Increased risk of cardiovascular events in end-stage renal disease patients with osteoporosis: a nationwide population-based cohort study.

SUMMARY: We investigated the cardiovascular disease risk and mortality in end-stage renal disease (ESRD) patients. A total of 12,535 patients with ESRD undergoing incident dialysis were enrolled, 4,153 (33.13 %) of whom had osteoporosis. The osteoporosis group was associated with a significantly higher risk of coronary artery disease, congestive heart failure, stroke, and mortality. INTRODUCTION: In this study, we aimed to investigate the risk of cardiovascular disease and mortality in a sample of end-stage renal disease patients with osteoporosis. METHODS: We conducted this retrospective cohort study of incident dialysis patients with and without osteoporosis to evaluate the risk of overall mortality and cardiovascular complications including stroke, coronary heart disease, and congestive heart failure between the two groups. A total of 12,535 patients with ESRD undergoing incident dialysis were enrolled, 4,153 (33.13 %) of whom had osteoporosis, from the National Health Insurance Research Database of Taiwan for the years 1998 through 2011. The osteoporosis group had more comorbidities than the group without osteoporosis including hypertension, hyperlipidemia, mental disorders, and hepatitis C infection. RESULTS: After adjusting for age, gender, and related comorbidities, the osteoporosis group was associated with a significantly higher risk of coronary artery disease (hazard ratio (HR)=1.32, 95 % confidence interval (CI)=1.20-1.45) which was significant in both genders (women, HR=1.35, 95% CI=1.20-1.50; men HR=1.27, 95% CI=1.06-1.52) and all age groups (≤49 years HR=1.41, 95% CI=1.16-1.70; >49 years HR=1.30, 95% CI=1.16-1.45). Similar results were observed for the outcomes of congestive heart failure, stroke, and mortality. CONCLUSIONS: The results showed that osteoporosis was significantly associated with the subsequent risk of cardiovascular events in patients with ESRD. When encountering patients with ESRD and osteoporosis, physicians should be alert to the subsequent cardiovascular risk in incident dialysis patients to prevent the subsequent occurrence of these adverse events.

Outcome of peritoneal dialysis in cirrhotic patients with end-stage renal disease: a 24-years' experience in Taiwan.

BACKGROUND: Use of peritoneal dialysis (PD) in liver cirrhosis patients with end-stage renal disease remains controversial. Moreover, the long-term outcome in cirrhotic patients is unclear. The aim of the present study was to analyze the outcome of cirrhotic patients treated with PD in our center during the past 24 years. METHODS: We retrospectively reviewed the data of cirrhotic patients who received PD between 1984 and 2009. A group of noncirrhotic patients who were age- and sex-matched during the same period were selected as controls. Peritonitis rates, complications and outcomes were compared. RESULTS: A total of 30 cirrhotic patients and 60 control patients were included in the analysis. Peritonitis-free survival did not differ between groups. Gram-positive organisms, especially coagulase-negative staphylococcus and streptococcus sp., were the major causes of peritonitis in the cirrhotic patients. Also in the cirrhotic patients, complications such as umbilical hernia, chronic hypotension and erythropoietin resistance were more common as compared with controls. An initially higher solute and water transport capacity was observed in the cirrhotic patients, which became comparable to controls by the end of the 2nd year of treatment. Serum albumin concentrations were lower in cirrhotic patients (p = 0.01), and the decline of renal Kt/V was slower in cirrhotic patients as compared to that of controls (p < 0.0001). There was no significant difference in patient and technique survival between the two groups. CONCLUSION: Our study suggests that PD is an effective therapy with a comparable risk of peritonitis and solute clearance in liver cirrhosis patients with end-stage renal failure.

Evolution of microbiological trends and treatment outcomes in peritoneal dialysis-related peritonitis.

BACKGROUND AND AIM: Peritoneal dialysis (PD)-related peritonitis is a major risk factor of technique failure and contributes to significant mortality in patients undergoing PD. The aim of this study was to examine the evolution of microbiological trends and treatment outcomes of PD-related peritonitis in our hospital over the past 26 years. METHODS: A total of 630 patients entered our CAPD program from February 1984 to June 2010. Among them, 119 patients (18.9%) experienced 599 episodes of peritonitis. Microbiological trends, treatment responses, techniques and patient survival were analyzed. RESULTS: The incidence rate of total peritonitis showed a steady decline from 1.08 episodes/patient-year in 1984 to 0.25 episode/ patient-year in 2009 (p < 0.001). A similar trend was found in gram-positive (p < 0.001) and gram-negative peritonitis (p = 0.015). In contrast, there was a trend toward an increased proportion of gram-negative peritonitis. This increase was not due to an increased rate of gram-negative peritonitis but to the more dramatic fall in gram-positive peritonitis. Treatment of peritonitis resulted in a complete cure in 78.0% of patients, while 16.7% of patients required catheter removal and 5.3% died. Gram-positive organisms were associated with a more favorable outcome compared to gram-negative pathogens as manifested by a higher cure rate (p = 0.023). The patient survival and technique survival were much improved after 2000 compared to that before 2000 (p < 0.0001). CONCLUSION: A remarkable improvement in the outcome of PD-related peritonitis has been achieved in the past 26 years in our hospital. To further decrease peritonitis rates, attention needs to be directed at reducing gram-negative peritonitis.

Mannitol-induced acute renal failure.

A 62-year-old man was admitted to the ophthalmologic department for operation of retinal detachment. Mannitol and acetazolamide were prescribed to reduce intraocular pressure. Seven days after operation, gradual onset of drowsy consciousness occurred. The laboratory findings of hypertonic hyponatremia (109 mEq/l), hyperosmolality (341 mosm/kg), metabolic acidosis (pH: 7.17) and acute renal failure (serum creatinine: 8.2 mg/dl) dictated a diagnosis of mannitol-induced acute kidney injury. First, 3% saline was given, but consciousness kept deteriorated with worsened dyspnea and metabolic acidosis. Hemodialysis was then performed subsequently and his consciousness and renal function completely recovered. A special emphasis on the treatment of hypertonic hyponatremia was given.

Malignant lymphoma of the kidney mimicking rapid progressive glomerulonephritis.

Primary renal lymphoma (PRL) is rare and often presents as rapidly progressive renal failure. Most cases of PRL are large-cell lymphomas of B-cell lineage. Herein, we report a 75-year-old female patient with infiltrative CD20 (+) B-cell lymphoma who underwent 4 consecutive courses of chemotherapy with R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone) and after 12 sessions became free from hemodialysis in good general condition. Her serum creatinine level gradually decreased to 4.1 mg/dl with adequate urine output. Unfortunately, a relapse of CD20 (-) lymphoma developed rapidly involving other organs. She died with severe hospital-acquired pneumonia and febrile neutropenia after the last chemotherapy with R-MINE almost 1 year after onset of symptoms. We conclude that renal biopsy enables prompt diagnosis in rapidly progressive renal failure and immunophenotyping and also staging workup of the lymphoma in case of positive biopsy. Though rituximab improved response rate of PRL, it reduced expression of CD20. This may relate to frequent relapse/resistance after rituximab therapy and poor long-term patient survival.

Multiple hepatic nodules in a renal transplant recipient.

A 55-year-old female received a cadaveric renal transplant in 2003. Sixteen months later, multiple liver nodules were found in a routine abdominal sonogram follow-up. Serial studies were all negative for malignancy. She was placed on a quadruple immunosuppressive regimen, including prednisolone, cyclosporine, mycophenolate mofetil and sirolimus. Her graft function was stable with serum creatinine of 1.0 mg/dl and there had been no rejection since transplantation. Liver function and lipid profile were within normal limits. Serum ferritin level was 1,466 ng/ml. Two liver biopsies, 4 months apart, showed fatty metamorphosis of the liver and no tumor. She was closely watched and no malignancy was found in the subsequent 3 years. Cyclosporine and sirolimus were tapered and corticosteroid withdrawn gradually. Serum ferritin level gradually declined to 600 - 800 ng/ml in subsequent years. Interestingly, the liver nodules gradually disappeared and there were only a few left on the last follow-up in April, 2008.

Impact of variability of sirolimus trough level on chronic allograft nephropathy.

The efficacy of sirolimus is strictly dose-dependent; an inappropriate exposure may cause either rejection episodes or drug toxicity. The variability of sirolimus trough levels (C0) may also have an impact on renal allograft function. We prospectively evaluated the impact of the dose-normalized C0 of sirolimus and the intrapatient coefficient of variation (% CV) on renal allograft function at 6 months after the administration of sirolimus to kidney transplant recipients with chronic allograft nephropathy (CAN). We enrolled 51 recipients with CAN who were treated with sirolimus. The dose-normalized C0 of sirolimus was 3.8 +/- 1.9 ng/mL/mg. The intra- and interpatient variabilities of sirolimus C0 were 26.1% and 51.9%, respectively. Based on receiver operating characteristic analysis, patients were divided into 2 groups: group I, sirolimus % CV <22.9% (n = 36) versus group II, sirolimus % CV >22.9% (n = 15). Patients in group II experienced significantly greater risk for progressive deterioration of allograft function (group I vs group II: 11.1% vs 73.3%; P < .05). Multiple logistic regression analysis revealed that higher baseline serum creatinine, but not age, gender, or concomitant immunosuppressants, positively correlated with the sirolimus % CV. In conclusion, both higher baseline serum creatinine and higher intraindividual variability of sirolimus C0 impact the outcome of renal allograft function in CAN. Thus, we suggest that close monitoring of sirolimus C0 is necessary for recipients treated with sirolimus, especially for patients with CAN.

Possible mechanism by which rapamycin increases cyclosporine nephrotoxicity.

It is well known that the combination of cyclosporine A (CsA) with rapamycin produces serious nephrotoxicity. Herein we suggest a mechanism by which rapamycin increases CsA nephrotoxicity. Previously, we demonstrated that activation of Akt/protein kinase B protects against cyclosporine nephrotoxicity and prevents apoptosis. Recently, it has been shown that Akt phosphorylation activates mammalian target of rapamycin (m-TOR) and inhibits programmed cell death including apoptosis and autophagy. Akt is believed to be an importance factor for cell survival. In theory, blockade of the Akt pathway through inhibition of m-TOR may increase cyclosporine-induced apoptosis. We added cyclosporine and rapamycin to cultures of ER52K proximal renal tubule cells, leading to a significantly decreased survival rate. The nephrotoxicity was associated with increased apoptosis by cleavage of caspase-3 and decreased phosphorylation of m-TOR and AktSer473, findings that support this hypothesis. This nephrotoxic effect may explain the clinical finding that patients treated with rapamycin alone exhibited better renal function than those treated with concomitant cyclosporine therapy.

Clinical Significance of Serum Visfatin in Renal Transplant Recipients.

Chronic antibody-mediated rejection is the most common cause of late graft loss in renal transplant recipients. Visfatin is a pre-B cell colony-enhancing factor secreted by activated lymphocytes. We hypothesize that visfatin may play a role in the augmentation of B cell colonies and facilitate antibody-mediated rejection. Renal transplant recipients were randomly selected for the study. Fasting blood samples were obtained for the assay of visfatin. The participants were prospectively followed up for 3 years. A total of 146 patients were recruited for the study and were divided into 3 groups according to tertile of serum visfatin level. At the end of follow-up, 6 patients had graft loss, including 1 graft loss in tertile 1, 3 in tertile 2, and 2 in tertile 3 (P = .60). Fourteen patients experienced at least 1 episode of acute rejection, while 21 patients were diagnosed as having chronic rejection. The distribution of acute rejection was 10.2% in tertile 1, 10.2% in tertile 2, and 8.3% in tertile 3 (P = .94); chronic rejection occurred in 10.2%, 16.3%, and 16.7%, respectively (P = .59). We conclude that serum visfatin level was not correlated with either graft failure or patient mortality in a 3-year observation period.

Effect of pentoxifylline on graft function of renal transplant recipients complicated with chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN) is characterized by a progressive deterioration of renal function with various degrees ofproteinuria. Currently, there is no effective treatment despite the introduction of new generations of immunosuppressants. Pentoxifylline (PTX) is a phosphodiesterase inhibitor that possesses antiproteinuric effect and has been proved to be effective in treating several glomerular diseases. The purpose of the current study was to examine the effect of PTX on renal transplant patients with established CAN. MATERIALS AND METHODS: Renal transplant recipients with biopsyproven CAN were recruited for the study. All the patients had been on angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for more than 1 year and were on a triple immunosuppressive regimen including corticosteroid, calcineurine inhibitor and mycophenolate mofetil. PTX in a dose of 1,200 mg/day was administered for at least 6 months. The following parameters were assessed at baseline, the 3rd and the 6th month post treatment: systolic and diastolic blood pressure, number of anti-hypertension drugs, serum creatinine (sCr),estimated glomerular filtration rate (eGFR), 24-hour urinary protein excretion (U/P), urinary N-acetylglucosaminidase (NAG) and intracytoplasmic Thl/Th2 cytokines production of peripheral blood CD4+ cells. RESULTS: A total of 17 (11 male and 6 female) patients were enrolled in the study. The mean duration of follow-up post transplant was 10.6+/- 4.4 years. The baseline data of sCr, eGFR and U/P were 1.83+/-0.46 mg/dl, 38+/-8 ml/min and 2.65+/-2.15 g/day, respectively. Corresponding values at the 3rd and 6th month post treatment were 1.90+/-0.43 mg/dl (p = NS), 33+/-7 ml/min (p=NS), 2.13 +/-1.13 g/day (p < 0.05) and 2.03+/-0.64 mg/dl (p < 0.05), 32+/-10 ml/min (p < 0.05), 2.74 +/-0.93 g/day (p = NS), respectively. When individual data were analyzed, five cases (29.4%) showed a U/P significant reduction of more than 50% of baseline value, while in 10 cases (58.8%) the graft function remained either stable (9 cases) or improved (1 case) at the end of treatment. Urinary NAG was elevated at the 3rd month, but stabilized thereafter. The Thl/Th2 intracytoplasmic cytokine pattern of peripheral blood CD4+ cells showed a significant decrease of cells bearing TNF-alpha (15.0+/-14.4% vs 14.2+/-17.0%, p < 0.05) and cells bearing IL-10 (1.60 +/-1.23% vs 0.90+/-0.66%, p < 0.05) at the 3rd month. CONCLUSION: In this pilot study, PTX seemed to be temporarily effective in reducing proteinuria. The graft function was stabilized in more than half of patients at the end of follow-up.