Dimitrios G. Oreopoulos

Continuous Ambulatory Peritoneal Dialysis in Diabetics with End-Stage Renal Disease

Twenty diabetics with end-stage renal disease who had never previously received dialysis treatment were treated with continuous ambulatory peritoneal dialysis for periods of two to 36 months (average, 14.5). Intraperitoneal administration of insulin achieved good control of blood sugar. Even though creatinine clearance decreased significantly (P = 0.001), control of blood urea nitrogen and serum creatinine was adequate. Hemoglobin and serum albumin levels increased significantly (P = 0.005 and 0.04, respectively). Similarly, there was a significant increase in serum triglycerides and alkaline phosphatase (P = 0.02 and 0.05). Blood pressure became normal without medications in all but one of the patients. Retinopathy, neuropathy, and osteodystrophy remained unchanged. Peritonitis developed once in every 20.6 patient-months--a rate similar to that observed in nondiabetics. The calculated survival rate was 93 per cent at one year; the calculated rate of continuation on ambulatory peritoneal dialysis was 87 per cent. We conclude that continuous ambulatory dialysis with intraperitoneal administration of insulin is a good alternative treatment for diabetics with end-stage renal disease.

Aging and Physiological Changes of the Kidneys Including Changes in Glomerular Filtration Rate

In addition to the structural changes in the kidney associated with aging, physiological changes in renal function are also found in older adults, such as decreased glomerular filtration rate, vascular dysautonomia, altered tubular handling of creatinine, reduction in sodium reabsorption and potassium secretion, and diminished renal reserve. These alterations make aged individuals susceptible to the development of clinical conditions in response to usual stimuli that would otherwise be compensated for in younger individuals, including acute kidney injury, volume depletion and overload, disorders of serum sodium and potassium concentration, and toxic reactions to water-soluble drugs excreted by the kidneys. Additionally, the preservation with aging of a normal urinalysis, normal serum urea and creatinine values, erythropoietin synthesis, and normal phosphorus, calcium and magnesium tubular handling distinguishes decreased GFR due to normal aging from that due to chronic kidney disease.

Arterial calcifications in severe chronic renal disease and their relationship to dialysis treatment, renal transplant, and parathyroidectomy.

The incidence, distribution, and progression of arterial calcification in severe chronic renal disease were studied from 364 skeletal survey examinations in 152 patients (ages 15-60). The incidence increased from 30% in the 15-30 age group to 50% in the 40-50 group. The earliest and commonest site of calcification was the ankles, followed in frequency by the abdominal aorta, feet, pelvis, and hands and wrists. Progression occurred in 36% of the nondialyzed, 19% of the peritoneally dialyzed, 13% of the post-transplant, and 8% of the hemodialyzed patients.

Improved Radiological Diagnosis of Azotemic Osteodystrophy

Radiological and histological (iliac crest biopsy) studies were performed concurrently in 16 nondialyzed and 16 hetnodialyzed patients with severe chronic renal disease. Radiological examination included skeletal survey, magnified viewing (8×) of fine-grained radiographs of the hand, and densitometric measurement of bone mineral mass and density in the radius. On histological examination, the incidence of osteitis fibrosa was 82% and osteomalacia 84%, while radiological evidence of bone loss was found in 73% of the examinations. The commonest radiological abnormality was subperiosteal resorption of the phalanges (50%), followed by decreased bone mineral density (47%) and mass (32%).

Renal Replacement Therapies in the Elderly: Part 1. Hemodialysis and Chronic Peritoneal Dialysis

Recent demographic data from the United States and Europe demonstrate that the dialysis population is growing progressively older. In the United States the median age at onset of end-stage renal disease (ESRD) had reached 61 years in 1990, and the fraction of ESRD patients older than 65 years will approach 60% by the year 2000. The primary treatment of geriatric ESRD is center hemodialysis (82% of elderly patients). Chronic peritoneal dialysis in this age group is limited in the United States to less than 10%. Only 2.7% of elderly patients have a functioning transplant. Despite their complex medical and psychosocial conditions, survival and rehabilitation are acceptable in the elderly dialysis patient and these patients tend to be more complaint. Five-year dialysis patient survival rates in the United States are 19% and 10%, respectively, for the 65 to 74 and 75 to 84 age groups compared with 32% and 19%, respectively, for the same age groups in Europe. Five-year survival, particularly in the elderly, is even higher in Japan. Several factors favor the delivery of low doses of hemodialysis in the elderly and discontinuing dialysis is more common in the elderly. Continuous ambulatory peritoneal dialysis is a satisfactory alternative treatment modality for geriatric ESRD. Most studies confirm that survival of elderly patients on continuous ambulatory peritoneal dialysis and hemodialysis is similar. The 1991 United States Renal Data System report showing higher mortality among diabetic continuous ambulatory peritoneal dialysis patients than among hemodialysis patients may reflect selection of such patients, who may have more co-morbid conditions. In special cases, continuous cyclic peritoneal dialysis can be an alternative treatment for elderly ESRD patients.

Reappraisal of Protein Losses in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

Dialysate effluent protein content was measured in 22 patients undergoing continuous ambulatory peritoneal dialysis (9 with and 13 without previous peritonitis). The average amount of protein in those patients without peritonitis was 1.3 g/2 liters exchanged over a 6-hour period, while that of patients with previous peritonitis was 2.6 g/2 liters exchanged over the same period. 71% of protein found in the dialysate of 2 patients was albumin. Despite the difference in the amount of protein lost between those without and those with peritonitis, there was no significant difference in their mean serum albumin levels (3.2 and 3.4 g%, respectively) which were only slightly below the normal range. The previously reported high protein losses in patients undergoing CAPD are probably the result of frequent episodes of peritonitis and a higher number (five) of daily exchanges.

Bone mineral density and its correlation with clinical and laboratory factors in chronic peritoneal dialysis patients

The aim of this study was to assess the clinical and laboratory correlations of bone mineral density (BMD) measurements among a large population of patients on chronic peritoneal dialysis (PD). This cross-sectional, multicenter study was carried out in 292 PD patients with a mean age of 56 ± 16 years and mean duration of PD 3.1 ± 2.1 years. Altogether, 129 female and 163 male patients from 24 centers in Canada, Greece, and Turkey were included in the study. BMD findings, obtained by dual-energy X-ray absorptiometry (DEXA) and some other major clinical and laboratory indices of bone mineral deposition as well as uremic osteodystrophy were investigated. In the 292 patients included in the study, the mean lumbar spine T-score was −1.04 ± 1.68, the lumbar spine Z-score was −0.31 ± 1.68, the femoral neck T-score was −1.38 ± 1.39, and the femoral neck Z score was −0.66 ± 1.23. According to the WHO criteria based on lumbar spine T-scores, 19.2% of 292 patients were osteoporotic, 36.3% had osteopenia, and 44.4% had lumbar spine T-scores within the normal range. In the femoral neck area, the prevalence of osteoporosis was slightly higher (26%). The prevalence of osteoporosis was 23.3% in female patients and 16.6% in male patients with no statistically significant difference between the sexes. Agreements of lumbar spine and femoral neck T-scores for the diagnosis of osteoporosis were 66.7% and 27.3% and 83.3% for osteopenia and normal BMD values, respectively. Among the clinical and laboratory parameters we investigated in this study, the body mass index (BMI) (P < 0.001), daily urine output, and urea clearance time × dialysis time/volume (Kt/V) (P < 0.05) were statistically significantly positive and Ca × PO4 had a negative correlation (P < 0.05) with the lumbar spine T scores. Femoral neck T scores were also positively correlated with BMI, daily urine output, and KT/V; and they were negatively correlated with age. Intact parathyroid hormone levels did not correlate with any of the BMD parameters. Femoral neck Z scores were correlated with BMI (P < 0.001), and ionized calcium (P < 0.05) positively and negatively with age, total alkaline phosphatase (P < 0.05), and Ca × P (P < 0.01). The overall prevalence of fractures since the initiation of PD was 10%. Our results indicated that, considering their DEXA-based BMD values, 55% of chronic PD patients have subnormal bone mass—19% within the osteoporotic range and 36% within the osteopenic range. Our findings also indicate that low body weight is the most important risk factor for osteoporosis in chronic PD patients. An insufficient dialysis dose (expressed as KT/V) and older age may also be important risk factors for osteoporosis of PD patients.

Use of ACE inhibitors or angiotensin receptor blockers and survival in patients on peritoneal dialysis

BACKGROUND Angiotensin-converting enzyme (ACE) inhibitors have been shown to improve outcome in patients with renal failure not on dialysis therapy and patients on haemodialysis (HD). However, their effect on survival has not been studied in peritoneal dialysis (PD) patients. The present study examined the association between therapy with ACE inhibitor/ARB and mortality in patients undergoing chronic PD. METHODS All patients who commenced PD between 1 January 2000 and 31 December 2005 at the University Health Network were included. Patients were grouped according to whether they had been treated with ACE inhibitor/ARB. They were followed up from the date of PD initiation until death, cessation of PD, transfer to other centres or to the end of the study (31 December 2006). RESULTS A total of 306 patients were included in the study. One hundred and sixty-five were treated with ACE inhibitors/ARB (treated group) and 141 were not (untreated group). The treated group patients were younger (56.9 +/- 16.6 versus 62.3 +/- 17.8 years, P < 0.01) and more likely to have a history of hypertension than the untreated group. At the initiation of PD, systolic and diastolic blood pressures were higher in the treated than the untreated group (138.8 +/- 21.8 versus 128.6 +/- 22.4 mmHg, P < 0.001; 79.8 +/- 14.1 versus 74.5 +/- 12.5 mmHg, P = 0.001) and remained significantly higher during the follow-up (133.5 +/- 16.4 versus 125.1 +/- 16.7 mmHg; 77.3 +/- 9.8 versus 73.2 +/- 9.7 mmHg, both P < 0.001). The treated group had a significantly longer survival compared to the untreated group (log rank 19.191, P < 0.001). After adjusting for age, blood pressure and other demographic and clinical parameters, multivariable Cox proportional hazards modelling showed that the use of ACE inhibitor/ARB was associated with 62% reduced risk for death (HR 0.382, 95% CI 0.232-0.631, P < 0.001). CONCLUSION In this retrospective analysis, ACE inhibitor/ ARB therapy was associated with a dramatically reduced mortality in patients on peritoneal dialysis independent of blood pressure and other clinical and demographic variables.

Geriatric Nephrology is Coming of Age

Contrary to predictions in the Gottschalk report to the US Congress in 1960 that the projected incidence of new end-stage renal disease patients will be on the order of 20 new patients per year, this number has been exceeded tenfold, mainly because no one anticipated the increase of elderly patients

• Periosteal New Bone Formation (Periosteal Neostosis) in Renal Osteodystrophy Relationship to Osteosclerosis, Osteitis Fibrosa, and Osteoid Excess!

Radiologic skeletal surveys in 117 patients with severe chronic renal disease revealed periosteal neostosis (periosteal new bone formation) in 10 patients (8.5%). Periosteal neostosis occurred in varied locations and was always accompanied by subperiosteal resorption in finger bones, and in 9 of 10 cases by osteosclerotic changes in the central skeleton. The most common finding in iliac crest biopsies, obtained from 8 patients, was osteoid excess (osteomalacia). The combination of periosteal neostosis, subperiosteal resorption, osteosclerosis, and osteoid excess may be a manifestation of secondary hyperparathyroidism, with high bone turnover and sustained ability to produce mineralized bone.