Does creatine supplementation harm renal function?

Enquanto o consumo de creatina por atletas e praticantes de atividade física tem crescido vertiginosamente, os efeitos adversos desse suplemento continuam sendo alvos de calorosos debates científicos, sobretudo no que se refere à função renal. O objetivo dessa revisão é descrever as falhas metodológicas e lacunas na literatura, que contribuem para a divergência do tema. Relatos de caso sugerem que a creatina é um potencial agente nefrotóxico. Em contrapartida, estudos longitudinais, embora possuam diversas limitações, indicam o oposto. Pesquisas com humanos não demonstram efeitos deletérios da suplementação de creatina à função renal, porém a falta de controle experimental e o caráter retrospectivo da maioria delas comprometem as conclusões dos autores. Já os estudos experimentais com ratos empregam bons marcadores de função renal e possuem controle de variáveis satisfatório. Contudo, os resultados destes são contraditórios. Estudos futuros devem investigar os efeitos da suplementação de creatina em diversas patologias renais, assim como em idosos, diabéticos do tipo 2 e hipertensos, cuja propensão a nefropatia é bem descrita. Não há evidências de que a suplementação de creatina prejudique a função renal em sujeitos saudáveis, quando consumida na dosagem preconizada. Diante disso, questiona-se a legitimidade científica da proibição do comércio de creatina no Brasil.While creatine consumption has been greatly increasing among athletes and physical activity practitioners, the adverse effects of this supplement remain scientifically controversial, especially concerning renal function. The aim of this review is to describe the methodological limitations and gaps in the literature which contribute to the topic’s divergence. Case reports suggest that creatine is a nephrotoxic agent. On the other hand, despite having several limitations, longitudinal studies have indicated the opposite. Research with humans does not demonstrate any deleterious effects as a consequence of creatine supplementation; however, the absence of experimental control as well as their retrospective characteristics compromise the authors’ conclusion. Experimental studies with animal models though, use both gold standard for renal function and have satisfactory variable control. However, the results remain controversial. Future studies should investigate the effects of creatine supplementation in several kidneys diseases as well as in the elderly, type 2 diabetis and hypertensive individuals, whose tendency to renal dysfunction is well-described. There is not evidence that creatine supplementation causes renal deterioration in healthy subjects when it is ingested in the recommended dosage. Thus, we have some concerns about the sale prohibition of creatine supplementation in Brazil

Efeito da hipomagnesemia e da suplementação de magnésio sobre a insuficiência renal aguda pós-isquêmica

Hypothesis:The aim of this study is to verify the effect of hypomagnesemia and magnesium supplementation on postischemic renal failure. Methods: Five groups of male Wistar rats were studied: control; posthypomagnesemic;post-ischemic; postischemic + hypomagnesemia and post-ischemic + magnesium supplementation. Clearance and hemodynamic measurements were performed.Results: In postischemic rats, hypomagnesemia induces a marked decrease in GFR, RBF and increases the RVR. In rats with Magnesium supplementation increased GFR and decreased FeH2O were observed when compared with rats on a normaldiet.Conclusion: Hypomagnesemia potentiates postischemic renal failure and magnesium supplementation protectsagainst renal ischemia.Hipótese: Este trabalho visa avaliar os efeitos da hipomagnesemia e da suplementação de magnésio nainsuficiência renal aguda pós- isquêmica. Materiais e Métodos: Foram utilizados ratos machos Wistar, divididos emcinco grupos: controle, hipomagnesêmico, isquêmico, hipoMg+ isquêmico, suplementado + isq. Foi feito o estudo de clearance de inulina e a determinação de medidas funcionais. Resultados: A hipomagnesemia no contexto de uma isquemia renal levou a uma queda mais acentuada do RFG (Cin) e FSR e aumento da RVR. Nos animaissuplementados, houve um aumento dos valores de Cin e FeH2O. Conclusões: A hipomagnesemia na insuficiênciarenal aguda (IRA) potencializa os efeitos desta sobre a função renal. A suplementação de Magnésio protege parcialmente dos efeitos da IRA pós-isquêmica

Immunohistochemical detection of Lp25 and LipL32 proteins in skeletal and cardiac muscles of fatal human leptospirosis

Leptospirosis is an acute infection caused by pathogenic species of the genus Leptospira, which affects humans and animals in all world. In severe forms of the disease, kidneys, liver and lungs are the main affected organs, resulting in acute kidney injury, jaundice and pulmonary hemorrhage. Previous post-mortem studies have shown that lesions are not limited to these organs. Cardiac and striated muscle injuries have already been reported, but the pathophysiology of cardiac and skeletal lesions in leptospirosis is not fully understood. It has been suggested that the tissue damage observed in leptospirosis could be directly mediated by leptospires or by their toxic cellular components. LipL32 and Lp25 are leptospira membrane proteins with unknown functions, that are present only in pathogenic strains of Leptospira spp. Both proteins induce skeletal muscle lesions similar to those observed when normal guinea pigs are inoculated with leptospires. Through immunohistochemistry, this study showed the presence of LipL32 and Lp25 proteins on muscle cell membranes and in the underlying cytoplasm of skeletal muscles, as well as focal lesions in cardiac tissues of fatal cases of leptospirosis. Altogether, these results reinforce that both proteins can be important factors in the pathogenesis of leptospirosis

Oxidative Stress in Cystinosis Patients

Background/Aims: Nephropathic cystinosis (NC) is a severe systemic disease and cysteamine improves its prognosis. Lysosomal cystine accumulation is the hallmark of cystinosis and is regarded as the primary defect due to mutations in the CTNS gene. However, there is great evidence that cystine accumulation itself is not responsible for all abnormalities observed in NC. Studies have demonstrated altered ATP metabolism, increased apoptosis, and cell oxidation. An increased number of autophagosomes and autophagic vacuoles have been observed in cystinotic fibroblasts and renal epithelial cells, suggesting that altered autophagy plays a role in NC, leading to increased production of reactive oxygen species. Therefore, cystinosis patients can be more susceptible to oxidative stress (OS) and it can contribute to the progression of the renal disease. Our goal was to evaluate a marker of OS (serum TBARS) in NC children, and to compare the results with those observed in healthy controls and correlated with renal function parameters. Methods: The study included patients aged under 18 years, with good adherence to the treatment and out of renal replacement therapy. The following parameters were evaluated: serum creatinine, BUN, creatinine clearance estimated by stature and serum TBARS levels. Results: We selected 20 patients aged 8.0 ±3.6 years and observed serum TBARS levels of 4.03 ±1.02 nmol/ml. Serum TBARS levels in the 43 healthy controls, aged 7.4 ±1.1 years, were 1.60 ±0.04 nmol/ml. There was a significant difference between the plasma TBARS levels among the 2 groups (p Conclusion: An increased level of serum TBARS in patients with NC was observed and this abnormality was not correlated with the renal function status degree. This is the first report that shows increased oxidative stress in serum of NC patients

N-acetylcysteine attenuates the progression of chronic renal failure

N-acetylcysteine attenuates the progression of chronic renal failure.BackgroundLipid peroxidation impairs renal function. Aldosterone contributes to renal injury in the remnant kidney model. This study aimed to determine the effects of the antioxidant N-acetylcysteine (NAC) on renal function and aldosterone levels in chronic renal failure.MethodsAdult male Wistar rats were submitted to 5/6 nephrectomy or laparotomy (sham-operated) and received NAC (600 mg/L in drinking water, initiated on postoperative day 7 or 60), spironolactone (1.5 g/kg of diet initiated on postoperative day 7), the NAC-spironolactone combination or no treatment. Clearance studies were performed on postoperative days 21, 60, and 120.ResultsMean daily NAC and spironolactone ingestion was comparable among the treated groups. Mean weight gain was higher in NAC-treated rats than in untreated rats. A significant decrease in urinary thiobarbituric acid reactive substances (TBARS) concentrations, a lipid peroxidation marker, was observed in NAC-treated rats. By day 120, glomerular filtration rate (GFR), which dropped dramatically in untreated rats, was stable (albeit below normal) in NAC-treated rats, which also presented lower proteinuria, glomerulosclerosis index, and blood pressure, together with attenuated cardiac and adrenal hypertrophy. These beneficial effects, observed even when NAC was initiated on postnephrectomy day 60, were accompanied by a significant reduction in plasma aldosterone and urinary sodium/potassium ratio. The NAC-spironolactone combination lowered blood pressure and improved GFR protection.ConclusionThe NAC-spironolactone combination improves renal function more than does NAC alone. In the remnant kidney model, early or late NAC administration has a protective effect attributable to decreased plasma aldosterone and lower levels of lipid peroxidation

Tenofovir-induced renal and bone toxicity: report of two cases and literature review

Tenofovir Disoproxil Fumarate (TDF) is one of the drugs in the initial first-line antiretroviral regimen for the treatment of hepatitis B and HIV infections. Despite its effectiveness and few adverse effects, it is related to renal and bone toxicity. We described two cases of HIV-positive middle-aged women who had been using TDF for two and four years (cases 1 and 2, respectively) and were admitted to the emergency room. Case 1 presented with metabolic ileum and diffuse bone pain while case 2 presented with bilateral coxo-femoral pain after a fall from standing height. Both cases had similar laboratory tests: hyperchloremic metabolic acidosis, hypophosphatemia, hypokalemia, hypouricemia and elevated plasma creatinine. In urinary exams, there was evidence of renal loss of electrolytes, justifying the serum alterations, in addition to glucosuria and proteinuria. The bone pain investigation identified bone fractures and reduced bone mineral density, together with increased levels of parathyroid hormone, alkaline phosphatase and vitamin D deficiency. These two cases illustrate the spectrum of adverse renal and bone effects associated with TDF use. TDF was discontinued and treatment was focused on correcting the electrolyte disturbances and acidosis, in addition to controlling the bone disease through vitamin D and calcium supplementation. The renal changes found in both cases characterized the Fanconi’s syndrome, and occurred due to TDF toxicity to proximal tubule cells mitochondria. Bone toxicity occurred due to direct interference of TDF in bone homeostasis, in addition to vitamin D deficiency and phosphaturia resulting from tubulopathy. During the follow-up, both cases evolved with chronic kidney disease and in one of them, the Fanconi’s syndrome did not revert. We emphasize the need to monitor markers of bone metabolism and glomerular and tubular functions in patients using TDF

N-acetylcysteine (NAC) Protects Against Acute Kidney Injury (AKI) Following Prolonged Pneumoperitoneum in the Rat

Background. Acute kidney injury (AKI) following prolonged laparoscopy is a documented phenomenon. Carbon dioxide pneumoperitoneum induces oxidative stress. Previous experimental studies have shown that the antioxidant, N-acetylcysteine, protects the rat from AKI following ischemia-reperfusion. The aim of this study was to evaluate the effects of N-acetylcysteine (NAC) on rat renal function after prolonged pneumoperitoneum. Methods. Normal rats treated or not with NAC were submitted to abdominal CO2 insufflation of 10 mmHg, at short and long periods of time of 1 and 3 h, respectively, and evaluated at 24, 72 h, and 1 wk after deinsufflation. Glomerular filtration rate (GFR) was measured by inulin clearance and oxidative stress was evaluated by serum thiobarbituric acid reactive substances (TBARS) Results. No significant alterations in GFR were observed in normal animals submitted to the pneumoperitoneum of 1 h and evaluated after 24 h desufflation. With 3 h of pneumoperitoneum, a significant and progressive decrease in GFR occurred 24 and 72 h after desufflation with an increase in serum TBARS. GFR returned to normal levels a week later. In the NAC-treated rats, a complete protection against GFR drops was observed 24 and 72 h following 3 h of pneumoperitoneum associated with a decrease in TBARS. Conclusion. These results suggest that NAC protects against acute kidney injury following prolonged pneumoperitoneum. These findings have significant clinical implications. (C) 2012 Elsevier Inc. All rights reserved

Human hemorrhagic pulmonary leptospirosis: pathological findings and pathophysiological correlations.

Abstract\ud Background: Leptospirosis is a re-emerging zoonosis with protean clinical manifestations. Recently, the importance of\ud pulmonary hemorrhage as a lethal complication of this disease has been recognized. In the present study, five human\ud necropsies of leptospirosis (Weil‘s syndrome) with extensive pulmonary manifestations were analysed, and the antibodies\ud expressed in blood vessels and cells involved in ion and water transport were used, seeking to better understand the\ud pathophysiology of the lung injury associated with this disease.\ud Principal Findings: Prominent vascular damage was present in the lung microcirculation, with decreased CD34 and\ud preserved aquaporin 1 expression. At the periphery and even inside the extensive areas of edema and intraalveolar\ud hemorrhage, enlarged, apparently hypertrophic type I pneumocytes (PI) were detected and interpreted as a non-specific\ud attempt of clearence of the intraalveolar fluid, in which ionic transport, particularly of sodium, plays a predominant role, as\ud suggested by the apparently increased ENaC and aquaporin 5 expression. Connexin 43 was present in most pneumocytes,\ud and in the cytoplasm of the more preserved endothelial cells. The number of type II pneumocytes (PII) was slightly\ud decreased when compared to normal lungs and those of patients with septicemia from other causes, a fact that may\ud contribute to the progressively low PI count, resulting in deficient restoration after damage to the alveolar epithelial\ud integrity and, consequently, a poor outcome of the pulmonary edema and hemorrhage.\ud Conclusions: Pathogenesis of lung injury in human leptospirosis was discussed, and the possibility of primary noninflammatory\ud vascular damage was considered, so far of undefinite etiopathogenesis, as the initial pathological\ud manifestation of the disease