The hemolytic uremic syndrome as a complication of adriamycin nephropathy

Rats treated with two injections of adriamycin (week 0 and week 12) developed glomerusclerosis and severe tubulointerstitial lesions as described in the literature. In addition, a number of glomerular alterations were present. These included capillary loop dilation, insudation of eosinophilic material, necrosis, duplication of the glomerular basement membrane, severe mesangiolysis with disruption of the mesangial matrix and segmental double- contours. The renal arterioles and interlobular arteries showed endothelial cell swelling. The subendothelial space was infiltrated by fibrinoid material and there was intensive fibrinoid necrosis of the wall of both arteries and arterioles extending into the glomerular tuft. These alterations were very similar to those observed in the hemolytic uremic syndrome. This observation suggests that the two injections of adriamycin, with a long interval in between them, might induce renal lesions similar to those observed in the hemolytic uremic syndrome.

Effect of allopurinol in the course of adriamycin induced nephropathy

The role of superoxide in adriamycin-induced nephropathy (single dose; i.v. 3 mg/kg) has been studied by blocking superoxide synthesis through the administration of allopurinol (500 mg/L in drinking water). In Experiment I (EI), allopurinol administration was started 3 days prior to nephropathy induction and continued until day 14. In Experiment II (EII) allopurinol administration was started 2 weeks after nephropathy induction and was maintained until the end of the experiment (26 weeks). Affected glomeruli frequency and tubulointerstitial lesion index (TILI) were determined at Weeks 2 and 4 (EI) and Week 26 (EII). In EI, and 24 h mean proteinuria in the nephrotic control group (NCG-I) differed from that of the treated nephrotic group (TNG-I) at Week 1 (TNG = 33.3 ± 6.39 mg/24 h; NCG = 59.8 ± 6.3 mg/24 h; p < 0.05) and 2 (NCG-I = 80.0 ± 17.5 mg/24h; TNG-I = 49.1 ± 8.4 mg/24 h; p < 0.05). No glomerular alterations were observed and TILI medians were not different in both nephrotic groups at week 2 (NCG-I = 1+: TNG = 1+) and 4 (NCG = 4+; TNG = 4+). In EII, NCG-II and TNG-II presented different 24 h proteinuria values only at Week 6, (136.91 ± 22.23 mg/24 h ad 72.66 ± 10.72 mg/24 h, respectively; p < 0.05). Between nephrotic groups, there was no statistical difference in the median of affected glomeruli (CNG-II = 56%; TNG-II = 48% and TILI (NCG-II = 8+; TNG-II = 9+). Thus, allopurinol was associated with a transient reduction in proteinuria and it did not alter the progression of the nephropathy.

Influence of cholecalciferol (Vitamin D3) on the course of experimental systemic lupus erythematosus in F1 (NZBxW) mice

The course of systemic lupus erythematosus (SLE), an autoimmune disease, is markedly affected by hormones such as estrogen and prolactin. It is well known that heavy exposure to sunlight has deleterious effects on SLE, triggering episodes of the disease. Classical explanations for this occurrence suggest that UV radiation damages DNA, which becomes immunogenic, or induces exposure of the Ro antigen in keratinocytes. In recent years, it has been shown that vitamin D3 has important effects on the immune system. Thus, we proposed an alternative hypothesis, suggesting that UV radiation, by promoting vitamin D3 synthesis, could be a factor aggravating the course of SLE after exposure to sunlight. To test this hypothesis, we injected F1(NZBxW) mice, which are prone to developing SLE, with vitamin D3, and we demonstrated a worsening of the histopathological findings in the kidney. (C) 2000 Wiley-Liss, Inc.

Chronic renal failure in male and female rats

Gender influences the progression of chronic renal failure (CRF). We studied male (M) and female (F) Wistar rats for 90 days: castrated (CMc, n=7; CFc, n=6) and non castrated controls (CM, n=9; CF, n=6); castrated (CRFMc, n=8; CRFFc, n=6) and non castrated animals submitted to 5/6 nephrectomy (CRFM, n=13; CRFF, n=6). Data are expressed as mean ± SEM. Proteinuria (PTN) was higher in CRFM (554 ± 69mg/24h) compared to CRFMc (277 ± 85 mg/24h), but not in females (CRFF=193 ± 20mg/24h, CRFFc=164 ± 71mg/24h). Mesangial fractional volume increased in all CRF animals. CRF animals showed an increase of glomerular sclerosis index (GSI) and tubulointerstitial damage (TID) but in a smaller proportion in male castrated animals; the opposite occurred with females: castration induced an increase of these parameters. CRF animals showed increased cortical and glomerular fibronectin (FN) rates. Castration decreased glomerular and cortical FN rates in CRFM but not in females. In conclusion, proteinuria was higher in CRFM and probably led to glomerular and interstitial damage, as well as to FN accumulation, castration seems to protect against development of PTN, TID and FN accumulation in males. Castrated female rats presented mesangial expansion, with no changes in PTN, TID and FN rates. It seems that female sex hormones do not protect against renal disease progression, instead, we suggest that male sex hormones lead to acceleration of CRF.

Maternal undernutrition and the offspring kidney: from fetal to adult life

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Bothrops leucurus venom induces nephrotoxicity in the isolated perfused kidney and cultured renal tubular epithelia

Bites from snake (Bothrops genus) cause local tissue damage and systemic complications, which include alterations such as hemostatic system and acute renal failure (ARF). Recent studies suggest that ARF pathogenesis in snakebite envenomation is multifactorial and involves hemodynamic disturbances, immunologic reactions and direct nephrotoxicity. The aim of the work was to investigate the effects of the Bothrops leucurus venom (BlV) in the renal perfusion system and in cultured renal tubular cells of the type MDCK (Madin-Darby Canine kidney). BlV (10 μg/mL) reduced the perfusion pressure at 90 and 120 min. The renal vascular resistance (RVR) decreased at 120 min of perfusion. The effect on urinary flow (UF) and glomerular filtration rate (GFR) started 30 min after BlV infusion, was transient and returned to normal at 120 min of perfusion. It was also observed a decrease on percentual tubular transport of sodium (%TNa+) at 120 min and of chloride (%TCl-) at 60 and 90 min. The treatment with BlV caused decrease in cell viability to the lowest concentration tested with an IC50 of 1.25 μg/mL. Flow cytometry with annexin V and propidium iodide showed that cell death occurred predominantly by necrosis. However, a cell death process may involve apoptosis in lower concentrations. BlV treatment (1.25 μg/mL) led to significant depolarization of the mitochondrial membrane potential and, indeed, we found an increase in the expression of cell death genes in the lower concentrations tested. The venom also evoked an increase in the cytosolic Ca2+ in a concentration dependent manner, indicating that Ca2+ may participate in the venom of B. leucurus effect. The characterization of the effects in the isolated kidney and renal tubular cells gives strong evidences that the acute renal failure induced by this venom is a result of the direct nephrotoxicity which may involve the cell death mechanism. © 2012.

Chaunus ictericus (Spix, 1824) as paratenic host of the giant kidney worm Dioctophyme renale (Goeze, 1782) (Nematoda: Enoplida) in Sao Cristovao district, Tres Barras county, Santa Catarina state, Brazil

Dioctophyme renale larvae have been found in cysts in the gastric wall of 5.17% (3/58) Chaunus ictericus specimens from Sao Cristovao district, Tres Barras municipality, Santa Catarina state, Brazil. However, larvae of this nematode were not found in sympatric Chaunus schneideri. The larvae caused a mild granulomatous reaction. This is the first report of paratenic hosts for D. renale in Brazil, and probably is also the first in the Neotropical region. (C) 2009 Elsevier B.V. All rights reserved.

Nutritional evaluation of stage 5 chronic kidney disease patients on dialysis

CONTEXTO E OBJETIVO: Portadores de insuficiência renal crônica em diálise apresentam alta prevalência de desnutrição proteico-energética. Não existe ainda um método uniforme para avaliar o estado nutricional desses pacientes. Recomenda-se a aplicação de um conjunto de métodos subjetivos e objetivos para se chegar aos diagnósticos nutricionais adequados. O objetivo deste estudo é traçar o perfil nutricional de pacientes submetidos a hemodiálise. TIPO DE ESTUDO E LOCAL: Estudo transversal descritivo realizado na Unidade de Tratamento Dialítico de Araraquara, São Paulo, Brasil, em 2008. MÉTODOS: 48 pacientes tiveram seus indicadores antropométricos e bioquímicos caracterizados, sendo também submetidos ao questionário Avaliação Global Subjetiva modificada (SGAm), verificando-se possíveis correlações entre esses indicadores. RESULTADOS: A frequência de desnutrição moderada e grave variou de 22% a 54%, de acordo com o parâmetro utilizado. Com relação à adequação do peso ideal, 29% da amostra estavam com porcentagem de adequação abaixo do percentil 75, classificados como portadores de desnutrição moderada e grave. As correlações mais significativas foram observadas entre índice de massa corporal (IMC) e adequações de prega triciptal (PCT), circunferência do braço (CB) e circunferência muscular do braço (CMB); e entre o SGAm e adequações de CB e CMB. CONCLUSÃO: A desnutrição apresentou grande variabilidade de frequência entre os pacientes de acordo com o critério escolhido para avaliação. O acompanhamento nutricional de rotina e a validação de métodos que avaliem a composição corporal desses pacientes são de extrema importância para diagnosticar precocemente a desnutrição e assim prevenir complicações e reduzir as taxas de morbimortalidade nesta população.

Caffeic Acid Phenethyl Ester Effects in the Kidney During Ischemia and Reperfusion in Rats Anesthetized with Isoflurane

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of haematocrit on pump and kidney dysfunction after myocardial revascularization

Objective - Kidney dysfunction is a common complication after cardiac surgery. It occurs in 7 to 31% of the patients. The lowest haematocrit after cardiopulmonary bypass surgery (LHCT) has been identified as a risk factor for kidney dysfunction after cardiac surgery. The aim of this study is to determine whether different levels of haematocrit during cardiopulmonary bypass surgery are related to kidney dysfunction.Methods and results-A prospective study was conducted on consecutive adult patients undergoing myocardial revascularization. Preoperative renal function was assessed by baseline serum creatinine level (CrPre). Peak postoperative creatinine (CrPost) was defined as the highest daily in-hospital postoperative value. Peak fractional change in creatinine (% Delta Cr) was defined as the difference between the CrPre and CrePost represented as a percentage of the preoperative value. The LHTC was defined as the lowest recorded haematocrit prior to weaning from the initial pump run. A category variable was created for haematocrit based on the distribution of values. The category variable had the following cut-off points: less than 23%, 23.1 to 28% and greater than 28.1 %. Lowest haematocrit (26.62 +/- 4.15%), CPB (74.71 +/- 24.90 min), CrPre (1.23 +/- 0.37 mg/dl) and highest CrPost (1.52 +/- 0.47 mg/dl) data varied in near-normal fashion. Statistical significance has been observed in the < 23% lowest haematocrit group (CrIPOD and Cr5POD; P = 0.006) and the 23.1 28% lowest haematocrit level group (CrPre and Cr2POD; P = 0.047). CrPre and Cr5POD did not differ between groups (P > 0.05). The multiple linear regression model confirmed that the determinants for higher %Delta Cr were age, body surface area and preoperative serum creatinine level.Conclusion - The LHTC was not identified as a risk factor for kidney dysfunction after myocardial revascularization.

Early initiation of dialysis: mortality and renal function recovery in acute kidney injury patients

INTRODUÇÃO: A decisão de quando iniciar a diálise em pacientes com lesão renal aguda (LRA) que apresentam síndrome urêmica está bem estabelecida, entretanto, com ureia < 200 mg/dl o melhor momento para iniciar a diálise torna-se incerto. OBJETIVO: Este estudo teve como objetivo avaliar a mortalidade e a recuperação da função renal em pacientes com LRA, cujo início da diálise ocorreu em diferentes níveis de ureia. MÉTODOS: Estudo retrospectivo desenvolvido em hospital escola, no estado de São Paulo, Brasil, envolvendo 86 pacientes submetidos à diálise. RESULTADOS: A diálise foi iniciada com uréia > 150 mg/dl em 23 pacientes (grupo I) e uréia > 150 mg/dl em 63 pacientes (grupo II). Hipervolemia e mortalidade foram mais frequentes no grupo I que no grupo II (65,2 x 14,2% - p < 0,05; 39,1 x 68,9% - p < 0,05, respectivamente). Entre os sobreviventes, a recuperação renal foi maior no grupo I (71,4 e 36,8%, respectivamente, p < 0,05). A análise multivariada mostrou risco independente de mortalidade relacionado à sepse, idade > 60 anos, diálise peritoneal e uréia > 150 mg/dl no início da diálise. CONCLUSÃO: Menor mortalidade e maior recuperação renal estão associadas com o diálise iniciada precocemente, conforme baixos níveis de ureia, em pacientes com LRA.

Can Delivery Dialysis Dose Affect Survival of Acute Kidney Injury Patients?

Intensity of dialysis dose in acute kidney injury (AKI) might benefit critically ill patients. The aim of this study was to evaluate the effect of intermittent hemodialysis (IHD) dose on mortality in patients with AKI. Methods: Prospective observational study was performed on AKI patients treated with IHD. The delivered dialysis dose per session was calculated based on single-pool Kt/V urea. Patients were allocated in two groups according to the weekly delivered median Kt/V: higher intensity dialysis dose (HID: Kt/V higher than median) and lower intensity dialysis dose (LID: Kt/V lower than median). Thereafter, AKI patients were divided according to the presence or absence of sepsis and urine output. Clinical and lab characteristics and survival of AKI patients were compared. Results: A total of 121 AKI patients were evaluated. Forty-two patients did not present with sepsis and 45 did not present with oliguria. Mortality rate after 30 days was lower in the HID group without sepsis (14.3% x 47.6%; p = 0.045) and without oliguria (31.8% x 69.5%; p = 0.025). Survival curves also showed that the HID group had higher survival rate when compared with the LID group in non-septic and non-oliguric patients (p = 0.007 and p = 0.003, respectively). Conclusion: Higher dialysis doses can be associated with better survival of less seriously ill AKI patients.