Rise In Blood Urea Nitrogen Research Articles

Blood Urea Nitrogen (BUN) for the Early Prediction of Mortality in Acute Pancreatitis

Purpose: We previously identified BUN as the most accurate routine laboratory test for prediction of mortality in acute pancreatitis (AP) in a large multi-center retrospective cohort study. The purpose of this study was to: 1) confirm accuracy of BUN during first 24 hours for prediction of mortality in a rigorously defined prospective AP cohort and; 2) identify factors associated with increased BUN. Methods: Prospective cohort study of consecutive AP patients treated in a tertiary care hospital from June 2005-May 2007. AP was defined as 2 or more of the following: characteristic abdominal pain, amylase/lipase elevation >3 times upper limit normal and/or confirmatory imaging findings. Routine laboratory tests were monitored throughout hospitalization. Accuracy of BUN for prediction of in-hospital mortality was evaluated using logistic regression including admission BUN and change in BUN at 24 hours as discreet variables. Logistic regression was also used to determine the extent to which hydration (cc/kg first 24 hours), renal insufficiency (serum creatinine) or systemic inflammation (SIRS) contributed to increases in BUN. Results: We enrolled a total of 397 AP cases during the study period. Among these, 17% were hospital transfers. There were 15 (3.7%) deaths. A logistic regression model incorporating admission BUN and change in BUN at 24 hours produced an AUC of 0.91 for mortality. Both admission BUN and change in BUN were independent predictors of mortality (p<0.0001) after adjusting for age, gender, Charlson comorbidity score and hospital transfer status. Reduced fluid resuscitation (p=0.03), worsened renal insufficiency (p<0.0001) and SIRS (p=0.03) were independently associated with rise in BUN. Conclusion: We have prospectively confirmed the accuracy of early rise in BUN for prediction of mortality in AP. Rise in BUN is multi-factorial, reflecting intravascular volume depletion, renal insufficiency and systemic inflammation.

Early amino acids and the metabolic response of ELBW infants (⩽1000 g) in three time periods

To evaluate early amino-acid (AA) administration in extremely low birth weight (ELBW) infants over three time periods, beginning with the initiation of this strategy. This was a retrospective study of ELBW infants between 2000 and 2007. Nutritional intake and laboratory results were monitored during the first 5 days of life. Growth rates and complications were followed until discharge. Infants were similar in birth weight (BW), gestational age (GA) and severity of illness. The age at initiation of AA decreased significantly over time. Age at weight nadir, return to BW and percent postnatal weight loss decreased in epoch 3. There were modest increases in blood urea nitrogen (BUN), but no significant metabolic disturbances were observed. Cholestasis was more prevalent in epoch 2. AA administration within the first hours of life appears to be safe and beneficial for ELBW infants. Absent signs of renal dysfunction, a modest rise in BUN is consistent with the neonate's utilization of AAs for energy.

Endotoxin and cisplatin synergistically induce renal dysfunction and cytokine production in mice

A major toxicity of the cancer chemotherapeutic agent cisplatin is acute renal failure. Sepsis is a common cause of acute renal failure in humans and patients who receive cisplatin are at increased risk for sepsis. Accordingly, this study examined the interactions between cisplatin and endotoxin in vivo with respect to renal function and cytokine production. Mice were treated with either a single dose of cisplatin or two doses of LPS administered 24 h apart, or both agents in combination. Administration of 10 mg/kg cisplatin had no effect on blood urea nitrogen or creatinine levels throughout the course of the study. LPS resulted in a modest rise in blood urea nitrogen at 24 and 48 h, which returned to normal by 72 h. In contrast, mice treated with both cisplatin and LPS developed severe renal failure and an increase in mortality. Urine, but not serum, TNF-alpha levels showed a synergistic increase by cisplatin and LPS. Urinary IL-6, MCP-1, KC, and GM-CSF also showed a synergistic increase with cisplatin+LPS treatment. The renal dysfunction induced by cisplatin+LPS was completely dependent on TLR4 signaling and partially dependent on TNF-alpha production. Increased cytokine production was associated with a moderate increase in infiltrating leukocytes which was not different between cisplatin+LPS and LPS alone. These results indicate that cisplatin and LPS act synergistically to produce nephrotoxicity which may involve proinflammatory cytokine production.

ACUTE INCREASE IN BLOOD UREA NITROGEN CAUSED BY ENTERIC NUTRITION

ACUTE INCREASE IN BLOOD UREA NITROGEN CAUSED BY ENTERIC NUTRITION

Increased Excretion of Urinary 20-HETE in Rats With Cyclosporine-Induced Nephrotoxicity

The present study examined the contribution of 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) in cyclosporine A (CsA)-induced renal nephrotoxicity. Treatment of rats with CsA (50 mg/kg) for 9 days induced renal damage as indicated by marked increase in urine flow (from 9.0 ± 0.3 ml/day to 46.6 ± 7.1 ml/day) and a 3 – 5-fold rise in blood urea nitrogen (BUN) levels. The urinary excretion of 20-HETE increased from 164 ± 5 ng/day (N = 5) to 2432 ± 290 ng/day (N = 5, P<0.01) after 9 days of CsA treatment. The increase in the urinary excretion of 20-HETE in the CsA treated rats was highly correlated with the increase in BUN levels (r = 0.819, P<0.001) and urine volume (r = 0.832, P<0.001). Immunohistochemical examination of kidney revealed that expression of cytochrome P450 4A (CYP4A) protein was markedly enhanced in the proximal tubules of CsA-treated rats. These results indicate that CsA-induced nephrotoxicity in rats is associated with a marked elevation in the renal production of 20-HETE and that 20-HETE may contribute to the pathophysiological condition of CsA-induced nephrotoxicity.

Bone marrow stem cells contribute to repair of the ischemically injured renal tubule.

The paradigm for recovery of the renal tubule from acute tubular necrosis is that surviving cells from the areas bordering the injury must migrate into the regions of tubular denudation and proliferate to re-establish the normal tubular epithelium. However, therapies aimed at stimulating these events have failed to alter the course of acute renal failure in human trials. In the present study, we demonstrate that Lin-Sca-1+ cells from the adult mouse bone marrow are mobilized into the circulation by transient renal ischemia and home specifically to injured regions of the renal tubule. There they differentiate into renal tubular epithelial cells and appear to constitute the majority of the cells present in the previously necrotic tubules. Loss of stem cells following bone marrow ablation results in a greater rise in blood urea nitrogen after renal ischemia, while stem cell infusion after bone marrow ablation reverses this effect. Thus, therapies aimed at enhancing the mobilization, propagation, and/or delivery of bone marrow stem cells to the kidney hold potential as entirely new approaches for the treatment of acute tubular necrosis.

Protective effect of tetramethylpyrazine on absolute ethanol-induced renal toxicity in mice.

Acute administration of absolute ethanol (10 ml/kg) per os to fasted mice produced extensive renal failure as measured by a rise in blood urea nitrogen and creatinine. Pretreatment with oral administration of tetramethylpyrazine (TMP) prevented such failure. The maximal effect against absolute ethanol-induced renal failure could be observed 1 h after TMP administration. In order to further investigate the renal protective mechanism of TMP, experiments on lipid peroxidation and superoxide scavenging activity were conducted. Renal homogenates made from mice treated with ethanol showed that TMP pretreatment had an antioxidant effect. Mice in acute renal failure had higher malonic dialdehyde concentrations than those pretreated with TMP. The renal protective mechanism of TMP was attributed, in part, to its prominent superoxide scavenging effect, which protects the kidney from superoxide-induced renal damage.

Complement is activated in kidney by endotoxin but does not cause the ensuing acute renal failure

Acute renal failure (ARF) in sepsis occurs when the release of multiple inflammatory mediators is induced by bacterial endotoxins. C3 mRNA is markedly up-regulated in mouse kidney after exposure to lipopolysaccharide (LPS). We hypothesized that LPS could induce tubular synthesis and secretion of C3, leading to activation of the complement cascade and direct renal tubular injury. ARF was induced in mice by intravenous injection of LPS and was confirmed by an acute rise in blood urea nitrogen (BUN) and histologically by acute tubular necrosis. Three separate strategies were used to investigate the role of the complement system in this model of ARF: (1) Crry-Ig, a recombinant protein containing the potent murine complement C3 activation inhibitor Crry was injected at the same time as LPS (N = 8). (2) LPS was injected into transgenic mice overexpressing Crry in glomeruli and tubules (N = 8), and (3) LPS was injected into C3-deficient mice (N = 5). Compared with unmanipulated mice, C3 staining by immunofluorescence (IF) microscopy in mice injected with LPS was greater in renal cortical tubular cells (IF score of 2. 1 +/- 0.1 vs. 1.4 +/- 0.2 in controls, P = 0.013), most prominently at the basolateral surface. LPS injection led to a 16- to 42-fold increase in urinary C3 excretion. Despite reduction or complete elimination of renal C3 with maneuvers suppressing complement activation, BUN values were not statistically different across all groups. In no experiment did BUN values correlate with the extent of C3 staining. Although LPS up-regulates renal C3 synthesis, resulting in basolateral tubular C3 deposition, this is not responsible for LPS-induced ARF in mice.

CO-ADMINISTRATION OF FUROSEMIDE AUGMENTS TACROLIMUS-INDUCED IMPAIRMENT IN KIDNEY FUNCTION IN RATS

Sodium-depletion in rats reproduces functional and morphological tacrolimus nephrotoxicity observed in man. Potent diuretics induce sodium-depletion. Our objective was to determine the effect of a loop diuretic furosemide on tacrolimus-mediated functional and pathological impairment of the kidney in rats. Sprague-Dawley rats were divided into four groups; group 1, rats received vehicle (saline) only; group 2, rats were treated with tacrolimus (1mg/kg body weight) and furosemide (5mg/kg body weight); group 3, rats were treated with tacrolimus alone; and group 4, rats were treated with furosemide (5mg/kg body weight) alone. On day 28, tail blood pressure was measured and the rats were placed in metabolic cages for urine collection. After 24 hr the rats were sacrificed. Tacrolimus alone tended to cause growth retardation, hypotension, hypomagnesemia and a rise in blood urea nitrogen. Furosemide co-administration enhanced the effects of tacrolimus on hypotension, hypomagnesemia and a rise in blood urea nitrogen. The renal histology characterized by cytoplasmic vacuolization of the proximal tubules was not different between the rats treated with both tacrolimus and furosemide and the rats treated with tacrolimus alone. A strong immunostaining for FKBP-12, a tacrolimus-binding protein, was observed in the medulla of the kidneys of rats treated with tacrolimus either with or without furosemide.These results indicate that furosemide further augments tacrolimus induced impairment in kidney function, and that furosemide should be used with discretion in patients on tacrolimus therapy.

Renal handling of amino acids in 5/6-nephrectomized rats: stimulation of renal amino acid reabsorption after treatment with triiodothyronine or dexamethasone under amino acid load.

In anaesthetized adult female rats, the renal amino acid handling was measured six days after 5/6 nephrectomy (5/6NX). The distinct rise in blood urea nitrogen as well as the significant reduction in urine flow and GFR indicate an impairment of kidney function. In principle, in 5/6NX rats amino acid plasma concentrations were comparable to those of control animals with two intact kidneys, whereas the fractional excretions (FEAA) of most endogenous amino acids measured were significantly enhanced. After bolus injection of leucine or taurine (each 20 mg/100 g b.wt.) or glutamine (90 mg/ 100 g b.wt.), dissolved in 2 ml normal saline per 100 g b.wt., the FEAA of both the amino acids administered and the endogenous amino acids increased as a sign of overloaded amino acid reabsorption capacity. This effect was more pronounced in 5/6NX rats than in controls. As early as one hour after amino acid load, plasma concentrations and FEAA returned to baseline values of 5/6NX rats. A pretreatment with triiodothyronine (20 micrograms/100 g b.wt.) or dexamethasone (60 micrograms/100 g b.wt.), both given intraperitoneally once daily for 3 days, stimulated the renal amino acid transport capacity in 5/6NX rats: the increase in FEAA after amino acid load was significantly lower compared to non-pretreated animals. This stimulation could be shown for the bolus amino acids and the endogenous amino acids and was more distinct in 5/6NX rats than in controls with two intact kidneys.

EFFECTS OF POST-WEANING NUTRITIONAL CONDITIONS ON ISOWEAN PIGS

This study quantifies the responses of isowean pigs to post-weaning nutritional conditions as may be encountered during extended shipment. PIC breeding stock pigs at 8 to 12 days of age (3.5 to 4.0 kg body weight) were subjected to four nutritional regimens for 72 h. The pigs were then raised with ad libitum feeding for 14 days. Thermoneutral environments were used throughout the experiment. Pigs deprived of feed and water (i.e., Fast) had higher body weight loss (of 0.61 kg/pig or 17% of their initial body weight) as compared with pigs provided with feed and water supplement (0.39 kg/pig or 11% of their initial body weight) or water supplement only (0.43 kg/pig or 11.5% IBW) (P < 0.05). All the treatments led to significant rise in blood urea nitrogen but fall in blood glucose (P < 0.05). However, the glucose levels were much higher than the generally considered hypoglycemic level (75 mg/dL). All pigs showed a similar degree of dehydration, as evidenced by elevated hematocrit and blood electrolyte concentrations (P < 0.05). The physiological responses returned to normal during the 14-day growth period and were similar for all the pigs. The results suggest that isowean pigs (PIC genetic line) responded well to post-weaning nutritional conditions typically encountered during extended shipments. Supply of bacteria-resistant water supplement such as Aqua-Jel seemed beneficial in reducing stress and may be considered for extended commercial shipment. However, in-transit supply of feed added little benefit to the pigs and thus may be omitted. This omission has special implications for international shipments because certain countries prohibit inclusion of feed in shipment. The energetics data of this study may be used to design and operate ventilation systems in transportation and production facilities for the isowean pigs.

Urea kinetic modeling for CRRT

Urea kinetic modeling (UKM) for dialysis quantification and prescription, although widely used in chronic renal failure (CRF), has been largely absent in the acute setting. A quantitative approach to prescription of continuous renal replacement therapies (CRRTs) for acute renal failure (ARF) based on UKM is presented. For patients with a relatively constant urea generation rate, G, who are receiving a fixed dose of CRRT, blood urea nitrogen (BUN) falls in an exponential fashion, approaching a plateau level after 3 to 4 days of continuous treatment. The CRRT clearance, K, necessary to achieve a desired plateau value of BUN, C goal, may be computed as G/C goal × K for all but predilutional CRRT modalities may be calculated as equal to the effluent (dialysate plus ultrafiltrate) flow rate from the filter. Urea mass balance equations are proposed for the determination of patient G value either during the pretreatment rise in BUN or during the decline in BUN with CRRT. In the absence of a reliable estimate of patient G, a reasonable CRRT starting prescription is to set the filter effluent rate in liters per hour (≈K) to 1.2 times the patient's body weight in kilograms divided by the desired C goal in milligrams per deciliter. This relationship assumes moderate hypercatabolism (normalized protein catabolic rate = 2.0 g/kg/d) and patient urea distribution volume equal to 60% of body weight. For C goal = 60 mg/dL, this reduces to an easily remembered formula for K (in L/hr) of twice the patient's body weight divided by 100.

Massive hydronephrosis associated with traumatic rupture

Twelve cases of traumatic rupture of a massive hydronephrosis are reported. The key points in the diagnosis are: injury around the loin, peritonitis, a fall of pH in the abdominal paracentesis fluid, a rise of blood urea nitrogen (BUN) and structural abnormality of the affected renal pelvis seen on ultrasonography. The treatment differed according to the disease causing the hydronephrosis before the injury. All patients were treated surgically with a satisfactory overall cure rate. Follow-up of 12 years has not revealed any significant sequelae.

Reduced renal accumulation and toxicity of cisplatin in experimental galactosemia.

The kidneys of streptozotocin (STZ)-diabetic rats are resistant to certain toxic effects of the antineoplastic drug cisplatin. The mechanism is unknown. This study used the galactosemic rat model to test the hypothesis that the apparent diabetes-induced protection is due to changes in the kidney secondary to chronically elevated hexose concentrations. Galactosemic rats are normoinsulinemic and are free from many of the multiple biochemical abnormalities seen in STZ diabetics. The experiments compared renal cortical platinum (Pt) and blood urea nitrogen (BUN) levels after intraperitoneal injection of 5 mg/kg of cisplatin in galactosemic, STZ-diabetic, and age-matched nondiabetic Sprague-Dawley rats. Nephrotoxicity was defined as a BUN concentration ratio (after to before cisplatin) > 2.5. The results demonstrate that the kidneys of both galactosemic and STZ-diabetic rats became resistant to cisplatin-induced elevation of BUN and, further, that the development of the protection was related to the duration of the diabetic state. Although the protective effect developed more slowly in the galactosemic rats, the attenuation of the rise in BUN was ultimately comparable to that seen in STZ diabetics. Renal cortex [Pt] after cisplatin injection was significantly lower in galactosemics and STZ diabetics compared with age-matched nondiabetics, with the order nondiabetics > galactosemics > STZ diabetics. It was noted, however, that renal Pt accumulation was maximally depressed within 4 weeks of experimental diabetes, whereas the BUN ratio continued to decline with increasing duration of both galactosemia and STZ diabetes. Thus, reduced renal Pt accumulation cannot by itself explain the progressive attenuation of the toxicity. The results support the hypothesis and suggest that the galactosemic rat will be a useful model for mechanistic study of diabetes-induced protection from cisplatin nephrotoxicity.

Treatment of Radiation Nephropathy with Captopril

Both experimental and clinical radiation nephropathy are typically progressive, evolving to kidney failure over weeks to months. Other late radiation injuries (spinal cord, lung) are also progressive and have no known specific antidote. Recent reports of the efficacy of captopril in modifying radiation injury of the lung prompted this trial of captopril in treating established radiation nephropathy. Six months after 15-27 Gy in 12 fractions bilateral renal irradiation, 72 rats with blood urea nitrogen > 4.1 mmol/liter were started on captopril (500 mg/liter) or no drug in the drinking water. Subsequent survival was significantly enhanced in rats receiving captopril as opposed to no drug (P = 0.0013), and the rate of rise of blood urea nitrogen was significantly diminished (P < 0.0001) in the animals on captopril. Urine protein excretion was also reduced from initially elevated levels in the rats on captopril compared to levels in rats given no drug. We conclude that captopril therapy preserves kidney function, reduces proteinuria, and enhances survival in experimental radiation nephropathy.

EVIDENCE THAT PENTOXIFYLLINE REDUCES ANTI-CD3 MONOCLONAL ANTIBODY-INDUCED CYTOKINE RELEASE SYNDROME

Pretreatment with pentoxifylline (PTX), a methylxanthine known for its beneficial effects on tissue lesions induced by the injection of endotoxin or recombinant cytokines, was shown to decrease the systemic release of tumor necrosis factor and interleukin 2 occurring after the administration of the anti-CD3 monoclonal antibody 145-2C11 in mice. In parallel, PTX attenuated the hypothermia and the rise in blood urea nitrogen observed in this model. The protective effect of PTX on the toxicity of 145-2C11 was confirmed by the reduction of the mortality among D-galactosamine-sensitized animals. The mitigation by PTX of the release of cytokines did not affect the immunosuppression entailed by 145-2C11 as assessed by the unmodified cytotoxic T lymphocytes (CTL) unresponsiveness against alloantigens measured 48 hr after the injection of the mAb. In vitro experiments on human peripheral blood leukocytes indicated that PTX alone or in synergy with methylprednisolone (m-PDS) also inhibited the release of TNF and IL-2 induced by OKT3. Finally, in a preliminary pilot trial conducted in kidney transplant recipients, we observed that pretreatment with PTX (20 mg/kg i.v.) in addition to m-PDS (2 g i.v.) reduced by half the amount of TNF released in the blood stream after the first injection of OKT3, while no further reduction of the low levels of IL-2 was found.

Glomerular angiotensin II receptor modulation in glycerol-induced acute renal failure

The objective of this study was to examine the relationship between plasma angiotensin II (ANG II) and ANG II receptor binding to the glomerulus following acute renal failure (ARF) induced by an injection of glycerol (50%, 10 ml/kg im). At 2 and 24 h after glycerol injection, ARF was documented by a rise in blood urea nitrogen (BUN) (normal, 18.6 +/- 0.7; 2 h after glycerol 29.3 +/- 2.3; 24 h after glycerol, 103.0 +/- 12.0 mg/dl; P less than 0.002 each experimental vs. normal) and creatinine (normal, 0.41 +/- 0.02; 2 h after glycerol, 0.96 +/- 0.10; 24 h after glycerol, 2.40 +/- 0.30 mg/dl; P less than 0.001, experimental vs. normal groups). Plasma ANG II rose from a control of 15.8 +/- 3.1 to 26.9 +/- 4.4 pg/ml at 2 h and 49.5 +/- 8.6 pg/ml at 24 h after glycerol (P less than 0.05, experimental vs. normal). No changes in affinity or density of glomerular ANG II receptors were detected either at 2 or 24 h after glycerol injection despite the significant rise in plasma ANG II (glomerular ANG II receptors: normal, 1,000 +/- 61; 2 h after glycerol, 896 +/- 120; 24 h after glycerol, 936 +/- 80 fmol/mg). The 24-h infusion of ANG II in normal rats to achieve plasma levels identical to the 24 h ARF group caused ANG II receptor density to fall to 58.1 +/- 8.6% of control values (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Vancomycin enhancement of experimental tobramycin nephrotoxicity.

The influence of vancomycin on tobramycin nephrotoxicity was assessed in male Fischer rats. Treatment groups included controls receiving diluent and groups receiving vancomycin alone at a dosage of 200 mg/kg (body weight) per day, tobramycin alone at a dosage of 80 mg/kg per day, and a combination of vancomycin and tobramycin at the above dosages. All regimens were injected on a twice-a-day schedule. The animals were sacrificed on days 1, 3, 10, 14, 17, and 21. When compared with controls, animals receiving vancomycin alone exhibited no detectable renal toxicity. Compared with the case with controls, tobramycin alone was toxic, as manifested by lower mean animal weights, increased blood urea nitrogen concentrations on days 14 and 17 (P less than 0.005), increased serum creatinine concentrations on days 17 and 21 (P less than 0.005), and the presence of renal cortical tubular necrosis and regeneration. When compared with tobramycin alone, the combination of vancomycin and tobramycin caused earlier and more severe toxicity. By day 10, the magnitude of weight loss, the rise in blood urea nitrogen, and the increase in serum creatinine concentration were all greater in the rats given the combination of vancomycin plus tobramycin than in the animals given tobramycin alone (P less than 0.005). In addition, there was more proximal tubular necrosis and regeneration in rats given vancomycin plus tobramycin compared with those given tobramycin alone. In this animal model, vancomycin alone caused no detectable renal injury, tobramycin alone produced minimal proximal tubular damage, and the combination of vancomycin and tobramycin resulted in a greater degree of kidney injury than observed with tobramycin alone.

Rapid diuresis in patients with ascites from chronic liver disease: The importance of peripheral edema

Serial measurements of plasma volume and ascites volume were made during treatment with large doses of oral diuretics in 14 patients with stable chronic liver disease. Eight patients had pitting edema in addition to ascites. Reproducibility of ascites and plasma volume measurements was verified in 10 control subjects not receiving diuretics. Six patients without edema undergoing rapid diuresis lost a mean of 1.2 ± 0.2 L of ascites and an equivalent amount of weight (1.3 ± 0.4 kg) per day. All had a rise in blood urea nitrogen or creatinine, or both, and a fall in creatinine clearance. Eight patients with edema undergoing rapid diuresis lost more weight (1.8 ± 0.5 kg/day, p = 0.06) but less ascites (0.7 ± 0.35 L/day, p < 0.05) than those without edema, and none developed renal insufficiency. After edema disappeared, ascites mobilization increased (1.4 ± 0.7 L/day) and renal dysfunction occurred. Plasma volume fell an average of 24% ± 9% in patients without edema but did not change in patients with edema (−0.4% ± 3%). When edema disappeared, plasma volume fell significantly (28% ± 8%, p < 0.001). Electrolyte changes including hyponatremia, hyperkalemia, and hypochloremia were seen only in the group without edema. Patients with ascites and no edema are able to mobilize more than 1 L/day during rapid diuresis, but at the expense of plasma volume contraction and renal insufficiency. Patients with peripheral edema appear to be protected from these effects because of the preferential mobilization of edema and may safely undergo diuresis at a rapid rate (> 2 kg/day) until edema disappears.

An experimental model of chronic renal failure in mice

Chronic renal failure (CRF) was induced in CBA J mice by a combination of surgery and diathermy to the right kidney followed 2 weeks later by complete removal of the left kidney. This procedure resulted in a progressive rise in blood urea nitrogen (BUN) levels accompanied by a fall in packed cell volume (PCV). In a typical group of mice BUN rose to 156.9 ± 9.1 mg 100 ml and PCV fell to 36.4 ± 1.9%, 8 weeks after removal of the left kidney, compared to 23.3 ± 2.8 mg 100 ml and 51.6 ± 2.1%, respectively, in normal mice. These changes were accompanied by other serum abnormalities in potassium, sodium, calcium, phosphate, chloride, and silicon levels. The surviving renal tissue showed histological changes, and skeletal changes were also evident on radiological examination. Mice in CRF had an increased mean survival time of tail skin allografts and a significant reduction in thymus weight, supporting the use of this model to investigate the well-documented phenomenon of immunosuppression in human patients with uremia.