Kidney injury and cell therapy: Preclinical study

The aim of this study is to show histological and immunofluorescence analysis of renal parenchyma of agoutis affected by gentamicin-induced renal disease after the infusion of bone marrow mononuclear cells (BMMC) stained with Hoechst (R). Nine agouti's males were divided into three groups: Test group (TG): renal disease by gentamicin induced (n = 3), cell therapy group (CTG): renal disease by gentamicin induced and BMMC infusion (n = 3), and control group (CG): nonrenal disease and BMMC infusion (n = 3). TG and CTG were submitted to the protocol of renal disease induction using weekly application of gentamicin sulfate for 4 months. CG and CTG received a 1 X 108 BMMC stained with Hoechst and were euthanized for kidney examination 21 days after BMMC injection and samples were collected for histology and immunofluorescence analysis. Histological analysis demonstrated typical interstitial lesions in kidney similarly to human disease, as tubular necrosis, glomerular destruction, atrophy tubular, fibrotic areas, and collagen deposition. We conclude that histological analysis suggest a positive application of agouti's as a model for a gentamicin inducing of kidney disease, beyond the immunofluorescence analysis suggest a significant migration of BMMC to sites of renal injury in CTG. Microsc. Res. Tech., 2012. (c) 2011 Wiley Periodicals, Inc.

Erythromycin versus neomycin in the treatment of hepatic encephalopathy in cirrhosis: A randomized double-blind study

Background: Hepatic encephalopathy (HE) is a severe complication in patients with hepatic cirrhosis, which causes numerous hospital admissions and deaths. Antibiotics are the best options in HE treatment, but head-to-head comparisons between these drugs are scarce. Erythromycin combines the antimicrobial effect and prokinetic properties in the same drug, but it has never been used in HE treatment. Our aim was to evaluate the efficacy of erythromycin as an HE treatment.Methods: We achieved a randomized controlled trial of adult patients with HE and hepatic cirrhosis admitted in our hospital. After randomization, the subjects received either erythromycin 250 mg or neomycin 1 g orally QID until hospital discharge or prescription of another antibiotic. All subjects were blindly evaluated every day towards quantifying clinical, neuropsychometric, hepatic and renal exams. Statistical analysis was employed to compare the groups and correlate the variables with hospitalization duration.Results: 30 patients were evaluated (15 treated with each drug). At hospital admission, the groups were homogeneous, but the erythromycin group subjects achieved a shorter hospitalization stay (p = 0.032) and a more expressive reduction in alanine aminotranspherase levels (p = 0.026). Hospitalization duration was positively correlated with C reactive protein levels measured previous to (p = 0.015) and after treatment (p = 0.01).Conclusions: In the sample evaluated erythromycin was associated with significant reductions in hospital stay and in alanine aminotranspherase values. Hospitalization time was positive correlated with C reactive protein levels measured before and after the treatments. © 2013 Romeiro et al.; licensee BioMed Central Ltd.

Frequency and clinical profile of patients with polycystic kidney disease in Southern Brazil

Background. Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic nephropathies, affecting one in every 800-1000 individuals in the worldwide general population and 5-10% of hemodialysis patients. Little data concerning the prevalence of ADPKD in Brazil are available. Thus, the aim of the present study was to investigate both the frequency and clinical profile of ADPKD among hemodialysis patients in south of Brazil. Methods. This cross-sectional study consisted of patients from 24 hemodialysis centers. Patients were screened for ADPKD by clinical, laboratorial, and image examination in medical records. Results. Of 1326 patients on hemodialysis in the south of Brazil that composed this study, 99 (7.5%) had polycystic kidney as primary cause for chronic renal failure. Comparisons between ADPKD and non-ADPKD patients revealed no differences regarding mean age, gender, and ethnicity. Conclusions. Our data revealed that ADPKD is prevalent among patients on hemodialysis in the south of Brazil. In addition, the clinical profile of ADPKD is similar to reported data from North America and Europe, putatively due to the similar ethnic composition mainly based on European descents.

Kidney function after left renal vein ligation in the dog

The ligature of the left renal vein is an alternative whenever this vessel is injured. The purpose of this study was to evaluate the capacity of the affluents of the left renal vein, proximal to the ligature, to maintain tissue vitality and function of the left kidney. Fifteen mongrel male dogs were divided in 3 groups of 5 dogs: Group I (control) - a laparotomy was performed, and the abdominal structures were only identified; Group II - the left renal vein was tied, close to vena cava; Group III - the same procedure as for Group II and a right nephrectomy. Blood urea nitrogen and serum creatinine levels were measured before the procedure, and every 3 days during 4 weeks in the postoperative period. Renal arteriography and an excretory urogram were performed on the animals that survived 60 days. Thereafter, or immediately after precocious death, the kidneys were removed for histological examination. All the animals of Group III died before two months (mean = 10.5 +-3.2 days), while the animals of Group II survived during that period. There was a complete exclusion of the left kidney in all dogs that underwent renal vein ligature. In the animals of Group II, the renal cortico-medullary limits could not be identified. At microscopy, the aspect was suggestive of nephrosclerosis. In the animals of Group III, the left kidney was enlarged, and a great amount of intravascular and intrapelvic blood clots were observed. At microscopy, extensive areas of necrosis, inflammatory infiltration, and hemorrhage were identified. In conclusion, the tributaries of the renal vein were not sufficient to maintain the tissue vitality and function of the left kidney after ligature of its main vein.

A soft computing approach to kidney diseases evaluation

Kidney renal failure means that one’s kidney have unexpectedly stopped functioning, i.e., once chronic disease is exposed, the presence or degree of kidney dysfunction and its progression must be assessed, and the underlying syndrome has to be diagnosed. Although the patient’s history and physical examination may denote good practice, some key information has to be obtained from valuation of the glomerular filtration rate, and the analysis of serum biomarkers. Indeed, chronic kidney sickness depicts anomalous kidney function and/or its makeup, i.e., there is evidence that treatment may avoid or delay its progression, either by reducing and prevent the development of some associated complications, namely hypertension, obesity, diabetes mellitus, and cardiovascular complications. Acute kidney injury appears abruptly, with a rapid deterioration of the renal function, but is often reversible if it is recognized early and treated promptly. In both situations, i.e., acute kidney injury and chronic kidney disease, an early intervention can significantly improve the prognosis.The assessment of these pathologies is therefore mandatory, although it is hard to do it with traditional methodologies and existing tools for problem solving. Hence, in this work, we will focus on the development of a hybrid decision support system, in terms of its knowledge representation and reasoning procedures based on Logic Programming, that will allow one to consider incomplete, unknown, and even contradictory information, complemented with an approach to computing centered on Artificial Neural Networks, in order to weigh the Degree-of-Confidence that one has on such a happening. The present study involved 558 patients with an age average of 51.7 years and the chronic kidney disease was observed in 175 cases. The dataset comprise twenty four variables, grouped into five main categories. The proposed model showed a good performance in the diagnosis of chronic kidney disease, since the sensitivity and the specificity exhibited values range between 93.1 and 94.9 and 91.9–94.2 %, respectively.

An assessment of chronic kidney diseases

Kidney renal failure means that one’s kidney have unexpectedlystoppedfunctioning,i.e.,oncechronicdiseaseis exposed, the presence or degree of kidney dysfunction and its progression must be assessed, and the underlying syndrome has to be diagnosed. Although the patient’s history and physical examination may denote good practice, some key information has to be obtained from valuation of the glomerular filtration rate, and the analysis of serum biomarkers. Indeed, chronic kidney sickness depicts anomalous kidney function and/or its makeup, i.e., there is evidence that treatment may avoid or delay its progression, either by reducing and prevent the development of some associated complications, namely hypertension, obesity, diabetes mellitus, and cardiovascular complications. Acute kidney injury appears abruptly, with a rapiddeteriorationoftherenalfunction,butisoftenreversible if it is recognized early and treated promptly. In both situations, i.e., acute kidney injury and chronic kidney disease, an early intervention can significantly improve the prognosis. The assessment of these pathologies is therefore mandatory, although it is hard to do it with traditional methodologies and existing tools for problem solving. Hence, in this work, we will focus on the development of a hybrid decision support system, in terms of its knowledge representation and reasoning procedures based on Logic Programming, that will allow onetoconsiderincomplete,unknown,and evencontradictory information, complemented with an approach to computing centered on Artificial Neural Networks, in order to weigh the Degree-of-Confidence that one has on such a happening. The present study involved 558 patients with an age average of 51.7 years and the chronic kidney disease was observed in 175 cases. The dataset comprise twenty four variables, grouped into five main categories. The proposed model showed a good performance in the diagnosis of chronic kidney disease, since the sensitivity and the specificity exhibited values range between 93.1 and 94.9 and 91.9–94.2 %, respectively.

Pathology and first occurrence of the kidney trematode Paratanaisia bragai (Santos, 1934) Freitas, 1959 (Digenea: Eucotylidae) in Phasianus colchicus L., 1758, from Brazil

The kidney trematode Paratanaisia bragai is reported for the first time parasitizing the ring-necked pheasant (Phasianus colchicus L., 1758) and the pathological alterations associated to the parasitism are referred on the basis of 50 specimens of this bird from backyard flocks in 11 counties of the state of Rio de Janeiro, Brazil after clinical examination, necropsies, and histopathological analysis. The counting of the kidney flukes was based on worms recovered from one of the kidneys, since the other was fixed in 10% formalin and then routinely processed for histopathological procedures. The prevalence of P. bragai was of 22%, with a mean intensity of 44.3, mean abundance of 9.7, and range of infection of 3-153. Parasitized birds did not present with clinical signs and kidney gross lesions. Microscopic lesions were mild and characterized by dilatation of the renal medullary collecting ducts, occasional flattening of the lining epithelium of the ducts and inflammatory reaction of variable intensity with granulocytes around the ureter branches and medullary collecting ducts. The severity and pattern of the microscopic lesions seem not to be associated to the size of the worm burden and could be related to the mechanic action of the parasites, without traumatism, in despite of the presence of the tegumentar spines in specimens of P. bragai.

Prenatal diagnosis of dysmorphic syndromes by routine fetal ultrasound examination across Europe.

OBJECTIVES: Ultrasound scan in the mid-trimester of pregnancy is now a routine part of prenatal care in most European countries. The objective of this study was to evaluate the prenatal diagnosis of dysmorphic syndromes by fetal ultrasound examination. METHODS: Data from 20 registries of congenital malformations in 12 European countries were included in the study. RESULTS: There were 2454 cases with congenital heart diseases, 479 of which were recognized syndromes, including 375 chromosomal anomalies and 104 syndromes without chromosomal anomalies. Fifty-one of the 104 were detected prenatally (49.0%). One hundred and ninety-two of 1130 cases with renal anomalies were recognized syndromes, including 128 chromosomal anomalies and 64 syndromes without chromosomal anomalies; 162 of them (84.4%) were diagnosed prenatally, including 109 chromosomal anomalies and 53 non-chromosomal syndromes. Fifty-four of the 250 cases with limb defects were recognized syndromes, including 16 chromosomal syndromes and 38 syndromes without chromosomal anomalies; 21 of these 54 syndromes were diagnosed prenatally (38.9%), including 9 chromosomal syndromes. There were 243 cases of abdominal wall defects including 57 recognizable syndromes, 48 with omphalocele and 9 with gastroschisis; 48 were diagnosed prenatally (84.2%). Twenty-six of the 187 cases with diaphragmatic hernia had recognized syndromes, including 20 chromosomal aberrations and 6 syndromes without chromosomal anomalies. Twenty-two of them (84.6%) were detected prenatally. Sixty-four of 349 cases with intestinal anomalies were recognized syndromes; 24 were diagnosed prenatally (37.5%). There were 553 cases of cleft lip and palate (CL(P)) and 198 of cleft palate (CP) including 74 chromosomal anomalies and 73 recognized non-chromosomal syndromes. Prenatal diagnosis was made in 51 cases of CL(P) (53.7%) and 7 of CP (13.7%). Twenty-two of 188 anencephalic cases were syndromic and all were diagnosed prenatally. Of 290 cases with spina bifida, 18 were recognized syndromes, and of them 17 were diagnosed prenatally. All 11 syndromic encephaloceles were diagnosed prenatally. CONCLUSIONS: Around 50% of the recognized syndromes which are associated with major congenital anomalies (cardiac, renal, intestinal, limb defects, abdominal wall defects and oral clefts) can be detected prenatally by the anomaly scan. However the detection rate varies with the type of syndrome and with the different countries' policies of prenatal screening.

Meningococcal disease in a kidney transplant recipient with mannose-binding lectin (MBL) deficiency

Background: There is an increasing amount of data associating MBL deficiency with a higher susceptibility to meningococca[ disease. In addition, meningococca[ disease has been reported in patients with various immunosuppressive conditions. However, to our knowledge, only three cases of meningococca[ disease have been reported in solid organ recipients (SOT). Methods & Results: A 32 year-old male patient underwent cadaveric kidney transplantation for endstage renal disease of unknown origin. On day 71 post-transplantation he developed fever (39.6°C), shaking chilis, and tachycardia without hypotension. At this time, immunosuppression consisted of tacro[imus, prednisone 10mg daily and mycopheno[ ate mofeti[ 2 g daily. Physical examination on admission was normal, except for two small petechia[ lesions on the forearm. No meningeal signs were present. Three sets of blood cultures grew Neisseria meningitidis group C susceptible to ceftriaxone (MIC=0.003mg/[). Antibiotic therapy consisted in intravenous ceftriaxone 2 g per day for a total duration of 7 days. Serum immunog[obu[in levels, C3, C4 and CHS0 were normal However, using a method to screen for the functional activity of a[[ three pathways of complement (Wies[ab, Lund, Sweden), no activation via the MBL pathway could be detected (0%). A subsequent quantification of MBL pathway components revealed normal levels of MASP 2 but undetectab[e amounts of MBL (below 10 ng/m[, normal range: >500 ng/m[). Conclusion: Since the exact incidence and the possible relationship between meningococca[ disease and organ transplantation is not we[[ understood, we strongly encourage transplantation centers to report additional cases. The potential clinical usefu[ ness of screening SOT candidates for MBL deficiency in relation to infectious complications after transplantation remains to be determined.

Prenatal detection of congenital renal malformations by fetal ultrasonographic examination: an analysis of 709,030 births in 12 European countries.

The study was performed to evaluate the prevalence of prenatal ultrasound diagnoses for renal anomalies in 20 registries of 12 European countries, and to compare the different prenatal scanning policies. Standardized data were acquired from 709,030 livebirths, stillbirths, and induced abortions during the study period of 2.5 years and transmitted for central analysis. At least one renal malformation was diagnosed in 1130 infants and fetuses. Prenatal diagnosis (PD) was given in 81.8% of all cases, 29% of these pregnancies were terminated. The highest detection rate was reported for unilateral multicystic dysplastic kidneys with 97% (102/105). An early diagnosis was documented for exstrophy of bladder at a mean gestational age of 18.5 weeks. Dilatations of the upper urinary tract were seen late in pregnancy at 28.3 weeks. Terminations of pregnancies (TOP) were performed in 67% (58/86) of the detected bilateral renal agenesis/dysgenesis, but only 4% of the unilateral multicystic dysplastic renal malformations (4/102). In about 1/3 of the cases, renal malformations are within the category of associated malformations, which include multiple non-syndromal malformations, chromosomal aberrations, and non-chromosomal syndromes. Renal malformations were detected in 2/3 of the associated category by the first prenatal ultrasound scan. Detection rates vary in the different countries of the European community due to diverse policies, ethical, and religious background. Countries with no routine ultrasound show the lowest rates in detection, and termination of pregnancy. Prenatally detected renal malformations should result in a careful examination for further anomalies. Prenatal ultrasound fulfills the needs of screening examinations and is a good tool in detecting lethal and severe renal malformations.

Copeptin is associated with kidney length, renal function, and prevalence of simple cysts in a population-based study.

Arginine vasopressin (AVP) has a key role in osmoregulation by facilitating water transport in the collecting duct. Recent evidence suggests that AVP may have additional effects on renal function and favor cyst growth in polycystic kidney disease. Whether AVP also affects kidney structure in the general population is unknown. We analyzed the association of copeptin, an established surrogate for AVP, with parameters of renal function and morphology in a multicentric population-based cohort. Participants from families of European ancestry were randomly selected in three Swiss cities. We used linear multilevel regression analysis to explore the association of copeptin with renal function parameters as well as kidney length and the presence of simple renal cysts assessed by ultrasound examination. Copeptin levels were log-transformed. The 529 women and 481 men had median copeptin levels of 3.0 and 5.2 pmol/L, respectively (P<0.001). In multivariable analyses, the copeptin level was associated inversely with eGFR (β=-2.1; 95% confidence interval [95% CI], -3.3 to -0.8; P=0.002) and kidney length (β=-1.2; 95% CI, -1.9 to -0.4; P=0.003) but positively with 24-hour urinary albumin excretion (β=0.11; 95% CI, 0.01 to 0.20; P=0.03) and urine osmolality (β=0.08; 95% CI, 0.05 to 0.10; P<0.001). A positive association was found between the copeptin level and the presence of renal cysts (odds ratio, 1.6; 95% CI, 1.1 to 2.4; P=0.02). These results suggest that AVP has a pleiotropic role in renal function and may favor the development of simple renal cysts.

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)

Hypothyroidism and acute kidney injury: An unusual association

Association between severe hypothyroidism and acute kidney injury (AKI) is rare. A 40-year-old woman presented with 15 days history of generalised muscle pain, weakness, weight gain and oedema. Medical history: hypertension and hypothyroidism. Physical examination: dry skin, peripheral/periorbital oedema, slow thought and speaking, thyroid increased. Laboratory examinations: high levels of creatine kinase , creatinine, uric acid and lactate dehydrogenase. Free T4 was very low (<0.3 ng/dL) and thyroid-stimulating hormone was high (21.7 mIU/mL). Urinalysis showed haem pigment without haematuria. We performed the diagnosis of AKI secondary to hypothyroidism-induced rhabdomyolysis. Intravenous fluids were started, urinary alkalisation and increased l-thyroxine dose replacement. On the day after admission, forced diuresis with furosemide was introduced leading to a progressive improvement of symptoms. Although hypothyroidism and AKI is unusual, it should be suspected in patients presenting decrease of renal function and high creatine kinase in the absence of other causes of rhabdomyolysis.

Functional independence in patients with chronic kidney disease being treated with haemodialysis

Purpose: This study has described and analysed the functional independence of the patients served in the haemodialysis services of a countryside town in the State of Sao Paulo, Brazil, using the Functional Independence Measure (FIM). Method: The population considered was that of 214 patients being treated with haemodialysis, assessed in 2011, by means of a social, demographic and clinical report, a Mini-Mental State Examination (MMSE) and also the FIM. Results: The mean age of the population under study was 58.01 years, while the mean FIM point score was 118.38 points, showing a level of complete or modified independence within this population. Even though the level of dependence found has been low, this can be highlighted, within the locomotion domain, in the activity of going up and down stairs (10.28%). Age, complications arising from haemodialysis, and comorbidities show a negative correlation with FIM. Conclusion: Awareness of the level of functional independence of the patients being subjected to treatment with haemodialysis is essential in order to back up intervention for the improvement of nursing assistance provided to this population.

Somatotroph pituitary adenoma with acromegaly and autosomal dominant polycystic kidney disease: SSTR5 polymorphism and PKD1 mutation

A 39-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) presented with acromegaly and a pituitary macroadenoma. There was a family history of this renal disorder. She had undergone surgery for pituitary adenoma 6 years prior. Physical examination disclosed bitemporal hemianopsia and elevation of both basal growth hormone (GH) 106 ng/mL (normal 0-5) and insulin-like growth factor (IGF-1) 811 ng/mL (normal 48-255) blood levels. A magnetic resonance imaging scan disclosed a 3.0 cm sellar and suprasellar mass with both optic chiasm compression and left cavernous sinus invasion. Pathologic, cytogenetic, molecular and in silico analysis was undertaken. Histologic, immunohistochemical and ultrastructural studies of the lesion disclosed a sparsely granulated somatotroph adenoma. Standard chromosome analysis on the blood sample showed no abnormality. Sequence analysis of the coding regions of PKD1 and PKD2 employing DNA from both peripheral leukocytes and the tumor revealed the most common PKD1 mutation, 5014_5015delAG. Analysis of the entire SSTR5 gene disclosed the variant c.142C > A (p.L48M, rs4988483) in the heterozygous state in both blood and tumor, while no pathogenic mutations were noted in the MEN1, AIP, p27Kip1 and SSTR2 genes. To our knowledge, this is the fourth reported case of a GH-producing pituitary adenoma associated with ADPKD, but the first subjected to extensive morphological, ultrastructural, cytogenetic and molecular studies. The physical proximity of the PKD1 and SSTR5 genes on chromosome 16 suggests a causal relationship between ADPKD and somatotroph adenoma.