Lloyd S. Ibels

Continuous ambulatory peritoneal dialysis. Eight years of experience at a single center.

One hundred and thirty-four patients using continuous ambulatory peritoneal dialysis (CAPD) for a mean time of 23.1 +/- 18.3 months (range, 1-76.6) from a single center are reviewed with respect to biochemistry, hematology, parameters of dialysis efficiency, nutrition, and the nature and frequency of complications. Cumulative patient survival was 90%, 86% and 75% at 1, 2 and 3 years, and survival of patients using this technique was 75%, 62% and 40% at corresponding time intervals with no difference demonstrated in diabetic patients or in those older than 50 years. Biochemical and hematologic parameters were well maintained with peritoneal creatinine clearance increasing and peritoneal protein loss remaining stable with ongoing CAPD. Loss of ultrafiltration, however, accounted for 17.7% of permanent transfers to alternative therapy. Low serum albumin and elevated serum triglyceride concentrations correlated with mortality, whereas low serum albumin, low cholesterol, and high phosphate levels correlated with morbidity as assessed by frequency of hospital admissions. Dietary protein intake assessed by urea generation rate was significantly lower than that estimated from a 24-hour dietary recall (0.82 vs. 1.02 g/kg/day, p less than 0.01) and with the exception of body mass index and serum albumin, anthropometric and visceral protein measurements showed few correlations with nutritional adequacy. Bacterial peritonitis remained the major complication, although fungal infections made a significant contribution to morbidity and mortality. Overall, CAPD is confirmed to be a satisfactory form of dialysis for all forms of end-stage renal failure and an integral part of any renal replacement program. However, nutritional adequacy and lowering of complication rates require further investigation.

Total-Body Nitrogen by Neutron Activation in Maintenance Dialysis

The nutritional status of 35 patients on continuous ambulatory peritoneal dialysis (CAPD) was assessed by the traditional methods of dietary history and anthropometric measurements, and was compared with simultaneous measurements of dietary protein intake (DPI) calculated from urea generation rate and total-body nitrogen (TBN) assessment by prompt neutron activation analysis (PNAA). DPI as determined by dietary recall was significantly higher than calculated DPI (1.04 +/- 0.42 v 0.84 +/- 0.28 g/kg/d; P less than 0.001). Anthropometric measurements did not differ significantly from the predicted normal values for sex, height, and age. However, PNAA measurements of TBN demonstrated significant nitrogen depletion, being 88.2% of normal for males (P less than 0.001) and 87.5% of normal for females (P less than 0.002); TBN correlated significantly with DPI calculated from urea generation rate (P less than 0.05). Assessment of these 35 patients 17.5 +/- 4.4 months later, demonstrated that patients who died or suffered serious morbidity requiring transfer from CAPD (n = 10) had significantly lower TBN than those who remained on CAPD or underwent successful renal transplantation (n = 25): 80.0% v 93.2% of normal (P less than 0.01). No difference in anthropometric measurements was observed between the two groups of patients. Eleven patients on maintenance home or satellite hemodialysis underwent identical dietary, anthropometric, and TBN assessments and results were similar to those obtained in the CAPD population, although no correlation with calculated DPI and TBN was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Peritoneal Morphology on Maintenance Dialysis

Thirty-eight peritoneal biopsies from 37 patients with normal renal function or with end-stage renal failure without replacement therapy or utilizing continuous ambulatory peritoneal dialysis (CAPD), haemodialysis (HD) or a functioning transplant were examined histologically. No abnormality in peritoneal membrane morphology was observed in uraemia in the absence of dialysis. Significant abnormalities of peritoneal membrane morphology were observed in association with CAPD, the predominant finding being the development of peritoneal fibrosis which had a deleterious effect on membrane function. Abnormal peritoneal morphology was less commonly observed in patients on maintenance HD and with functioning transplants but may have implications regarding the future use of CAPD in these patients.

Hyperlipidemia in Renal Transplant Recipients: Natural History and Response to Treatment

The lipid profiles of 192 patients with functioning renal transplants and their etiologic associations and response to therapy, in particular simvastatin, were assessed. Hypercholesterolemia was present in 71.3% of patients within 3 years following transplantation. There were independent associations of serum cholesterol with prednisone dosage (p < 0.05), renal function (p < 0.05), and smoking (p < 0.05) in the early posttransplant period (up to 3 months posttransplant). Those patients whose immunosuppression included cyclosporin had lower serum cholesterol levels than those receiving azathioprine and prednisone (p < 0.02). Plasma triglyceride levels reflected a marked interindividual variation, and no independent correlations were observed. The presence of diabetes mellitus, hypertension (or the use of antihypertensive agents), or the form or duration of prior dialysis did not independently influence the lipid profiles. During the study period 22 patients died, 54.5% due to vascular causes. Those who died of vascular causes had higher serum cholesterol levels than those who died of other causes, which reached statistical significance at 3 years posttransplant (7.74 +/- 0.4 versus 5.5 +/- 0.52 mmol/L; p < 0.02). Cholestyramine was introduced in 30 patients, only 2 of whom continued with therapy beyond 3 months. Simvastatin was used in 43 patients, 20 of whom were receiving cyclosporin, resulting in a mean reduction in serum cholesterol of 16.5% (p < 0.001) and in serum triglycerides of 21% (p < 0.05). No clinical or biochemical evidence of muscle, liver, or renal toxicity occurred in 15.4 +/- 0.9 months of follow-up.

Osteosclerotic Myeloma Complicated by Diffuse Arteritis, Vascular Calcification and Extensive Cutaneous Necrosis

Widespread, progressive skin necrosis developed in a 42-year-old male with a 5-year history of osteosclerotic myeloma. Biopsy of the necrotic lesions demonstrated a leucocytoclastic vasculitis with extensive vascular calcification. Radiological investigations demonstrated widespread arterial calcification. Clinical improvement of the established skin lesions followed the institution of a forced calciuresis and parathyroid hormone suppression by induced hypermagnesaemia and phosphate depletion. No further cutaneous necrosis developed. Subsequent treatment with oral immunosuppressive therapy and the diphosphonate, EHDP, has been associated with a complete 18-month remission. The relationship of this apparently unique pathological process to the osteosclerotic myeloma is discussed, together with the rationale for the therapeutic regime instituted.

Recommendations for the use of icodextrin in peritoneal dialysis patients.

SUMMARY: Icodextrin is a starch‐derived, high molecular weight glucose polymer, which has been shown to promote sustained ultrafiltration equivalent to that achieved with hypertonic (3.86%/4.25%) glucose exchanges during prolonged intraperitoneal dwells (up to 16 h). Patients with impaired ultrafiltration, particularly in the settings of acute peritonitis, high transporter status and diabetes mellitus, appear to derive the greatest benefit from icodextrin with respect to augmentation of dialytic fluid removal, amelioration of symptomatic fluid retention and possible prolongation of technique survival. Glycaemic control is also improved by substituting icodextrin for hypertonic glucose exchanges in diabetic patients. Preliminary in vitro and ex vivo studies suggest that icodextrin demonstrates greater peritoneal membrane biocompatibility than glucose‐based dialysates, but these findings need to be confirmed by long‐term clinical studies. This paper reviews the available clinical evidence pertaining to the safety and efficacy of icodextrin and makes recommendations for its use in peritonal dialysis.

Recognition and Management of IgA Nephropathy

SummaryIgA (immunoglobulin A) nephropathy is the most common form of primary glomerulonephritis worldwide. It generally has a good prognosis, with 15-year rates of kidney survival from the apparent onset of disease usually well in excess of 70%. Progression, when it occurs, is usually a slow, indolent process, and spontaneous remission of disease activity occurs in 7% of patients.It is possible to predict, from the initial presenting features and laboratory findings, renal biopsy and clinical course during follow-up, which patients are likely to have progressive renal disease. Identification of the factors likely to be associated with progression is of importance in helping to establish which patients will benefit from specific therapeutic intervention.For all patients, attention should be directed toward general health issues in an endeavour to reverse factors that are likely to have an adverse impact on renal function. This should include early detection and tight control of hypertension (present in 50% of all patients with IgA nephropathy during the course of their disease), along with utilisation of antihypertensive agents that have specific renoprotective effects, namely ACE inhibitors or calcium antagonists. Such therapy should also be considered in normotensive patients with heavy proteinuria, as a reduction of proteinuria is often achieved by this means.Other aims should include maintenance of desirable bodyweight, correction of hyperlipidaemia, cessation of smoking, participation in an active exercise programme, avoidance of exposure to nephrotoxins and maintenance of a high fluid intake. A low protein/low phosphate diet together with phosphate binder therapy should be commenced early in the course of renal impairment. Corticosteroid and/or cytotoxic drug therapy should be considered in the small percentage of patients with heavy proteinuria or a rapid decline in renal function. Such therapeutic endeavours are likely to delay the onset of renal failure in patients with progressive IgA nephropathy.

Acute Renal Failure due to Focal Necrotizing Glomerulonephritis in a Patient with Non-Hodgkin’s Lymphoma

Renal disease in association with lymphoma is more prevalent than generally recognized. Glomerulonephritis may occur as a paraneoplastic phenomenon. We report a patient who presented with acute renal

Afferent Arteriolar C3 Disease—A Distinct Pathological Entity

Afferent arteriolar C3 deposition was the sole histological abnormality in 79 and the major histological abnormality in an additional 39 of 959 renal biopsies performed over a 10-year period. Of these 79 patients, hematuria was the presenting symptom in 90%, with coincident loin pain in 49%. Urine microscopy of asymptomatic first-degree relatives revealed hematuria in 44% of children and siblings and 54% of parents, suggesting autosomal dominant inheritance. Arteriolar C3 deposition was confirmed by biopsy in four asymptomatic relatives with hematuria. Generalized thinning of glomerular basement membrane (less than 200 nm) was observed in five patients and focal thinning was observed in six patients with coincident afferent arteriolar C3 deposition. Seven other patients were identified as having generalized thinning of glomerular basement membrane in the absence of afferent arteriolar C3 deposition. Renal function was stable and similar in all groups studied over 37.9 +/- 23.7 months. No difference in clinical presentation or urinary abnormalities was evident between the groups. No arteriolar C3 deposition was evident in eight autopsy specimens with no known renal disease. It was concluded that afferent arteriolar C3 deposition is a marker of a distinct hereditary pathological entity, with differentiation from thin basement membrane disease not possible on clinical grounds. The medium- and long-term prognoses with respect to renal function are excellent.

Comparison of simultaneous renal clearances of true endogenous creatinine and subcutaneously administered lothalamate in man

125I-iothalamate and true endogenous creatinine clearances, measured over two short collections periods of 1 and 2 h, were compared simultaneously in 70 patients with a variety of renal diseases and a wide range of renal function. Reproducibility of the iothalamate clearance was 18.5% and that of the creatinine clearance 12.2%. The slope of the regression was not significantly different from 1 (95% confidence interval, CI, 0.964-1.155) for the whole group, nor in any subgroup chosen. The intercept at 12.6 ml/min (CI = 5.0-20.2) indicates that there is some creatinine secretion, but this was constant at all levels of GFR. It is concluded that although the clearance of true creatinine obtained during short collection periods consistently overestimates GFR by a constant proportion, it is a reproducible and accurate measure of GFR suitable for use in the clinical setting.