The importance of standardization of creatinine in the implementation of guidelines and recommendations for CKD: implications for CKD management programmes.

BACKGROUND: In an attempt to reduce late referral and to improve the care of patients with chronic kidney disease (CKD), different organizations have issued guidelines on when to refer patients to the nephrologist. Most suggest referral of patients with a GFR below 60 ml/min/1.73 m2, and demand referral if the GFR is below 30 ml/min/1.73 m2. It is recommended to use the abbreviated MDRD equation to estimate GFR. This formula is, however, sensitive to the creatinine assay methodology. In addition, the impact of the implementation of such guidelines on the nephrology practice has never been evaluated. This study (i) identifies the true burden of CKD in a population and simulates the effects of a 100% implementation of the guidelines on the nephrology work load, and (ii) evaluates the validity of the estimated GFR using the abbreviated MDRD formula when routinely provided. METHODS: Different laboratories (both hospital and private) in our region were asked to report on all the serum creatinine values performed during the first week of December 2004. If patients had more than one determination, only the lowest serum creatinine value was retained. Patients already known to a nephrology unit were not included. GFR was calculated using the abbreviated MDRD, using the serum creatinine as reported by these laboratories, or after correction to the MDRD-standard using different published equations. RESULTS: 20,108 patients, with a mean age of 53.4+/-16.2 years, 48% females, had at least one serum creatinine determination in the observation period. According to the K/DOQI CKD classification, 20.2, 1.6 and 0.8% of females and 13.3, 1.6 and 0.6% of males were in stage 3, 4 and 5, respectively, when the abbreviated MDRD formula was used with the serum creatinine value as reported by the laboratories. Important differences in classifications were obtained when the different correction formulae for creatinine were applied. According to the current recommendations, this would lead to a mandatory referral of 1650-2400 CKD stage 4 patients per 100 000 inhabitants and a suggested referral of another 4100-15 360 CKD stage 3 patients per 100,000 inhabitants to a nephrology unit. CONCLUSION: Implementation of the current guidelines for referral of CKD patients to nephrologists would lead to an overload of the nephrology care capacities. Large differences in estimated GFRs with different corrections for serum creatinine are observed, resulting in important CKD classification differences. Standardization of serum creatinine assays is mandatory before guidelines, and especially the routine provision of the estimated GFR by the abbreviated MDRD formula, can be implemented in clinical practice.     

Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand

Benign intracranial hypertension (BIH) is reported in three children from Australia and one from New Zealand, who were being treated with recombinant human growth hormone (rhGH). Three males and one female, aged between 10.5 and 14.2 y, developed intracranial hypertension within 2 weeks to 3 months of starting treatment. A national database, OZGROW, has been prospectively collecting data on all 3332 children treated with rhGH in Australia and New Zealand from January 1986 to 1996. The incidence of BIH in children treated with growth hormone (GH) is small, 1.2 per 1000 cases overall, but appears to be greater with biochemical GHD (<10IUml ^-1), i.e. 6.5/1000 (3 in 465 cases), relative risk 18.4, 95% confidence interval 1.9-176.1, than in all other children on the database. The incidence in patients with Turner's syndrome was 2.3/1000 (1 in 428 cases). No cases in patients with partial GHD (10–20 IUml ^-1) or chronic renal failure were identified. Possible causative mechanisms are discussed. The authors'practice is now to start GH replacement at less than the usual recommended dose of 14IUm-² week^-1 in those children considered to be at high risk of developing BIH. Ophthalmological evaluation is recommended for children before and during the first few months following commencement of rhGH therapy and is mandatory in the event of peripheral or facial oedema, persistent headaches, vomiting or visual symptoms. The absence of papilledema does not exclude the diagnosis.     

Iotrol versus metrizamide in lumbar myelography: a double-blind study

In a prospective, randomized, double-blind study, 49 patients underwent lumbar myelography using iotrol (24 patients) or metrizamide (25 patients). The diagnostic imaging adequacy of iotrol was comparable with that of metrizamide. After iotrol myelography, adverse reactions were fewer, less severe, and of shorter duration than were those following metrizamide myelography. Thirteen of 24 patients (54%) receiving iotrol reported some adverse reactions compared with 24 of 25 patients (96%) receiving metrizamide. Five moderate and one severe adverse reaction occurred in the group receiving iotrol. Fourteen moderate and eight severe adverse reactions occurred in the group receiving metrizamide. Thirty-eight patients underwent electroencephalography both before and after myelography (19 iotrol and 19 metrizamide). None of the EEGs obtained after iotrol myelography changed from baseline, while seven of the EEGs obtained after metrizamide myelography showed changes from baseline. Iotrol was judged superior to metrizamide as a contrast medium in this patient population.     

The effect of sodium lauryl sulphate on the expression of cytokeratin mRNA in hamster cheek pouch epithelium

The effect of sodium lauryl sulphate (SLS) on cytokeratin (CK) gene expression in hamster cheek pouch epithelium was studied with a hybridohistochemical technique. Using specific human anti-sense RNA probes, the plausible hamster mRNA counterparts for these human CK mRNAs were localized by detection of heterologous hybrids. In comparison with normal epithelium, the expression and distribution pattern of CK mRNAs in the hamster cheek pouch were obviously changed after application of SLS. There was a decreased expression of CK mRNAs in the hyperplastic basal layer, and increased expression in the hypertrophic granular layer. Strikingly, hybridization with the human CK 18 cRNA probe revealed an additionally expressed CK mRNA in the SLS-treated epithelium that was not found in the untreated epithelium. The present study indicates that cRNA probes for human CK mRNAs can be used successfully, not only to distinguish between different hamster CK mRNAs but also to investigate changes in CK gene expression upon the induction of non-neoplastic and neoplastic alterations in the hamster cheek pouch model. This may help elucidate the molecular changes involved in epithelial pathologies.     

Sulfasalazine treatment in juvenile chronic arthritis: an open study.

In an open study, the effect of sulfasalazine was evaluated in the treatment of juvenile chronic arthritis (JCA). Forty-one patients, i.e., 27 boys and 14 girls with JCA under 16 years of age, were included in the study. In all of them, treatment with nonsteroidal antiinflammatory drugs (NSAID) had been unable to control the disease. The patients were divided in 4 subgroups depending on the mode of onset and evolution (Type I = systemic onset, Type II = polyarticular form. Type IIIa and Type IIIb = pauciarticular form). Remission was achieved in 21 patients, significant improvement in 12. Status was unchanged in 4 patients and worsened in 3. In 5 patients side effects were observed, which forced interruption of treatment in 4. Sulfasalazine was stopped in 7 patients: for toxicity in 4 and for inefficacy in 3. In 7 other patients the treatment was terminated after a prolonged remission. These promising results must be confirmed in a double blind versus placebo study, preferably restricted to type III JCA.     

臂丛神经根性损伤膈神经移位术对青壮年患者早期呼吸功能的影响

目的研究臂丛神经损伤膈神经移位术对青壮年患者早期呼吸功能的影响.方法对16例接受膈神经移位治疗的患者,在术前、术后（10 d）进行肺功能指标的比较,同时定期进行门诊随访,观察呼吸系统自觉症状程度.结果13例术后出现了不同程度的供氧不足症状,16例全部出现一侧膈肌抬高,术后第10天肺活量（VC）、肺活量预计值百分数（VC%）分别比术前减少37.98%和26.88%,两者差异有统计学意义（tvc=11.532、tvc%=0,P＜0.01）.其它项目如残气量（RV）较术前轻度下降,肺总量（TLC）下降值达到术前肺总量的36.49%,残气量/肺总量比值（RV/TLC%）较术前上升了4.75%,上述各指标的差值均有统计学意义.1 s用力呼气量/用力肺活量比值（FEV1/FVC）和术前比基本无改变,但其差值有统计学意义.膈神经移位右侧（10例）与左侧（6例）术前、术后肺活量比较差异有统计学意义.术后随访8个月～2年,所有患者均无明显呼吸困难和胸闷等症状.结论膈神经移位术后对青壮年患者肺容量有较大的丧失,肺通气功能减弱和小气道阻力增加,但其丧失程度在机体自身代偿耐受范围内,不会导致急剧发生的严重呼吸功能障碍.建议对右侧臂丛神经根性损伤的患者,术前进行严格的肺、心功能检查,避免发生较为严重的并发症.