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Thomas H Hostetter

Publications and source records attributed to Thomas H Hostetter.

At least 19 recordsLinked to original sources
PubMed2006

Detection of chronic kidney disease in patients with or at increased risk of cardiovascular disease: a science advisory from the American Heart Association Kidney And Cardiovascular Disease Council; the Councils on High Blood Pressure Research, Cardiovascular Disease in the Young, and Epidemiology and Prevention; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: developed in collaboration with the National Kidney Foundation.

Chronic kidney disease (CKD) occurs commonly in patients with cardiovascular disease. In addition, CKD is a risk factor for the development and progression of cardiovascular disease. In this advisory, we present recommendations for the detection of CKD in patients with cardiovascular disease. CKD can be reliably detected with the combined use of the Modification of Diet in Renal Disease equation to estimate glomerular filtration rate and a sensitive test to detect microalbuminuria. All patients with cardiovascular disease should be screened for evidence of kidney disease with these two determinations.

American Hospital Association↗
PubMed2006

Chronic kidney disease: a public health problem that needs a public health action plan.

For a health problem or condition to be considered a public health issue, four criteria must be met: 1) the health condition must place a large burden on society, a burden that is getting larger despite existing control efforts; 2) the burden must be distributed unfairly (i.e., certain segments of the population are unequally affected); 3) there must be evidence that upstream preventive strategies could substantially reduce the burden of the condition; and 4) such preventive strategies are not yet in place. Chronic kidney disease meets these criteria for a public health issue. Therefore, as a complement to clinical approaches to controlling it, a broad and coordinated public health approach will be necessary to meet the burgeoning health, economic, and societal challenges of chronic kidney disease.

Humans↗
PubMed2005

Removal of P-cresol sulfate by hemodialysis.

Protein-bound solutes are poorly cleared by dialysis. Among the most extensively studied of these solutes is p-cresol, which has been shown to be toxic in vitro. This study examined the form in which p-cresol circulates and quantified its removal by hemodialysis. HPLC analysis of plasma from hemodialysis patients contained a peak whose mobility corresponded to synthetic p-cresol sulfate (PCS) but no detectable unconjugated p-cresol. Treatment with sulfatase resulted in recovery of this peak as p-cresol, confirming its identity. Subsequent studies compared the removal of PCS and another protein-bound solute, indican, to the removal of urea during clinical hemodialysis treatments. PCS and indican were 94 +/- 1% and 93 +/- 2% bound to plasma protein, respectively. Protein-binding caused a predictable decrease in measured dialytic clearance, which averaged 20 +/- 4 ml/min for PCS and 25 +/- 5 ml/min for indican as compared with 260 +/- 20 ml/min for urea. Volumes of distribution for the protein-bound solutes were greater than the plasma volume, averaging 15 +/- 7 L for PCS and 14 +/- 3 L for indican as compared with 37 +/- 7 for urea. Solute reduction ratios were 20 +/- 9% for PCS, 30 +/- 7% for indican, and 69 +/- 5% for urea. We conclude that p-cresol circulates in the form of its sulfate conjugate, PCS. PCS is poorly removed by hemodialysis because its clearance is limited by protein binding and the ratio of its volume of distribution to its clearance is high.

Adult↗
PubMed2005

A public health action plan is needed for chronic kidney disease.

In 2005, chronic kidney disease (CKD) meets all criteria for classification as a public health problem in the United States. It imposes a large burden on society that is increasing despite ongoing efforts to control the disease. The burden is unevenly distributed by race and economic status, whereas evidence suggests that preventive strategies could substantially reduce the burden. Finally, there are indications that such strategies are not yet in place. A broad and coordinated public health approach to the burgeoning health, economic, and societal challenges of CKD is needed to complement present clinical approaches, increase awareness, promote early detection, and facilitate prevention and treatment.

Humans↗
PubMed2005

Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO).

Chronic kidney disease (CKD) is a worldwide public health problem, with adverse outcomes of kidney failure, cardiovascular disease (CVD), and premature death. A simple definition and classification of kidney disease is necessary for international development and implementation of clinical practice guidelines. Kidney Disease: Improving Global Outcomes (KDIGO) conducted a survey and sponsored a controversies conference to (1) provide a clear understanding to both the nephrology and nonnephrology communities of the evidence base for the definition and classification recommended by Kidney Disease Quality Outcome Initiative (K/DOQI), (2) develop global consensus for the adoption of a simple definition and classification system, and (3) identify a collaborative research agenda and plan that would improve the evidence base and facilitate implementation of the definition and classification of CKD. The K/DOQI definition and classification were accepted, with clarifications. CKD is defined as kidney damage or glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) for 3 months or more, irrespective of cause. Kidney damage in many kidney diseases can be ascertained by the presence of albuminuria, defined as albumin-to-creatinine ratio >30 mg/g in two of three spot urine specimens. GFR can be estimated from calibrated serum creatinine and estimating equations, such as the Modification of Diet in Renal Disease (MDRD) Study equation or the Cockcroft-Gault formula. Kidney disease severity is classified into five stages according to the level of GFR. Kidney disease treatment by dialysis and transplantation should be noted. Simple, uniform classifications of CKD by cause and by risks for kidney disease progression and CVD should be developed.

Albuminuria↗
PubMed2005

The clearance of protein-bound solutes by hemofiltration and hemodiafiltration.

BACKGROUND: Hemofiltration in the form of continuous venovenous hemofiltration (CVVH) is increasingly used to treat acute renal failure. Compared to hemodialysis, hemofiltration provides high clearances for large solutes but its effect on protein-bound solutes has been largely ignored. METHODS: Standard clinical systems were used to remove test solutes from a reservoir containing artificial plasma. Clearances of the protein-bound solutes phenol red (C(PR)) and indican (C(IN)) were compared to clearances of urea (C(UREA)) during hemofiltration and hemodiafiltration. A mathematical model was developed to predict clearances from values for plasma flow Q(p), dialysate flow Q(d), ultrafiltration rate Q(f), filter size and the extent of solute binding to albumin. RESULTS: When hemofiltration was performed with Q(p) 150 mL/min and Q(f) 17 mL/min, clearance values were C(PR) 1.0 +/- 0.1 mL/min; C(IN) 3.7 +/- 0.5 mL/min; and C(UREA) 14 +/- 1 mL/min. The clearance of the protein-bound solutes was approximately equal to the solute-free fraction multiplied by the ultrafiltration rate corrected for the effect of predilution. Addition of Q(d) 42 mL/min to provide HDF while Q(p) remained 150 mL/min resulted in proportional increases in the clearance of protein-bound solutes and urea. In contrast, the clearance of protein-bound solutes relative to urea increased when hemodiafiltration was performed using a larger filter and increasing Q(d) to 300 mL/min while Q(p) was lowered to 50 mL/min. The pattern of observed results was accurately predicted by mathematical modeling. CONCLUSION: In vitro measurements and mathematical modeling indicate that CVVH provides very limited clearance of protein-bound solutes. Continuous venous hemodiafiltration (CVVHDF) increases the clearance of protein-bound solutes relative to urea only when dialysate flow rate and filter size are increased above values now commonly employed.

Acute Kidney Injury↗
PubMed2004

Chronic kidney disease awareness, prevalence, and trends among U.S. adults, 1999 to 2000.

The incidence of kidney failure treatment in the United States increased 57% from 1991 to 2000. Chronic kidney disease (CKD) prevalence was 11% among U.S. adults surveyed in 1988 to 1994. The objective of this study was to estimate awareness of CKD in the U.S. population during 1999 to 2000 and to determine whether the prevalence of CKD in the United States increased compared with 1988 to 1994. Analysis was conducted of nationally representative samples of noninstitutionalized adults, aged 20 yr and older, in two National Health and Nutrition Examination Surveys conducted in 1988 to 1994 (n = 15,488) and 1999 to 2000 (n = 4101) for prevalence +/- SE. Awareness of CKD is self-reported. Kidney function (GFR), kidney damage (microalbuminuria or greater), and stages of CKD (GFR and albuminuria) were estimated from calibrated serum creatinine, spot urine albumin to creatinine ratio (ACR), age, gender, and race. GFR was estimated using the simplified Modification of Diet in Renal Disease Study equation. Self-reported awareness of weak or failing kidneys in 1999 to 2000 was strongly associated with decreased kidney function and albuminuria but was low even in the presence of both conditions. Only 24.3 +/- 6.4% of patients at GFR 15 to 59 ml/min per 1.73 m(2) and albuminuria were aware of CKD compared with 1.1 +/- 0.3% at GFR of 90 ml/min per 1.73 m(2) or greater and no microalbuminuria. At moderately decreased kidney function (GFR 30 to 59 ml/min per 1.73 m(2)), awareness was much lower among women than men (2.9 +/- 1.6 versus 17.9 +/- 5.9%; P = 0.008). The prevalence of moderately or severely decreased kidney function (GFR 15 to 59 ml/min per 1.73 m(2)) remained stable over the past decade (4.4 +/- 0.3% in 1988 to 1994 and 3.8 +/- 0.4% in 1999 to 2000; P = 0.23). At the same time, the prevalence of albuminuria (ACR >/= 30 mg/g) in single spot urine increased from 8.2 +/- 0.4% to 10.1 +/- 0.7% (P = 0.01). Overall CKD prevalence was similar in both surveys (9% using ACR > 30 mg/g for persistent microalbuminuria; 11% in 1988 to 1994 and 12% in 1999 to 2000 using gender-specific ACR cutoffs). Despite a high prevalence, CKD awareness in the U.S. population is low. In contrast to the dramatic increase in treated kidney failure, overall CKD prevalence in the U.S. population has been relatively stable.

Adult↗
PubMed2004

Research opportunities for reducing racial disparities in kidney disease.

Several minority populations in the United States have higher risks for end-stage renal disease than does the white population. This article addresses some areas for research aimed at reducing the disproportionate risks. Four general areas are considered: health services, risk factors and causative agents, clinical trials, and awareness campaigns.

Black or African American↗
PubMed2004

Increasing dialysate flow and dialyzer mass transfer area coefficient to increase the clearance of protein-bound solutes.

Clinical hemodialysis systems achieve high single pass extraction of small solutes that are not bound to plasma proteins. But they clear protein-bound solutes much less effectively. This study examines the extent to which clearance of a protein-bound test solute is improved by increasing the dialyzer mass transfer area coefficient (KoA) and the dialysate flow rate (Qd). A reservoir containing test solutes and artificial plasma with albumin concentration approximately 4 g/dl was dialyzed with a standard clinical dialysate delivery system. The clearance of phenol red (ClPR) was compared with the clearances of urea and creatinine at a plasma flow rate (Qp) of 200 ml/min with varying values of KoA and Qd. ClPR increased from 11 +/- 2 ml/min to 23 +/- 2 ml/min when KoA for phenol red, KoAPR, was increased from 238 to 640 ml/min and Qd was increased from 286 +/- 6 ml/min to 734 +/- 9 ml/min. Increasing either KoAPR or Qd alone had lesser effects. Clearance values for phenol red were much lower than clearance values for the unbound solutes urea and creatinine, which ranged from 150 to 200 ml/min and were less affected by varying KoA and Qd. A mathematical model was developed to predict ClPR from values of Qp, Qd, the fraction of phenol red bound to albumin (94% +/- 1%) and KoAPR. The model accurately predicts the pattern of measured results and shows further that ClPR can be made to approach Qp only by very large increases in both KoAPR and Qd.

Albumins↗
PubMed2004

Association between serum homocysteine and markers of impaired kidney function in adults in the United States.

BACKGROUND: Circulating homocysteine, a risk factor for cardiovascular disease (CVD), is often elevated in chronic kidney disease and end-stage renal disease (ESRD) patients. Little is known about the risk of elevated homocysteine associated with less advanced renal insufficiency in the community. METHODS: Serum homocysteine concentration measures (umol/L) from the National Health and Nutrition Examination Survey (NHANES) 1991-1994 participants who were aged >/=40 years and fasted >/=6 hours (1558 men and 1829 women) were categorized as <9, 9 to 11.9, 12 to 14.9, and >/=15. Renal function levels were determined by Modified Diet in Renal Disease (MDRD) estimated glomerular filtration rate (GFRest) (mL/min/1.73 m(2)) and the urinary albumin-to-creatinine ratio (ACR) (mg/g). Cumulative odds ratios (OR) of exceeding any given homocysteine cut point were computed by gender, using ordinal logistic regression. Each model included GFRest (<60, 60 to 90, >/=90), ACR (<15, 15 to <30, >/=30), age, race/ethnicity, red blood cell folate, serum vitamin B(12), and dietary vitamin B(6) intake as independent variables. RESULTS: The adjusted ORs for elevated homocysteine risk were 9 to 11 times greater in adults with the lowest GFRest levels (<60 mL/min/1.73 m(2)) compared to those with normal GFRest levels. Association measures for marginal GFRest levels (60 to 90 mL/min/1.73 m(2)) were weaker but significant. Albuminuria (ACR >/=30 mg/g) was a significant, independent renal risk factor for elevated homocysteine in men and women (adjusted OR = 1.78, 95% CI 1.08-2.93, and adjusted OR = 1.83, 95% CI 1.21-2.76, respectively) relative to those with low normal albumin excretion, but high normal albuminuria (ACR = 15-30 mg/g) was not. CONCLUSION: In the general population, renal insufficiency is strongly associated with an increased risk of elevated circulating homocysteine, independent of B vitamin status. These results raise the possibility that elevated homocysteine may be an important risk factor to explain the heavy burden of CVD associated with kidney disease.

Adult↗
PubMed2004

Effect of aldosterone on renal transforming growth factor-beta.

Aldosterone participates in the pathophysiology of several models of progressive chronic renal disease. Because of the causal connection between transforming growth factor-beta(1) (TGF-beta) and scarring in many such models, we hypothesized that aldosterone could evoke TGF-beta in the kidney. Aldosterone infusion for 3 days in otherwise normal rats caused a more than twofold increase in TGF-beta excretion without changes in systolic pressure or evidence of kidney damage. Concurrent treatment with amiloride did not alter this effect, indicating that aldosterone's stimulation of TGF-beta was independent of its regulation of sodium or potassium transport. However, concurrent treatment with spironolactone did block the increase in TGF-beta, indicating that the effect depends on the mineralocorticoid receptor. Renal mRNA for serum glucocorticoid kinase rose, but no change in TGF-beta message occurred, suggesting posttranscriptional enhancement of renal TGF-beta. In summary, aldosterone provokes renal TGF-beta, and this action may contribute to aldosterone's fibrotic propensity.

Aldosterone↗
PubMed2004

Localization of discoidin domain receptors in rat kidney.

BACKGROUND/AIM: The discoidin domain receptors (DDRs) DDR1 and DDR2 are cardinal members of a receptor tyrosine kinase subfamily, activated by collagens. They are candidate effectors in tissue injury and fibrosis. We investigated the DDR expression in normal and remnant rat kidneys. METHODS: The DDR expression in kidney and other tissues was examined by indirect immunofluorescence, immunoblotting, and ribonuclease protection assays. The expression patterns in remnant and control kidneys were compared at 2-, 4-, and 8-week time points, following induction of injury. RESULTS: DDR1 is expressed in basolateral membranes of select nephron segments, from the connecting tubule to the renal papilla. DDR2 is expressed in apical membranes of select nephron segments, from the loop of Henle to the macula densa. The DDR1 protein expression is upregulated within the glomeruli of remnant kidneys. The distribution of DDR2 in remnant kidneys is similar to that in controls. The DDR mRNA levels in remnant and control kidneys were not significantly different, at any time point. CONCLUSIONS: The DDR1 localization in the rat kidney is consistent with roles in cell-matrix interactions. Upregulation within glomeruli of remnant kidneys suggests the possibility of additional roles in kidney injury. The DDR2 localization in adult rat kidneys is inconsistent with roles in cell-matrix interactions.

Animals↗
PubMed2003

Hyperfiltration and glomerulosclerosis.

Nearly 70 years ago, the association between reduction in renal mass and subsequent glomerular injury was established. Later the pathologic changes were attributed to adaptive hemodynamic changes in the residual nephrons. This relationship seems to exist in a number of experimental animal species, as well as humans. Among the various hemodynamic changes that occur within residual nephrons, the increase in glomerular pressure is the most important in generating subsequent pathologic changes. The renin-angiotensin-aldosterone system seems to contribute to the intrarenal pressure. Both angiotensin and aldosterone participate. Increases in glomerular pressure appear to act on the mesangial compartment causing it to increase its cell number and matrix volume. Deleterious interactions between higher pressures, increased capillary volume, and a relatively fixed podocyte number also appear to contribute to the sclerotic process. Endothelial cell changes occur perhaps in response to direct hemodynamic stimuli, but their role in the sclerotic process is less clear than those of mesangial and glomerular epithelial cells.

Animals↗
PubMed2003

Aldosterone in renal disease.

PURPOSE OF REVIEW: Interruption of the renin-angiotensin-aldosterone system, chiefly with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, has yielded beneficial results in retarding injury and progression in numerous intrinsic renal diseases. The renoprotection offered by these agents is incomplete and far from optimal. Studying mediators of progression other than angiotensin II is therefore extremely important. The emerging role of aldosterone in progression of renal disease and the utility of its antagonism is discussed here. RECENT FINDINGS: The experimental evidence linking aldosterone to renal disease is discussed. The exciting results from clinical studies employing mineralocorticoid receptor blockers are also described. SUMMARY: Aldosterone antagonism offers additional antiproteinuric benefits to those achieved with angiotensin-converting enzyme inhibition. Long-term trials addressing effectiveness and safety, especially in regards to hyperkalemia, are greatly needed.

Aldosterone↗
PubMed2003

Prevention of the development and progression of renal disease.

Prevention of the major causes of ESRD, hypertension, and diabetes, is possible. Careful glycemic control can prevent diabetes nephropathy. BP control can likely prevent the large majority of hypertensive renal disease. Testing for diabetic renal disease is well founded. In contrast, screening for hypertensive kidney disease is less well defined. Most established renal disease can be treated with glycemic control in the case of diabetes, BP treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and dietary protein restriction. Other therapeutic targets have been proposed, but are not well established. Future research should focus on defining the high risk patients, developing better markers of risk, and designing additional therapies.

Antihypertensive Agents↗
PubMed2003

National kidney disease education program.

The National Kidney Disease Education Program (NDKEP) is a program of the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health. It seeks to increase awareness of CKD among high risk groups and primary care providers. The NKDEP is a response to the rapidly escalating incidence of ESRD in the United States in the face of new treatment to prevent and mitigate CKD. The hope is that awareness will lead to action, testing, and treatment.

Female↗