Polypharmacy Predicts Onset and Transition of Frailty, Malnutrition, and Adverse Outcomes in Peritoneal Dialysis Patient.

BACKGROUND: Polypharmacy, frailty and malnutrition are known predictors of adverse outcomes in dialysis patients. Little has reported about their interaction and composite prognostic values. We aimed to describe the interaction between polypharmacy, frailty, nutrition, hospitalization, and survival in peritoneal dialysis patients. METHODS: In this prospective cohort study, we recruited 573 peritoneal dialysis patients. Drug burden was measured by medication number and daily pill load. Frailty and nutrition were assessed by the validated Frailty Score (FQ) and Subjective Global Assessment (SGA) respectively. All patients were followed for two years. Primary outcome was all-cause mortality. Secondary outcomes were fall and fracture episodes, hospitalization, change in FQ and SGA. RESULTS: At baseline, each patient took 7.5 ± 2.6 medications with 15.5 ± 8.5 tablets per day. Medication number, but not daily pill load predicted baseline FQ (p = 0.004) and SGA (p = 0.03). Over 2 years, there were 69 fall and 1,606 hospitalization episodes. In addition, 148 (25.8%) patients died, while FQ and SGA changed by 0.73 ± 4.23 and -0.07 ± 1.06 respectively in survivors. Medication number (hospitalization: p = 0.02, survival: p = 0.005), FQ (hospitalization: p < 0.001; survival: p = 0.01) predicted hospitalization and survival. Medication number also predicted fall episodes (p = 0.02) and frailty progression (p = 0.002). Daily pill load did not predict any of these outcomes. CONCLUSIONS: Drug burden is high in peritoneal dialysis patients, and it carries important prognostic implication. Medication number but not pill load significantly predicted onset and progression of frailty, malnutrition, fall, hospitalization, and mortality.

Characteristics and clinical outcomes of living renal donors in Hong Kong.

INTRODUCTION: In Asia, few reports are available on the outcomes for living renal donors. We report the short- and long-term clinical outcomes of individuals following living donor nephrectomy in Hong Kong. METHODS: We retrospectively reviewed the characteristics and clinical outcomes of all living renal donors who underwent surgery from January 1990 to December 2015 at a teaching hospital in Hong Kong. Information was obtained from hospital records and territory-wide electronic patient records. RESULTS: During the study period, 83 individuals underwent donor nephrectomy. The mean (± standard deviation) follow-up time was 12.0 ± 8.3 years, and the mean age at nephrectomy was 37.3 ± 10.0 years. A total of 44 (53.0%), four (4.8%), and 35 (42.2%) donors underwent living donor nephrectomy via an open, hand-port assisted laparoscopic, and laparoscopic approach, respectively. The overall incidence of complications was 36.6%, with most being grade 1 or 2. There were three (9.4%) grade 3a complications; all were related to open donor nephrectomy. The mean glomerular filtration rate was 96.0 ± 17.5 mL/min/1.73 m2 at baseline and significantly lower at 66.8 ± 13.5 mL/min/1.73 m2 at first annual follow-up (P<0.01). The latest mean glomerular filtration rate was 75.6% ± 15.1% of baseline. No donor died or developed renal failure. Of the donors, 14 (18.2%) developed hypertension, two (2.6%) had diabetes mellitus, and three (4.0%) had experienced proteinuria. CONCLUSION: The overall perioperative outcomes are good, with very few serious complications. The introduction of a laparoscopic approach has decreased perioperative blood loss and also shortened hospital stay. Long-term kidney function is satisfactory and no patients developed end-stage renal disease. The incidences of new-onset medical diseases and pregnancy-related complications were also low.

Public lacks knowledge on chronic kidney disease: telephone survey.

OBJECTIVES: To examine knowledge of chronic kidney disease in the general public. DESIGN: Cross-sectional telephone survey. SETTING: Hong Kong. PARTICIPANTS: Community-dwelling adults who spoke Chinese in Hong Kong. RESULTS: The response rate was 47.3% (516/1091) out of all subjects who were eligible to participate. The final survey population included 516 adults (55.6% female), of whom over 80% had received a secondary level of education or higher. Close to 20% of the participants self-reported a diagnosis of hypertension. Few (17.8%) realised the asymptomatic nature of chronic kidney disease. Less than half of these individuals identified hypertension (43.8%) or diabetes (44.0%) as risk factors of kidney disease. Awareness of high dietary sodium as a risk factor for chronic kidney disease was high (79.5%). CONCLUSIONS: The public in Hong Kong is poorly informed about chronic kidney disease, with major knowledge gaps regarding the influence of hypertension on kidney disease. We are concerned about the public's unawareness of hypertension being a risk factor for kidney disease. Future health education should target areas of knowledge deficits.

Fracture risk after thiazide-associated hyponatraemia.

BACKGROUND/AIM: Although thiazide-type diuretics can promote a positive calcium balance, thiazide can be associated with hyponatraemia, which is recently linked with heightened fracture risk. We examine the chance of developing fracture in patients with and without hyponatraemia after taking thiazide diuretics. METHODS: In this single-centre retrospective study, we followed up a previously published cohort of patients with (n= 223) and without (n= 216) thiazide-induced hyponatraemia. RESULTS: A total of 61 osteoporotic fractures was recorded during a mean follow-up period of 82 months. Using univariate regression analysis, the hazard ratio of thiazide-induced hyponatraemia was 1.78 (95% confidence interval (CI), 1.05-3.03; P= 0.033). Cox proportional hazards regression analysis, however, showed that age, body mass index and diabetes mellitus were the only independent predictors of osteoporotic fractures. No association of a history of thiazide-induced hyponatraemia and risk of fracture was evident in the final model. CONCLUSION: Since a history of thiazide-induced hyponatraemia is associated with osteoporotic fracture in univariate but not multivariate analyses, an alternative explanation is that confounding factors of older age and low body mass index accounted for the apparently increased risk of osteoporotic fracture in patients with thiazide-induced hyponatraemia.

Measurements on the routine chest radiograph as prognostic markers in Chinese peritoneal dialysis patients.

BACKGROUND: Fluid overload is a common problem in peritoneal dialysis (PD) patients. Cardiothoracic ratio (CTR) and vascular pedicle width (VPW) in routine chest radiograph are useful indicators of intravascular volume status and may represent important prognostic factors of PD patients. METHODS: We measured VPW and CTR in 286 unselected prevalent PD patients. VPW was further adjusted for the thoracic diameter (VPWR). One-year actuarial survival, technique survival, and duration of hospitalization were analyzed. RESULTS: The mean values of VPW, CTR, VPWR were 47.31 ± 4.73 mm, 0.542 ± 0.074, 0.170 ± 0.024, respectively. VPW correlated with age (r = 0.143; p = 0.016), body weight (r = 0.371; p < 0.001), body height (r = 0.271; p < 0.001), and Charlson's index score (r = 0.153; p = 0.01). One-year patient survival was 87.8%, and technique survival was 82.2%. None of the radiological measurements had an independent effect on one-year actuarial or technique survival by multivariate analysis. Both CTR and VPWR correlated with the duration of hospitalization (r = 0.192 and 0.186, respectively (p = 0.001 and 0.002). Multivariate regression analysis by log-linear modeling showed that independent predictors of one-year hospitalization were VPWR, serum albumin, and SGA overall score. CONCLUSIONS: In Chinese PD patients, VPW was significantly correlated with age, body weight, body height and Charlson's index score. VPWR was an independent predictor of the duration of hospitalization. Further studies are needed to confirm the prognostic value of these radiographic measurements in PD patients.

Sevelamer treatment strategy in peritoneal dialysis patients: conventional dose does not make best use of resources.

BACKGROUND: The significant incremental expense in the use of conventional sevelamer dose prompted us to evaluate the role of prescribing a lower dose of sevelamer. METHODS: To determine the optimum strategy for prescribing sevelamer in peritoneal dialysis patients, we conducted an open-label randomized study comparing the treat-to-goal strategy (4.0-g daily sevelamer dose) with lower sevelamer dose (1.2-g daily dose). RESULTS: Twenty-seven peritoneal dialysis patients with serum calcium x phosphorus product above 55 mg2/dL2 were recruited. Eighteen were randomized to the low-dose treatment group (1.2 g daily), and 9 to the treat-to-goal (4.0 g daily) group. Overall, significantly lower calcium x phosphorus product and serum phosphorus levels at 6 months were achieved by the treat-to-goal treatment. The proportions of patients who attained the Kidney Disease Outcomes Quality Initiative (K/DOQI) treatment target, however, did not differ significantly between the treat-to-goal and low-dose treatment groups (66.7% +/- 30.8% vs. 33.3% +/- 21.8%, p=0.10). The numbers needed to treat to benefit 1 patient who attains the K/DOQI recommendation are 1.5 patients (95% confidence interval [95% CI], 1.0-2.8) in the 4.0-g daily dose and 3 patients (95% CI, 1.8-8.7) in the 1.2-g daily dose group. Therefore, an extra 66.7% of subjects would be able to attain the treatment recommendation within the same budget if the daily dose of sevelamer used was 1.2 g instead of the usual 4.0 g. Compared with a 1.2-g daily dose of sevelamer, the 4.0-g daily dose had an incremental cost-effectiveness ratio (ICER) of US $2,353 per additional patient achieving the K/DOQI target. Multivariate analysis showed that only the calcium x phosphorus product after 1 month of sevelamer treatment was predictive of treatment response. CONCLUSIONS: Low-dose sevelamer treatment might be a cost-effective approach, which is "good for many rather than best for a few."

Elevation of pro-inflammatory cytokines, C-reactive protein and cardiac troponin T in chronic renal failure patients on dialysis.

Chronic renal failure (CRF) patients suffer from a chronic inflammation. They are at increased risk of cardiovascular disease. In order to investigate this inflammatory process and cardiovascular risk factors associated with haemodialysis (HD) and peritoneal dialysis (PD), we compared serum/plasma pro-inflammatory cytokines, C-reactive protein (CRP), and cardiac troponin T (cTnT) of 146 CRF patients treated or not treated with PD or HD. Serum cytokines and CRP as well as plasma cTnT were measured by enzyme-linked immunosorbent assay, chemiluminescence immunoassay, and electrochemiluminescence immunoassay, respectively. Results indicated that serum interleukin (IL)-18 concentrations were significantly higher in PD and low creatinine clearance pre-dialysis CRF (LCC) patients than HD patients (both p < 0.05). IL-6 and tumour necrosis factor (TNF)-alpha concentrations were significantly higher in PD patients than LCC patients (both p < 0.01). Serum hsCRP and plasma cTnT in HD were significantly higher than LCC (both p < 0.01). The elevation of pro-inflammatory cytokines should play an important role in the chronic inflammation and increased cardiovascular risk of CRF patients on dialysis. We are evaluating further the diagnostic and prognostic applications of pro-inflammatory cytokines and biochemical inflammatory markers for these patients.

Relation between number of prescribed medication and outcome in peritoneal dialysis patients.

BACKGROUND: Many patients with end-stage renal disease need to take a large number of medications. In the present study, we studied the magnitude of problem and explored the relationship between the number of prescribed medications and the clinical outcome of a large cohort of prevalent peritoneal dialysis (PD) patients. METHODS: We studied the medication list of 266 prevalent PD patients. Dialysis adequacy, residual renal function and nutritional assessment were also performed. The patients were followed for 33.7 +/- 20.7 months. RESULTS: On average, each patient required 4.7 +/- 1.8 type of medications or 10.0 +/- 4.9 tablets per day. 40 patients (15.0%) needed at least 7 types of medication; 33 patients (12.4%) had to take more than 15 tablets each day. There is a significant but weak correlation between the number of types of medication and the Charlson's comorbidity score (r = 0.252, p < 0.001). Despite the large number of medication prescribed, the blood pressure control, serum cholesterol level, and the use of aspirin after atherosclerotic disease remained suboptimal in many patients. By multivariate analysis, independent factors for patient survival were Charlson's comorbidity score, number of types of medication, duration of dialysis, overall SGA score, and mean arterial blood pressure. Each additional type of medication conferred 20% increase in risk of death (95% CI, 1.6-41.7%, p = 0.032), and the effect is independent on the Charlson's comorbidity score. The actual number of pills taken by a patient did not influence survival in this model. CONCLUSION: Our results indicate that the number of prescribed medications is related to the clinical outcome of PD patients. The number of prescribed medication may reflect the severity of uremic complications and comorbid diseases not reflected by the Charlson's comorbidity score. Nevertheless, dialysis physicians should carefully balance the clinical need of treating multiple medical conditions with the potential problems of a complicated therapeutic regimen.

Enterobacteriaceae peritonitis complicating peritoneal dialysis: a review of 210 consecutive cases.

Enterobacteriaceae peritonitis is a serious complication in peritoneal dialysis (PD), but the clinical course of PD-related Enterobacteriaceae peritonitis remains unclear. We reviewed all Enterobacteriaceae peritonitis in our dialysis unit from 1995 to 2004. During this period, there were 1748 episodes of peritonitis recorded; 210 episodes (12.0%) in 123 patients were caused by Enterobacteriaceae. The most common species was Escherichia coli, accounting for 111 episodes. The primary response rate was 84.8% and complete cure rate was 58.1%. The presence of exit site infection was associated with a lower complete cure rate (43.2 versus 61.3%, P = 0.034). A total of 82 episodes (39.0%) did not respond to single antibiotic treatment despite sensitivity in vitro, and a second antibiotic was added. Patients treated with two antibiotics had a marginally lower risk of relapse and recurrence than those with one antibiotic (21.4 versus 36.1%, P = 0.051). The episodes that had recent antibiotic therapy had a marginally lower complete cure rate (49.3 versus 62.8%, P = 0.06). There was a gradual increase in the prevalence of resistance to several commonly used antibiotics over the years. Recent antibiotic therapy was associated with resistance to cefotaxime, ceftazidime, cefoperazone/sulbactam, and piperacillin/tazobactam. We conclude that Enterobacteriaceae peritonitis is a serious complication of PD. Recent antibiotic therapy is the major risk factor of antibiotic resistance. Exit site infection, and probably recent antibiotic therapy, is associated with poor therapeutic response. Contrary to the current recommendation, treatment with two antibiotics may reduce the risk of relapse and recurrence.

Cardiovascular complications of severe acute respiratory syndrome.

BACKGROUND AND AIMS: Severe acute respiratory syndrome (SARS) is a virulent viral infection that affects a number of organs and systems. This study examined if SARS may result in cardiovascular complications. METHODS AND RESULTS: 121 patients (37.5 (SD13.2) years, 36% male) diagnosed to have SARS were assessed continuously for blood pressure, pulse, and temperature during their stay in hospital. Hypotension occurred in 61 (50.4%) patients in hospital, and was found in 28.1%, 21.5%, and 14.8% of patients during the first, second, and third week, respectively. Only one patient who had transient echocardiographic evidence of impaired left ventricular systolic function required temporary inotropic support. Tachycardia was present in 87 (71.9%) patients, and was found in 62.8%, 45.4%, and 35.5% of patients from the first to third week. It occurred independent of hypotension, and could not be explained by the presence of fever. Tachycardia was also present in 38.8% of patients at follow up. Bradycardia only occurred in 18 (14.9%) patients as a transient event. Reversible cardiomegaly was reported in 13 (10.7%) patients, but without clinical evidence of heart failure. Transient atrial fibrillation was present in one patient. Corticosteroid therapy was weakly associated with tachycardia during the second (chi(2) = 3.99, p = 0.046) and third week (chi(2) = 6.53, p = 0.01), although it could not explain tachycardia during follow up. CONCLUSIONS: In patients with SARS, cardiovascular complications including hypotension and tachycardia were common but usually self limiting. Bradycardia and cardiomegaly were less common, while cardiac arrhythmia was rare. However, only tachycardia persisted even when corticosteroid therapy was withdrawn.

Change in bacterial aetiology of peritoneal dialysis-related peritonitis over 10 years: experience from a centre in South-East Asia.

This study reviewed 1787 episodes of peritoneal dialysis (PD)-related peritonitis in 544 patients between 1994 and 2003. The overall rate of peritonitis was 0.68 episodes/year of PD, but decreased from 1.10 to 0.46 episodes/year between 1994 and 2003. The incidence of peritonitis caused by coagulase-negative staphylococci declined between 1994 and 1998 from 0.21 to 0.06 episodes/year of PD, coinciding with a reduction in the use of spike PD sets. There was a 60.1% response rate to antibiotics throughout the period, but the percentage of cases that required modification of the initial empirical antibiotic regimen rose from 13.6% to 58.7%, indicating that treatment should be individualised.

Use of convalescent plasma therapy in SARS patients in Hong Kong.

In order to evaluate the efficacy of convalescent plasma therapy in the treatment of patients with severe acute respiratory syndrome (SARS), 80 SARS patients were given convalescent plasma at Prince of Wales Hospital, Hong Kong, between 20 March and 26 May 2003. Good outcome was defined as discharge by day 22 following the onset of SARS symptoms. Poor outcome was defined as death or hospitalization beyond 22 days. A higher day-22 discharge rate was observed among patients who were given convalescent plasma before day 14 of illness (58.3% vs 15.6%; P<0.001) and among those who were PCR positive and seronegative for coronavirus at the time of plasma infusion (66.7% vs 20%; P=0.001).

Effect of a compensated Jaffe creatinine method on the estimation of glomerular filtration rate.

BACKGROUND: Roche Diagnostics has issued new c-fas calibrators for its automated systems. These produce creatinine values that are more comparable with those obtained by high-performance liquid chromatography. However, this results in an underestimation of measured creatinine at concentrations below 155 micromol/L and an overestimation at concentrations above this value. METHODS: Serum and urine creatinine concentrations were prospectively determined on samples from 60 patients using the new (compensated) and old (uncompensated) c-fas calibrators, and Passing-Bablok regression analysis was performed. The regression equations thus determined were then used retrospectively to determine the compensated creatinine results (i.e. those results that would have been obtained using the new calibrator) in those serum and urine samples analysed in the previous year using the old uncompensated c-fas calibrator. The compensated creatinine results were then used to estimate the glomerular filtration rate (GFR) by calculating creatinine clearance. This was done by using the formula: UV/Pt, in which U represents the urinary creatinine concentration (micromol/L), V the urinary collection volume (mL), P the serum creatinine concentration (micromol/L) and t the urinary collection time (min). It was also calculated using the abbreviated Modification of Diet in Renal Disease study group (MDRD) formula. RESULTS: The creatinine clearance as determined using either the UV/Pt calculation or the MDRD formula overestimated GFR by approximately 30% and approximately 50%, respectively, in normal individuals with a serum creatinine concentration below 155 micromol/L. However, in patients with mild to moderate renal failure (serum creatinine from 155 to 500 micromol/L), changes in creatinine clearances determined by the two procedures were minimal. CONCLUSION: When laboratories introduce this new, compensated calibrator into practice, it may be appropriate to discuss its potential impact with clinical staff who monitor patients using creatinine clearance.

Recurrent acute pancreatitis after isoniazid.

Drug-induced acute pancreatitis should be in the differential diagnosis of acute abdomen occurring soon after initiation of tuberculosis treatment and chemoprophylaxis. Isoniazid-induced pancreatitis is potentially reversible; early recognition and drug withdrawal are warranted in the appropriate clinical setting. We present a case of reversible acute pancreatitis after isoniazid treatment of genitourinary tuberculosis, followed by recurrence of pancreatitis 12 years later when the patient received isoniazid again for pulmonary tuberculosis. Isoniazid-induced pancreatitis, if highly suspicious or confirmed with re-challenge test, mandates permanent avoidance of the drug.

Risk factors for thiazide-induced hyponatraemia.

BACKGROUND: Thiazide-induced hyponatraemia is common and potentially life threatening. In the absence of well-defined risk factors for this complication, guidelines for prescribing cannot be established. AIM: To examine whether a subgroup of patients is particularly susceptible to this complication. DESIGN: Retrospective case-control study. METHODS: We defined and recruited cases of symptomatic hyponatraemia that necessitated hospitalization from January 1996 to April 2002. Controls were selected from 8420 patients being prescribed thiazides and seen at the same institution during that period of time. RESULTS: There were 223 cases and 216 controls, with a median 115 days thiazide use. Cases were older than controls (76 +/- 9 vs. 66 +/- 13 years, p < 0.001) and lighter (52.3 +/- 10.3 vs. 63.4 +/- 3 kg, p < 0.001). By univariate analysis, serum potassium level, use of indapamide, elderly home institutionalization and physical immobility were risk factors for thiazide-induced hyponatraemia, but gender, duration of thiazide use, concomitant therapy with loop diuretics, angiotensin-converting enzyme inhibitors or non-steroidal anti-inflammatory drugs, and renal function were not. By stepwise logistic regression analysis, patient age, body weight and serum potassium were the only independent predictive factors. Each 10-year increment of age was associated with a two-fold increase in risk (hazards ratio 2.14, 95%CI 1.59-2.88). For a 5 kg increment in mass, there was a 27% decrease in odds ratio (odds ratio 0.77, 95%CI 0.68-0.87). One SD increase in serum potassium (0.84 mmol/l) was associated with a 63% decrease in risk (odds ratio 0.37, 95%CI 0.27-0.50; p < 0.0001). DISCUSSION: Hyponatraemia is a common problem after thiazide therapy. Extra caution and close monitoring are warranted when prescribing thiazides for elderly patients with low body mass.