Protein intake seems to respond to increases in Kt/V despite baseline Kt/V greater than 1.2.

The nutritional status is a strong predictor of outcome in hemodialysis patients. Adequate delivery of dialysis is necessary for hemodialysis patients to maintain their protein nutrition. In general, a single-pool Kt/V of 1.2 has been considered adequate dialysis. We recently decided to maximize the blood flow during hemodialysis in all of our patients; this enabled us to increase the dose of delivered dialysis in those patients who were not initially utilizing their maximum blood flow. There were 18 patients who already received a Kt/V greater than 1.2. We were able to increase Kt/V even further in 10 of them, resulting in a significant increase in nPCR and a trend to increase serum albumin over the next 6 months of follow-up. The mean normalized protein catabolic rate (nPCR) and serum albumin remained unchanged in the remaining 8 patients whose Kt/V could not be increased. Our data provide evidence that protein intake in hemodialysis patients will increase with an increase in delivered dialysis above the level generally considered to be adequate.

Middle molecule clearance does not influence protein intake in hemodialysis patients.

Nutritional status in hemodialysis patients is a strong predictor of morbidity and mortality. To isolate the impact of dialyzer flux on nutrition in hemodialysis patients, we compared the nutritional effect of high-flux dialysis with that low-flux dialysis, using a biocompatible membrane for both. Sixty-five patients were monitored for 8 months after changing to high-flux dialysis with a F80 polysulfone dialyzer following a 6-month baseline period of low-flux dialysis with a F8 polysulfone dialyzer. The Kt/V and normalized protein catabolic rate (nPCR) were the same on both the F8 and F80 dialyzers. The regression of nPCR versus Kt/V was also nearly identical. Despite the unchanged protein intake, the serum albumin (3.86 to 4.04 g/dL; P < 0.01) and serum creatinine (10.3+/-0.2 mg/dL to 11.2+/-0.3 mg/dL; P < 0.05) significantly increased during 8 months of high-flux dialysis. Therefore, we conclude that the increased removal of middle molecules by high-flux dialysis has no apparent effect on appetite as measured by nPCR, but it has a beneficial effect on serum albumin and serum creatinine, suggesting a role for middle molecules in the control of albumin and protein synthesis in the body.

Peritoneal clearance of inorganic sulfate.

The peritoneal clearance of sulfate was studied in a group of 12 stable CAPD patients and compared to the clearance of other well-studied solutes such as urea, phosphate, and creatinine. For this purpose we obtained 24 h peritoneal dialysate collections and performed a modified 6-hour peritoneal equilibration test. The results showed that the peritoneal clearance of sulfate is very similar to those of creatinine and phosphate but significantly smaller than the clearance of urea. Decreased daily excretion of sulfate in relation to protein catabolic rate was noted and requires further studies to define its mechanisms.

Altered renal expression of the insulin-responsive glucose transporter GLUT4 in experimental diabetes mellitus.

Because the insulin-responsive glucose transporter, GLUT4, is expressed in renal vascular and glomerular cells, we determined the effects of experimental diabetes mellitus on GLUT4 expression and glucose uptake by these tissues. Quantitative reverse-transcription polymerase chain reaction studies of microdissected afferent microvessels and renal glomeruli showed that, after 1 wk of diabetes, GLUT4 mRNA was decreased to 26 and 34% of control values, respectively. GLUT4 immunoblots of renal glomerular and microvessel samples showed that GLUT4 polypeptide was decreased to 51% of control values. These results were confirmed by indirect immunofluorescence, which showed decreased GLUT4 expression in glomerular cells and in vascular smooth muscle cells of the afferent microvasculature of diabetic animals. Uptake of the glucose analogue, 2-deoxyglucose, was also depressed in microvessels of diabetic rats to 57% of control values, supporting the conclusion that fewer total glucose transporters were available for glucose uptake into diabetic renal glomerular and microvascular cells. Thus both GLUT4 expression and glucose uptake by glomerular and microvascular cells are decreased in diabetic animals. These results have led us to suggest a mechanism by which decreased renal GLUT4 expression could contribute to glomerular hyperfiltration and hypertension seen in early diabetes.

Serum albumin: associations and significance in peritoneal dialysis.

Hypoalbuminemia in hemodialysis patients is a strong predictor of mortality; however, the significance of hypoalbuminemia in peritoneal dialysis patients is less well-defined. We have analyzed the factors associated with hypoalbuminemia in a cross-sectional study of 36 peritoneal dialysis patients, and investigated the impact of hypoalbuminemia on the one-year clinical outcome in 53 peritoneal dialysis patients. We found hypoalbuminemia to be associated with low values for the kinetic parameters KT/V, creatinine clearance, and normalized protein catabolic rate (nPCR) by univariant analysis. In a multiple regression model, nPCR was the only significant predictor of serum albumin. Clinical outcome measures evaluated were days-hospitalized, peritonitis rate, and death. Days-hospitalized was inversely correlated with serum albumin, and deaths occurred only in patients with serum albumin less than 4.0 mg/dL. There were no associations with peritonitis episodes. In conclusion, our study provides evidence that hypoalbuminemia in peritoneal dialysis patients is associated with a low protein intake measured by the nPCR and, possibly, with a low delivered dose of dialysis. Our study also suggests that the serum albumin level correlates to clinical outcome measured by days-hospitalized.

Insulin-responsive glucose transporter expression in renal microvessels and glomeruli.

The insulin-responsive glucose transporter (GLUT4) is expressed at high levels in fat and skeletal muscle, which account for the majority of insulin-stimulated glucose uptake. However, GLUT4 is also expressed at lower levels in kidney and several other tissues. We have used a variety of protein and mRNA detection techniques to determine the sites of renal GLUT4 expression. Indirect immunofluorescence experiments with two specific anti-peptide antisera detected GLUT4 in the smooth muscle cells of the rat renal microvasculature, in renal glomerulus, and in cultured glomerular mesangial and epithelial cells. PCR amplification of cDNA derived from microdissected renal glomeruli, microvessels and tubules corroborated this distribution of GLUT4, and Northern blotting demonstrated GLUT4 mRNA in cultured glomerular mesangial cells. Both the immunofluorescence and PCR data suggested that GLUT4 is most highly expressed in renal microvessels. Our results show that certain renal cells, such as renal microvascular smooth muscle cells, express the insulin-responsive glucose transporter and therefore may demonstrate altered glucose uptake and metabolism in diabetes mellitus.

Peritoneal dialysis in end-stage renal disease patients with preexisting chronic liver disease and ascites.

PURPOSE: Hemodialysis in patients with chronic liver disease and ascites may be complicated by intradialytic hypotension, limiting the amount of ultrafiltration and resulting in massive ascites. Successful maintenance peritoneal dialysis (PD) has not been previously reported as an alternative to hemodialysis in this population. PATIENTS AND METHODS: Nine patients with chronic renal failure, chronic liver disease, and tense ascites prior to beginning PD are described. All chronic PD catheters were placed percutaneously by the nephrology staff. Seven patients were maintained primarily on continuous ambulatory peritoneal dialysis, whereas two were on intermittent peritoneal dialysis. RESULTS: PD catheters were placed without serious hemorrhage or bowel injury. PD provided adequate clearance and volume maintenance for each patient. Fifteen episodes of peritonitis occurred in 18 patient-years of PD. All episodes of peritonitis were successfully treated with intraperitoneal antibiotics without catheter removal. Only one patient had a decline in the serum albumin level of 0.5 g/dL or more during the course of chronic PD. Three of the nine patients are still alive and on PD for durations of 18 to 24 months. One patient insidiously developed sclerosing peritonitis after 8 years on PD and is now on hemodialysis, and another patient switched to hemodialysis because she was no longer able to care for herself or to manage her PD. Four patients died while maintained on PD; three deaths were due to complications of liver failure within the first 4 months of PD and the fourth was due to empyema after 4 years of PD. CONCLUSION: PD can be used successfully to treat chronic renal failure in patients with chronic liver disease and ascites when the liver disease itself is not rapidly fatal. PD may be better tolerated than hemodialysis and perhaps should be the renal replacement treatment of choice in these patients.

Prophylactic and therapeutic use of anticoagulants in inherited antithrombin III deficiency.

A family with a pronounced history of venous thrombotic disease is described. Several members were found to have reduced antithrombin III levels. Heparin cofactor activity was reduced in the antithrombin III-deficient plasma. The proposita, who presented with bilateral iliofemoral vein thrombosis early in pregnancy, was treated initially with heparin, and after the 12th week of pregnancy was maintained on oral anticoagulants until she was 38 weeks pregnant. Heparin was then given and continued throughout the delivery period and for 10 days postpartum with no evidence of recurrent thrombosis. The effect of infusing 5 units of fresh frozen plasma on the antithrombin III level and the response to heparin were minimal and short-lived. Oral anticoagulatns produced a rise in the antithrombin III level. These results demonstrate the importance of maintaining antithrombin III-deficient subjects on long-term oral anticoagulant therapy.

Pregnancy in renal transplant recipients.

Of the 48 female patients attending the outpatient clinic of the Johannesburg General Hospital Transplant Unit between January 1971 and December 1974, 10 became pregnant. Fifteen pregnancies were recorded, 6 of which ended in abortions. Ten infants were born from the remaining 9 pregnancies and 4 (40%) died in the neonatal period. The main cause of neonatal death was prematurity. One major congenital anomaly, a diaphragmatic hernia, was found. Maternal complications were mild and easily controlled, urinary infection being the commonest. One patient showed a moderate reduction in renal function. Obstruction of labour by the transplanted kidney was not encountered, and the two Caesarean sections were performed for obstetrical reasons unrelated to the renal transplant.

Suppression of lactation with high doses of pyridoxine.

Administration of high doses of vitamins B6, B1 and B12 successfully inhibited lactation without any untoward side-effects or discomfort in 96% of patients who had not yet established lactation, compared with 76,5% of control patients who received placebo.

Hepatitis B (surface) antigen in mothers and their infants.

Hepatitis B (surface) antigen (HBSAg) was found in the serum of 8 out of 4 245 women attending the antenatal clinic of the Queen Victoria Maternity Hospital Seven (0, 16%) were asymptomatic carriers of the antigen, while the eigth suffered from polyarteritis nodosa. Seven of the 8 babies born to these mothers were followed-up over periods of up to 18 months, and 1 has become a chronic carrier of HBSAg. The antigen was not detected in the colostrum (breast milk) of the 6 positive mothers tested, but it was present in amniotic fluid, placenta and cord blood of some of the mother-infant couples. The possible routes of transmission of the hepatitis B virus from mother to baby are discussed in the light of these findings. No cases of acute virus B hepatitis occurred in the latter months of pregnancy nor in the puerperium, among 4 088 women delivered at the hospital during this period.

Feto-maternal haemorrhage following successful and unsuccessful attempts at external cephalic version.

In the present study, 6 out of 100 patients who had an attempted or actual external cephalic version (ECV) showed significant feto-maternal haemorrhage, the amount being greatest in patients with "failed" external versions. Thus ECV may be a source of rhesus iso-immunization in a rhesus negative mother with a rhesus positive fetus and should not be performed unless the father is a rhesus negative. If, however, an ECV has been attempted, fetal cell counts should then be made and rhesus immunoprophylaxis administered if necessary.

The risk of Rh isoimmunization in ruptured tubal pregnancy.

In 9 (24%) out of 38 African women who had suffered a ruptured tubal pregnancy significant numbers of fetal erythrocytes (5 or more per 150,000 maternal cells) were found in the maternal circulation. This is a higher incidence than occurs after abortion and indicates that rupture of a tubal pregnancy is a potential source of Rh isoimmunization. The finding of fetal cells in the peritoneal cavity suggests that this is the main source of the fetal blood found in the maternal circulation. At operation on Rh-negative patients with ruptured tubal pregnancies, therefore, complete removal of the peritoneal blood should be attempted and the blood recovered should never be transfused into the patient, who should always receive prophylactic Rh immunoglobulin.