Hemodialysis during Lockdown Due to Coronavirus Disease 2019 Pandemic in Eastern Saudi Arabia.

The first case of Coronavirus disease-2019 (COVID-19) in the Kingdom of Saudi Arabia was confirmed in the city of Qatif in March 2020. As a result, Qatif was placed under lockdown for two months in an attempt to prevent the widespread of COVID-19. Doing hemodialysis (HD) during lockdown was a new and challenging experience that we recently have faced. Swift arrangements were made to accommodate patients with end-stage renal disease in need for HD. The challenges to healthcare facilities, healthcare providers, and patients are discussed with the hope that this experience would help mitigate some of the difficulties healthcare providers may face in a similar situation.

Novel Haplotype Indicator for End-Stage Renal Disease Progression among Saudi Patients.

BACKGROUND: End-stage renal disease (ESRD) is the result of hypertensive nephrosclerosis and chronic glomerular diseases and is associated with high morbidity and mortality. There are strong heritable components in the manifestation of the disease with a genetic predisposition to renal disorders, including focal segmental glomerulosclerosis and arterionephrosclerosis. Recent studies in genetics have examined modifiable risk factors that contribute to renal disease, and this has provided a deep insight into progressive kidney disease. Single-nucleotide polymorphisms at the proximity of SHROOM3, CST3, SLC7A9, and MYH9 genes have been associated with an increased risk of developing CKD and ESRD. METHODS: A total of 160 CKD patients and 189 control subjects of Saudi origin participated in the study. Eight polymorphisms (SHROOM3-rs9992101, rs17319721; SLC7A9-rs4805834; MYH9-rs4821480, rs4821481, rs2032487, rs3752462; CST3-rs13038305) were genotyped using TaqMan assay, and the haplotype analysis was done using the HaploView 4.2 software. RESULTS: Haplotype analysis revealed a novel haplotype "E6"-GTTT to be associated significantly with an increased risk for ESRD (p=0.0001) and CKD (p=0.03). CONCLUSION: CKD is often silent until symptomatic uremia during the advanced stages of the disease. The newly identified haplotype will help recognize patients at risk for a rapid progression of CKD to ESRD. Accurate detection and mapping of the genetic variants facilitates improved risk stratification and development of improved and targeted therapeutic management for CKD.

Assessing known chronic kidney disease associated genetic variants in Saudi Arabian populations.

BACKGROUND: Genome wide association studies of patients with European descent have identified common variants associated with risk of reduced estimated glomerular filtration rate (eGFR). A panel of eight variants were selected to evaluate their association and prevalence in a Saudi Arabian patient cohort with chronic kidney disease (CKD). METHODS: Eight genetic variants in four genes (SHROOM3, MYH9, SLC7A9, and CST3) were genotyped in 160 CKD patients and 189 ethnicity-matched healthy controls. Genetic variants were tested for association with the development of CKD (eGFR < 60 ml/min/1.73m2) and effects were compared with results obtained from 133,413 participants in the CKD genetics consortium. Multivariable regression was used to evaluate the role of these eight variants in improving prediction of CKD development. RESULTS: All eight variants were present in Saudi populations with minor allele frequency ranging from 16 to 46%. The risk variant in all four genes demonstrated the same direction of effect as observed in European populations. One variant, rs4821480, in MYH9 was significantly associated with increased risk of development of CKD (OR = 1.69, 95% CI 1.22-2.36, P = 0.002), but the additional variants were not statistically significant given our modest sample size. CONCLUSIONS: CKD risk variants identified in European populations are present in Saudis. We did not find evidence to suggest heterogeneity of effect size compared to previously published estimates in European populations. Multivariable logistic regression analysis showed a statistically significant improvement in predicting the CKD using models with either FGF23 and vitamin D or FGF23, vitamin D level, and MYH9 genotypes (AUC = 0.93, 95% CI 0.90-0.95, P <  0.0001).

End-stage renal disease in patients with sickle cell disease.

Sickle cell nephropathy is a severe complication of sickle cell disease (SCD) that has a wide range of manifestations, from asymptomatic microalbuminuria to end-stage renal disease (ESRD). The data on patients with SCD who develop ESRD are scarce. The aim of this study was to explore the course of patients with SCD who developed ESRD and received renal replacement therapy (RRT). The course of patients with SCD who developed ESRD and started dialysis at two centers in the Eastern Province of Saudi Arabia was retrospectively analyzed. Parameters included age at initiation of dialysis, survival until death or kidney transplantation, hospitalization due to pain crisis, disease-related parameters, and requirement for blood transfusion. Sixteen patients with SCD developed ESRD and started RRT with either hemodialysis or peritoneal dialysis. The mean age at initiation of dialysis was 46.6 years. The majority of patients (10 out of 16) were resistant to erythropoiesis-stimulating agents (ESA) and required blood transfusion repeatedly. Pain crises were infrequently encountered. Median survival was 54 months. Four patients received kidney transplantation with good outcome. In conclusion, most patients with SCD who developed ESRD were resistant to ESA and required repeated blood transfusion. The rate of hospitalization due to pain crisis was relatively low. Survival on dialysis was comparable to that of patients with no SCD, and the post-transplant course was relatively benign.

Concept and design of a genome-wide association genotyping array tailored for transplantation-specific studies.

BACKGROUND: In addition to HLA genetic incompatibility, non-HLA difference between donor and recipients of transplantation leading to allograft rejection are now becoming evident. We aimed to create a unique genome-wide platform to facilitate genomic research studies in transplant-related studies. We designed a genome-wide genotyping tool based on the most recent human genomic reference datasets, and included customization for known and potentially relevant metabolic and pharmacological loci relevant to transplantation. METHODS: We describe here the design and implementation of a customized genome-wide genotyping array, the 'TxArray', comprising approximately 782,000 markers with tailored content for deeper capture of variants across HLA, KIR, pharmacogenomic, and metabolic loci important in transplantation. To test concordance and genotyping quality, we genotyped 85 HapMap samples on the array, including eight trios. RESULTS: We show low Mendelian error rates and high concordance rates for HapMap samples (average parent-parent-child heritability of 0.997, and concordance of 0.996). We performed genotype imputation across autosomal regions, masking directly genotyped SNPs to assess imputation accuracy and report an accuracy of >0.962 for directly genotyped SNPs. We demonstrate much higher capture of the natural killer cell immunoglobulin-like receptor (KIR) region versus comparable platforms. Overall, we show that the genotyping quality and coverage of the TxArray is very high when compared to reference samples and to other genome-wide genotyping platforms. CONCLUSIONS: We have designed a comprehensive genome-wide genotyping tool which enables accurate association testing and imputation of ungenotyped SNPs, facilitating powerful and cost-effective large-scale genotyping of transplant-related studies.

Elevated Fibroblast Growth Factor 23 Concentration: Prediction of Mortality among Chronic Kidney Disease Patients.

BACKGROUND: The osteocyte-derived hormone, fibroblast growth factor 23 (FGF23), regulates the phosphorus metabolism and suppresses 1,25-dihydroxyvitamin D production, thereby mitigating hyperphosphatemia in patients with renal disorders. An elevated FGF23 level is suggested to be an early biomarker of altered phosphorus metabolism in the initial stages of chronic kidney disease (CKD) and acts as a strong predictor of mortality in dialysis patients. In the Saudi population, there is no report on the FGF23 level in CKD patients to date. This study aims to estimate the plasma FGF23 levels in the Saudi population and to correlate it with its clinical manifestations in order to ascertain its role in the pathogenesis of CKD patients. METHODS: The FGF23 level in the plasma samples was determined using ELISA in a diverse cohort of 89 cases with stage 3-5 CKD and 100 healthy subjects. The plasma FGF23 level was correlated with other biochemical parameters. RESULTS: The results revealed that the FGF23 level was markedly elevated among CKD patients compared to the control group, and a significant inverse correlation was observed between the FGF23 level and glomerular filtration rate. FGF23 elevation was approximately 40-fold among stage 5 patients compared to the control, while the elevation of phosphate, parathyroid hormone (PTH) and alkaline phosphatase was 2-, 3- and 8-fold in this stage, respectively. CONCLUSION: Elevated FGF23 levels may have a strong correlation with the disease pathogenesis. In addition, FGF23 might be a future therapeutic target to intervene against the progression of CKD as well as to increase patient survivability.

Polymorphism in methylenetetrahydrofolate reductase, plasminogen activator inhibitor-1, and apolipoprotein E in hemodialysis patients.

The methylenetetrahydrofolate reductase (MTHFR) gene polymorphism, apolipoprotein E (apo epsilon4) gene polymorphism and polymorphism of plasminogen activator inhibitor-1 (PAI-1) have been shown to be associated with end-stage renal disease (ESRD). To determine the prevalence of these mutations in Saudi patients with ESRD on hemodialysis, we studied the allelic frequency and genotype distribution in patients receiving hemodialysis and in a control group, all residing in the Eastern Province of Saudi Arabia. The genotypes were determined using allele specific hybridization procedures and were confirmed by restriction fragment length polymorphism. The T allele frequency and homozygous genotype of MTHFR in ESRD patients were 14% and 2.4%, respectively compared to 13.4% and 0%, respectively in the control group. The allele frequency and homozygous genotype of 4G/4G PAI-1 gene polymorphism were 46.4% and 4.8% respectively in ESRD patients compared to 57.1% and 32% respectively in the control group. The apo s4 allele frequency and homozygous genotype distribution in hemodialysis patients were 7% and 2.4%, respectively compared to 13% and 2% in the control group. Although allele frequency of C677T of MTHFR was statistically similar in the hemodialysis patients and in the control group, the homozygotes T allele genotype was over represented in the hemodialysis group compared to normal. The prevalence of PAI-1 4G/4G polymorphism in ESRD patients was lower when compared to the control group. The prevalence of apo s4 allele did not differ significantly between the two groups. The present results demonstrate that all three studied polymorphic mutations are present in our population and that they may contribute to the etiology of the disease in our area.

Increased Prevalence of Glycoprotein IIb/IIIa Leu 33 Pro Polymorphism in End Stage Renal Disease Patients on Hemodialysis.

Traditional atherosclerosis risk factors cannot elucidate the increased prevalence of cardiovascular events in end stage renal disease (ESRD) patients on hemodialysis. A previous study has indicated a strong association of the PI(A1/A2) polymorphism with myocardial infarction, diabetes and renal allograft rejection. In this investigation, we determined the prevalence of the PI(A1/A2) polymorphism of platelet glycoprotein (GP) IIb/IIIa in ESRD patients on hemodialysis in the Eastern Province of Saudi Arabia. The PI(A1/A2) polymorphism was determined in 42 ESRD patients receiving hemodialysis and in 49 subjects without current or past history of renal disease. Genotypes were determined by a reverse-hybridization assay and were confirmed by restriction fragment length polymorphism procedures. The PI(A2) allele frequency among the control sample was 28.6% (2 were homozygous for PI(A2), 23 were homozygous for PI(A1), and 24 were heterozygous PI(A1/A2)). The PI(A2) allele frequency among the hemodialysis sample was 50% (2 were homozygous for PI(A2), 2 were homozygous for PI(A1) and 38 were heterozygous for PI(A1/A2)). The PI(A2) allele frequency among the hemodialysis patients was significantly higher than that in the control group [Odds ratios 2.5 (1.35-4.61), p<0.003; Adjusted odds ratios of 2.21 (1.05-4.65), p<0.036 after adjustment for the presence of diabetes; Simultaneously adjusting the odds ratios for the presence of standard risk factors (diabetes and hypertension) gave an adjusted OR of 6.87 (1.54-30.71), p=0.064]. These results suggest that the PI(A2) polymorphism may contribute toward the etiology of cardiovascular diseases in ESRD patients. A further study with a larger sample size is needed to confirm above results.

Beneficial effects of maintenance intravenous iron saccharate in hemodialysis patients.

We evaluated in this study the effects of regular use of maintenance intravenous (IV) iron saccharate on the hematological parameters, iron stores and erythropoietin (EPO) requirement in a group of stable hemodialysis (HD) patients. We maintained 34 stable HD patients (14 (41.2%) males) with a mean age of 43.1 +/-16 years (range 17-69) and mean duration of HD of 39.3 +/- 34.5 months on EPO. We also added 50-100 mg IV iron saccharate every week during a 6-month period from May-October, 1999. At entry, 18 (47.1%) patients required loading doses of IV iron saccharate. We compared the results at entry with those at six months. The mean hemoglobin increased significantly from 97 +/- 10 to 117 +/- 20 g/l, (p< 0.0001), serum ferritin increased significantly from a mean of 160 +/- 224 to 377 +/- 216 ng/ml, (p< 0.0001), transferrin saturation increased from 21 +/-1.9 to 28 +/- 8 %, (p=.0002), EPO dose decreased significantly from a mean weekly dose of 8800 +/- 3200 to 5500 +/- 3000 units (p=0.002). The cost saving analysis suggested an annual savings of 6448 Saudi Riyals (1719 US $) per patient attributable to reduction in the administered EPO dose. We conclude that IV iron saccharate use to replenish and maintain iron stores in stable EPO treated HD patients is safe and effective. It results in achieving target hemoglobin with significantly lower doses of EPO.

Co-existence of tuberous sclerosis and the fanconi syndrome in two saudi male siblings: report on two cases.

In this report, we present two cases of familial tuberous sclerosis co-existing with the Fanconi Syndrome. Both cases presented with history of failure to thrive and mental retardation associated with hypokalemic metabolic acidosis. To our knowledge, the association between tuberous sclerosis and the Fanconi Syndrome has not been reported previously.

Renal replacement therapy in end-stage sickle cell nephropathy: presentation of two cases and literature review.

Chronic renal failure develops in 4-18% of patients with sickle cell anemia. Hemodialysis and kidney transplant are viable options in the management of end-stage renal disease in patients with sickle cell disease (SCD). Information on kidney disease among Saudi patients with SCD is non-existing. In this report, the clinical course of two adult males with end-stage sickle cell nephropathy from Eastern Saudi Arabia is described. Literature on renal replacement therapy in sickle cell anemia (SCA) is discussed.

Gastroduodenal lesions and Helicobacter pylori infection in hemodialysis patients.

OBJECTIVE: The purpose of this prospective study is to determine the prevalence of upper gastrointestinal (GI) abnormalities and Helicobacter pylori (H. pylori) infection among stable chronic hemodialysis (HD) patients. METHODS: The study was carried out at King Fahd Hospital of the University, Al-Khobar, Kingdom of Saudi Arabia during the period January 1996 to June 1997. Fifty-four chronic HD patients underwent upper GI endoscopy. Endoscopic changes were described and multiple antral gastric biopsies were taken for histological examination and detection of H. pylori infection. Gastric biopsy findings were compared to findings in 60 consecutive patients with normal renal function undergoing endoscopy for assessment of dyspepsia. RESULTS: Fifty-four stable chronic HD patients (32 men, mean age 42.4 +/- 18 years) underwent upper GI endoscopy and multiple antral gastric biopsies for histological examination and H. pylori detection. The endoscopic findings were abnormal in 49 (90.7%) patients. Chronic gastritis was seen in 20 (37%) patients, acute gastritis was seen in 13 (20.1%) patients, duodenal ulcer was seen in 6 (11.1%) patients, duodenitis with or without erosions was seen in 5 (9.3%) patients, gastroduodenitis was seen in 3 (5.56%) patients, and gastroesophageal reflux disease was seen in 2 (3.7%) patients. Histological examination of multiple antral gastric biopsies documented chronic active gastritis in 28 (51.9%) patients. Helicobacter pylori were present in 34(63%) patients. Helicobacter pylori were detected in the majority (85.7%) of patients with the histological diagnosis of chronic active gastritis. Patients harboring H. pylori were significantly older than negative patients (52 +/- 16.1 versus 33.9 +/- 17.3 years, p<0.018). In a group of 60 patients with normal renal function undergoing endoscopy for assessment of dyspeptic symptoms during the same period, chronic active gastritis was found in 40 (66.7%) patients and H. pylori was detected in 38 (63.3%) patients. CONCLUSION: Upper GI abnormalities are common among HD patients even in the absence of symptoms. Biopsy proven chronic active gastritis is the most common histological diagnosis among these patients and is highly associated with H. pylori infection. Prevalence of H.pylori infection in HD patients is similar to those with normal renal function undergoing endoscopy for dyspepsia. Helicobacter pylori infected HD patients tend to be older than patients without H.pylori infection.

Does Helicobacter pylori infection in chronic renal failure increase the risk of gastroduodenal lesions? A prospective study.

BACKGROUND: Helicobacter pylori (H.pylori) plays an important role in gastroduodenal disease. However, there are few data concerning the epidemiology of H.pylori in patients with chronic renal failure and on hemodialysis (HD) treatment. AIM OF THE STUDY: This study is aimed to determine the epidemiology of H.pylori infection in patients with end stage renal disease (ESRD) on Hemodialysis (HD). PATIENTS AND METHODS: Ninety-six patients with dyspeptic complaints were included in the study. They were divided into two groups; group one consisted of 46 patients with ESRD on HD and group two (control) of 50 patients without renal disease. All patients were subjected to upper gastrointestinal endoscopies, and gastric biopsies were obtained for histological evidence of H. pylori infection. RESULTS: The mean age of both groups was similar. The prevalence of H.pylori among the two groups was not significantly different (45.7% Vs 48%=p > 0.05). The prevalence of duodenal ulcers was significantly higher in H.pylori positive than in H.pylori negative ESRD patients (p < 0.05). GERD was significantly lower in H.pylori positive patients in both groups (p < 0.001 and p < 0.01 respectively). CONCLUSION: This study showed a similar prevalence of H.pylori infection in both groups. H.pylori infection in patients with ESRD is probably associated with increased risk of gastroduodenal lesions.

A prospective study of hemodialysis access-related bacterial infections.

The objective of this study was to describe hemodialysis vascular-access related infections that occurred in hemodialysis patients over an 18-month period. The study is a prospective descriptive analysis of incidence infection rates in a hemodialysis unit in a tertiary-care medical center. Prospective surveillance for hemodialysis vascular access-related infection was performed for all patients undergoing hemodialysis from November 1999 through April 2001 at King Fahd Hospital of King Faisal University, Al-Khobar, Saudi Arabia. The total number of dialysis sessions was calculated. The type of vascular access was noted. Cultures were obtained and all infections were recorded and infection rates were calculated. There were 9627 hemodialysis sessions (5437 via permanent fistulae or grafts, 2409 via temporary central catheters, and 1781 via permanent tunneled catheters) during the 18-month study period. We identified a total of 109 infections, for a rate of 11.32/1000 dialysis sessions (ds). Of the 109, 23 involved permanent fistulae or grafts (4.23/1000 ds); 18 involved permanent-tunneled central catheter infections (10.1/1000 ds); and 68 involved temporary-catheter infections (28.23/1000 ds). There were 38 bloodstream infections (3.95/1000 ds) and 34 episodes of clinical sepsis (3.53/1000 ds). Seventy-one vascular access infections without bacteremia were identified (7.38/1000 ds), including 16 permanent-fistulae or graft infections (2.94/1000 ds), 7 permanent-tunneled central catheter infections (3.93/1000 ds), and 48 temporary-catheter infections (19.92/1000 ds). Staphylococcal organisms were responsible for 77% of the infections, with Staphylococcus epidermidis being the strain most commonly implicated. Gram-negative organisms were responsible for 23% of the infections. In conclusion, infection rates were highest in hemodialysis patients with temporary vascular access, compared with rates in those with permanent arteriovenous fistulae and synthetic grafts. Most of the bacterial organisms isolated from the vascular access sites were gram-positive cocci, with S. epidermidis accounting for 50% of the organisms. The rate of infection with gram-negative bacilli was higher than in other reports. Our greater dependence on central venous catheters, due to local factors, coupled with the immune-compromising comorbid conditions of our patients, may be contributory to the pattern of infection reported. Delays in the creation of vascular grafts for hemodialysis access should be avoided.