De novo pyrimidine nucleotide biosynthesis in isolated rat glomeruli

De novo pyrimidine nucleotide biosynthesis in isolated rat glomeruli. Uracil ribonucleotide–sugars and aminosugars are required for glomerular basement membrane (GBM) biosynthesis. Since these nucleotides are metabolic derivatives of uridine 5′-triphosphate (UTP), we have studied the cellular pools of uridine 5′-diphosphoglucose (UDPG), uridine 5′-diphosphoglucuronic acid (UDPGA), uridine 5′-diphospho-N-acetyl glucosamine (UDPAG) and UTP, and measured UTP synthesis de novo in isolated glomeruli incubated in vitro. Improved techniques for nucleotide quantitation were established and the optimal conditions for glomerular isolation and incubation determined. Substantial quantities of uracil ribonucleotide coenzymes and an active utilization of orotate for the synthesis of pyrimidine nucleotides were demonstrated. UTP synthesis and the pools of UDPG and UDPG A varied markedly with changes in the experimental conditions. The adverse effects of suboptimal conditions were more apparent in glomeruli from diabetic animals than in controls. The use of suboptimal conditions could provide misleading information on GBM metabolism in isolated glomeruli since uracil ribonucleotide coenzyme availability might be reduced

Racial Differences in the Incidence of Steroid Diabetes in Renal Transplant Patients

We have studied the development of steroid-induced diabetes in a population of 143 renal allograft recipients who were nondiabetic before transplantation. Steroid-induced diabetes developed In 9.8% of patients. However, in blacks its incidence was significantly higher than in whites (17.3% vs 5.5% respectively; p \u3c .01). The development of steroid-induced diabetes was not associated with a higher frequency of HLA-B8 or HLA-Bw15 in either race. In black graft recipients, HLA-B14 was significantly more frequent (p \u3c .001) among those who developed steroid-induced diabetes than in insulin-dependent diabetic (Type I) and nondiabetic recipients. The clinical course of patients with steroid-induced diabetes has been similar to that of noninsulin-dependent diabetics (Type II)

Estimation of body fluid changes during peritoneal dialysis by segmental bioimpedance analysis

Estimation of body fluid changes during peritoneal dialysis by segmental bioimpedance analysis.BackgroundCommonly used bioimpedance analysis (BIA) is insensitive to changes in peritoneal fluid volume. The purpose of this study was to show, to our knowledge for the first time, that a new segmental approach accurately measures extracellular fluid changes during peritoneal dialysis (PD).MethodsFourteen stable PD patients were studied during a standard exchange with fluids of known conductivity. Bioimpedance was continuously measured in the arm, trunk, and leg and from wrist to ankle. Volume changes were calculated using both a newly developed sum of segmental BIA (SBIA) and current wrist-to-ankle BIA (WBIA) and were compared with actual volume changes measured gravimetrically.ResultsWhen 2.19 ± 0.48 L were removed from the peritoneal cavity during draining, 95.2 ± 13.8% of this volume was detected by SBIA compared with only 12.5 ± 24.3% detected by WBIA. When 2.11 ± 0.20 L of fresh dialysate was infused into the peritoneal cavity during filling, 91.1 ± 19.6% of this volume was detected by SBIA compared with only 8.8 ± 21.1% detected by WBIA.ConclusionThe good agreement between measured and calculated data using SBIA was due to: (a) improved placement of electrodes, (b) estimation of trunk extracellular volume based on a new algorithm, and (c) consideration of changes in dialysate conductivity. Correct estimation of fluid volume in the trunk is a prerequisite for applications in which direct analysis of fluid changes cannot be performed such as with peritoneal equilibration tests and continuous flow PD

Renal Involvement in Type 2 Diabetes Mellitus: A Clinicopathologic Study of the Henry Ford Hospital Experience

To better understand renal dysfunction in type 2 diabetes mellitus, we studied the clinical and autopsy findings in comparable cohorts of 108 diabetic and 77 nondiabetic patients. In the diabetic group, no differences were noted between black and white patients in blood glucose concentrations, mean blood pressure, or the prevalence of diabetic glomerulosclerosis. However, the prevalence of renal insufficiency was significantly greater (P = 0.002) in black diabetics (58%) than in white diabetics (35%). black controls (28%), and white controls (20%). Logistic regression analysis demonstrated a significant association of renal insufficiency with diabetes (P = 0.006) and race (P = 0.032). butnot with mean blood pressure, age, or sex. An additional nonspecific glomerular lesion commonly found was global sclerosis. The occurrence of this lesion was significantly greater (P = O.OOI) in black diabetics (42% ± 5%) than in white diabetics (26% ± 5%), black controls (19% ± 4%), and white controls (21% ± 4%), and was highly correlated (P = O.OOI) to serum creatinine concentrations. In patients with serum creatinine concentrations lower than 1.6 mg/dL, kidney weight was significantly greater (P = 0.03) in diabetics with diabetic glomerulosclerosis (405 ± 32 g) as compared to those without it (300 ± 25 g) or to control patients (329 ± 13 g). This study demonstrates that the overall prevalence of diabetic glomerulosclerosis in this group of type 2 diabetics is 45%, and that renal enlargement is present in these patients prior to the development of significant renal insufficiency. In addition, renal insufficiency and end-stage renal failure are more common in black than in white diabetics

Inflammation and dietary protein intake exert competing effects on serum albumin and creatinine in hemodialysis patients

Inflammation and dietary protein intake exert competing effects on serum albumin and creatinine in hemodialysis patients.BackgroundCross-sectional studies have shown an inverse correlation between serum C-reactive protein (CRP) and serum albumin concentration in hemodialysis patients. The net effects of inflammation and dietary protein intake on nutritional markers over time are unknown.MethodsTo explore the effects of CRP and normalized protein catabolic rate (nPCR) on serum albumin and creatinine, we analyzed six consecutive months of laboratory data from 364 hemodialysis patients, using a multivariable Mixed model with conservative biases.ResultsThe overall trend over time in serum albumin was slightly positive (0.039 g/dL/month) and in serum creatinine slightly negative (-0.052 mg/dL/month). With increasing CRP, serum albumin declined significantly (-0.124 g/dL/month per unit increase in log CRP, adjusted for age, gender, race, diabetes, and nPCR, P < 0.0001). Serum albumin increased with increasing nPCR (0.021 g/dL/month per 0.1 g/kg/day, P < 0.0001). The effect of CRP on albumin was attenuated in African Americans and at a higher nPCR. Corresponding values for creatinine mirrored those for albumin. With increasing CRP, creatinine declined significantly [-0.142 mg/dL/month per unit increase in log CRP, adjusted for age, gender, race, diabetes (time since initiation of dialysis; vintage), Kt/V, and nPCR, P = 0.002]. Serum creatinine increased with increasing nPCR (0.183 mg/dL/month per g/kg/day, P < 0.0001).ConclusionsProxies of inflammation and dietary protein intake exert competing effects on serum albumin and creatinine in hemodialysis patients. These data provide a rationale for prospective testing of dietary protein supplementation in hemodialysis patients with biochemical evidence of ongoing inflammation and “malnutrition.

The acute-phase response varies with time and predicts serum albumin levels in hemodialysis patients

The acute-phase response varies with time and predicts serum albumin levels in hemodialysis patients.BackgroundCross sectional studies have established that the serum albumin level is dependent on serum levels of acute-phase proteins (APPs) or cytokine levels in hemodialysis patients. While the acute-phase response is generally associated with acute inflammatory events, a cross sectional analysis relating laboratory values to outcomes assumes these values to be unchanging. The longitudinal relationship among laboratory measurements and how they vary over time in a population of patients are unknown.MethodsPatients who were enrolled in the HEMO Study were recruited into an ancillary longitudinal study to establish the predictive effect of temporal variation in the levels of APPs and of temporal variation in normalized protein catabolic rate (nPCR) on the serum albumin concentration. nPCR was measured monthly using a double-pool method. The positive APPs—C-reactive protein (CRP), α1 acid glycoprotein (α1-AG), and ceruloplasmin—and the negative APP—transferrin (Trf)—were measured in serum obtained before each dialysis session for six weeks and then monthly in 37 hemodialysis patients. A random coefficient regression analysis was used to assess the association of serum albumin with other measured parameters at each time point, as well as fixed patient characteristics.ResultsThe within-subject coefficients of variation of albumin (median, range of 25th to 75th percentiles; median, 0.0614; range, 0.0485 to 0.0690) were significantly less than that of APPs (CRP, median, 0.878; range, 0.595 to 1.314, P < 0.05; and α1 AG, median, 0.173; range, 0.116 to 0.247, P < 0.05). The levels of APPs and albumin varied considerably over time. The primary predictor of current albumin was the current CRP level (P = 0.0014). nPCR also was a significant predictor for albumin levels (P = 0.0440) after controlling for the effect of APPs, suggesting an effect of nPCR on serum albumin concentration irrespective of the acute-phase response. Age and the presence of an arteriovenous graft were significant predictors that were associated with reduced albumin.ConclusionsThe acute-phase response is intermittent and is not a continuous feature in individual dialysis patients. Levels of APPs are the most powerful predictors for the levels of albumin concentration in hemodialysis in a longitudinal setting. Since variations in albumin are small, measurement of variations in APPs may provide greater insight into the dynamics of clinically relevant processes

Treatment of Uremic Diabetic Patients: Hemodialysis or Transplantation?

Eighty-one patients with chronic renal failure associated with or secondary to diabetic nephropathy were treated with dialysis and/or transplant. Twenty-five had juvenile diabetes and 56 had adult onset diabetes. Juvenile diabetics did poorly on hemodialysis with 13 patients having a 19% four-year survival rate, whereas those who had cadaveric transplantation did well with a four-year patient and graft survival rate of 56% in nine patients. The three juvenile diabetics who received related kidney grafts are presently alive with good function. Patients with adult onset diabetes did well on hemodialysis with a four-year survival rate of 63% in 45 patients. In this last group 11 patients received cadaveric transplants, but none survived 18 months

Effect of frequent hemodialysis on residual kidney function.

Frequent hemodialysis can alter volume status, blood pressure, and the concentration of osmotically active solutes, each of which might affect residual kidney function (RKF). In the Frequent Hemodialysis Network Daily and Nocturnal Trials, we examined the effects of assignment to six compared with three-times-per-week hemodialysis on follow-up RKF. In both trials, baseline RKF was inversely correlated with number of years since onset of ESRD. In the Nocturnal Trial, 63 participants had non-zero RKF at baseline (mean urine volume 0.76 liter/day, urea clearance 2.3 ml/min, and creatinine clearance 4.7 ml/min). In those assigned to frequent nocturnal dialysis, these indices were all significantly lower at month 4 and were mostly so at month 12 compared with controls. In the frequent dialysis group, urine volume had declined to zero in 52% and 67% of patients at months 4 and 12, respectively, compared with 18% and 36% in controls. In the Daily Trial, 83 patients had non-zero RKF at baseline (mean urine volume 0.43 liter/day, urea clearance 1.2 ml/min, and creatinine clearance 2.7 ml/min). Here, treatment assignment did not significantly influence follow-up levels of the measured indices, although the range in baseline RKF was narrower, potentially limiting power to detect differences. Thus, frequent nocturnal hemodialysis appears to promote a more rapid loss of RKF, the mechanism of which remains to be determined. Whether RKF also declines with frequent daily treatment could not be determined

Comparison of methods to predict equilibrated Kt/V in the HEMO Pilot Study

Comparison of methods to predict equilibrated Kt/V in the HEMO Pilot Study. The ongoing HEMO Study, a National Institutes of Health (NIH) sponsored multicenter trial to test the effects of dialysis dosage and membrane flux on morbidity and mortality, was preceded by a Pilot Study (called the MMHD Pilot Study) designed to test the reliability of methods for quantifying hemodialysis. Dialysis dose was defined by the fractional urea clearance per dialysis determined by the predialysis BUN and the equilibrated postdialysis BUN after urea rebound is completed (eKt/V). In the Pilot Study the blood side standard for eKt/V was calculated from the predialysis, postdialysis, and 30-minute postdialysis BUN. Four techniques of approximating eKt/V that eliminated the requirement for the 30-minute postdialysis sample were also evaluated. The first adjusted the single compartment Kt/V using a linear equation with slope based on the relative rate of solute removal (K/V) to predict eKt/V (rate method). The second and third techniques used equations or mathematical curve fitting algorithms to fit data that included one or more samples drawn during dialysis (intradialysis methods). The fourth technique (dialysate-side) predicted eKt/V from an analysis of the time-dependent profile of dialysate urea nitrogen concentrations (BioStat method; Baxter Healthcare, Inc., Round Lake, IL, USA). The Pilot Study demonstrated the feasibility of conventional and high dose targets of about 1.0 and 1.4 for eKt/V. Based on the blood side standard method, the mean ± SD eKt/V for patients randomized to these targets was 1.14 ± 0.11 and 1.52 ± 0.15 (N = 19 and 16 patients, respectively). Single-pool Kt/Vs were about 0.2 Kt/V units higher. Results were similar when eKt/V was based on dialysate side measurements: 1.10 ± 0.11 and 1.50 ± 0.11. The approximations of eKt/V by the three blood side methods that eliminated the delayed 30-minute post-dialysis sample correlated well with eKt/V from the standard blood side method: r = 0.78 and 0.76 for the single-sample (Smye) and multiple-sample intradialysis methods (N = 295 and 229 sessions, respectively) and 0.85 for the rate method (N = 295). The median absolute difference between eKt/V computed using the standard blood side method and eKt/V from the four other methods ranged from 0.064 to 0.097, with the smallest difference (and hence best accuracy) for the rate method. The results suggest that, in a dialysis patient population selected for ability to achieve an equilibrated Kt/V of about 1.45 in less than a 4.5 hour period, use of the pre and postdialysis samples and a kinetically derived rate equation gives reasonably good prediction of equilibrated Kt/V. Addition of one or more intradialytic samples does not appear to increase accuracy of predicting the equilibrated Kt/V in the majority of patients. A method based on dialysate urea analysis and curve-fitting yields results for equilibrated Kt/V that are similar to those obtained using exclusively blood-based techniques of kinetic modeling