Long-term outcome according to renal histological lesions in 118 patients with monoclonal gammopathies.

BACKGROUND: The prognosis of monoclonal gammopathies with multiple myeloma and renal involvement is poor, and the indication for renal replacement therapy is controversial. Few studies address the value of renal histology for determining prognosis according to initial pathology findings. METHODS: We studied the course of 118 patients with multiple myeloma according to renal biopsy lesions. The monoclonal component was identified and quantified in serum and urine. Tumor cell mass was classified as stage 1, 2 or 3, according to Durie and Salmon. End-points were death, or survival on dialysis, or serum creatinine level at last examination. RESULTS: Renal biopsy showed myeloma kidney in 48 cases (41%), AL-amyloidosis in 35 (30%), light chain deposit disease in 22 (19%), chronic tubulointerstitial nephritis in 12 (10%) and cryoglobulinaemic kidney with multiple myeloma in 1. Maintenance haemodialysis was required in 46 patients (39%), earlier (P<0.0001) in myeloma kidney (mean: 3 months after diagnosis) than in AL-amyloidosis (mean: 15 months) and light chain deposit disease (mean: 18 months). Median survival was 12 months in myeloma kidney, 24 months in AL-amyloidosis and 48 months in light chain deposit disease. Dialysis increased survival in light chain deposit disease, in contrast with myeloma kidney and AL-amyloidosis patients whose survival was shorter when dialysed. The main cause of death during first year of dialysis was cardiac involvement in AL-amyloidosis, and sepsis or cardiac insufficiency in myeloma kidney. There was a trend to increased survival with multidrug chemotherapy which seemed to slow progression to end-stage renal failure. At last follow-up (median: 12 months, range 1-297), 65 (55%) patients had died. By multivariate analysis, independent predictors of survival were: age < 70, serum creatinine < or = 300 micromol/l, and serum calcium < or = 2.5 mmol/l. CONCLUSIONS: Initial renal biopsy helps predict prognosis in patients with multiple myeloma and renal involvement. Maintenance haemodialysis is a reasonable indication in light chain deposit disease and AL-amyloidosis, especially in patients aged < 70. Multidrug therapy tends to prolong survival and slow progression to end-stage renal disease.

[Epidemiology and prognosis of acute renal insufficiency in 1997. Recent data]. / Epidémiologie et pronostic de l'insuffisance rénale aiguë en 1997. Données récentes.

In an unselected population, the annual incidence of acute renal failure (ARF) seems close to 200 patients per million inhabitants. In elderly patients, this incidence is five times higher than that of younger patients. Mortality is particularly high in intensive care units and doubles if ARF develops after rather than before admission. Death is mainly due to hypovolemic and septic shock, and to cardiovascular diseases. An increasing number of deaths is related to therapeutic limitation. In many cases, ARF can be prevented, e.g. by correcting any sodium deficit and hypovolemia before a surgical procedure, and by considering the true GFR of a given patient before prescribing a potentially nephrotoxic drug, especially in older patients. A poor previous health status, hospitalization prior to admission, and ARF occurring after admission are important predictive factors of mortality, as well as any acute organ dysfunction. Second generation severity scores seem to have a better performance than older ones. The use of continuous hemodialysis and hemofiltration is increasing in ARF patients, but it is not proven that mortality is thereby reduced. A beneficial effect of biocompatible membranes is not clearly demonstrated in these patients. Later, most ARF patients recover a normal, or nearly normal, renal function. Recovery is delayed in older patients and in those whose oliguric period is prolonged. Lastly, the high cost of therapy in ARF justifies the use of all currently preventive measures in patients at risk.

Enalapril plus frusemide MAG3 scintigraphy in hypertensive patients with atherosclerosis and moderate renal insufficiency.

We performed a retrospective study on 26 patients with moderate renal failure (mean GFR = 51 +/- 21 ml min-1 1.73 m-2), hypertension and atherosclerosis. Apart from three patients who had completely normal renal Doppler ultrasonography, all patients underwent renal angiography. Three groups of kidneys with different atherosclerotic renal artery involvement were identified: Group 1, 24 kidneys with no renal artery stenosis (RAS); Group 2, 18 kidneys with mild (> 25% and < 50% diameter) RAS; and Group 3, 10 kidneys with moderate (> 50% diameter) RAS. We used a two-day protocol with frusemide plus enalapril 99Tcm-MAG3 scintigraphy. The mean parenchymal transit time (MPTT), time to the maximum activity (time to peak) of the renal curve (Tmax), residual activity and split renal uptake were evaluated. The measured parameters did not differ before and after enalapril in Group 1 or in Group 2. In Group 3, MPTT and residual activity differed significantly (P < 0.025) before and after enalapril. The Tmax before and after enalapril, MPTT before and after enalapril and residual activity after enalapril differed significantly (P < 0.05) between Groups 1 and 3 and between Groups 2 and 3. Threshold values were obtained to maximize diagnostic accuracy. The Tmax, MPTT and residual activity after enalapril gave satisfactory results, and MPTT performed best with a 75% positive predictive value and a 98% negative predictive value for the diagnosis of renal artery stenosis. We conclude that MPTT, measured after enalapril administration, is a useful parameter to detect renal artery stenosis in patients with hypertension, atherosclerosis and moderate renal insufficiency.

Prognostic factors in acute renal failure due to sepsis. Results of a prospective multicentre study. The French Study Group on Acute Renal Failure.

BACKGROUND: Sepsis is a major cause of acute renal failure in hospital patients, but its incidence and the associated prognostic factors have rarely been assessed prospectively by multivariate analysis. METHODS: We conducted a prospective 6-month study in 20 multidisciplinary intensive care units to assess the prognosis of patients hospitalized with acute renal failure due to sepsis. Sepsis syndrome and septic shock were defined according to the criteria of the Society of Critical Care Medicine Consensus Conference. Severity scoring indexes (SAPS, APACHE II, and organ system failure (OSF)) were measured on ICU admission and on inclusion. The end-point was hospital mortality. RESULTS: Acute renal failure had a septic origin in 157 patients (Group 1), comprising 68 with septic shock and 89 with sepsis syndrome, and did not result from infection in 188 patients (Group 2). Patients with septic acute renal failure were older (mean age: 62.2 versus 57.9 years, P<0.02) and had on inclusion a higher SAPS (19.3 versus 16.1, P<0.001), APACHE II (29.6 versus 24.3, P<0.001), and OSF (2.07 versus 1.52, P<0.001) than patients with non-septic acute renal failure. They had a higher need for mechanical ventilation (69.1% versus 47.3%, P<0.001), and acute renal failure was more often delayed during the ICU stay than was present on admission (47.7% versus 32.4% respectively, P<0.005). Hospital mortality was higher in patients with septic acute renal failure (74.5%) than in those whose renal failure did not result from sepsis (45.2%, P<0.001). Mortality was influenced by the presence of a septic shock (79.4%) or of a sepsis syndrome on inclusion (70.8%). Using a stepwise logistic regression model, sepsis was an independent predictor of hospital mortality (OR, 2.51; 95% CI, 1.44-4.39) as well as a delayed occurrence of acute renal failure, oliguria, an altered previous health status hospitalization prior to ICU, need for mechanical ventilation, age and severity scoring indexes on inclusion. In total patients, mortality was higher in dialyzed than in non-dialyzed patients (P<0.001), and in those treated by continuous compared to intermittent techniques (P<0.01). Patients dialyzed with biocompatible membranes had a lower mortality than those treated with cellulose membranes (P<0.005). CONCLUSIONS: Patients with acute renal failure due to sepsis have a worse prognosis than those with non-septic acute renal failure. Sepsis and the above-defined predictive factors are to be considered in studies on prognosis of ARF patients. Our results suggest that the use of biocompatible membranes may reduce significantly mortality in these patients.

Acute renal failure in intensive care units--causes, outcome, and prognostic factors of hospital mortality; a prospective, multicenter study. French Study Group on Acute Renal Failure.

OBJECTIVE: To assess the causes, the prognostic factors, and the outcome of patients with severe acute renal failure. DESIGN: Prospective, multicenter study. SETTING: Twenty French multidisciplinary intensive care units (ICUs). PATIENTS: All patients with severe acute renal failure were prospectively enrolled in the study for a 6-month period. Severe acute renal failure was defined by the following criteria: a) a serum creatinine concentration of > or = 3.5 mg/dL ( > or = 310 mumol/L) and/or a blood urea nitrogen concentration of > or = 100 mg/dL ( > or = 36 mmol/L); or b) an increase in blood urea nitrogen or serum creatinine concentration, such that the concentration is 100% above the baseline value in patients with previous chronic renal insufficiency (serum creatinine concentration of > 1.8 mg/dL [ > 150 mumol/L]), excluding those patients with a basal serum creatinine concentration of > 3.4 mg/dL ( > 300 mumol/L). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Age, sex, previous health status and preexisting organ dysfunction, and type and origin of acute renal failure were recorded. The Simplified Acute Physiology Score, the Acute Physiology and Chronic Health Evaluation (APACHE II) score, and the number of Organ System Failures were calculated on ICU day 1 and at the time of inclusion in the study. Prognostic factors were determined by univariate methods and stepwise logistic regression analysis. There were 360 patients in the study; 217 patients were admitted to the study at the time of ICU admission and 143 patients were admitted to the study after ICU admission. Only 41% of these patients were in good health 3 months before ICU entry. The reason for admission was medical in 78% of cases. The type of acute renal failure was prerenal (n = 16), renal (n = 282), or postrenal (n = 17). Renal replacement therapy was used in 174 patients. Two hundred ten (58%) patients died during the hospital stay. Using stepwide logistic regression, seven variables were predictive of death. These variables were advanced age, altered previous health status, hospitalization before ICU admission, delayed occurrence of acute renal failure, sepsis, oliguria, and severity of illness as assessed at the time of study inclusion by Simplified Acute Physiology Score, APACHE II, or Organ System Failure. CONCLUSIONS: The hospital mortality rate of patients with severe acute renal failure in patients requiring intensive care remains high. In order to compare patient groups in further trials concerning acute renal failure, recorded characteristics of the population should include age, previous health status, disease characteristics (initial or delayed acute renal failure, oliguria, sepsis), and the severity of the illness as assessed by physiologic scoring systems recorded at the time of study inclusion.

[Acute kidney failure induced by drugs or contrast media]. / Insuffisances rénales aiguës provoquées par des médicaments ou des produits de contraste.

The incidence of in-hospital acute renal failure (ARF) due to drugs is estimated at 20% of all patients hospitalized for ARF. According to recent surveys, analgesic and non-steroidal anti-inflammatory drugs are now more frequently involved than antibiotics. The incidence of ARF in patients taking angiotensin-converting enzyme inhibitors is increasing. More than half of the patients have a non-oliguric course. Acute tubular necrosis and acute interstitial nephritis are found in most biopsied cases. The mortality rate ranges between 6% and 12%. Most patients recover but 15% to 20% have some degree of residual renal impairment, particularly older and oliguric patients, those with previous chronic renal insufficiency and whose ARF period is prolonged. The long-term renal effects of NSAIDs is a concern. ARF due to drugs is a preventable disease since two-thirds of patients received inappropriately high or prolonged doses of the offending drug and or were patients at risk to develop ARF.

Interstitial nephritis, the nephrotic syndrome, and chronic renal failure secondary to nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) may induce a variety of acute and chronic renal lesions. Acute interstitial nephritis can follow the use of nearly all NSAIDs, but the number of reported cases is low. Most of these patients are elderly and develop a nephrotic syndrome with acute renal failure while taking NSAID for months. Renal biopsy shows acute tubulo-interstitial lesions with minimal changes in the glomeruli. The renal signs usually improve after discontinuing the drug, with or without steroid therapy, but chronic renal insufficiency or even end-stage renal disease (ESRD) are possible hazards. There is evidence that interstitial nephritis results mainly from a delayed hypersensitivity response to NSAID, and nephrotic syndrome results from changes in glomerular permeability mediated by prostaglandins and other hormones. Nephrotic syndrome without interstitial nephritis may occur, as well as immune-complex glomerulopathy, in a small subset of patients receiving NSAIDs. Patients taking NSAID for months or years may develop papillary necrosis, chronic interstitial nephritis, or even ESRD. Case-control studies suggest that patients at risk are older men who suffer from chronic heart disease and renal hypoperfusion. Impaired medullary circulation and direct toxicity due to a drug metabolite seem to play a critical role in inducing interstitial fibrosis, which can be facilitated by a sustained production of some growth factors and cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of severity scoring systems in ICUs--translation, conversion and definition ambiguities as a source of inter-observer variability in Apache II, SAPS and OSF.

OBJECTIVE: To explore translation, conversion and definition ambiguities, when using severity scoring systems in patients admitted to intensive care units (ICUs). DESIGN: A prospective study of the prognosis of acute renal failure in ICUs. SETTING: The study was conducted in 20 French ICUs. PATIENTS: 360 patients presenting with severe acute renal failure were studied during their ICU stay. MEASUREMENTS AND RESULTS: The inter-observer variability of Apache II (acute physiology and chronic health evaluation), SAPS (simplified acute physiology score), and OSF (organ-system failure) was considered. For Apache II, we explored the uncertainty of measurements arising from conversion into SI units, the rounding procedures used for the non-inclusive intervals defined for quantitative parameters such as age, mean arterial pressure (MAP) or serum creatinine, the absence of definition of acute renal failure (ARF) and its consequence on doubling serum creatinine values, and the absence of guidelines in the case of spontaneous ventilation when arterial blood gases (ABG) and forced inspiratory oxygen (FIO2) were not measured. The resulting variability was evaluated, calculating the lowest and the highest value of the scoring system for each patient. The mean difference by patient was greater than 1.5 (p < 0.0001). Other examples were presented and discussed for SAPS and OSF. CONCLUSIONS: Translation, conversion and definition ambiguities are a source of inter-observer variability and increase the risk of classification and/or selection biases. This gives rise to particular concern in the design and analysis of multicenter trials of meta-analysis, and improvement of these scoring systems should be envisaged in the future.

The current spectrum of infectious glomerulonephritis. Experience with 76 patients and review of the literature.

To identify the demographic, clinical, and pathologic features and the prognosis of renal disease in a series of patients with infectious or postinfectious proliferative glomerulonephritis (GN), data were collected from records of 76 adult patients admitted from 1976 to 1993 to 2 neighboring suburban hospital nephrology units, whose catchment population consists of patients living in a suburban borough of Paris with a below-average socioeconomic status. Thirty-four patients (45%) were alcoholics, diabetics, or intravenous illicit-drug users. Sixty-six patients presented with acute nephritic and/or nephrotic syndrome. Acute renal failure was present in 56 (76%) and required dialysis in 14. The diagnostic workup comprised at least 1 renal biopsy in each case. The patient's background, site of infection, clinical course, laboratory variables, and, when available, bacteriologic findings were analyzed in each case to interpret the evolution of the disease. Initial renal biopsy disclosed endocapillary GN in 44 patients, crescentic GN in 26, and membranoproliferative GN in 6. Ten patients had endocarditis. Staphylococci and Gram-negative strains, not streptococci, were the most common bacteria identified. The origin of sepsis was mainly the oropharynx (21), the skin (19) and the lung (14); 19 cases involved multiple sites of infection. Eight patients died (11%), and 20 (26%) recovered renal function, but GN followed a chronic course in 38 (50%), rapidly requiring maintenance dialysis in 6. Poor prognostic factors included age over 50 years, purpura, endocarditis, and glomerular extracapillary proliferation. Twenty-six patients underwent repeat renal biopsy 1 month to 11 years after the initial presentation. The main finding, irrespective of the interval since the first biopsy, was that ongoing or new iatrogenic infection acquired during hospitalization was almost invariably acquired during hospitalization was almost invariably associated with developing glomerular proliferative changes. This study shows that infectious proliferative GN remains common, but that its epidemiology has changed from what was observed until 2 decades ago. The responsible bacteria, when identified, now comprise a majority of staphylococci and Gram-negative strains, in contrast to the streptococci which predominated 3 decades ago. Infectious GN affects with increasing frequency patients with an underlying condition responsible for immunosuppression, especially alcoholism, even in the absence of cirrhosis. Destructive glomerular proliferation persists, especially but not exclusively until infection has been eradicated, and despite rescue treatment with corticosteroids and/or cytostatic drugs. Thus, the prognosis is poor, and infectious GN often ends in renal death. Infection continues in this decade to represent a frequent and probably often overlooked cause of end-stage renal failure.(ABSTRACT TRUNCATED AT 400 WORDS)

[Epidemiology and prognosis of acute renal insufficiency]. / Epidémiologie et pronostic de l'insuffisance rénale aiguë.

The annual incidence of acute renal failure (ARF) in the general population seems close to 150 per million inhabitants. For the past 20 years, there has been an increase in ARF of medical origin and a simultaneous decrease in surgical, traumatic and obstetrical ARF. Drug-induced ARF accounts for 20% of total cases. Factors of poor prognosis include a poor previous health status, the presence of oliguria, cardiac or respiratory insufficiency, sepsis, coma, a need for mechanical ventilation and, most importantly, the number of failing organs. The three main severity scoring systems used are SAPS, APACHE II and OSF. The predictive value of these scoring systems seems acceptable provided the data are collected when ARF is diagnosed and not on the patients' admission. After years, the overall survival rate does not exceed 30% to 50%. Full renal recovery is observed in 1/3 to 2/3 of surviving patients and varies according to the type of nephropathy. The social and financial consequences of these results emphasize the importance of preventing ARF, especially in its iatrogenic form.

[Cardiac manifestations of phospholipid antibody syndrome. Study of 2 cases]. / Les manifestations cardiaques du syndrome des anticorps antiphospholipides. Etude de deux observations.

Cardiac manifestations of phospholipid antibody syndrome may include mitral and/or aortic valve disease, pseudo-infectious endocarditis, thrombi of the right atrium, myocardial infection, pulmonary artery hypertension and cardiomyopathy with global or segmental left ventricular dysfunction. The authors report two patients showing evidence simultaneously of a circulating anticoagulant, dissociated syphilis serology and cardiolipin antibodies at a very high level. They had the majority of cardiac complications described in phospholipid antibody syndrome. Both also had renal involvement and one of them had recurrent venous thromboses and a cerebrovascular accident. Prolonged corticosteroid treatment, combined with anticoagulants in one patient, was accompanied by stability of lesions with follow-up of five years and ten months respectively.

[Rapidly progressive glomerulonephritis of infectious origin]. / Glomérulonéphrites rapidement progressives d'origine infectieuse.

Among 64 patients who presented with glomerulonephritis of infectious origin, 17 cases (26%) of crescentic glomerulonephritis were studied retrospectively. Five patients had bacterial endocarditis and the identified primary infections were cutaneous or oropharyngeal. At the time of diagnosis, 15 patients had acute nephritic syndrome, 3 were anuric and only 2 had normal renal function. Despite symptomatic treatment, the prognosis in these patients was poor: 5 died of infectious disease, 3 are definitively on dialysis and 7 suffer from chronic renal failure. Initiation of immunosuppressive regimens prior to the development or irreversible renal lesions could possibly improve renal prognosis, but entail the risk of life threatening infections in such patients.