Adverse events associated with currently used medical treatments for cystinuria and treatment goals: results from a series of 442 patients in France.

OBJECTIVE: To evaluate medical treatments, in terms of adverse events (AEs) and therapeutic goals, in a large series of patients with cystinuria. PATIENTS AND METHODS: Data from 442 patients with cystinuria were recorded retrospectively. Crystalluria was studied in 89 patients. A mixed-effects logistic regression model was used to estimate how urine pH, specific gravity and cysteine-binding thiols (CBT) correlate with risk of cystine crystalluria. RESULTS: Alkalizing agents and CBT agents were given to 88.8% (n = 381) and 55.3% (n = 238) of patients, respectively. Gastrointestinal AEs were reported in 12.3%, 10.4% and 2.6% of patients treated with potassium bicarbonate, potassium citrate and sodium bicarbonate, respectively (P = 0.008). The percentages of patients who experienced at least one AE with tiopronin (24.6%) and with D-penicillamine (29.5%) were similar (P = 0.45). Increasing urine pH and decreasing urine specific gravity significantly reduced the risk of cystine crystalluria, whereas D-penicillamine and tiopronin treatments did not reduce this risk (odds ratio [OR] 1 for pH ≤6.5; OR 0.52 [95% confidence interval {95% CI} 0.28-0.95] for 7.0 8.0, P <0.001). CONCLUSION: Adverse events were frequent with D-penicillamine and tiopronin. Alkaline hyperdiuresis was well tolerated and reduced cystine crystalluria. Urine specific gravity ≤1.005 and urine pH >7.5, while warning about calcium-phosphate crystallization, should be the goals of medical therapy.

CKD and Its Risk Factors among Patients with Cystinuria.

BACKGROUND AND OBJECTIVES: Cystinuria is an autosomal recessive disorder affecting renal cystine reabsorption; it causes 1% and 8% of stones in adults and children, respectively. This study aimed to determine epidemiologic and clinical characteristics as well as comorbidities among cystinuric patients, focusing on CKD and high BP. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective study was conducted in France, and involved 47 adult and pediatric nephrology and urology centers from April 2010 to January 2012. Data were collected from 442 cystinuric patients. RESULTS: Median age at onset of symptoms was 16.7 (minimum to maximum, 0.3-72.1) years and median diagnosis delay was 1.3 (0-45.7) years. Urinary alkalinization and cystine-binding thiol were prescribed for 88.8% and 52.2% of patients, respectively, and 81.8% had at least one urological procedure. Five patients (1.1%, n=4 men) had to be treated by dialysis at a median age of 35.0 years (11.8-70.7). Among the 314 patients aged ≥16 years, using the last available plasma creatinine, 22.5% had an eGFR≥90 ml/min per 1.73 m(2) (calculated by the Modification of Diet in Renal Disease equation), whereas 50.6%, 15.6%, 7.6%, 2.9%, and 0.6% had an eGFR of 60-89, 45-59, 30-44, 15-29, and <15, respectively. Among these 314 patients, 28.6% had high BP. In multivariate analysis, CKD was associated with age (odds ratio, 1.05 [95% confidence interval, 1.03 to 1.07]; P<0.001), hypertension (3.30 [1.54 to 7.10]; P=0.002), and severe damage of renal parenchyma defined as a past history of partial or total nephrectomy, a solitary congenital kidney, or at least one kidney with a size <10 cm in patients aged ≥16 years (4.39 [2.00 to 9.62]; P<0.001), whereas hypertension was associated with age (1.06 [1.04 to 1.08]; P<0.001), male sex (2.3 [1.3 to 4.1]; P=0.003), and an eGFR<60 ml/min per 1.73 m(2) (2.7 [1.5 to 5.1]; P=0.001). CONCLUSIONS: CKD and high BP occur frequently in patients with cystinuria and should be routinely screened.

Prognostic survival factors in elderly renal failure patients treated with peritoneal dialysis: a nine-year retrospective study.

BACKGROUND: Few studies specifically investigating elderly patients on peritoneal dialysis (PD) have been conducted and great uncertainty remains on the factors involved in the vital prognosis. The objective of this study was to describe our population of patients aged 75 years or older at the time PD was initiated and to study their survival in terms of the relevant nephro-geriatric criteria inventoried at the beginning of treatment. METHODS: We retrospectively analyzed the data of all the elderly patients that began first-line PD in our center between 1 January 1997 and 31 July 2006 (n = 112). RESULTS: Mean duration of survival on PD was 19.6 +/- 13.9 months; by the end of the study 87 patients had died and 7 had been transferred to hemodialysis. The Cox model multivariate analysis of survival allowed us to select 5 independent predictive variables that had a considerable impact on survival: absence of nephrologic care before dialysis, associated comorbidities (Charlson Comorbidity Index), loss of physical and/or mental autonomy (AGGIR group), and polymedication. Above and beyond the weight of these clinical variables, institutionalization or, more generally, social isolation was a determining factor for the duration of survival in PD. CONCLUSION: Any patient considered for peritoneal dialysis should be evaluated by a multidisciplinary team in collaboration with geriatric specialists for both the overall medical situation and the social and family environment.

[Delayed measurement of PTH in patients with CKD: storage of the primary tube in the dialysis unit, which temperature? Which kind of tube?]. / Conservation du tube primaire sur le site de dialyse en vue du dosage différé de la PTH : quels tubes ? Quelle température ?

Parathyroid hormone (PTH) is measured in patients with chronic kidney disease (CKD) to evaluate the spread of secondary hyperparathyroidism and to identify renal osteodystrophy subtypes. An important intermethod variability that can significantly influence the clinical decision has been highlighted recently. Similarly, it is acknowledged that the preanalytical conditions are important to optimize the interpretation of a PTH level by comparison with the K/DOQI guidelines. Considering the frequent case of a dialysis patient in whom blood is handled in the evening and addressed to the clinical laboratory the next morning, we have evaluated the stability of the PTH concentration during a 18-hour period. We thus measured PTH with three automated assays in three kinds of tubes (plain tubes with a gel separator, EDTA tubes, EDTA+aprotinin tubes) which were either immediately centrifugated with a prompt freezing of the serum or plasma, or stored for 18hours at room temperature or at 4 degrees C. Our results demonstrate that, whatever the kind of tube, the PTH concentration is not altered by a 18-hour storage at 4 degrees C which is not the case at room temperature. Using a tube with a gel separator necessitates however to centrifugate the tube in the dialysis unit. On the other hand, the use of serum, by contrast with EDTA plasma, allows the measurement of other biological parameters including calcium, does not need that the tube is fully filled and, according to our results, reduces the intermethod variability. In conclusion, this study shows that the measurement of PTH may be delayed by 18hours if the primary tube is kept at 4 degrees C. Assuming that the primary tube is centrifugated but not opened in the dialysis unit, serum may be the sample of choice for the measurement of PTH in patients with CKD.

Low-density lipoprotein apheresis in children with familial hypercholesterolemia: follow-up to 21 years.

Twenty-seven patients (14 girls, 13 boys) affected by familial hypercholesterolemia who had begun low-density lipoprotein (LDL) apheresis treatment before the age of 15 were studied. The median age at diagnosis was 4 years and the blood LDL cholesterol level was 704 +/- 163 mg/dL. Screening was performed for homozygous or double heterozygous mutations of the LDL cholesterol receptor gene and mutations were found in 24 of the patients. The mean age at the beginning of treatment was 8.5 years and the mean length of follow up was 12.6 years. The two main procedures used were direct adsorption of lipoproteins and dextran sulfate cellulose adsorption. Nine patients experienced anaphylactic reactions due to bradykinin and six had to have their treatment changed. The LDL cholesterol level before the session was lowered by 45 +/- 11% of the value at diagnosis. The LDL cholesterol reduction in a session was 72 +/- 10%. Tendinous xanthomas disappeared or diminished dramatically in 62% of the children. In 22 patients no cardiovascular event occurred during LDL apheresis treatment. Three had angina pectoris; two others had surgical management of aortic stenosis, but no clinical manifestations. Seven children had normal cardiovascular pictures while on treatment. Eleven had abnormalities of the aortic root or coronary arteries, which in six cases had appeared before treatment; the other five children did not undergo prior cardiac evaluation. In five children the abnormalities appeared during treatment. Based on these data, LDL-apheresis can be recommended for the treatment of homozygous familial hypercholesterolemia, even in young children, with good efficiency on biological parameters, cutaneous lesions and cardiovascular events.