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The scarcity of donor organs for transplant results in long waiting times for kidney transplantation and low transplant rate worldwide. Utilization of kidneys from donors with acute kidney injury (AKI) is one of the strategies that has attracted attention recently. This article reviewed the outcomes of transplanted renal allografts from donors with acute kidney injury. Key findings about the transplant outcomes included a higher incidence of delayed graft function and primary non function, but respectable outcomes in the context of similar acute rejection rates, and graft function and graft survival. Against this background and with evidence of high mortality for patients remaining on waiting list of transplant, we advocate consideration of AKI donors for kidney transplantation. [ABSTRACT FROM AUTHOR]

Background: We tested the strategy of mTOR inhibitors with calcineurin inhibitor minimization in renal transplant recipients with known chronic allograft dysfunction. Methods: In this open-label, single-arm study, renal transplant patients were recruited after biopsy-confirmed chronic allograft dysfunction in the absence of acute rejection episode within 2 months, with proteinuria <0.8 g/day, and serum creatinine <220 μmol/L or estimated glomerular filtration rate >40 mL/min/1.73 m2. They were converted to everolimus (aiming for trough everolimus level 3-8 ng/mL) with cyclosporine minimization, to assess the effect on renal function, rate of glomerular filtration rate decline, and longitudinal transplant biopsy at 12 months. Results: Seventeen Chinese patients (median transplant duration, 4.2 years) were recruited; no patients discontinued study medication. The mean slope of the glomerular filtration rate over time was -4.31±6.65 mL/min/1.73 m2 per year in the year before everolimus, as compared with 1.29±5.84 mL/min/1.73 m2 per year in the 12 months of everolimus therapy, a difference of 5.61 mL/min/1.73 m2 per year (95% confidence interval [CI], 0.40-10.8) favoring everolimus therapy (P=0.036). Serial renal biopsy histology showed significant decrease of tubular atrophy (15.7%±11.3% versus 7.1%±7.3%, P=0.005) and interstitial fibrosis (14.8%±11.5% versus 7.2%±8.2%, P=0.013). Intrarenal expression of TGF-β1 mRNA showed a nonsignificant decrease after everolimus treatment. Conclusion: In renal transplant recipients with biopsy-confirmed chronic allograft dysfunction, we found a significant beneficial effect of everolimus rescue therapy and calcineurin inhibitor minimization strategy on the improvement of glomerular filtration rate decline rate. In secondary analysis, everolimus was shown to slow down the disease progression by reducing the tubular atrophy and interstitial fibrosis scoring. [ABSTRACT FROM AUTHOR]

Background A territory-wide diabetes management program (Risk Assessment Management Program - RAMP) was recently established, providing comprehensive management for all diabetics, helping to delineate current level of control and complications prevalence among primary care diabetic patients in Hong Kong. Method This cross-sectional study captured anonymous clinical data from RAMP patients. Data obtained include sociodemographic details, type of diabetes, illness duration, family history, drug usage, coexisting illnesses, diabetic complications and other clinical parameters. Results Data from 15,856 type 2 diabetic patients were analyzed. 57.1% were above 60 years old, with mean disease duration of 7.3 years. Hypertension was the commonest coexisting chronic illness (57.6%). 30.2% and 61.8% have their systolic and diastolic pressure controlled to below 130 mmHg and 80 mmHg respectively. Over half (51.5%) had an HbA1c level of less than 7.0%. 88.4% did not achieve target lipid level. 15% were on diet control alone . Only 22.2% were on statins. In patients with microalbuminuria and macroalbuminuria, 40.7% and 54.5% were on angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) respectively. 12.9%, 38.8% and 2.4% had diabetic retinopathy, nephropathy and neuropathy respectively. Overall, 37.9%, 7.3% and 0.4% had single, two and three concurrent microvascular complications respectively. Conclusion The level of diabetic control is comparable with other developed countries. We demonstrated a high prevalence of microvascular complications among Chinese primary care patients despite achieving adequate HbA1c levels, highlighting the importance of managing all aspects of diabetes including weight, lipid and blood pressure. Efforts to improve holistic management must be tailored according to the needs of our population, with the challenges that the majority have low educational background and in the older age group. [ABSTRACT FROM AUTHOR]

This Review focuses on the changing epidemiology of infections among patients with end-stage renal disease who are undergoing dialysis, in particular, bloodstream infections related to vascular access in patients undergoing hemodialysis, and peritonitis in patients undergoing peritoneal dialysis, are highlighted. Gram-positive (staphylococcal and enterococcal) bloodstream infections and Gram-negative peritonitis (especially extended-spectrum βlactamase-producing organisms) contribute substantially to excess health-care use owing to infection caused by dialysis access. Although the management of peritoneal-dialysis-related peritonitis has been hampered by a dearth of randomized, controlled studies, epidemiological data have provided useful information. To overcome the problem of differing methods used to monitor infections within various dialysis centers, uniform reporting systems for vascular-access-related infection and peritoneal-dialysis-related peritonitis, as recommended by the Centers for Disease Control and Prevention and the International Society for Peritoneal Dialysis, respectively, are discussed. Infections unrelated to the port of entry for dialysis are also examined, namely hepatitis and respiratory infection. To address the disease burden, we examine the infection-related mortality as well as the implications for subsequent cardiovascular mortality. [ABSTRACT FROM AUTHOR]

AFCKDI RECOMMENDATIONS FOR EARLY DETECTION OF CHRONIC KIDNEY DISEASE 1. Targets Patients with diabetes, hypertension Those with family history of chronic kidney disease (CKD) Individuals receiving potentially nephrotoxic drugs, herbs or substances or taking indigenous medicine Patients with past history of acute kidney injury Individuals older than 65 years 2. Tools Spot urine sample for protein with standard urine Dipstick test (need a repeat confirmatory test if positive) Dipstick for red blood cells (need confirmation by urine microscopy) An estimate of glomerular filtration rate based on serum creatinine concentration 3. Frequency of screening Screening frequency for targeted individuals should be yearly if no abnormality is detected on initial evaluation. 4. Who should perform the screening Doctors, nurses, paramedical staff and other trained healthcare professionals 5. Intervention after screening Patients detected to have CKD should be referred to primary care physicians with experience in management of kidney disease for follow up. A management protocol should be provided to the primary care physicians. Further referral to nephrologists for management will be based on the protocol together with clinical judgment of the primary care physicians with their assessment of the severity of CKD and the likelihood of progression. 6. Screening for cardiovascular disease risk It is recommended that cardiovascular disease risk factors should be screened in all patients with CKD. [ABSTRACT FROM AUTHOR]

Background. The response to recombinant hepatitis B vaccine remains suboptimal among the dialysis population. [ABSTRACT FROM PUBLISHER]

Aim: Interleukin-18 (IL-18) is a pro-inflammatory cytokine and possibly plays an important role in the pathogenesis of cardiovascular disease. The relationship between two IL-18 gene polymorphisms, namely C-607A and G-137C, and cardiovascular disease in patients with diabetic nephropathy was examined. Methods: Two hundred and twenty patients (91 male) with diabetic nephropathy were studied. The IL-18 promoter genotypes were determined. All patients were then prospectively followed for the cardiovascular events. Cardiovascular mortality and all-cause mortality were also compared. Results: Mean age was 64.3 ± 10.6 years; average follow up was 73.9 ± 33.6 months. The frequencies of CC, CA and AA genotypes of the C-607A polymorphism were 25.5%, 48.2% and 26.8%, respectively; GG, GC and CC genotypes of the G-137C polymorphism were 71.8%, 25.0% and 3.2%, respectively. Neither of the polymorphisms were associated with the development of primary cardiovascular end-point. Cardiovascular survival was 84.8% and 70.6% at 60 months for GG and GC/CC genotypes of the G-137C polymorphism, respectively ( P = 0.027); the corresponding actuarial survival was 69.0% and 54.8%, respectively ( P = 0.053). However, the G-137C genotype was not an independent predictor of cardiovascular or actuarial survival after adjusting for confounders by multivariate analysis with the Cox model. The C-607A polymorphism had no significant effect on cardiovascular or actuarial survival. Conclusion: The G-137C polymorphism of the IL-18 promoter is associated with the cardiovascular mortality, and a trend of association with all-cause mortality, in patients with diabetic nephropathy. The association, however, becomes insignificant after adjusting for confounding factors. Further studies are needed to test other genetic determinants of the association between systemic inflammation and cardiovascular disease in renal failure patients. [ABSTRACT FROM AUTHOR]

This article reviews the clinical aspects and epidemiological links between diabetes mellitus and renal transplantation, and emphasizes areas that warrant further clarification. In particular, we summarize the data for various immunosuppression medications on the risk of new-onset diabetes after transplantation (NODAT). An increased mechanistic understanding of new-onset diabetes might provide new insights into the pathophysiology of this complication after solid organ transplantation. Claims that selecting immunosuppression regimen to minimize the risk of NODAT, nevertheless, are currently not supported by the scientific published work. Intuitively, strategies that aim to change the underlying biology of the disease process of NODAT are desirable; among them, lifestyle modification is currently the most promising in terms of real benefit with the least risk. [ABSTRACT FROM AUTHOR]

Iodide mumps can occur after administration of any iodinated contrast media, irrespective of the osmolality of the contrast preparation. This condition is characterized by acute salivary gland swelling shortly after contrast study, presumably secondary to toxic accumulation of iodide in salivary glands with high iodide concentration. In this article, a case of iodide mumps is presented, along with a discussion of vulnerability due to renal impairment, which causes prolongation of the half-life of contrast media. A total of 30 additional cases of iodide mumps published in the English literature were reviewed. Despite the clinical observations that iodide mumps resolved with conservative management, it should be emphasized that recurrence is common if vulnerable patients are subjected to further iodinated contrast media. [ABSTRACT FROM AUTHOR]

Background/Aim: In the setting of empiric antibiotic treatment of peritoneal-dialysis-related peritonitis complications, the speed with which a bacteriological diagnosis can be achieved is of importance. We compare the clinical performance of two culture methods to diagnose the causative microorganisms as suggested by the International Society for Peritoneal Dialysis and the United Kingdom Health Protection Agency. Methods: We prospectively evaluated microbiological cultures of peritoneal fluid samples by the direct broth culture versus water lysis. Samples from 17 consecutive patients with dialysis-associated peritonitis were examined. Results: Of the 17 dialysates cultured, 14 (82.4%) were positive by one of the two methods. The final culture results agreed in 16 of 17 specimens (94.1%). The preliminary organism identification rate by Gram staining with the broth culture method was 70.6%, which was significantly greater than 17.6% by the water lysis method (p = 0.0019). In particular, the broth culture technique demonstrated superior Gram stain performance to identify Gram-positive organisms. Among the 13 dialysate samples positive by both methods, the broth culture method detected organisms faster than the water lysis method (1.3 ± 0.7 vs. 2.6 ± 1.6 days, p = 0.005). Conclusions: Our results support the routine use of the broth culture technique using BacT/Alert blood culture bottles in order to facilitate early streamlining of empiric antibiotic therapy. Gram staining of sediments after centrifugation is associated with low diagnostic yield. Whether the lysis-centrifugation technique could provide additional value in case of peritonitis with a high likelihood of culture-negative results needs to be evaluated. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. Shortening behaviour during peritoneal dialysis training can be easily measured, and likened to the skipping behaviour in haemodialysis subjects, although its effect on peritoneal dialysis outcomes is now well understood. We studied the clinical impact of failing to adhere to a peritoneal dialysis training programme among incident dialysis patients.Methods. This study included 159 consecutive inception peritoneal dialysis patients in a single centre from September 1999 through November 2002. We evaluated the effects of behavioural compliance quantified by the per cent time arriving late for scheduled peritoneal dialysis training. The patients were categorized by whether they arrived late in >20% of their peritoneal dialysis training sessions.Results. Of the 159 incident peritoneal dialysis patients (mean age 57 ± 13 years) who attended peritoneal dialysis training, 70 subjects (44%) arrived late in >20% of the sessions. They were younger by 5 years than patients who arrived late ≤20%. Mean peritonitis-free time for subjects who arrived late for training in >20% the of sessions was 30.9 months, as compared with 41.8 months in subjects with ≤20% late attendance behaviour (log rank test, P = 0.038). Multivariable Cox proportional hazards analysis showed that late attendance behaviour and baseline serum albumin were the only independent risk factors for the time to a first peritonitis after adjustment for diabetes mellitus and relevant coexisting medical factors. Late arrival in >20% of the peritoneal dialysis training sessions was associated with >50% increased likelihood of subsequent peritonitis, with an adjusted risk ratio of 1.56 (95% confidence interval, 1.02–2.39; P = 0.04).Conclusion. These findings show that the behavioural measure of late attendance for peritoneal dialysis training has a crucial role in predicting peritonitis. It may therefore represent a practical strategy for identifying poor adherence or predicting medical outcomes. [ABSTRACT FROM AUTHOR]

Background. Chronic utilization of a bio-incompatible peritoneal dialysis (PD) solution with acidic pH and a high content of glucose degradation product (GDP) has been implicated as a contributing cause of peritoneal failure. We compared a newly formulated solution of neutral pH and low levels of GDP to a standard PD solution.Methods. Fifty new PD patients were randomized to a conventional lactate-buffered fluid (control) and a pH neutral, lactate-buffered, low GDP solution (balance). Patients were followed for 12 months. Serum samples were assayed for C-reactive protein (CRP). PD effluent was collected and assayed for cancer antigen-125 (CA125) and hyaluronan (HA). Clinical end points were the residual renal function and dialysis adequacy indices.Results. After 52 weeks of treatment, PD fluid CA125 rose from 2.45 ± 0.96 to 14.30 ± 2.17 U/ml (P < 0.001), and HA declined from 2.26 ± 0.60 to 1.45 ± 0.32 μg/ml (P = 0.07) in the balance group. The balance group had a higher PD fluid CA-125 (14.30 ± 2.17 vs 7.36 ± 2.23 U/ml, P = 0.007), lower HA (1.45 ± 0.32 vs 2.55 ± 0.32 μg/ml, P = 0.007), and lower serum CRP level (1.77 ± 0.42 vs 7.73 ± 2.42 mg/l, P = 0.026) than the control group at 52 weeks. There was no difference in dialysis adequacy indices, ultrafiltration volume, urine output, residual renal function, peritonitis rate or need of hospitalization in 1 year.Conclusion. As compared to conventional PD solution, the use of balance, a neutral pH, low GDP solution resulted in a superior profile of PDE mesothelial cell marker and a lower degree of systemic inflammation, and the difference was maintained for 1 year. It remains to be determined whether these effects could result in better long-term clinical outcome. [ABSTRACT FROM AUTHOR]

Genetics of common progressive renal disease. Familial aggregation of common chronic kidney diseases provides a unique opportunity to investigate the susceptibility genetic and environmental factors. In the past decade, a wealth of new data has become available concerning the genetic susceptibility leading to numerous nephropathies. Knowledge of the genetic components allows better understanding of initiation and progression of these chronic kidney diseases. In addition, one can envision that identification of genetically susceptible individuals might lead to earlier diagnosis and potential reversal of the current epidemic of end-stage renal disease. The goal of the current discussion is to review various issues pertaining to the role of genetic factors in common chronic kidney diseases, as exemplified by two leading causes of end-stage renal diseases worldwide, nephropathy of type 2 diabetes and IgA nephropathy. The genetic and environmental interplay leading to the nephropathies is highlighted. [ABSTRACT FROM AUTHOR]

Acidosis is a classic uremic toxin that causes protein catabolism, mainly by selective breakdown of skeletal muscle protein. However, the importance of acidosis is often overlooked in dialysis patients. In the presence of acidosis, there is activation of the ubiquitin-proteasome machinery as well as the branched-chain keto acid dehydrogenase, resulting in catabolism of muscle protein. Acidosis acts synergistically with other catabolic factors, such as inflammatory cytokines and insulin resistance, in inducing protein catabolism. There is ample laboratory evidence showing that correction of acidosis prevents the up-regulation of the ubiquitin-proteasome machinery and reduces protein degradation. Randomized control trials further show that acidosis in dialysis patients can be treated successfully by a higher dialysate bicarbonate or lactate concentration, or by oral bicarbonate supplement. Correction of mild acidosis in dialysis patients is effective in improving nutritional status and reducing the duration of hospitalization. [ABSTRACT FROM AUTHOR]

Genetic polymorphism of VEGF: Impact on longitudinal change of peritoneal transport and survival of peritoneal dialysis patients. Background. Vascular endothelial growth factor (VEGF) plays a pivotal role in the peritoneal angiogenesis and hyperpermeability in patients on peritoneal dialysis. We hypothesis that VEGF genetic polymorphism may affect the longitudinal change of peritoneal transport and clinical outcome of peritoneal dialysis patients. Methods. We studied 135 consecutive new peritoneal dialysis patients. VEGF genetic polymorphism at –1154 and –2578 positions were determined by polymerase chain reaction (PCR) methodologies. Standard peritoneal test and dialysis adequacy and transport test (DATT) were performed at the initiation of peritoneal dialysis. After 12 months, DATT was repeated in 83 patients. In 35 patients, VEGF production in vivo was determined by its levels in serum and peritoneal dialysis effluent, and mRNA expression in peritoneal dialysis effluent. Patients were followed for 19.4 ± 8.5 months for survival study. Results. There was no relation between VEGF genotype and baseline peritoneal transport group. The changes in 24-hour dialysate-to-plasma (D/P) creatinine after 12 months were 0.028 ± 0.159, -0.013 ± 0.137, and 0.141 ± 0.231 for CC, CA, and AA genotype at –2578 position, respectively [one-way analysis of variance (ANOVA), P= 0.028]. The AA genotype had significantly higher increase in 24-hour D/P creatinine than the other genotypes. Similar results were found with the genotype at −1154 position, which had marked linkage disequilibrium with the genotype at –2578 position. Actuarial patient survival was 90.3% and 74.9% at 24 months for CC and CA/AA genotypes at –2578 position, respectively ( P= 0.036). After correcting for confounding covariates, the adjusted hazard ratio of death was 3.04 (95% CI, 1.10 to 8.36) for the CA/AA group as compared to CC group. Although baseline serum VEGF level was higher in patients with CC genotype than those with CA/AA genotype at –2578 position (541.5 ± 322.8 pg/mL vs. 298.8 ± 209.4 pg/mL, P= 0.012), VEGF mRNA expression in peritoneal dialysis effluent was significantly lower in patients with CC genotype (1.82 ± 2.77 vs 4.48 ± 3.28, P= 0.021). VEGF protein level in peritoneal dialysis effluent was also marginally lower in patients with CC genotype, although the difference was not significant. Genotype at –1154 position was not associated with VEGF production in vivo or patient survival. Conclusion. We conclude that in peritoneal dialysis patients, the AA genotype of VEGF promoter at –2578 position was associated with progressive increase in peritoneal transport. The CA/AA genotype at –2578 position was also associated with an excess mortality. Our finding also suggests that systemic and local peritoneal VEGF production may be differentially regulated. [ABSTRACT FROM AUTHOR]

Abstract Hydrothorax as a result of pleuroperitoneal communication occurs in approximately 2% of continuous ambulatory peritoneal dialysis (CAPD) patients. Although our understanding of its mechanisms is incomplete, it is apparent that the key to successful therapy is obliteration of a transdiaphragmatic route of dialysate leakage (pleuroperitoneal communication), possibly coupled with reduction of intra-abdominal pressure. This review corroborated the findings from 10 major population-based case series in which 60 of the 104 cases (58%) were able to resume long-term peritoneal dialysis (PD). Temporary interruption of PD alone was successful in half of them. As compared to this conservative approach, as well as chemical pleurodesis via intercostal chest drain, video-assisted thoracoscopic intervention (including direct pleurodesis and diaphragmatic repair) has shown a promising role. Efficacy of thoracoscopic treatment has been confirmed by several case series from various centers and the demonstration of a success rate in excess of 90%. With accumulating experience using the thoracoscopic technique, it remains to be seen whether this mode of treatment will obviate the traditional closed pleurodesis. [ABSTRACT FROM AUTHOR]

Background: Residual renal function is an important determinant of mortality and morbidity in patients receiving peritoneal dialysis. However, few studies have evaluated therapeutic approaches for preserving residual renal function after the initiation of dialysis. Objective: To test the hypothesis that the angiotensin-converting enzyme (ACE) inhibitor ramipril slows the decline in residual renal function in patients with end-stage renal failure treated with peritoneal dialysis. Design: Randomized, open-label, controlled trial. Setting: Single-center study in the dialysis unit of a university teaching hospital. Patients: 60 patients receiving peritoneal dialysis. Measurements: Patients were randomly assigned to ramipril (5 mg daily) or no treatment. The target blood pressure was 135/85 mm Hg or less. Rate of decline in residual glomerular filtration rate (GFR) and development of complete anuria were compared among groups. Results: Over 12 months, average residual GFR declined by 2.07 mL/min per 1.73 m[SUP2]in the ramipril group versus 3.00 mL/min per 1.73 m[SUP2]in the control group (P 3 0.03). The difference between the average changes in residual GFR in the ramipril and control groups from baseline to 12 months was 0.93 mL/min per 1.73 m[SUP2](95% CI, 0.09 to 1.78 mL/min per 1.73 m[SUP2]). At 12 months, 14 patients in the ramipril group and 22 in the control group developed anuria. With intention-to-treat multivariable analysis using the Cox model, it was estimated that at 3, 6, and 9 months, patients assigned to ramipril had a higher adjusted hazard of complete anuria than did patients assigned to no treatment. Of the 25 patients who still did not have complete anuria at 12 months, those assigned to ramipril had a better prognosis than did those assigned to no treatment (adjusted hazard ratio, 0.58 [CI, 0.36 to 0.94]). The rates of death from any cause, duration of hospitalization, and cardiovascular events did not differ significantly between groups.... [ABSTRACT FROM AUTHOR]

We reviewed 42 cases of cefepime-induced neurotoxicity and 12 cases of ceftazidime-induced neurotoxicity from the literature and our institution.Clinical characteristics and timing of diagnosis were examined. Common findings were confusion with temporospatial disorientation (96% of patients),myoclonus (33%), and seizures (13%). These neurologic disorders frequently are encountered in uremic and elderly patients, who often are in a confused state when they visit their physician. The risk of delayed diagnosis was greater with cefepime than ceftazidime neurotoxicity. The median intervalbetween symptom onset and diagnosis of cefepime versus ceftazidimc neurotoxicity was 5 and 3 days, respectively (p=0.005). Delayed diagnosis of cefepime neurotoxicity may be due to lack of awareness of the adverse effect. Data gathered since these two broad-spectrum antibiotics were first marketed underscore the potential for neurologic adverse events secondary to their administration. Thus, clinicians' awareness must be increased so that the time between symptom onset and diagnosis can be reduced. [ABSTRACT FROM AUTHOR]

The article discusses the study "ß-lactam antibiotic concentrations during continuous renal replacement therapy," by M. Beumier and colleagues in the May 22, 2014 issue of the journal "Critical Care." Topics addressed include avoiding the risk of overdose during continuous renal replacement therapy (CRRT), improved dose precision and patient outcomes via therapeutic drug monitoring, pharmacokinetic modeling and dose simulation, and reasons for subtherapeutic antibiotic concentrations.

In this article, the authors report on the importance of peritoneal dialysis catheter insertion by nephrologists. The main aim of the practice is to provide timely and effective catheter insertion without unduly long waiting times or delay. The next important concern is the feasibility and safety of peritoneal access creation by nephrologists. A table is also presented in support of the article.

The article discusses the result of a survey by the Dialysis Advisory Group of the American Society of Nephrology, which compared reimbursement policies for dialysis care in Canada, the U.S., France, Germany, Great Britain, the Netherlands and Belgium. The survey made a comparison of the reimbursement rates for hospital dialysis and home dialysis strategies, as well as reimbursement between peritoneal dialysis and hemodialysis. Recommendation that will improve home-based dialysis are offered.

The authors reflects on successful embolization of transplant kidney arteriovenous fistula. Biopsy-related vascular injuries in renal transplants, although relatively common, are usually of little clinical significance. Arteriovenous fistula after percutaneous renal biopsy, for instance, have been reported in 10-17.5% of patients in prospective observational study using serial colour-coded duplex sonographic examination.

A letter to the editor is presented concerning the effects of association in cohort studies of metformin and Vitamin B12 deficiency.

We describe a case of pronounced symptomatic hypercalcemia as a consequence of thyrotoxicosis alone. Primary hyperparathyroidism and other secondary causes of hypercalcemia were excluded. Hypercalcemia completely abated after treatment of thyrotoxicosis. Notwithstanding that hypercalcemia is an unusual manifestation of hyperthyroidism, asymptomatic elevation of serum calcium concentration had been documented in up to one-fourth of patients with proved hyperthyroidism. The current case is unusual in that the patient demonstrated a significant degree of hypercalcemia secondary to hyperthyroidism alone, with a serum calcium level as high as 3.14 mmol/L. We further discuss the putative pathophysiology of this "thyroid bone disease," highlighting the repercussion on calcium and bone metabolism in hyperthyroidism. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor on the effect of low dose amiodarone on pseudo-alcoholic cirrhosis.

Background. Mitochondrial dysfunction plays an important role in the pathogenesis and progression of diabetic nephropathy (DN). We study the relation between urinary and intra-renal mitochondrial deoxyribonucleic acid (mtDNA) levels and renal dysfunction in DN. Methods. We recruited 92 patients with biopsy-proven DN. Urinary sediment, urinary supernatant and intra-renal mtDNA levels were measured and compared with baseline renal biopsy, kidney scarring and renal function decline in the subsequent 24 months. Results. mtDNA could be detected in all urine supernatant, urine sediment and renal biopsy specimens. There was a modest but statistically significant inverse correlation between urinary supernatant and intra-renal mtDNA levels (r =-0.453, P = 0.012). Urinary supernatant mtDNA level had modest but statistically significant correlations, inversely with estimated glomerular filtration rate (r =-0.214, P = 0.04), and positively with interstitial fibrosis (r = 0.300, P = 0.005). Intra-renal mtDNA had significant inverse correlation with interstitial fibrosis (r =-0.537, P = 0.003). However, there was no significant relation between renal function decline and urinary supernatant, urinary sediment or intra-renal mtDNA levels. Conclusions. mtDNA is readily detectable in urinary supernatant and kidney tissue, and their levels correlate with renal function and scarring in DN. Further studies are needed to determine the accuracy of urinary supernatant mtDNA level as a prognostic indicator of DN, as well as its role in other kidney diseases. [ABSTRACT FROM AUTHOR]

Background: Recombinant human erythropoietin (rHuEPO) is an effective treatment for renal anemia. Recently, there is evidence to suggest that rHuEPO may reduce podocyte injury in diabetic kidney disease (DKD). However, there is no published study on the change in podocyte injury marker levels before and after rHuEPO treatment in DKD. Methods: We measured serum nephrin and podocalyxin level, and their corresponding plasma mRNA levels, in 49 DKD patients before rHuEPO treatment, and then 12 and 36 weeks afterward. Results: There were reductions in serum nephrin (p = 0.002) and podocalyxin levels (p = 0.09), as well as their corresponding plasma mRNA levels (p < 0.0001 for both) after rHuEPO treatment. The change in serum nephrin and podocin level had significant inverse correlation with the concomitant change in hemoglobin level (r = -0.670 and -0.739 respectively, p < 0.0001 for both), but not with the change in kidney function or proteinuria. Conclusion: Serum nephrin and podocalyxin levels and their corresponding plasma mRNA levels were significant reduced after rHuEPO treatment in DKD patients, and the change in serum nephrin and podocalyxin levels correlated with the change in hemoglobin level. The effect of rHuEPO on podocyte injury deserves further study. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article on paraproteinemia-associated pseudohypercreatininemia, published in a previous issue of the journal.

The article reports on the case of a 59-year-old hemodialysis patient who was hospitalized for bilateral painful knee swelling after a fall and mild contusion injury. The relatively uncommon occurrence of bilateral quadriceps rupture has been described in association with secondary hyperparathyroidism. Details about treatment and patient recovery are cited.

Background. After prolonged peritoneal dialysis (PD) and exposure to a non-physiological dialysis solution, peritoneal mesothelial cells undergo the epithelial-to-mesenchymal transition. In other biological systems, bone morphogenic protein-7 (BMP-7) is a key factor that controls this process. However, the role of BMP-7 in peritoneal physiology has not been studied. Methods. We studied the peritoneal transport characteristics of 50 consecutive new PD patients at 4 and 52 weeks after PD. Peritoneal permeability will be determined by the standard peritoneal equilibration test (PET). BMP-7 in PD effluent (PDE) at mRNA and protein level at 4 weeks was quantified. Results. At 4 weeks, the mRNA expression of BMP-7 in PDE significantly correlated with peritoneal transport characteristics, including the dialysate-to-plasma creatinine ratio at 4 h (D/P4) (r = 0.422, P = 0.015) and mass transfer area coefficient (MTAC) of creatinine (r = 0.457, P = 0.008). The PDE BMP-7 level by ELISA also had marginal correlation with D/P4 (r = 0.287, P = 0.072) and MTAC creatinine (r = 0.287, P = 0.073), although the result did not reach statistical significance. For the subgroup of patients who remained free of peritonitis, the PDE BMP-7 level by ELISA had significant correlation with the change in D/P4 (r = 0.441, P = 0.017) and MTAC creatinine in 52 weeks (r = 0.415, P = 0.025). The PDE BMP-7 level remained independently associated with the change in peritoneal transport adjusting for age, sex, serum C-reactive protein and PDE transforming growth factor-beta level. In patients who had peritonitis during the study period, the PDE BMP-7 level did not affect the change in peritoneal transport. Conclusion. We find that the peritoneal BMP-7 level correlates with peritoneal transport characteristics, and a high PDE BMP-7 level is associated with a gradual increase in peritoneal transport parameters with time. It remains unclear, however, whether this effect is beneficial, and the therapeutic role of exogenous BMP-7 on peritoneal transport requires a further study. [ABSTRACT FROM AUTHOR]

Background. Diabetic patients often have reduced insulin requirements when they progress to renal failure. Since peritoneal dialysis (PD) solution contains glucose, the insulin requirement of these patients often increases after commenced on PD. However, the change in insulin requirement has not been studied systematically. Methods. We study 60 consecutive patients (32 male) with diabetic nephropathy newly started on PD. Their insulin requirement before and 6 months after initiation of dialysis is compared. Clinical factors affecting insulin requirement are explored. Results. All patients received a standard 6 l/day dialysis exchange. The mean age was 60.3 ± 8.9 years. Twelve patients did not require insulin before PD; four of them were started on insulin 6 months after dialysis. The average dosages of insulin 6 months before and after PD were 0.27 ± 0.28 and 0.37 ± 0.29 unit/kg/day, respectively (paired t-test, P r = −0.307, P = 0.017) and haemoglobin level (r = 0.284, P = 0.028), but not with body mass index (BMI). The change in insulin dosage correlates with the number of 2.5% dialysis cycle required per day (r = 0.433, P = 0.001), but not with peritoneal transport status or BMI. In patients who did not receive hypertonic exchange, the dosage of insulin increased by 1.5 ± 11.1 unit/day. Each extra 2.5% 2 l exchange results in a 7.5 unit/day (95%CI 3.2–11.8, P = 0.001) increase in insulin requirement. Conclusion. Diabetic patients have a minimal increase in insulin requirement after initiation of PD per se, but the dosage of insulin increased markedly after exposure to hypertonic glucose solution. Our result provides a basis for the dosage adjustment of insulin in diabetic patients newly commenced on PD. [ABSTRACT FROM AUTHOR]

The article presents information on a patient with end-stage renal disease. The 50-year-old patient was on peritoneal dialysis for 9 years and developed complication of severe secondary hyperparathyroidism. Peculiar changes suggestive of finger clubbing in him were noticed by his nephrologist. Clinicians said that digital pseudoclubbing due to secondary hyperparathyroidism is seemingly unrelated to the clubbing of cardiopulmonary disease.

Background: Previous studies found that transforming growth factor-β (TGF-β) induces mesothelial production of connective tissue growth factor (CTGF), which may be downstream mediators of TGF-β. Since high dose TGF-β induces apoptosis of peritoneal mesothelial cells (PMC), we study the effect of CTGF blockade in the system of TGF-β-induced PMC apoptosis. Method: We examined the effect of TGF-W in primary culture of rat peritoneal mesothelial cells (PMC). PMC apoptosis was studied by flow cytometry. The effect of CTGF was blocked by antibody and short-interfering RNA (siRNA). Expression of apoptotic gene was studied by real-time polymerase chain reaction. Result: In cultured unstimulated rat PMC, there is a low but definite incidence of spontaneous apoptosis. Stimulation with TGF-β 50 pg/ml induces an upregulation of apoptotic gene BAX expression and a downregulation of anti-apoptotic gene BCL-2L expression, and a 4-fold increase in PMC apoptosis. The effect of TGF-β-induced PMC apoptosis was partly prevented by antibody against CTGF, and completely abolished by CTGF-specific siRNA, while CTGF-blockade by siRNA had no effect on PMC necrosis. CTGF silencing by siRNA prevented the down-regulation of BCL-2L expression induced by TGF-β, had no effect on the BAX expression. Conclusion: Our results indicate that CTGF is an important downstream mediator of TGF-β-induced PMC apoptosis. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: This retrospective and comparative study evaluated the relationship between different factors which may contribute to suboptimal immunological response to intramuscular recombinant hepatitis B vaccine in end-stage renal disease (ESRD) subjects. Methods: From a cohort of 64 dialysis subjects undergoing primary vaccination with Engerix-B®, we determined the predictive factors that impinged on patients’ response to vaccine, as defined by anti-HBs level ≥10 mIU/l. Dose efficacy was further evaluated by comparing three historical cohorts vaccinated by the regimens of 20, 40 and 80 μg/dose, respectively. Results: We identified 64 ESRD patients (mean age 43 ± 12 years, 81% receiving peritoneal dialysis) who received primary vaccination from April 1997 to September 2004. Median follow-up was 6.5 years. They achieved 81% seroconversion rate. Older age, diabetes mellitus, obesity and low Engerix-B dose were risk factors of inadequate anti-HBs response by univariate analysis. By stepwise logistic regression analysis, hepatitis B vaccine dose was the only independent predictive factor of impaired antibody response. An Engerix-B vaccine dose of 20 μg was associated with more than tenfold increase in risk of non-response to hepatitis B vaccine (hazards ratio 32.2 (95% CI 3.85–250.0)). Immunization with 80 μg of Engerix-B increased the likelihood of persistent protective antibody (log-rank test, p = 0.014). Immunization with Engerix-B 80-μg dose is estimated to prevent one extra ESRD subject who would lose seroprotective anti-HBs level at 1 year for every 5.6 patients treated (number needed to treat to benefit, 5.6 (95% CI 5.4–5.8)). Conclusions: Our results suggest the potential for the three-dose schedule of recombinant vaccine Engerix-B 80 μg to prolong the immune response among ESRD population. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Presents a letter to the editor that focuses on vancomycin concentrations in autosomal dominant polycystic kidney disease.

Presents the letter to the editor about the risks of anemia on pregnant women.

The article focuses on perioperative management of anticoagulated patients. Whereas oral mucosa and saliva are rich in plasminogen activators, local administration of the drug blocks the binding of plasminogen to fibrin and its activation and transformation to plasmin. Tranexamic acid had been proven to attenuate the bleeding risk among patients undergoing oral surgery in two well-conducted prospective randomized trials. Based on the foregoing evidence, it is therefore recommended that for patients undergoing dental procedures, tranexamic acid mouthwash can be applied without interrupting oral anticoagulant therapy.

Comments on E. Lautenbach and colleague's article regarding the use of fluoroquinolones for the treatment of urinary tract infections. Problem of fluoroquinolone antibiotic resistance; Percentage of fluoroquinolone advertisements.

Presents a radiograph of an elderly Chinese women with a history of genito-urinary tuberculosis. Renal cortical calcification, autonephrectomy and calcified urinary bladder.

Peritonitis is a debilitating infectious complication of peritoneal dialysis (PD). Drug-resistant bacterial peritonitis typically has a lower response rate to antibiotics. In the past 15 years, newer antibiotics with activities against drug-resistant Gram-positive bacteria have been developed. In most circumstances, peritonitis due to methicillin-resistant staphylococci responds to vancomycin. If vancomycin cannot be used due to allergy and/or non-susceptibility, there is increasing evidence that linezolid and daptomycin are the drugs of choice. It is reasonable to start linezolid orally or intravenously, but subsequent dose reduction may be necessary in case of myelosuppression. Daptomycin can be given intravenously or intraperitoneally and has excellent anti-biofilm activity. Other treatment options for drug-resistant Gram-positive bacterial peritonitis include teicoplanin, tigecycline and quinupristin/dalfopristin. Teicoplanin is not available in some countries (e.g. the USA). Tigecycline can only be given intravenously. Quinupristin/dalfopristin is ineffective against Enterococcus faecalis and there is only low-quality evidence to support its efficacy in the treatment of peritonitis. Effective newer antibiotics against drug-resistant Gram-negative bacteria are lacking. Polymyxins can be considered, but evidence on its efficacy is limited. In this review, we will discuss the potential use of newer antibiotics in the treatment of drug-resistant bacterial peritonitis in PD patients. [ABSTRACT FROM AUTHOR]

Background: Peritoneal dialysis (PD) and hemodialysis (HD) are often regarded as equivalent choices of renal replacement therapy. However, little is known about the outcome of patients who failed PD and converted to long-term HD. Methods: We reviewed 197 patients who received long-term HD after failed PD in a University hospital from 1994 to 2008 (the PD-first group) and 140 patients who received long-term HD as their initial therapy during that period (the primary-HD group). Their survival rates are compared. Results: The two groups are highly comparable in terms of baseline demographic data. The PD-first group required more temporary dialysis catheters than the primary-HD group (3.1 ± 3.4 vs. 1.5 ± 1.8, p < 0.0001). At 5 years, the actuarial survival of the PD-first group was significantly lower than that of the primary-HD group (39.9 vs. 59.7%, p < 0.0001), while technique survival was similar (30.4 vs. 30.1%, p = 0.7). When analysis on actuarial survival was performed for patients who survived the first 12 months on HD, the 5-year survival became similar (65.2 vs. 68.8%, p = 0.5). During the first 12 months on HD, independent predictors of actuarial survival of the PD-first group were duration of PD, Charlson's comorbidity score, type of permanent access and serum albumin before conversion; after 12 months, independent predictors of actuarial survival were Charlson's comorbidity score, total Kt/V, residual renal function, fat-free edema-free body mass before conversion and baseline peritoneal transport. Conclusion: Patients who were converted to long-term HD after failed PD had a higher mortality than patients who used HD as the primary modality of renal replacement therapy. The excessive mortality, however, was limited to the first 12 months after conversion, and the technique survival was similar between the two groups. Vascular access is a common problem in patients who failed PD. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Volume overload is an important contributing factor of cardiovascular disease (CVD) in peritoneal dialysis (PD) patients. Vascular pedicle width (VPW) and cardiothoracic ratio (CTR) in routine chest radiograph are indicators of intravascular volume. Longitudinal changes of VPW and CTR may be important prognostic factors of PD patients. Method: We studied 212 PD patients. Longitudinal changes in VPW (ΔVPW) and CTR (ΔCTR) were calculated. The relationship between radiologic measurements and clinical outcome was analyzed. Results: During the 12 months prior to enrollment, VPW rose from 53.35 ± 5.66 to 55.40 ± 6.30 mm (p < 0.001) and CTR rose from 53.3 ± 7.1 to 56.0 ± 7.8% (p < 0.001). After adjusting for confounding variables by Cox regression model, ΔCTR is an independent predictor of hospitalization-free survival; 1% increase in CTR confers 2.9% higher risk of hospitalization (95% confidence interval 0.2–5.7%, p = 0.034). None of the radiologic measurements correlated with actuarial patient survival. Conclusions: In chronic PD patients, ΔCTR is an independent predictor of hospitalization-free survival. This simple radiological parameter may serve as an important parameter for the risk stratification of PD patients. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We report a patient with chronic diabetes and was referred for recent onset proteinuria. Light microscopy of the renal biopsy specimen showed mildly expanded mesangium with mesangial hypercellularity and segmental sclerosis, features compatible with diabetic glomerulosclerosis. However, crystalglobulin-induced nephropathy with crystal deposit was identified on electron microscopy. Renal biopsy is often performed for diabetic patients who present with proteinuria and light microscopy often shows features of diabetic glomerulosclerosis. Additional information may occasionally be revealed on electron microscopy, altering the subsequent plan of management. [ABSTRACT FROM AUTHOR]

Background: Previous studies found that transforming growth factor-β (TGF-β) plays a conflicting role in peritoneal fibrosis. We hypothesise that TGF-β acts on peritoneal mesothelial cells (PMC) via VEGF and CTGF as downstream mediators. Methods: The effect of TGF-β in primary culture of rat PMC was studied. VEGF and CTGF mRNA expression was examined by real time quantitative polymerase chain reaction (RT-QPCR), and VEGF antigen level in cell supernatant by ELISA. Results: Incubation of rat PMC with TGF-β resulted in a time- (3–72 h) and concentration- (0–50 pg/ml) dependent increase in VEGF mRNA expression, and VEGF protein level in the cell supernatant. When stimulated with TGF-β 100 pg/ml, there was a 20-fold up-regulation of VEGF mRNA expression (p < 0.001). The CTGF mRNA expression and protein level of PMC was slightly increased at low concentration of TGF-β (50 pg/ml) but decreased at a higher concentration (100 pg/ml or above). The effect of TGF-β on PMC CTGF, but not VEGF, gene expression was inhibited by Smad decoy oligodeoxynucleotide. The effect of TGF-β on PMC VEGF gene expression and protein synthesis was inhibited by PD98059 (a specific MAP kinase inhibitor) and chelerythrine (a specific protein kinase C inhibitor), but not cholera toxin (activator of cyclic AMP) or herbimycin A (inhibitor of protein tyrosine kinase). The up-regulation of CTGF mRNA expression was inhibited by PD98059, but not chelerythrine, cholera toxin or herbimycin A. Furthermore, CTGF gene expression in TGF-β-stimulated PMC was inhibited by co-administration of recombinant VEGF. Conclusions: Our data demonstrate that TGF-β induces PMC production of VEGF and CTGF via different signalling pathways. At high concentration of TGF-β, VEGF production predominates and CTGF production was inhibited. Since CTGF and VEGF have different biologic effects, our results may explain the complex activity of TGF-β in peritoneal physiology. [ABSTRACT FROM AUTHOR]

Ion-exchange resins, sodium or calcium polystyrene sulfonate, are commonly used medications for management of hyperkalaemia. However, the drug can be associated with serious bowel injury. We report a case of a renal transplant recipient who developed duodenal ulcer perforation secondary to the use of calcium polystyrene sulfonate. Characteristic eosinophilic non-polarisable rhomboid shaped crystals were evident in the affected area of ulceration on histologic examination in addition to features of cytomegalovirus inclusions. We also hypothesised that gastroparesis secondary to autonomic dysfunction could have led to prolonged luminal contact time with polystyrene, further predisposing to bowel injury. [ABSTRACT FROM AUTHOR]

Background/Aims: Frailty and depression both contribute to malnutrition and adverse clinical outcome of peritoneal dialysis (PD) patients. However, their interaction is incompletely defined. Methods: We studied 178 adult Chinese PD patients. Physical frailty was assessed by a validated in-house questionnaire; depressive symptoms was screened by the Geriatric Depression Scale; nutritional status was determined by subjective global assessment (SGA) and malnutrition inflammation score (MIS). All patients were followed for up to 24 months for survival and hospitalization analysis. Results: There were 111 patients (62.4%) physically frail, amongst those 48 (43.2%) had depressive symptoms. Only 1 patient had depressive symptoms without frailty. There was an additive effect of depressive symptoms and physical frailty on nutritional status. For the groups with no frailty, frail but no depressive symptoms, and frail with depressive symptoms, serum albumin decreased in a stepwise manner (35.8 ± 5.6, 34.9 ± 4.4, and 32.9 ± 5.3 g/L, respectively, p=0.025); overall SGA score was 5.75 ± 0.61, 5.41 ± 0.59, and 5.04 ± 0.77, respectively (p< 0.0001), and MIS was 5.12 ± 2.30, 7.13 ± 3.22, and 9.48 ± 3.97, respectively (p< 0.0001). At 24 months, patient survival was 86.6%, 71.4%, and 62.5% for patients with no frailty, frail but no depressive symptoms, and frail with depressive symptoms, respective (p=0.001). The median number of hospital stay was 8.04 (inter-quartile range [IQR] 0.91 – 19.42), 14.05 (IQR 3.57 – 37.27), and 26.62 (IQR 10.65 – 61.18) days per year of follow up, respectively (p< 0.0001). Conclusion: Physical frailty and depressive symptoms are both common in Chinese PD patients, and they have additive adverse effect on the nutritional status and clinical outcome. [ABSTRACT FROM AUTHOR]

Background: Evidence indicates that microRNAs (miRNA) play a role in the pathogenesis of chronic kidney diseases (CKD). We explored the possibility of using urinary miRNA as non-invasive biomarkers for CKD. Methods: We quantified miRNA expression in urinary sediment of 56 CKD patients who underwent kidney biopsy. Patients were followed for 16.2 ± 15.5 months. Results: Patients with diabetic glomerulosclerosis had lower urinary miR-15 expression, while those with IgA nephropathy had higher urinary miR-17 expression, than other diagnosis groups. Baseline proteinuria had significant inverse correlation with urinary expression of miR-15, miR-192, and miR-216a; baseline renal function correlated with urinary expression of miR-15, miR-17, miR-192, and miR-217. The rate of renal function decline correlated with urinary expression of miR-21 (r=0.301, p=0.026) and miR-216a (r=0.515, p < 0.0001). Patients with a high urinary expression of miR-21 and miR-216a had better dialysis-free survival than those with low expression (log rank test, p=0.005 and p=0.003, respectively). Conclusions: Urinary miR-21 and miR-216a expression correlated with the rate of renal function decline and risk of progression to dialysis-dependent renal failure. Our results suggest that urinary miRNA profiling has the potential of further development as biomarkers of CKD. [ABSTRACT FROM AUTHOR]

Background: The interplay between intrarenal angiotensin-converting enzyme (ACE) and type 2 ACE (ACE2) might play important roles in the pathogenesis of hypertensive nephrosclerosis (HTN), but human data are limited. Methods: Renal biopsy specimens of 41 patients with HTN and 10 transplant donors as controls (CTL) were studied. The glomerular and tubulointerstitial mRNA expression of ACE and ACE2 was measured by laser microdissection and real-time quantitative polymerase chain reaction. The corresponding protein level was determined by immunohistochemistry. Results: Neither the glomerular nor tubulointerstitial mRNA expression of ACE or ACE2 correlated with the corresponding protein level by immunohistochemistry. The tubulointerstitial levels of ACE and ACE2 were significantly lower in HTN than CTL, while the glomerular ACE and ACE2 levels were similar between the groups. The tubulointersitial ACE and ACE2 levels significantly correlated with the estimated glomerular filtration rate (GFR) and inversely with the degree of histological damage. The glomerular ACE and ACE2 levels significantly correlated with the rate of GFR decline. The ratio of glomerular ACE and ACE2 level correlated with the estimated GFR and the degree of glomerulosclerosis. Conclusion: Our results suggest that intrarenal ACE and ACE2 may play an important role in the pathogenesis and progression of HTN. Studies based on the mRNA expression of ACE and ACE2 should be cautiously interpreted. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]