Inflammation, peritoneal transport, and response to erythropoietin in peritoneal dialysis patients.

The aim of the present study was to examine the association between 4-hour dialysate-to-plasma ratio of creatinine (D/PCr), erythropoietin (EPO) responsiveness [EPO (U/week)/hemoglobin (g/L)], and C-reactive protein (CRP). Subjects were 54 prevalent peritoneal dialysis (PD) patients [mean age: 58 years; 30 women, 24 men; 28 with diabetes; 15 on continuous ambulatory peritoneal dialysis (CAPD); 39 on continuous cycling peritoneal dialysis (CCPD); mean Kt/V: 2.44]. In 17 patients, CRP was elevated (> 15 mg/L), and in 39 patients, 4-hour D/PCr was high or high-average (> or = 0.65). Mean hemoglobin (Hb) was 115.5 +/- 12.9 g/L; median EPO dose was 2800 U/week, and median EPO/Hb was 24.5. A nonsignificant negative correlation was noted between CRP and hemoglobin (r = -0.25, p = 0.07), but no correlations were seen between CRP and 4-hour D/PCr, or hemoglobin and 4-hour D/PCr. No correlation was seen between EPO/Hb and 4-hour D/PCr or CRP. Multiple linear regression (stepwise, alpha = 0.05) was performed with outcome hemoglobin and independent variables EPO [U/week (forced in)], percent transferrin saturation [TSAT (forced in)], age, sex, diabetes mellitus, serum albumin, CRP, time on PD, 4-hour D/PCr, normalized protein catabolic rate (nPCR), ferritin, intact parathyroid hormone (iPTH), aluminum, and angiotensin converting enzyme inhibitor (ACEI) use. Serum albumin (1.27, p < 0.01) and diabetes mellitus (-6.69, p = 0.04) were the only significant predictors of hemoglobin. With serum albumin removed from the model, age (but not CRP) became significant. These results do not support an association between peritoneal transport and EPO responsiveness, mediated by inflammation. The association between serum albumin and hemoglobin appears to be confounded by age more than by inflammation.

The relationship between dialysate protein loss and membrane transport status in peritoneal dialysis patients.

Peritoneal dialysis (PD) patients lose significant quantities of protein and albumin during the dialysis procedure. The losses are greater in high transporters. The aim of the present study was to investigate the relationship between peritoneal membrane transport characteristics and protein losses. We studied 33 PD patients [14 men, 19 women; mean age: 53.5 years (range: 21-80 years)]. Fourteen patients had diabetes, and 22 were on automated PD. Dialysis adequacy was good, with a mean Kt/V of 2.63 (range: 1.51-4.89). Patients underwent a standard peritoneal equilibration test (PET). In addition, dialysate albumin (Alb) and protein (Pro) were measured at 0, 1, 2, and 4 hours, after lack of interference from unspent dialysate was ensured. Of the 33 patients, 23 were high or high-average transporters [based on 4-hour dialysate-to-plasma ratio of creatinine (D/PCr > or = 0.65)]. Protein losses owing to PD ranged from 3.5 g/day to 13.2 g/day (median: 5.9 g/day), of which 1.9-7.14 g/day (median: 3.21 g/day) was albumin. The 4-hour D/PCr correlated with the 4-hour D/PAlb (r = 0.62, p < 0.01), and 4-hour D/PPro (r = 0.63, p < 0.01). This finding persisted after correction for volume, indicating that it was not simply a concentration effect. The 4-hour D/PAlb and 4-hour D/PPro also correlated with the 24-hour PD albumin and protein losses. These results suggest a strong association between D/PCr and D/P for proteins. This observation is consistent with the increased protein losses through PD in high transporters and may be related to the inferior outcomes in this group.

Metformin-associated lactic acidosis in a low risk patient.

Metformin is an oral hypoglycemic agent belonging to the class of biguanides that are commonly used in the treatment of type II diabetes mellitus. Lactic acidosis is a rare but severe adverse reaction that occurs primarily in patients with contraindications such as renal failure. The case of a 71-year-old woman with type II diabetes, in whom severe metformin-associated lactic acidosis was precipitated by acute renal failure in the absence of pre-existing chronic renal failure or other absolute contraindications to biguanide use, is presented. Aggressive correction of the acidosis and prolonged dialysis resulted in a favourable outcome despite severe acidosis. The present case report shows that metformin-associated lactic acidosis can occur in patients without pre-existing renal insufficiency. Metformin should be temporarily stopped when acute renal failure occurs or is anticipated.

Apolipoprotein(a) phenotype, albumin clearance, and plasma levels of lipoprotein(a) in peritoneal dialysis.

This cross-sectional study was undertaken to examine the relationship between plasma lipoprotein(a) [Lp(a)] level and peritoneal dialysis (PD) albumin clearance while controlling for the influence of the apolipoprotein(a) [apo(a)] phenotype. Plasma Lp(a) level, PD albumin clearance, and apo(a) phenotype (high vs. low molecular weight, HMW vs. LMW) were determined in 54 PD patients. Apo(a) phenotypes were 24 LMW and 30 HMW. The plasma Lp(a) level was high (> 65 nmol/l) in 17 of 24 patients with LMW phenotype versus 2 of 30 with HMW phenotype (chi2, p < 0.01). Spearman correlation coefficients of Lp(a) with PD, urine, and total albumin clearances were -0.05 (p = 0.74), -0.04 (p = 0.80), and -0.09 (p = 0.51), respectively. The apo(a) isoform size was the only significant predictor of Lp(a) in multivariate analysis. In this study, there was no association between PD albumin clearance and Lp(a) level. The association between apo(a) phenotype and Lp(a) level is in keeping with studies in the general population. There is a strong genetic influence on Lp(a) level in PD patients.

Do patients with obstructive sleep apnea have clinically significant proteinuria?

AIM: Previous studies report a high prevalence of proteinuria in patients with obstructive sleep apnea syndrome (OSAS). This common syndrome may therefore be an important cause ofproteinuria and renal failure in the general population. This study was undertaken to assess the prevalence of proteinuria among OSAS patients, and to identify the factors associated with urine protein excretion in these patients. METHODS: Overnight polysomnography, urine protein to creatinine ratio (PTCR), body mass index (BMI), mean arterial pressure (MAP), and hematocrit were assessed prospectively in 224 patients referred for evaluation of suspected OSAS. Sleep apnea was defined as apnea-hypopnea score (AHS) > or = 5 events/hour. Proteinuria was defined as PTCR > 0.2 mg/mg. RESULTS: Sleep apnea was present in 143 subjects (63.8%), and proteinuria in 10 (4.5%). The highest PTCR was 0.677 mg/mg. PTCR and AHS were weakly correlated (r = 0.12, p = 0.08). PTCR correlated (alpha = 0.05) with lowest oxygen saturation (r = -0.18, p = < 0.01), time spent with oxygen saturation below 90% (r = 0.19, p = < 0.01), and BMI (r= 0. 17, p = < 0.01). The mean PTCR was similar in subjects with and without sleep apnea. Proteinuria was present in 7 of 143 (4.9%) subjects with AHS > or = 5 and 3 of 81 (3.7%) subjects with AHS < 5, a relative risk of 1.34, 95% CI (0.34, 5.32). Predictors of LogPTCR in multiple linear regression (model R2 - 0.104) were: AHS (< 5 or > or = 5), baseline oxygen saturation, sex, and MAP. CONCLUSIONS: Clinically significant proteinuria is uncommon in OSAS. The prevalence and severity of proteinuria are similar in both OSAS patients and patients without sleep-disordered breathing. Sleep apnea severity is weakly associated with urine protein excretion, related more to hypoxemia than to frequency of apneic events.

DDAVP to prevent rapid correction in hyponatremia.

Correction of hyponatremia can be complicated by brisk free water diuresis with a rise in the serum sodium (s-Na) in excess of the generally accepted rate of 10-15 mmol/l/24 hours. We describe this complication and its treatment with desmopressin (dD-AVP), in a 56-year-old female with severe hyponatremia secondary to polydipsia and antidiuretic (ADH) activity. The patient developed a large free water diuresis with a markedly dilute urine (urine osmolality 61 mmol/kg) and a rise in the serum sodium of 19 mmol/l in 19 hours despite the addition of large volumes of free water intravenously and orally. To reduce the free water excretion, desmopressin (dD-AVP) 8 microg was given intravenously. This resulted in a rise in the urinary osmolality, a reduction in the urine volume, and a 2 mmol/l reduction in the serum sodium. Thereafter, the serum sodium rose 4 mmol/l in 24 hours. There were no neurological sequellae. In cases of appropriate but rapid correction of hyponatremia secondary to rapid free water diuresis, dD-AVP can safely reduce the free water excretion, slow the rate of correction of the serum sodium and simplify the fluid therapy of the patient.

Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in peritoneal dialysis patients.

OBJECTIVE: The aim of the present study was to examine the association between infection with Chlamydia pneumoniae and symptomatic atherosclerosis in peritoneal dialysis (PD) patients. DESIGN: Cross-sectional study. SETTING: Peritoneal Dialysis Unit of Kingston General Hospital. PATIENTS: Fifty-five prevalent PD patients. OUTCOME MEASURES: (1) Infection with C. pneumoniae diagnosed by detection of DNA in peripheral blood mononuclear cells (PBMCs) using polymerase chain reaction. (2) Symptomatic atherosclerosis involving the coronary, cerebral, or peripheral circulation. RESULTS: The DNA of C. pneumoniae was detected in PBMCs in 33 patients (60.0%). Atherosclerosis was present in 16 of 33 (48%) PBMC C. pneumoniae DNA-positive patients, and in 10 of 22 (45%) PBMC C. pneumoniae DNA-negative patients (p = 0.83). Using multiple logistic regression and controlling for a number of known cardiovascular risk factors, PBMC C. pneumoniae DNA status was not predictive of atherosclerosis. The only significant independent predictors of atherosclerosis were diabetes and age. CONCLUSIONS: In prevalent PD patients, a high prevalence of symptomatic atherosclerosis and of Chlamydia pneumoniae DNA in PBMCs were seen; however, the results of the present study do not support the presence of an association between infection with C. pneumoniae and atherosclerosis.

The influence of total, dialysis, and residual renal urea clearances on serum albumin in peritoneal dialysis.

Though serum albumin (SA) and Kt/V predict mortality in peritoneal dialysis (PD), the relationship between them remains unclear. We report a cross-sectional study of factors associated with SA in PD, and a prospective study of the effect of increasing dialysis dose on SA in hypoalbuminemic patients with Kt/V < 2.1. Multiple linear regression was performed in 56 subjects with dependent variable SA at 4 months after starting PD (SA2), and independent variables: age, sex, diabetes, 4h-D/Pcr, predialysis SA (SA1), nPCR, PD-duration, modality, Kt/V, Ccr, and daily volume excreted normalized to body water (Vt/V). Forward stepwise selection (alpha = 0.05) produced a model (r2 = 0.492, P < 0.001) containing predictors of SA2: SA1 and nPCR (positive), and Vt/V (negative). With Vt/V excluded, Kt/V became significant (negative). Broken into components, dialysate Kt/V was significant, but residual Kt/V was not significant. In 14 hypoalbuminemic patients with Kt/V < 2.1, PD prescription was changed, targeting a Kt/V > 2.1. After 3.3 months, Kt/V rose from 1.7 +/- 0.25 to 2.21 +/- 0.36 (P = 0.0001), and nPCR rose slightly, 0.71 +/- 0.13 to 0.78 +/- 0.19 (P = NS), with no significant change in SA, 30.5 +/- 3.0 g/L to 31.4 +/- 3.8 g/L (P = 0.268). Dialysate and urine volumes are negative predictors of SA. Volume-dependent dialysate-protein loss could account for poor correlation between Kt/V and SA, and lack of improvement in SA with increased Kt/V.