Graziana Battini

Variability of clinical phenotype in a large Alport family with Gly 1143 Ser change of collagen alpha 5(IV)-chain.

In a large Italian family with adult-onset Alport syndrome, molecular analysis of the COL4A5 gene, which encodes the alpha 5(IV)-chain of glomerular basement membrane collagen, revealed a GGC-->AGC change in exon 38, resulting in substitution of a serine for a glycine in position 1143 of the polypeptide chain, between interruptions 19 and 20 of the triple helical domain. The mutation leads to loss of a restriction site for the enzyme Msp I, and could thus be easily recognized in several female and male relatives. Among relatives of both sexes who carried the same mutation, the clinical phenotype of Alport syndrome was variable as for the onset of renal failure and the presence of associated ear and eye abnormalities.

Renal transplantation from living donor parents in two brothers with Alport syndrome. Can asymptomatic female carriers of the Alport gene be accepted as kidney donors

Renal transplantation from living donor parents was performed in two brothers with end-stage renal failure due to Alport syndrome (AS). Two years later, the patient receiving the kidney graft from the mother, obligate carrier of AS, presented persistent microhematuria and proteinuria with normal renal function. The histological study demonstrated ultrastructural glomerular lesions consistent with AS. The authors conclude that: (1) Alport patients should not be deprived of renal transplantation from living donors, since anti-GBM nephritis is a rare complication; (2) an oligosymptomatic female carrier of the Alport gene may be considered as living renal donor, although a longer follow-up is needed in order to draw definitive conclusions.

Acute Renal Failure Due to Hypersensitivity Interstitial Nephritis Induced by Warfarin Sodium

Dr. A. Volpi, Unità Operativa di Nefrologia e Dialisi, Ospedale di Vimercate, Via Cereda, 2, I-20059 Vimercate (Italy) Sir, Adverse reaction to a growing number of drugs is being recognized as a cause of acute renal failure [1]. The clinician should suspect the possibility of acute drug-induced tubulointerstitial nephritis in all cases of acute renal failure of unknown etiology. Acute drug-induced hypersensitivity reaction is a common form of tubulointerstitial nephritis with sudden deterioration of renal function and oliguria. Renal function usually returns toward baseline after withdrawal of the drug. Systemic signs and symptoms such as fever, skin rash, arthralgias, myalgias, eosinophilia and seldom lym-phoadenopathy suggest a hypersensitivity mechanism; certain observations suggest that immunologically mediated tissue damage is the consequence of cell-mediated injury [2]. We have observed a 65-year-old female who developed fever, arthralgias, gross hematuria, sterile pyuria and oliguric acute renal failure (serum creatinine rose from 1.2 to 6.8 mg/dl). She was treated for 25 days with diltiazem, nitroglycerine discs and warfarin sodium (20 mg/day) because of myocardial infarction. Renal biopsy showed a typical picture of acute tubulointerstitial nephritis, with several interstitial eosino-phils, mononuclear cells, patchy focal tubular necrosis and intratubular casts of eosinophil cells (fig. 1). The glomeruli showed mild mesangial hypercellularity with IgA and C3 mesangial deposits at immunofluorescence. Late assay of serum IgE was normal. Withdrawal of warfarin sodium and treatment with corticosteroids (1 mg/kg/day) returned renal function to the normal level in 45 days (serum creatinine 1 mg/dl). Acute renal failure due to acute drug-induced tubulointerstitial nephritis is seen more frequently in older patients and, usually, the mean latent period of treatment is 15 days (from 2 to 44 days) [2]. In the absence of other apparent causes we think that warfarin sodium hypersensitivity has likely been the

Two Brothers With Idiopathic Membranous Nephropathy and Familial Sensorineural Deafness

Genetic factors could play an important role in the pathogenesis of idiopathic membranous nephropathy, and a few cases of familial membranous nephropathy have been described: an increased incidence of some HLA antigens as DR3 and others has been reported. We present two brothers with idiopathic membranous nephropathy and sensorineural deafness. HLA typing was performed in the two patients and in the members of the family, and it showed the absence of linkage of an HLA antigen with the renal disease in the family.

Renal transplantation in patients with Fabry disease.

Anderson-Fabry disease (AFd) is a rare X-linked disorder characterized by deficiency of α-galactosidase A that leads to systemic accumulation of neutral glycosphingolipids, predominantly globotriaosylceramide (Gb3), in body fluids and visceral tissues, including the kidney. End-stage renal failure is a common manifestation in hemizygous males that often occurs by the third to fourth decade of life. Usually transplanted patients exhibit improvement in clinical symptoms of the disease, probably related to the production of α-galactosidase A from the grafted kidney, but mainly related to the increase in Gb3 clearance by the functioning kidney, and increased survival of red cells due to the correction of the uremic status with an evident decrease in the production of Gb3 depending from hemolysis. Several Fabry patients with successful kidney graft survived for 10–15 years and died for cardiovascular complications related to the metabolic disease. The loss of grafted kidney is due to rejection, thrombosis or sepsis. An important issue considering renal transplantation in AFd is the recurrence of the disease in the kidney graft; however, no evidence regarding this possibility has occurred up to now. We report herein the ultrastructural study of the urinary sediment of a 35-year-old male Fabry patient with a severe clinical form of the disease with progression to ESRF at age 29, and submitted to renal transplantation at 33 years. Ultrastructural findings of the urinary sediment documented several cells, probably tubular epithelial cells, with typical accumulation of myelinic bodies resulting from intracellular storage of neutral glycosphingolipids. This morphological evidence arises the problem of the possible recurrence of AFd in the kidney graft in patients with severe phenotype of the metabolic disease.

Hypocomplementemic Type II Membranoproliferative Glomerulonephritis in a Male Patient with Familial Lecithin-Cholesterol Acyltransferase Deficiency due to Two Different Allelic Mutations

Patients with familial lecithin-cholesterol acyltransferase (LCAT) deficiency very often show progressive glomerulosclerosis with evolution to end-stage disease. High levels of an abnormal lipoprotein (lipoprotein X) cause glomerular capillary endothelial damage. The ultrastructural study of renal biopsy specimens shows characteristic glomerular deposits of membrane-like, cross-striated structures and vacuole structures. The gene encoding for LCAT has been mapped to chromosome 16q22.1, and several mutations of this gene cause LCAT deficiency which is inherited as an autosomal recessive trait and which is characterized by corneal opacities, normochromic normocytic anemia, and renal dysfunction. Herein we report clinical features and renal histological findings concerning a 24-year-old male patient with classical familial LCAT deficiency due to two different allelic mutations: a nonsense mutation inherited from the father and a missense mutation inherited from the mother. Moreover, the patient showed glomerular histological lesions and an immunofluorescent glomerular pattern typical of hypocomplementemic membranoproliferative type II glomerulonephritis (dense-deposit disease). The nature of electron-dense material that characterizes dense-deposit disease is still unkwown, but there are suggestions that some chemical modifications might occur in the renal basement membranes. Therefore, this clinical case might induce to consider possible relations between disorders of the lipoprotein metabolism and renal dense-deposit disease.

Alport syndrome with type I membranoproliferative glomerulonephritis.

Alport Syndrome with Type I Membranoproliferative Glomerulonephritis M. Meroni A. Sessa G. Battini L.T. Torri Tarelli T. Bertani A. Renieri M. Seri M. De Marchi UO Nefrologia e Dialisi, Vimercate, Istituto di Anatomia Umana Normale, Università degli Studi, Milano, Divisione di Nefrologia, Ospedali Riuniti, Bergamo, Cattedra di Genetica Medica, Dipartimento di Biologia Molecolare, Università di Siena, Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Ospedale San Luigi Gonzaga, Orbassano, Italia

Lactic Acidosis Coma in Continuous Ambulatory Peritoneal Dialysis

Dr. A. Tommasi, Servizio di Nefrologia e Dialisi, Ospedale di Vimercate, Via Cereda 2, 20059 Vimercate (Italy) Dear Sir, We have recently observed a case of lactic acidosis coma in a patient on continuous ambulatory peritoneal dialysis (CAPD). The patient, a 69-year-old female, weighing 78.5 kg and 162 cm tall, had been on CAPD treatment for 2 months because of analgesic nephropathy, proved by anamnestic investigation and by kidney biopsy. She developed severe lactic acidosis with abrupt onset and without warning, during an episode of peritonitis and circulatory failure. The maintenance therapy consisted of digoxine, nifedipine and aluminum hydroxide. Laboratory data were: arterial blood pH 7.19, Pa02 64.1 mm Hg, PaC02 32.6 mm Hg, plasma bicarbonate 11.5 mEq/1, plasma lactate concentration 120 mg/l00 ml (normal values 5–22 mg/l00 ml), sodium 136 mEq/1, potassium 6.49 mEq/1, chloride 95 mEq/1, BUN 77 mg/l00 ml, creatinine 8.35 mg/l00 ml, glucose 91 mg/l00 ml, hema-tocrit 24.7%, hemoglobin 7.6 g/l00 ml. We treated lactic acidosis with sodium bicarbonate infusion (600 mEq in 48 h) and acetate hemodialysis (4 h twice a day for the 1st day and once a day for the following 2 days). The patient recovered after 2 days of treatment. Laboratory data were: arterial blood pH 7.41, Pa02 59.7 mm Hg, PaC02 37.9 mm Hg, plasma bicarbonate 24.7 mEq/l, plasma lactate 17 mg/l00 ml; and after 4 days of treatment: arterial blood pH 7.43, Pa02 68.8 mm Hg, PaC02 46 mm Hg, plasma bicarbonate 30 mEq/l, plasma lactate 13 mg/l00 ml. An increased plasma lactate concentration has been reported to occur during intermittent peritoneal dialysis (IPD) [1], but lactic acidosis has never been reported during CAPD. It is possible that more concomitant mechanisms have determined the severe lactic acidosis in our patient: (a) hepatic failure because of hepatitis following long-term exposure to paracetamol [2,3]; that may justify the lack of a metabolic way of lactate to piruvate; (b) circulatory failure, which may induce a shift from aerobic metabolism to anaerobic glycolysis and thereby produce lactic acidosis [4]; (c) fasting in the presence of obesity, which may induce accumulation of lactic acid in significant amounts [4].

Thrombolysis in Myocardial Infarction and Double Aortocoronary Bypass in a Patient on Continuous Ambulatory Peritoneal Dialysis

Dr. A. Volpi, Servizio di Nefrologia e Dialisi, Ospedale di Vimercate Via C. Battisti 23, I-20059 Vimercate (Italy) Sir, Cardiovascular diseases appear to be the leading cause of death in patients receiving long-term dialysis, and accelerated atherosclerosis is mainly responsible for vascular lesions in uremic patients [1,2]. Moreover hypertension, coronary artery disease, myocardial failure, cardiac calcifications, arrhythmias, and pericarditis are more common in these patients compared to the general population [3]. We have observed a 53-year-old woman admitted in October 1983 because of microhematuria and proteinuria with clinical and renal histological features of Henoch-Schönlein syndrome: her serum creatinine was 1.4 mg/dl. In November 1984 she was readmitted for rapid deterioration of renal function (serum creatinine, 6 mg/dl) and she was treated with pulses of steroid and plasma exchange: serum creatinine returned to 3.17 mg/dl. She developed diabetes and hypertension during steroid treatment. Eighteen months later (March 1985) she was begun on continuous ambulatory peritoneal dialysis for end-stage renal failure. She had experienced angina pec-toris during the previous 6 months and therefore she was treated with calcium channel blockers and nitrates. In April 1986 she presented with prolonged anginal pain and hypotension: ECG tracings showed signs of an acute ischemic lesion of the inferior cardiac wall. Laboratory examinations showed: lactate dehydrogenase 1,031 IU, and creatine kinase 1,366 IU with high levels of MB isoenzyme. She was treated with urokinase by intravenous infusion (a ‘pulse’ of 600,000 U followed by 1,500,000 U in 60 min) with partial regression of the ischemic lesion; afterwards the patient was treated with heparin and nitrates.

Plasma Exchange in Acute Renal Failure Due to Postpartum Hemolytic-Uremic Syndrome

Dr. A. Sessa, Servizio di Nefrologia e Dialisi, Ospedale di Vimercate, Via C. Battisti 23, I-20059 Vimercate (Italy) Dear Sir, In females with early or late postpartum hemolytic-uremic syndrome (HUS), the features of the illness are acute renal failure and microangiopathic hemolytic anemia in association with thrombocytopenia and increased serum bilirubin levels [1]. Severe irreversible renal failure is the rule; nevertheless, cases have been reported with a favorable outcome [2]. The pathogenesis of the HUS is still unknown: circulating substances (en-dotoxins, vasoactive amines, etc.) are likely to produce the primary injury to the endothelial cells of the glomeru-lar capillaries [3]. Moreover, some patients appear to have a lack of a prostaglandin plasma inhibitor [4], and intravascular coagulation also might be induced by im-munoglobulin factors [5]. Therefore, plasma exchange treatment with fresh plasma infusion has been suggested [6]. We have observed a 32-year-oîd female affected with early postpartum HUS. The kidney biopsy showed glom-erular thrombotic microangiopathy. The patient received plasma exchange treatment for 3 consecutive days and then every 3rd day the following week with an exchange of one plasma volume at each procedure, using fresh plasma as 50% of the substitution fluids. Regression of the HUS and partial recovery of renal function were observed. The patient was discharged on the 16th hospital day with normal blood pressure, renal function, and hematologic picture. For 3 years she has been well (fig. 1). The early treatment with plasma exchange and fresh plasma infusion possibly conditioned a favorable course of the disease. ππ Plasmapheresis Bilirubin, mg/l00 ml Pla†ele† 500 · coun†/mm3 ¿λ∩ 300 200–100 Serum crea†inine, mg/l00 ml Urine 1,500