Forty-two consecutive patients with leptospirosis and acute lung injury who were mechanically ventilated were analyzed in a prospective cohort study. Nineteen patients (45%) survived, and 23 (55%) died. Multivariate analysis revealed that 3 variables were independently associated with mortality: hemodynamic disturbance (odds ratio [OR], 6.0; 95% confidence interval [CI], 0.9-38.8; P=. 047), serum creatinine level >265.2 micromol/L (OR, 10.6; 95% CI, 0. 9-123.7; P =.026), and serum potassium level >4.0 mmol/L (OR, 19.9; 95% CI, 1.2-342.8; P=.009). These observations can be used to identify factors associated with mortality early in the course of severe respiratory failure in leptospirosis.

In this study, p21(-/-) mice were more susceptible to ischemia-induced acute renal failure, with similarly elevated levels of parameters of cell cycle activity. We propose that the increased and inappropriate cell cycle activity in kidney cells is responsible for the increased kidney impairment and mortality.

Sepsis is the leading cause of death in intensive care units. Although many different treatments for sepsis have been tested, sepsis-related mortality rates remain high. It was hypothesized in this study that treatment with human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) would protect renal, hepatic, and endothelial function in a model of sepsis in rats. Treatment with WJ-MSCs improved the glomerular filtration rate, improved tubular function, decreased expression of nuclear factor κB and of cytokines, increased expression of eNOS and of Klotho, attenuated renal apoptosis, and improved survival. Sepsis-induced acute kidney injury is a state of Klotho deficiency, which WJ-MSCs can attenuate.

BackgroundDespite a significant improvement in the management of chronic kidney disease (CKD), its incidence and prevalence has been increasing over the years. Progressive renal fibrosis is present in CKD and involves the participation of several cytokines, including Transforming growth factor-β1 (TGF-β1). Besides cardiovascular diseases and infections, several studies show that Vitamin D status has been considered as a non-traditional risk factor for the progression of CKD. Given the importance of vitamin D in the maintenance of essential physiological functions, we studied the events involved in the chronic kidney disease progression in rats submitted to ischemia/reperfusion injury under vitamin D deficiency (VDD).MethodsRats were randomized into four groups: Control; VDD; ischemia/reperfusion injury (IRI); and VDD+IRI. At the 62 day after sham or IRI surgery, we measured inulin clearance, biochemical variables and hemodynamic parameters. In kidney tissue, we performed immunoblotting to quantify expression of Klotho, TGF-β, and vitamin D receptor (VDR); gene expression to evaluate renin, angiotensinogen, and angiotensin-converting enzyme; and immunohistochemical staining for ED1 (macrophages), type IV collagen, fibronectin, vimentin, and α-smooth mucle actin. Histomorphometric studies were performed to evaluate fractional interstitial area.ResultsIRI animals presented renal hypertrophy, increased levels of mean blood pressure and plasma PTH. Furthermore, expansion of the interstitial area, increased infiltration of ED1 cells, increased expression of collagen IV, fibronectin, vimentin and α-actin, and reduced expression of Klotho protein were observed. VDD deficiency contributed to increased levels of plasma PTH as well as for important chronic tubulointerstitial changes (fibrosis, inflammatory infiltration, tubular dilation and atrophy), increased expression of TGF-β1 and decreased expression of VDR and Klotho protein observed in VDD+IRI animals.ConclusionThrough inflammatory pathways and involvement of TGF-β1 growth factor, VDD could be considered as an aggravating factor for tubulointerstitial damage and fibrosis progression following acute kidney injury induced by ischemia/reperfusion.

Background: Leptospirosis is a public health problem, the severe form of which (Weil's disease) includes acute respiratory distress syndrome, typically accompanied by acute kidney injury (AKI), and is associated with high mortality rates. Recent evidence suggests that dialysis dosage affects outcomes in critically ill patients with sepsis-induced AKI. However, this population varies widely in terms of age, gender, and concomitant conditions, making it difficult to determine the appropriate timing (door-to-dialysis time) and dialysis dosage.Design, setting, participants, and measurements: It is logical to assume that increasing the dialysis dosage would minimize uremic complications and improve outcomes in such patients. Patients with Weil's disease constitute a homogeneous population and are typically free of comorbidities, therefore presenting an ideal model in which to test this assumption.Results Conclusions: On the basis of this result, it is believed that alternate-day hemodialysis is no longer appropriate for critically ill patients with Weil's disease.

In chronic renal failure patients, the improvement in renal function induced by post-radiocontrast administration of N-acetylcysteine is strongly associated with suppression of oxidant stress-mediated proximal tubular injury.

Background Chronic kidney disease (CKD) is a public health problem worldwide, and proteinuria is a well-established marker of disease progression in CKD patients. Propolis, a natural resin produced by bees from plant materials, has anti-inflammatory, immunomodulatory, and anti-oxidant properties, as well as having been shown to have an antiproteinuric effect in experimental CKD. The aim of this study was to evaluate the impact of Brazilian green propolis extract on proteinuria reduction and the changes in the estimated glomerular filtration rate (eGFR). Methods This was a randomized, double-blind, placebo-controlled study including patients with CKD caused by diabetes or of another etiology, 18–90 years of age, with an eGFR of 25–70 ml/min per 1.73 m 2 and proteinuria (urinary protein excretion > 300 mg/day) or micro- or macro-albuminuria (urinary albumin-to-creatinine ratio > 30 mg/g or > 300 mg/g, respectively). We screened 148 patients and selected 32, randomly assigning them to receive 12 months of Brazilian green propolis extract at a dose of 500 mg/day ( n = 18) or 12 months of a placebo ( n = 14). Results At the end of treatment, proteinuria was significantly lower in the propolis group than in the placebo group—695 mg/24 h (95% CI, 483 to 999) vs. 1403 mg/24 h (95% CI, 1031 to 1909); P = 0.004—independent of variations in eGFR and blood pressure, which did not differ between the groups during follow-up. Urinary monocyte chemoattractant protein-1 was also significantly lower in the propolis group than in the placebo group—58 pg/mg creatinine (95% CI, 36 to 95) vs. 98 pg/mg creatinine (95% CI, 62 to 155); P = 0.038. Conclusions Brazilian green propolis extract was found to be safe and well tolerated, as well as to reduce proteinuria significantly in patients with diabetic and non-diabetic CKD. Trial Registration. ( ClinicalTrials.gov number NCT02766036. Registered: May 9, 2016). Electronic supplementary material The online version of this article (10.1186/s12882-019-1337-7) contains supplementary material, which is available to authorized users.

BackgroundMesenchymal stromal cells (MSCs) represent an option for the treatment of acute kidney injury (AKI). It is known that young stem cells are better than are aged stem cells at reducing the incidence of the senescent phenotype in the kidneys. The objective of this study was to determine whether AKI leads to premature, stress-induced senescence, as well as whether human umbilical cord-derived MSCs (huMSCs) can prevent ischaemia/reperfusion injury (IRI)-induced renal senescence in rats.MethodsBy clamping both renal arteries for 45 min, we induced IRI in male rats. Six hours later, some rats received 1 × 106 huMSCs or human adipose-derived MSCs (aMSCs) intraperitoneally. Rats were euthanised and studied on post-IRI days 2, 7 and 49.ResultsOn post-IRI day 2, the kidneys of huMSC-treated rats showed improved glomerular filtration, better tubular function and higher expression of aquaporin 2, as well as less macrophage infiltration. Senescence-related proteins (β-galactosidase, p21Waf1/Cip1, p16INK4a and transforming growth factor beta 1) and microRNAs (miR-29a and miR-34a) were overexpressed after IRI and subsequently downregulated by the treatment. The IRI-induced pro-oxidative state and reduction in Klotho expression were both reversed by the treatment. In comparison with huMSC treatment, the treatment with aMSCs improved renal function to a lesser degree, as well as resulting in a less pronounced increase in the renal expression of Klotho and manganese superoxide dismutase. Treatment with huMSCs ameliorated long-term kidney function after IRI, minimised renal fibrosis, decreased β-galactosidase expression and increased the expression of Klotho.ConclusionsOur data demonstrate that huMSCs attenuate the inflammatory and oxidative stress responses occurring in AKI, as well as reducing the expression of senescence-related proteins and microRNAs. Our findings broaden perspectives for the treatment of AKI.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0475-8) contains supplementary material, which is available to authorized users.