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

1998 ◽  
Vol 76 (2-3) ◽  
pp. 553-559 ◽  
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.

Soy protein modification of rat polycystic kidney disease

1998 ◽  
Vol 274 (3) ◽  
pp. F541-F549 ◽  
Author(s):  
Malcolm R. Ogborn ◽  
Neda Bankovic-Calic ◽  
Christen Shoesmith ◽  
Richard Buist ◽  
James Peeling
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Rat Model ◽  
Soy Protein ◽  
Proton Nuclear Magnetic Resonance ◽  
Renal Tubular Cell ◽  
Ammonium Excretion ◽  
Polycystic Kidney ◽  
Nmr Studies ◽  
H Nmr

We undertook a study to determine whether soy protein feeding would ameliorate renal injury in the Han:SPRD- cy rat model of polycystic kidney disease (PKD). Male offspring of Han:SPRD- cy heterozygotes received isocaloric diets based on 20% casein or 20% heat-treated soy protein at weaning ad libitum for 8 wk. Soy-fed animals demonstrated lower serum creatinine (66 vs. 125 μmol/l; P = 0.002), lower urinary ammonium excretion (0.080 vs. 0.173 mmol/kg; P= 0.01), reduced renal cysts (0.98 vs. 4.92 ml/kg body wt, P < 0.0001), renal fibrosis (0.79 vs. 1.4 ml/kg; P = 0.016), macrophage infiltration, renal tubular cell proliferation, and apoptosis. Proton nuclear magnetic resonance (1H-NMR) studies of urine demonstrated that soy diet was associated with increased losses of citric acid cycle organic anions.1H-NMR of perchloric acid-extracted tissue found that levels of succinate were not depleted in soy-fed animals, despite increased urinary losses. Soy-fed animals had marked elevation of tissue betaine ( P < 0.001), with reduced taurine and cholines, compared with casein-fed animals ( P < 0.001). Soy feeding dramatically reduces both tubular and interstitial pathology in the Han:SPRD- cy rat model of PKD, through mechanisms that remain to be determined.

scholarly journals Organic anion secretion in polycystic kidney disease.

1997 ◽  
Vol 8 (8) ◽  
pp. 1222-1231
Author(s):  
G A Tanner ◽  
N Gretz ◽  
Y Shao ◽  
A P Evan ◽  
M Steinhausen
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Organic Anion ◽  
Left Kidney ◽  
Organic Anions ◽  
Maximal Rate ◽  
Polycystic Kidney ◽  
Fluid Accumulation ◽  
Anion Secretion ◽  
Organic Anion Secretion

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.

Effects of Potassium Citrate/Citric Acid Intake in a Mouse Model of Polycystic Kidney Disease

Nephron ◽  
2000 ◽  
Vol 84 (3) ◽  
pp. 270-273 ◽  
Author(s):  
George A. Tanner ◽  
Kodi Vijayalakshmi ◽  
Judith A. Tanner
Keyword(s):  
Citric Acid ◽  
Kidney Disease ◽  
Mouse Model ◽  
Polycystic Kidney Disease ◽  
Potassium Citrate ◽  
Polycystic Kidney ◽  
Acid Intake

scholarly journals Serum bicarbonate is associated with kidney outcomes in autosomal dominant polycystic kidney disease

2020 ◽  
Author(s):  
Charles J Blijdorp ◽  
David Severs ◽  
Usha M Musterd-Bhaggoe ◽  
Ronald T Gansevoort ◽  
Robert Zietse ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Kidney Function ◽  
Autosomal Dominant ◽  
Hazard Ratio ◽  
Ammonium Excretion ◽  
Serum Bicarbonate ◽  
Polycystic Kidney ◽  
Baseline Serum ◽  
Autosomal Dominant Polycystic Kidney

Abstract Graphical Abstract Background Metabolic acidosis accelerates progression of chronic kidney disease, but whether this is also true for autosomal dominant polycystic kidney disease (ADPKD) is unknown. Methods Patients with ADPKD from the DIPAK (Developing Interventions to halt Progression of ADPKD) trial were included [n = 296, estimated glomerular filtration rate (eGFR) 50 ± 11 mL/min/1.73 m2, 2.5 years follow-up]. Outcomes were worsening kidney function (30% decrease in eGFR or kidney failure), annual eGFR change and height-adjusted total kidney and liver volumes (htTKV and htTLV). Cox and linear regressions were adjusted for prognostic markers for ADPKD [Mayo image class and predicting renal outcomes in ADPKD (PROPKD) scores] and acid–base parameters (urinary ammonium excretion). Results Patients in the lowest tertile of baseline serum bicarbonate (23.1 ± 1.6 mmol/L) had a significantly greater risk of worsening kidney function [hazard ratio = 2.95, 95% confidence interval (CI) 1.21–7.19] compared with patients in the highest tertile (serum bicarbonate 29.0 ± 1.3 mmol/L). Each mmol/L decrease in serum bicarbonate increased the risk of worsening kidney function by 21% in the fully adjusted model (hazard ratio = 1.21, 95% CI 1.06–1.37). Each mmol/L decrease of serum bicarbonate was also associated with further eGFR decline (−0.12 mL/min/1.73 m2/year, 95% CI −0.20 to −0.03). Serum bicarbonate was not associated with changes in htTKV or htTLV growth. Conclusions In patients with ADPKD, a lower serum bicarbonate within the normal range predicts worse kidney outcomes independent of established prognostic factors for ADPKD and independent of urine ammonium excretion. Serum bicarbonate may add to prognostic models and should be explored as a treatment target in ADPKD.

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

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.

Dietary betaine modifies hepatic metabolism but not renal injury in rat polycystic kidney disease

2000 ◽  
Vol 279 (6) ◽  
pp. G1162-G1168 ◽  
Author(s):  
Malcolm R. Ogborn ◽  
Evan Nitschmann ◽  
Neda Bankovic-Calic ◽  
Richard Buist ◽  
James Peeling
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Nmr Spectroscopy ◽  
Kidney Disease ◽  
Renal Disease ◽  
Polycystic Kidney Disease ◽  
Hepatic Metabolism ◽  
Polycystic Kidney ◽  
H Nmr ◽  
Betaine Supplementation

We undertook a morphometric and proton nuclear magnetic resonance (1H-NMR) study to test the hypothesis that 1% dietary betaine supplementation would ameliorate renal disease in the heterozygous Han:SPRD- cyrat, a model of polycystic kidney disease (PKD) and progressive chronic renal failure. After 8 wk of pair feeding, betaine had no effect on renal cystic change, renal interstitial fibrosis, serum creatinine, serum cholesterol, or serum triglycerides. 1H-NMR spectroscopy of renal tissue revealed no change in renal osmolytes, including betaine, or renal content of other organic anions in response to diet. 1H-NMR spectroscopy of hepatic tissue performed to explore the metabolic fate of ingested betaine revealed that heterozygous animals fed the control diet had elevated hepatic levels of gluconeogenic amino acids, increased β-hydroxybutyrate, and increased levels of some citric acid cycle metabolites compared with animals without renal disease. Betaine supplementation eliminated these changes. Chronic renal failure in the Han:SPRD- cy rat is associated with disturbances of hepatic metabolism that can be corrected with betaine therapy, suggesting the presence of a reversible methylation defect in this form of chronic renal failure.

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