Treatment of high output entero-cutaneous fistulae associated with large abdominal wall defects: single center experience.

BACKGROUND AND AIM: Enteric fistulas are defined by their sites of origin, communication and flow. We evaluate the treatment of complex patients with entero-cutaneous fistulae with large abdominal wall defects. MATERIALS AND METHODS: Retrospective case note review of 19 patients (15 males, median age 46 years) treated at the Department of Surgical Sciences, University of Insubria, Varese, Italy. These were distinguished by multiple/wide gastrointestinal fistula orifices, with total discontinuity of bowel. Fistulas were not covered by abdominal wall thus presenting with a giant abdominal wall defects. Surgery was planned once adequate nutritional status was present. RESULTS: All fistulas resulted from previous surgery for IBD in 7 cases (37%), abdominal trauma 4 (21%), acute necrotic infected pancreatitis 3 (16%), intra-abdominal malignancy 3 (16%), and diverticular disease 2 (10%). The most common site of presentation was ileum (80%). Median fistula output was 800ml/day (range 400-1600ml/day). Seltzer's prognostic index identified malnutrition in 70% of patients at the time of presentation. The elapsed mean time from onset of fistula and elective time of surgical management were 184 days (range 20-2190 days). The VAC system was used in the last 7 patients preoperatively and in 6 patients with postoperative abdominal wound dehiscences that could not be closed immediately and who were at high risk for healing complications. There were no complications from the VAC therapy. Surgery was successful in 69% of cases. Mortality rate was 21%. Factors related to mortality were persistent malignancy, malnutrition and sepsis. CONCLUSIONS: After optimization of nutritional status surgery with en bloc resection of fistula offers best results. In this series, cancer and sepsis were unfavourable factors for outcome. These fistulas may be successfully managed with a multidisciplinary approach.

New and old tools for abdominal imaging in critically ill patients.

Diagnostic imaging technology has advanced considerably during the past two decades. Different imaging techniques have been proposed for abdominal imaging in critically ill patients like plain radiography, sonography, computed tomography (CT), magnetic resonance and positron emission tomography. Sonography has been proven to be effective to detect free intra-peritoneal fluid and it is considered one of the primary diagnostic modalities for abdominal evaluation for trauma assessment. In our opinion sonography should replace other invasive techniques to rapidly triage blunt trauma patients with unstable vital signs and examine the peritoneal cavity as a site of major haemorrhage to expedite exploratory laparotomy. On the other hand, CT has become the imaging modality of choice in hemodynamically stable patients with multisystem blunt and penetrating trauma. New developments in the quantitative analysis of the CT images will improve our knowledge of pathophysiology, diagnostic and therapeutic management of abdominal pathologies in critically ill patients.

New and old tools for abdominal imaging in critically ill patients.

Diagnostic imaging technology has advanced considerably during the past two decades. Different imaging techniques have been proposed for abdominal imaging in critically ill patients like plain radiography, sonography, computed tomography (CT), magnetic resonance and positron emission tomography. Sonography has been proven to be effective to detect free intra-peritoneal fluid and it is considered one of the primary diagnostic modalities for abdominal evaluation for trauma assessment. In our opinion sonography should replace other invasive techniques to rapidly triage blunt trauma patients with unstable vital signs and examine the peritoneal cavity as a site of major haemorrhage to expedite exploratory laparotomy. On the other hand, CT has become the imaging modality of choice in hemodynamically stable patients with multisystem blunt and penetrating trauma. New developments in the quantitative analysis of the CT images will improve our knowledge of pathophysiology, diagnostic and therapeutic management of abdominal pathologies in critically ill patients.

Analysis of deaths due to injury in Milano: preliminary results.

We reviewed all trauma deaths occurring in the urban area of Milan during one year. Autopsy reports were cross-referenced with pre- and in-hospital records and the Injury Severity Score was calculated by a senior surgeon. Causes of deaths were defined as central nervous system injury (CNS), hemorrhage (HEM), combined central nervous system injury and hemorrhage (CNS + HEM), and burns (BURN). Places of death were considered the scene (DOS), during transportation (DOA), the emergency room (DER), and hospital. Two multidisciplinary commissions reviewed patient reports and deaths were judged non-preventable, possibly preventable or frankly preventable, using the unanimous decision rule. The TRISS method was used to calculate the probability of survival for in-hospital deaths. Overall trauma deaths were 255 with 78.04% blunt and 16.08% penetrating traumas. Burns accounted for 5.88%. CNS and CNS + HEM caused 171 (67.05%) deaths. DOS were 91, DOA 48, DER 34, and in-hospital deaths 33. Victims found dead (49 individuals) were excluded from further analysis. The commissions classified 56.31% of deaths as non-preventable, 32.03% as possibly preventable and 11.65% as frankly preventable. The Injury Severity Score decreased from DOS to in-hospital deaths (p < 0.05). The preventability rate was higher for in-hospital deaths (p < 0.05). The results of this study suggest that the development of a tiered trauma system in Milan is mandatory.

Inhibition of CD11-CD18 complex prevents acute lung injury and reduces mortality after peritonitis in rabbits.

Acute lung injury is frequent after severe peritonitis. The aim of this study was to investigate whether inhibition of the adhesion molecule CD11-CD18 on polymorphonuclear leukocytes (PMNs) would have any beneficial effects on pulmonary function and mortality in an animal model reproducing these clinical conditions. Acute peritonitis was induced in 36 rabbits by intraperitoneal injection of zymosan (0.6 g/kg) suspended in mineral oil; 20 were pretreated with a murine-specific IgG2a anti-CD18 monoclonal antibody, 16 (controls) with nonspecific purified murine IgG (1 mg/kg). The animals were followed for 10 d, then killed for histologic examination of the lungs. Blood samples were taken on Days 0, 1, 3, 7, and 10 for red blood cell (RBC), white blood cell (WBC), and platelet counts, pH, PO(2), PCO(2), carbon dioxide content (HCO(3)(-)) measurements, and renal and liver tests. Treatment with the anti-CD18 monoclonal antibody reduced mortality by approximately 40% (p < 0.05). PO(2) was higher in these treated animals than in the control animals throughout the study (p < 0.05 on Day 1, 3, and 10). On Day 1 control animals had significant leukopenia, whereas anti-CD18-treated animals had a moderate increase of the number of circulating WBC compared with baseline values (p < 0.05 between groups). The lungs of the anti-CD18-treated animals showed minor signs of inflammation and PMN infiltration whereas controls had interstitial and intra-alveolar edema and a large number of granulocytes. Quantification of PMNs by morphometry showed that there were constantly less granulocytes in the lungs of the animals treated with the anti-CD18 antibody (p < 0.001). PMN infiltration correlated with the levels of PO(2) (p < 0.001). Lung tissue of anti-CD18-treated rabbits contained less malonyldialdehyde, a by-product of membrane lipid peroxidation by PMN oxygen radicals (950 +/- 120 versus 1,710 +/- 450 pM/mg of protein) and, conversely, more of the antioxidant alpha-tocopherol (136 +/- 22 versus 40 +/- 9 ng/mg of protein), than the control rabbits (p < 0.01). In this particular model of ARDS the monoclonal antibody against the CD11-CD18 complex had a beneficial effect, reducing PMN infiltration and oxygen radical release in the lungs, preventing alveolocapillary membrane damage, improving gas exchange and, finally, significantly reducing mortality.

[Emergency surgical management of lesions from ingestion of caustics. Role of primary endoscopic classification]. / Indicazioni alla chirurgia d'urgenza nelle lesioni da ingestione di caustici. Ruolo di una classificazione endoscopica originale.

Management of caustic ingestion in adults improved in the last decade due to the new diagnostic developments, the better predictability of injuries from signs and symptoms, the intensive care improvements and the more aggressive surgical approach for the most severe lesions. In fact, the early surgical treatment of severe lesions for ingestion of caustic and corrosive substances may reduce mortality, morbidity and hospitalization. The role of early endoscopic examination is today worldwide accepted: is herein proposed a new endoscopic classification of caustic lesions adjusted after a retrospective analysis of a twenty years experience in this field, and applied in twelve patients affected by severe esophageal and gastric injuries then submitted to emergency surgical treatment and survived. It showed a great usefulness in selection of patients to submit immediately to surgery and may play a fundamental role in indications and timing of surgical management of severe injuries by caustic ingestion.

The effect of intermittent slow-release sodium fluoride and continuous calcium citrate therapy on calcitropic hormones, biochemical markers of bone metabolism, and blood chemistry in postmenopausal osteoporosis.

A detailed examination of calcitropic hormones and biochemical markers of bone turnover, serum chemistry, and blood hematology was performed in 75 postmenopausal women allocated to two groups: placebo plus calcium citrate (400 mg Ca B.I.D.) (n = 36) or intermittent slow-release sodium fluoride (SRNaF, 25 mg B.I.D.) plus calcium citrate (n = 39). After 2 years of therapy, a significant reduction in serum immunoreactive parathyroid hormone (PTH) was seen for both groups (43 +/- 18 SD-30 +/- 11 ng/liter, in placebo and 46 +/- 24-36 +/- 10, in SRNaF P < 0.0001 for both groups). Serum 1, 25(OH)2D significantly fell in placebo-treated patients (91 +/- 31-75 +/- 34 pmol/liter, P = 0.001) but did not change for SRNaF-treated patients. This difference in response between placebo and SRNaF-treated groups was significant, P = 0.005. Urinary hydroxyproline significantly declined during treatment in both groups (130 +/- 61-76 +/- 38 micromol/day, for placebo and 138 +/- 84-84 +/- 38 for SRNaF, P = 0.001). Similar decreases in urinary N-telopeptide of type I collagen were also observed for both groups (305 +/- 192-252 +/- 197 nmoles BCE/day for placebo and 356 +/- 230-220 +/- 197, P = 0.0001 for SRNaF). Serum carboxyterminal propeptide of type I collagen (PICP) declined significantly in both the placebo and SRNaF groups (118 +/- 38-101 +/- 36 microg/liter, and 116 +/- 47-105 +/- 39, P = 0.0027). Serum osteocalcin did not change significantly for either group, but bone-specific alkaline phosphatase (BS-ALPase), another marker of bone formation, demonstrated a significant fall in the placebo group at 2 years of therapy (16.2 +/- 6.7 U/liter-12.1 +/- 3.5, P = 0.009) and a small increase in the SRNaF-treated patients (13.0 +/- 4.1-15.0 +/- 4.5). The observed difference in response of BS-ALPase between the placebo and treated groups was significant (P = 0.007). There were no significant changes within or between treatment groups for blood hematology or serum chemistries. Mean values for all parameters remained within established normal ranges. These findings suggest that administration of calcium citrate inhibited PTH secretion and thereby reduced bone resorption in both groups, indicated by a decline in serum PTH, urinary hydroxyproline, and N-telopeptide. A low turnover state of bone may have been produced in the placebo group taking calcium citrate alone, since serum PICP, BS-ALPase, and 1,25(OH)2D also decreased. The addition of SRNaF prevented serum 1, 25(OH)2D from falling by an unknown mechanism. However, its anabolic action on the skeleton was best reflected by changes in BS-ALPase. Moreover, SRNaF appeared to exert no deleterious effects on blood chemistries or hematology during 2 years of administration.

The lack of influence of long-term potassium citrate and calcium citrate treatment in total body aluminum burden in patients with functioning kidneys.

BACKGROUND: It has been suggested that citrate salts might enhance aluminum (Al) absorption from a normal diet, posing a threat of Al toxicity even in subjects with normal renal function. We have recently reported that in normal subjects and patients with moderate renal failure, short-term treatment with tricalcium dicitrate (Ca3Cit2) does not significantly change urinary and serum Al levels. However, we have not assessed total body Al stores in patients on long-term citrate treatment. OBJECTIVE: The objective of this study was to ascertain body content of Al non-invasively using the increment in serum and urinary Al following the intravenous administration of deferoxamine (DFO) in patients with kidney stones and osteoporotic women undergoing long-term treatment with potassium citrate (K3Cit) or Ca3Cit2, respectively. METHODS: Ten patients with calcium nephrolithiasis and five with osteoporosis who were maintained on potassium citrate (40 mEq/day or more) or calcium citrate 800 mg calcium/day (40 mEq citrate) for 2 to 8 years, respectively, and 16 normal volunteers without a history of regular aluminum-containing antacid use participated in the study. All participants completed the 8 days of study, during which they were maintained on their regular home diet. Urinary Al excretion was measured during a two-day baseline before (Days 5, 6) and for 1 day (Day 7) immediately following a single intravenous dose of DFO (40 mg/kg). Blood for Al was obtained before DFO administration, and at 2, 5 and 24 hours following the start of the infusion. RESULTS: The median 24-hour urinary Al excretion (microgram/day) at baseline versus post-DFO value was 15.9 vs. 44.4 in the normal subjects and 13.3 vs. 35.7 in the patients. These values were all within normal limits and did not change significantly following DFO infusion (p = 0.003 and p = 0.0001, respectively). The median change of 17.1 micrograms/day in urinary Al in the normal subjects was not significantly different from the 18.7 micrograms/day change measured in the patient group (p = 0.30). Similarly, no change in the mean serum Al was detected at any time following the DFO infusion, either in the patient or control group (patients 4.1 to 4.3 ng/ml, controls 7.4 to 4.6 ng/ml). CONCLUSION: The results suggest that abnormal total body retention of Al does not occur during long-term citrate treatment in patients with functioning kidneys.

[Simultaneous multiregional embolization from a cardiac myxoma. Case report]. / Embolizzazione sincrona pluridistrettuale da mixoma cardiaco. Presentazione di un caso clinico.

Atrial myxoma is the most frequent cardiac tumor. Distal embolization occurs in about one third of the patients with this nosological entity; a simultaneous embolization to three different arterial districts, however, is a rare event. Of particular interest is also, in our opinion, the evolution of the clinical picture and the surgical treatment performed.

Physicochemical effects of a new slow-release potassium phosphate preparation (UroPhos-K) in absorptive hypercalciuria.

A new slow-release, neutral potassium phosphate salt (UroPhos-K) has been formulated in order to minimize gastrointestinal side effects and avoid sodium-induced calciuria. It was tested in a prospective randomized, double-blind trial in a group of 21 kidney stone patients with absorptive hypercalciuria type I (AH). Twelve patients allocated to the UroPhos-K group received four tablets twice daily with breakfast and an evening snack providing 1240 mg of phosphorus and 63.5 mEq of potassium daily. Nine patients assigned to the placebo group received placebo tablets of the same appearance containing excipient only. Subjects were studied during a 3-day period in the hospital while consuming a constant metabolic diet containing 400 mg Ca, 100 mEq Na, and 800 mg P per day before and after 3 months of treatment. Treatment with UroPhos-K did not cause any significant gastrointestinal side effects; nor did it raise fasting serum K or phosphorus, or reduce hemoglobin or creatinine clearance. It was associated with a rise in urinary K from 46 +/- 7 to 98 +/- 9 mEq per day and phosphorus from 744 +/- 185 to 1535 +/- 112 mg per day (p < 0.001 each). UroPhos-K treatment reduced urinary Ca from 288 +/- 63 to 171 +/- 49 mg/day (p < 0.001), without altering oxalate excretion. It reduced the urinary saturation of calcium oxalate without altering that of brushite. Moreover, by increasing urinary excretion of inhibitors (citrate and pyrophosphate), it reduced the propensity for spontaneous nucleation of brushite (increased formation product of brushite) and inhibited crystal agglomeration of calcium oxalate.(ABSTRACT TRUNCATED AT 250 WORDS)

[Open treatment in acute severe pancreatitis]. / Trattamento aperto nella pancreatite acuta severa.

Technical procedures normally used for open packing in our Institute (ICU) are described. Results of this procedure, utilized in thirteen patients suffering from infected pancreatic necrosis and multiple organ failure are reported. The grade of pancreatitis severity has been studied in detail. At admission patients presented a mean Ranson score of 6 and the morphological alteration sec. Balthazar was D in six patients and E in seven. At least two organs were insufficient at the beginning of our observation and the mean number of insufficient organs was 4. The mean APACHE II score was 20. Necrosis was documented in all patients. They were all admitted to ICU and the mean time of treatment was 50 days. Daily debridement was performed and continuous lavage was later added to daily open review. Three patients died, one from local bleeding and two from respiratory insufficiency. No patient died of sepsis and no mortality was observed in the last six cases. According to the severity of Ranson score, APACHE II, the number of insufficient organs and TAC morphological alteration predicted mortality rate should have been 70-80%; on the contrary, it was 25%. In conclusion open packing seems to be the correct treatment for infected pancreatic necrosis, particularly when it is complicated by multiple organ dysfunction.

[Pancreatic and duodenal injuries. Considerations on 40 observed cases]. / I traumi del pancreas e del duodeno. Considerazioni su 40 casi osservati.

Traumatic lesions of the pancreas and duodenum are uncommon. The anatomic situation of the viscera makes early diagnosis of such lesions difficult to be achieved; this fact, together with the high incidence of associated lesions, justify the high morbidity and mortality of duodeno-pancreatic traumas. In the present paper we report the two-decades experience (40 traumatic lesions of the pancreas and/or the duodenum) of the Department of Emergency Surgery, University of Milan. The overall mortality (32.5%), even if correlated with the importance of the duodeno-pancreatic lesions, was strictly dependent to the presence of associated injuries which lead to most of the morbidity and mortality.

[Artificial nutrition in the management of lesions caused by caustic ingestion]. / La nutrizione artificiale nelle lesioni da ingestione di caustici.

Ingestion of a large amount of corrosive agent results in a life-threatening condition which requires a much more aggressive diagnostic and therapeutic approach than was formerly recommended. Based on experience with a wide spectrum of upper g-i injuries in 56 patients treated through a 5-year-period, the Authors suggest an early staging of the lesions by immediate endoscopy, followed by adequate resective surgery for high-degree esophago-gastric lesions. Indications, techniques of artificial nutrition and the nutritional requirements of this condition are presented and fully discussed. The prompt institution of total parenteral nutrition is an essential part of the emergency management of these lesions. Fourteen patients underwent surgical treatment for the lesions; in all cases a Witzel's feeding jejunostomy was performed and postoperative enteral nutrition was started. Eight patients underwent a reconstructive operation of colon interposition and received home-based total enteral nutrition for a period of 8-25 weeks. No major complications relate to nutritional support occurred and nutritional indexes were normal at the end of the treatment.

The potential role of salt abuse on the risk for kidney stone formation.

The kidney stone-forming risk of a high sodium diet was evaluated by assessing the effect of such a diet on the crystallization of stone-forming salts in urine. Fourteen normal subjects participated in 2 phases of study of 10 days duration each, comprising a low sodium phase (basal metabolic diet containing 50 mmol. sodium per day) and a high sodium phase (basal diet plus 250 mmol. sodium chloride per day). The high sodium intake significantly increased urinary sodium (34 +/- 12 to 267 +/- 56 mmol. per day), calcium (2.73 +/- 1.03 to 3.93 +/- 1.51 mmol. per day) and pH (5.79 +/- 0.44 to 6.15 +/- 0.25), and significantly decreased urinary citrate (3.14 +/- 1.19 to 2.52 +/- 0.83 mmol. per day). Arterialized venous blood bicarbonate and total serum carbon dioxide concentrations decreased significantly during the high sodium diet, whereas serum chloride concentration increased. However, no change in arterialized venous pH was detected. Thus, a high sodium intake not only increased calcium excretion, but also increased urinary pH and decreased citrate excretion. The latter effects are probably due to sodium-induced bicarbonaturia and a significant decrease in serum bicarbonate concentration, respectively. Commensurate with these changes, the urinary saturation of calcium phosphate (brushite) and monosodium urate increased, and the inhibitor activity against calcium oxalate crystallization (formation product) decreased. The net effect of a high sodium diet was an increased propensity for the crystallization of calcium salts in urine.

Alkali absorption and citrate excretion in calcium nephrolithiasis.

The role of net gastrointestinal (GI) alkali absorption in the development of hypocitraturia was investigated. The net GI absorption of alkali was estimated from the difference between simple urinary cations (Ca, Mg, Na, and K) and anions (Cl and P). In 131 normal subjects, the 24 h urinary citrate was positively correlated with the net GI absorption of alkali (r = 0.49, p < 0.001). In 11 patients with distal renal tubular acidosis (RTA), urinary citrate excretion was subnormal relative to net GI alkali absorption, with data from most patients residing outside the 95% confidence ellipse described for normal subjects. However, the normal relationship between urinary citrate and net absorbed alkali was maintained in 11 patients with chronic diarrheal syndrome (CDS) and in 124 stone-forming patients devoid of RTA or CDS, half of whom had "idiopathic" hypocitraturia. The 18 stone-forming patients without RTA or CDS received potassium citrate (30-60 mEq/day). Both urinary citrate and net GI alkali absorption increased, yielding a significantly positive correlation (r = 0.62, p < 0.0001), with the slope indistinguishable from that of normal subjects. Thus, urinary citrate was normally dependent on the net GI absorption of alkali. This dependence was less marked in RTA, confirming the renal origin of hypocitraturia. However, the normal dependence was maintained in CDS and in idiopathic hypocitraturia, suggesting that reduced citrate excretion was largely dietary in origin as a result of low net alkali absorption (from a probable relative deficiency of vegetables and fruits or a relative excess of animal proteins).

Complement activation and polymorphonuclear neutrophil leukocyte elastase in sepsis. Correlation with severity of disease.

Complement activation is necessary for an adequate immune and inflammatory response to infections. Activation releases anaphylatoxins that cause vasodilation, increase vascular permeability, and trigger release of polymorphonuclear neutrophil leukocyte (PMN) lysosomal enzyme and oxygen radicals. Under normal circumstances, an orderly progression of such events has a beneficial antimicrobial effect. The same mechanism, however, when uncontrolled, may damage host tissues. To provide information about the clinical importance of such events in sepsis, different complement parameters (C3, C4, and the desarginated forms of C3a [C3a(des)-Arg] and C5a [C5a(des)-Arg]), PMN elastase, and malondialdehyde (a by-product of membrane peroxidation by oxygen radicals) were measured daily in 26 septic patients and correlated with two objectively assessed and previously validated severity scores (acute physiology and chronic health evaluation [APACHE II] and Sepsis Severity Score [SSS]). Nonsurvivors (n = 12) had significantly greater and longer lasting complement activation than that in survivors, as reflected by higher levels of catabolic peptides (C3a(des)-Arg) and lower levels of native proteins (C3 and C4). C3a(des)-Arg, C3, C4, and the C3a(des)-Arg-C3 ratio were correlated with Sepsis Severity Scores. Polymorphonuclear neutrophil leukocyte elastase levels were higher in nonsurvivors and were correlated with C3a(des)-Arg and the C3a(des)-Arg-C3 ratio. Malondialdehyde levels were significantly higher in all patients than in controls, without, however, any relationship to severity of disease or clinical outcome. Since the higher and more persistent the complement activation and polymorphonuclear neutrophil leukocyte stimulation, the worse the patient's prognosis, we conclude that these mechanisms may be important in the clinical development of sepsis.

Physicochemical action of potassium-magnesium citrate in nephrolithiasis.

Effect of potassium-magnesium citrate on urinary biochemistry and crystallization of stone-forming salts was compared with that of potassium citrate at same dose of potassium in five normal subjects and five patients with calcium nephrolithiasis. Compared to the placebo phase, urinary pH rose significantly from 6.06 +/- 0.27 to 6.48 +/- 0.36 (mean +/- SD, p less than 0.0167) during treatment with potassium citrate (50 mEq/day for 7 days) and to 6.68 +/- 0.31 during therapy with potassium-magnesium citrate (containing 49 mEq K, 24.5 mEq Mg, and 73.5 mEq citrate per day). Urinary pH was significantly higher during potassium-magnesium citrate than during potassium citrate therapy. Thus, the amount of undissociated uric acid declined from 118 +/- 61 mg/day during the placebo phase to 68 +/- 54 mg/day during potassium citrate treatment and, more prominently, to 41 +/- 46 mg/day during potassium-magnesium citrate therapy. Urinary magnesium rose significantly from 102 +/- 25 to 146 +/- 37 mg/day during potassium-magnesium citrate therapy but not during potassium citrate therapy. Urinary citrate rose more prominently during potassium-magnesium citrate therapy (to 1027 +/- 478 mg/day from 638 +/- 252 mg/day) than during potassium citrate treatment (to 932 +/- 297 mg/day). Consequently, urinary saturation (activity product) of calcium oxalate declined significantly (from 1.49 x 10(-8) to 1.03 x 10(-8) M2) during potassium-magnesium citrate therapy and marginally (to 1.14 x 10(-8) M2) during potassium citrate therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Free and total 1,25-dihydroxyvitamin D levels in subjects with renal disease.

Patients with nephrotic syndrome and varying degrees of renal failure, including those on chronic hemo- and peritoneal dialysis, may have low serum concentrations of total 1,25-dihydroxyvitamin D [1,25(OH)2D]. However, it is unknown whether the true activity of 1,25(OH)2D is better reflected by the free 1,25(OH)2D fraction. We measured total 1,25(OH)2D, free 1,25(OH)2D, and vitamin-D-binding protein (DBP) in normal subjects (group A), subjects with moderate renal failure (group B), subjects on hemodialysis (group C), subjects on peritoneal dialysis (group D), and subjects with nephrotic syndrome (group E). The serum concentrations of total and free 1,25(OH)2D decreased with worsening renal function in groups A through C, with a high degree of correlation (r = 0.974, P less than 0.0001). Levels of DBP and the percent free 1,25(OH)2D remained constant in these groups. Patients on peritoneal dialysis and nephrotic patients had lower levels of DBP (203 +/- 14 micrograms/ml and 371 +/- 46 micrograms/ml, respectively) than normal subjects (436 +/- 33 micrograms/ml) and had significantly higher percent free 1,25(OH)2D (0.98 +/- 0.13% and 1.27 +/- 0.14%, respectively) compared to 0.63 +/- 0.03% (P less than 0.05). Thus, the loss of DBP in these patients correlated with a rise in the percent free 1,25(OH)2D. We conclude that levels of total 1,25(OH)2D are an accurate representation of 1,25(OH)2D status in normal subjects, subjects with renal insufficiency without nephrotic syndrome, and hemodialysis patients. In peritoneal dialysis and nephrotic patients, who lose DBP, measurements of free 1,25(OH)2D may be necessary in order to accurately assess 1,25(OH)2D status.