Cardiovascular risk modification in participants with coronary disease screened by the Kidney Early Evaluation Program.

BACKGROUND: Coronary artery disease (CAD) identifies the need for intensive treatment of risk factors among individuals with chronic kidney disease (CKD), a high-risk, complex cardiovascular risk state. METHODS: An estimated glomerular filtration rate<60 mL/min/1.73 m2 or a urine albumin:creatinine ratio (ACR)≥30 mg/g (3.4 mg/mmol) defined CKD. RESULTS: Of 70,454 volunteers screened the mean age was 53.5±15.7 years and 68.3% were female. A total of 5410 (7.7%) had a self-reported history of CAD; 1295 (1.8%) had a history of prior percutaneous coronary intervention (PCI); and 1124 (1.6%) had a prior history of coronary artery bypass surgery (CABG). Multivariate analysis for the outcome of suboptimal CAD risk management (composite of systolic blood pressure≥130 mmHg, glucose≥125 mg/dL (6.9 mmol/L) for diabetics, total cholesterol≥200 mg/dL (5.2 mmol/L), or current smoking; n=38,746/53,403, 72.5%) revealed older age (per year) (odds ratio (OR)=1.04, 95% confidence interval (CI) 1.03-1.04, P<0.0001), male gender (OR=1.40, 95% CI 1.34-1.47, P<0.0001), ACR≥30 mg/g (3.4 mg/mmol) (OR=1.66, 95% CI 1.55-1.79, P<0.0001), body mass index (per kg/m2) (OR=1.06, 95% CI 1.06-1.06, P<0.0001), CAD without a history of revascularization (OR=1.14, 95% CI 1.02-1.28, P=0.02) and care received by a nephrologist (OR=1.49, 95% CI 1.22-1.83, P<0.0001) were associated with worse risk factor control. Prior coronary revascularization and being under the care of a cardiologist were not associated with either improved or suboptimal risk factor control. CONCLUSIONS: Chronic kidney disease is associated with overall poor rates of CAD risk factor control.

Low birth weight is associated with chronic kidney disease only in men.

The association of low birth weight and chronic kidney disease was examined in a screened volunteer population by the National Kidney Foundation's Kidney Early Evaluation Program. This is a free, community-based health program enrolling individuals aged 18 years or older with diabetes, hypertension, or a family history of kidney disease, diabetes, or hypertension. Self-reported birth weight was categorized and chronic kidney disease defined as an estimated glomerular filtration rate less than 60 ml per min per 1.73 m(2) or a urine albumin/creatinine ratio >or=30 mg/g. Among 12 364 participants, 15% reported a birth weight less than 2500 g. In men, significant corresponding odds ratios were found after adjustment for demographic characteristics and health conditions to this low birth weight and chronic kidney disease, but there was no association among women. There was no significant interaction between birth weight and race for either gender. Efforts to clinically understand the etiology of this association and potential means of prevention are essential to improving public health.

Clay pica has no hematologic or metabolic correlate in chronic hemodialysis patients.

OBJECTIVE: Clay pica is a form of compulsive ingestion of non-nutritive substances frequently practiced by dialysis patients. Its consequences are unknown. In this study, we evaluated the effect of regular consumption of clay on hematologic and metabolic profiles in hemodialysis patients. DESIGN: A prospective, case-control study with use of structured questionnaire. SETTING: Free-standing hemodialysis units. PATIENTS: One hundred thirty-eight patients on hemodialysis for at least 12 months were interviewed. Thirteen of 138 (9.4%) confessed to clay pica. Ten randomly selected patients with no history of pica served as control. INTERVENTION: Average of all laboratory profiles and interdialytic weight gain (IDWG) over a 3-month period were recorded. Assay of the aluminum (Al), silica (Si), and iron (Fe) content of commercially purchased clay was performed. MAIN OUTCOME MEASURE: Comparison of laboratory profiles and IDWG between cases and control. Estimation of the daily consumption of Al, Fe, and Si from clay and their relationship to the laboratory profiles. RESULTS: There was no statistically significant difference in the levels of Al, albumin, calcium, ferritin, hematocrit, iron saturation, phosphorus, and IDWG between pica cases and control. Iron was significantly higher in pica patients (13.0 +/- 7.9 micromol/L v 7.5 +/- 2.5 micromol/L, P =.04), but potassium was higher among control than pica cases (4.9 +/- 0.7 mmol/L v 4.4 +/- 0.6 mmol/L, P =.07). Estimated metal exposure from daily clay consumption per patient were: Al (1-2 mg), Fe (11-23.5 mg), and Si (2-4.5 g). Multivariate logistic regression analysis failed to show any association between clay consumption and nutrition, anemia, or mineral metabolism (R(2) = 0.0, P =.79). CONCLUSION: Clay pica does not appear to be detrimental to the hematologic and metabolic milieu of hemodialysis patients. The practice should, however, be discouraged, because of potential for ingestion of unknown substances, and reported potential for gastrointestinal complications.

Tunneled hemodialysis catheter survival: comparison of radiologic and surgical implantation.

Cuffed, tunneled hemodialysis catheters (caths) are often implanted in the operating rooms (OR) by surgeons or by interventional radiologists in radiology suites (RS). Comparative outcome studies between OR and RS placed caths are few and tend to favor the specialty of the authors. In this longitudinal study, we monitored cath survival in patients while awaiting maturation of their fistulae, and compared outcomes between OR and RS placement. A total of 95 caths were placed in 50 patients between July 1996 and July 1999. Radiologically placed caths had a shorter primary patency duration than OR placed caths (80 +/- 40 days vs. 100 +/- 31 days, p = 0.04) and a lower primary patency rate at 120 days than OR placed caths (42% vs. 67%, p = 0.04). Cumulative infection rate per 1,000 catheter days was higher in RS than OR cases (3.8 Vs 2.2, p = 0.09), whereas mean sepsis free duration was shorter in RS than OR (60 +/- 45 days vs. 88 +/- 40 days, p = 0.02). The risk of infection was 1.7 times greater in RS than OR cases (chi-square = 6.4, p = 0.01). The RS placed caths also had a higher rate of primary nonfunction (31% vs. 8.3%, p = 0.04) and bleeding complications (42% vs. 17%, p = 0.04), but significantly shorter procedure scheduling time than OR cases (1.1 +/- 0.3 days vs. 2.5 +/- 0.6 days, p < 0.0001). In conclusion, radiologically placed caths seem to have higher rates of infection, bleeding, and functional failure but shorter scheduling time than surgically placed caths. Discussions are under way to improve the survival of RS placed caths at our affiliated hospitals.

Epidemiology of de novo acute renal failure in hospitalized African Americans: comparing community-acquired vs hospital-acquired disease.

BACKGROUND: The high incidence and prevalence of end-stage kidney disease among African Americans is well known, but the epidemiology of acute renal failure (ARF) among African Americans is unknown. This study was designed to determine the incidence, associated risk factors, and prognosis of ARF in hospitalized African Americans and to compare these variables in hospital-acquired ARF (HA-ARF) against community-acquired ARF (CA-ARF). METHODS: A 3-year (1994-1996), computer-assisted retrospective analysis of hospital discharges with confirmed diagnoses of ARF. One hundred of 240 cases met the inclusion criteria for de novo ARF. Demographic, laboratory, and clinical profiles of all patients were retrieved and subdivided into CA-ARF and HA-ARF. Both analysis of variance and chi2 tests were used for analysis. Survival regression used both the Cox proportional hazards and Kaplan-Meier models. RESULTS: The incidence of CA-ARF was 3.5 times greater than that of HA-ARF (0.55% vs 0.15%). The mean age of all patients was 54 years with a 67% male predominance. There were no significant differences in age, sex, peak serum creatinine levels, or underlying medical history. Prerenal causes of ARF were more common among CA-ARF than HA-ARF (35% vs 19%; P = .07), but intra-renal causes were more common among HA-ARF (81% vs 55%; P = .07). All cases of obstruction occurred in CA-ARF. Mortality was higher in HA-ARF (59% vs 33%; P = .03), and the incidence of recognized predictors of mortality was higher in patients with HA-ARF than in those with CA-ARF: oliguria (59% vs 35%; P = .04); sepsis (73% vs 35%; P = .004); stay in the intensive care unit (ICU) or mechanical ventilation (55% vs 6%; P<.001); and multiorgan failure (59% vs 24%; P = .002). Those with HA-ARF were twice as likely to require dialysis as those with CA-ARF. The mortality was high in younger patients with CA-ARF and in older patients with HA-ARF, but the dialysis-related mortality rate was 3-fold higher among patients with HA-ARF. While mean +/- SD length of hospital stay was more prolonged in HA-ARF than CA-ARF (26 +/- 28 days vs 12 +/- 11 days; P<.001), the 120-day survival rate was lower in HA-ARF than CA-ARF (43% vs 66%; P = .05). The HA-ARF status was associated with a relative risk of 2.5 (confidence interval, 1.1-5.5; P = .03) for shortened survival. CONCLUSIONS: The overall epidemiologic characteristics of ARF among hospitalized African Americans seem to be comparable to those in whites, but the difference in incidence between CA-ARF and HA-ARF was much higher in African Americans. In view of the high mortality and morbidity rates associated with ARF and the fact that younger African American patients with CA-ARF were more likely to die than their older counterparts, we recommend that renal failure awareness be incorporated into community-based health educational programs in African American populations.

Role of hypoalbuminemia and hypocholesterolemia as copredictors of mortality in acute renal failure.

UNLABELLED: Role of hypoalbuminemia and hypocholesterolemia as co-predictors of mortality in acute renal failure. BACKGROUND: Hypoalbuminemia (LA) and hypocholesterolemia (LC) have been reported to portend high mortality in both older patients and in patients with end-stage renal disease. Even though low levels have been reported in critically ill patients, they have not been clearly defined as predictors of mortality in acute renal failure (ARF). The impact of LA and LC on mortality in ARF is evaluated in this study. METHODS: We conducted a computer-assisted three-year retrospective review of all cases of de novo ARF seen at an inner city tertiary-care facility. One hundred cases met the criteria for inclusion in the study. We employed both univariate and multivariate logistic regression models to estimate the relative risks (RR) and 95% confidence intervals (CI) of mortality associated with several variables. RESULTS: Predictors associated with a high risk of death identified in this study include LC < or = 150 mg/dl (< or = 3.9 mmol/liter; RR, 7.4; CI, 2.7 to 20.3), LA < or =35 g/liter (RR, 5.0; CI, 1.9 to 13.2), sepsis (RR, 9.4; CI, 3.7 to 23.9), mechanical ventilation (RR, 10.8; CI, 2.8 to 41.0), oliguria (RR 17.0; CI, 6.2 to 46.6), and multisystem organ failure (RR 24.7; CI, 10.3 to 59.1). The overall gross mortality was 39%, but mortality among intensive care unit patients was 82%. Survival was 82% among patients with serum albumin >35 g/liter versus 48% among those with serum albumin < or =35 g/liter (chi2 = 11.9, P = 0.0006). Similarly, survival was higher among patients with cholesterol >150 mg/dl (>3.9 mmol/liter) than those whose levels were < or =150 mg/dl (< or =3.9 mmol/liter; 85 vs. 44%, ch 17.3, P<0.0001). Significant association between LA and LC was observed (R = 0.4, P<0.0001). Age, gender, level of plasma creatinine, and underlying chronic medical conditions were not predictive of mortality. CONCLUSION: Survival in ARF is significantly altered by the levels of albumin and cholesterol. Because both LC and LA can be cytokine mediated, their presence in ARF should be considered ominous.

Delivered dialysis dose is suboptimal in hospitalized patients.

Underdialyzed patients have high hospitalization and mortality rates. It is unclear if such patients receive adequate dialysis during hospitalization. In this cross-sectional study, we evaluated single treatment delivered dialysis dose during hospitalization and compared this to the dosage received at the free-standing outpatient clinics in the same patients. Eighty-four patients (54% male) aged 23-63 years (means +/- SD 55.5 +/- 14.6) who have been on dialysis for at least 3 months were evaluated. Hypertension and diabetes were the most common diagnoses, while thrombosed graft or fistula accounted for 40% of admissions. The mean dialysis treatment time (Td) was 30 min longer in the outpatient (OP) setting than the hospital (H): 3.6 +/- 0.3 vs. 3.1 +/- 0.2 h (p < 0.0001). Attained blood flow (QB) was 15% greater in the OP than H: 394 +/- 40 vs. 331 +/- 54 ml/min (p < 0.0001). The Kt/V was analyzed in 49 of 84 patients; the OP Kt/V was 20% greater than the H Kt/V: 1.38 +/- 0.2 vs. 1.11 +/- 0.1 (p < 0.0001). A further breakdown of H Kt/V according to access and membrane types showed that patients with functional grafts/fistula had a higher Kt/V than those with temporary accesses 1.14 +/- 0.1 vs. 1.07 +/- 0.1 (p = 0.01). We conclude that hospitalized patients receive suboptimal dialysis dose, this could have a negative impact on survival if hospitalization is recurrent and prolonged. Kinetic modeling should be routinely performed in such patients and Td should be increased in patients with temporary accesses.

Rapid progression to end-stage renal disease in young hypertensive African Americans with proteinuria.

Hypertensive nephrosclerosis (HN) remains the most common cause of end-stage renal disease (ESRD) in blacks. This study examined whether renal histology corresponds with clinical hypertension in proteinuric blacks. Nondiabetic hypertensive blacks who satisfied inclusion criteria were enrolled in this study. Four male patients, each with a family history of hypertension and mean age 41 years, consented to kidney biopsy. Their mean arterial pressure was 116.5 mm Hg, mean urine protein excretion was 7.7 +/- 3.5 g/day. All patients progressed to ESRD within a mean duration of 14 months; the mean rate of decline in glomerular filtration rate was 53 mL/min/y, with an ESRD incidence of 80%/y. The histologic findings were consistent with previously described features of HN. Prominent glomerulosclerosis involved 30% to 75% of the glomeruli and extensive arteriolosclerosis/arteriosclerosis, tubular atrophy, and interstitial fibrosis. There was no evidence of immune complex disease by either immunofluorescence, electron microscopy, or serologic studies. The mean arterial pressure showed a strong but nonsignificant correlation with progression to ESRD (r = 0.8) and arteriosclerosis/arteriolosclerosis (r = 0.8). Glomerular sclerosis correlated with the reciprocal of serum creatinine (r = 0.6), interstitial fibrosis (r = 0.8), and arteriosclerosis/arteriolosclerosis (r = 0.3). Urine protein excretion correlated weakly with progression to ESRD (r = 0.4). These results indicate a poor correlation between clinical findings and histologic features on renal biopsy in young hypertensive African Americans. Hypertension remains a major cause of ESRD among African Americans, and progression to ESRD may be rapid in patients with marked proteinuria. Early and aggressive intervention is warranted.

Hemodialysis vascular access: variable thrombus-free survival in three subpopulations of black patients.

Hemodialysis vascular access-related problems account for most hospitalizations in chronic hemodialysis patients. Although some co-morbid risk factors for early fistula failures have been described, a great deal of unknown exists as to why access survival is favorable in some patients. In this longitudinal study, fistulae patency and thrombosis episodes were monitored from placement date in three groups of end-stage renal disease (ESRD) patients who have been on dialysis for > or =90 days. Thirty-six patients (29 male; 80%) with a mean age of 42+/-2 years were monitored. The groups consisted of eight patients with biopsy-confirmed focal segmental glomeruloscierosis (FSGS), 13 with acquired immunodeficiency syndrome-related nephropathy (human immunodeficiency virus [HIV]), and 15 with hypertensive ESRD (hypertensive nephrosclerosis [HTN]) who served as controls. Diabetics and patients aged > or =64 years were excluded. Twenty-five of 36 (69%) fistulae were prosthetic (AVG), while 11 (31%) were native (AVF). The FSGS group was more likely to have an AVG (87.5%), while 54% of the HIV group had an AVG. The thrombosis event rate was significantly greater among the FSGS patients (3/patient-year) than the HIV (0.15/patient-year) and HTN (0.5/patient-year) patients (P < 0.0001 and P < 0.002, respectively). The mean thrombosis-free duration for both AVG and AVF among the HIV and HTN groups were 318.5+/-17 days and 311.7+/-22.5 days, respectively. These were significantly greater than in the FSGS group (26.5+/-7 days; P < 0.0001). The cumulative 1-year patency rate for AVG among the HIV and HTN groups was 85% and 65%, respectively, while that of the FSGS group was 0%. Kaplan-Meier hazard analysis showed that all groups were at risk of access thrombosis as time progressed, but the FSGS group had the highest risk of access thrombosis, which began from the date of placement and increased exponentially with time. The increased thrombosis rate among the patients in the FSGS group correlated with their weight (R = 0.8, P = 0.003) and pre-ESRD 24-hour urinary protein excretion (R = 0.9, P = 0.001). The HIV status appeared to confer enhanced hemodialysis access survival. This may be related to the high rate of native fistulae placement and favorable vascular reactivity to shear stress. Accelerated atherosclerosis and small caliber vessels may be responsible for the poor fistulae outcome among the FSGS group. More studies will be necessary to further explore these findings.

Recombinant human erythropoietin (rHuEPO) increases endothelin-1 release by endothelial cells.

Hypertension is a major complication of rHuEPO therapy in hemodialysis (HD) patients. We have previously reported that patients receiving rHuEPO intravenously (i.v.) had higher mean arterial pressure (MAP) and plasma endothelin-1 (ET-1) levels than those in which the hormone was administered subcutaneously (s.c.). To test whether the increased serum ET-1 levels associated with i.v. rHuEPO administration are the result of a direct effect of the hormone on ET-1 release by the endothelial cells (EC), we examined the effects of rHuEPO in vitro. Bovine pulmonary artery endothelial cells (BPAEC) were exposed to doses of rHuEPO of 0.8; 1.6; 3.3 and 6.6 U/ml. A 24 hour-time course showed maximal ET-1 production at 12 hours for all the doses tested. A significant increase in cell proliferation over controls was observed at 24 hours, for all rHuEPO doses, and no correlation was found between ET-1 values and cell proliferation. Inhibition of protein synthesis by cycloheximide (10 micrograms/ml) abolished the stimulation of ET-1 release by rHuEPO. Thrombin (4 U/ml) and angiotensin II (10(-7) M), two potent stimulators of ET-1 release, had additive effects to those of rHuEPO. Specific thrombin and angiotensin II antagonists blocked these additive effects, reducing ET-1 release to the level of rHuEPO stimulation alone. In summary, rHuEPO stimulates vascular EC in culture to increase ET-1 release through an increase in synthesis and in a time dependent fashion. The routes of stimulation seem to differ from other known ET-1 secretogoges. Our data also confirm a significant mitogenic effect of rHuEPO on the endothelial cell.

Intravenous erythropoietin (rHuEPO) administration increases plasma endothelin and blood pressure in hemodialysis patients.

The correction of anemia in end stage renal disease with recombinant human erythropoietin (rHuEPO) is associated with hypertension in about a third of hemodialysis patients. In the present study, we investigated the role of endothelin (ET-1) on rHuEPO associated hypertension and the effect of the rHuEPO administration route on plasma ET-1 levels. We studied 50 stable chronic hemodialysis patients who were divided into three groups: 26 patients received rHuEPO intravenously (IV) and 21 subcutaneously (SC). The control group was nine patients who were treated with nandrolone decanoate (ND). Prehemodialysis ET-1 plasma levels were correlated with mean arterial pressure (MAP), hematocrit (Hct), time on dialysis, and rHuEPO doses. The antihypertensive therapeutic index (ATI) was used to determine the changes in blood pressure medication intake. We observed that the ET-1 levels were significantly higher in the IV group (19.3 +/- 2) than the SC (5.0 +/- 0.6) or ND groups (3.6 +/- 0.4 pg/mL) (P < 0.001, IV v SC or ND). After IV rHuEPO treatment, there were increases in both MAP (pre- v post-rHuEPO, P < .001) and in ATI (pre- v post-rHuEPO, P < .001). In the SC group, the increases in MAP and ATI were not significant. Only the IV group showed a significant correlation between MAP and ET-1 levels (r = .05, P = .02). To accomplish the same Hct, the IV group received higher rHuEPO doses than those of the SC (180 +/- 15 v 87 +/- 12 U/kg/week) (P < .001). No significant correlations were found between the plasma ET-1 levels and Hct, time on dialysis and rHuEPO doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathogenesis of nephrolithiasis post-partial ileal bypass surgery: case-control study. The POSCH Group.

Between 1975 and 1983, 838 patients were randomized into the Program on the Surgical Control of Hyperlipidemias (POSCH) trial: 417 to standard medical care and 421 to partial ileal bypass (PIB) surgery. During the course of the trial, an increased incidence of kidney stone formation was found in the surgery group (4%/year) as compared to the control group (0.4%/year). A matched triplet case-control study was conducted to assess the possible causes for the increased incidence of kidney stones. Three groups were studied: PIB stone-formers (S); PIB non-stone formers (N); and non-PIB, non-stone formers in the control group (C). Initially, 162 patients (54 triplets) were selected. Ten percent of the patients declined to participate which resulted in a sample size of 146 patients. The PIB patients had statistically significant (P less than 0.05) lower levels of serum vitamin D metabolites; lower urine volume, pH, citrate, magnesium, carbon dioxide, and sulfate, and higher urinary oxalate, ammonia and relative supersaturation for calcium oxalate and uric acid than the control patients. Although S and N had similar results, those S with no prior history of stones had a higher calcium oxalate supersaturation than similar N with a negative prior history of stones (P less than 0.025). Based on these results, all PIB patients appear to be at risk for kidney stone formation. The combination of reduced urinary volume and calcium oxalate precipitation inhibitor substance with increased calcium oxalate relative supersaturation produced an increase in nephrolithiasis risk in the PIB groups.

Renal tubular acidosis.

Renal tubular acidosis refers to a group of disorders that result from pure tubular damage without concomitant glomerular damage. They could be hereditary (primary) or acquired (secondary to various disease states like sickle cell disease, obstructive uropathy, postrenal transplant, autoimmune disease, or drugs). The hallmark of the disorder is the presence of hyperchloremic metabolic acidosis with, or without, associated defects in potassium homeostasis, a UpH greater than 5.5 in the presence of systemic acidemia, and absence of an easily identifiable cause of the acidemia. There are three physiologic types whose basic defects are impairment of or a decrease in acid excretion, i.e., type 1 (dRTA); a failure in bicarbonate reabsorption, i.e., type 2 (pRTA); and deficiency of buffer or impaired generation of NH4+, i.e., type 4 RTA. Several pathophysiologic mechanisms have been postulated for these various types. pRTA is the least common of all in the adult population. It rarely occurs as an isolated defect. It is frequently accompanied by diffuse proximal tubule transport defects with aminoaciduria, glycosuria, hyperphosphaturia, and so forth (Fanconi syndrome). dRTA is associated with a high incidence of nephrolithiasis, nephrocalcinosis, osteodystrophy, and growth retardation (in children). Osteodystrophy also occurs in pRTA to a lesser degree and is believed to be secondary to hypophosphatemia. Patients with type 4 RTA usually have mild renal insufficiency from either diabetes mellitus or interstitial nephritis. Acute bicarbonate loading will result in a high fractional excretion of bicarbonate greater than 15% (FEHCO3- greater than 15%) in patients with pRTA, but FEHCO3- less than 3% in patients with dRTA. Type I patients will also have a low (U - B) PCO2 with bicarbonate loading. They are also unable to lower their urine pH to less than 5.5 with NH4Cl loading. The treatment of these patients involves avoidance of precipitating factors when possible, treatment of underlying disease, correction of electrolyte imbalance, particularly hypokalemia and hyperkalemia, and most importantly, the use of alkali. This will prevent or reduce all the various complications.