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Urinary protein markers predict the severity of renal histological lesions in children with mesangial proliferative glomerulonephritis
Background:
Several renal histopathological features, including mesangial hypercellularity,glomerulosclerosis, tubular atrophy and interstitial fibrosis, are considered to be independentpredictors of end-stage renal failure in patients with glomerular diseases. Mesangialproliferative glomerulonephritis (MesPGN) is characterized by proliferations of mesangialcells with increase in mesangial matrix and/or deposits in mesangial region. The purpose ofthis study is to determine the association between urinary protein markers measured at thesame time as renal biopsy and the severity of renal histological lesions in children withMesPGN, and to evaluate whether these markers could serve as predictors of severe renalhistological lesions in this population.
Methods:
Ninety-eight children with MesPGN (40 with IgA nephropathy, 37 with IgM nephropathy,and 21 with MesPGN without IgA/IgM deposition) were enrolled. Urinary level of IgG,albumin, transferrin, alpha1-microglobulin, beta2-microglobulin and N-acetyl-beta-glucosaminidasefrom a morning sample before biopsy was measured.The scores of mesangial hypercellularity, glomerulosclerosis, and tubule-interstitial damagewere used to semi-quantitatively evaluate renal histological lesions.
Results:
The urine proteins, as independent factors associated with severe mesangial cellularity (> 5mesangial cells/ mesangial area) were transferrin, albumin, alpha1-microglobulin, IgG and 24-hour total protein, with severe glomerulosclerosis ([greater than or equal to] 10 % glomeruli showing segmentaladhesions or sclerosis) were transferrin and 24-hour total protein, and with severe tubuleinterstitialdamage (focal or diffuse tubular and interstitial lesions) were transferrin and Nacetyl-beta-glucosaminidase. Urinary transferrin achieved the area under-the-receiver-operatingcharacteristiccurve (AUC) of 0.86 and 0.82, respectively, for predicting severe mesangialcellularity and glomerulosclerosis. Urinary N-acetyl-beta-glucosaminidase achieved the highestAUC of 0.82 for predicting severe tubule-interstitial damage. The combination of urinaryprotein markers, however, did not improve the predictability for renal histological lesions.
Conclusions:
Urinary protein markers are useful to predict the severity of renal histological lesions inchildren with MesPGN, which suggests that urinary proteins might be useful to predict thedevelopment and progression of renal histological lesions, and assist in evaluating theoutcome and prognosis in children with MesPGN as non-invasive and easily repeatableindicators on the follow-up examination.
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Exsanguination of a home hemodialysis patient as a
result of misconnected blood-lines during the wash
back procedure: a case report
Background:
Home hemodialysis is common in New Zealand and associated with lower cost, improvedsurvival and better patient experience. We present the case of a fully trained homehemodialysis patient who exsanguinated at home as a result of an incorrect wash backprocedure.Case presentationThe case involves a 67 year old male with a history of well controlled hypertension andimpaired glucose tolerance. He commenced on peritoneal dialysis in 2006 following thedevelopment of end stage kidney failure secondary to focal segmental glomerulosclerosis. Hetransferred to hemodialysis due to peritoneal membrane failure in 2010, and successfullytrained for home hemodialysis over a 20 week period. Following one month ofuncomplicated dialysis at home, he was found deceased on his machine at home in the midstof dialysis. His death occurred during the wash back procedure performed using the "opencircuit" method, and resulted from misconnection of the saline bag to the venous end of theextracorporeal blood circuit instead of the arterial end. This led to approximately 2.3L of hisblood being pumped into the saline bag resulting in hypovolaemic shock and death fromexsanguination.
Conclusions:
Despite successful training, critical procedural errors can still be made by patients on homehemodialysis. In this case, the error involved misconnection of the saline bag for wash back.This case should prompt providers of home hemodialysis to review their training protocolsand manuals. Manufacturers of dialysis machinery should be encouraged to design machinesspecifically for home hemodialysis, and consider distinguishing the arterial and venous endsof the extracorporeal blood circuit with colour coding or incompatible connectivity, toprevent occurrences such as these in the future.
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A complex microdeletion 17q12 phenotype in a
patient with recurrent de novo membranous
nephropathy
Background:
Microdeletions on chromosome 17q12 cause of diverse spectrum of disorders and have onlyrecently been identified as a rare cause of Mayer-Rokitansky-Kuester-Hauser-Syndrome(MRKH), which is characterized by uterus aplasia +/- partial/complete vaginal aplasia infemales with a regular karyotype. For the first time we report about a patient with a 17q12microdeletion who is affected by MRKH in combination with a vascular and soft tissuedisorder. Repeatedly she suffered from kidney transplant failure caused by consumingmembranous nephropathy.Case presentationA 38-year-old female patient had been diagnosed with right kidney aplasia, left kidneydysplasia and significantly impaired renal function during infancy. Aged 16 she had to starthemodialysis. Three years later she received her first kidney transplant. Only then she wasdiagnosed with MRKH. The kidney transplant was lost due to consuming nephroticsyndrome caused by de novo membranous nephropathy, as was a second kidney transplantyears later. In addition, a hyperelasticity syndrome affects the patient with congenital jointlaxity, kyphoscoliosis, bilateral hip dysplasia, persistent hypermobility of both elbows, kneesand hips. Her clinical picture resembles a combination of traits of a hypermobile and avascular form of Ehlers-Danlos-Syndrome, but no mutations in the COL3A1 gene wasunderlying. Instead, array-based comparative genomic hybridisation (CGH) detected aheterozygous 1.43 Mb deletion on chromosome 17q12 encompassing the two renaldevelopmental genes HNF1beta and LHX1.
Conclusions:
Deletions of HNF1beta have recently drawn significant attention in pediatric nephrology as animportant cause of prenatally hyperechogenic kidneys, renal aplasia and renal hypodysplasia.In contrast, membranous nephropathy represents an often-unaccounted cause of nephroticsyndrome in the adult population. A causative connection between theses two conditions hasnever been postulated, but is suggestive enough in this case to hypothesize it.
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Ethnic differences in the association between waist-to-height ratio and albumin-creatinine ratio: the observational SUNSET study
Background:
Ethnic differences in the association between central obesity and raised albumin-creatinineratio (ACR) have not been investigated. Our aim was to determine whether the associationbetween central obesity, defined by the waist-to-height ratio (WHtR), and ACR differedbetween subjects of Hindustani-Surinamese, African-Surinamese and Dutch origin.
Methods:
In total, 334 Hindustani-Surinamese (~South Asian), 589 African-Surinamese (~African),and 493 Dutch (~European) men and women, aged 35-60 years, randomly selected from themunicipal register of Amsterdam, participated in an interview and physical examination.We calculated the WHtR by dividing the waist circumference by height and the log ACR(logACR, log mg/mmol) by log-transforming the albumin concentration by the creatinineconcentration in urine. The association between WHtR and logACR was studied in the totalpopulation and stratified by ethnicity. We also tested for interaction.
Results:
In the total population, a higher WHtR was associated with a higher logACR, afteradjustment for sex, age, and smoking, body mass index and the presence of type 2 diabetes orhypertension. Among the Hindustani-Surinamese, the adjusted association between WHtRand logACR appeared somewhat stronger than among the other ethnic groups: for every 0.1increase in the WHtR, the log-ACR increased by 0.522 (0.096-0.949) log mg/mmol amongthe Hindustani-Surinamese, by 0.334 (0.047-0.622) among the African-Surinamese and by0.356 (0.010-0.721) among the Dutch. However, the interaction was not statisticallysignificant.
Conclusions:
WHtR was associated with a higher ACR among populations of Hindustani-Surinamese,African-Surinamese and Dutch origin. Our study seems to support global use of WHtR inrelation to ACR across ethnic groups. However, although not significant, the associationappeared slightly stronger among the Hindustani-Surinamese than among the other ethnicgroups. If confirmed, this could have implications for use of the WHtR across ethnic groups.
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Renal neutrophil gelatinase associated lipocalin expression in lipopolysaccharide-induced acute kidney injury in the rat
Background:
Neutrophil gelatinase associated lipocalin (NGAL) is a highly predictive biomarker of acutekidney injury. To understand the role of NGAL in renal injury during sepsis, we investigatedthe temporal changes and biological sources of NGAL in a rat model of acute kidney injury,and explored the relationship between renal inflammation, humoral NGAL and NGALexpression during endotoxemia.
Methods:
To induce acute renal injury, rats were treated with lipopolysaccharide (LPS, 3.5 mg/kg, ip),and the location of NGAL mRNA was evaluated by in situ hybridization. Quantitative RTPCRwas also used to determine the dynamic changes in NGAL, tumor necrosis factor alpha(TNFalpha) and interleukin (IL)-6 mRNA expression 1, 3, 6, 12, and 24 hours following LPStreatment. The correlation among NGAL, TNFalpha and IL-6 was analyzed. Urinary and plasmaNGAL (u/pNGAL) levels were measured, and the relationship between humoral NGAL andNGAL expression in the kidney was investigated.
Results:
Renal function was affected 3-12 hours after LPS. NGAL mRNA was significantlyupregulated in tubular epithelia at the same time (P < 0.001). The course of NGAL mRNAupregulation occurred in parallel with renal damage. There was a transient increase in TNFalphaand IL-6 mRNA levels within 3 hours following LPS administration, and a strong correlationbetween TNFalpha and NGAL mRNA (r = 0.995, P <0.001) but not with IL-6 mRNA. BothpNGAL and uNGAL levels were markedly increased compared with those in the controlgroup (P < 0.001); however, only uNGAL levels were correlated with NGAL mRNA(r = 0.850, P <0.001).
Conclusions:
\NGAL upregulation is sensitive to LPS-induced renal TNFalpha increase and injury, which areobserved in the tubular epithelia. Urinary NGAL levels accurately reflect changes in NGALin the kidney.
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Chronic kidney disease among high school students of Kinshasa
Background:
Chronic kidney disease (CKD) is a major worldwide health problem. However, its burden amongadolescents and young adults is unknown, especially in sub-Saharan Africa. The aim of this study wasto investigate its prevalence in the school environment. The concordance of usual formulas used toestimate renal function was also assessed.
Methods:
In an epidemiological cross sectional study, a random sample of 524 pupils (263 boys, mean age of 18.7+/- 1.4 years) from school environment of Kinshasa were studied. Recorded parameters of interest were anthropometric, proteinuria, serum creatinine and estimated glomerular filtration rate (eGFR) according to the Schwartz formula using uncalibrated creatinine levels from one random measurement. CKD was defined as the presence of kidney damage (daily proteinuria [greater than or equal to] 300 mg) and/or reduced kidney function (eGFR < 60 ml/min/1.73 m2). Concordances between eGFR according to Schwartz, Cockcroft-Gault (C-G) indexed for BSA and modification of diet in renal disease (MDRD) study equations were computed using the kappa coefficient.
Results:
The prevalence of CKD by the Schwartz formula was 1.5%. By stage, 0.8 % had CKD stage 1 (proteinuria with normal eGFR) and 0.8% had CKD stage 3 (eGFR, 30 to 59 ml/min/1.73 m2). The prevalence of proteinuria [greater than or equal to] 300 mg/day was 1% (one case had 2.7g/day). Agreement between eGFR according to Schwartz formula and the MDRD formula was excellent (kappa: 88.8%). Although correlations between all formulas were excellent (0.99; 0.87, and 0.89), agreement was poor between eGFR according to Schwartz and C-G indexed BSA equation (kappa: 52.7%) and, poorer with C-G unadjusted for BSA (kappa: 26.9%).
Conclusion:
In the large African city of Kinshasa, 2% of high school students have CKD. This high prevalence rateemphasizes the need for appropriate detection and prevention measures in this vulnerable young age population group.Keys words: equation of reduced renal function, CKD, High School students, Prevalence, Kinshasa
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CDKD: a clinical database of kidney diseases
Background:
The main function of the kidneys is to remove waste products and excess water from theblood. Loss of kidney function leads to various health issues, such as anemia, high bloodpressure, bone disease, disorders of cholesterol. The main objective of this database system isto store the personal and laboratory investigatory details of patients with kidney disease. Theemphasis is on experimental results relevant to quantitative renal physiology, with aparticular focus on data relevant for evaluation of parameters in statistical models of renalfunction.DescriptionClinical database of kidney diseases (CDKD) has been developed with patient confidentialityand data security as a top priority. It can make comparative analysis of one or moreparameters of patient's record and includes the information of about whole range of dataincluding demographics, medical history, laboratory test results, vital signs, personal statisticslike age and weight.
Conclusions:
The goal of this database is to make kidney-related physiological data easily available to thescientific community and to maintain & retain patient's record. As a Web based application itpermits physician to see, edit and annotate a patient record from anywhere and anytime whilemaintaining the confidentiality of the personal record. It also allows statistical analysis of alldata.
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The impact of pretransplant 25-hydroxy vitamin D
deficiency on subsequent graft function: An
observational study
Background:
In addition to its canonical role in musculoskeletal health, several reports have demonstratedthat serum vitamin D level may influence kidney function. However, the effect ofpretransplant serum vitamin D level on subsequent graft function has not been explored.Therefore, this study was undertaken to examine the effect of serum vitamin D level at thetime of kidney transplantation (KT) on subsequent graft function.
Methods:
We analyzed 106 patients who underwent KT and for whom 25-hydroxy vitamin D (25-OHD) levels were measured during hospitalization prior to transplantation. We measuredestimated glomerular filtration rates (eGFR) using the Modification of Diet in Renal Disease(MDRD) formula at baseline and at six-month intervals up to 36 months after KT.
Results:
38.7% of the patients were diagnosed with 25-OHD deficiency defined as less than10 ng/mL. Recipient gender (female vs. male, odds ratio [OR] 3.30, 95% CI 1.33-8.21,P = 0.010), serum albumin level (per 1 mg/dl increase, OR 0.35, 95% CI 0.13-0.98,P = 0.047), and predominant renal replacement therapy modality before KT (P < 0.001) werefound to be independent pretransplant risk factors for 25-OHD deficiency by multivariatelogistic regression analysis. Subsequent repeated measures analysis of covariance revealedthat 25-OHD level had the only significant main effect on eGFR during the 36-month followupperiod [F (1, 88) = 12.07, P = 0.001].
Conclusions:
Pretransplant 25-OHD deficiency was significantly associated with a lower post-transplanteGFR, suggesting that 25-OHD may play an important role in maintaining graft function afterKT.
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Juxtaglomerular apparatus hyperplasia under dual angiotensin blockade. A footprint of adequate RAS inhibition or a concern for renal fibrosis?
Background:
Dual renin-angiotensin system blockade with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers has been advocated to minimize proteinuria. However, recent trials have questioned the renal safety of this approach. Our understanding on the molecular effects of dual blockade in humans is incomplete.Case presentationWe present a patient with corticoid resistant nephrotic syndrome who developed marked juxtaglomerular apparatus hyperplasia and renin expression in the context of dual angiotensin system blockade.
Conclusions:
Although renin may have profibrotic effects mediated by (pro)renin receptor activation, this report raises questions on the potential consequences of local renin activation on chronic kidney disease in patients with dual angiotensin blockade.
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The association of moderate renal dysfunction with impaired preference-based health-related quality of life: 3rd Korean national health and nutritional examination survey
Background:
Only a few large-scale studies have investigated the association between health-related quality of life (HRQOL) and renal function. Moreover, the HRQOL of patients with moderate renal dysfunction is frequently underestimated by healthcare providers. This study assessed the impact of renal function on preference-based HRQOL in Korean adult population.
Methods:
We analyzed data for 5,555 adults from the 3rd Korean National Health and Nutritional Examination Survey 2005. The EuroQol-5D (EQ-5D) utility score was used to evaluate HRQOL. The study subjects were stratified into three groups based on their estimated glomerular filtration rates (eGFRs): [greater than or equal to]90.0, 60.0-89.9 and 30.0-59.9 mL/min/1.73 m2. Individuals with advanced renal dysfunction were excluded from the analysis.
Results:
The proportions of participants who reported problems in each of the five EQ-5D dimensions increased significantly with decreasing eGFR. However, a significant decrease in the EQ-5D utility score was observed among participants with an eGFR of 30.0-59.9 mL/min/1.73 m2. Participants with an eGFR of 30.0-59.9 mL/min/1.73 m2 had an almost 1.5-fold higher risk of impaired health utility (the lowest quartile of EQ-5D utility score) compared with those participants with eGFRs [greater than or equal to]90.0 mL/min/1.73 m2, after adjustment for age, gender, health-related behaviors, socioeconomic and psychological variables, and other comorbidities. Among the five dimensions of the EQ-5D, an eGFR of 30.0-59.9 mL/min/1.73 m2 was an independent determinant of self-reported problems in the mobility and pain/discomfort dimensions.
Conclusions:
Although age affects the association between renal dysfunction and the EQ-5D, moderate renal dysfunction seems to be an important determinant of impaired health utility in a general population and may affect the mobility and pain/discomfort dimensions of health utility.
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