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Biomedical subjects

J R Klinenberg

Publications and source records attributed to J R Klinenberg.

At least 73 records · Page 4Linked to original sources
PubMed1977

Uptake of uric acid by separated renal tubules of the rabbit. I. Characteristics of transport.

A rapid filtration procedure was used to determine rates of uric acid uptake by a preparation of separated renal cortical tubules of the rabbit. The rate of uric acid uptake was temperature dependent and showed saturation kinetics with a K of 3.2 mM. The uptake was 50% lower when measured under nitrogen as compared with uptake under oxygen. The uptake rate increased with increasing sodium concentration and decreased with increasing potassium concentration. Uptake was stimulated by citrate, succinate and pyruvate, and inhibited by alpha-ketoglutarate. Parathyroid hormone and 10(-4) M adenosine 3':5'-monophosphate increased the uric acid uptake rate when preincubated with the tubules for 130 minutes before the addition of uric acid. Uric acid uptake in this preparation appears to occur by some form of carrier-mediated active transport.

Animals↗
PubMed1977

Uptake of uric acid by separated renal tubules of the rabbit. II. Effects of drugs.

The effect of various drugs on the rate of uptake of uric acid by separated renal tubules of the rabbit was investigated. Determinations were made of 150 values and slopes of the inhibition curves. The most potent inhibitor of uric acid uptake was sulfinpyrazone, with an 150 of 0.02 mM. Calcium ipodate and benzbromarone were also potent inhibitors. Uricosuric drugs, with the exception of benzbromarone, had shallow inhibition slopes. Diuretic drugs had steep inhibition slopes. More than one mechanism of action is probably involved in the inhibition of uric acid uptake in separated renal tubules by drugs.

Animals↗
PubMed1976

A brief note on the ultrastructure of renal glomeruli in acutely hyperuricemic rats.

Male Wistar rats fed 2 per cent oxonic acid plus 3 per cent uric acid for 3 weeks developed hyperuricemia and an extraordinary uricosuria. The kidneys had gross abnormalities similar to those seen in humans with gouty nephropathy. The cortical surfaces were granular and the kidneys had uric acid and urate deposits in the intratubular and intestitial spaces of the medullary region. Both histologic and ultrastructural studies of the glomeruli failed to disclose any unusual morphologic changes. Glomerular cells were normal and glomerular basement membranes maintained the granular structure of the lamina densa with a clear demarcation between the lamina rara externa and lamina rara interna. These morphologic findings suggest that in acutely hyperuricemic rats with a lesion comparable to hyperuricemic tubular blockade, there is no associated glomerular alteration.

Animals↗
PubMed1975

Hyperuricemic nephropathy: pathologic features and factors influencing urate deposition.

The three general types of renal pathology associated with hyperuricemia are reviewed. Factors influencing urate solubility are discussed, as well as the effect of uricosuric drugs on renal urate handling, with particular emphasis upon their efficacy in competing with urate for protein binding sites. In addition, a new experimental model of hyperuricemic nephropathy is described which could yield valuable data concerning the complex relationships between hyperuricemia, urate deposition and renal function.

Acute Kidney Injury↗
PubMed1975

Chronic experimental hyperuricemic nephropathy.

Sustained, moderately severe hyperuricemia and severe uricosuria were produced in male Wistar rats by feeding dietary supplements of oxonic acid (0.4 gm. per day) and uric acid (0.6 gm per day). After 1 month, the kidneys showed the previously described histologic features of urate-blockade nephropathy characterized by intratubular deposits, tubular injury, and an exudative response consisting of neutrophilic granulocytes with early tophus formation. After 36 and 52 weeks of hyperuricemia, and with no gross evidence of renal failure, the kidneys showed a predominantly interstitial mononuclear cell infiltrate around regenerated tubules, an increase in interstitial fibrous tissue, infrequent renal tophi, and renal stones. The glomeruli and blood vessels appeared completely normal. There was no evidence of arthritis and no other target organ damage was detected. The chronic renal changes present in this animal model of induced hyperuricemia resemble those seen in human gouty nephropathy. The evolution of the experimental urate nephropathy observed during 1 year suggests that a primary acute inflammatory tubular injury is followed by a diffuse chronic interstitial nephritis and that the glomeruli and blood vessels are not primarily involved in the renal disease. This animal model may provide the opportunity to study factors influencing the renal sequelae of sustained hyperuricemia.

Animals↗
PubMed1975

Acute hyperuricemic nephropathy in rats. An electron microscopic study.

Hyperuricemia and uricosuria were induced in rats fed uric acid and oxonic acid. Kidneys then were studied by light and electron microscopy. After 1 day of hyperuricemia, animals had deposits of uric acid and urate crystals within collecting tubules of the renal papillae, and tubular cells were altered. By 10 days, there was an exudative response with further injury to epithelium. Clear spaces within lumens, epithelium, and neutrophils suggested the presence of crystals; however, there was no direct ultrastructural evidence that neutrophils or epithelial cells ingested crystals and suffered injury. Presumably, crystals readily seen in frozen, unfixed tissue were lost during preparation for electron microscopy. Nonetheless, the ultrastructural findings indicated that hyperuricemic nephropathy was initiated in a fashion analogous to urate arthropathy. Urate crystals formed within collecting tubules, epithelial cells were altered, and most likely there was chemotaxis of neutrophils which underwent degranulation and vacuolation followed by lysis freeing any ingested urate. Release of ingested crystals plus precipitation of new crystals both might serve to sustain the nephritis.

Animals↗