Recurrence rates of urinary calculi according to stone composition and morphology.

Few studies have examined the relative risk of recurrence of different stone types. The object of the present study was to evaluate the tendency for stone recurrence as a function of major mineral composition of the stones and morphological characteristics of the stones. This study was carried out using 38,274 stones for which we had data available to specify if the stone was from the first or a subsequent urinary stone episode. Stones were analyzed for morphology by stereomicroscope and for composition by infrared spectroscopy. Overall, 42.7% of stones were from patients who had had a previous stone event, with these being more frequent in men (44.4%) than in women (38.9%, p < 0.0001). Age of first stone occurrence was lowest for dihydroxyadenine (15.7 ± 16.6 years) and highest for anhydrous uric acid (62.5 ± 14.9 years), with the average age of first stones of calcium oxalate falling in the middle (40.7 ± 14.6 years for calcium oxalate dihydrate, and 48.4 ± 15.1 years for calcium oxalate monohydrate, COM). By composition alone, COM was among the least recurrent of stones, with only 38.0% of COM stones coming from patients who had had a previous episode; however, when the different morphological types of COM were considered, type Ic-which displays a light color, budding surface and unorganized section-had a significantly greater rate of recurrence, at 82.4% (p < 0.0001), than did other morphologies of COM. Similarly, for stones composed of apatite, morphological type IVa2-a unique form with cracks visible beneath a glossy surface-had a higher rate of recurrence than other apatite morphologies (78.8 vs. 39-42%, p < 0.0001). Stone mineral type alone is insufficient for identifying the potential of recurrence of the stones. Instead, the addition of stone morphology may allow the diagnosis of highly recurrent stones, even among common mineral types (e.g., COM) that in general are less recurrent.

Drug-Induced Kidney Stones and Crystalline Nephropathy: Pathophysiology, Prevention and Treatment.

Drug-induced calculi represent 1-2% of all renal calculi. The drugs reported to produce calculi may be divided into two groups. The first one includes poorly soluble drugs with high urine excretion that favour crystallisation in the urine. Among them, drugs used for the treatment of patients with human immunodeficiency, namely atazanavir and other protease inhibitors, and sulphadiazine used for the treatment of cerebral toxoplasmosis, are the most frequent causes. Besides these drugs, about 20 other molecules may induce nephrolithiasis, such as ceftriaxone or ephedrine-containing preparations in subjects receiving high doses or long-term treatment. Calculi analysis by physical methods including infrared spectroscopy or X-ray diffraction is needed to demonstrate the presence of the drug or its metabolites within the calculi. Some drugs may also provoke heavy intra-tubular crystal precipitation causing acute renal failure. Here, the identification of crystalluria or crystals within the kidney tissue in the case of renal biopsy is of major diagnostic value. The second group includes drugs that provoke the formation of urinary calculi as a consequence of their metabolic effects on urinary pH and/or the excretion of calcium, phosphate, oxalate, citrate, uric acid or other purines. Among such metabolically induced calculi are those formed in patients taking uncontrolled calcium/vitamin D supplements, or being treated with carbonic anhydrase inhibitors such as acetazolamide or topiramate. Here, diagnosis relies on a careful clinical inquiry to differentiate between common calculi and metabolically induced calculi, of which the incidence is probably underestimated. Specific patient-dependent risk factors also exist in relation to urine pH, volume of diuresis and other factors, thus providing a basis for preventive or curative measures against stone formation.

Validation of Surrogates of Urine Osmolality in Population Studies.

BACKGROUND: The importance of vasopressin and/or urine concentration in various kidney, cardiovascular, and metabolic diseases has been emphasized recently. Due to technical constraints, urine osmolality (Uosm), a direct reflect of urinary concentrating activity, is rarely measured in epidemiologic studies. METHODS: We analyzed 2 possible surrogates of Uosm in 4 large population-based cohorts (total n = 4,247) and in patients with chronic kidney disease (CKD, n = 146). An estimated Uosm (eUosm) based on the concentrations of sodium, potassium, and urea, and a urine concentrating index (UCI) based on the ratio of creatinine concentrations in urine and plasma were compared to the measured Uosm (mUosm). RESULTS: eUosm is an excellent surrogate of mUosm, with a highly significant linear relationship and values within 5% of mUosm (r = 0.99 or 0.98 in each population cohort). Bland-Altman plots show a good agreement between eUosm and mUosm with mean differences between the 2 variables within ±24 mmol/L. This was verified in men and women, in day and night urine samples, and in CKD patients. The relationship of UCI with mUosm is also significant but is not linear and exhibits more dispersed values. Moreover, the latter index is no longer representative of mUosm in patients with CKD as it declines much more quickly with declining glomerular filtration rate than mUosm. CONCLUSION: The eUosm is a valid marker of urine concentration in population-based and CKD cohorts. The UCI can provide an estimate of urine concentration when no other measurement is available, but should be used only in subjects with normal renal function.

Comparison between copeptin and vasopressin in a population from the community and in people with chronic kidney disease.

CONTEXT: Vasopressin plays a central role in water homeostasis but it has also been recognized to be associated with adverse effects in several chronic diseases. Recently, copeptin has been increasingly used as a surrogate for vasopressin, as they are co-secreted, and copeptin is easier to measure. However, the relationship between plasma concentrations of copeptin (P(cop)) and vasopressin (P(vp)) has only been studied in relatively small numbers of selected people. OBJECTIVE: This study sought to evaluate the relationship between P(vp) and P(cop) in a community-based population and in people with chronic kidney disease (CKD). DESIGN, SETTING, AND PARTICIPANTS: P(vp), P(cop), and urinary osmolarity (Uosm) were compared in 500 participants of the DESIR study, and in 83 ambulatory people with CKD. RESULTS: Median [interquartile range] of P(cop) and P(vp) in the DESIR study were 4.13 [3.58] pmol/L and 0.92 [1.93] pmol/L, respectively. Log-transformed P(cop) and P(vp) concentrations correlated significantly and positively (r = 0.686, P < .001) and they correlated inversely with estimated U(osm) (P < .001). Copeptin explained only approximately half of the vasopressin variation. In CKD, P(cop) and P(vp) both increased with decreasing estimated glomerular filtration rate (eGFR), but P(cop) increased much faster than P(vp). The P(cop)/P(vp) ratios in the lower and upper quintile groups of eGFR were 14.3 [18.3] and 5.3 [4.5], P < .001, respectively. CONCLUSIONS: This study in a normal population, the largest ever with measurements of both peptides, shows that copeptin and vasopressin concentrations correlated well. But their relationship is distorted in CKD, suggesting that the peptide clearances differ when the renal function is impaired.

The pathogenesis of Randall's plaque: a papilla cartography of Ca compounds through an ex vivo investigation based on XANES spectroscopy.

At the surface of attached kidney stones, a particular deposit termed Randall's plaque (RP) serves as a nucleus. This structural particularity as well as other major public health problems such as diabetes type-2 may explain the dramatic increase in urolithiasis now affecting up to 20% of the population in the industrialized countries. Regarding the chemical composition, even if other phosphate phases such as whitlockite or brushite can be found as minor components (less than 5%), calcium phosphate apatite as well as amorphous carbonated calcium phosphate (ACCP) are the major components of most RPs. Through X-ray absorption spectroscopy performed at the Ca K-absorption edge, a technique specific to synchrotron radiation, the presence and crystallinity of the Ca phosphate phases present in RP were determined ex vivo. The sensitivity of the technique was used as well as the fact that the measurements can be performed directly on the papilla. The sample was stored in formol. Moreover, a first mapping of the chemical phase from the top of the papilla to the deep medulla is obtained. Direct structural evidence of the presence of ACCP as a major constituent is given for the first time. This set of data, coherent with previous studies, shows that this chemical phase can be considered as one precursor in the genesis of RP.

Stone formation and pregnancy: pathophysiological insights gained from morphoconstitutional stone analysis.

PURPOSE: We examined whether stone composition in pregnant women reflects peculiar pathophysiological conditions. MATERIALS AND METHODS: We analyzed in detail the composition of stones from 244 pregnant women 17 to 44 years old and from 5,712 nonpregnant women in the same age range, as recorded between January 1991 and December 2007. Clinical features were also recorded. All stones were analyzed by morphological examination coupled with infrared spectroscopy. The 2 patient groups were compared by clinical and biochemical characteristics. RESULTS: Stone episodes in pregnant women manifested mainly in trimesters 2 and 3 (39% and 46%, respectively). Spontaneous passage was noted in 81% of pregnant vs 47% of nonpregnant women (p <0.0001). Calcium phosphate, mainly in the form of carbapatite, was the main stone component in 65.6% of pregnant vs 31.4% of nonpregnant women (p <0.0001). Octacalcium phosphate pentahydrate, a transition phase in calcium phosphate stone formation, was found in a 5-fold higher proportion in carbapatite stones in pregnant than in nonpregnant women, a finding also suggesting recent stone formation during pregnancy. CONCLUSIONS: The composition of stones manifesting during pregnancy clearly differs from that of stones formed in nonpregnant women of childbearing age, suggesting a different pathophysiology specific to the pregnant state. In view of the pH dependency of calcium phosphate stones factors that increase the physiological elevation in maternal urinary calcium excretion and pH are likely to have a role in the preferential formation of calcium phosphate stones during pregnancy.

Revisiting the localisation of Zn(2+) cations sorbed on pathological apatite calcifications made through X-ray absorption spectroscopy.

The role of oligo-elements such as Zn in the genesis of pathological calcifications is widely debated in the literature. An essential element of discussion is given by their localisation either at the surface or within the Ca apatite crystalline network. To determine the localisation, X-ray absorption experiments have been performed at SOLEIL. The Exafs results suggest that Zn atoms, present in the Zn(2+) form, are bound to about 4 O atoms at a distance of 2.00 A, while the interatomic distance R(CaO) ranges between 2.35 A and 2.71 A. Taking into account the content of Zn (around 1000 ppm) and the difference in ionic radius between Zn(2+) (0.074 nm) and Ca(2+) (0.099 nm), a significant longer interatomic distance would be expected in the case of Zn replacing Ca within the apatite crystalline network. We thus conclude that Zn atoms are localised at the surface and not in the apatite nanocrystal structure. Such structural result has essential biological implications for at least two reasons. Some oligoelements have a marked effect on the transformation of chemical phases, and may modify the morphology of crystals. These are both major issues because, in the case of kidney stones, the medical treatment depends strongly on the precise chemical phase and on the morphology of the biological entities at both macroscopic and mesoscopic scales.

Relationships between carbonation rate of carbapatite and morphologic characteristics of calcium phosphate stones and etiology.

OBJECTIVES: To examine the significance of the carbonation rate (CR) in carbonated apatite (carbapatite [CA]) stones and its relationships with the morphologic characteristics of CA and etiology. CA stones without struvite can result from metabolic disorders or urinary tract infection, but the latter etiology is still debated. Infection stones caused by urea-splitting bacteria are made of CA admixed with struvite and exhibit a high CO(3)(2-)/PO(4)(3-) ratio (CR). However, little is known as to the significance of the CR of CA in the absence of struvite in idiopathic calcium phosphate stones. METHODS: We studied 39 urinary calculi mainly composed of CA without struvite. Of the 39 patients, 13 had a past or present history of urinary tract infection, 24 had hypercalciuria, and 2 had medullary sponge kidney. The stones were examined by Fourier transform infrared spectroscopy and scanning electron microscopy. The presence of amorphous carbonated calcium phosphate or whitlockite was also considered. RESULTS: The CR of CA was 14% +/- 9%. On scanning electron microscopy, the CA particles appeared as spherules of 4.5 +/- 3.0 mum in diameter and were significantly larger in females than in males. In 16 cases, scanning electron microscopy showed bacterial imprints. In these calculi, the CR was significantly greater (22% +/- 7%) than in those without a visible bacterial imprint (8% +/- 5%, P < .0001). Amorphous carbonated calcium phosphate was found in 15 of 16 stones (93.8%) with imprints and in none of the 23 stones without imprints (P < .0001). CONCLUSIONS: A close relationship was observed between the presence of bacterial imprints, indicative of past or current urinary tract infection, and both the presence of amorphous carbonated calcium phosphate (or whitlockite) and a high CR of CA.

Nonprogressive kidney dysfunction and outcomes in older adults with chronic kidney disease.

OBJECTIVES: To determine whether a subgroup of patients with severe but nonprogressive renal dysfunction exist and to characterize this subgroup. DESIGN: Retrospective longitudinal monocentric cohort study. SETTING: Nephrology clinic for chronic kidney disease (CKD). PARTICIPANTS: Between January 1998 and December 2004, 177 consecutive patients aged 80 and older were referred for the first time to nephrology for CKD. MEASUREMENTS: The characteristics of patients with nonprogressive or progressive CKD (estimated glomerular filtration rate (eGFR) decline of < and > or =1 mL/min per 1.73 m(2) per year, respectively) were observed and analyzed, and their risk of dying or requiring dialysis was determined. After exclusion of subjects requiring immediate dialysis or followed up for less than 6 months, 138 patients remained eligible for analysis. RESULTS: In the study cohort (initial mean eGFR 31.8 mL/min per 1.73 m(2), median follow-up 47 months), patients were more likely to require dialysis than to die; 36% of patients had nonprogressive CKD. This characteristic, predicted by low proteinuria, lack of hypertension, and low cardiovascular comorbidity, was the strongest predictor of global survival. In progressors, two independent covariates (eGFR <30 mL/min per 1.73 m(2) and hemoglobin < or =11 g/dL at inclusion) predicted the risk of requiring dialysis. CONCLUSION: More than one-third of subjects aged 80 and older referred to a nephrology center had severe but nonprogressive kidney dysfunction. This subgroup had a lower mortality rate than those with progressive kidney dysfunction. Simple covariates (low proteinuria, lack of hypertension, low cardiovascular comorbidity) predicted nonprogression of CKD. Distant nephrology follow-up of such patients may be sufficient.

Very first tests on SOLEIL regarding the Zn environment in pathological calcifications made of apatite determined by X-ray absorption spectroscopy.

This very first report of an X-ray absorption spectroscopy experiment at Synchrotron SOLEIL is part of a long-term study dedicated to pathological calcifications. Such biological entities composed of various inorganic and/or organic compounds also contain trace elements. In the case of urinary calculi, different papers already published have pointed out that these oligo-elements may promote or inhibit crystal nucleation as well as growth of mineral. Use of this analytical tool specific to synchrotron radiation, allowing the determination of the local environment of oligo-elements and thus their occupation site, contributes to the understanding of the role of trace elements in pathological calcifications.

[Inherited monogenic kidney stone diseases: recent diagnostic and therapeutic advances]. / Lithiases rénales héréditaires monogéniques : récents acquis diagnostiques et thérapeutiques.

Hereditary monogenic kidney stone diseases are rare diseases, since they account for nearly 2% of nephrolithiasis cases in adults and 10% in children. Most of them are severe, because they frequently are associated with nephrocalcinosis and lead to progressive impairment of renal function unless an early and appropriate etiologic treatment is instituted. Unfortunately, treatment is often lacking or started too late since they are often misdiagnosed or overlooked. The present review reports the genotypic and phenotypic characteristics of monogenic nephrolithiases, with special emphasis on the recent advances in the field of diagnosis and therapeutics. Monogenic stone diseases will be classified into three groups according to their mechanism: (1) inborn errors of the metabolism of oxalate (primary hyperoxalurias), uric acid (hereditary hyperuricemias) or other purines (2,8-dihydroxyadeninuria), which, in addition to stone formation, result in crystal deposition in the renal parenchyma; (2) congenital tubulopathies affecting the convoluted proximal tubule (such as Dent's disease, Lowe syndrome or hypophosphatemic rickets), the thick ascending limb of Henlé's loop (such as familial hypomagnesemia and Bartter's syndromes) or the distal past of the nephron (congenital distal tubular acidosis with or without hearing loss), which are frequently associated with nephrocalcinosis, phosphatic stones and extensive tubulointerstitial fibrosis; (3) cystinuria, an isolated defect in tubular reabsorption of cystine and dibasic aminoacids, which results only in the formation of stones but requires a cumbersome treatment. Analysis of stones appears of crucial value for the early diagnosis of these diseases, as in several of them the morphology and composition of stones is specific. In other cases, especially if nephrocalcinosis, phosphatic stones or proteinuria are present, the evaluation of blood and urine chemistry, especially with regard to calcium, phosphate and magnesium, is the key of diagnosis. Search for mutations is now increasingly performed in as much as genetic counselling is important for the detection of heterozygotes in autosomic recessive diseases and of carrier women in X-linked diseases. In conclusion, better awareness to the rare monogenic forms of nephrolithiasis and/or nephrocalcinosis should allow early diagnosis and treatment which are needed to prevent or substantially delay progression of end-stage renal disease. Analysis of every first stone both in children and in adults should never be neglected, in order to early detect unusual forms of nephrolithiasis requiring laboratory evaluation and deep etiologic treatment.

[Difference in urine concentration according to gender and ethnicity: possible involvement in the different susceptibility to various renal and cardiovascular diseases]. / Différence de concentration urinaire selon le sexe ou l'origine ethnique: implications possibles dans la susceptibilité variable à différentes pathologies rénales et cardiovasculaires.

Men and African-Americans are known to be at greater risk of urolithiasis and cardiovascular and renal diseases than women and Caucasians. Previous studies suggest that the antidiuretic effects of vasopressin and/or a greater urine concentration are associated with the rate of progression of these diseases. The present review addresses possible sex and ethnic-related differences in urine volume and osmolality which could participate in this male and black higher predominance. We reanalyzed 24h-urine data collected previously by different investigators for other purposes. In studies concerning healthy subjects (six studies) or patients with chronic kidney disease or Diabetes mellitus (three studies), men excreted a larger osmolar load than women, with a 15 to 30% higher urinary osmolality (or another index of urine concentration based on the urine/plasma creatinine concentration ratio) and a similar 24h urine volume than in women. In two American studies, African-Americans showed a significantly higher urinary concentration than Caucasians and a lower 24h-urine volume. Sex and ethnic differences in thirst threshold, vasopressin level, or other regulatory mediators may contribute to the higher urinary concentration of men and of African Americans. These differences could play a role in the greater susceptibility of these subjects to these pathologies. New prospective studies should take into account the antidiuretic effects of vasopressin as a potential risk factor in the initiation and progression of cardiovascular and renal diseases.

[Encrusted pyelitis: early diagnosis facilitates conservative management]. / Pyélite incrustante: un diagnostic précoce facilite la prise en charge conservatrice.

Diagnosis of encrusted pyelitis in predisposed patients is difficult. The bacteriology laboratory must be specifically asked to perform the appropriate tests. Computed tomography without injection is very important for diagnosis and follow-up. Conservative treatment is essential insofar as possible. Long-term follow-up is also necessary.

Specific changes in plasma concentrations of matrix metalloproteinase-2 and -9, TIMP-1 and TGF-beta1 in patients with distinct types of primary glomerulonephritis.

BACKGROUND: Dysregulated renal expression of matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMP) and TGF-beta1 contribute to the development of tubulo-interstitial fibrosis characteristic of progressive forms of primary glomerulonephritis (GN). There is little information on the circulating levels of these proteins in human GNs. Here, we assessed whether different histopathological GN types could be associated with distinct plasma patterns of MMPs and regulatory proteins. METHODS: Protein levels of MMP-2, MMP-9, TGF-beta1 and TIMP-1 were measured by ELISA in plasma from venous blood of 108 untreated patients with various types of primary GN defined by kidney biopsy, namely IgAN (n=63), membranous GN (MN, n=26), minimal change nephrotic syndrome (MCNS, n=12) and focal and segmental glomerular sclerosis (FSGS, n=7), and were compared with levels in 50 healthy subjects. Plasma samples were assayed for gelatinolytic activity (zymography). RESULTS: Zymography detected the proforms of MMP-2 and MMP-9. Compared with controls, IgAN patients exhibited a significant, parallel decrease in plasma levels of MMP-2, MMP-9 and TGF-beta1. In MN patients, decreased MMP-9 level contrasted with a high MMP-2 level and a normal TGF-beta1 level. In the MCNS/FSGS group, increased MMP-2 level contrasted with unchanged MMP-9 and decreased TGF-beta1 levels. Plasma concentration of TIMP-1 was elevated in all GN groups. There was no correlation between baseline MMP-2/MMP-9/TIMP-1/TGF-beta1 levels and the degree of renal dysfunction or with progression toward ESRD. CONCLUSIONS: Plasma concentrations of MMP-2, MMP-9 and TGF-beta1 significantly differed between the various histopathological types of primary GNs, thus suggesting the involvement of different underlying mechanisms in the regulation of glomerular and tubulointerstitial fibrosis in these renal diseases.

Diabetes and nephrolithiasis.

Type 2 diabetes is associated with an increased risk of nephrolithiasis, specifically in the form of uric acid (UA) nephrolithiasis. Diabetic patients who produce uric stones exhibit a low urine pH, the key factor of UA crystallization. Production of such acidic urine appears to result from the insulin-resistant state characteristic of diabetes mellitus. Insulin resistance is also involved in the pathogenesis of primary UA nephrolithiasis observed in overweight subjects with the metabolic syndrome. Therefore, UA nephrolithiasis should be considered a possible manifestation of insulin resistance, as it already is for hyperuricemia. Occurrence of UA stones in a patient, especially if overweight or hypertensive, should prompt a search for components of the metabolic syndrome in order to implement therapeutic intervention aimed at preventing the development of type 2 diabetes and atherosclerotic complications. Reciprocally, diabetologists should be aware of the risk of UA stones in their patients.

Type 2 diabetes increases the risk for uric acid stones.

An increased prevalence of nephrolithiasis has been reported in patients with diabetes. Because insulin resistance, characteristic of the metabolic syndrome and type 2 diabetes, results in lower urine pH through impaired kidney ammoniagenesis and because a low urine pH is the main factor of uric acid (UA) stone formation, it was hypothesized that type 2 diabetes should favor the formation of UA stones. Therefore, the distribution of the main stone components was analyzed in a series of 2464 calculi from 272 (11%) patients with type 2 diabetes and 2192 without type 2 diabetes. The proportion of UA stones was 35.7% in patients with type 2 diabetes and 11.3% in patients without type 2 diabetes (P < 0.0001). Reciprocally, the proportion of patients with type 2 diabetes was significantly higher among UA than among calcium stone formers (27.8 versus 6.9%; P < 0.0001). Stepwise regression analysis identified type 2 diabetes as the strongest factor that was independently associated with the risk for UA stones (odds ratio 6.9; 95% confidence interval 5.5 to 8.8). The proper influence of type 2 diabetes was the most apparent in women and in patients in the lowest age and body mass index classes. In conclusion, in view of the strong association between type 2 diabetes and UA stone formation, it is proposed that UA nephrolithiasis may be added to the conditions that potentially are associated with insulin resistance. Accordingly, it is suggested that patients with UA stones, especially if overweight, should be screened for the presence of type 2 diabetes or components of the metabolic syndrome.

Influence of body size on urinary stone composition in men and women.

A larger body size has been shown to be associated with increased excretion of urinary lithogenic solutes, and an increased risk of nephrolithiasis has been reported in overweight patients. However, the type of stones produced in these subjects has not been ascertained. Based on a large series of calculi, we examined the relationship between body size and the composition of stones, in order to assess which type of stone is predominantly favoured by overweight. Among 18,845 consecutive calculi referred to our laboratory, 2,100 came from adults with recorded body height and weight. Excluding calculi from patients with diabetes mellitus, as well as struvite and cystine stones, the study material consisted of 1,931 calcium or uric acid calculi. All calculi were analysed by infrared spectroscopy and categorized according to their main component. Body mass index (BMI) values were stratified as normal BMI (< 25 kg/m2), overweight (BMI 25-29.9) or obese (BMI > or = 30). Overall, 27.1% of male and 19.6% of female stone formers were overweight, and 8.4 and 13.5% were obese, respectively. In males, the proportion of calcium stones was lower in overweight and obese groups than in normal BMI group, whereas the proportion of uric acid stones gradually increased with BMI, from 7.1% in normal BMI to 28.7% in obese subjects (P<0.0001). The same was true in females, with a proportion of uric acid stones rising from 6.1% in normal BMI to 17.1% in obese patients (P=0.003). In addition, the proportion of uric acid stones markedly rose with age in both genders (P<0.0001). The average BMI value was significantly higher in uric acid stone formers aged < 60 years than in all other groups, whereas it did not differ from other groups in those aged > or = 60 years. Stepwise regression analysis identified BMI and age as significant, independent covariates associated with the risk of uric acid stones. Our data provide evidence that overweight is associated with a high proportion of uric acid stones in patients less than 60 years of age, whereas beyond this limit, advancing age is the main risk factor.

[Continued late referral of patients with chronic kidney disease. Causes, consequences, and approaches to improvement]. / Retard persistant au suivi néphrologique de l'insuffisance rénale chronique. Causes, conséquences et moyens d'amélioration.

OBJECTIVES: Efforts in recent years have aimed at increasing physicians' awareness of the frequent and harmful consequences of late referral to nephrologists of patients with chronic kidney disease (CKD), shown in repeated concordant studies. We sought to determine whether these efforts have led to improved predialysis care of these patients. METHODS: This study included all 1391 consecutive patients who began maintenance dialysis at Necker Hospital between January 1989 and December 2000. We examined baseline data and outcomes and determined for four three-year periods the percentage of patients who received early specialized care (at least 6 months before onset of dialysis). RESULTS: Late referral (<6 months before dialysis) did not change significantly over the four periods, remaining around 30%, even during the most recent period (1998-2000). Clinical condition and laboratory indicators of patients referred early but not those referred late improved in the latest period, compared with the initial period (1989-1991). Overall, prevalence of major cardiovascular events (myocardial or cerebral infarction, peripheral arteriopathy, or heart failure) was more than twice as high in patients who received nephrologic care for less than 6 months and nearly twice as high even in those followed 6-35 months than in patients followed for at least 36 months before beginning dialysis. Subsequent mortality after maintenance dialysis was also significantly higher in patients with late referral than in those followed at least 3 years before dialysis. Multivariate Cox proportional model analysis identified graded duration of predialysis nephrologic care as a significant independent factor predictive of risk of mortality while on dialysis. CONCLUSION: Late referral of CKD patients for specialist care remains frequent, around 30%, although it is most often unjustified. Late referral deprives the patient of early implementation of a reno- and cardioprotective therapeutic strategy that reduces cardiovascular comorbidity and mortality. Better coordinated cooperation between family doctors and nephrologists, through the implementation of regional healthcare networks, now appears as the most effective way to improve the care of CKD patients.