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- Recurrent Membranoproliferative Glomerulonephritis Type I After Kidney Transplantation: A 17-Year Single-Center Experience. [JOURNAL ARTICLE]
- Transplantation 2014 Oct 21.
Most previously published studies of patients with membranoproliferative glomerulonephritis type I are small or have short follow-up period. We report the outcome of a fairly large cohort of patients followed up for nearly 10 years.Retrospective cohort study. Graft survival, recurrence rate and risk factors for recurrence were analyzed for 43 patients transplanted between the years 1995 and 2012.At a mean overall follow-up of 118±61 months (median, 127.8; range, 4.9-217), 12 patients lost their graft (28%). Death-censored actuarial 15-year graft survival rate was 56%. Membranoproliferative glomerulonephritis recurred in eight patients (19%) at a median time of 15.4 months (range, 4.4-70 months). Recurrence led to graft loss in seven patients (88%) within a median of 11.6 months (range, 1.3-54 months) from diagnosis. Median graft survival was 30.5 months for recurrence (range, 7-86). Actuarial 15-year graft survival was 71% for nonrecurrent. The risk for recurrence was higher for patients with human leukocyte antigen (HLA) B49 (odds ratio, 16.9; 95% confidence interval, 1.1-246; P=0.038) and HLA DR4 (odds ratio, 15.9; 95% confidence interval, 1.07-237; P=0.044) alleles. A trend toward increased risk was found with shorter duration of dialysis before transplantation. Four of 16 (25%) living-related versus none of the living-unrelated donors' recipients recurred. The HLA B49, acute tubular necrosis after transplantation, previous transplantations, and Arab origin were all associated with decreased graft and patient survival.Patients without recurrence in the first years should expect an excellent graft survival. Nonrelated living donors should be preferred. The HLA B49 and DR4 alleles may increase the risk for recurrence.
- Nephronophthisis-Associated CEP164 Regulates Cell Cycle Progression, Apoptosis and Epithelial-to-Mesenchymal Transition. [JOURNAL ARTICLE]
- PLoS Genet 2014 Oct; 10(10):e1004594.
We recently reported that centrosomal protein 164 (CEP164) regulates both cilia and the DNA damage response in the autosomal recessive polycystic kidney disease nephronophthisis. Here we examine the functional role of CEP164 in nephronophthisis-related ciliopathies and concomitant fibrosis. Live cell imaging of RPE-FUCCI (fluorescent, ubiquitination-based cell cycle indicator) cells after siRNA knockdown of CEP164 revealed an overall quicker cell cycle than control cells, although early S-phase was significantly longer. Follow-up FACS experiments with renal IMCD3 cells confirm that Cep164 siRNA knockdown promotes cells to accumulate in S-phase. We demonstrate that this effect can be rescued by human wild-type CEP164, but not disease-associated mutants. siRNA of CEP164 revealed a proliferation defect over time, as measured by CyQuant assays. The discrepancy between accelerated cell cycle and inhibited overall proliferation could be explained by induction of apoptosis and epithelial-to-mesenchymal transition. Reduction of CEP164 levels induces apoptosis in immunofluorescence, FACS and RT-QPCR experiments. Furthermore, knockdown of Cep164 or overexpression of dominant negative mutant allele CEP164 Q525X induces epithelial-to-mesenchymal transition, and concomitant upregulation of genes associated with fibrosis. Zebrafish injected with cep164 morpholinos likewise manifest developmental abnormalities, impaired DNA damage signaling, apoptosis and a pro-fibrotic response in vivo. This study reveals a novel role for CEP164 in the pathogenesis of nephronophthisis, in which mutations cause ciliary defects coupled with DNA damage induced replicative stress, cell death, and epithelial-to-mesenchymal transition, and suggests that these events drive the characteristic fibrosis observed in nephronophthisis kidneys.
- Antagonism of Ca2+ Influx via L-Type Ca2+ Channels Mediates the Vasorelaxant Effect of Catharanthus roseus-Derived Vindorosine in Rat Renal Artery. [JOURNAL ARTICLE]
- Planta Med 2014 Oct 23.
Catharanthus roseus is a traditional herbal medicine used in Asian and African countries for the treatment of various diseases including hypertension. The present study examined possible cellular mechanisms for the relaxation of rat renal arteries induced by vindorosine extracted from C. roseus. Intrarenal arteries were isolated from 200-300 g male Sprague-Dawley rats and treated with different pharmacological blockers and inhibitors for the measurement of vascular reactivity on a Multi Myograph System. Fluorescence imaging by laser scanning confocal microscopy was utilized to determine the intracellular Ca(2+) level in the vascular smooth muscles of the renal arteries. Vindorosine in micromolar concentrations relaxes renal arteries precontracted by KCl, phenylephrine, 11-dideoxy-9α,11α-epoxymethanoprostaglandin F2α, and serotonin. Vindorosine-induced relaxations were unaffected by endothelium denudation or by treatment with the nitric oxide synthase inhibitor N (G)-nitro-L-arginine methyl ester hydrochloride, the guanylyl cyclase inhibitor 1H-[1, 2, 4]oxadiazolo[4,3-a]quinoxalin-1-one, the cyclooxygenase inhibitor indomethacin, or K(+) channel blockers such as tetraethylammonium ions, glibenclamide, and BaCl2. Vindorosine-induced relaxations were attenuated in the presence of 0.1 µM nifedipine (an L-type Ca(2+) channel blocker). Vindorosine also concentration-dependently suppressed contractions induced by CaCl2 (0.01-5 mM) in Ca-free 60 mM KCl solution. Furthermore, fluorescence imaging using fluo-4 demonstrated that 30 min incubation with 100 µM vindorosine reduced the 60 mM KCl-stimulated Ca(2+) influx in the smooth muscles of rat renal arteries. The present study is probably the first report of blood vessel relaxation by vindorosine and the possible underlying mechanisms involving the inhibition of Ca(2+) entry via L-type Ca(2+) channels in vascular smooth muscles.
- Pharmacological Management of Pulmonary Arterial Hypertension. [JOURNAL ARTICLE]
- AACN Adv Crit Care 2014 October/December; 25(4):317-318.
- Pharmacological Management of Pulmonary Arterial Hypertension. [JOURNAL ARTICLE]
- AACN Adv Crit Care 2014 October/December; 25(4):309-316.
- Building an Evidence Base for the Co-Occurrence of Chronic Disease and Psychiatric Distress and Impairment. [JOURNAL ARTICLE]
- Prev Chronic Dis 2014.:E188.
Mental disorders and chronic diseases have been reported to independently affect half of the US population. The objective of this study was to evaluate the comorbid nature of these conditions.We analyzed data from 39,954 participants from the 2009 California Health Interview Survey who reported both psychological distress and impairment, on the basis of the Kessler 6 and the Sheehan Disability Scale, and 1 or more of 4 chronic diseases (type 2 diabetes, high blood pressure, asthma, heart disease). Weighted and nonweighted multivariable logistic regression were used to investigate the association between psychological distress and impairment and chronic disease, after adjusting for sex, age, race, current smoking, binge drinking in the previous year, moderate physical activity, and body mass index.After controlling for covariates in the model, we found a significant dose-response relationship between reported chronic diseases and psychiatric distress and impairment that ranged from 1.50 for 1 reported chronic disease to 4.68 for 4 reported chronic diseases.The growing chronic disease burden should be understood clinically in the context of mental health conditions. Further research is needed to identify ways to integrate mental health and chronic disease prevention in primary care.
- Correlates of Measured Prehypertension and Hypertension in Latina Women Living Along the US-Mexico Border, 2007-2009. [JOURNAL ARTICLE]
- Prev Chronic Dis 2014.:E186.
Although Latinos have lower hypertension rates than non-Latino whites and African Americans, they have a higher prevalence of undiagnosed and uncontrolled hypertension. Research on predictors of hypertension has mostly focused on intrapersonal factors with no studies assessing the combined influence of intrapersonal, interpersonal, and environmental factors. The purpose of this study was to assess a broad range of correlates including intrapersonal, interpersonal, and environmental factors on measured blood pressure category (nonhypertensive, prehypertensive, and hypertensive) in a sample of Latina women residing in San Diego, California.This cross-sectional study used baseline data from the San Diego Prevention Research Center's Familias Sanas y Activas program, a promotora-led physical activity intervention. The sample was 331 Latinas who self-selected into this program. Backward conditional logistic regression analysis was conducted to determine the strongest correlates of measured blood pressure category.Logistic regression analysis suggested that the strongest correlates of prehypertension were soda consumption (odds ratio [OR] = 1.34, [1.00-1.80], P ≤ .05) and age (OR = 1.03, [1.00-1.05], P ≤ .05). The strongest correlates of hypertension were soda consumption (OR = 1.92, [1.20-3.07], P ≤ .01), age (OR = 1.09, [1.05-1.13], P ≤ .001), and measured body mass index (OR = 1.13, [1.05-1.22], P ≤ .001). All analyses controlled for age and education. No interpersonal or environmental correlates were significantly associated with blood pressure category.Future research should aim to further understand the role of soda consumption on risk for hypertension in this population. Furthermore, interventions aimed at preventing hypertension may want to focus on intrapersonal level factors.
- Effect of Acute Arteriolar Vasodilation on Capacitance and Resistance in Pulmonary Arterial Hypertension. [JOURNAL ARTICLE]
- Chest 2014 Oct 23.
Pulmonary vascular capacitance (PVC) is reduced in pulmonary arterial hypertension (PAH). In normal lung PVC is largely a function of vascular compliance. In PAH, increased resistance (PVR) arises from the arterioles. PVR and PVC share pressure and volume variables. The dependency between the two qualities of the vascular bed is unclear in a state of intense vasoconstriction.We compared PVC and PVR before and during nitric oxide (NO) inhalation during right heart catheterization in 8 NO responsive PAH patients. NO only directly affects tone in parenchymal vessels.During NO inhalation, Pa systolic decreased, 80± 20 STD to 48 ± 20 mmHg and stroke volume increased , 62 ± 19 to 86 ± 24 ml. (p<0.01). PVR dropped from 10 ± 4.4 to 4.7 ± 2.2 Wood units (p<0.012), and PVC increased from 1.4 ± 1.1 to 3.2 ± 1.8 ml/mmHg (p <0.018). The magnitude of PVR drop was 57± 6% and the decrease in 1/PVC was 54 ± 14%, p=ns.In vasoresponsive PAH, PVC is a function of the pressure response of the vasoconstricted arterioles to stroke volume. Immediately upon vasodilation, the capacitance increases markedly. The compliance vessels are thus the same as the resistance vessels. The immediate reduction in Pa pressure during NO suggests that large vessel remodeling is not a major contributor to systolic pressure in these patients.
- Neuroblastoma accompanied by hyperaldosteronism. [Journal Article]
- J Renal Inj Prev 2014; 3(3):79-82.
Tumors known derived from kidneys which take place in secondary hyperaldosteronism etiology are juxtaglomerular cell tumor and Wilms' tumor. Neuroblastoma presenting with hyperaldosteronism is rare.A 15-month-old girl who had been having diarrhea and fever for 2 weeks presented with a 3 day history of bilious vomiting, metabolic acidosis and severe hypokalemia. She was referred to our hospital with the pre-diagnosis of unknown manifest hypertension etiology, diarrhea, and paralytic ileus after having therapy-resistant hypokalemia and severe resistant acidosis. On her examination after being admitted to our clinic, she was weak, unwell and lethargic with a blood pressure of 140/93 mmHg. Due to the hypertension and severe hypokalemia, the patient was considered to be hyperaldosteronism. Serum aldosterone level, plasma renin activity and cortisol level were elevated. Radiologic findings were compatible with neuroblastoma. The patient underwent an abdominal surgery and the mass excision. The histopathological examination was proved neuroblastoma.Hyperaldosteronism can be presented by unexpected atypical forms as in our patient.
- Role of endothelial nitric oxide synthase VNTR (intron 4 a/b) polymorphism on the progression of renal disease in autosomal dominant polycystic kidney disease. [Journal Article]
- J Renal Inj Prev 2014; 3(3):69-73.
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder, and it is mainly associated with renal cyst formation. Several studies have also shown that these mutations regulate the physiology of epithelial tissues and determine renal cyst formation and growth in polycystic kidney disease (PKD). Nitric oxide (NO) is also considered to be an important factor involved in the deterioration of renal function.The aim of the current study is to determine the frequency of NOS3 27-bp VNTR in ADPKD patients and to investigate the role of NOS3 27-bp VNTR genotypes in the modification of progression of renal disease in ADPKD.The hypothesis was investigated by studying the South Indian population of 53 ADPKD patients and 94 unrelated healthy controls. The genotyping was performed by polymerase chain reaction and electrophoresis. Genotypes were compared between ADPKD and controls using the χ(2)-test. Univariate and multivariate logistic regression analyses were performed to assess the effect of genotypes and hypertension on the progress of chronic kidney disease (CKD). A stratified analysis was also performed to assess the evidence of the modification of hypertension-CKD relationship among VNTR genotypes.The NOS3 4a allele frequencies were 21.3% and 13.2% respectively for controls and ADPKD groups. The NOS3 VNTR genotypes and alleles were not associated with ADPKD. The univariate analysis showed that age, hypertension and NOS3 VNTR influenced the advancement of CKD.The present study confirms the significant association between the 27-bp VNTR and CKD advancement among the ADPKD patients in the South Indian population.