Current Issue : October - December Volume : 2015 Issue Number : 4 Articles : 8 Articles
Background: The recently suggested distinct pathogenic pathways for myeloperoxidase (MPO) and proteinase 3 (PR3)\nanti-neutrophilic cytoplasmic antibodies (ANCA) associated vasculitis could result in different modes of presentation\nand outcome. Moreover, kidney outcome was related to a new histopathologic classification of pauci-immune\nglomerulonephritis. As reports were not always concordant, possible because differences in severity of organ\nlesions and ethnicity, we evaluated the outcome of a cohort of Central-East European patients with crescentic\nglomerulonephritis in relation with ANCA specificity and histopathological classification.\nMethods: Seventy-five patients were consecutively diagnosed by kidney biopsy (76 % MPO-ANCA specificity,\n52 % crescentic) and followed for a median period of 3.2 years. Study end-points were response to therapy, end\nstage renal disease (ESRD) and death.\nResults: PR3-ANCA patients were younger, in higher proportion male and had higher Birmingham Vasculitis\nActivity Scores (BVAS). The kidney disease was severe at presentation (median creatinine 5 mg/dL; 27 % required\ntemporary dialysis) and worst in PR3-ANCA positive patients (50 % patients needed temporary dialysis vs. 19 %). The\nlung was the second most affected organ (31 % severe lung hemorrhage). Lung and kidney damage were related; the\nodds of hemorrhagic alveolitis in patients needing dialysis at presentation were 4 (95 % CI 1ââ?¬â??13; p = 0.006) times higher\nthan in those who did not. The rate of response to therapy (without signs of active vasculitis and stable or declining\nserum creatinine) was 60 % and was associated with dialysis independency, older age and higher platelet number at\npresentation. The probabilities to survival 1 and 5 years for kidney and patient were 93 and 64 %, and respectively 88\nand 67 %. Kidney survival was predicted by response to therapy and dialysis independency at presentation. Patients\nwith BVAS < 15 and responding to induction therapy had better chances of survival. Neither response to therapy nor\noutcome was influenced by ANCA specificity or by the histopathological class.\nConclusions: When kidney damage is severe in ANCA vasculitis, the need of dialysis at presentation and the response\nto induction therapy overcome the prognostic utility of both ANCA specificity and histopathological class....
Background: The leading cause of death in end stage renal disease is cardiovascular disease (CVD). Kidney\ntransplantation is associated with improved survival over dialysis. We hypothesized that arterial stiffness, a marker\nof CVD, would improve in patients post kidney transplant, potentially explaining one mechanism of survival benefit\nfrom transplant.\nMethods: After obtaining Institutional Review Board approval and informed consent, we performed a longitudinal\nprospective cohort study of 66 newly transplanted adult kidney transplant recipients, using aortic pulse wave velocity\n(PWV) to assess arterial stiffness over a 12 month period. All patients were assessed within one month of transplant\n(baseline) and 12 months post transplant. The primary outcome was change in PWV score at 12 months which we\nassessed using Wilcoxon Signed Rank test. Secondary analyses included correlation of predictors with PWV score at\nboth time points.\nResults: The median age of the cohort was 49.7 years at transplant, with 27 % Black and 27 % female. At baseline,\n43 % had tobacco use, 30 % had a history of CVD, and 42 % had diabetes. Median baseline calcium was 9.1 mg/dL\nand median phosphorus was 5.1 mg/dL. Median PWV score was 9.25 and 8.97 m/s at baseline versus month 12,\nrespectively, showing no significant change (median change of ?0.07, p = 0.7). In multivariable regression, subjects\nwith increased age at transplant (p = 0.008), diabetes (p = 0.002), and a higher baseline PWV score (p < 0.001) were at\nincreased risk of having a high PWV score 12 months post transplant.\nConclusion: Aortic arterial stiffness does not progress in the first year post kidney transplant. Increasing age, diabetes,\nand higher baseline PWV score identify patients at risk for increased arterial stiffness. Further research that assesses\npatients for greater than one year and includes a control dialysis group would be helpful in further understanding the\nchange in arterial stiffness post transplantation...
Background: It is widely accepted that metabolic syndrome is associated with an increased risk of chronic kidney\ndisease (CKD). To investigate whether coexisting metabolic syndrome is a necessary condition for CKD in\noverweight and obese.\nMethods: A cohort study of 6852 Chinese individuals from August 2007 to December 2012. Examinations included\na questionnaire, physical measurements, and blood sampling. Hazard ratios for incident CKD were estimated\naccording to combinations of BMI category and absence or presence of metabolic syndrome.\nResults: For CKD, multivariable adjusted hazard ratios vs. normal weight individuals without metabolic syndrome\nwere 1.31 (95 % CI, 0.89ââ?¬â??1.92) in overweight and 2.39 (95 % CI, 1.27ââ?¬â??4.52) in obese without metabolic syndrome\nand 1.54 (95 % CI, 1.18ââ?¬â??3.95) in normal weight, 2.06 (95 % CI, 1.27ââ?¬â??3.36) in overweight, and 2.77 (95 % CI, 1.42ââ?¬â??4.31)\nin obese with metabolic syndrome. There were no interactions between BMI and absence or presence of metabolic\nsyndrome on risk of CKD when BMI was categorized (normal weight, overweight, obese) (P = 0.17). Among\nindividuals both with and without metabolic syndrome there were increasing cumulative incidences of CKD from\nnormal weight through overweight to obese individuals (log-rank trend P = 0.04 to P < 0.001). Although the\nmultivariable adjusted hazard ratio for CKD in individuals with vs. without metabolic syndrome was 1.82 (95 % CI,\n1.20ââ?¬â??2.78) within overweight and obese individuals (log-rank P = 0.005), only 26.1 % of the increased risk observed\nfor BMI is explained by metabolic syndrome.\nConclusions: These findings suggest overweight and obesity are risk factors for CKD regardless of the presence or\nabsence of metabolic syndrome....
Background: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is a rare autosomal recessive renal\ndisease characterized by tubular disorders at the thick ascending limb of Henle�s loop. It is caused by mutations in\nthe tight junction structural proteins claudin-16 or claudin-19, which are encoded by the CLDN16 and CLDN19\ngenes, respectively. Patients exhibit excessive wasting of calcium and magnesium, nephrocalcinosis, chronic kidney\ndisease, and early progression to end-stage renal failure during infancy.\nCase presentation: We here report the phenotype and molecular analysis of a female Brazilian patient with a novel\nlarge homozygous deletion in the CLDN16 gene. The proband, born from consanguineous parents, presented the first\nsymptoms at age 20. Clinical examination revealed hypocalcemia, hypomagnesemia, nephrocalcinosis, mild myopia,\nhigh serum levels of uric acid and intact parathyroid hormone, and moderate chronic kidney disease (stage 3). She and\nher mother were subjected to CLDN16 and CLDN19 mutational analysis. In addition, the multiplex ligation-dependent\nprobe amplification method was used to confirm a CLDN16 multi-exon deletion. Direct sequencing revealed a normal\nCLDN19 sequence and suggested a large deletion in the CLDN16 gene. Multiplex ligation-dependent probe amplification\nshowed a homozygous CLDN16 multi-exon deletion (E2_E5del). The patient initiated conventional treatment for familial\nhypomagnesemia with hypercalciuria and nephrocalcinosis and progressed to end-stage kidney disease after five years.\nConclusions: This study provides the first report of a large homozygous deletion in the CLDN16 gene causing familial\nhypomagnesemia with hypercalciuria and nephrocalcinosis with late onset of the first symptoms. This description\nexpands the phenotypic and genotypic characterization of the disease. The late-onset chronic kidney disease in the\npresence of a homozygous deletion in the CLDN16 gene reinforces the great variability of genotype-phenotype\nmanifestation in patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis...
Background: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary\nkidney diseases that frequently result in renal failure. In this cross-sectional observational cohort study, we evaluated\nurinary angiotensinogen (AGT) as a potential biomarker to assess renal function in ADPKD.\nMethods: Urinary AGT was measured in 233 ADPKD patients and its association with estimated glomerular filtration\nrate (eGFR) and height-adjusted total kidney volume (htTKV) were evaluated. The localization of AGT and other\nrenin-angiotensin system (RAS)-related molecules were identified using immunohistochemistry in human ADPKD tissues.\nResults: Baseline urinary AGT/Cr was negatively correlated with CKD-EPI eGFR (r2 = 0.162, P < 0.001) and positively\ncorrelated with htTKV (r2 = 0.107, P < 0.001). Both urinary AGT/Cr and plasma renin activity levels were significantly\nelevated in hypertensive ADPKD patients. Among hypertensive subjects, urinary AGT/Cr was significantly increased\nin the advanced CKD stages (III-V) compared to early CKD stages (I-II) (28.6 �± 60.3 vs. 93.2 �± 139.3 ?g/g, P < 0.001).\nImmunohistochemical study showed strong expression of AGT along the cyst-lining epithelial cells as well as the\nnearby compressed tubular epithelial cells.\nConclusions: Our results suggested that urinary AGT/Cr may be a valuable biomarker for renal damage in ADPKD\nsince intrarenal ischemic insults induced by cyst growth and subsequent intrarenal RAS activation may play a\npotential role in the development of hypertension and renal dysfunction in ADPKD...
Background: A number of studies have provided information regarding the risks and benefits of mammalian target\nof rapamycin inhibitors (mTOR-I) combined with calcineurin inhibitors (CNI) versus mycophenolic acid (MPA).\nMethods: Medline, Embase and the Cochrane Central Register of Controlled Trials were searched. Randomized\ncontrolled trials comparing mTOR-I to MPA as the primary immunosuppressive regimen in combination with CNI\nwere selected and meta-analyzed.\nResults: Eleven randomized controlled trials consisting of 4930 patients in total were included. No significant\ndifference was observed in the risk of biopsy-proven acute rejection and patient death between the two groups.\nHowever, an increased risk of graft loss (relative risk (RR) = 1.20) and inferior graft function (creatinine clearance,\nweighted mean difference (WMD) = ?2.41 ?mol/L) were demonstrated in mTOR-I-treated patients. Patients treated\nwith mTOR-I had a higher risk of new-onset diabetes mellitus (RR = 1.32), dyslipidemia, proteinuria (RR = 1.79), peripheral\nedema (RR = 1.34), thrombocytopenia (RR = 1.97) and lymphocoele (RR = 1.80), but a lower risk of cytomegalovirus\ninfection (RR = 0.40), malignancy (RR = 0.64) and leucopenia (RR = 0.43). There was no difference in diarrhea, anemia,\nurinary tract infection, polyoma virus infection and impaired wound healing when mTOR-I was compared with MPA.\nConclusions: mTOR-I showed no particular superiority to MPA. Notably, mTOR-I had an increased risk of graft loss\nwhen combined with CNI, even when combined with a reduced dose of CNI. Therefore, the optimal dosage strategies\nfor mTOR-I and CNI need to be further explored....
Background: ANCA-associated vasculitis (AAV) with renal involvement is not uncommon in older individuals.\nUnfortunately, this can be catastrophic requiring hemodialysis (HD) and may lead to end stage renal disease (ESRD).\nHowever, more than 50 % of patients with AAV who require HD initially have renal recovery and discontinue HD.\nThe aim of this study was to describe a retrospective cohort of older patients with AAV and severe renal involvement\nwhich required hemodialysis.\nMethods: Between 1995 and 2013 a total of 30 patients with histologic evidence of pauci-immune glomerulonephritis\nwho required HD were evaluated at a single university center. The association of demographic and clinical parameters\nwith age was assessed. Older age of disease onset was defined as age ?60 years. The risk of developing ESRD at 3\nmonths was examined using univariate logistic regression analysis.\nResults: Among 30 patients with AAV who required HD, the mean age of disease onset was 59 �± 17 years (range\n22-88 years). Twelve patients were in the older age group, and 18 were in the younger group. Three months after\ndiagnosis, 43 % of the cohort had ESRD with a statistically similar proportion of older (n = 9, 50 %) versus younger\n(n = 4, 33 %) patients (p = 0.367). Most patients (93 %) received immunosuppressive therapy. There was not a\nstatistically significant association between age and ESRD.\nConclusions: These data suggest that age alone does not predict renal recovery among individuals on HD due to\nAAV. Renal recovery is a realistic expectation and outcome, if patients are treated, even among older patients with\nAAV who require HD initially....
Background: The FAVOURED study is an international multicentre, double-blind, placebo-controlled trial which\ncommenced recruitment in 2008 and examines whether omega-3 polyunsaturated fatty acids (omega-3 PUFAs)\neither alone or in combination with aspirin will effectively reduce primary access failure of de novo arteriovenous\nfistulae (AVF) in patients with stage 4 and 5 chronic kidney disease. Publication of new evidence derived from\nadditional studies of clopidogrel and a high screen failure rate due to prevalent aspirin usage prompted an updated trial\ndesign.\nMethods/design: The original trial protocol published in 2009 has undergone two major amendments, which were\nimplemented in 2011. Firstly, the primary outcome ââ?¬Ë?early thrombosisââ?¬â?¢ at 3 months following AVF creation was broadened\nto a more clinically relevant outcome of ââ?¬Ë?AVF access failureââ?¬â?¢; a composite of thrombosis, AVF abandonment and\ncannulation failure at 12 months. Secondly, participants unable to cease using aspirin were allowed to be enrolled and\nrandomised to omega-3 PUFAs or placebo. The revised primary aim of the FAVOURED study is to test the hypothesis that\nomega-3 PUFAs will reduce rates of AVF access failure within 12 months following AVF surgery. The secondary aims are\nto examine the effect of omega-3 PUFAs and aspirin on the individual components of the primary end-point, to examine\nthe safety of study interventions and assess central venous catheter requirement as a result of access failure.\nDiscussion: This multicentre international clinical trial was amended to address the clinically relevant question of whether\nthe usability of de novo AVF at 12 months can be improved by the early use of omega-3 PUFAs and to a lesser\nextent aspirin. This study protocol amendment was made in response to a large trial demonstrating that clopidogrel is\neffective in safely preventing primary AVF thrombosis, but ineffective at increasing functional patency. Secondly,\nincluding patients taking aspirin will enrol a more representative cohort of haemodialysis patients, who are significantly\nolder with a higher prevalence of cardiovascular disease and diabetes which may increase event rates and the power of\nthe study....
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