Residual Creatinine Clearance Research Articles

Building a model to predict the risk of multiple severe neurotoxicities in cancer survivors after cisplatin treatment.

e24066 Background: Cisplatin treatment is used for many cancers, including testicular, ovarian, and head and neck malignancies. Cancer survivors with multiple cisplatin-related toxicities can have poor health-related quality of life (HRQOL). Identification of clinical and genetic factors that predict the risk of these neurotoxicities is critical. Methods: Testicular cancer survivors (TCS) enrolled in the Platinum Study completed surveys, underwent physical examination, extensive audiometric testing, and phlebotomy for genotyping and serum platinum analysis. Cases included TCS with two or more severe toxicities (hearing loss [HL], tinnitus, and peripheral sensory neuropathy [PSN]), defined as follows: hearing threshold > 40dB based on geometric mean of 4-12kHz, responding yes to “Do you have ringing or buzzing in the ears?” and/or EORTC-CIPN20 scores in the severe range for items related to sensory neuropathy. Controls were restricted to TCS without any toxicities. TCS with a single toxicity were excluded from analyses. Penalized logistic regression lasso method was used to create the model to predict the binary outcome. Creatinine clearance and residual serum platinum levels were calculated. Polygenic risk scores (PRS) for traits commonly associated with pharmacokinetics and HL, tinnitus, and PSN were calculated for TCS in the training (n = 284) and validation (n = 157) data sets using PRS publicly available in The Polygenic Score Catalog using PRSice 2.3.3. Models were trained and tested in R 4.1.2. Results: A model to assess the risk of developing multiple severe neurotoxicities that could be used without blood work and additional analysis was developed. Clinical predictors incorporated into the model were age at testicular cancer diagnosis, age at phlebotomy, weight and height. PRS incorporated were age-related sensorineural hearing loss (PGS000762), body fat percentage (PGS002133), creatinine in urine (PGS001944), and peripheral nervous system disease (PGS002039). The accuracy of this model was 77.71%, which was significantly greater than the no information rate (NIR) of 65.61% (p = .00067). The positive and negative predictive values (PPV and NPV) were 72.09% and 79.82%, respectively. The AUC-ROC was 0.804. Adding residual platinum levels and creatinine clearance increased the accuracy of the model to 78.34%, which was significantly greater than the NIR (p = .00035). The PPV was 75.00% and the NPV was 79.49%. The area under the receiver operating characteristic curve (AUC-ROC) was 0.832. Conclusions: TCS are often faced with multiple severe neurotoxicities such as HL, tinnitus, and PSN, which impact HRQOL for many decades. If confirmed, a penalized regression model using clinical and genetic characteristics can predict the risk of developing these phenotypes to guide clinicians in treatment and post-treatment management plans.

Beta-trace protein as a potential biomarker of residual renal function in patients undergoing peritoneal dialysis

BackgroundResidual renal function is closely linked to quality of life, morbidity and mortality in dialysis patients. Beta-trace protein (BTP), a low molecular weight protein, has been suggested as marker of residual renal function, in particular in patients on hemodialysis. We hypothesized that BTP also serves as a marker of residual renal function in pertioneal dialysis patients.MethodsIn this study 34 adult patients on peritoneal dialysis were included. BTP, creatinine, cystatin C and urea concentrations were analyzed simultaneously in serum and dialysate to calculate renal and peritoneal removal of the analytes.ResultsIn peritoneal dialysis patients with residual diuresis, mean serum BTP was 8.16 mg/l (SD ± 4.75 mg/l). BTP correlated inversely with residual diuresis (rs = − 0.58, p < 0.001), residual creatinine clearance (ClCr) (rs = − 0.69, p < 0.001) and total urea clearance (Clurea) (rs = − 0.56, p < 0.001). Mean peritoneal removal of BTP was 3.36 L/week/1.73m2 (SD ± 1.38) and mean renal removal 15.14 L/week/1.73m2 (SD ± 12.65) demonstrating a significant renal contribution to the total removal. Finally, serum BTP inversely correlated with alterations in residual diuresis (r = − 0.41, p = 0.035) and renal creatinine clearance over time (r = − 0.79, p = p < 0.001).ConclusionBTP measurement in the serum may be a simple tool to assess residual renal function in peritoneal dialysis patients.

Oral Bicarbonate Slows Decline of Residual Renal Function in Peritoneal Dialysis Patients

Background/Aims: Metabolic acidosis is a common consequence of end-stage renal disease (ESRD) which may result in a substantial adverse outcome. The effect of oral bicarbonate on the preservation of residual renal function (RRF) in peritoneal dialysis (PD) patients has been rarely reported. Methods: We randomly assigned 40 continuous ambulatory peritoneal dialysis (CAPD) patients to the oral bicarbonate group or placebo group at a 1: 1 ratio. All enrollments were followed for a duration of 104 weeks. We took residual creatinine clearance (CCr), a measure of residual renal function (RRF), as the primary outcome. Residual CCr was calculated as the average of urea and creatinine clearance from a 24-hour urine collection. Results: Thirteen patients in the placebo group and 15 patients in the treatment group completed the 104 weeks of follow-up with a comparable dropout rate (placebo group: 35% vs treatment group: 25%). Compared with the placebo group, serum bicarbonate in treatment group was significantly increased at each time point, and oral bicarbonate resulted in a slower declining rate of residual CCr (F=5.113, p=0.031). Baseline residual CCr at enrollment also had a significant effect on residual CCr (F=168.779, P<0.001). Charlson Comorbidity Index which was adopted to calculate a comorbidity score had no significant effect on residual CCr loss (F=0.168, P=0.685). Conclusion: Oral bicarbonate may have a RRF preserving effect in CAPD patients, and a normal to high level of serum bicarbonate (≥24mmol/L) may be appropriate for RRF preservation.

Proposal of a Pharmacokinetically Optimized Dosage Regimen of Antibiotics in Patients Receiving Continuous Hemodiafiltration

The aim of the study was to quantitatively predict the clearance of three antibiotics, amikacin, vancomycin, and teicoplanin, during continuous hemodiafiltration (CHDF) and to propose their optimal dosage in patients receiving CHDF. For this goal, in vitro CHDF experiments with a polyacrylonitrile (PAN) membrane were first performed using these antibiotics, and then the clearances were compared with in vivo CHDF situations determined in 16 critically ill patients. The in vitro CHDF clearances were described as the product of the outflow rate of a drain (Q(outflow)) and the drug unbound fraction in artificial plasma, indicating that drug adsorption to the PAN membrane has minor effect on drug clearance in our settings. The observed in vivo clearances also agreed very well with the predicted values, with a product of Q(outflow) and plasma unbound fraction, when residual creatinine clearance (CL(CR)) was taken into account (within a range of 0.67- to 1.5-fold for 15 of 16 patients). Based on these results, a nomogram of the optimized dosages of amikacin, vancomycin, and teicoplanin was proposed, and it was evident that Q(outflow) and residual CL(CR) are major determinants of the dosage and dosing interval for these antibiotics. Although the applicability needs to be confirmed with another type of membrane or higher Q(outflow), our nomogram can help determine the dosage setting in critically ill patients receiving CHDF.

Inotropic support and peritoneal dialysis adequacy in neonates after cardiac surgery

We describe the impact of cardiovascular pharmacologic support on peritoneal dialysis adequacy in 20 neonates who required postoperative renal replacement therapy following cardiopulmonary bypass exposure. Peritoneal dialysis was administered for 2.5 (2) days. Peritoneal dialysis creatinine clearance was 3.4 (2.1) ml/min/1.73 m(2) and ultrafiltration rate was 9.75 (10) ml/h. Residual creatinine clearance was 31 (26) ml/min/1.73 m(2). Peritoneal dialysis creatinine clearance appeared to be a function of dialysate flow up to 100 ml/h. No correlation was present between inotropes and vasopressors infusion and peritoneal dialysis creatinine clearance/ultrafiltration rate. LDH clearance was 0.59 (0.85) ml/min/1.73 m(2) and it did not appear to have a correlation with dialysate flow. Patients in-hospital mortality was 20%, significantly higher than overall neonatal population admitted to our ICU (4.8%, P=0.02). Peritoneal dialysis in neonates allows optimal ultrafiltration rate and adequate small solute clearance, irrespective of hemodynamic status or vasopressor support.

Dosing of Gentamicin in Patients With End‐Stage Renal Disease Receiving Hemodialysis

The aim of this study was to evaluate dosing schedules of gentamicin in patients with end-stage renal disease and receiving hemodialysis. Forty-six patients were recruited who received gentamicin while on hemodialysis. Each patient provided approximately 4 blood samples at various times before and after dialysis for analysis of plasma gentamicin concentrations. A population pharmacokinetic model was constructed using NONMEM (version 5). The clearance of gentamicin during dialysis was 4.69 L/h and between dialysis was 0.453 L/h. The clearance between dialysis was best described by residual creatinine clearance (as calculated using the Cockcroft and Gault equation), which probably reflects both lean mass and residual clearance mechanisms. Simulation from the final population model showed that predialysis dosing has a higher probability of achieving target maximum concentration (Cmax) concentrations (> 8 mg/L) within acceptable exposure limits (area under the concentration-time curve [AUC] values > 70 and < 120 mg x h/L per 24 hours) than postdialysis dosing.

Kidney Transplantation Without Prior Dialysis in Children: The Eurotransplant Experience

Kidney transplantation without prior dialysis may prevent dialysis-associated morbidity. We analyzed the outcome of 1113 first kidney transplants in children performed between 1990 and 2000 in the Eurotransplant community. Enlistment for a deceased donor kidney before start of dialysis (127/895, 14%) made dialysis redundant in 55% of cases. Mean residual creatinine clearance at transplantation of these patients was 8 mL/min/1.73 m(2). Pre-emptive transplantations of deceased donor kidneys showed less acute rejections (52% vs. 37% rejection-free at 3 years, p = 0.039), compared to transplantations following dialysis. The difference in graft survival between non-dialyzed and dialyzed patients (82% vs. 69% at 6 year) did not reach statistical significance (p = 0.055). No differences were noted after living donor transplantation. Multivariate analysis showed that the period of transplantation was the strongest predictor of graft survival (p < 0.001). Congenital structural abnormalities such as primary kidney disease predominated in nondialyzed patients as compared to dialyzed patients (p < 0.001); this factor did not influence graft survival. Based on our conclusion that pre-emptive transplantation is at least as good as post-dialysis transplantation, as well as on quality of life arguments, we recommend to consider pre-emptive transplantation in children with end-stage renal failure.

Residual renal function and nutritional status in patients on continuous ambulatory peritoneal dialysis

During the last years, an increasing number of patients with end-stage renal failure caused by various underlying diseases, all over the world, is treated by renal replacement therapy. NUTRITIONAL STATUS: Malnutrition is often found in patients affected by renal failure; it is caused by reduced intake of nutritional substances due to anorexia and dietary restrictions hormonal and metabolic disorders, comorbid conditions and loss of proteins, amino-acids, and vitamins during the dialysis procedure itself. Nutritional status significantly affects the outcome of patients on chronic dialysis treatment. Recent epiodemiological trials have proved that survival on chronic continuous ambulatory peritoneal dialysis program depends more on residual renal function (RRF) than on peritoneal clearances of urea and creatinine. The aim of the study was to analyze the influence of RRF on common biochemical and anthropometric markers of nutrition in 32 patients with end-stage renal failure with various underlying diseases during the first 6 months on continuous ambulatory peritoneal dialysis (CAPD). The mean residual creatinine clearance was 8,3 ml/min and the mean RRF was 16,24 l/week in our patients at the beginning of the chronic peritoneal dialysis treatment. During the follow-up, the RRF slightly decreased, while the nutritional status of patients significantly improved. Gender and age, as well as the leading disease and peritonitis didn't influence the RRF during the first 6 months of CAPD treatment. We found several positive correlations between RRF and laboratory and anthropometric markers of nutrition during the follow-up, proving the positive influence of RRF on nutritional status of patients on chronic peritoneal dialysis.

Vancomycin and Ciprofloxacin: Systemic Antibiotic Administration for Peritoneal Dialysis-Associated Peritonitis

Peritonitis due to peritoneal dialysis (PD) is best treated empirically while waiting for the results of the dialysate culture. Thus, antibiotic therapy must cover both gram-positive and gram-negative micro-organisms. First, over a period of 9 years in a multicenter study we evaluated the efficiency of a vancomycin and ciprofloxacin combination given as the first-line treatment protocol for PD peritonitis. Second, we evaluated whether a systemic route of administration of the antibiotics could be an interesting alternative to the usual cumbersome intraperitoneal drug administration. Vancomycin 15 mg/kg body weight, intravenous, and oral ciprofloxacin 250 mg two times per day (500 mg twice per day if residual creatinine clearance was above 3 mL/minute) were prescribed at diagnosis of peritonitis. Vancomycin injections were repeated (when blood trough level was expected to be below 12 microg/mL) in cases of gram-positive organisms for a total duration of 3 weeks. Ciprofloxacin was given for a total of 3 weeks in cases of gram-negative and a total of 10 days for susceptible gram-positive infections. A total of 129 episodes of peritonitis occurred; 28 of them were not included in the study because of protocol violation (n = 15) or fungal (n = 7) or fecal (n = 6) peritonitis, leaving 101 peritonitis episodes for analysis. 52 (51.5%) gram-positive and 28 (27.7%) gram-negative organisms were grown; 38 gram-positive organisms were coagulase-negative staphylococci. No organism was identified in 8 peritonitis episodes, whereas 13 peritonitis episodes were caused by more than 1 organism. 35% of the coagulase-negative staphylococci were resistant to first-generation cephalosporin and methicillin, whereas all were susceptible to vancomycin. For gram-negative bacilli, the susceptibility rate was 96% and 95% for ciprofloxacin and ceftazidime respectively. The overall treatment success rate was 77.2% (78 of the 101 peritonitis episodes): 61.4% at first intention and 15.8% after optimization of the antibiotic therapy (second intention). The protocol failed in 22.8% of the peritonitis episodes. Hospitalization was required in 52% of the peritonitis episodes; average hospitalization was 11 (range 1-45) days. Systemic vancomycin and ciprofloxacin administration is a simple and efficient first-line protocol antibiotic therapy for PD peritonitis. In our opinion, vancomycin should still be used for gram-positive infections because of its high susceptibility rate compared with first-generation cephalosporins, providing a close monitoring of the local epidemiology. Oral ciprofloxacin provides satisfactory results in gram-negative infections, comparable to those obtained with intraperitoneal ceftazidime or aminoglycosides.

Long-term use of 1.1% amino acid dialysis solution in hypoalbuminemic continuous ambulatory peritoneal dialysis patients.

Malnutrition is a common problem in patients treated with continuous ambulatory peritoneal dialysis (CAPD). Hypoalbuminemia in CAPD patients is an independent risk factor for death and is associated with malnutrition. Previous short-term studies have examined the use of amino acid based PD solutions in terms of albumin levels and anthropometric changes, but not clinical outcome. We report on the extended use of 1.1% amino acid based peritoneal dialysis solution (Nutrineal) and have assessed clinical utility in terms of nutrition, biochemical indices, dialysis adequacy and clinical outcomes. The effect of Nutrineal was studied retrospectively in 22 patients during the past 30 months. All patients had an albumin level of < 35 g/l prior to commencing Nutrineal, and had either a protein intake < 1.2 g/kg or weight loss of > 5% in the previous 3 months. 19 of the 22 patients underwent an 8-week trial of oral nutritional supplements with no improvement in serum albumin level. Albumin level, normalized protein catabolic rate, weight, Kt/V and creatinine clearance were assessed for all patients prior to Nutrineal and at the end of the study period. The mean time on Nutrineal therapy was 13.6 months (range 6-26 months). There were no reported side effects of the treatment. There was an average of 1 episode of peritonitis per 23 treatment months, and only 1 patient died (4% annually adjusted mortality cf 8.9% on the peritoneal dialysis program as a whole). There was a significant increase in albumin level from 22.45 +/- 0.97 range 14-33 g/l to 25.68 +/- 1.159 range 16-35 g/l (p = 0.0036). Normalized protein catabolic rate increased significantly, from 0.898 +/- 0.053 to 1.085 +/- 0.056 g/kg/day (p = 0.0057). Weight decreased slightly although this did not reach statistical significance. Kt/V and creatinine clearance both decreased significantly, but remained within the adequate range in > 80% of the patients. There was no significant change in residual renal function (mean residual creatinine clearance 3.8 +/- 0.59 ml/min at the start of the study period, cf 3.4 +/- 0.61 ml/min at the end). These data suggest that Nutrineal can be used safely and effectively for an extended period of time. Such use is associated with a low mortality rate and a low peritonitis rate, although dialysis adequacy is compromised to a degree.

Pre-dialysis clinic attendance improves quality of life among hemodialysis patients.

BackgroundAlthough previous research has demonstrated that referral to pre-dialysis clinics is associated with favourable objective outcomes, the benefit of a pre-dialysis clinic from the perspective of patient-perceived subjective outcomes, such as quality of life (QOL), is less well defined.MethodsA retrospective incident cohort study was conducted to determine if pre-dialysis clinic attendance was a predictor of better QOL scores measured within the first six months of hemodialysis (HD) initiation. Inclusion criteria were HD initiation from January 1 1998 to January 1 2000, diagnosis of chronic renal failure, and completion of the QOL questionnaire within six months of HD initiation. Patients receiving HD for less than four weeks were excluded. An incident cohort of 120 dialysis patients was identified, including 74 patients who attended at least one pre-dialysis clinic and 46 patients who did not. QOL was measured using the SF 36-Item Health Survey. Independent variables included age, sex, diabetes, pre-dialysis clinic attendance and length of attendance, history of ischemic heart disease, stroke, peripheral vascular disease, heart failure, malignancy, and chronic lung disease, residual creatinine clearance at dialysis initiation, and kt/v, albumin and hemoglobin at the time of QOL assessment. Bivariate and multivariate linear regression analyses were used to identify predictors of QOL scores.ResultsMultivariate analysis suggested that pre-dialysis clinic attendance was an independent predictor of higher QOL scores in four of eight health domains (physical function, p < 0.01; emotional role limitation, p = 0.01; social function, p = 0.01; and general health, p = 0.03), even after statistical adjustment for age, sex, residual renal function, kt/v, albumin, and co-morbid disease. Pre-dialysis clinic attendance was also an independent predictor of the physical component summary score (p = 0.03).ConclusionsWe conclude that pre-dialysis clinic attendance favourably influences patient-perceived quality of life within six months of dialysis initiation.

A Genome Scan for Renal Function among Hypertensives: the HyperGEN Study

Decreased renal function is often a complication of hypertension. Although it has been suggested that the response of the kidney to hypertension has an underlying genetic component, there is limited information suggesting that specific genetic regions or candidate genes contribute to the variability in creatinine clearance, a commonly used measure of kidney function. As part of the Hypertension Genetic Epidemiology Network (HyperGEN) study, creatinine clearance measurements were assessed in a large biracial sample of hypertensive siblings (466 African American subjects and 634 white subjects in 215 and 265 sibships, respectively). All participants were hypertensive before the age of 60 years, and the mean age of the siblings was 52 years among the African American subjects and 61 years among the white subjects. Two residual models were created for creatinine clearance: a minimally adjusted model (which included age and age(2)) and a fully adjusted model (which included age, age(2), lean body mass, pulse rate, pulse pressure, hormone-replacement therapy, educational status, and physical activity). Standardized residuals were calculated separately for men and women in both racial groups. The heritability of the residual creatinine clearance was 17% and 18% among the African American and white subjects, respectively. We conducted multipoint variance components linkage analysis using GENEHUNTER2 and 387 anonymous markers (Cooperative Human Linkage Center screening set 8). The best evidence for linkage in African American subjects was found on chromosome 3 (LOD = 3.61 at 214.6 cM, 3q27) with the fully adjusted model, and the best evidence in white subjects was found on chromosome 3 (LOD = 3.36 at 115.1 cM) with the minimally adjusted model. Positional candidate genes that are contained in and around the region on chromosome 3 (214.6 cM) that may contribute to renal function include enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (EHHADH) and apolipoprotein D (ApoD). These findings suggest there may be genetic regions related to the variability of creatinine clearance among hypertensive individuals.

Pharmacokinetics of Recombinant Hirudin in Hemodialyzed End-stage Renal Failure Patients

Recently, hirudin was used for the first time as an anticoagulant during hemodialysis in men. Pharmacokinetic data of this compound in end-stage renal failure are however not available. In this study, the pharmacokinetics of recombinant hirudin (HBW 023) was evaluated in hemodialysis-treated end-stage renal failure patients. HBW 023 was administered as a bolus at the start of a single dialysis (0.02 to 0.08 mg/kg) in 20 patients, and plasma hirudin levels were followed during this and the 5 following dialyses, without additional hirudin administration. The initial dialysis (HD1) was performed with a low flux polysulfone dialyzer, the following dialyses (up to HD6) with a high flux polysulfone dialyzer and regular heparin. Hirudin levels averaged 504.0 +/- 214.0 and 527.7 +/- 217.1 ng/ml in the middle and at the end of HD1, and then gradually decreased to 15.2 +/- 15.2 ng/ml at the end of HD6. Pharmacokinetic data were compared to those obtained in healthy controls (n = 5), receiving the same dose, and reaching the same peak hirudin level. Hirudin half-life was > 30 times longer in hemodialysis patients (51.8 +/- 15.6 vs. 1.7 +/- 1.5 h, p < 0.001), whereas area under the curve was > 60 times higher (34,669 +/- 14,898 vs. 545 +/- 205 ng/ml x h, p < 0.001). Distribution volume was lower in hemodialysis patients (11.0 +/- 3.1 vs. 14.1 +/- 2.01, p < 0.05). Hirudin disappearance rate was the same during high flux polysulfone dialysis as during interdialytic periods. Hirudin removal was markedly higher in those patients still maintaining some residual renal function and parameters of hirudin removal were significantly correlated to residual creatinine clearance. It is concluded that hirudin removal from the body is markedly depressed in hemodialyzed end-stage renal failure patients and that even minor residual renal function may increase this removal rate.

Sensitivity of residual nephrons to high dose furosemide described by diuretic efficiency.

Ten haemodialysis (HD) patients with a median residual creatinine clearance (CLCR) of 1.9 ml.min-1 x 1.73 m-2 (range 0.6-5.3) were treated with oral furosemide (F) 2.0 g. Overall-efficiency (O-E, daily sodium excretion/total urinary F) and total-efficiency (delta-E, increase in daily sodium excretion/total urinary F) were measured on the last 24 hours of each interdialysis interval. In addition, O-E was measured during the complete interdialysis interval in 10 HD patients with a median CLCR of 5.6 ml.min-1 x 1.73 m-2 (range 0.7-6.8) treated for 1 year with a fixed oral dose of F between 250-1000 mg (median 625 mg). In the short study the median O-E was 10.6 mmol.mg-1 (range 1.9-22.0) and delta-E 6.2 mmol.mg-1 (range 1.3-11.2). The fractional excretion of sodium FENa was significantly increased from 9.6% (range 4.1-22.9) to 27% (range 14.6-56.2) during F treatment. A positive correlation was found between the basal FENa and delta-E. In the long-term study median O-E was 6.4 mmol.mg-1. O-E and FENa showed no change over time although median RCC decreased from 5.6 to 1.9 ml.min-1 x 1.73 m-2 and median F excretion from 11.8 to 7.5 mg per day. It can be concluded that diuretic efficiency in haemodialysis patients is dependent on FENa and the state of hydration during the interdialysis interval.

Contributing factors to the inhibition of phagocytosis in hemodialyzed patients

Although polymorphonuclear (PMNL) glucose consumption as an index of metabolic response to phagocytosis in the production of free radical species is depressed in hemodialyzed patients, substantial interindividual differences are registered. Studies evaluating to what variables these differences are related are, however, lacking. In the present study, the relation of several factors to PMNL functional capacity in the breakdown of glucose to CO2 by the hexose monophosphate shunt (HMS) is considered in an individual and multifactorial regression analysis. Starting from a database, collected in 126 stabilized hemodialysis patients, PMNL HMS-response to standard quantities of latex and zymosan was correlated to 14 numerical parameters: time since the start of dialysis, hematocrit, serum creatinine, phosphorus, ferritin, albumin, parathormone, albumin before and after administration of desferrioxamine, residual creatinine clearance, PCR, TACurea, Kt/V and age. In addition, the non-numeric parameters of sex, biocompatibility of dialyzers, and primary diagnosis were also considered. A significant correlation was found for time on dialysis (P < 0.001), hematocrit (P < 0.001), ferritin (P < 0.05), PTH (P < 0.001) and aluminum (P < 0.05). The highest correlation coefficients were found for time on dialysis (latex: N = 126, r = 0.50, P < 0.001; zymosan: N = 126, r = 0.58, P < 0.001). Multivariate correlation analysis of one clinical parameter together with time on dialysis to PMNL response showed that the correlation was strongly weakened or disappeared for ferritin, aluminum and PTH, but not for hematocrit. Our data indicate that time since the start of dialysis is an important, but not unique factor, influencing polymorphonuclear functional capacity in a hemodialysis population.

Hematocrit and Residual Renal Creatinine Clearance in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis (CAPD)

In a recent report, the relationship between renal creatinine clearance and hematocrit in patients with renal creatinine clearances, ranging from 55 to 8 mL per min. per 1.73 square meters of body surface area, was analyzed. The authors of this study have performed a cross-sectional analysis of the relationship of hematocrit to residual renal creatinine clearance in patients on continuous ambulatory peritoneal dialysis (CAPD). The authors of this study wanted to examine whether or not these hematocrits fall within extrapolations of the published 95% confidence limits for males and females with renal failure prior to end-stage renal disease and dialytic intervention. Authors also compared regression intercepts at residual creatinine clearances of 0. Most of the CAPD patients had hematocrits within the upper half or above the extrapolated 95% confidence limits for the predialysis population. Within the CAPD population, there were no significant correlations of hematocrit with residual creatinine clearance at these lower ranges. The degree of scatter in the CAPD population for hematocrit values was similar to that in the predialysis population. Residual creatinine clearance appears to be a crude index of the increasing severity of multiple factors that may contribute to the anemia. CAPD appears to maintain or improve hematocrit as renal mass and function decline.

Peritoneal Functional Parameters after Five Years on Continuous Ambulatory Peritoneal Dialysis (CAPD): The Effect of Late Peritonitis

Functional stability of the peritoneum is essential for patients on long-term continuous ambulatory peritoneal dialysis (CAPD) treatment. Sixteen patients on CAPD treatment for at least 4 years were studied. Their mean age was 47 +/- 15 years, 5 were males, and none were diabetic. Residual creatinine clearance at the beginning was 2.1 +/- 2.6 mL/min. Once yearly since starting CAPD, we have evaluated their peritoneal ultrafiltration (UF) and diffusion capacities by calculating the peritoneal mass transfer coefficient (MTC, mL/min) for urea and creatinine. Patients were categorized so that we could distinguish the effect of peritonitis, betablockers, and hypertension. For all patients the average initial and final MTCs and UF values were not different. Early episodes of peritonitis (those occurring less than 36 months after starting CAPD) did not influence long-term function. However, late peritonitis (occurring greater than 36 months since initiation) induced a decrease in urea-MTC (22.3 +/- 6 to 15.8 +/- 3.9, p less than 0.05), creatinine-MTC (9.4 +/- 3.1 to 7.4 +/- 2.5, p less than 0.05), and a corresponding increase in UF (1.25 +/- 0.4 to 1.4 +/- 0.3, mL/min, p less than 0.05). Age, sex, betablockers and hypertension did not influence the peritoneal parameters followed. After 5 years on CAPD, functional stability of the peritoneum is evident, except for patients who suffer late episodes of peritonitis. We speculate that the peritoneum in patients who have been on long-term CAPD are more susceptible to injuries, such as peritonitis, and that this results in functional deterioration.

Analysis of Factors in the Prognosis of Diabetics on Continuous Ambulatory Peritoneal Dialysis (CAPO): Long Term Experience

After five years of treating diabetics by continuous ambulatory peritoneal dialysis (CAPD), we analyzed the factors involved in prognosis. Forty-one patients were included in the study, with a cumulative experience of 784 months. Good control of blood glucose was obtained with intraperitoneal (i.p.) insulin and the blood pressure was controlled in 87% of patients without medication, which probably favored the stabilization of visual acuity in 60% of 15 patients evaluated after two years. The follow-up of patients was longer in those who began CAPD with a higher residual creatinine clearance. In spite of large number of patients who were blind or had very poor vision, 83% of all patients were self-sufficient and well-trained for CAPD, and 39% were able to work full time. The incidence of peritonitis declined to 1 episode per 17.5 patient months associated with the introduction of new preventive measures. Patients over 50 years old had the highest mortality rate and myocardial infarction was the main cause of death. Patient survival at 6, 12, 24, 36, and 42 months was 100, 90, 80, 62, and 62%, respectively. Age and cardiac problems are important factors in survival. Self-sufficiency, rehabilitation, and low incidence of peritonitis are also important factors in the life quality of diabetic patients on CAPD.

Continuous Ambulatory Peritoneal Dialysis vs Haemodialysis: A Lesser Risk of Amyloidosis?

We compared plasma beta-2-microglobulin (beta 2M) at a 1-year interval in 25 CAPD patients and 25 patients haemodialysed with cuprophane membranes and matched for residual renal function and duration of renal replacement therapy. Plasma beta 2M remained lower in CAPD patients throughout the study, and increased significantly with time both in CAPD and haemodialysis patients, as renal function decreased. In both groups, plasma beta 2M was negatively correlated with residual creatinine clearance, the influence of the latter being much greater in haemodialysis, as demonstrated by comparison of the regression lines. In haemodialysis, but not in CAPD, plasma beta 2M also correlated with time on dialysis. In CAPD patients, the daily peritoneal output averaged 38 mg (range 16-59 mg), and was directly correlated with plasma beta 2M. CAPD thus allows a significant peritoneal removal of beta 2M, which progressively takes over from the declining renal function, resulting in lower plasma beta 2M than in matched haemodialysis patients. However, the peritoneal removal of beta 2M remains insufficient and values increase with time as renal function declines. Thus, if beta 2M amyloidosis is related to raised plasma levels, the risk of beta 2M amyloidosis in CAPD should simply be delayed as compared to haemodialysis.

LONG-TERM FOLLOW-UP OF PATIENTS WHO UNDERWENT UNILATERAL NEPHRECTOMY IN CHILDHOOD

The long-term damaging potential of remnant nephron hyperperfusion was investigated in patients who had undergone unilateral nephrectomy in childhood. 27 such patients were examined after a mean of 23·3 years postnephrectomy. The average creatinine clearance was 83·9±16·5 ml/min/1·73 m 2 or 74·3% of that in healthy controls with two kidneys; it was a value similar to that reported 3 to 6 months postnephrectomy in kidney donors. Age at the time of nephrectomy, duration of follow-up, or sex had no influence on the residual creatinine clearance. None of these patients had clinically important hypertension or proteinuria. Since so little evidence of kidney damage could be documented after such a long observation period, hyperperfusion would seem to be seldom of clinical importance in man unless other factors were present.