Hong Kong study using valsartan in IgA nephropathy (HKVIN): a double-blind, randomized, placebo-controlled study.

BACKGROUND: Previous studies showed that angiotensin-receptor blocker (ARB) therapy decreased proteinuria and possibly slowed the rate of renal function decline in patients with chronic proteinuric nephropathies. We performed a double-blind, randomized, placebo-controlled, multicenter study on the ARB valsartan in the treatment of patients with immunoglobulin A (IgA) nephropathy. METHODS: From 6 centers, we recruited 109 patients with IgA nephropathy who had either: (1) proteinuria with protein greater than 1 g/d and serum creatinine level less than 2.8 mg/dL (< 250 micromol/L), or (2) serum creatinine level of 1.4 to 2.8 mg/dL (120 to 250 micromol/L) regardless of degree of proteinuria. Patients were randomly assigned to administration of either valsartan, 80 mg/d (titrated up to 160 mg/d for blood pressure control), or placebo for 104 weeks. Additional antihypertensive therapy was allowed to achieve a target blood pressure of 140/90 mm Hg. The primary end point was doubling of serum creatinine level or dialysis-dependent renal failure. Secondary outcomes included change in proteinuria and decrease in glomerular filtration rate (GFR). RESULTS: There were 54 patients in the treatment group and 55 patients in the placebo group. Baseline clinical characteristics were similar between groups, although the treatment group had a marginally greater baseline GFR (87 +/- 36 versus 78 +/- 38 mL/min/1.73 m2 [1.45 +/- 0.60 versus 1.30 +/- 0.63 mL/s/1.73 m2];P = 0.29) and less proteinuria (protein, 1.8 +/- 1.2 versus 2.3 +/- 1.7 g/d; P = 0.21) than the placebo group. Average blood pressures during the study were 92.7 +/- 10.6 mm Hg in the treatment group and 100.9 +/- 9.1 mm Hg in the placebo group (P < 0.001). During the study period, 4 patients in the placebo group and 1 patient in the treatment group reached the primary end point (log-rank test, P = 0.18). Proteinuria decreased significantly in the treatment group (protein, 1.8 +/- 1.2 to 1.2 +/- 1.2 g/d; P = 0.03), but did not change in the placebo group. With multiple linear regression models, valsartan treatment resulted in a 33.0% decrease in proteinuria (95% confidence interval, 10.9 to 55.1) after adjusting for other confounding factors. There was a significant decrease in mean rate of GFR decrease in the valsartan-treated group (-5.62 +/- 6.79 mL/min/y [-0.09 +/- 0.11 mL/s/y]) compared with the placebo group (-6.98 +/- 6.17 mL/min/y [-0.12 +/- 0.10 mL/s/y]) throughout the study period after adjustment for average blood pressure and proteinuria (P = 0.014). CONCLUSION: Valsartan significantly decreases proteinuria and slows renal deterioration in patients with IgA nephropathy after adjustment for confounding factors, notably blood pressure. The long-term benefit of valsartan needs to be confirmed with additional studies.

Genetic polymorphism of vascular endothelial growth factor: impact on progression of IgA nephropathy.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays a pivotal role in the capillary endothelial cell growth and proliferation and has known effects on glomerular microvascular permeability. Because certain VEGF polymorphisms are correlated with alterations in VEGF expression, we hypothesized that VEGF genetic polymorphisms may affect the renal survival and progression of primary IgA nephropathy. METHODS: The study population consisted of 195 biopsy-proven IgA nephropathy patients at our center between 1984 and 2004. VEGF genotype polymorphism at -2578 positions was determined from peripheral blood leukocytes DNA using polymerase chain reaction methodologies. The primary end point was kidney survival as measured by the time interval from renal biopsy to end-stage renal disease or the requirement of renal replacement therapy. RESULTS: In total, we studied 119 women (61%) and 76 men (39%), with a mean age of 35 +/- 10 yr at the time of renal biopsy. Observed genotype frequency was 55.6%, 38.8%, and 5.1% for CC, CA, and AA genotypes respectively. Baseline characteristics did not differ significantly between three genotype groups for patient age, sex, prevalence of hypertension, degree of proteinuria, initial serum creatinine concentration, and the histological grading. After a median follow-up period of 11 yr, doubling of the baseline serum creatinine occurred in 107 of them; 99 patients reached end-stage renal disease requiring renal replacement therapy with a median renal survival of 88 months. The kidney survival in the CC genotype subgroup was similar to that of the CA/AA genotype subgroup during the first 2 yr but became worse than the latter thereafter (log-rank test P = 0.023). The kidney survival rates at the end of 6 yr were 76.8% in the CA genotype, 67.0% in the CC, and 50.0% in the AA genotype groups. Unadjusted hazard ratio of developing end-stage renal disease was 2.65 (95% CI, 1.16 to 6.06) for the CC group as compared to the CA/AA group. The influence of VEGF genotype upon renal survival, however, was not significant after multivariate Cox regression analysis. CONCLUSION: Our preliminary results raise the concern that the CC genotype of the VEGF promoter at -2578 position might be associated with increased risk of renal progression in patients with IgA nephropathy.

Rosiglitazone reduces insulin requirement and C-reactive protein levels in type 2 diabetic patients receiving peritoneal dialysis.

BACKGROUND: Glycemic control is important in determining the outcome of patients with diabetes on dialysis therapy. However, the choice of oral hypoglycemia agent is limited in these patients. Very often, a high dose of insulin is required because of the uremia-associated insulin-resistant state. Rosiglitazone (RSG), a thiazolidinedione, can improve insulin resistance, and its excretion does not rely on renal function. Moreover, it has an anti-inflammatory effect that might be beneficial in patients with renal failure. METHODS: An open-label randomized study was performed in which 52 patients with type 2 diabetes on peritoneal dialysis therapy administered a constant dosage of subcutaneous insulin with stable glycemic control were randomly assigned to the administration of either RSG (fixed dose, 4 mg) plus insulin or insulin alone. Insulin was titrated to maintain hemoglobin A1c (HbA1c) and blood glucose at pretreatment levels. Study duration was 24 weeks. RESULTS: Both groups had similar baseline demographic characteristics, HbA1c and glucose levels, insulin requirement, and C-reactive protein (CRP) levels. Insulin requirement was decreased significantly in the RSG group (27.88 +/- 17.6 to 22.4 +/- 15.21 U/d; P < 0.001). There was a significantly greater decrease in insulin dosage in the RSG than control group (-21.5% versus +0.5%; P = 0.03), whereas glycemic control was similar between groups. At the end of the study, the RSG group also had significantly lower CRP levels than the control group (2.21 versus 8.59 mg/L; P = 0.03). No significant increase in such adverse effects as hypoglycemia, liver impairment, and fluid overload was observed in the RSG group. However, the RSG group was associated with more weight gain. Multivariate regression analysis (using decrease in HbA1c and lipid levels, change in insulin dosage, and treatment with RSG, with lipid-lowering agents) showed that only treatment with RSG was an independent predictor for posttreatment CRP level (P = 0.016). CONCLUSION: RSG in combination with insulin is well tolerated and beneficial in the treatment of patients with type 2 diabetes on peritoneal dialysis therapy by improving insulin sensitivity and decreasing inflammatory response.

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.

Differential effects of transforming growth factor-beta on the synthesis of connective tissue growth factor and vascular endothelial growth factor by peritoneal mesothelial cell.

BACKGROUND: Previous studies found that transforming growth factor-beta (TGF-beta) plays a conflicting role in peritoneal fibrosis. We hypothesise that TGF-beta acts on peritoneal mesothelial cells (PMC) via VEGF and CTGF as downstream mediators. METHODS: The effect of TGF-beta 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-beta 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-beta 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-beta (50 pg/ml) but decreased at a higher concentration (100 pg/ml or above). The effect of TGF-beta on PMC CTGF, but not VEGF, gene expression was inhibited by Smad decoy oligodeoxynucleotide. The effect of TGF-beta 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-beta-stimulated PMC was inhibited by co-administration of recombinant VEGF. CONCLUSIONS: Our data demonstrate that TGF-beta induces PMC production of VEGF and CTGF via different signalling pathways. At high concentration of TGF-beta, 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-beta in peritoneal physiology.

Expression of chemokine and fibrosing factor messenger RNA in the urinary sediment of patients with lupus nephritis.

OBJECTIVE: Lupus nephritis is characterized by intrarenal inflammation. To assess the extent and severity of disease activity and renal involvement, this study examined the expression of transforming growth factor beta (TGFbeta) and monocyte chemoattractant protein 1 (MCP-1) in the urinary sediment of patients with systemic lupus erythematosus (SLE). METHODS: We studied 106 patients with SLE who were classified according to their disease status as those with active disease, those with disease in remission, and those with nonrenal SLE. Ten healthy subjects were used as controls. Lupus activity was assessed by the SLE Disease Activity Index (SLEDAI). If renal biopsy was performed, the histologic activity index and chronicity index were determined, and a morphometry analysis of renal scarring was performed. The urinary expresssion of TGFbeta and MCP-1 messenger RNA (mRNA) was studied by real-time quantitative polymerase chain reaction, and the corresponding protein concentrations of TGFbeta and MCP-1 in the urine were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Expression of TGFbeta and MCP-1 mRNA in the urinary sediment was significantly elevated in the active disease group (P < 0.001 for both). These expression levels of TGFbeta and MCP-1 mRNA correlated with the SLEDAI score (TGFbeta r = 0.71, P < 0.001; MCP-1 r = 0.72, P < 0.001), and also significantly correlated with the histologic activity index (TGFbeta r = 0.487, P = 0.004; MCP-1 r = 0.357, P = 0.038). The urinary protein concentration of MCP-1, but not of TGFbeta, correlated with the SLEDAI score (r = 0.66, P < 0.001). However, neither the protein concentration of TGFbeta nor that of MCP-1 as measured by ELISA in the urine correlated with the histologic activity index. CONCLUSION: The measurement of urinary mRNA expression may be a noninvasive method for the assessment of lupus disease activity and the severity of renal involvement in patients with lupus nephritis.

Independent effects of renal and peritoneal clearances on the mortality of peritoneal dialysis patients.

OBJECTIVE: Previous studies show that peritoneal Kt/V is an independent predictor of survival in anuric patients receiving continuous ambulatory peritoneal dialysis (CAPD). We studied whether peritoneal Kt/V has the same effect in CAPD patients with residual renal function. DESIGN: Observational cohort study. SETTING: Single dialysis center in a university teaching hospital. PATIENTS: New and prevalent CAPD patients. METHODS: We examined the 5-year follow-up results of our prospective study previously reported (Kidney Int 2000; 58:400-7). A total of 270 CAPD patients were followed for up to 6 years. Dialysis adequacy indices, residual renal function, and nutritional data were monitored. OUTCOME MEASURES: Primary outcomes included mortality and technique failure. Peritoneal Kt/V rather than total Kt/V was used for multivariate survival analysis. RESULTS: Average duration of follow-up was 35.1 +/- 22.0 months. Average peritoneal Kt/V throughout the study was 1.59 +/- 0.37; median residual glomerular filtration rate (GFR) 0.82 mL/minute. Five-year actuarial patient survival was 41.5%, and technique survival was 23.1%. Multivariate analysis showed that sex, age, duration of dialysis, presence of diabetes, serum albumin, dialysate-to-plasma creatinine ratio at 24 hours, peritoneal Kt/V, residual GFR, and normalized protein nitrogen appearance were independent factors of both actuarial patient survival and technique survival. For every 0.1 unit higher peritoneal Kt/V, relative mortality risk was 0.94 (95% Cl 0.89 - 0.99, p = 0.03). When prevalent and new CAPD cases were analyzed separately, peritoneal Kt/V predicted survival only for prevalent CAPD patients. CONCLUSION: We conclude that, in prevalent CAPD patients with relatively low levels of peritoneal clearance and residual renal function, a higher peritoneal Kt/V is associated with better survival. Peritoneal clearance below 1.6-1.7 likely has a major detrimental effect on the clinical outcome of CAPD patients with little residual renal function.

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.

Association of ENOS polymorphism with basal peritoneal membrane function in uremic patients.

BACKGROUND: Basal peritoneal permeability has a major impact on the outcome of peritoneal dialysis (PD) patients, but the determinant of this is unknown. Early evidence suggests that peritoneal permeability is affected by nitric oxide (NO) activity. Recently, a gene polymorphism of the endothelial NO synthase (ENOS) gene was identified that is associated with circulating nitrate levels. METHODS: We performed a cross-sectional study to examine the relationship between ENOS4(a/b) gene polymorphism and basal peritoneal function in 86 Chinese incident PD patients. ENOS genotypes for variable number tandem repeats in intron 4 (a/b) were identified by polymerase chain reaction. Patients were classified into 2 groups according to results of a basal peritoneal equilibration test (PET) performed within 2 months of dialysis therapy: group A consisted of patients with low (L)/L average (LA) PET results, and group B consisted of those with H and HA PET results. RESULTS: Group A (L/LA) had a significantly greater prevalence of ENOS aa/ab genotype than group B (H/HA; 30% versus 12%; P < 0.05). Frequencies of the ENOS a allele also were greater in group A (L/LA) than group B (H/HA) (16% versus 6%; P = 0.03). ENOS genotype remained an independent predictor for peritoneal transport after adjustment for sex, body weight, and prevalence of diabetes by multivariate analysis (adjusted odds ratio, 3.3; confidence interval, 1.1 to 3.7; P = 0.03). Subjects with the aa/ab genotype had significantly lower mass transfer area coefficients (7.35 +/- 3.4 versus 9.48 +/- 5.21 mL/min; P = 0.023) and dialysate-plasma creatinine ratios at 4 hours (0.55 +/- 0.13 versus 0.62 +/- 0.14; P = 0.048) than those with the bb genotype. CONCLUSION: ENOS4(a/b) gene polymorphism is associated with basal peritoneal permeability in uremic Chinese patients.

The clinical course of culture-negative peritonitis complicating peritoneal dialysis.

BACKGROUND: Culture-negative peritonitis is a serious complication in peritoneal dialysis patients. METHODS: We studied all consecutive episodes of culture-negative peritonitis in our unit from 1995 to 2001. We identified 1,182 episodes of peritonitis recorded; 212 episodes in 149 patients had negative culture results. RESULTS: The overall primary response rate was 67.5%, and the complete cure rate was 37.7%. In 95 episodes (44.8%), technical problems during the collection of dialysis effluent were suspected. There was a history of antibiotic therapy within 30 days before the onset in 56 episodes (26.4%). Recent antibiotic therapy was associated with a lower primary response rate (31 of 56 versus 113 of 156 episodes; P = 0.019) and lower complete cure rate (12 of 56 versus 68 of 156 episodes; P = 0.003). Furthermore, a history of peritonitis from 31 to 120 days before the onset also was associated with a lower complete cure rate (P = 0.001). Multivariate analysis showed that recent peritonitis was the only independent predictor of treatment failure (odds ratio, 2.87; 95% confidence interval, 1.56 to 5.29). CONCLUSION: Most of the culture-negative peritonitis could be explained by recent antibiotic therapy or technical problems during dialysate culture. Recent peritonitis and antibiotic therapy are associated with a poor treatment response. Early Tenckhoff catheter removal is recommended in this group of patients.

Oral sodium bicarbonate for the treatment of metabolic acidosis in peritoneal dialysis patients: a randomized placebo-control trial.

Acidosis causes malnutrition in peritoneal dialysis (PD) patients. The effect of oral bicarbonate in PD patients with Kt/V <2.1 has not been studied. We randomly assigned 60 PD patients with acidosis and Kt/V <2.1 to oral sodium bicarbonate (0.9 g thrice daily) or placebo. Patients were followed for 12 mo. We compared their nutritional status, including subjective global assessment (SGA) score and normalized protein nitrogen appearance (NPNA), hospitalization and all-cause mortality. Treatment with oral bicarbonate resulted in a higher plasma bicarbonate level at 4 wk (27.8 +/- 2.6 versus 24.7 +/- 3.9 mmol/L, P = 0.002), and the difference persisted until 52 wk. Bicarbonate treatment had a significant effect on the change in overall SGA score (repeated measures ANOVA, P = 0.0003). The overall SGA score of the treatment group was higher than the placebo group at 24 wk (5.07 +/- 0.94 versus 4.40 +/- 1.00, P = 0.015), and the difference persisted thereafter. NPNA rose in the treatment group (1.17 +/- 0.32 to 1.28 +/- 0.26 g/kg per d, P = 0.034), but declined in placebo group (1.13 +/- 0.25 to 1.03 +/- 0.28 g/kg per d, P = 0.054). The treatment group had a shorter hospitalization than the placebo group (8.4 +/- 17.7 versus 16.8 +/- 21.7 d/yr; P = 0.02). Mortality was not significantly different. Although our trial has limited statistical power, we find that in PD patients with mild acidosis and Kt/V <2.1, oral sodium bicarbonate probably improve nutritional status and reduce the duration of hospitalization.

Effects of an angiotensin-converting enzyme inhibitor on residual renal function in patients receiving peritoneal dialysis. A randomized, controlled study.

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 m2 in the ramipril group versus 3.00 mL/min per 1.73 m2 in the control group (P = 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 m2 (95% CI, 0.09 to 1.78 mL/min per 1.73 m2). 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. CONCLUSIONS: Although the trial was small and had a limited ability to exclude effects of potential confounding factors, the angiotensin-converting enzyme inhibitor ramipril may reduce the rate of decline of residual renal function in patients with end-stage renal failure treated with peritoneal dialysis.

Assessment of protein nitrogen appearance in Chinese peritoneal dialysis patients-which method to use?

OBJECTIVE: We compared the Bergstrom's and Randerson's formula for PNA determination, and compared the normalization of PNA by ideal body weight (IBW) and standard body weight (SBW) as estimated by the Watson's formula. METHODS. We studied 208 Chinese PD patients. Two 24-h dialysate and urine collections were performed six months apart. Protein nitrogen appearance was determined by the Randerson's formula (PNA-Rand) and Bergstrom's formula (PNA-Berg), the latter used as the gold standard. PNA-Berg was normalized with IBW and SBW, denoted as NPNA-IBW and NPNA-Watson respectively. The change of PNA over six months, denoted as APNA-Rand and APNA-Berg, were calculated. The results were compared by the Bland and Altman's method. RESULTS: At zero month, the average PNA-Berg was 61.8 +/- 14.8 g/day, and the average PNA-Rand was 58.1 +/- 14.5 g/day. The value of PNA-Rand was consistently lower than the corresponding PNA-Berg. The bias of PNA-Rand was -3.7g/day. The limits of agreement were -9.2 to +1.8 g/day. When NPNA-Watson was compared to NPNA-IBW, the bias of NPNA-Watson, using NPNA-IBW as gold standard, was 0.01 g/kg/day; the limits of agreement were -0.22 to +0.23 g/kg/day. The difference between NPNA-Watson and NPNA-IBW correlated with the body mass index (r = -0.820, p < 0.001) and body weight (r = -0.834, r < 0.001). After six month, there was a significant reduction in urine protein loss. However, total protein loss was only slightly reduced (7.3 +/- 3.0 to 6.9 +/- 2.8 g/day, p = 0.029). The correlation between APNA-Berg and APNA-Rand remained excellent (r = 0.983, p < 0.001). The bias of APNA-Rand was +0.3 g/day; the limits of agreement were -4.7 to +5.2 g/day. CONCLUSION: Ideal body weight that is validated for specific ethnic group, rather than the Watson's formula, should be used for normalization of PNA. Although the Randerson's formula under-estimates PNA when compared to the Bergstrom's formula, it is a reliable method for serial PNA monitoring because dialysate protein loss is stable in most patients.

Are peritoneal dialysis patients with and without residual renal function equivalent for survival study? Insight from a retrospective review of the cause of death.

BACKGROUND: It remains unknown whether results of survival studies in anuric patients can be extrapolated to those who still have significant urine output. It is possible that after a prolonged period on dialysis, anuric patients are qualitatively different from patients with residual renal function. METHODS: We performed a retrospective review to study the cause of death of 296 peritoneal dialysis patients of our centre over a 7 year period, and compared the mortality and distribution of cause of death between patients with and without residual renal function. RESULTS: One hundred and forty-two cases (48.0%) died of vascular diseases, 82 cases (27.7%) died of infections and 72 cases (24.3%) died of other causes. Anuric patients had a higher overall mortality rate than non-anuric patients (14.9 vs 9.9%, P=0.0005), and the difference was almost completely attributed to the difference in mortality from vascular diseases (8.0 vs 4.1%, P<0.0001). Vascular disease was a more common cause of death in anuric patients than those with residual renal function (55.3 vs 40.8%, P=0.011). The difference was largely explained by the higher prevalence of sudden cardiac death in anuric patients (39 in 149 vs 19 in 147 cases). Patients without pre-existing cardiovascular disease more commonly died of vascular disease after they became anuric (47.4 vs 34.0%, P=0.017). The difference could not be explained by the longer duration of dialysis in anuric patients because there was no significant change in the distribution of cause of death with time on dialysis (chi-square test, P=0.341). CONCLUSIONS: Our observation suggests that peritoneal dialysis patients with and without residual renal function are qualitatively different. Studies on peritoneal dialysis adequacy and survival in anuric patients should only be extrapolated to the general dialysis population with caution.

Association of transforming growth factor-beta (TGF-beta) T869C (Leu 10Pro) gene polymorphisms with type 2 diabetic nephropathy in Chinese.

INTRODUCTION: Transforming growth factor-beta (TGF-beta) is known to play a pivotal role in the regulation of extracellular matrix (ECM) accumulation. Since diabetic nephropathy (DMN) is characterized by basement membrane thickening and mesangial expansion, control of ECM deposition is believed to be important in the pathogenesis of the disease. Recently, TGF-beta T869C (Leu 10Pro) gene polymorphism has been identified which may be associated with circulating TGF-beta levels. METHODS: In order to examine the relationship between TGF-beta gene polymorphism with DMN in Chinese, we carried out a case-control study, which recruited 123 Chinese type 2 diabetic patients with an average duration of diabetes for 12 years. A total of 58 patients who developed DMN (micro- or macroalbuminuria, with or without renal impairment) were compared with 65 diabetic patients without DMN despite similar duration of disease (normoalbuminuric and creatinine <120 micromol/L). TGF-beta T869C (Leu 10Pro) gene polymorphism was determined by polymerase chain reaction (PCR). RESULTS: Both groups of patients had similar baseline characteristics, including blood pressure, diabetic control, and duration of diabetes. Distribution of TGF-beta T869C (Leu 10Pro) genotype among the whole group is confined to Hardy Weinberg equilibrium. The DMN+ group has higher frequency of TGF-beta CC/CT genotypes than the DMN- group [CC, CT, TT = (DMN+) 46, 45, 9 (%) vs. (DMN-) 37, 37, 26 (%), P < 0.05]. C allele frequency is also higher in the DMN+ group than DMN- group (69% vs. 55%, P < 0.05). The adjusted odds ratio for TGF-beta CC/CT vs. TT genotype to develop DMN is 3.8 (3.2 to 4.4). Multivariate logistic regression analysis [hypertension, gender, age, duration of diabetes, hemoglobin (HbA1c), usage of angiotensin-converting enzyme (ACE) inhibitor, and cholesterol level] showed that TGF-beta genotype (P = 0.03) is an independent predictor for type 2 DMN. Among patients with DMN, those with TGF-beta CC/CT genotypes also had worse renal function and increased risk for macroalbuminuria. CONCLUSION: Our results suggest that TGF-beta T869C (Leu 10Pro) gene polymorphism is associated with DMN in Chinese.

Retrospective review of neurotoxicity induced by cefepime and ceftazidime.

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 interval between symptom onset and diagnosis of cefepime versus ceftazidime 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.

Influence of climate on the incidence of peritoneal dialysis-related peritonitis.

OBJECTIVE: The use of peritoneal dialysis has expanded in many developing subtropical countries; however, the role of climatic factors in dialysis-related peritonitis has not been studied in detail. DESIGN: Retrospective study. SETTING: A single regional dialysis unit in a university teaching hospital. PATIENTS: We reviewed all cases of dialysis-related peritonitis treated in our dialysis unit from January 1995 to December 2001. Information was collected on demographic data, microbiologic etiology, associated catheter exit-site infection, and clinical response. RESULTS: In 24,059 patient-months of follow-up, 1344 episodes of peritonitis were recorded. There were significantly more peritonitis episodes in July and August [odds ratio 1.17, 95% confidence interval (CI) 1.03-1.32], and fewer peritonitis episodes in December (odds ratio 0.79, 95% CI 0.61-0.98). There was also a trend of more peritonitis in March (odds ratio 1.18, 95% CI 0.97-1.41), but the difference was not statistically significant. When the incidence of peritonitis caused by individual bacterial species was further analyzed, we found a significant seasonal variation in the rate of peritonitis caused by gram-negative bacteria, except Pseudomonas (overall chi-square test, p = 0.002). A similar trend of seasonal variation was also observed in gram-positive peritonitis, but the result was not statistically significant. There was significant seasonal variation in the rate of peritonitis that had coexisting exit-site infection (overall chi-square test, p = 0.02), with peak incidence in July. However, the proportion of peritonitis that had coexisting exit-site infection did not have significant seasonal variation. There was significant correlation between monthly peritonitis rate and average humidity (r = -0.346, p < 0.002) and temperature (r = -0.264, p = 0.015). CONCLUSIONS: There is substantial seasonal variation in the incidence of dialysis-related peritonitis, with peak incidence in the months that are hot and humid. Keeping a cool and dry living environment may help to reduce peritonitis in peritoneal dialysis patients in tropical countries.

Rhodococcus equi peritonitis in continuous ambulatory peritoneal dialysis.

The human Rhodococcus equi (R. equi) infection is now emerging, although extrapulmonary manifestation and isolation from patients without human immunodeficiency virus (HIV) infection remains unusual. Considerable effort is required to correctly identify and diagnose this facultative pathogen in patients with peritonitis in end-stage renal failure (ESRF) on continuous ambulatory peritoneal dialysis (CAPD). In the six cases of R. equi CAPD peritonitis reported in this series, diagnoses were made, on average, after 15 days and prolonged antibiotic therapy with morbidity in two patients. A diagnosis of R. equi should be considered in patients with suspected diphtheroid or Nocardia CAPD peritonitis, even with no history of animal contact. This study is the largest series on R. equi CAPD peritonitis and highlights the impact of this disease.

Improved health-related quality of life and left ventricular hypertrophy among dialysis patients treated with parathyroidectomy.

BACKGROUND: We prospectively studied changes in the perception of health-related quality of life, pruritus, and degree of left ventricular hypertrophy in end-stage renal disease patients with tertiary hyperparathyroid disorder, before and 6 months after total parathyroidectomy treatment. METHODS: A series of 12 consecutive patients were enrolled. Throughout the follow-up period, all subjects completed the Kidney Disease Quality of Life Short Form-36 (KDQOL SF-36) questionnaire at inclusion and after 6 months. Serial clinical and physiological parameters including uremic pruritus, blood pressure control and left ventricular hypertrophy measured by echocardiography were recorded. RESULTS: Mean scores of the KDQOL SF-36 questionnaires were substantially higher 6 months after parathyroidectomy, with reference to physical functioning, bodily pain, role-physical, role-emotional, symptom list and burden of kidney disease. Parathyroidectomy resulted in a 22% reduction in left ventricular mass index, with significant improvement from the baseline value of 246 +/- 131 to 192 +/- 131 g/m2 (p = 0.03). CONCLUSION: Our findings highlight the potential importance of parathyroidectomy in improving health-related quality of life and left ventricular hypertrophy among dialysis patients with tertiary hyperparathyroidism.