Sergio De Marchi

Renal Tubular Dysfunction in Chronic Alcohol Abuse -- Effects of Abstinence

BACKGROUND Alcohol abuse may be accompanied by a variety of disorders of electrolyte and acid-base metabolism. The role of the kidney in the pathogenesis of these disturbances is obscure. We sought to evaluate the alcohol-induced abnormalities of renal function and improvement during abstinence and to assess the relation between renal dysfunction and electrolyte and acid-base disorders. METHODS We measured biochemical constituents of blood and renal function before and after four weeks of abstinence in 61 patients with chronic alcoholism who had little or no liver disease. RESULTS On admission, 18 patients (30 percent) had hypophosphatemia and hypomagnesemia, 13 patients (21 percent) had hypocalcemia, and 8 patients (13 percent) had hypokalemia. Twenty-two patients (36 percent) had a variety of simple and mixed acid-base disorders. Twenty of these patients had metabolic acidosis, and among them, 80 percent had alcoholic acidosis. A wide range of defects in renal tubular function, with normal glomerular filtration rate, were detected in these patients. The defects included decreases in the threshold and maximal reabsorptive ability for glucose (38 percent of patients) and in the renal threshold for phosphate excretion (36 percent); increases in the fractional excretion of beta 2-microglobulin (38 percent), uric acid (12 percent), calcium (23 percent), and magnesium (21 percent); and aminoaciduria (38 percent). Seventeen patients (28 percent) had a defect in tubular acidification, and five an impairment in urinary concentrating ability. Urinary excretion of N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase were increased in 41 and 34 percent of patients, respectively. The abnormalities of blood chemistry and renal tubular function disappeared after four weeks of abstinence. CONCLUSIONS Transient defects in renal tubular function are common in patients with chronic alcoholism and may contribute to their abnormalities of serum electrolyte and blood acid-base profiles.

Relief of pruritus and decreases in plasma histamine concentrations during erythropoietin therapy in patients with uremia

BACKGROUND The pathophysiologic aspects of pruritus in patients with chronic renal insufficiency are poorly understood, and there is no universally effective treatment. The improvement of pruritus in several patients receiving erythropoietin therapy raised the possibility that erythropoietin affects uremic pruritus directly. METHODS We undertook a 10-week placebo-controlled, double-blind, crossover study in a group of patients receiving hemodialysis who had severe pruritus, to investigate the effects of recombinant human erythropoietin on their pruritus and plasma histamine levels. Twenty patients with uremia, of whom 10 had severe pruritus and 10 did not, received erythropoietin (36 units per kilogram of body weight three times weekly) and placebo in random order, each for five weeks. The severity of pruritus was scored weekly, and plasma histamine levels were measured at the beginning and end of each five-week period. RESULTS Eight of the 10 patients with pruritus had marked reductions in their pruritus scores during erythropoietin therapy. The mean (+/- SE) pruritus score decreased from 25 +/- 3 to 6 +/- 1 in these patients. The pruritus returned within one week after the discontinuation of therapy. The improvement was not related to the change in hemoglobin level. These eight patients were successfully treated again with low doses of erythropoietin (18 units per kilogram three times weekly), and the effect has persisted for six months. The patients with pruritus had elevated plasma histamine concentrations (20.7 +/- 2.7 nmol per liter), as compared with the patients without pruritus (4.2 +/- 0.6 nmol per liter; P less than 0.001) and normal subjects (2.1 +/- 0.2 nmol per liter; P less than 0.001). Therapy with erythropoietin induced a decrease in plasma histamine concentrations in both groups of patients with uremia, and recurrences of pruritus after the discontinuation of erythropoietin were accompanied by increases in plasma histamine concentrations. CONCLUSIONS Erythropoietin therapy lowers plasma histamine concentrations in patients with uremia and can result in marked improvement of pruritus.

Relationship of fibrinogen levels and hemostatic abnormalities with organ damage in hypertension.

Elevated plasma levels of fibrinogen and activated coagulation pathways are risk factors of cardiovascular disease in the general population. In a cross-sectional study of a case series, we investigated the relationship between fibrinogen and hemostatic markers with target-organ damage (TOD) in patients with arterial hypertension. Prothrombin time, partial thromboplastin time, fibrinogen, fibrin D-dimer, prothrombin fragment 1+2 (F1+2), and antithrombin III were measured in 352 untreated patients with mild to moderate essential hypertension and 92 normotensive controls. Staging of TOD was assessed according to W.H.O. guidelines by clinical evaluation and laboratory tests including measurements of creatinine clearance, proteinuria, ophthalmoscopy, electrocardiography, echocardiography, and ultrasound examination of major arteries. F1+2 concentrations were significantly greater in hypertensive patients than normotensive controls and were positively correlated with blood pressure. Age, blood pressure levels, duration of hypertension, smoking, HDL-cholesterol, triglycerides, and plasma fibrinogen, fibrin D-dimer, and F1+2 levels were significantly related to the presence and severity of TOD in univariate analysis. Plasma fibrinogen and D-dimer levels were related to organ damage independent of age, blood pressure, duration of hypertension, and smoking status. Separate analysis indicated significant association of fibrinogen and D-dimer levels with cardiac, cerebrovascular, peripheral vascular, and renal damage. In conclusion, elevated plasma levels of fibrinogen and a prothrombotic state are associated with the presence and severity of TOD in patients with essential hypertension and may contribute to the development of atherosclerotic disease in these patients.

Alcohol misuse and renal damage

Recent clinical and experimental studies have demonstrated that the habitual consumption of large amounts of ethanol has deleterious effects on the kidney. A variety of tubular defects have been described in patients with chronic alcoholism. Evidence is emerging that tubular dysfunction has an important pathophysiological role in a wide range of electrolyte and acid‐base disturbances commonly observed in these patients, and possibly in alcohol‐induced bone disease. These renal abnormalities are often reversible, disappearing with abstinence. However, since 1990 a few cases of a syndrome of acute tubular necrosis due to binge drinking of ethanol in the absence of other evident nephrotoxic mechanisms, or in association with the use of nonsteroidal anti‐inflammatory drugs, have been reported. A link between glomerulonephritis and alcoholism has become evident. IgA nephropathy has been demonstrated at autopsy in 64% of chronic alcoholics and, more recently, the association between alcoholism and postinfectious glomerulonephritis has been described. Structural and functional abnormalities of the kidney are reported with increasing frequency in the fetal alcohol syndrome seen in children who have been prenatally exposed to ethanol. In addition, over the last few years experimental studies in vitro or in animal models have provided information about the biochemical and molecular basis of alcohol‐induced injury to kidney. It is hoped that future experimental and clinical research will provide us with a more comprehensive knowledge of the mechanisms of renal damage in alcohol misuse.

Intraocular Pressure Changes During Hemodialysis: Prevention of Excessive Dialytic Rise and Development of Severe Metabolic Acidosis Following Acetazolamide Therapy

The response of intraocular pressure (IOP) to hemodialysis was investigated in 55 patients with end-stage kidney disease enrolled in a chronic dialysis program. The mean level of IOP, measured by the Goldman applanation tonometer, before dialysis was slightly lower than that of a control group of 50 healthy subjects (14.9 +/- 2 mm Hg vs 15.6 +/- 1.9 mm Hg. p = .07). During dialysis IOP underwent an excessive rise (7.8 to 12.5 mm Hg) in 10 patients (group 1), remained unchanged (variations below 2 mm Hg) in 41 patients (group 2), and decreased (3.1 to 5.1 mm Hg) in 4 patients (group 3). In group 1 patients, gonioscopy showed a narrow angle between iris and lateral cornea. Conversely, the anterior chamber angle was normal in patients of groups 2 and 3. The effect of a 7-day course of acetazolamide therapy (500 mg per day orally) on IOP was investigated in group 1 patients. Acetazolamide was capable of preventing the excessive IOP rise during dialysis. The mean reduction of such a dialytic rise was 8.1 mm Hg. However, despite this effect, in these patients the IOP level after dialysis still remained significantly higher than that of patients of group 2 (18.1 +/- 1 mm Hg vs 14.9 +/- 0.8 mm Hg. p less than .0001). Acetazolamide therapy precipitated in all patients a severe metabolic acidosis (blood pH fell from 7.38 +/- 0.02 to 7.24 +/- 0.03, p less than .0001; and bicarbonate concentration from 21 +/- 2.5 mmol/liter to 12.3 +/- 2.4 mmol/liter, p less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Close genetic linkage between HLA and renal glycosuria

Renal glycosuria is an inherited disorder of renal tubule function in which significant amounts of glucose are excreted in the urine in the simultaneous presence of normal blood glucose levels. Renal glucose titration analyses and HLA genotypes were performed in 5 unrelated affected families with a total of 25 patients and 40 healthy relatives. In each family the gene responsible for renal glycosuria segregates with the HLA complex suggesting a close genetic linkage. 2 cases carry intra-HLA recombinant haplotypes; in these subjects our findings indicate that the abnormal gene is closer to the HLA-A locus than the HLA-B locus. No HLA-A, HLA-B or HLA-C specific antigen is selectively increased among the 5 unrelated families affected with renal glycosuria.

Intraocular Pressure and Hemodialysis

Dr. Sergio De Marchi, Department of Internal Medicine, Hospital of Codroipo, Viale Duodo, 52, I-33033 Codroipo, Udine (Italy) Dear Sir, We were very interested in the article by Gafter et al. [1], whose study was designed to evaluate intraocular pressure (IOP) changes during 4-hour hemodialysis sessions in uremic patients receiving chronic hemodialysis treatment. These authors reported that their patients had a low IOP and hemodialysis did not increase it significantly. Thus they concluded that the risk of severe IOP rise following hemodialysis is only a remote possibility. We report here our experience in a group of 34 patients with end-stage renal failure enrolled in a chronic hemodialysis program. Dialysis took place 3 times weekly for 4–5 h. IOP readings were taken before, during (approximately 2 h after start) and within 30 min after dialysis using a Schiötz tonometer. The average IOP in uremic patients before dialysis was 14.9 ± 1.4 mm Hg and its average increase was 1.2 mm Hg during dialysis and 0.6 mm Hg after the end of the session. These data confirm, at least in part, the findings of Gafter et al. [1]. Indeed, in our patients IOP both before and after hemodialysis was less than the mean IOP observed in control subjects (16.5 mm Hg). However, the analysis of the IOP changes during the dialysis session led us to identify three groups of patients on the basis of the different tonometric behavior. Group 1 consisted of 25 patients in which IOP did not change significantly. Group 2 consisted of 6 patients (18%) in which there was a significant increase of IOP (13.5 ± 03 mm Hg before, 23.2 ± 1 mm Hg 2 h after start, 18.1 ± 2 mm Hg after dialysis). Group 3 consisted of 3 patients in which IOP significantly decreased during hemodialysis. During the dialysis session group 2 patients often developed complications such as headache, nausea and vomiting and in some cases these symptoms were observed in association with the rise in IOP. Goni-oscopy revealed in these patients a narrow angle between pupil and lateral cornea. In contrast, this angle appeared normal in patients of group 1 and 3. The mechanism leading to the rise of IOP during hemodialysis is still controversial. It has been reported that during dialysis there is an increase in aqueous humor formation [2]. Our findings suggest that this does not induce a significant change in IOP in patients with normal outflow capacity. However, if there exists an outflow obstruction the rise becomes significant. In group 2 patients, the administration of acetazolamide (500 mg/day orally) resulted in preventing intradialytic increase of IOP or associated symptoms, particularly headache. Nevertheless, acetazolamide caused in all patients a metabolic acidosis which induced us to interrupt the therapy after approximately 6–8 days.

Chemotherapy and/or Removal of the Peritoneal Catheter in the Management of Fungal Peritonitis Complicating CAPD?

Emanuela Cecchin, MD, Unit of Nephrology and Dialysis, Hospital of Pordenone, I-33170 Pordenone (Italy) Dear Sir, Fungal peritonitis in patients undergoing peritoneal dialysis is gaining in importance because of its increasing frequency. Medical therapy remains a critical problem and so far has not been uniformly successful. Peritoneal catheter removal is, at present, the recommended method for its treatment [1, 2]. We read with interest the recent paper by Pocheville et al. [3] which reports a case of Candida peritonitis during chronic ambulatory peritoneal dialysis (CAPD) recovered with intraperitoneal administration of 5-fluorocytosine (5-FC) without removing the catheter. We report here our experience with this drug in the treatment of fungal peritonitis in patients on CAPD. Between 1980 and 1983 34 patients with end-stage renal disease were submitted to CAPD. There were 51 episodes of peritonitis 6% of which were caused by fungi predominantly of Candida and Torulopsis species. The strategy of therapy we used in patients with fungal peritonitis consisted in a protracted course of oral 5-FC with the Tenckhoff catheter left in situ [4]. The minimum inhibitory concentration of 5-FC against the etiologic agent was determined before starting therapy. It usually ranged between 0.1 and 1 μg/ml.5-FC was administered orally daily in a dose of 40 mg/kg body weight the first 2 days followed by 30 mg/kg daily for the next 2 days and then by a maintenance dose of 15 mg/kg daily for the remainder of the course of therapy. The drug was continued for 1 week after the dialysate leukocyte counts were normalized resulting approximately in a 5 week course of therapy. In 2 cases of peritonitis caused by Torulopsis glabrata we measured 5-FC levels in serum and peritoneal fluid [5]. In both cases the concentration of 5-FC in the peritoneal effluent ranged between 50 and 80 μg/ml well above the minimum inhibitory concentration of susceptible fungal strains. The drug was well tolerated in all patients and its serum peak levels never exceeded 100 μg/ml. Thus, our experience agreed with the current opinion that excess toxicity comes out only when serum levels exceed 100–125 μg/ml [6]. Medical management was successful in all cases with disappearance of symptoms and return of dialysate leukocyte counts to normal ( < 50/mm3) in 4 weeks. Dialysate cultures became sterile after 1–2 weeks of therapy but 5-FC treatment was continued for approximately 1 week after the return of dialysate leukocyte counts to normal in order to have a better probability of sterilization. In fact, there is recent evidence [7] that, though the findings from the cultures of peritoneal fluid became negative during therapy, catheters when removed were found to be heavily colonized by fungi. In

Fungal Peritonitis in Ambulatory Peritoneal Dialysis

Excerpt To the editor: Kerr and associates (1) conclude that the benefit of chemotherapy in the management of fungal peritonitis in patients on chronic ambulatory peritoneal dialysis is of secondar...

A pheochromocytoma with high adrenocorticotropic hormone and a silent lung nodule.

Pheochromocytoma (PCC) is a challenging and life-threatening neoplasm. Herein, the authors report an interesting and unexpected solution for a clinical case concerning a patient with a PCC, who developed delayed ectopic adrenocorticotropic hormone Cushing syndrome originating from the PCC. In addition, after a misleading I-labeled metaiodobenzylguanidine single-photon emission computed tomography/computed tomography, an F-fluorodeoxyglucose positron emission tomography/computed tomography, executed to confirm the diagnosis of PCC, showed a silent pulmonary nodule that unexpectedly turned out to be a lung nocardiasis.