[Randomized trials in the prevention of recurrent calcium oxalate stones]. / Les essais cliniques randomisés dans la prévention des récidives des lithiases oxalo-calciques.

Kidney stone, with or without lumbar pain, is a major health care problem because of its prevalence and cost for both the patient and the society. Although, surgical procedures are well known, medical treatment and recurrences prophylaxis are uncodified. Fifteen stone recurrence prevention studies have been reviewed, evaluating dietary intake and drugs. The most important factor is a daily diuresis of at least 2 liters. Calcium intake shouldn't be restricted, whereas oxalate, sodium, and protein intakes have to be limited. Hyper and normocalciuretic kidney stone formers improve their outcome with thiazide or indapamide treatment. Hyperuricosuria justifies allopurinol. Potassium citrate (without sodium) may decrease recurrence risk, even in patients without hypocitraturia.

[Renal osteodystrophy (2): its treatment in renal insufficiency before dialysis]. / Ostéodystrophie rénale (2): Son traitement chez l'insuffisant rénal avant la dialyse.

1. In the patient with renal insufficiency before dialysis, the phosphocalcic disorders appear insidiously. They are dominated by hyperparathyroidism which will be diagnosed on the initially yearly determination of plasma intact PTH as soon as creatinine clearance decreases below 60 ml/min, eventhough there is still no modification in plasma concentrations of calcium and phosphate. Its diagnosis should lead to initiate the therapeutic measures in order to prevent the irreversible thining of the corticals by endosteal resorption and later the occurrence of histological and radiological osteitis fibrosa favoring fractures. 2. Hyperparathyroidism prevention relies on two main measures: prevention of phosphate retention and hypocalcemia is implemented by progressive phosphate and protein restriction (from 1 g/kg/day when Ccr < 60 ml/min to 0.6 g/kg/day when Ccr < 20 ml/min) and administration of CaCO3 (1.5 g at lunch and dinner to better complex the phosphate) as soon as PTH is above normal; optimal vitamin D repeletion will be implemented by systematic supplementation of native vitamin D or 25OH vitamin D3 in order to bring P25OHD between 30-60 ng/ml (75-150 nmol/l) or more generally around the upper limit of the epidemiologic range of the laboratory; these measures should aim at maintaining plasma intact PTH in its optimal range variable with the degree of renal insufficiency: 0.5-1; 1-2.5 and 2-3 folds the upper limit of normal for creatinine clearance respectively at 60-30; 30-10 and < 10 ml/min. 3. Because of their hyperphosphatemic and hypercalcemic effect, 1 alpha-hydroxylated vitamin D derivatives will be regularly efficient and safe only when non-calcemic non-aluminic phosphate binder will be available and proven to be without side-effects. 4. Instrumental (surgical or by alcohol injection) parathyroidectomy should be considered when plasma intact PTH is > 5 to 7 times the upper limit of normal in the presence of hypercalcemia (> 2.60 mmol/l) and/or hyperphosphatemia (> 1.70 nmol/l) in spite of the above measures, the decision being reinforced by coexistence of bone radiologic abnormalities and metastatic calcifications. 5. Adynamic bone diseases are rare before hemodialysis in the absence of aluminum exposition by the drinking water or the aluminum-phosphate binders. In absence of aluminum it will be prevented by maintaining PTH in its optimal range. 6. Osteomalacia before hemodialysis is mainly due, in the absence of aluminum exposition, to vitamin D deficiency, hypocalcemia and acidosis. It is readily cured by physiological doses of native vitamin D or 25OH vitamin D3 bringing plasma 25 OHD above 16 ng/ml, in association with alkaline salts of calcium and if necessary of sodium bicarbonate.

[Renal osteodystrophy (1): invasive and non-invasive diagnosis of its pathologic varieties]. / Ostéodystrophie rénale (1); Diagnostic invasif et non invasif des variétés histopathologiques.

1. Renal osteodystrophy is a general term encompassing all the disturbances of the phosphocalcic metabolism and their associated bone and soft tissue abnormalities, which progressively occur in chronic renal failure. In this article we detail their main histopathological and etiopathogenic aspects as well as their invasive and non invasive diagnostic approach. 2. Osteitis fibrosa is characterized by extensive medullary fibrosis and osteoclastic hyperresorption linked to PTH hypersecretion. 3. Adynamic bone disease is mainly related to iatrogenic oversuppression of PTH secretion. It is favored by aluminum overload which directly inhibits the osteoblasts. It is characterized by a low bone formation rate without primary mineralization defect so that the osteoid seam thickness is normal or low, in contrast to osteomalacia in which by definition osteoid thickness is increased. 4. Osteomalacia is mainly due to aluminum intoxication, vitamin D insufficiency, hypocalcemia, acidosis and exceptionally to hypophosphatemia. 5. The differential diagnosis between the histopathological entities may be oriented on clinical, radiological and biochemical means. Only the bone biopsy can make the diagnosis with certainty. This latter is however necessary for appropriate treatment only in the patients who have been exposed to aluminum and who are symptomatic or hypercalcemic in order to distinguish severe osteitis fibrosa from aluminic bone disease, and more particularly from mixed osteopathy. Indeed surgical parathyroidectomy in patients with mixed osteopathy associating bone hyperremodeling and mineralization defect with inappropriately thick osteoid seam may induce fracturing low turn over aluminic bone disease.

[Renal and hypertensive complications of extracorporeal lithotripsy]. / Complications rénales et hypertensives de la lithotritie extracorporelle: les patients à risque.

HISTOLOGICAL AND FUNCTIONAL CONSEQUENCES OF ESWL: Extracorporeal shock wave litotripsy is now used for the treatment of about 90% of stones. Because of the nonpunctual delivery of energy into the stone, a small volume of renal parenchyma is injured, giving rise to a fibrous scar which can be visualized by morphological techniques such as magnetic nuclear resonance. Isotopic techniques point out a 15% reduction of renal plasma flow on the side of the litotripsy. For a majority of patients, this alteration is transient. HYPERTENSION: In a few cases, abrupt onset of transient hypertension has been reported in clear relation with a compressive perirenal hematoma. The causal effect of ESWL on late occurrence of permanent hypertension is however still uncertain, probably because of the difficulty to show that this occurrence is not related to the older age of the patient alone. The FDA sponsored multicentric study begun in 1993 should solve this issue in the future. PATIENTS AT RISK: Recent articles suggest that altered renal function prior to ESWL would predict late occurrence of hypertension and worsening of renal failure. Furthermore, age and the resistance index of arcuate or interlobular renal arteries (measured by Doppler) could help to screen the patients at risk of developing hypertension. Practical attitude: In practice, renal function and blood pressure should be carefully monitored in patients aged over 60 and/or who have a serum creatinine > 300 mumol/l.

[Renal osteodystrophy (3); its treatment in dialysis patients]. / Ostéodystrophie rénale (3); Son traitement chez le dialysé.

The prevalence and the clinical gravity of the various histopathological varieties of renal osteodystrophy in dialysis patients depends on the severity of both the aluminium intoxication and that of hyperparathyroidism. The prevalence of bone pains, fractures and hypercalcemias are the highest in adynamic bone diseases (ABD) with severe aluminium intoxication, then in osteitis fibrosa and mixed osteopathy, in the ABD with moderate aluminium intoxication and rare in the mild lesion in spite of similar moderate aluminium intoxication. In the absence of aluminium intoxication, hypercalcemia and hyperphosphatemia prevalence is higher only when intact PTH is more that 4 times the upper limit of normal. When PTH is between 1 and 2 folds the ULN this prevalence is null and bone mineral density is the highest. 2. The low turnover aluminic bone diseases (osteomalacic or adynamic) will be cured by long term deferoxamine treatment. The hazards of such treatment justify the performance of a bone biopsy to ensure the diagnosis. Their prevention relies on adequate treatment of tapwater and definitive exclusion of long term administration of aluminum phosphate binders. 3. Non aluminic osteomalacia will be treated according to the same guidelines given for the uremic patients before dialysis. 4. Non aluminic adynamic bone disease will be cured by means aiming at stimulating PTH secretion as discontinuing 1 alpha hydroxylated vitamin D derivatives, and, if there is no hyperphosphatemia by discontinuation of calcium supplement. In case of hyperphosphatemia in dialysis patients CaCO3 doses have to be nevertheless increased after the dialysate calcium concentration (DCa) has been decreased in order to induce a negative perdialytic calcium balance for PTH secretion stimulation. In the near future substitution of CaCO3 by non calcemic non aluminic phosphate binders will suffice. 5. Osteitis fibrosa due to hyperparathyroidism will be treated first by securing an optimal vitamin D repletion (bringing plasma 25OH vitamin D around 30 and 60 ng/ml or 75-150 nmol/l) and by correcting hypocalcemia and hyperphosphatemia by CaCO3 at high doses (3-12 g/day) taken with the meals. In case of hypercalcemia dialysate calcium concentration will be decreased to correct it or, in a near future, CaCO3 will be decreased to 3 g/day and hyperphosphatemia will be controlled by non calcemic, non aluminic phosphate binders. When hyperphosphatemia is controlled whereas plasma calcium is normal or low, 1 alpha hydroxylated vitamin D derivatives can be administered. 6. Instrumental parathyroidectomy should be considered when plasma levels of intact PTH remain above 7 folds the upper limit of normal whereas hyperphosphatemia persists and hypercalcemia occurs in order to prevent thining of the corticals and subsequent fracture risk. In case of previous exposition to aluminum, a deferoxamine test and/or a bone biopsy will be performed to decide a long term DFO treatment before the parathyroidectomy in order to prevent the transformation of a mixed osteopathy into an aluminic adynamic bone disease. 7. The difficulty of hyperparathyroidism control in dialysis patients is due to poor compliance to phosphate binders and to irreversible parathyroid hyperplasia with occured before the dialysis stage. This stress the primary importance if its early prevention without iatrogenia by first CaCO3 and vitamin D repletion, as soon as the creatinine clearance decreases below 60 ml/min/1.73 m2.

Renal and hypertensive complications of extracorporeal shock wave lithotripsy: who is at risk?

Extracorporeal shock wave lithotripsy (ESWL) is now used in the treatment of about 90% of renal and ureteral stones. Because of the non-punctual delivery of energy to the stone, a small volume of renal parenchyma is injured giving place to a fibrous scar which can be shown by highly resolutive imaging techniques like magnetic nuclear resonance. Isotopic clearances point to a reduction of 15% in the renal plasma flow on the side of the lithotripsy, but this alteration appears to be transient in nature. In a few cases an abrupt onset of transient hypertension has been reported in clear relation to a compressive perirenal hematoma. The responsibility of ESWL in the late occurrence of permanent hypertension is, however, still uncertain, probably because of the difficulty in showing that this occurrence is not only related to the older age of the patient. The American Food and Drug Administration-sponsored multicentric study begun in 1992 should solve this issue in the future. Recent articles suggest that altered renal function prior to ESWL would predict the late occurrence of hypertension and worsening of renal failure. Furthermore, age and the resistance index of arcuate or interlobar renal arteries (measured by Doppler) could help to screen patients at risk of developing hypertension. In practice in patients over 60 years of age and/or with a plasma creatinine of >to 300 micromol/l, ESWL should be performed with caution, and renal function and blood pressure should be carefully monitored.

Risk factors of renal failure progression two years prior to dialysis.

AIM: The respective contribution of sex, type of nephropathy, degree of proteinuria, blood pressure, protein and sodium daily intakes, blood lipid profile, protidemia, hemoglobinemia, acidosis and CaPO4 product on the rate of renal failure progression is debated. PATIENTS AND METHODS: The link between these parameters and the decrease of creatinine clearance, deltaCcr (according to Cockroft) was assessed in uni- and multivariate analysis in a population of 49 patients (26 women; age 60+/-15 years, weight 79+/-15 kg) selected out of 173 presently treated hemodialysis patients on the basis of availability of a quarterly follow-up for 2 years before starting dialysis. The patients were advised a moderate protein and salt restriction which could be retrospectively assessed (on urinary excretion of urea and sodium) at, respectively, 0.82 g/kg/day and 6.5 g/day. RESULTS: The 2-year deltaCcr was 14+/-14 ml/min. It was not different in men and women. This decrease in Ccr was neither significantly different in gomerular disease (17+/-8, n = 14), diabetic nephropathy (12+/-6, n = 7), nephroangiosclerosis (15+/-8, n = 5), interstitial nephritis (12+/-10, n = 14), and PKD (11 +/-12, n = 9). Patients with antihypertensive drugs (n = 42) had a faster progression than those without drugs (n = 7): deltaCcr = 15+/-14 vs 7+/-7 ml/min (p < 0.05) in spite of comparable blood pressure but with higher proteinuria. Linear regression of deltaCcr with the initial and 2-year averaged values of the quantitative parameters showed a significant positive link for both values with cholesterol, hemoglobine and proteinuria and a negative one with protidemia. A positive link was observed with the initial value of bicarbonate and the 2-year mean of diastolic and mean blood pressures. No link at all was observed with urea and Na excretion, CaPO4 product and triglycerides. Multiple regression disclosed a significant link only for protidemia (negative with both initial and 2-year averaged value), diastolic BP (only for the 2-year averaged value and hemoglobinemia (for the initial value). When the patients were classified according to a threshold value of their protidemia, DBP, hemoglobinemia, and cholesterolemia those with the combination of 2 risk factors of progression (protidemia > or = 66 g/l, DBP > or = 90 mmHg, hemoglobinemia > 11 g/dl, proteinuria > or = 3 g/d, CT > 5 mmol/l) had a significantly greater decrease of Ccr than those with the 3 other combinations at the exception of the association of low protidemia with DBP. CONCLUSION: Diastolic hypertension and low protidemia are the 2 most important factors predicting progression of renal failure. A predictive synergy was furthermore pointed out between low protidemia or diastolic hypertension with proteinuria and cholesterol. On the contrary anemia attenuates progression linked to low protidemia, diastolic hypertension, proteinuria and high cholesterol.

[Factors in the progression of renal insufficiency during the 2 years preceding the use of dialysis]. / Facteurs de progression de l'insuffisance rénale dans les deux ans précédant la mise en dialyse.

UNLABELLED: The respective contribution of sex, type of nephropathy, degree of proteinuria, blood pressure, protein and sodium daily intake, lipid profile, protidemia, hemoglobinemia, acidosis and CaPO4 product on the rate of renal failure progression is debated. The link between these parameters and the decrease of creatinine clearance, delta Ccr (according to Cockroft) was assessed in uni and multivariate analysis in a population of 49 patients (26 men, 23 women; age 60 +/- 15 years, weight 73 +/- 15 kg) selected out of 173 presently treated hemodialysis patients on the basis of availability of a quarterly follow-up for two years before starting dialysis. The patients were advised a moderate protein and salt restriction which could be retrospectively assessed (on urinary excretion of urea and sodium) at respectively 0.82 g/kg/day and 6.5 g/day. The two years delta Ccr was 14 +/- 14 ml/min. It was not different in men and women (specially when expressed in % of initial value). This decrease in Ccr was neither significantly different in glomerular disease (17 +/- 8, n = 14), diabetic nephropathy (12 +/- 6, n = 7), nephroangiosclerosis (15 +/- 8, n = 5), interstitial nephritis (12 +/- 10, n = 14), and PKD (11 +/- 12, n = 9). Patients with antihypertensive drugs (n = 42) had a faster progression than those without drugs (n = 7): delta Ccr = 15 +/- 14 vs 7 +/- 7 ml/min (p < 0.05) in spite of comparable blood pressure but with higher proteinuria. Linear regression of delta Ccr with the initial and two year averaged values of the quantitative parameters showed a significant positive link for both values with cholesterol, hemoglobin and proteinuria and a negative one with protidemia. A positive link was observed with the initial value of bicarbonate and the two year mean of diastolic and mean blood pressures. No link at all was observed with urea and Na excretion, CaPO4 product and triglycerides. Multiple regression disclosed a significant link only for protidemia (negative with both initial and two years averaged value), diastolic BP (only for the two year averaged value and hemoglobinemia (for the initial value). When the patients were classified according to a threshold value of their protidemia, DBP, hemoglobinemia, and cholesterolemia those with the combination of two risk factors of progression (pro-tidemia < 66 g/l, DBP > or = 90 mmHg, hemoglobinemia > 11 g/dl, proteinuria > 3g/d, CT > 5 mmol/l) had a significantly greater decrease of Ccr than those with the three other combinations at the exception of the association of low protidemia with DBP. CONCLUSION: 1. diastolic hypertension and low protidemia are the two most important factors predicting progression of renal failure; 2. a predictive synergy was furthermore pointed out between on one hand low protidemia and diastolic hypertension and on the other hand proteinuria and cholesterol; 3. on the contrary, anemia attenuates progression linked to low protidemia, diastolic hypertension, proteinuria and high cholesterol.

[Fenofibrate increases blood creatinine, but does not change the glomerular filtration rate in patients with mild renal insufficiency]. / Le fénofibrate augmente la créatininémie mais n'altère pas le débit de filtration glomérulaire chez les patients présentant une insuffisance rénale modérée.

Fenofibrate is a potent hypolipemic agent, widely used in patients with mild to severe renal failure in whom hyperlipoproteinemia is frequent. A moderate reversible increase in creatinine plasma levels has been reported with fenofibrate therapy; however, it is not known whether this increased creatininemia reflects a fenofibrate induced alteration of renal function or if fenofibrate interferes with creatinine tubular handling. We prospectively examined the effect of 2 weeks fenofibrate treatment (200 mg daily) on renal function in thirteen hyperlipidemic patients with normal renal function or mild to moderate renal failure (Creat Cl: 110 to 30 ml/min). This study confirms that fenofibrate therapy significantly increases creatininemia in patients with mild to moderate renal failure (147 +/- 12 versus 170 +/- 15 mmol/l; p = 0.014), but does not alter renal hemodynamic nor glomerular filtration rate as assessed by the stability of PAH (304 +/- 56 versus 311 +/- 49 ml/min; p = NS) and inulin clearances (51.7 +/- 6 versus 52.3 +/- 7 ml/min; p = NS). The increase in creatininemia is neither due to an inhibition of creatinine tubular excretion, since no change in creatinine clearance was observed (69 +/- 8 versus 68 +/- 8 ml/min; p = NS), but appears to be associated to a parallel increase in creatinine daily urinary excretion (13.7 +/- 5 versus 15.4 +/- 4 mmol; p = 0.03). In conclusion, fenofibrate therapy in renal patients does not worsen renal function, nor diminish the reliability of creatinine clearance for its follow-up in spite of a significant rise in creatininemia. The mechanism of the fenofibrate-induced increase in urinary creatinine excretion remains to be determined.

Renal osteodystrophy in dialysis patients: diagnosis and treatment.

This article reviews the clinical, biological, radiological, and pathological procedures and their respective indications for the practical diagnosis of the following various histological patterns of renal osteodystrophy: osteitis fibrosa due to parathyroid hormone (PTH) hypersecretion: osteomalacia or rickets due to native vitamin D deficiency and/or aluminum overload; and adynamic bone disease (ABD) due to aluminum overload and/or PTH secretion oversuppression. Our advice regarding bone biopsy is to restrict it to patients with symptoms and hypercalcemia, especially those who have been previously exposed to aluminum. In other cases, we propose relying merely on the determination of the plasma concentrations of calcium, protide, phosphate, bicarbonate, intact PTH, aluminum, 25(OH)D3, and alkaline phosphatase (total and bony if hepatic disease is associated) to choose the appropriate treatment. Because of the danger of the desferrioxamine treatment necessary to chelate and remove aluminum, the suspicion of aluminic bone disease (osteomalacia or ABD) will always be confirmed by a bone biopsy. In the case of nonaluminic osteomalacia, correction of the vitamin D deficiency by native vitamin D or 25(OH)D3, and of the calcium deficiency and acidosis by alkaline salts of calcium and if necessary sodium bicarbonate are sufficient to cure the disease. In the case of nonaluminic ABD, the stimulation of PTH secretion by the discontinuation of 1alpha hydroxylated vitamin D and the induction of a negative calcium balance during dialysis by decreasing the calcium concentration in the dialysate will allow an increase of the CaCO3 dose to correct for hyperphosphatemia without inducing hypercalcemia. For hyperparathyroidism, i.e., plasma intact PTH levels greater than two- or four-fold the upper limit of normal levels (according to the absence or presence of previous aluminum exposure), the treatment will consist in increasing the CaCO3 dose to correct for hyperphosphatemia together with a decrease of the calcium concentration in the dialysate if the dose of CaCO3 is so high that it induces hypercalcemia. When the hyperphosphatemia has been corrected and there is still a low or normal corrected plasma calcium level, 1alpha(OH)D3 in an oral bolus 2 or 3 times a week should be given at the minimal dose of 1 microg. When the PTH level stays above 400 pg while hypercalcemia occurs and hyperphosphatemia persists, surgical subtotal parathyroidectomy is recommended or the injection of calcitriol into the big nodular hyperplastic parathyroid glands under sonography control in high surgical risk patients. Special recommendations are given for children.

Percutaneous recanalization of occlusion of central and proximal veins in chronic hemodialysis. Technical note.

Occlusion of the central and proximal veins in chronic hemodialysis patients results in considerable edema of the arm of the vascular access that is unable to drain normally. This is a formidable problem because it is very often necessary to close the vascular access, which is sometimes the last available one. To avoid resorting to this disastrous solution, recanalization of the occluded vein by percutaneous recanalization followed by endoluminal angioplasty was successfully performed in five patients (4 innominate veins and one axillary vein). Immediate failure occurred in a sixth patient, and delayed failure after two months of patency (innominate vein) in another patient for whom there had been no systematic stent placement. Recanalization was still patent in four other patients at 3, 6, 12 and 26 months. These results are an encouragement to attempt percutaneous recanalization by angioplasty of occluded central veins because, when successful, this technique makes it possible to preserve the vascular access and to avoid onerous surgery. We believe that this technique should therefore become better known.