John F. Mahony

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)

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.

Renal Function in Unilateral Nephrectomy Subjects

Renal function in 32 subjects who had undergone unilateral nephrectomy (17 transplant donors and 15 subjects with unilateral renal disease) was compared with that of 22 normal subjects. The age-adjusted glomerular filtration rate was lower in transplant donors (79 +/- 15% of normal) than in those whose nephrectomy was performed for unilateral renal disease (90 +/- 12% of normal). The donors were also significantly older at nephrectomy (48 +/- 10 years versus 24 +/- 13 years, p less than 0.001). This finding may represent less capacity for compensatory hypertrophy. Proximal tubular and medullary function as assessed by 15-minute phenolsulfonphthalein excretion, maximum urinary concentration in response to water deprivation plus exogenous vasopressin, and urinary acidification in response to an oral acid load were all within normal limits for glomerular filtration rate. Overall renal function was well preserved after nephrectomy. A small number of patients did have increased cast excretion, which may signify the presence of mild renal disease in these subjects.

Factors influencing glomerular filtration rate in renal transplantation after cyclosporine withdrawal using sirolimus-based therapy: a multivariate analysis of results at five years.

Abstract:  Changes in calculated glomerular filtration rate (GFR) from baseline to five yr were analyzed in relation to risk factors among renal transplant recipients. At three months after transplantation (baseline), 430 eligible patients receiving sirolimus (SRL), cyclosporine (CsA), and steroids (ST) were randomly assigned (1:1) to continue SRL–CsA–ST or have CsA withdrawn and SRL trough levels increased (SRL–ST group). For each risk factor, changes from baseline were compared within each treatment using a t‐test and between treatments using ANCOVA. Univariate then multivariate robust linear regression analyses were also performed. In the SRL–ST group, changes from baseline were not significantly different for any risk factor. With the exception of cold ischemia time >24 h, GFR values declined significantly for all risk factors in SRL–CsA–ST patients. For all risk factors, except second transplant or cold ischemia time >24 h, renal function was significantly different between groups. By order of significance in the multivariate analysis, treatment (p < 0.001), donor age (p < 0.001), proteinuria (p < 0.001), and biopsy‐confirmed rejection (p = 0.010) were significant predictors of GFR change from baseline. In conclusion, patients with risk factors for reduced renal function benefit from SRL maintenance therapy without CsA vs. those remaining on CsA.

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.

Problems associated with pregnancy in renal allograft recipients.

Of 18 pregnancies in 11 renal transplant recipients, three were terminated and in the remaining 15 (in 8 women) there were 10 live births (including one set of twins), five intrauterine deaths, and one spontaneous abortion. Graft function deteriorated in six women, from obstruction of the transplanted ureter in two, recurrent glomerulonephritis in two, rejection in one, and pelvi-ureteric junction obstruction in one. Hypertension worsened or developed in all but one of the pregnancies and proteinuria appeared in eight. Of the 10 live births only one reached 38 weeks gestation (mean 35 weeks) and four neonates were small for gestational age. One infant died early from intraventricular hemorrhage and hyaline membrane disease, one fetus had hydrocephalus, and the others were normal. Factors associated with a poor fetal outcome were deterioration in graft function during pregnancy, pre-existing hypertension, or the development of hypertension before the third trimesterOf 18 pregnancies in 11 renal transplant recipients, three were terminated and in the remaining 15 (in 8 women) there were 10 live births (including one set of twins), five intrauterine deaths, and one spontaneous abortion. Graft function deteriorated in six women, from obstruction of the transplanted ureter in two, recurrent glomerulonephritis in two, rejection in one, and pelvi-ureteric junction obstruction in one. Hypertension worsened or developed in all but one of the pregnancies and proteinuria appeared in eight. Of the 10 live births only one reached 38 weeks gestation (mean 35 weeks) and four neonates were small for gestational age. One infant died early from intraventricular hemorrhage and hyaline membrane disease, one fetus had hydrocephalus, and the others were normal. Factors associated with a poor fetal outcome were deterioration in graft function during pregnancy, pre-existing hypertension, or the development of hypertension before the third trimester.

Primary focal sclerosing glomerulonephritis: A clinicopathological analysis

The clinical and laboratory features, renal biopsy findings, and outcome of 68 patients with primary focal sclerosing glomerulonephritis were studied. The cumulative probability of not progressing to end‐stage renal failure (ESRF) was 0.92 at 5 years and 0.73 at 10 years after presentation, and was significantly worse in patients with hypertension or severe renal impairment (serum creatinine >0.24 mmol/L) at presentation. Proteinuria of up to 1gm/day was associated with an excellent prognosis, whereas proteinuria of 1–3 gm/day and >3 gm/day had similar and poorer survivals. An adverse outcome was associated with, at presentation, age less than 30 years, hypertension, a family history of glomerulonephritis, cigarette smoking, impaired renal function, and heavy proteinuria. Renal biopsy findings which correlated with progressive renal failure included a higher percentage of glomeruli with global or segmental sclerosis, and the degrees of tubular atrophy, interstitial fibrosis, interstitial inflammation and arterial thickening. During follow‐up the degrees of renal impairment and proteinuria, persistence or development of hypertension, transient decreases of renal function of >10%, and the total number of red cells and casts on centrifuged urine microscopy were all predictive of progressive renal disease. Multivariate analysis demonstrated that the indices with adverse effects on outcome included all of the above except tubulointerstitial and vascular changes on renal biopsy. It is concluded that the prognosis may be better than has been suggested in the literature. It is possible to predict which patients are likely to have an adverse outcome, and this should assist with therapeutic decisions likely to retard progression of disease.

Pathological Hip Fracture Due to Amyloidosis Occurring after Successful Renal Transplantation. A Case Report

A fifty-six year old man who had been on haemodialysis for a total of seventeen years sustained a pathological fracture of the femoral neck six months after successful renal transplantation. Multiple cystic lesions were present in both hips and a bone specimen from the fracture site confirmed amyloid deposition on immunohistochemical staining. Renal transplantation may prevent further deposition of amyloid but the long-term complications of dialysis-related amyloidosis may still occur.A fifty-six year old man who had been on haemodialysis for a total of seventeen years sustained a pathological fracture of the femoral neck six months after successful renal transplantation. Multiple cystic lesions were present in both hips and a bone specimen from the fracture site confirmed amyloid deposition on immunohistochemical staining. Renal transplantation may prevent further deposition of amyloid but the long-term complications of dialysis-related amyloidosis may still occur.

Lipoprotein (a): Relationship to vascular disease in dialysis and renal transplantion

Summary: Serum lipids and lipoprotein (a) concentrations were measured in 91 renal transplant and 60 dialysis patients and correlations sought with clinically evident vascular disease. Serum lipoprotein (a) concentrations were greater than 300 mg/L in 24% of the renal transplant recipients and 40% of the dialysis patients. In the renal transplant recipients, low high density lipoprotein (HDL) cholesterol (P<0.05) and high total cholesterol to HDL cholesterol ratio (P<0.01) were more strongly associated with the presence of vascular disease than was elevated lipoprotein (a). In the dialysis patients, a low serum albumin (P<0.05) and low serum creatinine (P<0.001), indicative of a poor nutritional state, were associated with the presence of vascular disease. A high total serum cholesterol to HDL cholesterol ratio (P<0.05) was indicative of ischaemic heart disease, and high total serum cholesterol (P<0.01) and low density lipoprotein (LDL) cholesterol (P<0.01) of cerebrovascular disease. In the subpopulation on CAPD, elevated lipoprotein (a) levels were associated with cerebrovascular disease (P<0.01). the present study demonstrates that an elevation in serum lipoprotein (a) concentration is not as strongly associated with the presence of vascular disease in patients with end‐stage renal failure as are the total serum cholesterol, HDL and LDL cholesterol and the ratio of total cholesterol to HDL cholesterol.