Bernard Jones

The effect of low glucose degradation product, neutral pH versus standard peritoneal dialysis solutions on peritoneal membrane function: the balANZ trial

Background The balANZ trial recently reported that neutral pH, low glucose degradation product (biocompatible) peritoneal dialysis (PD) solutions significantly delayed anuria and reduced peritonitis rates compared with conventional solutions. This article reports a secondary outcome analysis of the balANZ trial with respect to peritoneal membrane function. Methods Adult, incident PD patients with residual renal function were randomized to receive either biocompatible or conventional (control) PD solutions for 2 years. Peritoneal equilibration tests were performed at 1, 6, 12, 18 and 24 months. Peritoneal small solute clearances and ultra-filtration (UF) were measured at 3, 6, 9, 12, 18 and 24 months. Results Of the 185 patients recruited into the trial, 85 patients in the Balance group and 82 patients in the control group had peritoneal membrane function evaluated. Mean 4-h dialysate:plasma creatinine ratios (D:P Cr 4h) at 1 month were significantly higher in the Balance group compared with controls (0.67 ± 0.10 versus 0.62 ± 0.10, P = 0.002). Over the 2-year study period, mean D:P Cr 4 h measurements remained stable in the Balance group but increased significantly in controls [difference −0.004 per month, 95% confidence interval (95% CI) −0.005 to −0.002, P < 0.001]. Similar results were obtained for dialysate glucose ratios (D/D0 glucose). Peritoneal UF was significantly lower in the Balance group than in controls at 3 and 6 months. Over the 2-year study period, peritoneal UF increased significantly in the Balance group but remained stable in controls (difference 24 mL/day/month, 95% CI 9–39, P = 0.002). No differences in peritoneal small solute clearances, prescribed dialysate fill volumes or peritoneal glucose exposure were observed between the two groups. Conclusions Biocompatible and conventional PD solutions exert differential effects on peritoneal small solute transport rate and UF over time. Adequately powered trials assessing the impact of these differential membrane effects on PD technique and patient survival rates are warranted.

The effects of biocompatible compared with standard peritoneal dialysis solutions on peritonitis microbiology, treatment, and outcomes: The balANZ trial

♦ Background: A multicenter, multi-country randomized controlled trial (the balANZ study) recently reported that peritonitis rates significantly improved with the use of neutral-pH peritoneal dialysis (PD) solutions low in glucose degradation products (“biocompatible”) compared with standard solutions. The present paper reports a secondary outcome analysis of the balANZ trial with respect to peritonitis microbiology, treatment, and outcomes. ♦ Methods: Adult incident PD patients with residual renal function were randomized to receive either biocompatible or conventional (control) PD solutions for 2 years. ♦ Results: The safety population analysis for peritonitis included 91 patients in each group. The unadjusted geometric mean peritonitis rates in those groups were 0.30 [95% confidence interval (CI): 0.22 to 0.41] episodes per patient-year for the biocompatible group and 0.49 (95% CI: 0.39 to 0.62) episodes per patient-year for the control group [incidence rate ratio (IRR): 0.61; 95% CI: 0.41 to 0.90; p = 0.01]. When specific causative organisms were examined, the rates of culture-negative, gram-positive, gram-negative, and polymicrobial peritonitis episodes were not significantly different between the biocompatible and control groups, although the biocompatible group did experience a significantly lower rate of non-pseudomonal gram-negative peritonitis (IRR: 0.41; 95% CI: 0.18 to 0.92; p = 0.03). Initial empiric antibiotic regimens were comparable between the groups. Biocompatible fluid use did not significantly reduce the risk of peritonitis-associated hospitalization (adjusted odds ratio: 0.80; 95% CI: 0.48 to 1.34), but did result in a shorter median duration of peritonitis-associated hospitalization (6 days vs 11 days, p = 0.05). Peritonitis severity was more likely to be rated as mild in the biocompatible group (37% vs 10%, p = 0.001). Overall peritonitis-associated technique failures and peritonitis-related deaths were comparable in the two groups. ♦ Conclusions: Biocompatible PD fluid use was associated with a broad reduction in gram-positive, gram-negative, and culture-negative peritonitis that reached statistical significance for non-pseudomonal gram-negative organisms. Peritonitis hospitalization duration was shorter, and peritonitis severity was more commonly rated as mild in patients receiving biocompatible PD fluids, although other peritonitis outcomes were comparable between the groups.

Xanthogranulomatous Pyelonephritis in a Renal Allograft: A Case Report

We report a case of xanthogranulomatous pyelonephritis in a renal allograft. The kidney was not removed and there was an initial response to antibiotic therapy, with amelioration of toxicity and improvement in renal function. However, the kidney failed 10 months later in association with histological changes of chronic rejection.

Acute Renal Failure due to Acute Pyelonephritis

We report a case of biopsy-proved acute pyelonephritis which caused acute renal failure. Despite appropriate antibiotic therapy, recovery of renal function was slow and incomplete. Renal papillary necrosis was an apparent complication, which the patient may have been predisposed to by alcoholism. Although rare, acute pyelonephritis is an important consideration in the differential diagnosis of acute renal failure because of the need for specific therapy.

Haemodialysis‐unresponsive blood pressure: Cardiovascular mortality predictor?

Aim:  The importance of ‘conventional’ cardiovascular risk factors in haemodialysis (HD) patients has been questioned following evidence that pre‐HD blood pressure (BP) might be inversely related to mortality in contrast to post‐HD BP. To evaluate this reverse BP epidemiology in HD patients, HD‐induced BP changes were compared with aortic pulse wave velocity (PWV), an independent predictor of cardiovascular mortality.

Membranous Nephropathy Associated with Sarcoidosis

B.F. Jones, MD, Department of Nephrology, Royal Newcastle Hospital, Newcastle NSW 2300 (Australia) Dear Sir, Sarcoidosis may be associated with glomerulonephri-tis, most commonly membranous nephropathy [1]. There is limited information available on the response of this glomerulopathy to therapy [2–4]. We have observed a case of membranous nephropathy associated with sarcoidosis which showed a response to high-dose alternate-day prednisolone. In September 1978 a 32-year-old female presented with erythema nodosum, fever, polyarthralgia, and generalized rash. Chest X-ray demonstrated hilar lymphaden-opathy, and lymph nodes obtained at mediastinoscopy were replaced by granulomata showing central necrosis without caseation. Creatinine clearance was 100 ml/min and urine protein excretion 70 mg/day. Treatment with prednisolone 50 mg daily was commenced which resulted in a dramatic improvement in the constitutional symptoms and resolution of the hilar lympadenopathy. Steroids were ceased 2 years later after progressive reduction. In September 1983 she again presented with erythema nodosum, fever, and hilar lymphadenopathy. The serum angiotensin-converting enzyme level was 53.4 (normal 16–34) nmol/ml/min, and the erythrocyte sedimentation rate was 100 mm/h. Serum creatinine was 0.8 mg/dl (70 μmol/l) and urine protein excretion 2.0 g/day. There was a rapid clinical response ofthe systemic manifestations to prednisolone 25 mg daily, accompanied by a return to normal of serum angiotensin-converting enzyme level and erythrocyte sedimentation rate. However, 6 months later urine protein excretion had stabilized at 1 g/day, and renal biopsy was, therefore, carried out. This showed changes of membranous nephropathy on light microscopy, and immunofluorescence showed granular deposits of IgG and C3 along capillary loops. Prednisolone was increased to 120 mg on alternate days, and over the next 3 months protein excretion became normal. Prednisolone was reduced to 25 mg on alternate days and then to 12.5 mg on alternative days 4 months later. The urine protein excretion remained normal till March 1987, when it was found to be 6.9 g/day on a regular review. Serum creatinine remained normal, the serum angiotensin-converting enzyme level was 36.1 nmol/ml/min, and the erythrocyte sedimentation rate was 23 mm/h. Renal biopsy was carried out and the diagnosis of membranous nephropathy was again made on light and immunofluorescent microscopy. Electron microscopy (fig. 1) showed subepithelial deposits and basement membrane ‘spikes’ indicative of membranous nephropathy. Prednisolone was increased to 120 mg on alternate days. There was a progressive fall in urine protein excretion

Cyclophosphamide Pulse Therapy in Frequently Relapsing Nephrotic Syndrome

Bernard F. Jones, Department of Nephrology, John Hunter Hospital, Newcastle, N.S.W. (Australia) Dear Sir, Gandhi and Thomas [1] report success with pulse cyclophosphamide therapy in frequently relapsing nephrotic syndrome. Using a similar regime, I have also observed a favourable outcome for this condition. A 23-year-old male presented with generalised oedema. Urinary protein excretion was 7.2 g/day, serum albumin 18 g/l (1.8 g/dl) and serum creatinine 0.10 mmol/l (0.9 mg/dl). Urinalysis did not show haematuria. Renal biopsy was normal when examined by light and immunofluorescent microscopy. Remission of nephrotic syndrome occurred following steroid therapy, but relapse occurred shortly after stopping treatment. Despite two courses of oral cyclophosphamide (2 and 2.5 mg/kg body weight), a course of chloram-bucil 6 mg daily and treatment with cyclos-porin 5-7 mg/kg body weight for 20 months, he remained steroid dependent and experienced 14 relapses during the next 7 years. During a relapse 5 years after diagnosis, acute renal failure developed which required dialysis. Renal biopsy on this occasion showed mild interstitial oedema. Immunofluorescent microscopy showed IgM 1 + in the mesan-gium. Due to failure of all other therapies, he was treated with monthly intravenous cyclophosphamide 0.5 g/m2 body surface area (equivalent to 12.5 mg/kg body weight) for 6 months. During this time he continued pred-nisolone 40 mg on alternate days, known to be sufficient to maintain remission of nephrotic syndrome. Prednisolone was stopped 2 weeks after the last dose of cyclophosphamide. There has been no recurrence of nephrotic syndrome 6 months later. No side-effects of treatment were apparent. Although spontaneous remission of nephrotic syndrome cannot be excluded, this experience supports that of Gandhi and Thomas [1] and suggests that consideration should be given to pulse cyclophosphamide in steroid-dependent minimallesion nephrotic syndrome which is refractory to conventional therapy. Reference Gandhi R, Thomas C: Cyclophosphamide pulse therapy in frequently relapsing nephrotic syndrome. Nephron 1990; 55:444.

Continuous Ambulatory Peritoneal Dialysis in Scleroderma

Bernard Jones, Department of Nephrology, Royal Newcastle Hospital, Newcastle NSW 2300 (Australia) Dear Sir, The best treatment for end stage renal disease due to scleroderma is uncertain. Haemodialysis [1] and transplantation [1, 2] have been used but experience is limited and success has been variable. There is also little experience with continuous ambulatory peritoneal dialysis (CAPD) and thus far only 3 cases have been reported [3, 4]. We have successfully treated a 55-year-old female with biopsy-proved renal failure due to scleroderma with CAPD for 12 months. Other complications of scleroderma which had developed prior to CAPD included malignant hypertension, pericarditis, upper limb peripheral vascular insufficiency, reflux oesophagitis, scler-odactyly, carpal tunnel syndrome and Raynaud’s phenomenon. A Tenckhoff catheter was used, the insertion of which was complicated by peritonitis. However, there have been no further episodes of peritonitis. Fluid balance has been easily controlled and serum creatinine, blood urea nitrogen and haemoglobin levels have been approximately 5.3 mg/dl (0.47 mmol/l), 34 mg/dl (12 mmol/l) and 8.9 g/dl (89 g/l), respectively. A 24-hour kidney creatinine clearance was 4.8 ml/min. Dialysate/plasma concentration ratios for urea and creatinine were 0.93 and 0.81, respectively. A measurement of dialysate protein loss was 11.3 g/day. Small amounts of phosphate binders and antihypertensive drugs have been required. During the first 9 months body weight fell progressively by 6 kg, and serum albumin averaged 3.2 g/dl (32 g/l). A dietary assessment showed inadequate protein and caloric intake. She attributed this to a feeling of fullness caused by peritoneal dialysis fluid. Encouragement to increase caloric intake and to have smaller more frequent meals resulted in stabilisation of body weight and a rise in serum albumin to 3.9 g/l (39 g/l) during the next 3 months. She did not perceive any improvement in her skin changes. Two small abdominal incisional hernias have developed. She becomes fatigued on moderate or sustained exertion, but manages her usual household tasks. This report accords with others [3, 4] which show that CAPD is a satisfactory treatment for renal failure due to scleroderma. Although the good biochemistry would have been partly due to the residual renal function, equilibration of urea and creatinine between blood and dialysate was similar to that measured when CAPD has been used to treat renal failure due to other causes [5], which does not support the suggestion that peritoneal clearances in scleroderma may be suboptimal [6]. Dialysate protein loss was also comparable to patients receiving CAPD for renal failure due to other causes [7]. Special attention was necessary to diet in order to maintain adequate nutrition, which may have been improved by the use of smaller volume exchanges. Difficulties with nutrition [4] and gastrointestinal symptoms though due to dialysis fluid in the

URINE OSMOLALITY AND URINARY RED CELL MORPHOLOGY

Bernard F. Jones, Department of Nephrology, Royal Newcastle Hospital, Newcastle, NSW 2300 (Australia) Dear Sir, In their study of the effect of urine osmolality on urinary red cell morphology, Turitzin et al. [1] conclude that red cell lysis occurs at a urine osmolality less than 210 mosm/kg because they were able to demonstrate a left shift in red cell size distribution below this osmolality, and they also demonstrate a normal cell size frequency distribution of erythrocytes incubated in urine with osmolality of 247 mosm/kg. It is of importance, however, that urine tonicity is considerably less than the osmolality value would suggest because of urinary urea, which, passing freely across cell membranes, does not effect fluid shifts. Although the urea content of urine is diet dependent, the normal range of 450– 700 mmol/day [2] indicates that urea contributes substantially to urine osmolality, and a recent study from this department in 105 randomly selected outpatients having urine microscopy performed showed that urine tonicity was only 0.53 ± 0.12 (mean ± SD) the osmolality value. This compares to other values in the literature, varying between 0.49 ± 0.07 and 0.70 which can be calculated from data of Hulet and Smith [3] and Steinmetz and Smith [4], respectively. Thus Turitzin et al. have shown a normal red cell size distribution when urine tonicity is presumably in the range 120–170 mosm/kg and a left shift in red cell size distribution when urine tonicity is presumably in the range 105–150 mosm/kg. However, plasma tonicity of approximately 150 mosm/kg causes lysis of 50% of red cells, and plasma tonicity of approximately 110 mosm/kg causes lysis of all red cells [5]. Therefore, although the study has practical implications for evaluation of urinary red cell morphology by cell counter, it seems likely that cell size distribution is not affected until red cell lysis is marked, and the study does not allow the conclusion that red cell lysis occurs only when urine osmolality is less than 210 mosm/kg. To reach this conclusion, the sensitivity of red cell size frequency distribution in detecting red cell lysis needs to be compared to a standard method of measuring red cell lysis. In addition to an effect of urine concentration on red cell size measured by cell counter, work from this department has shown that reduced urine tonicity affects urine red cell count as determined by phase contrast microscopy, which may explain failure to confirm by microscopy a positive urine dipstick test for blood [6]. Thus, the influence of urine concentration needs to be considered with this method of urine examination also. References Turitzin SN, Rotellar C, Winchester JF et al: Effect of urine osmolality and urinary red cell morphology. Nephron 1990; 55:344_345. Editorial: Now hear this: The SI units are here. JAMA 1986; 255:2329–2339.