Effect of carbohydrate intake on kidney function and structure in SHR/N-cp rats. A new model of NIDDM.

The SHR/N corpulent (cp) rat is a genetically obese rat that develops hyperglycemia, hyperinsulinemia, and proteinuria. This study was designed to evaluate the effects of high carbohydrate (CHO) intake on renal function and structure in this animal model and to determine whether the renal effects are related to the type of CHO ingested. Two groups of 5-wk-old obese male SHR/N-cp rats and lean male littermates were fed diets containing 54% CHO in the form of sucrose or starch. After 12 wk, renal function parameters, including creatinine clearance, urinary glucose excretion, and urinary protein excretion, were measured. Renal morphology was evaluated by semiquantitative light and electron microscopy. On either diet, obese rats had significantly higher urinary glucose and protein excretions than their lean littermates. Mean creatinine clearance (ml/min) in obese rats did not differ significantly from values observed in lean rats. When corrected for body weight, creatinine clearance (ml.min-1.kg-1) tended to be lower in obese than in lean rats, but the difference was significant (P less than .02) only for obese and lean sucrose-fed animals. Obese rats fed sucrose compared with their obese counterparts fed starch had higher body weight (+8%, P less than .05), glucose excretion (+63%, P less than .02), and protein excretion (+242%, P less than .005). In obese rats, protein excretion correlated with glucose excretion (r = .71, P less than .01). Glomerular lesions consisting of mesangial expansion and intercapillary nodules were found in obese but not in lean rats. Moreover, obese rats fed sucrose had a significantly greater number of involved glomeruli than obese rats fed starch.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of race on expression of acquired immunodeficiency syndrome-associated nephropathy.

The prevalence of renal disease associated with the acquired immunodeficiency syndrome (AIDS) is unknown, but appears to vary in different regions. Centers in New York, NY, and Miami, Fla, have reported patients with renal disease complicating AIDS. These populations have included large proportions of black patients and intravenous drug abusers. Reports from San Francisco, Calif, have suggested the prevalence of renal disease complicating AIDS is low, but the population was composed primarily of white patients, with a low proportion of drug abusers. The George Washington University Medical Center was the site of treatment for 31.4% of the patients with AIDS in Washington, DC. This population was split roughly evenly between black and white patients. A retrospective survey of patients with both AIDS and renal disease revealed approximately two thirds of the patients were black, reflecting the demographics of the population with AIDS; 11% of patients had intravenous drug abuse as a risk factor for the development of AIDS; and 74% had acute renal failure. Of these patients, approximately equal proportions were black and white. Twenty-six percent of the population had chronic renal failure, but the overwhelming proportion were black. There were no differences between proportions of patients in age, sex, race, or risk factors in patients with acute renal failure and chronic renal failure, but there was a significant difference in the proportions of black and white patients with chronic renal failure. The reason for these differences is unknown, but differences in host responses to viral proteins, physiologic adaptations, or socioeconomic factors in these populations may play an important role in mediating the expression of renal disease in individual patients.

Studies of carbohydrate metabolism after hemodialysis and hemofiltration in uremic patients.

To assess the effects of dialysis or hemofiltration on carbohydrate metabolism in uremia, we performed intravenous (IV) glucose tolerance tests (IV GTTs) after an overnight fast 48 hours following the last treatment in ten patients with chronic renal failure. Samples were obtained for plasma glucose, insulin, glucagon, and growth hormone levels throughout the GTTs in addition to basal samples for levels of plasma potassium and bicarbonate. The IV GTTs were performed at the end of a four-month period of standard hemodialysis (period 1) and then at the end of a four-month period of hemofiltration (period 2). Patients had mild glucose intolerance that did not change after hemofiltration, although the exaggerated insulin responses to glucose administration did significantly decrease in period 2. The fasting hyperglucagonemia did not decrease after hemofiltration but exhibited normal suppression with IV glucose. Levels of basal plasma bicarbonate and basal plasma potassium did not change significantly in period 2. Further studies investigating the beneficial metabolic effect of hemofiltration would seem to be indicated based on the data reported herein.

Short-term protein loading in assessment of patients with renal disease.

The effect of short-term protein loading on the glomerular filtration rate in normal persons and patients with renal disease was evaluated. Previous studies have demonstrated that in healthy subjects, protein loading results in an increased glomerular filtration rate. By determining the glomerular filtration rate preceding (baseline glomerular filtration rate) and following (test glomerular filtration rate) oral protein loading, it was possible to define (1) the filtration capacity (test glomerular filtration rate) and (2) the renal reserve (test glomerular filtration rate - baseline glomerular filtration rate) of the kidney. In normal persons, filtration capacity averaged 157 +/- 13 ml per minute and renal reserve 34 ml per minute. The test glomerular filtration rate was reproducible and independent of protein intake, whereas baseline glomerular filtration rate was significantly influenced by diet. Patients with renal disease were found to have a reduced renal reserve and/or a diminished filtration capacity. The reduction in filtration capacity appears to correlate with the damage sustained by the organ. It is suggested that an abnormal response to protein loading in renal disease may herald the fall in the baseline glomerular filtration rate and the rise in plasma creatinine level.

Renal hemodynamic changes in humans. Response to protein loading in normal and diseased kidneys.

This study was undertaken to define the renal hemodynamic changes that mediate the acute response to an oral protein load. Three groups of subjects were studied: (1) disease-free subjects; (2) patients with chronic renal disease of various causes, except for diabetes mellitus, documented by history and/or renal biopsy; and (3) patients with diabetes mellitus, that is, a history of hyperglycemia requiring antihyperglycemic therapy. All subjects were studied before (baseline) and after (test) ingestion of a protein load. Glomerular filtration rate and effective renal plasma flow were evaluated by inulin and para-amino-hippurate, respectively. In the disease-free subjects, the mean baseline glomerular filtration rate and renal plasma flow were 122 +/- 10 ml/minute/1.73 m2 and 644 +/- 64 ml/minute/1.73 m2, whereas test glomerular filtration rate and renal plasma flow were 151 +/- 15 ml/minute/1.73 m2 and 791 +/- 111 ml/minute/1.73 m2, respectively. In patients with chronic renal disease, the test glomerular filtration rate and renal plasma flow were related to the severity of the disease. The more severe the disease, the lower the absolute test values and the smaller the increment from baseline to test values. Patients with diabetes mellitus had a paradoxic response to ingestion of a protein load. Glomerular filtration rate fell while renal plasma flow remained unchanged. This response was observed in all diabetic patients regardless of the type of diabetes or whether clinical evidence of diabetic nephropathy was absent, minimal, or severe.

Renal functional reserve in humans. Effect of protein intake on glomerular filtration rate.

This study was designed to investigate the effect of protein intake on glomerular filtration rate, and to demonstrate and evaluate the functional reserve of the kidney. Normal subjects ingesting a protein diet had a significantly higher creatinine clearance than a comparable group of normal subjects ingesting a vegetarian diet. A progressive increment in protein intake in normal volunteers resulted in a significant increase in creatinine clearance. Diurnal variations in creatinine clearance were found. These daily variations correlated well with the periods of food intake. The capacity of the kidney to increase its level of function with protein intake suggests a renal function reserve. In short-term studies, the effect of a protein load on glomerular filtration rate was evaluated. Normal subjects showed an increase in glomerular filtration rate two and a half hours after protein load to a maximal glomerular filtration rate of 171.0 +/- 7.7 ml per minute. In patients with a reduced number of nephrons, renal functional reserve may be diminished or absent.

Equal levels of blood pressure control in ESRD patients receiving high-efficiency hemodialysis and conventional hemodialysis.

The present study compared the status of hypertension and adequacy of blood pressure control in 73 end-stage renal disease (ESRD) patients treated with four different modalities of hemodialysis, namely, conventional hemodialysis (CHD) with cuprophan 1.1 m2 at a blood flow rate of 300 mL/min, high-efficiency hemodialysis (HED) with cuprophan 1.6 m2 at a blood flow rate of 450 to 500 mL/min, high-flux hemodialysis (HFD) with F80 polysulfone 1.8 m2 at a blood flow rate 500 mL/min, and high-flux hemodiafiltration (HDF) with F80 2 x 1.8 m2 in series at a blood flow rate of 600 to 650 mL/min. Thirty of the 73 patients (41%) were receiving one or more antihypertensive agents to control their hypertension. The percentage of patients taking antihypertensive medication was less in the groups treated with HED, HFD, and HDF compared with the CHD group: 38%, 39%, and 39%, respectively, in the HED, HFD, and HDF groups versus 56% in the CHD group. Control of systolic and diastolic hypertension was achieved in a higher percentage of patients treated with HED, HFD, and HDF compared with patients treated with CHD. Sixty-two percent of HED, 58% of HFD, and 61% of HDF patients compared with 44% of CHD patients had systolic blood pressure less than 150 mm Hg, whereas 77% of HED, 76% of HFD, and 78% of HDF patients compared 56% of CHD patients had diastolic blood pressure less than 90 mm Hg. However, the differences in the use of antihypertensive medication and control rates of hypertension did not reach statistical significance. The average blood pressure of all patients was 144/89 mm Hg; this did not differ significantly between the four groups. There also were no significant differences in etiology of ESRD, hematocrit, biochemical data, as well as use and dose of recombinant human erythropoietin between the four groups. Compared with the CHD patients, the average treatment times with high-efficiency treatments were shorter, with HDF patients showing the shortest mean treatment time of 157+/-41 minutes per hemodialysis session. The mean Kt/V was higher in the groups treated with HED, HFD, or HDF (1.31+/-0.3, 1.30+/-0.4, and 1.43+/-0.3, respectively) than in the CHD group (1.12+/-0.3; P < 0.05). Interdialytic weight gain also did not differ among the four groups. There was no correlation between predialysis mean arterial pressure and either treatment time (r = 0.04, P = NS), Kt/V (r = 0.03, P = NS), ultrafiltration rate (r = 0.06, P = NS), or interdialytic weight gain (r= -0.08, P = NS). There also was no significant association between Kt/V and use of antihypertensive medications (chi-square = 1.76, P = NS). There was, however, a significant positive correlation between interdialytic weight gain and treatment time (r = 0.33, P < 0.01). We conclude that the use of short dialysis sessions with efficient hemodialysis treatments, namely, HFD and HDF, was associated with similar levels of blood pressure control in ESRD patients.

Peritoneal dialysis-associated peritonitis caused by Propionibacteria species.

There are an increasing number of reports about unusual causes of peritonitis in peritoneal dialysis (PD) patients. The Propionibacteria species is a microorganism that is a normal skin flora. Under the presence of certain risk factors, it may produce serious infections. Patients at risk of having Propionibacteria sp infections have malignancy, diabetes mellitus, foreign bodies, or immunodeficiency. We describe a PD-associated peritonitis in a 51-year-old woman that was caused by Propionibacteria sp. This patient's risk factors for developing Propionibacteria sp peritonitis include a history of CREST syndrome, malignancy of the breast, and recent catheter surgery. To our knowledge, this is the first case of a PD-associated peritonitis caused by Propionibacteria sp reported in the literature.

Renal reserve: a functional view of glomerular filtration rate.

The hyperfiltration theory challenged the view that glomerular filtration rate is a fixed function as well as that there is a good correlation between GFR and renal parenchymal damage. Glomerular filtration rate is a dynamic parameter that is diet-dependent and can be altered by hemodynamic maneuvers. Therefore, it is not a good indicator of renal lesion. The renal reserve is an indicator of the workload per nephron and may be a useful parameter to assess the progression of renal disease in the presence of dietary or pharmacological intervention.

Treatment of human immunodeficiency virus (HIV)-associated nephropathy.

Patients with human immunodeficiency virus (HIV) nephropathy (HIVN) face improved outlooks both before and after starting renal replacement therapy for end-stage renal disease, compared with the situation a little over a decade and a half before, when the disease was first recognized. Therapy with cyclosporin, glucocorticoids, and angiotensin-converting enzyme inhibitors provides the prospect of longer courses of renal insufficiency for patients with HIVN, and perhaps the hope of blunting progression of the disease when patients are treated early. Trials of patients with biopsy-proven HIVN are important to evaluate further the role of such newer therapies. HIV-infected patients with end-stage renal disease have been treated with hemodialysis, peritoneal dialysis, and renal transplantation. The course of therapy for dialysis patients may be improving, but ultimately depends on the stage of the viral illness. The disparities in the demographic composition of the patient populations probably underlies findings reported from different centers. Transplantation is currently a low-priority treatment option for HIV-infected patients with ESRD, but several studies provide fascinating insights into viral-host interactions.

The impact of residual renal function and total body water volume on achieving adequate dialysis in CAPD.

AIMS: The objective is to evaluate the impact of residual renal function (RRF) and total body water (TBW) on achieving adequate dialysis. METHODS: Sixty three CAPD patients performing four 2 liter exchanges daily were evaluated for RRF, total weekly Kt/V (TWKt/V), total weekly creatinine clearance (TWCC) and TBW. RESULTS: In patients with residual renal function (N = 41), TWKt/V and TWCC were 2.2 +/- 0.8 and 77.4 +/- 24.5 L, respectively. In patients without RRF (N = 22), TWKt/V was 1.6 +/- 0.4 and TWCC 42.6 +/- 9.2 L. TBW correlated negatively with TWKt/V in the group without RRF (r = -0.75, P<0.001). CONCLUSION: It is not possible for larger patients without RRF treated with CAPD (2L x 4 exchanges) to achieve the acceptable targets for TWKt/V and TWCC due to TBW.

The effects of increasing exchange volume and frequency on peritoneal dialysis adequacy.

AIM: Peritoneal dialysis adequacy guidelines are generally not met with the standard prescription of continuous ambulatory peritoneal dialysis (CAPD), four 2-liter (1) exchanges daily. The aim of this study is to determine the effects of increasing exchange volume singularly or in combination with frequency on peritoneal dialysis adequacy. PATIENTS AND METHODS: Fourteen stable ESRD patients receiving peritoneal dialysis were evaluated for adequacy and nutritional status between the fourth and sixth months during a six-month baseline period in which the dialysis prescription was four two-liter exchanges daily and during a six-month intervention period in which patients (n = 7) from group 1 were prescribed CAPD four 2.5-liter exchanges daily while patients (n = 7) from group 2 were prescribed continuous cycling peritoneal dialysis (CCPD - 12 l) using four 2.5 liters during the night and a 2-liter wet day. RESULTS: Mean total weekly urea Kt/V (TWKt/V) increased significantly from 1.6 +/- 0.2 to 2.1 +/- 0.2, p <0.01 in group 1, and from 1.6 +/- 0.4 to 2.1 +/- 0.5, p <0.001 in group 2. Mean normal total weekly creatinine clearance increased significantly from 51 +/- 11 to 60 +/- 8 l/1.73 m2, p <0.05 in group 1, and from 45 +/- 6 to 58 +/- 9 l/1.73 m2, p <0.01 in group 2. Serum albumin of almost all patients in the intervention groups were higher than in the baseline groups. Mean serum albumin increased from 3.6 +/- 0.4 to 4.0 +/- 0.4 g/dl, p <0.01 in group 1, and from 3.8 +/- 0.2 to 4.0 +/- 0.4, p <0.05 in group 2. The magnitude of the decrement in BUN and serum creatinine were greater in group 2 than group 1 (p <0.001 and p <0.05, respectively). When the two intervention groups were compared to each other, no significant differences in the delivered dialysis dose or nutritional status were noted. CONCLUSION: In conclusion, it is possible to achieve currently proposed adequacy target by increasing the exchange volume singularly or in combination with frequency in most peritoneal dialysis patients.

Abnormal urinary protein excretion in HIV-infected patients.

HIV infection has been associated with a variety of renal diseases, although the pathogenesis of such dysfunction is unknown. To determine whether HIV-infection is associated with glomerular permeability defects, and if so, the prevalence of the finding, we studied patients with various stages of HIV infection. Urine samples from 505 outpatients with HIV infection (without hypertension, azotemia, or dipstick proteinuria), 41 normal controls and 40 febrile non-HIV positive, hospitalized patients with infectious diseases were analyzed for the urinary microalbumin/creatinine ratio (U microA/Cr), a sensitive indicator of incipient renal disease in diabetes mellitus and hypertension, and the urinary beta 2-microglobulin/creatinine ratio (U beta 2/Cr), an indicator of renal tubular function. Microalbumin concentration was measured by ELISA. Beta 2-microglobulin concentration was measured by an enzyme immunoassay. HIV-infected outpatients had higher mean U microA/Cr than normal subjects, but not febrile hospitalized controls. The prevalence of an increased U microA/Cr was 29.8% in the HIV-infected outpatient population. There was no difference in the ratio between Black and White HIV-infected outpatients, HIV-infected outpatients treated or untreated with zidovudine (AZT), or HIV infected outpatients untreated with any drug. There was no difference between U microA/Cr in stage II, III or IV HIV-infected patients when assessed by analysis of variance. A similar pattern was noted with U beta 2/Cr. The prevalence of an increased U beta 2/Cr ratio was 37.7% in HIV-infected outpatients. Increased urinary albumin and beta 2-microglobulin excretion, not associated with drug therapy, is present in patients with early HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of PD treatment delivered by 125I-Iothalamate plasma disappearance.

The calculation of treatment delivered to PD patients requires the collection of PD effluent, plasma and urine samples. 125I-Iothalamate plasma disappearance, which eliminates the need for PD effluent collections, was tested as an alternate method to measure the weekly PD treatment delivered. Two protocols were designed. In protocol A, a 35 microCi dose of 125I-Iothalamate was injected in three subjects and allowed to equilibrate. A plasma sample was taken and patients returned on both of the following two days with timed labeled effluent bags and a 24-hour urine collection for each day. The timed PD effluent and 24-hour urine collections were measured for 125I-Iothalamate, urea and creatinine concentrations. 125I-Iothalamate and urea clearances were strongly correlated for both PD (R2 = 0.76, n = 24) and renal (R2 = 0.92, n = 6) clearances. In protocol B, thirteen subjects were given a 35 microCi injection of 125I-Iothalamate. A blood sample was taken one hour post injection and a second blood sample taken on day five. Kt/V were calculated from the 125I-Iothalamate plasma disappearance curve and compared to weekly Kt/V values extrapolated from one day's collections (Traditional Method). The comparison of Kt/V values found by 125I-Iothalamate Method vs. the "Traditional Method" yielded R2 = 0.79, n = 13. In conclusion, the plasma disappearance of 125I-Iothalamate is an alternate method of determining weekly Kt/V, over an extended period of time, which eliminates the need for PD effluent collections.

Control of hypertension is better during hemodialysis than during continuous ambulatory peritoneal dialysis in ESRD patients.

This study compared the status and adequacy of blood pressure (BP) control in 21 ESRD patients treated with HD and CAPD at different time periods. Patients were considered to be hypertensive it they were receiving antihypertensive medications during the study period. During HD, 9 of the 21 patients (43%) required antihypertensive drugs to control their hypertension; whereas, during CAPD, the number of patients taking antihypertensive drugs increased to 15 (71%) (p < 0.05). Adequate control of hypertension (systolic BP < 150 mmHg and/or diastolic BP < 90 mmHg) was achieved in 17 patients (81%) during HD compared to 11 patients (52%) during CAPD (p < 0.05). Average ultrafiltration rate was 1.28 +/- 0.1 l/day during HD and 1.30 +/- 0.2 l/day during CAPD (p = NS). Mean Kt/V during HD was 1.24 +/- 0.1; whereas, mean weekly Kt/V during CAPD was 1.81 +/- 0.2. There were no significant differences in hematocrit or usage of recombinant human erythropoietin (rHuEPo) between the two treatment modalities. However, the weekly dose of rHuEpo was higher during HD than during CAPD (p < 0.05). Mean body weight was significantly higher (p < 0.01) and serum albumin was lower (p < 0.05) during CAPD than during HD in the same group of patients. We conclude that hypertension appears to be controlled better by HD than by CAPD in ESRD patients. The gain in body weight observed with CAPD treatment may reflect an increase in total body fluid volume which may partly explain why hypertension is less adequately controlled during CAPD than during HD treatment.

Hepatitis C virus RNA in patients with anti-HCV on hemodialysis. Relationship to transaminase levels.

This study was performed in patients with hepatitis C virus (HCV) who were treated with hemodialysis to determine the relationships among alanine amino-transferase (ALT) levels, immunoglobulin (Ig) G anti-HCV, IgM anti-HCV core, and HCV RNA. Of 107 patients on hemodialysis, 27 had positive IgG anti-HCV. Eight of the patients who had HCV were evaluated every 8 months during a period of 2 years, using the following selection criteria: positive IgG against c-22, c33-c, 5-1-1, and c100-3 viral peptides; absence of infection by hepatitis A virus, hepatitis B virus, cytomegalo-virus, Epstein-Barr virus, herpes simplex virus, and human immunodeficiency virus, as well as absence of hepatotoxic drugs or cholelithiasis. We considered elevated ALT values as those more than 150% of the upper limit of normal. Three of the patients had persistent elevation of ALT levels, two had alternating elevation of ALT levels, and three had normal ALT levels in all blood samples. Of the 24 blood samples, 11 had elevation of ALT (45.8%) levels that showed positive IgM anti-HCV, but only 7 of these 11 had positive HCV RNA (63.6%). None of the 13 blood samples without elevation of ALT had positive IgM anti-HCV, but 5 had positive HCV RNA (38.5%). We found an excellent correlation between IgM anti-HCV and ALT levels (r = 0.81). There was no statistically significant difference between the mean ALT values on the 12 blood samples that had positive HCV RNA and the mean ALT values of the negative HCV RNA samples (53.5 +/- 28.0 IU/l vs. 37.4 +/- 17.5 IU/l, respectively). IgM anti-HCV is related to the elevation of ALT levels and can be used as a serologic marker to indicate the presence of active HCV induced liver damage. Serum ALT levels do not correlate with the detection of viral genome in sera. IgG anti-HCV is not necessarily associated with HCV RNA or IgM anti-HCV. The absence of IgM and HCV RNA in patients with IgG anti-HCV and normal ALT levels does not necessarily suggest the absence of active HCV infection.

Inflammatory pseudotumor of the liver: report of two cases.

Inflammatory pseudotumor of the liver is a very rare lesion. Herein we describe two cases of this entity which occurred in two women aged 22 and 49 years, respectively. Both cases were considered to be clinically malignant and only the histopathologic examination revealed the non-neoplastic nature of the disease. Ultrastructural and immunohistochemical studies further supported the evidence of a reactive disease.

How a multidisciplinary vascular access care program enables implementation of the DOQI guidelines. Part I.

This comprehensive, proactive, multidisciplinary team approach to access management has enabled the achievement of center-specific best-demonstrated clinical practiCes for vascular access care. It has also resulted in significant cost savings to the health care delivery process. It has not been an easy task; if it were, access care outcomes would be better nationally than they are today. The VACP approach to vascular access care improvement employs four key implementation principles that ensure the success of Gambro's program and form the infrastructure supporting any successful team approach to care. These core processes, known as the four "C's, include: 1. Commitment, 2. Continuous Quality Improvement, 3. Core Competency, and 4. Communication.

Lessons learned. Implementing a vascular access quality improvement program. Part II.

Implementing a CQI program for vascular access can seem an overwhelming task. It encompasses many areas that are not in the nephrologists' or dialysis facilities' control. However, involving the right multidisciplinary team members in the process and aligning the goals and objectives creates an environment conducive to success. Ongoing communication is critical. Everyone needs to be a part of the change process.