[Haemoptysis : Intensive care management of pulmonary hemorrhage]. / Hämoptoe : Intensivmedizinisches Management von Lungenblutungen.

There is a wide spectrum of severities in patients with pulmonary bleeding with a range from mild haemoptysis to severe bleeding with an acute risk of asphyxiation. For the management of acute pulmonary haemorrhage, it is essential to identify the underlying cause in order to initiate a target-oriented or causal therapy. The most common causes of localized pulmonary bleeding are lung cancer as well as infections, anticoagulant therapy or bronchiectasis. Diffuse alveolar haemorrhage is mostly due to pulmonary vasculitis or connective tissue disease, but may also occur in pulmonary metastasis, congestive heart failure, coagulation disorders and from many other causes. In a case of severe pulmonary bleeding it is essential to secure the airways and ensure sufficient ventilation, i. e. by intubation with a double-lumen endotracheal tube and by appropriate positioning of the patient. Stabilizing haemodynamics is crucial. Simultaneously basic diagnostic measures, i. e. appropriate laboratory tests, chest X­ray, computed tomography scan of the chest and bronchoscopy, are performed. Localized pulmonary bleeding usually requires local treatment, like bronchoscopic therapy, bronchial artery embolization or surgery. Diffuse alveolar haemorrhage must be treated systemically, i. e. by immunosuppressive therapy in cases of vasculitis or by medical treatment of coagulation disorders. Even with optimal interdisciplinary management the in-hospital mortality of severe pulmonary bleeding remains high. There is a significant risk of recurrent bleeding depending on the cause of haemorrhage. In patients with "cryptogenic" haemoptysis there is an increased rate of lung cancer within the following years and follow-up of these patients is recommended.

[Evaluation of the tolerance and effectiveness of Diltiazem LP 300 mg in hypertensive patients with chronic renal insufficiency]. / Evaluation de la tolérance et de l'efficacité du Diltiazem LP 300 mg chez des patients hypertendus et insuffisants rénaux chroniques.

31 male and female patients, between the ages of 18 and 65 years, presenting mild-to-moderate hypertension (DBP between 95 and 114 mmHg) and stable chronic renal failure (creatinine clearance between 60 and 25 ml/min) after a preinclusion placebo phase were included in a multicentre open study designed to evaluate the clinical, electrocardiographic and laboratory safety, as well as the antihypertensive efficacy of Diltiazem 300 mg Retard, as monotherapy for 3 months, or combined with a diuretic (furosemide) or angiotensin converting enzyme inhibitor (captopril) for 45 days. After an 8-day placebo run-in period, the study consisted of a 45-day phase of strict monotherapy with Diltiazem 300 mg Retard, followed by a final 45-day phase during which either monotherapy was continued (if safety was satisfactory and supine DBP < or = 90 mmHg), or two-agent combination therapy was instituted (when supine DBP was between 91 and 115 mmHg), 6 clinical evaluations were performed during the 3 months of this trial. Overall, 21 patients (mean age: 50 +/- 14 years) completed the study until the 3rd month: 13 remained on monotherapy, and 8 required two-agent combination therapy. Supine and standing systolic and diastolic blood pressures and heart rate were significantly decreased. The number of responding patients controlled (supine DBP < or = 90 mmHg) progressed between D10 (40%) and D90 (57%). The observed adverse events and reasons for drop-outs from the trial for adverse events were mostly related to the vasodilator effects of Diltiazem. The cardiac safety was good, with no significant variation of the PR interval on the ECG (0.15 +/- 0.03 sec on D-8, 0.17 +/- 0.02 sec on D90). No marked modification of blood and urinary laboratory constants (serum electrolytes, blood glucose, liver function tests) was observed during this trial. Renal function, evaluated by creatinine clearance, was not altered by treatment (40.5 +/- 15.2 ml/min on D0, 41.7 +/- 16.9 ml/min on D90). Overall, this study confirmed the good clinical, laboratory and electrocardiographic safety as well as the antihypertensive efficacy of Diltiazem 300 mg Retard administered as monotherapy for 3 months or possibly in combination for 45 days, in hypertensive patients with chronic renal failure.

IgA nephropathy complicating diabetic glomerulosclerosis.

A retrospective study was done on 66 diabetic patients who had renal biopsies performed during 1979-1994. This review shows 10 patients who presented IgA nephropathy associated with diabetic nephropathy. Six patients had insulin-dependent diabetes mellitus and 4 patients non-insulin-dependent diabetes mellitus. All patients presented with proteinuria and 7 had hematuria. Four patients presented with renal impairment. Histologic evaluation disclosed the presence of thickened glomerular basement membranes and increased mesangial matrix in all cases, associated with nodular sclerosis in 8 cases. By immunofluorescence, diffuse mesangial IgA deposits were observed in all cases. The high incidence of the coexistence of IgA nephropathy and diabetes seems not merely coincidental. Structural and/or functional abnormalities of the glomerular basement membranes might facilitate the development of immune complex glomerular diseases. In patients with diabetes, the appearance of urinary abnormalities and/or deterioration in renal function altered the clinical history of diabetic nephropathy. The disorders are clinically suggestive of the presence of nondiabetic renal disease and raised the possibility of another pathogenetic mechanism.

High rate of hepatitis C virus clearance in hemodialysis patients after interferon-alpha therapy.

To gain insight into the long-term effect of interferon-alpha (IFN-alpha) therapy on hepatitis C virus (HCV) RNA-positive hemodialysis patients, 23 subjects were given 3 MU of IFN-alpha 3 times a week for 6 (n = 12) or 12 months (n = 11). They were followed for 19 months after cessation of therapy. Sustained serum HCV RNA clearance occurred in 42% of patients treated for 6 months and in 64% of those treated for 12 months. HCV was eradicated from 6 of 13 patients infected with HCV genotype 1b and from 2 of 6 patients also infected with hepatitis G virus. HCV RNA remained undetectable in both serum and a liver biopsy of 2 patients who were given cadaveric kidney transplants after IFN-alpha treatment. These data suggest that HCV RNA-positive dialysis patients can be considered for treatment while receiving dialysis, particularly those awaiting transplant.

[HCV RNA clearance after treatment with interferon-alpha in chronic hemodialysis patients with or without coinfection by HGV/HGBV-C]. / Clairance de l'ARN du VHC après traitement par interféron alpha chez des hémodialysés chroniques avec ou sans coinfection par le VHG/VHGB-C.

Patients on maintenance hemodialysis are frequently infected with hepatitis C virus (HCV). The long-term effect of alpha interferon therapy has not yet been assessed, or the influence of co-infection with the newly discovered hepatitis G/hepatitis GB virus-C (HGV/HGBV-C) upon therapy outcome. Eleven anti-HCV and HCV RNA-positive hemodialysis patients, 3 of whom had HGV/HGBV-C infection were given 3 mega-units of alpha 2b recombinant interferon subcutaneously 3 times weekly for six months. The mean follow-up after cessation of therapy was 24 +/- 8 months (range: 18-30 months). Sustained serum HCV RNA clearance, as assessed by PCR analysis, occurred in 5/11 patients (45.5%). Two had received a cadaveric kidney transplant at 16 and 18 months post-treatment and were treated by immunosuppressive therapy; HCV RNA remained undetectable in both serum and a liver biopsy. HCV was eradicated in 3 of the 6 patients infected with HCV genotype 1b, which is less sensitive to alpha-interferon than other HCV genotypes. Among the 3 patients infected with both HCV and HGV/HGBV-C, alpha-interferon cleared the HCV RNA from one patient, but not the HGV/HGBV-C RNA. In view of the high rate of HCV eradication after alpha-interferon therapy and its fair tolerance, we suggest that HCV RNA-positive dialysis patients should be treated before transplantation, regardless of their aminotransferase levels or liver histological score, since alpha interferon therapy after renal allografting is associated with an unacceptable rate of renal failure. Our preliminary data indicate that HGV/HGBV-C does not interfere with sustained HCV RNA clearance.

Renal functional reserve in kidney and heart transplant recipients.

Renal functional impairment paradoxically often seems less severe in kidney than in heart-transplant recipients (KTR and HTR, respectively) when both are submitted to cyclosporine therapy. Renal functional reserve (RFR), elicited by a 3-h intravenous amino acid infusion, was examined in 12 KTR and 13 HTR at 7 to 8 months, appropriately compared with either eight one-kidney or 12 two-kidney healthy control subjects (1K.C and 2K.C, respectively). Baseline GFR was 54 +/- 4 mL/min in KTR and 71 +/- 4 mL/min in HTR (P < 0.05). During amino acid infusion, the maximum increase in GFR (which represented RFR) was 17 +/- 3 mL/min in both KTR and HTR (P < 0.001). RFR in KTR was 96 +/- 18% of that in 1K.C, whereas RFR in HTR was only 59 +/- 9% of that in 2K.C. Effective RPF increased (41 +/- 8 mL/min, P < 0.001), and renal vascular resistances decreased (48 +/- 17 mm Hg/L per min, P < 0.05) in KTR but not in HTR. These results demonstrate that both KTR and HTR possess a renal reserve but that the single renal graft in KTR retains a proportionally higher baseline GFR and a better ability to exhibit a RFR than the two native kidneys in HTR. This dissimilar impairment could result from slightly higher cyclosporine dosage, activation of the intact renal sympathetic innervation accentuated by cardiac denervation, renal consequences of former heart failure and potential alterations in the cardiac graft function, and/or higher prevalence of hypertension and additive therapies in HTR.

[Acute renal insufficiency in renal transplants treated with interferon-alpha for chronic hepatitis C]. / Insuffisance rénale aiguë chez des transplantés rénaux traités par interferon alpha pour une hépatite chronique C.

Sixteen renal transplant (RT) patients (10 men, 6 women, aged 49 +/- 10 years) with chronic hepatitis C received alpha interferon (IFN alpha) therapy (Intron A, Schering Plough) at a dose of 3 x 10(6) units s.c. 3 times a week, scheduled for 24 consecutive weeks. At the beginning of the study all had a stable renal function since at least 12 months (mean serum creatinine -SCr- 121 +/- 38 mmol/l). Fourteen patients were receiving cyclosporin A (CsA) either alone (1) or in combination with steroids and/or azathioprine -AZA- (double therapy: 8; triple therapy: 5); two patients were on conventional therapy. The mean daily doses of CsA were 2.6 mg/kd i.e. a mean whole blood trough level of 104 ng/ml. Six patients experienced renal failure either acute (5) or subacute (1) within 7 to 24 weeks after the start of IFN alpha therapy. Their mean SCr increased from 105 +/- 31 mmol/l to 207 +/- 63 mmol/l (p = 0.02) with de-novo proteinuria in one case (1 g/d) and an increase in pre-existing proteinuria in 2; 3 remained without proteinuria. The histological study showed in all cases a diffuse interstitial edema associated with dilatation of peritubular capillaries; mild inflammatory infiltrates were present in only 3 cases; mild glomerular lesions were not always found (glomerular ischemia, mesangial hypertrophy). There was no vascular lesions IFN alpha was withdrawn in these 6 patients, associated with methylprednisolone pulses in 5 cases. Renal function improved in two cases, stabilized in one and progressed to end stage renal failure in 3 within 4 to 12 months. Four patients had iterative renal biopsies showing in all cases diffuse interstitial fibrosis. This subgroup of patients did not statistically differ at the start of the study from those who did not develop renal failure according to baseline immunosuppression, HLA matching, total peripheral blood lymphocyte (PBL) count. PBL subtypes. INF alpha therapy was associated with acute or subacute renal failure in 37% of patients. The most prominent histological finding was a diffuse interstitial edema of rapid onset, without signs of cellular or vascular rejection. Thus we do not recommend to use IFN alpha therapy in RT patients with chronic hepatitis C, until the mechanisms of the subsequent renal failure be more understood.

Epidemiology of HCV infection: disease and renal transplantation.

We studied the prevalence of HCV infection in a cohort of 346 patients who received renal transplantation between January 1989 and April 1994. Assessments were made at the time of surgery, one year later and at the last follow-up visit. The hepatic consequences of HCV infection were also studied. The prevalence of HCV infection at the time of surgery was 21.4% (74/346). The risk factors associated with the presence of anti-HCV antibodies were: duration of haemodialysis, the number of transfusions and the number of previous renal transplantations. The incidence of HCV infection was 3% (8/272) and was accompanied by either transient (n = 4) or chronic (n = 3) hepatic cytolysis; five patients underwent liver biopsy which revealed persistent chronic hepatitis (n = 2) or active chronic hepatitis (n = 3). Seroconversion always occurred within one year following transplantation. In the long-term, 91% of HCV+ patients remained viraemic. The HCV genotype was predominantly 1b. Fifty-six per cent (56%) of HCV+ patients had normal ALAT at the time of transplantation, which remained normal on follow-up in two-thirds of cases. After transplantation, 39 HCV+ patients underwent liver biopsy. ALAT were normal in 13 of those; liver biopsy elicited either normal liver (n = 1) or chronic persistent hepatitis (CPH) (n = 8) or chronic active hepatitis (CAH) (n = 4). ALAT were chronically elevated in 26 patients; liver histology revealed: 7 CPH, 19 CAH including 12 cases with bridging fibrosis. No deleterious effect of azathioprine on liver histology was found. Lastly, four patients were co-infected with HBV: all had elevated ALAT; liver biopsy always revealed severe chronic active hepatitis. Post-transplantation hepatitis C is a worrying problem. Liver enzymes are not correlated with the severity of histological disorders, which are frequent. Interferon-alpha therapy should be proposed to HCV+ patients before renal transplantation.

Henoch-Schönlein purpura and membranoproliferative-like glomerulonephritis.

A 17-year-old man presented Henoch-Schönlein purpura with renal impairment, nephrotic syndrome needing transitory hemodialysis and hematuria. By light microscopy, the renal biopsy revealed membranoproliferative-like lesion associated with massive subendothelial deposits, some subepithelial deposits, hyalin thrombi and intracapillary neutrophils. By immunofluorescence, intense nodular and segmental deposits of IgG, IgM, IgA, C3, fibrinogen and C1q were found to be present in the intracapillary area and the mesangium. By electron microscopy, large subendothelial and rare subepithelial deposits were observed. A skin biopsy demonstrated leukocytoclastic skin vasculitis with IgA deposits in the arterial walls. Treatment with corticosteroids resulted in return renal to normal renal function but persistent proteinuria and hematuria. A second renal biopsy, performed after 2 months, showed a marked decrease in lesions and deposits. Fifteen months later, the patient presented normal serum creatinine level but proteinuria and hematuria persisted. At this time, a third renal biopsy was performed and showed segmental mesangial sclerosis and the decrease of disappearance of deposits. Two years after the first hospitalization, no abnormal serum creatinine or urinalysis were present. This report describes a detailed study of a case presented with Henoch-Schönlein purpura and morphologic features consistent with membranoproliferative-like lesion, who recovered normal renal function and urinalysis; repeat biopsies performed at intervals of 2 months and 1 year confirmed the disappearance of mesangial proliferation, double contours and deposits.

[Nephro-angiosclerosis in the graft: impact on graft survival. Study of 33 cases]. / Néphroangiosclérose du transplant: influence sur la survie du greffon. Etude de 33 cas.

UNLABELLED: When early kidney transplant biopsies showed benign hypertensive nephrosclerosis, i.e. hyalin arteriosclerosis and/or interlobular arteries intimal thickening, they are thought to be of donor origin. Between 1987 and 1992, 439 cadaveric renal transplantations have been performed in our department: amongst them 97, i.e. 22% patients underwent a graft biopsy before the end of the first post transplant month (13 +/- 9.5 days). To ascertain if findings of early renal biopsy was predictive of eventual clinical outcome we analyzed renal function and blood pressure (BP) in the short and mid term. Nephrosclerosis lesions were found in 33 cases (group I) and were absent in the remaining 64 cases (group II). The 2 groups were not statistically different according to the time on dialysis, the recipient's age, the HLA matching, the cold ischemia time. The only statistically significant difference was the donor's age: 39.1 +/- 7 years in group I vs 26.9 +/- 8 years in group II (p = 0.0001). Delayed graft function was not different in the 2 groups (13 +/- 9 days group I vs 11 +/- 6 days group II). On the other hand, 30% of group I, patients required hemodialysis (9.8% in group II; p < 0.005). The incidence in graft rejection episodes was similar in both groups (50%) as well as surgical complications. Renal function was assessed by creatinine clearance at 1 and 2 years and at last follow-up visit (mean follow-up: 50.5 +/- 44 months in group I and 46.9 +/- 24 months in group II; p = Ns): it was similar in both groups (see table). The prevalence of hypertension (HTA) was significantly higher in group I than in group II at two years and last follow-up (*: p < 0.005). [table: see text] CONCLUSIONS: The age of donor is of importance in determining nephrosclerosis of the graft observed on early biopsies. Donor-related nephrosclerosis is a risk factor for the recipient of developing HTA without impairment of graft function in the mid term. In the context of early nephrosclerosis, the occurrence of acute rejection episode(s) is detrimental for the graft function.

Renal involvement in POEMS syndrome.

We describe a patient with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) who was found to have renal involvement with particular renal pathological findings. So far, 17 other cases, most of them from Japan, of POEMS syndrome with renal involvement, have been published. Clinical features are variable: acute renal failure with anasarca or moderate chronic renal insufficiency with mild proteinuria. This latter presentation often passes unnoticed. There is no severe hypertension, no microangiopathic hemolytic anemia. Renal biopsy shows prominent glomerular changes which are unusual and distinct from membranoproliferative glomerulonephritis (MPGN) and from glomerular thrombotic microangiopathy (TMA). Mesangial proliferation and thickening of the capillary wall with double contour on light microscopy suggest an MPGN. By immunofluorescent microscopy, no immunoglobulins or complement deposits were found. The occurrence of mesangiolytic lesions has led to the term of "mesangiolytic glomerulonephritis". The presence, on electron microscopy, of lucent subendothelial spaces could indicate TMA. But there are neither thrombi nor arteriolar changes. We are inclined to consider that the microangiopathic lesions are due to chronic injury of glomerular endothelial cells, exacerbated at outbreaks of the disease. Increased production of IL 6 could support the efficacy of corticosteroid therapy, particularly in acute clinical situations.

Renal functional reserve in calcium channel blocker-treated hypertensive recipients of kidney transplant.

Renal functional reserve during infusion of an amino acid solution was examined in 12 cyclosporin-treated kidney recipients at 1 (T1) and 8 months (T2) after transplantation. Patients were retrospectively divided into six normotensive (NT) and six hypertensive recipients (HT) maintained on monotherapy with a calcium channel blocker. Baseline glomerular filtration rates (GFR) were similar in NT and HT at T1 and T2. Renal functional reserve was identical in NT and HT at T1 (15 +/- 7 vs 18 +/- 13 ml/min/1.73 m2) but significantly greater in HT at T2 (11 +/- 5 vs 23 +/- 10 ml/min/1.73 m2; P < 0.05). At T2, baseline proximal tubule outflow (lithium clearance) was greater in HT (26 +/- 8 vs 16 +/- 3 ml/min/1.73 m2; P < 0.05), whereas fractional proximal reabsorption was less (54 +/- 11% vs 67 +/- 5%; P < 0.05). These results indicate that: (i) hypertensive recipients on calcium channel blocker therapy do not exhibit permanent glomerular hyperfiltration until 8 months after transplantation, and have a reduced proximal reabsorption; (ii) measurement of amino acid-stimulated GFR and renal functional reserve is a more sensitive method than that of baseline GFR for evaluating renal function and the effects of therapy in kidney recipients.