[Renal vascular lesions and the occurrence of hypertension in patients with IgA nephropathy]. / Lésions vasculaires rénales et développement d'une HTA chez les patients atteints d'une glomérulonéphrite à dépôts mésangiaux d'IgA. Une histoire familiale d'hypertension artérielle.

Worse prognosis of IgA nephropathy (IgAN) is associated to hypertension, high proteinuria, glomerular and vascular sclerosis. A family story of hypertension (FHT) in relatives could be a strong predictor of the occurrence of hypertension (HT) in children. Renal vascular lesions (RVL) are often observed in normotensive patients with IgAN. In order to evaluate a possible association between FHT and LVR in patients with IgAN, we investigated two groups of 73 IgAN patients, sex (56 males and 17 females) and age matched, according to the presence or not of FHT. FHT was diagnosed if relatives and/or at least one child under 60 years of age had treatment for HT or systolic and diastolic BP over 140/90 mmHg at the time of the survey. Patients entering into the study were followed during an average period of 5 to 8 years. At the end of the study, all patients were explored for HT and renal function. Creatinine clearance (CrCl) was evaluated by Cockcroft and Gault formula and renal failure was defined as CrCl<60mL/min. The results were as follow: at the time of renal biopsy, RVL were observed in 73% of males with FHT vs 16% of males without FHT (p<0.0001) and 70.6% of females with FHT vs 29.4% of females without FHT (p<0.001); at the end of the study period, HT was significantly associated to FHT in 89.6% of patients group with FHT vs 22.6% of HT patients in the group without FHT (p<.0001). Renal failure was present in 45.2% of patients with FHT vs 4.1% of patients without FHT (p<0.0001). These data suggest: VRL could be dependent of genetic factors; FHT should be an early predictor of VRL in patients with IgAN; FHT might be a risk factor for renal failure in patients with this renal disease.

[Arterial hypertension in the hemodialysis patient. A model of salt-sensitive hypertension in man]. / L'hypertension artérielle du patient hémodialysé. Un modèle d'hypertension sensible au sel chez l'homme.

In uremic patient treated by hemodialysis (HD), a low potassium intake and a salt load due to diet and or a high sodium concentration in dialysate are often associated to refractory hypertension. Numerous reports in general population, based on epidemiologic and demographic data, have pointed to the relationship between sodium intake and hypertension. The degree of blood pressure fall in patients who have evidence of salt-sensitivity varies directly with the severity of the hypertension, being most prominent in those with higher pressures. Recent studies have suggested that a reduction of dialysate sodium can control hypertension in maintenance haemodialysis patients. In this study, five hypertensive haemodialysis patients were assigned to a regime of lowering the dialysate sodium concentration from 142 to 135 mmol/L in combination with an attempt to lower salt intake by advising the patients to eat a NaCl-restricted diet of no more than 6-8 g/day. During the period under study, dialysis time was kept constant. A significant increase of ultrafiltrate sodium concentration was observed during the first week after lowering the dialysate sodium concentration. Post dialysis systolic and diastolic pressures showed a clear trend to fall (systolic pressure 174 +/- 18 vs 118 +/- 13 mmHg, diastolic pressure 96 +/- 7 vs 75 +/- 13 mmHg) without a change of dry weight. The reduction of the mean arterial pressure on 48 h was demonstrated with ambulatory blood pressure recording. The results of this study suggest that reducing the dialysate sodium concentration lead to a decrease in peripheral resistance. A link between sympathetic overactivity as it is found in haemodialysis patients and sodium load could be a stimulating hypothesis. It is concluded that increasing dialysate sodium in short dialysis is responsible for the high prevalence of arterial hypertension often insufficiently controlled by antihypertensive medication. In hemodialysis patients with refractory hypertension, the lowering of the dialysate sodium concentration is indicated.

[Ischemic renal diseases have become the most frequent causes of end stage renal disease in the elderly]. / La néphroangiosclérose et la néphropathie ischémique athéromateuse sont devenues les causes les plus fréquentes d'insuffisance rénale terminale chez le sujet âgé de plus de 60 ans.

In the 80s it was established that atherosclerotic renal artery stenosis (ARAS) is a leading cause of renal insufficiency and that this condition ranks among the rare etiologies of chronic renal failure amenable to improvement or stabilization particularly in the white. Nephroangiosclerosis (NAS) is an increasing cause of ESRD in the western countries, especially in blacks. Epidemiological data on the vascular nephropathies leading to ESRD are still rare. In this study, we compare annual incidence of ESRD due to ARAS and NAS during two five-year periods: period A = 1982-1986, period B = 1992-1996. The region of the survey comprised 410,664 inhabitants (99.6% of Caucasians), of whom 100,230 were aged over 60 years. Diagnosis of ARAS required arteriography and that of NAS a renal biopsy. Undetermined vascular nephropathy was diagnosed when ESRD patients had had previously no arteriography or no histological examination. Major results were as follow (A vs B, incidence = n/million inhabitants): 1) Increasing incidence of ESRD due to all causes: 76 vs 95 per million, mean age at ESRD 56 vs 62 yrs, percentage of patients over 65 yrs 28 to 59% (p < 0.001). 2) Increasing incidence of ESRD due to vascular nephropathies: 5.5 vs 27.5 per million (p < 0.0001) in general population and 22 vs 110 per million (p < 0.0001) in population aged over 60 years, mean age at ESRD 68 vs 73 yrs. 3) Increasing incidence of different types of ischemic renal diseases leading to ESRD: ARAS 2.5 vs 15 per million (p < 0.0001) in general population and 10 vs 60 per million (p < 0.001) in those aged over 60 yrs, mean age 69 vs 74 yrs, NAS: 1 vs 8 and 4 vs 32 per million (p < 0.001), mean age 67 vs 72 yrs, undetermined VN 0.5 vs 2.5 and 2 vs 10 per million, 65 vs 73 yrs. Our study demonstrates that ischemic renal diseases 1) have become the most frequent causes of ESRD (27% of all patients and 43% of those aged over 6C years) in the Caucasian elderly. 2) are the only cause of increasing incidence of ESRD in this French region.

[Intravascular malignant B-cell lymphomatosis with renal glomerular involvement: a case]. / Lymphomatose maligne intravasculaire de type B avec atteinte rénale glomérulaire: une observation.

We report a case of intravascular malignant lymphomatosis observed in a 71 year-old male and characterised by the presence of a proteinuria in relation to the specific intraglomerular localisation. This malignant lymphoma, usually of the B phenotype, is rare and affects predominantly the central nervous system and the skin. Neoplastic cells home selectively to endothelium. Histological renal infiltration is frequent but a glomerular localisation, with proteinuria, is rare. The mechanism whereby lymphocytes home to endothelium cells is unclear but it could be related to the expression of lymphocyte-endothelium adhesion molecules. When present the nephrotic syndrome is associated with minimal change disease.

[A familial history of hypertension is associated with the development of hypertension and nephroangiosclerosis in patients with glomerulonephritis caused by mesangial IgA deposits]. / Une histoire familiale d'hypertension artérielle est associée à la survenue d'une hypertension artérielle et d'une néphro-angiosclérose chez les patients atteints de glomérulonéphrite à dépôts mésangiaux d'IgA.

The progress of IgA Nephropathy (IgAN) is correlated with glomerular and vascular sclerosis. Renal vascular lesions, i.e. nephrosclerosis, often precede the onset of hypertension (HBP) in young patients with IgAN. It is also recognized that a family history of HBP (FHBP) is strongly predictive of future onset of HBP in family members, when two or more first-degree relatives with HBP are identified. In order to examine the possible link between FHBP and nephrosclerosis, we compared 2 groups of 29 pts each (23 M and 6 F) with IgAN, matched for age and sex, according to the presence or absence of FHBP. FHBP was considered present if at least 2 or more 1st degree relatives under 60 years of age received antihypertensive Rx. Parents and siblings of patients were examined at home by two investigators. Patients with FHBP (+) and FHBP (-) were aged 36 +/- 12 and 35 +/- 12, respectively, at the time of renal biopsy and the follow-up was conducted for an average of 4.6 years. At the end of this survey, HBP and renal failure (Cr Cl < 80 ml/min) were reevaluated in all patients. At the time of renal biopsy, nephrosclerosis was significantly associated with FHBP: FHBP (+): 96.5% versus FHBP(-): 10.3%; p < 0.0001. At the end of the follow-up, FHBP was found to be associated with HBP (89.6% versus 10.3%; p < 0.001) and with renal failure (44.8% versus 3.4%; p < 0.001). These data suggest that nephrosclerosis has a strong genetic component in patients with IgAN, FHBP is an early clinical indicator of nephrosclerosis in these patients and that FHBP is a strong indicator of unfavorable prognosis in IgAN.

Plasma total versus bone alkaline phosphatase as markers of bone turnover in hemodialysis patients.

Plasma total versus bone alkaline phosphatase as markers of bone turnover in hemodialysis patients. Plasma bone-specific alkaline phosphatase (bAP) has been demonstrated to be more reliable than total alkaline phosphatases (tAP) in providing information about bone turnover in patients with metabolic bone diseases. This study surveyed 42 hemodialysis patients who underwent a systematic transiliac bone biopsy for histomorphometry study. Plasma bAP was determined by using a new immunoassay (Tandem-R Ostase, Hybritech, Liège, Belgium). Plasma bAP values were compared with those of two other plasma markers of bone metabolism, namely tAP and intact parathyroid hormone (iPTH), for the correlations with bone histomorphometric parameters. Patients with high-turnover bone disease (HTBD) (N = 32) had significantly higher plasma bAP levels than patients with normal or low bone turnover (N/LTBD) (N = 10) (66.9 +/- 63.5 ng/mL versus 10.8 +/- 4.2 ng/mL, respectively). Bone formation and resorption were highly correlated in these patients, and plasma bAP levels were positively correlated with bone resorption parameters, including osteoclast surface (r = 0.39, P < 0.0001) and osteoclast number/mm2 (r = 0.36, P < 0.001), and with bone formation parameters, osteoblast surface (r = 0.50, P < 0.005), and bone formation rate (r = 0.91, P < 0.0001). The bone formation rate was better correlated with plasma bAP levels than with either plasma tAP or iPTH concentrations. Plasma bAP level equal or higher than 20 ng/mL, either alone or combined with plasma iPTH of 200 pg/mL, had the highest sensitivity, specificity, and predictability values for the diagnosis of high-turnover bone disease, and formally excluded patients with normal or LTBD. In conclusion, plasma bAP can be measured with a reliable immunoassay in hemodialysis patients. It represents a highly sensitive and specific biochemical marker of skeletal remodeling in these patients. Therefore, both serum iPTH and bAP are complementary in diagnoses of the type of renal osteodystrophy.

[Epidemiologic data, clinical and prognostic features of autosomal dominant polycystic kidney disease in a French region]. / Données épidémiologiques, cliniques et pronostiques de la maladie polykystique autosomique dominante dans une région française.

Epidemiological study on autosomal dominant polycystic kidney disease (ADPKD) was undertaken in a French region from 1988 to 1993. This survey was led in a population of 410,000 inhabitants and 84 kindreds with ADPKD and 296 affected members were studied. Prevalence of ADPKD in the studied region was calculated to 1/1111 inh. Renal prognosis was evaluated according to the Kaplan-Meier method in 296 affected subjects of whom 212 were members of propositus kindreds. In our region 17% of patients had ESRD by the age of 50 years, 47% by the age of 60 years and 70% by the age of 70. No significance difference was found between males and females. The influence of the sex of the parent from whom ADPKD was received on the renal prognosis of the disease in affected descendants was evaluated. Anticipation of ESRD for at least one offspring inheriting ADPKD from parent was found in 15 (38%) out of 39 families, without genetic imprinting linked to gender. Mean survival to ESRD for fathers transmitting ADPKD to offspring (52 +/- 10 years) was significantly earlier compared to that for mothers transmitting ADPKD (61 +/- 10 years, p < 0.001), therefore that for siblings inheriting the disease from their fathers (sons: 49 +/- 7 years, daughters: 51 +/- 9 years) and for those inheriting ADPKD from their mothers (sons: 57 +/- 10 yrs, p < 0.01, daughters: 55 +/- 6 yrs, p < 0.02). Prevalence of de novo mutations was evaluated to 1/135,000 inh. Adult polycystic disease of the liver (APLD) was studied in 82 kindreds with 158 ADPKD affected members by ultrasonography and/or CT. In patients with APLD, 49/84 (58.3%) were females compared to 46/74 (62.2%) in those without APLD. Familial APLD (at least 2 affected members and all with APLD) was demonstrated in 22/27 APLD kindreds (81.5%). Familial ADPKD without APLD (at least 2 affected members and all without APLD) was demonstrated in 12/12 kindreds (100%). Renal prognosis of ADPKD in 84 APLD pts was compared to that in 71 non-APLD pts, in whom mean age was not different at the time of the study. In APLD pts 28/84 (33.3%) had reached ESRD compared to 23/71 (32.3%) non-APLD pts (ns). The occurrence of stroke in ADPKD patients was documented in 24/231 pts (10.4%) from 11/82 kindreds (13.4%). Family history of cerebro-vascular event was found in 4/11 kindreds (36%).

Serum pyridinoline as a specific marker of collagen breakdown and bone metabolism in hemodialysis patients.

Type I collagen represents more than 90% of bone matrix. Quantitative analysis of collagen cross-link molecules such as pyridinoline (PYD) provides valuable information on bone resorption rate. We have studied 37 hemodialysis patients who underwent a systematic transiliac bone biopsy for histomorphometry study. Eighteen of them had tetracycline double labeling, allowing to determine dynamic, in addition to static bone parameters. Measurement of serum-free PYD was performed using a new competitive enzyme immunoassay. Serum PYD values were compared with those of three other serum markers of bone metabolism, namely intact PTH (iPTH), bone-specific alkaline phosphatase (bAP), and osteocalcin, for the correlations with bone histomorphometric parameters. Serum PYD levels (mean +/- SD) were significantly higher in dialysis patients than in normal individuals, 90.6 +/- 99.6 nM versus 1.9 +/- 0.4 nM, respectively. Patients with high turnover bone disease had significantly higher serum PYD levels than patients with normal or low bone turnover, 108.8 +/- 108.0 nM versus 34.1 +/- 12.8 nM, respectively. Serum PYD levels were positively correlated with bone resorption parameters including osteoclast surface (r = 0.59, p < 0.0001) and osteoclast number/mm2 (r = 0.61, p < 0.0001), and also with bone formation parameters, osteoblast surface (r = 0.43, p < 0.008), double-labeled surface (r = 0.81, p < 0.001), and BFR (r = 0.91, p < 0.0001). The BFR was better correlated with serum PYD levels than with either serum iPTH or osteocalcin concentrations. However, correlation with serum bAP was comparable.(ABSTRACT TRUNCATED AT 250 WORDS)

[Epidemiology of primary glomerulopathies in a French region. Variations as a function of age in patients]. / Epidémiologie des glomérulopathies primitives dans une région française. Variations en fonction des périodes et de l'âge des sujets.

Between January 1st, 1976 and December 31st, 1990, histological diagnosis of primary glomerular diseases (PGD) was made in 480 patients born and living at the time of diagnosis in a region of France comprising 410,664 inhabitants, of whom 390,574 were aged from 10 to 80 years. The prevalence of PGD during a 70-year exposure to risk (10-80 years of age) was evaluated to 5.7 in 1000 (7.6 in 1000 males and 3,8 in 1000 females). The most common PGD was IgA nephropathy with a prevalence of 1.9 in 1000 (3.3 in 1000 males, 1 in 1000 females). The annual incidence of the disease was evaluated separately for 3 consecutive 5-year periods: period A (1976-80), period B (1981-85), and period C (1986-90). Within each of these 3 periods the number of patients with PGD was 179, 170 and 131 respectively, and annual incidence was 9.3, 8.8 and 6.7 in 100,000. The incidence of IgA nephropathy remained the same throughout the 3 periods: 2.6, 3.1 and 2.5 in 100,000. The incidence of membranoproliferative glomerulonephritis decreased from 1981 onward (0.9, 0.5 and 0.15/100,000). Acute streptococcal glomerulonephritis virtually disappeared during periods B and C. Lipoid nephrosis was less frequent in period C and idiopathic proliferative glomerulonephritis with crescents slightly increased (0.3, 0.3 and 0.6 in 100,000). There was no significant difference between the 3 periods regarding the incidence of other PGD. Incidence of IgA nephropathy was 3 to 4-fold higher in the adult aged from 20 to 60 years than in the elderly. In contrast, membranous nephropathy was 3 fold more frequent in the elderly than in the adult. Therefore only some histopathological forms have a different incidence according to age, but the major information furnished by this study is that the risk of occurrence of a PGD is similar in the population living in the area, whatever the age group (10-19 years: 6.4/10(5) inhabitants, 20-39: 7.1/10(5), 40-59: 8.4/10(5), 60-79: 8.4/10(5)). Finally, we confirm that the most common PGD going to end stage renal disease was IgA nephropathy, particularly under 60 years of age (0.8/10(5)). In contrast, membranous nephropathy was a less frequent cause of ESRD (0.2/10(5)).

Relationship between serum beta 2-microglobulin, bone histology, and dialysis membranes in uraemic patients.

BACKGROUND: beta 2-Microglobulin (beta 2M) is the main constituent of osteoarticular amyloid deposits in haemodialysis patients. When dialysed with cellulosic (C) membrane such patients present a higher incidence of beta 2M-related amyloid arthropathy than with synthetic high-flux (SHF) membrane, and they have higher serum levels of beta 2M. This could favour beta 2M deposition as amyloid fibrils and/or modify bone and cartilage metabolism. METHODS: We examined 56 uraemic patients dialysed in the same centre for 7.5 +/- 4.8 years (mean +/- SD). Based on bone histomorphometry criteria they were classified into either high-turnover bone disease (HTBD, 45 patients) or normal/low-turnover bone disease (N/LTBD, 11 patients). A subgroup of 30 patients had been dialysed with the same dialysis membrane for at least 18 months prior to study, 8 on C and 22 on SHF membrane. RESULTS: Serum intact parathyroid hormone levels were not different between the two patient subgroups. In contrast, serum beta 2M levels were higher in patients on C than on SHF membrane: 59.8 +/- 14.1 versus 32.8 +/- 8.7 mg/l, and so were serum total alkaline phosphatase and osteocalcin levels: 323 +/- 167 versus 173 +/- 50 IU/l, and 656 +/- 395 versus 288 +/- 263 ng/ml respectively. The increase of these serum markers of bone formation was associated with a higher bone cell number: osteoblast surface, 21.7 +/- 5.1 versus 9.8 +/- 11%; osteoclast surface, 4.27 +/- 1.86 versus 1.96 +/- 1.34%; and osteoclast number/mm2, 2.85 +/- 1.26 versus 1.27 +/- 0.88 respectively. Serum beta 2M was positively correlated with serum osteocalcin (r = 0.58, P < 0.001), bone-specific alkaline phosphatase (bAP) (r = 0.46, P < 0.008), and free pyridinoline (PYD) (r = 0.62, P < 0.002), and negatively correlated, only for HTBD, with osteoid volume: r = -0.40, P < 0.006. Serum beta 2M was higher in patients with HTBD than N/LTBD: CONCLUSION: The bone metabolism of chronic haemodialysis patients may be influenced by dialysis membrane biocompatibility. Moreover, the association of high serum beta 2M with increased bone cell number and serum markers of bone turnover suggests that beta 2M is either another marker of bone cell activity or an activator of bone cells.

Epidemiology of primary glomerular diseases in a French region. Variations according to period and age.

Between January 1, 1976 and December 31, 1990, histological diagnosis of primary glomerular diseases (PGD) was made in 480 patients born and living at the time of diagnosis in a region of France, comprising 410,664 inhabitants, of whom 390,574 were aged from 10 to 80 years. The prevalence of PGD during a 70 year exposure to risk (10 to 80 years of age) was evaluated to 5.7 in 1000 (7.6 in 1000 males and 3.8 in 1000 females). The most common PGD was IgA nephropathy with a prevalence of 1.9 in 1000 (3.3 in 1000 males, 1 in 1000 females). The annual incidence of the disease was evaluated separately for three consecutive five-year periods: period A (1976-80), period B (1981-85), and period C (1986-90). Within each of these three periods the number of patients with PGD was 179, 170 and 131, respectively, and annual incidence was 9.3, 8.8 and 6.7 in 100,000. The incidence of IgA nephropathy remained the same throughout the three periods: 2.6, 3.1 and 2.5 in 100,000. The incidence of membranoproliferative glomerulonephritis decreased from 1981 onward (0.9, 0.5 and 0.15 in 100,000), while that of membranous nephropathy increased slightly (1.2, 1.6 and 1.7 in 100,000). Acute streptococcal glomerulonephritis virtually disappeared during periods B and C. Lipoid nephrosis was less frequent in period C and idiopathic proliferative glomerulonephritis with crescents slightly increased (0.3, 0.4 and 0.6 in 100,000). There was no significant difference between the three periods regarding the incidence of other PGD.(ABSTRACT TRUNCATED AT 250 WORDS)

Indices of adequate dialysis in patients hemodialyzed with AN 69 membrane.

The objective of this study was to evaluate the incidence of morbidity (at least one hospitalization) during the first twelve months of hemodialysis (thrice weekly for 4 hours) in 54 (27 males and 27 females) sex and age matched patients, of whom 32 were treated with AN 69 (M/F = 13/19, 62 +/- 14 years) and 22 with Cuprophan (M/F = 14/8, 61 +/- 14 years). Patients were classified according to the value of TAC urea during the period under study: constantly superior or equal to 20 mmol/liter in Group A (high TAC urea) or inferior to 20 mmol/liter in Group B (low TAC urea). Dialysis quantification (Kt/V) and estimation of the patient's protein catabolic rate (PCR) were based on measurement of the midweek pre- and post-dialysis blood urea nitrogen. In the patients of Group B, incidence of morbidity was significantly increased when age was over 50 years and when AN 69 membrane was used (P < 0.02). Furthermore, in Group A, the risk of hospitalization was significantly higher in patients treated by Cuprophan than in those treated by AN 69 (P < 0.02). The survival rate was also studied. Better survival (70%) at four years was observed in patients with high TAC urea who were treated by AN 69. The difference was highly significant with the survival rate (22%) in patients with high TAC urea who were treated by Cuprophan (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[Genetic and environmental factors implicated in recurrent calcium lithiasis]. / Facteurs génétiques et environnementaux impliqués dans la lithiase calcique récidivante.

In this prospective study, we compared the frequency of some genetic and environmental factors possibly implicated in the occurrence of calcium stone disease. A group of 439 patients (258 males and 181 females) with one episode of calcium stone was compared to a group of 191 patients (131 males and 60 females) with recurrent calcium stone disease. Population with stones was also compared to control population (n = 78, 40 males and 38 females) matched to age. Major results were as follow: 1) Family history of urinary calculi was more frequent in patients than in controls (28.4% vs 9%, p < 0.01). No difference was observed between patients with one episode and those with recurrent episodes (27% vs 31%, ns). 2) The recurrence was earlier in female than in male, so that in female with family history of urinary calculi (p < 0.05). 3) Mean plasma levels of 1-25OH2D3 was significantly higher in patients with family history than in controls (60% vs 38%, p < 0.01) 5) Restricted calcium diet (< 400 mg per day) was more often observed in patients than in controls (31% vs 14%, p < 0.05) and the most significant difference was found in patients with recurrent calcium stones.

[Short and long term complications of lithotripsy on renal function]. / Séquelles à court et moyen termes de la lithotripsie sur la fonction rénale.

Today, most stones can be removed by minimally invasive means. Extracorporeal Shock Wave Lithotripsy (ESWL) is the preferred form of treatment for symptomatic upper ureteral and renal calculi less than 2 cm a diameter. The short and long term complications of ESWL are underestimated. Thus, ESWL may cause renal trauma and such trauma may induce later hypertension. In this retrospective study, we reviewed the frequency of deleterious effects of ESWL in 45 patients who had undergone ESWL from January 1988 to September 1989. Short-term complications were macroscopic hematuria (15%), lumbar pain (11%) and peri- or intrarenal hematomas (4.4%). Two years later CT scan was performed in 20 patients. It was normal in 7 (35%). In others, it shown a recurrence of stone in 8 (40%) and a focal scarring in 5 (25%). Only 1 out of 43 patients had developed hypertension.