Role of the kidneys in the metabolism of circulating mevalonate in humans.

Previous studies in several animal species have demonstrated that the kidneys are the primary site of mevalonate metabolism by the oxidative or shunt pathway. To determine the role of the human kidney in mevalonate oxidation, we studied mevalonate shunt activity in patients undergoing hemodialysis for varying degrees of renal failure. Surprisingly, at least half of the uremic patients and even anephric patients had normal ability to oxidize mevalonate by the shunt pathway.

Mechanisms and consequences of proteinuria.

The glomerulus is a complex structure containing a remarkable capillary bed which is freely permeable to water and solutes up to the size of inulin. Many small proteins are filtered, reabsorbed, and catabolized by the kidney; but most large proteins, such as albumin or immunoglobulins, are almost entirely excluded from the glomerular ultrafiltrate due to the charge-size permselectivity of the glomerular capillary basement membrane. These large proteins appear in the urine when diseases reduce the charge selectivity or result in the development of large pores in this membrane.

Effect of dietary protein intake on albumin homeostasis in nephrotic patients.

Animals with experimental renal disease maintained on diets restricted in protein develop less severe renal lesions and less proteinuria than do animals maintained on a normal or high protein diet. To determine whether restriction of dietary protein will reduce urinary albumin excretion in patients with established nephrosis and whether such dietary restriction will result in decreased albumin pools, we performed paired studies on nine nephrotic patients. They were fed sequential diets with a protein content of 1.

Creatine kinase: purification, characterization, and tissue distribution of the MM subtypes.

The MM isozyme of creatine kinase can be separated into four subtypes by isoelectric focusing: MM3 (pI 6.90), MM2 (pI 6.70), MM1 (pI 6.

Combined hepatic and renal injury in alcoholics during therapeutic use of acetaminophen.

Combined hepatocellular injury and renal tubular necrosis developed in five alcoholic patients who were receiving acetaminophen therapeutically. Two patients were taking doses prescribed by a physician. The hepatitis was characterized by extremely high serum transaminase values that were maximal on admission.

Biochemical changes in the pancreas of rats with chronic renal failure.

Chronic renal failure (CRF) was produced in female Sprague-Dawley rats by 7/8 nephrectomy. Creatinine clearance was depressed significantly (P less than 0.005) and blood urea nitrogen (BUN) increased in CRF rats when compared with the sham-operated (S) controls.

Plasma volume expansion is necessary for edema formation in the rate with Heymann nephritis.

Edema formation in nephrotic syndrome has been attributed to intravascular volume depletion resulting from leakage of plasma water into the interstitial space and activating secondary renal sodium retention. However, clinical studies indicate that edematous patients with nephrotic syndrome may have normal or expanded plasma volumes. We evaluated the relationship between plasma volume and edema formation in control rats and rats with chronic renal failure (CRF) produced by 7/8 nephrectomy.

The aging kidney.

The aging kidney suffers reduction both in mass and in glomerular filtration rate. These changes may be totally or partially due to atherosclerosis and hypertension, which reduce renal blood flow. Superimposed on these processes, and perhaps responsible for primary loss of renal mass irrespective of renal vascular disease, is glomerular damage and involution that is a consequence of adaptive increases in glomerular perfusion pressure that occurs as the number of nephrons decline with age.

Albumin homeostasis in the nephrotic rat: nutritional considerations.

Albumin catabolism and the relationship between plasma albumin concentration and albuminuria were studied in male Sprague-Dawley rats with Heymann nephritis. The rats were placed on isocaloric diets of 8.5, 21, or 40% protein.

Effects of chronic renal failure on protein synthesis and albumin messenger ribonucleic acid in rat liver.

Previously we reported that chronic renal failure in rats leads to preferential disaggregation of liver membrane-bound polysomes associated with a decrease in albumin synthesis. To determine whether reduced albumin synthesis results from reduced cellular levels of albumin messenger RNA (mRNA) or some other molecular mechanism, we have employed mRNA-DNA hybridization in conjunction with cell-free protein synthesis to determine albumin mRNA sequence content and biological activity in subcellular fractions from control and uremic rat liver. Using high specific activity albumin [3H]-complementary DNA prepared from purified-albumin mRNA, we found that total liver polysomes and albumin mRNA sequence content are increased in uremic animals.

Albumin homeostasis in patients undergoing continuous ambulatory peritoneal dialysis.

Albumin and protein removal rates were studied in 18 patients undergoing continuous ambulatory peritoneal dialysis (CAPD). In nine patients simultaneous studies of albumin distribution and turnover were performed. Total albumin loss was 4.

The effects of alcohol on blood pressure and electrolytes.

The interaction between alcohol abuse, changes in blood pressure, and electrolyte abnormalities is complex. Some effects of alcohol are seen only with acute ingestion, some during withdrawal, and some only in chronic drinkers. Careful attention to the interactions between the metabolism of various electrolytes can prevent unnecessary morbidity and mortality in alcoholic patients.

Long-term renal function in kidney donors. Sustained compensatory hyperfiltration with no adverse effects.

Twenty patients who underwent uninephrectomy for kidney donation between 1964 and 1968 participated in a long-term study of the function of the solitary kidney. Mean follow up after uninephrectomy was 15.8 +/- .

Dietary tryptophan supplementation prevents proteinuria in the seven-eighths nephrectomized rat.

Surgical reduction of renal mass in the rat leads to proteinuria, hypertension, and progressive renal failure beyond that of the original physical destruction of renal mass. Both hypertension and proteinuria have been implicated in the process of progression of renal failure. The seven/eighths nephrectomized rats fed a diet supplemented with 4% tryptophan (UT) had a urinary albumin excretion rate of 0.

Mechanism of hypoalbuminemia in the 7/8-nephrectomized rat with chronic renal failure.

Hypoalbuminemia has been observed consistently in patients and experimental animals with chronic renal failure (CRF). A defect in albumin synthesis, catabolism, or distribution has been invoked as the cause, but there is no agreement as to which, if any, of these disorders results from the uremic state. We studied albumin homeostasis in 7/8-nephrectomized rats with CRF.

Potential pitfalls in the evaluation of the usefulness of hemodialysis for the removal of lithium.

A 50-year old female who was comatose from an overdose of lithium was treated with hemodialysis. Serum lithium concentrations declined 47% during a 3-h hemodialysis but increased afterwards, peaking 8 h after hemodialysis was stopped. Hemodialysis clearances were estimated by equations using extraction ratios of lithium from whole blood, serum, and red cells, and flows of whole blood, serum or red cells.

Massive intoxication with acetaminophen and propoxyphene: unexpected survival and unusual pharmacokinetics of acetaminophen.

A 28-year-old woman ingested an estimated 58 g acetaminophen and 9 g propoxyphene 20 h before hospitalization. Her serum acetaminophen concentration at 22 h was 485 micrograms/mL and declined with an unusually long half-life of 14 h. Hemodialysis for 4 h (started at 36 h) reduced the acetaminophen concentration from 250 to 32 micrograms/mL.

Anion-stimulated phosphohydrolase activity of intestinal alkaline phosphatase.

Phosphohydrolase activity of a highly enriched commercial preparation of calf intestinal alkaline phosphatase was stimulated in the presence of HCO3. SO4, Cl, SCN, and acetate did not stimulate hydrolysis, whereas SO3 exhibited a bimodal effect, stimulating at low (25mM) concentration but inhibiting at high (100 mM) concentration. The pH optimum of this stimulation by HCO3 or SO3 was 8.

Requirement of Zn to demonstrate HCO3-stimulated ATPase activity of rat small intestinal brush border.

The existence of a membrane-bound HCO3-stimulated ATPase in intestinal mucosa is controversial. A crude brush border fraction of rat small intestinal homogenates contained HCO3-ATPase activity which was inhibited by preincubation with 3 mM EDTA. Alkaline phosphatase activity of this preparation was also inhibited in a parallel, time-dependent fashion by preincubation with EDTA.

Purification and properties of arginase of rat kidney.

l-Arginase from rat kidney was partially purified and some properties were compared with those of l-arginase of rat liver. The kidney enzyme was firmly bound to the mitochondrial fraction and after solubilization required arginine or an unknown factor in tissue extracts for stabilization after dialysis. The two enzymes differed also in stability with respect to acetone treatment, heating or freezing.