Showing papers in "Clinical Nephrology in 2006"

Lanthanum carbonate versus standard therapy for the treatment of hyperphosphatemia: safety and efficacy in chronic maintenance hemodialysis patients.

Abstract: Aims: No conventional phosphate binder is entirely satisfactory for the treatment of hyperphosphatemia in patients with end-stage renal disease (ESRD). Consequently, there is a need for new agents. One such agent is lanthanum carbonate (La). This large-scale study compares the safety of La with standard therapy (any approved phosphate binder) in patients who were treated for up to 2 years. Efficacy, having previously been demonstrated, was a secondary endpoint. Materials and methods: After washout, patients were randomized to receive La (n = 682) or their pre-study phosphate binder (n = 677). Over a 6-week period, La was titrated to a maximum daily dose of 3,000 mg elemental lanthanum (serum phosphorus target levels for titration were ≤ 5.9 mg/dl (1.90 mmol/l)). Safety assessments included adverse events (AEs), full laboratory parameters and blood profiles. Efficacy assessments included serum phosphorus, calcium, calcium × phosphorus product and parathyroid hormone (PTH) levels. Results: Average treatment exposure was greater in the standard therapy group (501.4 days) than in the La group (370.3 days) because standard therapy patients who switched or combined treatments were allowed to continue in the study. The most common AEs were gastrointestinal. The incidences of AEs in the La and treatment exposure-corrected standard therapy groups were nausea, 37 versus 29%; vomiting, 27 versus 22% and diarrhea (24% in each group). Hypercalcemia that was reported as an AE (La versus treatment exposure-corrected standard therapy) occurred in 4.3% and 8.4% of patients, respectively. There was no indication of liver toxicity, suppression of erythropoiesis or changes in the mini-mental state examination. Over 2 years, phosphorus control was similar in both groups; in the La group, however, serum calcium was lower and serum PTH levels were maintained in the range recommended by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI). Conclusions: The 2-year tolerability and efficacy of La are similar to those seen with standard therapy, although lower serum calcium levels and improved PTH levels were observed in the La group. These results support La as a viable new option for the management of hyperphosphatemia in ESRD.

Incidence and factors predictive of acute renal failure in patients with advanced liver cirrhosis.

Abstract: BACKGROUND Acute renal failure (ARF) is a life-threatening entity that frequently complicates advanced liver disease. This study documents a number of factors that may predispose to or precipitate ARF and influence outcomes in patients with advanced liver disease. Comparisons are also made between subgroups of patients with viral and alcohol-induced liver cirrhosis in those with ARF. PATIENTS AND METHODS We conducted a retrospective chart review over one year of 127 consecutive hospital admissions in 82 patients who were diagnosed with advanced liver cirrhosis (Child-Pugh Class C) in a tertiary care center. A diagnosis of ARF was made in 29 admissions and another 98 admissions not complicated by ARF served as controls. This study evaluated different etiologies of ARF and developed a database which included clinical features, biochemical parameters, the etiology of cirrhosis, possible predisposing factors, and precipitating events. Version II of the Acute Physiology and Chronic Health Physiology Scoring system (APACHE II) was applied to predict short-term hospital mortality rates. RESULTS ARF occurred in 29 admissions over the one-year study period (23%). The mean age of these patients was 56.8 +/- 12.0 years, and 73% were men. The patients with ARF had significant hyponatremia and higher levels of serum bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and white cell counts on admission than the controls. Patients who developed ARF were more likely to have had infection, especially septicemia, and gastrointestinal (GI) bleeding. Mortality rate in the patients with ARF was much higher than in those patients without ARF (72% vs. 13%, p < 0.001). The patients with viral cirrhosis and ARF were found to have higher leukocyte counts, serum bilirubin levels, and more frequent incidence of infection, septicemia and GI bleeding compared to the patients with alcoholic liver cirrhosis and ARF. Those with viral hepatitis were also significantly older and had more frequent incidence of ascites, but had lower levels of gamma-glutamyl transpeptidase and less frequent incidence of encephalopathy. CONCLUSIONS The risk of ARF is significantly increased in patients with advanced liver cirrhosis presenting with marked hyperbilirubinemia, hyponatremia, elevated liver enzymes, infection, and GI bleeding. The presence of ARF leads to higher mortality rates in both viral and alcohol-induced liver cirrhosis.

Uremic pruritus is associated with higher kt/V and serum calcium concentration

Abstract: Background The prevalence and characteristics of uremic pruritus have not recently been investigated in a US dialysis cohort. This study examined uremic pruritus and associated risk factors in hemodialysis patients treated in the year 2005. Methods The prevalence and characteristics of pruritus (short version McGill pain questionnaire), severity (10 cm visual analogue scale), and effect on quality of life (Skindex-16) were determined in thrice weekly hemodialysis patients. Daugirdas single-pool Kt/V, clinical and laboratory data were recorded. Results 105 of 307 screened hemodialysis patients met inclusion criteria and were evaluated, 49% (151) were excluded due to advanced age, 3% (9) other skin diseases, and 14% (42) refused. Participants were 55% male (58/105) and 65% African-American (68) with a mean +/- SD age of 48 +/- 11 years. The overall prevalence of pruritus was 57% (60/105, 95% CI 47 - 67%) and a positive correlation was observed between the presence of uremic itch and serum calcium concentration (p = 0.04). Intact PTH and serum phosphorus concentration were not associated with either the presence or intensity of itch. Intensity of pruritus was positively correlated with increasing months on dialysis (64 +/- 63 vs. 51 +/- 46 months for itch and non-itch, respectively; p = 0.02), higher Kt/V (1.82 +/- 0.7 vs. 1.70 +/- 0.56 for itch and non-itch, respectively; p = 0.01) and skin dryness (p = 0.01). Patients receiving statins were significantly less likely to report pruritus (p = 0.02) and uremic itch adversely impacted several aspects of quality of life. Conclusions Pruritus remains a common and significant symptom in adequately hemodialyzed patients. Higher serum calcium concentrations, longer durations of ESRD and higher Kt/V appear to be important factors associated with uremic pruritus.

Enzyme replacement therapy and renal function in 201 patients with Fabry disease.

Abstract: Aim: Fabry disease is a rare lysosomal storage disorder caused by deficient activity of alpha-galactosidase A, resulting in progressive cellular accumulation of glycolipids, which may ultimately result in end-stage renal disease. We examined the effects of enzyme replacement therapy (ERT) with Agalsidase-alpha on renal function using data from a large international database, the Fabry Outcome Survey (FOS). Methods: This analysis was based on 1,040 serum creatinine measurements in 201 patients with Fabry disease, aged 20-60 years, with serum creatinine concentrations of less than 2 mg/dl and duration of ERT of up to 4.7 years. Both pretreatment and treatment data were used to examine independent predictors of changes in serum creatinine. In a second approach longitudinal serum creatinine measurements from 1 year before treatment, at baseline and 1 and 2 years after the start of treatment were analyzed in 20 patients with chronic kidney disease (CKD) Stage 2 and 3. Results: We found an independent negative association between serum creatinine and time on Agalsidase-alpha treatment (p<0.05). Renal function declined significantly (p<0.05) in the year before treatment. After 1 year of treatment, however, the decline in estimated glomerular filtration rate had been halted, and renal function was preserved for up to 2 years. Conclusions: In conclusion, ERT with Agalsidase-alpha is associated with decrease of serum creatinine and may prevent the deterioration of renal function in patients with Fabry disease.

Renal osteodystrophy: what's in a name? Presentation of a clinically useful new model to interpret bone histologic findings.

Abstract: Renal osteodystrophy begins early in the course of chronic kidney disease and occurs almost without exception in all patients with Stage 5 disease (CKD-5). Bone biopsies and evaluation of mineralized bone sections after double tetracycline-labeling are currently considered the gold standard for diagnosis and classification of renal osteodystrophy. Nevertheless, bone biopsies are rarely employed. This is, at least in part, related to the paucity of nephrologists trained in performance of the procedure and the fact that reports of the histologic results are not easily translatable to clinical practice. Results are usually given qualitatively, using non-uniform classifications or by histomorphometric evaluations which are esoteric to most nephrologists. We suggest here that histomorphometric evaluation can be reserved for research and special situations. Also, the customarily used qualitative classification should be replaced by a clinically useful nomenclature, provided the interpretation is done by an individual with sufficient experience in bone pathology. We present a new interactive nomenclature for renal osteodystrophy that addresses abnormalities of turnover, abnormalities of bone balance, and abnormalities of mineralization. The new nomenclature, thus, includes disorders of high- and low-turnover with consideration of the interrelation with positive or negative bone balance with or without mineralization defect. In this schema, changes in bone status are described as deviations from a norm, and treatment is geared toward normalizing values rather than creating any absolute change in one direction or another. It is hoped that such a classification will be easily usable, clinically more relevant, and more amenable to individualized treatment guidance.

Restless legs syndrome in hemodialysis patients: health-related quality of life and laboratory data analysis.

Abstract: Aims To compare clinical data, sleep quality and health-related quality of life (HRQOL) with and without RLS in HD patients. Materials and methods The international RLS study group diagnosis questionnaire was completed by 228 HD patients. The Pittsburg Sleep Quality Index (PSQI) for the evaluation of sleep quality and the Kidney Disease Quality of Life (KDQOL-SF) for the analysis of HRQOL were also used. Results 53 (23%) patients were diagnosed as RLS. Age and age at the initiation of HD were significantly younger in the RLS group. Serum calcium concentration (Ca) was significantly higher in the RLS group. Sleep quality evaluated by PSQI was significantly lower in the RLS group. In SF-36 domains of KDQOL-SF, bodily pain, general health perceptions, vitality, role functioning emotional, mental health and mental component score were significantly lower in the RLS group. In kidney targeted scales of KDQOL-SF, symptoms/problems, burden of kidney disease, cognitive function, quality of social interaction, sleep and patient satisfaction were significantly lower in the RLS group. Conclusion High Ca was possibly connected to the pathophysiology of RLS which impaired sleep quality as well as HRQOL including mental health and many kidney disease related scales.

Nephrotoxicity of iso-osmolar versus low-osmolar contrast media is equal in low risk patients.

Abstract: Background Contrast media-induced nephropathy (CIN) is an increasing cause of hospital-acquired acute kidney injury and leads to a significant increase in mortality. There is uncertainty whether the use of iso-osmolar contrast media as opposed to the use of low-osmolar contrast media would be associated with a lower incidence of CIN. Therefore, we compared the nephrotoxicity of isoosmotic contrast media iodixanol with the low-osmotic contrast media iopromid in patients receiving contrast media during coronary angiography. Methods In this prospective double-blind study we examined 221 patients with normal renal function who received up to 1,000 ml of contrast media during coronary angiography, and compared the effect of iodixanol and iopromid on inducing contrast media nephropathy. Patients received 800 ml fluid orally before contrast media administration and 1,000 ml saline i.v. thereafter. Creatinine clearance, serum creatinine and urine-N-acetyl-beta-D-glucosaminidase (NAG) concentration was obtained 24 h before and 48 h after contrast media administration. Decrease of 20% of the creatinine clearance, increase of 25% of serum creatinine and increase of 20% of the urine concentration of NAG was defined as CIN. Results Incidence of CIN assessed by decreased creatinine clearance was 22.2% in the iopromid group and 19.7% in the iodixanol group. CIN defined by increased serum creatinine was 6.9% in the iopromid group and 8.6% in the iodixanol group. The difference between these two groups was not significant. Subgroup analysis of the diabetic patients or the patients that received high dose of contrast media revealed no significant difference in the incidence of CIN between the two contrast media. Conclusion The iso-osmolar and the low-osmolar contrast media exhibited the same incidence of CIN in our study population. If fluid administration is sufficient, the selection of either iopromid or iodixanol has no impact on the risk of developing CIN in patients with normal renal function, even when they are diabetic or receive a high dose of more than 500 ml contrast media.

Withdrawal from dialysis: a palliative care perspective.

Abstract: A retrospective chart review was conducted in this pilot study of 35 patients who withdrew from dialysis and were followed by a palliative care team. Data included etiology of end-stage renal disease, comorbid illnesses, mode of dialysis and duration, survival time after withdrawal, reason for withdrawal, mental competency, symptom management, and the nature of death. Mean survival time was 10 days. The most frequent symptoms following withdrawal were confusion, agitation, pain and dyspnea. 1/3 of the sample were cognitively impaired at the time of the withdrawal decision. 17% experienced suffering during the withdrawal period, 24% had unrelieved symptoms, 19% psychological distress, while just over 1/3 of patients died alone. With the provision of palliative care, symptom prevalence in the last 24 hours dropped from 53 to 20% for pain, 68 to 33% for agitation and 46 to 26% for dyspnea. Opioids and benzodiazepines were used in the treatment of over 90% of patients. Palliative medicine has the potential to improve the care of patients who discontinue dialysis.

Acute renal failure following liver transplantation with induction therapy.

Abstract: AIMS: To identify the predictive factors for acute renal failure (ARF) in a retrospective study of 100 orthotopic liver transplantations (OLT) performed in 94 patients between 2000 and 2003. METHODS: Acute renal failure (ARF) was defined using the RIFLE criteria, i.e. injury when creatinine doubles or GFR halves, and failure when creatinine trebles or GFR decreases by > 75%. Patients on dialysis pre OLT (n = 3) were excluded from the study. Immunosuppression included steroids, calcineurin inhibitors (CNIs), with (n = 32) or without mycophenolate mofetil. A total of 85% of patients also received induction therapy with antithymocyte globulins (29%) or anti-CD25 monoclonal antibodies (56%). RESULTS: 39 patients (41.5%) and 21 (22.3%) patients developed injury, and failure, respectively. Of these, 10 (10.6%) underwent dialysis. Univariate analysis revealed that acute renal dysfunction with a RIFLE score > or = 3 was significantly associated with a pre-operative serum creatinine level of > 100 micromol/l, pre-operative creatinine clearance of 10 red packed units), post-operative diuresis of 20 and > 24 hours, respectively, relaparotomy, CNIs transient discontinuation, and the use of lower daily dosage of CNIs at post-OLT Days 3, 5, 7 and 15. In multivariate analysis, failure was significantly associated with time to AST peak (> 20 h) (OR 6.35 (1.2 - 33.6), p = 0.029), post-operative diuresis (< 100 ml/h) (OR 9.8 (2.03 47.3), p = 0.004), post-operative use of vasopressive drugs (OR 9.91 (2.02 - 48.7), p = 0.004), and transient CNIs withdrawal (OR 51.08 (7.58-344.1), p < 0.0001). Finally, the occurrence of ARF was significantly associated with an increased number of days on mechanical ventilation, on stay-in intensive care unit (ICU), and on overall hospitalization time. CONCLUSION: ARF is quite common after OLT and significantly increases the post-operative time at the hospital, thereby increasing the OLT cost. Its independent predictive factors are mainly related to perioperative events.

Severe vitamin D deficiency in chronic renal failure patients on peritoneal dialysis.

Abstract: The aim of this study was to evaluate the prevalence of vitamin D deficiency in chronic renal failure (CRF) patients on peritoneal dialysis (PD) and to correlate the findings with various demographic and renal osteodystrophy markers. Method: This cross-sectional, multicenter study was carried out in 273 PD patients with a mean age of 61.7 ± 10.9 years and mean duration of PD 3.3 ± 2.2 years. It included 123 female and 150 male patients from 20 centers in Greece and Turkey, countries that are on the same latitude, namely, 36 - 42° north. We measured 25(OH)D 3 and 1.25(OH) 2 D 3 levels and some other clinical and laboratory indices of bone mineral metabolism. Results: Of these 273 patients 92% (251 patients) had vitamin D deficiency i.e. serum 25(OH)D 3 levels less than 15 ng/ml, 119 (43.6%) had severe vitamin D deficiency i.e. serum 25(OH)D 3 levels, less than 5 ng/ml, 132 (48.4%) had moderate vitamin D deficiency i.e. serum 25(OH)D 3 levels, 5 - 15 ng/ml, 12 (4.4%) vitamin D insufficiency i.e. serum 25(OH)D 3 levels 15 - 30 ng/ml and only 10 (3.6%) had adequate vitamin D stores. We found no correlation between 25(OH)D 3 levels and PTH, serum albumin, bone alkaline phosphatase, P, and Ca x P. In multiple regression analyses, the independent predictors of 25(OH)D 3 were age, presence of diabetes (DM-CRF), levels of serum calcium and serum 1.25(OH) 2 D 3 . Conclusion: We found a high prevalence (92%) of vitamin D deficiency in these 273 PD patients, nearly one half of whom had severe vitamin D deficiency. Vitamin D deficiency is more common in DM-CRF patients than in non-DM-CRF patients. Our findings suggest that these patients should be considered for vitamin D supplementation.

Tacrolimus in steroid-resistant and steroid-dependent nephrotic syndrome.

Abstract: Background Steroid resistance and steroid dependence constitute a major problem in the treatment of minimal-change disease and focal segmental glomerulosclerosis (FSGS). Cyclophosphamide and cyclosporine are well-established alternative immunomodulating agents, whereas data on FK 506 (tacrolimus) are rare. Methods The present work provides data from 10 patients of an open, monocentric, non-randomized, prospective trial. Five patients with steroid-dependent minimal-change nephrotic syndrome, 1 patient with steroid-refractory minimal-change disease and 4 patients with steroid-refractory FSGS were started on tacrolimus at trough levels of 5 10 microg/l. In case of steroid-dependence, prednisolone was tapered off in presence oftacrolimus within one month. Results Within 6 months, complete remission was achieved in 5 patients (50%) and partial remission in 4 patients (40%), yielding a final response rate of 90%. One patient was primarily resistent to tacrolimus (steroid-refractory minimal-change), another patient became secondarily resistant to tacrolimus after an initial remission (steroid-refractory FSGS). Average proteinuria significantly decreased by 77% from 9.5 +/- 1.4 - 2.2 +/- 1.1 g/day (p Conclusions Our data suggest that tacrolimus may be a promising alternative to cyclosporine both in steroid-resistant and steroid-dependent nephrotic syndrome.

Treatment with antidepressive drugs improved quality of life in chronic hemodialysis patients.

Abstract: BACKGROUND Despite some improvements in dialysis therapies, depression still remains an important problem in chronic hemodialysis (HD) patients. In this study, we aimed to investigate the association of depression and its treatment with quality of life (QOL) in HD patients. PATIENTS AND METHODS 97 HD patients (52 male, 45 female, mean age 55 +/- 16 years) were enrolled. All patients had been dialyzed for more than 6 months. In order to evaluate QOL of the patients, a short form of Medical Outcomes Study (SF-36) was used. Depression was assessed by using Beck Depression Inventory (BDI). Patients who had BDI score > or = 15 were diagnosed as to have depression. Patients with depression received antidepressive treatment (sertralin HCl, 50 mg/day) for an 8-week period. After 8-week antidepressive treatment, all biochemical analysis, SF-36 and BDI were performed again. RESULTS 40 patients (20 male, 20 female, mean age 56 +/- 14 years) had depression. All parameters related to QOL were significantly decreased in patients with depression as compared to patients without depression. Severity of depression was correlated with QOL parameters. After 8 weeks of treatment, as parallel to changes in BDI, QOL parameters improved in patients with depression. CONCLUSION Decrease in QOL, associated with depression and antidepressive treatment, improves QOL in HD patients. Hemodialysis patients should be followed-up closely for presence of depression. Treatment of depression with antidepressive drug regimen would lead to relieve the symptoms related to depression and improvement of QOL in these patients. Antidepressive treatment should be required more often than we prescribe in routine clinical practice now.

Roles of TGF-beta1 and apoptosis in the progression of glomerulosclerosis in human IgA nephropathy.

Abstract: Apoptotic glomerular cells have been detected in the severely damaged glomeruli that are a consequence of human IgA nephropathy. Transforming growth factor-(TGF) beta1 is known to induce apoptosis in cultured mesangial cells. To clarify whether TGF-beta1 contributes to the progression of IgA nephropathy by activating apoptosis in glomerular cells, we examined the expression of TGF-beta1 gene and apoptotic changes in kidney biopsy samples, and assessed those relations to the severity of nephropathy. 32 patients with IgA nephropathy, showing proteinuria (> 1 g/day) and serum creatinine less than 1.5 mg/dl were classified according to glomerular sclerosis index (GSI) into 3 groups (Group I: GSI or = 1.0). Computer-aided morphometry of glomeruli and arteries, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling of fragmented DNA (TUNEL) staining were performed. Expression of TGF-beta1 and caspase-3 mRNAs in renal biopsy samples was analyzed by real-time PCR (Taq Man method). Increased glomerular area, interstitial fibrosis, lymphocytic infiltration, and tubulointerstitial changes were observed to accompany increased severity of GSI. TUNEL index was higher in Group III. The levels of TGF-beta1 and caspase-3 mRNAs were significantly increased in Group III (183 and 190%, respectively). Furthermore, caspase-3 mRNA levels were tightly associated with TGF-beta1 mRNA expression (r = 0.677, p < 0.0001). The present study suggests that the activation of TGF-beta1 plays a role in the progression of IgA nephropathy even in the moderate degree of glomerular injury, in part via activation of apoptosis of glomerular cells.

A clinicopathologic study of thrombotic microangiopathy in the setting of IgA nephropathy.

Abstract: Background IgA nephropathy is the most common glomerulonephritis in the world. Thrombotic microangiopathy occurs in a number of clinical settings, including but not limited to thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, malignant hypertension, anti-phospholipid antibody syndrome and radiation nephropathy. Renovascular complications, such as thrombotic microangiopathy, in the setting of IgA nephropathy may be overlooked and their significance as a concomitant histologic finding is unclear. Methods We conducted a clinicopathologic study to understand the possible relationship between IgA nephropathy and a concurrent thrombotic microangiopathy injury process. We identified 10 patients with an established diagnosis of IgA nephropathy and concurrent findings of thrombotic microangiopathy based on their renal biopsies. Results Six patients presented with malignant hypertension, while three others had severe hypertension (> or = 100 mmHg, diastolic). Five patients had nephrotic-range proteinuria. Seven patients had occasional arteriolar thrombi identified by light microscopy and prominent glomerular subendothelial space widening by electron microscopy, while three patients demonstrated only ultrastructural features of thrombotic microangiopathy. Other possible etiologic causes of thrombotic microangiopathy were not identified with the available clinical information. Conclusion Our study suggests that a thrombotic microangiopathy injury, when present, is usually found in advanced stages of IgA nephropathy and can be associated with severe proteinuria. Although other possible causes of thrombotic microangiopathy, such as anti-phospholipid antibody syndrome, were excluded in only two patients, the thrombotic microangiopathy injury process may be a cause or a consequence of the severe hypertension encountered in most of the patients which, in turn, may be a consequence of the disease progression of IgA nephropathy.

Performance of creatinine clearance equations on the original Cockcroft-Gault population.

Abstract: Background: Prediction of endogenous creatinine clearance by mathematical equations such as the Cockcroft-Gault formula is used in clinical practice in spite of the reported concern for their limited predictability. The aim of this study is to determine whether the measured creatinine clearance can be predicted accurately by a number of published equations including the recently modified Cockcroft-Gault formula = Cockcroft-Gault formula × 1.73 m 2 /body surface area from the original Cockcroft-Gault population. Methods: The performance ofthe mathematical equations in patients with different creatinine clearance and body mass indices was assessed by computing accuracy at different percentiles, bias and precision from the original Cockcroft-Gault data. Results: Refitting the modified formula to the Cockcroft-Gault data gave superior results compared to the original Cockcroft-Gault formula with an overall accuracy in the general and subgroup analysis above 70% agreement within 30% estimate of the measured creatinine clearance. On the other hand, analysis of the other equations, including the original Cockcroft-Gault, demonstrated a limited accuracy to predict creatinine clearance particularly in patients with creatinine clearance below 50 ml/min with an overall accuracy in less than 1/3 of the calculated creatinine clearance within 30% range from the measured creatinine clearance. Conclusion: The current creatinine clearance equations and even the original Cockcroft-Gault formula did not accurately predict the measured creatinine clearance. Normalization for body surface area in the original Cockcroft-Gault formula demonstrated more accuracy to estimate creatinine clearance, particularly in patients with diminished renal function and is recommended to physicians who wish to use the Cockcroft-Gault formula in their practice until more credible formulas are developed.

Effects of pentoxifylline on the urinary protein excretion profile of type 2 diabetic patients with microproteinuria: a double-blind, placebo-controlled randomized trial.

Abstract: AIMS The purpose of this study was to identify the effect of pentoxifylline on the urinary protein excretion profile in type 2 diabetic patients. METHODS 40 type 2 nonhypertensive diabetic patients were randomly allocated to receive either pentoxifylline 400 mg t.i.d. or placebo daily for 16 weeks. Eligible subjects were those with urinary albumin excretion between 20 and 200 microg/min. Subjects receiving angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), calcium antagonists, and diuretics as well as those with reduced renal function, pregnancy, urinary tract infection, and smoking were not included. A 6-month pretreatment stabilization phase aimed to reduce and stabilize fasting serum glucose levels was carried out. Urinary proteins were identified by electrophoresis, and immunodetection was identified by Western blot. Electrophoretic analysis was performed using molecular weight markers of 150, 132, 77, and 66 kDa to identify high-weight proteins, and 54, 41, 36, 27, 21, 14.3, and 12 kDa to identify low-weight proteins. RESULTS At baseline, subjects in both groups who showed a glomerular tubular pattern did not differ in their urinary excretion profile. The urinary proteins identified were immunoglobulin G, ceruloplasmin, transferrin, and albumin (glomerular pattern) as well as alpha1-antitrypsin, alpha1-acid glycoprotein, collagenase inhibitor, alpha1-microglobulin, trypsin inhibitor, lysozyme, and beta2-microglobulin (tubular pattern). Subjects who received pentoxifylline had reduced urinary excretion of high- and low-molecular weight proteins. CONCLUSIONS Urinary protein excretion in type 2 diabetic subjects shows a mixed, glomerular and tubular, pattern. Pentoxifylline reduces the excretion of both high and low molecular-weight urinary proteins.

Outpatient versus inpatient renal biopsy: a retrospective study.

Abstract: Objective and methods: There is a growing interest in the safety and efficacy of percutaneous kidney biopsy for outpatients in Taiwan. We conducted a retrospective study for patients receiving the biopsy in 2002 and 2003. Complication and mortality associated with the biopsy were compared between 147 inpatients and 183 outpatients who had been judged to need no hospitalization. All biopsies were performed using the ultrasound guidance and an automated springloaded biopsy device. Results: There were no death and no significant difference in complication rates between the two groups. No delayed gross hematuria, delayed pain, fever or biopsy site bleeding developed in outpatients, who were followed-up by telephone contacts for 1 - 5 days after they had been discharged. Both outpatients and inpatients with hematoma were younger than those without (p < 0.05). Template bleeding time was longer for inpatients with hematuria compared with inpatients without (12.0 vs. 5.8 minutes in average, p = 0.036), but not for outpatients (4.5 vs. 6.0 minutes in average, p = 0.282). There were moderate differences in platelet count between outpatients with hematuria and those without (p = 0.057), and in serum creatinine between inpatients with hematuria and those without (p = 0.069). Conclusion: The outpatient renal biopsy appears to be equally as safe and efficient as the inpatient biopsy. However, we suggest checking template bleeding time and platelet count before biopsy for patients with clinical bleeding tendency, such as patients with a serum creatinine level over 4 mg/dl (approaching CKD stages IV, V) due to a higher risk of prolonged bleeding time. Outpatient biopsy with a 6-hour inpatient observation can be considered as a medically adequate procedure.

Fanconi's syndrome and distal (type 1) renal tubular acidosis in a patient with primary Sjögren's syndrome with monoclonal gammopathy of undetermined significance.

Abstract: Tubulointerstitial nephritis is a well-recognized complication in primary Sjogrens syndrome. Fanconi's syndrome is a far less frequent complication compared with distal tubular dysfunction. We here describe a 49-year-old woman with primary Sjogren's syndrome. In 1997, she was diagnosed with primary Sjogren's syndrome with tubulointerstitial nephritis, and was then treated with oral prednisolone for the tubulointerstitial nephritis. In 2002, she was referred to our hospital because of progressive fatigue. At that time, biclonal spike on serum protein (IgG-kappa and IgA-kappa) and Bence-Jones protein in urine were found. Bone marrow aspiration showed 1.0% plasma cell infiltration. Thus, a diagnosis of monoclonal gammopathy of undetermined significance (MGUS) was made. In 2004, she was again admitted to our hospital because of mild renal dysfunction and hypokalemia. Laboratory evaluation showed inappropriate, alkaline urine in hyperchloremic metabolic acidosis and a positive urine anion gap, indicating the presence of distal (Type 1) renal tubular acidosis (RTA). The urine concentration defect was also found. Further studies revealed proximal tubular dysfunction, including renal glycosuria, generalized aminoaciduria, phosphaturia, uricosuria and proximal RTA. The kidney biopsy represented diffuse and severe tubulointerstitial nephritis with dense infiltrates of lymphocytes and IgA and K light chain-positive plasma cells. No findings of multiple myeloma or malignant lymphoma were observed. In conclusion, our patient had Sjogren's syndrome with MGUS and exhibited dysfunction of both proximal tubule (Fanconi's syndrome) and distal tubule, which may be attributed to diffuse tubulointerstitial nephritis.

Effect of ethanol/trisodium citrate lock on the mechanical properties of carbothane hemodialysis catheters.

Abstract: AIMS The objective of this study was to investigate the effect of three locking solutions on the mechanical properties of carbothane hemodialysis catheters. METHODS Catheters were exposed in vitro to one of three locking solutions (heparin 5000 U/ml; 4% trisodium citrate (TSC) or 30% ethanol/4% TSC). Each solution was locked in six catheters and bathed at 37 degrees C for 9 weeks. Changes in the mechanical properties namely, force at break, elongation at break and elastic modulus of the catheters were determined by tensile testing. RESULTS The ethanol/TSC lock has an effect on the properties of carbothane hemodialysis catheters. The force at break was significantly lower in the ethanol/TSC group compared to the heparin and TSC groups (113.26 N, 191.97 N and 229.72 N, respectively, p < 0.01). Similarly, elongation at break was lower in the ethanol/TSC group, compared to the heparin and TSC groups (stretched 21.97, 38.29, and 42.42 times original length respectively, p < 0.01). The elastic modulus was not significantly different. CONCLUSIONS The effect of the ethanol/TSC lock on the catheters is unlikely to prohibit clinical use. After 9 weeks of exposure to the solution, the catheter segments could still be stretched to 22 times their length and withstand 11.5 kg (113 N) of force. Clinically produced forces during dialysis are many times smaller than the force required to break the catheters examined in this study. Therefore, the ethanol/TSC lock shows promise as a new catheter locking solution for the treatment of catheter-related infections. Further clinical studies are required.

Concurrent anti-glomerular basement membrane disease and membranous glomerulonephritis: a case report and literature review.

Abstract: Background Anti-glomerular basement membrane disease (anti-GBM) is a relatively rare entity characterized by antibodies to collagen type IV of glomerular and alveolar basement membranes. The sequential or simultaneous presentation of anti-glomerular basement membrane disease with membranous glomerulonephritis has been infrequently described. Case We present the case of a 49-year-old man who had fatigue, flank pain, hematuria and renal failure. Serology was positive for anti-GBM antibodies; crescentic glomerulonephritis was seen on renal biopsy. Immunofluorescence and electron microscopy demonstrated evidence of both anti-GBM glomerulonephritis and membranous deposits. Discussion Simultaneous anti-GBM disease and membranous glomerulonephritis is the most common temporal presentation of this rare entity. However, cases of membranous glomerulonephritis preceding or following recovery from anti-GBM disease have been described. Study of such cases provides insight into pathophysiologic mechanisms, including the possibility of increased antigen synthesis, exposure of cryptic epitopes, and/or capping and shedding of antigen-antibody complexes, in analogy to Heymann nephritis.

Differential effects of very high doses of doxercalciferol and paricalcitol on serum phosphorus in hemodialysis patients.

Abstract: Background Treatment of secondary hyperparathyroidism (SHPT) includes use of calcitriol (1,25D(3)) to suppress parathyroid hormone (PTH), but dosing of 1,25D(3) is limited by the development of hypercalcemia and a high calcium x phosphorus (Ca x P) product due to gut absorption of calcium and phosphorus as well as enhanced bone resorption. The vitamin D analog 19-Nor-1,25(OH)2-vitamin D2 (paricalcitol) and the prohormone 1alpha-OH-vitamin D2 (doxercalciferol) have been proposed as alternatives which may cause less hypercalcemia and elevated Ca x P, while still suppressing PTH. Methods We performed a prospective study to assess the acute bone mobilization effects of very high doses of paricalcitol and doxercalciferol. 13 hemodialysis patients received 160 mcg of paricalcitol and 120 mcg of doxercalciferol on 2 separate occasions in a research center while on a low calcium, low phosphorus diet, and sevelamer alone as a phosphorus binder. Changes in Ca, PO4, and PTH were measured over 36 h. Results Serum phosphorus rose faster, and peaked significantly higher at 36 h following doxercalciferol (2.12 +/- 0.11 mmol/l) than paricalcitol (1.85 +/- 0.07 mmol/l; p = 0.025). Ca x P product also rose more following doxercalciferol than paricalcitol, and peaked higher at 36 h (5.02 +/- 0.26 vs. 4.54 +/- 0.21 mmol/l; p = 0.061). In contrast, suppression of PTH at 36 h was comparable (63% after paricalcitol and 65% with doxercalciferol). Conclusion Consistent with animal studies, paricalcitol provides profound PTH suppression, while stimulating bone resorption and/or intestinal absorption less than doxercalciferol, resulting in less elevation of serum phosphorus and Ca x P.

Clinical study of influenza-associated rhabdomyolysis with acute renal failure.

Abstract: Aims Influenza-associated rhabdomyolysis induces renal failure with a fatal outcome. The aim of this study is to evaluate the clinical features, diagnosis, and treatment efficacy of influenza-associated rhabdomyolysis patients with acute renal failure (ARF). Materials and methods The subjects included 6 patients who had presented with rhabdomyolysis and ARF due to influenza infection on admission to our university hospital and its 2 affiliated hospitals between January 2002 and February 2004. We retrospectively examined the cases. Results All the patients (n = 6) were males, and none of them had received an influenza vaccine. The viruses were identified as influenza A (n = 5) and B (n = 1). Muscular weakness was observed in many cases (n = 5), whereas pain or tenderness was observed in only 1 case (n = 1). For anuric or oliguric patients (n = 4), blood purification therapy was performed, while for patients in whom the urine volume was normal (n = 2), conservative therapy was administered. Conclusion Careful medical attention is necessary when patients have muscle pain and weakness. Early recognition of rhabdomyolysis allows prompt institution of an appropriate therapy that includes blood purification and may minimize the renal dysfunction associated with this disorder.

Rhabdomyolysis and acute renal failure following arthroscopic knee surgery in a college football player taking creatine supplements.

Abstract: We describe a college football player and weight-lifter who unexpectedly developed rhabdomyolysis and nonoliguric acute renal failure (ARF) following arthroscopic knee surgery. There was swelling and pain without evidence of a compartment syndrome postoperatively. The patient reported that he was an avid weight-lifter and that he was taking up to 10 g/d of a creatine supplement during the 6 weeks prior to this surgery. His ARF resolved over several days, with a peak serum creatinine of 2.3 mg/dl and peak creatine kinase (CK) of 194,000 U/l, following administration of intravenous fluids, mannitol, and sodium bicarbonate. Given the rarity of clinically significant rhabdomyolysis with this type of operation, we suggest that the patient's use of creatine increased the risk of skeletal muscle injury due to ischemia from intra-operative tourniquet application.

The "nutcracker phenomenon" with orthostatic proteinuria: case reports.

Abstract: The nutcracker phenomenon refers to compression of the left renal vein between the aorta and the superior mesenteric artery. Clinical features are hematuria, abdominal pain, left flank pain, pelvic or scrotal discomfort due to varicocele or ovarian vein syndrome. In this report, 2 patients with orthostatic proteinuria, in whom nutcracker phenomenon was detected as a cause, are presented. One of them had posterior nutcracker with also asymptomatic varicocele that was detected during ultrasonographic examination. Nutcracker phenomenon is a rare but important clinical condition that should be considered in the differential diagnosis of patients with proteinuria and hematuria.

Excess risk of renal allograft loss and early mortality among elderly recipients is associated with poor exercise capacity.

Abstract: Background Successful renal transplantation in the elderly offers substantial benefits in quality and life expectancy. However, in this group of patients there is an early increased risk of death compared with those remaining on dialysis. Materials and methods Graft and patient outcomes in 64 older transplant recipients were compared with 338 patients aged 18 - 59 years. We identified potential risk factors that may predict clinical outcomes in older transplant recipients. A log-rank test and Cox regression analyses were performed to assess the impact of various patient characteristics on graft and patient survival. Results Among older patients, graft survival was 76.6% and 67% at 1 and 3 years, respectively. When graft survival was censored for death with functioning graft, the 1- and 3-year graft survival was 83% and 82%, respectively. Patient survival was 78% and 71% at 1 and 3 years, respectively. These survival rates were significantly lower than those of younger recipients. Pretransplant inactivity, delayed graft function, smoking history and longer waiting time predicted poor graft and patient survival. A history of chronic obstructive pulmonary disease, and peripheral vascular disease also predicted a higher mortality among older recipients. Conclusion Older kidney transplant recipients are at high risk for allograft failure and early death. Poor functional capacity predicts a poor outcome for older patients undergoing renal transplantation. Therefore, careful patient selection is paramount, and every effort should be made to initiate timely interventions aimed at increasing physical activity in those with low fitness level.

Effects of an increase in time vs. frequency on cardiovascular parameters in chronic hemodialysis patients.

Abstract: UNLABELLED Cardiovascular mortality is still high and many risk factors are inadequately controlled in patients on conventional chronic hemodialysis. Recent studies on intensified treatment schedules by either increasing length or frequency of dialysis sessions have shown promising results with better control of blood pressure, reduction of left ventricular hypertrophy and easier control of calcium/phosphate metabolism. AIM The present observational study compared the effect of different forms of "intensified dialysis treatment" i.e. either long nightly intermittent (LNHD, 3 x 7.5 - 8 h) or short daily dialysis sessions (DHD, 6 x 2.5 - 3 h) on cardiovascular parameters, phosphate and anemia control in comparison to standard treatment schedules (SHD, 3 x 4 - 5 h). METHODS All patients stable on hemodialysis between 18 and 80 years of age and with either uncontrolled hypertension and/or left ventricular hypertrophy and/or frequent intradialytic hypotension, were asked to participate in intensified dialysis therapy by either LNHD or DHD. Patients not willing to change their dialysis regime were asked to participate as control group (SHD). Primary end point was 24-h ambulatory blood pressure, secondary end points were predialysis blood pressure, left ventricular mass index (LVMI) and fractional shortening (FS), control of calcium, phosphate and anemia. Patients were followed up for 1 year. RESULTS 17 patients opted for LNHD, 8 for DHD, 19 patients served as control group. After 1 year of treatment 24-h blood pressure was unchanged in all groups. Predialysis systolic blood pressure decreased in LNHD and DHD, but increased in SHD. Mean LVMI decreased in all treatment groups (DHD -20.1 +/- 24.0%, SHD -13.6 +/- 33.4%, LNHD -6.1 +/- 32.2%). The mean number of antihypertensive tablets/day was reduced in DHD by 3.3 tablet units, in LNHD by 1.2 tablet units, but increased in SHD patients. FS improved in patients on LNHD and DHD, but decreased in patients on SHD. Regression of LVMI was independent of dry weight which was unchanged in LNHD and SHD but increased in DHD. In contrast to SHD, phosphate control and Ca x P product improved in DHD and LNHD with less phosphate binding tablets. Intact PTH did not change in SHD, but decreased in DHD and LNHD. Hemoglobin increased in groups on intensified treatments, but fell in SHD. EPO resistance index fell in LNHD, but increased in DHD and SHD. CONCLUSION While reduction in 24-h blood pressure was not achieved by intensified dialysis, both schedules showed favourable effects on LVMI and FS with less antihypertensive medication. This was independent of reduction in dry weight. These effects were more pronounced in DHD patients. In contrast, in SHD patients, stable 24-h blood pressure and reduction in LVMI were achieved on the expense of an increasing amount of antihypertensive medication and with worsening of FS.

Timely transfer of peritoneal dialysis patients to hemodialysis improves survival rates.

Abstract: AIMS: The two main renal replacement therapies (RRT)--hemodialysis (HD) and peritoneal dialysis (PD)--have been considered to be antagonistic in most published studies on the clinical outcomes of dialysis patients. Recently, it has been suggested that the complementary use of both modalities as an integrated care (IC) strategy might improve the survival rate of end-stage renal disease patients. The aim of this study was to estimate the final clinical outcome of PD patients when they transfer to HD because of complications related to PD. MATERIALS AND METHODS: We retrospectively analyzed data from the following patients that started RRT during the last 10 years: 33 PD patients (IC group; age 55 +/- 15 years, mean +/- SD) who transferred to HD, 134 PD patients (PD group, age 64 +/- 11 years) who remained in PD, and 132 HD patients (HD group, age 48 +/- 16 years) who started and continued in HD. The main reasons for the transfer to HD were relapsed peritonitis and loss of ultrafiltration, while various comorbid risk factors were adjusted by Cox hazards regression model (age, presence of diabetes or/and cardiovascular disease, serum hemoglobin and albumin levels, as well as the modality per se). RESULTS: 3- and 5-year survival rates for the IC, PD and HD groups were 97% and 81%, 54% and 28%, and 92% and 83%, respectively. The 5-year survival rate was significantly higher in IC patients than in PD patients (p < 0.00001) but, was not different from that in HD patients. CONCLUSIONS: Our results show that the IC of dialysis patients undergoing RRT improves the survival of patients on PD if they are transferred to HD upon the appearance of PD related complications.

Plasma pentosidine and total homocysteine levels in relation to change in common carotid intima-media area in the first year of dialysis therapy.

Abstract: Background Homocysteine and advanced glycation end-products (AGEs), which accumulate in chronic kidney disease (CKD), are recently proposed cardiovascular risk factors. In this study, we evaluated the association between changes in calculated intima media (cIM) area of the common carotid artery during the first year of dialysis therapy and plasma total homocysteine (tHcy) level as well as circulating AGEs such as plasma pentosidine level. Methods We studied 63 CKD patients (38 males) aged 52 +/- 12 years at a time-point close to start of dialysis treatment and after 12 months of dialysis treatment (41 on peritoneal and 22 on hemodialysis). The tHcy and plasma pentosidine levels were measured by HPLC. Change in cIM area was evaluated by non-invasive B mode ultrasonography. Malnutrition was assessed by subjective global assessment (SGA). Results At basal, 70% of the patients had carotid plaques, 32% had symptomatic CVD, 38% had malnutrition, 30% had inflammation (CRP > or = 1 mg/dl) and 23% had diabetes mellitus, respectively. At baseline, the mean plasma pentosidine levels were similar in the patients with and without carotid plaques (36 +/- 21 vs 36 +/- 19 pmol/mg albumin, respectively), whereas the median plasma tHcy was significantly lower in the patients with carotid plaques than in the patients without carotid plaques (32 +/- 21 vs 52 +/- 42 pmol/l, p 13.7 micromol/l) was 95%. In univariate analysis, the change in cIM area during the first year of dialysis was significantly correlated with basal plasma pentosidine level (p = 0.31, p = 0.01), but not with basal tHcy (p = -0.11). However, neither pentosidine nor tHcy levels were correlated with cIM area at basal or at 12 months. In a stepwise multiple regression model, age and plasma pentosidine content, but not the tHcy level, associated with changes in the cIM area. Conclusion Progression of atherosclerosis, as indicated by changes in carotid intima-media area during the course of dialysis treatment, was associated with pentosidine, but not with tHcy, levels at baseline in these CKD patients. This suggests that the accumulation of AGEs in CKD patients may have a role in the pathogenesis of CVD in these patients. Since almost all CKD patients have hyperhomocysteinemia, this finding, however, does not exclude a role ofhomocysteine as a risk factor for CVD in CKD patients.

Acute renal failure associated with use of inhaled tobramycin for treatment of chronic airway colonization with Pseudomonas aeruginosa.

Abstract: Aminoglycoside nephrotoxicity is a well-known clinical entity that complicates the course of infectious diseases treated under this antibiotic regime. Recently, a new administration form of tobramycin, inhaled tobramycin (TOBI), has been approved to improve the antibacterial activity and reduce nephrotoxicity. We describe the clinical case of a 73-year-old woman with chronic-obstructive pulmonary disease (COPD) who developed acute renal failure (ARF) after using TOBI. Clinical presentation and biochemical parameters were compatible with aminoglycoside-induced renal failure. Based on the clinical findings presented here, a surveillance program should be established to monitor the presence of factors predisposing to renal failure, and to measure serum levels of tobramycin.

Prevalence of weight gain in patients with better renal transplant function.

Abstract: Aims: This study investigates the association between renal function and change in weight after kidney transplantation. Methods: Retrospective analyses of 165 transplant patients on maintenance steroids who were followed-up for 6.2 ± 2.4 years. Re- sults: 101 males and 64 females participated in the study. Results are expressed as mean ± SD. At the first post-transplant outpatient visit (time 0), BMI was 25.3 ± 4.8 kg/m 2 .I t in- creased significantly by 7.7 ± 10.8% and 10.9 ± 12.6% at 1 and 5 years. 18 and 29% of pa- tients had a BMI > 30 kg/m2 at times 0 and 5 years, respectively. Thereafter, diminishing glomerular filtration rate (GFR) was associ- ated with the loss of the excess weight. Multivariate analysis showed that GFR, but not age, race, sex, source of graft, number of HLA mismatches or length of dialysis was significant to post-transplant weight gain. 38 patients gained weight > 1 SD above the mean of the population and were designated the high weight gain (HWG) group. 41 patients gained weight < the mean - 1 SD of the popu- lation and were designated the low weight gain (LWG) group. GFR in the high and low weight gain groups at time 0 was 71.8 ± 20.3 ml/min/1.73 m2 and 66.4 ± 23.1 ml/min/1.73 m 2 , respectively (p = NS), as compared to 77.4 ± 23.3 ml/min/1.73 m 2 and 61.5 ± 24.5 ml/min/1.73 m 2 at 6 months, respectively (p < 0.01) and continued to be significant thereaf- ter (72.7 ± 17.2 ml/min/1.73 m2 and 58.9 ± 19.8 ml/min/1.73 m 2 , p < 0.05 at 6 years). Conclusions: Patients with relatively better renal transplant function gained more weight, suggesting a pivotal role of improved appetite on weight gain post transplantation. Most of the weight gain occurred during the first year.