Organic anion secretion in polycystic kidney disease.

This study examined whether organic anion secretion contributes to fluid accumulation in cysts in polycystic kidney disease. Clearance and micropuncture studies were done on young (7 to 16 wk old), mostly male, heterozygous Han:SPRD cystic rats and healthy control littermate rats. Heterozygous Han:SPRD rats manifest a slowly progressive autosomal dominant polycystic kidney disease that closely resembles the human disorder. Left kidney GFR (polyfructosan clearance), in microl/min per 100 g body wt, averaged 331 +/- 36 (SD) in seven healthy rats and 278 +/- 75 in seven cystic rats. The maximal rate of p-aminohippurate (PAH) secretion, in micromol/min per 100 g body wt, averaged 0.94 +/- 0.24 in healthy rats and 0.83 +/- 0.11 in cystic rats. In these young rats, there were no significant differences in GFR or the maximal rate of PAH secretion despite the presence of cystic disease. Using fluorescence microscopy, it was found that 27 of 29 proximal cysts secreted sulfonefluorescein, an organic anion transported by the PAH system. Transmission electron micrographs of superficial cysts that had secreted sulfonefluorescein demonstrated the presence of both normal-appearing and poorly differentiated proximal tubule cells. Segments of superficial proximal convoluted tubules or cysts, isolated by upstream and downstream wax blocks, failed to accumulate fluid when PAH was infused intravenously. With the stationary microperfusion technique, PAH secretion by both normal and cystic nephrons was demonstrated. It is concluded that most proximal cystic epithelia retain the ability to secrete organic anions. Secretion of organic anions, however, does not appear to contribute in any substantial way to fluid accumulation in cysts in the rat kidney.

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Factors determining the maximal rate of organic anion secretion by the liver and further evidence on the hepatic site of action of the hormone secretin

The Journal of Physiology ◽

10.1113/jphysiol.1966.sp008044 ◽

1966 ◽

Vol 186 (2) ◽

pp. 424-438 ◽

Cited By ~ 98

Author(s):

E. R. L. O'Máille ◽

T. G. Richards ◽

A. H. Short

Keyword(s):

Organic Anion ◽

Maximal Rate ◽

Anion Secretion ◽

Site Of Action ◽

Organic Anion Secretion

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Potassium citrate/citric acid intake improves renal function in rats with polycystic kidney disease.

Journal of the American Society of Nephrology ◽

10.1681/asn.v971242 ◽

1998 ◽

Vol 9 (7) ◽

pp. 1242-1248

Author(s):

G A Tanner

Keyword(s):

Citric Acid ◽

Kidney Disease ◽

Polycystic Kidney Disease ◽

Tap Water ◽

Left Kidney ◽

Potassium Citrate ◽

Dramatic Improvement ◽

Long Term Effects ◽

Polycystic Kidney ◽

Modest Improvement

Polycystic kidney disease (PKD) has been shown to be exacerbated by acidosis or a low potassium intake, and there is evidence that administration of alkali might have a beneficial effect. This study determined whether ingestion of potassium citrate and citric acid would ameliorate PKD. Healthy normal and heterozygous littermate Han:SPRD rats with autosomal dominant PKD were provided with either tap water or 55 mM K3citrate/67 mM citric acid solution (KCitr) to drink starting at the age of 1 mo. Renal clearance measurements and histologic assessments were performed when the rats were 3 mo old. KCitr intake did not affect body weight or urine flow, but completely prevented the decline in GFR found in untreated rats with PKD. In rats that drank tap water, left kidney GFR averaged (in microliter/min per 100 g body wt) 503 +/- 78 (n = 9) in normal animals and 242 +/- 56 (n = 6) in rats with PKD. In rats that drank KCitr, GFR averaged 562 +/- 123 (n = 7) in normal animals and 534 +/- 103 (n = 7) in rats with PKD. Kidneys of rats with PKD were approximately double normal size. KCitr treatment did not affect kidney size, but led to fewer interstitial abnormalities and smaller cysts in cystic kidneys. KCitr ingestion led to a significantly lower (P < 0.001) plasma [K+] in rats with PKD (3.3 +/- 0.2 versus 4.1 +/- 0.2 mEq/L in rats on tap water). Chronic KCitr intake in the young heterozygous Han:SPRD rat with PKD yields a modest improvement of kidney histology and a dramatic improvement in GFR. The mechanism of action of KCitr and the long-term effects of this treatment on renal structure and function in PKD deserve further study.

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Nocodazole inhibition of organic anion secretion in teleost renal proximal tubules

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1994.267.3.r695 ◽

1994 ◽

Vol 267 (3) ◽

pp. R695-R704 ◽

Cited By ~ 7

Author(s):

D. S. Miller ◽

J. B. Pritchard

Keyword(s):

Organic Anion ◽

Basolateral Membrane ◽

Organic Anions ◽

Tubular Secretion ◽

Anion Secretion ◽

Proximal Tubular ◽

Renal Tubular ◽

The Impact ◽

Organic Anion Secretion

The impact of the microtubule-disrupting drug nocodazole on renal tubular secretion of organic anions was examined in vitro using proximal tubular masses from teleost fish. Nocodazole reversibly inhibited 20-30% of the tubular accumulation of two model organic anions, p-aminohippurate and fluorescein (FL), by winter flounder tubular masses. However, the drug had no effect on the initial rate of organic anion uptake. Thus it did not reduce transport into the cells at the basolateral membrane, either directly by affecting basolateral organic anion transport proteins or indirectly by altering metabolism or ion gradients. Instead, epifluorescence video microscopy and digital image analysis of killifish tubules showed that nocodazole greatly reduced luminal accumulation of FL and had a smaller effect on cellular dye accumulation. Luminal FL accumulation returned to control levels when tubules were incubated in drug-free medium. Confocal fluorescence microscopy confirmed the marked reduction in luminal FL concentration and demonstrated that intracellular punctate FL accumulation was also markedly reduced. Finally, immunohistochemistry with an anti-tubulin antibody showed that the concentrations of nocodazole used in the above experiments reversibly disrupted microtubules within renal epithelial cells. These data indicate that a component of organic anion secretion in teleost proximal tubule is dependent on an intact microtubular network.

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The effect of dietary flaxseed supplementation on organic anion and osmolyte content and excretion in rat polycystic kidney disease

Biochemistry and Cell Biology ◽

10.1139/o98-040 ◽

1998 ◽

Vol 76 (2-3) ◽

pp. 553-559 ◽

Cited By ~ 9

Author(s):

Malcolm R Ogborn ◽

Evan Nitschmann ◽

Neda Bankovic-Calic ◽

Richard Buist ◽

James Peeling

Keyword(s):

Citric Acid ◽

Kidney Disease ◽

Polycystic Kidney Disease ◽

Citric Acid Cycle ◽

Organic Anion ◽

Ammonium Excretion ◽

Polycystic Kidney ◽

Acid Cycle ◽

H Nmr ◽

Metabolic Role

Progression of chronic renal failure in the Han:SPRD-cy rat polycystic kidney disease is associated with renal depletion of citric acid cycle metabolites and betaine. Amelioration of this disease by a soy protein diet is associated with retention of citric acid cycle anions, despite increased excretion, and preservation of tissue levels of betaine. As we have recently found that modest dietary supplementation with flaxseed preserves renal function and reduces histologic injury in the Han:SPRD-cy rat, we undertook a high-resolution 1H NMR spectroscopic study of urine and renal tissue extracts from Han:SPRD-cy rats to explore the renal biochemical consequences of a flaxseed diet. There was no significant dietary effect upon organic anion, methylamine, or osmolyte excretion in healthy animals. There was increased citrate excretion in Han:SPRD-cy rats fed flaxseed. Urinary ammonium excretion did not differ, suggesting that the observed increase in citrate excretion was not due to an alkaline effect of diet. Tissue extract studies revealed that disease amelioration was associated with tissue retention of succinate and betaine. Amelioration of Han:SPRD-cy rat polycystic kidney disease by diet is associated with alteration in the handling of citric acid cycle metabolites. Betaine may have a metabolic role in the reduction of chronic renal injury.Key words: 1H NMR spectroscopy, polycystic kidney disease, rat, flaxseed.

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