Recognition and management of IgA nephropathy.

IgA (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.

Protein intake in renal disease.

The dietary protein intake (DPI) of 766 patients (aged 7 to 88 yr) was determined from 24-h urinary urea and protein excretion by urea kinetic modelling. Five hundred sixty-five patients had a normal serum creatinine concentration, and of these 565, 385 patients had no dietary modification advised and 180 were advised to follow a low-protein diet. The remaining 201 patients had an increased serum creatinine concentration; 148 of these 201 patients had been advised to restrict their DPI. Patients with a normal serum creatinine concentration who had no dietary restriction had a significantly higher DPI than those advised to restrict their protein intake (1.08 +/- 0.01 versus 0.96 +/- 0.02 g/kg per day (mean +/- SEM), P < 0.01). Similarly, patients with abnormal renal function who were advised to follow a low-protein diet had a reduced DPI (0.93 +/- 0.01 versus 0.87 +/- 0.02 g/kg per day; P < 0.05). A lower DPI correlated with level of renal dysfunction, independent of dietary advice (P < 0.0001). In the overall population, DPI correlated with body mass index (BMI; P < 0.0001) and serum albumin (P < 0.0001), and inverse correlations were evident between age (P < 0.0001), blood glucose level (P < 0.01), serum cholesterol level (P < 0.0001), and triglyceride levels (P < 0.0001) independently of renal function. Fifty-two patients were assessed within the 3 months before the commencement of dialysis, and 47 were reassessed within 3 months after the commencement of dialysis. Despite advice regarding an increase in dietary protein after the commencement of dialysis, this increase failed to occur within the 3 months of commencement of dialytic therapy (0.79 +/- 0.04 versus 0.82 +/- 0.03 g/kg per day); P = 0.64). However, 6 to 9 months after the commencement of dialysis, a significant increase in protein intake was evident (1.04 +/- 0.04 g/kg per day; P < 0.005 versus both prior measurements). Hence a low DPI in renal impairment occurs independently of dietary advice, but compliance with such advice is evident because patients advised to consume a low-protein diet had significantly lower protein intake than did patients receiving no dietary advice. Adaptation to a high-protein diet after instigation of dialysis is unsuccessful in the short term, irrespective of whether or not advice is given regarding a low-protein diet before dialysis is initiated. However, 6 to 9 months after the commencement of dialysis, a significant increase in protein intake occurs, which in the hemodialysis population correlates with dialysis delivery.

Dialysis adequacy and nutrition determine prognosis in continuous ambulatory peritoneal dialysis patients.

Peritoneal membrane function was assessed in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) using parameters derived from urea kinetic modeling and the peritoneal equilibration test (PET). Their relationships with other nutritional markers and overall morbidity were determined. Data regarding the patients' nutritional status as determined by total body nitrogen (TBN) measurements, hospital admissions, and infectious complications within the last 12 months were reviewed. Total dialysate clearance (Kt/V) delivered was highly dependent on residual renal function (P < 0.0001). Kt/V derived from peritoneal clearance diminished with increasing age (P < 0.05). A higher delivered total Kt/V was associated with higher normalized protein catabolic rates (P < 0.002), which in turn were associated with improved TBN (P < 0.05). Hospital admissions decreased with improved normalized protein catabolic rates (P < 0.05), and higher serum albumin and total protein levels (P < 0.01 and P < 0.002, respectively). Infectious complications correlated positively with time on dialysis (P < 0.01), and correlated negatively with TBN measurements (P = 0.05). No correlations were found between infectious complications and serum albumin level or peritoneal protein loss. However, the total duration of hospitalization was shortened with higher serum albumin and total protein levels (P < 0.0001 and P < 0.002, respectively). Although Kt/V determinations did not correlate with clearances determined by the PET, the PET-determined creatinine transport rate correlated with TBN (P < 0.05) but not with infectious complications. In conclusion, nutritional parameters correlate with outcome on continuous ambulatory peritoneal dialysis. An integral relationship exists between nutritional status and dialysis delivery, which is best assessed by urea kinetic modeling.

Total body nitrogen as a prognostic marker in maintenance dialysis.

In order to assess long-term nutritional adequacy, 154 patients on maintenance dialysis (78 on hemodialysis (HD), 76 on continuous ambulatory peritoneal dialysis (CAPD)) underwent measurement of total body nitrogen (TBN) with concurrent recording of dietary history, anthropometrics, and serum albumin. Seventy-one patients were reassessed 23.3 +/- 2.2 (5 to 76) months later. In cross-sectional analyses, anthropometric measurements and dietary intake remained stable over time in all patients. However, a significant fall in TBN occurred in the HD population with increasing time on dialysis (P < 0.05). In the prospective analyses, CAPD patients (N = 26) had a significant increase in TBN (P < 0.02). In contrast, longitudinal measurements of TBN in HD patients (N = 36) tended to fall but did not reach significance (P = 0.18). TBN correlated with total caloric intake estimated from the dietary history (P < 0.05), but not with estimated protein intake. During follow-up, 38 patients died. These patients were older (P < 0.05), and in the CAPD population, they had been on dialysis for a longer time (P < 0.05). Those who died had a lower TBN expressed both as grams per kilogram lean body mass (P < 0.005) and as the nitrogen index (P < 0.05). The probability of death within 12 months in the patients with a nitrogen index (ratio of the measured nitrogen to the predicted nitrogen for a sex-, age-, and height-matched control) less than 80% of the predicted normal value was 48%. The relative risk of death in this population was 4.1.(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.

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)

Effect of dialysis on circulating Na,K ATPase inhibitor in uremic patients.

Deproteinized plasma from patients with renal failure had an inhibitory effect on Na,K ATPase activity measured in vitro by a linked-enzyme assay. No inhibitory effect was observed with plasma from normal subjects or from patients undergoing chronic ambulatory peritoneal dialysis. The inhibition of Na,K ATPase whether measured by the linked-enzyme assay or by 86Rb uptake in guinea pig aortic strips was decreased acutely by a single hemodialysis treatment, but was unaffected during a time-control study or ultrafiltration. Changes in Na,K ATPase activity and in Rb uptake were correlated, indicating that the presence of the enzyme inhibitor in uremic plasma was associated with depressed Na pump activity. Change in inhibition of Na,K ATPase activity did not correlate with change in body weight. Dialysis in vitro against a membrane of molecular weight 3,500 cut-off decreased the inhibitory effect of uremic plasma on Na,K ATPase. It was concluded that a dialyzable, low-molecular-weight Na,K ATPase inhibitor circulates in uremia but has no demonstrable role in volume homeostasis.

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.

Immunoglobulin abnormalities in renal transplant recipients.

Five renal transplant recipients were observed to have recurrent infections in association with low serum immunoglobulin levels. They have benefited from parenteral gamma globulin therapy. Following this observation, 110 renal transplant recipients were assessed; 46% had abnormal serum immunoglobulins with 4 patients identified as having monoclonal gammopathies, 8 polyclonal gammopathies, and 39 low levels of 1 or more immunoglobulins. Those with abnormal serum immunoglobulins had been immunosuppressed longer, but maintenance immunosuppression dosage was not different from those with normal immunoglobulins. Respiratory tract infection and skin cancer were more frequent in those with low immunoglobulin levels.

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 trimester.

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.

Loss of ultrafiltration in continuous ambulatory peritoneal dialysis (CAPD).

Fifteen patients on long-term continuous ambulatory peritoneal dialysis (CAPD) were assessed with respect to net ultrafiltration capacity. Eight patients were defined as having good and seven as having poor ultrafiltration on the basis of net ultrafiltrate obtained/mmol glucose infused. Subsequently, dialysate was sampled at times 0, 1, 15, 30, 60, 90, 120, 180, and 240 min. No difference in residual volume was observed between the groups. A significantly greater decrease in dialysate sodium during the initial dialysis period in those patients with good as compared to those with poor ultrafiltration occurred, reflecting a greater transcapillary movement of electrolyte poor ultrafiltrate. In those with good ultrafiltration, glucose transfer was normal in five and rapid in three, suggesting the latter had low rates of lymphatic reabsorption. Five of seven patients with poor ultrafiltration had no fall in dialysate sodium in association with a high rate of glucose transfer, suggesting a low rate of transcapillary water movement and normal to high lymphatic absorption. Two patients with low ultrafiltration had an initial fall in dialysate sodium with a normal glucose transfer and thus net ultrafiltration is low due to elevated lymphatic reabsorption. We thus propose that the relative contribution of transcapillary water movement and lymphatic reabsorption can be determined by assessing net ultrafiltration and dialysate sodium concentration in conjunction with solute transfer.