Comparing different methods of assessing body composition in end-stage renal failure.

BACKGROUND: Accurate measurement of nutritional status in patients with end-stage renal disease is important because of its clear association with prognosis. Total body water (TBW) has additionally been recently recognized as an independent prognostic value because of its relationship with hypertension and cardiac morbidity. The current study was designed to assess the utility of surrogate markers of nutritional state and TBW in patients with end-stage renal disease. METHODS: Fifty-four patients with renal disease were studied. TBW obtained using the deuterium dilution technique was compared with estimates derived from anthropometric measures of TBW, including 58% body weight, Watson equations, and bioelectrical impedance analysis (BIA). Anthropometrically derived fat-free mass (FFM) was compared with BIA-derived estimates. Total body nitrogen (TBN) measurements were correlated with TBW estimates and BIA-derived resistance. RESULTS: TBW was significantly underestimated by the Watson equation (mean difference, -1.751 L, P = 0.01) and the 58% body weight approximation significantly overestimated it (mean difference, 1.792 L, P = 0.04). The Kushner BIA estimation of TBW did not significantly differ from that of the gold standard determined from D2O dilution (mean difference, -1.221 L, P = 0.12) and was also the method that showed the best agreement with the D2O estimate. However, the limits of agreement were large. Accurate prediction equations for FFM (FFM = -21.768 + 0.001 x ht2 + 6630.669 x 1/R + 0.312 x wt, R2 = 0.95) and TBN (TBN = -668.324 - 3.963 x age + 10.133 x wt + 0. 045 x ht2 + 32141.457 x 1/R, R2 = 0.91) were derived from BIA obtained resistance. CONCLUSIONS: The estimation of TBW varies significantly depending on the method of calculation. BIA is the most accurate surrogate marker for the measurement of both TBW and other parameters of body composition.

Evaluation of the loin pain/hematuria syndrome treated by renal autotransplantation or radical renal neurectomy.

Some patients with the loin pain/hematuria syndrome suffer incapacitating flank pain. No effective therapy has been reported. Uncertainty persists concerning the authenticity of the pain and the role of surgery in treatment. Forty-six patients with loin pain/hematuria syndrome and intractable pain were evaluated following treatment either by renal autotransplantation (30 patients, 10 bilaterally) or by renal denervation (20 patients, four bilaterally) over a 13-year period. All patients had concomitant renal nerve excision and ligation and capsulotomy. There were 37 (80%) women and nine men aged 18 to 61 years (mean age, 33 years). Excretion urography and angiography were normal in all patients. Nineteen of 25 (76%) patients in whom renal autotransplantation was successfully accomplished and who completed a follow-up questionnaire were free of pain, including eight of 10 with bilateral procedures. The follow-up periods ranged from 1 to 13 years (mean, 8.4 years). Six patients have been free of pain for 10 to 13 years. Of 18 patients treated with renal neurectomy who were available for follow-up examination, 12 (67%) developed recurrent renal pain, including four who had pain relief on the other side following previous renal autotransplantation. The follow-up period for these patients ranged from 6 to 9.9 years (mean, 8.0 years). Three of four patients with recurrent renal pain following neurectomy were treated successfully by renal autotransplantation. The loin pain/hematuria syndrome is a rare cause of incapacitation, predominantly of relatively young females. The pain of the syndrome is organic. Renal autotransplantation achieves pain relief in three quarters of patients, but the procedure is often (30%) required bilaterally and has significant complications. Renal neurectomy is followed by an excessive incidence of recurrent renal pain.

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.

Glomerulonephritis secondary to Barmah Forest virus infection.

Clinical infection with Barmah Forest virus (BFV) is becoming increasingly recognised with serological testing. We report the first case of glomerulonephritis after BFV infection. The patient required diuretic and antihypertensive therapy, but made an almost complete recovery. BFV infection should be considered in the differential diagnosis of glomerulonephritis.

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.

IgA nephropathy: analysis of the natural history, important factors in the progression of renal disease, and a review of the literature.

To clarify the natural history of IgA nephropathy and to determine important factors in the progressive loss of renal function in affected patients, 121 patients with IgA nephropathy were followed for a median of 92 months. The cumulative probability of not progressing to end-stage renal failure (that is, of renal survival) was 0.87 at 15 years after the onset of 1st symptoms and 0.86 at 10 years after presentation and biopsy. Eight percent of patients progressed to end-stage renal failure, and 12% had a greater than 20% decline in renal function. A complete remission of disease activity was seen in 12% of patients, and the remaining 68% maintained stable renal function. When the final serum creatinine was expressed as a percentage of the initial serum creatinine for each patient and compared with all other variables, a number of factors were found to affect renal outcome. Of the presenting features, increased age, family history of nephritis, longer duration of symptoms, and presence of either nephrotic-range proteinuria or hypertension were all associated, by univariate analysis, with an adverse outcome, while a history of recurrent macroscopic hematuria and infection-associated exacerbations of disease activity were associated with a favorable outcome. Multivariate analysis showed that nephrotic-range proteinuria had an independent adverse effect. Of the initial laboratory findings, by univariate analysis, the number of hyaline casts, the degree of impairment of renal function, the degree of proteinuria, raised beta globulins on serum protein electrophoresis, and serum C4 concentrations were all associated with an adverse outcome, while the severity of initial hematuria and pyuria were associated with a favorable outcome. Renal biopsy findings associated with an adverse outcome by univariate analysis include, on light microscopy, the percentage of glomeruli with global sclerosis or segmental sclerosis or adhesions, the degrees of tubular atrophy or interstitial fibrosis, interstitial inflammation and blood-vessel thickening, and, on immunofluorescence, the intensity of IgA deposition. Multivariate analysis showed independent adverse effects on renal outcome of global glomerulosclerosis, segmental glomerulosclerosis or adhesions, and a combined mesangial and capillary wall deposition of IgM. Features at final assessment or during follow-up associated with an adverse outcome include, by univariate analysis, the number of hyaline casts, the degree of impairment of renal function, the degree of proteinuria, reduced serum IgG and IGM concentrations, reduced final IgA expressed as a percentage of the initial IgA concentration, transient decreases of creatinine clearance during follow-up of > 10% or > 20%, and persistence or development of hypertension.(ABSTRACT TRUNCATED AT 400 WORDS)

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)

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.

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.

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.