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Biomedical subjects

H H Parving

Publications and source records attributed to H H Parving.

At least 181 records · Page 10Linked to original sources

Protective effect of captopril on the blood-retina barrier in normotensive insulin-dependent diabetic patients with nephropathy and background retinopathy.

The effect of 18 months' inhibition of angiotensin-converting enzyme by captopril on the leakage of fluorescein through the blood-retina barrier was examined in a prospective, randomized control study of 20 normotensive insulin-dependent diabetic patients with nephropathy and background retinopathy. After 18 months, 15 patients remained in the study. Fluorescein leakage remained nearly unchanged in the captopril-treated group, being 4.1 +/- 4.1 (mean +/- SD) x 10(-7) cm/s at baseline and 4.2 +/- 4.1 x 10(-7) cm/s after 18 months' treatment. The permeability increased significantly (P less than 0.01) from 3.3 +/- 2.2 x 10(-7) cm/s to 5.6 +/- 3.5 x 10(-7) cm/s at 18 months in the control group. Arterial blood pressure was nearly constant in both groups throughout the study. The results indicate that angiotensin-converting enzyme inhibition with captopril can arrest or delay a progressive breakdown of the blood-retina barrier in normotensive insulin-dependent diabetic patients with nephropathy and background retinopathy.

Adult↗

Pathophysiological aspects of edema formation in diabetic nephropathy.

The present study was undertaken to evaluate some pathophysiological mechanisms of edema formation in diabetic nephropathy. Sixty-three subjects were investigated: 9 normal subjects (I), 9 normoalbuminuric Type 1 (insulin-dependent) diabetic patients (II), 15 microalbuminuric Type 1 diabetic patients (III), 16 Type 1 diabetic patients with nephropathy without edema (IV), and 14 Type 1 diabetic patients with nephropathy and edema (V). Plasma volume (125I-albumin), glomerular filtration rate and extracellular fluid volume (51Cr-EDTA) were measured. Colloid osmotic pressure and albumin concentration were measured in plasma and in subcutaneous interstitial fluid (suction blister technique). The ratio between plasma volume and interstitial fluid volume was reduced in patients with edema compared with group 1 (P less than 0.05). The interstitial colloid osmotic pressure (mm Hg) was significantly reduced (P less than 0.05) in group V compared with the other groups (V: 4.3 +/- 1.1, I: 7.9 +/- 1.7, II: 7.5 +/- 1.8, III: 6.6 +/- 1.5, IV: 6.6 +/- 1.1), but the transcapillary colloid osmotic gradient in patients with edema was comparable with the remaining subjects. The ratio between interstitial and plasma albumin concentration was significantly reduced in group V compared with groups I and II (V: 0.31 +/- 0.1, I: 0.43 +/- 0.06, II: 0.44 +/- 0.06; P less than 0.01; III: 0.41 +/- 0.07, IV: 0.41 +/- 0.08). This reduction was mainly due to enhanced lymph flow. The wash-down of subcutaneous interstitial protein indicated increased capillary filtration, but at the same time limited the increase in net filtration pressure and thereby prevented progressive edema formation in diabetic nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A nation-wide cross-sectional study of urinary albumin excretion rate, arterial blood pressure and blood glucose control in Danish children with type 1 diabetes mellitus. Danish Study Group of Diabetes in Childhood.

Nation-wide screening for microalbuminuria in Denmark was performed in 22 paediatric departments treating children with Type 1 diabetes. Over a period of 6 months 1020 children (less than or equal to 12 years) and adolescents (greater than 12 to 19 years) were screened (81% of total). Of these, 957 (94%) performed at least two timed overnight urine collections. In 209 non-diabetic subjects the upper 95% limit for normal albumin excretion rate (AER) was 20 micrograms min-1. Mean overnight AER was significantly (p less than 0.001) elevated in diabetic (3.0 x/divided by 2.3 (SD tolerance factor) micrograms min-1) and in non-diabetic (2.5 x/divided by 2.2 micrograms min-1) adolescents compared with diabetic (1.7 x/divided by 2.1 micrograms min-1) and non-diabetic (1.3 x/divided by 2.2 micrograms min-1) children. In the diabetic patients AER was positively correlated with the body surface area and age. Among the patients with Type 1 diabetes, 4.3% (18 males and 23 females) had AER greater than 20 to 150 micrograms min-1 (persistent microalbuminuria). A further 7 adolescents (0.7%) had overt proteinuria (greater than 150 micrograms min-1). Clinical data for the 41 diabetic patients with AER greater than 20 to 150 micrograms min-1 were compared with those for 569 diabetic adolescents with AER less than or equal to 20 micrograms min-1 and duration of diabetes more than 2 years. The group with AER greater than 20 to 150 micrograms min-1 had significantly higher mean age (16.5 years) than the group with AER less than or equal to 20 micrograms min-1 (15.0 years; p less than 0.001). Females with AER greater than 20 to 150 micrograms min-1 had significantly higher mean HbA1c level (10.8 +/- 1.9%) than those with AER less than or equal to 20 micrograms min-1 (9.8 +/- 1.9%, p less than 0.003); they also had impaired linear growth (standard deviation score -0.25 vs + 0.16; p = 0.003). These associations were not found in males. Mean body mass index (BMI) was significantly increased in both females (22.2 +/- 2.9 kg m-2) and males (20.8 +/- 2.7 kg m-2) with AER greater than 20 to 150 micrograms min-1, compared with diabetic patients with AER less than or equal to 20 micrograms min-1 (females 20.8 +/- 3.0 kg m-2, p = 0.02; males 19.7 +/- 2.4 kg m-2, p less than 0.006).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

A comparative study of microvascular complications in patients with secondary and type 1 diabetes.

The prevalence of retinopathy, albuminuria, and neuropathy were assessed in 25 patients with insulin-requiring diabetes secondary to chronic pancreatitis and in 25 patients with Type 1 (insulin-dependent) diabetes, matched for age at diabetes onset (secondary, 39 +/- 11 (+/- SD) years vs Type 1, 38 +/- 11 years) and duration of diabetes (10 +/- 6 vs 10 +/- 7 years). The prevalence of retinopathy was significantly higher in Type 1 diabetic patients (52%) than those with secondary diabetes (20%) (p less than 0.02). Median urinary excretion of albumin was 9 (range 1-206) mg 24-h-1 in patients with Type 1 diabetes and 7 (1-90) mg 24-h-1 in patients with secondary diabetes (NS). One secondary diabetic patient and five Type 1 diabetic patients had microalbuminuria (NS). Vibration perception threshold (measured at the big toe) was identical in the two groups of patients, and no patient had a threshold indicating somatic neuropathy (biothesiometry greater than 20 V). Retinopathy is more frequent in patients with Type 1 diabetes than in patients with insulin-requiring diabetes secondary to chronic pancreatitis. Retinopathy is so frequent in the latter group, however, that regular ophthalmoscopic examination is still required.

Albuminuria↗

Glomerular structure and function in diabetic nephropathy. Early to advanced stages.

Kidney biopsies from 14 insulin-dependent diabetes mellitus patients with persistent albuminuria were studied by light and electron microscopy. In terms of kidney function, the patients spanned stages from early to advanced nephropathy. The clinical parameters were (ranges, with medians in parentheses) urinary albumin excretion (UAE) 158-5494 micrograms/min (1153 micrograms/min), glomerular filtration rate (GFR) 30-128 ml.min-1 x 1.73 m-2 (90 ml.min-1 x 1.73 m-2) and mean arterial blood pressure (BP) 87-122 mmHg (109 mmHg). The severity of clinical nephropathy (UAE, GFR, and BP together) correlated with an index of the structural lesions (basement membrane [BM] thickness, mesangial expansion, and glomerular occlusion together; r = 0.62, 2P less than 0.05). GFR compared with remnant surface of glomerular capillaries (filtration surface; FS) gave values of r = 0.72 and 2P = 0.004, and UAE compared with the percentage of the peripheral BM surface carrying fluffy loose intrinsic fine structure gave r = 0.62 and 2P = 0.02. BP per se did not correlate with structural parameters. The area of FS per open glomerulus did not decrease with increasing mesangial volume fraction, which indicates compensatory changes of the capillaries in early and advanced stages of glomerulopathy. In 7 patients with less than 10% occluded glomeruli, correlations between glomerular volume and the parameters of diabetic glomerulopathy (i.e., BM thickness and volume fractions of mesangium and mesangial matrix) failed to reach statistical significance. The actual glomerular volume, however, is a product of the individual's original glomerular volume, probably the early diabetic hypertrophy and modifying changes consequent to the development of glomerulopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Hearing disorders in patients with insulin-dependent diabetes mellitus.

The cochlear and retrocochlear hearing function was evaluated in patients with long- and short-term insulin-dependent diabetes mellitus (IDDM) by means of psychoacoustic testing and auditory brain stem responses (ABR). Twenty patients with diabetic microangiopathy (median age 41 years, range 25-66 years) were examined. The median duration of their diabetes was 26 years (range 13-46 years). In addition, 19 patients without microangiopathy (median age 27 years, range 17-42 years) and with a median duration of the diabetes of 2 years (range 0-6 years) were examined. The metabolic control estimated by blood glucose concentration and glycosylated haemoglobin was identical in the two groups of IDDM patients. After correction for age and sex, no significant differences in hearing thresholds or discrimination scores were present between the two diabetic groups, or between the diabetic patients and an age- and sex-matched normal background population. In the patients with long-term IDDM, ABR produced abnormal responses in 40%, indicating the presence of diabetic encephalopathy, whereas ABR were abnormal in only 5% of the patients with short-term IDDM.

Acoustic Impedance Tests↗

The impact of hypertension and antihypertensive treatment on the course and prognosis of diabetic nephropathy.

The primary cause of arterial hypertension and of the increased morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM) is diabetic nephropathy. About 35% of IDDM patients develop persistent albuminuria, an irreversible decline in the glomerular filtration rate and elevated blood pressure, which collectively contribute to the clinical syndrome of diabetic nephropathy. The excess mortality of IDDM patients with nephropathy is 80-100 times greater than that of an age- and sex-matched non-diabetic population. Diabetic nephropathy is the single most important cause of end-stage renal disease in the Western world, accounting for over a quarter of all such cases. Blood pressure elevation is a frequent finding, even in the early stages of diabetic nephropathy. Elevated blood pressure accelerates diabetic nephropathy, while an effective blood pressure reduction delays the progression of nephropathy and reduces albuminuria. A reduction in glomerular capillary hydraulic pressure may be the crucial factor. All previous reports dealing with the natural history of diabetic nephropathy have demonstrated a cumulative death rate of between 50% and 77% 10 years after the onset of nephropathy. Effective antihypertensive treatment has reduced this rate to 15-20%.

Antihypertensive Agents↗

Effect of captopril on blood pressure and kidney function in normotensive insulin dependent diabetics with nephropathy.

OBJECTIVE: To assess whether inhibition of angiotensin converting enzyme protects kidney function in diabetic nephropathy. DESIGN: Open, randomised follow up study of normotensive insulin dependent diabetics with nephropathy either treated or not with captopril for one year. SETTING: Outpatient diabetic clinic in a tertiary referral centre. PATIENTS: 32 Normotensive patients with insulin dependent diabetes complicated by nephropathy who were randomised either to the treatment group (n = 15) or to the control group (n = 17). INTERVENTIONS: The treatment group was given captopril (25-100 mg/day) for 12 months, the average dose during the second six months of the study being 40 mg daily. Controls were not treated. MAIN OUTCOME MEASURES: Albuminuria, arterial blood pressure, and the glomerular filtration rate. RESULTS: Mean arterial blood pressure fell by 3 (SE 2) mm Hg in the captopril treated group and rose by 6 (1) mm Hg in the controls. In addition, albuminuria declined by 11% in the captopril treated group and rose by 55% in the controls, fractional albumin clearance fell by 17% in the captopril treated group and increased by 66% in the controls, and the glomerular filtration rate declined by 3.1 (2.8)ml/min/1.73 m2 with captopril and by 6.4 (3.1) ml/min/1.73 m2 in the controls. CONCLUSION: Inhibition of angiotensin converting enzyme arrests the progressive rise in albuminuria in normotensive insulin dependent diabetics with nephropathy.

Adult↗

Prognosis in diabetic nephropathy.

OBJECTIVE: To assess the effect of long term antihypertensive treatment on prognosis in diabetic nephropathy. DESIGN: Prospective study of all insulin dependent diabetic patients aged under 50 with onset of diabetes before the age of 31 who developed diabetic nephropathy between 1974 and 1978 at Steno Memorial Hospital. SETTING: Outpatient diabetic clinic in tertiary referral centre. PATIENTS: Forty five patients (20 women) with a mean age of 30 (SD 7) years and a mean duration of diabetes of 18 (7) years at onset of persistent proteinuria were followed until death or for at least 10 years. INTERVENTIONS: Antihypertensive treatment was started a median of three (0-13) years after onset of nephropathy. Four patients (9%) received no treatment, and 9 (20%), 13 (29%), and 19 (42%) were treated with one, two, or three drugs, respectively. The median follow up was 12 (4-15) years. MAIN OUTCOME MEASURES: Arterial blood pressure and death. RESULTS: Mean blood pressure at start of antihypertensive treatment was 148/95 (15/50) mm Hg. Systolic blood pressure remained almost unchanged (slope -0.01 (95% confidence interval -0.39 to 0.37) mm Hg a year) while diastolic blood pressure decreased significantly (0.87 (0.65 to 1.10) mm Hg a year) during antihypertensive treatment. The cumulative death rate was 18% (8 to 32%) 10 years after onset of nephropathy, in contrast to previous reports of 50% to 77% 10 years after onset of nephropathy. As in previous studies, uraemia was the main cause of death (9 patients; 64%). CONCLUSIONS: The prognosis of diabetic nephropathy has improved during the past decade largely because of effective antihypertensive treatment.

Adult↗

Effect of antihypertensive treatment on blood-retinal barrier permeability to fluorescein in hypertensive type 1 (insulin-dependent) diabetic patients with background retinopathy.

The effect of antihypertensive treatment on blood-retinal barrier leakage of fluorescein in background retinopathy was studied in nine hypertensive Type 1 (insulin-dependent) diabetic patients suffering from nephropathy. The patients were investigated before and after 7 (3 to 13) months of treatment with captopril (n = 8; 25 to 100 mg daily) and a diuretic, either frusemide (n = 4; 80 to 200 mg daily) or bendrofluazide (n = 2; 2.5 mg daily). Retinal function was assessed by fundus photography, fluorescein angiography, vitreous fluorometry, and renal function by glomerular filtration rate, and albuminuria. The antihypertensive treatment induced a significant reduction (p less than 0.05) in: blood pressure from 152/97 +/- 14/8 mmHg to 134/82 +/- 11/6 mmHg; blood-retinal barrier leakage of fluorescein from 2.4 +/- 1.1 to 1.4 +/- 0.5.10(-7) cm/second; albuminuria from 1391 (range: 168-4852) micrograms/min to 793 (range: 35-2081) micrograms/min. Glomerular filtration rate declined from 88 +/- 15 to 78 +/- 23 ml.min-1.1.73 m2 (0.05 less than p less than 0.10). The metabolic control of the patients as reflected by their blood glucose and HbA1c levels remained stable during the study. Our study suggests that systemic blood pressure elevation contributes to the abnormal blood-retinal barrier permeability to fluorescein characteristically found in diabetic background retinopathy and that this abnormality can be reversed during antihypertensive treatment.

Adult↗

Effects of insulin on kidney function and sodium excretion in healthy subjects.

Insulin action on kidney function was evaluated in 8 healthy subjects, (mean age 27 years) using the euglycaemic clamp technique. Insulin was infused at rates of 0, 20 and 40 mU.min-1.m-2 over consecutive periods of 120 min resulting in plasma insulin concentrations of 8 +/- 2, 29 +/- 7 and 66 +/- 14 mU/l. The renal clearance of 51Cr-EDTA, lithium, sodium and potassium was determined during the last 90 min of each period. Sodium clearance declined with increasing plasma insulin concentrations (1.3 +/- 0.4, 1.0 +/- 0.3 and 0.5 +/- 0.2 ml.min-1.1.73 m-2, p less than 0.001), while glomerular filtration rate (108 +/- 21, 104 +/- 21 and 108 +/- 20 ml.min-1. 1.73 m-2) and lithium clearance (a marker of fluid flow rate from the proximal tubules) 29 +/- 5, 29 +/- 4 and 30 +/- 4 ml.min-1.1.73 m-2) remained unchanged. Calculated proximal tubular reabsorption of sodium and water was unchanged, while calculated distal fractional sodium reabsorption increased (95.5 +/- 1.5, 96.4 +/- 1.2 and 98.1 +/- 0.7%, p less than 0.001). Potassium clearance and plasma potassium concentration declined, whereas plasma aldosterone and plasma renin concentrations were unchanged. In conclusion, elevation of plasma insulin concentration within the physiological range has a marked antinatriuretic action. This effect is located distally to the proximal renal tubules.

Adult↗

The increased proximal tubular reabsorption of sodium and water is maintained in long-term insulin-dependent diabetics with early nephropathy.

Proximal tubular reabsorption of sodium and water was investigated in long-term insulin-dependent diabetic patients with normoalbuminuria (group I, n = 19), microalbuminuria (group II, n = 39), diabetic nephropathy (group III, n = 12) and in 13 healthy age-matched subjects. Glomerular filtration rate was measured with the single injection, 51Cr-EDTA technique. The fluid flow rate out of the proximal tubules was assessed by the renal lithium clearance. Although glomerular filtration rate was significantly elevated in the diabetic patients (Group I: 122 +/- 16, Group II: 121 +/- 18, Group III: 110 +/- 17, CONTROLS: 105 +/- 13 ml/min X 1.73 m2), lithium clearance was similar in the four groups (Group I: 19 +/- 6, Group II: 22 +/- 7, Group III: 19 +/- 5, CONTROLS: 23 +/- 4 ml/min X 1.73 m2). Both absolute and fractional proximal reabsorption of sodium and water was enhanced in diabetes. Indices of distal tubular function did not differ between controls and patients with insulin-dependent diabetes. Sodium clearance was about the same in the four groups. Our study suggests that the enhanced proximal reabsorption of sodium and water in insulin-dependent diabetic patients is still observed despite the presence of incipient or overt diabetic nephropathy.

Adult↗

Monitoring kidney function in diabetic nephropathy.

We investigated the validity of a one plasma sample method (I) compared with a multiple plasma sample method (II) for routine clinical determination of glomerular filtration rate (GFR) in 35 insulin-dependent diabetic patients suffering from nephropathy. GFR was measured after an intravenous bolus injection of 100 microCi 51Cr-EDTA by determination of plasma radioactivity in venous blood samples taken from the other arm 180, 200, 220 and 240 min after the injection (II). The plasma radioactivity in the sample drawn 240 min after injection was used in method I. During the mean investigation period of 32 months (12-62 months) a total of 184 GFR determinations were performed. The average interval between the GFR measurements was 6 months (1-21 months). In 127/184 of the study intervals method I indicated a decrease in GFR. The corresponding figure for method II was almost identical, 130/184. The mean decline in GFR was 8.1 +/- 7.2 and 7.8 +/- 6.9 ml year-1 1.73 m-2 using methods I and II, respectively (NS). The methods essentially provided the same GFR values in absolute terms (r = 0.98, P less than 0.001). We conclude that the one plasma sample method can be used as a valid routine technique in non-uraemic patients with nephropathy.

Adult↗

Reduced urinary excretion of epidermal growth factor in incipient and overt diabetic nephropathy.

To study the relationship between glomerular and tubular function we investigated glomerular filtration rate (GFR), urinary albumin excretion, and urinary excretion of epidermal growth factor (EGF, a mitogenic peptide synthesized in the renal tubular cells) in normal subjects (group I, n = 7) and in Type 1 (insulin-dependent) diabetic patients with normoalbuminuria (group II, n = 11); with incipient nephropathy (microalbuminuria) (group III, n = 9); with nephropathy and normal GFR (group IV, n = 12); and with reduced GFR (group V, n = 8). EGF (nmol 24 h-1) decreased with progressive glomerular involvement, from 7.9 (4.1-10.5) (median and range) in group I, to 6.7 (1.3-9.2) in group II, 5.0 (3.6-7.4) in group III, 4.1 (2.5-9.5) in group IV, and 1.1 (0.1-2.5) in group V. The urinary excretion of EGF was significantly reduced in patients with elevated UAE (group III, IV, and V) compared with normal control subjects (p less than 0.05). A significant correlation between urinary excretion of EGF and GFR (r = 0.71, p less than 0.001) and an inverse correlation between the urinary excretion of EGF and albumin (r = -0.35, p less than 0.05) was demonstrated in the Type 1 diabetic patients with GFR greater than 90 ml min-1. Our study demonstrates that urinary excretion of epidermal growth factor diminishes with increasing nephron impairment, and that renal tubular function as judged by the excretion of EGF is reduced early in the development of diabetic kidney disease.

Adult↗

The effect of short-term near-normal blood glucose control on oscillatory potential and macular recovery time in insulin-dependent diabetic patients with long-standing metabolic dysregulation.

Seven insulin-dependent diabetic patients (mean age 36 years and mean duration of diabetes 19 years) underwent intensified treatment with continuous subcutaneous insulin infusion (CSII) for one week. The patients were selected for the study due to long-standing hypergycemia in an endeavour to determine possible influence on retinal neurosensory function by even short-term near-normalization of blood glucose concentrations. During CSII treatment, near-normalization of the blood glucose levels was obtained (mean blood glucose concentration before treatment; 13.7 +/- 1.6 mmol/l-during treatment; 6.3 +/- 0.4 mmol/l. Recording of the oscillatory potentials by electroretinography and the macular recovery by nyctometry remained about the same in the course of this short-term treatment. Our study suggests that short-term strict metabolic control does not reverse the retinal neural abnormalities in long-standing insulin-dependent diabetes. Consequently; this regimen does not enable prediction of possible beneficial effect of sustained near-normoglycemic treatment.

Adult↗

On the pathogenesis of arterial blood pressure elevation early in the course of diabetic nephropathy.

We measured plasma- and extracellular fluid volume (125I-albumin, 51Cr-EDTA), plasma concentrations of renin, angiotensin I and II, aldosterone and atrial natriuretic peptide by radio-immunoassays in insulin-dependent diabetic (IDDM) patients with (n=28) and without (n=11) nephropathy and in 14 normal control subjects matched for sex and age. Glomerular filtration rate (GFR) (ml/min/1.73 m2, single intravenous bolus 51Cr-EDTA technique) was within normal range in all nephropathic patients; 107 (range 78-134). Mean arterial blood pressure (mmHg) was elevated 102 +/- 13 (+/- S.D.) compared to the diabetic and normal control group, 92 +/- 8 and 87 +/- 5, respectively (p less than 0.01). Plasma volume was identical in all three groups while extracellular volume (1/1.73 m2) was expanded in nephropathic patients, 14.5 +/- 1.5 vs 13.1 +/- 0.9 and 12.4 +/- 1.3 in the diabetic and non-diabetic control groups, respectively (p less than 0.05). A significant correlation between extracellular fluid volume and mean arterial blood pressure was found (n=53, r=0.49, p less than 0.001). Active renin was significantly increased in patients with diabetic nephropathy compared with the normal control subjects, while all the remaining hormones were about the same in the three groups. Our study suggests that fluid retention plays a dominant role in the initiation and maintenance of arterial blood pressure elevation early in the course of diabetic nephropathy.

Adult↗

The acute effect of acetazolamide on glomerular filtration rate and proximal tubular reabsorption of sodium and water in normal man.

The acute effects on kidney function of acetazolamide (250 mg) given intravenously were evaluated in seven healthy subjects. Glomerular filtration rate was measured as the renal clearance of 51Cr-EDTA, and fluid flow rate out of the proximal tubules was assessed by measurement of the renal lithium clearance. An 18% decline in glomerular filtration rate (ml/min) was observed after acetazolamide administration (109 +/- 16 vs 89 +/- 14, p less than 0.02), while lithium clearance (ml/min) increased by 35% (30 +/- 5 vs 38 +/- 8, p less than 0.02). Absolute proximal tubular reabsorption of water (ml/min) was reduced by about one third (79 +/- 12 vs 51 +/- 9, p less than 0.02), and fractional proximal reabsorption of water and sodium (%) declined (73 +/- 2 vs 58 +/- 6, p less than 0.02). Renal sodium clearance and absolute distal reabsorption of sodium increased, while fractional distal reabsorption of sodium declined. Acetazolamide reduces absolute and fractional proximal tubular reabsorption of sodium and water, and glomerular filtration rate. Primarily, this induces an increase in the output of fluid from the proximal tubules accounting for the diuretic effect of the drug. The acute fall in glomerular filtration rate is probably mediated by a temporary increase in proximal intratubular pressure and activation of the tubuloglomerular feedback mechanism.

Acetazolamide↗