RASA2 ablation in T cells boosts antigen sensitivity and long-term function.

The efficacy of adoptive T cell therapies for cancer treatment can be limited by suppressive signals from both extrinsic factors and intrinsic inhibitory checkpoints1,2. Targeted gene editing has the potential to overcome these limitations and enhance T cell therapeutic function3-10. Here we performed multiple genome-wide CRISPR knock-out screens under different immunosuppressive conditions to identify genes that can be targeted to prevent T cell dysfunction. These screens converged on RASA2, a RAS GTPase-activating protein (RasGAP) that we identify as a signalling checkpoint in human T cells, which is downregulated upon acute T cell receptor stimulation and can increase gradually with chronic antigen exposure. RASA2 ablation enhanced MAPK signalling and chimeric antigen receptor (CAR) T cell cytolytic activity in response to target antigen. Repeated tumour antigen stimulations in vitro revealed that RASA2-deficient T cells show increased activation, cytokine production and metabolic activity compared with control cells, and show a marked advantage in persistent cancer cell killing. RASA2-knockout CAR T cells had a competitive fitness advantage over control cells in the bone marrow in a mouse model of leukaemia. Ablation of RASA2 in multiple preclinical models of T cell receptor and CAR T cell therapies prolonged survival in mice xenografted with either liquid or solid tumours. Together, our findings highlight RASA2 as a promising target to enhance both persistence and effector function in T cell therapies for cancer treatment.

Diabetic Nephropathy, Retinopathy, and Functional Hypogonadism in a Patient with MODY10: A Case Report.

(1) Background and objectives: Maturity-onset diabetes of the young (MODY) is a group of diabetes caused by gene defects related to insulin secretion. MODY1, MODY2, and MODY3 are the most common and account for approximately 80% of all cases. Other types are relatively rare. This study describes the clinical, analytical, and genetic characteristics of a patient with MODY10, and diabetic nephropathy, retinopathy, and functional hypogonadism diagnosis. (2) Materials and methods: A clinical case was analyzed and whole exome generation sequencing (WES) was used to detect mutations related to a monogenic variant. (3) Results: A seventeen-year-old male patient, who was diagnosed with apparent type 1 diabetes at the age of eight was started with insulin therapy. He came to the emergency room with glycemic decompensation, facial, and lower limb edema. During his evaluation, he had near-nephrotic range proteinuria of 2902 mg/24 h, a kidney ultrasound showing mild pyelocalyceal dilation, proliferative diabetic retinopathy, and was also diagnosed with functional hypogonadotropic hypogonadism. These comorbidities improved with adequate glycemic control. WES showed missense variant c.94G>A (p.Gly32Ser) in the INS gene, according to Clinvar corresponding to MODY10. It was a "de novo" variant not reported in his parents. (4) Conclusions: Monogenic diabetes (MD) is rare and MODY10 is among the less frequent types. MODY should be suspected in patients with type 1 phenotype with negative autoimmunity even in the absence of a family history of diabetes. To the best of our knowledge, we present here the first patient with these phenotypic traits of MODY10 reported in Latin America.

Ammonium affects the wet chemical network of HCN: feedback between prebiotic chemistry and materials science.

Prebiotic chemistry one-pot reactions, such as HCN-derived polymerizations, have been used as stimulating starting points for the generation of new multifunctional materials due to the simplicity of the processes, use of water as solvent, and moderate thermal conditions. Slight experimental variations in this special kind of polymerization tune the final properties of the products. Thus, herein, the influence of NH4Cl on the polymerization kinetics of cyanide under hydrothermal conditions and on the macrostructures and properties of this complex system is explored. The kinetics of the process is consistent with an autocatalytic model, but important variations in the polymerization reaction are observed according to a simple empirical model based on a Hill equation. The differences in the kinetic behaviour against NH4Cl were also revealed when the structural, morphological, thermal, electronic and magnetic properties of the synthesized cyanide polymers were compared, and these properties were evaluated by elemental analysis, FTIR, XPS, UV-vis, and ESR spectroscopies, X-ray diffraction, SEM and thermoanalytical techniques. As a result, this hydrothermal prebiotic polymerization is not only pH dependent, as previously thought, but also ammonium subservient. From this result, a hypothetical reaction mechanism was proposed, which involves the active participation of ammonium cations via formamidine and serves as a remarkable point against previous reports. The results discussed here expand the knowledge on HCN wet chemistry, offer an extended view of the relevant parameters during the simulation of hydrothermal scenarios and describe the production of promising paramagnetic and semiconducting materials inspired by prebiotic chemistry.

[Evaluation of kidney function beyond the laboratory: role and current state of kidney imaging]. / Evaluación de la función renal más allá del laboratorio: rol y desarrollo actual de la imagenología renal.

The evaluation of kidney function is usually performed through the estimation of the glomerular filtration rate and urine analysis. The evaluation of the kidney morphology through an image complements and enriches this information. However, many of the applications of current imaging techniques are unknown to clinicians. In addition, communication between clinicians and imaging specialists is less common than desirable. In this review, we will describe the imaging methods most frequently used for evaluating kidney function and other clinical situations, in addition to analyzing the most significant advances, particularly in ultrasonography and magnetic resonance imaging, for the early detection and follow-up of kidney damage.

[Disappearing bone disease of the shoulder (Gorham-Stout Syndrom)]. / Enfermedad del hueso evanescente en hombro. Reporte de un caso (Síndrome De Gorham-Stout).

The spontaneous disappearance of a segment of bone in a short period without the existence of a tumoral disease that justifies it is an exceptional event. We report the case of an older adult in whom the upper epiphysis of the right humerus and part of the acromion disappeared in a period of 3 weeks in the absence of a malignant tumor. Bone biopsy revealed osteoclasts, lymphatic vessels, and blood vessels. This disorder was first reported in 1838 and in 1955 it was established as a specific disease by Gorham and Stout. Since then, it has been named in their honor.

Sildenafil for treating patients with COVID-19 and perfusion mismatch: a pilot randomized trial.

BACKGROUND: SARS-CoV-2 seems to affect the regulation of pulmonary perfusion. Hypoperfusion in areas of well-aerated lung parenchyma results in a ventilation-perfusion mismatch that can be characterized using subtraction computed tomography angiography (sCTA). This study aims to evaluate the efficacy of oral sildenafil in treating COVID-19 inpatients showing perfusion abnormalities in sCTA. METHODS: Triple-blinded, randomized, placebo-controlled trial was conducted in Chile in a tertiary-care hospital able to provide on-site sCTA scans and ventilatory support when needed between August 2020 and March 2021. In total, 82 eligible adults were admitted to the ED with RT-PCR-confirmed or highly probable SARS-COV-2 infection and sCTA performed within 24 h of admission showing perfusion abnormalities in areas of well-aerated lung parenchyma; 42 were excluded and 40 participants were enrolled and randomized (1:1 ratio) once hospitalized. The active intervention group received sildenafil (25 mg orally three times a day for seven days), and the control group received identical placebo capsules in the same way. Primary outcomes were differences in oxygenation parameters measured daily during follow-up (PaO2/FiO2 ratio and A-a gradient). Secondary outcomes included admission to the ICU, requirement of non-invasive ventilation, invasive mechanical ventilation (IMV), and mortality rates. Analysis was performed on an intention-to-treat basis. RESULTS: Totally, 40 participants were enrolled (20 in the placebo group and 20 in the sildenafil group); 33 [82.5%] were male; and median age was 57 [IQR 41-68] years. No significant differences in mean PaO2/FiO2 ratios and A-a gradients were found between groups (repeated-measures ANOVA p = 0.67 and p = 0.69). IMV was required in 4 patients who received placebo and none in the sildenafil arm (logrank p = 0.04). Patients in the sildenafil arm showed a significantly shorter median length of hospital stay than the placebo group (9 IQR 7-12 days vs. 12 IQR 9-21 days, p = 0.04). CONCLUSIONS: No statistically significant differences were found in the oxygenation parameters. Sildenafil treatment could have a potential therapeutic role regarding the need for IMV in COVID-19 patients with specific perfusion patterns in sCTA. A large-scale study is needed to confirm these results. TRIAL REGISTRATION: Sildenafil for treating patients with COVID-19 and perfusion mismatch: a pilot randomized trial, NCT04489446, Registered 28 July 2020, https://clinicaltrials.gov/ct2/show/NCT04489446 .

Comparative Study of the Efficiency of Additives in the Extraction of Phycocyanin-C from Arthrospira maxima Using Ultrasonication

Several phycocyanin extraction methods have been proposed, however, most of them present economical or productive barriers. One of the most promising methods that has been suggested is ultrasonication. We have analyzed here the effect of operational conditions and additives on the extraction and purity of phycocyanin from Arthrospira maxima. We followed three experimental designs to determine the best combination of buffered pH solutions, additives, fresh and lyophilized biomass. We have found that additives such as citric acid and/or disaccharides could be beneficial to the extraction process. We concluded that the biomass-solvent ratio is a determining factor to obtain high extraction and purity ratios with short ultrasonication times.

[IGG4-related disease. Report of 52 patients]. / Enfermedad relacionada a IgG4. Serie clínica de pacientes chilenos.

BACKGROUND: IgG4-related disease (IgG4 RD) is an immune-mediated fibro-inflammatory disorder, with tissue infiltration of IgG4+ plasma cells. It causes pseudotumors, tumors, and a wide spectrum of clinical manifestations. AIM: To report the clinical, laboratory, histopathological and treatment characteristics of a group of Chilean patients with IgG4 RD. MATERIAL AND METHODS: Review of medical records of 52 patients aged 18 to 76 years with IgG4 RD seen at six medical centers. RESULTS: Elevated IgG4 serum levels (> 135 mg/dl) were found in 18 of 44 (41%) patients. There was histological confirmation of the disease in 46 patients. The most common sites of involvement were lungs, eyes and kidneys. Eighteen (35%) patients had only one organ involved, 34 (65%) patients had two organs and 13 (25%) patients had three or more organs. The involvement of two organs was significantly more common in men (p < 0.05). In patients with only one organ involvement, the most frequent location was orbital and meningeal. All patients with kidney or lung disease had multiorgan involvement. All patients received corticosteroid therapy, 67% synthetic immunosuppressants, and 16% rituximab. CONCLUSIONS: ER-IgG4 can affect any tissue. Multiorgan involvement was more common in this series, with preference for lungs, eyes and kidneys. An excellent response to steroids is characteristic of the disease, but with a high relapse rate that requires additional immunosuppression.

Cellular and molecular regulation of the programmed death-1/programmed death ligand system and its role in multiple sclerosis and other autoimmune diseases.

Programmed Cell Death 1 (PD-1) receptor and its ligands (PD-Ls) are essential to maintain peripheral immune tolerance and to avoid tissue damage. Consequently, altered gene or protein expression of this system of co-inhibitory molecules has been involved in the development of cancer and autoimmunity. Substantial progress has been achieved in the study of the PD-1/PD-Ls system in terms of regulatory mechanisms and therapy. However, the role of the PD-1/PD-Ls pathway in neuroinflammation has been less explored despite being a potential target of treatment for neurodegenerative diseases. Multiple Sclerosis (MS) is the most prevalent, chronic, inflammatory, and autoimmune disease of the central nervous system that leads to demyelination and axonal damage in young adults. Recent studies have highlighted the key role of the PD-1/PD-Ls pathway in inducing a neuroprotective response and restraining T cell activation and neurodegeneration in MS. In this review, we outline the molecular and cellular mechanisms regulating gene expression, protein synthesis and traffic of PD-1/PD-Ls as well as relevant processes that control PD-1/PD-Ls engagement in the immunological synapse between antigen-presenting cells and T cells. Also, we highlight the most recent findings regarding the role of the PD-1/PD-Ls pathway in MS and its murine model, experimental autoimmune encephalomyelitis (EAE), including the contribution of PD-1 expressing follicular helper T (TFH) cells in the pathogenesis of these diseases. In addition, we compare and contrast results found in MS and EAE with evidence reported in other autoimmune diseases and their experimental models, and review PD-1/PD-Ls-targeting therapeutic approaches.

Thyroid cancer overdiagnosis and overtreatment: a cross- sectional study at a thyroid cancer referral center in Ecuador.

BACKGROUND: In contrast to the rapid increase in thyroid cancer incidence, the mortality has remained low and stable over the last decades. In Ecuador, however, thyroid cancer mortality has increased. The objective of this study is to determine possible drivers of high rates of thyroid cancer mortality, through a cross-sectional analysis of all patients attending a thyroid cancer referral center in Ecuador. METHODS: From June 2014 to December 2017, a cross-sectional study was conducted at the Hospital de Especialidades Eugenio Espejo, a regional reference public hospital for endocrine neoplasia in adults in Quito, Ecuador. We identified the mechanism of detection, histopathology and treatment modalities from a patient interview and review of clinical records. RESULTS: Among 452 patients, 74.8% were young adults and 94.2% (426) were female. 13.7% had a family history of thyroid cancer, and patients' median tumor size was 2 cm. The incidental finding was 54.2% whereas 45.8% was non-incidental. Thyroid cancer histology reported that 93.3% had papillary thyroid cancer (PTC), 2.7% follicular, 1.5% Hurtle cells, 1.6% medullary, 0.7% poor differentiated, and 0.2% anaplastic carcinoma. The mean MACIS (metastasis, age, completeness, invasion, and size) score was 4.95 (CI 4.15-5.95) with 76.2% of the thyroid cancer patients having MACIS score less than or equal to 6. The very low and low risk of recurrence was 18.1% (79) and 62% (271) respectively. An analysis of 319 patients with non-metastatic thyroid cancer showed that 10.7% (34) of patients had surgical complications. Moreover, around 62.5% (80 from 128 patients with thyroglobulin laboratory results) of TC patients had a stimulated-thyroglobulin value equal or higher than 2 ng/ml. Overall, a poor surgical outcome was present in 35.1% (112) patients. Out of 436 patients with differentiated thyroid carcinoma, 86% (375) received radioactive iodine. CONCLUSION: Thyroid cancer histological characteristics and method of diagnosis are like those described in other reports without any evidence of the high frequency of aggressive thyroid cancer histology. However, we observed evidence of overtreatment and poor surgical outcomes that demand additional studies to understand their association with thyroid cancer mortality in Ecuador.

[Evaluation of kidney function in older adults]. / Evaluación de la función renal en adultos mayores.

The evaluation of renal function in older adults is usually carried out with a creatinine clearance or an estimation of glomerular filtration rate using formulas such as Cockcroft-Gault, MDRD or CKD-EPI. The results obtained with these formulas are often regarded as equivalent. However, in adults older than 70 years, the Cockcroft-Gault formula frequently underestimates the glomerular filtration rate with respect to reference methods and the MDRD formula overestimates it. CKD-EPI has a more unpredictable behavior. This leads to erroneously classifying patients in the stages of chronic kidney disease (CKD), artificially increasing the prevalence of this condition, overloading health systems and generating emotional disorders in patients mistakenly classified as carriers of CKD. Also, when kidney function is overestimated, CKD patients are prevented from receiving the treatments appropriate for their condition. In recent years, new formulas have been proposed (FAS, BIS) with a greater accuracy to estimate glomerular filtration rate in older adults. This review describes the behavior of these formulas in a significant number of older adults, from various countries, and proposes using those equations with the best performance in older adults.

[Comparative performance of urinary creatinine excretion estimating equations]. / Desempeño comparativo de ecuaciones de estimación de excreción urinaria de creatinina.

BACKGROUND: 24-hour urine collection accuracy is generally evaluated based on the values of urine creatinine (UCr) excretion, usually using ranges adjusted by weight. UCr excretion depends on several factors. Equations to estimate UCr in 24-hour collection (UCr/24h) that consider these factors have been developed. However, these formulas have not been evaluated in a sample of Latinamerican origin. AIM: To evaluate the performance of the existing UCr/24 h estimation equations in a sample of Latinamerican origin. MATERIAL AND METHODS: 24-hour urine collections from 181 ambulatory patients were analyzed. Measured UCr/24h was compared with estimated UCr (eUCr) through the equations of Ix (CKD-EPI), Gerber-Mann, Goldwasser, Cockcroft-Gault, Rule, Walser, Kawasaki, Tanaka and Huidobro. Performance of the nine equations to estimate UCr/24h was evaluated with the Pearson correlation and Lin concordance coefficients, and Bland-Altman method. Bias, precision, and accuracy (percentage of collections within 30% of measured UCr or P30) were also calculated. RESULTS: Measured UCr/24h in the 181 patients was 1236 + 378 mg. Correlation coefficient (Pearson) of the eUCr/24h with the equations of Walser, Ix and Huidobro and the measured UCr/24h was strongly positive. Rule and Kawasaki equations had the lowest positive correlation coefficients. Bias was similar using the formulas of Walser, Goldwasser, Kawasaki, Ix and Huidobro. Walser, Ix, Huidobro, Cockcroft-Gault and Goldwasser equations had good accuracy (P30 > 85%), while Gerber-Mann, Tanaka, Rule and Kawasaki formulas had a P30 < 65%. CONCLUSIONS: Walser, Ix and Huidobro equations had the best performance to estimate UCr/24h excretion in a population of latinamerican origin.

[Comparison of different methods to estimate glomerular filtration rate in older adults]. / ¿Son equivalentes los diferentes métodos para estimar la función renal en los adultos mayores?

BACKGROUND: Glomerular filtration rate (GFR) estimation in older adults using a creatinine clearance/24-hour (CrCl) or an equation based on serum creatinine, are often considered equivalent by clinicians. AIM: To compare GFR estimated (eGFR) with the available equations and measured CrCl in patients ≥ 70 years. A secondary aim was to know the differences in chronic kidney disease (CKD) classification, when using the different eGFR formulas. PATIENTS AND METHODS: In 144 patients aged 77 ± 5 years (58% men), CrCl was measured and GFR was estimated using MDRD, CKD-EPI, BIS-1 and FAS formulas. The eGFR and the stage of CKD were compared according to the different equations used. RESULTS: GFR estimated by MDRD and CKD-EPI equations was 7.8 and 8.4 mL/min/1.73 m2 lower than 24-hour ClCr, respectively. This difference was even greater using the BIS-1 and FAS equations. Twenty-four-hour CrCl classified 47.2% of the patients in a category of renal function > 60 mL/min/1.73 m2, while MDRD and CKD-EPI equations classified just over a third, and BIS-1 and FAS formulas around 20% of the patients. CONCLUSIONS: The practice of considering equivalent the GFR estimation using the creatinine-based equations with measured creatinine clearance in older adults should be reconsidered, because their results differ markedly.

[Performance of formulas for the evaluation of 24-hour urine collections using urine creatinine excretion]. / Evaluación de la recolección de orina de 24 horas a partir de la creatininuria: fórmulas para estimarla y su rendimiento.

Creatinine excretion is widely used as a method to evaluate the adequacy of urine collection in different clinical settings. Many factors influence its elimination, such as protein intake, exercise, muscle mass, age, and sex, among many others. As 24-hour urine collections can be cumbersome, several equations have been developed to aid clinicians to correctly interpret results derived from them. In this review article, we report the factors that can modify creatinine excretion and we evaluate the accuracy of different published equations to estimate 24-hour urine creatinine excretion.

A report of congenital adrenal hyperplasia due to 17α-hydroxylase deficiency in two 46,XX sisters.

Congenital adrenal hyperplasia (CAH) is a group of rare orphan disorders caused by mutations in seven different enzymes that impair cortisol biosynthesis. The 17α-hydroxylase deficiency (17OHD) is one of the less common forms of CAH, corresponding to approximately 1% of the cases, with an estimated annual incidence of 1 in 50,000 newborns. Cases description - two phenotypically female Ecuadorian sisters, both with primary amenorrhea, absence of secondary sexual characteristics, and osteoporosis. High blood pressure was present in the older sister. Hypergonadotropic hypogonadism profile was observed: decreased cortisol and dehydroepiandrosterone sulfate (DHEAS), increased adrenocorticotropic hormone (ACTH) and normal levels of 17-hydroxyprogesterone, extremely high deoxycorticosterone (DOC) levels, and a tomography showed bilateral adrenal hyperplasia in both sisters. Consanguinity was evident in their ancestors. Furthermore, in the exon 7, the variant c.1216T > C, p.Trp406Arg was detected in homozygosis in the CYP17A1 gene of both sisters. We report a homozygous missense mutation in the CYP17A1 gene causing 17OHD in two sisters from Loja, Ecuador. According to the authors, this is the first time such deficiency and mutation are described in two members of the same family in Ecuador.

[C1q nephropathy. Report of one case]. / Nefropatía por C1q: una rara variedad de síndrome nefrótico. Caso clínico.

C1q nephropathy is a rare glomerulopathy characterized by mesangial deposition of the complement component C1q. These deposits can be isolated or associated with immunoglobulins or complement fractions, which are observed by immunofluorescence or immunohistochemical microscopy. In ultramicroscopy, dense mesangial deposits and alterations of the podocyte are observed. Clinically it presents as a nephrotic syndrome (NS) or by alterations of the urinalysis such as proteinuria and/or hematuria in children and young adults. In light microscopy, it is expressed with a morphological pattern of minimal change disease (MCD), mesangial proliferative glomerulonephritis or focal segmental glomerulosclerosis (FSGS). The NS during its evolution usually evolve in steroid resistance or steroid dependency, often requiring the association of immunosuppressants to obtain remission. We report a 14 years old male with a history of NS and its evolution under various treatments during a 12-year follow-up.

Thyroid Cancer in Ecuador, a 16 years population-based analysis (2001-2016).

BACKGROUND: Thyroid cancer is the most frequent endocrine neoplasia worldwide. Information from Andean countries is scarce. In Ecuador there is no reports available of the epidemiology of this type of cancer. The aim of this study is to present the epidemiology and the burden of disease of thyroid cancer. METHODS: This is a cross-sectional population-based analysis of thyroid cancer epidemiology in Ecuador from 2001 to 2016. The variables studied were the overall mortality rate, socio-demographics characteristics of the hospitalized patients, geographical trends and the burden of thyroid cancer in Ecuador. All the data was obtained from the official records reported by the Ministry of Public Health's and retrieved from the public databases of the Vital Statistics Deaths and Births Databases and the National Institute of Census and Statistics (INEC). RESULTS: In Ecuador, over a period of 16 years from 2001 to 2016 a total of 23,632 hospital admissions were reported, which caused 1539 deaths due thyroid cancer. Data demonstrated an annual mean of 1477 cases, which caused 96 deaths per year in average. The annual incidence fluctuated from 3 in 2001 to 22 in 2016 per 100,000 inhabitants. Women were 5 times more likely than men to have thyroid cancer. The average length of stay for both sexes were 4 days. The mortality attributable to thyroid cancer represent less than 0.3% of all cancer deaths. CONCLUSION: Ecuador has one of the highest rates of thyroid cancer in Latin America, ranking first among women in Latin America. Although this cancer is frequent, mortality rate is relatively low. As this is the first national report of thyroid cancer in the country, a further analysis of the pathological variants and the grading of this neoplasia is needed.

[Triple expressor lymphoma in a kidney transplant patient]. / Evolución de un linfoma no Hodgkin "triple expresor" en un paciente trasplantado renal con quimioterapia DA-R-EPOCH. Caso clínico.

Patients transplanted from solid organs have an increased risk of cancer, especially lymphomas. Lymphomas correspond to 4 to 5% of malignant neoplasms in the general population and in solid organ transplant patients it reaches an incidence of 21%. The incidence of non-Hodgkin lymphomas is 10 times higher than in the non-transplanted population. We report the case of a 68-year-old man with a kidney transplant who 6 years after transplantation, developed a non-Hodgkin diffuse large cells B lymphoma with lymph node and pulmonary involvement, with markers of very poor prognosis (triple MYC expressor, BCL2 and BCL6). and its evolution with chemotherapy with DA R EPOCH.

[Renal functional reserve. Concept and potential application in clinical practice]. / Reserva funcional renal. Concepto y aplicabilidad potencial en la práctica clínica.

Renal functional reserve (RFR) is the capacity of the kidney to increase its glomerular filtration rate (GFR) in response to physiological or pathological stimuli. The most commonly used stimuli to assess this reserve are an oral load of proteins of animal origin, amino acid infusions, dopamine, glucagon or combinations of them. RFR is calculated as the difference between stimulated and baseline GFR. Vegetarians have lower baseline GFR than the general population and an increased RFR. Subjects with only one kidney and those suffering from chronic nephropathies usually have a reduced or absent RFR despite having normal basal GFR. Quantification of RFR may be useful to detect subclinical renal damage, physiological conditions that reduce baseline GFR, evaluation of potential donors for kidney transplantation, suspected hyperfiltration, detection of renal lability against acute injuries or pregnancy and the evaluation after an acute renal injury when renal function seems to be recovered and residual subclinical damage is suspected.

[Effects of creatine supplementation on renal function]. / Efectos en la función renal de la suplementación de creatina con fines deportivos.

Creatine supplements may transitorily rise serum creatinine levels and mimic a kidney disease. If its use is associated with a high protein diet, the resulting increase in blood urea nitrogen will increase the confusion. Since clinical laboratories usually inform the estimated glomerular filtration rate based on serum creatinine, its elevation may lead to over diagnose a chronic renal failure, with the inherent personal and public health consequences. Creatine supplements are safe and do not cause renal disease. Reports of kidney damage associated with its use are scanty. However, creatine supplements should not be used in people with chronic renal disease or using potentially nephrotoxic medications.