Characteristics and clinical relevance of chronic anemia in adult heart transplant recipients.

BACKGROUND: Mild chronic anemia following heart transplantation (HTX), with hemoglobin (Hb) values of 10-14 g/dL in men and 10-12 g/dL in women, is frequent. It has continued to be of uncertain etiology yet clinical relevance. Nonetheless, therapeutic immunosuppression has been regarded as a major cause of chronic anemia in HTX patients. METHODS: Sixty outpatients were observed over a period of 5 yr after HTX. Laboratory values related to anemia such as Hb, erythropoietin (EPO), ferritin, transferrin, iron, and vitamin levels were obtained and analyzed monthly. Patients were divided into two groups retrospectively. Patients with persistent anemia for more than 1 yr were compared with non-anemic patients. RESULTS: Forty-three (72%) of the 60 patients were anemic. Anemia was normochromic, normocytic, and slightly anisocytic. Anemic and non-anemic patients showed EPO levels within the expected range as defined by Erslev (Erythropoietin. N Engl J Med 1991: 324: 1339). Reticulocyte counts were found to be normal in all patients. Iron deficiency and deficiency of vitamin B12 or folic acid were not observed. Patients with persistent anemia showed a significantly shorter survival period than non-anemic patients (p<0.02). CONCLUSIONS: Mild anemia following HTX shows the same characteristics as anemia in chronic diseases. Persisting mild anemia used to be associated with a shorter life expectancy. There is no evidence that standard immunosuppression causes anemia.

Cholestasis and liver cell damage due to hypersensitivity to erythromycin stearate--recurrence following therapy with erythromycin succinate.

Erythromycin is a frequently used antibiotic in patients with atypical respiratory infection and/or an allergy to penicillin. We report the case of a young woman who developed severe cholestasis and jaundice following treatment with erythromycin stearate. Two years later her general practitioner prescribed erythromycin succinate for pharyngitis. She experienced a severe second episode of jaundice and malaise. Different esters of erythromycin have been introduced to reduce side effects such as allergic reactions to erythromycin. The findings in our patient underline the fact that hypersensitivity is caused by the erythromycin molecule, independent from the type of esterification. Because of these side effects newer makrolides should be given preference over erythromycin.

Mild chronic anemia following heart transplantation: a syndrome with prognostic relevance?

The clinical relevance of mild chronic anemia in patients after heart transplantation (HTX) has not yet been demonstrated. Forty-five outpatients who had undergone HTX 2-99 months prior to investigation and who had not received blood transfusions or erythropoietin (EPO) before data acquisition were observed over a period of 37 months. Anemia was found in 36 of the 45 patients and was normocytic, normochromic, and slightly anisocytotic (coefficient of variation = 16 +/- 2, normal 11.5-14.5). Anemic patients showed elevated EPO levels, whereas in nonanemic patients EPO levels were normal. Survival after HTX differed significantly in anemic and nonanemic patients (P < 0.02), with 100% survival in the nonanemic and 85% in the anemic group. Chronic anemia in patients after HTX shows a typical pattern. Even when mild, anemia in patients after HTX seems to be of prognostic value and thus might be an indicator of chronic disorders.

End-stage renal failure from mushroom poisoning with Cortinarius orellanus: report of four cases and review of the literature.

Mushrooms of the ubiquitous Cortinarius species (Cs) contain nephrotoxins that can cause acute and chronic renal failure by an unknown pathomechanism. Typical is a long symptom-free interval before the onset of clinical disease. A causal form of therapy is not known. Early hemodialysis can improve the prognosis of this potentially life-threatening condition. Diagnosis of Cs poisoning can be made by detecting the responsible toxin--orellanine--in plasma or renal tissue by fluorimetry after thin-layer chromatography or by identifying the spores of left-over mushrooms as Cs. Renal histology shows nonspecific changes such as tubular dilatation and flattening of the epithelium and signs of interstitial edema followed by interstitial fibrosis. We present four cases of Cs poisoning with different outcomes and a review of the literature.

Functional magnetic resonance imaging of human renal allografts during the post-transplant period: preliminary observations.

Graft dysfunction is a common occurrence during the first weeks following renal transplantation. The current study was designed to evaluate the potential of renal magnetic resonance (MR) perfusion imaging to differentiate acute allograft rejection (AAR) from acute tubular necrosis (ATN) during the post-transplant period. Twenty-three consecutive patients with clinically suspected ATN and/or AAR and eight consecutive control patients (asymptomatic, serum creatinine concentration < 1.5 mg/dL) underwent MR perfusion imaging of the renal allograft within 64 days after transplantation. Histopathology was obtained in all cases with clinical suspicion of ATN or AAR. Sixty sequential fast gradient-recalled-echo MR images were acquired in each patient after intravenous administration of gadolinium-DTPA (0.1 mmol/kg). Histopathology revealed 6 patients with pure AAR, 4 patients with a combination of AAR and ATN, 12 patients with ATN and 1 patient with normal findings. Kidney graft recipients with normal renal function showed a moderate increase in signal intensity (SI) of the renal cortex and medulla after administration of contrast agent followed by an immediate and short decrease in SI of the medulla (biphasic medullary enhancement pattern). The increase in cortical SI of patients with AAR was significantly smaller (61 +/- 4% increase above baseline) than that measured in normal allografts (136 +/- 9% increase above baseline) (p < 0.05) and patients with ATN (129 +/- 3% increase above baseline) (p < .05). Patients with ATN had a slightly delayed and diminished cortical enhancement and an uniphasic and lesser medullary enhancement pattern compared to that observed in normal allografts (p < 0.05). A close correlation (r = 0.72) was found between serum creatinine concentration levels and changes in SI. Thus, MR imaging results and histopathology were in agreement in 22 of 23 patients (96%). MR perfusion imaging of renal allografts can be used to noninvasively differentiate ATN from AAR during the post-transplant period, and may also be helpful in cases were covert AAR is superimposing ATN during a phase of anuria. Patients with ATN can be separated from normals in the majority of cases as reflected by an uniphasic medullary enhancement pattern.

Differentiation of delayed kidney graft function with gadolinium-DTPA-enhanced magnetic resonance imaging and Doppler ultrasound.

RATIONALE AND OBJECTIVES: The authors differentiate acute tubular necrosis from transplant rejection in patients with delayed kidney graft function using gadolinium (Gd)-DTPA enhanced magnetic resonance (MR) imaging. METHODS: Twenty-four patients after renal transplantation (10 with normal graft function, 14 with delayed graft function) underwent conventional and Doppler sonography and MR imaging examination after bolus application of Gd-DTPA. Within a time period of 512 seconds, 39 single-slice MR images were obtained. Measurements of signal intensity in three regions of interests (cortex, medulla, renal pelvis) resulted in a graphic description of the dynamics of the contrast enhancement. The time between the start of the scan and the peaks of the curves was measured. RESULTS: In patients with normal graft function the curves reached the peaks between 39 and 55 seconds (cortex), 44 and 61 seconds (medulla), and between 161 and 318 seconds (renal pelvis). Six patients with acute tubular necrosis showed normal values for the curves 1 and 2 but markedly prolonged time for curve 3 (between 420 and 512 seconds). In all patients with histologically proven transplant rejection, the peaks of all curves were not reached before the ends of the scans. CONCLUSION: The authors' preliminary results suggest that MR imaging seems to be a sensitive, noninvasive diagnostic tool to differentiate acute tubular necrosis from transplant rejection in the critical early postoperative period.

Spontaneous bacterial peritonitis in a patient with nephrogenic ascites during an episode of acute renal transplant rejection.

Spontaneous bacterial peritonitis (SBP) is a primary infection of asci tes without signs of perforation or penetration. It occurs most often in patients with liver cirrhosis but can also be diagnosed in patients with ascites from other causes. We report a kidney transplant recipient who developed nephrogenic ascites during an episode of acute rejection. The patient complained of fever, abdominal tenderness, and loose stools and showed all of the signs of peritonitis on physical examination. The patient's serum creatinine was elevated, and Duplex sonography of the graft was highly suggestive for acute rejection. Ascites puncture was performed. The ascitic fluid contained 4,000 leukocytes per microliter. No source of infection was detected, so the diagnosis of SBP was made. The patient was treated with ciprofloxacin intravenously and received low-dose steroid pulse therapy. The ascites culture grew Staphylococcus aureus that was highly sensitive to ciprofloxacin. The patient recovered rapidly. We could avoid laparotomy, which is associated with high mortality in patients suffering from SBP. No relapses of SBP occurred. Renal function has improved and remained stable.

Impact of long-term hemodialysis on nutritional status in patients with end-stage renal failure.

We evaluated the way in which duration of hemodialysis treatment affects nutritional status in 96 end-stage renal failure patients. According to the length of previous hemodialysis treatment patients were divided into the groups: onset hemodialysis (ON-HD), early-stage hemodialysis (ES-HD, 1-8 months), mid-stage hemodialysis (MS-HD, 9-69 months), and advanced-stage hemodialysis (AS-HD, 70-207 months). Nutritional status was assessed by laboratory data (serum proteins, total lymphocyte count), intradermal skin antigen testing, anthropometric measurements (body mass index [BMI], infrared interactance), and records of food intake. ON-HD patients on a low-protein diet exhibited abnormally low values for serum total protein, albumin, transferrin, and total lymphocyte count and a high prevalence of anergy to skin antigens (69%). In the ES-HD and MS-HD groups values for serum proteins and total lymphocyte count were in the normal range and significantly higher than in ON-HD patients. In addition, a lower proportion of cutaneous anergy was observed (50% and 27%, respectively). Long-term hemodialysis therapy for 6-17 years (AS-HD) was associated with normal levels for all measured serum proteins. Subnormal levels of total lymphocyte count, significantly lower than in MS-HD patients, were associated with an increase in anergy to skin antigens (46%). Serum prealbumin, complement C3c, BMI, body fat, and lean body mass exhibited normal values in all patients and showed no differences between groups. These results indicate that diminished visceral protein stores, lymphopenia, and anergy to skin antigens are widespread in undialyzed uremic patients with end-stage renal failure but become uncommon after the initiation of regular hemodialysis therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Glomerulonephritis as late manifestation of severe alpha 1-antitrypsin deficiency.

An association of alpha 1-antitrypsin deficiency with glomerulonephritis is rare and has so far been observed only in children or young adults. We report a 63-year-old man with severe alpha 1-antitrypsin deficiency associated with pulmonary emphysema, cirrhosis of the liver, and mesangioproliferative glomerulonephritis with nephrotic syndrome. Following initial presentation with nephropathy, further work-up revealed alpha 1-antitrypsin deficiency of proteinase inhibitor Z. In the absence of glomerular alpha 1-antitrypsin deposits the relationship between renal disease and alpha 1-antitrypsin deficiency remains unclear. alpha 1-Antitrypsin deficiency should be considered in adults with abnormal renal function and chronic liver disease.

Increased susceptibility for CsA-induced hepatotoxicity in kidney graft recipients with chronic viral hepatitis C.

CsA-induced hepatotoxicity is a rare disorder in renal transplant recipients when low doses are administered and whole blood trough levels of CsA are regularly monitored. However, there is controversy about the clinical value of measuring CsA-metabolites, whose contribution to immunosuppression and toxicity is not fully understood. To assess the relation between low-dose CsA therapy and hepatotoxicity, we studied 128 renal transplant recipients attending our nephrology clinic. Eight of these patients had markedly elevated liver function tests. Three patients while receiving very low doses of oral CsA (< 3.8 mg/kg of body weight) presented marked derangements of CsA metabolism with abnormally increased CsA-metabolite levels. Parent drug levels were in the normal range. All 3 patients had chronic infection with hepatitis C virus and revealed histomorphologic evidence of hepatotoxicity. Hepatic dysfunction normalized when CsA was withdrawn or reduced by 50%. It is likely that hepatitis C virus infection interferes with CsA metabolism and/or biliary CsA-excretion and thus is responsible for CsA and/or metabolite-induced hepatotoxicity despite very low doses of CsA.

Treatment of anemia in inflammatory bowel disease with recombinant human erythropoietin: results in three patients.

Inflammatory bowel disease (IBD) is often associated with anemia. Of 85 patients with IBD, 28 were anemic and had an inadequately low plasma erythropoietin (EPO) concentration. Three patients with a long-standing history of IBD and refractory chronic anemia (hemoglobin values < 10 g/dL, plasma EPO concentrations below 100 mU/mL) were treated with recombinant human EPO, which was administered subcutaneously three times per week at a dose of 200-300 U/kg of body weight. Bone marrow biopsy specimens taken before therapy showed slightly decreased erythropoiesis with a shift of erythroid precursors toward more immature stages. EPO treatment resulted in a marked increase in hemoglobin values in all 3 patients. Bone marrow biopsies after EPO therapy showed quantitatively and qualitatively normal erythropoiesis in all of them. Correction of anemia was followed by improved well-being, and all patients were able to cope much better with their IBD. In all three patients, there was an increase in body weight and their Karnofsky index improved. After a complete workup and exclusion of any other cause for anemia, erythropoietin treatment, although expensive, should be considered in patients with IBD and refractory anemia.

Spontaneous bacterial peritonitis in a hemodialysis patient with systemic lupus erythematosus.

Spontaneous bacterial peritonitis (SBP) is defined as infection of preexisting ascites without evidence for any intraabdominal source for secondary infection. SBP is now recognized with rising frequency and has mainly been reported in patients with alcohol-induced cirrhosis of the liver. We report SBP in a female dialysis patient whose ascites was not due to liver disease, but was possibly due to lupus erythematosus or represented 'nephrogenic ascites'. The patient had severe abdominal pain and a positive rebound phenomenon, fever and an elevated peripheral white cell count of 21,000 cells/microliters. Ascitic fluid analysis revealed an exudate with a protein concentration of 5.2 g/dl, 13,000 white cells/microliters with 94% neutrophils and positive cultures for Streptococcus morbillorum. Because of the dramatic clinical features the patient underwent laparotomy which did not reveal a source for secondary infection and in retrospect was unnecessary. The patient responded well to antibiotic therapy. This case report draws attention to SBP as a cause of acute abdomen in patients on chronic hemodialysis.