Thyroid Dysfunction and Kidney Dysfunction.

Objectives: The incidence and prevalence of chronic kidney disease (CKD) are rising worldwide. It is becoming more common in the developing world with the increasing impact of non-communicable diseases in these countries. Also, autoimmune disorders, including thyroid dysfunction are more common and may worsen the clinical status of patients with CKD. We sought to determine the thyroid status in patients with CKD and explore the clinical, biochemical, immunological, and hematological parameters that can be affected by thyroid dysfunction among CKD patients. Methods: We conducted a cross-sectional observational study at the Royal Hospital, Muscat. The data was progressively collected for all newly diagnosed CKD patients with no known history of thyroid disease from January 2018 to December 2019. Assessment of thyroid status was performed at their initial diagnosis. Results: During the study period, 121 females (40.3%) and 179 males (59.7%) were diagnosed with CKD with no prior thyroid diseases. The mean age for females and males were 53.6±16.5 and 49.5±16.5 years, respectively. There were 35 patients with thyroid dysfunction with a prevalence of 11.7%. Of these, 22 patients (62.9%) had subclinical hypothyroidism, and 13 (37.1%) had subclinical hyperthyroidism. Total cholesterol and low-density lipoprotein were higher in hypothyroid patients. Urea was higher in hyperthyroid patients with CKD, and hemoglobin level was significantly lower. Conclusions: Thyroid dysfunction was not uncommon among CKD patients, with subclinical hypothyroidism more common than subclinical hyperthyroidism. Thyroid dysfunctions coexisted with kidney dysfunction. These hormonal axis dysfunctions may not be apparent at first presentation; and therefore, may require close clinical and laboratory evaluations.

Transplant Associated Graft versus Host Disease.

Graft versus host disease (GVHD) occurs quite often after hematopoietic cell transplantation. However, it is a rare complication after solid organ transplantation and consists of a reaction of donor-derived immune cells directed against host tissues, which is mostly seen in liver, small intestine, and pancreas transplantation. We are presenting a 54-year-old man with a long-standing history of hypertension, hypertensive nephrosclerosis, and stage V terminal chronic kidney disease, who was on a regular hemodialysis thrice weekly. He had a living kidney transplantation done abroad. On returning, he had a normal kidney function with no obvious complications. Three years later, he presented with jaundice, anorexia, diarrhea, and abdominal pain. Laboratory evaluation showed marked elevated liver enzymes, and severe pancytopenia with evidence of hepatosplenomegaly. Liver biopsy was compatible with graft-versus-host-disease and toxic hepatitis. The patient was not cooperative with the management and he traveled abroad for the 2nd opinion. Based on the clinical presentations, laboratory, radiological, and pathological findings, transplant-associated GVHD (ta-GVHD) was confirmed. Unfortunately, this patient was complicated by severe sepsis, and confounded by a lack of cooperation with the management plan, which resulted in his demise. In the presence of a highly immunocompromised state, patients presenting with transaminitis/hyperbilirubinemia, and when drug-induced liver injury is excluded, the diagnosis of ta-GVHD needs to be highly considered.

Birth weight, gestational age, and blood pressure: Early life management strategy and population health perspective.

The incidence of hypertension (HTN) is rising worldwide with an estimated prevalence of 22%, 7.5 million deaths (12.8%). It is a major risk factor for coronary heart diseases and hemorrhagic strokes. In Oman, the crude prevalence of HTN was 33.1%, whereas the age-adjusted prevalence was 38.3%. Among Gulf Cooperation Countries, 47.2% of the individuals were hypertensive, and women were more likely to have HTN than men. Similarly, the prevalence of low-birth-weight (LBW) is also rising globally with the more prevalent incidence in developing countries reaching almost a rate just lower than 20.0/100 births. In Oman, the prevalence of LBW was 4.2% in 1980, which doubled (8.1%) in 2000 and has shown a slow but steady increase reaching 10.2% in 2013. LBW term is the most commonly used surrogate measure of intrauterine growth retardation and has been related to increased cardiovascular mortality, due to increased risk of cardiovascular risk factors, including blood pressure (BP), diabetes, cholesterol level, and other risk factors. The epidemiologic evidence clearly points to an inverse association between birth weight and many hemodynamic cardiovascular risk markers. Possible mechanisms operating in fetal life that might determine BP include the structural development of resistance arteries, the setting of hormone levels, and nephron endowment. Retarded fetal growth leads to permanently reduced cell numbers in the kidney. Patients with high BP had almost 50% less number of glomeruli compared to that of the normotensive individuals, and subsequent accelerated growth may lead to excessive metabolic demand on this limited cell mass. It is not merely a reduced nephron number that is responsible for HTN, but compensatory maladaptive changes that occur internally when nephrogenesis is compromised. The likelihood of an adverse outcome is greatly amplified in those born with LBW who later develop obesity or an increased ponderal index.

Clinical and laboratory findings of patients with diabetes undergoing kidney biopsy.

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.

Elimination of BK viremia in renal transplant recipients by optimization of immunosuppressive medications without precipitating acute rejection.

BK Polyomavirus-associated nephropathy (BKVAN) has been recognized as an increasing threat in renal transplant patients (RTP) for more than a decade. Reduction in immunosuppression is the mainstay of treatment through various options of treatment has been suggested. Published reports on these protocols have shown mixed results, and no randomized controlled trials have compared one strategy with another. In this context, we hypothesize that the appearance of BKV in the blood compels one to optimize the immunosuppression with possible long-term beneficial effects. We conducted a retrospective study among the RTP being followed up by the Renal Medicine Department at Royal Hospital who tested positive for BKV-polymerase chain reaction and whose immunosuppression was altered with a final aim to get rid of BK viremia, yet avoiding acute rejection. Results were analyzed by the clinical and statistical approach. Extensive literature review was carried out to look into the prevalence, prognosis, and treatment of BKVAN. In all the patients in whom BKV was detected alteration in immunosuppression resulted in eliminating the virus without precipitating acute rejection. The study shows that in the exercise of eliminating BKV by alteration of immunosuppression, we have "tailored" the immunosuppression in each particular RTPs, without precipitating acute rejection.

Mineral bone disorder and its management among hemodialysis patients in the Gulf Cooperation Council: Initial findings from the dialysis outcomes and practice patterns study (2012-2015).

The prospective cohort Dialysis Outcomes and Practice Patterns Study (DOPPS) initiated data collection in national samples of hemodialysis (HD) units (total of 41 study sites) in all six Gulf Cooperation Council (GCC) countries (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates) in late 2012. Here, we report initial results regarding mineral bone disorders (MBDs) and its management in the GCC countries. Forty-one randomly selected HD facilities, treating >23 HD patients each, were sampled and represent care for >95% of GCC HD patients. Descriptive results for the GCC countries based on a random sample of 20-30 HD patients in each study facility. Initial results for the GCC are from 931 HD patients treated at 41 dialysis units (ranging from 1 unit in Bahrain to 21 in Saudi Arabia). Results are presented as weighted estimates, accounting for the sampling fraction in each unit. Baseline descriptive statistics (e.g., mean, median, or percentage), weighted by facility sampling fraction were calculated for the study sample. For analyses examining the percent of facility patients having (a) serum phosphorus >6.0 mg/dL or (b) parathyroid hormone (PTH) >600 pg/mL, analyses were restricted to facilities having at least 10 HD patients with a reported serum phosphorus or PTH measurement, respectively. Logistic regression analyses of the indicated binary outcomes were based on the use of generalized estimating equations and were adjusted for GCC country, patient age category (<45 years, 45-65 years, and >65 years old), sex, and whether the patient was diagnosed with diabetes mellitus. Logistic models accounted for clustering of patients within facilities, assuming an exchangeable working correlation matrix. Mean age of HD patients in the GCC countries was 53 years vs. 61-64 years in the three other DOPPS regions. MBD markers showed slightly lower mean serum Calcium in the GCC countries, similar mean serum phosphorus, and intermediate median PTH levels compared with the three other DOPPS regions. Among GCC countries, the country mean value of MBD markers ranged from 8.6-9.0 mg/dL for serum calcium, 4.4-5.4 mg/dL for serum phosphorus, whereas median PTH ranged from 163-389 pg/mL. Similar to other DOPPS regions, PTH was higher among patients who were younger or without diabetes, and serum phosphorus was lower with older age (P <0.001 for each). History of parathyroidectomy was lower in the GCC countries versus other regions but did not differ when adjusted for age and dialysis vintage. Among treatments used for managing MBD, the GCC countries showed one of the highest uses of cinacalcet (24%) and phosphorus binder use (81%), whereas intravenous Vitamin D use (24%) was slightly higher than that in EURANZ. A much larger fraction of HD patients in the GCC countries had a dialysate calcium bath ≥3.5 mEq/L (43%) versus 0-4% in the three other DOPPS regions. Although many aspects of MBD management and MBD marker achievement are similar in the GCC countries to that seen in other DOPPS study regions, large variability was seen across countries and facilities in the GCC. Mean serum calcium was lower in the GCC despite the much greater use of dialysate Ca of ~3.5 mEq/L which may be due to the relatively low use of vitamin D and higher cinacalcet use, meriting further study. Future work will focus on GCC facility HD practices and patient characteristics most strongly related to the achievement of MBD target levels and associated outcomes.

Impact of demographic and comorbid conditions on quality of life of hemodialysis patients: a cross-sectional study.

To assess the quality of life (QOL) of Saudi Arabian patients undergoing hemo-dialysis (HD) and to determine the impact of gender, age, education and comorbidities on the QOL of these patients, we conducted a cross-sectional study and used the short form-36 (SF-36) questionnaire, a generic instrument for measuring QOL. This questionnaire is composed of eight scales that summarize the physical component scale (PCS) and mental component scale (MCS) of health status. We calculated the PCS and MCS scores for each patient. We studied 205 HD patients (123 men; ages 18-75 years) from the King Fahd General Hospital, Jeddah, Saudi Arabia. The mean SF-36 score was 59.4 ± 21.7 in men and 41.9 ± 20.9 in women (P <0.0001). Patients older than 60 years had the worst score (41.5 ± 21.2), followed by patients aged 40-59 years (53.6 ± 22.8); patients aged 18-39 years had the best SF-36 score (57.5 ± 22.5; P <0.0001). Education had a positive impact on QOL (P <0.0001), whereas comorbid conditions had a negative impact. Peripheral vascular disease was associated with the worst outcome (SF-36 score, 40.4 ± 23.0; P <0.0001), followed by dyslipidemia (42.9 ± 22.4; P = 0.001) and diabetes mellitus (45.0 ± 22.0; P = 0.012). Among the comorbid conditions, hypertension was associated with the best SF-36 score (50.6 ± 22.7; P = 0.034). We conclude that old age, female gender, poor education and comorbid conditions have a negative impact on the QOL of HD patients in Saudi Arabia. These findings indicate a general need for social support for female patients on HD and early diagnosis and management of comorbid conditions.

Cytomegalovirus disease in a renal transplant recipient: the importance of pre-transplant screening of the donor and recipient.

A 16-year-old female patient who was born with a single kidney developed chronic kidney disease during her early childhood due to reflux nephropathy and recurrent urinary tract infection. She progressed to end-stage renal disease (ESRD) and was commenced on renal replacement therapy in the form of peritoneal dialysis in May 2011. Subsequently, she underwent living unrelated donor kidney transplantation in China. She was hospitalized soon after returning to Saudi Arabia for management of high-grade fever, shortness of breath, and deterioration of renal function, which was found to be due to cytomegalovirus (CMV) disease, proved by kidney biopsy and presence of high level of anti-CMV immunoglobulins. Allograft biopsy showed mature viral particles sized between 120 and 149 nm in the nuclei of the glomerular endothelial cells. The patient was treated with valgancyclovir and specific CMV immunoglobulin, as well as by reducing and even stopping the dose of tacrolimus and mycophenolate. Despite all these measures, her condition continued to deteriorate and she finally died. Our study emphasizes that unrelated renal transplantation, especially if unplanned and improperly prepared, is a very risky procedure that might transfer dangerous diseases and increase the morbidity and mortality of the patients. We strongly stress the need for mandatory and proper screening for CMV carrier status among donors as well as recipients prior to transplantation. Also, a recommendation is made to reject CMV-positive donors.

Attitude of physicians towards the evaluation and treatment of the glomerulonephritis patients.

To survey the attitude of the physicians in Saudi Arabia toward the evaluation and treatment of glomerulonephritis (GN) patients, a questionnaire was sent to the medical directors of 175 dialysis centers in the KSA. The study was performed from July to November 2010. A total of 171 (97.7%) medical directors of dialysis centers answered the questionnaire. There were 131 (77%) respondents who followed up hospitalized or out-patients with nephrological problems other than dialysis at their corresponding hospitals. Only 111 (65%) of the respondents attended general nephrology clinics. Furthermore, 115 (80%) respondents followed up GN patients at their corresponding hospitals, with an average of more than 6 patients/year reported by 70 (61%) respondents. The availability of the specific serologic tests, performance of kidney biopsies and a pathologist to read them were disclosed by 55 (32%), 50 (29%), and 46 (27%) respondents, respectively. There were 46 (27%) respondents who encountered very often minimal change disease in the patients they followed up in their corresponding hospitals, 26 (15%) encountered it sometimes, and 21 (12%) encountered the disease rarely, while 78 (46%) never encountered this disease. Similar patterns were stated by the respondents for the rest of the primary and secondary GN; IgAN was the least encountered among the other types of GN. For the steroids and immunosuppressive agents use in the treatment of GN, the respondents were close in frequency to the current practice for the different types of this disease. There were 52 (30%) respondents who believed that the current protocols for treatment of GN are satisfactory, with a minimal room for improvement, while 74 (43%) had no idea about this issue. Moreover, there were only 44-49 (26-29%) respondents who answered the questions about the use of rituximab in the different types of GN and believed that the indications of it could cover most GN with variable degrees; the most popular use of rituximab in GN included MGN and lupus nephritis. We conclude that the set-up for the evaluation and treatment of GN patients is restricted in Saudi Arabia. The exposure and expertise in treatment of the GN is limited and needs better addressing through more availability of nephrologists and performance of kidney biopsies. The quest for innovative effective therapy, such as rituximab, to prevent progression of CKD secondary to GN is still warranted.

Novel 5-flucytosine-resistant clade of Candida dubliniensis from Saudi Arabia and Egypt identified by Cd25 fingerprinting.

DNA fingerprinting of Candida dubliniensis isolates using the species-specific probe Cd25 previously showed that this species consists of two distinct groups, termed Cd25 group I and Cd25 group II. The present study investigated the population structure of 30 C. dubliniensis oral isolates from Saudi Arabia and Egypt using Cd25 fingerprinting and rRNA gene internal transcribed spacer region-based genotyping. Cd25 fingerprinting analysis of these isolates revealed two distinct populations, the first of which consisted of 10 closely related genotype 1 isolates (average similarity coefficient [S(AB)] value, 0.86). The second population of 20 isolates was much more heterogeneous (average S(AB) value, 0.35) and consisted of two distinct subpopulations, one of which consisted of genotype 3 isolates (n = 13) and the other of genotype 4 isolates (n = 7). A mixed dendrogram generated from the fingerprint data from the 30 Saudi Arabian and Egyptian isolates, 5 Israeli isolates, and 51 previously characterized international isolates (32 of Cd25 group I and 19 of Cd25 group II) revealed the presence of three distinct main clades. The first corresponded to the previously described Cd25 group I and contained all the Saudi Arabian, Egyptian, and Israeli genotype 1 isolates mixed with international isolates. The second clade corresponded to the previously described Cd25 group II and contained three Israeli isolates, one genotype 2 isolate, one genotype 3 isolate, and a genotype 4 variant isolate, which were mixed with international isolates. The third clade has not been described before and consisted solely of the 20 Saudi Arabian and Egyptian genotype 3 and 4 isolates identified in this study and a previously described genotype 4 Israeli isolate. All 20 Cd25 group III isolates exhibited high-level resistance to 5-flucytosine (MIC > or = 128 microg/ml), whereas all Cd25 group I and Cd25 group II isolates tested (10 Saudi Arabian and Egyptian, 16 Israeli, and 24 international) were susceptible to 5-flucytosine (MIC < or = 0.125 microg/ml). The results of this study show for the first time the presence of a novel 5-flucytosine-resistant clade of C. dubliniensis (Cd25 group III) that is predominant among isolates from Saudi Arabia and Egypt and absent from a previously characterized international collection of 98 isolates from 15 countries.

Attitude of Physicians toward the Use of Erythropoietin in Hemodialysis Patients.

We attempted in this study to evaluate the attitude of the physicians in The Kingdom of Saudi Arabia (KSA) towards the use of recombinant human erythropoietin (r-HuEPO) in patients on hemodialysis (HD). We sent a questionnaire to 181 physicians in the 147 active dialysis centers in KSA; 110 (74.9 %) of them were under the Ministry of Health (MOH), 14 (9.5%) in Governmental non-MOH hospitals and 23 (15.6 %) were in private hospitals. This covered a population of more than 7300 chronic HD patients. The study was conducted from October to December 2004. Response was obtained from 144 physicians (79.5%), working in 135 dialysis centers (92.5%) that totally treated 7107 (97%) HD patients in the KSA. Of the 144 respondents, 99 (72.8%) responded that they would use r-HuEPO therapy for all new HD patients not guided by hemoglobin (Hb) level. Almost all the respondents would start the patients on a weekly dose of 70% of the dialysis patients with the drug in comparison with the non-MOH and private sector centers (81% vs 100%, respectively P< 0.04). There was a significantly less percentage of MOH than the non-MOH centers to have a written protocol for administration of r-HuEPO (49.1% vs 95% respectively, P< 0.0002). In conclusion, a protocol to guide the r-HuEPO therapy in HD patients is lacking in many centers of the KSA and there is a need for increased awareness of the physicians working in those centers in the practical aspects of the use of this drug in the treatment of anemia in this population.

How to improve organ donation in the MESOT countries.

There are more than 29 countries that have membership of the Middle East Society for Organ Transplantation (MESOT) with more than 600 million populations. These include all Arab countries, Iran, Turkey, Pakistan and countries of Central Asia. There are common features of organ transplantation in the Middle East Countries that include inadequate preventive medicine, uneven health infrastructure, poor awareness of the medical community and public at large of the importance of the organ donation and transplantation, high level of ethnicity and poor government support of organ transplantation. In addition, there is lack of team spirit among transplant physicians, lack of planning for organ procurement and transplant centers and lack of effective health insurance. Patients seek commercial transplantation most of the time. Patients on waiting lists for organ transplantation increase with time and there is a considerably growing gap between supply and demand of organs in the MESOT countries. Living organ donation is the most widely practiced type of donation in the Middle East and includes kidney and partial liver. Cadaver organ donation has a great potential in the Middle East. Nevertheless, this source is still not utilized properly due to the continued debate in the medical community about the concept of brain death and inadequate awareness of the public of the importance of organ donation and transplantation in many countries in this region.. There are three dominant and distinctive models for practice including the Saudi, Iranian and Pakistani models. The Saudi model includes the presence of a national organ procurement center as a governmental agency to supervise organ donation and transplantation. The Iranian model consists of renal grafts donation from the living genetically unrelated persons to the benefit of patients with end-stage renal disease. The Pakistani model is an interesting funding model for management of end-stage organ failure in the developing countries. We conclude that organ donation and transplantation are hampered with obstacles in the MESOT countries. Solutions need continuous work on many fronts. Local experiences can be implemented into new improved models that can help overcoming current obstacles.

Efficacy and safety of sevelamer. Comparison with calcium carbonate in the treatment of hyperphosphatemia in hemodialysis patients.

OBJECTIVE: Current phosphate binders used in hemodialysis patients include calcium-based binders that result in frequent hypercalcemia. The use of a calcium- and aluminum-free phosphate-binding polymer in hemodialysis (sevelamer) disclosed efficacy in the short and long-term studies. However, due to race differences we performed a short-term study on the Saudi hemodialysis patients and compared sevelamer with a standard calcium-based phosphate binder. METHODS: An open-label, randomized, cross-over study was performed to evaluate the safety and effectiveness of sevelamer hydrochloride in controlling hyperphosphatemia in hemodialysis patients. After a 2-week phosphate binder washout period, stable hemodialysis patients were given either sevelamer or calcium carbonate, and the dosages were titrated to achieve phosphate control over an 8-week period. After a 2-week washout period, patients crossed over to the alternate agent for 8 weeks. Twenty patients from the Dialysis Unit of King Fahd Hospital, Jeddah, Kingdom of Saudi Arabia, were recruited for the study between March 2003 and June 2003. RESULTS: There was a similar decrease in serum phosphate values over the course of the study with both sevelamer (-3.3 +/-2.2 mg/dL) and calcium carbonate (-3.9 +/-2.8 mg/dL). Fifty-two percent of patients developed serum calcium greater than 2.75 mmol/L (11.0 mg/dL) while receiving calcium carbonate versus 26% of patients receiving sevelamer (p<0.05). The incidence of hypercalcemia for sevelamer was not different from the incidence of hypercalcemia during the washout period. Patients treated with sevelamer also sustained a 13% mean decrease in serum cholesterol levels. CONCLUSION: Sevelamer was effective in controlling hyperphosphatemia without resulting in an increase in the incidence of hypercalcemia seen with calcium carbonate. This agent appears quite effective in the treatment of hyperphosphatemia in hemodialysis patients, and its usage may be advantageous in the treatment of dialysis patients.