDNA, and 23.3% had positive extractable nuclear antigens. Also, p-antineutrophil cytoplasmic antibody (p-ANCA) was positive in 30% and c-ANCA was positive in 9.7%. This study represents the findings of the whole country for more than 10 years. It showed that only a small percentage of patients with DM undergo kidney biopsy. These patients have many clinical and laboratory abnormalities including those of specific immuno-logical investigations. Progression of DM nephropathy seems to be further aggravated by many coexisting risk factors of dyslipidemia and/or obesity. The prevalence of non-DKD is remarkably frequent in diabetics in whom nephrologists should consider kidney biopsy as an appropriate measure to enable better management.


A single-center 4-year experience with 47 pediatric renal transplants: Evolving trends
Hany M El Hennawy, Ahmed Al Hashemy, Nafaa Al Harbi, Wael T Habhab, Ahmed E Fahmy

Saudi Journal of Kidney Diseases and Transplantation 2018 29(6):1303-1310

Outcome of pediatric kidney transplantation (KT) has improved over the last several decades. We retrospectively reviewed the outcomes pediatric KT in King Faisal Specialist Hospital and Research Center-Jeddah, Saudi Arabia. Between May 2013 and November 2016, we performed renal transplantation in 47 children, 30 (64%) males, and 17 (36%) females. All patients received antibody induction with basiliximab or antithymocyte globulin along with triple immunosuppressive therapy with tacrolimus, mycophenolate mofetil and steroids. Twenty-four (51%) and 14 (30%) patients were on hemodialysis and peritoneal dialysis, respectively. Average duration on dialysis was 18.3 months. Nine patients (19%) had preemptive transplant. Forty-five patients (95.7%) received kidneys from living donors, 38 (83%) males and nine (17%) females, mean age (years), and body mass index were 30.8 ± 8.82 and 23.8 ± 4.54, respectively. Forty-one donors had left nephrectomy. Four right nephrectomies were reported, all of them were through open nephrectomy. Open nephrectomy was reported in 21 (46%) patients. Several laparoscopic nephrectomy techniques were performed; conventional laparoscopic donor nephrectomy, laparo-endoscopic single-site donor nephrectomy, and hand-assisted laparoscopic surgery in 10, 11, and three patients, respectively. The most common etiologies of end-stage renal disease were focal segmental glomerulosclerosis 19%, posterior urethral valve 8.5%, and congenital abnormalities 8.5% respectively. With a mean follow-up of 54 months, one and 4-year graft survival rates were 95.7% and 91.5%, respectively. One-and four-year patient survival rates were 100%. Outcomes were similar in patients < or ≥10 years. The graft survival was comparable in laparoscopic versus open donor nephrectomy (P = 0.72). Average serum creatinine was 0.85, 0.79, 0.79, and 0.84 at 7, 30, 90, 365 days, respectively. Four patients lost their graft due to renal vein thrombosis, chronic allograft nephropathy (cadaveric donor), Antibody-mediated rejection, and hemolytic-uremic syndrome at 0.75, 9, 19, and 24 months, respectively. The incidences of acute rejection and major infection were 2% and 4%, respectively. One patient developed posttransplant lympho-proliferative disease that was treated and is still with excellent graft function. Our pediatric KT experience is encouraging. Acute rejection, patient, and graft survival rates are similar and even better than many of western reports.


Impact of Enterobacteriaceae bacteremia on survival in patients with hepatorenal failure
Amin Roshdy Soliman, Rabab Mahmoud Ahmed, Ahmed Abdalla, Mahmoud Soliman, Magee Saeed

Saudi Journal of Kidney Diseases and Transplantation 2018 29(6):1311-1319

Enterobacteriaceae are now the predominant pathogens isolated in patients with liver cell failure associated with bloodstream infections. We conducted a retrospective cohort study of patients who were admitted for the diagnosis of hepatorenal failure (HRF) between June 1999 and May 2008 to investigate the risk factors of Enterobacteriaceae bacteremia (EB). EB was defined as the isolation of an EB species from at least one blood culture within three months following diagnosis of HRF. Variables were collected from the medical records and analyzed in relation to EB. Twenty-four (32.5%) of the 73 patients developed EB. The origin of EB was abdominal in 21% of the patients, urinary in 12.5%, pulmonary in 16.5%, and primary in the remaining patients (50%). Two-thirds of EB occurred within 10 days following the development of HRF. The main pathogens were Escherichia coli (44%), Enterobacter species (20%) and Klebsiella pneumoniae (22%). Eighteen patients (75%) with EB died. Variables significantly associated with EB after multivariate analysis were a model for end-stage liver disease score >20 [odds ratio (OR): 2.84, P <0.02], posthepatitis B liver cirrhosis (OR: 4.72, P <0.05), posthepatitis C liver cirrhosis (OR: 3.48, P <0.05), and initial level of serum creatinine on admission to intensive care unit (OR: 2.56, P <0.02). EB is a frequent and severe complication of HRF. Patients with posthepatitis cirrhosis B and C, higher serum creatinine, and severe liver cell failure score have a high risk of developing EB.


Posttransplant diabetes mellitus among live-related kidney transplant recipients: Sindh Institute of Urology and Transplantation experience
Khadija Gul Mohammad, Muhammad Khalid Idrees, Tariq Ali, Fazal Akhtar

Saudi Journal of Kidney Diseases and Transplantation 2018 29(6):1320-1325

This cross-sectional study conducted at Sindh Institute of Urology and Transplantation, Karachi, Pakistan aimed to determine the frequency and risk factors of posttransplant diabetes mellitus (PTDM) among live-related kidney transplant recipients and their short-term prognosis and included renal transplant recipients (nondiabetic before transplant) of either gender, aged 18–60 years with transplant duration two to six months. Patients with two reading of fasting plasma glucose ≥126 mg/dL were labeled as diabetic. A total of 191 patients (154 males and 37 females) with the age between 18 to 60 years (31.5 ± 9.33 years) were included and 30 patients (15.8%) including 23 males and seven females had PTDM. Age of the patients between 26 and 35 years, previous hepatitis C virus (HCV) infection/antiviral therapy, and Tacrolimus as maintenance immunosuppression were found to be more frequent among those with PTDM. After six months of follow-up, the serum creatinine of patients with PTDM was significantly higher than that of those without PTDM (1.15 ± 0.28 vs. 1.01 ± 0.16, P ≤0.0121); however at one year follow up, there was no significant difference between the serum creatinine of both groups (1.28 ± 0.38 vs. 1.37 ± 0.59, P = 0.332). PTDM is an important metabolic derangement affecting a number of kidney transplant recipients. Its risk factors are previous HCV infection, tacrolimus as immunosuppression and young age. It can have an adverse effect on graft function and survival. Therefore, long-term follow-up is warranted to optimize the graft function and patient survival.


Assessment of knowledge and attitude toward organ donation among the Saudi population in Riyadh City
Dalia Saleh Alsharidah, Fay Saad Al-Dossari, Nouf AlMahmoud, Bothayna Abdullah Alanzan, Rawan Jamal Binkhulaif, Esraa Mohammad Bakhsh, Abeer Ali Alkhalaf, Budur Abdullah Bin Huzim, Nora Tarig Sarhan, Lujain Mohammad Sulayem, Dalia Saad ElFeky, Sadiqa Syed

Saudi Journal of Kidney Diseases and Transplantation 2018 29(6):1326-1332

We aimed to assess the knowledge and attitude of the Saudi population and students of health science colleges as well as healthcare workers in Riyadh city about organ donation (OD). Data of this study were collected from 648 Saudi residents of Riyadh city using interviewer-administered questionnaires and online surveys. The participants included 503 from the general population and 145 health science professionals. The subjects included 252 males and 396 females with mean age of 27.09 ± 9 years. Majority of the participants (60%) were aware of OD from media as the main source of information, while only 30% had knowledge about Saudi center for organ transplantation (SCOT). It was found that 47.7% of the population agreed to donate both organs and tissue and 26% of them accepted the idea of OD to please Allah. The most important barrier (13%) was the belief that their bodies should be kept intact after death followed by ignorance about OD. Among health science professionals, 63% thought that everyone should be automatically registered as an organ donor while 15% believed that the donated organs could be misused. The majority of Riyadh’s population knew the concept and procedure of OD; however, there was a lack of awareness of the presence of SCOT. Religion is not a barrier for OD in the Saudi population. Awareness programs are urgently needed to emphasize the importance of donation as well as clarification of wrong beliefs.


Impact of correction of anemia in end-stage renal disease patients on cerebral circulation and cognitive functions
Amr Mohamed Shaker, Osama Mohamady Mohamed, Moataz Fatthy Mohamed, Sahier Omar El-Khashaba

Saudi Journal of Kidney Diseases and Transplantation 2018 29(6):1333-1341

End-stage renal disease (ESRD) patients have been associated with accelerated vascular disease of the cerebral circulation due to uremic toxins. Furthermore, anemia increases cerebral oxygen extraction fraction which impairs the cerebral vasodilatory capacity. We evaluated the effect of correction of anemia on cerebral blood flow by measuring the mean blood flow velocity, resistance index (RI), and pulsatility index (PI) in the middle cerebral artery (MCA) in relation to cognitive functions. We measured the mean blood flow velocity, RI, and PI in MCA of 120 ESRD patients when the hemoglobin (Hb) ranges between 8 and 10 g/dL and after correction of anemia to two Hb ranges between 10–11.5 g/dL and 11.5–12.5 g/dL in the same patients using transcranial Doppler (TCD) ultrasound in relation to cognitive functions assessment by Mini–Mental State Examination. We observed that there is a mild-to-moderate cognitive impairment in hemodialysis (HD) patients associated with anemia. With the improvement of anemia, the cognitive functions improved. There was an improvement of blood flow of MCA with improvement of Hb. The improvement was obvious at Stage 3 (Hb 11.5–≤12.5 g/dL) in comparison to Stage 2 (Hb 10–<11.5 g/dL) with P <0.001 at all. The optimal Hb for HD patients ranges from 11.5 to ≤12.5 g/dL which associated with better improvement of cognitive function and cerebral circulation investigated by TCD ultrasound for MCA.


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