Relação entre as variações da impedância elétrica renal com alterações da taxa de filtração glomerular em cães

Records of the electrical impedance were obtained by means of surface electrodes placed on ventral and dorsal sides of the left kidney of anesthetized dogs. Changes of the renal electrical impedance resulted from alterations of the glomerular filtration rate caused by decrease of blood renal pressure to 80 and 50 mm Hg either due to constriction of the aorta or bleeding. The relation was established also by using physiological infusion. The results showed that changes of the means of renal electrical impedance were in opposite direction to changes in glomerular filtration rate. The electrodes employed were constituted of two parts: one fixed and another adjustable and flexible, allowing good contact with the renal surface independent of the kidney size.

Avaliação tardia da função renal em doentes com paracoccidioidomicose tratados com anfotericina B por meio da determinação do ritmo de filtração glomerular com EDTA Cr51

A late survey of the renal function was performed in eighteen patients with paracoccidioidomycosis treated with amphotericin B, according to the glomerular filtration rate (RFG). The method was compartment analysis by single injection using EDTA Cr51, determined by its 'half biological life' and dosages of blood urea nitrogen and creatinine. The patients were seventeen males and one female. They were from 22 to 76 years old. Ten of these patients received 2 g of amphotericin B and eight of them received 4 g. There were no expressive difference between the two groups, taking into account age, dose in mg/kg of weight/day, time of conclusion of the treatment, urea, creatinine, glomerular filtration was smaller than the normal, and average of the half biological life of the EDTA Cr51 was large than the normal. The achieved results permitted us to consider that the amphotericin B determines deficit of renal function. However, by the present study, it hasn't been possible to affirm if the modifications are definitive.

Avaliação da função glomerular de cães sadios e nefropatas sob estimulação dopaminérgica

Dopamine is an endogenous compound widely used in intensive care. It has a broad spectrum of action, on the cardiovascular system and urinary tract. Increased glomerular filtration rate, renal blood flow and fractional excretion of sodium and phosphorus are expected renal effects in normal individuals, but are poorly explored in veterinary medicine. This study was conducted to evaluate the glomerular function of dogs with renal disease submitted to continuous infusion of dopamine. Different doses of dopamine were administered in healthy and nephropathic dogs. Laboratory evaluations of creatinine clearance and urinary protein/creatinine ratio were performed during and after treatments. Creatinine clearance showed dose-dependent increase in healthy dogs. In dogs with renal disease, the dose of 1μg/kg/min GFR increased slightly, without changing the urine P/C and blood pressure, while the dose of 3μg/kg/min increased urinary protein excretion.

Avaliação da taxa de filtração glomerular e excreção fracionada de eletrólitos de cães com doença renal crônica tratados com dimetilsulfóxido (DMSO)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Cistatina C e taxa de filtração glomerular em cirurgia cardíaca com circulação extracopórea

Pós-graduação em Bases Gerais da Cirurgia - FMB

Biomarcadores renais de lesão glomerular em pacientes submetidos à anestisia para cirurgia arterial

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Comparação entre as diferentes formas de avaliar a taxa da Filtração Glomerular na população idosa atendida no Centro de Atenção Integrada de Melhor Idade – CAIMI na cidade de Manaus

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Serum cystatin C is a sensitive early marker for changes in the glomerular filtration rate in patients undergoing laparoscopic surgery

OBJECTIVE: Pneumoperitoneum during laparoscopy results in transient oliguria and decreased glomerular filtration and renal blood flow. The presence of oliguria and elevated serum creatinine is suggestive of acute renal injury. Serum cystatin C has been described as a new marker for the detection of this type of injury. In this study, our aim was to compare the glomerular filtration rate estimated using cystatin C levels with the rate estimated using serum creatinine in patients with normal renal function who were undergoing laparoscopic surgery. METHODS: In total, 41 patients undergoing laparoscopic cholecystectomy or hiatoplasty were recruited for the study. Blood samples were collected at three time intervals: first, before intubation (T1); second, 30 minutes after the establishment of pneumoperitoneum (T2); and third, 30 minutes after deflation of the pneumoperitoneum (T3). These blood samples were then analyzed for serum cystatin C, creatinine, and vasopressin. The Larsson formula was used to calculate the glomerular filtration rate based on the serum cystatin C levels, and the Cockcroft-Gault formula was used to calculate the glomerular filtration rate according to the serum creatinine levels. RESULTS: Serum cystatin C levels increased during the study (T1 = T2T3; p<0.05). The calculated eGlomerular filtration rate-Larsson decreased, whereas the eGlomerular filtration rate-Cockcroft-Gault increased. There was no correlation between cystatin C and serum creatinine. Additionally, Pearson's analysis showed a better correlation between serum cystatin C and the eGlomerular filtration rate than between serum creatinine and the eGlomerular filtration rate. CONCLUSION: This study demonstrates that serum cystatin C is a more sensitive indicator of changes in the glomerular filtration rate than serum creatinine is in patients with normal renal function who are undergoing laparoscopic procedures.

Chronic VEGF Blockade Worsens Glomerular Injury in the Remnant Kidney Model

VEGF inhibition can promote renal vascular and parenchymal injury, causing proteinuria, hypertension and thrombotic microangiopathy. The mechanisms underlying these side effects are unclear. We investigated the renal effects of the administration, during 45 days, of sunitinib (Su), a VEGF receptor inhibitor, to rats with 5/6 renal ablation (Nx). Adult male Munich-Wistar rats were distributed among groups S+V, sham-operated rats receiving vehicle only; S+Su, S rats given Su, 4 mg/kg/day; Nx+V, Nx rats receiving V; and Nx+Su, Nx rats receiving Su. Su caused no change in Group S. Seven and 45 days after renal ablation, renal cortical interstitium was expanded, in association with rarefaction of peritubular capillaries. Su did not worsen hypertension, proteinuria or interstitial expansion, nor did it affect capillary rarefaction, suggesting little angiogenic activity in this model. Nx animals exhibited glomerulosclerosis (GS), which was aggravated by Su. This effect could not be explained by podocyte damage, nor could it be ascribed to tuft hypertrophy or hyperplasia. GS may have derived from organization of capillary microthrombi, frequently observed in Group Nx+Su. Treatment with Su did not reduce the fractional glomerular endothelial area, suggesting functional rather than structural cell injury. Chronic VEGF inhibition has little effect on normal rats, but can affect glomerular endothelium when renal damage is already present.

The IgA1 immune complex-mediated activation of the MAPK/ERK kinase pathway in mesangial cells is associated with glomerular damage in IgA nephropathy

IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide, has significant morbidity and mortality as 20-40% of patients progress to end-stage renal disease within 20 years of onset. In order to gain insight into the molecular mechanisms involved in the progression of IgAN, we systematically evaluated renal biopsies from such patients. This showed that the MAPK/ERK signaling pathway was activated in the mesangium of patients presenting with over 1 g/day proteinuria and elevated blood pressure, but absent in biopsy specimens of patients with IgAN and modest proteinuria (<1 g/day). ERK activation was not associated with elevated galactose-deficient IgA1 or IgG specific for galactose-deficient IgA1 in the serum. In human mesangial cells in vitro, ERK activation through mesangial IgA1 receptor (CD71) controlled pro-inflammatory cytokine secretion and was induced by large-molecular-mass IgA1-containing circulating immune complexes purified from patient sera. Moreover, IgA1-dependent ERK activation required renin-angiotensin system as its blockade was efficient in reducing proteinuria in those patients exhibiting substantial mesangial activation of ERK. Thus, ERK activation alters mesangial cell-podocyte crosstalk, leading to renal dysfunction in IgAN. Assessment of MAPK/ERK activation in diagnostic renal biopsies may predict the therapeutic efficacy of renin-angiotensin system blockers in IgAN. Kidney International (2012) 82, 1284-1296; doi:10.1038/ki.2012.192; published online 5 September 2012

The effects of PTK787/ZK222584, an inhibitor of VEGFR and PDGFR? pathways, on intussusceptive angiogenesis and glomerular recovery from Thy1.1 nephritis

The aim of our study was to investigate the phenomenon of intussusceptive angiogenesis with a focus on its molecular regulation by vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor β (PDGFRβ) pathways and biological significance for glomerular recovery after acute injury. Glomerular healing by intussusception was examined in a particular setting of Thy1.1 nephritis, where the lysis of mesangial cells results in an initial collapse and successive rebuilding of glomerular capillary structure. Restoration of capillary structure after induction of Thy1.1 nephritis occurred by intussusceptive angiogenesis resulting in i) rapid expansion of the capillary plexus with reinstatement of the glomerular filtration surface and ii) restoration of the archetypical glomerular vascular pattern. Glomerular capillaries of nephritic rats after combined VEGFR2 and PDGFRβ inhibition by PTK787/ZK222584 (PTK/ZK) were tortuous and irregular. However, the onset of intussusceptive angiogenesis was influenced only after long-term PTK/ZK treatment, providing an important insight into differential molecular regulation between sprouting and intussusceptive angiogenesis. PTK/ZK treatment abolished α-smooth muscle actin and tensin expression by injured mesangial cells, impaired glomerular filtration of microspheres, and led to the reduction of glomerular volume and the presence of multiple hemorrhages detectable in the tubular system. Collectively, treatment of nephritic patients with PTK/ZK compound is not recommended.

Podocyte EphB4 signaling helps recovery from glomerular injury

Eph receptor tyrosine kinases and their ligands (ephrins) have a pivotal role in the homeostasis of many adult organs and are widely expressed in the kidney. Glomerular diseases beginning with mesangiolysis can recover, with podocytes having a critical role in this healing process. We studied here the role of Eph signaling in glomerular disease recovery following mesangiolytic Thy1.1 nephritis in rats. EphB4 and ephrinBs were expressed in healthy glomerular podocytes and were upregulated during Thy1.1 nephritis, with EphB4 strongly phosphorylated around day 9. Treatment with NPV-BHG712, an inhibitor of EphB4 phosphorylation, did not cause glomerular changes in control animals. Nephritic animals treated with vehicle did not have morphological evidence of podocyte injury or loss; however, application of this inhibitor to nephritic rats induced glomerular microaneurysms, podocyte damage, and loss. Prolonged NPV-BHG712 treatment resulted in increased albuminuria and dysregulated mesangial recovery. Additionally, NPV-BHG712 inhibited capillary repair by intussusceptive angiogenesis (an alternative to sprouting angiogenesis), indicating a previously unrecognized role of podocytes in regulating intussusceptive vessel splitting. Thus, our results identify EphB4 signaling as a pathway allowing podocytes to survive transient capillary collapse during glomerular disease.

Persistent decline in estimated but not measured glomerular filtration rate on tenofovir may reflect tubular rather than glomerular toxicity

Tenofovir disoproxil fumarate (TDF) has been associated with proximal renal tubulopathy and reduction in estimated glomerular filtration rate (eGFR), without accounting for the tubular secretion of creatinine.

Fluid balance, glomerular filtration rate, and urine output in dogs anesthetized for an orthopedic surgical procedure

OBJECTIVE: To determine fluid retention, glomerular filtration rate, and urine output in dogs anesthetized for a surgical orthopedic procedure. ANIMALS: 23 dogs treated with a tibial plateau leveling osteotomy. PROCEDURES: 12 dogs were used as a control group. Cardiac output was measured in 5 dogs, and 6 dogs received carprofen for at least 14 days. Dogs received oxymorphone, atropine, propofol, and isoflurane for anesthesia (duration, 4 hours). Urine and blood samples were obtained for analysis every 30 minutes. Lactated Ringer's solution was administered at 10 mL/kg/h. Urine output was measured and glomerular filtration rate was estimated. Fluid retention was measured by use of body weight, fluid balance, and bioimpedance spectroscopy. RESULTS: No difference was found among control, cardiac output, or carprofen groups, so data were combined. Median urine output and glomerular filtration rate were 0.46 mL/kg/h and 1.84 mL/kg/min. Dogs retained a large amount of fluids during anesthesia, as indicated by increased body weight, positive fluid balance, increased total body water volume, and increased extracellular fluid volume. The PCV, total protein concentration, and esophageal temperature decreased in a linear manner. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs anesthetized for a tibial plateau leveling osteotomy retained a large amount of fluids, had low urinary output, and had decreased PCV, total protein concentration, and esophageal temperature. Evaluation of urine output alone in anesthetized dogs may not be an adequate indicator of fluid balance.

A comparison of measured and estimated glomerular filtration rate in successfully treated HIV-patients with preserved renal function

Monitoring of renal function becomes increasingly important in the aging population of HIV-1 infected patients. We compared Cockroft & Gault (C&G), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD), Cystatin C- and 24 h urine-based estimated GFR (eGFR) with the gold standard, measured GFR (mGFR) using [125I]-iothalamate.