Glomerular lesions in HIV-positive patients: a 20-year biopsy experience from Northern Italy.

AIM: Glomerular involvement in HIV-positive patients is quite heterogeneous. In the present paper we reviewed 73 renal biopsies performed during a period of more than 20 years in a single Nephrology Unit, Milan, Northern Italy, in order to evaluate the aspects of single types of glomerular lesions (including HIV associated nephropathy-HIVAN), grouped according to histological patterns and clinical presentation. Moreover, in the group of non-HIVAN patients, the possible differences in histological characteristics from non-HIV lesions were investigated. MATERIALS AND METHODS: Renal tissues were obtained by percutaneous biopsies and were studied by light microscopy, immunofluorescence and electron microscopy. For the histological description three histological groups were identified: HIVAN, immune complex glomerulonephritis (GN) and glomerulopathies not related to immune-mediated mechanisms (so-called "various" glomerulopathies). RESULTS: HIVAN was observed in 9 cases, immune complex GNs in 40 cases (10 mesangial proliferative GN, 8 membranoproliferative GN, 5 lupus-like GN, 4 "acute" GN, 2 crescentic GN, 4 IgA nephropathy, 4 membranous GN and 3 immunotactoid GN) and "various" glomerulopathies in 24 cases (13 non-collapsing focal segmental glomerulosclerosis, 3 minimal changes, 3 end-stage renal disease, 4 diabetic nephropathy and one amyloidosis). CONCLUSIONS: Our 20-year biopsy series of HIV-related glomerular involvement confirmed the heterogeneity of lesions. In our series, the vast majority of HIV-related GN are the so-called immune complex GNs, with some peculiar aspects, as multiple site location of deposits and a frequent tendency towards sclerosis, in agreement with experimental data regarding HIV and fibrosis.

[Post-infectious glomerulonephritis]. / Glomerulonefriti post-infettive.

Post-infectious glomerulonephrites (GNs) include a wide spectrum of nephropathies, with known etiological agent, bacterial, parasitic, viral. Among GNs secondary to bacterial infections, post-streptococcal GN is the most frequent; nevertheless, its incidence in developed countries has decreased during the last 20 years, while some of the characteristics such as types of infection, exposed subjects, clinical and evolutionary patterns have changed. Prognosis has worsened and is correlated with some clinical and histological parameters. The viral infection-related GNs include those associated with HBV, HCV, HIV plus other rarer forms. Membranous GN (MGN), membranoproliferative GN (MPGN) and IgA nephropathy may occur in the course of HBV infection, while different GNs can be detected in relation to HCV, the most frequent being mixed cryoglobulinemic GN, a MPGN with peculiar morphological features. Multiple glomerular involvements are seen from HIV infection, the more characteristic form being the so-called HIV associated nephropathy (HIVAN), a focal segmental glomerulosclerosis with tuft collapse affecting African subjects, which starts with a nephrotic syndrome and rapidly develops into uraemia. Other GNs derive from HIV-related immunecomplexes, some with diffuse proliferative characteristics, or lupus like, with less severe clinical manifestations compared with HIVAN. Among the rare viral infections, we ultimately, mention the association between Parvovirus B19 and "collapsing" focal segmental glomerulosclerosis.

[Borderline indications for renal biopsy]. / Indicazioni "borderline" della biopsia renale.

The Authors report 3 cases with clinical renal manifestations where the indication to perform a renal biopsy was defined as borderline. The uncertain indication was related to the clinical presentation, with a pattern of urinary abnormalities, such as isolated microscopic hematuria, microscopic hematuria associated with mild proteinuria, and isolated proteinuria. In addition, similar questions on biopsy are raised for chronic renal failure and elderly patients. In the literature, microscopic hematuria without significant proteinuria shows that 25% of adult patients have no histological abnormalities. A higher percentage is found among children. The other cases exhibit a pattern of IgA nephropathy, Alport's syndrome, thin BM nephropathy and arteriolar C3 deposition. The percentage of an abnormal histological picture increases if the patients have a family history of hematuria, and if there are concomitant episodes of macroscopic hematuria, because of an increase in IgA nephropathy and Alport's syndrome, respectively. In the last cases, therefore the indication to perform a renal biopsy increases. For those patients without these characteristics, a renal biopsy can be delayed whereas in cases of microscopic hematuria with proteinuria or isolated proteinuria the indication for a renal biopsy is stronger, because the spectrum of glomerulopathies is wider, and the possible evolution to renal failure after 10 years is higher (10-14% of cases). In patients with chronic renal failure the biopsy is contraindicated for cases where the thickness of the cortical section of the kidney is lower than 8-10 mm, because of possible technical difficulties, lower diagnostic information due to sclerosis and higher risk of complications. The prolonged bleeding time and the consequent risk of bleeding can be avoided by i.v. infusion of vasopressin 2 hours prior to biopsy. The higher indications are for those patients who may be susceptible to a medical treatment, capable to slowing down the progression of nephropathy. Finally, in elderly patients the biopsy is indicated in almost all cases because of the recently confirmed high incidence of glomerulopathies. In the aged there is a higher frequency of membranous GN, crescentic-ANCA associated GN, amyloidosis and, according to some Authors, post-infectious GN. In all cases a precise histological diagnosis can correct an erroneous diagnosis made according to clinical data alone. In the elderly the indication for biopsy aims at making an exact diagnosis of nephropathy, especially for acute renal failure: for this purpose age itself should not become an obstacle.

HIV infection in dialysis centers in Italy: a nationwide multicenter study.

The prevalence of HIV infection in dialysis populations varies according to different countries and geographic areas. We performed a nationwide epidemiological study by means of a questionnaire in the period from January 1990 to December 1995. Questions were about whether and which HIV tests were performed and which preventive measures were adopted. A separate survey evaluated the data the HIV-positive patients. Only 62% of the centers responded to the questionnaire, corresponding to 21,500 dialysis patients in 1990 and 27,000 in 1995. The prevalence of HIV-positive subjects was 0,13% for 1995. A total of 48 patients with HIV infection were identified: risk factors were drug abuse in 16 cases, homosexuality in 9, heterosexual contact in 8, transfusion in 7, renal transplant in 3 and unknown cause in 5. Forty-five patients were on hemodialysis, and 3 were receiving peritoneal dialysis. At follow-up, 19 patients died: infection and malnutrition were the most frequent causes of death. The death rate of patients who were already HIV positive when dialysis was started (group 1, 29 cases) was 19.36 deaths/1,000 patient/month. The correlations, performed only for group 1, showed a significantly worse prognosis for patients with CD4 < 200/mm3 and for those with AIDS. In conclusion, in Italy the prevalence of HIV infection in the dialysis population is low, and the outcome of HIV-positive patients in dialysis was found to be better than earlier literature reports. The use of chronic dialysis for HIV patients with uremia should not be discouraged.

Pattern of glomerular involvement in human immunodeficiency virus-infected patients: an Italian study.

Renal biopsy specimens from 26 adult human immunodeficiency virus (HIV)-infected patients with glomerular involvement were reviewed from the files of three hospital pathology services in Northern Italy. All the patients were Italian and most (19 of 26 patients) were intravenous drug addicts. The types of glomerular lesions were as follows: minimal-change glomerulopathy (two cases), mesangial proliferative glomerulonephritis (GN) with scanty immunoglobulin deposits (four cases), and various patterns of immune complex-mediated glomerulonephritis, including postinfectious GN (six cases), membranoproliferative GN (one case), membranous GN (three cases), immunoglobulin (Ig) A nephropathy (four cases), a mixed membranous and proliferative (three cases) and diffuse proliferative lupus-like pattern with subendothelial deposits, and intraluminal thrombi (two cases) or subepithelial and subendothelial deposits (one case). None of the patients had evidence of HIV-associated nephropathy. Our study confirms previous observations on the low incidence of HIV-associated nephropathy among white HIV-infected patients in Europe, where immune complex-mediated GN seems to predominate. Apart from the frequent electron microscopic observation of endothelial tubuloreticular structures, none of the reported lesions could be distinguished on morphologic grounds from those occurring in uninfected patients. The high variability of the glomerular lesions upholds the need for accurate diagnosis for the clinician confronted with an HIV-positive patient with suspected glomerular involvement.

Reduced blood levels of coagulation inhibitors in chronic hemodialysis compared with CAPD.

The aim of this study was to measure the coagulation inhibitors in two groups of uremic patients treated with hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) to evaluate the differences in anticoagulant activity. In 20 patients on HD and 20 on CAPD, mean age 66 +/- 8 and 58 +/- 14 years, respectively, the following parameters were determined between dialysis exchanges: protein C (PC), protein S (PS), antithrombin III (AT III), electrophoresis, prothrombin activation fragment (F1+2), alpha 1 antitripsin (alpha 1 AT), prothrombin time (PT), and activated partial thromboplastin time (PTT). The mean values of PC, PS, and AT III were respectively, 95.7 +/- 16 on HD and 92 +/- 23 on CAPD; 82.2 +/- 13.6 on HD and 90.5 +/- 13.6 on CAPD; the mean value F1+2 was 1.2 +/- 0.5 on HD and 1.04 +/- 0.5 on CAPD (p < 0.05). A good correlation between PS and AT III% functional activity (p < 0.03, r = 0.5) in both groups was found. More-over, PS functional activity was inversely correlated with duration of dialysis (p < 0.05, r = -0.3). HD patients showed a reduction of coagulation inhibitors compared with CAPD patients. Such a phenomenon could justify the increased thrombotic risk in HD patients. Since 80% of those on HD and only 20% of those on CAPD received erythropoietin (EPO), the prothrombotic state in HD could be due to reduced PS activity secondary to EPO treatment.

Absence of HIV antigens in renal tissue from patients with HIV-associated nephropathy.

HIV-associated nephropathy (HIV-N) is considered a distinctive disease, the pathogenesis of which is still undefined. Direct virus-induced renal cell damage has been postulated. The numerous cytolytic ultrastructural changes and a few studies by immunoperoxidase support this hypothesis, but there has been no demonstration of virus by electron-microscopy (EM) or by tissue culture. In seven out of 12 cases with histological characteristics of HIV nephropathy, with proteinuria (five cases) or with nephrotic syndrome (two cases), we tested renal tissue for HIV antigens: core p18 and p25; envelope gp45 and gp110, by means of immunoperoxidase avidin-biotin complex monoclonal antibodies (MoAbs). Light-microscopy (LM) showed in five patients a focal and segmental glomerular sclerosis, and in two a mesangial hyperplasia with vacuolisation of visceral epithelium and protein inclusions. Electron-microscopy, performed in five of seven patients, showed several protein inclusions in podocyte cytoplasm, tubuloreticular inclusions in endothelial cell cytoplasm in all cases, nuclear degranulation of tubular cells in four cases and nuclear bodies in two. HIV antigens by MoAbs on renal tissue were negative in all cases, in both glomeruli and tubules. These results do not confirm the presence of HIV proteins in renal tissue of patients with HIV nephropathy. A possible explanation, apart from no direct HIV in the disease, may be the low viral load in tissues, because of the early phases of renal damage in most cases.

HIV-associated nephropathy: a new entity. A study of 12 cases.

The existence of an HIV-related nephropathy as a distinct disease entity is controversial. Twelve patients affected by HIV infection (eight drug-abusers, three homosexuals and one black heterosexual) who showed nephrotic syndrome (five patients) or urinary abnormalities (seven patients), four with renal insufficiency, were submitted to renal biopsy. Six patients were in pre-AIDS, six had AIDS. Light microscopy, performed in all cases, showed focal segmental glomerular sclerosis in nine patients, a moderate hypercellularity in six, vacuolisation of visceral epithelium in ten, focal collapsed tuft in seven, and tubular microcystic dilatation with large dense protein casts in lumina in seven. Immunofluorescence, available in 11 patients, showed small deposits in mesangium or mesangial and subendothelial spaces. IgG, IgM, and C3 were more frequently found, while three cases were negative. Electron-microscopy (five patients), besides confirming light-microscopy changes, showed several tubuloreticular inclusions (four patients), nuclear bodies (mainly complex) in nuclei of tubular cells (three patients), and nuclear granulofibrillary transformation of tubular cells. Various histological aspects and clinical data confirm the hypothesis that HIV nephropathy can be considered as a separate entity, different from heroin nephropathy and idiopathic focal glomerulosclerosis.

Cardiac output with CO2 rebreathing method in CAPD patients.

The aim of this study is to evaluate cardiac output (CO) with CO2 rebreathing method (RCO2) in patients (pts) on CAPD. We have studied 15 pts on CAPD from at least 6 months, the mean (+/- SD) age was 55 +/- 4 years, mean (+/- SD) hemoglobin was 10 +/- 2 gr/dl. The respiratory tests excluded obstructive or restrictive broncopneumopathies. Electrocardiograms and B-mode echocardiograms were normal. RCO2 was evaluated using the FICK formula: CO = VCO2/CvCO2 - CaCO2 where VCO2 is CO2 production; CvCO2 is the CO2 content in venous mixed blood; CACO2 is arterial CO2. VCO2 was obtained by collecting expired air into a Douglas bag during respiration at rest for 4 minutes. CvCO2 was obtained after 10-15 seconds of respiration in a mixture of 7% CO2 in O2. CaCO2 was obtained at CO2 end-tidal capnogram. RCO2 was performed in CAPD with full and empty abdomen. The mean (+/- SD) CO was 2.3 +/- 1.04 l/min with both full and empty abdomen, values below those theoretically calculated, taking into account the age and body surface (4.7 +/- 0.6 l/min P less than 0.0005). The reduction of CO is not induced by left ventricular insufficiency, but such phenomenon could be attributed to a redistribution of body fluid between intra and extracellular, in favour of the intracellular compartment. Therefore the increase in hematocrit and total plasma proteins can be fictitious.

Clearances and solutes extraction in biofiltration and hemodialysis with the AN 69 S.

Clearances and solutes extraction were assessed in biofiltration (BF) and in hemodialysis (HD) with the new polyacrylonitrile AN 69 S membrane. Three patients treated for three months by acetate dialysis (4 hours X 3) and subsequently by BF (3 hours X 3) were studied after achievement of steady state. Total intradepurative clearances (diffusive and convective) and solutes extraction of urea, creatinine, uric acid and phosphate were determined. Clearance of small molecular weight solutes was better in BF than in HD especially for uric acid and phosphate. This confirms the high depurative efficiency of the AN 69 S. BF gave better total clearances than HD, but the extraction of lower molecular weight solutes (due to the one-hour reduction of dialysis time) suggests that adequate treatment time is needed with this technique.

[An isometric exercise for the diagnosis of chronic obliterating arteriopathies of the lower extremities]. / Uno sforzo isometrico per la diagnosi delle arteriopatie obliteranti chroniche degli arti inferiori.

A non invasive method for the diagnosis of occlusive diseases of the peripheral arteries and the follow-up of therapy is proposed. The method consists in the performance of an isometric effort of the inferior limbs and the Doppler detection of the dorsalis pedis systolic pressure. 41 patients with different degrees of peripheral artery involvement have been studied and the results compared with those obtained in a control group of 12 normal subjects, equally matched for ages and sex. In the normal subjects the maximal dorsiflection of the feet for 30 seconds caused a mean increase of the heart rate of 20% and no changes of the systolic blood pressure. In the patients with peripheral artery disease the isometric effort caused, contemporary to the increase of the heart rate, a decrease of the dorsalis pedis systolic pressure, that varied from 15 to 100% according to the degree of the arterial involvement. A close correlation was found between the degree of the percent reduction of peripheral systolic pressure and the entity of the arterial involvement, as evidenced by other invasive and non-invasive methods. The method proposed appears useful for a proper diagnosis of peripheral vascular diseases in those patients who cannot undergo invasive investigations or the treadmill effort test.