Relatives in silent kidney disease screening (RISKS) study: A Chinese cohort study.

AIM: Family members of patients with end-stage renal disease (ESRD) have higher risk for chronic kidney disease (CKD). Limited study has examined the risk of developing CKD in relatives of patients in earlier stages of CKD. METHODS: From January 2008 to June 2009, the Hong Kong Society of Nephrology studied first-degree relatives of stage 1-5 CKD patients from 11 local hospitals. A total of 844 relatives of 466 index CKD patients (stages 1-2: 29.6%; stage 3: 16.7%; stage 4: 10.9%; stage 5: 42.7%) were reviewed for various risk factors of CKD. We also defined a composite marker of kidney damage by the presence of one or more following features: (i) positive urine protein, (ii) spot urine protein-to-creatinine ratio ≥0.15 mg/mg, (iii) hypertension and (iv) estimated glomerular filtration rate (eGFR) ≤60 mL/min per 1.73 m2 and determine its association with participant and index patient factors. RESULTS: Among these 844 relatives, 23.1%, 25.9% and 4.4% of them had proteinuria (urine protein ≥1+), haematuria (urine red blood cell ≥1+) and glycosuria (urine glucose ≥1+), respectively. Proteinuria (P = 0.10) or glycosuria (P = 0.43), however, was not associated with stages of CKD of index patients. Smoking participants had a significantly lower eGFR (102.7 vs. 107.1 mL/min per 1.73 m2 ) and a higher prevalence of proteinuria (33.6% vs. 21.4%). Multivariate analysis showed that older age, male gender, obesity, being parents of index patients and being the relatives of a female index patient were independently associated with a positive composite marker. CONCLUSION: First-degree relatives of all stages of CKD are at risk of developing CKD and deserve screening. Parents, the elderly, obese and male relatives were more likely to develop markers of kidney damage.

Hepatocellular carcinoma after kidney transplantation: analysis of Hong Kong Renal Registry.

Kidney transplant recipients have increased risk of cancers when compared with the general population. Hepatocellular carcinoma (HCC) is extremely important in Asia where hepatitis B virus (HBV) infection is endemic. The aim is to study the epidemiological and clinical aspects of all de novo HCC in our kidney transplant recipients. Moreover, various preventive strategies which may help to optimize the outcome will also be discussed. A retrospective review of all patients who developed HCC after kidney transplantation between May 1972 and December 2011 in Hong Kong, based on the data from Hong Kong Renal Registry. After a follow-up period of 40,246 person-years, 20 patients (males 15: females 5) developed HCC. The annual incidence was 49.7/100,000 persons per year. Among them, 16 were HBV carriers, 2 were hepatitis C (HCV) carriers and 2 had HBV and HCV co-infection. Presence of HBV infection was associated with 78-fold higher risk for HCC development. Majority (85%) were asymptomatic when HCC was diagnosed by ultrasound or alpha-fetoprotein surveillance. All patients diagnosed by surveillance received active treatment while 2/3 of symptomatic patients could only receive symptomatic care and died rapidly. In conclusion, HBV infection is the major etiological factor for HCC development in kidney transplant recipients in HBV endemic areas. Regular HCC surveillance appeared to be able to detect early stage cancers which are amenable to treatment and offer the best hope of cure.

A combination of biocompatible peritoneal dialysis solutions and residual renal function, peritoneal transport, and inflammation markers: a randomized clinical trial.

BACKGROUND: The benefits of biocompatible peritoneal dialysis (PD) fluids, particularly for residual renal function (RRF), are controversial. Moreover, the clinical effects of a PD regimen consisting of different biocompatible PD fluids have not been fully established. STUDY DESIGN: Prospective, randomized, controlled, open-label study. SETTING & PARTICIPANTS: Patients with end-stage kidney disease newly started on continuous ambulatory PD therapy (N = 150). INTERVENTION: A 12-month intervention with 3 biocompatible PD fluids (a neutral-pH, low glucose degradation product, 1.5% glucose solution; a solution with 1.1% amino acid; and a fluid with 7.5% icodextrin) or conventional PD fluid. OUTCOMES: The primary outcome was change in RRF and daily urine volume. Secondary outcomes were peritoneal transport and inflammation markers. MEASUREMENTS: RRF, daily urine volume, serum and dialysate cytokine levels. RESULTS: RRF(3.24 ± 1.98 vs 2.88 ± 2.43 mL/min/1.73 m(2); P = 0.9) and rate of decline in RRF (-0.76 ± 1.77 vs -0.91 ± 1.92 mL/min/1.73 m(2) per year; P = 0.6) did not differ between the biocompatible- and conventional-PD-fluid groups. However, patients using the biocompatible PD fluids had better preservation of daily urine volume (959 ± 515 vs 798 ± 615 mL/d in the conventional group, P = 0.02 by comparison of difference in overall change by repeated-measures analysis of variance). Their dialysate-plasma creatinine ratio at 4 hours was higher at 12 months (0.78 ± 0.13 vs 0.68 ± 0.12; P = 0.01 for comparison of the difference in overall change by repeated-measures analysis of variance). They also had significantly higher serum levels of adiponectin and overnight spent dialysate levels of cancer antigen 125, adiponectin, and interleukin 6 (IL-6). No differences between the 2 groups were observed for serum C-reactive protein and IL-6 levels. LIMITATIONS: Unblinded, relatively short follow-up; no formal sample-size calculations. CONCLUSIONS: Use of a combination of 3 biocompatible PD fluids for 12 months compared with conventional PD fluid did not affect RRF, but was associated with better preservation of daily urine volume. The biocompatible PD fluids also lead to changes in small-solute transport and an increase in dialysate cancer antigen 125, IL-6, adiponectin, and systemic adiponectin levels, but have no effect on systemic inflammatory response. The clinical significance of these changes, while of great interest, remains to be determined by further studies.

Impact of nephrotic edema of the lower limbs on obstructive sleep apnea: gathering a unifying concept for the pathogenetic role of nocturnal rostral fluid shift.

BACKGROUND: Nocturnal rostral fluid shift has been suggested to be a risk factor for obstructive sleep apnea (OSA) in healthy subjects after lower body positive pressurization. It remains unclear whether this may apply to subjects with nephrotic lower limb edema and, if so, whether disease remission may reverse the accompanying OSA. METHODS: Patients who presented with steroid-responsive primary nephrotic syndrome with lower limb edema as the predominant presenting clinical feature were recruited. They underwent one overnight polysomnography (PSG) before treatment and a repeat testing after achieving remission of the nephrotic edema. RESULTS: Among 23 consecutive nephrotic subjects, 11 (48%) had polysomnographic evidence of sleep apnea [apnea-hypopnea index (AHI)≥5] upon presentation. After steroid-based treatment, there was remission of proteinuria associated with complete disappearance of lower limb edema, significant reduction of body mass index, waist, hip and calf circumferences and total body water mainly in the extracellular compartment. Repeat PSG, performed 8.1±2.6 months later, showed that the overall (N=23) respiratory disturbance index (RDI) and AHI fell from 17.3±5.0 to 8.7±2.5 (P<0.05) and from 16.3±5.1 to 7.8±2.3 (P=0.057), respectively. Among the 11 subjects with sleep apnea detected at baseline, their AHI and RDI fell from 33.4±7.8 to 15.0±3.7 (P<0.05) and from 34.8±7.6 to 16.5±4.0 (P<0.05), respectively. There was also concomitant improvement in sleep efficiency, mean nocturnal oxygen saturation, shorter duration during sleep with oxygen saturation<95 and <90% and reduced desaturation index. There was also subjective improvement in self-reported daytime sleepiness. CONCLUSIONS: Nephrotic lower limb edema is associated with disturbed respiratory breathing and increased propensity to OSA, which was reversed upon remission of the nephrosis. This gathers a unifying concept for the role of nocturnal rostral fluid shift in the pathogenesis of OSA.

A study of the clinical and biochemical profile of peritoneal dialysis fluid low in glucose degradation products.

OBJECTIVE: Although peritoneal dialysis (PD) is a widely accepted form of renal replacement therapy, concerns remain regarding the bioincompatible nature of standard PD fluid (PDF). Short-term studies of new biocompatible PDFs low in glucose degradation products (GDPs) reveal divergent results with respect to peritoneal integrity. METHODS: We studied 125 patients on maintenance PD who were assigned, by simple randomization, to receive either conventional or low-GDP PDF at PD initiation. Parameters of dialysis adequacy and peritoneal transport of small solutes were determined at initiation and after a period of maintenance PD at the time when serum and overnight effluent dialysate were simultaneously collected and assayed for various cytokines, chemokines, adipokines, and cardiac biomarkers. All patients were further followed prospectively for an average of 15 months from the day of serum and effluent collection to determine patient survival and cardiovascular events. RESULTS: Patients treated with conventional or low-GDP PDF were matched for sex, age, duration of dialysis, dialysis adequacy, and incidence of cardiovascular disease or diabetes. After an average of 2.3 years of PD treatment, the weekly total and peritoneal creatinine clearance, and the total and peritoneal Kt/V were comparable in the groups. However, urine output was higher in patients using low-GDP PDF despite there having been no difference between the groups at PD initiation. Patients using low-GDP PDF also experienced a slower rate of decline of residual glomerular filtration and urine output than did patients on conventional PDF. Compared with serum concentrations, effluent concentrations of tumor necrosis factor α, hepatocyte growth factor, macrophage migration inhibitory factor, interleukins 8 and 6, C-reactive protein, and leptin were found to be higher in both groups of patients after long-term PD, suggesting that the peritoneal cavity was the major source of those mediators. Compared with patients on low-GDP PDF, patients on conventional fluid showed elevated leptin and reduced adiponectin levels in serum and effluent. The effluent concentration of interleukin 8 was significantly lower in patients using low-GDP PDF. The survival rate and incidence of cardiovascular complications did not differ between these groups after maintenance PD for an average of 3.6 years. CONCLUSIONS: It appears that low-GDP PDF results in an improvement of local peritoneal homeostasis through a reduction of chronic inflammatory status in the peritoneum.

Aliskiren combined with losartan in immunoglobulin A nephropathy: an open-labeled pilot study.

BACKGROUND: Aliskiren is a relatively new oral direct renin inhibitor (DRI) that has been increasingly used for the treatment of diabetic nephropathy and hypertension. Its potential efficacy in nondiabetic chronic kidney diseases that are driven by renin-angiotensin system activation remains to be explored. METHODS: From a teaching and regional hospital in Hong Kong between July 2009 and March 2010, patients with biopsy-proven immunoglobulin A nephropathy (IgAN) in whom the ratio of protein to creatinine, as measured in early morning urine samples, remained >113 mg/mmol (1000 mg/g), despite receiving the maximum recommended dose of losartan (100 mg daily) were recruited to receive additional DRI treatment. They were followed prospectively for 12 months with changes in proteinuria as the main outcome measure. RESULTS: Twenty-five consecutive patients were enrolled. Treatment with aliskiren for 12 months reduced the mean urinary protein-to-creatinine ratio by 26.3% (95% confidence interval, 20.1-43.6; P = 0.001 versus baseline), with a reduction of ≥ 50% in 24% of patients. There were significant reductions in plasma renin activity (P < 0.0001) and serum interleukin-6 (P < 0.05) and transforming growth factor-ß (P = 0.01) levels, compared with baseline. Two patients (8%) developed mild allergic reactions and six (24%) had transient hyperkalemia (K >5.5 mmol/L) during the study. CONCLUSION: Aliskiren confers an antiproteinuric effect in IgAN patients with significant residual proteinuria, despite receiving the recommended renoprotective treatment. Further prospective randomized trials are warranted to examine its long-term renoprotective potential. This trial is registered with the ClinicalTrials.gov number NCT00922311.

The acetyl-coenzyme A carboxylase beta (ACACB) gene is associated with nephropathy in Chinese patients with type 2 diabetes.

BACKGROUND: A single-nucleotide polymorphism (SNP), rs2268388, in the acetyl-coenzyme A carboxylase beta (ACACB) gene is associated with susceptibility to type 2 diabetic nephropathy (T2DN) in Japanese and European-American populations. Whether this association also exists in Chinese patients is unclear. Attempts at replication in small Singaporean and Korean samples were not significant. METHODS: Eight ACACB SNPs were genotyped in 595 subjects with type 2 diabetes mellitus born in Hong Kong or southern China, 295 with advanced T2DN and 300 with long-standing diabetes lacking nephropathy. Association analyses were focused primarily on SNP rs2268388 and secondarily on flanking SNPs and haplotypes. RESULTS: Adjusting for age, gender and diabetes duration, ACACB SNP rs2268388 was significantly associated with advanced T2DN (odds ratio = 2.39; recessive model; P = 0.0129). CONCLUSION: These results in the Chinese replicate the association between T2DN and rs2268388, as seen in Japanese and European Americans. The ACACB gene and attendant alterations in fatty acid oxidation may play important roles in susceptibility to T2DN. Targeting this pathway may provide novel treatment options for the prevention of diabetic nephropathy.

Sleep apnea is a novel risk predictor of cardiovascular morbidity and death in patients receiving peritoneal dialysis.

Sleep apnea syndrome is increasingly recognized in peritoneal dialysis patients; however, its prognostic implication in this population is unknown. To study this, we prospectively followed the clinical outcome of 93 peritoneal dialysis patients with baseline polysomnography. Of these, 51 were diagnosed with the syndrome defined by an apnea-hypopnea index (AHI) of at least 15 per hour. During a median follow-up of 41 months, there were 30 deaths, of which 17 were due to cardiovascular causes. Kaplan-Meier analysis for the entire follow-up period indicated that patients with sleep apnea at baseline had significantly higher all-cause and cardiovascular mortality during follow-up than those without. Minimal nocturnal saturation and desaturation indices were predictors of mortality and cardiovascular events at univariate analysis. Multivariable Cox regression analysis identified significant sleep apnea syndrome at baseline as an independent predictor of increased all-cause mortality independent of age, male gender, and diabetic status. Further, an absolute increase in the AHI was associated with an incremental risk of cardiovascular events. Thus, sleep apnea syndrome, detected at the start of peritoneal dialysis, is a novel risk predictor for subsequent mortality and cardiovascular events.

Long-term study of mycophenolate mofetil treatment in IgA nephropathy.

Since the efficacy of mycophenolate mofetil (MMF) to treat immunoglobulin A (IgA) nephropathy is controversial, we extended our original study by following 40 Chinese patients with established IgA nephropathy for 6 years. All patients were maintained on their angiotensin blockade medication and half were randomized to receive MMF for 6 months. After 6 years, 11 patients required dialysis (2 from the MMF and 9 from the control group). Significantly, only 3 treated (as compared to 10 control) patients reached the composite end point of serum creatinine doubling or end-stage renal disease. Linear regression showed the annualized decline in the estimated glomerular filtration rate was significantly less in the MMF-treated group. Urinary protein excretion and the albumin-to-creatinine ratio were lower with MMF treatment during the first 24 months, beyond which there was no difference between groups. Multivariable Cox regression analysis showed that the baseline estimated glomerular filtration rate and proteinuria, and change in the urine albumin-to-creatinine ratio at 1 year to be important predictors of progression to end-stage renal disease. We found that among Chinese patients with IgA nephropathy who had mild histologic lesions and persistent proteinuria despite maximal angiotensin blockade, MMF treatment may result in transient and partial remission of proteinuria in the short-term and renoprotection in the long-term.

Renal registry and peritoneal dialysis management: the Hong Kong perspective.

The Hong Kong Renal Registry (HKRR) is an electronic paperless registry that services as database for patients on various renal replacement therapies in the territory. The database consists of demographic data, dialysis and transplant treatments, complications, and inquiries and reports. The HKRR can be helpful for individual patient's management, for renal center management, and for territory-wide management.

Preparing patients for peritoneal dialysis.

When told of their need for dialysis, patients often cannot accept it and are fearful toward dialysis. Pre-dialysis counseling programs help patients to face dialysis, to make the right choice of dialysis modality, and to prepare themselves for life on dialysis. Clear explanations of peritoneal dialysis (PD) help patients choosing PD. Patients should be referred to pre-dialysis programs at least 4 - 6 months before commencement of dialysis or when their glomerular filtration rate is around 15 mL/min/1.73 m(2). The pre-dialysis program is best conducted by experienced staff such as renal nurses and multidisciplinary staff including nephrologists, dietitians, physiotherapists, psychologists, social workers, or even dialysis patient representatives depending on availability. The program should be designed according to the culture, settings, staff availability, and patient load in individual hospitals. Pre-dialysis home visits may be needed in some cases to assess suitability and prepare the home for PD.

Prospective controlled study on mycophenolate mofetil and prednisolone in the treatment of membranous nephropathy with nephrotic syndrome.

BACKGROUND: Retrospective and anecdotal data suggest that mycophenolate mofetil (MMF) might be effective when given as rescue therapy for membranous nephropathy (MN). Prospective controlled data on MMF and prednisolone as primary therapy are lacking. METHODS: A prospective, randomized, controlled, open-label study was performed to investigate the efficacy and tolerability of MMF and prednisolone as primary treatment in MN with nephrotic syndrome. MMF and prednisolone given for 6 months was compared against a modified Ponticelli regimen in 20 patients, with follow up of 15 months. RESULTS: MMF with prednisolone and the comparative immunosuppressive regimen showed similar efficacy in proteinuria reduction, despite a lower cumulative prednisolone dose in the MMF group (3.80 +/- 0.28 vs 9.93 +/- 0.25 g, P < 0.001). Remission (composite of 'complete' and 'partial') rates were 63.6% and 66.7% in the MMF group and control group, respectively (P = 1.000). Serum creatinine and creatinine clearance remained stable during follow up. Cumulative relapse rate was 23.1% at 2 years. Chlorambucil resulted in more leucopenia compared with MMF. CONCLUSION: Data from this pilot study indicate that more than 60% of patients with MN and nephrotic syndrome respond to combined MMF and prednisolone treatment, and suggest potential benefits of MMF as being steroid-sparing and having less adverse effects compared with other commonly used cytotoxic agents.

Development of the "peritoneal dialysis first" model in Hong Kong.

Maintenance dialysis is an expensive treatment modality for patients with end-stage renal-disease (ESRD). The number of patients on maintenance dialysis is rising rapidly and will reach 2.5 million globally by 2010. The predicted expenditure will be US$1 trillion. Since the 1960s, Hong Kong has faced financial restraints on the provision of dialysis. Continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis at home were found to be less expensive than in-centre chronic hemodialysis. The development of a "peritoneal dialysis first" (PD-First) policy has contributed significantly to a successful dialysis program in Hong Kong since 1960. Currently in Hong Kong, 80% of ESRD patients on maintenance dialysis are on PD, mainly CAPD; 20% are on hemodialysis. The success of the PD-First policy is a combination of accumulated experience of PD in each dialysis unit that has at least 200 CAPD patients under care and of impressive technique and patient survival rates for this modality. Concerted effort by government and charity organizations and commitment on the part of nephrologists and nursing staff to patient education are also important in making the PD program in Hong Kong a successful one.

Improvement of anemia after parathyroidectomy in Chinese patients with renal failure undergoing long-term dialysis.

HYPOTHESIS: Most patients undergoing long-term dialysis are anemic because of underproduction of erythropoietin and its inhibition by high parathyroid hormone levels due to secondary hyperparathyroidism. Renal anemia can be improved by parathyroidectomy. DESIGN: Retrospective cohort study. SETTING: Regional hospital. PATIENTS: Twenty-three Chinese patients without a previous functioning renal transplant underwent parathyroidectomy for severe secondary hyperparathyroidism in a 3-year period. INTERVENTION: Total parathyroidectomy with or without parathyroid autograft at the forearm. MAIN OUTCOME MEASURES: The preoperative and 6-month postoperative hematological and biochemical variables were compared for any differences by means of a paired t test. RESULTS: The mean +/- SD follow-up duration was 17.7 +/- 8.1 (range, 6-34) months. Three patients (13%) developed persistent or recurrent hyperparathyroidism and 2 patients (9%) were biochemically hypoparathyroid. The other 18 patients (78%) were euparathyroid. Surgical morbidity was minimal; only 1 patient had complications, consisting of a postoperative fever of unknown origin that resolved with conservative treatment. The mean +/- SD hemoglobin level (8.6 +/- 2.1 vs 9.4 +/- 2.1 g/dL) but not the mean platelet level was significantly (P = .04) increased 6 months postoperatively. Likewise, the following other mean +/- SD biochemical values improved after surgery: parathyroid hormone (2235 +/- 500 vs 151 +/- 312 pg/mL; P<.001), alkaline phosphatase (645 +/- 349 vs 123 +/- 82 U/L; P<.001), calcium (10.8 +/- 4.0 vs 9.3 +/- 1.0 mg/dL; P<.001), phosphate (1.93 +/- 0.73 vs 1.50 +/- 0.51 mmol/L; P = .02), and albumin (3.5 +/- 0.5 vs 3.8 +/- 0.6 g/dL; P = .006). CONCLUSIONS: Parathyroidectomy is highly effective to control secondary hyperparathyroidism with an exceedingly low complication rate. The hemoglobin level was significantly elevated 6 months postoperatively. The long-term effect warrants future trials.

Delaying initiation of dialysis till symptomatic uraemia--is it too late?

BACKGROUND: The optimal timing of initiating renal replacement therapy in patients with chronic renal failure remains uncertain. The primary objective of our study is to determine whether delaying dialysis initiation as a result of patients' choice may have any impact on survival in subjects with end-stage renal disease. METHODS: We prospectively studied the clinical outcome during the first year of all consecutive patients (n=233) deemed suitable for peritoneal dialysis (PD) after pre-dialysis counselling over a 2-year period from 2002 to 2004. All patients who were offered dialysis were included in the analysis from the day of initial counselling regardless of whether or not they were eventually established on PD. RESULTS: There were 151 'elective starters' (50.3% male, mean+/-SD age=57.7+/-13.9 years, 39.7% diabetic) who were electively initiated on dialysis when glomerular filtration rate reached 10 ml/min/1.73 m2 or below. The remaining 82 subjects (53.7% male, mean+/-SD age=58.4+/-11.3 years, 46.3% diabetic, P=0.33 vs elective starters) declined dialysis initially (initial refusers). On follow-up, 45 (55%) initial refusers developed a uraemic emergency and agreed to undergo dialysis, and 39 (48%) were eventually established on maintenance PD (late starters). Kaplan-Meier analysis of 1-year survival showed a significantly higher rate of all-cause (18.3% vs 6.6%, P=0.004, log-rank test) and cardiovascular (9.8% vs 2.6%, P=0.014) mortality among the initial refusers. CONCLUSION: Patients who refuse timely start of dialysis have worse overall outcome at one year after the offer of dialysis, compared with elective starters.

Diagnostic challenges of tuberculosis peritonitis in patients with and without end-stage renal failure.

BACKGROUND: Information about diagnostic features of tuberculosis (TB) peritonitis among patients with end-stage renal failure (ESRF), compared with those without ESRF, is limited. Here, we review our experience with TB peritonitis in patients with and without ESRF over a period of 11 years, with special reference to the clinical features of and diagnostic tools for TB peritonitis. METHODS: The records of all patients with TB peritonitis who were seen at United Christian Hospital (Hong Kong) from 1996 through 2006 were reviewed. The diagnosis of TB peritonitis was based on (1) detection of mycobacteria on smear and/or Mycobacterium tuberculosis on culture of ascitic fluid and/or peritoneal biopsy specimens and/or (2) demonstration of caseating granulomata on histological assessment of peritoneal biopsy specimens. RESULTS: During the study period, 52 patients (19 without ESRF and 33 with ESRF) had TB peritonitis. Patients with ESRF tended to have more-acute onset of symptoms and neutrophil-predominant peritoneal fluid, which mimicked bacterial peritonitis. Diagnosis was made earlier among patients without ESRF than among those with ESRF. Laparotomy or laparoscopy was the initial diagnostic tool for 12 patients (63%) without ESRF, whereas mycobacterial culture was the diagnostic method for 18 patients (55%) with ESRF. CONCLUSIONS: TB peritonitis has nonspecific and protean manifestations. It should be considered in the context of culture-negative peritonitis and in the context of culture-positive peritonitis that fails to respond to appropriate antibiotics. Laparoscopy with biopsy should be considered at an early stage when TB peritonitis is suspected.

Conversion of ciclosporin A to tacrolimus in kidney transplant recipients with chronic allograft nephropathy.

BACKGROUND: Tacrolimus and ciclosporin might have different effects on intra-renal fibrosis and allograft function in chronic allograft nephropathy (CAN). It is difficult to predict the response to calcineurin inhibitor minimization in patients with CAN. METHODS: This prospective randomized study compared ciclosporin A (CsA)-to-tacrolimus conversion (group A, target tacrolimus trough level 6-8 ng/ml) vs CsA minimization (group B, target CsA trough level 80-100 ng/ml) with regard to efficacy and safety in patients with CAN and deteriorating allograft function. The primary efficacy endpoint was improvement in the slope of inverse serum creatinine (1/SCr) vs time plot. RESULTS: There were 34 evaluable patients (n=16 in group A; n=18 in group B), with similar baseline characteristics. Both groups reached target drug levels after a 3-month run-in period. Over the ensuing 12 months, nine (56.3%) subjects in group A and 10 (55.6%) in group B reached the primary end point (P=0.968). Both groups showed considerable improvement in the slope of 1/SCr vs time plot. There was no significant difference in the slope between groups before and after intervention. Graft survival was 87% in group A and 100% in group B (P=0.121). Acute rejection was encountered in two group A subjects. There was no significant change or difference in blood glucose, lipids, and blood pressure between groups. CONCLUSION: Our results suggest that in patients with CAN and deteriorating allograft function, CsA-to-tacrolimus conversion or CsA minimization achieved comparable efficacies in retarding the decline of graft function. Such contention may be biased by the low patient number. Further studies with a larger cohort are needed for validation.

Alleviation of sleep apnea in patients with chronic renal failure by nocturnal cycler-assisted peritoneal dialysis compared with conventional continuous ambulatory peritoneal dialysis.

Nocturnal hemodialysis has been shown to improve sleep apnea in patients who receive conventional hemodialysis. It was hypothesized that nocturnal peritoneal dialysis (NPD) also is effective in correcting sleep apnea in patients who receive continuous ambulatory PD (CAPD). Overnight polysomnography (PSG) was performed in 46 stable NPD and CAPD patients who were matched for demographic and clinical attributes. The prevalence of sleep apnea, defined as an apnea-hypopnea index (AHI; or frequency of apnea and hypopnea per hour of sleep) > or =15, was 52% for NPD patients and 91% for CAPD patients (P = 0.007). The mean (+/-SD) AHI in NPD and CAPD patients was 31.6 +/- 25.6 and 50.9 +/- 26.4 (P = 0.025), respectively. For validation of the efficacy of NPD in alleviating sleep apnea, a fixed sequence intervention study was performed in which 24 incident PD patients underwent one PSG study during mandatory cycler-assisted NPD while awaiting their turn for CAPD training and a second PSG recording shortly after they were established on stable CAPD. The prevalence of sleep apnea was 4.2% during NPD and 33.3% during CAPD (P = 0.016). AHI increased from 3.4 +/- 1.34 during NPD to 14.0 +/- 3.46 during CAPD (P < 0.001). With the use of bioelectrical impedance analysis, total body water content was significantly lower during stable NPD than CAPD (32.8 +/- 7.37 versus 35.1 +/- 7.35 L; P = 0.004). NPD delivered greater reductions in total body water (-2.81 +/- 0.45 versus -1.34 +/- 0.3 L; P = 0.015) and hydration fraction (-3.63 +/- 0.64 versus -0.71 +/- 0.52%; P = 0.005) during sleep. Pulmonary function tests remained unchanged before and after conversion from NPD to CAPD. These findings suggest that NPD may have a therapeutic edge over CAPD in sleep apnea that is associated with renal failure as a result of better fluid clearance during sleep.

Predictive value of dialysate cell counts in peritonitis complicating peritoneal dialysis.

Early prediction of outcomes has major potential implications regarding the management of dialysis-related peritonitis. The outcomes of 565 consecutive episodes of peritonitis complicating peritoneal dialysis between August 2001 and July 2005 were evaluated in relation to the dialysate cell counts. Discriminatory power, based on the area under the receiver-operating characteristic (ROC) curves, of the cell counts was assessed. The findings then were validated externally in a cohort of 217 peritonitis episodes from another dialysis unit. During the study period, 565 episodes of peritonitis were included for analysis, 465 of which had treatment success defined as complete resolution of peritonitis without the need for Tenckhoff catheter removal. Of the remaining 100 episodes (treatment failure), 70 required Tenckhoff catheter removal and 30 had peritonitis-related death. The peritoneal dialysate total white blood cell count on day 3 of peritonitis predicted treatment failure independent of standard risk factors, and it had a higher area under the ROC curve than the dialysate white cell count on day 1 (0.80 versus 0.58; P < 0.0001). Using a peritoneal dialysate white count cut point > or = 1090/mm3 on day 3, the sensitivity was 75% and the specificity was 74% for the prediction of treatment failure (defined as catheter loss or peritonitis-related death). In multiple logistic regression analyses, peritoneal dialysate white count > or = 1090/mm3 on day 3 was an independent prognostic marker for treatment failure after adjustment for conventional risk factors (hazard ratio 9.03; 95% confidence interval 4.40 to 18.6; P < 0.0001). Number of years on peritoneal dialysis; diabetes; gram-negative organisms; and Pseudomonas, fungal, or Mycobacterium species were other independent risk factors that were predictive of treatment failure. Findings from an independent validation set of peritonitis (217 episodes after exclusion of Mycobacterium and fungal causes) also favored the peritoneal dialysate white count on day 3, as compared with day 1 and day 2, to predict treatment failure. Area under the ROC curve for the white counts on day 3 was 0.98 (95% confidence interval 0.95 to 0.99) in the validation set. This study demonstrated and cross-validated the superiority of peritoneal dialysate white cell count on day 3 to predict outcomes of dialysis-related peritonitis. These results call attention to the value of validating prognostic factors of peritonitis complicating peritoneal dialysis.