Effects of acetazolamide on proximal tubule C1, Na, and HCO3 transport in normal and acidotic dogs during distal blockade.

It has been suggested that the establishment of a tubular fluid to plasma chloride gradient in the late proximal tubule by the reabsorption of bicarbonate (and other anions) in the early proximal tubule is responsible for a significant part of sodium chloride and water reabsorption in the proximal tubule. In the present study the effects of acetazolamide on proximal tubule water and electrolyte excretion were examined in 6 normal dogs and 10 chronic ammonium chloride-loaded dogs during distal blockade produced by ethacrynic acid and chlorothiazide administration. During distal blockade control urine/plasma osmolality and urine/plasma sodium were close to unity in all experiments. Urine/plasma chloride and urine/plasma bicarbonate were 1.21+/-0.02 and 0.75+/-0.07 in normal and 1.24+/-0.01 and 0.04+/-0.01 in acidotic dogs, respectively. After the administration of acetazolamide (20 mg/kg i.v.), there was a significant increase in urine flow, absolute and fractional excretion of sodium, bicarbonate, and chloride in all animals. Associated with these effects, urine/plasma osmolality and urine/plasma sodium remained unchanged but urine/plasma chloride decreased significantly to 1.15+/-0.01 in normal and to 1.19+/-0.01 in acidotic dogs. In acidotic dogs there was a significant correlation between the increase in bicarbonate, sodium, or chloride excretion after acetazolamide and the plasma bicarbonate level (range 6.8-12.5 meq/liter). These data demonstrate a significant effect of acetazolamide on bicarbonate, sodium, and chloride reabsorption in the proximal tubule even in the face of severe acidosis. Moreover, the data suggest that the decrease in chloride reabsorption (and accompanying sodium) after acetazolamide is related to the decrease in bicarbonate reabsorption and the associated decrease in the transtubular chloride gradient.

Cholesterol and lipid disturbances in renal disease: the natural history of uremic dyslipidemia and the impact of hemodialysis and continuous ambulatory peritoneal dialysis.

Lipid abnormalities have been postulated to contribute to renal insufficiency by a mechanism that is analogous to atherogenesis. The majority of patients treated for chronic renal failure die of cardiovascular complications. Lipid abnormalities in this group are thought to contribute to this high mortality. Proving a causal association between dyslipidemia and accelerated atherosclerosis in the end-stage renal disease population has been confounded by the presence of other pro-atherogenic conditions in this population. The current study compiles the lipid data we have accumulated from our renal population for the years 1987 to 1989. The report is divided into three main parts: The first is a survey of lipid levels and atherogenicity indicators in groups with different types of renal disease or modalities of treatment. The second is a multivariate analysis of the relationship of clinical and biochemical variables (and their interactions) to the serum lipid and apolipoprotein levels and their ratios and their change over time in a large dialysis population. In the third study, we quantitate the peritoneal clearances of apolipoproteins A-I and B in patients undergoing continuous ambulatory peritoneal dialysis and assess the relationship of these clearances to serum lipid and lipoprotein levels and risk ratios.

Predictors of survival in continuous ambulatory peritoneal dialysis patients: a five-year prospective study.

Our objective was to examine the influence of various demographic, clinical, and enrollment biochemical variables on the long-term survival of continuous ambulatory peritoneal dialysis (CAPD) patients. This was a prospective cohort study investigating the relationship between demographics and enrollment biochemical markers and mortality in CAPD patients in a CAPD unit in a large tertiary care teaching hospital. One hundred and sixty-nine patients in the CAPD program were enrolled between 1989 and 1994, and were followed up to 60 months. Independent predictors of mortality determined by Cox proportional hazards model included age, diabetes, serum albumin and creatinine. Enrollment level of serum albumin, and creatine can predict mortality in CAPD patients up to 60 months. Markers of visceral and somatic nutrition at enrollment are important predictors of mortality in CAPD patients up to five years.

Successful treatment of tuberculous peritonitis while maintaining patient on CAPD.

Although conventional wisdom advises removal of the Tenckhoff catheter as part of the therapy for tuberculous peritonitis, there are a few recent reports of cases successfully treated while maintaining the patients on CAPD. We wish to report three cases treated without interrupting CAPD. In two of the patients, cultures were positive for Mycobacterium tuberculosis and in the third case, although the cultures were negative, the patient improved on anti-Tb medications. Smear for AFB was positive in one patient; and two had a positive PPD. All had predominance of lymphocytes and monocytes in effluent. The total WBC count was 160-300 and two patients had fever. All had abdominal pain. One patient was treated with INH and ethambutol; one with INH and rifampin and one (who was suspected of being HIV+) also received pyrazinamide (PZA) until culture was available. Cultures grew in 4-6 weeks. All were started on therapy prior to having the culture results, and all showed clinical improvement within two weeks. One patient had his catheter replaced two months later because of pseudomonas peritonitis, continued on CAPD for an additional five months, then changed to HD because of recurrent bacterial peritonitis. One patient died of complications of diabetic vascular disease three months later with no evidence of peritonitis. One patient has remained on anti-Tb treatment for seven months and is doing well on CAPD.

Peritonitis and the patient with human immunodeficiency virus (HIV).

The prevalence of HIV positive patients (HIV pts) with ESRD is likely to increase and many will be going on CAPD. There are, however, factors which cause one to be concerned about a possible increased risk of peritonitis in these patients. These include not only their impaired immune and nutritional status, but often their mental status. We examined the incidence and type of peritonitis among the 184 patients who have been in our program since December 1983 for a total of 4,017 patient months (pt mo). During this time we treated 9 known HIV pts (4 drug users and 5 homosexuals) for a total of 114 pt mos. We also looked at albumin, cholesterol, and creatinine as possible risk markers. We found a greater than two fold incidence of peritonitis in the HIV positive patients and that low albumin was a significant risk factor in the HIV negative patients, but not in the HIV positive patients.

The impact of CAPD treatment on lipid metabolism and cardiovascular risk.

The metabolism of lipids in CAPD has not been fully elucidated. To further clarify the behavior of dyslipidemia in this setting we followed the values of total cholesterol (TC), HDL-cholesterol (HDL-C) and apolipoprotein (apo) parameters over time (12-24 months) in 40 patients and correlated these values and their ratios with clinical (age, gender, race, weight, diabetes, etc.) and biochemical (multiphastic screen) information. Mean HDL-C was lower in men (p less than 0.04), in whites, (p less than 0.03) and in diabetic patients (p less than 0.05), but there were no group differences for mean total cholesterol, mean apolipoprotein values, the atherogenic risk ratio TC/HDL-C, or the anti-atherogenic ratio apo A-I/apo B. Total months on CAPD was found to correlate positively with TC/HDL-C (p less than 0.05), an atherogenic risk factor, and to correlate negatively with HDL-C (p less than 0.02), an anti-atherogenic index. There was also a negative correlation with another anti-atherogenic index, apo A-I/apo B, which did not reach statistical significance (r = -0.41, p = NS). Counterbalancing this apparently increased atherogenic risk is the stability of individual parameters for each patient over time in this study. In fact, the good news appears to be that TC, HDL-C, apolipoproteins and the risk ratios TC/HDL-C and apo A-I/apo B all remained stable over 12-24 months (p = NS by paired t-test for all). Thus, we find no evidence for worsening of the uremic dyslipidemia over time with CAPD treatment.

Variability of peritoneal clearances for apolipoprotein and its relationship to susceptibility for atherosclerotic changes in CAPD.

Apolipoprotein Clearance and Atherogenicity in CAPD: Protein and lipoprotein loss is one of the disadvantages of CAPD. The impact of these losses on serum constituents is not fully understood. Lipoprotein disorders are observed in patients with chronic or acute renal failure or undergoing dialytic therapy with resultant increase in atherosclerotic clinical events yet these phenomenon are poorly understood, underinvestigated and underreported. Thus the impact of dietary and pharmacological steps to prevent these events are limited by lack of clinical facts. The recent emergence of effective lipid lowering agents makes a rapid analysis of parameters important. We studied the relationships between peritoneal clearance of apolipoproteins and serum atherogenicity indicators in a preliminary study of 10 CAPD patients with and without peritonitis. We measured total cholesterol (TC), HDL-Cholesterol (HDL-C), Apo A-I and Apo B and dialysate levels of Apo A-I and Apo B. Apo levels were determined immunotubidimetrically, and dialysate was concentrated by ultrafiltration. A subsequent prospective group of 10 additional patients was studied to test the relationship found in the preliminary study. In both preliminary and prospective nonperitonitis groups, the ratio of peritoneal clearance of Apo A-I to Apo B correlated strongly with the serum TC/HDL-C (r = 0.9 preliminary, r = 0.78 prospective group). There was an inverse correlation between the clearance ratio and both serum HDL-C (r = -0.71 preliminary, r = -0.77 prospective group) and serum Apo A-I/Apo B (r = -0.74 preliminary, r = -0.62 prospective group).(ABSTRACT TRUNCATED AT 250 WORDS)

Outcome of percutaneous endoscopic gastrostomy feeding in patients on peritoneal dialysis.

Protein malnutrition is now well established as an important contributory factor to the high mortality in peritoneal dialysis (PD) patients. Low dietary protein calorie intake is one of the factors leading to protein malnutrition. If PD patients develop difficulty eating, percutaneous endoscopic gastrostomy (PEG) feeding may prove beneficial in providing adequate nutrition. Studies on the effectiveness of PEG feeding in PD patients are limited to pediatric patients. The objective of the present study was to assess the outcome of PEG feeding in adult patients with end-stage renal disease (ESRD) on PD. We retrospectively reviewed charts from May 1992 to February 2000 of 10 consecutive patients in our center who had had feeding tubes inserted. The patients' ages ranged from 37 to 81 years, with mean age of 65. Of the 10 patients, 7 were male, 5 were diabetic, and 1 was infected with the human immunodeficiency virus. Two patients had cerebrovascular accident (CVA) with dysphagia, 3 had multi-infarct dementia, 2 had anoxic encephalopathy, 2 had dementia, and 1 had calciphylaxis with anorexia. Of the 10 patients, 9 failed to eat because of neurologic disorders. Two patients who had functioning PEG feedings before starting PD had no complications. Only 2 of 8 patients already on PD continued with long-term PD after a PEG was inserted. Both patients whose PD was not interrupted at the time of PEG placement immediately developed peritonitis. Of the 6 patients who were maintained on hemodialysis (HD), 2 developed peritonitis within one week of starting PEG feedings. The other 4 had no complications from PEG feedings while being maintained on HD, but 1 developed peritonitis when PD was resumed. Of the 5 patients who developed peritonitis, 3 experienced fungal peritonitis. In PD patients, PEG feeding is associated with frequent complications. However, PEG placement prior to PD initiation appears to be safe. Maintaining patients on HD for at least 6 weeks appears to decrease the incidence of peritonitis, but does not eliminate it. Use of anti-fungal prophylaxis and maintenance of the patient on HD for longer than 6 weeks may produce better results.

Longitudinal survey of apolipoproteins and atherogenic risk in hemodialysis and continuous ambulatory peritoneal dialysis patients.

Total cholesterol (TC) and HDL-cholesterol (HDL-C) have been studied in dialysis patients, but a systematic study of apolipoprotein (apo) A-I, apo B, and the anti-atherogenic risk ratio, apo A-I/apo B, over time has not been done. We report lipid and apo values over 12-14 months in 55 hemodialysis (HD) and 40 continuous ambulatory peritoneal dialysis (CAPD) patients. For HD patients, mean TC fell, but not significantly, and HDL-C and TC/HDL-C, an atherogenic risk ratio, did not change over time. Apo A-I/apo B correlated with months on HD (r = 0.30, p less than 0.04) and rose significantly (p less than 0.005) during the study period. Paired t-test analysis by race, gender, and diabetes showed that in nondiabetics, apo A-I rose, apo B fell (p less than 0.05), and apo A-I/apo B improved (p less than 0.002). Similar trends were seen in all subgroups except for diabetics. For CAPD patients, total months of treatment correlated with TC/HDL-C (r = 0.46, p less than 0.05) and with HDL-C (r = -0.53, p less than 0.02), but paired t-test analysis of longitudinal data showed no significant changes in TC, HDL-C, apo A-I, apo B, TC/HDL-C, or apo A-I/apo B. The lipoprotein patterns of all patients who died were not significantly different from those of the surviving patients. Our longitudinal data reveal that lipids, apolipoproteins, and risk ratios remain stable over time on HD and CAPD. In fact, the anti-atherogenic index of apo A-I/apo B improved in HD patients, especially in nondiabetics.

Predictors of survival in continuous ambulatory peritoneal dialysis patients: the importance of prealbumin and other nutritional and metabolic markers.

Serum markers of visceral and somatic protein status are directly correlated with the survival of hemodialysis patients. We prospectively examined the relationship of single baseline levels of serum albumin, cholesterol, creatinine, and urea to prognosis in 80 continuous ambulatory peritoneal dialysis patients monitored for up to 33 months. Other variables tested included age, race, gender, diabetes, cause of end-stage renal disease, and number of months on dialysis. The Cox proportional hazards model was used to determine independent predictors of mortality risk. In a subgroup of 33 patients followed for up to 21 months, the predictive value of single measurements of baseline serum prealbumin also was tested. Overall, 29 patients died during the study. Independent predictors of mortality risk included serum albumin (P = 0.024) and creatinine (P = 0.006), diabetes (P < 0.06), prior months on dialysis (P < 0.05), and older age (P = 0.18). In a subgroup of 33 patients with prealbumin measurements, there were nine deaths over 21 months. A serum prealbumin level less than 30 mg/dL was associated with an increased mortality rate compared with higher prealbumin values (odds ratio, 3.8; P = 0.09). We conclude that markers of visceral and somatic nutrition are important and independent predictors of mortality risk in continuous ambulatory peritoneal dialysis patients. We are unable to suggest whether the relationship is causal or causative. However, the predictive value of these single baseline markers were valid for up to 33 months. We also note that patients with diabetes are at an increased risk even after adjusting for somatic and visceral protein status.

Comparative survival of 673 patients with chronic uremia treated with renal transplantation (RT) and maintenance hemodialysis (MD).

We performed a retrospective analysis of 673 patients with chronic uremia treated from 1973 through 1978. While MD had a high mortality during the first year, overall mortality was less than 50% in 5 yrs. Diabetics treated by MD have lower survival than do nondiabetics, though 14% may live for 4 yrs. Our local experience with RT has not been good with only 17% of 69 patients living through their third post-transplant year. Until the reasons(s) for our unsatisfactory transplant experience is discerned and remedies introduced, it can be expected that patient preference will be biased toward MD.

The uremic dyslipidemia: a cross-sectional and longitudinal study.

Patients on maintenance hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) exhibit numerous disturbances of serum lipids and apoproteins that may contribute to their high cardiovascular mortality. Cross-sectional studies have found that lipid levels are inversely related to time on dialysis. However, it is not known whether this association is the result of the attrition of hyperlipidemic patients or a decrease in lipid levels over time in all patients. Additionally, few studies have investigated the effect of dialysis modality on the lipoprotein disturbances of uremia adjusting for the confounding influences of demographics, or nutritional and endocrine status. To address these issues, we undertook a cross-sectional and longitudinal study of lipids, apoproteins, and atherogenic risk ratios in patients maintained on HD and CAPD. Patients were enrolled in annual cohorts from 1987 to 1990 and monitored until 1991. A total of 196 HD and 77 CAPD patients were studied. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), apoprotein (apo) A-I, and apo B were measured on enrollment and remeasured annually in survivors through 1990. Using multivariate methods, we examined the relationship of the lipids, apoproteins, their respective ratios, and their changes over time, to a broad range of clinical factors and to mortality. Compared with HD patients, CAPD patients had significantly higher TC, apo A-I, and apo B, and a significantly lower apo A-I/apo B ratio. Serum albumin correlated directly with TC and apo B and inversely with apo A-I/apo B. For patients with normal serum albumin (> or = 3.5 g/dL [35 g/L]), CAPD patients had a significantly higher TC/HDL-C than HD patients; otherwise the ratios were similar for CAPD and HD. Independent influences on lipoprotein levels in HD and CAPD patients were also demonstrated for race, gender, and diabetes, but not for parathyroid hormone (PTH) levels. For both dialysis modalities, patients who died had significantly lower TC and apo B, and significantly higher apo A-I/apo B throughout their entire courses compared with survivors. In the subset of patients followed longitudinally for 2 or more years, apo B tended to decrease with time, but TC, HDL-C, and apo A-I were stable. The longitudinal changes in lipoproteins did not correlate with outcome or other factors. In conclusion, CAPD patients have more atherogenic lipoprotein profiles than HD patients. Improved visceral protein nutritional status, as defined by serum albumin level, is associated with hyperlipidemia and, especially vor CAPD, worsened atherogenic risk ratios.(ABSTRACT TRUNCATED AT 400 WORDS)

Prealbumin and lipoprotein(a) in hemodialysis: relationships with patient and vascular access survival.

The high morbidity and mortality of hemodialysis patients has led to a search for early markers of risk. Because cardiovascular and nutritional risk are prevalent in this population, we examined the prognostic value of the serum levels of two markers of risk in the general population: (1) lipoprotein(a) [Lp(a)], a low-density lipoprotein-like particle linked to myocardial infarction and coronary bypass stenosis, and (2) prealbumin, a marker of visceral protein status, with a shorter half-life than that of serum albumin. Baseline demographics, clinical information, dialysis prescription, and serum biochemistry measurements of 125 hemodialysis patients followed for up to 14 months were recorded on enrollment. Vascular access events and deaths were recorded prospectively. The hypotheses tested were that increased serum Lp(a) levels would predict cardiovascular mortality and vascular access stenosis and thrombosis, and that reduced serum prealbumin levels would predict mortality risk independently of established risk predictors. Cross-sectional analysis of serum Lp(a) demonstrated a skewed distribution with a median value of 38.3 mg/dL (upper tertile, > or = 57 mg/dL). Lipoprotein(a) was significantly higher in black patients (P < 0.001) and was significantly correlated (P < 0.005) with total cholesterol and apoprotein B (apoB), but not with a history of prior coronary disease. Serum prealbumin was strongly correlated with serum albumin (r = 0.49, P < 0.001). However, prealbumin correlated (P < 0.001) more strongly with other serum nutrition markers (total cholesterol, apoB, creatinine, urea) than did serum albumin. Fourteen-month cumulative survival was 80%. Age, diabetes, and serum levels of albumin, prealbumin, creatinine, total cholesterol and apoB, but not Lp(a), were correlated with survival in univariate analysis. Using the Cox proportional hazards model, independent predictors of mortality risk were prealbumin less than 15 mg/dL versus higher values (relative risk [RR] = 4.48, P < 0.01), apoB (RR = 0.97 per 1 mg/dL increase, P < 0.02), creatinine less than 10 mg/dL versus higher values (RR = 3.51, P = 0.04), and age (RR = 1.04 per year, P = 0.10). Thirty-eight patients experienced at least one vascular access thrombosis (n = 33) or stenosis (n = 5) during the study. Patients with Lp(a) > or = 57 mg/dL had decreased vascular access event-free survival compared with patients with Lp(a) less than 57 mg/dL (56% v 73%, P < 0.06). This trend was increased in magnitude and statistically significant for white and Hispanic patients (31% v 79%, P < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Fall of cholesterol with time on dialysis: impact on atherogenicity.

The majority of patients treated for chronic renal failure die from cardiovascular complications. Lipid abnormalities in this group are thought to contribute to this high mortality. The authors have shown that hemodialysis patients with longer months on dialysis tend to have lower total cholesterol (TC) levels. This study extends data to examine lipid disturbances in 53 continuous ambulatory peritoneal dialysis (CAPD) and 126 hemodialysis patients using multivariate analysis. Longitudinal values after 9-10 months were measured in 16 CAPD patients and 52 hemodialysis patients. Analysis of covariance for all patients demonstrated an inverse correlation of TC (p = 0.003), high-density lipoprotein (HDL) cholesterol (p = 0.01), and apolipoprotein A-I levels (p less than 0.02) with months on dialysis. In addition, the TC level was higher in women (p less than 0.001) and CAPD patients (p less than 0.001), and correlated with age (p = 0.02) and albumin (p less than 0.001). HDL cholesterol was higher in blacks (p less than 0.001) but was not affected by gender, dialysis modality, age, or albumin. Diabetic status, serum parathyroid hormone, and blood pressure were not significant variables for TC or HDL-C. The atherogenic risk indicators, TC/HDL cholesterol (p less than 0.001) and apolipoprotein B (p less than 0.02) were higher in whites than in blacks. Longitudinal study revealed lower TC levels in individual hemodialysis patients (p less than 10(-6) by paired t-test), the fall being greater for patients with fewer total months on dialysis (p less than 0.04, by analysis of covariance). CAPD patients had no change in TC by paired t-test.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipid abnormalities in black renal patients.

Racial differences in lipoprotein (LP) and cardiovascular (CV) abnormalities have been noted in the general population and in the population of patients on dialysis. Few studies have investigated the interaction of race and LP and CV disturbances in other renal disease groups. We studied lipid profiles and risk ratios (total cholesterol (TC)/high density lipoprotein-cholesterol) (HDL-C) and apolipoprotein (apo) A-I/apo B (A-I/B)) and the influence of race across a spectrum of renal disease groups (normal renal function (NRD), nephrotic range proteinuria (NS), hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD), post-transplant (TR), renal insufficiency (RI)). We also performed a longitudinal study of lipid profiles in patients with end stage renal disease (ESRD) and the relationship of these profiles to race and other variables. There was a general tendency towards a better CV risk profile for blacks than whites in all the groups. Blacks tended to have lower TC, higher HDL-C, lower TC/HDL-C, higher apo A-I, lower apo B, and higher A-I/B. We analyzed four yearly cross-sections of the HD and CAPD populations using ANOVA with adjustment for appropriate covariates. Whites had lower HDL-C and a higher TC/HDL-C risk ratio than blacks. HD patients had lower TC, TC/HDL-C, apo A-I, and apo B than CAPD patients, and women had higher TC than men. When lipid profiles were studied longitudinally by yearly intervals, no consistent significant changes were seen, but over two years, levels of apo B fell and A-I/B rose. Race had no significant effect on any of the longitudinal data.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipids in diabetic and nondiabetic hemodialysis and CAPD patients.

To examine the question of "accelerated atherogenesis" in ESRD patients, the authors conducted a lipid survey among their hemodialysis and CAPD populations and evaluated data relevant to the lipid and diabetic status of these groups. Interestingly, longer duration of hemodialysis in nondiabetic patients was associated with lower cholesterol but not HDL, which may reflect diminished cardiac risk and mortality in the long-term survivors. Diabetic patients showed lower HDL but no cholesterol change with longer duration on hemodialysis. Type I diabetics showed the highest HDL and lowest risk ratio and a strong inverse correlation between PTH and HDL. This study highlights the role of lipids in the atherogenesis of uremia and serves as a baseline for a longitudinal study.