Stringent glycaemic control prolongs survival in diabetic patients with end-stage renal disease on haemodialysis

Aim: No suitable index or optimal target for diabetic control has been established for diabetic patients with end‐stage renal disease (ESRD) undergoing haemodialysis. To address these issues, the single‐centre observational study was conducted. Methods: Two hundred and forty‐five diabetic ESRD patients (23.3% female; age at initiation of haemodialysis 61.7 ± 10.7 years) at start of haemodialysis between 1 January 1995 and 31 December 2004 were enrolled. Subjects were grouped according to glycaemic control level throughout the observational period as follows: mean postprandial plasma glucose (PPG) <8.9 mmol/L, 8.9 mmol/L ≤ PPG < 10.0 mmol/L, 10.0 mmol/L ≤ PPG < 11.1 mmol/L, 11.1 mmol/L ≤ PPG < 12.2 mmol/L and PPG ≥ 12.2 mmol/L; and HbA1c < 6.0%, 6.0–6.4%, 6.5–6.9% and ≥7.0%. Survival was then followed until 31 December 2005. Results: Cumulative survival of groups of 10.0 mmol/L ≤ PPG < 11.1 mmol/L, 11.1 ≤ PPG < 12.2 and PPG ≥ 12.2 mmol/L was significantly lower than that for PPG < 8.9 mmol/L as determined by Kaplan–Meier estimation (P = 0.016, 0.009 and 0.031, respectively; log–rank test). In both uni‐ and multivariate Cox proportional hazard models, mortality hazard ratios were significantly higher for PPG ≥ 10.0 mmol/L than for PPG < 8.9 mmol/L (P = 0.002–0.021). Kaplan–Meier survival curves grouped by HbA1c levels showed no correlation between HbA1c and survival during the observational period. No significant difference in mortality hazard ratios was seen for any HbA1c groups evaluated by Cox proportional hazard model. Conclusion: Intensive management of diabetic control at a stringent mean on‐study PPG < 10.0 mmol/L will improve the life expectancy in diabetic dialysis patients. However, no range of HbA1c values obtained in this study showed any clear difference in clinical outcomes.     

Better recovery of kidney function in patients with de novo chronic kidney disease after partial nephrectomy compared with those with pre‐existing chronic kidney disease

We compared kidney functional recovery between patients with pre‐existing chronic kidney disease, those with de novo chronic kidney disease and those with normal kidney function, after partial nephrectomy. A total of 311 patients who underwent partial nephrectomy at Tokyo Women's Medical University Hospital, Tokyo, Japan, between January 2004 and July 2011 with sufficient kidney functional data participated in the study. Patients with pre‐existing chronic kidney disease (group1: 78 patients) were defined as those with estimated glomerular filtration rate under 60 mL/min/m² before partial nephrectomy. Patients with de novo chronic kidney disease (group 2: 49) were defined as those with estimated glomerular filtration rate over 60 mL/min/m² before surgery and who developed estimated glomerular filtration rate under 60 mL/min/m² 3 months after partial nephrectomy. Normal patients (group 3: 184) were defined as those with estimated glomerular filtration rate over 60 mL/min/m² both before and after partial nephrectomy. Group 1 was associated with older age and higher comorbidity, including hypertension and diabetes mellitus, compared with other groups. R.E.N.A.L. score was not significantly different between the groups. Although the percent change of estimated glomerular filtration rate between the preoperative period and 3 months after partial nephrectomy in group 2 was significantly decreased compared with that in other groups (group 1: ?6.8%, group 2: ?18%, group 3: ?7.3%), the renal functional recovery between 3 and 12 months after partial nephrectomy in group 2 was better than that in other groups (group 1: ?0.5%, group 2: 5.6%, group 3: ?0.4%). Patients with de novo chronic kidney disease had better kidney functional recovery than the other two groups, which might suggest that they were surgically assaulted and developed chronic kidney disease in the early postoperative period, and were essentially different from those with pre‐existing chronic kidney disease.     

慢性肾脏病患者24小时动态血压的特点分析

目的采用24h动态血压监测的方法,分析慢性肾脏病（CKD）不同分期患者24h动态血压特点。方法将152例CKD患者分为5组：CKD1期组（A组）15例;CKD2期组（B组）29例;CKD3期组（C组）42例;CKD4期（D组）组34例;CKD5期组（E组）32例。所有患者均无糖尿病、非肾脏替代治疗。采用携带式的动态血压检测仪测定各组患者动态血压参数和昼夜节律。结果①随着肾功能下降,24h、日间和夜间平均收缩压越来越高;②CKD患者总体非杓型血压比例为81．6o,4,肾功能下降组（CKD2～5期）非杓型血压比例显著高于肾功能正常组（CKD1期）;③夜间收缩压与24h尿蛋白定量呈正相关（r=0．427,P〈0．01）,与。肾小球滤过率（GFR）呈负相关（r=-0．352,P〈0．05）。结论CKD患者的血压非杓型节律现象比较普遍,并随着肾功能下降,其发生率逐渐升高;夜间收缩压与尿蛋白排泄、肾功能有相关性。     

慢性肾脏病患者心血管钙化的影响因素分析

慢性肾脏病(chronic kidney disease,CKD)患者因高龄、高血压、高血脂、糖尿病、吸烟、男性等传统心血管钙化危险因素,加上CKD特有因素:矿物质代谢紊乱、含钙磷结合剂及活性维生素D的不合理使用、微炎症状态、氧化应激等常引起严重的心血管钙化,病情进一步发展会加速心血管事件的发生,影响CKD患者的预后。使用磷结合剂、活性维生素D及其类似物、西那卡塞等药物控制高钙、高磷、高PTH对预防心血管钙化至关重要。药物治疗无效或在治疗过程中出现不能控制的矿物质代谢异常,则要考虑手术切除甲状旁腺。甲状旁腺切除术(parathyroidectomy,PTX)作为难治性继发性甲状旁腺功能亢进患者的有效治疗之一,可迅速降低甲状旁腺素(parathyroid hormone,PTH)和血清钙磷水平,减少活性维生素D等药物的使用,缓解骨痛、瘙痒、肌无力等症状,但PTX后是否可以减轻心血管钙化?术后长期的低PTH状态与心血管钙化的关系如何?目前还没有明确的结论,本文就CKD患者心血管钙化的影响因素,尤其是PTX对CKD患者心血管钙化的影响作一综述。     

Early kidney transplantation improves neurocognitive outcome in patients with severe congenital chronic kidney disease

Renal replacement therapy has become available for the majority of patients suffering from severe congenital chronic kidney disease (CKD). Data on the long‐term neurocognitive outcome and the impact of early kidney transplantation (KTx) in this setting is unclear. Neurocognitive outcomes in 15 patients (11 male) with isolated congenital CKD (stage 3–5) requiring KTx at a mean age of 2.8 ± 1.3 were assessed at a mean age of 8.3 ± 1.4 years. Patients underwent neurological examination and testing for neuromotor and neurocognitive function using three independent tests. Pre‐emptive KTx was performed in six patients, and nine patients were dialyzed prior to KTx for a mean period of 11.1 ± 8.6 months. Neuromotor function was abnormal in 8/15 patients. HAWIK‐III showed a global intelligence quotient (IQ) of 93.5 ± 11.4 (P = 0.05) due to a significantly reduced performance IQ of 89.1 ± 11.3 (P < 0.01). In three patients, the global IQ was clinically significantly reduced by >1 SD to <85. In patients with neuromotor dysfunction, performance IQ was lower than in patients with normal neuromotor function (83.8 ± 10.2 vs. 96.2 ± 9.0, P = 0.04). Time on dialysis was inversely correlated to verbal IQ (r = 0.78, P = 0.02). Pre‐emptive KTx and duration of dialysis treatment <3 months was associated with superior neurocognitive outcome. Early (pre‐emptive) KTx results in superior long‐term neurocognitive outcome in children with severe congenital CKD.     

慢性肾脏疾病患者左室结构及功能改变的超声评价

目的：应用超声心动图评价慢性肾脏疾病（CKD）患者左室结构及功能改变,探讨不同程度CKD患者左室改变情况。方法：对CKD非透析患者39例（CKD2～3期组19例,CKD4～5期组20例）及对照组40例进行常规肾脏扫查及超声心动图检查,通过二维超声观察CKD患者肾脏形态结构、实质回声、皮髓质分界、血流信号改变;通过超声心动图获得左室结构参数：左房内径（LAD）、左室舒张末期内径（I。VID）,左室质量指数（LV—MI）、左室相对室壁厚度（RWT）;左室功能参数：左室射血分数（EF）、二尖瓣口舒张早期血流速度E峰、晚期A峰、E／A、舒张早期二尖瓣环运动速度Em,E／Era。结果：①CKD2～3期组19例患者中6例患者肾脏声像图有明显改变,CKD4～5期组中18例患者肾脏声像图有显著改变;②与正常组比较,cKD2～3期组LVM、RWT、LAD均显著增高,CKD4～5期组LVID、LVMI、E、A、E／Em增高,DTE、E／A、Em减低,与CKD2～3期组比较,CKD4～5期组LVM、RWT、LAD、LVID、LVMI、E、A、EjEm显著增加,DTE显著减低,E／A、Em无明显差异;③CKD2～3期组中有5例左室重构（26．3％）,CKD4～5期组患者中有17例左室壁重构（85％）。结论：早中期CKD患者其肾脏结构二维超声改变不明显,而超声心动图能早期检测到CKD患者左室构型及左室舒张功的改变,为临床上该病治疗及心血管并发症的预防提供有价值的参考信息。     

Febuxostat for treating allopurinol-resistant hyperuricemia in patients with chronic kidney disease

Background: Availability of the novel xanthine oxidase inhibitor febuxostat, which has multiple excretion pathways, enables investigation of the significance of serum uric acid control on renal function in patients with chronic kidney disease (CKD). Methods: This was an exploratory, retrospective, observational study conducted at a single Japanese center. Serum uric acid concentrations and serum creatinine levels in the 6 months before and after the start of febuxostat treatment were collected for CKD patients switched from allopurinol after failing to achieve serum uric acid concentrations ≤6.0?mg/dL. Results: Evaluable data were available for 60 patients, 67% of whom had advanced CKD (eGFR <30?mL/min/1.73?m²). Mean dose of febuxostat was 15.9 (±?8)?mg/day. Mean serum uric acid concentration decreased from 8.4 (±1.4) mg/dL at baseline to 6.2 (±1.2)?mg/dL at 6 months; 47.5% of patients achieved a level ≤6.0?mg/dL. The change from baseline in eGFR was positive at all time points during febuxostat treatment and the increase of 2.3 (±5.6)?mL/min/1.73?m² at 6 months was significant (p?=?0.0027). Whereas the eGFR slope was negative during allopurinol treatment, it became positive after the switch to febuxostat. The change in eGFR slope before and after febuxostat treatment was significant for all patients (p?p?2 (p?Conclusions: In patients with CKD, febuxostat reduces serum uric acid concentrations effectively and may suppress the progressive decline in renal function.     

Quality of sleep in patients with chronic kidney disease.

BACKGROUND: Sleep disorders are common in patients with renal failure on dialysis; however, the prevalence of "poor sleep" in patients with chronic kidney disease (CKD) not yet on dialysis is not known. This study aimed to measure the prevalence of "poor sleep" in CKD patients and to examine the association between quality of sleep and the degree of renal impairment in this population. METHODS: Quality of sleep was measured using the Pittsburgh Sleep Quality Index (PSQI) in 120 prevalent CKD patients. RESULTS: Sixty-three subjects (53%) had "poor sleep" defined as a global PSQI score >5. There was no statistically significant relationship between the global PSQI score and the blood urea nitrogen level (BUN), serum creatinine level or calculated creatinine clearance, but the sleep efficiency component score correlated with BUN (r = 0.19, P = 0.04) and serum creatinine (r = 0.20, P = 0.03). A history of depression was the only independent predictor of "poor sleep" (global PSQI >5). CONCLUSIONS: "Poor sleep" is common in CKD patients. Quality of sleep decreases in the early stages of CKD and does not appear to be associated with the subsequent degree of renal failure. Large prospective longitudinal studies of quality of sleep in CKD patients are needed to confirm the high prevalence of impaired quality of sleep in this population and examine the association between renal function and quality of sleep while controlling for potential confounding variables.     

Haemodynamic and renal effects of endothelin receptor antagonism in patients with chronic kidney disease.

BACKGROUND: Endothelin-1 (ET-1) has been implicated in the pathophysiology of chronic kidney disease (CKD) and ET receptor blockade has shown renoprotective effects in animals. We examined the haemodynamic and renal effects of an ET receptor antagonist, TAK-044, in patients with CKD. METHODS: Seven patients with CKD (mean arterial pressure 103 mmHg; mean plasma creatinine 3.5 mg/dl) received three 15 min intravenous infusions, each separated by at least 7 days, of either placebo or TAK-044 (100 or 750 mg) in a randomized, double blind crossover study. Systemic and renal haemodynamics, and plasma immunoreactive ET-1, big ET-1 and C-terminal fragment concentrations, were determined before and after the infusions of placebo and drugs. RESULTS: Compared with placebo, TAK-044 reduced mean arterial pressure (MAP) (100 mg: 7.4 +/- 1.9 mmHg, 750 mg: 8.4 +/- 2.3 mmHg, P < 0.01) and systemic vascular resistance index (100 mg: 650 +/- 140 dyne.s.cm(-5).m(-2), 750 mg: 829 +/- 141 dyne.s.cm(-5).m(-2), P < 0.01) at both doses. TAK-044 increased cardiac index and heart rate to a similar degree at both doses. With regards to renal haemodynamics, TAK-044 had no significant effect on the glomerular filtration rate at either dose but tended to increase renal plasma flow (100 mg: 9.6 +/- 5.0 ml/min, 750 mg: 25.3 +/- 19.5 ml/min) and decreased the effective filtration fraction (100 mg: 3.6 +/- 1.1%, 750 mg: 4.7 +/- 1.7%, P < 0.01), in a dose-dependent manner. TAK-044 had no significant effect on sodium or lithium clearance, or on fractional excretion of sodium and lithium. Plasma ET-1 concentrations rose more than two-fold after 750 mg TAK-044 while big ET-1 and C-terminal fragment concentrations were unchanged. CONCLUSIONS: These findings suggest an important role for ET-1 in controlling systemic and renal haemodynamics in patients with CKD. The antihypertensive and potentially renoprotective actions of ET receptor antagonists shown in this study may prove useful in slowing the progression of CKD. Clinical trials are now needed to address these key questions for CKD.     

Hematopoietic stem cell transplantation in patients with chronic kidney disease

Patients with significant medical comorbidities such as chronic kidney disease (CKD) traditionally have been excluded from hematopoietic stem cell transplantation (HSCT) because of unacceptably high transplant-related morbidity and mortality, an exclusion that can have enormous consequences for patients with CKD from myeloma in particular. Much of the excess HSCT-related morbidity among CKD patients relates to the toxic effects of conditioning regimens, which have a narrow therapeutic index even in patients with normal renal function. Common posttransplant complications are more challenging to prevent and manage in patients with CKD. In selected centers, autologous HSCT is performed with some frequency in patients with advanced CKD and even dialysis-dependent end-stage renal disease (ESRD), with acceptable outcomes, but cure from malignancy rarely is obtained. Allogeneic transplants using reduced-intensity conditioning regimens are being used with increasing frequency in patients with CKD, for both nonmalignant and malignant conditions, relying in the latter case on a graft-versus-malignancy effect to eliminate residual malignancy. In patients with ESRD from myeloma who have suitable donors, simultaneous allogeneic HSCT and kidney transplantation from a human leukocyte antigen-identical sibling provides the opportunity to treat both the malignant condition and the ESRD, avoiding the risks of posttransplant care in a dialysis-dependent patient and freeing the patient of the subsequent burdens of both ongoing dialysis and immunosuppression.     

Prevalence and risk factors of chronic kidney disease in first-degree relatives of chronic kidney disease patients in Southern China

Aim: The aim of this study was to estimate the prevalence and risk factors of chronic kidney disease (CKD) in first‐degree relatives (FDRs) of CKD patients. Methods: A cross‐section study of first‐degree relatives of CKD patients was conducted between November 2007 and March 2009 in southern China. A total of 1187 first‐degree relatives (494 male and 693 female; mean age 41.26 years) of 419 CKD patients (194 male and 225 female; mean age 32.10 years) were reviewed and tested for haematuria, albuminuria and reduced glomerular filtration rate. CKD risk factors, including age, gender, body mass index, hypertension and the causes of index case were also investigated. CKD was diagnosed according to the criteria of the National Kidney Foundation‐Kidney Disease Outcomes Quality Initiative. Results: The prevalence of CKD in first‐degree relatives of CKD patients was 29.7% (95% confidence interval [CI]: 27.1%–32.2%). After adjusting for all the potential confounders, older age, female gender, hypertension, hyperglycaemia, hyperuricaemia, hypertriglyceridemic, low level of high density lipoproteins, increased body mass index and nephrotoxic medications were independently associated with increased risk of CKD. Furthermore, relatives of index cases with chronic glomerulonephritis were at higher risk haematuria (ORs = 2.12, 95% CI: 1.45–3.10) compared with relatives of index cases with other kinds of renal diseases. Conclusion: The first‐degree relatives of CKD patients are at high risk of CKD, especially those relatives of CKD patients with chronic glomerulonephritis. Screening in this high risk population might help to identify early CKD patients and make a proper intervention strategy to prevent the disease from quick progression.     

The comparison of the diuretic and natriuretic efficacy of continuous and bolus intravenous furosemide in patients with chronic kidney disease

Aim: To compare natriuretic, kaliuretic, diuretic and free water clearance efficacy of continuous versus bolus intravenous furosemide administration in patients with chronic renal insufficiency. Material and methods: In a prospective randomized cross‐over trial, 42 patients of chronic renal insufficiency were randomized to receive the same dose of intravenous furosemide as bolus and continuous infusion. The effects of bolus and intravenous administration of furosemide on the volume of urine, sodium and potassium excretion were assessed. Results: Mean age was 53.6 ± 14 years and 23 (55%) were male. The mean modification of diet in renal disease glomerular filtration rate was 20.5 ± 17 mL/min per 1.73 m². The urinary excretion of sodium in intravenous bolus and infusion was 98.1 ± 78 and 114.4 ± 100 mmol, respectively (P = 0.001). Total urinary volume following bolus and infusion of furosemide was 1064 ± 627 and 1170 ± 764 mL, respectively (0.001). The excretion of potassium was similar in bolus (15.8 ± 16.6) and infusion (14.3 ± 9) administration (P = 0.11). The fractional excretion of sodium was higher following infusion (16.63 ± 16.1) than bolus administration (12.87 ± 9) of furosemide (P = 0.016). Conclusion: Continuous intravenous infusion of furosemide has significantly better natriuretic and diuretic effect than bolus administration of the same dose of the drug in patients with advanced chronic renal insufficiency.     

The impact of glycaemic control on outcomes in patients with end-stage renal disease and type 2 diabetes

SUMMARY:   In Australia and New Zealand the prevalence and incidence of end-stage renal disease (ESRD) has increased. In Australia alone the financial burden is estimated to reach $500 million by 2007 (data from the National Chronic Kidney Disease Strategy Workshop Report 2005). The leading cause of ESRD in Australia and New Zealand, and throughout the developed world, is type 2 diabetes, having overtaken glomerulonephritis in 2004. ¹ To date, management of patients with diabetes and ESRD has been, according to guidelines, given for patients without ESRD. This commentary raises three important emerging concerns in the clinical care of these patients: (i) the lack of reliable tools to measure glycaemic control; (ii) limitations of the current data set supporting a relationship between outcome and glycaemic control in ESRD; and (iii) lack of studies examining the effect of intensive diabetes care and glucose control in patients with ESRD.     

Monogenic causes of chronic kidney disease in adults

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