Progressive Renal Disorders Research Articles

Kualitas Hidup Pasien Gagal Ginjal Kronis yang Menjalani Hemodialisa

Chronic renal failure is a progressive and irreversible renal function disorder in which the body's ability fails to maintain metabolism and fluid and electrolyte balance, causing uremia (retention of urea and other nitrogenous wastes in the blood). In Indonesia, the increase in patients with this disease has reached 20%. The data and information center of the Indonesian Hospital Association (PDPERSI) states that the number of patients with chronic kidney failure is estimated at around 50 people per one million population. Hemodialysis is very important for patients with chronic kidney failure because hemodialysis is one of the measures that can prevent death. However, hemodialysis cannot cure or restore kidney disease because it is unable to compensate for the loss of metabolic activity of kidney or endocrine diseases carried out by the kidneys and the impact of kidney failure and therapy on the patient's quality of life. Objective to determine the quality of life of chronic kidney failure patients undergoing hemodialysis. Using a literature review study method from scientific journals with keyword guidance. Scientific journals that were selected were 6 journals, each journal representing one quality of life of chronic kidney failure patients undergoing hemodialysis. The quality of life of patients with chronic kidney failure are mostly in the good or high category with many factors affecting the quality of life of patients with chronic failure who are undergoing hemodialysis. Based on the analysis that has been carried out, it shows that the quality of life of patients with chronic failure at the good or high category level the biggest influencing factors are family support and self-efficacy.

Kualitas Hidup Pasien Gagal Ginjal Kronik yang Menjalani Hemodialisa di RSUD Linggajati Kuningan

Chronic kidney failure or end-stage renal disease (ESRD) is a progressive and irreversible renal function disorder, where kidney function decreases in maintaining metabolism, fluid and electrolyte balance, resulting in uremia (retention of urea and other nitrogenous wastes in the blood. This study used a descriptive approach to hemodialysis patients at Linggarjati Kuningan Hospital. The population and sample are 49 respondents. The results of the study on the Quality of Life of Chronic Kidney Failure Patients Undergoing Hemodialysis at the Linggajati Kuningan Hospital showed the quality of life of the majority of respondents were in bad condition, namely 30 people (61%) and 19 people (39%). The results showed the quality of life based on the physical dimensions of the majority in the bad category as much as 55.1%, based on the psychological health dimensions the majority in the bad category as much as 57.3%. While the category of social relations is in the good category as much as 51% and the environmental dimension as much as 53.1%.

Kualitas Hidup Pasien Gagal Ginjal Kronik yang Menjalani Hemodialisa di RSUD Linggajati Kuningan

Chronic kidney failure or end-stage renal disease (ESRD) is a progressive and irreversible renal function disorder, where kidney function decreases in maintaining metabolism, fluid and electrolyte balance, resulting in uremia (retention of urea and other nitrogenous wastes in the blood. This study used a descriptive approach to hemodialysis patients at Linggarjati Kuningan Hospital. The population and sample are 49 respondents. The results of the study on the Quality of Life of Chronic Kidney Failure Patients Undergoing Hemodialysis at the Linggajati Kuningan Hospital showed the quality of life of the majority of respondents were in bad condition, namely 30 people (61%) and 19 people (39%). The results showed the quality of life based on the physical dimensions of the majority in the bad category as much as 55.1%, based on the psychological health dimensions the majority in the bad category as much as 57.3%. While the category of social relations is in the good category as much as 51% and the environmental dimension as much as 53.1%.

EXPLANATION OF THE BENEFITS OF MUSIC THERAPY IN CHRONIC RENAL FAILURE PATIENTS THAT ARE TAKING HEMODIALIZATION

Chronic kidney disease or end-stage renal disease (ERSD) is a progressive and irreversible renal function disorder in which the kidneys are unable to maintain metabolism. Problems that often occur in hemodialysis patients with sleep quality problems. To improve the quality of sleep can be done by using music therapy. This action is very practical, cheap and easy and can be done by everyone. This action is still rarely performed by patients with chronic renal failure on hemodialysis when experiencing a decrease in sleep quality. The service was carried out on 27 patients with chronic renal failure who had hypertension. The service implementation team provides training on how to do music therapy at the Sembiring General Hospital. The team conducted counseling and evaluation when the patient underwent further hemodialysis. The outreach activities went smoothly. There were 7 patients who asked about the counseling material. The importance of conducting routine outreach activities to patients undergoing hemodialysis about their other complaints to improve their health status.

Coping mechanism with anxiety levels in chronic kidney disease patients undergoing hemodialysis at Toto Kabila Hospital

Chronic kidney disease is a progressive and irreversible renal disorder in which the body fails to maintain metabolism, balance, and electrolytes. Patients with such a disease should undergo regular hemodialysis therapy, leading to physical and psychological problems, i.e., anxiety. Inappropriately treated anxiety will cause the patients to not stick to the dietary pattern, hemodialysis, and infantilism. They need to strive to deal with their problems, known as a coping mechanism. The purpose of this study was to determine the correlation between coping mechanisms and anxiety levels of patients with chronic kidney disease that underwent hemodialysis at Toto Kabila Regional Public Hospital. It relied on a quantitative method with the cross-sectional approach. A total of 30 respondents were taken as the sample using the purposive sampling technique. Moreover, the Somers’D test with a questionnaire instrument was applied to analyze the data. It was shown that coping mechanisms correlated with anxiety levels of patients with chronic kidney disease who underwent hemodialysis therapy (p-Value = 0.005) in the site area.

Roles of telomeres and telomerase in age‑related renal diseases (Review).

Age-related renal diseases, which account for various progressive renal disorders associated with cellular and organismal senescence, are becoming a substantial public health burden. However, their aetiologies are complicated and their pathogeneses remain poorly understood. Telomeres and telomerase are known to be essential for maintaining the integrity and stability of eukaryotic genomes and serve crucial roles in numerous related signalling pathways that activate renal functions, such as repair and regeneration. Previous studies have reported that telomere dysfunction served a role in various types of age-related kidney disease through various different molecular pathways. The present review aimed to summarise the current knowledge of the association between telomeres and ageing-related kidney diseases and explored the contribution of dysfunctional telomeres to these diseases. The findings may help to provide novel strategies for treating patients with renal disease.

PENGUKURAN KUALITAS HIDUP PASIEN HEMODIALISIS GAGAL GINJAL KRONIK DI RSUD ULIN BANJARMASIN MENGGUNAKAN INSTRUMEN EQ5D

Chronic renal failure is a progressive and irreversible renal function disorder in which the body's ability to fail to maintain metabolism, fluid and electrolyte balance. Chronic kidney failure can interfere with the quality of life of patients, it is necessary to measure the quality of life of patients with chronic renal failure. Measuring the quality of life of patients with chronic renal failure using the Indonesian version of the EQ5D questionnaire. The purpose of this study was to determine the quality of life of chronic renal failure hemodialysis patients in RSUD Ulin Banjarmasin using the EQ5D instrument. This study is an observational study conducted prospectively. Data was collected by filling out the EQ5D questionnaire by all patients with chronic renal failure. The population of this study were chronic renal failure patients who underwent hemodialysis in Hemodialysis Outpatient Services at Ulin Banjarmasin Hospital in June-July 2018 as many as 360 patients and a sample of 207 patients who met the inclusion and exclusion criteria using non random sampling / non-probability sampling techniques accidental sampling. Based on the research that has been done in the Hemodialysis Outpatient Hospital Ulin Banjarmasin, it was found that the average quality of life was 0.792, with a quality of life ≥ 0.792 of 69 patients (33.33%) in the category of good quality of life and quality of life ≤ 0.792 138 patients (66.66%) in the poor quality of life category.

Identification of a Novel COL4A4 Variant in Compound-Heterozygous State in a Patient With Alport Syndrome and Histological Findings Similar to Focal Segmental Glomerulosclerosis (FSGS).

Alport syndrome (AS) is a rare and inherited renal disorder with an autosomal recessive mode of inheritance. AS patients usually manifest with hematuria and progressive renal disorder also occasionally accompanied by hearing loss and ophthalmic disease. Germline variants in collagen type IV α-4 (COL4A4) gene lead to autosomal recessive Alport syndrome. In the present study, we investigated a Chinese family with Alport syndrome. The index patient is a 24-year-old Chinese woman who has been suffering from proteinuria. Renal biopsy and renal pathology were performed and found focal segmental glomerulosclerosis (FSGS) like lesion in the index patient. The index patient also presented with binocular edema and blurred vision. However, binocular edema dissipated gradually without any further treatment. Unlikely, the index patient was not diagnosed with hearing impairment. Index patient’s parents are phenotypically normal. Targeted next generation sequencing and Sanger sequencing was performed. A novel heterozygous single nucleotide insertion, c.4760_4761insC and a previously reported likely pathogenic variant, c.1323_1340delTGGCTTGCCTGGAGCACC in the COL4A4 gene were identified in the index patient. The novel heterozygous single nucleotide insertion (c.4760_4761insC) leads to a frameshift which eventually results in the formations of a truncated COL4A4 protein. In addition, the other heterozygous likely pathogenic variant, c.1323_1340delTGGCTTGCCTGGAGCACC, has been already identified with causing AS an autosomal recessive mode of inheritance. Sanger sequencing confirmed that these two variants were inherited in the index patient from her father and mother, respectively. These two variants were not found in 100 normal control individuals. In conclusion, our present finding emphasizes the significance of high throughput targeted next generation sequencing technology for rapid and cost-effective genetic screening which allows us easy and accurate clinical diagnosis of AS patients.

Inhibition of RAS in diabetic nephropathy.

Diabetic kidney disease (DKD) is a progressive proteinuric renal disorder in patients with type 1 or type 2 diabetes mellitus. It is a common cause of end-stage kidney disease worldwide, particularly in developed countries. Therapeutic targeting of the renin–angiotensin system (RAS) is the most validated clinical strategy for slowing disease progression. DKD is paradoxically a low systematic renin state with an increased intrarenal RAS activity implicated in its pathogenesis. Angiotensin II (AngII), the main peptide of RAS, is not only a vasoactive peptide but functions as a growth factor, activating interstitial fibroblasts and mesangial and tubular cells, while promoting the synthesis of extracellular matrix proteins. AngII also promotes podocyte injury through increased calcium influx and the generation of reactive oxygen species. Blockade of the RAS using either angiotensin converting enzyme inhibitors, or angiotensin receptor blockers can attenuate progressive glomerulosclerosis in animal models, and slows disease progression in humans with DKD. In this review, we summarize the role of intrarenal RAS activation in the pathogenesis and progression of DKD and the rationale for RAS inhibition in this population.

Predictive Value of Endostatin in Chronic Heart Failure Patients with Poor Kidney Function

Objectives: Increased circulating endostatin levels have been demonstrated in progressive cardiovascular (CV) and renal disorders. We investigated the predictive value of endostatin in patients with chronic heart failure (HF) and the association between endostatin and renal function. Methods: The interaction between serum endostatin, estimated glomerular filtration rate (eGFR) and predefined endpoints, including the primary endpoint (CV death, nonfatal myocardial infarction, nonfatal stroke; n = 397), all-cause mortality (n = 410), CV death (n = 335) or the coronary endpoint (n = 317), was evaluated in 1,390 patients >60 years of age with ischemic systolic HF in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) population, who were randomly assigned to 10 mg rosuvastatin or placebo. Results: In the population as a whole, endostatin added no predictive information after full multivariable adjustment including eGFR and N-terminal pro-brain natriuretic peptide. Serum endostatin was strongly correlated with eGFR (r = 0.59, p < 0.001). After full multivariable adjustment, an association between high serum endostatin and increased risk of all-cause mortality and decreased risk of the primary and coronary endpoints was seen in HF patients with impaired and preserved renal function, respectively. Conclusions: Endostatin added no predictive information regarding the adverse outcome in patients with chronic systolic HF of ischemic etiology. An increased risk of all-cause mortality was seen in patients with decreased renal function. i 2014 S. Karger AG, Basel

Assessment of lower urinary tract function in children with Down syndrome.

BackgroundDespite the fact that functional lower urinary tract symptoms are common among people with Down syndrome (DS), their voiding function has not been studied precisely. Our goal was to assess the lower urinary tract functions in DS.MethodsFifty-five DS children aged 5–15 years old and 35 age-matched control children were evaluated by ultrasonography and uroflowmetry.ResultsEleven (20%) DS children had no uresiesthesia, 21 (38%) were urinated under guidance, nine (16%) urinated fewer than three times a day, two (4%) urinated more than 10 times a day, three (5%) used diapers, and 26 (47%) had urinary incontinence. Seven (13%), 15 (27%), and 10 (18%) DS children had weak, prolonged and intermittent urination, respectively, and seven (13%) had urination with straining. In contrast, none of the control subjects had urinary problems. In the uroflowmetrical analysis, 10 (18%), 20 (37%), 11 (20%) and five (9%) DS children showed “bell-shaped,” “plateau,” “staccato” and “interrupted” patterns, respectively; the remaining nine (16%) could not be analyzed. In contrast, 21 (60%), one (3%), four (11%), three (9%) and two (6%) control subjects showed bell-shaped, tower-shaped, plateau, staccato and interrupted patterns, respectively; the remaining four (11%) could not be analyzed. Residual urine was demonstrated in four (7%) DS children and one (3%) control child.ConclusionsLower urinary tract symptoms and abnormal uroflowmetry findings, which can lead to further progressive renal and urinary disorders, are common in DS children. Therefore, lower urinary tract functions should be assessed at the life-long regular medical check-ups for subjects with DS.

NOS3 tagSNPs does not modify the chronic kidney disease progression in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary and progressive renal disorder. It is also recognised as the most frequent genetic cause of chronic kidney diseases (CKD). In the present study, four tagging SNPs and two more well studied polymorphisms (Intron 4 VNTR and Glu298Asp) the NOS3 gene were investigated to unravel the potential modifier effect of NOS3 gene on the progression of CKD in ADPKD. A total of 102 ADPKD patients and 106 controls were selected for the study. The tagSNPs and Glu298Asp polymorphisms were genotyped using FRET-based KASPar method and intron-4 VNTR by polymerase chain reaction electrophoresis. The genotypes and haplotypes in the controls and ADPKD subjects were analysed by χ(2) tests and haploview software. Mantel-Haenszel stratified and univariate analyses were performed to estimate the influence of different genotypes between different CKD stages and hypertension. The tagSNPs of NOS3 genotypes and haplotypes did not exhibit any significant differences between controls and ADPKD patients. The significant linkage disequilibrium was observed between the rs3918184 and rs2853796 by forming LD block. In univariate analysis, the age and family history of Diabetes mellitus (DM) showed significant association with advancement of CKD, but not with the eNOS polymorphisms. Our data suggests that there is no evidence for the involvement of NOS3 tag SNPs in the progression to CKD in ADPKD patients. A systematic study using well validated functional SNPs is necessary to clarify the role of the NOS3 gene in the development of CKD in ADPKD.

Ultrassonografia Doppler na avaliação renal de cadelas diagnosticadas com piometra antes e após tratamento com ovariosalpingohisterectomia

O objetivo do presente estudo foi avaliar a hemodinâmica renal de cadelas com piometra por meio de exames laboratoriais, ultrassonografia Modo B e Doppler, antes e após o tratamento cirúrgico com ovariosanpigohisterectomia (OSH). Foram utilizadas 30 cadelas com diagnóstico de piometra, todas foram submetidas a OSH (momento 1) e 20 foram reavaliadas sete dias após a cirurgia (momento 2). A perfusão renal, o índice de resistividade da artéria renal principal e de cada artéria interlobar (cranial, média e caudal) foi estatisticamente diferente entre os momentos 1 e 2 (p&lt;0,05). Não foi observada diferença estatística para a perfusão renal entre o rim direito e esquerdo no momento 1 e 2. As correlações entre o índice de resistividade da artéria renal principal e as variáveis utilizadas para verificar a função renal foram estabelecidas no momento 1. Para as variáveis correlacionadas ureia, creatinina, proteinúria, relação GGT/creatinina e proteína/creatinina ocorreram associações curvilíneas e positivas com o índice de resistividade da artéria renal principal (p&lt;0,05), no entanto essas correlações foram consideradas de média e fracas. Ao comparar o IR da artéria renal principal com diferentes escores de desidratação e perfusão renal, este foi estatisticamente diferente, e demonstrou aumento da resistência renal em cadelas com moderada redução da perfusão renal, assim como em cadelas desidratadas. Foram avaliadas diversas características de morfologia renal na ultrassonografia Modo B, no entanto, somente as variáveis presença de dilatação de pelve, sinal da medular e outras alterações como áreas de infartos e pontos hiperecogênicos difusos na cortical e medular renal foram estatisticamente distintas de um momento para o outro, com maior frequência no momento 2. Os resultados do presente trabalho demonstram que a ultrassonografia Doppler pode identificar alterações de redução na perfusão renal, por meio do Doppler colorido e o aumento do índice de resistividade das artérias renais em cadelas com piometra. Assim como, a ultrassonografia modo B, embora apresente alterações inespecíficas, pode detectar alterações renais progressivas em cadelas com piometra.

Angiogenesis and hypoxia in the kidney

Loss of glomerular function associated with the presence of tubulointerstitial lesions, which are characterized by peritubular capillary loss, is a common finding in progressive renal disorders. Dysregulated expression of angiogenic factors (such as vascular endothelial growth factor [VEGF] and angiopoietins) and endogenous angiogenic inhibitors (such as thrombospondin-1, angiostatin and endostatin) underlie these conditions and negatively influence the balance between capillary formation and regression, resulting in capillary rarefaction. Recent studies have provided unequivocal evidence for a pathogenic role of tubulointerstitial hypoxia and the involvement of hypoxia-inducible transcription factors in the advanced stages of chronic kidney disease. The mainstay of potential angiogenic therapies is the application of angiogenic factors with the primary aim of ameliorating reduced oxygenation in the ischaemic tubulointerstitium. However, this strategy is strongly associated with inflammation and changes in vascular permeability. For example, supraphysiological expression of VEGF results in glomerular expansion and proteinuria, whereas VEGF blockade using neutralizing antibodies can cause hypertension and thrombotic microangiopathy. These effects highlight the importance of tight regulation of angiogenic factors and inhibitors. Novel therapeutic approaches that target vascular maturation and normalization are now being developed to protect kidneys from capillary rarefaction and hypoxic injury.

Adult Care of Children From Pediatric Urology

In this article we highlight the difference, from established adult urology, in required approach to the care of adolescents and young adults presenting with the long-term consequences of the major congenital anomalies of the genitourinary tract. We review some abnormalities of the kidneys, progressive renal failure and disorders of bladder function from which general conclusions can be drawn. The published literature was reviewed and augmented with material from our institutional databases. For renal function the CAKUT (congenital abnormalities of the kidney and urinary tract) database at University College London Hospitals was used, which includes 101 young adult patients with CAKUT in whom the urinary tract has not been diverted or augmented. For bladder function some data are from patient records at Boston Children's Hospital. Adolescents who grow up with the burden of a major congenital anomaly have an overwhelming desire to be normal. Many achieve high levels of education and occupy a wide range of employment scenarios. Babies born with damaged kidneys will usually experience improvement in renal function in the first 3 years of life. Approximately 50% of these cases will remain stable until puberty, after which half of them will experience deterioration. Any urologist who treats such patients needs to test for proteinuria as this is a significant indicator of such deterioration. In its absence, the urologist must have a reasonable strategy for seeking a urological cause. The most effective management for nephrological renal deterioration is with angiotensin converting enzyme inhibitors, which slow but do not prevent end stage renal failure. Renal deterioration is generally slower in these patients than in those with other forms of progressive renal disease. The bladder is damaged by obstruction or by functional abnormalities such as myelomeningocele. Every effort should be made to stabilize or reconstruct the bladder in childhood. A dysfunctional bladder is associated with or causes renal damage in utero, but continued dysfunction will cause further renal damage. Bladder function often changes in puberty, especially in boys with posterior urethral valves who may experience high pressure chronic retention. Dysfunction is managed with antimuscarinic drugs, clean intermittent self-catheterization and intestinal augmentation. Adult urologists must be able to manage the long-term problems associated with these treatments. Pediatric conditions requiring management in adolescence are rare but have major, lifelong implications. Their management requires a broad knowledge of pediatric and adult urology, and could well be a specialty in its own right. Therefore, adult urologists must remain aware of the conditions, the problems that they may encounter and the special management required for these patients to live normal lives.

Fabry disease, do we think enough about this multisystemic disorder?: A presentation of three cases in a Serbian family

Fabry Disease is a rare, X-chromosomal inherited lysosomal storage disease with a consequent intracellular accumulation of neutral glycosphingolipids in various tissues. This can cause skin and ocular lessions, progressive renal, cardiac or cerebrovascular disorders. If a person in a family has Fabry disease, other family members including even extended relatives, may also be at risk. We presented three cases pointed out various manifestation of Fabry disease, that illustrate a possible cause for otherwise unexplained cardiac hypertrophy and various rhythm and conduction abnormalities. Although most symptoms begin in childhood, various manifestations often lead to misdiagnosis and clinical diagnosis is frequently delayed for many years, even decades. Enzyme replacement therapy has become available, pointing out the importance of early diagnosis so that treatment can be initiated before irreversible organ damage.

Rho Kinase Inhibition by Fasudil Attenuates Cyclosporine-Induced Kidney Injury

It has been shown that the inhibition of the Rho/Rho kinase (ROCK) pathway prevents tubulointerstitial fibrosis and ameliorates renal function in various progressive renal disorders. The present study was to determine whether fasudil, a ROCK inhibitor, has a protective effect on cyclosporine A (CsA)-induced nephropathy. Male Sprague-Dawley rats were treated with CsA (n = 10, 20 mg · kg(-1) day(-1) s.c.), CsA + fasudil (n = 10, 3 mg · kg(-1) day(-1) i.p.), or vehicle alone (n = 10) for 28 days. Fasudil cotreatment ameliorated CsA-induced changes and restored renal function. CsA decreased the expression of endothelial nitric-oxide synthase and increased inducible nitric-oxide synthase/3-nitrotyrosine in the kidney. Accordingly, there was infiltration of inflammatory cells and up-regulation of inflammatory cytokines. Fasudil also significantly suppressed the expression of transforming growth factor-β1, Smad signaling, and subsequent epithelial-to-mesenchymal processes. In addition, fasudil augmented p27(kip1) expression and decreased the number of proliferating cell nuclear antigen-positive cells. In another series of experiments using HK-2 cells in culture, fasudil also suppressed CsA-induced increases in mitogen-activated protein kinase phosphorylation. CsA induced expression of p53, the degree of which was attenuated by fasudil in association with decreases of proapoptotic markers such as Bad, Bax, and total/cleaved caspase-3. These results suggest that inhibition of the Rho/ROCK pathway attenuates CsA-induced nephropathy through the suppression of the induction of inflammatory, apoptotic, and fibrogenic factors, along with inhibition of Smad, mitogen-activated protein kinases, and nitric oxide signaling pathways.

Endothelin receptor selectivity in chronic renal failure

Chronic kidney diseases are increasing worldwide at an alarming rate, and they are emerging as a major public health problem. Treatments that slow the progression of chronic kidney disease are needed. Endothelin-1 (ET-1) is a potent vasoconstrictor with proinflammatory, mitogenic and profibrotic effects that is closely involved in both normal renal physiology and pathology. Increasing evidence suggests that ET-1 and its cognate receptors are involved in a variety of progressive renal disorders to the extent that renal ET-1 expression correlates with disease severity and renal function impairment. Endothelin receptor antagonists have been used in renoprotection studies owing to their capacity of improving renal hemodynamics and reducing proteinuria. Whether selective ET(A) or non-selective ET(A)/ET(B) receptor antagonists are preferable is still a matter of debate. As angiotensin II blockers are not invariably effective in retarding disease progression when treatment is started late in the course of the disease, it is foreseeable that an ET-1 antagonist in addition to angiotensin-converting enzyme inhibitors could represent a combined treatment for progressive nephropathies. The focus of this review is to examine the role endothelin-1 plays in kidney diseases and to determine the ideal setting for antagonizing its biological activity in chronic nephropathies.

Genetic variation of apolipoprotein E does not contribute to the lipid abnormalities secondary to childhood minimal change nephrotic syndrome

Minimal change nephrotic syndrome (MCNS) is a common progressive renal disorder occurring in childhood that is characterized by alterations of permselectivity at the glomerular capillary wall, resulting in its inability to restrict the urinary loss of protein. Hyperlipidemia (HLP) is not only an important clinical manifestation of MCNS but is also involved in cardiovascular disease and in progressive renal damage. ApoE is a polymorphic protein. Besides modulation of lipid metabolism, apoE can also elevate the sulfate-proteoglycan in glomerular filtration membrane and inhibit the proliferation of mesengial cells. The present study aimed mainly to determine whether genetic polymorphism of apoE is involved in the HLP secondary to childhood MCNS. Genomic DNA was extracted from 250 children diagnosed with MCNS and 200 healthy controls. ApoE genotype was determined by PCR-restriction fragment length polymorphism (RFLP) analysis. The fasting serum lipoprotein (a) [Lp(a)], total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (apoA1), and apoB were measured. Serum concentrations of Lp(a), TC, TG, HDL-C, nonHDL-C, LDL-C, and apoB were higher in the MCNS than in the control group (P < 0.05). No significant differences in genotypes and alleles frequencies were observed for the apoE Hha I restriction sites in MCNS patients as compared to controls (P > 0.05). No significant differences in serum lipid levels were observed for variant genotypes and alleles of apoE Hha I restriction site in both MCNS and healthy children (P > 0.05). Genetic variation of apoE does not contribute to the lipid abnormalities secondary to childhood MCNS.

Improved Elucidation of Biological Processes Linked to Diabetic Nephropathy by Single Probe-Based Microarray Data Analysis

BackgroundDiabetic nephropathy (DN) is a complex and chronic metabolic disease that evolves into a progressive fibrosing renal disorder. Effective transcriptomic profiling of slowly evolving disease processes such as DN can be problematic. The changes that occur are often subtle and can escape detection by conventional oligonucleotide DNA array analyses.Methodology/Principal FindingsWe examined microdissected human renal tissue with or without DN using Affymetrix oligonucleotide microarrays (HG-U133A) by standard Robust Multi-array Analysis (RMA). Subsequent gene ontology analysis by Database for Annotation, Visualization and Integrated Discovery (DAVID) showed limited detection of biological processes previously identified as central mechanisms in the development of DN (e.g. inflammation and angiogenesis). This apparent lack of sensitivity may be associated with the gene-oriented averaging of oligonucleotide probe signals, as this includes signals from cross-hybridizing probes and gene annotation that is based on out of date genomic data. We then examined the same CEL file data using a different methodology to determine how well it could correlate transcriptomic data with observed biology. ChipInspector (CI) is based on single probe analysis and de novo gene annotation that bypasses probe set definitions. Both methods, RMA and CI, used at default settings yielded comparable numbers of differentially regulated genes. However, when verified by RT-PCR, the single probe based analysis demonstrated reduced background noise with enhanced sensitivity and fewer false positives.Conclusions/SignificanceUsing a single probe based analysis approach with de novo gene annotation allowed an improved representation of the biological processes linked to the development and progression of DN. The improved analysis was exemplified by the detection of Wnt signaling pathway activation in DN, a process not previously reported to be involved in this disease.