A 30-year-old black male with end-stage renal disease of 8 years' duration had undergone 16 prior access operations and was still without an adequate access for dialysis. A spiral saphenous vein graft conduit was constructed from the left saphenous vein and used as a straight arterial conduit graft between the superficial femoral artery at Hunter's canal and the saphenofemoral vein junction in the groin. The spiral vein graft tube was used as the sole means of dialysis for the next consecutive 750 dialysis procedures over nearly 6 years without any complication.

We studied angiographically the access route 1-27 months after the insertion temporary dialysis catheters in 52 patients: 32 subclavian and 20 internal jugular. The two groups were statistically similar with respect to age, sex and race. The subclavian catheters were left in for a mean of 11.5 days (2-22) while the internal jugular ones were inserted for 15.8 days (5-25; p = 0.0015). One hundred percent of the internal jugular patients were free of any venogram abnormalities in their venous access return. In marked contrast, 50% of the subclavian sites had mild to severe stricutures with 90% having 70-100% occlusion of the subclavian vein. Six patients had bilateral severe strictures. The long-term stricture rate of subclavian catheters in the subclavian vein was unacceptably high compared to the internal jugular route.

The potential contribution of the splanchnic tissues to the carbohydrate intolerance of uremia was studied in fasted, partially nephrectomized rats. The livers of sham operated (C) and partially nephrectomized (Nx) rats were perfused with physiologic concentrations of potential gluconeogenic substrates using a nonrecirculating perfusion apparatus. Glucose release was slightly greater in the livers of Nx rats as compared to C rats. The portal vein concentrations of the potential gluconeogenic precursors were not different in the two groups. Moreover, there were no differences in the net hepatic extraction of alanine, glutamine or glutamate between the two groups of rats. There was also no difference in the production of glucose from U14C alanine. The livers of Nx rats, however, demonstrated less net extraction of lactate and released greater concentrations of betahydroxybutyrate. The increased release of glucose by livers of Nx rats may be at least partially due to their greater hepatic glycogen content.

Renal osteodystrophy is a universal complication of ' chronic renal disease characterized histologically by several alterations in bone structure. The pathological changes seen in the skeleton of uremic patients include osteitis fibrosa cystica, which reflects the resorptive effect of increased osteoclastic activity owing to secondary hyperparathyroidism, and osteomalacia, which is a defect in bone mineralization secondary, at least in part, to alterations in the metabolism of vitamin D and characterized by a widening of the osteoid seam and absence of or abnormal mineralization front. Less commonly, osteosclerosis and osteoporosis are also seen in patients with renal insufficiency. The pathogenetic mechanisms responsible for the development of renal osteodystrophy in patients with renal failure are multifactorial and poorly understood. However, in the past decade some of the factors involved in the development of renal osteodystrophy have been clarified. The manifestations of deranged mineral metabolism in uremia include hypocalcemia, hyperphosphatemia, hypermagnesemia, hyperplasia of the

The rate of change of the serum creatinine concentrations in 63 patients with chronic progressive renal disease of varied etiology was examined by linear regression analysis using the logarithm or the reciprocal of the serum creatinine concentration versus time. A single straight line was described by one or the other of these relationships in 53 patients. Six patients had an accelerated rate of nephron destruction terminally (two slopes) regardless of the mathematical analysis. The remaining four patients had course changes either due to apparent spontaneous remissions or temporally related to therapy. These data suggest that (functional) nephron loss in chronic progress disease is orderly and mathematically definable. The theoretical implications are that functional nephron loss is either exponential (log Cr) or constant (1/Cr).

Previous studies from this laboratory demonstrated that secondary hyperparathyroidism in dogs with chronic renal disease may occur, at least in part, as a consequence of the need for progressive adaptation in renal phosphorus (P) excretion that occurs as glomerular filtration rate falls. However, the studies were of relatively short duration. Moreover, no information emerged regarding a potential role of calcium malabsorption in the pathogenesis of secondary hyperparathyroidism. The short duration of the protocol did not lend itself to the study of the effect of P control or the administration of vitamin D in the pathogenesis of renal osteodystrophy. In the present studies, 14 dogs with experimental chronic renal disease were studied serially for a period of 2 yr. Each animal was studied first with two normal kidneys on an intake of P of 1,200 mg/day. Then, renal insufficiency was produced by 5/6 nephrectomy. The dogs then were divided into three groups. In group I, 1,200 mg/day P intake was administered for the full 2 yr. In group II, P intake was reduced from the initial 1,200 mg/day, in proportion to the measured fall in glomerular filtration rate, in an effort to obviate the renal adaptation in P excretion. In group III, "proportional reduction" of P intake also was employed; but in addition, 20 mug of 25(OH)D(3) were administered orally three times a week. In group I, parathyroid hormone (PTH) levels rose throughout the 2-yr period reaching a final concentration of 557+/-70 U (normal 10-60). In group II, values for PTH remained normal throughout the 1st yr, increased modestly between the 12th and the 18th mo, but then did not rise after the 18th mo. In group III, no elevation of PTH levels was observed at any time; however, these animals were hypercalcemic. Histomorphologic analyses of the ribs of these dogs were performed serially throughout the 2-yr period. A linear relationship was obtained between the osteoclastic resorption surface and the concentration of circulating immunoreactive PTH. The osteoid volume was greater in group I animals when compared to those in group II. None of the morphologic abnormalities associated with renal osteodystrophy were observed in the animals in the third group.

Serum phosphorus concentrations are maintained within narrow limits in humans. In the extracellular fluid most of the phosphorus is present in the inorganic form and at the level of the glomerulus greater than 90% of PO4 is ultrafilterable. The kidney plays a key role in PO4 homeostasis. Micropuncture experiments have demonstrated that 60 to 70% of the filtered PO4 is reabsorbed in the proximal tubule; however, there is evidence that a significant amount of PO4 is reabsorbed in the distal tubule. Phosphate secretion probably plays a minor role in the overall renal regulation of phosphate. In normal individuals the amount of PO4 ingested plays a key role in the amount that ultimately will be excreted in the urine. The reabsorption of PO4 along the nephron is regulated by a series of factors of which parathyroid hormone is the most important one. Hyperphosphatemia is seen frequently in clinical medicine and by far, the most common cause is a decrease in urinary PO4 excretion secondary to renal failure. From the practical point of view, the most effective way to treat hyperphosphatemia is to decrease PO4 absorption in the GI tract by the use of PO4 binders.

Elevated levels of fibrinogen/fibrin degradation products (FDP) occur in uremia, and have been thought to be in part related to intravascular coagulation in the kidney. More recent data indicated that delayed catabolism of fibrinogen fragment D occurred in anephric animals. To further evaluate FDP catabolism in the kidney, turnover studies of purified dog 131I-Fg-D and 125I-Fg-E were performed on dogs before and after acute subtotal nephrectomies, and later during chronic uremia. 131I-fibrinogen clearances were also perfomed. Slowed catabolism of Fg-D and Fg-E was observed in both the acute and chronic uremic stages. Altered urinary excretion was not a factor as only minimal amounts of Fg-D and Fg-E were excreted in the urine of the control animals. In the 131I-fibrinogen studies, there were significant changes in plasma volume, fibrinogen t 1/2, and intravascular/extravascular distribution, but not in fractional catabolic rate. To differentiate fully, the effects of uremia from those of loss of catabolic renal tissue, the Fg-D and Fg-E turnover studies were repeated on other animals with intact kidneys whose ureters were diverted into the peritoneum and compared to subsequent studies after total nephrectomy. The control and ureter-severed studies had the same clearance pattern, whereas decreased catabolism occurred in the nephrectomized dogs. The results demonstrate uremia per se does not have a major effect upon the catabolism of fibrinogen, Fg-D, and Fg-E. Loss of renal tissue does impair the clearance of Fg-D and Fg-E, indicating these proteins are normally catabolized in part by the kidneys. Thus elevated plasma FRA in uremic patients may reflect decreased Fg-D and Fg-E catabolism rather than increased FDP production from primary or secondary fibrinolysis.

The relative contributions of Ca++, phosphorus, and parathyroid hormone (PTH) on insulin secretion were evaluated in three groups of dogs. Dogs were studied with glucose infusions (group I) or standard intravenous glucose tolerance tests (IVGTT) (group II) before and after the development of diet-induced hypophosphatemia. Mean serum phosphorus levels for both groups fell from 4.1 to 1.1 mg/100 ml. Animals in group I demonstrated a fall in glucose disappearance rates (Kg) from 5.3+/-0.6% min to 3.5+/-0.5% after induction of hypophosphatemia (P less than 0.001). Mean insulin response was significantly greater in the hypophosphatemic animals than in controls in this group. In group II animals, mean insulin areas obtained during the IVGTT increased from 1,426+/-223 to 2,561+/-141 muU/ml/60 min after induction of hypophosphatemia, and were unaffected by Ca++ or PTH administration. Ca++ administration, but not hypophosphatemia or PTH infusion, increased significantly the mean insulin response to tolbutamide. Secondary hyperparathyroidism was induced by dietary manipulation in four dogs (group III). Mean PTH values increased from 71.4+/-2.1 to 3,012+/-372 pg/ml (P less than 0.001). Mean insulin response to an IVGTT was similar to group III animals, but increased from 1,352+/-128 to 1,894+/-360 muU/ml/60 min after the excessive dietary phosphorus was reduced for 3 mo, and plasma phosphorus fell from 3.2+/-0.1 to 2.8+/-0.3 mg/100 ml. PTH values decreased to 647+/-53 pg/ml. The insulin response to tolbutamide was comparable to that in group II animals, but increased significantly after calcium administration. Immunoreactive insulin disappearance rates were unaffected by hypophosphatemia or diet-induced secondary hyperparathyroidism. These data demonstrate that hypophosphatemia is associated with an augmented glucose-stimulated insulin release, without any effect on tolbutamide-stimulated insulin release. Hypercalcemia produces an augmented tolbutamide-stimulated insulin release with no apparent effect on glucose-stimulated insulin release. Finally, PTH does not appear to be an insulin antagonist and has no apparent effect on either glucose- or tolbutamide-stimulated insulin release in animals with dietary-induced secondary hyperparathyroidism.

Calcium absorption was measured in eight uremic patients before and after eight days of treatment with 100 or 500 mug of 25-hydroxycholecalciferol (25(OH)D3) per day. Fractional calcium absorption was estimated by administering 47Ca i.v. and orally on separate days and counting forearm radioactivity four hours later. Calcium absorption in four patients with residual renal function rose from 16.3 +/- 2.5 to 40.8 +/- 5.5% after treatment. In order to determine if the increased calcium absorption was mediated by an increase in the production of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) by virtue of increased substrate delivery to the 25-hydroxycholecalciferol-1-hydroxylase system present in the residual renal tissue, identical studies were performed in four anephric patients. Calcium absorption in these patients averaged 15.7 +/- 2.2% during the control period and rose to 46.0 +/- 11.1% after treatment. Increments in serum calcium after treatment were similar in both groups of patients; the mean concentration rose from 9.6 +/- 0.3 to 11.0 +/- 0.6 mg/100 ml. The results indicate that 25(OH)D3 can improve calcium absorption in the absence of renal tissue suggesting that its conversion to 1,25(OH)2D3 may not be necessary for its effect on the gastrointestinal tract in the uremic patient.

Calcium absorption was determined in 6 patients with chronic renal disease (GFR values 4.8 to 37 ml/min) on a constant diet before and after administration of 5,6-trans vitamin D3. Administration of 0.5 to 1.0 mg of 5,6-trans D3 for 8 days did not improve calcium absorption. In two of these same patients (the most uremic) administration of 5 mg of 5,6-trans D3 for 8 day sincreased calcium absorption markedly. Two other uremic patients who were studied under the same conditions and received 5 mg of native vitamin D3 for 8 days had no significant in crease incalcium absorption. Since 5,6-trans D3 normalized calcium absorption in patients with far-advanced renal disease, it is suggested that this analogue of vitamin D may be a useful agent in the treatment of hypocalcemia in patients with renal failure.

The role of the kidney in the metabolism of parathyroid hormone (PTH) was examined in the dog. Studies were performed in awake normal and uremic dogs after administration of bovine parathyroid hormone (b-PTH) or synthetic amino terminal tetratricontapeptide of b-PTH (syn b-PTH 1-34). The renal clearance of immunoreactive PTH was determined from the product of renal plasma flow and the percent extraction of PTH immunoreactivity by the kidney. Blood levels of circulating immunoreactive PTH were determined by radioimmunoassay. The normal dog kidney extracted 20 plus or minus 1% of the immunoreactive b-PTH delivered to it, and renal clearance (RC) of immunoreactivity was 60 ml/min. When RC was compared to an estimate of total metabolic clearance (MCR) of immunoreactivity, it accounted for 61% of the total. Both MCR and RC were markedly decreased in dogs with chronic renal disease. However, the percent extraction of immunoreactive PTH was unchanged in chronic renal disease, and the observed decrease in RC was due to changes in renal plasma flow. The largest portion of the reduction in total MCR was accounted for by the decrease in RC, and there was no compensation for the decrease in RC by extrarenal sites of PTH metabolism.

ARTICLESEffects of phosphate depletion and parathyroid hormone on renal glucose reabsorptionHR Harter, A Mercado, WE Rutherford, H Rodriguez, E Slatopolsky, and S KlahrHR Harter, A Mercado, WE Rutherford, H Rodriguez, E Slatopolsky, and S KlahrPublished Online:01 Dec 1974https://doi.org/10.1152/ajplegacy.1974.227.6.1422MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByThe early days of nephrology in ColombiaKidney International, Vol. 69, No. 2The Role of Hemodynamic Factors in the Initiation and Progression of Renal DiseaseJournal of Urology, Vol. 133, No. 3Complications of total parenteral nutritionKidney International, Vol. 27, No. 3Intestinal Phosphate TransportRenal glycosuria in renal homograft recipientsKlinische Wochenschrift, Vol. 62, No. 18Phosphate uptake by superficial and deep nephron brush border membranesPfl�gers Archiv European Journal of Physiology, Vol. 400, No. 4Phosphate transport in the kidney8 July 2005Clinical Spectrum of Phosphate Depletion and Its Effects on Urinary AcidificationMechanisms of Progression of Renal DiseaseHemodynamically mediated glomerular injury and the progressive nature of kidney diseaseKidney International, Vol. 23, No. 4Effects of vitamin D metabolites on protein catabolism of muscle from uremic ratsKidney International, Vol. 23, No. 3Compensatory Renal Hemodynamic Injury: A Final Common Pathway of Residual Nephron DestructionAmerican Journal of Kidney Diseases, Vol. 1, No. 5Parathyroid hormone-independent adaptation of the renal handling of phosphate in response to renal mass reductionKidney International, Vol. 21, No. 3Parathyroid HormoneParathyroid hormone inhibition of phosphate transport in renal brush border vesicles from phosphate-depleted dogsBiochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 645, No. 2Studies on the role of the liver and splanchnic tissues in the production of carbohydrate intolerance in uremiaMetabolism, Vol. 30, No. 7Renal handling of calcium and phosphateKlinische Wochenschrift, Vol. 58, No. 19The Effects of Parathyroid Hormone on Renal Phosphate HandlingTubular Adaptation to the Supply and Requirement of PhosphateReversal of hyperparathyroidism in response to dietary phosphorus restriction in the uremic dogKidney International, Vol. 15, No. 1Renal response to phosphorus deprivation in the isolated rat kidneyKidney International, Vol. 13, No. 2Regulation of the Tubular Transport of Phosphate in the Rat: Role of Parathyroid Hormone and 1,25-Dihydroxyvitamin D3Urinary Phosphate and Cyclic AMP in PseudohypoparathyroidismPhosphate Depletion and Adenine Nucleotide Metabolism in Kidney and LiverImpaired distal nephron acidification in chronically phosphate depleted ratsPfl�gers Archiv European Journal of Physiology, Vol. 377, No. 3Spontaneous Fanconi syndrome in the dogMetabolism, Vol. 27, No. 1Renal response to phosphorus deprivation: Effect of the parathyroids and bicarbonateKidney International, Vol. 11, No. 5 More from this issue > Volume 227Issue 6December 1974Pages 1422-1427 Copyright & PermissionsCopyright © 1974 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1974.227.6.1422PubMed4374094History Published online 1 December 1974 Published in print 1 December 1974 Metrics