Discordance Between Using Estimated and Measured Glomerular Filtration Rate for Drug Dosing in Kidney Transplant Recipients.

INTRODUCTION: Estimating glomerular filtration rate (eGFR) using different formulas is common clinical practice for evaluating kidney function and drug dosing. But, the performance of available eGFR equations is questionable during early days after kidney transplantation. METHODS: This study compared the performance of three common eGFR equations (Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) in relation with measured GFR (mGFR) using clearance of Tc-99m-diethylenetriaminepentaacetic acid, 7 to 10 days post kidney transplantation. Agreement of mGFR and different eGFR equations in the staging of kidney function and dosing of 8 common antimicrobials were assessed. RESULT: Thirty kidney and 5 simultaneous pancreas-kidney transplant recipients were included. CG applying total body weight (CGTBW) had the lowest bias (-12 mL/min/ 1.73 m2) and the highest percentage of estimation within 30% of mGFR (71.4%). MDRD showed the best precision (13.14 mL/min/ 1.73m2) and linear correlation with mGFR. CKD-EPI and MDRD acted better than CG for staging the level of kidney function. CGTBW had the lowest discordance rate with mGFR for antimicrobials dosing (33.6%). Discordance rates of drug dosing between mGFR and eGFR formulas were greater for drugs that have higher dosing levels such as (val)-ganciclovir (≥ 54.3%). CONCLUSION: Until developing more accurate methods for estimating kidney function during first 1 to 2 weeks after kidney transplantation, CGTBW method is suggested for drug dose adjustment and MDRD or CKD-EPI equation for the staging of kidney function in these patients, keeping in mind that these formulas underestimate the level of kidney function in new transplant recipients.

Vitamin C and kidney transplantation: Nutritional status, potential efficacy, safety, and interactions.

BACKGROUND AND AIM: There are several observational and interventional studies regarding the advantages of sufficient serum levels of vitamin C and the evaluation of the effects of vitamin C supplementation post kidney transplantation. These studies have been put together to investigate the role of vitamin C post-kidney transplantation and make suggestions for designing future studies based on the use of vitamin C supplements or nutritional interventions among these patients. METHODS: This narrative review was done by searching in the Embase, PubMed, and SCOPUS databases. RESULTS: The results are presented in several sections as follows; nutritional status, potential protective effects, safety concerns, and medications/laboratory tests interactions of vitamin C. CONCLUSIONS: Kidney transplant recipients are prone to vitamin C deficiency, which is related to higher mortality based on several long-term observational studies. Vitamin C supplementation improves endothelial function and creatinine clearance. Vitamin C is considered as a safe supplement, however, side effects such as kidney stones, pro-oxidant effect, hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency, impact on lymphocytic activity, acid-base disturbance, and increased sodium load following its administration have been reported. Interaction of vitamin C and cyclosporine is the most important interaction with post-renal transplant medications. Vitamin C also interferes with creatinine assay using Jaffe and enzymatic methods.

Serum albumin is incrementally associated with increased mortality across varying levels of kidney function.

OBJECTIVES: Serum albumin (sAlb) may be a strong predictor of longevity in the general population and in chronic kidney disease. This study aimed to determine the relationship between sAlb concentrations and mortality risk independent of kidney function. METHODS: This was a retrospective cohort study of 31 274 adults from the 1999-2010 National Health and Nutrition Examination Survey. The estimated glomerular filtration rate (eGFR) was examined as both a confounder and modifier of the association of sAlb with mortality risk. We examined the association of sAlb (categorized as <3.8, 3.8 to <4.0, 4.0 to <4.2, 4.2 to <4.4, 4.4 to <4.6, 4.6 to <4.8, and ≥4.8 g/dL) with mortality using Cox models. Subsequently, we conducted spline analyses to estimate the association of sAlb with all-cause mortality across varying eGFR levels. RESULTS: In unadjusted analyses, participants with incrementally lower sAlb concentrations of <4.6 g/dL had an increasingly higher mortality risk compared with those with sAlb levels ranging from 4.6 to <4.8 g/dL (reference), whereas those with higher sAlb levels of ≥4.8 g/dL had a lower mortality risk (hazard ratios [95% confidence interval]: 3.88 [3.26-4.62], 3.59 [3.01-4.27], 2.79 [2.37-3.29], 2.10 [1.79-2.48], 1.72 [1.45-2.03], and 0.71 [0.55-0.92] for sAlb concentrations of <3.8, 3.8 to <4.0, 4.0 to <4.2, 4.2 to <4.4, 4.4 to <4.6, and ≥4.8 g/dL, respectively). Adjusted analyses showed similar findings, although the association of higher sAlb levels of ≥4.8 g/dL with better survival was attenuated to the null. Spline analyses showed that participants with sAlb levels of <4.6 g/dL had higher mortality across all concentrations of eGFR, ranging from 30 to 120 mL/min/1.73 m2 (reference: sAlb ≥ 4.6 g/dL). CONCLUSIONS: Among a nationally representative U.S. cohort, a graded association was observed between lower sAlb concentrations and higher death risk, which was robust across varying levels of kidney function.

Association Between Pre-Transplant Magnesemia and Post-Transplant Dysglycemia in Kidney Transplant Recipients.

BACKGROUND: Serum magnesium (Mg) status in kidney transplant recipients has been a center of attention in the past few years. Current evidence suggests an association between pre-transplant hypomagnesemia and post-transplant hyperglycemia. OBJECTIVE: The purpose of this study was to assess the associations of pre-transplant magnesemia with blood glucose disturbances within 6 months post-kidney transplantation. METHODS: In this retrospective cohort, 89 first-time kidney transplant recipients with 6 months of follow-up were included. None of the participants had a positive history of rejection, pre-transplant history of diabetes mellitus or fasting plasma glucose ≥ 100 mg/dL. RESULTS: Post-transplant diabetes mellitus (PTDM) and impaired fasting glucose (IFG) 6 months post-transplant was found in 7.9% and 41.6% of the study group, respectively. The mean pre-transplant serum Mg level was 1.92 ± 0.30 mg/dL in the study population (n = 89), and it was significantly lower in IFG (n = 37) and IFG/PTDM (n = 44) groups compared to normoglycemic (n = 45) recipients (1.83 ± 0.31 mg/dL vs. 2.00 ± 0.27 mg/dL, P = 0.008, and 1.84 ± 0.31 mg/dL vs. 2.00 ± 0.27 mg/dL, P = 0.012, respectively). Patients with serum Mg less than 1.9 mg/dL were nearly 2.6 times more likely to develop IFG or IFG/PTDM within 6 months post-transplant (P = 0.044 and P = 0.040, respectively). CONCLUSIONS: Pre-transplant hypomagnesemia may be considered a risk factor for developing post-transplant glycemic disturbances, and patients with lower pre-transplant Mg concentration could be at a higher risk for developing IFG.

Association of Pre-End-Stage Renal Disease Serum Albumin With Post-End-Stage Renal Disease Outcomes Among Patients Transitioning to Dialysis.

OBJECTIVE: Serum albumin is a marker of malnutrition and inflammation and has been demonstrated as a strong predictor of mortality in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. Yet, whether serum albumin levels in late-stage CKD are associated with adverse outcomes after the transition to ESRD is unknown. We hypothesize that lower levels and a decline in serum albumin in late-stage CKD are associated with higher risk of mortality and hospitalization rates 1 year after transition to ESRD. DESIGN AND METHODS: This retrospective cohort study included 29,124 US veterans with advanced CKD transitioning to ESRD between 2007 and 2015. We evaluated the association of pre-ESRD (91 days before transition) serum albumin with 12-month post-ESRD all-cause, cardiovascular, and infection-related mortalities and hospitalization rates as well as the association of 1-year pre-ESRD albumin slope and 12-month post-ESRD mortality using hierarchical multivariable adjustments. RESULTS: There was a negative linear association between serum albumin and all-cause mortality, such that risk doubled (hazard ratio [HR]: 2.07, 95% confidence interval [CI]: 1.87, 2.28) for patients with the lowest serum albumin <2.8 g/dL (ref: ≥4.0 g/dL) after full adjustment. A consistent relationship was observed between serum albumin and cardiovascular and infection-related mortality, and hospitalization outcomes. An increase in serum albumin of >0.25 g/dL/year was associated with reduced mortality risk (HR: 0.76, 95% CI: 0.63, 0.91) compared with a slight decline in albumin (ref: >-0.25 to 0 g/dL/year), whereas a decline more than 0.5 g/dL/year was associated with a 55% higher risk in mortality (HR: 1.55, 95% CI: 1.43, 1.68) in fully adjusted models. CONCLUSIONS: Lower pre-ESRD serum albumin was associated with higher post-ESRD all-cause, cardiovascular, and infection-related mortalities and hospitalization rates. Declining serum albumin levels in the pre-ESRD period were also associated with worse 12-month post-ESRD mortality.

Obesity Paradox in Advanced Kidney Disease: From Bedside to the Bench.

While obesity is associated with a variety of complications including diabetes, hypertension, cardiovascular disease and premature death, observational studies have also found that obesity and increasing body mass index (BMI) can be linked with improved survival in certain patient populations, including those with conditions marked by protein-energy wasting and dysmetabolism that ultimately lead to cachexia. The latter observations have been reported in various clinical settings including end-stage renal disease (ESRD) and have been described as the "obesity paradox" or "reverse epidemiology", engendering controversy. While some have attributed the obesity paradox to residual confounding in an effort to "debunk" these observations, recent experimental discoveries provide biologically plausible mechanisms in which higher BMI can be linked to longevity in certain groups of patients. In addition, sophisticated epidemiologic methods that extensively adjusted for confounding have found that the obesity paradox remains robust in ESRD. Furthermore, novel hypotheses suggest that weight loss and cachexia can be linked to adverse outcomes including cardiomyopathy, arrhythmias, sudden death and poor outcomes. Therefore, the survival benefit observed in obese ESRD patients can at least partly be derived from mechanisms that protect against inefficient energy utilization, cachexia and protein-energy wasting. Given that in ESRD patients, treatment of traditional risk factors has failed to alter outcomes, detailed translational studies of the obesity paradox may help identify innovative pathways that can be targeted to improve survival. We have reviewed recent clinical evidence detailing the association of BMI with outcomes in patients with chronic kidney disease, including ESRD, and discuss potential mechanisms underlying the obesity paradox with potential for clinical applicability.

Comparing the Effect of Immediate versus Delayed Initiation of Tacrolimus on Delayed Graft Function in Kidney Transplant Recipients: A Randomized Open-label Clinical Trial.

OBJECTIVE: Delayed graft function (DGF) is an early complication after kidney transplantation with negative impact on allograft outcomes. This study assessed the effect of delayed initiation of tacrolimus as a nephrotoxic drug, on DGF occurrence and allograft function. METHODS: This randomized, open-label clinical trial was conducted on kidney transplant recipients with the age of at least 14 years who underwent the first kidney transplantation from deceased or living donor. Patients were randomly allocated to immediate (n = 26) or delayed tacrolimus (n = 27) groups. All patients received thymoglobulin as induction therapy and similar maintenance immunosuppression including tacrolimus, mycophenolate, and prednisolone with the difference in the time of initiation of tacrolimus either on the day of transplantation (immediate tacrolimus group) or day 3 after transplant (delayed tacrolimus group). FINDINGS: DGF incidence (46.15% vs. 37.04%; P = 0.501) and duration (9.75 ± 6.41 vs. 8.6 ± 6.16 days; P = 0.675) were not different between the immediate and delayed tacrolimus groups. Estimated creatinine clearance using Cockcroft-Gault equation (63.14 ± 18.81 vs. 58.19 ± 19.42 mL/min in immediate and delayed tacrolimus groups respectively; P = 0.373) and estimated acute rejection-free survival were also comparable between the groups over the 3 months of follow-up. Compared with the immediate group, the delayed tacrolimus group showed higher estimated 3-month grafts' survival (100% vs. 84.27%; P = 0.072). CONCLUSION: Delayed initiation of tacrolimus after kidney transplantation under the umbrella of thymoglobulin induction did not result in either lower incidence or duration of DGF or improved the level of graft function in kidney transplant recipients but non-statistically significant increased 3-month grafts' survival.

Inverse Association Between Serum Non-High-Density Lipoprotein Cholesterol Levels and Mortality in Patients Undergoing Incident Hemodialysis.

BACKGROUND: There is accumulating evidence that serum levels of non-high-density lipoprotein cholesterol (non-HDL-C) are a more accurate predictor of cardiovascular outcomes when compared with low-density lipoprotein cholesterol. However, we recently found that higher serum concentrations of triglycerides are associated with better outcomes in patients undergoing hemodialysis. Therefore, we hypothesized that the association of serum levels of non-HDL-C (which includes triglyceride-rich lipoproteins) with outcomes may also be different in patients undergoing hemodialysis when compared with other patient populations. METHODS AND RESULTS: We studied the association of baseline and time-dependent serum levels of non-HDL-C with all-cause and cardiovascular mortality using Cox proportional hazard regression models in a nationally representative cohort of 50 118 patients undergoing incident hemodialysis from January 1, 2007, to December 31, 2011. In time-dependent models adjusted for case mix and surrogates of malnutrition and inflammation, a graded inverse association between non-HDL-C level and mortality was demonstrated with hazard ratios (95% confidence intervals) of the lowest (<60 mg/dL) and highest (≥160 mg/dL) categories: 1.88 (1.72-2.06) and 0.73 (0.64-0.83) for all-cause mortality and 2.07 (1.78-2.41) and 0.75 (0.60-0.93) for cardiovascular mortality, respectively (reference, 100-115 mg/dL). In analyses using baseline values, non-HDL-C levels <100 mg/dL were also associated with significantly higher mortality risk across all levels of adjustment. Similar associations were found when evaluating non-HDL/HDL cholesterol ratio and mortality, with the highest all-cause and cardiovascular mortality being observed in patients with decreased non-HDL/HDL-C ratio (<2.5). CONCLUSIONS: Contrary to the general population, decrements in non-HDL-C and non-HDL/HDL cholesterol ratio were paradoxically associated with increased all-cause and cardiovascular mortality in patients undergoing incident hemodialysis. The underlying mechanisms responsible for these associations await further investigation.

Medical students' attitudes towards early clinical exposure in Iran.

OBJECTIVE: This study was carried out to investigate the medical students' attitudes towards early clinical exposure at Tehran University of Medical Sciences. METHODS: A cross-sectional study was conducted during 2012-2015. A convenience sample of 298 first- and second-year students, enrolled in the undergraduate medical curriculum, participated in an early clinical exposure program. To collect data from medical students, a questionnaire consisting of open-ended questions and structured questions, rated on a five-point Likert scale, was used to investigate students' attitudes toward early clinical exposure. RESULTS: Of the 298 medical students, 216 (72%) completed the questionnaires. The results demonstrated that medical students had a positive attitude toward early clinical exposure. Most students (80.1%) stated that early clinical exposure could familiarize them with the role of basic sciences knowledge in medicine and how to apply this knowledge in clinical settings. Moreover, 84.5% of them believed that early clinical exposure increased their interest in medicine and encouraged them to read more. Furthermore, content analysis of the students' responses uncovered three main themes of early clinical exposure, were considered helpful to improve learning: "integration of theory and practice", "interaction with others and professional development" and "desire and motivation for learning medicine". CONCLUSIONS: Medical students found their first experience with clinical setting valuable. Providing clinical exposure in the initial years of medical curricula and teaching the application of basic sciences knowledge in clinical practice can enhance students' understanding of the role they will play in the future as a physician.

Metastatic transitional cell carcinoma of the skin presenting as painful zosteriform eruptions.

Metastatic skin disease is an uncommon manifestation of visceral malignancies and failure to diagnose this early may result in incorrect treatment. Here, we report a 65-year-old man with bilateral painful eruptions on the abdominal skin and a past history of transitional cell carcinoma of urinary bladder.

An inverse association between serum vitamin D levels with the presence and severity of impaired nerve conduction velocity and large fiber peripheral neuropathy in diabetic subjects.

Diabetic neuropathy (DN) is the most common complication of diabetes mellitus (DM) and also the major cause of morbidity and mortality in diabetic patients. There have been recent speculations that circulating 25-hydroxyvitamin D (25(OH)-D) could be involved in DN development and progression. This study explored the association between serum 25(OH)-D and DN in diabetic subjects by performing strict matching of possible confounders. Overall, 33 diabetic subjects with DN and 29 controls matched in terms of age, sex, BMI, height and disease duration entered this study. Nerve conduction velocity (NCV) was performed to determine the existence and severity of large fiber neuropathy. 25(OH)-D had significantly lower value in DN group (21.2 ± 11.5 vs. 13.5 ± 5.1 ng/mL, P = 0.001). None of the other observed variables showed a significant association with existence and severity of DN. After adjustment for all studied variables, serum vitamin D had an independent and inverse association with both DN presence and severity, as each 1 ng/mL increase in serum 25(OH)-D was correlated with 2.2 and 3.4 % decrease in the presence and severity of NCV impairment, respectively. While adjusted for demographic variables, comorbidities and treatment of DM, our results imply that decreased levels of circulating 25(OH)-D may contribute to increased risk of large fiber neuropathy in type 2 diabetic subjects.

Bilateral complex regional pain syndrome in a woman with major depressive disorder.

Complex regional pain syndrome type 1 (CRPS1) refers to a disorder usually caused by trauma; it is characterized by pain, swelling, limited range of motion, vasomotor instability, skin changes, joint stiffness, and patchy bone demineralization. Most often it occurs after trauma. Other etiologies include myocardial ischemia, cerebrovascular accidents, infection and emotional stress. We report a case of bilateral CRPS1 of the upper extremities in a 52-year-old woman suffering from major depressive disorder. She was complaining about her hands' stiffness and pain. She also reported swelling of both upper extremities and anhydrosis, thickening of the skin and muscle wasting, finger movement limitation, contracture of the digits and trophic skin changes. The diagnosis of CRPS1 was suspected, according to history, physical examination, radiographic changes and bone scintigraphy.

Non-Hodgkin lymphoma with primary involvement of skeletal muscle.

Non-Hodgkin lymphoma usually presents with generalized lymphadenopathy, but it can also involve any part of the human body. Lymphomatous involvement of muscles is a rare presentation and has been reported to occur in only 1.1% in non-Hodgkin lymphoma. Here we, present a 32 year-old Iranian man with primary involvement of spleen, bone, bone marrow and muscle, mimicking soft tissue sarcoma; core needle biopsy of the gluteal muscle showed diffuse large B cell lymphoma.

A salty cause of cough in a 24-year-old man.

With improvement in the diagnosis and treatment of cystic fibrosis cases in recent years, the survival of these cases has been increased. On the other hand, an increasing number of cases are presented during adulthood. Here we report a 24-year-old man with a history of productive cough, bilateral paranasal sinusitis and polyps, and recurrent abdominal pain. Thoracic computed tomography revealed a bilateral scattered tree in bud pattern and some bronchiectatic changes. Semen analysis showed azoospermia. A sweat chloride test was >60 mEq/l in two occasions.

Secondary Sjogren's syndrome presenting with hypokalemic periodic paralysis.

Renal tubular acidosis (RTA) may develop in a large population of patients with Sjogren's syndrome (SS), but most of the subjects are asymptomatic. Here, we report a patient with known rheumatoid arthritis and symptoms of xerostomia, xerophthalmia and periodic paralysis. SS should be considered as a cause of RTA. The treatment of the underlying disorder may ameliorate the symptoms.