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Biomedical subjects

J F Wetzels

Publications and source records attributed to J F Wetzels.

At least 109 records · Page 6Linked to original sources
PubMed1991

Erythrocyte sodium-lithium countertransport is not different in type 1 (insulin-dependent) diabetic patients with and without diabetic nephropathy.

We studied erythrocyte sodium-lithium countertransport in 33 patients with Type 1 (insulin-dependent) diabetes mellitus with diabetic nephropathy, 18 patients with Type 1 diabetes without diabetic nephropathy and in 42 non-diabetic patients with various other renal diseases. No significant differences were found in sodium-lithium countertransport between these three groups (median (range) 322 (162-676) vs 321 (189-627) vs 300 (142-655) mumol.l cells-1.h-1). We conclude, that sodium-lithium countertransport cannot be used as a marker for diabetic nephropathy.

Adult↗
PubMed1991

Cimetidine improves the reliability of creatinine as a marker of glomerular filtration.

To investigate whether the administration of cimetidine can improve the reliability of creatinine as a marker of GFR, we compared the creatinine clearance (CCr) to the clearance of the true filtration markers 51Cr-EDTA (CEDTA) and inulin (CIn), after oral ingestion of cimetidine in 10 healthy men and 29 patients with varying degrees of renal dysfunction. After administration of cimetidine for three to six days, serum creatinine level rose in all participants, while CEDTA and CIn remained stable in a subgroup of 14 subjects in whom they were measured before as well as after the administration of cimetidine. The mean (+/- SD) ratios of CCr to CEDTA (N = 39) and of CCr to CIn (N = 19) after ingestion of cimetidine were 1.02 +/- 0.13 and 1.01 +/- 0.13, respectively, and did not differ significantly from unity. This high degree of accuracy of the cimetidine-aided CCr was present over the entire range of renal function in the study population. Our results also indicated an improved precision of the cimetidine-aided measurement of CCr, resulting in a variability that did not differ significantly from that of the measurement of CEDTA or CIn. We conclude that after oral administration of cimetidine, the creatinine clearance can be used as a reliable measure of GFR within a broad range of renal function.

Adult↗
PubMed1990

Decreases of proteinuria during alternate-day prednisone therapy in nephrotic syndrome.

Treatment of patients with membranous glomerulonephritis with prednisone on alternate days results in a decreased proteinuria on non-prednisone days. We have studied this phenomenon in more detail in 14 patients (11 M, 3 F) with membranous glomerulonephritis. Mean age +/- SD of the patients was 47 +/- 14 years, mean endogenous creatinine clearance 94 +/- 35 ml/min, and median proteinuria 8.8 g/24 h (range 5.0-30.0 g/24 h). Glomerular filtration rate (GFR, inulin clearance), effective renal plasma flow ERPF, PAH clearance), and proteinuria were measured on a control day (C), and six days after the start of alternate-day prednisone treatment, on the third non-prednisone day (NP3, 24-28 h after the last dose of prednisone). Proteinuria decreased from 6.1 mg/min (3.2-9.8 mg/min) (C) to 2.5 mg/min (1.0-7.7 mg/min) at NP3 (median, interquartile range; P less than 0.01), the percentage decrease averaged 45 +/- 8%. The decrease of proteinuria was correlated with baseline GFR (r = 0.75; P less than 0.01). GFR and ERPF did not change significantly, but filtration fraction decreased significantly from 14.5 +/- 0.8% (C) to 13.5 +/- 0.9% (NP3; P less than 0.05). Fractional excretion of albumin, IgG, and transferrin decreased significantly, by -40 +/- 8%, -52 +/- 6%, and -52 +/- 7% respectively. Fractional excretion of beta 2-microglobulin decreased significantly less by -12 +/- 10%. We conclude that proteinuria is decreased on non-prednisone days in patients with membranous glomerulonephritis treated with alternate-day steroids. The observed decrease of filtration fraction suggests that a reduction of glomerular pressure is involved. In addition, the magnitude of the decrease of proteinuria might indicate a change in glomerular permselectivity characteristics.

Adult↗
PubMed1990

Effects of nitrendipine and cilazapril on renal hemodynamics and albuminuria in hypertensive patients with chronic renal failure.

In 11 hypertensive patients with chronic renal failure we studied the short-term effects of the calcium antagonist nitrendipine, the angiotensin-converting enzyme inhibitor cilazapril, and the combination of both drugs on blood pressure, renal hemodynamics, and proteinuria in a randomized, double-blind, placebo-controlled way. After one week of treatment, blood pressure at 2-5 h after drug administration amounted to 159 +/- 5/101 +/- 3 mm Hg (means +/- SEM) during placebo. Nitrendipine, cilazapril, and the combination lowered mean arterial pressure by 1.4 +/- 1.6 (NS), 6.0 +/- 1.7 (p less than 0.10), and 10.3 +/- 2.1% (p less than 0.01), respectively. Glomerular filtration rate did not change. As compared to placebo, renal blood flow increased and renal vascular resistance decreased significantly during the combination. Filtration fraction amounted to 22.7 +/- 1.2% during placebo and was 22.0 +/- 1.4 (NS), 20.4 +/- 1.2 (p less than 0.01), and 20.5 +/- 1.4% (p less than 0.05) during nitrendipine, cilazapril, and the combination, respectively. During nitrendipine, albuminuria was slightly higher than during placebo: 0.86 +/- 0.39 vs. 0.58 +/- 0.25 mg/min (NS). During cilazapril alone and during the combination of both drugs, albuminuria was lower as compared to nitrendipine: 0.38 +/- 0.14 mg/min (p less than 0.01) and 0.44 +/- 0.18 mg/min (p less than 0.01), respectively. The data suggest that the combination of nitrendipine and cilazapril is an effective treatment in renal hypertension. In addition, cilazapril alone as well as the combination with nitrendipine reduced albuminuria, possibly by decreasing filtration fraction and/or reduction of blood pressure.

Adult↗
PubMed1989

Triamterene increases lithium excretion in healthy subjects: evidence for lithium transport in the cortical collecting tubule.

The possible presence of lithium transport beyond the proximal tubule was examined by measuring lithium excretion after administration of triamterene, a potassium-sparing diuretic, exclusively acting in the cortical collecting tubule. Eight young and healthy volunteers were studied on two occasions during maximal water diuresis. After obtaining baseline values triamterene (100 mg orally) or placebo was administered, and measurements continued for 4 hours. Creatinine clearance was used as a marker of glomerular filtration rate, and phosphate excretion was used as an additional marker of proximal sodium transport. Compared to placebo (P), triamterene (T) caused a significant increase in fractional excretion of sodium (P, 0.74 +/- 0.08%; T, 1.73 +/- 0.24%, mean +/- SEM; P less than 0.01), and lithium (P, 21.2 +/- 1.3%; T, 27.5 +/- 1.5%; P less than 0.01), whereas fractional excretion of phosphate remained unchanged (P, 9.8 +/- 1.3%; T, 9.4 +/- 1.5%; P = NS). These results indicate that lithium is transported in the cortical collecting tubule, and provide further evidence that the use of lithium as a marker of purely proximal tubular sodium transport is of limited value.

Adult↗
PubMed1989

Antihypertensive effects of nitrendipine and cilazapril alone, and in combination in hypertensive patients with chronic renal failure.

1. It has been reported that calcium antagonists lower blood pressure more effectively in salt replete hypertensive patients with a low plasma renin activity (PRA), whereas angiotensin converting enzyme (ACE) inhibitors are more effective in salt depleted patients with a high level of PRA. An inverse relationship between the antihypertensive effects of these two groups of drugs might therefore be expected. 2. Since salt retention and inappropriately high levels of PRA are said to contribute to hypertension in patients with chronic renal failure (CRF), an additive antihypertensive effect with both drugs might also be expected in such patients. 3. To test these hypotheses, we investigated the acute and chronic antihypertensive effects of the calcium antagonist nitrendipine and the new ACE inhibitor cilazapril, given alone, and in combination, in a double-blind, randomized, placebo controlled study of 11 hypertensive patients with chronic renal failure who had a mean pretreatment blood pressure of 149 +/- 3/96 +/- 2 mm Hg. Patients received nitrendipine 10 mg, cilazapril 1.25 or 2.5 mg depending on creatinine clearance, or placebo once daily orally. Nitrendipine and cilazapril were also combined at the same doses. 4. Nitrendipine and cilazapril were equally effective, with a maximal acute reduction of mean arterial pressure (MAP) of 5.3 +/- 1.8% and 8.0 +/- 1.9%, and after 1 week of treatment 5.0 +/- 2.4% and 8.1 +/- 1.8%, respectively. In individual patients no inverse relationship between the blood pressure responses to the two drugs was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Short-term protein restriction in healthy volunteers: effects on renal hemodynamics and renal response to a meat meal.

We have studied the renal hemodynamic effects of short-term protein restriction and short-term protein loading in 12 healthy volunteers, who adhered to a low protein diet (0.6 g/kg/day) for three weeks and then switched to a high protein diet (1.8 g/kg/day) for another three weeks. Baseline glomerular filtration rate (GFR) was not influenced by dietary protein intake. Effective renal plasma flow (ERPF), however, was significantly lower on the low protein diet (491 +/- 23 ml/min; mean +/- SEM) as compared to values on the high protein diet (538 +/- 19 ml/min; p less than 0.01). The increase of GFR after a meat meal (providing 1.8 g protein/kg body weight) was higher on the high protein diet (GFR: +23.6 +/- 5.1 ml/min) than on the low protein diet (GFR: +13.0 +/- 2.4 ml/min; p less than 0.05). We conclude that three weeks of dietary protein restriction do not decrease glomerular filtration rate and do not enhance the renal response to a meat meal. Therefore, it seems doubtful that dietary protein restriction decreases glomerular capillary pressure through vasoconstriction of the afferent glomerular arteriole. Furthermore, measurement of the renal hemodynamic response to an acute protein load seems of doubtful physiological significance.

Adult↗
PubMed1988

Prednisolone can increase glomerular permeability to proteins in nephrotic syndrome.

In patients with a nephrotic syndrome administration of prednisolone causes an increase of proteinuria. To elucidate the mechanism of this effect we have studied the acute proteinuric effect of prednisolone, 125 to 150 mg intravenously, in nine patients (7 M, 2F) with a nephrotic syndrome. Mean age (+/- SD) of the patients was 53 +/- 6 years, mean endogenous creatinine clearance 104 +/- 30 ml/min, and mean proteinuria 7.7 +/- 3.0 g/24 hr. After administration of prednisolone, urinary total protein excretion rose in all patients from a mean (+/- SEM) of 4.89 +/- 0.59 mg/min before to 9.09 +/- 0.99 mg/min at five hours after administration (P less than 0.01). Glomerular filtration rate (inulin clearance), effective renal plasma flow (PAH clearance), and filtration fraction did not change significantly. The increases of urinary excretion of albumin (median %: +92%), IgG (median %: +88%), and transferrin (median %: +76%) were comparable and correlated significantly. Urinary excretion of beta 2-microglobulin did not change significantly however. We conclude that intravenous administration of prednisolone to patients with a nephrotic syndrome causes an increase in urinary protein excretion rate which cannot be explained by changes in renal hemodynamics or tubular protein reabsorption, and which therefore must be the result of a change in glomerular permselectivity characteristics.

Capillary Permeability↗
PubMed1988

Antihypertensive effect of beta blockade in renal transplant recipients with or without host kidneys.

Host kidneys may contribute considerably to hypertension after renal transplantation. Their role in sustaining hypertension is more prominent if glomerulonephritis (GN) than if interstitial nephritis (IN) is the original renal disease. We compared the antihypertensive effect of beta-blockade in IN (n = 10) and GN (n = 19) hypertensive renal transplant recipients with host kidneys in situ with those who had undergone bilateral nephrectomy (BN, n = 10). Pretreatment blood pressures were comparable in BN, IN, and GN patients, being 165 +/- 6/108 +/- 3, 172 +/- 5/104 +/- 3, and 161 +/- 3/104 +/- 1, mmHg, respectively. Blood pressure did not change on beta-blockade in BN patients, whereas it decreased significantly more (P less than 0.001) in GN than in IN patients, changes of mean arterial pressure being -107 +/- 1.0, -14.9 +/- 1.3, and -6.8 +/- 1.6%, respectively. This failure to respond to beta-blockade in patients without host kidneys may be related to low activity of the renin-angiotensin system or to functional denervation of the grafted kidney. Further investigations of this phenomenon may clarify the mechanism of antihypertensive action of beta-blockade as well as the nature of hypertension after renal transplantation.

Adrenergic beta-Antagonists↗
PubMed1988

Diuretic and natriuretic effects of nifedipine in healthy persons.

1. We have studied the diuretic and natriuretic effects and the tubular site of action of nifedipine using free water clearance (CH2O) and lithium clearance. 2. We have compared the effects of nifedipine (10 mg p.o.) with those of placebo and of frusemide (40 mg p.o.) in seven healthy volunteers during maximal water diuresis. 3. Compared with placebo, nifedipine caused a significant rise in urinary flow rate and CH2O, paralleled by significant increases in fractional excretion of sodium and lithium. The rise in sodium excretion was not accompanied by an increase in potassium excretion. 4. Frusemide caused increases in sodium and lithium excretion, comparable with the effects seen after nifedipine. CH2O did not change however. 5. Our study demonstrates that nifedipine has a clear diuretic and natriuretic effect in healthy volunteers, which is predominantly established by interference with proximal tubular sodium reabsorption. Lithium clearance did not allow us to differentiate between nifedipine and frusemide effects, thus questioning the reliability of lithium as a marker of proximal tubular sodium reabsorption.

Adult↗
PubMed1988

Renal clearance of pancreatic and salivary amylase relative to creatinine clearance in patients with renal disease and proteinuria.

To study the charge-selective properties of the glomerular filter in renal disease, we measured the fractional clearance, relative to creatinine clearance (ECC), of the amylase isoenzymes pancreatic amylase and salivary amylase, which have identical size but different charge. In 63 healthy subjects the mean (and SD) fractional excretion of pancreatic amylase, 4.07% (1.24%), was fourfold that of salivary amylase: 1.02% (0.54%). For 29 patients with renal disease and proteinuria, the mean fractional excretion of pancreatic amylase was significantly lower, 3.31% (1.94%), and that of salivary amylase significantly higher, 2.06% (1.41%), than in controls. In these patients, fractional excretions of both these isoenzymes were negatively correlated with urinary excretion of beta 2-microglobulin and ECC. Evidently, differences in clearances of pancreatic and salivary amylase are a consequence of differences in charge-related glomerular filtration. The relative increase of salivary amylase clearance in patients with renal disease and proteinuria is most probably caused by a loss of the charge-selective properties of the glomerular basement membrane.

Adult↗
PubMed1988

Renal hemodynamic effects of a short-term high protein and low protein diet in patients with renal disease.

The renal hemodynamic effects of short-term protein loading and short term protein restriction were studied in patients with renal disease. Eleven patients adhered to a high protein diet (1.8 g/kg/day) and, subsequently, to a low protein diet (0.6 g/kg/day) for four weeks each. Renal hemodynamics were studied at the end of the respective dietary periods. Glomerular filtration rate (inulin clearance) did not change significantly (delta %: -1.5 +/- 5.4%; mean +/- s.e.m.), whereas endogenous creatinine clearance was lower on the low protein diet (delta %: -7.8 +/- 2.8%; p less than 0.02), suggesting an interference with the tubular secretion of creatinine. Effective renal plasma flow was significantly lower on the low protein diet (223.7 +/- 47.6 ml/min vs 282.1 +/- 67.1 ml/min; delta %: -15.4 +/- 4.9%; p less than 0.02). As a result, filtration fraction increased from 0.18 +/- 0.01 on the high protein diet to 0.22 +/- 0.02 on the low protein diet (p less than 0.01). The low protein diet caused a significant decrease in protein excretion from 4.0 +/- 0.9 g/24 h to 3.1 +/- 0.7 g/24 h (p less than 0.02). Our study demonstrates that renal hemodynamic responses to more sustained protein loading and protein restriction differ from the reported responses to acute protein loading. Different mechanisms may be involved. In this light it is doubtful if the renal hemodynamic response to acute protein loading can predict a beneficial effect of protein restriction.

Adult↗