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1.
J Clin Hypertens (Greenwich) ; 21(6): 786-791, 2019 06.
Article in English | MEDLINE | ID: mdl-31127691

ABSTRACT

Previous studies suggest an increased cancer risk in hypertension. Patients with hypertensive nephropathy have not been studied. A national registry study was performed to assess the presence and size of this association. Clinical data and cancer diagnoses for all patients with biopsy-proven hypertensive nephropathy between 1985 and 2015 in Denmark were extracted from four national registries and compared with age- and sex-adjusted national cancer rates. The risk of cancer was twice the background population. It was raised for renal cancer (odds ratio 10.4), myeloma (13.2), skin cancer (7.9), and other/unspecified (1.8). No increase in incidence was seen until 1 year before renal biopsy and then rose rapidly. It was again normal 5 years after biopsy. Hypertensive nephropathy is associated with an increased risk of myeloma, skin, renal, and other cancers. Screening of patients with hypertensive nephropathy, in the presence of reduced renal function or significant proteinuria, may be indicated.


Subject(s)
Hypertension, Renal/complications , Kidney Neoplasms/etiology , Multiple Myeloma/etiology , Nephritis/complications , Skin Neoplasms/etiology , Adult , Aged , Biopsy , Case-Control Studies , Denmark/epidemiology , Humans , Hypertension/complications , Hypertension, Renal/epidemiology , Hypertension, Renal/mortality , Hypertension, Renal/pathology , Incidence , Kidney Neoplasms/epidemiology , Middle Aged , Multiple Myeloma/epidemiology , Nephritis/epidemiology , Nephritis/mortality , Nephritis/pathology , Prevalence , Proteinuria/diagnosis , Registries , Renal Insufficiency/complications , Renal Insufficiency/physiopathology , Risk Factors , Skin Neoplasms/epidemiology , Survival Analysis
2.
BMC Gastroenterol ; 18(1): 79, 2018 Jun 07.
Article in English | MEDLINE | ID: mdl-29879915

ABSTRACT

BACKGROUND: Portopulmonary hypertension (PPH) was once regarded as a contraindicaton to liver transplantation (LT). However, growing evidence has indicated that PPH patients undergoing LT may show similar outcomes compared to those without PPH, and researchers have recommended it not be an absolute contraindication. Given this controversy, we aimed to identify and review the current evidence on this topic and to provide a comparison of the outcomes after LT between candidates with PPH and those without. METHODS: We systematically searched the MEDLINE, EMBASE and Cochrane Library databases for all studies that compared the outcomes of PPH patients and those without PPH after LT. All studies reporting outcomes of PPH patients versus those without PPH (Control) were further considered for inclusion in this meta-analysis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to compare the pooled data between PPH and Control groups. RESULTS: Eleven retrospective trials and one prospective, randomized, controlled trial, involving 37,686 transplant recipients were included. The PPH patients had increased 1-year mortality with an OR of 1.59 (95% CI = 1.26-2.01, P = 0.0001) compared to the control group. There was no significant difference in graft loss and 30-day mortality after LT between the two groups. CONCLUSIONS: Patients with PPH who underwent LT had increased 1-year mortality compared to those without PPH, while graft loss and 30-day mortality were similar. Nevertheless, LT may be a reasonable therapeutic option for some patients with PPH, but further studies are needed to identify those select patients with PPH who would benefit most from LT.


Subject(s)
Hypertension, Pulmonary/surgery , Hypertension, Renal/surgery , Liver Transplantation , Adolescent , Adult , Aged , Graft Survival , Hemodynamics , Humans , Hypertension, Pulmonary/mortality , Hypertension, Pulmonary/physiopathology , Hypertension, Renal/mortality , Hypertension, Renal/physiopathology , Liver Transplantation/adverse effects , Middle Aged , Survival Analysis , Treatment Outcome , Young Adult
3.
Int J Mol Sci ; 18(8)2017 Aug 02.
Article in English | MEDLINE | ID: mdl-28767097

ABSTRACT

The incidence of chronic kidney disease (CKD) is increasing worldwide, with more than 26 million people suffering from CKD in the United States alone. More patients with CKD die of cardiovascular complications than progress to dialysis. Over 80% of CKD patients have hypertension, which is associated with increased risk of cardiovascular morbidity and mortality. Another common, perhaps underappreciated, feature of CKD is an overactive sympathetic nervous system. This elevation in sympathetic nerve activity (SNA) not only contributes to hypertension but also plays a detrimental role in the progression of CKD independent of any increase in blood pressure. Indeed, high SNA is associated with poor prognosis and increased cardiovascular morbidity and mortality independent of its effect on blood pressure. This brief review will discuss some of the consequences of sympathetic overactivity and highlight some of the potential pathways contributing to chronically elevated SNA in CKD. Mechanisms leading to chronic sympathoexcitation in CKD are complex, multifactorial and to date, not completely understood. Identification of the mechanisms and/or signals leading to sympathetic overactivity in CKD are crucial for development of effective therapeutic targets to reduce the increased cardiovascular risk in this patient group.


Subject(s)
Hypertension, Renal/physiopathology , Renal Insufficiency, Chronic/physiopathology , Sympathetic Nervous System/physiopathology , Animals , Humans , Hypertension, Renal/mortality , Renal Insufficiency, Chronic/mortality
4.
Clin Exp Hypertens ; 38(5): 476-81, 2016.
Article in English | MEDLINE | ID: mdl-27367452

ABSTRACT

BACKGROUND: Hypertension is a crucial risk factor for cardiovascular death and loss of residual kidney function. Absence of the nocturnal decline in blood pressure (BP) predicts cardiovascular events and poor prognosis. However, characteristics of hypertension in moderate-to-severe chronic kidney disease (CKD) have not been fully evaluated. We aimed to assess the circadian variation of BP and kidney survival in CKD patients. METHODS: Patients who were examined by 24-h ambulatory BP monitoring (ABPM) and estimated glomerular filtration rate (eGFR), <45 ml/min/1.73 m(2), were enrolled in the study. The impacts of BP circadian rhythm and brain natriuretic peptide (BNP) on kidney survival were evaluated. RESULTS: A total of 124 patients were enrolled. The average age was 64 ± 14 years, 57% were male, and 43% had diabetes. Forty-five percent of patients had a non-dipper pattern, 35% had a riser pattern, 19% had a dipper pattern, and 1% had an extreme-dipper pattern. The prevalence of diabetes and plasma BNP levels was higher and eGFR was lower in the riser-pattern group than in the non-riser-pattern group. Kidney survival rates were significantly worse in the riser-pattern group than in the non-riser-pattern group (p < 0.05). Moreover, among riser and non-riser pattern groups divided by BNP levels, the riser group with higher BNP level showed the worst kidney survival (p < 0.05). CONCLUSION: The riser pattern is frequently associated with several conditions at higher risk for kidney survival. Patients with a rising pattern and higher BNP levels have a worse kidney prognosis.


Subject(s)
Circadian Rhythm/physiology , Hypertension, Renal/mortality , Renal Insufficiency, Chronic/mortality , Blood Pressure/physiology , Blood Pressure Monitoring, Ambulatory , Female , Glomerular Filtration Rate/physiology , Humans , Hypertension, Renal/complications , Hypertension, Renal/physiopathology , Kaplan-Meier Estimate , Male , Middle Aged , Natriuretic Peptide, Brain/metabolism , Prevalence , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/physiopathology , Risk Factors
5.
Zhonghua Nei Ke Za Zhi ; 54(2): 125-9, 2015 Feb.
Article in Chinese | MEDLINE | ID: mdl-25907843

ABSTRACT

OBJECTIVE: To analyze the clinical features, laboratory tests, treatments and outcome of patients with scleroderma renal crisis (SRC). METHODS: We retrospectively reviewed the clinical and laboratory data of 16 patients with scleroderma renal crisis in Peking Union Medical College Hospital from May 2004 to May 2013. The treatment and outcome of SRC patients were also retrospectively analyzed. RESULTS: There were a total of 16 SRC patients including 5 male patients and 11 females. The median age at SRC onset was (49.9 ± 12.3) years. It usually took 3.2 years from the diagnosis of systemic sclerosis (SSc) to SRC attack. Ten SRC patients belonged to diffuse cutaneous systemic sclerosis (dcSSc), and 6 patients were limited cutaneous systemic sclerosis (lcSSc). Among SRC patients, 16/16 were negative of anti-centromere antibodies (ACAs). All these 16 patients had hypertension and renal insufficiency, including 8 dialysis dependent after the onset of SRC and 7 with thrombotic microangiopathy. There were 3 patients receiving renal biopsy. The pathological findings were mainly summarized as intimal thickening and stenosis of renal arterioles. Among 13 patients with long-term followed-up, 11 patients received angiotensin converting enzyme inhibitors (ACEI), 5 patients died, 2 patients were dialysis dependent. Only 1 patient stopped dialysis after the combination treatment of ACEI and endothelin receptor antagonist. Another 5 patients didn't need dialysis. CONCLUSION: SRC usually occurred at the early course of SSc. dcSSc was more frequent than lcSSc. ACAs were rarely found in SRC patients. The immediate and sufficient use of ACEIs was still the cornerstone of SRC treatment. Future studies are needed to evaluate the efficacy of endothelin receptor antagonist in the treatment of SRC.


Subject(s)
Acute Kidney Injury/etiology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antibodies, Antinuclear/therapeutic use , Hypertension, Renal/etiology , Scleroderma, Systemic/therapy , Acute Kidney Injury/mortality , Acute Kidney Injury/therapy , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Female , Humans , Hypertension, Renal/mortality , Hypertension, Renal/therapy , Kidney Diseases , Male , Middle Aged , Renal Dialysis , Renal Insufficiency , Retrospective Studies , Scleroderma, Systemic/complications , Survival Analysis , Treatment Outcome
6.
Curr Atheroscler Rep ; 16(12): 459, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25301353

ABSTRACT

The diagnosis of renal artery stenosis (RAS) has become increasingly common in part due to greater awareness of ischemic renal disease and increased use of diagnostic techniques. Over 90 % of RAS cases are caused by atherosclerotic renovascular disease (ARVD). Patients with ARVD are at high risk for fatal and nonfatal cardiovascular and renal events. The mortality rate in patients with ARVD is high, especially with other cardiovascular or renal comorbidities. Recent clinical studies have provided substantial evidence concerning medical therapy and endovascular interventional therapeutic approaches for ARVD. Despite previous randomized clinical trials, the optimal therapy for ARVD remained uncertain until the results of the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial were released recently. CORAL demonstrated that optimal medical therapy was equally effective to endovascular therapy in the treatment of ARVD. Clinicians can now practice with more evidence-based medicine to treat ARVD and potentially decrease mortality in patients with ARVD using optimal medical therapy.


Subject(s)
Angioplasty, Balloon/methods , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Atherosclerosis/pathology , Renal Artery Obstruction/therapy , Aged , Antihypertensive Agents/therapeutic use , Endovascular Procedures/methods , Evidence-Based Medicine , Female , Humans , Hypertension, Renal/mortality , Hypertension, Renal/pathology , Hypertension, Renal/therapy , Male , Middle Aged , Prognosis , Randomized Controlled Trials as Topic , Renal Artery Obstruction/mortality , Renal Artery Obstruction/pathology , Risk Assessment , Severity of Illness Index , Stents , Survival Rate , Treatment Outcome
7.
Adv Chronic Kidney Dis ; 21(3): 273-80, 2014 May.
Article in English | MEDLINE | ID: mdl-24780455

ABSTRACT

Diabetic nephropathy is the most common cause of CKD and represents a large and ominous public health problem. Patients with diabetic kidney disease have exceptionally high rates of cardiovascular morbidity and mortality. In fact, the excess mortality among patients with diabetes appears to be largely limited to the subgroup with kidney disease and explained by their high burden of cardiovascular disease. The mechanisms underlying the strong association between diabetic kidney disease and various forms of cardiovascular disease are poorly understood. Traditional risk factors for cardiovascular disease, although prevalent among those with diabetes, do not fully account for the heightened risk observed. Despite their susceptibility to cardiovascular disease, patients with CKD are less likely to receive appropriate risk factor modification than the general population. Moreover, because patients with CKD have commonly been excluded from major cardiovascular trials, the evidence for potential treatments remains limited. The mainstays of treatment for diabetic kidney disease currently include blockade of the renin-angiotensin-aldosterone system and control of hypertension, hyperglycemia, and dyslipidemia. Increased awareness of the vulnerability of this patient population and more timely interventions are likely to improve outcomes while large evidence gaps are filled with newer studies.


Subject(s)
Coronary Artery Disease , Diabetic Nephropathies , Dyslipidemias , Hypertension, Renal , Coronary Artery Disease/drug therapy , Coronary Artery Disease/mortality , Coronary Artery Disease/physiopathology , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/mortality , Diabetic Nephropathies/physiopathology , Dyslipidemias/drug therapy , Dyslipidemias/mortality , Dyslipidemias/physiopathology , Humans , Hypertension, Renal/drug therapy , Hypertension, Renal/mortality , Hypertension, Renal/physiopathology , Morbidity , Prevalence , Risk Factors
8.
BMC Nephrol ; 15: 42, 2014 Mar 06.
Article in English | MEDLINE | ID: mdl-24602391

ABSTRACT

BACKGROUND: Hypertension (HTN) is one of the major causes of cardiovascular morbidity and mortality. The objective of the study was to investigate the burden and predictors of HTN in India. METHODS: 6120 subjects participated in the Screening and Early Evaluation of Kidney disease (SEEK), a community-based screening program in 53 camps in 13 representative geographic locations in India. Of these, 5929 had recorded blood pressure (BP) measurements. Potential predictors of HTN were collected using a structured questionnaire for SEEK study. RESULTS: HTN was observed in 43.5% of our cohort. After adjusting for center variation (p < 0.0001), predictors of a higher prevalence of HTN were older age ≥ 40 years (p < 0.0001), BMI of ≥ 23 Kg/M2 (p < 0.0004), larger waist circumference (p < 0.0001), working in sedentary occupation (p < 0.0001), having diabetes mellitus (p < 0.0001), having proteinuria (p < 0.0016), and increased serum creatinine (p < 0.0001). High school/some college education (p = 0.0016), versus less than 9th grade education, was related with lower prevalence of HTN. Of note, proteinuria and CKD were observed in 19% and 23.5% of HTN subjects. About half (54%) of the hypertensive subjects were aware of their hypertension status. CONCLUSIONS: HTN was common in this cohort from India. Older age, BMI ≥ 23 Kg/M2, waist circumference, sedentary occupation, education less, diabetes mellitus, presence of proteinuria, and raised serum creatinine were significant predictors of hypertension. Our data suggest that HTN is a major public health problem in India with low awareness, and requires aggressive community-based screening and education to improve health.


Subject(s)
Cost of Illness , Hypertension, Renal/diagnosis , Hypertension, Renal/mortality , Kidney Diseases/diagnosis , Kidney Diseases/mortality , Mass Screening/statistics & numerical data , Adult , Early Diagnosis , Female , Humans , India/epidemiology , Male , Middle Aged , Prevalence , Prognosis , Risk Assessment , Survival Rate
9.
Pharmacol Res ; 80: 9-13, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24368192

ABSTRACT

Multiple studies indicate that endothelin antagonism may have a protective effect for chronic kidney disease. Despite that, clinical studies using avosentan have been halted due to adverse effects including fluid overload. Therefore, we aimed at investigating whether avosentan may have protective effects against hypertensive nephropathy at doses below those inducing fluid-retention. We used double transgenic rats (dTGR), overexpressing both the human renin and angiotensinogen gene, which develop malignant hypertension. Effects of avosentan alone or in combination with low-dose of valsartan (angiotensin AT1 receptor antagonist) on end-organ damage were studied. Avosentan induced a decrease of diuresis (18.3%) with a consequent decrease in hematocrit (8.3%) only at the highest dose investigated (100mg/kg). Treatment with the combination of avosentan and valsartan (10 and 0.1mg/kg, once daily by gavage, respectively) decreased albuminuria to a greater extent than each compound given alone (avosentan: 19.6mg/24h; valsartan: 12.9mg/24h; avosentan+valsartan: 1.7mg/24h, data are median values). Histological severity score also showed a drastic reduction of kidney damage. Furthermore, avosentan alone or in combination therapy dramatically decreased mortality compared to the 100% in untreated animals. These data support a therapeutic effect of avosentan at doses below those inducing fluid overload.


Subject(s)
Hypertension, Renal/drug therapy , Nephritis/drug therapy , Pyridines/administration & dosage , Pyridines/therapeutic use , Pyrimidines/administration & dosage , Pyrimidines/therapeutic use , Albuminuria/drug therapy , Angiotensin II Type 1 Receptor Blockers/administration & dosage , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensinogen/biosynthesis , Angiotensinogen/genetics , Animals , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/therapeutic use , Diuresis/drug effects , Dose-Response Relationship, Drug , Drug Therapy, Combination , Hematocrit , Humans , Hypertension, Renal/mortality , Hypertension, Renal/pathology , Kidney/drug effects , Kidney/pathology , Male , Nephritis/mortality , Nephritis/pathology , Pyridines/adverse effects , Pyrimidines/adverse effects , Rats , Rats, Transgenic , Renin/biosynthesis , Renin/genetics , Tetrazoles/administration & dosage , Tetrazoles/therapeutic use , Valine/administration & dosage , Valine/analogs & derivatives , Valine/therapeutic use , Valsartan
10.
Int Urol Nephrol ; 46(6): 1201-7, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24097274

ABSTRACT

OBJECTIVES: The objective of the study is to identify and compare the different causes of death among peritoneal dialysis (PD) patients varying in baseline characteristics, including gender, age, primary diseases, and comorbidities and to assess risk factors for first-year death. METHODS: The clinical data of 179 PD patients who were regularly followed up in our hospital and died between January 2006 and February 2011 were retrospectively reviewed. RESULTS: Median age at PD catheter implantation was 73 years. The most common primary diseases leading to ESRD were diabetic nephropathy (DN; 26.3 %), chronic glomerulonephritis (CGN; 24.6 %), and hypertensive nephropathy (HN; 21.8 %). The main causes of death in the DN and CGN groups were infections (42.6 %) and cardiocerebrovascular accidents (34.1 %), respectively. Patients with systemic vasculitis (SV) had the highest mortality rate from infection (71.4 %). Cox regression model showed that, compared with patients with CGN, those who had primary disease of DN, renal amyloidosis, multiple myeloma, or vasculitis were at higher risk of first-year death. Cerebrovascular disease, chronic heart failure, and/or lower serum albumin at baseline were also risk factors for first-year death. CONCLUSIONS: The main causes of death in PD patients with DN and CGN were infections and cardiocerebrovascular accidents, respectively. Risk factors for first-year death included the primary diseases, cerebrovascular diseases, chronic heart failure, and lower serum albumin at baseline.


Subject(s)
Amyloidosis/mortality , Kidney Failure, Chronic/mortality , Kidney Failure, Chronic/therapy , Peritoneal Dialysis/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Cause of Death , China/epidemiology , Comorbidity , Diabetic Nephropathies/complications , Diabetic Nephropathies/mortality , Female , Glomerulonephritis/complications , Glomerulonephritis/mortality , Heart Failure/mortality , Humans , Hypertension, Renal/complications , Hypertension, Renal/mortality , Infections/mortality , Kidney Failure, Chronic/etiology , Male , Middle Aged , Multiple Myeloma/mortality , Nephritis/complications , Nephritis/mortality , Retrospective Studies , Serum Albumin/metabolism , Stroke/mortality , Vasculitis/mortality , Young Adult
11.
Nat Rev Nephrol ; 9(11): 634-5, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24080799

ABSTRACT

Current guidelines recommend lowering blood pressure (BP) in patients with chronic kidney disease and hypertension. However, a new study suggests that achieving ideal systolic BP targets at the expense of low diastolic BP <70 mmHg is not advantageous for outcomes.


Subject(s)
Antihypertensive Agents/therapeutic use , Blood Pressure , Hypertension, Renal , Practice Guidelines as Topic , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/mortality , Humans , Hypertension, Renal/drug therapy , Hypertension, Renal/etiology , Hypertension, Renal/mortality
12.
J Am Soc Hypertens ; 7(1): 24-31, 2013.
Article in English | MEDLINE | ID: mdl-23321402

ABSTRACT

Atherosclerotic renal artery stenosis (ARAS) is a predictor of increased morbidity and mortality. However, whether ARAS itself accelerates the arteriosclerotic process or whether ARAS is solely the consequence of atherosclerosis is unclear. We imaged renal arteries of 1561 hypertensive patients undergoing coronary angiography and followed this cohort for 9 years (range, 2.4-15.1 years; median, 31.2 months, interquartile range, 13.4/52.9 months). All patients received aspirin, renin-angiotensin system blockade, statins, and beta blockade as indicated. One hundred seventy-one patients had ARAS >50% diameter stenosis and 126 patients an arteriosclerotic plaque (ARAP) without significant stenosis. Blood pressures were not different in ARAS, ARAP, and non-ARAS patients. After adjustment for cardiovascular risk factors by propensity scores and matched pair analysis, ARAS patients had a lower ejection fraction and more coronary artery disease (CAD) than non-ARAS patients. The same was true for brain natriuretic peptide values, troponin I, and highly sensitive C-reative protein. Over 9 years, more ARAS patients died of any cause (34% vs 23%; P < .05). The prevalence of CAD in ARAP patients was higher than in non-ARAS patients and lower than in ARAS patients. The mortality of the ARAP patients at 9 years was 37%, not different from the ARAS patients. Atherosclerotic renal artery disease appears to be a marker for the severity of atherosclerosis rather than a causative factor for atherosclerosis progression.


Subject(s)
Atherosclerosis/mortality , Hypertension, Renal/mortality , Renal Artery Obstruction/mortality , Aged , Angiography , Atherosclerosis/diagnostic imaging , Atherosclerosis/physiopathology , Blood Pressure/physiology , Comorbidity , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/mortality , Coronary Artery Disease/physiopathology , Disease Progression , Female , Follow-Up Studies , Humans , Hypertension, Renal/diagnostic imaging , Hypertension, Renal/physiopathology , Male , Middle Aged , Prevalence , Renal Artery Obstruction/diagnostic imaging , Renal Artery Obstruction/physiopathology , Risk Factors
13.
Int J Urol ; 20(4): 382-9, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23003206

ABSTRACT

OBJECTIVES: To investigate mortality rates and to comprehensively analyze prognostic indicators after radical nephrectomy for renal cell carcinoma. METHODS: Data were collected from 147 patients who underwent potentially curative radical nephrectomy for renal cell carcinoma. The following data were analyzed: tumor pathology, patient demographics and clinical parameters, such as pre- and postoperative estimated glomerular filtration rate, as well as the cause of death. Cause-specific survival rates were calculated including deaths caused by renal cell carcinoma and cardiovascular disease. A Cox proportional hazard model was used for statistical analysis. RESULTS: A univariate analysis showed that age at surgery (≥70 years), postoperative estimated glomerular filtration rate (<45 mL/min/1.73 m(2)), pathological high T stage, grade and venous invasion were significant poor prognostic indicators. The multivariate analysis provided evidence that pathological venous invasion was a significant poor prognostic indicator, whereas age at surgery (≥70 years), pre- (<65 mL/min/1.73 m(2)) or postoperative (<45 mL/min/1.73 m(2)) estimated glomerular filtration rate and pathological high grade were significant poor prognostic indicators in T1 tumor cases. CONCLUSIONS: Post-radical nephrectomy renal function insufficiency can lead to a poor prognostic outcome, especially in patients with T1 renal cell carcinoma. Physicians should consider a comprehensive follow up focusing on possible causes of death, including those related to both renal cell carcinoma and cardiovascular disease events after radical nephrectomy.


Subject(s)
Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Nephrectomy/methods , Postoperative Complications/mortality , Adenocarcinoma, Clear Cell/mortality , Adenocarcinoma, Clear Cell/surgery , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/mortality , Comorbidity , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Hypertension, Renal/mortality , Kaplan-Meier Estimate , Kidney Neoplasms/mortality , Male , Middle Aged , Multivariate Analysis , Nephrectomy/mortality , Prognosis , Proteinuria/mortality , Risk Factors
14.
Clin J Am Soc Nephrol ; 8(1): 75-81, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23085727

ABSTRACT

BACKGROUND AND OBJECTIVES: The African American Study of Kidney Disease Trial identified risk factors for CKD progression and suggested that GFR level may modify the association between these risk factors and CKD progression or death. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Enrollment in the African American Study of Kidney Disease Trial occurred between June of 1995 and September of 2001, with median follow-up of 48.6 months. Among 1094 patients with hypertensive kidney disease in the trial, this study tested whether the association between six previously identified risk factors for CKD progression (or death) and a composite clinical outcome (progression of CKD, ESRD, or death) depends on level of GFR. Multivariate Cox regression was used to control for other baseline risk factors. RESULTS: After controlling for baseline risk factors, only proteinuria was more closely associated with the composite clinical outcome at lower levels of GFR (P value for interaction term=0.002); increased hazards of the clinical composite outcome associated with a doubling of proteinuria ranged from 30% (95% confidence interval=21%-39%) with a GFR of 50 to 55% (95% confidence interval=40%-72%) with a GFR of 25. CONCLUSIONS: The magnitude of the association between proteinuria and CKD progression, ESRD, or death in the African American Study of Kidney Disease Trial cohort depends on the level of GFR; proteinuria is a stronger independent predictor of the composite clinical outcome at lower levels of GFR. This finding reinforces that African Americans with proteinuria and lower GFR represent a population at particularly high risk for adverse outcomes.


Subject(s)
Black or African American/statistics & numerical data , Glomerular Filtration Rate , Renal Insufficiency, Chronic/ethnology , Renal Insufficiency, Chronic/mortality , Adult , Aged , Disease Progression , Female , Follow-Up Studies , Humans , Hypertension, Renal/ethnology , Hypertension, Renal/mortality , Kaplan-Meier Estimate , Kidney Failure, Chronic/ethnology , Kidney Failure, Chronic/mortality , Male , Middle Aged , Morbidity , Multivariate Analysis , Proteinuria/ethnology , Proteinuria/mortality , Risk Factors , United States/epidemiology
15.
Am J Physiol Renal Physiol ; 304(4): F348-55, 2013 Feb 15.
Article in English | MEDLINE | ID: mdl-23220723

ABSTRACT

Oxidative stress is acknowledged to play a role in kidney disease progression. Genetic variants that affect the capacity to handle oxidative stress may therefore influence the outcome of kidney disease. We examined whether genetic variants of the GSTM1 gene, a member of a superfamily of glutathione S-transferases, influence the course of kidney disease progression in participants of the African American Study of Kidney Disease (AASK) trial. Groups with and without the common GSTM1 null allele, GSTM1(0), differed significantly in the time to a glomerular filtration rate (GFR) event or dialysis (P = 0.04) and in the time to GFR event, dialysis, or death (P = 0.02). The hazard ratios (HR) for the time to a GFR event or dialysis in those with two or one null allele relative to those possessing none were 1.88 [95% confidence interval (CI), 1.07 to 3.30, P = 0.03] and 1.68 (95% CI, 1.00 to 2.84, P < 0.05), respectively. For the time to GFR event, dialysis, or death, the HR for two null alleles was 2.06 (95% CI, 1.20 to 3.55, P = 0.01) and for one null allele 1.70 (95% CI, 1.02 to 2.81, P = 0.04). We demonstrated that GSTM1 directly regulates intracellular levels of 4-hydroxynonenal (4-HNE) in vascular smooth muscle cells. Furthermore, we showed that renal 4-HNE levels and GSTM1 are both increased after reduction of renal mass (RRM) in the mouse. We conclude that GSTM1 is normally upregulated in chronic kidney disease (CKD) in a protective response to increased oxidative stress. A genetic variant that results in loss of GSTM1 activity may be deleterious in CKD.


Subject(s)
Glutathione Transferase/genetics , Glutathione Transferase/physiology , Hypertension, Renal/ethnology , Hypertension, Renal/genetics , Nephritis/ethnology , Nephritis/genetics , Aldehydes/metabolism , Animals , Black People/genetics , Black People/statistics & numerical data , Cells, Cultured , Disease Progression , Female , Gene Silencing/physiology , Glomerular Filtration Rate/genetics , Glomerular Filtration Rate/physiology , Humans , Hypertension, Renal/enzymology , Hypertension, Renal/mortality , Male , Mice , Mice, Inbred C57BL , Middle Aged , Muscle, Smooth, Vascular/physiology , Myocytes, Smooth Muscle/physiology , NF-E2-Related Factor 2/physiology , Nephritis/enzymology , Nephritis/mortality , Oxidative Stress/genetics , Oxidative Stress/physiology , Randomized Controlled Trials as Topic , Renal Insufficiency, Chronic/enzymology , Renal Insufficiency, Chronic/genetics , Renal Insufficiency, Chronic/physiopathology
16.
Am J Nephrol ; 36(4): 324-31, 2012.
Article in English | MEDLINE | ID: mdl-23007099

ABSTRACT

BACKGROUND: Chronic kidney disease (CKD) is associated with increased risk for cardiovascular (CV) disease and is also associated with elevated uric acid, which is emerging as a nontraditional CV risk factor. We therefore evaluated uric acid as a risk factor for CV disease in subjects presenting to nephrologists with CKD who were not on medications known to alter endothelial function. METHODS: 303 subjects with stage 3-5 CKD were followed for a mean of 39 months (range 6-46) and assessed for fatal and nonfatal CV events. Hyperuricemia was defined as uric acid >6.0 mg/dl for women and >7.0 mg/dl for men. In addition to other CV risk factors, endothelial function (flow-mediated dilatation), inflammatory markers (hsCRP), and insulin resistance (HOMA index and fasting insulin levels) were included in the analysis. We evaluated the association between uric acid and flow-mediated dilatation with linear regression. The impact of uric acid on composite CV events was assessed with Cox regression analysis. RESULTS: Of a total of 303 patients, 89 had normouricemia and 214 had hyperuricemia. Both fatal (32 of 214 vs. 1 of 89 subjects) and combined fatal and nonfatal (100 of 214 vs. 13 of 89 subjects) CV events were more common in subjects with hyperuricemia compared with normal uric acid levels, and this was independent of estimated glomerular filtration rate, traditional CV risk factors including diabetes, hypertension and BMI, and nontraditional risk factors (hsCRP and endothelial function). The 46-month survival rate was 98.7% in the group with low uric acid compared to 85.8% in patients with high uric acid (p = 0.002). CONCLUSIONS: Hyperuricemia is an independent risk factor for CV events in subjects presenting with CKD who are not on medications known to alter endothelial function.


Subject(s)
Cardiovascular Diseases/blood , Cardiovascular Diseases/mortality , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/mortality , Uric Acid/blood , Adult , Aged , Biomarkers/blood , Diabetes Mellitus/blood , Diabetes Mellitus/mortality , Endothelium, Vascular/metabolism , Female , Humans , Hypertension, Renal/blood , Hypertension, Renal/mortality , Longitudinal Studies , Male , Middle Aged , Peripheral Vascular Diseases/blood , Peripheral Vascular Diseases/mortality , Predictive Value of Tests , Risk Factors , Stroke/blood , Stroke/mortality
17.
Kidney Blood Press Res ; 35(5): 382-92, 2012.
Article in English | MEDLINE | ID: mdl-22487948

ABSTRACT

Our previous studies in rats with ablation nephrectomy have shown similar cardiorenal protective effects of renin-angiotensin system (RAS)-dependent treatment (combination of angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker) and RAS-independent treatment (combination of α- and ß-adrenoreceptor antagonist and diuretics). Moreover, selective blockade of endothelin (ET) receptor type A (ET(A)) improved survival rate and attenuated hypertension and organ damage in Ren-2 transgenic rats. Therefore, we were interested in whether ET(A) receptor blockade could have additive effects to the classical blockade of the RAS. Transgenic rats underwent 5/6 renal ablation at the age of 2 months and were treated for 20 weeks with RAS blockers alone (angiotensin II receptor blocker - losartan, and angiotensin-converting enzyme inhibitor - trandolapril), ET(A) receptor blocker alone (atrasentan) or with the combination of RAS and ET(A) receptor blockade. RAS blockade normalized blood pressure and improved survival. It decreased cardiac hypertrophy and proteinuria as well as tissue angiotensin II and ET-1 levels. In contrast, ET(A) receptor blockade only partially improved survival rate, reduced blood pressure, attenuated the development of cardiac hypertrophy and transiently reduced proteinuria. However, no additive cardio- and renoprotective effects of ET(A) and RAS blockade were noted at the end of the study.


Subject(s)
Endothelin A Receptor Antagonists , Hypertension, Renal/drug therapy , Indoles/pharmacology , Losartan/pharmacology , Renin-Angiotensin System/drug effects , Angiotensin II Type 1 Receptor Blockers/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Atrasentan , Disease Models, Animal , Drug Therapy, Combination , Hypertension, Renal/mortality , Hypertension, Renal/pathology , Kidney/pathology , Male , Nephrectomy/methods , Pyrrolidines/pharmacology , Rats , Rats, Sprague-Dawley , Rats, Transgenic , Receptor, Angiotensin, Type 1/metabolism , Receptor, Endothelin A/metabolism , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/mortality , Renal Insufficiency, Chronic/pathology , Renin-Angiotensin System/physiology , Survival Analysis , Treatment Outcome
18.
Kidney Blood Press Res ; 35(5): 326-31, 2012.
Article in English | MEDLINE | ID: mdl-22398387

ABSTRACT

BACKGROUND: Hypertension is common and contributes to high cardiovascular morbidity and mortality in hemodialysis (HD) patients. It is unknown which blood pressure (BP) better defines the influence on cardiovascular mortality. The purpose of our study was to analyze the relationship between various BP measurements, traditional risk factors, markers of asymptomatic atherosclerosis [left ventricular mass (LVM), carotid intima media thickness (IMT)], and cardiovascular mortality in HD patients. METHODS: Seventy-three patients (44 males and 29 females; mean age: 54.2 years) were included. BP was measured before and after HD and 48-hour ambulatory blood pressure monitoring (ABPM) was performed. Using sonography, the LVM index and carotid IMT were measured. RESULTS: During a follow-up period up to 3,664 days, 28 patients died - 16 of them from cardiovascular causes. In a Cox regression model, which included age, gender, smoking, diabetes, sensitive C-reactive protein, albumin, hemoglobin, troponin T, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, calcium, phosphorus, carotid IMT, and LVM index, only 48-hour systolic ABPM (p = 0.037) and 48-hour diastolic ABPM (p = 0.006) turned out to be independent predictors of cardiovascular death. CONCLUSION: Only 48-hour ABPM and not single BP measurements before or after HD were associated with cardiovascular mortality in HD patients.


Subject(s)
Blood Pressure Monitoring, Ambulatory/statistics & numerical data , Hypertension, Renal/mortality , Kidney Failure, Chronic/mortality , Renal Dialysis/statistics & numerical data , Adult , Aged , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/mortality , Female , Follow-Up Studies , Humans , Hypertension, Renal/diagnosis , Kidney Failure, Chronic/therapy , Male , Middle Aged , Morbidity , Prognosis , Proportional Hazards Models , Risk Factors , Smoking/mortality , Ultrasonography
19.
J Am Soc Hypertens ; 6(2): 124-31, 2012.
Article in English | MEDLINE | ID: mdl-22197317

ABSTRACT

BACKGROUND: There is little evidence regarding the target blood pressure level in patients with type 2 diabetes mellitus without overt proteinuria. METHODS AND RESULTS: We followed 608 Japanese patients with type 2 diabetes without apparent cardiovascular disease and overt proteinuria who underwent cerebral magnetic resonance imaging for a mean of 7.5 years. The patients were categorized according to their mean systolic blood pressure during the follow-up period (strict: <130 mm Hg, moderate: ≥130 and <140 mm Hg, poor: ≥ 140 mm Hg). The risks for the primary composite outcome of death or end-stage renal disease were not different among the three groups. The renal risk of the doubling of serum creatinine for the poor group was significantly higher than those in other groups. In addition, among the patients without silent cerebral infarction (SCI), the renal risk was significantly lower in the strict group than in the moderate group. Further, in both the SCI and non-SCI groups, strict blood pressure control slowed the progression of albuminuria. CONCLUSIONS: In nonproteinuric diabetic patients without SCI, strict blood pressure control was associated with improved renal outcomes. There may be different effects of intensive blood pressure control on the renoprotection of diabetic patients according to their complications.


Subject(s)
Diabetes Mellitus, Type 2/mortality , Diabetic Nephropathies/mortality , Diabetic Nephropathies/prevention & control , Hypertension, Renal/drug therapy , Hypertension, Renal/mortality , Aged , Blood Pressure/drug effects , Cerebral Infarction/mortality , Cerebral Infarction/pathology , Disease Progression , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Kidney Failure, Chronic/mortality , Magnetic Resonance Imaging , Male , Middle Aged , Prognosis , Proteinuria , Risk Factors
20.
Hypertens Res ; 34(10): 1106-10, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21796127

ABSTRACT

To examine the clinical significance of hypertensive nephropathy (HN) among non-diabetic chronic kidney disease (CKD) patients. The study comprised 2692 CKD patients recruited from 11 outpatient nephrology clinics; these included 1306 patients with primary renal disease (PRD), 458 patients with HN, 283 patients with diabetic nephropathy (DN) and 645 patients with other nephropathies (ONs). All patients fulfilled the criteria of CKD, with a persistent low estimated glomerular filtration rate (eGFR) <60 ml min(-1) per 1.73 m(2) or proteinuria as determined by a urine dipstick test. The risk factors for cardiovascular disease (CVD), such as ischemic heart disease, congestive heart failure and stroke; all-cause mortality; and progression to end-stage renal failure (dialysis induction) were analyzed using a Cox proportional hazards model in each group. During a mean follow-up period of 22.6 months from recruitment, 100 patients were lost to follow-up and 192 patients began chronic dialysis therapy. A total of 115 CVD events occurred (stroke in 37 cases), and 44 patients died. Regarding CVD events and death, there were significant differences in the hazard ratios (HRs) for the groups of patients with different underlying renal diseases as determined by both univariate and multivariate analysis adjusted for confounding factors including estimated glomerular filtration rate: PRD, 1.0 (reference); HN, 3.33 (95% confidence interval, 1.82-6.09); DN, 5.93 (2.80-12.52); and ON, 2.22 (1.22-4.05). However, there were no differences in the hazard ratio for dialysis induction for the groups of patients with different underlying renal diseases. HN is associated with an increased risk of CVD events and death among non-diabetic CKD patients, which highlights the clinical significance of HN.


Subject(s)
Cardiovascular Diseases/mortality , Hypertension, Renal/mortality , Renal Insufficiency, Chronic/mortality , Adult , Aged , Aged, 80 and over , Ambulatory Care Facilities/statistics & numerical data , Diabetic Nephropathies/mortality , Disease Progression , Female , Heart Failure/mortality , Humans , Japan/epidemiology , Male , Middle Aged , Myocardial Ischemia/mortality , Prospective Studies , Proteinuria/mortality , Risk Factors , Stroke/mortality , Survival Analysis
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