Ascorbic acid supplements in patients receiving chronic peritoneal dialysis

Ascorbic acid supplements are commonly prescribed to patients with end-stage renal disease receiving peritoneal dialysis. To establish the need for ascorbic acid supplements, we evaluated seven chronic peritoneal dialysis patients during a supplement-free (phase I) period, and while receiving oral ascorbic acid (0.57 mmol/d [100 mg/d]) (phase II). Because of a proposed interaction with vitamin B6, patients were additionally supplemented with pyridoxine HCl (59.6 mumol/d [10 mg/d]) (phase III). Plasma levels and dialysate removal rates of total ascorbic acid and plasma pyridoxal-5-phosphate (PLP) were measured at the end of each phase. During phase I, plasma ascorbic acid levels (normal, 45 to 57 mumol/L [0.8 to 1.0 mg/dL]) declined slightly from 74 +/- 11 mumol/L (1.3 +/- 0.2 mg/dL) to 62 +/- 11 mumol/L (1.1 +/- 0.2 mg/dL) (P less than 0.02) at the end of the third week, and then remained stable to the end of the fourth week. Plasma ascorbic acid levels were no different in patients with or without residual renal function. With the addition of vitamin C supplements, plasma ascorbic acid levels increased by 45% of the baseline value at the end of phases II (P less than 0.001). The dialysate removal rate of ascorbic acid was 0.28 +/- 0.03 mmol/d (50 +/- 6 mg/d) at the end of phase I, and increased by 57% of the baseline value at the end of phases II (P less than 0.001). However, the peritoneal clearance of ascorbic acid remained unchanged during all phases the study. Pyridoxine depletion or repletion had no effect on plasma ascorbic acid levels (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Vitamin B6 requirements of patients on chronic peritoneal dialysis

Patients with chronic renal failure often develop vitamin B6 deficiency, which is of clinical concern because the multiorgan system manifestations are similar to those of uremia. Vitamin B6 deficiency in hemodialysis patients has been previously studied, but the need for daily pyridoxine supplementation in patients on chronic peritoneal dialysis (CPD) remains unclear. Therefore, we studied a group of 11 stable patients, nine on CAPD and two CCPD, to test for vitamin B6 deficiency and to establish daily requirements. Adequacy of vitamin B6 nutrition was assessed by measurement of plasma and dialysate effluent total vitamin B6 and pyridoxal 5'-phosphate (PLP), the latter using a very sensitive modification of the tyrosine apodecarboxylase enzyme assay. After four weeks without vitamin B6 supplements on a diet containing 1.3 +/- 0.2 mg vitamin B6/day (7.7 +/- 1.2 mumol/day), all patients had subnormal plasma PLP levels, 16 +/- 3 nmol/liter (nml 40 to 60), seven having a severe deficiency (less than or equal to 20 nmol/liter). Plasma total vitamin B6 levels (which includes non-PLP forms of the vitamin) were normal in all patients at baseline, 116 +/- 29 nmol/liter. Peritoneal losses were small, 8 +/- 2 nmol PLP/day and 545 +/- 61 nmol total vitamin B6/day. Supplementation with 5 mg/day oral pyrodoxine HCl for up to 16 weeks adequately repleted eight patients (65 +/- 7 nmol PLP/L), while three patients required 10 mg/day to achieve normal plasma PLP levels. During three episodes of peritonitis, dialysate losses of PLP did not increase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Taurine levels in plasma and blood cells in patients undergoing routine maintenance hemodialysis

We compared taurine levels in plasma, erythrocytes, platelets, lymphocytes, and granulocytes from 11 normal adults and 11 maintenance hemodialysis (MHD) patients immediately before and following a routine hemodialysis treatment. Taurine concentrations were elevated in plasma predialysis, as compared with normal subjects (90 +/- 16 [SEM] v 54 +/- 2 mumol/L [1.1 +/- 0.2 v 0.7 +/- 0.03, mg/dL]), but decreased with a dialysis treatment (to 34 +/- 3 mumol/L [0.4 +/- 0.04 mg/dL]). Erythrocyte taurine levels tended to be higher in MHD patients predialysis (1.2 +/- 0.2 v 0.7 +/- 0.1 nmol/10(9) cells, P less than 0.05 where P less than 0.025 is significant) as compared with controls; erythrocyte taurine was increased after dialysis (to 1.8 +/- 0.3 nmol/10(9) cells, P less than 0.006). In contrast, platelet taurine concentrations in MHD patients were lower than normal predialysis (18 +/- 2 v 27 +/- 2 nmol/10(9) cells) and declined further during the dialysis procedure (to 14 +/- 1). Granulocyte and lymphocyte taurine levels were not different in MHD patients, as compared with normal adults, either before or after dialysis. The observed differences in blood cell taurine content (expressed per 10(9) cells) could not be explained by variation in cell volumes among the groups examined. Thus, both chronic renal failure and a routine hemodialysis treatment produce changes in cell and plasma taurine levels that tend to be specific for the individual cell type.     

Aseptic hip necrosis after renal transplantation

To help determine the etiology of posttransplant aseptic hip necrosis, 11 stable renal allograft recipients (group A) who developed aseptic hip necrosis were compared with 89 patients (group B) without this complication. A comparison of mean age, duration of dialysis, mean daily prednisone dose, and incidence of rejection in the first year following transplant, sex, donor source, incidence of posttransplant parathyroidectomy, and mean serum calcium and alkaline phosphatase levels identified no significant differences between groups A and B. The mean serum creatinine value at three (2.2 +/- 0.31 mg/dL [190 +/- 30 mumol/L] vs 1.9 +/- 0.10 mg/dL [170 +/- 10 mumol/L]) and 12 (2.3 +/- 0.35 mg/dL [200 +/- 30 mumol/L] vs 1.9 +/- 0.10 mg/dL [170 +/- 10 mumol/L]) months and the serum phosphate value at three (3.0 +/- 0.19 mg/dL [0.97 +/- 0.06 mmol/L] vs 2.8 +/- 0.08 mg/dL [0.90 +/- 0.03 mmol/L]) and six (3.2 +/- 0.25 mg/dL [1.03 +/- 0.08 mmol/L] vs 2.9 +/- 0.25 mg/dL [0.94 +/- 0.08 mmol/L]) months were significantly greater in group A. Eight patients in group A underwent 13 total hip replacement an average of 16.5 +/- 3.1 months following transplant without significant complications. In conclusion, posttransplant aseptic hip necrosis occurs frequently, and renal allograft dysfunction may contribute significantly to its pathogenesis. When indicated, total hip replacement is both safe and effective.     

The metabolic effects of oral L-carnitine administration in infants receiving total parenteral nutrition with fat

beta-Oxidation, an important pathway in the metabolism of free fatty acids, occurs within the mitochondria in mammals. L-Carnitine is an essential cofactor in the transfer of long-chain fatty acids across the inner mitochondrial membrane. Maintenance of normal carnitine concentrations in whole blood and tissues, either through diet or biosynthesis, would appear necessary for adequate utilization of fat as an energy source. Infants, especially premature ones, without an exogenous dietary source of carnitine, have decreased plasma carnitine levels compared with infants receiving carnitine-supplemented feedings. To determine the importance of carnitine supplementation in a total parenteral nutrition program in infants in which a fat emulsion serves as a major calorie source, the following study was undertaken. Twelve infants receiving total parenteral nutrition (TPN) with fat for seven days were divided into two treatment groups. Group 1 was orally supplemented for seven days with carnitine (70 mumol/l/kg/24 h in 24 mL of 5% dextrose), while the second group received seven days of placebo supplementation (dextrose 5%, 24 cc/24 h). Plasma carnitine levels in the carnitine-supplemented group were significantly higher (29 +/- 8 nmol/mL) than in the control group (12.4 +/- 3.5 nmol/mL) after seven days of treatment. However, clearance of serum triglycerides and free fatty acids was not significantly different between the two groups. Baseline triglyceride levels in the carnitine-supplemented group were 96 +/- 42 mg/dL, increased to 242 +/- 101 mg/dL after the lipid challenge and decreased to 121 +/- 47 mg/dL two hours after the lipid infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma exchange and heart–liver transplantation in a patient with homozygous familial hypercholesterolemia

A female patient born in 1950 underwent plasma exchange and concomitant drug therapy for 20 yr due to homozygous familial hypercholesterolemia. Plasma exchange reduced total cholesterol levels from 25-30 mmol/L (967-1160 mg/dL) before treatment to 9.5 mmol/L (363 mg/dL) with regression of xanthomas and no side effects of long-term treatment. Due to end-stage calcific left ventricular outflow tract obstruction not amenable to standard valve reconstructive surgery, a combined heart-liver transplantation was successfully performed in 1996. She is without symptoms and living a normal life 4 yr after transplantation. Total cholesterol value is normal (4.7 mmol/L [182 mg/dL]) using a moderate dose of statins. Selective coronary angiography is without signs of graft vascular disease and the liver function is normal.     

Improved lipid profiles in patients undergoing high-flux hemodialysis.

Hyperlipidemia is one of many atherogenic risk factors encountered by patients undergoing chronic hemodialysis (HD). We have studied lipid profiles in these patients and have found less hypertriglyceridemia in those undergoing high-flux HD than those receiving traditional HD. Mean +/- SEM triglyceride level was 1.62 +/- 0.15 mmol/L (143.3 +/- 13.6 mg/dL) in high-flux dialysis patients, 2.39 +/- 0.27 mmol/L (211.6 +/- 24.1 mg/dL) in conventional dialysis patients, and 1.55 +/- 0.13 mmol/L (137.1 +/- 11.5 mg/dL) in normal age- and sex-matched controls. In addition, we found that in patients undergoing high-flux HD, females had higher high-density lipoprotein2 (HDL2) levels (0.62 +/- 0.03 mmol/L [23.8 +/- 1.3 mg/dL]) than males (0.33 +/- 0.04 mmol/L [12.9 +/- 1.7 mg/dL]) (P < 0.01). The mechanism(s) responsible for divergent lipid profiles in subsets of HD patients deserves further investigation. Whether reductions of hypertriglyceridemia and/or increases of HDL2 will diminish the incidence of cardiovascular disease in dialysis patients is unknown.     

Short-term hypothyroidism and vasopressin gene expression in the rat.

Hypothyroidism is associated with abnormalities in renal water handling, which include a delay in excretion of an acute water load, decreased urinary concentrating ability, and increased urine volume. In the present study, we investigated the role of vasopressin in aminotriazole-induced hypothyroidism by measuring vasopressin concentration in the plasma and pituitary along with vasopressin mRNA levels in the hypothalamus. After 5 weeks of aminotriazole treatment, L-thyroxine levels were significantly lower in the experimental animals (122 +/- 8 v 26 +/- 1 nmol/L [9.5 +/- 0.6 v 2.0 +/- 0.1 micrograms/dL]; P less than 0.001). Serum sodium (148 +/- 0.5 v 144 +/- 1.2 mmol/L [mEq/L]; P less than 0.01), and plasma osmolality (311 +/- 2.5 v 304 +/- 1.8 mmol/kg [mOsm/kg] H2O; P less than 0.05) were also lower in the experimental animals. There were no differences in plasma (1.9 +/- 0.4 v 1.5 +/- 0.2 pg/mL) or pituitary (1.5 +/- 0.4 v 1.5 +/- 0.2 microgram/pituitary) vasopressin levels. In addition, steady-state vasopressin mRNA levels were not different between the two groups (1,286 +/- 210 v 1,093 +/- 138 pg/hypothalamus). One week of L-thyroxine replacement resulted in significant increases in serum thyroxine levels without changes in the other variables measured. These results indicate that short-term hypothyroidism, which has been shown to exert substantial effects on renal function, causes only a modest central alteration in the plasma vasopressin-osmolality relationship, which occurs in the absence of detectable changes in vasopressin synthesis.     

Plasma oxalate concentration in chronic renal disease

Plasma oxalate was measured with use of the enzyme oxalate oxidase (EC 1.2.3.4; normal values 3.3 +/- 1.5 mumol/L, n = 24) in 50 patients with different degrees of renal failure. The following mean concentrations +/- SD (in mumol/L) were found: for glomerular diseases, 12.7 +/- 7.8 (n = 21); tubular diseases, 20.4 +/- 14.0 (n = 16); chronic renal failure before dialysis, 32.5 +/- 13.5, and after dialysis, 17.8 +/- 3.8 (n = 10); and primary hyperoxalemia, 72.2 +/- 14.5 14.5 (n = 2). The course of plasma oxalate was followed in one of these two patients after renal transplantation and in a patient recovering from acute tubular necrosis. No significant differences were found between patients with glomerular and tubular disorders. Overall, plasma oxalate was correlated with plasma creatinine in patients with glomerular and tubular diseases and dialysis patients (r = .84, P less than .001). Patients with primary hyperoxalemia had values outside the 95% confidence area of the regression line. It is concluded that the values obtained with this method, although probably still tending to overestimate the true oxalate concentration to some extent, provide reliable information about relative differences in plasma oxalate levels. In patients with terminal renal failure, plasma oxalate sometimes rises to levels at which deposition of calcium oxalate in tissues can occur.     

Health and nutritional status of wild Australian psittacine birds: an evaluation of plasma and hepatic mineral levels, plasma biochemical values, and fecal microflora

To evaluate the health and nutritional status of 3 wild Australian psittacine species, plasma and hepatic mineral concentrations and plasma biochemical values were measured in wild-caught galahs (Eolophus roseicapilla), long-billed corellas (Cacatua tenuirostris), and sulphur-crested cockatoos (Cacatua galerita). No correlations were found between hepatic and plasma mineral levels. Mean plasma calcium (1.79 mmol/L [7.16 mg/dL]) and sodium (103 mmol/ L [103 mEq/L]) concentrations were lower, whereas mean total phosphorus (6.53 mmol/L [20.22 mg/dL]) and potassium (8.87 mmol/L [8.87 mEq/L]) concentrations were higher than values for captive counterparts. Plasma iron levels were higher than those reported for captive counterparts, with evidence of interspecific (sulphur-crested cockatoos, 109 micromol/L [609 microg/dL]; corellas, 57 micromol/L [318 microg/dL]; galahs, 90 micromol/L [503 microg/dL]) and temporal variation (galahs: May, 107 micromol/L [598 microg/dL]; July, 59 micromol/L [330 microg/dL]). Hepatic iron concentrations were as high as 1030 mg/kg. Interspecific variation was minimal in mean plasma selenium (11.8 micromol/L [929 microg/L]) and zinc (31.2 micromol/L [204 microg/dL]) concentrations. Plasma biochemical values varied significantly from reported reference ranges. Ranges for total protein, albumin, and bile acid concentrations were lower, whereas uric acid, glutamate dehydrogenase, amylase, and cholesterol concentrations were higher than those previously reported for these species, and interspecific variation was evident. Variation in measures of mineral status or plasma biochemical values between males and females were negligible. An evaluation of fecal microflora showed a distinct absence of gram-negative bacteria or budding yeast. Results of this study show that analyte values used to determine health and nutritional status of wild birds differ from those published for captive counterparts. Although analyte values appear to vary minimally by sex, distinct taxonomic and some temporal differences exist in values from wild birds of these 3 species.     

Plasma oxalate levels rise in hemodialysis patients despite increased oxalate removal

The cause of secondary hyperoxalemia and oxalosis in patients on maintenance dialysis is unknown. The oxalate removal rate was determined in 26 patients on maintenance hemodialysis and 6 on continuous ambulatory peritoneal dialysis by measuring oxalate removed by dialysis and urinary excretion. The role of vitamin B6 deficiency and ascorbate in the raised plasma oxalate concentrations of these patients was evaluated. Plasma oxalate in hemodialysis patients, 442 +/- 41 micrograms/100 mL (mean +/- SE), and peritoneal patients, 394 +/- 115 micrograms/100 mL, were significantly higher than that in normal subjects, 11 +/- 1 microgram/100 mL (P less than 0.001). Average daily oxalate removal in subjects on hemodialysis, based on dialysis losses and urinary excretion, 35 +/- 3 mg/24 h, was significantly greater than urinary excretion of normal subjects, 26 +/- 1 (P less than 0.01). Oxalate removal from peritoneal dialysis patients, 28 +/- 2 mg/24 h, was not significantly different from that of hemodialysis patients or urinary excretion of normal subjects. Plasma ascorbate and B6 status were not correlated with plasma oxalate. A positive correlation between B6 deficiency and oxalate removal rate was not found. Plasma oxalate was correlated with time on dialysis (all patients) (P = 0.02). In a separate study of 15 hemodialysis patients followed over 2.3 +/- 0.2 yr, both plasma oxalate and oxalate removal rate significantly increased, P less than 0.001 and 0.05, respectively. It was concluded that oxalate removal rate is increased in hemodialysis patients and that the increased total body oxalate burden in these patients is not due to decreased removal. Although the increase may result from increased oxalate synthesis or gastrointestinal absorption, B6 deficiency and increased plasma ascorbate do not play a role.     

The acute metabolic effects of tumor necrosis factor administration in humans

It has been suggested that the monokine tumor necrosis factor (TNF) (cachectin) is responsible for metabolic abnormalities frequently accompanying malignant neoplasms. The acute metabolic effects of TNF in patients with cancer were studied. Subcutaneous administration of recombinant human TNF led to a rise in the C-reactive protein level (4.4 +/- 1.2 mg/dL vs 11.6 +/- 1.8 mg/dL) and a reduction in the serum zinc level (12.9 +/- 0.8 mumol/L vs 7.3 +/- 0.8 mumol/L [79 +/- 5 mg/dL vs 48 +/- 5 mg/dL]) (values are the mean +/- SEM). Forearm efflux of total amino acids more than doubled after intravenous TNF injection, principally because of increases in release of the gluconeogenic amino acids alanine and glutamine. Concomitantly, the arterial levels of alanine, glutamine, and total amino acids fell, indicating that TNF also stimulated the uptake of amino acids by other tissues. The observed amino acid pattern cannot be explained solely on the basis of measured changes in cortisol, glucagon, or insulin levels. These findings are discussed in relation to known alterations of amino acid metabolism in cancer-associated cachexia.     

Adult minimal change glomerulopathy with acute renal failure

Oliguric acute renal failure occurs in some adult patients with minimal change glomerulopathy. To look for clinical and pathologic factors that increase the risk for developing acute renal failure, 21 adults with minimal change glomerulopathy and a serum creatinine greater than 177 mumol/L (mean, 486 mumol/L; range, 194 to 1,344 mumol/L) (greater than 2.0 mg/dL [mean, 5.5 mg/dL; range, 2.2 to 15.2 mg/dL]) were compared with 50 adults with minimal change glomerulopathy and a serum creatinine less than 133 mumol/L (mean, 88 mumol/L; range, 53 to 124 mumol/L) (less than 1.5 mg/dL [mean, 1.0 mg/dL; range, 0.6 to 1.4 mg/dL]). Minimal change glomerulopathy patients with acute renal failure were older (59.5 v 40.3 years, P less than 0.001), and had higher systolic blood pressure (158 v 138 mm Hg, P = 0.001), more proteinuria (13.5 v 7.9 g/24 h, P = 0.01), and more arteriosclerosis in the renal biopsy specimen (1.7 + v 0.7 + on a scale of 0 to 4+, P = 0.005). Tubular epithelial simplification identical to that observed with ischemic acute renal failure (acute tubular necrosis) was observed in 71% of the patients with serum creatinine greater than 177 mumol/L (greater than 2.0 mg/dL) and 0% of those with less than 133 mumol/L (less than 1.5 mg/dL). All 18 patients with renal failure for whom follow-up data were available had recovery of function (mean creatinine, 539 +/- 301 mumol/L [6.1 +/- 3.4 mg/dL] at the time of biopsy and 106 +/- 27 mumol/L [1.2 +/- 0.3 mg/dL] at last follow-up), but sometimes only after weeks of dialysis support.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oxalate removal by hemodialysis in end-stage renal disease

Because of mounting evidence of precipitation of calcium oxalate in the soft tissues of patients with end-stage renal disease (ESRD) on maintenance hemodialysis, the plasma oxalate concentrations and calculated dialysis removal of oxalate were studied in seven patients without evidence of either primary or absorption hyperoxaluria prior to ESRD. A reversed-phase high-pressure liquid chromatographic method was developed to quantitate serum oxalate. Mean value +/- SE in four healthy controls was 28 +/- 5 mumol/L, and in the seven patients it was 187 +/- 15 mumol/L predialysis and 89 +/- 11 mumol/L postdialysis. Oxalate deposition in the soft tissues of ESRD patients is the consequence of sustained hyperoxalemia. Oxalate removal by dialysis was calculated from the four-hour oxalate clearance. Since the ionic radii of phosphate and oxalate are similar, total oxalate clearance was calculated midpoint of dialysis. Mean oxalate removal/dialysis was 3.01 +/- 0.283 mmol. On a daily basis this value was 1.645 +/- 0.155 mmol, which is about threefold the normal oxalate excretion rate. It is not significantly different from the excretion rate in absorption oxalurias but is less than that in primary hyperoxaluria. Therefore, it is concluded that hyperoxalemia in ESRD results from loss of renal excretion, failure of hemodialysis to remove enough oxalate to maintain a normal serum concentration, and increased intestinal absorption of oxalate and/or increased endogenous production.     

Pulse oral calcitriol for the treatment of hyperparathyroidism in patients on continuous ambulatory peritoneal dialysis: preliminary observations.

A direct effect of calcitriol on the regulation of the secretion of parathyroid hormone (PTH) has been shown in vitro and in vivo. In patients with renal failure on maintenance hemodialysis, it has been shown that intravenous (IV) administration of calcitriol appears to be superior to continuous oral administration. This may be due to the higher levels of calcitriol obtained in blood with consequent improved delivery of calcitriol to peripheral target tissues including the parathyroid glands. However, IV administration of calcitriol, is not practical for patients with end-stage renal disease (ESRD) who are maintained on continuous ambulatory peritoneal dialysis (CAPD). The present studies were designed to investigate whether intermittent administration of large doses of calcitriol orally ("pulse therapy") could mimic the effects of IV calcitriol in hemodialysis patients and achieve suppression of PTH secretion. Studies were performed in five patients who had been maintained on CAPD for more than 6 months. After basal determinations of calcium, phosphorus, and PTH, therapy was begun with calcitriol administered orally in a dose of 5 micrograms given twice per week. Calcium carbonate was continued as a phosphate binder. Dialysate calcium concentration was 1.75 mmol/L (3.5 mEq/L). With this therapy, PTH levels decreased rapidly, and, after 4 to 6 weeks of therapy, reached values 60% lower than pretreatment values. Mean values for serum calcium did not change significantly (2.29 +/- 0.12 mmol/L [9.6 +/- 0.5 mg/dL] before treatment compared with 2.32 +/- 0.08 mmol/L [9.7 +/- 0.25 mg/dL] after therapy). Mean serum phosphorus was also unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of vitamin C supplementation and withdrawal on the mortality and morbidity of regular hemodialysis patients

The present study was undertaken to evaluate the effects of vitamin C supplementation (VC-S) on the morbidity and mortality of 61 clinically stable outpatients maintained on regular hemodialysis (HD). All patients were given vitamin C (500 mg daily) for 2 years and observed for a further 2 years on no treatment. VC-S significantly increased the plasma levels of ascorbic acid up to 7.8 mg/dl (mean 3.3 +/- 0.4 s.e.m.) which fell after withdrawal to the normal range (mean 1.2 +/- 0.2 mg/dl). Hyperoxalemia was aggravated by VC-S (mean 61.5 +/- 3.3 mumol/l, range 33.3 to 165.5) while plasma oxalate levels in the unsupplemented period decreased to 36.3 +/- 3.3 mumol/l (p less than 0.01). There were no differences in creatinine, hematocrit, blood transfusion requirement, morbidity (including hospitalization) or mortality between the two periods of time in the same patients. In conclusion, we could not find any beneficial effects on morbidity or mortality as a result of using VC-S in regular HD patients. However, secondary hyperoxalemia was aggravated. As a result of these observations it appears that VC-S is harmful and unnecessary in these patients provided they are on an adequate diet.     

Chronic amphotericin B nephrotoxicity in the rat, protective effect of prophylactic salt loading

Amphotericin B (AMPHO) is the most effective and widely used antifungal agent for the treatment of systemic fungal disease in man. Its use is frequently limited by the development of nephrotoxicity, including renal vasoconstriction with depressed glomerular filtration rate (GFR) and renal plasma flow (RPF), inability to concentrate the urine, and renal potassium wasting. We investigated the effects of oral NaCl loading during chronic administration of AMPHO, on renal function in the rat. Rats were provided 150 mmol/L NaCl (AMPHO plus NaCl) or tap water (AMPHO plus H2O) as drinking water, 3 days prior to, and during chronic AMPHO (5 mg/kg/d intraperitoneal [IP] for 21 days). At the end of the experimental period, renal functional parameters were determined, including serum creatinine, urinary volume and electrolyte excretion rates, ability to maximally concentrate the urine after water deprivation, and renal hemodynamics. NaCl supplementation prevented the rise in serum creatinine (AMPHO plus NaCl, initial v final, 0.39 +/- 0.03 v 0.40 +/- 0.03 mg/dL [34.6 +/- 2.7 v 35.4 +/- 2.7 mumol/L], P = NS) seen in AMPHO plus H2O (0.34 +/- 0.01 v 0.51 +/- 0.04 mg/dL [30.0 +/- 0.9 v 45.2 +/- 3.5 mumol/L], P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of liver transplantation in a 13-year-old boy with erythropoietic protoporphyria

A 13-year-old boy who had had recurrent photosensitive skin reactions due to erythropoietic protoporphyria from 18 months of age, suddenly developed rapidly progressive hepatic failure with increasing cholestatic jaundice and variceal bleeding. Liver biopsy confirmed extensive protoporphyrin deposition with cirrhosis, and so orthotopic liver transplantation was performed. Postoperatively his skin rash settled within 72 hr, and in spite of subsequent exposure to the sun he has had no further skin reaction or blistering, although he does still have some itching. He made a good recovery and was able to return to school within six months of operation. Prior to liver transplantation, the hepatic ferrochelatase activity was reduced to only 0.81 nmol zinc-protoporphyrin formed/mg protein/hr (controls 3.30 +/- 1.00 nmol zinc-protoporphyrin formed/mg protein/hr, while the red cell protoporphyrin level was markedly elevated at 188 mumol/L red cells (normal less than 1.6 mumol/L red cells). The free plasma porphyrin level of 0.95 mumol/L (normal less than 0.02 mumol/L), and the urinary and fecal porphyrin levels were also raised. Following liver grafting these elevated porphyrin levels fell rapidly, with the red cell protoporphyrin level dropping to 10% of its preoperative value, and the rest returning to virtually normal within three months of operation.     

Renal handling of enalaprilat.

Most converting enzyme inhibitors share a predominantly renal dual elimination pathway consisting of glomerular filtration and tubular secretion. Since enalaprilat has two functional acidic groups, it is likely that it may be secreted via the proximal tubule organic acid system and, thus, its clearances would exceed that of glomerular filtration rate markers. We therefore examined the renal clearance of enalaprilat in normal volunteers and compared it with simultaneously measured inulin and creatinine clearances to explore the contribution of tubular secretion to the renal elimination of the drug. Twelve healthy male subjects with an age range of 24 to 58 years (mean +/- SE, 33.1 +/- 2.8) were studied. They had representative height (178.6 +/- 1.99 cm) and weight (73.3 +/- 2.1 kg) and had normal renal function as judged by blood urea nitrogen (BUN) (6 +/- 0.3 mmol/L [17 +/- 0.8 mg/dL]), plasma creatinine (88 +/- 3 mumol/L [1.0 +/- 0.03 mg/dL]), and creatinine clearance determined by a prestudy 24-hour urine collection (123.2 +/- 6.2 mL/min). Results are as follows: mean creatinine clearance, 2.12 mL/s (127 mL/min); mean inulin clearance, 119.1 ml/min mean creatinine clearance/inulin clearance, 1.07 mean enalaprilat protein binding, 37.9% unbound enalaprilat clearance, 222.4 ml/min; and the mean fractional enalaprilat clearances were: enalaprilat clearance/creatinine clearance, 1.72 (P less than 0.05, difference from 1.0); enalaprilat clearance/inulin clearance, 1.85, (P less than 0.05, difference from 1.0). Our results demonstrate that the clearance of free enalaprilat exceeds that of inulin and creatinine, suggesting that elimination of the drug proceeds through two complementary pathways, namely glomerular filtration and tubular secretion.