Regular Dialysis Therapy Research Articles

PAX 2 Mutation in an Indian Family with Renal Coloboma Syndrome

The transcription factor encoded by the PAX2 gene plays a significant role in the development of the urogenital tract, eyes, ears, and central nervous system. Heterozygous mutations in the PAX2 gene cause renal coloboma syndrome, a rare autosomal dominant disorder characterized by optic nerve coloboma and renal anomalies. In this study, two siblings with chronic kidney disease (CKD) receiving regular dialysis therapy were investigated. DNA sequencing was performed on blood samples from both patients, which revealed four novel heterozygous variations in the PAX2 gene in both patients. Sequencing analysis showed a C to G transversion at position c.352 of the PAX2 gene in a heterozygous state.

Outcomes of Patients on Maintenance Hemodialysis Admitted to a Tertiary Care Hospital with COVID-19

Background: The coronavirus disease-2019 pandemic has caused a disastrous world health crisis. The patients with renal disease, particularly those who are receiving regular dialysis therapy have elevated risk of COVID-19 infection-associated complications as well as poor prognosis including enhanced risk of hospital admission, mechanical ventilation and mortality.Objective: The objective of the study is to assess the outcomes of patients on maintenance dialysis admitted to a tertiary care hospital with COVID-19.Material and Methods: This retrospective study was performed in a Tertiary Care Hospital from March 2020 to August 2020. A total of 44 patients were included in the study. Data collected through questionnaire was analyzed using the computer software SPSS 24.0. Frequencies and percentages were calculated for categorical data while mean+SD was calculated for quantitative data.Results: Among 44 patients, 63.6% were males and the mean age was 46.86+12.413 years. Mean number of dialysis were 3.57+2.214. The mean ferritin level was 2067.05+788.412 ng/ml and mean C-reactive protein level was 111.59+32.998 mg/L. Among these patients, 65.9% were discharged and 34.1% patients expired.Conclusion: Study concluded that elevated levels of inflammatory markers such as ferritin and CRP are found among patients on maintenance dialysis with COVID-19.

A Comparison of Erectile Dysfunction Improvement Between Patients With Regular Hemodialysis and Patients With Continuous Ambulatory Peritoneal Dialysis

Erectile dysfunction (ED) is one of the sexual dysfunctions that are often encountered as a complication of male patients with stage 5 chronic kidney disease (stage 5 CKD). ED can be caused by psychological factors in patients with regular dialysis therapy. Currently, Hemodialysis (HD) therapy is the first choice in dialysis therapy and only 2% of stage 5 CKD patients are using Continuous Ambulatory Peritoneal Dialysis (CAPD) as a dialysis therapy. ED in stage 5 CKD patients should become a part of the treatment of patients with dialysis, which hopefully will improve the quality of life of patients. This study aims to compare the improvement in ED degree in patients with HD and CAPD. This study is an observational analytic comparative study involving 44 male patients with stage 5 CKD; 22 of whom underwent HD and the remaining 22 patients underwent CAPD. The differences evaluated were changes in the ED degree before and after dialysis, which were assessed using the International Index of Erectile Function-5 (IIEF-5). There were significant differences in the improvement in ED degree and IIEF-5 scores in CAPD group. In the HD group, no significant difference was obtained in the improvement in ED degree and IIEF-5 score. A significant difference was obtained in the improvement in ED degree between the HD and CAPD groups by comparing the improvement in IIEF-5 score. Patients with CAPD have a better improvement in ED degree than patients with HD. Duarsa GWK, Kandarini Y, Winarta GK, etal. A Comparison of Erectile Dysfunction Improvement Between Patients With Regular Hemodialysis and Patients With Continuous Ambulatory Peritoneal Dialysis. J Sex Med Rev 2021;18:920-925.

Epidemiological survey and risk factor analysis of dialysis-related amyloidosis including destructive spondyloarthropathy, dialysis amyloid arthropathy, and carpal tunnel syndrome.

The RDT population, initially at 215 patients, exceeded 300,000 in 2011, with a total of 329,609 patients at the end of December 2016. In our Institute, the number of patients with destructive spondylosis is increasing with the increase in the number of dialysis patients in Japan. We had 14 Cases in the 1990s, and then 82 cases in the 2000s and have already had 131 cases in the 2010s. The purpose of this study was to investigate the incidence of dialysis-related amyloidosis (DRA) such as destructive spondyloarthropathy (DSA), dialysis amyloid arthropathy (DAA), and carpal tunnel syndrome (CTS). In addition, another purpose was to examine the risk factors of the DRA. DAA made its own assessment on radiographs based on stage. Survey items were patient's basic data, laboratory data and X-ray view. Patient's basic data included such as sex, age, height, and weight and RDT-related factors such as kidney disease that led to RDT, age at start of RDT, RDT history, medical history (past and present), and history of surgery. The frequency of DRA was examined by medical history and radiological examination in 199 dialysis patients who obtained informed consent. The patients were divided into two groups according to the presence or absence of DRA, and risk factors of DRA were investigated from the medical history, basic data of patients, and blood tests. Of the 199 patients on regular dialysis therapy, 41 (20.6%) showed DRA. Based on the X-ray images, 21 patients (10.6%) showed DSA, while 22 patients (11.1%) showed DAA. Sixteen patients (8.0%) had CTS, determined through a history of surgery. Regarding overlap of conditions, 14 had both DSA and DAA, 3 had both DSA and CTS, and 2 had both DAA and CTS. There were statistically significant differences between the two groups in the cause of disease in Chronic glomerulonephritis and Diabetic Nephropathy, age at the start of RDT, period of RDT, body weight, blood platelet count, and blood Ca level. When multivariate analysis was performed on these items, statistical differences were recognized only during the dialysis period. In conclusion, long dialysis period was a risk factor for DRA.

Heparin-induced thrombocytopaenia (HIT)-an overview: what does the nephrologist need to know and do?

In an era where medical and critical care patients are more commonly subject to thromboprophylaxis, prompt recognition and appropriate treatment of Heparin-induced thrombocytopaenia (HIT) is required to reduce the risk of serious thrombotic events. In this issue of the Clinical Kidney Journal, Thong et al. present two cases of HIT after initiation of dialysis therapy with heparin as anticoagulant (see ‘Management of heparin-induced thrombocytopaenia (HIT) in patients with systemic vasculitis and pulmonary haemorrhage’ in this issue). This prompts us to present the following overview on diagnosis and management of patients with HIT requiring regular dialysis therapy.

Clinical Outcomes of Japanese MPO-ANCA-related Nephritis: Significance of Initial Renal Death for Survival

Anti-myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)- related nephritis constitutes 60% of rapidly progressive glomerulonephritis (RPGN) in Japan. The reported 1-year survival rate is over 80%, however, the long-term prognosis remains unknown. We therefore investigated the prognosis and factors affecting the clinical course of patients. We retrospectively investigated 74 patients (female, n=42; median age, 73.0 years) with MPO-ANCA-related nephritis. The patients were admitted to Fukushima Medical University and two affiliated hospitals between 2000 and 2010. Median estimated GFR (eGFR) was 12.1 mL/min/1.73 m2 at admission. The Birmingham Vasculitis Activity Score (BVAS version 3: max 63 points) at diagnosis and at 4 weeks after start of treatment were 15.0 and 5.0, respectively. Twenty-three patients (31%) died during a median observation period of 30.5 months. Sixteen patients (22%) presented with end-stage renal disease (ESRD) at the initial phase, and needed regular dialysis therapy. Multivariate Cox proportional hazards model analysis revealed that renal death at the initial phase was a significant risk factor for all-cause death (Hazard ratio, 5.72; 95% confidence interval, 2.49-13.09; p<0.001). Furthermore, BVAS>6, evaluated 4 weeks after start of treatment, is an independent risk factor for ESRD and patient survival. This is the first investigation to demonstrate clinical features focusing on MPO-ANCA-related nephritis. Renal death at the initial phase of treatment is a powerful risk factor for all-cause death in patients with MPO-ANCA-related nephritis. Patients at high risk of death and ESRD could be stratified according to BVAS.

Native Kidney Function After Renal Transplantation Combined With Other Solid Organs in Preemptive Patients

Kidney transplantations combined with other solid organs are progressively increasing in number. There are no guidelines regarding the nephrologic indications for combined transplantations, namely liver–kidney (LKT), or heart–kidney (HKT), in preemptive patients with chronic kidney failure who are not on regular dialysis therapy. The objective of this study was to assess the functional contribution of the native kidneys after preemptive kidney transplantation combined with other solid organs. From 2004, 9 patients (aged 50.3 ± 8.5 years) with chronic kidney failure (creatinine 2.5 ± 1.0 mg/dL) caused by polycystic kidney disease ( n = 4), vascular nephropathy ( n = 2), interstitial nephropathy ( n = 1), glomerulonephritis ( n = 1), or end-stage kidney disease ( n = 1), underwent combined transplantations (8 LKT, 1 HKT). A scintigraphic functional study (Tc-99DMSA or Tc-99mMAG3), was performed at 4 ± 3 months after transplantation to evaluate the functional contribution of both the native kidneys and the graft. All patients were given immunosuppressive drugs, including a calcineurin inhibitor (tacrolimus/or cyclosporine). At the time of scintigraphy, renal function in all patients was 1.3 ± 0.3 mg/dL. The functional contribution of the transplanted kidneys was on average 77 ± 18%. Only in 1 patient was the contribution of the graft <50%. At follow-up after 36 months, patient and kidney survivals were 100%. The study confirmed a high risk of loss of native kidney function in the presence of organic nephropathy. In light of our experience, a creatinine clearance <30 mL/min in an appropriate cutoff for a combined transplantation. Close clinical and instrumental assessment pretransplant is essential before proceeding with a combined transplant program to exclude functional forms and to optimize the use of organs.

Racial and Ethnic Differences in Albuminuria in Individuals With Estimated GFR Greater Than 60 mL/min/1.73 m 2: Results From the Kidney Early Evaluation Program (KEEP)

Albuminuria is an important marker for chronic kidney disease and progression to end-stage renal disease in the general population; understanding racial and ethnic differences can help inform efforts to reduce health disparities. We sought to estimate independent associations of race/ethnicity with albuminuria to determine whether observed differences were attributable to known kidney disease risk factors. This cross-sectional study included 64,161 Kidney Early Evaluation Program (KEEP) participants, 2000-2008, with estimated glomerular filtration rate > or = 60 mL/min/1.73 m(2), not on regular dialysis therapy, and without a previous kidney transplant. Albuminuria (urine albumin-creatinine ratio > or = 30 mg/g) was examined by self-reported race and ethnicity. Covariates were age, sex, educational level, body mass index, diabetes status or glucose level, hypertension status or blood pressure measurement, smoking status, health insurance status, and geographic region. Albuminuria prevalences were 8% (n = 2,303) in whites, 11% (n = 2,310) in African Americans, 9% (n = 730) in Hispanics, 10% (n = 381) in Asians, and 15% (n = 344) in American Indians/Alaska Natives. Compared with whites, odds of albuminuria were higher for all groups after multivariate adjustment. Odds were highest for American Indians/Alaska Natives (adjusted OR, 1.93; 95% CI, 1.70-2.20), then Asians (adjusted OR, 1.42; 95% CI, 1.26-1.61), African Americans (adjusted OR, 1.38; 95% CI, 1.29-1.47), and Hispanics (adjusted OR, 1.19; 95% CI, 1.08-1.31). In the KEEP study population, albuminuria prevalence was higher in African Americans, Hispanics, Asians, and American Indians/Alaska Natives than in non-Hispanic whites, suggesting a need for screening for early detection of kidney damage, especially in people at increased risk, in the community primary care setting.

Validation of a Two-Pool Model for the Kinetics of ß2-Microglobulin

Secondary amyloidosis due to beta-2-microglobulin (beta2-m) is a serious long-term complication in patients on regular dialysis therapy. Beta2-m can be considered a middle-molecule marker used to facilitate the assessment of dialysis efficacy. For this purpose, a validated model that calculates characteristic efficacy parameters, such as Kt/V, TAC and generation rate, is needed. There is general agreement that beta2-m-kinetics should be described by a two-pool model, but little has been published to validate such an approach. We measured the beta2-m concentration profiles of eight stable patients during hemodialysis (HD) at the start of treatment, after 30 minutes, after 60 minutes, and every hour until the end. Thereafter they were measured at 10-minute intervals for an hour. The dialyser clearances were determined from the plasma concentrations in front of and behind the dialyser twice during each session - after 1 hour, and 4 hours from the start of treatment. The kinetic parameters of a two-pool model (e.g. the compartment volumes V1 and V2, the mass transfer coefficient K12 and the generation rate G) were determined from the optimal fit of the measured concentration profile. The table below summarises the results by giving the mean and standard deviation for each parameter: [table: see text]. Inter-individual differences in V1/V2 and K12 were high, ranging from 2.5 to 10.0 for V/V2 and from 26 to 140 for K12. Error analysis suggested that these wide ranges were due to the method and that in reality the probable range of V is 25-36% of TBW, of V1/V2 3.5-5.3, and of K12 30-80 ml/min. With standard values for these three parameters (V = 30% of TBW, V/V2 = 4.4 and K12 = 55 ml/m), equal for all patients, and their respective ranges, Kt/W can be calculated with a standard deviation of 13%. Kt/W > 1.2 secures the maximum possible beta2-m removal with three HD treatments a week. The parameters of a two-pool model of beta2-m kinetics can be derived from concentration profiles obtained under routine dialysis conditions, but accuracy is not completely satisfactory. Similar to the dialysis dose for urea (Kt/Vurea) the dialysis dose for beta2-m (Kt/Vbeta2-m) can be calculated from the pre- and post-dialysis concentrations of beta2-m, body weight, ultrafiltration and dialysis time. Kt/Vbeta2-m > 1.2 secures the maximum possible removal of beta2-m in HD with three sessions per week.

Savings in dialysis treatment?

The steadily increasing number of dialysis patients prompts considerations on possibilities for budget reductions with maintenance of treatment quality. A literature survey is presented concerning trends of population increase, individual treatment costs, rationing of patient intake, and consequences of delayed progress of renal insufficiency as well as of savings during both the initial and the later phases of regular dialysis therapy. Cost reduction in one area may well induce rising total budgets and influence clinical outcome. A multidisciplinary approach is suggested to obtain answers to several questions: Can the economic burden of the changing patient demography be counterbalanced by a reorganized staff structure? Will early referral, good predialysis control, and incremental dialysis start imply longer survival? Will increased dialysis doses be economically neutralized by less staff requirements, drug consumption, and patient morbidity? Should dialyzer reuse be abandoned? Can pretransplant dialysis periods be reduced or omitted by improved planning?

Accuracy and safety of online clearance monitoring based on conductivity variation

Haemodialysis dose has been shown to have a distinct impact upon the morbidity and mortality rate in patients on regular dialysis therapy. Accordingly, the adequacy of dialysis treatment should be guaranteed. In 200 dialysis sessions two or three +/-10% dialysate conductivity variations were applied to test patient compliance and the accuracy of an electrolyte based online clearance measurement (OCM) reflecting the total clearance of urea. Using a step profile the electrolytic clearance showed highly significant correlation with the reference data in the blood side (n=118, r=0.867, P<0.001) and dialysate side (n=118, r=0.820, P<0.001) if only reference values were taken into account for which the error in mass balance did not exceed 5%. Kt/V according to the single pool model (n=35, r=0.940, P<0.001), the equilibrated single pool variable volume kinetic model (n=36, r=0.982, P<0.001), Daugirdas formula (n=34, r=0.951, P<0.001) and direct quantification of dialysance via spent dialysate (n=26, r=0.900, P<0.001) showed outstanding correlations with electrolyte-based Kt/V at mass balance error below 5%. No adverse clinical effect of OCM was reported. Serum sodium, body weight, heart rate and breathing rate at rest, arterial pO(2) and pCO(2) and blood pressure before haemodialysis remained unaffected in OCM measurements in comparison with baseline parameters. A small influx of sodium (1.53+/-7.62 mmol) into the patient was seen following the impulse, but no signs associated with fluid overload were observed during the study period of 10 consecutive dialysis sessions. The OCM option of the haemodialysis machine provides a safe and accurate tool for continuous online monitoring of total urea clearance.

The effect of vitamin B6 and folate supplements on plasma homocysteine and serum lipids levels in patients on regular hemodialysis.

Hyperhomocysteinemia is an independent risk factor for cardiovascular events. The aim of this study was to show the results of the reduction of homocysteine in end stage renal failure patients on hemodialysis, as it is known, have higher levels of homocysteine than other groups of subjects. Plasma homocysteine concentration was determined before and after the administration of vitamin B6 and folic acid in 12 patients (males: 6) on regular dialysis therapy. Mean monthly fasting serum concentrations of total cholesterol (TCHOL), HDL-chol, LDL-chol and triglycerides (TRG) were determined for a period 68 months (12-120 months) before and 26 months after the administration of vitamin B6 and folic acid. Mean serum concentrations for folic acid and vitamin B12 before and after the administration were: folic acid: 5.03 +/- 4.9 and 18.0 +/- 19.2 ng/mL, (p < 0.0001) and B12: 456 +/- 257 and 514.38 +/- 307 pg/mL respectively). Plasma homocysteine was reduced significantly after the administration of above drugs (from 47 +/- 14 to 29 +/- 9 micromol/mL, p < 0.001). This reduction of homocysteine resulted in a modification of the patients' lipidemic profile: Serum LDL-chol was decreased significantly (119 +/- 38 mg/dL to 110 +/- 35 mg/dL, p<0.005). TCHOL and TRG were also decreased but not significantly (190 +/- 45 mg/dL to 187 +/- 43 mg/dL and 116 +/- 63 mg/dL to 108 +/- 47 mg/dL respectively)). Serum concentrations HDL-chol were increased significantly (from 42 +/- 10 mg/dL to 47 +/- 10 mg/dL, p < 0.001). The atherogenic index for cholesterol, LDL/HDL, was 1.6 times lower after the drugs receiving (before: LDL/HDL = 3.1 and after: LDL/HDL = 2.5, p < 0.001). These results indicate that the folate and vitamin B6 supplementation resulted in reduction of homocysteine levels and improvement of lipidemic profile in regular dialysis patients.

Iron and infection

Intravenous iron therapy maintains iron stores and decreases erythropoietin demand in patients undergoing regular dialysis therapy. Microbiology studies show a close relationship between the availability of iron and bacterial virulence. Iron is also an essential requirement of bacteria for multiplication in the host. Therefore, clinical conditions associated with iron excess in the host may increase the risk for infection. Parenteral iron has already been shown in human and animal studies to be harmful when administered during infection. There is now convincing evidence that hydroxyl radicals, produced either by the Fenton reaction or by the iron-catalyzed Haber-Weiss reaction, are species responsible for the damaging effects of iron. The unavailability of iron limits microbial growth but also impairs host resistance. In end-stage renal disease, patients' overtreatment with iron enhances the pre-existing risk for infectious complications caused by dialysis procedure per se, malnutrition, increased intracellular calcium, as well as low and high molecular weight uremic toxins. Intravenous iron therapy may not only adversely affect phagocytes in end-stage renal disease patients, but also T and B lymphocytes.

Impact of renal cadaveric transplantation on survival in end-stage renal failure: evidence for reduced mortality risk compared with hemodialysis during long-term follow-up.

Despite a superior quality of life and a favorable cost effectiveness, it has not been well established thus far whether renal cadaveric transplantation contributes to superior survival probability of end-stage renal disease patients in Europe, because the mortality rate on dialysis is lower compared with the United States. This analysis was undertaken to compare the mortality of wait-listed patients and transplant recipients during long-term follow-up, including the possibility of a retransplant in a single-center study. The study cohort included 309 consecutive patients, ages 17 to 72 yr, being registered on the waiting list of the Renal Transplantation Center of Mannheim since the initiation of the transplantation program on June 3, 1989. Follow-up was terminated on September 30, 1997, with a mean of 4.15 yr. A total of 144 renal cadaveric transplants (four retransplants) was performed during the follow-up period. A Cox regression model considering the time-dependent exposure to the different therapy modalities was applied for statistical analysis. Patients being removed from the waiting list or coming back to dialysis after transplantation were censored at time of withdrawal or graft failure. Transplantation resulted in a lower hazard ratio, which was 0.36 (95% confidence interval, 0.15 to 0.87) when the hazard of the wait-listed group was taken as 1.00. The underlying incidence rate of death was 0.026 per patient-year (0.032 on dialysis versus 0.016 with functioning graft). Performing the evaluation on an intention-to-treat basis without censoring the lower risk of the transplanted group was still pronounced according to a hazard ratio of 0.44 (95% confidence interval, 0.22 to 0.89). Thus, patients receiving a renal cadaveric transplantation have a substantial survival advantage over corresponding end-stage renal disease patients on the waiting list even in the setting of a single transplantation center where mortality on regular dialysis therapy was comparatively low.

Survivors of acute renal failure who do not recover renal function.

Overall survival in 1095 patients with severe acute renal failure (ARF) between 1984 and 1995 was 59.5%. Of these, 107 (16.2%) remained dependent on long-term dialysis. The frequency of end-stage renal failure (ESRF) in survivors of ARF varied between 3% and 41% according to the cause of ARF, being highest in those with acute renal parenchymal disease (in whom survival was also among the highest at 84%) and lowest in ARF due to obstetrics and trauma. Patients failing to regain adequate renal function did not appear to differ on clinical grounds from survivors who became dialysis-independent. Survival in those requiring long-term dialysis was less good than for other patients with ESRF, partly due to excess mortality in those for whom vascular disease or surgery was the precipitating cause of ARF. Six patients recovered sufficient renal function to become independent of dialysis after 3-18 months on regular dialysis therapy (6-21 months after onset of ARF). ESRF resulting from ARF is more frequent than previously reported. This increase may be due to a changing case-mix, increasing age of patients (and hence reduced capacity for renal recovery), and an increase in aggressive surgery for patients with advanced vascular disease. This presents a significant and increasing problem, with implications for both clinical management and the provision of dialysis services.

Current status of renal replacement therapy in Japan

The study of the current status of renal replacement therapy in Japan is based on the analysis of data from the registry reports for regular dialysis therapy and kidney transplantation. The total number of patients receiving regular dialysis therapy was 123,926 at the end of 1992: 117,809 (95.1%) on hemodialysis and 6,117 (4.9%) on peritoneal dialysis. The primary diseases of newly accepted patients were chronic glomerulonephritis (42.2%), diabetic nephropathy (28.4%), nephrosclerosis (5.9%), polycystic kidney disease (2.7%), chronic pyeronephritis (1.6%), and others. The number of kidney transplant patients in Japan was 8,384 at the end of 1991: 6,154 (73.4%) received a living donor transplantation and 2,230 (26.9%) received a cadaver donor transplantation. Overall 5-year survival rates of dialysis patients were 60.4%: 69.7% for chronic glomerulonephritis, 41.7% for diabetic nephropathy, 39.6% for nephrosclerosis, 73.6% for diffuse polycyustic kidney disease, and 66.6% for chronic pyeronephritis. The causes of death of dialysis patients were heart failure (31.1%), cerebrovascular accident (13.6%), infectious dieases (11.3%), malignancies (7.1%), cahexia/uremia (6.7%), myocardial infarction (5.8%), and others. The gross mortality rate of dialysis patients was increased in cases of less than 4 hours of the average length of each dialysis session, less than 4% and more than 9% of the average weight loss during each dialysis session, less than 1.0 of Kt/V, and less than 0.9 and more than 1.7 g/kg/d of protein catabolic rate. Overall 5-year patient and graft survival rates of kidney transplant patients since 1964 were 82.7% and 60.3%: 84.4% and 65.0% in living donor cases, and 77.4% and 46.2% in cadaver donor case, respectively. Those since 1983 were 90.1% and 68.2%: 91.3% and 72.6% in living donor cases, and 87.8% and 59.3%, respectively. Graft survival rates were superior in cases treated with combined steroid, cyclosporine and azathioprine or mizoribine, to those treated with other immunosuppressive regimens, and they decreased as the number of HLA-A, -B and -DR increased.

Technology and clinical application of large-bore and implantable catheters.

The access of choice for patients receiving regular dialysis therapy remains the surgically created arteriovenous fistula. In a number of such patients as well as those requiring treatment for acute renal failure, plasmapheresis or hemoperfusion alternative techniques of access are used. Of the techniques used subclavian and femoral catheterization are preferred for short-term vascular access while in patients requiring long term vascular access the use of a surgically inserted central venous line is favoured. The technology performance and clinical aspects of the use of large bore and implantable catheters are reviewed.

Oxalate Balance Studies in Patients on Hemodialysis for Type I Primary Hyperoxaluria

Primary hyperoxaluria type I (PH1) always leads to end-stage renal failure (ESRF) due to deposition of calcium oxalate in the kidney. Regular dialysis therapy (RDT) can not overcome the excess production of oxalate, hence, systemic oxalate deposition occurs. The extent of tissue deposition and the rate at which oxalate accumulates influence the quality of life and survival of the patients. Therefore, an estimate of the oxalate balance needs to be made for patients on RDT. In this study, we suggest a simple model by which some of the main parameters of oxalate turnover can be assessed without using radioactive materials. Levels of oxalate, glycolate, and urea, and degrees of calcium oxalate saturation, were assessed on plasma ultrafiltrates from two patients with PH1, sampled before, at the end of a dialysis session, and over the entire interdialytic interval. In patients with PH1, oxalate increased linearly during the early phases and then the curve flattened at a concentration corresponding to approximately threefold saturation. The initial phase of the relationship was used to estimate generation rate of oxalate. The delayed phase was ascribed to the deposition of newly generated oxalate out of its miscible pool. Conversely, the relationship for glycolate and urea remained linear. This was also different from the values obtained in four patients with oxalosis-unrelated ESRF, whose oxalate levels increased linearly over the entire interdialytic interval. In the two patients with PH1, the overall oxalate generation was assessed at 4 to 7 mmol/d. The difference between generation and dialysis removal indicated that tissue deposition was greater than 50 δmol/kg body weight/d. Pyridoxine therapy produced some improvement in only one of these patients. On the contrary, all of the patients with oxalosis-unrelated ESRF maintained oxalate balance with the current dialysis schedules. We suggest that this simple model may represent a valuable and reproducible means to routinely perform oxalate balance studies on patients on RDT for PH1.

Hyaluronic Acid in End-Stage Renal Failure Treated by Haemodialysis: Clinical Correlates and Implications

Serum hyaluronic acid was measured in 176 adults and 15 children receiving regular dialysis therapy. Hyaluronic acid was elevated to greater than 80 micrograms/l in more than 90%, with median value 182 micrograms/l (range 39-898 micrograms/l). Concentrations did not correlate with serum creatinine, but showed a significant correlation with duration of dialysis and serum beta 2-microglobulin. Values greater than 400 micrograms/l were frequent in patients whose clinical condition deteriorated, but in others, hyaluronic acid remained stable over 4-15 months. Serum hyaluronic acid is mainly in a high-molecular-weight form, which in the presence of normal hepatic function suggests that there is a metabolic disorder involving connective tissue and/or vascular endothelium that increases with progressive loss of renal function. Hyaluronic acid may also be a biochemical marker of patients whose condition deteriorates despite renal replacement therapy.

140 VARIATION OF ERYTHROPOIETIN LEVELS IN CHILDREN WITH CHRONIC RENAL FAILUREDEFECT OF DIRECT HEMATOLOGIC COMPENSATION IN RENALANEMIA

Erythropoietin (EPO), the primary humoral regulator of erythropoiesis, an indicator of direct hematologic compensation in anemia, increases with decreasing hemoglobin levels. Material and Method: To evaluate deficient EPO production or the lack of a regulatory feedback mechanism between EPO and hemoglobin (Hb), we obtained EPO data with the IBL-erythropoietin ELISA and hematologic parameters in 144 children (aged 1-19 yrs) with different anemias. Of these anemic (Hb<12 g/dl) patients 39 were recieving conservative treatment (I). 31 on regular dialysis therapy (II), 34 after transplantation (III); variation of EPO concentration in children with these various stages of chronic renal failure (CRF) were compared to 40 controls with nonrenal anemia(IV)and healthy controls (V). Results (figure): a relative EPO deficiency could be detected in I and less after renal transplantation, an absolute deficiency was found on regular dialysis. An inverse linear correlation between EPO levels and hemoglobin in IV occured, however in II the rise of EPO was insufficient compared to IV. In our study we could demonstrate successfully a feedback mechanism between EPO and oxygen supply (low hemoglobin). Conclusion: The interrelationships between EPO and Hb in anemicchildren on regular dialysis indicates an EPO deficiency and lack of a regulatory feedback mechanism due to CRF, possibly an inhibition of erythropoiesis by uremic toxins. We emphasize renal anemia could be correct successfully with small side effects only by substituion of recombinant human erythropoietin.