CLINICAL STUDY

Oxygen Therapy Improves Renal Function in Patients with Chronic ObstructivePulmonary Disease

Marisa Richard Pontes da Costa Lima, M.D.Division of Pneumology, Hospital de Base, Sao Jose do Rio Preto Medical School, Sao Jose do Rio Preto, Sao Paulo, Brazil

Emmanuel A. Burdmann, M.D., Ph.D.Division of Nephrology, Hospital de Base, Sao Jose do Rio Preto Medical School, Sao Jose do Rio Preto, Sao Paulo, Brazil

Jose Paulo Cipullo, M.D., Ph.D.Division of Medicine, Hospital de Base, Sao Jose do Rio Preto Medical School, Sao Jose do Rio Preto, Sao Paulo, Brazil

Chronic obstructive pulmonary disease (COPD) may

cause edema independently of cardiac function. This study

assessed the effects of oxygen therapy in renal hemodynamics

and excretion of sodium and water in COPD patients. Twelve

COPD patients without cor pulmonale (PaO2�60 mmHg),

aged 66±9 years, were studied before and after 72 h of O2

therapy. Oxygen increased PaO2 from 56±4 to 85±22 mmHg

( p<0.0001), whereas PaCO2 did not change significantly.

Oxygen induced significant increments in glomerular filtration

rate (90±21 to 111±36 mL/min/1.73 m2, p=0.03), sodium

filtered load (10±3 to 12±5 mEq/min, p=0.004), sodium

excreted load (79±67 to 194±106 mEq/day, p=0.0006),

fractional excretion of sodium (0.51±0.49 to 1.30±1.32%,

p=0.015) diuresis (1048±548 to 1893±440 mL/day, p=0.002),

osmolar clearance (1.43 ± 0.7 to 2.08 ± 0.6 mOsm/min,

p = 0.008) and decreased hematocrit (48 ± 4 to 44 ± 3%,

p=0.0038). Renal plasma flow and filtration fraction did

not change after oxygen. In summary, use of oxygen caused

increases of 36% in GFR, 35% in filtered load of sodium,

118% in diuresis, 258% in excreted load of sodium, and 178%

in fractional excretion of sodium. These data suggest that

oxygen-induced natriuresis and diuresis were likely more

dependent of changes in the tubular manipulation of sodium

than in glomerular hemodynamics. These changes occurred

with a mild increase in PCO2, showing that oxygen therapy

caused renal improvement independently of amelioration

of hypercapnia.

Keywords oxygen therapy, hypercapnia, renal function,

chronic obstructive pulmonary disease, renal

sodium excretion

INTRODUCTION

The development of edema in patients with chronic

obstructive pulmonary disease (COPD) has been related

to right ventricular failure due to cor pulmonale-induced

pulmonary hypertension.[1 – 9] However, late appearance

of edema in the course of hypoxic COPD has also been

described regardless of the presence of cor pulmonale. In

these patients, edema started or increased when exacer-

bation of hypoxemia occurred.[1,2,9] Other authors also

reported sodium and water retention independent of right

heart failure by mechanisms not yet clarified in

individuals with COPD.[2,4 – 7,10,11] Moreover, Fulton and

colleagues did not find right ventricular hypertrophy at

the necropsy of hypoxic patients with COPD and edema,

which again does not agree with the hypothesis of

development of cor pulmonale-induced edema in COPD

patients.[12] In patients with COPD without cor pulmo-

nale, the mechanisms of edema and impairment in the

renal regulation of salt and water are likely multifactorial

and have been related to changes in kidney function

caused by hypoxemia or hypercapnia.[1,3,13,14]

Some authors believe that hypercapnia is the major

cause for water and sodium retention and for the

Address correspondence to Emmanuel A. Burdmann, M.D.,

Ph.D., Division of Nephrology, Hospital de Base, Sao Jose do

Rio Preto Medical School, Av. Brigadeiro Faria Lima 5416, Sao

Jose do Rio Preto, SP 15090-000, Brazil; Fax: 55-17-2275733

extension 1135; E-mail: burdmann@famerp.br

373

Renal Failure, 27:373–379, 2005

Copyright D 2005 Taylor & Francis Inc.

ISSN: 0886-022X print / 1525-6049 online

DOI: 10.1081/JDI-200065279

Order reprints of this article at www.copyright.rightslink.com

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development of edema in patients with COPD.[7,8,13,15 – 18]

Campbell et al. suggested that in order to compen-

sate respiratory acidosis caused by CO2 increase in

COPD patients, there is an increase in tubular sodium

bicarbonate reabsorption with consequent water and

sodium retention and edema formation.[7] There is also

evidence that patients with COPD and hypercapnia have

decreased glomerular filtration rates, renal plasma flows,

and sodium urinary excretion, despite normal cardiac

indexes.[9,16 – 19]

The available data regarding the role of hypoxemia

in the development of edema in hypoxemic COPD

patients without cor pulmonale are scarce and contro-

versial. Severe hypoxemia induces polycythemia, which

may contribute to the development of pulmonary

hypertension, renal arteriolar vasoconstriction, and renal

plasma flow reduction.[12,15,20] On the other hand, al-

though peripheral edema is frequent in hypoxemic pa-

tients with COPD, patients with pulmonary fibrosis and

similar levels of hypoxemia rarely present edema, which

is occasionally observed only in advanced stages of the

disease.[17]

In the present study, we aimed to evaluate the effects

of hypoxemia correction on renal hemodynamics and in

renal sodium and water excretion in hypoxemic patients

with COPD and without cor pulmonale.

METHODS

Patients

This study was approved by the Ethics and Research

Committee of the Sao Jose do Rio Preto Medical School.

Patients only entered the study after receiving infor-

mation about the procedures, risks, and benefits of the

study and signing the informed consent. Individuals

were evaluated at the Pneumology Outpatient Clinic,

Hospital de Base (HB), Sao Jose do Rio Preto Medical

School (FAMERP).

Patients with COPD due to chronic bronchitis or

emphysema were included. COPD was defined accord-

ing typical clinical picture and hematocrit �45%,

PaO2�60 mmHg, spirometry with a pattern of moder-

ate/severe COPD, chest x-ray showing pulmonary hyper-

insufflation or increased bronchovascular markings, or

decreased peripheral pulmonary vasculature or emphy-

sema bubbles.[21 – 23]

Excluded from the study were patients with hypo-

xemia due to other pulmonary diseases, due to car-

diologic diseases, and due to hematologic causes, and

those with active pulmonary infection, right, left, or

congestive heart failure, systemic hypertension, diabe-

tes mellitus, and those receiving diuretics or corti-

costeroids, with serum creatinine above 2 mg/dL, pre-

vious renal diseases, and right ventricular overload in

the electrocardiogram.

Basic Protocol

Initially, all patients were submitted to history and

physical examination, chest x-ray, computerized chest

tomography, electrocardiogram, arterial blood gas analy-

sis at rest in room air, complete blood count, measurement

of serum creatinine, and spirometry.

Spirometry was carried out using a VITATRACE

VT130 SL spirometer (Promed, Brazil). Forced vital

capacity (FVC), forced expiratory volume in 1 second

(FEV1), and the FEV1/FVC ratio were evaluated.

Patients with inclusion criteria and no exclusion

criteria were hospitalized; blood pressure, weight, and

height were obtained; and the protocol procedures were

carried out:

1. Puncture of the humeral or radial artery for arterial

gasometry.

2. Venipuncture to obtain blood samples for complete

blood count, serum sodium, potassium, glucose,

creatinine, and osmolality.

3. Venous access to maintain adequate hydration, stan-

dardized at 1.5 L of DW 5% for 24 h.

4. Twenty-four hour urine collection for volume mea-

surement and assessment of osmolality, sodium,

potassium, and creatinine.

5. Venous access in one of the upper limbs for injection

of a single dose of EDTA-Cr51 individually calculat-

ed according to body surface. Two plasma samples

were then obtained within 60 and 120 min for the

analysis of the glomerular filtration rate. The fol-

lowing day, a new venous access was obtained in one

of the upper limbs for injection of a single dose of

Hippuran-I131, individually calculated according to

body surface. Two plasma samples were then obtained

within 20 and 30 min for the analysis of the renal

plasma flow.

Subsequently, oxygen therapy was started at the dose

of 2 L/min by nasal catheter for a period of 72 h, and then

the same procedures and measurements described above

were repeated.

The dosages of serum creatinine, sodium and osmo-

lality and urinary (24 h collection) creatinine, sodium, and

osmolality were used for calculation of creatinine clear-

ance, osmolar clearance, filtered load of sodium, and

fractional excretion of sodium by the formulas shown

below. The values obtained for GFR and RPF were used

for filtration fraction calculation.

M. R. Pontes da Costa Lima, E. A. Burdmann, and J. Paulo Cipullo374

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Formulas

Creatinine clearance: ClCr (mL/min)=U �V’/P, where U

is the urinary concentration of creatinine (mg/dL), P

is the serum concentration of creatinine (mg/dL), and

V’ is the urinary volume in mL/min.

Sodium filtered load: FLNa (mEq/min)=SNa�GFR,

where SNa is the serum concentration of sodium

(mEq/L), and GFR is the glomerular filtration rate

measured by the ClCr.

Sodium excreted load: UNaV (mEq/day)=UNa�V, where

UNa is the urinary concentration of sodium (mEq/L),

and V is the 24 h urinary volume.

Osmolar clearance: ClOsm (mOsm/min)=UOsm�V’/POsm, where UOsm is the urinary osmolality, POsm is

the serum osmolality, and V’ is the urinary volume in

mL/min.

Free water reabsorption: TcH2O=V’�ClOsm, where V’ is

the urinary volume in mL/min, and ClOsm is the

osmolar clearance.

Fractional excretion of sodium: FeNa (%)=UNa�V’�100/ClCr�PNa, where UNa is the urinary concentra-

tion of sodium, V’ is the urinary volume in mL/min,

ClCr is the creatinine clearance, and PNa is the serum

concentration of sodium.

Filtration fraction: FF=GFR/RPF, where GFR is the

glomerular filtration rate measured by EDTA-Cr51,

and RPF is the renal plasma flow measured by

Hippuran-I131.

Analytical Methods

Arterial blood gases measurement was performed

using an ABL 5 radiometer (Copenhagen Radiometer,

Denmark). Complete blood count was performed using a

Sysmex SF-3000 device (Sysmex, Japan). Plasma and

urinary sodium and potassium counts were assessed by

selective electrode ion using an EML 105/100 radiometer

(Copenhagen Radiometer, Denmark). Plasma and urinary

creatinine were measured by the colorimetric method

(Jaffe’s method) using a Cobas Mira Plus (Roche,

Switzerland). Urinary and plasma osmolality were

determined by the freezing point method (Fiske mark 3

Osmometer, USA). Effective renal plasma flow and

glomerular filtration rates were determined by radioiso-

topic techniques[24,25] using, respectively, Hippuran I131

and EDTA Cr51.

Statistical Analysis

Results are reported as mean±standard deviation

(SD) or as percentage values. Two-tailed paired Student’s

t-test was used for comparing results before and after

oxygen therapy. A p value <0.05 was considered

statistically significant.

RESULTS

Twelve individuals, nine men and three women, ages

ranging from 48 to 78 years (66±9 years), with chronic

obstructive pulmonary disease (COPD) and without cor

pulmonale were evaluated. Spirometry results showed a

mean forced vital capacity value of 2.08±0.06 (62% of

the anticipated value), forced expiratory volume in 1 sec

of 0.91±0.42 (37% of the anticipated value), and a FEV1/

FVC ratio of 42.19±8.47% (42% of the anticipated

value), characterizing moderate to severe chronic venti-

latory obstruction.

Weight was 62±15 kg, systolic blood pressure was

129±12 mmHg, and diastolic blood pressure was 80±

7 mmHg. After oxygen therapy, weight decreased to

61±15 kg, systolic blood pressure to 120±10 mmHg, and

diastolic blood pressure to 77±7 mmHg. These changes

were not statistically significant.

Hematocrit values decreased from 48%±4 to 44±3%

after the use of oxygen ( p=0.0038).

There were no changes in pH values with the use of

oxygen (7.40 ± 0.05 prior oxygen therapy versus

7.40±0.05 after oxygen therapy). Partial arterial O2

pressure increased from 56±4 mmHg to 85±22 mmHg

( p<0.0001) with oxygen therapy. Partial arterial CO2

pressure and serum bicarbonate did not present statisti-

cally significant changes after oxygen therapy (PaCO2

45±6 mmHg before versus 50±11 mmHg after, p=0.077

and HCO3 27±4 mEq/L before versus 27±8 mEq/L after,

p=0.664).

Although renal plasma flow (RPF) increased with the

use of oxygen, this change was not statistically significant

(389±101 mL/min to 428±131 mL/min, p=0.19). The

use of oxygen induced a GFR increase from 91±21 mL/

min/1.73 m2 to 111±36 mL/min/1.73 m2 ( p=0.030), an

increase of 35%. There was no significant change in the

FF after oxygen therapy (0.25 ± 0.1 before versus

0.24±0.1 after). Creatinine clearance (CrCl) increased

significantly after oxygen, from 67±21 mL/min/1.73 m2

to 86±34 mL/min/1.73 m2 ( p=0.035), an increase of

36%.

There was a significant increase in 24 h diuresis

from 1048±548 mL to 1893±440 mL (an increase of

118%, p=0.0018) after oxygen therapy. The filtered load

of sodium changed significantly from 10±3 mEq/min to

12 ± 5 mEq/min (an increase of 35%, p = 0.0042).

Excreted sodium had a striking increase from 79±

67 mEq/24 h to 194±106 mEq/24 h ( p=0.0006),

corresponding to a percent increase of 258%. This

375Oxygen Therapy Improves Renal Function in Patients with COPD

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increase was observed in all patients, with a mean

variation of 115 mEq/24 h (from 24 to 312 mEq/24 h).

There was also an impressive and statistically significant

increase of 178% in the fractional excretion of sodium

( p=0.015) with the use of oxygen. Osmolar clearance

increased from preoxygen values of 1.43±0.7 mOsm/

min to 2.08±0.6 mOsm/min after oxygen use ( p=

0.008). Oxygen therapy did not significantly change free

water reabsorption ( p=0.623).

These results are illustrated in Tables 1 and 2 and

Figure 1.

DISCUSSION

The renal function of patients with COPD has

been studied since 1950, and the most consistent

change observed has been effective renal plasma flow

decrease in hypoxemic and hypercapnic patients with

COPD.[8,13,15 – 17,26,29] Farber et al. reported a normal

RPF in hypoxemic and normocapnic patients with COPD,

but a significant RPF decrease in patients with similar

levels of hypoxemia combined with hypercapnia.[28]

Anand et al. observed that 63% of COPD patients with

hypoxia, significant hypercapnia, and edema had de-

creased RPF.[16,17] For these authors, RPF decrease would

be mainly related to hypercapnia throughout direct release

of catecholamines.[16,17]

The present study found that oxygen therapy induced

a significant increase in GFR and ClCr and a moderate

and statistically nonsignificant RPF increase in COPD

patients. Those improvements in renal hemodynamics

occurred despite a concomitant PaCO2 increase (also

nonstatistically significant). Thus, these results suggest

that RPF and GFR increases might be related to the

correction of hypoxemia, and may be independent of

PaCO2 changes. Our results are consistent with those

obtained by Mannix et al., who also reported a statistically

nonsignificant improvement in the RPF with the use of

oxygen therapy for 1 week in hypoxemic and hypercapnic

patients with COPD.[19] The increment in RPF (although

not statistically significant) and the simultaneous increase

in GFR without FF changes observed in our patients

might be due to renal microcirculation vasodilation,

leading to improvements in GFR and sodium filtered

load. In fact, hypoxemia correction has been related to

Table 2Renal hemodynamics creatinine clearance and tubular function

before and after oxygen therapy (n=12)

Before O2 After O2 P

RPF (mL/min) 389±101 421±131 0.27

GFR

(mL/min/1.73 m2)

90±21 111±36 0.030*

FF 0.25±0.1 0.24±0.09 0.075

ClCr (mL/min/1.73 m2) 67±21 86±34 0.035*

FLNa (mEq/min) 10±3 12±5 0.0042*

UVNa (mEq/dia) 79±67 194±106 0.0006*

FeNa (%) 0.51±0.49 1.30±1.32 0.015*

UV (mL/day) 1048±548 1893±440 0.0018*

ClOsm (mOsm/min) 1.43±0.7 2.08±0.6 0.008*

TcH2O 0.6±0.6 0.7±0.6 0.623

Mean ± SD; RPF: renal plasma flow; GFR: glomerular

filtration rate; FF: filtration fraction; ClCr: clearance of creatinine;

FLNa: filtered load of sodium; UVNa: urinary sodium excretion;

FeNa: fractional excretion of sodium; UV: urinary volume; ClOsm:

osmolar clearance; TcH2O: free water reabsorption.*p<0.05.

Table 1

Weight, systolic and diastolic blood pressure, hematocrit, and

arterial blood gases before and after oxygen therapy (n=12)

Before O2 After O2 P

Weight (Kg) 62±15 61±15 0.25

SBP (mmHg) 129±12 120±10 0.33

DBP (mmHg) 80±7 77±7 0.32

Ht (%) 48±4 44±3 0.0038*

pH 7.40±0.05 7.40±0.05 0.88

PaO2 (mmHg) 56±4 85±22 0.0001*

PaCO2 (mmHg) 45±6 50±11 0.077

HCO3 (mEq/L) 27±4 27±8 0.664

Mean±SD; SBP: systolic blood pressure; DBP: diastolic

blood pressure; Ht: hematocrit; PaO2: partial pressure of oxy-

gen; PaCO2: partial pressure of carbon dioxide; HCO3: serum

bicarbonate.*p<0.05.

Figure 1. Comparison of percentage changes before and after

oxygen therapy for osmolar clearance (ClOsm), diuresis, creatinine

clearance (ClCr), filtered sodium load (FLNa), fractional excre-

tion of sodium (FeNa), and urinary sodium excretion (UVNA).

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decreases in the blood levels of vasoconstrictor substances

like catecholamines, renin, and arginine vasopressin,

which are usually increased in COPD patients.[20,26 – 34]

In the same way, increased levels of erythropoietin have

been documented in COPD patients, leading to polycy-

themia and renin–angiotensin–aldosterone system acti-

vation.[11,33 – 39] The decrease in Hct observed in this

study was probably due to decreased blood levels of

erythropoietin after hypoxemia corrections, contributing

to less RAA system activation and, consequently, renal

vasodilation. Increased renal production of endothelin[38]

and impaired renal blood flow response to L-arginine

infusion[39] have also been reported in hypoxic COPD

patients and might be influenced by oxygen therapy.

Excreted load of sodium had a striking increase with

oxygen therapy in all patients, with a mean variation of

115 mEq/24 h and an impressive percentage increase of

258%. Our results are in accordance with those obtained

by Reihman et al., who reported that the abrupt removal

of oxygen in patients with COPD receiving continuous

oxygen therapy caused hypoxemia and a significant

decrease in the renal excretion of sodium.[26] Similarly,

other authors found increased renal sodium excretion in

COPD patients exposed to short- or long-term oxygen

therapy.[40,41]

This significant increase observed in the excreted

load of sodium may have been caused by an increase in

the filtered load of sodium or decrease in the tubular

reabsorption of this ion, or both. Oxygen therapy was

associated with an increase of 35% in the GFR, 46% in

osmolar clearance, and 36% in filtered load of sodium,

which could hardly explain in totality the increase of

258% in the excreted load of sodium. On the other hand,

FeNa, which evaluates the tubular handling of this ion,

had an increase of 178% after oxygen therapy. The vaso-

dilation that almost certainly occurred in the renal micro-

circulation would increase hydrostatic pressure at the

peritubular capillaries, decreasing the reabsorption of

sodium and water. It is improbable that changes in the

loop of Henle are responsible for the increase in sodium

excretion, because there were no significant changes in

free water clearance. These findings indicate that oxygen

had a more important effect in tubular reabsorption than

in the filtered load of sodium. In accordance with this

hypothesis, de Angelis et al. showed that oxygen ad-

ministration increased plasma digoxin-like substance and

urinary sodium excretion in COPD patients.[42]

Oxygen therapy also induced a significant increase in

diuresis. Granberg submitted healthy individuals with

normal renal function and adequate hydration to acute

hypoxia, observing a marked decrease in the urinary flow

with O2 saturation <60% and hypocapnia.[43] The in-

crease in diuresis with a concomitant increase in osmolar

clearance without significant changes in free water

reabsorption observed in the present study may be ex-

plained by an increased natriuresis due to a lower tubular

reabsorption of sodium after the use of oxygen therapy.

Different authors reported that hypoxemia might be

associated with changes in PaCO2 and serum bicarbonate

in order to cause salt and water retention in patients with

COPD. However, oxygen administration in hypoxemic

COPD patients in this study corrected hypoxemia without

inducing significant changes in PaCO2 and serum

bicarbonate levels. Moreover, some of the studied patients

had a mild PaCO2 increase after the use of oxygen, and

nonetheless, an increase in the fractional excretion of

sodium was observed. Therefore, the changes in renal

sodium excretion found in this study were not related to

changes in PaCO2 and in HCO3.

In summary, the use of oxygen for 72 h in COPD

hypoxic patients increased diuresis, GFR, and filtered and

excreted loads of sodium. However, these increments

were not proportional: GFR increased 35% and filtered

load of sodium increased 36%, whereas diuresis increased

118%, the excreted load of sodium increased 258%, and

the fractional excretion of sodium increased 178%. These

differences indicate that the tubular effects resulting from

oxygen therapy were more expressive than those depend-

ing on the glomerular filtration rate and the filtered load

of sodium.

REFERENCES

1. Renal function in respiratory failure (Editorial).

JAMA 1971, 216, 131–132.

2. Biernacki, W.; Flenley, D.C.; Muir, A.L.; MacNee,

W. Pulmonary hypertension and right ventricular

function in patients with chronic obstructive pulmo-

nary disease. Chest 1988, 94, 1169–1175.

3. Farber, M.O.; Bright, T.P.; Strawbridge, R.A.;

Robertson, G.L.; Manfredi, F. Impaired water

handling in chronic obstructive lung disease. J.

Lab. Clin. Med. 1975, 85, 41–49.

4. MacNee, W. Right ventricular function in cor

pulmonale. Cardiology 1988, 75, 30–40.

5. MacNee, W. Pathophysiology of cor pulmonale in

chronic obstructive pulmonary disease. Am. J.

Respir. Crit. Care Med. 1994, 150, 833–852.

6. MacNee, W.; Wathen, C.G.; Frenley, D.C.; Muir,

A.D. The effects of controlled oxygen therapy on

ventricular function in patients with stable and

decompensated cor pulmonale. Am. Respir. Dis.

1988, 137, 1289–1295.

7. Campbell, E.J.M.; Short, D.S. The cause of edema in

cor pulmonale. Lancet 1960, 1, 1184–1186.

377Oxygen Therapy Improves Renal Function in Patients with COPD

Ren

Fai

l Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Uni

vers

itat A

uton

oma

Bar

celo

na o

n 11

/04/

14Fo

r pe

rson

al u

se o

nly.

8. Platts, M.M.; Hammond, J.D.S.; Stuart Harris, C.H.

A study of cor pulmonale in patients with chronic

bronchitis. Q. J. Med. 1960, 29, 559.

9. Bishop, J.M. Cardiovascular complications of chron-

ic bronchitis and emphysema. Med. Clin. North Am.

1973, 57, 771–780.

10. Johnson, B.A.; Weil, M.H. Redefining ischemia due

to circulatory failure as dual defects of oxygen

deficits and of carbon dioxide excesses. Crit. Care

Med. 1991, 19, 1432–1438.

11. Weil, J.V.; Jamieson, G.; Brown, D.J.; Grover, R.F.

The red cell mass arterial oxygen relationship in

normal man. Application to patients with chronic

obstructive airway disease. J. Clin. Invest. 1968, 47,

1627–1635.

12. Fulton, R.M.; Hutchison, E.C.; Jones, A.M. Ven-

tricular weight in cardiac hypertrophy. Br. Heart J.

1952, 14, 413–420.

13. Daggett, P. An investigation of renal function in

chronic bronchitis. Postgrad. Med. J. 1977, 53, 24–

27.

14. Berger, E.Y.; Galdston, M.; Horwitz, S.A. The

effect of anoxic anoxia on the human kidney. J.

Clin. Invest. 1949, 28, 648–652.

15. Kilburn, K.H.; Dowell, A.R. Renal function in res-

piratory failure. Effects of hypoxia, hyperoxia and

hypercapnia. Arch. Intern. Med. 1971, 127, 754–

762.

16. Anand, I.S.; Chandrashekhar, Y.; Rao, S.K.; et al.

Body fluid compartments, renal blood flow, and

hormones at 6,000m in normal subjects. J. Appl.

Physiol. 1993, 74, 1234–1239.

17. Anand, I.S.; Ferrari, R.; Kalra, G.S.; Wahi, P.L.;

Poole-Wilson, P.A.; Harris, P. Edema of cardiac

origin: studies of body water and sodium, renal

function, hemodynamic indexes, and plasma hor-

mones in untreated congestive cardiac failure.

Circulation 1989, 80, 299–305.

18. Anand, I.S.; Chandrashekhar, Y.; Ferrari, R.; et al.

Pathogenesis of congestive state in chronic obstruc-

tive pulmonary disease. Circulation 1992, 86, 12–

20.

19. Mannix, E.T.; Dowdeswell, I.; Carlone, S.; Palange,

P.; Aronoff, G.R.; Farber, M.O. The effect of oxy-

gen on sodium excretion in hypoxemic patients with

chronic obstructive lung disease. Chest 1990, 94,

840–844.

20. Palevsky, H.T.; Fishman, A.P. Chronic cor pulmo-

nale: etiology and management. JAMA 1990, 263,

2347–2353.

21. ATS statement: standards for the diagnosis and care

of patients with chronic obstructive pulmonary dis-

ease. Am. J. Respir. Crit. Care Med. 1995, 152,

578–587.

22. Oliveira, J.C.A.; Jardim, J.R.B.; Rufino, R.L.

Brazilian Consensus on Chronic Obstructive Pul-

monary Disease. J. Pneumol. 2000, 26, S8–S23.

23. First Brazilian Consensus on Spirometry. J. Pneu-

mol. 1996, 22.

24. Lear, J.L.; Feyerabend, A.; Gregory, C. Two-

compartmental, two-sample technique for accurate

estimation of effective renal plasma flow: theoret-

ical development and comparison with other meth-

ods. Radiology 1989, 172, 431–436.

25. Peters, A.M. Quantification of renal hemodynamics

with radionucleotides. Eur. J. Nucl. Med. 1991, 18,

274–286.

26. Rehman, D.H.; Farber, M.O.; Weinberger, M.H.;

Henry, D.P.; Fineberg, N.S.; Dowdeswell, I.R.

Effect of hypoxemia on sodium and water excretion

in chronic obstructive lung disease. Am. J. Med.

1985, 78, 87–94.

27. Kellaway, G. Acute anoxic cardiac failure in pul-

monary heart disease. Lancet 1959, 2, 768–773.

28. Farber, M.O.; Roberts, L.R.; Weinberger, M.H.;

Robertson, G.L.; Fineberg, N.S.; Manfredi, F.

Abnormalities of sodium and H2O handling in

chronic obstructive lung disease. Arch. Intern. Med.

1982, 142, 1326–1330.

29. Baudouin, S.V.; Bott, J.; Ward, A. Short-term effect

of oxygen on renal hemodynamics in patients with

hypoxaemic chronic obstructive airways disease.

Thorax 1992, 47, 550–554.

30. Howes, T.Q.; Deane, C.R.; Levin, G.E.; Baudouin,

S.V.; Moxham, J. The effects of oxygen and

dopamine on renal and aortic blood flow in chronic

obstructive pulmonary disease with hypoxemic and

hypercapnia. Am. J. Respir. Crit. Care Med. 1995,

151, 378–383.

31. Palange, P. Renal and hormonal abnormalities in

chronic obstructive pulmonary (COPD). Thorax

1998, 53, 989–991.

32. Turino, G.M.; Goldring, R.M.; Heinemann, H.G.

Water, electrolytes and acid-base relationships in

chronic cor pulmonale. Prog. Vasc. Dis. 1970, 12,

467–483.

33. Gould, A.B.; Goodman, S.A. The effect of hypoxia

on the renin angiotensin system. Lab. Invest. 1970,

22, 443–447.

34. Bratel, T.; Wennlun, A.; Carlstrom, K. Impact of

hypoxemia on neuroendocrine function and cate-

cholamine secretion in chronic obstructive pulmo-

nary disease (COPD). Effects on long-term oxygen

treatment. Respir. Med. 2000, 94, 1221–1228.

M. R. Pontes da Costa Lima, E. A. Burdmann, and J. Paulo Cipullo378

Ren

Fai

l Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Uni

vers

itat A

uton

oma

Bar

celo

na o

n 11

/04/

14Fo

r pe

rson

al u

se o

nly.

35. Vlahakos, D.V.; Kosmas, E.N.; Dimopoulou, I.;

et al. Association between activation of the renin-

angiotensin system and secondary erythrocytosis in

patients with chronic obstructive pulmonary dis-

ease. Am. J. Med. 1999, 106, 158–164.

36. Pham, I.; Andrivet, P.; Sediame, S.; et al. Increased

erythropoietin synthesis in patients with COLD or

left heart failure is related to alterations in renal

hemodynamics. Eur J. Clin. Invest. 2000, 31, 103–

109.

37. Guidet, B.; Offenstadt, G.; Boffa, G.; et al. Polycy-

themia in chronic obstructive pulmonary disease. A

study of serum and urine erythropoietin and

medullary erythroid progenitors. Chest 1987, 92,

867–870.

38. Sofia, M.; Maniscalco, M.; Celentano, L.; Faraone,

S.; Mormile, M.; Alifano, C.L. Abnormalities of

renal endothelin during acute exacerbation in

chronic obstructive pulmonary disease. Pulm. Phar-

macol. Ther. 2001, 14, 321–327.

39. Howes, T.Q.; Keilty, S.E.; MasKrey, V.L.; Deane,

C.R.; Baudoiun, S.V.; Moxhan, J. Effect of L-argi-

nine on blood flow in normal subjects and patients

with hypoxic chronic obstructive pulmonary dis-

ease. Thorax 1996, 51, 516–519.

40. Skwarski, K.M.; Morrison, D.; Barrat, A.; Lee, M.;

MacNee, W. Effects of hypoxia on renal hormonal

balance in normal subjects and in patients with

COPD. Respir. Med. 1998, 92, 1331–1336.

41. Bratel, T.; Ljungman, S.; Runold, M.; Stenvinkel, P.

Renal function in hypoxemic chronic obstructive

pulmonary disease: effects on long-term oxygen

treatment. Respir. Med. 2003, 97, 308–316.

42. De Angelis, C.; Perrone, A.; Ferri, C. Oxygen

administration increases plasma digoxin-like sub-

stance and renal sodium excretion in chronic hypoxic

patients. Am. J. Nephrol. 1993, 13, 173–177.

43. Granberg, P. Effect of acute hypoxia on renal

hemodynamics and water diuresis in man. Scand.

J. Clin. Lab. Invest. 1962, 14, 5–62.

379Oxygen Therapy Improves Renal Function in Patients with COPD

Ren

Fai

l Dow

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rmah

ealth

care

.com

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Uni

vers

itat A

uton

oma

Bar

celo

na o

n 11

/04/

14Fo

r pe

rson

al u

se o

nly.