No abstract

Background Despite a plethora of studies on the effect of urate-lowering therapy (ULT) in patients with chronic kidney disease (CKD), current guidelines on the treatment of hyperuricaemia and gout vary, especially concerning the need for dose adjustment of allopurinol, whose main metabolite is accumulating with declining renal function. Data on allopurinol dosing and its relationship to renal function, co-medication and sex and the resulting urate level in large cohorts are missing. Methods We studied a subgroup of 2378 patients of the German Chronic Kidney Disease (GCKD) study to determine prescription patterns of ULT among CKD patients under nephrological care and the relationship of ULT dose to urate levels. Prescription and dosing of ULT were manually abstracted from the patient’s paper charts at the baseline visit, in which all currently used medications and their dosing were recorded. Results In this cohort, 39.6% were women, the mean estimated glomerular filtration rate (eGFR) was 51.3 ± 19.3 mL/min/1.73 m2 and the mean age was 59.0 ± 12.4 years. Of the 2378 examined patients, 666 (28.0%) received ULT. The dose of ULT was available for 572 patients. The main ULT agent was allopurinol (94.4%), followed by febuxostat (2.9%) and benzbromarone (2.6%). Of the 540 patients who used allopurinol with a reported daily dose, 480 had an eGFR <60 mL/min/1.73 m2 and 320 had an eGFR <45 mL/min/1.73 m2, 31.5% of the latter (n = 101) received a dose >150 mg/day, the recommended maximal dose for this level of eGFR. The prescribed dose was not related to eGFR: the median eGFR for patients taking 100, 150 and 300 mg/day was 40 [interquartile range (IQR) 32–49], 43 (34–52) and 42 (35–54) mL/min/1.73 m2, respectively. Patients with lower doses of allopurinol had higher serum urate levels than patients with higher (than recommended) allopurinol doses. Sex, alcohol intake, eGFR, use of diuretics and treatment with allopurinol were independent determinants of serum urate levels in multivariate regression analysis. Conclusions The most frequently used drug to lower serum urate levels in this CKD cohort was allopurinol. Even in patients regularly seen by nephrologists, the dose of allopurinol is often not adjusted to the current eGFR. Patients with higher ULT doses achieved better control of their serum urate levels. Lowering of serum urate in CKD patients requires balancing potential adverse effects of allopurinol with suboptimal control of serum urate levels.

Direct reconstruction of an extensive, biomechanically loaded defect with an osteoinductive implant proved to be the superior method. The osseous regeneration observed shows an immediate functional orientation. The necessity for extensive adaptive remodeling is thus minimized.

Urodynamic parameters are changed by stress incontinence surgery. Our study, comparing pre- and postoperative measurements in 141 women with urinary stress incontinence, shows an increase of the transmission ratio in the proximal urethra and a decrease of depression factors in the proximal and mid urethra after surgery. The functional urethral length remains unchanged while the maximum urethral pressure decreases. Except for the maximum pressure decrease, these changes were only found after successful surgery and not in failures. Thus, effectiveness of operations can be quantificated by urodynamic measurements. The unfavourable prognostic influence of a preoperative hypotonic urethra on the results of surgery was confirmed by this study.