Pediatric chronic kidney disease mortality in Brazil-A time trend analysis.

Chronic kidney disease (CKD) is defined based on structural or functional abnormalities of the kidneys, or a glomerular filtration rate (GFR) below the threshold of 60 ml/min per 1.73 m2 for more than 3 months. It is an important noncommunicable disease with a rising worldwide, becoming a global public health problem. There are few studies about this problem, especially in low- and middle-income countries (LMIC), including Brazil, an upper-middle-income country. The objective of the study was to determine the cause-specific mortality rates for pediatric CKD patients (CKDMR) from 0 to 19 years old, based on the 10th revision of the International Classification of Diseases (ICD-10) and the Global Burden of Diseases Injuries and Risk Factors Study's (GBD) list. We calculated the impact of the annual human development indexes (HDI) in CKDMR in Brazil and its regions at two different times and compared it with the literature results. We obtained data from the Department of Informatics of the Brazilian Unified Health System (DATASUS) from 1996 to 2017. The Joinpoint regression analyses estimated the average annual percentage changes (AAPCs). The correlation between the HDI values and the number of deaths from each age group in Brazil and its different regions were assessed using the time series autoregressive integrated moving average (ARIMA) models. There were 8838 deaths in a pediatric and adolescent population of about 1.485 x 109 person-years observed in Brazil from 1996 to 2017. Our results demonstrated a significant increase in the AAPC in Brazil's less than 1-year-old age group and a decrease in children from 5 to 19 years old. We observed a positive correlation between CKDMR and HDI among children under 1 year of age. Conversely, there is a negative association in the age groups ranging from 5 to 19 years, indicating an inverse relationship between CKDMR and HDI.

Bone marrow mononuclear cells attenuate interstitial fibrosis and stimulate the repair of tubular epithelial cells after unilateral ureteral obstruction.

The growing number of patients suffering from chronic renal disease is a challenge for the development of innovative therapies. Benefits of cell therapy in acute renal diseases in animal models have been reported but seldom for chronic lesions. We present evidence for the improvement of renal morphology in a model of tubulointerstitial fibrosis. Wistar rats were submitted to unilateral ureteral obstruction (UUO), treated with bone-marrow mononuclear cells (UUO+BMMC) infused via the cava vein, and killed on day 14. Labeled BMMC were seen in renal tissue after 7 days in the group UUO+BMMC. UUO+BMMC also showed a reduction in ED1(+) cells and tubular apoptotic cells together with enhanced tubular proliferation. Myofibroblasts were also reduced after BMMC which is consistent with a decrease in collagen deposition (picro Sirius staining) and RT-PCR data showing lower levels of procollagen-I mRNA. Simultaneously, nestin+ cells increased in the interstitium and decreased in the tubules. Double stained nestin(+)/alpha-SMA(+) cells were present only in the interstitium, and their levels did not change after BMMC infusion. These data indicate a renoprotective effect of BMMC through increased tubular cell regeneration, inhibition of tubular cell apoptosis and partially blocking of the inflammatory and fibrotic events that occur after unilateral ureteral obstruction.

The protective role of fucosylated chondroitin sulfate, a distinct glycosaminoglycan, in a murine model of streptozotocin-induced diabetic nephropathy.

BACKGROUND: Heparanase-1 activation, albuminuria, and a decrease in glomerular heparan sulfate (HS) have been described in diabetic nephropathy (DN). Glycosaminoglycan (GAG)-based drugs have been shown to have renoprotective effects in this setting, although recent trials have questioned their clinical effectiveness. Here, we describe the effects of fucosylated chondroitin sulfate (FCS), a novel GAG extracted from a marine echinoderm, in experimentally induced DN compared to a widely used GAG, enoxaparin (ENX). METHODS: Diabetes mellitus (DM) was induced by streptozotocin in male Wistar rats divided into three groups: DM (without treatment), FCS (8 mg/kg), and ENX (4 mg/kg), administered subcutaneously. After 12 weeks, we measured blood glucose, blood pressure, albuminuria, and renal function. The kidneys were evaluated for mesangial expansion and collagen content. Immunohistochemical quantifications of macrophages, TGF-ß, nestin and immunofluorescence analysis of heparanase-1 and glomerular basement membrane (GBM) HS content was also performed. Gene expression of proteoglycan core proteins and enzymes involved in GAG assembly/degradation were analyzed by TaqMan real-time PCR. RESULTS: Treatment with GAGs prevented albuminuria and did not affect the glucose level or other functional aspects. The DM group exhibited increased mesangial matrix deposition and tubulointerstitial expansion, and prevention was observed in both GAG groups. TGF-ß expression and macrophage infiltration were prevented by the GAG treatments, and podocyte damage was halted. The diabetic milieu resulted in the down-regulation of agrin, perlecan and collagen XVIII mRNAs, along with the expression of enzymes involved in GAG biosynthesis. Treatment with FCS and ENX positively modulated such changes. Heparanase-1 expression was significantly reduced after GAG treatment without affecting the GBM HS content, which was uniformly reduced in all of the diabetic animals. CONCLUSIONS: Our results demonstrate that the administration of FCS prevented several pathological features of ND in rats. This finding should stimulate further research on GAG treatment for this complication of diabetes.