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Biomedical subjects

P S Avasthi

Publications and source records attributed to P S Avasthi.

At least 19 recordsLinked to original sources

Serum albumin in continuous peritoneal dialysis: its predictors and relationship to urea clearance.

We investigated the predictors of serum albumin and the relationship between serum albumin and urea kinetic indices in continuous peritoneal dialysis (CPD). In a training set (TS) of 143 urea kinetic studies performed in 92 CPD patients, stepwise logistic regression identified high/high-average peritoneal solute transport, diabetes, advanced age and high daily drain volume normalized by body water as predictors of low serum albumin (< 35 g/liter). This analysis was then substantiated in a validation set (VS) of 187 kinetic studies performed in another 102 CPD patients. The calculated area under the receiver operating characteristic (ROC) curve by this logistic regression model was 0.782 (95% CI, 0.745 to 0.819). Logistic regression was repeated in the TS using only the first kinetic study from each patient, and it identified high/high-average peritoneal solute transport, diabetes, and advanced age as predictors of low albumin. Using only the first kinetic study from each patient in the VS, the second logistic regression model calculated an area under the ROC curve equal to 0.850 (95% CI, 0.810 to 0.890). The relative risk (RR) of serum albumin < 35 g/liter was computed for all kinetic studies after combining the TS and the VS and using non-diabetic CPD subjects aged < or = 61 years with low/low average peritoneal solute transport as the reference group. The RR with only one risk factor present ranged from 1.076 (age > 61 years) to 6.792 (high/high-average transport). The RR with two risk factors present ranged from 5.200 to 9.729. The RR with all three risk factors present was 9.100 (95% CI, range 3.923 to 21.111). A subset of 37 CPD patients had a second urea kinetic study 8 +/- 5 months after an increase in the amount of dialysis due to low urea clearance and/or uremic symptoms. The weekly KT/V urea increased from 1.40 +/- 0.24 to 2.10 +/- 0.31 after the increase in the CPD dose. With the increase in dialysis, the protein catabolic rate increased substantially; however, the mean serum albumin remained stable (from 33.9 +/- 4.6 to 33.3 +/- 6.2 g/liter; decrease 18; increase 15; same 4). In comparison to the subjects who had a decrease in serum albumin after the increase in KT/V, those with the increase in serum albumin were younger (44.2 +/- 11.2 vs. 54.3 +/- 16.2 years, P = 0.044) and had a higher serum urea after the increase in the dose of CPD (22.4 +/- 7.8 vs. 17.0 +/- 6.0 mmol/liter, P = 0.037). We conclude that the major predictors of low serum albumin in CPD are advanced age, diabetes, and high/high-average peritoneal solute transport, but not urea kinetic studies. An increase in the dose of dialysis does not cause a consistent rise in serum albumin in underdialyzed CPD subjects. However, a subset of younger patients may be able to increase their serum albumin in response to the increase in KT/V.

Adult

Gastroparesis in diabetics on chronic dialysis: clinical and laboratory associations and predictive features.

Clinical and laboratory features and risk factors for diabetic gastroparesis (DGP) were investigated in 226 diabetics on chronic dialysis; 106 subjects (43%) had DGP diagnosed by persistent vomiting improved with the use of prokinetic agents and 120 (control group) had no clinical DGP. Type 1 diabetics had DGP more frequently than type 2 diabetics (70 vs. 37%). The DGP group had longer duration of diabetes (21 +/- 8 vs. 13 +/- 6 years), higher frequency of diabetic orthostatic hypotension (95 vs. 33%), enteropathy (49 vs. 5%), blindness (52 vs. 23%), myocardial infarction (86 vs. 42%), extremity gangrene (54 vs. 27%) and cerebrovascular accidents (43 vs. 25%), lower serum albumin 32.3 +/- 3.9 vs. 35.4 +/- 3.8 g/l), urea (24.0 +/- 5.5 vs. 25.5 +/- 5.5 mmol/l) and creatinine (710 +/- 210 vs. 820 +/- 220 mumol/l), and higher serum TCO2 (20.9 +/- 3.1 vs. 19.8 +/- 2.7 mmol/l) than the control group (all differences significant at p +/- 0.004). Glycemic control was adequate in 24% of the DGP group subjects and 83% of the control subjects (p < 0.001). Annual hospitalization rate was 49 +/- 48 days/patient in the DGP group and 16 +/- 27 days/patient in the control group (p < 0.001). Median patient survival was 24 +/- 2 months in the DGP group and 61 +/- 9 months in the control group (p < 0.0001). Logistic regression identified long duration of diabetes and poor glycemic control as risk factors for DGP. In diabetics on dialysis, DGP is associated with high frequency of other diabetic complications, low serum albumin and creatinine, and high morbidity and mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

The minimal dose of dialysis required for a target KT/V in continuous peritoneal dialysis.

This study attempted to define the minimal dose of dialysis needed to produce a target KT/V in continuous peritoneal dialysis (CPD). In a training set of 143 clearance studies performed in 92 CPD patients, logistic regression identified low urine volume (UV) and low dialysate drain volume normalized by body water (DV/V) as predictors of weekly KT/V urea < or = 1.70. Solution of the regression equation with UV fixed at 0.00 1/24 h and at different probabilities of low KT/V provided a series of minimal DV/V values consistent with weekly KT/V > or = 1.70 in anuria. The accuracy of the logistic regression model and of the DV/V cut-offs was tested in a validation set (VS) of 189 urea kinetic studies performed in another 102 CPD patients. In the VS, the area under the Receiver Operating Characteristic curve generated by the regression model was 0.832 (95% Confidence Interval: 0.798-0.866). The DV/V cut-off value of 0.301 per 24 h, calculated by solving the regression model at p = 0.442 and with UV = 0, identified studies with weekly KT/V < 1.70 with a sensitivity of 89.3% and a specificity of 78.1% in anuric VS subjects (n = 60). Use of only the first urea kinetic study from each patient did not modify the predictors of KT/V or the cut-off values derived from solution of the regression model. The DV/V cut-off of 0.324 per 24 h, derived from the logistic regression model predicting KT/V < or = 1.90, identified KT/V < 1.90 in VS anuric subjects with a sensitivity of 94.3% and a specificity of 81.0%. Low UV and DV/V predict low KT/V urea in CPD. Prescribed 24 h exchange volume in anuric CPD subjects should be calculated to produce DV/V values exceeding 0.301 1/24 h per 1 body water for a KT/V of 1.70 and 0.324 1/24 h per 1 body water for a target weekly KT/V of 1.90.

Creatinine

Clinical associations of glycemic control in diabetics on CAPD.

Diabetic control in 110 diabetics (39 type I and 71 type II), who had been on continuous ambulatory peritoneal dialysis (CAPD) for at least 3 months, was considered good (group G, n = 63) or poor (group P, n = 47) if > 50% or < or = 50% of glucose measurements, respectively, were within 3.3-11.1 mmol/L. Compared to group P, group G had more type I diabetics and fewer type II diabetics; higher serum cholesterol and lower serum creatinine; higher rates of blindness, autonomic neuropathy, congestive heart failure, myocardial infarction, cerebrovascular accidents and extremity gangrene; higher annual rates of peritonitis (1.47 +/- 1.31 vs 0.98 +/- 1.19 episodes/patient-year), exit-site/tunnel infection (0.83 +/- 1.14 vs 0.39 +/- 0.68 episodes/patient-year), and catheter loss (0.81 +/- 0.59 vs 0.39 +/- 0.52 episodes/patient-year); and longer hospitalization (38 +/- 31 vs 14 +/- 15 days yearly). All differences were significant at p = 0.05 or lower. According to life-table analysis, median patient survival was 25 +/- 3 months in group P and 85 +/- 17 months in group G (p < 0.0001). Technique survival was 14 +/- 2 months for group P and 28 +/- 4 months for group G (p < 0.0001). Good diabetic control in diabetics on CAPD is associated with better outcome and constitutes, therefore, a desirable therapeutic goal.

Blood Glucose

Hypoglycemia in diabetics on dialysis with poor glycemic control: hemodialysis versus continuous ambulatory peritoneal dialysis.

Eight diabetic men with poor glycemic control, probably worsened by severe congestive heart failure and gastroparesis, were sequentially dialyzed by CAPD and hemodialysis. Mean blood glucose concentration, blood glycosylated hemoglobin, and insulin dose were higher during CAPD than during hemodialysis. Among blood glucose determinations, however, the frequency of hypoglycemia (glucose less than 3.3 mmol/L) was higher during hemodialysis (13.2 +/- 8.9%) than during CAPD (2.8 +/- 2.1% p = 0.012), whereas the frequencies of hyperglycemia (glucose greater than 11.1 mmol/L) and euglycemia (glucose between 3.5 and 11.1 mmol/l) did not differ between the two dialysis modalities. Furthermore, hypoglycemia was severe during hemodialysis and was associated with two deaths. There were no deaths linked to abnormalities in blood glucose concentration during CAPD. When hypoglycemia is frequent in diabetics with poor glycemic control, CAPD is preferable to hemodialysis.

Blood Glucose

Intraperitoneal thrombolytic agents in relapsing or persistent peritonitis of patients on continuous ambulatory peritoneal dialysis.

Urokinase or streptokinase was instilled intraperitoneally as an adjunct to the antibiotic therapy in 16 episodes of relapsing or persistent peritonitis in CAPD patients. In eight patients the combination of antibiotics and intraperitoneal thrombolytic agents resulted in clearing of the infection with no recurrences. The treatment failed in eight other patients, who had their peritoneal catheters removed. Six of the last eight patients had either abdominal wall abscesses or persistence of the bacteria on the wall of the peritoneal catheter. Elevated post-intraperitoneal instillation peritoneal fluid neutrophil counts and positive post-instillation peritoneal fluid cultures predicted failure of the intraperitoneal instillation of thrombolytic agents in most instances. Intraperitoneal instillation of urokinase or streptokinase may help cure approximately 50% of the episodes of relapsing for persistent peritonitis. Post-instillation peritoneal fluid cell counts and cultures should be monitored. Radiologic investigation for abdominal wall or intraabdominal abscesses is indicated if intraperitoneal instillation of urokinase or streptokinase fails to eradicate peritonitis.

Anti-Bacterial Agents

Vascular disease: the critical risk factor for mortality in older patients on CAPD.

Clinical course, complications and outcome were analyzed in 75 patients (14 women, 61 men) who started CAPD at age 55 years or older (55-81). These patients were separated in three groups. Group A patients had high risk for vascular disease (diabetes, hypertension, N = 45), group B patients had a presumed lower risk for vascular disease (primary renal disease, N = 22), and group C patients had miscellaneous conditions (N = 8). Group A was compared to group B. Patient and technique survival was statistically higher for group B than for group A. The rates of peritoneal dialysis related complications (peritonitis, tissue infections, catheter loss, hernias) were comparable between groups A and B. Hernias were seen frequently in all groups and had severe sequellae, including discontinuation of CAPD. Catastrophic vascular events were also seen in all groups, but the frequency of such events, particularly of catastrophic vascular events of the limbs, was statistically higher in group A than in group B. Vascular disease accounted for the majority of deaths in all groups. Four patients died from cardiovascular instability soon after changing from CAPD to hemodialysis. In conclusion, vascular disease is the major factor limiting survival in older CAPD patients. CAPD is superior to hemodialysis for a relatively small fraction of older patients with severe cardiovascular instability.

Aged

Femoral neck fractures in patients receiving long-term dialysis.

The morbidity and mortality of 11 femoral neck fractures were analyzed to compare operative and conservative management of femoral neck fractures in dialysis patients. All fractures occurred in older men with severe cardiac, pulmonary, gastro-intestinal, and neurologic conditions and with advanced renal osteodystrophy. Six of the seven operated patients survived the surgery and achieved varying degrees of ambulation. Stability of the operated hip was excellent in each case. Post-operative complications included transient confusional state related to narcotics, pneumonia, decubitus ulcers, and severe hypoalbuminemia. All four patients who were managed conservatively died from complications of the fracture. Progressive deterioration was noted in each nonoperated patient, with confusion caused by narcotics and analgesics, pneumonia, hepatic coma, decubitus ulcers, severe depression, and severe hypoalbuminemia. Therefore, operative management was superior to conservative management for femoral neck fractures of patients receiving chronic dialysis with multiple medical problems and advanced renal osteodystrophy. Narcotics must be used with great caution, and efforts should be directed toward prevention of malnutrition and decubitus ulcers.

Aged

Glycosylated hemoglobin measured by affinity chromatography in diabetic and nondiabetic patients on long-term dialysis therapy.

We measured by affinity chromatography glycosylated hemoglobin levels in the blood of 43 diabetic and nondiabetic patients (139 measurements) on long-term dialysis therapy (continuous ambulatory peritoneal dialysis and hemodialysis) to determine the usefulness of this method of estimating glycemic control in diabetic persons on dialysis therapy. In nondiabetic patients, glycosylated hemoglobin levels were within the normal range (4.0% to 6.8% of total blood hemoglobin levels) for both continuous ambulatory peritoneal dialysis and hemodialysis. Glycosylated hemoglobin values correlated significantly with fasting blood glucose levels, serum urea levels, and serum total carbon dioxide content. By stepwise regression, fasting blood glucose values accounted statistically for .54 of the variability (R2) in glycosylated hemoglobin. The contribution of the other variables to this variability was minimal. In 9 diabetic patients (3 on hemodialysis), glycosylated hemoglobin levels correlated significantly with average daily blood glucose levels. Regression of the fasting blood glucose value on glycosylated hemoglobin was similar between continuous ambulatory peritoneal dialysis and hemodialysis. Measuring glycosylated hemoglobin levels by affinity chromatography is a suitable method for assessing glycemia in dialysis patients.

Blood Glucose

Clinical significance of hemodialysis performed during the course of continuous ambulatory peritoneal dialysis.

We analyzed causes and clinical associations of hemodialysis performed during the course of CAPD in 71 patients (34 diabetic) on CAPD between 1978 and 1988. Thirty seven patients had at least one hemodialysis during CAPD. Causes (multiple for some patients) included poor compliance with CAPD (20 patients), peritoneal catheter loss from infection (16 patients), and miscellaneous other conditions (18 patients). Hemodialysis rates were similar between diabetic and non-diabetic CAPD patients. Compared to non-hemodialyzed patients, CAPD patients hemodialyzed for poor compliance had higher rates of peritonitis (one episode per 8.3 patient months vs one episode per 23.4 patient months, p less than 0.001) and catheter loss (one loss per 27.7 patient months vs one loss per 112.0 patient months, p less than 0.001), and exhibited a trend towards more deaths (annual mortality 30.9% vs 14.3%, p = 0.067). Hemodialysis performed in CAPD patients because of poor compliance is associated with higher rates of peritonitis and catheter loss, and, probably, with increased mortality.

Adult

Effect of a high-protein meal on blood flow to transplanted human kidneys.

Renal blood flow in normal adults increases after protein ingestion. The mechanisms that create this hyperperfusion are unclear. A neurogenic factor in humans has not been definitively ruled out. Accordingly, we tested the hypothesis that a high-protein meal significantly increases renal blood flow to the denervated human kidney. We studied 11 transplant recipients (TR) with denervated kidneys and 4 kidney donors (KD) with a single innervated kidney. All subjects had normal urinalysis. Using noninvasive Doppler flowmetry that was previously validated, we determined renal blood flow (RQ, ml/min) after a 12-hr fast (F) and 1, 2, and 3 hr after a high-protein meal (500 ml) of 150 g protein, 30 g fat, and 30 g carbohydrate. The RQ (mean +/- SD, ml/min) at fasting and at 1, 2, and 3 hr postprandially was 409 +/- 100, 446 +/- 100, 493 +/- 122 (P less than 0.05 vs. F), and 500 +/- 123 (P less than 0.05 vs. F), respectively, for the TR, and was 654 +/- 60 (P less than 0.05 vs. TR), 667 +/- 86 (P less than 0.05 vs. TR), 776 +/- 80 (P less than 0.05 vs. F and TR), and 809 +/- 81 (P less than 0.05 vs. F and TR) for KD. We conclude that RQ in TR increases significantly after protein ingestion. Thus, in the noninstrumented, unanesthetized human with a transplanted kidney, neural control is not a factor in the increase in renal blood flow after a high protein meal.

Cyclosporins

The anionic matrix at the rat glomerular endothelial surface.

The anionic macromolecules at the glomerular endothelial cell surface are visualized only when stained with cationic stains. We investigated the arrangement and composition of this anionic matrix at the luminal surface. Rat kidneys were perfused with anionic ferritin (pI 4.5), ferritin (pI 7.4), or cationized ferritin (CF, pI 8.3). Anionic ferritin (pI 4.5) did not bind to the capillary wall, ferritin (pI 7.4) bound discontinuously only to the laminae rarae of the basement membrane, but cationized ferritin (CF, pI 8.3) bound as a thick continuous layer to the cell plasmalemma and bound to the anionic matrix in the fenestral spaces. These observations show that an anionic matrix lines the entire capillary lumen surface, fills the fenestrae, and is interposed between the blood and the basement membrane at the fenestrae. The anionic constituents at the capillary luminal surface were identified by in vivo digestion with specific enzymes. Absence of CF binding following digestion with specific enzymes was taken to indicate the presence of the particular glycoprotein known to be susceptible to the enzyme used. Neuraminidase digestion revealed that anionic sites over the surface plasmalemma are mainly from sialoproteins. In contrast, the matrix in fenestral channels contains heparan sulfate, hyaluronic acid, and sialoproteins. Papain digestion showed no glycolipids at the luminal surface. The functions of this continuous anionic layer located at the luminal surface of glomerular capillaries have not yet been established.

Animals

The anionic sites at luminal surface of peritubular capillaries in rats.

Anionic sites have been demonstrated in the basement membranes of peritubular capillaries. The anionic barrier function of peritubular capillary wall has been ascribed to these sites. Fenestrated capillaries in other organs have anionic sites in the endothelial cell glycocalyx and at the luminal surface of the fenestral diaphragms. The purpose of this study was to map anionic sites at the luminal surface of peritubular capillaries and to assess whether a concentration gradient for albumin exists across the endothelium. Partial chemical characterization of these anionic sites was done by in vivo enzymatic degradation. The difference in distribution of albumin following enzyme digestion was also studied. The binding of cationized ferritin to the luminal surface indicated that the rat peritubular capillaries have anionic sites along the entire luminal surface of the endothelial cell, including the fenestral diaphragms. Partial biochemical characterization of these sites shows that the sites in the glycocalyx are mainly from neuraminic acid, while the fenestral diaphragms have mainly heparan sulfate proteoglycans. Intravascular albumin extended to the endothelial luminal plasmalemma and to the luminal surface of fenestral diaphragms. Digestion with heparitinase was associated with the leakage of albumin outside the capillary wall. These findings suggest that the anionic surface of fenestrae constitutes a charge barrier of the peritubular capillaries.

Animals

Noninvasive Doppler assessment of human postprandial renal blood flow and cardiac output.

We compared the effects of protein, carbohydrate, or water ingestion on human renal blood flow (RBF) and cardiac output (CO). We validated and applied a noninvasive ultrasonic Doppler method to measure blood velocities and lumen diameters in the right renal artery and the ascending aorta of five healthy adults. From these measurements, we calculated the average RBF and CO over five cardiac cycles. Normalizing to body surface area, renal blood flow index to one kidney (RI) and cardiac index (CI) were calculated. The percentage of the CI distributed to a single kidney was determined as %CI = RI/CI. Subjects were studied randomly on three separate days after ingestion of each of the following equivolume (500 ml) meals: 1) 150 g protein, 30 g fat, and 30 g carbohydrate (P); 2) 150 g carbohydrate, 30 g fat, and 30 g protein (C); and 3) water. Data were obtained after 12 h of fasting and at 30, 60, 90, 120, 180, and 240 min postprandially. Analysis of covariance revealed significant (P less than 0.05) increases from fasting levels in postprandial RI at 90 to 240 min after P. Postprandial RI with P was significantly higher than with C at 180 and 240 min. Postprandial %CI with P and C decreased significantly from the fasting value at 30 to 180 min. Heart rate and mean arm cuff blood pressure did not change significantly with any diet. Results suggest that the protein-rich meal evokes a more sustained increase in postprandial RI than the carbohydrate rich meal. Despite the increase in postprandial RI, the percentage of cardiac output perfusing a kidney declines similarly with both diets.

Adult

Temporal profile of serum potassium concentration in nondiabetic and diabetic outpatients on chronic dialysis.

We analyzed routine serum potassium concentration measurements and conditions temporally associated with abnormalities in potassium concentration in outpatients on chronic hemodialysis (136 nondiabetics, 36 diabetics) and continuous ambulatory peritoneal dialysis (16 nondiabetics, 10 diabetics). The following potassium concentration frequencies were found: prehemodialysis, nondiabetics: normal 51.3%, severe hyperkalemia (greater than 6.0 mmol/l) 10%, severe hypokalemia (less than 3.0 mmol/l) 0.3%; diabetics: normal 57.8%, severe hyperkalemia 8.7%, severe hypokalemia 0.5%. Peritoneal dialysis, nondiabetics: normal 73.7%, severe hyperkalemia 0.6%, severe hypokalemia 4.9%; diabetics: normal 72.5%, severe hyperkalemia 0.9%, severe hypokalemia 2.9%. Normokalemia and severe hypokalemia were significantly (chi 2 test) more frequent in peritoneal dialysis than in prehemodialysis, whereas severe hyperkalemia was more frequent in prehemodialysis serum samples. No difference was found between nondiabetics and diabetics for either form of dialysis. 50% of prehemodialysis episodes of hyperkalemia were diet-induced. Hyperkalemic drugs and anuria were not associated with a higher risk of prehemodialysis hyperkalemia, but each one of 3 abnormalities, very high BUN (greater than 40 mmol/l), metabolic acidosis (TCO2 less than 15 mmol/l) and, in diabetics, severe hyperglycemia (serum glucose greater than 30 mmol/l), was associated with a statistically higher risk of hyperkalemia.

Diabetes Mellitus, Type 1