PubMed Health⌕ Search

PubMed · 1211456

Effect of renal decapsulation on renal function.

Abstract

Marked increases in renal volume commonly occur in acute tubular necrosis and acute transplant rejection. Based on studies in the dog, we have previously suggested that the renal swelling observed in states of acute renal injury may be due principally to an increase in compliance of the kidney. The present study was undertaken in an effort to assess whether compliance-mediated increases in renal volume might affect renal function. In 15 dogs we compared the function of a decapsulated kidney (DK) to that of the contralateral intact kidney (IK); in 12 dogs we compared the function of a partially decapsulated kidney (PDK) to that of the contralateral IK. We compared the function of DK or PDK to IK, first under control conditions (ureteral pressure (UP) equals 0 mmHg), then at increased intrarenal pressure (UP equals 30 mmHg for both kidneys plus iv saline loading), and then during a recovery period (UP of both kidneys restored to 0 mmHg). The rationale is that probably DK is more compliant than IK; thus at increased intrarenal pressure DK volume should increase more than IK volume. Under control conditions DK and IK function were normal and equal; however, during increased intrarenal pressure, glomerular filtration rate (GFR) was about 20% less and Na and H20 excretion were about 30% less in DK than in IK. When intrarenal pressure was restored toward control by lowering UP to 0 mmHg, DK and IK function were once again equal. Similar but less marked changes occurred in the experiments comparing PDK and IK function. The impairment of renal function in DK vs. IK at increased intrarenal pressure was not explained by renal blood flow distribution, backdiffusion of glomerular filtrate, or by surface losses of fluid from DK. We suggest that impairment of renal function in DK vs. IK during increased intrarenal pressure is in some way related to the greater expansion of DK (21.0 +/- 0.02%) vs. IK (9.7 +/- 0.03%) at increased intrarenal pressure.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

L A Hebert, K A Stuart, J A Stemper. 1975. Effect of renal decapsulation on renal function.. https://doi.org/10.1152/ajplegacy.1975.229.3.632

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Simple HPLC-UV method for determination of iohexol, iothalamate, p-aminohippuric acid and n-acetyl-p-aminohippuric acid in human plasma and urine with ERPF, GFR and ERPF/GFR ratio determination using colorimetric analysis.

A simple high-performance liquid chromatographic (HPLC) method was developed for the simultaneous determination of iohexol, iothalamate, p-aminohippuric acid (PAH) and n-acetyl-p-aminohippuric acid (n-acetyl-PAH) in human plasma and urine. A C(18) column at a flow rate of 1 ml/min with an aqueous mobile phase of trifluoroacetic acid (0.1% TFA in deionized water (pH 2.2), v/v) and methanol gradient was used for component separation. The plasma and urine assay demonstrated linearity from 10 to 50 microg/ml for iohexol and iothalamate, 5 to 40 microg/ml for PAH and 2.5 to 40 microg/ml for n-acetyl-PAH. The HPLC plasma and urine results obtained for PAH were used to calculate the subject kidney effective renal plasma flow (ERPF) and the iohexol results were used to calculate the subject kidney glomerular filtration rate (GFR). The HPLC results for PAH were then compared to an alternative colorimetric method for analyzing PAH to determine if subject metabolism (acetylation) of PAH affected the ERPF results obtained using the colorimetric method, the subsequent ERPF/GFR ratio and clinical impression of subject patient kidney function. The method was utilized in several different clinical studies evaluating the effect of kidney function from medications (phase IV evaluations) marketed for patients with cardiovascular disease.

Aminohippuric Acids↗

Specific determination of PAH and its N-acetyl metabolite by HPLC increases the accuracy and precision of PAH clearance measurements.

PAH (N-(4-aminobenzoyl)-glycin) clearance measurements have been used for 50 years in clinical research for the determination of renal plasma flow. The quantitation of PAH in plasma or urine is generally performed by colorimetric method after diazotation reaction. Although straightforward, the measurements must be corrected for the nonspecific residual response observed in blank plasma. We have therefore developed an HPLC method for the specific determination of PAH and its metabolite NAc-PAH using a gradient elution ion-pair reverse-phase chromatography with UV detection. The Nacetyltransferase (NAT-1 or NAT-2 dependent) activity does not seem clinically relevant nor does it affect notably PAH clearances, although NAc-PAH represents 10.2 +/- 2.7% of the PAH excreted unchanged in 12 healthy subjects. The performance of the HPLC technique has been compared with the colorimetric method using urine and plasma samples collected from 12 healthy volunteers following a priming dose of PAH followed by a constant rate infusion. Good correlations (r = 0.94 and 0.97, for plasma and urine respectively) are found between the results obtained with both techniques. However, the colorimetric method gives higher concentrations of PAH in urine while the concentrations in plasma are lower than those determined by HPLC. Hence, both renal (CLR = U x V/P) and systemic (CLS = Rinf/Css) clearances are systematically higher (35.1%, resp. 17.8%) with the colorimetric method. The fraction of PAH excreted by the kidney CLR/CLS calculated from HPLC data (n = 143) is, as expected, always < 1 (mean = 0.73 +/- 0.11), whereas the colorimetric method gives a mean extraction ratio of 0.87 +/- 0.13 implying unphysio-logical values (> 1) in some cases. In conclusion HPLC not only enables the simultaneous quantitation of PAH and NAc-PAH, but may also provide more accurate and precise PAH clearance measurements.

Aminohippuric Acids↗

The cytotoxic effect of paraquat to isolated renal proximal tubular segments from rabbits.

Paraquat (PQ) induces lung, liver and kidney damage. Since PQ mainly is eliminated by the kidney, the kidney damage is of particular importance to the outcome of PQ poisoning. The exact toxic mechanism of PQ is still unclear but it is assumed to involve redox cycling and formation of reactive oxygen species. In this study, further investigations on the toxic mechanism and metabolic effects of PQ were performed using isolated renal proximal tubules from rabbits. Proximal tubules were isolated using a combined iron perfusion and collagenase method. Suspended tubules were incubated for varying periods and concentrations of PQ at 25 or 37 degrees C in Krebs-Ringer phosphate buffer or HCO3-/CO2 buffer. The cytotoxic effect of PQ was evaluated by (1) markers of oxidative stress: status of glutathione (GSH/GSSG) and formation of malondialdehyde (MDA); and (2) markers of tubular metabolism: oxygen consumption (QO2), transport of 14C-p-aminohippuric acid (PAH) and 14C-tetraethylammonium (TEA). Using 0.5 and 5 mM PQ, the GSH/GSSG ratio decreased whereas formation of MDA increased indicating oxidative stress. PQ reduced the accumulation of PAH and TEA, the basal QO2 and the ouabain sensitive QO2 indicating inhibition of the Na/K-ATPase. Nystatin-stimulated QO2 was reduced by PQ, excluding inhibition of Na+ entry as a possible cytotoxic mechanism and suggesting mitochondrial injury. This was confirmed by measuring FCCP-uncoupled QO2. Thus high concentrations of PQ appear to disrupt mitochondrial electron chain transfer resulting in reduction of metabolic functions.

Aminohippuric Acids↗