Cimetidine administration and tubular creatinine secretion in patients with compensated cirrhosis

2001 ◽  
Vol 102 (1) ◽  
pp. 91-98 ◽  
Author(s):  
Giovanni SANSOÈ ◽  
Alberto FERRARI ◽  
Carmen Nives CASTELLANA ◽  
Lorenzo BONARDI ◽  
Erica VILLA ◽  
...  
Keyword(s):  
Oral Administration ◽  
Fractional Excretion ◽  
Tubular Secretion ◽  
Inulin Clearance ◽  
Sodium Reabsorption ◽  
Lithium Clearance ◽  
Clearance Ratio ◽  
Compensated Cirrhosis ◽  
Tubular Sodium Reabsorption ◽  
Sodium Load

Cimetidine inhibits the tubular secretion of creatinine, without altering the glomerular filtration rate (GFR). During cimetidine administration the creatinine/inulin clearance ratio approaches unity in patients with renal failure. We determined the clearance of lithium (an index of fluid delivery to the distal nephron), inulin (a measure of the actual GFR) and creatinine during cimetidine administration to investigate the occurrence of tubular creatinine secretion in patients with compensated cirrhosis. A total of 12 patients with Child-Pugh A cirrhosis were studied initially. The subjects consumed a stable diet containing 100mmol of sodium. On successive days, 9h creatinine clearances were measured, first without and then with the oral administration of cimetidine (400mg as a priming dose, followed by 200mg every 3h). During the first study day, 4h renal lithium clearance was also calculated. A further group of five patients with fully compensated cirrhosis underwent the measurement (on successive days) of plasma inulin clearance, first without and then with the oral administration of cimetidine (same schedule of drug administration). Cimetidine administration unmasked a marked overestimation of GFR when calculated as creatinine clearance (baseline, 138±20ml/min; +cimetidine, 89±13ml/min; P < 0.01). Consequently, during cimetidine administration the calculated lithium fractional excretion (a measure of the fraction of filtered sodium load that is delivered to the loop of Henle) rose from 21.4±13.2% to 32.3±18.9% (P < 0.05), and the ratio between absolute distal tubular sodium reabsorption and filtered sodium load rose from 20.6±13.1% to 31.6±19.3% (P < 0.01). Cimetidine caused no significant decrease in the actual GFR (i.e. inulin clearance) when administered to the second group of patients with compensated cirrhosis. Our data demonstrate significant tubular secretion of creatinine in patients with compensated cirrhosis and, consequently, a marked overestimation of GFR and filtered sodium load and an underestimation of the fractional distal tubular sodium reabsorption when these parameters are calculated by means of the traditional creatinine and lithium clearance computation. The true GFR (measured as inulin clearance) is unaffected by cimetidine administration.

scholarly journals Renal effects of a urodilatin infusion in patients with liver cirrhosis, with and without ascites.

1998 ◽  
Vol 9 (8) ◽  
pp. 1489-1498
Author(s):  
J Carstens ◽  
J Greisen ◽  
K T Jensen ◽  
H Vilstrup ◽  
E B Pedersen
Keyword(s):  
Liver Cirrhosis ◽  
Fractional Excretion ◽  
Controlled Study ◽  
Sodium Reabsorption ◽  
Lithium Clearance ◽  
Renal Effects ◽  
Fluid Delivery ◽  
Tubular Sodium Reabsorption ◽  
Proximal Tubular ◽  
Cirrhotic Patients

This study reports the effects of a short-term (60 min) low-dose (20 ng x kg(-1) x min(-1)) infusion of synthetic urodilatin (URO) in patients with liver cirrhosis. URO is a natriuretic peptide. A total of 15 cirrhotic patients with ascites and nine without ascites participated in a randomized, double-blind, placebo-controlled study in a crossover design. Renal hemodynamics were estimated by a clearance technique using radioactive tracers, and tubular handling of sodium was evaluated by the lithium clearance method. The renal effects of URO were characterized by a significant increase in urine sodium excretion rate (UNa) and urine flow rate (V) in the cirrhotic patients without ascites (UNa: 173%; V: 94%) and with ascites (UNa: 219%, P < 0.01; V: 42%, P < 0.01) when compared with placebo infusions. Fractional excretion of sodium increased significantly, indicating a tubular effect of URO on sodium handling. Filtration fraction, lithium clearance (a marker of end-proximal fluid delivery), and fractional excretion of lithium increased, fractional proximal tubular sodium reabsorption decreased, and absolute proximal tubular sodium reabsorption remained unchanged, suggesting increased delivery of isotonic fluid from the proximal tubule during URO infusion. In addition, a significant decrease in fractional distal tubular sodium reabsorption contributed to the natriuresis. In conclusion, URO improved sodium and urine output in cirrhotic patients with and without ascites by enhancing fluid delivery from the proximal tubules in addition to inhibiting fractional sodium reabsorption in the distal nephron.

Natriuretic effect of caffeine: assessment of segmental sodium reabsorption in humans

2002 ◽  
Vol 103 (5) ◽  
pp. 461-466 ◽  
Author(s):  
D.G. SHIRLEY ◽  
S.J. WALTER ◽  
F.H. NOORMOHAMED
Keyword(s):  
Control Period ◽  
Fractional Excretion ◽  
Experimental Period ◽  
Caffeine Intake ◽  
Sodium Reabsorption ◽  
Lithium Clearance ◽  
Distal Nephron ◽  
Clearance Ratio ◽  
Fractional Excretion Of Sodium ◽  
Natriuretic Effect

In order to assess the intrarenal mechanisms responsible for the natriuretic action of caffeine, the renal clearances of 51Cr-EDTA [used as a measure of glomerular filtration rate (GFR)] and lithium (used as an index of end-proximal fluid delivery) were measured in eight healthy males before (control period) and immediately after (experimental period) a 400mg oral dose of caffeine (given over 90min) or placebo. In caffeine-treated subjects, the fractional excretion of sodium rose from 1.00±0.25% in the control period to 1.47±0.18% in the experimental period, while corresponding values on the placebo day were 1.04±0.16% and 0.70±0.07% respectively. GFR was unchanged following either caffeine or placebo. When compared with the placebo day, caffeine caused increases in lithium clearance (experimental period values: caffeine, 37±1ml/min; placebo, 28±2ml/min; P<0.001), the fractional excretion of lithium (caffeine, 34±1%; placebo, 26±2%; P<0.001) and the sodium/lithium clearance ratio (used as an index of the fraction of sodium delivered to the distal nephron that escapes reabsorption therein: caffeine, 4.4±0.3%; placebo, 2.8±0.2%; P<0.001). These results suggest that reduced fractional sodium reabsorption in both the proximal tubule and the distal nephron contributes to the acute natriuretic effect of caffeine. The data also confirm the importance of controlling caffeine intake when investigating renal function using lithium clearance.

Renal Handling of Creatinine in Nephrotic and Non-Nephrotic Patients

1970 ◽  
Vol 38 (5) ◽  
pp. 555-562 ◽  
Author(s):  
C. F. Anderson ◽  
D. M. Jaecks ◽  
H. S. Ballon ◽  
J. R. De Palma ◽  
R. E. Cutler
Keyword(s):  
Renal Function ◽  
Normal Subjects ◽  
Tubular Secretion ◽  
Inulin Clearance ◽  
Clearance Ratio ◽  
Renal Handling ◽  
Secretory Rate ◽  
Ureteral Catheterization ◽  
Iothalamate Clearance

1. The endogenous creatinine/GFR (inulin or free [57Co]cyanocobalamin or [125I]iothalamate) clearance ratios were determined in ninety-nine non-nephrotic patients and subjects and in sixteen nephrotic patients. The clearance ratios of the nephrotic patients were not significantly different from those of the non-nephrotic patients and normal subjects. 2. The clearance ratios increased as the GFR fell from 176 to below 15 ml/min, then decreased toward unity at lower GFR values. 3. In an attempt to explain this biphasic relationship, two further studies were performed. Endogenous creatinine/inulin and [14C]creatinine/inulin clearance ratios were simultaneously determined in seventeen additional patients. The [14C]creatinine/inulin clearance ratio was the larger of the two in all patients with a GFR greater than 15 ml/min. In another group of eight patients with unequal-sized kidneys, who were studied during bilateral ureteral catheterization, the endogenous creatinine/inulin clearance ratios were determined and found not to differ significantly. 4. The three studies suggest that there is significant tubular secretion of creatinine at all levels of renal function. The increasing clearance ratio of endogenous creatinine/GFR as the GFR decreases is not due to increased tubular secretion of creatinine nor a result of a difference in creatinine handling by diseased kidneys, but rather a reflection of the decreasing fraction of non-creatinine chromogen to the total creatinine chromogen. The smaller clearance ratio at a very low GFR would be expected if the maximal tubular secretory rate of creatinine was exceeded.

Endogenous versus Exogenous Lithium Clearance for Evaluation of Dopamine-Induced Changes in Renal Tubular Function

1996 ◽  
Vol 90 (6) ◽  
pp. 511-515 ◽  
Author(s):  
Niels V. Olsen ◽  
Niels Fogh-Andersen ◽  
Svend Strandgaard ◽  
Paul P. Leyssac
Keyword(s):  
Plasma Concentrations ◽  
Fractional Excretion ◽  
Random Order ◽  
Baseline Period ◽  
Tubular Function ◽  
Sodium Reabsorption ◽  
Lithium Clearance ◽  
Double Blind ◽  
Baseline Values ◽  
Induced Changes

1. The present randomized, double-blind cross-over study compared endogenous and exogenous lithium clearance (CLi) for estimation of the effect of dopamine on tubular sodium reabsorption. Twelve normal, salt-repleted male subjects were investigated on three different occasions with either placebo or 450 mg or 600 mg of lithium given in random order at 22.00 hours. After an overnight fast, renal clearance studies were performed during a 1 h baseline period and subsequently during the second hour of an infusion of 3 μg min−1 kg−1 of dopamine. 2. Baseline values of endogenous CLi and fractional excretion of lithium (FELi) [27.0 (23.5–30.5) ml/min and 24.2 (203–28.2)% (means with 95% confidence interval)] were lower than exogenous values [lithium, 450 mg: 32.7 (29.9–35.4) ml/min (P < 0.05) and 27.4 (25.2–29.6)% (P < 0.05); lithium, 600 mg: 33.4 (29.2–37.6) ml/min (P < 0.05) and 28.6 (26.3–31.0)% (P < 0.01)]. Both test doses of lithium increased the baseline sodium clearance (CNa), but glomerular filtration rate and urine flow rate remained unchanged. 3. Dopamine increased CNa to similar values on the three study days. CLi increased to 40.9 (35.5–46.5) ml/min (endogenous lithium, P < 0.001), 43.2 (40.8–45.6) ml/min (450 mg of lithium, P < 0.01) and 44.9 (41.3–48.4) ml/min (600 mg of lithium, P < 0.001), respectively. FELi increased to 32.2 (27.5–37.0)% (P < 0.01), 35.4 (33.0–37.7)% (P < 0.01) and 35.9 (32.8–38.9)% (P < 0.01), respectively. Values during dopamine infusion did not differ significantly. 4. The lower baseline values of endogenous CLi and FELi compared with exogenous values suggest that CLi in humans depends on the plasma concentrations of lithium. However, the effect of dopamine on CLi and FELi was expressed to the same extent with endogenous and exogenous lithium, indicating that the two methods are interchangeable for estimation of dopamine-induced changes in tubular function.

Lithium clearance and renal tubular sodium handling during acute and long-term nifedipine treatment in essential hypertension

1988 ◽  
Vol 75 (6) ◽  
pp. 609-613 ◽  
Author(s):  
Niels Eske Bruun ◽  
Hans Ibsen ◽  
Peter Skøtt ◽  
Dorthe Toftdahl ◽  
Jørn Giese ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Sodium Reabsorption ◽  
Lithium Clearance ◽  
Tubular Sodium Reabsorption ◽  
Potassium Clearance ◽  
Renal Tubular ◽  
Sodium Clearance

1. In two separate studies the lithium clearance method was used to evaluate the influence of acute and long-term nifedipine treatment on renal tubular sodium reabsorption. 2. In the acute study, after a 4 week placebo period two doses of 20 mg of nifedipine decreased supine blood pressure from 155/101 (20.6/13.5) ± 11/4 (1.5/0.5) to 139/88 (18.5/11.7) ± 16/9 (2.1/1.2) mmHg (kPa) (means ± sd; P < 0.01). Lithium clearance, glomerular filtration rate and sodium clearance did not change. Therefore the calculated values of absolute proximal and absolute distal sodium reabsorption rates were also unchanged, as were potassium clearance, urine flow and body weight. 3. In the long-term study, lithium clearance, glomerular filtration rate, sodium clearance, potassium clearance, urine flow and body fluid volumes were measured after a 4 weeks placebo period and after 6 and 12 weeks of nifedipine treatment. As compared with placebo, mean supine blood pressure decreased significantly. The glomerular filtration rate did not change but lithium clearance fell by 30%. Consequently, the absolute and the fractional proximal sodium reabsorption increased significantly. The fractional distal sodium reabsorption did not change. Sodium clearance, fractional sodium excretion, potassium clearance, plasma volume and extracellular fluid volume were also unchanged. 4. In conclusion, we found no changes of renal tubular sodium reabsorption during acute nifedipine treatment, whereas long-term nifedipine treatment caused a redistribution of tubular sodium reabsorption without a change in overall sodium excretion or body fluid compartments.

Effect of DIDS on renal tubular transport

1980 ◽  
Vol 238 (2) ◽  
pp. F99-F106
Author(s):  
F. J. Koschier ◽  
M. F. Stokols ◽  
J. M. Goldinger ◽  
M. Acara ◽  
S. K. Hong
Keyword(s):  
Transport System ◽  
Organic Anion ◽  
Tubular Secretion ◽  
Inulin Clearance ◽  
Clearance Ratio ◽  
Renal Cortical Slice ◽  
Anion Transport System ◽  
Renal Tubular ◽  
Renal Slice Transport ◽  
Perfused Kidney

Two stilbene derivates that had been used to covalently label the Cl- carrier in the erythrocyte were investigated for reactivity with the renal organic anion system. These compounds, 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) and (4,4'-diisothiocyano)-dihydrostilbene-2,2'-disulfonate (H2DIDS), were found to be potent inhibitors (Ki congruent to 35 microM) of p-aminohippurate (PAH) transport in the renal cortical slice without affecting tetraethylammonium (TEA) transport or tissue viability. During renal clearance studies performed in the perfused kidney, DIDS decreased the PAH/inulin clearance ratio to congruent to 1. When the possible renal transport of [3H]H2DIDS was investigated, the renal slice transport or binding of [3H]H2DIDS reached a slice-to-medium ratio of congruent to 6, and this accumulation was decreased by probenecid. In perfused kidney experiments, the [3H]H2DIDS/inulin clearance ratio was congruent to 0.8. Since probenecid reduced this clearance ratio to congruent to 0.5, there was the possibility that H2DIDS underwent tubular secretion. In conclusion, DIDS and H2DIDS interacted with the renal organic anion transport system, which indicated that these compounds were possible probes for this transport system.

Proximal and distal tubular activity in chronically catheterized fetal sheep compared with the adult

1988 ◽  
Vol 66 (6) ◽  
pp. 697-702 ◽  
Author(s):  
Eugenie R. Lumbers ◽  
Karen J. Hill ◽  
Victoria J. Bennett
Keyword(s):  
Sodium Reabsorption ◽  
Fetal Life ◽  
Fetal Sheep ◽  
Adult Sheep ◽  
Tubular Sodium Reabsorption ◽  
Sodium Load ◽  
Proximal Tubular ◽  
Proximal Tubular Function ◽  
Nonpregnant Adult ◽  
Glomerulotubular Balance

Renal function was studied in unanaesthetized fetal sheep aged 112–120 and 126–132 days and in adult nonpregnant ewes. The clearance of lithium was used to measure proximal and distal fractional sodium reabsorption. In five nonpregnant adult sheep, 80.6 ± 1.7% (SE) of the filtered sodium load was reabsorbed proximaily and 18.2 ± 1.53% distally. This was different from all groups of fetal sheep (p < 0.001). In younger fetuses, proximal fractional sodium reabsorption was less (51.3 ± 2.3% (SE), p < 0.05) and distal fractional sodium reabsorption greater (42.4 ± 2.3% (SE), p < 0.05) than older fetuses (126–132 days old) in which 61.4 ± 2.4% (SE) was reabsorbed proximaily and 33.6 ± 2.5% (SE) distally. In another group of fetuses aged 125–137 days, in which proximal tubular sodium reabsorption was measured after distal tubular blockade, proximal fractional sodium reabsorption was 57.8 ± 2.95% (SE) and distal fractional sodium reabsorption, 38.7 ± 2.64% (SE). In adult sheep there was no relationship between distal tubular sodium reabsorption and glomerular filtration rate, i.e., proximal tubular function was responsible for glomerulotubular balance. However, in the fetuses, both proximal and distal tubular sodium reabsorption contributed to glomerulotubular balance. Thus in fetal life, the proximal tubule participates to a lesser extent in reabsorbing the filtered sodium load possibly because its function is suppressed by its relatively "volume-expanded" state or because it is functionally immature. Therefore, a greater proportion is reabsorbed distally and the distal nephron participates under physiological conditions in glomerulotubular balance.

Compensatory phosphaturia after unilateral nephrectomy in the rat

1976 ◽  
Vol 231 (5) ◽  
pp. 1625-1629 ◽  
Author(s):  
C Lehne ◽  
FL Coe
Keyword(s):  
Parathyroid Hormone ◽  
Secondary Hyperparathyroidism ◽  
Renal Mass ◽  
Hormone Replacement ◽  
Fractional Excretion ◽  
Unilateral Nephrectomy ◽  
Sodium Reabsorption ◽  
Tubular Sodium Reabsorption ◽  
Fractional Excretion Of Phosphate

Within 24 hr after unilateral nephrectomy, fractional excretion of phosphate (FEp) by the remaining kidney is markedly increased. This increase in FEp occurs in throparathyroidectomized rats receiving fixed replacement doses of parathyroid hormone and, therefore, cannot be due to secondary hyperparathyroidism occurring in response to unilateral nephrectomy. In the avsence of any hormone replacement, the increase in FEp is much reduced, but still present. The increase in FEp cannot be ascribed to depression of overall tubular sodium reabsorption because it could be demonstrated in the absence of an increase in FENa. Phosphaturia following unilateral nephrectomy in the rat appears to be part of the complex of events that occur after acute reduction of renal mass; the exact mechanisms of its genesis are uncertain.

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