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P Deetjen

Publications and source records attributed to P Deetjen.

At least 19 recordsLinked to original sources
PubMed1995

Ultrapure polymerized bovine hemoglobin (UPPBHb) improves integrity of the isolated perfused rat kidney (IPRK): effects on function and structure.

To test the oxyphoretic properties and potential nephrotoxic side-effects of polymerized hemoglobin solutions, isolated rat kidneys were perfused in a recirculating system for 180 min. Group I was perfused with a substrate enriched Ringer solution containing hydroxyethylstarch (HES) to produce isoncotic conditions. In group II HES was substituted in part by UPPBHb (34 g/l) with a high portion of low molecular weight molecules (= UPPBHb1). In group III 34 g/l of UPPBHb containing an increased fraction of high molecular weight polymers (= UPPBHb2) was used. Only UPPBHb2-perfused kidneys showed a reduced renal perfusate flow (RPF, 13.3 +/- 1.1 ml/min g kw), when compared to HES-perfused controls (15.5 +/- 0.8) and UPPBHb1 (15.1 +/- 1.2). Glomerular filtration rate (GFR) was significantly higher in UPPBHb1-perfused kidneys (902 +/- 107 vs 633 +/- 55 microliters/min g kw for HES). This difference became even more pronounced in the third hour of perfusion (474 +/- 125 vs. 103 +/- 33). In contrast, UPPBHb2 produced low initial GFR levels of 385 +/- 25, which had only a minor tendency to decline with time. Parallel to GFR, absolute reabsorption of sodium (TNa) andoxygen consumption (QO2) showed values of 110 +/- 16 and 5.46 +/- 0.33 mumol/min g kw in UPPBHb1-kidneys vs 83 +/- 6 and 5.09 +/- 0.27 in controls and vs 53 +/- 4 and 3.66 +/- 0.12 in UPPBHb2-kidneys. Fractional excretion of sodium (FENa), of potassium (FEK), and of water (FEH2O) in UPPBHb1 and UPPBHb2-perfused kidneys were not significantly different from HES-perfused controls at any time of perfusion. Urinary flow rate (UFR) was similar in UPPBHb1- and HES-kidneys. Nevertheless, control kidneys tended to render oliguric during the third hour of perfusion (UFR 19.9 +/- 4.1 microliters/min g kw), whereas UPPBHb1 preserved urinary flow in a better way (83.7 +/- 32.4). UFR of UPPBHb2-kidneys was significantly reduced initially (30.2 +/- 5.1 vs. 105 +/- 33 for HES), but increased steadily up to 67 +/- 23. In the UPPBHb1 and HES group, all functional parameters determined declined dramatically within the third hour of perfusion, whereas UPPBHb2 produced functional stability. The in vivo reaction pattern of renal autoregulation was better preserved in UPPBHb-perfused kidneys than in HES-perfused controls: 74 +/- 6 vs. 59 +/- 5 vs. 42 +/- 4% (of full autoregulatory response) for UPPBHb1, UPPBHb2, and HES kidneys, respectively. Light- and electron microscopic analysis revealed major alterations only for the outer medulla of HES-kidneys.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Damaging effects of high energy shock waves on cultured Madin Darby canine kidney (MDCK) cells.

Shock wave lithotripsy (ESWL) has become an almost non-invasive standard treatment modality for urolithiasis. Several investigations, however, demonstrated that ESWL is not completely free of side effects. Among others alteration of renal tubular function has been reported. To study the effect of shock waves on tubular cells directly an in-vitro model with cultured Madin Darby Canine Kidney (MDCK) cells was established. Suspensions of MDCK cells (7 groups of 6 containers each) were exposed to 0, 16, 32, 64, 128, 256 shock waves (Dornier HM4, 18 kV). Before and 0, 1, 3, 6, 9, 12, 24 h after ESWL the following parameters were measured in the nutrient medium: lactate dehydroxygenase (LDH), glutamate oxalacetate transaminase (GOT), electrolytes. LDH and GOT increased depending on the number of shock waves indicating a membrane damage of MDCK cells. The MDCK model seems suitable for further studies on the effect of shock waves on renal tubular cells.

Animals↗
PubMed1989

[The remarkable accomplishments of the kidney--from molecular mechanisms to organ function].

The kidneys control chemical composition and volume of the extracellular fluid. Total extracellular volume passes about 10 times per day through the kidneys. Only 1% is excreted including metabolic waste products and excess intake by nutrition. While the proximal tubules are adapted to mass transport, the distal tublar cells are specialized to selectively retain or reject water and electrolytes, controlled by exrenal hormonal factors. For these purposes an optimal adjustment of morphologic, encymatic, physico-chemical and molecular features has developed in the course of evolution. With modern experimental techniques it is possible to demonstrate the mode of operation of single protein molecules in the cell membranes as sites of active or passive transport processes. This enables us to describe the basic mechanism of kidney function and to better understand the sequence of events leading to pathological disturbances of this organ.

Aldosterone↗
PubMed1985

[Renal handling of alcohol and its tubular effects].

The renal handling of ethanol comprises glomerular filtration and tubular reabsorption. Due to its high permeability alcohol concentration in the tubular fluid approaches that of peritubular fluid and under steady state conditions alcohol concentration in the final urine is almost the same as in serum water. Even in high concentrations alcohol does not significantly interfere with kidney cell function. This seems to be due to the fact that renal tissue is almost free from alcohol dehydrogenase. Thus, acetaldehyde, the cytotoxic intermediate of alcohol metabolism, is not accumulated in effective doses. If applied directly in micropuncture experiments alcohol is without distinct effects while acetaldehyde inhibits the main parameters of cellular vitality as measured by electrical membrane potentials and intracellular ion activities.

Acetaldehyde↗
PubMed1984

The effect of ouabain on intracellular activities of K+, Na+, Cl-, H+ and Ca2+ in proximal tubules of frog kidneys.

Using conventional and ion selective microelectrodes, the effect of ouabain (10(-4) mol/l) on peritubular cell membrane potential (PDpt), on intracellular pH (pHi) as well as on the intracellular ion activities of Cl- (Cli-), K+ (Ki+), Na+ (Nai+) and Ca2+ (Ca2i+) was studied in proximal tubules of the isolated perfused frog kidney. In the absence of ouabain (PDpt = -57.0 +/- 1.9 mV), the electrochemical potential difference of chloride (apparent mu Cl- = -22 +/- 2 mV) and of potassium (mu K+ = +24 +/- 3 mV) is directed from cell to bath, of H+ (mu H+ = -42 +/- 5 mV), of Na+ (mu Na+ = -102 +/- 4 mV) and of Ca2+ (mu Ca2+ = -148 +/- 6 mV) from bath to cell. Ouabain leads to a gradual decline of PDpt, which is reduced to half (PDpt, 1/2) within 31 +/- 4.6 min (in presence of luminal glucose and phenylalanine), and to a decline of the absolute values of apparent mu Cl+, of mu H+, mu Na+ and mu Ca2+. In contrast, an increase of mu K+ is observed. At PDpt, 1/2 apparent Cl-i increases by 6.2 +/- 1.0 mmol/l, pHi by 0.13 +/- 0.03, Ca2+i by 185 +/- 21 nmol/l, and Nai+ by 34.2 +/- 4.6 mmol/l, whereas Ki+ decreases by 37.7 +/- 2.2 mmol/l. The results suggest that the application of ouabain is followed by a decrease of peritubular cell membrane permeability to K+, by an accumulation of Ca2+, Na+ and HCO3- in the cell and by a dissipation of the electrochemical Cl- gradient.

Animals↗
PubMed1984

The influence of intracellular sodium activity on the transport of glucose in proximal tubule of frog kidney.

Inhibition of basolateral Na+/K+ ATPase by ouabain eventually abolishes transport of glucose. The present study was performed to test, if this effect is due to a dissipation of the electrochemical gradient for sodium or due to a regulatory inhibition of sodium-coupled glucose entry across the luminal membrane at increasing intracellular sodium activity. To this end, proximal convoluted tubules of the doubly perfused isolated frog kidney were perfused alternatively with solutions containing either 5 mmol/l glucose or raffinose. The potential difference across the peritubular cell membrane (PDpt) and across the epithelium (PDte) has been recorded with conventional and across the peritubular cell membrane with ion selective microelectrodes (PDpt). In the absence of luminal glucose PDpt is (+/- SEM) -54.0 +/- 2.4 mV, PDte = -1.2 +/- 2.0 mV and PDNapt = -96 +/- 5 mV. The electrochemical gradient for sodium (mu Na+) amounts to 95 mV and intracellular sodium activity to 14 mmol/l (extracellular sodium activity is 74 mmol/l). Luminal application of glucose leads to a rapid depolarisation of PDpt (delta PDpt = 8.6 +/- 0.9 mV and PDNapt (delta PDNapt = 11.1 +/- 3.0 mV) and to hyperpolarisation of PDte (delta PDte = -0.8 +/- 0.2 mV). The peritubular application of ouabain leads to a gradual, reversible and proportional decline of PDpt, PDNapt and mu Na+. Glucose induced delta PDpt and delta PDNapt decrease in parallel to PDpt and PDNapt, resp. In a separate series, the lumped conductance (Gm) of the luminal and basolateral cell membrane has been determined, which amounts to 2.4 +/- 0.3 microS/mm (tubule length). Gm decreases 23 +/- 4%, when PDpt is decreased to half.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Evidence for an amiloride sensitive Na+ pathway in the amphibian diluting segment induced by K+ adaptation.

The effect of amiloride on cell membrane potentials and intracellular Na activity (Nai) was tested in early distal tubules of the isolated perfused kidney of control and of K-adapted (high-K diet) Amphiuma. Conventional and Na-sensitive liquid ion-exchanger microelectrodes were employed to measure the peritubular cell membrane potential (PDpt), the transepithelial potential difference (PDte) and the Na electrochemical gradient across the peritubular cell membrane (ENapt), in the absence and the presence of amiloride (1 X 10(-4) mol X 1(-1] in both groups of animals. Amiloride did not affect PDpt and ENapt in control animals but depolarized PDpt and ENapt by about 8 mV in K-adapted animals. Nai (11.0 +/- 0.6 mmol X 1(-1) in early distal cells of control animals) did not change significantly by this maneuver. However, Nai decreased to extremely low values (2.3 +/- 0.2 mmol X 1(-1] when the luminal cotransport system for Na, Cl and K was inhibited by the luminal application of furosemide (5 X 10(-5) mol/l) and when the luminal cell membrane was exposed simultaneously to amiloride. The amiloride-induced effects on PDpt, ENapt and Nai occurred within seconds and were fully reversible. We conclude that high-K diet (K adaptation) induces an amiloride-sensitive pathway in the luminal cell membrane of early distal cells of Amphiuma which exists in parallel with the furosemide-sensitive cotransport system located in this cell barrier. The results suggest a luminal amiloride-sensitive Na/H exchange mechanism which regulates the luminal K permeability.

Adaptation, Physiological↗
PubMed1981

Inefficacy of bicarbonate infusions on the course of postischaemic acute renal failure in the rat.

Since bicarbonate has been reported to elicit fast recovery from acute renal failure in man, clearance studies were performed to compare the effects of sodium bicarbonate and saline infusion on renal function in postischaemic renal failure in the rat. In a first set of experiments the left kidney and in a second both kidneys were clamped for a period of 45 min and renal function monitored up to 210 min after release of the clamp. Glomerular filtration rate (ml/min) decreased following clamping from (mean values +/- SEM) 1.33 +/- 0.09 to 0.12 +/- 0.02 (saline) or 1.43 +/- 0.1 to 0.08 +/- 0.01 (bicarbonate) in the unilaterally clamped kidney and from 2.94 +/- 0.20 to 0.41 +/- 0.10 (saline) or 2.81 +/- 0.17 to 0.22 +/- 0.03 (bicarbonate) when both kidneys were clamped. Fractional excretion of water and sodium increased to a similar extent in saline and bicarbonate treated animals. Plasma potassium decreased (from 3.37 +/- 0.10 to 2.95 +/- 0.07 [unilaterally clamped kidneys] or from 5.2 +/- 0.4 to 4.4 +/- 0.2 [bilaterally clamped kidneys]) in bicarbonate treated but remained constant in saline treated animals, an effect not related to altered renal potassium excretion. In conclusion, no evidence was found that bicarbonate improves renal function in postischaemic renal failure.

Acute Kidney Injury↗
PubMed1980

[Additive phosphaturic action of parathyrin and calcitonin (author's transl)].

Parathyrin and calcitonin exert their effects on phosphate metabolism by influencing the functions of at least three organ systems, i. e. bone, gut and kidneys. To study the renal effects of these hormones under exclusion of systemic effects microinfusion studies were performed in anesthetised rats. After thyroparathyroidectomy radioactively labelled phosphate containing solutions were microinfused into single proximal convoluted tubules. The tracer recovery in the urine allowed calculation of phosphate reabsorption in the nephron segments beyond the micropuncture site. After a control period of 6 minutes the hormones were superfused to the nephron surface and tracer recovery measured during the following 36 minutes. Within few minutes both, parathyrin and calcitonin, clearly reduced phosphate reabsorption. Infusions of supramaximal doses of either hormone abolished the local action of this hormone but did not influence the effect of the other. Thus the phosphaturic actions of parathyrin and calcitonin are additive, indicating that the hormones involve different mechanisms and/or nephron sites.

Animals↗
PubMed1980

Renal handling of urate in healthy man in hyperuricaemia and renal insufficiency: circadian fluctuation, effect of water diuresis and of uricosuric agents.

To differentiate between extrarenal and renal causes of hyperuricaemia and gout, clearances of urate and creatinine were monitored for 3 1/2 days in fifty-two individuals (seven with a history of gout) with no gross impairment of renal function (creatinine clearance 52-137 ml/min). Dietary purine intake was kept constant. Monophasic circadian fluctuations of fractional urate excretion (= urate clearance over creatinine clearance) were observed with peak values in the afternoon, about 50% higher than during the night. Circadian fluctuations of urinary flow rate were almost identical. However, enhancement of urinary flow rate due to water diuresis had no effect on urate clearance. Despite wide variation of plasma urate concentrations among different individuals (+/- 30% SD), daily urate excretion varied little (+/- 4% SD) and did not correlate with plasma urate (r = 0.03). Thus extrarenal factors appear not to account for the occurrence of hyperuricaemia in these patients. In contrast, a clearcut negative correlation was apparent between plasma urate concentration and fractional urate clearance (r = 0.72), which could fully account for the variations of plasma urate concentration. To elucidate further the mechanism responsible for antiuricosuria in hyperuricaemic patients, the effects of the uricosuric agents benzbromarone and probenecid were tested. A clearcut correlation was apparent between control fractional urate excretion and uricosuric effect of both benzbromarone and probenecid (r = 0.83 and 0.88, respectively), suggesting that anti-uricosuria was due to defective secretion. In an additional series, the uricosuric effect of probenecid was tested in ten patients with renal insufficiency. In these patients the uricosuric effect was clearly blunted, indicating that urate reabsorption is reduced in renal insufficiency.

Adult↗
PubMed1979

Renal handling of urate and oxalate: possible implications for urolithiasis.

Both urate and oxalate are organic acids of considerable clinical interest, owing to their limited solubility. Calcium oxalate is the most frequent constituent of renal calculi and occasionally precipitates in body fluids. Urate precipitations are common in the kidney and in various other tissues. In this paper, a short outline of the present knowledge of renal handling of these substances will be followed by some conclusions as to the possible relevance of this knowledge for the understanding of urolithiasis and intrarenal precipitation. Direct (micropuncture) data are available for urate in the rat (1, 6, 7, 10, 21, 23, 28, 36, 42), rabbit (35), dog (34) and cebus monkey (33) and in the rat only for oxalate (11, 15, 20).

Alkalies↗
PubMed1979

Maleic acid induced aminoaciduria, studied by free flow micropuncture and continuous microperfusion.

The injection of 200 mg/kg BW maleic acid was found to be a suitable dose for exploring the experimental Fanconi syndrome by micropuncture techniques in rats. In clearance experiments, the fractional excretion of glycine, L-alanine, L-aspartate and taurine was measured. After intraperitoneal administration of maleic acid the excretion of these amino acids was increased in the range between the 20-fold and the 230-fold. Free flow micropuncture experiments showed that the reabsorption of these amino acids is reduced drastically along the whole proximal tubule. Continuous microperfusion experiments lead to the result that, in maleic acid pretreated rats, the reabsorption of 14C-glycine from the proximal convolution was strongly inhibited. It was found, furthermore, that after blocking the saturable glycine transport by L-phenylalanine, the remaining reabsorption of glycine (corresponding to passive diffusion) was exactly the same with and without maleic acid. Microinfusion experiments with 8 mumol.1(-1) L-3H-alanine into the early distal tubule showed a fractional recovery of 103 +/- 4.2% (S.D.) in the control and of 101 +/- 6.5% in presence of maleic acid. It is concluded that maleic acid inhibits the saturable reabsorption mechanism of amino acids along the proximal tubule. Passive permeability of the tubular membrane does not seem to be altered by maleic acid.

Animals↗
PubMed1979

Kinetics of L-proline reabsorption in rat kidney studied by continuous microperfusion.

Renal tubular reabsorption of 3H and 14C labelled L-proline was measured in vivo et situ by continuous microperfusion of single proximal tubules of the rat. The reabsorption is shown to be saturable. Passive diffusion plays a relatively small role in the reabsorption. A maximum possible permeability coefficient of 25 micrometers 2.s-1 for proline was calculated. Two transport systems were found, one with a small affinity and a high capacity, the other with a very high affinity and a small capacity. The following values were estimated. Jmax 1 = 2.6 +/- 0.28 (SEM) nmol.m-1.S-1 Km1 = 11.8 +/- 1.7 (SEM) mmol.1-1 Jmax 2 = 9.6 +/- 1.92 (SEM) pmol.m-1.s-1 Km2 = 29.3 +/- 7.8 (SEM) mumol.1-1. Whereas the first system reabsorbs the bulk of the filtered load, the activity of the second system explains the extremely small amount of proline found in the final urine. Diisopropylphosphorofluoridate--a specific inhibitor of dipeptidyl peptidase IV--decreases the reabsorption of L-proline and L-alanine but has no influence on the reabsorption of the basic amino acid L-arginine and the acidic amino acid L-glutamic acid. This result correlates with a recent speculation that dipeptidyl peptidase IV is involved in proline and alanine reabosrption.

Animals↗