The Effectiveness of Vitamin D Supplementation on Oxidative and Inflammatory Markers in Patients Suffering from End-stage Renal Disease, a Randomized Controlled Trial.

Vitamin D insufficiency is common in patients suffering from end-stage renal disease (ESRD). In contrast, vitamin D supplementation could improve the status of ESRD patients (ESRDP). However, this effect's molecular mechanism is not fully understood. Therefore, this study aimed to assess vitamin D supplementation's impact on inflammation and oxidative signaling pathways in ESRDP. 104 ESRDP were divided into placebo (53) and vitamin D (51) groups. They were also categorized into four subgroups based on the severity of vitamin D deficiency. The dose of vitamin D3 (0.25-0.5mg/day) supplementation was determined based on plasma levels of calcium and parathyroid hormone (PTH). Vitamin D supplementation was performed for eight weeks. Serum levels of calcium, phosphorus, PTH, albumin, creatinine, ALP, and glomerular filtration along with antioxidant enzymes, malondialdehyde, and pro-inflammatory factors were measured. Moreover, the Nrf2 and NF-ĸB expression was evaluated in whole blood. According to the results, vitamin D supplementation improved the status of patients with ESRD significantly as compared with the placebo group (p<0.05). In addition, the expression of NF-ĸB and the serum levels of pro-inflammatory factors and malondialdehyde were significantly reduced. Finally, the expression of Nrf-2 and the serum of antioxidant enzymes were raised in the vitamin D group as compared with the placebo group (p<0.05). Vitamin D reduces clinical and metabolic symptoms in ESRDP by modulating gene expression (in oxidative stress and inflammation).

The causes and frequency of kidney allograft failure in a low-resource setting: observational data from Iraqi Kurdistan.

BACKGROUND: In the developing world, transplantation is the most common long-term treatment for patients with end-stage renal disease, but rates and causes of graft failure are uncertain. METHODS: This was a retrospective outcomes study of renal transplant patients seen in Iraqi Kurdistan nephrology clinics in the year 2019. In 2019, 871 renal transplant patients were registered and outcomes followed through 12/31/2020. Indicated renal biopsies were obtained on 431 patients at 1 day to 18 years post-transplantation. Outcomes were compared with United States Renal Data System (USRDS) living donor reports. RESULTS: All donors were living. The recipient age was 38.5 ± 13.3 years, 98.2% were < 65 years old, 3.7% had previous transplants, and 2.8% had pretransplant donor-specific antibodies (DSA). Gehan-Breslow estimated failure rates for all-cause, return to HD, and death with functional graft were 6.0, 4.2, and 1.9% at 1 year and 18.1, 13.7, and 5.1% at 5 years post-engraftment (USRDS 2000; 1 year: 7.0, 5.0, 2.6%; 5 year: 22.3, 15.2, 10.6%. USRDS 2010; 1 year: 3.7, 2.4, 1.4%; 5 year: 15.3, 9.6, 7.3%). The median graft survival was 15 years. Acute tubular injury (ATI), infarction, and acute T cell-mediated rejection accounted for 22.2% of graft loss, with > 75% of these failures taking place in the first year. Most graft failures occurred late, at a median post-transplant time of 1125 (interquartile range, 365-2555) days, and consisted of interstitial fibrosis and tubular atrophy (IF/TA) (23.8%), transplant glomerulopathy (13.7%), and acquired active antibody-mediated rejection (12.0%). The significant predictors of graft loss were C4d + biopsies (P < 0.01) and advanced IF/TA (P < 0.001). CONCLUSIONS: Kurdistan transplant patients had graft failure rates similar to living donors reported by the USRDS for the year 2000 but higher than reported for 2010. Compared to USRDS 2010, Kurdistan patients had a moderate excess of HD failures at one and 5 years post-engraftment. Nevertheless, prolonged survival is the norm, with chronic disorders and acquired DSA being the leading causes of graft loss.

Effect of TNF-α -308G/A (rs1800629) Promoter Polymorphism on the Serum Level of TNF-α Among Iraqi Patients with Generalized Vitiligo.

BACKGROUND: Vitiligo is a chronic acquired pigmentary disorder of the skin; it results from immunological distruction of functioning melanocytes. The cytokine TNF-α plays a central role in the initiation of melanocyte apoptosis in vitiligo. Single nucleotide polymorphism (SNP) in the promoter region of the gene coding for serum TNF-α may affect its production. OBJECTIVE: The aim of this study is to assess serum TNF-α as a risk factor for generalized vitiligo among Iraqi patients and to rule out that polymorphism at the -308 position affects serum TNF-α. MATERIALS AND METHODS: This case-control study was conducted at Sulaymaniyah Dermatology Teaching Center (SDTC), Iraq. Serum concentration of TNF-α was measured using enzyme linked immunosorbent assay (ELISA) technique in 80 patients with generalized vitiligo and 40 clinically healthy controls. The amplification refractory mutation system polymerase chain reaction (ARMS-PCR) technique was used for detection of TNF-308G/A gene polymorphism. TNF-α level correlated with TNF-308G/A gene polymorphism. Serum concentration and TNF -308G/A gene polymorphism have been analyzed in correlation with demographic features and clinical characteristics of patients with generalized vitiligo. RESULTS: Statistically significant elevation of serum TNF-α seen in patients compared to a control group (p-value 0.01). Significantly higher TNF-α level (p-value 0.01) found among patients with active generalized vitiligo. Elevated serum levels of TNF-α were significantly associated with both TNFA1 (TNF-308G) allele (p-value 0.04) and TNFA2 (TNF-308A) allele (p-value 0.03). TNF-α -308GA polymorphism was not affected by demographic features and clinical characteristics of patients with generalized vitiligo. CONCLUSION: TNF-α in the serum is a risk factor for generalized vitiligo among Iraqi patients. Patients with active vitiligo have a higher serum TNF-α level. No difference was found between serum level of TNF-α with TNF-α polymorphism at position -308 (TNF -308). This involves substituting G allele for the A allele.

Effects of bodybuilding supplements on the kidney: A population-based incidence study of biopsy pathology and clinical characteristics among middle eastern men.

BACKGROUND: The incidence of kidney diseases among bodybuilders is unknown. METHODS: Between January 2011 and December 2019, the Iraqi Kurdistan 15 to 39 year old male population averaged 1,100,000 with approximately 56,000 total participants and 25,000 regular participants (those training more than 1 year). Annual age specific incidence rates (ASIR) with (95% confidence intervals) per 100,000 bodybuilders were compared with the general age-matched male population. RESULTS: Fifteen male participants had kidney biopsies. Among regular participants, diagnoses were: focal segmental glomerulosclerosis (FSGS), 2; membranous glomerulonephritis (MGN), 2; post-infectious glomeruonephritis (PIGN), 1; tubulointerstitial nephritis (TIN), 1; and nephrocalcinosis, 2. Acute tubular necrosis (ATN) was diagnosed in 5 regular participants and 2 participants training less than 1 year. Among regular participants, anabolic steroid use was self-reported in 26% and veterinary grade vitamin D injections in 2.6%. ASIR for FSGS, MGN, PIGN, and TIN among regular participants was not statistically different than the general population. ASIR of FSGS adjusted for anabolic steroid use was 3.4 (- 1.3 to 8.1), a rate overlapping with FSGS in the general population at 2.0 (1.2 to 2.8). ATN presented as exertional muscle injury with myoglobinuria among new participants. Nevertheless, ASIR for ATN among total participants at 1.4 (0.4 to 2.4) was not significantly different than for the general population at 0.3 (0.1 to 0.5). Nephrocalcinosis was only diagnosed among bodybuilders at a 9-year cumulative rate of one per 314 vitamin D injectors. CONCLUSIONS: Kidney disease rates among bodybuilders were not significantly different than for the general population, except for nephrocalcinosis that was caused by injections of veterinary grade vitamin D compounds.

Incidence of glomerulonephritis and non-diabetic end-stage renal disease in a developing middle-east region near armed conflict.

BACKGROUND: Estimates of the incidence of glomerulonephritis (GN) and end-stage renal disease (ESRD) in an Iraqi population are compared with the United States (US) and Jordan. METHODS: The study set consist of renal biopsies performed in 2012 and 2013 in the Kurdish provinces of Northern Iraq. The age specific and age standardized incidence of GN was calculated from the 2011 population. ESRD incidence was estimated from Sulaimaniyah dialysis center records of patient's inititating hemodialysis in 2017. RESULTS: At an annual biopsy rate of 7.8 per 100,000 persons in the Kurdish region, the number of diagnoses (2 years), the average age of diagnosis, and annual age standardized incidence (ASI)/100,000 for focal segmental glomerulosclerosis (FSGS) was n = 135, 27.3 ± 17.6 years, ASI = 1.6; and for all glomerulonephritis (GN) was n = 384, 30.4 ± 17.0 years, ASI = 5.1. FSGS represented 35% of GN biopsies, membranous glomerulonephritis 18%, systemic lupus erythematosus 13%, and immunoglobulin A nephropathy 7%. For FSGS and all GN, the peak age of diagnoses was 35-44 years of age with age specific rates declining after age 45. The unadjusted annual ESRD rate was 60 per million with an age specific peak at 55-64 years and a decline after age 65. The assigned cause of ESRD was 23% diabetes, 18% hypertension, and 12% GN with FSGS comprising 41% of biopsy-diagnosed, non-diabetic ESRD. CONCLUSIONS: The regional incidence of ESRD in Northern Iraq is much lower than the crude incidences of 100 and 390 per million for Jordan and the US respectively. This is associated with low renal disease rates in the Iraqi elderly and an apparent major contribution of FSGS to ESRD.