Aleck M. Brownjohn

The clinical and biochemical features of acute renal failure due to rhabdomyolysis.

Rhabdomyolysis caused 28 out of 903 (3.1%) of cases of severe acute renal failure (ARF) treated at Leeds General Infirmary over a 14-year period (1980-1993). The commonest cause of rhabdomyolysis was muscle compression, usually due to drug- or alcohol-induced coma. Other causes included fits, infection, acute limb ischemia, trauma, and heat stroke. Prognosis was relatively good, with a 78.6% survival rate and recovery of renal function to normal in all survivors who were followed up. The creatinine/urea ratio was higher in ARF due to rhabdomyolysis than in an unselected group of patients with other causes of ARF but not when the comparison was with sex- and age-matched controls with ARF. This suggests that this previously described feature of rhabdomyolysis simply reflects the increased muscle mass of a younger group of patients, rather than a specific effect of muscle damage. Clinical features of muscle damage were often absent and so the possibility of rhabdomyolysis should be considered in appropriate settings if the diagnosis is to be made early enough to administer treatment that may prevent ARF and the consequences of the compartment syndrome.

Assessment of Renal Osteodystrophy in Dialysis Patients: Use of Bone Alkaline Phosphatase, Bone Mineral Density and Parathyroid Ultrasound in Comparison with Bone Histology

Bone biopsies were studied in 73 patients to determine if a two-site radioimmunometric assay for serum bone alkaline phosphatase (BAP), total serum alkaline phosphatase (ALP), serum intact parathyroid hormone (iPTH), hand X-rays, regional bone mineral density (BMD) measurements and parathyroid enlargement detected by ultrasonography could accurately predict renal osteodystrophy. In the patients studied 57 had hyperparathyroid bone disease, 4 mixed renal osteodystrophy, 3 adynamic bone disease, 1 osteomalacia and 8 normal histology. Serum BAP, ALP and iPTH correlated positively with mineral apposition rate, osteoblastic, osteoid and eroded surface. In the diagnosis of hyperparathyroid bone disease serum iPTH was the most sensitive investigation, detecting 81% of patients at a level > 100 pg/ml but with a specificity of only 66%. Serum BAP was more sensitive, 70% at a level of > 10 ng/ml, than serum total ALP, 30% at a level of 300 IU/l, with similar specificities, 92 and 100%, respectively. Ultrasound detection of an enlarged parathyroid gland had a sensitivity of 64% and a specificity of 100% for the diagnosis of hyperparathyroid bone disease. Hand X-rays had a poor sensitivity, 47%, but a high specificity, 92%, for the detection of hyperparathyroid bone disease. The majority of patients had regional BMD values within the normal reference range and this test was of poor discriminatory value. The non-invasive markers were unable to distinguish between patients with low turnover, mild hyperparathyroidism and patients with normal histology. In conclusion the measurement of serum iPTH is a useful screening tool for the detection of hyperparathyroid bone disease which can be confirmed by the finding of a raised serum BAP or parathyroid enlargement. For definitive diagnosis, however, the gold standard remains bone biopsy and at present one cannot recommend any non-invasive method as an adequate substitute.

Protein Losses in Patients Receiving Continuous Ambulatory Peritoneal Dialysis

Total protein and 12 specific proteins were measured in dialysates from 8 patients on continuous ambulatory peritoneal dialysis during training. Mean daily loss of total protein was 10.5 g and this included 5.2 g albumin, 805 mg of the immunoglobulins G, A and M, 323 mg transferrin and 530 mg of the remaining 7 proteins measured. The plasma to dialysate ratio of protein concentrations correlated with the natural logarithm of molecular weight, suggesting that proteins in dialysate are an ultrafiltrate of plasma. A greater loss of proteins overnight was due to longer dwell time as the mean rate of loss was similar for all exchanges. Losses were similar with 1.36% and 3.86% dextrose fluids, suggesting that the initial effects of hypertonicity are diminished or reversed by dilution and absorption of dextrose. Daily outflow volumes for 4 patients correlated inversely with the quantities of several proteins removed, probably due to effects of osmolality. It is concluded that protein losses are related to plasma concentration, molecular weight and osmolality of the dialysis solution and to the physiology of the patient.

Evaluation of RBC ferritin and reticulocyte measurements in monitoring response to intravenous iron therapy.

Intravenous (IV) iron therapy can reduce erythropoietin (EPO) requirements in dialysis patients. Monitoring this response accurately is difficult. Estimation of red blood cell ferritin (RBCFer) and reticulocyte indices may give additional valuable information about iron availability to the erythroblasts (erythron). We evaluated the use of RBCFer, mean hemoglobin content of reticulocytes (CHr), and mean hemoglobin concentration of reticulocytes (CHCMr) in a prospective, nonblinded study of 22 hemodialysis patients (16 men and six women with a mean age of 62 years [range, 24 to 80 years]). All patients had an initial serum ferritin of < or = 60 microg/L. Patients with features known to produce EPO resistance and underlying bleeding/hematologic disorders were excluded. Patients were established on subcutaneous EPO and given IV iron therapy. The mean hemoglobin level remained constant throughout the study (P = 0.087). Serum ferritin and RBCFer increased significantly (P < 0.001 and 0.015, respectively) while a reduction in transferrin saturation became significant at the end of the study (P = 0.0047). A sharp increase in reticulocytes occurred in the first 14 days after commencement of IV iron, and there was an initial decrease in the percentage of hypochromic RBCs. An early decline in RBCFer was apparent. CHr increased with IV iron, indicative of increased iron supply to the developing erythron. Measurement of RBCFer and CHr provide evidence of increased iron supply for erythropoiesis during IV iron therapy. These measures help identify patients with functional iron deficiency and allow more accurate monitoring of response to IV iron therapy.

Failure of renal dopamine response to salt loading in chronic renal disease.

Eight patients with chronic glomerulonephritis and five age-matched normal volunteers were given additional sodium chloride by mouth under conditions of metabolic balance. Whereas in the normal volunteers plasma renin activity was suppressed and urinary excretion of free dopamine increased, in the patients dopamine was not mobilised and plasma renin activity was not completely suppressed. Abnormal retention of sodium and water in glomerulonephritis may be due partly to a failure to mobilise dopamine in the kidney. Specific renal dopamine agonists may be natriuretic and hypotensive in chronic glomerulonephritis.

Effective utilization of erythropoietin with intravenous iron therapy

Introduction: Iron replacement therapy reduces the demand for erythropoietin (EPO) in some dialysis patients. It has been postulated that iron supply to the bone marrow is a rate-limiting step in the process of erythropoiesis under erythropoietin stimulation. Methods: We evaluated the economic benefit of intravenous iron therapy for this purpose in a prospective, non-blinded study of 22 haemodialysis patients, 16 male, six female, mean age 62 years (range 24–80 years). All patients had a serum ferritin (SF) of 460 μg/L, despite oral iron therapy. Patients with high aluminium and/or parathyroid hormone (PTH) levels, underlying bleeding/haematological disorders or active inflammatory diseases were excluded. Patients were established on subcutaneous EPO and given intravenous iron over seven consecutive dialysis sessions (total dose 1050 mg) and supplemental monthly doses with regular monitoring for 4 months. Results: The median EPO dose was 4000 units/week (mean 6050 units/week) pre-treatment and 2000 units/week (mean 3700 units) at 6 weeks post intravenous iron therapy ( P=0·03). No serious adverse events occurred in the 154 treatment sessions of intravenous iron. Mean haemoglobin (Hb) level remained constant at 6 and 12 weeks ( P=0·087). Serum ferritin levels (P< 0·0001) rose significantly, while a reduction in transferrin saturation (TS) became significant at the end of the study ( P=0·0047). The use of intravenous iron allowed a substantial monthly cost saving per patient in our unit. Conclusion: Intravenous iron therapy is a safe and cost-effective method for maintaining or improving Hb levels with a more effective utilization of EPO in patients with low SF levels despite oral iron therapy.Introduction: Iron replacement therapy reduces the demand for erythropoietin (EPO) in some dialysis patients. It has been postulated that iron supply to the bone marrow is a rate‐limiting step in the process of erythropoiesis under erythropoietin stimulation. Methods: We evaluated the economic benefit of intravenous iron therapy for this purpose in a prospective, non‐blinded study of 22 haemodialysis patients, 16 male, six female, mean age 62 years (range 24–80 years). All patients had a serum ferritin (SF) of 460 μg/L, despite oral iron therapy. Patients with high aluminium and/or parathyroid hormone (PTH) levels, underlying bleeding/haematological disorders or active inflammatory diseases were excluded. Patients were established on subcutaneous EPO and given intravenous iron over seven consecutive dialysis sessions (total dose 1050 mg) and supplemental monthly doses with regular monitoring for 4 months. Results: The median EPO dose was 4000 units/week (mean 6050 units/week) pre‐treatment and 2000 units/week (mean 3700 units) at 6 weeks post intravenous iron therapy ( P=0·03). No serious adverse events occurred in the 154 treatment sessions of intravenous iron. Mean haemoglobin (Hb) level remained constant at 6 and 12 weeks ( P=0·087). Serum ferritin levels (P< 0·0001) rose significantly, while a reduction in transferrin saturation (TS) became significant at the end of the study ( P=0·0047). The use of intravenous iron allowed a substantial monthly cost saving per patient in our unit. Conclusion: Intravenous iron therapy is a safe and cost‐effective method for maintaining or improving Hb levels with a more effective utilization of EPO in patients with low SF levels despite oral iron therapy.

Low thrombogenicity of polyethylene glycol–grafted cellulose membranes does not influence heparin requirements in hemodialysis

Heparin is the most commonly used anticoagulant for hemodialysis despite potentially serious side effects. Polyethylene glycol-grafted cellulose (PGC) membranes produce less activation of the coagulation cascade than cuprophane membranes. Anecdotally, we found some patients required a surprisingly low level of anticoagulation using these membranes. We compared the anticoagulant requirement of the PGC membrane with that of the cuprophane membrane in this randomized, prospective, crossover study. Sixty-three patients were randomized to treatment using either membrane, and heparin administration was progressively reduced to the lowest dose that prevented visible clotting in excess of that normally encountered. Patients underwent dialysis at this dose for 1 month, after which the heparin requirement and Kt/Vurea (1.162 x ln [urea pre/urea post]) were assessed. This process was then repeated for each patient using the other membrane, and the results were compared. Heparin administration during dialysis was reduced from a mean loading dose of 29.0 +/- 9.4 to 1.5 +/- 3.2 IU/kg for both membranes and a mean maintenance infusion of 14.0 +/- 6.7 to 0.77 +/- 1.6 IU/kg/h for both membranes (both P < 0.0001 v full anticoagulation; no difference between membranes). The Kt/Vurea was not significantly altered. Forty-six patients with PGC and 45 patients with cuprophane membranes underwent dialysis successfully without heparin during dialysis, and the other patients were using considerably reduced doses. Aspirin and warfarin had no effect on the heparin requirement. These results do not support the theory that PGC membranes have a lower anticoagulant requirement than cuprophane membranes; however, they suggest that dialysis can be performed successfully with much smaller anticoagulant doses than are currently in common use.

Uterine prolapse and urinary tract obstruction.

A propos de 2 observations. Le prolapsus uterin peut provoquer une obstruction urinaire et une insuffisance renale, reversibles apres des traitements simples

Lesson of the week: Causes of haematuria in adult polycystic kidney disease.

Do not assume that haematuria in association with adult polycystic kidney disease is always benign

Plasma and dialysate immunoglobulin G in continuous ambulatory peritoneal dialysis patients : a multicenter study

Peritoneal dialysate immunoglobulin (Ig)G concentrations were measured in 120 continuous ambulatory peritoneal dialysis (CAPD) patients evaluated at four dialysis centers in different countries to assess the normal range for dialysate IgG and to investigate the relationships of this protein levels with peritoneal episodes, For 65 of these patients, plasma IgG levels were determined, and IgG clearances were calculated. The mean dialysate concentration of IgG was 6.9 +/- 4.2 mg/dl, and there was no difference between men and women or between patients who had or had not previously undergone hemodialysis. Dialysate IgG concentrations were significantly related to residual renal creatinine clearance and negatively correlated with dialysate volume, plasma albumin and total protein. There were no significant correlations between IgG levels in the dialysate and age, protein losses in the dialysate, time on CAPD or time from the last peritonitis episode. Plasma and dialysate IgG were unrelated to the incidence of peritonitis, statistical analysis being performed with different methods. These results suggest that IgG levels in the dialysate or plasma are not a major factor in the prevention of CAPD peritonitis.