Volumetric reduction and dissolution prediction of monosodium urate crystal during urate-lowering therapy - a study using dual-energy computed tomography.

METHODS: Baseline and follow-up DECTs were performed under a standard ULT protocol. Monthly dissolution rates were calculated by simple and compound methods. Correlations with average SU were compared and analyzed. Best-fit regression model was identified. MSU dissolution times were plotted against SU at different endpoints. RESULTS: In 29 tophaceous gout patients, MSU volume reduced from baseline 10.94 ± 10.59 cm3 to 2.87 ± 5.27 cm3 on follow-up (p = .00). Dissolution rate had a stronger correlation with SU if calculated by compound method (Pearson's correlation coefficient r= -0.77, p = .00) and was independent of baseline MSU load. The ensuing dissolution model was logarithmic and explained real-life scenarios. When SU > 0.43 mmol/l, dissolution time approached infinity. It improved to 10-19 months at SU = 0.24 mmol/l. When SU approximated zero (as with pegloticase), dissolution flattened and still took 4-8 months. CONCLUSION: MSU dissolution is better described as a logarithmic function of SU, which explains, predicts, and facilitates understanding of the dissolution process.

Donor-Derived Genotype 4 Hepatitis E Virus Infection, Hong Kong, China, 2018.

Hepatitis E virus (HEV) genotype 4 (HEV-4) is an emerging cause of acute hepatitis in China. Less is known about the clinical characteristics and natural history of HEV-4 than HEV genotype 3 infections in immunocompromised patients. We report transmission of HEV-4 from a deceased organ donor to 5 transplant recipients. The donor had been viremic but HEV IgM and IgG seronegative, and liver function test results were within reference ranges. After a mean of 52 days after transplantation, hepatitis developed in all 5 recipients; in the liver graft recipient, disease was severe and with progressive portal hypertension. Despite reduced immunosuppression, all HEV-4 infections progressed to persistent hepatitis. Four patients received ribavirin and showed evidence of response after 2 months. This study highlights the role of organ donation in HEV transmission, provides additional data on the natural history of HEV-4 infection, and points out differences between genotype 3 and 4 infections in immunocompromised patients.

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.

Early detection and prevention programs for kidney diseases in Hong Kong.

Two local studies were performed in Hong Kong for early detection and prevention of chronic kidney disease (CKD) which demonstrated the efficacy for screening asymptomatic individuals in the population for silent kidney disease while first degree relatives of known CKD patients should have a higher priority on future screening in view of their higher prevalence of silent CKD. Simple measures like urine dipstick tests and blood pressure measurement would suffice for screening. Regular health education programs are useful for conveying the key messages of kidney protection to the general public.

Cordyceps sinensis (a traditional Chinese medicine) for treating chronic kidney disease.

BACKGROUND: Cordyceps sinensis (Cordyceps, Dong Chong Xia Cao), a herbal medicine also known as Chinese caterpillar fungus, is one of the most commonly used ingredients in traditional Chinese medicine for the treatment of people with chronic kidney disease (CKD). OBJECTIVES: This review aimed to evaluate the therapeutic effects and potential adverse effects of Cordyceps sinensis for the treatment of people with CKD. SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register to 14 April 2014 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. We also searched CINAHL, AMED, Current Controlled Trials, OpenSIGLE, and Chinese databases including CBM, CMCC, TCMLARS, Chinese Dissertation Database, CMAC and Index to Chinese Periodical Literature. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing Cordyceps or its products with placebo, no treatment, or conventional treatment were considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Two authors independently assessed data quality and extracted data. Statistical analyses were performed using the random-effects model and the results expressed as risk ratio (RR) for dichotomous outcomes or mean difference (MD) for continuous data with 95% confidence intervals (CI). MAIN RESULTS: We included 22 studies that involved 1746 participants. Among people with CKD who were not receiving dialysis, Cordyceps preparations were found to significantly decrease serum creatinine (14 studies, 987 participants): MD -60.76 µmol/L, 95% CI -85.82 to -35.71); increase creatinine clearance (6 studies, 362 participants): MD 9.22 mL/min, 95% CI 3.10 to 15.34) and reduce 24 hour proteinuria (4 studies, 211 participants: MD -0.15 g/24 h, 95% CI -0.24 to -0.05). However, suboptimal reporting and flawed methodological approaches meant that risk of bias was assessed as high in four studies and unclear in 18 studies, and hence, these results need to be interpreted with caution. AUTHORS' CONCLUSIONS: We found that Cordyceps preparation, as an adjuvant therapy to conventional medicine, showed potential promise to decrease serum creatinine, increase creatine clearance, reduce proteinuria and alleviate CKD-associated complications, such as increased haemoglobin and serum albumin. However, definitive conclusions could not be made because of the low quality of evidence.

Melamine toxicity and the kidney.

The toxicity of melamine caught the attention of physicians as a result of a recent spate of renal injury after exposure to melamine-tainted milk in China. Melamine is an organic nitrogenous compound used in the production of plastics, dyes, fertilizers, and fabrics. In the current incident, melamine was added to milk to elevate falsely assay results for protein content. A variety of toxic effects from melamine, including nephrolithiasis, chronic kidney inflammation, and bladder carcinoma, all have been studied in animals. We review here the epidemiology, clinical features, and investigative findings concerning the only outbreak of melamine poisoning in humans. We also examine the renal toxicities of melamine and cyanuric acid--a by-product of its synthesis--and the associated risk factors on exposure and provide guidance on levels in foods.

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.

The use of enteric-coated mycophenolate sodium in the treatment of relapsing and steroid-dependent minimal change disease.

We report on the successful treatment of 5 consecutive adult patients with steroid-dependent or frequently relapsing minimal change disease (MCD), using a regimen of enteric-coated mycophenolate sodium (E-MPS) and prednisolone. E-MPS was used for induction therapy in 3 patients, and maintenance therapy in 2, all in conjunction with steroid treatment in tapering doses. Eventually 4 patients managed to discontinue steroid treatment, and 2 of them were also withdrawn from E-MPS. This combination therapy resulted in sustained remission and was well tolerated by our patients, with no signs of gastrointestinal upset, marrow suppression or increased incidence of infections. Our preliminary experience suggests that E-MPS is a promising new alternative in the management of steroid-dependent and relapsing MCD with a possibility of improving gastrointestinal tolerance.

Palliative care for patients with end-stage renal disease: experiences from Hong Kong.

As the number of patients with end-stage renal disease continues to grow in Hong Kong, many are opting to be managed conservatively without dialysis. A new service was initiated in Tuen Mun Hospital in 2004 aimed at offering palliative care to dying patients with renal failure. This paper presents retrospective data reflecting our dealings with patients who decided not to initiate or considered discontinuation of dialysis. In total, 107 patients received palliative care from the inception of the new service in August 2004 until July 2006. The findings illustrate that decisions related to initiation or withdrawal of dialysis are often related to personal beliefs and sentiments. Further exploration using qualitative methodology is recommended. The case history expounds a situation in which the patient cannot participate in decision-making concerning treatment options and offers some exploration of the ethical intricacies involved in treating very sick patients with dialysis therapy.

Influence of different allelic variants of the CYP3A and ABCB1 genes on the tacrolimus pharmacokinetic profile of Chinese renal transplant recipients.

Tacrolimus has a narrow therapeutic window and a wide interindividual variation in its pharmacokinetics. The cytochrome P450 3A (CYP3A) and the ATP-binding cassette B1 (ABCB1) genes play an important role in the tacrolimus disposition. Therefore, the aim of this study was to evaluate whether CYP3A and ABCB1 polymorphisms are associated with the area under the time concentration curve (AUC0-12) calculated using a two time point sample strategy. The CYP3A and ABCB1 genotypes were determined by real-time polymerase chain reaction (RT-PCR) fluorescence resonance energy transfer (FRET) assays in 103 Chinese renal transplant recipients and consequently related to their dose-normalized (dn)AUC0-12. A significant allele-dependent effect (Kruskal-Wallis; p < 0.001) was observed between the CYP3A5*3 polymorphism and the dnAUC0-12. Multiple regression analysis showed that the CYP3A5*3 polymorphism is the most significant independent variable and explained 35% of the dose requirement variability in relation to tacrolimus use. Regarding the ABCB1 G2677T/A and C3435T polymorphisms, a trend was observed between the different genotypes and the dnAUC0-12. In conclusion, the CYP3A5*3 polymorphism may be an important factor in determining the dose requirement for tacrolimus and genotyping can help determine the initial daily dose required by individual patients for adequate immunosuppression.

Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level.

BACKGROUND: Hyperuricemia is associated strongly with the development of hypertension, renal disease, and progression. Allopurinol decreases serum uric acid levels by inhibiting the enzyme xanthine oxidase. We hypothesized that administrating allopurinol to decrease serum uric acid levels to the normal range in hyperuricemic patients with chronic kidney disease may be of benefit in decreasing blood pressure and slowing the rate of renal disease progression in these patients. METHODS: We conducted a prospective, randomized, controlled trial of 54 hyperuricemic patients with chronic kidney disease. Patients were randomly assigned to treatment with allopurinol, 100 to 300 mg/d, or to continue the usual therapy for 12 months. Clinical, hematologic, and biochemical parameters were measured at baseline and 3, 6, and 12 months of treatment. We define our study end points as: (1) stable kidney function with less than 40% increase in serum creatinine level, (2) impaired renal function with creatinine level increase greater than 40% of baseline value, (3) initiation of dialysis therapy, and (4) death. RESULTS: One patient in the treatment group dropped out because of skin allergy to allopurinol. Serum uric acid levels were significantly decreased in subjects treated with allopurinol, from 9.75 +/- 1.18 mg/dL (0.58 +/- 0.07 mmol/L) to 5.88 +/- 1.01 mg/dL (0.35 +/- 0.06 mmol/L; P < 0.001). There were no significant differences in systolic or diastolic blood pressure at the end of the study comparing the 2 groups. There was a trend toward a lower serum creatinine level in the treatment group compared with controls after 12 months of therapy, although it did not reach statistical significance (P = 0.08). Overall, 4 of 25 patients (16%) in the allopurinol group reached the combined end points of significant deterioration in renal function and dialysis dependence compared with 12 of 26 patients (46.1%) in the control group (P = 0.015). CONCLUSION: Allopurinol therapy significantly decreases serum uric acid levels in hyperuricemic patients with mild to moderate chronic kidney disease. Its use is safe and helps preserve kidney function during 12 months of therapy compared with controls. Results of this study need to be confirmed with an additional prospective trial involving a larger cohort of patients to determine the long-term efficacy of allopurinol therapy and in specific chronic kidney disease subpopulations.

Fatal case of Aspergillus coinfection in a renal transplant recipient suffering from cytomegalovirus pneumonitis.

Cytomegalovirus (CMV) disease is common in postrenal transplant recipients, and may predispose the patients to secondary bacterial or fungal infections. However, simultaneous coinfection is rare and often makes diagnosis difficult. We report a case of CMV pneumonitis in a renal transplant recipient presenting with elevated CMV pp65 antigen level and abnormal chest radiograph. Despite potent and broad-spectrum antimicrobial therapy, his condition deteriorated rapidly - he soon went into respiratory failure, septic shock and died several days later. Transbronchial biopsy and bronchoalveolar lavage obtained before the patient's death showed evidence of invasive pulmonary aspergillosis with concomitant CMV pneumonitis. High index of suspicion and early and empirical initiation of antifungal therapy may be necessary for successful management of fulminant pneumonia in solid organ transplant recipients.

Clinical outcomes of systemic lupus erythematosus patients undergoing continuous ambulatory peritoneal dialysis.

OBJECTIVES: The purpose of this study was to evaluate the outcome of systemic lupus erythematosus (SLE) patients on continuous ambulatory peritoneal dialysis (CAPD). METHODS: Eighteen SLE patients who had been undergoing CAPD for at least 3 months in our unit were compared with 36 other age- and gender-matched non-diabetic CAPD patients with an underlying primary chronic glomerulonephritis (CGn). The clinical outcome, infective complications, lupus activities, biochemical parameters, haemoglobin level and the use of erythropoietin were reviewed. RESULTS: The duration of dialysis of the two studied groups was not different, with a mean of 35.4 months for the SLE group and 36.7 months for the CGn group. Before dialysis, SLE patients had a significantly lower albumin level (30.4+/-6.6 vs 35.4+/-5.59 g/dl, P<0.01), while the mean haemoglobin levels of the two groups were similar (8.5+/-1.8 g/dl for SLE vs 9.0+/-1.9 g/dl for the control group). However, the weekly dose of erythropoietin (EPO) used was significantly higher in the SLE group (6000 vs 3818 U/week, P<0.01) to maintain a similar haemoglobin level during dialysis. Regarding the infective complications, the SLE group had a higher peritonitis rate (5.7 episodes/100 patient-months vs 2.4 episodes/100 patient-months, P<0.05), and an increase in the non catheter related infection rate (6.67 episodes/100 patient-months vs 1.1 episodes/100 patient-months, P<0.001). However, no significant difference could be demonstrated in the Tenckhoff catheter exit site infection rate (2 episodes/100 vs 1.7 episode/100 patient-months). The number of patients who received a kidney transplant or required a change of mode to haemodialysis was similar among the two groups. Seven patients died during the follow-up period, and the overall mortality rate was much higher in the SLE group than in the control group (0.83/100 vs 0.15/100 patient-months, P<0.05). CONCLUSIONS: SLE patients on CAPD have a significantly lower pre-dialysis serum albumin level and use a higher dose of Epo to achieve a comparable haemoglobin level than other non-diabetic CGn CAPD patients. They also have a poorer prognosis in terms of infective complications and mortality rate.

Use of intraperitoneal urokinase for resistant bacterial peritonitis in continuous ambulatory peritoneal dialysis.

Intraperitoneal (IP) urokinase is a fibrinolytic agent that has been used in the adjunctive treatment of continuous ambulatory peritoneal dialysis (CAPD) and resistant and relapsing peritonitis. However, its efficacy and role in treating resistant CAPD bacterial peritonitis remain unclear and results from previous prospective studies have been conflicting. We prospectively randomized 88 CAPD patients with bacterial peritonitis resistant to initial empirical IP antibiotics into two groups: IP urokinase 60,000 IU and a placebo group. Patients were treated concomitantly with susceptible antibiotics according to culture results. Peritoneal dialysate grew pseudomonas aeruginosa in 13 patients (14.8%), non-pseudomonas bacteria in 63 patients (71.6%) and negative cultures in 12 patients (13.6%). For the clinical outcomes, there were no significant differences in the primary response rates (61.4 vs. 50%), relapse rates (9.1 vs. 13.6%), Tenckhoff catheter removal rates (22.7 vs. 29.5%) and mortality rates (6.8 and 6.8%) between the urokinase group and the controls (p=ns). Subgroup analysis of culture negative patients (n=12) also demonstrated no sgnificant benefit for urokinase treatment. No significant adverse effects were encountered with the IP urokinase instillation. Total median peritonitis-related length of hospitalization for the urokinase group and controls were 7 and 11 days, respectively (p=0.32). We concluded that IP urokinse plays no significant role as an adjuvant therapy in the treatment of bacterial CAPD peritonitis resistant to initial IP antibiotic therapy.

Prevalence of silent kidney disease in Hong Kong: the screening for Hong Kong Asymptomatic Renal Population and Evaluation (SHARE) program.

BACKGROUND: End-stage renal disease (ESRD) is epidemic worldwide. In Hong Kong, the annual incidence of ESRD has risen from 100 pmp (per million population) in 1996 to 140 pmp in 2003. SHARE (Screening for Hong Kong Asymptomatic Renal Population and Evaluation program) is a population-based screening program aimed at identifying the prevalence of unrecognized renal disease in asymptomatic individuals, allowing further evaluation and disease-modifying interventions. METHODS: From November to December 2003, SHARE was conducted in several large residential communities in Hong Kong. The screening tool included a questionnaire documenting demographics and history or family history of diabetes mellitus (DM), hypertension (HT), and chronic kidney disease (CKD), together with on-site measurements of blood pressure (BP) and urine dipstick for protein, blood, and glucose. RESULTS: There were a total of 1811 participants. One thousand two hundred and one subjects were entered into the final analysis. Among the 1201 who were apparently "healthy" (asymptomatic and without history of DM, HT, or CKD), the prevalence of positive (> or =1+) urine dipstick for protein, glucose, blood, protein or blood, any urine abnormality, and HT (BP> or =140/90) was 3.2%, 1.7%, 13.8%, 16%, 17.4%, and 8.7%, respectively. Thirty three percent of the age over 60 years old group had either hypertension or urine abnormalities, compared with 24.0% in the 41- to 60-year-old group and 9.7% in the 20- to 40-year-old group. Having a family history of diabetes or hypertension increases the risk of having urine abnormalities, while a family history of hypertension also increases the risk of high blood pressure. CONCLUSION: It is concluded that subclinical abnormalities in urinalysis or BP readings are prevalent across all age groups in the adult population. An effective screening program at the primary care level that identifies these subjects for further evaluation is warranted, and the public in Hong Kong should be educated toward the significance of such findings in order to have regular health check for asymptomatic renal diseases.

Haemodialysis catheter-related right transverse cervical artery pseudoaneurysm and treatment by coil embolization.

In patients with end-stage renal disease, temporary placement of venous catheters for haemodialysis (HD) is often necessary, and the right internal jugular (RIJ) vein is the usual preferred site of HD catheter placement. We report here a patient who experienced complications because of the development of a pseudoaneurysm of the transverse cervical artery following an apparently uneventful RIJ vein cannulation for temporary HD, using the blind landmark-guided technique. This is a rare complication of RIJ vein cannulation and HD catheter placement. The pseudoaneurysm presented 3 weeks after the procedure and was diagnosed by using colour-Doppler ultrasound, followed by an angiogram, and it was successfully occluded using endovascular coil embolization.

Ultrasonography in the management of exit site infections in peritoneal dialysis patients.

AIM: To assess the efficacy of using ultrasonography (USG) in monitoring the progress of exit site infection (ESI) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). METHODS: Twenty-two cases of newly diagnosed ESI and 20 cases with normal exit sites as controls were assessed by using USG. The exit sites were reassessed by using USG after finishing a course of antibiotic therapy, and the sonographic findings were correlated with the clinical outcome. RESULTS: Out of the 22 cases of ESI, 21 cases had definite sonolucent zones around the external cuffs, while one case had normal sonographic findings. Of the 20 control cases of normal exit sites, 16 had normal sonographic findings, and four had sonolucent zones around the external cuffs. Exit site infections correlated with positive sonographic findings as compared to normal exits (P <0.0001). The 21 cases of ultrasonic-positive ESI were re-examined after antibiotic therapy, and 10 of these had a post-treatment sonolucent rim around the distal cuff < or =1 mm thick, while 11 cases were persistently > mm thick. The former group was shown to have a more favourable outcome (P=0.013). And despite variable USG findings, all eight patients with Pseudomonas aeruginosa-related ESI had an unfavourable clinical outcome. CONCLUSION: Ultrasonography of the exit sites in CAPD patients is a useful adjunctive tool in the management of ESI. A sonolucent zone around the external cuff >1 mm thick following a course of antibiotic treatment and the involvement of the proximal cuff are associated with poor clinical outcome. In ESI caused by Pseudomonas aeruginosa, the clinical outcome was uniformly poor irrespective of the sonographic findings.