Foscarnet nephrotoxicity: mechanism, incidence and prevention

Foscarnet is a pyrophosphate analogue that has been successfully used in severe cytomegalovirus (CMV) infections. Little is known of the incidence and mechanisms of foscarnet-induced nephrotoxicity as most data comes from recipients of renal allografts or from patients with severe underlying disease or with other nephrotoxic drugs. We have retrospectively analyzed the evolution of renal function after 56 courses of foscarnet. In addition, we have prospectively studied the protective effects of hydration on foscarnet nephrotoxicity (2.5 liters of saline/day during the night before the foscarnet therapy and throughout the course of treatment). Foscarnet-induced acute renal failure was defined as a rise in serum creatinine of at least 25% from the basal value. An increase in serum creatinine occurred in 37 cases out of the 56 courses of foscarnet (66%). The mean serum creatinine prior to foscarnet was 80.5 +/- 3.3 mumol/l and the mean increase was 190 +/- 28.3 mumol/l (range 80-1,000). Peak serum creatinine was higher than 200 and 300 mumol/l in 16 and 13 patients, respectively. Kidney obtained at autopsy from a 30-year-old male with AIDS, CMV pneumonitis and acute renal failure secondary to foscarnet administration showed an extensive tubular necrosis. In the group which was prospectively hydrated only 1 patient had an acute renal failure. The mean serum creatinine at the peak (96 +/- 4 mumol/l) and at the end of the treatment (83 +/- 4 mumol/l) was significantly lower (p less than 0.05) than in non hydrated patients. In conclusion, foscarnet is a highly nephrotoxic drug which induces acute tubular necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Improved physical performance after treatment of renal anemia with recombinant human erythropoietin

The physical performance of 12 anemic patients on renal dialysis was investigated following treatment of renal anemia with recombinant human erythropoietin (rhEPO; 40-120 U/kg, 3 times a week). Exercise intensity at a heart rate of 130 beats/min (PWC130) on a bicycle ergometer was assessed before rhEPO treatment, after reaching the target hematocrit (73 +/- 18 days), and in the maintenance phase (211 +/- 53 days). Hemoglobin concentrations measured at these time points were 7.3 +/- 1.2, 11.9 +/- 1.5, and 12.1 +/- 1.4 g/dl, respectively. PWC130 rose from 77 +/- 27 to 104 +/- 37 and 104 +/- 51 W, respectively. Aerobic threshold (i.e. blood lactic acid concentration of 2 mmol/l) shifted to higher workloads indicating improved muscle oxygen supply.     

Oral l-carnitine does not decrease erythropoietin requirement in pediatric dialysis

The use of recombinant human erythropoietin (rhEPO) has greatly facilitated the treatment of anemia in children with chronic renal failure, but is expensive. Several reports on adult patients have shown that supplementation with l-carnitine can decrease the requirement for rhEPO. The objective of this study was to investigate the effect of oral supplementation with l-carnitine on the rhEPO requirement in children on dialysis. We investigated 16 children on dialysis (11 hemodialysis, 5 peritoneal dialysis) with a median age of 10.2 years. All children were stable on rhEPO treatment at least 3 months before study entrance. After obtaining baseline data, all children were supplemented with l-carnitine 20 mg/kg/day. Data were collected for 26 weeks. Follow-up was completed for 12 patients (8 hemodialysis, 4 peritoneal dialysis). At baseline free carnitine (32±18 μmol/l) and total carnitine levels (54±37 μmol/l) were normal. At the end of the study free carnitine levels had increased to 97±56 μmol/l (P<0.05) and total carnitine levels to 163±90 μmol/l (P<0.05). There was no significant change in rhEPO requirement. Hemoglobin level or hematocrit did not change significantly during the study. In conclusion we could not demonstrate a beneficial effect of supplementation with l-carnitine on rhEPO requirement in children on dialysis. Received: 17 September 1999 / Revised: 14 April 2000 / Accepted: 17 April 2000     

Deterioration in renal function associated with fibrate therapy

BACKGROUND: Fibric acid derivatives (fibrates) are commonly used for the treatment of hyperlipidemia. A side-effect of these medications that is not well recognized is deterioration in renal function during therapy. This study reviewed a series of patients who showed such a deterioration. METHODS: The design was a retrospective chart review. Data extracted included creatinine, urea, cyclosporine levels, medical history, and medications. Charts were examined for other potential reasons for a change in creatinine. RESULTS: There were a total of 10 patients. All were males between the ages of 37 and 71. All had a history of renal insufficiency. Six had received a renal transplant and, of these, 5 were on cyclosporine. Reasons for underlying renal impairment included diabetes, hypertension, nephrosclerosis, and renal disease of unknown etiology. Most patients had risk factors for or the presence of vascular disease. The mean pre-treatment creatinine was 182 +/- 14 micromol/l (2.1 +/- 0.2 mg/dl) (mean +/- SE), compared to a peak creatinine on the medication of 247 +/- 16 micromol/l (2.8 +/- 0.2 mg/dl) (p < 0.001). The post-medication mean was 183 +/- 13 (2.1 +/- 0.1 mg/dl) (p < 0.001 vs maximum creatinine). Urea values also increased with therapy and decreased following discontinuation of the fibrate. Cyclosporine levels did not change with treatment. All recorded creatine kinase values were within the normal range. CONCLUSIONS: A group of 10 men showed a reversible deterioration in renal function while being treated with a fibrate for hyperlipidemia. The mechanism involved in the deterioration in renal function is not clear. The most plausible mechanism is one based on renal hemodynamics, given the rapid and complete reversibility that was noted and the finding that most patients had risk factors for vascular disease. If patients with pre-existing renal dysfunction are to receive a trial of fibrate therapy, this should be done with caution and     

Adult minimal change glomerulopathy with acute renal failure

Oliguric acute renal failure occurs in some adult patients with minimal change glomerulopathy. To look for clinical and pathologic factors that increase the risk for developing acute renal failure, 21 adults with minimal change glomerulopathy and a serum creatinine greater than 177 mumol/L (mean, 486 mumol/L; range, 194 to 1,344 mumol/L) (greater than 2.0 mg/dL [mean, 5.5 mg/dL; range, 2.2 to 15.2 mg/dL]) were compared with 50 adults with minimal change glomerulopathy and a serum creatinine less than 133 mumol/L (mean, 88 mumol/L; range, 53 to 124 mumol/L) (less than 1.5 mg/dL [mean, 1.0 mg/dL; range, 0.6 to 1.4 mg/dL]). Minimal change glomerulopathy patients with acute renal failure were older (59.5 v 40.3 years, P less than 0.001), and had higher systolic blood pressure (158 v 138 mm Hg, P = 0.001), more proteinuria (13.5 v 7.9 g/24 h, P = 0.01), and more arteriosclerosis in the renal biopsy specimen (1.7 + v 0.7 + on a scale of 0 to 4+, P = 0.005). Tubular epithelial simplification identical to that observed with ischemic acute renal failure (acute tubular necrosis) was observed in 71% of the patients with serum creatinine greater than 177 mumol/L (greater than 2.0 mg/dL) and 0% of those with less than 133 mumol/L (less than 1.5 mg/dL). All 18 patients with renal failure for whom follow-up data were available had recovery of function (mean creatinine, 539 +/- 301 mumol/L [6.1 +/- 3.4 mg/dL] at the time of biopsy and 106 +/- 27 mumol/L [1.2 +/- 0.3 mg/dL] at last follow-up), but sometimes only after weeks of dialysis support.(ABSTRACT TRUNCATED AT 250 WORDS)     

Peritoneovenous shunt in the management of the hepatorenal syndrome

The hepatorenal syndrome (HRS) is a terminal complication of severe liver disease associated with a mortality of 80 to 90%. Although the renal functional abnormalities in the HRS suggest prerenal azotemia, volume expansion with saline, albumin or ascitic fluid rarely results in reversal of the HRS because fluid redistributes from the vascular space. Since the peritoneovenous (PV) shunt causes sustained central volume expansion, it has been advocated for the treatment of the HRS. We prospectively compared the PV shunt (N = 10) to Medical Therapy (MED) (N = 10) on renal function and mortality in 20 patients with the HRS associated with alcoholic liver disease. The HRS was diagnosed on the basis of clinical, hemodynamic, and laboratory criteria. The insertion of a PV shunt resulted in an increase in pulmonary capillary wedge pressure (4.2 +/- 1.1 vs. -1.5 +/- 1.0 mm Hg, P less than 0.01) and in cardiac index (0.8 +/- 0.3 vs. -0.2 +/- 0.3 1/min/m2, P less than 0.05). After 48 to 72 hours, weight (+3.1 +/- 1.1 kg) and serum creatinine (3.9 +/- 0.5 to 5.5 +/- 0.7 mg/dl, P less than 0.001) were increased with MED therapy and decreased (weight: -3.7 +/- 0.7 kg; serum creatinine: 3.6 +/- 0.4 to 3.0 +/- 0.5, P less than 0.05) with the PV shunt. Despite improvement in renal function, only one patient with the PV shunt had prolonged survival (210 days). In the remainder, survival was 13.8 +/- 2.2 days compared to 4.1 +/- 0.6 days with MED therapy. We conclude that the PV shunt often stabilizes renal function, but does not prolong life in patients with the HRS.     

Effect of recombinant human erythropoietin on renal function in humans

To assess the effect of recombinant human erythropoietin (r-HuEPO) treatment on renal function, the slopes of the regression lines of the reciprocal of serum creatinine versus time were compared in 26 patients with renal insufficiency (serum creatinine ranged from 2.3 to 11.7 mg/dl) followed for a period of 2.7 to 24 months. Ten patients received r-HuEPO and the anemia was corrected (Group I). Sixteen patients did not receive r-HuEPO. Ten of them were anemic (Group II) and six had normal hematocrits (Group III). All study groups were matched for age, diagnosis and degree of renal insufficiency. All cohorts were followed prospectively (Period B, from the first day of the study to the time of data analysis or dialysis and transplantation); renal function was also examined retrospectively (Period A, from the first day of the study to the time of first renal function measurement). Hematocrit was lowest in Group II control patients, 27%, highest in the Group III control subjects, 43%, and intermediate in Group I EPO-treated patients, 36%. Serum creatinine uniformly increased in all three groups of patients. The rate of progression, as measured by the slopes of the reciprocal of serum creatinine versus time, however, was similar in all three groups of subjects and during both periods. The mean slopes for Group I patients before and after r-HuEPO were, respectively, -0.0058 and -0.0054, that of the control cohorts with low and normal hematocrit during period B were -0.0063 and -0.0010, respectively. Thus, it appeared that neither r-HuEPO administration nor a normal hematocrit accelerated the deterioration of renal function in these patients with renal insufficiency.     

The effect of vitamin C supplementation and withdrawal on the mortality and morbidity of regular hemodialysis patients

The present study was undertaken to evaluate the effects of vitamin C supplementation (VC-S) on the morbidity and mortality of 61 clinically stable outpatients maintained on regular hemodialysis (HD). All patients were given vitamin C (500 mg daily) for 2 years and observed for a further 2 years on no treatment. VC-S significantly increased the plasma levels of ascorbic acid up to 7.8 mg/dl (mean 3.3 +/- 0.4 s.e.m.) which fell after withdrawal to the normal range (mean 1.2 +/- 0.2 mg/dl). Hyperoxalemia was aggravated by VC-S (mean 61.5 +/- 3.3 mumol/l, range 33.3 to 165.5) while plasma oxalate levels in the unsupplemented period decreased to 36.3 +/- 3.3 mumol/l (p less than 0.01). There were no differences in creatinine, hematocrit, blood transfusion requirement, morbidity (including hospitalization) or mortality between the two periods of time in the same patients. In conclusion, we could not find any beneficial effects on morbidity or mortality as a result of using VC-S in regular HD patients. However, secondary hyperoxalemia was aggravated. As a result of these observations it appears that VC-S is harmful and unnecessary in these patients provided they are on an adequate diet.     

Relationship between hematocrit and renal function in men and women

BACKGROUND: Anemia is a known complication of renal insufficiency, but the relationship between level of renal function and magnitude of reduction in hematocrit is not well defined. Men have higher hematocrit and absolute glomerular filtration rate (GFR) than women; however, it is unknown whether the level of clearance associated with decreased hematocrit is the same in men and women. METHODS: We conducted a cross-sectional study of 12,055 adult ambulatory patients. General linear models were used to analyze the relationship between hematocrit and Cockcroft-Gault equation estimated creatinine clearance (C(Cr); mL/min) and Modification of Diet in Renal Disease (MDRD) formula estimated the GFR indexed to body surface area (mL/min/1.73 m(2)). RESULTS: The hematocrit decreased progressively below estimated C(Cr) 60 mL/min in men and 40 mL/min in women. Compared with subjects with C(Cr)> 80 mL/min, men with C(Cr) 60 to 50 mL/min, 50 to 40 mL/min, 40 to 30 mL/min, 30 to 20 mL/min, and < or =20 mL/min had mean hematocrits that were lower by 1.0, 2.4, 3.7, 3.5, and 10.0%, respectively; the corresponding reductions in women with C(Cr) 40 to 30 mL/min, 30 to 20 mL/min, and < or =20 mL/min were 1.7, 2.9, and 6.3% (all P < 0.05). This between-sex difference diminished when renal function measurement was indexed to body size. Compared with subjects with GFR> 80 mL/min/1.73 m(2), men with GFR 50 to 40 mL/min/1.73 m(2), 40 to 30 mL/min/1.73 m(2), 30 to 20 mL/min/1.73 m(2), and < or =20 mL/min/1.73 m(2) had mean hematocrits that were lower by 2.0, 4.4, 5.3, and 9.4%; the corresponding reductions in women with GFR 50 to 40 mL/min/1.73 m(2), 40 to 30 mL/min/1.73 m(2), 30 to 20 mL/min/1.73 m(2) and < or =20 mL/min/1.73 m(2) were 0.6, 1.6, 3.8, and 5.3% (all P < 0.05). CONCLUSIONS: A decrease in hematocrit is apparent even among patients with mild to moderate renal insufficiency. At any given level of renal function below estimated C(Cr) 60 mL/min, men have a larger decrease in hematocrit than women.     

Incidence of acquired renal cysts in biopsy specimens

AIMS: This study investigated whether or not acquired renal cysts develop in patients with mild chronic renal failure. METHODS: A retrospective study was carried out using renal biopsy specimens from 720 patients. A renal cyst was defined as a tubule dilated >200 microm. RESULTS: Renal cysts were found in 21 of 720 renal biopsy specimens. Serum creatinine of 21 patients with renal cysts was significantly higher than that of 699 patients without cysts (2.59 +/- 2.64 vs. 1.09 +/- 0.79 mg/dl) (p < 0.0001). Poor renal function (serum creatinine >1.6 mg/dl) reveals more cyst formation on biopsy specimens than good renal function (serum creatinine <1.5 mg/dl). Cysts were observed in 11 of 607 (1.8%) patients less than 50 years of age and in 10 of 113 (8.8%) patients over 51 years. To exclude simple cysts which are commonly observed in older subjects, 11 patients under 50 years of age were extensively examined. Mean serum creatinine was 2.98 +/- 3.06 mg/dl (0.7-10.4 mg/dl). These 11 patients revealed low creatinine clearance of 47.5 +/- 25.6 ml/min (5-71 ml/min). Creatinine clearances in 7 patients were 52-71 ml/min (serum creatinine 0.7-2.0 mg/ dl). One of 11 biopsy specimens with cysts was examined by immunohistochemistry on lectin. This specimen was positive for tetragonolobus lectin and negative for peanut lectin, suggesting that the epithelial cells lining the cyst were derived from proximal tubules, unlike those of simple cysts. CONCLUSION: These results suggest that low normal renal function such as creatinine clearances 52-71 ml/min due to nephron loss is sufficient to induce acquired cyst development in various renal diseases.     

Community-acquired acute renal failure

Acute renal failure usually occurs during hospitalization, but may also be present on admission to the hospital. To define the causes and outcomes of community-acquired acute renal failure, we undertook a prospective study of patients admitted to the hospital with acute elevations in serum creatinine concentrations. Over a 17-month period, all admission serum creatinine determinations were screened for patients with values greater than 177 mumol/L (2 mg/dL). These values were compared with baseline creatinines to select patients with an acute elevation in serum creatinine occurring outside the hospital. One hundred patients were entered into the study, with an overall incidence of 1% of hospital admissions. Seventy percent of the patients had prerenal azotemia, 11% had intrinsic acute renal failure, 17% had obstruction, and 2% could not be classified. Mean peak serum creatinine (318 +/- 18 mumol/L [3.6 +/- 0.2 mg/dL]) and mortality (7%) was lowest in the group with prerenal azotemia. In this group, volume contraction due to vomiting, decreased fluid intake, diarrhea, fever, glucosuria, or diuretics was the most common underlying cause. The group with intrinsic acute renal failure had the most severe renal failure and the highest mortality (55%). Although ischemic acute tubular necrosis is the most common cause of hospital-acquired intrinsic acute renal failure, this etiology was seen in only one patient. Drug-induced nephrotoxicity and infection-related causes were the most common underlying etiologies of intrinsic acute renal failure. Obstructive renal failure had a mortality of 24% and was most commonly due to benign prostatic hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of famotidine, a new histamine H2-receptor antagonist, on renal function

The effects of famotidine on renal function were investigated. Eight healthy men (N) and 8 renal patients with varying degrees of renal failure (R.F.) participated in the trial. They were given either famotidine (40 mg) or cimetidine (800 mg) for 7 days. Cimetidine produced a significant decrease in creatinine clearance (from 131.6 +/- 12.9 to 107.7 +/- 3.4 ml/min (N), and 22.2 +/- 3.9 to 18.1 +/- 3.5 ml/min (R.F.], and increase in serum creatinine (from 0.96 +/- 0.05 to 1.09 +/- 0.04 mg/dl (N), and 3.46 +/- 0.62 to 3.86 +/- 0.51 mg/dl (R.F.], and a decrease in creatinine excretion (from 24.0 +/- 1.1 to 22.6 +/- 0.8 mg/kg/24 hr (N], respectively, although the reduction in creatinine excretion in the renal failure group was small. On the other hand, the famotidine treatment produced no significant changes in renal function in both subjects (creatinine clearance, 136.5 +/- 5.7 to 133.6 +/- 6.0 ml/min (N), and 21.9 +/- 3.6 to 20.9 +/- 4.1 ml/min (R.F.); serum creatinine, 0.98 +/- 0.02 to 0.99 +/- 0.02 mg/dl (N), and 3.24 +/- 0.43 to 3.46 +/- 0.55 mg/dl (R.F.); and urinary creatine, 25.1 +/- 1.0 to 25.3 +/- 1.0 mg/kg/24 hr (N), and 17.2 +/- 1.4 to 16.6 +/- 1.5 mg/kg/24 hr (R.F.]. There were no changes in the percent sodium excretion, or the serum and urinary beta 2-microglobulin in both groups.     

Renal and systemic oxygen consumption in patients with normal and abnormal renal function.

Systemic and renal oxygen consumption and hemodynamics were studied in patients with normal renal function (NI; serum creatinine concentration (Screat), 1.0 +/- 0.04 mg/dL) and those with moderate chronic renal failure with diabetes mellitus Screat, 2.7 +/- 0.2 mg/dL) or without diabetes mellitus (Screat, 2.4 +/- 0.1 mg/dL). Patients with chronic renal failure were anemic and had normal systemic oxygen consumption (NI, 10,564 +/- 277; chronic renal failure, 9,669 +/- 362 mumol of O2/min) and elevated systemic oxygen extraction (NI, 22.9 +/- 1; chronic renal failure, 30.9 +/- 1.2%) (P less than 0.02). Cardiac output and index and arterial oxygen saturation were equivalent in normal patients and in patients with chronic renal failure. Patients with chronic renal failure had higher renal oxygen extraction (NI, 7.3 +/- 0.8; chronic renal failure, 13.9 +/- 1%), lower RBF (NI, 572 +/- 146; chronic renal failure, 197 +/- 20 mL/min/kidney), and lower renal oxygen consumption per kidney (NI, 391 +/- 101; chronic renal failure, 177 +/- 20 mumol of O2/min/kidney) than did normal patients (P less than 0.02). There was a linear relationship between hemoglobin and RBF (r = 0.47, P less than 0.02). Patients with chronic renal failure and diabetes had lower RBF (diabetes mellitus, 146 +/- 23; without diabetes, 242 +/- 28 mL/min/kidney) and renal oxygen consumption per kidney (diabetes mellitus, 131 +/- 21; without diabetes, 218 +/- 29 mumol of O2/min/kidney (P less than 0.03) but equivalent renal oxygen extraction when compared with patients without diabetes. Patients with chronic renal failure without diabetes mellitus had higher renal oxygen consumption when expressed per 100 mL of creatinine clearance (diabetes mellitus, 1,016 +/- 150; without diabetes mellitus, 1,453 +/- 175 mumol of O2/min/100 mL of creatinine clearance; P less than 0.03). There was a significant linear relationship (P less than 0.005, r = 0.38) between calculated creatinine clearance and renal oxygen consumption with a y intercept representing basal renal oxygen consumption (115 mumol of O2/min/kidney) and a slope of 2.3 mumol of O2/mL. Patients with moderate chronic renal failure have normal systemic oxygen consumption but reduced RBF and renal oxygen consumption. The latter parameters are even lower in patients with chronic renal failure and diabetes. Renal hypermetabolism is more likely to exist in nondiabetic than diabetic renal disease. Basic human renal physiology and pathophysiology are described by the relationships between renal oxygen consumption, blood flow, oxygen extraction, and creatinine clearance in patients with normal and abnormal renal function of varied cause.     

Clinical and laboratory features of patients with chronic renal disease at the start of dialysis

We examined clinical and laboratory features retrospectively in 402 patients at the start of chronic hemodialysis in order to define better the "uremic syndrome" in the dialysis era. The information gathered included demographic data, renal diagnoses, uremic symptoms, biochemical values, and prevalences of hypertension (69%), diabetes mellitus (23%) and ischemic heart disease (16%). Unexpected findings were the wide ranges of serum creatinine levels (3.5 to 35 mg/dl) and blood urea nitrogen levels (35 to 345 mg/dl), and the frequency of hyponatremia (27%), hypoalbuminemia (52%), and anion gaps above 25 mg/dl (5%). There were higher hematocrits in males and diabetics, lower serum creatinine levels in females, diabetics and older patients, and lower blood urea nitrogen levels in blacks. The time interval from diagnosis of diabetes mellitus to initiation of dialysis in patients with diabetic nephropathy due to juvenile-onset diabetes mellitus (20.6 +/- 6.8 years) was twice that in adult onset diabetes mellitus (10.3 +/- 8.3 years).     

Bone histology in patients with nephrotic syndrome and normal renal function

BACKGROUND: The prevalence of metabolic bone disease in patients with nephrotic syndrome (NS) at normal level of renal function remains uncertain. METHODS: To address this issue, we studied 30 patients (20 men and 10 women, mean age 27.3 +/- 11.7 years) with NS who had normal renal function (mean creatinine clearance 103 +/- 4 ml/min). We evaluated their serum calcium, phosphorus, alkaline phosphatase, immunoreactive parathyroid hormone (iPTH), vitamin D metabolites, urinary calcium, and skeletal survey. The extent of bone mineralization was analyzed by histomorphometric analysis of iliac crest bone biopsy specimens in all patients. The findings on bone histology were correlated with biochemical parameters. RESULTS: The mean duration of NS was 35.5 +/- 26.9 months, with a protein excretion of 7.3 +/- 3.2 g/24 hr and a serum albumin of 2.2 +/- 0.8 g/dl. Total serum calcium was 7.8 +/- 0.8 mg/dl, whereas ionized calcium was 5.7 +/- 0.7 mg/dl, phosphorus 3.2 +/- 1.2 mg/dl, and alkaline phosphatase 149 +/- 48.6 U/liter. Serum iPTH levels were normal in all except two patients. The mean serum 25-hydroxyvitamin D [25(OH)D] level was 3.9 +/- 1.2 ng/ml (normal 15 to 30 ng/ml), whereas 1,25-dihydroxyvitamin D was 24 +/- 4.7 pg/ml (normal 16 to 65). There was an inverse correlation between serum levels of 25(OH)D and the magnitude of proteinuria (r = -0.42, P < 0.05). The mean 24-hour urinary calcium excretion was 82 +/- 21 mg/day. The skeletal survey was normal in all patients. Bone histology was normal in 33.3% of the patients, whereas 56.7% had isolated osteomalacia (OSM), and 10% had an increased bone resorption in association with defective mineralization. The severity of OSM measured by mineralization lag time correlated linearly with the duration (r = 0.94, P < 0.0001) and the amount (r = 0.97, P < 0.0001) of proteinuria. All patients with NS for more than three years had histological changes. Patients with OSM had lower 25(OH)D and serum albumin as compared with those with normal histology (P < 0.005). Bone mineralization had no significant correlation with serum iPTH, divalent ions, or vitamin D levels. CONCLUSIONS: OSM is a frequent finding in adult patients with NS, even at a normal level of renal function. Its severity correlates with the amount and duration of proteinuria.     

Effects of erythropoietin on left ventricular hypertrophy in adults with severe chronic renal failure and hemoglobin <10 g/dL

BACKGROUND: Left ventricular hypertrophy (LVH) frequently complicates chronic renal insufficiency. Anemia is also common in these patients and may contribute to LVH. METHODS: We conducted an open-label interventional trial to evaluate the effect of recombinant erythropoietin (rhEPO) on left ventricular mass index (LVMI) in anemic patients with renal insufficiency. Adults with creatinine clearance 10 to 30 mL/min (nondiabetics) or 20 to 40 mL/min (diabetics) were recruited, and rhEPO was given to those with anemia (hemoglobin level <10 g/dL). Baseline and 6-month LVMI and LVH (LVMI >130 g/m(2) in men and >100 g/m(2) in women), hemoglobin levels, creatinine clearance, blood pressure, medications, and medical history were obtained. Forty anemic and 61 nonanemic control subjects were enrolled. RESULTS: Overall, the prevalence of LVH was 68.3% (95% CI 58.3-77.2), and entry hemoglobin level was the only significant predictor of baseline LVH (adjusted OR 0.69 per g/dL increase in hemoglobin, 95% CI 0.50-0.94). After 6 months, LVMI decreased in anemic patients receiving rhEPO (142 +/- 56 vs. 157 +/- 56 g/m(2)) (P= 0.007), with an increase in hemoglobin (11.3 +/- 1.9 vs. 9.1 +/- 0.7 g/dL) (P= 0.001). There were no changes in LVMI or hemoglobin level among controls. After adjusting for confounders and change in hemoglobin, receipt of rhEPO was associated with a significant reduction in LVMI (P= 0.01). CONCLUSION: Treatment with rhEPO was not independently associated with significant changes in blood pressure or renal function. LVH is a common finding in chronic renal insufficiency and is associated with lower hemoglobin levels. Treatment with rhEPO may decrease LVH in patients with severe renal insufficiency and anemia.     

Effect of normalization of hematocrit on brain circulation and metabolism in hemodialysis patients

Full correction of anemia with recombinant human erythropoietin (rhEPO) has been reported to reduce the risk of cardiovascular morbidity and mortality and improve the quality of life in hemodialysis (HD) patients. Effects of normalization of hematocrit on cerebral blood flow and oxygen metabolism were investigated by positron emission tomography. Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction ratio (rOER), and metabolic rate for oxygen (rCMRO2) were measured in seven HD patients before and after correction of anemia and compared with those in six healthy control subjects. In addition, blood rheology before and on rhEPO therapy was measured in HD patients, which included blood viscosity, plasma viscosity, erythrocyte fluidity, and erythrocyte aggregability. The results showed that plasma viscosity was high (1.51+/-0.19 mPa x s) and erythrocyte fluidity was low (85.8+/-4.8 Pa(-1) x s(-1)), while whole blood viscosity was within the normal range (3.72+/-0.38 mPa x s) before rhEPO therapy. After treatment, the hematocrit rose significantly from 29.3+/-3.3 to 42.4+/-2.2% (P<0.001), accompanied by a significant increase in the whole blood viscosity to 4.57+/-0.16 mPa x s, nonsignificant decrease in erythrocyte fluidity to 79.9+/-7.4 mPa(-1) x s(-1) and nonsignificant change in plasma viscosity (1.46+/-1.3 mPa x s). Positron emission tomography measurements revealed that by normalization of hematocrit, rCBF significantly decreased from 65+/-11 to 48+/-12 ml/min per 100 cm3 (P<0.05). However, arterial oxygen content (caO2) significantly increased from 5.7+/-0.7 to 8.0+/-0.4 mmol/L (P<0.0001), rOER of the hemispheres significantly increased from 44+/-3 to 51+/-6% (P<0.05) and became significantly higher than healthy control subjects (P<0.05). In addition, rCBV significantly increased from 3.5+/-0.5 to 4.6+/-0.6 ml/100 cc brain tissue. The results showed that oxygen supply to the brain tissue increased with normalization of hematocrit, but it was accompanied by increased oxygen extraction in the brain tissue. This may be assumed to be related to the decrease of erythrocyte velocity in the cerebral capillaries as a result of the decreased blood deformability and the increased plasma viscosity.     

Influence of hematocrit on cardiopulmonary function after acute hemorrhage

The 'optimal' hematocrit to which patients should be resuscitated after shock and trauma is controversial. To test the hypothesis that sufficient oxygen delivery can be provided at a lower hematocrit without impairing oxygen consumption or hemodynamic function, 25 patients were prospectively studied immediately following injury and/or acute hemorrhage. Patients were randomized to have their hematocrits (HCT) maintained near 30% (29.7 +/- 0.4% (M +/- SEM); n = 12) or 40% (38.4 +/- 0.6%, n = 13). Cardiopulmonary parameters were measured twice a day for 3 days. Statistical analysis used a repeated measures analysis of variance with patient age, and ventilator parameters (FIO2, PEEP, and ventilator mode) as covariates. Arterial and venous O2 saturations were not significantly different at different hematocrits, although arterial and venous O2 contents were lower at 30% HCT (a = 14.1 +/- 0.2 m10(2)/dl, v = 10.1 +/- 0.3 m10(2)/dl; vs. a = 17.4 +/- 0.4 m10(2)/dl, v = 13.6 +/- 0.6 m10(2)/dl; p less than 0.05). This resulted in a lower oxygen delivery at the lower HCT. Between the two groups, there also was no significant difference in cardiac index (overall mean, 3.64 +/- 0.16 ml/min/m2), heart rate (99 +/- 4 bpm), systemic vascular resistance (1,058 +/- 55 dyne-sec/cm5), or left ventricular stroke work index (4.3 +/- 0.3 X 10(6) dyne-cm/m2). Intrapulmonary shunt was higher with higher hematocrit (22.6 +/- 2.4% at 40% HCT vs. 14.6 +/- 1.6% at 30% HCT; p less than 0.05) with no difference in end-expiratory pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biochemical abnormalities of platelets in renal failure. Evidence for decreased platelet serotonin, adenosine diphosphate and Mg-dependent adenosine triphosphatase

The platelet content of adenosine triphosphate (ATP), adenosine diphosphate (ADP), serotonin and ouabain-insensitive, magnesium-dependent adenosine triphosphatase (ATPase) was determined in patients with chronic renal failure, patients on chronic hemodialysis, and kidney transplant recipients. Platelet ATP content was normal in all. By contrast, ADP content, expressed in mumol/10(11) platelets, was significantly lower in renal failure: 1.82 +/- 0.96 compared to 2.51 +/- 0.97 in normals (p less than 0.05), but not in dialyzed or transplanted patients; 2.27 +/- 0.96 and 1.87 +/- 0.87, respectively. The mean content of serotonin was also significantly lower in renal failure patients: 0.52 microgram/10(9) platelets as compared to 0.90 microgram/10(9) platelets in normals (p less than 0.05) but was not significantly different in dialyzed and transplanted patients. ATPase was significantly lower in renal failure: 3.13 +/- 1.2 mumol Pi/10(9) platelets in whole suspension and 0.71 +/- 0.22 Pi/mg protein/h in membrane preparation compared to 4.74 +/- 1.1 and 1.18 +/- 0.19, respectively, in normals, and was significantly lower in dialyzed and transplanted patients. Experimental azotemia (BUN 65-86 mg/100 ml), induced by the oral ingestion of urea 2-3 g/kg body weight over 24 h, failed to induce any of these abnormalities. The abnormality in platelet ADP and serotonin content in renal failure paralleled the functional platelet defects which characterize these patients and were reversible following dialysis and transplantation.     

Low risk of contrast nephropathy in high-risk patients undergoing spiral computed tomography angiography with the contrast medium iopromide and prophylactic oral hydratation

BACKGROUND: Spiral computed tomography angiography (CTA) is a sensitive and specific technique for visualizing renal arteries and diagnosing renal artery stenosis (RAS). Whether spiral CTA is associated with increased risk of contrast nephropathy (CN) in patients with impaired renal function is unknown. METHODS: We prospectively studied 50 patients with chronic renal insufficiency (serum creatinine concentration greater than 1.58 mg/dl) who underwent spiral CTA with iopromide, a nonionic, low-osmolar contrast agent. Fourteen patients had diabetes mellitus. Patients were encouraged to drink 1 l of water 12 hours before and 2 l over 24 hours after the procedure. The presence of CN was defined by an increase of 20% or more in the baseline serum creatinine level within or 72 hours after administration of the radio-contrast agent. RESULTS: In the entire group, mean serum creatinine levels increased significantly from 2.92 +/- 1.39 to 3.06 +/- 1.55 mg/dl (p = 0.02) and mean creatinine clearance decreased from 29.8 +/- 12.9 to 28.9 +/- 12.8 ml/min (p = 0.009) 72 h after administration of the contrast medium. Two patients experienced an increase in serum creatinine level of 20%. Renal function returned to baseline within seven days in the 2 patients. Absolute changes in creatinine clearance after the administration of radiocontrast medium were similar in nondiabetic and diabetic patients and in the subgroup of patients, with a baseline serum creatinine of < 3 mg/dl and > or = 3 mg/dl. CONCLUSIONS: In patients with chronic renal insufficiency, spiral CTA performed with iopromide, a nonionic, low-osmolar contrast medium and a prophylactic oral hydratation, is a minimally invasive technique with low risk of contrast nephropathy.